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  1. Reduced cytosolic carboxypeptidase 6 (CCP6) level leads to accumulation of serum polyglutamylated DNAJC7 protein: A potential biomarker for renal cell carcinoma early detection

    PubMed Central

    Li, Yi; Zhu, Xiaoxiao; Ding, Juan; Ren, Shuangchun; Zhao, Heping; Wu, Song; Tian, Yong; Wang, Guo-Qing

    2016-01-01

    Renal cell carcinoma (RCC) is frequently diagnosed at advanced stages of disease, although early diagnosis has much favorable prognosis. This study assessed aberrant expression of cytosolic carboxypeptidase 6 (CCP6) leading to accumulation of serum polyglutamylated DNAJC7 as a biomarker for early RCC detection. A total of 835 RCCs, 143 chronic nephritis, 170 kidney stones and 415 health controls were collected for qRT-PCR, immunohistochemistry and Western blot analysis of CCP6 expression and mass spectrometry of DNAJC7 and polyglutamylated DNAJC7. The data showed that CCP6 expression was significantly decreased in 30 RCC tissues and that mass spectrometric and pull-down analysis identified DNAJC7 as a substrate of CCP6 and showed upregulated polyglutamylated-DNAJC7 (polyE-DNAJC7) in sera of RCC patients. The electrochemiluminescence immunoassay of large-scale serum samples from multi-institutes further confirmed the remarkable increase of polyE-DNAJC7 in 805 RCCs compared to that of 385 healthy controls (p < 0.001), 128 patients with chronic nephritis (p < 0.001), and 153 with kidney stone (p < 0.001). Serum level of DNAJC7-polyE protein was also associated with advanced RCC stage and grade in 805 patients. The data from the current study for the first time demonstrated increased serum polyglutamylated DNAJC7 as a potential biomarker for RCC early detection and association with advanced tumor stages and grade, which provides support of further polyglutamylation research in RCC. PMID:26993597

  2. Self-report of Fruit and Vegetable Intake that meets the 5 A Day Recommendation is Associated with Reduced Levels of Oxidative Stress Biomarkers and Increased Levels of Antioxidant Defense in Premenopausal Women

    PubMed Central

    Rink, Stephanie M.; Mendola, Pauline; Mumford, Sunni L.; Poudrier, Jill K.; Browne, Richard W.; Wactawski-Wende, Jean; Perkins, Neil J.; Schisterman, Enrique F.

    2013-01-01

    Background Oxidative stress has been associated with a variety of chronic diseases and reproductive disorders. Fruits and vegetables may contribute to antioxidant vitamin and micronutrient levels and reduce oxidative stress. Objective To investigate the effect of meeting the 5 A Day recommendation for fruit and vegetable consumption on biomarkers of oxidative damage and antioxidant defense. Design In this longitudinal study, healthy premenopausal women (n=258) were followed for ≤2 menstrual cycles with ≤16 oxidative stress measures timed to cycle phase. Main outcome measures Plasma concentrations of F2-isoprostane, 9-hydroxyoctadecadieneoic acid (9-HODE), and 13-hydroxyoctadecadieneoic acid (13-HODE), erythrocyte activity of superoxide dismutase (SOD), glutathione reductase (GSHR), and glutathione peroxidase (GPx), as well as blood micronutrient concentrations were measured. Dietary intake was assessed by Food Frequency Questionnaires (FFQ, 1/cycle) and 24-hour recalls (≤4/cycle). Statistical analyses performed Fruit and vegetable servings were dichotomized based on the 5 A Day recommendation. Linear mixed models with repeated measures were used to analyze lipid peroxidation markers, antioxidant vitamins, and antioxidant enzymes by cycle phase and in association with usual fruit and vegetable intake. Results For both 24-hour recall (timed to cycle phase) and cycle-specific FFQ, meeting the 5 A Day recommendation was associated with decreased F2-isoprostanes (24-hour recall β= −0.10 (95% CI: −0.12, −0.07); FFQ β= −0.14 (95% CI: −0.18, −0.11)). GSHR was lower in association with typical 5A Day consumption by FFQ but not in the phase-specific analysis. Higher levels of ascorbic acid, lutein, β-carotene and β-cryptoxanthin were observed with both 5 A Day measures. Conclusions Meeting the 5 A Day recommendation was associated with lower oxidative stress and improved antioxidant status in analyses of typical diet (FFQ) and in menstrual cycle phase

  3. Insulin Resistance is Associated with Increased Levels of Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease and Reduced Memory Function in At-Risk Healthy Middle-Aged Adults

    PubMed Central

    Hoscheidt, Siobhan M.; Starks, Erika J.; Oh, Jennifer M.; Zetterberg, Henrik; Blennow, Kaj; Krause, Rachel A.; Gleason, Carey E.; Puglielli, Luigi; Atwood, Craig S.; Carlsson, Cynthia M.; Asthana, Sanjay; Johnson, Sterling C.; Bendlin, Barbara B.

    2016-01-01

    Background Type 2 diabetes is associated with an increased risk for Alzheimer disease (AD). Regulation of normal insulin function may be important in reducing the prevalence of dementia due to AD, particularly in individuals who harbor genetic risk for or have a parental family history of AD. The relationship between insulin resistance (IR) and AD pathology remains poorly understood, particularly in midlife prior to the onset of clinical metabolic disease or cognitive decline. Objective We examined associations between IR as indexed by HOMA-IR, cerebral spinal fluid (CSF) biomarkers of AD pathology and memory in middle-aged adults enriched for AD. We postulated that higher HOMA-IR and APOE ε4 carriage would be associated with greater CSF AD pathology and poor memory performance. Methods Cognitively asymptomatic middle-aged adults (N=70, mean age=57.7 years) from the Wisconsin Alzheimer’s Disease Research Center with a parental family history of dementia due to AD underwent lumbar puncture, blood draw and neuropsychological testing. CSF AD biomarkers including soluble amyloid precursor protein β (sAPP-β), β–amyloid42 (Aβ42) and phosphorylated tau (P-tau181) were examined with respect to HOMA-IR and APOE ε4 status. Delayed memory performance was examined with respect to HOMA-IR, CSF AD biomarkers and APOE ε4 status. Results Higher HOMA-IR was associated with higher sAPP-β and Aβ42. APOE ε4 carriers had significantly higher levels of sAPP-α, sAPP-β and P-tau181/Aβ42 compared to noncarriers. The concurrent presence of higher HOMA-IR and CSF AD pathology predicted worse delayed memory performance. Conclusion Overall, the findings suggest that IR and APOE ε4 are contributing factors to the development of AD pathology in midlife, and provide support for targeting insulin function as a potentially modifiable risk factor for AD. PMID:27079723

  4. Biomarkers of Heart Failure with Preserved and Reduced Ejection Fraction.

    PubMed

    Senni, Michele; D'Elia, Emilia; Emdin, Michele; Vergaro, Giuseppe

    2017-02-09

    Biomarkers are increaingly being used in the management of heart failure not only for the purpose of screening, diagnosis, and risk stratification, but also as a guide to evaluate the response to treatment in the individual patient and as an entry criterion and/or a surrogate marker of efficacy in clinical trials testing novel drugs. In this chapter, we review the role of established biomarkers for heart failure management, according to the main classification of HF phenotypes, based on the measurement of left ventricular ejection fraction, including heart failure with reduced (<40%), preserved (≥50%), and, as recently proposed, mid-range (40-49%) ejection fraction.

  5. BIOMARKERS OF ENDOCRINE DISRUPTION AT THE MRNA LEVEL

    EPA Science Inventory

    Denslow, Nancy D., Christopher J. Bowman, Gillian Robinson, H. Stephen Lee, Ronald J. Ferguson, Michael J. Hemmer and Leroy C. Folmar. 1999. Biomarkers of Endocrine Disruption at the mRNA Level. In: Environmental Toxicology and Risk Assessment: Standardization of Biomarkers for ...

  6. Baroreflex function is reduced in Alzheimer's disease: a candidate biomarker?

    PubMed

    Meel-van den Abeelen, Aisha S S; Lagro, Joep; Gommer, Erik D; Reulen, Jos P H; Claassen, Jurgen A H R

    2013-04-01

    The baroreflex (BR) reflects autonomic blood pressure control. Alzheimer's disease (AD) affects the autonomic system. Detailed properties of BR in AD are unknown. We hypothesized that BR is reduced in AD, and is influenced by autonomic effects of cholinesterase inhibitors (ChEI). BR was determined in 18 AD patients, 11 patients with mild cognitive impairment (MCI) and 19 healthy control subjects. In AD, BR was measured again after ChEI treatment. Receiver operating characteristic analysis was used to define a BR cutoff value, which was then tested in an independent validation sample of 16 AD, 18 MCI, and 18 control subjects. BR was lower in AD compared with MCI (p < 0.05) and in MCI compared with healthy control subjects (p < 0.01). Receiver operating characteristic analysis between AD and healthy control subjects yielded a sensitivity of 89% and a specificity of 94%. ChEI treatment increased BR with 66% (p < 0.01). BR was reduced in AD and increased after treatment with ChEI. BR might be a good biomarker to further explore the link between cardiovascular disease and AD.

  7. Kidney biomarkers in MCPA-induced acute kidney injury in rats: reduced clearance enhances early biomarker performance.

    PubMed

    Wunnapuk, Klintean; Liu, Xin; Gobe, Glenda C; Endre, Zoltan H; Peake, Philip W; Grice, Jeffrey E; Roberts, Michael S; Buckley, Nicholas A

    2014-03-21

    For improved early detection and assessment of severe acute kidney damage following accidental or intentional ingestion of the herbicide MCPA, we compared a panel of 14 novel kidney injury biomarkers with plasma creatinine. Male Wistar rats received four different oral doses of MCPA and plasma and urine biomarker levels were measured at 8, 24 and 48 h after MCPA exposure. Diagnostic performances using absolute levels, urine levels normalized to urine creatinine or urinary excretion rate were determined by ROC analysis. Plasma creatinine remained the best early biomarker for predicting histological changes at 48 h. The performance of plasma cystatin C in mirroring kidney function was similar to that of plasma creatinine. While urine concentrations were generally less predictive, normalization by urine creatinine greatly improved the performance of several biomarkers. This may be due to an apparent amplification of the biomarker signal on normalizing to creatinine, in the presence of a declining glomerular filtration rate prior to reaching steady state. Normalized 8 h osteopontin and albumin concentrations outperformed other normalized biomarkers in predicting histological changes at later times. Normalized urinary kidney injury molecule-1 at 48 h also correlated well with the degree of kidney damage.

  8. Biomarkers to assess the utility of potential reduced exposure tobacco products.

    PubMed

    Hatsukami, Dorothy K; Benowitz, Neal L; Rennard, Stephen I; Oncken, Cheryl; Hecht, Stephen S

    2006-08-01

    To date, we have no valid biomarkers that serve as proxies for tobacco-related disease to test potential reduced exposure products. This paper represents the deliberations of four workgroups that focused on four tobacco-related heath outcomes: Cancer, nonmalignant pulmonary disease, cardiovascular disease, and fetal toxicity. The goal of these workgroups was to identify biomarkers that offer some promise as measures of exposure or toxicity and ultimately may serve as indicators for future disease risk. Recommendations were based on the relationship of the biomarker to what is known about mechanisms of tobacco-related pathogenesis, the extent to which the biomarker differs among smokers and nonsmokers, and the sensitivity of the biomarker to changes in smoking status. Other promising biomarkers were discussed. No existing biomarkers have been demonstrated to be predictive of tobacco-related disease, which highlights the importance and urgency of conducting research in this area.

  9. Reduced chromosomal puffing in Chironomus tentans as a biomarker for potentially genotoxic substances

    SciTech Connect

    Bentivegna, C.S. . Dept. of Environmental Sciences); Cooper, K.R. . Joint Graduate Program in Toxicology)

    1993-06-01

    Chromosomal puffing in the salivary glands of larval Chironomus tentans was developed as a biomarker for genotoxic substances. Reduced chromosomal puffing was considered an indication of decreased RNA synthesis. Third- or fourth-instar larvae were exposed to test chemicals in an artificial substrate under static conditions. Chromosomes from glands of individual larvae were stained with methyl green and pyronin Y. The widths of Balbiani rings 1 and 2 were measured. Three carcinogens with different mechanisms of action were tested, benzo[a] pyrene(BaP), actinomycin D(Act D), and dimethylnitrosamine (DMN). Puff size was statistically reduced by all three chemicals with varying potency. Lowest-observable-effect levels were 0.5 nmol BaP, 6.0 nmol Act D, and 24443,000 nmol DMN. The degree of response was influenced by exposure time, applied dose, individual sensitivity, and possibly chemical hydrophobicity. Biomarker specificity was determined by testing a weak carcinogen, benzo[e]pyrene(BeP), and an acutely toxic noncarcinogen, naphthalene(NP). The effective dose of BaP was four orders of magnitude higher than that of BaP. Only lethal doses of NP had statistically significant effects on puff size, LD50 = 25,000 nmol. Approximately 40% of the larvae in the laboratory population appeared tolerant to the effects of BaP. Advantages of this biomarker were its association with a known mechanism of action and measurement of the whole-organism integrated response.

  10. ErbB3 mRNA leukocyte levels as a biomarker for major depressive disorder

    PubMed Central

    2012-01-01

    Background In recent years, the identification of peripheral biomarkers that are associated with psychiatric diseases, such as Major Depressive Disorder (MDD), has become relevant because these biomarkers may improve the efficiency of the differential diagnosis process and indicate targets for new antidepressant drugs. Two recent candidate genes, ErbB3 and Fgfr1, are growth factors whose mRNA levels have been found to be altered in the leukocytes of patients that are affected by bipolar disorder in a depressive state. On this basis, the aim of the study was to determine if ErbB3 and Fgfr1 mRNA levels could be a biomarkers of MDD. Methods We measured by Real Time PCR ErbB3 and Fgfr1 mRNA expression levels in leukocytes of MDD patients compared with controls. Successively, to assess whether ErbB3 mRNA levels were influenced by previous antidepressant treatment we stratified our patients sample in two cohorts, comparing drug-naive versus drug-free patients. Moreover, we evaluated the levels of the transcript in MDD patients after 12 weeks of antidepressant treatment, and in prefrontal cortex of rats stressed and treated with an antidepressant drug of the same class. Results These results showed that ErbB3 but not Fgfr1 mRNA levels were reduced in leukocytes of MDD patients compared to healthy subjects. Furthermore, ErbB3 levels were not affected by antidepressant treatment in either human or animal models Conclusions Our data suggest that ErbB3 might be considered as a biomarker for MDD and that its deficit may underlie the pathopsysiology of the disease and is not a consequence of treatment. Moreover the study supports the usefulness of leukocytes as a peripheral system for identifying biomarkers in psychiatric diseases. PMID:22989054

  11. Reduced creatine kinase as a central and peripheral biomarker in Huntington’s disease

    PubMed Central

    Kim, Jinho; Amante, Daniel J.; Moody, Jennifer P.; Edgerly, Christina K.; Bordiuk, Olivia L.; Smith, Karen; Matson, Samantha A.; Matson, Wayne R.; Scherzer, Clemens R.; Rosas, H. Diana; Hersch, Steven M.; Ferrante, Robert J.

    2010-01-01

    A major goal of current clinical research in Huntington’s disease (HD) has been to identify preclinical and manifest disease biomarkers, as these may improve both diagnosis and the power for therapeutic trials. Although the underlying biochemical alterations and the mechanisms of neuronal degeneration remain unknown, energy metabolism defects in HD have been chronicled for many years. We report that the brain isoenzyme of creatine kinase (CK-BB), an enzyme important in buffering energy stores, was significantly reduced in presymptomatic and manifest disease in brain and blood buffy coat specimens in HD mice and HD patients. Brain CK-BB levels were significantly reduced in R6/2 mice by ~18% to ~68% from 21–91 days of age, while blood CK-BB levels were decreased by ~14% to ~44% during the same disease duration. Similar findings in CK-BB levels were observed in the 140 CAG mice from 4–12 months of age, but not at the earliest time point, 2 months of age. Consistent with the HD mice, there was a grade-dependent loss of brain CK-BB that worsened with disease severity in HD patients from ~28% to ~63%, as compared to non-diseased control patients. In addition, CK-BB blood buffy coat levels were significantly reduced in both premanifest and symptomatic HD patients by ~23% and ~39%, respectively. The correlation of CK-BB as a disease biomarker in both CNS and peripheral tissues from HD mice and HD patients may provide a powerful means to assess disease progression and to predict the potential magnitude of therapeutic benefit in this disorder. PMID:20460152

  12. Reduced Prepulse Inhibition as a Biomarker of Schizophrenia.

    PubMed

    Mena, Auxiliadora; Ruiz-Salas, Juan C; Puentes, Andrea; Dorado, Inmaculada; Ruiz-Veguilla, Miguel; De la Casa, Luis G

    2016-01-01

    The startle response is composed by a set of reflex behaviors intended to prepare the organism to face a potentially relevant stimulus. This response can be modulated by several factors as, for example, repeated presentations of the stimulus (startle habituation), or by previous presentation of a weak stimulus (Prepulse Inhibition [PPI]). Both phenomena appear disrupted in schizophrenia that is thought to reflect an alteration in dopaminergic and glutamatergic neurotransmission. In this paper we analyze whether the reported deficits are indicating a transient effect restricted to the acute phase of the disease, or if it reflects a more general biomarker or endophenotype of the disorder. To this end, we measured startle responses in the same set of thirteen schizophrenia patients with a cross-sectional design at two periods: 5 days after hospital admission and 3 months after discharge. The results showed that both startle habituation and PPI were impaired in the schizophrenia patients at the acute stage as compared to a control group composed by 13 healthy participants, and that PPI but not startle habituation remained disrupted when registered 3 months after the discharge. These data point to the consideration of PPI, but not startle habituation, as a schizophrenia biomarker.

  13. Reduced Prepulse Inhibition as a Biomarker of Schizophrenia

    PubMed Central

    Mena, Auxiliadora; Ruiz-Salas, Juan C.; Puentes, Andrea; Dorado, Inmaculada; Ruiz-Veguilla, Miguel; De la Casa, Luis G.

    2016-01-01

    The startle response is composed by a set of reflex behaviors intended to prepare the organism to face a potentially relevant stimulus. This response can be modulated by several factors as, for example, repeated presentations of the stimulus (startle habituation), or by previous presentation of a weak stimulus (Prepulse Inhibition [PPI]). Both phenomena appear disrupted in schizophrenia that is thought to reflect an alteration in dopaminergic and glutamatergic neurotransmission. In this paper we analyze whether the reported deficits are indicating a transient effect restricted to the acute phase of the disease, or if it reflects a more general biomarker or endophenotype of the disorder. To this end, we measured startle responses in the same set of thirteen schizophrenia patients with a cross-sectional design at two periods: 5 days after hospital admission and 3 months after discharge. The results showed that both startle habituation and PPI were impaired in the schizophrenia patients at the acute stage as compared to a control group composed by 13 healthy participants, and that PPI but not startle habituation remained disrupted when registered 3 months after the discharge. These data point to the consideration of PPI, but not startle habituation, as a schizophrenia biomarker. PMID:27803654

  14. Ecological relevance of Sentinels' biomarker responses: a multi-level approach.

    PubMed

    Seabra Pereira, Camilo D; Abessa, Denis M S; Choueri, Rodrigo B; Almagro-Pastor, Victor; Cesar, Augusto; Maranho, Luciane A; Martín-Díaz, María Laura; Torres, Ronaldo J; Gusso-Choueri, Paloma K; Almeida, João E; Cortez, Fernando S; Mozeto, Antonio A; Silbiger, Helcy L N; Sousa, Eduinetty C P M; Del Valls, Tommas Angel; Bainy, Afonso C D

    2014-05-01

    In response to the need for more sensitive and rapid indicators of environmental quality, sublethal effects on the lowest levels of biological organization have been investigated. The ecological relevance of these responses assumes a prevailing role to assure effectiveness as indicator of ecological status. This study aimed to investigate the linkages between biomarker responses of caged bivalves and descriptive parameters of macrobenthic community structure. For this purpose a multi-level environmental assessment of marine and estuarine zones was performed in São Paulo coast, Brazil. Multivariate analysis was applied to identify linkages between biological responses and ecological indices, as well as to characterizing the studied stations. Individuals of the marine mussel Perna perna caged along Santos Bay showed signs of oxidative stress, lysosomal membrane destabilization, histological alterations and reduced embryonic development. The estuarine oyster Crassostrea rhizophorae caged along Santos Port Channel showed alterations on biotransformation enzymes and antioxidant system, DNA damage and lysosomal membrane destabilization. The benthic community analysis showed reduced richness and diversity in the same areas of the Santos bay and estuary where biomarker responses were altered. Our results revealed that xenobiotics are inducing physiological stress, which may lead to changes of the benthic community structure and deterioration of the ecological status over time. Integrating biomarker responses and ecological indexes improved certainty that alterations found at community level could be related to xenobiotic as stressors, which was very useful to improve the discriminatory power of the environmental assessment.

  15. Biomarkers of oxidative stress and its association with the urinary reducing capacity in bus maintenance workers

    PubMed Central

    2011-01-01

    Background Exposure to particles (PM) induces adverse health effects (cancer, cardiovascular and pulmonary diseases). A key-role in these adverse effects seems to be played by oxidative stress, which is an excess of reactive oxygen species relative to the amount of reducing species (including antioxidants), the first line of defense against reactive oxygen species. The aim of this study was to document the oxidative stress caused by exposure to respirable particles in vivo, and to test whether exposed workers presented changes in their urinary levels for reducing species. Methods Bus depot workers (n = 32) exposed to particles and pollutants (respirable PM4, organic and elemental carbon, particulate metal content, polycyclic aromatic hydrocarbons, NOx, O3) were surveyed over two consecutive days. We collected urine samples before and after each shift, and quantified an oxidative stress biomarker (8-hydroxy-2'-deoxyguanosine), the reducing capacity and a biomarker of PAH exposure (1-hydroxypyrene). We used a linear mixed model to test for associations between the oxidative stress status of the workers and their particle exposure as well as with their urinary level of reducing species. Results Workers were exposed to low levels of respirable PM4 (range 25-71 μg/m3). However, urinary levels of 8-hydroxy-2'-deoxyguanosine increased significantly within each shift and between both days for non-smokers. The between-day increase was significantly correlated (p < 0.001) with the concentrations of organic carbon, NOx, and the particulate copper content. The within-shift increase in 8OHdG was highly correlated to an increase of the urinary reducing capacity (Spearman ρ = 0.59, p < 0.0001). Conclusions These findings confirm that exposure to components associated to respirable particulate matter causes a systemic oxidative stress, as measured with the urinary 8OHdG. The strong association observed between urinary 8OHdG with the reducing capacity is suggestive of protective

  16. Biomarker Levels of Toxic Metals among Asian Populations in the United States: NHANES 2011–2012

    PubMed Central

    Awata, Hiroshi; Linder, Stephen; Mitchell, Laura E.; Delclos, George L.

    2016-01-01

    Introduction: The Centers for Disease Control and Prevention (CDC) recently found that Asians have considerably higher biomarker levels of cadmium, lead, mercury, and arsenic than whites, blacks, Mexican Americans, and other Hispanics in the United States.Introduction: The Centers for Disease Control and Prevention (CDC) recently found that Asians have considerably higher biomarker levels of cadmium, lead, mercury, and arsenic than whites, blacks, Mexican Americans, and other Hispanics in the United States. Objective: Our goal was to further evaluate the higher metal biomarker levels among Asians.Objective: Our goal was to further evaluate the higher metal biomarker levels among Asians. Methods: Biomarker data (blood cadmium, blood lead, blood mercury, urinary total arsenic, and urinary dimethylarsinic acic) from individuals ≥ 6 years of age were obtained from the 2011–2012 National Health and Nutrition Examination Survey (NHANES). We compared geometric mean levels of these five metal biomarkers in Asians with those of four other NHANES race/ethnic groups (white, black, Mexican American, and other Hispanic), and across three Asian subgroups (Chinese, Asian Indian, and other Asian). We also evaluated associations between biomarker levels and sociodemographic, physical, dietary, and behavioral covariates across the Asian subgroups.Methods: Biomarker data (blood cadmium, blood lead, blood mercury, urinary total arsenic, and urinary dimethylarsinic acic) from individuals ≥ 6 years of age were obtained from the 2011–2012 National Health and Nutrition Examination Survey (NHANES). We compared geometric mean levels of these five metal biomarkers in Asians with those of four other NHANES race/ethnic groups (white, black, Mexican American, and other Hispanic), and across three Asian subgroups (Chinese, Asian Indian, and other Asian). We also evaluated associations between biomarker levels and sociodemographic, physical, dietary, and behavioral covariates across the

  17. Reduction in the urinary aflatoxin M1 biomarker as an early indicator of the efficacy of dietary interventions to reduce exposure to aflatoxins.

    PubMed

    Mitchell, Nicole J; Kumi, Justice; Johnson, Natalie M; Dotse, Eunice; Marroquin-Cardona, Alicia; Wang, Jia-Sheng; Jolly, Pauline E; Ankrah, Nii-Ayi; Phillips, Timothy D

    2013-08-01

    Aflatoxin B1 is a persistent public health issue in Ghana. Assessment of AFB1 intervention efficacy is currently dependent on long-term biomarkers. This study was designed to determine whether daily AFM1 biomarker levels could be utilized as an early detection method for intervention efficacy. Participants were treated with a refined calcium montmorillonite clay (UPSN) or a placebo (calcium carbonate) in a crossover study. Urine samples were assessed for AFM1 levels daily. UPSN treatment reduced AFM1 biomarkers by 55% compared to the placebo. This is the first study to show that daily urinary AFM1 levels can be used as a biomarker of internal aflatoxin B1 exposure in short-term intervention trials to determine efficacy.

  18. Fatigue biomarker index: an objective salivary measure of fatigue level.

    PubMed

    Michael, Darren J; Daugherty, Sheena; Santos, Adrienne; Ruby, Brent C; Kalns, John E

    2012-03-01

    Fatigue changed the composition of the small-molecular weight (sMW) proteome of saliva during a 10h session of moderate (70% of maximum ventilatory threshold) physical exertion. Saliva samples were collected from nine recreationally trained cyclists participating in a cross-over study designed to simulate prolonged manual labor, a military operation or wildfire-suppression work. During each hour of the study, participants performed an exercise program that included upper and lower body exercises separated by short periods of recovery. Over the course of the study, fatigue level increased as suggested by a significant increase in the participants' relative perceived exertion. The composition of the sMW proteome was investigated using reversed-phase liquid chromatography with mass-spectrometric detection. Isotopes of acetic anhydride were used for mass-specific labeling of samples and subsequent identification of ions with significant changes in intensity. Cluster analysis was used to identify a pair of peptides with concentrations that changed in opposite directions with fatigue level, i.e. concentration of one peptide increased while concentration of the other decreased. The sequences of the two peptides were determined by high-resolution mass spectrometry. The ratio of the ion intensities of these two peptides, referred to as the fatigue biomarker index, was calculated for subjects throughout the study. The FBI values from the start of the study likely arose from a different distribution than the FBI values measured at the end of the study (Mann-Whitney test, P<.05). While this study is restricted to a small population of recreationally trained cyclists performing exercise under controlled conditions, it holds promise for the development of an objective salivary measurement of fatigue that is applicable to a much broader population performing in uncontrolled environments.

  19. Within-subject Pooling of Biological Samples to Reduce Exposure Misclassification in Biomarker-based Studies

    PubMed Central

    Perrier, Flavie; Giorgis-Allemand, Lise; Philippat, Claire

    2016-01-01

    Background: For chemicals with high within-subject temporal variability, assessing exposure biomarkers in a spot biospecimen poorly estimates average levels over long periods. The objective is to characterize the ability of within-subject pooling of biospecimens to reduce bias due to exposure misclassification when within-subject variability in biomarker concentrations is high. Methods: We considered chemicals with intraclass correlation coefficients of 0.6 and 0.2. In a simulation study, we hypothesized that the chemical urinary concentrations averaged over a given time period were associated with a health outcome and estimated the bias of studies assessing exposure that collected 1 to 50 random biospecimens per subject. We assumed a classical type error. We studied associations using a within-subject pooling approach and two measurement error models (simulation extrapolation and regression calibration), the latter requiring the assay of more than one biospecimen per subject. Results: For both continuous and binary outcomes, using one sample led to attenuation bias of 40% and 80% for compounds with intraclass correlation coefficients of 0.6 and 0.2, respectively. For a compound with an intraclass correlation coefficient of 0.6, the numbers of biospecimens required to limit bias to less than 10% were 6, 2, and 2 biospecimens with the pooling, simulation extrapolation, and regression calibration methods (these values were, respectively, 35, 8, and 2 for a compound with an intraclass correlation coefficient of 0.2). Compared with pooling, these methods did not improve power. Conclusion: Within-subject pooling limits attenuation bias without increasing assay costs. Simulation extrapolation and regression calibration further limit bias, compared with the pooling approach, but increase assay costs. PMID:27035688

  20. Clinical Neuropathology Practice News 4-2012: levels of evidence for brain tumor biomarkers.

    PubMed

    Berghoff, Anna Sophie; Stefanits, Harald; Heinzl, Harald; Preusser, Matthias

    2012-01-01

    The National Comprehensive Cancer Network (NCCN) recently published a task force report on the evaluation of the clinical utility of tumor biomarkers in oncology. In this report, common terminology and the use of levels of evidence scores to aid the evaluation of biomarker tests in oncology were proposed. Furthermore, the task force applied a level of evidence system to selected biomarkers of several cancer types. According to this system, the highest level of evidence, IA, is granted to a biomarker only if it has been evaluated in at least one adequately powered and specifically designed prospective controlled trial. For gliomas, only 1p/19q testing in oligodendroglial tumors was classified as IA by the NCCN task force. For all of the following biomarkers the present evidence level for clinical utility was regarded as lower than that of 1p/19q status: MGMT gene promoter methylation testing (glioblastoma), IDH mutation testing (diffusely growing gliomas), BRAF fusion testing (pilocytic astrocytoma) and CIMP testing (diffusely growing gliomas). The task force acknowledged that the exact application of levels of evidence needs further refinement. To our mind, the implementation of a brain tumor expert panel seems vital to evaluate the evidence levels of neurooncological biomarkers according to generally accepted criteria on a regular basis. Systematic identification of current research needs and widely accepted up-to-date recommendations for efficient biomarker application in everyday practice could be gained.

  1. Pre-transplant Evaluation of Donor Urinary Biomarkers can Predict Reduced Graft Function After Deceased Donor Kidney Transplantation

    PubMed Central

    Koo, Tai Yeon; Jeong, Jong Cheol; Lee, Yonggu; Ko, Kwang-Pil; Lee, Kyoung-Bun; Lee, Sik; Park, Suk Joo; Park, Jae Berm; Han, Miyeon; Lim, Hye Jin; Ahn, Curie; Yang, Jaeseok

    2016-01-01

    Abstract Several recipient biomarkers are reported to predict graft dysfunction, but these are not useful in decision making for the acceptance or allocation of deceased donor kidneys; thus, it is necessary to develop donor biomarkers predictive of graft dysfunction. To address this issue, we prospectively enrolled 94 deceased donors and their 109 recipients who underwent transplantation between 2010 and 2013 at 4 Korean transplantation centers. We investigated the predictive values of donor urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and L-type fatty acid binding protein (L-FABP) for reduced graft function (RGF). We also developed a prediction model of RGF using these donor biomarkers. RGF was defined as delayed or slow graft function. Multiple logistic regression analysis was used to generate a prediction model, which was internally validated using a bootstrapping method. Multiple linear regression analysis was used to assess the association of biomarkers with 1-year graft function. Notably, donor urinary NGAL levels were associated with donor AKI (P = 0.014), and donor urinary NGAL and L-FABP were predictive for RGF, with area under the receiver-operating characteristic curves (AUROC) of 0.758 and 0.704 for NGAL and L-FABP, respectively. The best-fit model including donor urinary NGAL, L-FABP, and serum creatinine conveyed a better predictive value for RGF than donor serum creatinine alone (P = 0.02). In addition, we generated a scoring method to predict RGF based on donor urinary NGAL, L-FABP, and serum creatinine levels. Diagnostic performance of the RGF prediction score (AUROC 0.808) was significantly better than that of the DGF calculator (AUROC 0.627) and the kidney donor profile index (AUROC 0.606). Donor urinary L-FABP levels were also predictive of 1-year graft function (P = 0.005). Collectively, these findings suggest donor urinary NGAL and L-FABP to be useful biomarkers for RGF, and support

  2. Calcium montmorillonite clay reduces urinary biomarkers of fumonisin B1 exposure in rats and humans

    PubMed Central

    Robinson, A.; Johnson, N.M.; Strey, A.; Taylor, J.F.; Marroquin-Cardona, A.; Mitchell, N.J.; Afriyie-Gyawu, E.; Ankrah, N.A.; Williams, J.H.; Wang, J.S.; Jolly, P.E.; Nachman, R.J.; Phillips, T.D.

    2012-01-01

    Fumonisin B1 (FB1) is often a co-contaminant with aflatoxin (AF) in grains and may enhance AF’s carcinogenicity by acting as a cancer promoter. Calcium montmorillonite (i.e. NovaSil, NS) is a possible dietary intervention to help decrease chronic aflatoxin exposure where populations are at risk. Previous studies show that an oral dose of NS clay was able to reduce AF exposure in a Ghanaian population. In vitro analyses from our laboratory indicated that FB1 (like aflatoxin) could also be sorbed onto the surfaces of NS. Hence, our objectives were to evaluate the efficacy of NS clay to reduce urinary FB1 in a rodent model and then in a human population highly exposed to AF. In the rodent model, male Fisher rats were randomly assigned to either, FB1 control, FB1 + 2% NS or absolute control group. FB1 alone or with clay was given as a single dose by gavage. For the human trial, participants received NS (1.5 or 3 g day−1) or placebo (1.5 g day−1) for 3 months. Urines from weeks 8 and 10 were collected from the study participants for analysis. In rats, NS significantly reduced urinary FB1 biomarker by 20% in 24 h and 50% after 48 h compared to controls. In the humans, 56% of the urine samples analyzed (n = 186) had detectable levels of FB1. Median urinary FB1 levels were significantly (p < 0.05) decreased by > 90% in the high dose NS group (3 g day−1) compared to the placebo. This work indicates that our study participants in Ghana were exposed to FB1 (in addition to AFs) from the diet. Moreover, earlier studies have shown conclusively that NS reduces the bioavailability of AF and the findings from this study suggest that NS clay also reduces the bioavailability FB1. This is important since AF is a proven dietary risk factor for hepatocellular carcinoma (HCC) in humans and FB1 is suspected to be a dietary risk factor for HCC and esophageal cancer in humans. PMID:22324939

  3. Increased urinary levels of podocyte glycoproteins, matrix metallopeptidases, inflammatory cytokines, and kidney injury biomarkers in women with preeclampsia.

    PubMed

    Wang, Yuping; Gu, Yang; Loyd, Susan; Jia, Xiuyue; Groome, Lynn J

    2015-12-15

    To investigate kidney injury in preeclampsia, we analyzed 14 biomarkers in urine specimen from 4 groups of pregnant women (normotensive pregnant women and those with pregnancy complicated with chronic hypertension or mild or severe preeclampsia). These biomarkers included 1) podocyte glycoproteins nephrin and podocalyxin, 2) matrix metallopeptidase (MMP)-2 and MMP-9 and their inhibitor tissue inhibitor of metalloproteinase-2, 3) inflammatory molecules and cytokines soluble VCAM-1, TNF-α, soluble TNF receptor receptor-1, IL-6, IL-8, IL-10, and IL-18, and 4) kidney injury biomarkers neutrophil gelatinase-associated lipocalin and kidney injury molecule-1. Postpartum urine specimens (6-8 wk) from normotensive women and those with severe preeclampsia were also evaluated. We found that, first, urine levels of nephrin, MMP-2, MMP-9, and kidney injury molecule-1 were significantly higher before delivery in severe preeclampsia than normotensive groups. The increased levels were all reduced to levels similar to those of the normotensive control group in postpartum specimens from the severe preeclampsia group. Second, soluble VCAM-1, soluble TNF receptor-1, and neutrophil gelatinase-associated lipocalin levels were significantly increased in the severe preeclampsia group compared with the normotensive control group before delivery, but levels of these molecules were significantly reduced in postpartum specimens in both groups. Third, IL-6 and IL-8 levels were not different between preeclampsia and normotensive groups but significantly increased in pregnancy complicated with chronic hypertension. Finally, tissue inhibitor of metalloproteinase-2 and IL-18 levels were not different among the study groups before delivery but were significantly reduced in postpartum specimens from normotensive controls. Our results indicate that the kidney experiences an increased inflammatory response during pregnancy. Most interestingly, tubular epithelial cell injury may also occur in severe

  4. Cancer Screening: A Mathematical Model Relating Secreted Blood Biomarker Levels to Tumor Sizes

    PubMed Central

    Lutz, Amelie M; Willmann, Juergen K; Cochran, Frank V; Ray, Pritha; Gambhir, Sanjiv S

    2008-01-01

    Background Increasing efforts and financial resources are being invested in early cancer detection research. Blood assays detecting tumor biomarkers promise noninvasive and financially reasonable screening for early cancer with high potential of positive impact on patients' survival and quality of life. For novel tumor biomarkers, the actual tumor detection limits are usually unknown and there have been no studies exploring the tumor burden detection limits of blood tumor biomarkers using mathematical models. Therefore, the purpose of this study was to develop a mathematical model relating blood biomarker levels to tumor burden. Methods and Findings Using a linear one-compartment model, the steady state between tumor biomarker secretion into and removal out of the intravascular space was calculated. Two conditions were assumed: (1) the compartment (plasma) is well-mixed and kinetically homogenous; (2) the tumor biomarker consists of a protein that is secreted by tumor cells into the extracellular fluid compartment, and a certain percentage of the secreted protein enters the intravascular space at a continuous rate. The model was applied to two pathophysiologic conditions: tumor biomarker is secreted (1) exclusively by the tumor cells or (2) by both tumor cells and healthy normal cells. To test the model, a sensitivity analysis was performed assuming variable conditions of the model parameters. The model parameters were primed on the basis of literature data for two established and well-studied tumor biomarkers (CA125 and prostate-specific antigen [PSA]). Assuming biomarker secretion by tumor cells only and 10% of the secreted tumor biomarker reaching the plasma, the calculated minimally detectable tumor sizes ranged between 0.11 mm3 and 3,610.14 mm3 for CA125 and between 0.21 mm3 and 131.51 mm3 for PSA. When biomarker secretion by healthy cells and tumor cells was assumed, the calculated tumor sizes leading to positive test results ranged between 116.7 mm3 and 1

  5. Agitation in Dementia: Relation to Core Cerebrospinal Fluid Biomarker Levels

    PubMed Central

    Bloniecki, Victor; Aarsland, Dag; Cummings, Jeffrey; Blennow, Kaj; Freund-Levi, Yvonne

    2014-01-01

    Background The objective of this study was to examine the associations of agitation with the cerebrospinal fluid dementia biomarkers total-tau (T-tau), phosphorylated-tau (P-tau) and Aβ1-42. Methods One hundred patients (mean age ± SD, 78.6 ± 7.5 years) with dementia and neuropsychiatric symptoms, of whom 67% were female, were included. Agitation was measured using the Cohen-Mansfield Agitation Inventory (CMAI; 46.5 ± 11.8 points). Results Total CMAI correlated with T-tau [rs (31) = 0.36, p = 0.04] and P-tau [rs (31) = 0.35, p = 0.05] in patients with Alzheimer's disease (AD; n = 33) but not in the total dementia population (n = 95). Conclusions Our results suggest that tau-mediated pathology including neurofibrillary tangles and the intensity of the disease process might be associated with agitation in AD. PMID:25298777

  6. Type IV collagen is a novel DEJ biomarker that is reduced by radiotherapy.

    PubMed

    McGuire, J D; Gorski, J P; Dusevich, V; Wang, Y; Walker, M P

    2014-10-01

    The dental basement membrane (BM) is composed of collagen types IV, VI, VII, and XVII, fibronectin, and laminin and plays an inductive role in epithelial-mesenchymal interactions during tooth development. The BM is degraded and removed during later-stage tooth morphogenesis; however, its original position defines the location of the dentin-enamel junction (DEJ) in mature teeth. We recently demonstrated that type VII collagen is a novel component of the inner enamel organic matrix layer contiguous with the DEJ. Since it is frequently co-expressed with and forms functional complexes with type VII collagen, we hypothesized that type IV collagen should also be localized to the DEJ in mature human teeth. To identify collagen IV, we first evaluated defect-free erupted teeth from various donors. To investigate a possible stabilizing role, we also evaluated extracted teeth exposed to high-dose radiotherapy--teeth that manifest post-radiotherapy DEJ instability. We now show that type IV collagen is a component within the morphological DEJ of posterior and anterior teeth from individuals aged 18 to 80 yr. Confocal microscopy revealed that immunostained type IV collagen was restricted to the 5- to 10-µm-wide optical DEJ, while collagenase treatment or previous in vivo tooth-level exposure to > 60 Gray irradiation severely reduced immunoreactivity. This assignment was confirmed by Western blotting with whole-tooth crown and enamel extracts. Without reduction, type IV collagen contained macromolecular α-chains of 225 and 250 kDa. Compositionally, our results identify type IV collagen as the first macromolecular biomarker of the morphological DEJ of mature teeth. Given its network structure and propensity to stabilize the dermal-epidermal junction, we propose that a collagen-IV-enriched DEJ may, in part, explain its well-known fracture toughness, crack propagation resistance, and stability. In contrast, loss of type IV collagen may represent a biochemical rationale for the DEJ

  7. Type IV Collagen is a Novel DEJ Biomarker that is Reduced by Radiotherapy

    PubMed Central

    McGuire, J.D.; Gorski, J.P.; Dusevich, V.; Wang, Y.; Walker, M.P.

    2014-01-01

    The dental basement membrane (BM) is composed of collagen types IV, VI, VII, and XVII, fibronectin, and laminin and plays an inductive role in epithelial-mesenchymal interactions during tooth development. The BM is degraded and removed during later-stage tooth morphogenesis; however, its original position defines the location of the dentin-enamel junction (DEJ) in mature teeth. We recently demonstrated that type VII collagen is a novel component of the inner enamel organic matrix layer contiguous with the DEJ. Since it is frequently co-expressed with and forms functional complexes with type VII collagen, we hypothesized that type IV collagen should also be localized to the DEJ in mature human teeth. To identify collagen IV, we first evaluated defect-free erupted teeth from various donors. To investigate a possible stabilizing role, we also evaluated extracted teeth exposed to high-dose radiotherapy – teeth that manifest post-radiotherapy DEJ instability. We now show that type IV collagen is a component within the morphological DEJ of posterior and anterior teeth from individuals aged 18 to 80 yr. Confocal microscopy revealed that immunostained type IV collagen was restricted to the 5- to 10-µm-wide optical DEJ, while collagenase treatment or previous in vivo tooth-level exposure to > 60 Gray irradiation severely reduced immunoreactivity. This assignment was confirmed by Western blotting with whole-tooth crown and enamel extracts. Without reduction, type IV collagen contained macromolecular α-chains of 225 and 250 kDa. Compositionally, our results identify type IV collagen as the first macromolecular biomarker of the morphological DEJ of mature teeth. Given its network structure and propensity to stabilize the dermal-epidermal junction, we propose that a collagen-IV-enriched DEJ may, in part, explain its well-known fracture toughness, crack propagation resistance, and stability. In contrast, loss of type IV collagen may represent a biochemical rationale for the

  8. Wafer-scale high-resolution patterning of reduced graphene oxide films for detection of low concentration biomarkers in plasma

    PubMed Central

    Kim, Jinsik; Chae, Myung-Sic; Lee, Sung Min; Jeong, Dahye; Lee, Byung Chul; Lee, Jeong Hoon; Kim, YoungSoo; Chang, Suk Tai; Hwang, Kyo Seon

    2016-01-01

    Given that reduced graphene oxide (rGO)-based biosensors allow disposable and repeatable biomarker detection at the point of care, we developed a wafer-scale rGO patterning method with mass productivity, uniformity, and high resolution by conventional micro-electro-mechanical systems (MEMS) techniques. Various rGO patterns were demonstrated with dimensions ranging from 5 μm up to several hundred μm. Manufacture of these patterns was accomplished through the optimization of dry etching conditions. The axis-homogeneity and uniformity were also measured to verify the uniform patternability in 4-inch wafer with dry etching. Over 66.2% of uniform rGO patterns, which have deviation of resistance within range of ±10%, formed the entire wafer. We selected amyloid beta (Aβ) peptides in the plasma of APP/PS1 transgenic mice as a study model and measured the peptide level by resistance changes of highly uniform rGO biosensor arrays. Aβ is a pathological hallmark of Alzheimer’s disease and its plasma concentration is in the pg mL−1 range. The sensor detected the Aβ peptides with ultra-high sensitivity; the LOD was at levels as low as 100 fg mL−1. Our results provide biological evidences that this wafer-scale high-resolution patterning method can be used in rGO-based electrical diagnostic devices for detection of low-level protein biomarkers in biofluids. PMID:27506288

  9. Wafer-scale high-resolution patterning of reduced graphene oxide films for detection of low concentration biomarkers in plasma

    NASA Astrophysics Data System (ADS)

    Kim, Jinsik; Chae, Myung-Sic; Lee, Sung Min; Jeong, Dahye; Lee, Byung Chul; Lee, Jeong Hoon; Kim, Youngsoo; Chang, Suk Tai; Hwang, Kyo Seon

    2016-08-01

    Given that reduced graphene oxide (rGO)-based biosensors allow disposable and repeatable biomarker detection at the point of care, we developed a wafer-scale rGO patterning method with mass productivity, uniformity, and high resolution by conventional micro-electro-mechanical systems (MEMS) techniques. Various rGO patterns were demonstrated with dimensions ranging from 5 μm up to several hundred μm. Manufacture of these patterns was accomplished through the optimization of dry etching conditions. The axis-homogeneity and uniformity were also measured to verify the uniform patternability in 4-inch wafer with dry etching. Over 66.2% of uniform rGO patterns, which have deviation of resistance within range of ±10%, formed the entire wafer. We selected amyloid beta (Aβ) peptides in the plasma of APP/PS1 transgenic mice as a study model and measured the peptide level by resistance changes of highly uniform rGO biosensor arrays. Aβ is a pathological hallmark of Alzheimer’s disease and its plasma concentration is in the pg mL‑1 range. The sensor detected the Aβ peptides with ultra-high sensitivity; the LOD was at levels as low as 100 fg mL‑1. Our results provide biological evidences that this wafer-scale high-resolution patterning method can be used in rGO-based electrical diagnostic devices for detection of low-level protein biomarkers in biofluids.

  10. Metabolic polymorphisms and biomarkers of effect in the biomonitoring of occupational exposure to low-levels of benzene: state of the art.

    PubMed

    De Palma, G; Manno, M

    2014-12-01

    Current levels of occupational exposure to benzene, a genotoxic human carcinogen, in Western countries are reduced by two-three orders of magnitude (from ppm to ppb) as compared to the past. However, as benzene toxicity is strongly dependent on biotransformation and recent evidence underlines a higher efficiency of bio-activation pathways at lower levels of exposure, toxic effects at low doses could be higher than expected, particularly in susceptible individuals. Currently, biological monitoring can allow accurate exposure assessment, relying on sensitive and specific enough biomarkers of internal dose. The availability of similarly reliable biomarkers of early effect or susceptibility could greatly improve the risk assessment process to such an extent that risk could even be assessed at the individual level. As to susceptibility biomarkers, functional genetic polymorphisms of relevant biotransformation enzymes may modulate the risk of adverse effects (NQO1) and the levels of biomarkers of internal dose, in particular S-phenylmercapturic acid (GSTM1, GSTT1, GSTA1). Among biomarkers of early effect, genotoxicity indicators, although sensitive in some cases, are too aspecific for routine use in occupational health surveillance programmes. Currently only the periodical blood cell count seems suitable enough to be applied in the longitudinal monitoring of effects from benzene exposure. Novel biomarkers of early effect are expected from higher collaboration among toxicologists and clinicians, also using advanced "omics" techniques.

  11. Association of Elevated Amyloid Levels With Cognition and Biomarkers in Cognitively Normal People From the Community

    PubMed Central

    Petersen, Ronald C.; Wiste, Heather J.; Weigand, Stephen D.; Rocca, Walter A.; Roberts, Rosebud O.; Mielke, Michelle M.; Lowe, Val J.; Knopman, David S.; Pankratz, Vernon S.; Machulda, Mary M.; Geda, Yonas E.; Jack, Clifford R.

    2015-01-01

    IMPORTANCE The role of amyloid in the progression of Alzheimer disease (AD) pathophysiology is of central interest to the design of randomized clinical trials. The presence of amyloid has become a prerequisite for enrollment in several secondary prevention trials for AD, yet the precise effect of elevated amyloid levels on subsequent clinical and biomarker events is less certain. OBJECTIVE To explore the effect of elevated amyloid levels on subsequent changes in cognition and biomarkers. DESIGN, SETTING, AND PARTICIPANTS A total of 564 cognitively normal individuals (median age, 78 years) from the Mayo Clinic Study of Aging, a population-based longitudinal study in Olmsted County, Minnesota, with serial cognitive data were selected for this study. The data used in this study were collected from January 12, 2006, to January 9, 2014. Individuals included in this study had undergone magnetic resonance imaging, fluorodeoxyglucose positron emission tomography (FDG-PET), and Pittsburgh Compound B (PiB) PET at baseline were not cognitively impaired at baseline and had at least 1 clinical follow-up. A subset of 286 individuals also underwent serial imaging. Elevated amyloid level was defined as a standardized uptake value ratio of greater than 1.5 on PiB PET. Associations with baseline amyloid status and baseline and longitudinal change in clinical and imaging measures were evaluated after adjusting for age and hippocampal volume. APOE4 effects were also evaluated. MAIN OUTCOMES AND MEASURES Cognitive measures of memory, language, attention/executive function, visuospatial skills, PiB levels, hippocampal and ventricular volumes, and FDG-PET measures. RESULTS At baseline, 179 (31.7%) individuals with elevated amyloid levels had poorer cognition in all domains measured, reduced hippocampal volume, and greater FDG-PET hypometabolism. Elevated amyloid levels at baseline were associated with a greater rate of cognitive decline in all domains (0.04 to 0.09 z score units per year

  12. [The level of evidence for the use of biomarkers in the early detection of prostate cancer].

    PubMed

    Lamy, Pierre-Jean; Gauchez, Anne-Sophie; Salomon, Laurent; Haugh, Margaret; Ceraline, Jocelyn; Fulla, Yvonne; Georges, Agnès; Larré, Stéphane; Loric, Sylvain; Luporsi, Elisabeth; Martin, Pierre-Marie; Mazerolles, Catherine; Molinié, Vincent; Mongiat-Artus, Pierre; Piffret, Jacques; Thuillier, François; Perrin, Paul; Rebillard, Xavier

    2016-01-01

    To systematically review the evidence for the use of PSA and other biomarkers in the early detection of prostate cancer, we searched PubMed for clinical trials and studies assessing PSA and other biomarkers in the early detection of prostate cancer, published between 2000 and May 2013 that included >200 subjects. The level of evidence (LOE) for clinical utility was evaluated using the tumor marker utility grading system. A total of 84 publications, corresponding to 70 trials and studies were selected for inclusion in this review. We attributed a level of evidence (LoE) of IA to PSA for early PCa detection, but we do not recommend its use in mass screening. Emerging biomarkers were assessed in prospective case-control and cohort studies: PCA3 (n=3); kallikreins (n=3); [-2]proPSA (n=5); fusion oncogenes (n=2). These studies used biopsy results for prostate cancer to determine specificity and sensitivity, but they did not assess the effect on PCa mortality. The LoE attributed was III-C. PSA can be used for early prostate cancer detection but mass screening is not recommended. Studies on other biomarkers suggest that they could be used, individually or in combination, to improve the selection of patients with elevated PSA levels for biopsy, but RCTs assessing their impact on prostate cancer management and mortality are needed. A better use of available tests is possible for men at risk in order to maximize the risk-benefit ratio.

  13. Biomarkers of endocrine disruption at the mRNA level

    SciTech Connect

    Denslow, N.D.; Bowman, C.J.; Robinson, G.; Lee, H.S.; Ferguson, R.J.; Hemmmer, M.J.; Folmar, L.C.

    1999-07-01

    A large number of estrogen-mimicking, anthropogenic chemicals capable of disrupting normal reproductive function have been identified. The ubiquitous distribution of these compounds, many as components of complex industrial or municipal waste, has spurred an effort to develop methods to screen for chemicals which disrupt normal endocrine regulation of reproduction. The authors have developed assays that both allow exposure of animals in vivo and measure the response at the level of gene activation. The authors have developed a probe for measuring the induction of vitellogenin mRNA by Northern Blot in livers of sheepshead minnows treated with 17-{beta}-estradiol. The authors have also developed a strategy for using Differential Display Polymerase Chain Reaction for determining gene induction profiles following exposure to estradiol. These methods should be adaptable to a variety of structurally diverse estrogen mimics.

  14. Increased plasma levels of CK-18 as potential cell death biomarker in patients with HELLP syndrome.

    PubMed

    John, K; Wielgosz, S; Schulze-Osthoff, K; Bantel, H; Hass, R

    2013-10-24

    HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome represents a life-threatening pregnancy disorder with high fetal and maternal mortality, but its underlying molecular mechanisms remain unknown. Although apoptosis has been implicated in HELLP syndrome, its pathogenic role remains largely unclear. In the present study, we investigated whether the detection of apoptosis by novel plasma biomarkers is of diagnostic value in HELLP patients. For this purpose, we analyzed two biomarkers that specifically detect apoptosis or overall cell death of epithelial cells, such as hepatocytes or placental trophoblasts, through the release of caspase-cleaved or total (caspase-cleaved and uncleaved) cytokeratin-18 (CK-18) in plasma of HELLP patients compared with pregnant as well as non-pregnant healthy women. In addition, caspase activation and cell death were determined in placental tissues of HELLP patients and individuals with normal pregnancy. In contrast to pregnant or non-pregnant healthy controls, we observed significantly increased levels of both caspase-cleaved and total CK-18 in plasma of HELLP patients. Following delivery, CK-18 levels rapidly decreased in HELLP patients. Caspase activation and cell death were also elevated in placental tissues from HELLP patients compared with healthy pregnant women. These data demonstrate not only that apoptosis is increased in HELLP syndrome, but also that caspase-cleaved or total CK-18 are promising plasma biomarkers to identify patients with HELLP syndrome. Thus, further studies are warranted to evaluate the utility of these biomarkers for monitoring disease activity in HELLP syndrome.

  15. Confidence interval estimation for sensitivity at a fixed level of specificity for combined biomarkers.

    PubMed

    Tian, Lili

    2013-05-01

    In diagnostic studies, we often need to combine several biomarkers to increase the diagnostic accuracy. For continuous-scaled biomarkers or diagnostic tests, it is often of interest to estimate the confidence interval for sensitivity at a fixed level of specificity. Despite the fact that there exist many literature reports on confidence interval estimation of sensitivity at a fixed level of specificity for a single marker, the inference procedures for sensitivity at a fixed level of specificity for combined markers have rarely been addressed. This article fills this gap by investigating a generalized variable procedure for this purpose. The performance of the proposed generalized approach is numerically studied. For the optimal linear combination proposed by Su and Liu ( 1993 ), simulation study demonstrates that the proposed approach generally can provide confidence intervals with excellent coverage probabilities. The robustness of the proposed approach is investigated for categorical data. In the end, the proposed approach is applied to a real-life data set.

  16. Albumin binding as a potential biomarker of exposure to moderately low levels of organophosphorus pesticides.

    PubMed

    Tarhoni, Mabruka H; Lister, Timothy; Ray, David E; Carter, Wayne G

    2008-06-01

    We have evaluated the potential of plasma albumin to provide a sensitive biomarker of exposure to commonly used organophosphorus pesticides in order to complement the widely used measure of acetylcholinesterase (AChE) inhibition. Rat or human plasma albumin binding by tritiated-diisopropylfluorophosphate ((3)H-DFP) was quantified by retention of albumin on glass microfibre filters. Preincubation with unlabelled pesticide in vitro or dosing of F344 rats with pesticide in vivo resulted in a reduction in subsequent albumin radiolabelling with (3)H-DFP, the decrease in which was used to quantify pesticide binding. At pesticide exposures producing approximately 30% inhibition of AChE, rat plasma albumin binding in vitro by azamethiphos (oxon), chlorfenvinphos (oxon), chlorpyrifos-oxon, diazinon-oxon and malaoxon was reduced from controls by 9+/-1%, 67+/-2%, 56+/-2%, 54+/-2% and 8+/-1%, respectively. After 1 h of incubation with 19 microM (3)H-DFP alone, the level of binding to rat or human plasma albumins reached 0.011 or 0.039 moles of DFP per mole of albumin, respectively. This level of binding could be further increased by raising the concentration of (3)H-DFP, increasing the (3)H-DFP incubation time, or by substitution of commercial albumins for native albumin. Pesticide binding to albumin was presumed covalent since it survived 24 h dialysis. After dosing rats with pirimiphos-methyl (dimethoxy) or chlorfenvinphos (oxon) (diethoxy) pesticides, the resultant albumin binding were still significant 7 days after dosing. As in vitro, dosing of rats with malathion did not result in significant albumin binding in vivo. Our results suggest albumin may be a useful additional biomonitor for moderately low-level exposures to several widely used pesticides, and that this binding differs markedly between pesticides.

  17. Altered Biomarkers of Mucosal Immunity and Reduced Vaginal Lactobacillus Concentrations in Sexually Active Female Adolescents

    PubMed Central

    Madan, Rebecca Pellett; Carpenter, Colleen; Fiedler, Tina; Kalyoussef, Sabah; McAndrew, Thomas C.; Viswanathan, Shankar; Kim, Mimi; Keller, Marla J.; Fredricks, David N.; Herold, Betsy C.

    2012-01-01

    Background Genital secretions collected from adult women exhibit in vitro activity against herpes simplex virus (HSV) and Escherichia coli (E. coli), but prior studies have not investigated this endogenous antimicrobial activity or its mediators in adolescent females. Methodology/Principal Findings Anti-HSV and anti-E.coli activity were quantified from cervicovaginal lavage (CVL) specimens collected from 20 sexually active adolescent females (15–18 years). Soluble immune mediators that may influence this activity were measured in CVL, and concentrations of Lactobacillus jensenii and crispatus were quantified by PCR from vaginal swabs. Results for adolescents were compared to those obtained from 54 healthy, premenopausal adult women. Relative to specimens collected from adults, CVL collected from adolescent subjects had significantly reduced activity against E. coli and diminished concentrations of protein, IgG, and IgA but significantly increased anti-HSV activity and concentrations of interleukin (IL)-1α, IL-6 and IL-1 receptor antagonist. Vaginal swabs collected from adolescent subjects had comparable concentrations of L. crispatus but significantly reduced concentrations of L. jensenii, relative to adult swabs. Conclusions/Significance Biomarkers of genital mucosal innate immunity may differ substantially between sexually active adolescents and adult women. These findings warrant further study and may have significant implications for prevention of sexually transmitted infections in adolescent females. PMID:22808157

  18. Stable Carbon Isotope Ratios of Lipid Biomarkers and Biomass for Sulfate-reducing Bacteria Grown with Different Substrates

    NASA Technical Reports Server (NTRS)

    Londry, K. L.; Jahnke, L. L.; Des Marais, D. J.

    2001-01-01

    We have determined isotope ratios of biomass and Fatty Acids Methyl Esters (FAME) for four Sulfate-Reducing Bacteria (SRB) grown lithotrophically and heterotrophically, and are investigating whether these biomarker signatures can reveal the ecological role and distribution of SRB within microbial mats. Additional information is contained in the original extended abstract.

  19. Lysosomal and tissue-level biomarkers in mussels cross-transplanted among four estuaries with different pollution levels.

    PubMed

    Lekube, Xabier; Izagirre, Urtzi; Soto, Manu; Marigómez, Ionan

    2014-02-15

    A 3-4 wk cross-transplantation experiment was carried out in order to investigate the sensitivity, rapidity, durability and reversibility of lysosomal and tissue-level biomarkers in the digestive gland of mussels. Four localities in the Basque coast with different levels of chemical pollution and environmental stress were selected. Lysosomal membrane stability (LP) and lysosomal structural changes (VvL; S/VL; NvL) and changes in cell-type composition in digestive gland epithelium (VvBAS) were investigated to determine short (2d) and mid-term (3-4 wk) responses after cross-transplantation. Mussels from Txatxarramendi presented VvBAS<0.1 μm(3)/μm(3) (unstressed) whilst VvBAS>0.12 μm(3)/μm(3) was recorded in mussels from Plentzia (moderate stress) and VvBAS>0.2 μm(3)/μm(3) in Arriluze and Muskiz (high stress). Accordingly, LP<10 min (high stress) was recorded in mussels from Muskiz and Arriluze and LP~15 min (low-to-moderate stress) in those from Plentzia and Txatxarramendi. According to the VvL, S/VL and NvL data, a certain lysosomal enlargement was envisaged in mussels from Arriluze in comparison with those from Txatxarramendi and Plentzia. Mussels from Muskiz exhibited a peculiar endo-lysosomal system made of abundant tiny lysosomes (low VvL and high S/VL and NvL values). Lysosomal and tissue-level biomarkers were responsive after 2d cross-transplantation between the reference and the polluted localities, which indicated that these biomarkers were quickly induced and, to a large extent, reversible. Moreover, the tissue-level biomarker values were maintained during the entire period (3-4 wk) of cross-transplantation, which evidenced the durability of the responsiveness. In contrast, comparisons in the mid-term were unfeasible for lysosomal biomarkers as these exhibited a seasonal winter attenuation resulting from low food availability and low temperatures. In conclusion, lysosomal enlargement and membrane stability and changes in cell-type composition were

  20. Increased levels of oxidative stress biomarkers in metal oxides nanomaterial-handling workers.

    PubMed

    Liou, Saou-Hsing; Chen, Yu-Cheng; Liao, Hui-Yi; Wang, Chien-Jen; Chen, Jhih-Sheng; Lee, Hui-Ling

    2016-11-01

    This study assessed oxidatively damaged DNA and antioxidant enzyme activity in workers occupational exposure to metal oxides nanomaterials. Exposure to TiO2, SiO2, and ITO resulted in significant lower antioxidant enzymes (glutathione peroxidase and superoxide dismutase) and higher oxidative biomarkers 8-hydroxydeoxyguanosine (8-oxodG) than comparison workers. Statistically significant correlations were noted between plasma and urine 8-oxodG, between white blood cells (WBC) and urine 8-oxodG, and between WBC and plasma 8-oxodG. In addition, there were significant negative correlations between WBC 8-oxodG and SOD and between urinary 8-oxodG and GPx levels. The results showed that urinary 8-oxodG may be considered to be better biomarker.

  1. Carbon isotopes of plant biomarkers record past changes in the carbon cycle, but separating signal from noise is key to reducing uncertainties

    NASA Astrophysics Data System (ADS)

    Diefendorf, A. F.; Freeman, K. H.; Wing, S. L.; Currano, E. D.

    2014-12-01

    The carbon isotopic composition of plant biomarkers (δ13C) can provide unique insights into the past carbon cycle perturbations and associated climate change, however local records are influenced by ecological processes, local climate, as well as changes in the carbon isotope composition of the atmosphere. To examine the sources and amounts of geographic variation, we focused on long-term changes in the carbon cycle. We combined modern calibrations, δ13C of biomarkers in sediment, and Monte Carlo analyses to measure and predict the fractionation of carbon isotopes by plants (Δleaf) and to estimate error. We used data from multiple sites of different ages, in the western U.S. For each age and location, Δleaf was calculated from the δ13C of plant biomarkers and atmospheric δ13C values inferred from marine carbonates. Δleaf values calculated from n-alkanes and triterpenoids (angiosperm biomarkers) were found to be the same at each site. Δleaf calculated from diterpenoids (conifer biomarkers) was 2‰ lower. This is consistent with differences in Δleaf between living angiosperms and conifers. Predicted Δleaf values, from modern calibrations and paleoclimate data, were consistently offset (0.7‰) from measured values indicating that modern calibrations are useful for reconciling past changes in plant fractionation and that vegetation and precipitation, like modern plants, were the key controls on Δleaf in ancient vegetation. However, uncertainties in the measured and predicted Δleaf values were very large (>2‰, 1σ). A one-at-a-time sensitivity analysis indicates that 'biological noise' in modern calibrations explains most of this uncertainty. If the full extent of this biological noise were transferred to sediments, then extracting signal from noise would be challenging. However, we speculate that the process of deposition homogenizes variability at the leaf and tree level thereby reducing 'biological noise' observed in modern calibrations.

  2. Aronia berry polyphenol consumption reduces plasma total and low-density lipoprotein cholesterol in former smokers without lowering biomarkers of inflammation and oxidative stress: a randomized controlled trial.

    PubMed

    Xie, Liyang; Vance, Terrence; Kim, Bohkyung; Lee, Sang Gil; Caceres, Christian; Wang, Ying; Hubert, Patrice A; Lee, Ji-Young; Chun, Ock K; Bolling, Bradley W

    2017-01-01

    Former smokers are at increased risk for cardiovascular disease. We hypothesized that dietary aronia polyphenols would reduce biomarkers of cardiovascular disease risk, inflammation, and oxidative stress in former smokers. We also determined the extent these effects were associated with polyphenol bioavailability. A 12-week, randomized, placebo-controlled trial was conducted in 49 healthy adult former smokers (n = 24/placebo, n = 25/aronia) to evaluate if daily consumption of 500 mg aronia extract modulated plasma lipids, blood pressure, biomarkers of inflammation and oxidative stress, and lipid transport genes of peripheral blood mononuclear cells. The primary outcome was change in low-density lipoprotein cholesterol (LDL-C) from baseline, and multivariate correlation analysis was performed to determine if changes in lipids were associated with urinary polyphenol excretion. Aronia consumption reduced fasting plasma total cholesterol by 8% (P = .0140), LDL-C by 11% (P = .0285), and LDL receptor protein in peripheral blood mononuclear cells (P = .0036) at 12 weeks compared with the placebo group. Positive changes in the urinary polyphenol metabolites peonidin-3-O-galactoside, 3-(4-hydroxyphenyl) propionic acid, and unmetabolized anthocyanin cyanidin-3-O-galactoside were associated with lower plasma total cholesterol and LDL-C in the aronia group. Aronia consumption did not change blood pressure or biomarkers of inflammation and oxidative stress. Aronia polyphenols reduced total and LDL-C in former smokers but did not improve biomarkers of oxidative stress and chronic inflammation. The cholesterol-lowering activity of aronia extract was most closely associated with urinary levels of cyanidin-3-O-galactoside and peonidin-3-O-galactoside, its methylated metabolite. This trial was registered at ClinicalTrials.gov as NCT01541826.

  3. Changes in plasma catecholamines levels as preclinical biomarkers in experimental models of Parkinson's disease.

    PubMed

    Kim, A R; Ugryumov, M V

    2015-01-01

    The goal of this study was to investigate the changes in the concentrations of blood plasma catecholamines as possible biomarkers of Parkinson's disease (PD) in the mouse experimental model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). A significant decrease was detected in the levels of dopamine and L-DOPA in the PD preclinical stage model as a result of the catecholamines systemic metabolism disfunction. In the PD early clinical stage models, the level of L-DOPA and dihydroxyphenylacetic acid decreased, which is consistent with the results of blood tests in untreated patients.

  4. Levels and types of alcohol biomarkers in DUI and clinic samples for estimating workplace alcohol problems.

    PubMed

    Marques, Paul R

    2012-02-01

    Widespread concern about illicit drugs as an aspect of workplace performance potentially diminishes attention on employee alcohol use. Alcohol is the dominant drug contributing to poor job performance; it also accounts for a third of the worldwide public health burden. Evidence from public roadways--a workplace for many--provides an example of work-related risk exposure and performance lapses. In most developed countries, alcohol is involved in 20-35% of fatal crashes; drugs other than alcohol are less prominently involved in fatalities. Alcohol biomarkers can improve detection by extending the timeframe for estimating problematic exposure levels and thereby provide better information for managers. But what levels and which markers are right for the workplace? In this paper, an established high-sensitivity proxy for alcohol-driving risk proclivity is used: an average eight months of failed blood alcohol concentration (BAC) breath tests from alcohol ignition interlock devices. Higher BAC test fail rates are known to presage higher rates of future impaired-driving convictions (driving under the influence; DUI). Drivers in alcohol interlock programmes log 5-7 daily BAC tests; in 12 months, this yields thousands of samples. Also, higher programme entry levels of alcohol biomarkers predict a higher likelihood of failed interlock BAC tests during subsequent months. This paper summarizes the potential of selected biomarkers for workplace screening. Markers include phosphatidylethanol (PEth), percent carbohydrate deficient transferrin (%CDT), gammaglutamyltransferase (GGT), gamma %CDT (γ%CDT), and ethylglucuronide (EtG) in hair. Clinical cut-off levels and median/mean levels of these markers in abstinent people, the general population, DUI drivers, and rehabilitation clinics are summarized for context.

  5. Leopard frog PCB levels and evaluation of EROD as a biomarker in Green Bay ecosystem

    SciTech Connect

    Huang, Y.W.; Karasov, W.H.; Patnode, K.P.

    1995-12-31

    The induction of mixed function oxidases has been shown to be a promising biomarker in many taxa of wildlife, though not yet tested for amphibians. The three hypotheses tested in this study were (1) activities of hepatic EROD of leopard frog (Rana pipiens) are induced following exposure to planar chlorinated PCBs, (2) tissue PCB residue levels of leopard frogs are positively correlated with their wetland sediment PCB levels, and (3) EROD activities are positively correlated with tissue PCB concentrations and sediment PCB. In the laboratory, EROD was increased 2--3 times seven days after i.p. injection with PCB 126 at doses {ge} 2.3 ppm (wet mass basis). Leopard frogs from seven sites along the Lower Fox River and Green Bay in 1994--1995 were assayed for hepatic EROD activities and total PCB levels in carcasses. Tissue PCB levels ranged from 3 to 152 ppb (including coplanar congeners) and were highest from sites with higher sediment PCB. EROD activity in frogs collected in August--September was not significantly correlated with frog body mass and was similar among sites with one exception. There was no significant correlation between EROD activity and tissue PCB concentration. This result was consistent with the fact that the frogs collected from the Green Bay ecosystem had relatively low PCB levels compared with what was required for induction in the laboratory. The authors conclude that EROD activity is not a sensitive biomarker of PCB exposure in leopard frogs in this ecosystem.

  6. d-serine levels in Alzheimer's disease: implications for novel biomarker development

    PubMed Central

    Madeira, C; Lourenco, M V; Vargas-Lopes, C; Suemoto, C K; Brandão, C O; Reis, T; Leite, R E P; Laks, J; Jacob-Filho, W; Pasqualucci, C A; Grinberg, L T; Ferreira, S T; Panizzutti, R

    2015-01-01

    Alzheimer's disease (AD) is a severe neurodegenerative disorder still in search of effective methods of diagnosis. Altered levels of the NMDA receptor co-agonist, d-serine, have been associated with neurological disorders, including schizophrenia and epilepsy. However, whether d-serine levels are deregulated in AD remains elusive. Here, we first measured D-serine levels in post-mortem hippocampal and cortical samples from nondemented subjects (n=8) and AD patients (n=14). We next determined d-serine levels in experimental models of AD, including wild-type rats and mice that received intracerebroventricular injections of amyloid-β oligomers, and APP/PS1 transgenic mice. Finally, we assessed d-serine levels in the cerebrospinal fluid (CSF) of 21 patients with a diagnosis of probable AD, as compared with patients with normal pressure hydrocephalus (n=9), major depression (n=9) and healthy controls (n=10), and results were contrasted with CSF amyloid-β/tau AD biomarkers. d-serine levels were higher in the hippocampus and parietal cortex of AD patients than in control subjects. Levels of both d-serine and serine racemase, the enzyme responsible for d-serine production, were elevated in experimental models of AD. Significantly, d-serine levels were higher in the CSF of probable AD patients than in non-cognitively impaired subject groups. Combining d-serine levels to the amyloid/tau index remarkably increased the sensitivity and specificity of diagnosis of probable AD in our cohort. Our results show that increased brain and CSF d-serine levels are associated with AD. CSF d-serine levels discriminated between nondemented and AD patients in our cohort and might constitute a novel candidate biomarker for early AD diagnosis. PMID:25942042

  7. Calculations for Adjusting Endogenous Biomarker Levels During Analytical Recovery Assessments for Ligand-Binding Assay Bioanalytical Method Validation.

    PubMed

    Marcelletti, John F; Evans, Cindy L; Saxena, Manju; Lopez, Adriana E

    2015-07-01

    It is often necessary to adjust for detectable endogenous biomarker levels in spiked validation samples (VS) and in selectivity determinations during bioanalytical method validation for ligand-binding assays (LBA) with a matrix like normal human serum (NHS). Described herein are case studies of biomarker analyses using multiplex LBA which highlight the challenges associated with such adjustments when calculating percent analytical recovery (%AR). The LBA test methods were the Meso Scale Discovery V-PLEX® proinflammatory and cytokine panels with NHS as test matrix. The NHS matrix blank exhibited varied endogenous content of the 20 individual cytokines before spiking, ranging from undetectable to readily quantifiable. Addition and subtraction methods for adjusting endogenous cytokine levels in %AR calculations are both used in the bioanalytical field. The two methods were compared in %AR calculations following spiking and analysis of VS for cytokines having detectable endogenous levels in NHS. Calculations for %AR obtained by subtracting quantifiable endogenous biomarker concentrations from the respective total analytical VS values yielded reproducible and credible conclusions. The addition method, in contrast, yielded %AR conclusions that were frequently unreliable and discordant with values obtained with the subtraction adjustment method. It is shown that subtraction of assay signal attributable to matrix is a feasible alternative when endogenous biomarkers levels are below the limit of quantitation, but above the limit of detection. These analyses confirm that the subtraction method is preferable over that using addition to adjust for detectable endogenous biomarker levels when calculating %AR for biomarker LBA.

  8. Improving low-level plasma protein mass spectrometry-based detection for candidate biomarker discovery and validation

    SciTech Connect

    Page, Jason S.; Kelly, Ryan T.; Camp, David G.; Smith, Richard D.

    2008-09-01

    Methods. To improve the detection of low abundance protein candidate biomarker discovery and validation, particularly in complex biological fluids such as blood plasma, increased sensitivity is desired using mass spectrometry (MS)-based instrumentation. A key current limitation on the sensitivity of electrospray ionization (ESI) MS is due to the fact that many sample molecules in solution are never ionized, and the vast majority of the ions that are created are lost during transmission from atmospheric pressure to the low pressure region of the mass analyzer. Two key technologies, multi-nanoelectrospray emitters and the electrodynamic ion funnel have recently been developed and refined at Pacific Northwest National Laboratory (PNNL) to greatly improve the ionization and transmission efficiency of ESI MS based analyses. Multi-emitter based ESI enables the flow from a single source (typically a liquid chromatography [LC] column) to be divided among an array of emitters (Figure 1). The flow rate delivered to each emitter is thus reduced, allowing the well-documented benefits of nanoelectrospray 1 for both sensitivity and quantitation to be realized for higher flow rate separations. To complement the increased ionization efficiency afforded by multi-ESI, tandem electrodynamic ion funnels have also been developed at PNNL, and shown to greatly improve ion transmission efficiency in the ion source interface.2, 3 These technologies have been integrated into a triple quadrupole mass spectrometer for multiple reaction monitoring (MRM) of probable biomarker candidates in blood plasma and show promise for the identification of new species even at low level concentrations.

  9. [Pilot study on predictive value of plasmatic levels of 9 angiogenetic biomarkers in selection of patients candidate to prostate biopsy].

    PubMed

    Serretta, Vincenzo; Scurria, Salvatore; Dispensa, Nino; Chiapparrone, Gaetano; Provenzano, Sandro; Caruso, Stefano; Bronte, Giuseppe; Cicero, Giuseppe; Russo, Antonio

    2013-01-01

    To reduce the number of negative prostate biopsies in patients with elevated PSA serum levels represents a major challenge in urological oncology. Angiogenetic factors might be involved in initial stages of prostate cancer and might represent useful tools in patients' selection for prostate biopsy. The plasmatic levels of Angiopoietin-2, Follistatin, G-CSF, HGF, IL-8, Leptin, PDGF-BB, PECAM-1 and VEGF were measured by BioPlex immunoassay in patients undergoing prostate biopsy for palpable prostate nodule and/or elevated PSA levels (≥4 ng/mL). They were related with biopsy results. ROC curve analysis was exploited to test the diagnostic accuracy of each biomarker by AUC calculation. A potential cut-off level was computed. Fifty patients were entered. Median PSA was 6.8 ng/mL. A prostate nodule was palpable in 18 (36%) patients. The median number of biopsy cores was 12. Prostate cancer was detected in 25 (50%) and ASAP and PIN in 2 more patients (4%) respectively. Among the 9 considered biomarkers, only leptin showed an interesting diagnostic performance with an AUC of 0.781, at a cut-off value of 2.11 ng/mL, demonstrating a sensitivity of 78%, a specificity of 77% and a positive predictive value of 85%. Main limitations of our study are the exploratory design and the criteria adopted for patients' selection determining a detection rate for prostate cancer above the usual range. Leptin only, in our preliminary study, shows promising diagnostic accuracy for the selection of patients candidate to prostate biopsy. Further studies are required to confirm its diagnostic value and its relation with BMI.

  10. Serum Midkine and Osteopontin Levels as Diagnostic Biomarkers of Hepatocellular Carcinoma

    PubMed Central

    Hodeib, Hossam; ELshora, Ola; Selim, Amal; Sabry, Nesreen Mohammed; EL-ashry, Heba Mohamed

    2017-01-01

    Introduction Hepatocellular Carcinoma (HCC) is a primary tumor of the liver; it is one of the most common cancers worldwide. Osteopontin (OPN) is a phosphorylated glycoprotein which is implicated in enhancing invasive and metastatic progression of many tumors. Midkine (MDK) is a 13-kDa small heparin-binding growth factor which plays a significant role in carcinogenesis related activities. The aim of this study was to assess the efficacy of serum Midkine and Osteopontin levels as diagnostic biomarkers of Hepatocellular Carcinoma. Methods This study was carried out from January 2014 to January 2016 in Internal Medicine, Clinical Oncology and Tropical Medicine Departments of Tanta University Hospital (Egypt). One hundred forty subjects were enrolled in our study, they were divided into four groups: Group I included 35 patients presented with HCV without cirrhosis; Group II included 35 patients presented with HCV with liver cirrhosis; Group III included 35 patients presented with HCC on top of cirrhosis; and Group IV included 35 apparently healthy subjects as a control group. The studied groups were age and sex matched. Routine and specific (OPN and MDK) laboratory investigations were performed in all included subjects. Results The main finding of the present work was that the mean serum levels of OPN and MDK were significantly elevated in HCC patients either by comparing HCC patients vs. HCV patients without cirrhosis, HCC patients vs. HCV patients with cirrhosis or HCC patients vs. healthy subjects. Interestingly, by performing a ROC analysis, serum MDK levels had better sensitivity and specificity than OPN and AFP levels in the diagnosis of HCC (98.4 %, 97.1% and 97%) and (96.2%, 95.3% and 95%) for MDK, OPN and AFP respectively. Conclusion Serum MDK and OPN levels are comparable to AFP levels and could be used as potential diagnostic biomarkers of HCC in HCV patients with liver cirrhosis and in the prediction of liver cirrhosis in HCV patients without cirrhosis

  11. Levels and Types of Alcohol Biomarkers in DUI and Clinic Samples for Estimating Workplace Alcohol Problemsa

    PubMed Central

    Marques, Paul R

    2013-01-01

    Widespread concern about illicit drugs as an aspect of workplace performance potentially diminishes attention on employee alcohol use. Alcohol is the dominant drug contributing to poor job performance; it also accounts for a third of the worldwide public health burden. Evidence from public roadways – a workplace for many – provides an example for work-related risk exposure and performance lapses. In most developed countries, alcohol is involved in 20-35% of fatal crashes; drugs other than alcohol are less prominently involved in fatalities. Alcohol biomarkers can improve detection by extending the timeframe for estimating problematic exposure levels and thereby provide better information for managers. But what levels and which markers are right for the workplace? In this report, an established high-sensitivity proxy for alcohol-driving risk proclivity is used: an average 8 months of failed blood alcohol concentration (BAC) breath tests from alcohol ignition interlock devices. Higher BAC test fail rates are known to presage higher rates of future impaired-driving convictions (DUI). Drivers in alcohol interlock programs log 5-7 daily BAC tests; in 12 months, this yields thousands of samples. Also, higher program entry levels of alcohol biomarkers predict a higher likelihood of failed interlock BAC tests during subsequent months. This report summarizes selected biomarkers’ potential for workplace screening. Markers include phosphatidylethanol (PEth), percent carbohydrate deficient transferrin (%CDT), gammaglutamyltransferase (GGT), gamma %CDT (γ%CDT), and ethylglucuronide (EtG) in hair. Clinical cutoff levels and median/mean levels of these markers in abstinent people, the general population, DUI drivers, and rehabilitation clinics are summarized for context. PMID:22311827

  12. Effects of exposure to low levels of environmental cadmium on renal biomarkers.

    PubMed Central

    Noonan, Curtis W; Sarasua, Sara M; Campagna, Dave; Kathman, Steven J; Lybarger, Jeffrey A; Mueller, Patricia W

    2002-01-01

    We conducted a study among residents of a small community contaminated with heavy metals from a defunct zinc smelter and residents from a comparison community to determine whether biologic measures of cadmium exposure were associated with biomarkers of early kidney damage. Creatinine-adjusted urinary cadmium levels did not differ between the smelter and comparison communities; thus we combined individuals from both communities (n = 361) for further analyses. The overall mean urinary cadmium level was low, 0.26 microg/g creatinine, similar to reference values observed in the U.S. general population. For children ages 6-17 years, urinary concentration of N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and albumin were positively associated with urinary cadmium, but these associations did not remain statistically significant after adjusting for urinary creatinine and other potential confounders. For adults ages 18 or older, urinary concentration of NAG, AAP, and albumin were positively associated with urinary cadmium. The associations with NAG and AAP but not with albumin remained statistically significant after adjusting for creatinine and other potential confounders. We found a positive dose-effect relationship between levels of creatinine-adjusted urinary cadmium and NAG and AAP activity, and statistically significant differences in mean activity for these two enzymes between the highest (> or =1.0 microg cadmium/g creatinine) and the lowest (< or =0.25 microg cadmium/g creatinine) exposure groups. The findings of this study indicate that biologic measures of cadmium exposure at levels below 2.0 microg/g creatinine may produce measurable changes in kidney biomarkers. PMID:11836143

  13. Calcium montmorillonite clay reduces AFB1 and FB1 biomarkers in rats exposed to single and co-exposures of aflatoxin and fumonisin

    PubMed Central

    Mitchell, Nicole J.; Xue, Kathy S.; Lin, Shuhan; Marroquin-Cardona, Alicia; Brown, Kristal A.; Elmore, Sarah E.; Tang, Lili; Romoser, Amelia; Gelderblom, Wentzel C. A.; Wang, Jia-Sheng; Phillips, Timothy D.

    2014-01-01

    Aflatoxins (AFs) and fumonisins (FBs) can co-contaminate foodstuffs and have been associated with hepatocellular and esophageal carcinomas in humans at high risk for exposure. One strategy to reduce exposure (and toxicity) from contaminated foodstuffs is the dietary inclusion of a montmorillonite clay (UPSN) that binds AFs and FBs in the GI tract. In this study, the binding capacity of UPSN was evaluated for AFB1, FB1 and a combination thereof in Fischer-344 rats. Rats were pre-treated with different dietary levels of UPSN (0.25 or 2%) for 1 week. Rats were gavaged with a single dose of either 0.125 mg AFB1 or 25 mg FB1/kg b.w. and a combination thereof in the presence and absence of an aqueous solution of UPSN. The kinetics of mycotoxin excretion were monitored by analyzing serum AFB1-albumin, urinary AF (AFM1), and FB1 biomarkers over a period of 72 hr. UPSN decreased AFM1 excretion by 88-97%, indicating highly effective binding. FB1 excretion was reduced, to a lesser extent, ranging between 45 to 85%. When in combination, both AFB1 and FB1 binding occurred, but capacity was decreased by almost half. In the absence of UPSN, the combined AFB1 and FB1 treatment decreased the urinary biomarkers by 67 and 45% respectively, but increased levels of AFB1-albumin, presumably by modulating its cytochrome metabolism. UPSN significantly reduced bioavailability of both AFB1 and FB1 when in combination; suggesting that it can be utilized to reduce levels below their respective thresholds for affecting adverse biological effects. PMID:24193864

  14. Baseline levels of oxidative stress biomarkers in species from a subtropical estuarine system (Paranaguá Bay, southern Brazil).

    PubMed

    Sardi, Adriana E; Renaud, Paul E; da Cunha Lana, Paulo; Camus, Lionel

    2016-12-15

    Offshore petroleum exploration has increased the risks of oil spills in coastal tropical and subtropical habitats. Monitoring tools are needed to assess and protect environmental health. We determined baseline values of antioxidant biomarkers (CAT, SOD, GPx, GST, MDA) for five ecologically relevant species in a subtropical system in southern Brazil. Regional baseline levels are compared with literature data as a basis to eventually test their efficacy as post-spill monitoring tools. Differences in the antioxidant response among species, contamination, and seasons were tested using univariate and multivariate analyses. The bivalves Anomalocardia flexuosa and Crassostrea rhizophorae and the catfish Genidens genidens emerge as suitable sentinel species. Seasonality is the main factor accounting for biomarkers variability, and not background contamination level. However, interactions between season and contamination level are also significant, indicating that biomarkers respond to complex environmental settings, a fact that needs to be fully understood for designing proper monitoring programs.

  15. Glutathione enzyme and selenoprotein polymorphisms associate with mercury biomarker levels in Michigan dental professionals

    SciTech Connect

    Goodrich, Jaclyn M.; Wang, Yi; Gillespie, Brenda; Werner, Robert; Franzblau, Alfred; Basu, Niladri

    2011-12-15

    Mercury is a potent toxicant of concern to both the general public and occupationally exposed workers (e.g., dentists). Recent studies suggest that several genes mediating the toxicokinetics of mercury are polymorphic in humans and may influence inter-individual variability in mercury accumulation. This work hypothesizes that polymorphisms in key glutathione synthesizing enzyme, glutathione s-transferase, and selenoprotein genes underlie inter-individual differences in mercury body burden as assessed by analytical mercury measurement in urine and hair, biomarkers of elemental mercury and methylmercury, respectively. Urine and hair samples were collected from a population of dental professionals (n = 515), and total mercury content was measured. Average urine (1.06 {+-} 1.24 ug/L) and hair mercury levels (0.49 {+-} 0.63 ug/g) were similar to national U.S. population averages. Taqman assays were used to genotype DNA from buccal swab samples at 15 polymorphic sites in genes implicated in mercury metabolism. Linear regression modeling assessed the ability of polymorphisms to modify the relationship between mercury biomarker levels and exposure sources (e.g., amalgams, fish consumption). Five polymorphisms were significantly associated with urine mercury levels (GSTT1 deletion), hair mercury levels (GSTP1-105, GSTP1-114, GSS 5 Prime ), or both (SEPP1 3 Prime UTR). Overall, this study suggests that polymorphisms in selenoproteins and glutathione-related genes may influence elimination of mercury in the urine and hair or mercury retention following exposures to elemental mercury (via dental amalgams) and methylmercury (via fish consumption). -- Highlights: Black-Right-Pointing-Pointer We explore the influence of 15 polymorphisms on urine and hair Hg levels. Black-Right-Pointing-Pointer Urine and hair Hg levels in dental professionals were similar to the US population. Black-Right-Pointing-Pointer GSTT1 and SEPP1 polymorphisms associated with urine Hg levels. Black

  16. Blood Occludin Level as a Potential Biomarker for Early Blood Brain Barrier Damage Following Ischemic Stroke

    PubMed Central

    Pan, Rong; Yu, Kewei; Weatherwax, Theodore; Zheng, Handong; Liu, Wenlan; Liu, Ke Jian

    2017-01-01

    Concern about intracerebral hemorrhage (ICH) is the primary reason for withholding tPA therapy from patients with ischemic stroke. Early blood brain barrier (BBB) damage is the major risk factor for fatal post-thrombolysis ICH, but rapidly assessing BBB damage before tPA administration is highly challenging. We recently reported that ischemia induced rapid degradation of tight junction protein occludin in cerebromicrovessels. The present study investigates whether the cleaved occludin is released into the blood stream and how blood occludin levels correlate to the extent of BBB damage using a rat model of ischemic stroke. Cerebral ischemia induced a time-dependent increase of blood occludin with a sharp increase at 4.5-hour post-ischemia onset, which concurrently occurred with the loss of occludin from ischemic cerebral microvessels and a massive BBB leakage at 4.5-hour post-ischemia. Two major occludin fragments were identified in the blood during cerebral ischemia. Furthermore, blood occludin levels remained significantly higher than its basal level within the first 24 hours after ischemia onset. Our findings demonstrate that blood occludin levels correlate well with the extent of BBB damage and thus may serve as a clinically relevant biomarker for evaluating the risk of ICH before tPA administration. PMID:28079139

  17. The human BDNF gene: peripheral gene expression and protein levels as biomarkers for psychiatric disorders

    PubMed Central

    Cattaneo, A; Cattane, N; Begni, V; Pariante, C M; Riva, M A

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of neurons, and influences synaptic efficiency and plasticity. The human BDNF gene consists of 11 exons, and distinct BDNF transcripts are produced through the use of alternative promoters and splicing events. The majority of the BDNF transcripts can be detected not only in the brain but also in the blood cells, although no study has yet investigated the differential expression of BDNF transcripts at the peripheral level. This review provides a description of the human BDNF gene structure as well as a summary of clinical and preclinical evidence supporting the role of BDNF in the pathogenesis of psychiatric disorders. We will discuss several mechanisms as possibly underlying BDNF modulation, including epigenetic mechanisms. We will also discuss the potential use of peripheral BDNF as a biomarker for psychiatric disorders, focusing on the factors that can influence BDNF gene expression and protein levels. Within this context, we have also characterized, for we believe the first time, the expression of BDNF transcripts in the blood, with the aim to provide novel insights into the molecular mechanisms and signaling that may regulate peripheral BDNF gene expression levels. PMID:27874848

  18. Increased levels of etheno-DNA adducts and genotoxicity biomarkers of long-term exposure to pure diesel engine exhaust.

    PubMed

    Shen, Meili; Bin, Ping; Li, Haibin; Zhang, Xiao; Sun, Xin; Duan, Huawei; Niu, Yong; Meng, Tao; Dai, Yufei; Gao, Weimin; Yu, Shanfa; Gu, Guizhen; Zheng, Yuxin

    2016-02-01

    Etheno-DNA adducts are biomarkers for assessing oxidative stress. In this study, the aim was to detect the level of etheno-DNA adducts and explore the relationship between the etheno-DNA adducts and genotoxicity biomarkers of the diesel engine exhaust (DEE)-exposed workers. We recruited 86 diesel engine testing workers with long-term exposure to DEE and 99 non-DEE-exposed workers. The urinary mono-hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and etheno-DNA adducts (εdA and εdC) were detected by HPLC-MS/MS and UPLC-MS/MS, respectively. Genotoxicity biomarkers were also evaluated by comet assay and cytokinesis-block micronucleus assay. The results showed that urinary εdA was significantly higher in the DEE-exposed workers (p<0.001), exhibited 2.1-fold increase compared with the non-DEE-exposed workers. The levels of urinary OH-PAHs were positively correlated with the level of εdA among all the study subjects (p<0.001). Moreover, we found that the increasing level of εdA was significantly associated with the increased olive tail moment, percentage of tail DNA, or frequency of micronucleus in the study subjects (p<0.01). No significant association was observed between the εdC level and any measured genotoxicity biomarkers. In summary, εdA could serve as an indicator for DEE exposure in the human population.

  19. Elevated urinary level of vitamin D-binding protein as a novel biomarker for diabetic nephropathy

    PubMed Central

    TIAN, XIAO-QIN; ZHAO, LI-MIN; GE, JIA-PU; ZHANG, YAN; XU, YAN-CHENG

    2014-01-01

    Improving the early prediction and detection of diabetic nephropathy (DN) remains a great challenge in disease management. The aim of this study was to evaluate the early detection power of urinary vitamin D-binding protein (VDBP) for the diagnosis of DN. Urine samples were obtained from 45 healthy volunteers and 105 diabetic patients with normoalbuminuria (DM group), microalbuminuria (DN1 group) and macroalbuminuria (DN2 group) (n=35 per group). The VDBP expression patterns in urine from patients and controls were quantified by western blot analysis. The excretion levels of urinary VDBP were quantified with enzyme-linked immunosorbent assay. The quantification results were obtained by correcting for creatinine expression and showed that urinary VDBP levels were significantly elevated in the patients of the DN1 and DN2 groups compared with those of the DM group and normal controls (1,011.33±325.30 and 1,406.34±239.66 compared with 466.54±213.63 and 125.48±98.27 ng/mg, respectively) (P<0.001). Receiver operating characteristic analysis of urinary VDBP levels for the diagnosis of DN rendered an optimum cut-off value of 552.243 ng/mg corresponding to 92.86% sensitivity and 85.00% specificity, which also showed an area under the ROC curve of 0.966. In conclusion, the findings of the present study suggest that urinary VDBP may be a potential biomarker for the early detection and prevention of DN. Further studies are required to examine the pathogenic mechanisms of elevated VDBP levels and their role in the diagnosis of DN. PMID:24396416

  20. EGFR Exon-Level Biomarkers of the Response to Bevacizumab/Erlotinib in Non-Small Cell Lung Cancer

    PubMed Central

    Baty, Florent; Rothschild, Sacha; Früh, Martin; Betticher, Daniel; Dröge, Cornelia; Cathomas, Richard; Rauch, Daniel; Gautschi, Oliver; Bubendorf, Lukas; Crowe, Susanne; Zappa, Francesco; Pless, Miklos; Brutsche, Martin

    2013-01-01

    Activating epidermal growth factor receptor (EGFR) mutations are recognized biomarkers for patients with metastatic non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). EGFR TKIs can also have activity against NSCLC without EGFR mutations, requiring the identification of additional relevant biomarkers. Previous studies on tumor EGFR protein levels and EGFR gene copy number revealed inconsistent results. The aim of the study was to identify novel biomarkers of the response to TKIs in NSCLC by investigating whole genome expression at the exon-level. We used exon arrays and clinical samples from a previous trial (SAKK19/05) to investigate the expression variations at the exon-level of 3 genes potentially playing a key role in modulating treatment response: EGFR, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and vascular endothelial growth factor (VEGFA). We identified the expression of EGFR exon 18 as a new predictive marker for patients with untreated metastatic NSCLC treated with bevacizumab and erlotinib in the first line setting. The overexpression of EGFR exon 18 in tumor was significantly associated with tumor shrinkage, independently of EGFR mutation status. A similar significant association could be found in blood samples. In conclusion, exonic EGFR expression particularly in exon 18 was found to be a relevant predictive biomarker for response to bevacizumab and erlotinib. Based on these results, we propose a new model of EGFR testing in tumor and blood. PMID:24039832

  1. Biomarker correlations of urinary 2,4-D levels in foresters: genomic instability and endocrine disruption.

    PubMed Central

    Garry, V F; Tarone, R E; Kirsch, I R; Abdallah, J M; Lombardi, D P; Long, L K; Burroughs, B L; Barr, D B; Kesner, J S

    2001-01-01

    Forest pesticide applicators constitute a unique pesticide use group. Aerial, mechanical-ground, and focal weed control by application of herbicides, in particular chlorophenoxy herbicides, yield diverse exposure scenarios. In the present work, we analyzed aberrations in G-banded chromosomes, reproductive hormone levels, and polymerase chain reaction-based V(D)J rearrangement frequencies in applicators whose exposures were mostly limited to chlorophenoxy herbicides. Data from appliers where chlorophenoxy use was less frequent were also examined. The biomarker outcome data were compared to urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D) obtained at the time of maximum 2,4-D use. Further comparisons of outcome data were made to the total volume of herbicides applied during the entire pesticide-use season.Twenty-four applicators and 15 minimally exposed foresters (control) subjects were studied. Categorized by applicator method, men who used a hand-held, backpack sprayer in their applications showed the highest average level (453.6 ppb) of 2,4-D in urine. Serum luteinizing hormone (LH) values were correlated with urinary 2,4-D levels, but follicle-stimulating hormone and free and total testosterone were not. At the height of the application season; 6/7 backpack sprayers, 3/4 applicators who used multinozzle mechanical (boom) sprayers, 4/8 aerial applicators, and 2/5 skidder-radiarc (closed cab) appliers had two or more V(D)J region rearrangements per microgram of DNA. Only 5 of 15 minimally exposed (control) foresters had two or more rearrangements, and 3 of these 5 subjects demonstrated detectable levels of 2,4-D in the urine. Only 8/24 DNA samples obtained from the exposed group 10 months or more after their last chlorophenoxy use had two rearrangements per microgram of DNA, suggesting that the exposure-related effects observed were reversible and temporary. Although urinary 2,4-D levels were not correlated with chromosome aberration frequency, chromosome

  2. In situ impact assessment of wastewater effluents by integrating multi-level biomarker responses in the pale chub (Zacco platypus).

    PubMed

    Kim, Woo-Keun; Jung, Jinho

    2016-06-01

    The integration of biomarker responses ranging from the molecular to the individual level is of great interest for measuring the toxic effects of hazardous chemicals or effluent mixtures on aquatic organisms. This study evaluated the effects of wastewater treatment plant (WWTP) effluents on the freshwater pale chub Zacco platypus by using multi-level biomarker responses at molecular [mRNA expression of catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), and metallothionein (MT)], biochemical (enzyme activities of CAT, SOD, GST, and concentration of MT), and physiological [condition factor (CF) and liver somatic index (LSI)] levels. The mRNA expression levels of GST and MT in Z. platypus from a site downstream of a WWTP significantly increased by 2.2- and 4.5-fold (p<0.05) when compared with those from an upstream site. However, the enzyme activities of CAT, SOD, and GST in fish from the downstream site significantly decreased by 43%, 98%, and 13%, respectively (p<0.05), except for an increase in MT concentration (41%). In addition, a significant increase in LSI (46%) was observed in Z. platypus from the downstream site (p<0.05). Concentrations of Cu, Zn, Cd, and Pb in the liver of Z. platypus were higher (530%, 353%, 800%, and 2,200%, respectively) in fish from a downstream site than in fish from an upstream location, and several multi-level biomarker responses were significantly correlated with the accumulated metals in Z. platypus (p<0.05). Integrated biomarker responses at molecular, biochemical, and physiological levels (multi-level IBR) were much higher (about 4-fold) at the downstream site than at the upstream site. This study suggests that the multi-level IBR approach is very useful for quantifying in situ adverse effects of WWTP effluents.

  3. Periodontal Treatment Reduces Matrix Metalloproteinase Levels in Localized Aggressive Periodontitis

    PubMed Central

    Gonçalves, Patricia Furtado; Huang, Hong; McAninley, Suzanna; Alfant, Barnett; Harrison, Peter; Aukhil, Ikramuddin; Walker, Clay; Shaddox, Luciana Macchion

    2015-01-01

    Background Matrix metalloproteinases (MMPs) are a family of host-derived proteinases reported to mediate multiple functions associated with periodontal destruction and inflammation. We have previously reported high MMP levels in African-American children with localized aggressive periodontitis (LAP). However, little is known about MMP reductions in gingival crevicular fluid (GCF) after therapy. This study aimed to evaluate MMP levels in the GCF following treatment of LAP and to correlate these levels with clinical response. Methods GCF samples were collected from 29 African-American individuals diagnosed with LAP. GCF was collected from one diseased site (pocket depth [PD]>4mm, bleeding on probing [BoP] and clinical attachment level [CAL] ≥2mm) and one healthy site (PD≤3mm, no BoP) from each individual at baseline, 3 and 6 months after periodontal treatment, which consisted of full-mouth SRP and systemic antibiotics. The volume of GCF was controlled using a calibrated gingival fluid meter and levels of MMP-1, 2, 3, 8, 9, 12 and 13 were assessed using fluorometric kits. Results MMP-1, 8, 9 12, and 13 levels were reduced significantly up to 6 months, at which point were comparable with healthy sites. Significant correlations were noted between MMP-2, 3, 8, 9, 12 and 13 levels and % of sites with PD>4mm. MMP-3, 12 and 13 levels also correlated with mean pocket depth of affected sites. Conclusion Treatment of LAP with SRP and systemic antibiotics was effective in reducing the local levels specific MMPs in African-American individuals, which correlated positively with some clinical parameters. PMID:23537121

  4. Biomarkers of sulfate reducing bacteria from a variety of different aged samples including a modern microbial mat

    NASA Astrophysics Data System (ADS)

    Pages, A.; Grice, K.; Lockhart, R.; Holman, A.; Melendez, I.; Van Kranendonk, M.; Jaraula, C.

    2011-12-01

    Most biomarkers present in sediments occur in only trace concentrations, trapped in kerogen or may be highly functionalised especially in recent sedimentary deposits making them difficult to chromatographically resolve, thus presenting considerable analytical challenges, especially for isotope studies. Innovative hydro (Hy) pyrolysis (Py) techniques are able to target or convert many of these compounds into free hydrocarbons more amenable to gas chromatography mass-spectrometry (GC-MS) and compound-specific isotope analysis (CSIA). HyPy has been applied to a modern layered smooth mat from Shark Bay, Western Australia. Saturate and aromatic fractions from different layers of the mat have been analysed by GC-MS and CSIA. After HyPy, an even-odd distribution of n-alkanes has been revealed as well as very long-chain n-alkanes up to n-C38. Stable carbon isotopic values of the n-alkanes indicated the presence of at least two bacterial communities. The short-chain n-alkanes were likely to be representative of a cyanobacteria community (δ13C, C15-C23, - 18 to -25 %VPDB) while the carbon isotopic values of the long-chain n-alkanes supported the presence of sulfate reducing bacteria (δ13C, C25-C33, - 30 to - 34 %VPDB). Long-chain fatty acids have been previously reported in sulfate reducing bacteria. It is hypothesised that this distribution and isotopic character representing sulfate reducing bacteria consortia may be preserved in the rock record. This hypothesis has been tested in Australian rocks: a Devonian carbonaceous concretion containing an exceptionally well preserved fossil invertebrate from the Canning Basin, Western Australia, a Paleoproterozoic sample (1.6 billion years old) from a lead-zinc ore deposit from the McArthur Basin, Northern Territories and a Paleoproterozoic chert (2.3 billion years old) from the Pilbara, Western Australia. Biomarkers of these samples showed a strong predominance of long-chain n-alkanes, up to n-C38 with an even-odd distribution

  5. From tissue iron retention to low systemic haemoglobin levels, new pathophysiological biomarkers of human abdominal aortic aneurysm.

    PubMed

    Martinez-Pinna, R; Lindholt, J S; Madrigal-Matute, J; Blanco-Colio, L M; Esteban-Salan, M; Torres-Fonseca, M M; Lefebvre, T; Delbosc, S; Laustsen, J; Driss, F; Vega de Ceniga, M; Gouya, L; Weiss, G; Egido, J; Meilhac, O; Michel, J-B; Martin-Ventura, J

    2014-07-03

    Iron deposits are observed in tissue of abdominal aortic aneurysm (AAA) patients, although the underlying mechanisms are not completely elucidated. Therefore we explored circulating markers of iron metabolism in AAA patients, and tested if they could serve as biomarkers of AAA. Increased red blood cell (RBC)-borne iron retention and transferrin, transferrin receptor and ferritin expression was observed in AAA tissue compared to control aorta (immunohistochemistry and western blot). In contrast, decreased circulating iron, transferrin, mean corpuscular haemoglobin concentration (MCHC) and haemoglobin concentration, along with circulating RBC count, were observed in AAA patients (aortic diameter >3 cm, n=114) compared to controls (aortic diameter <3 cm, n=88) (ELISA), whereas hepcidin concentrations were increased in AAA subjects (MS/MS assay). Moreover, iron, transferrin and haemoglobin levels were negatively, and hepcidin positively, correlated with aortic diameter in AAA patients. The association of low haemoglobin with AAA presence or aortic diameter was independent of specific risk factors. Moreover, MCHC negatively correlated with thrombus area in another cohort of AAA patients (aortic diameter 3-5 cm, n=357). We found that anaemia was significantly more prevalent in AAA patients (aortic diameter >5 cm, n=8,912) compared to those in patients with atherosclerotic aorto-iliac occlusive disease (n=17,737) [adjusted odds ratio=1.77 (95% confidence interval: 1.61;1.93)]. Finally, the mortality risk among AAA patients with anaemia was increased by almost 30% [adjusted hazard ratio: 1.29 (95% confidence interval: 1.16;1.44)] as compared to AAA subjects without anaemia. In conclusion, local iron retention and altered iron recycling associated to high hepcidin and low transferrin systemic concentrations could lead to reduced circulating haemoglobin levels in AAA patients. Low haemoglobin levels are independently associated to AAA presence and clinical outcome.

  6. Mercury levels assessment and its relationship with oxidative stress biomarkers in children from three localities in Yucatan, Mexico.

    PubMed

    Rangel-Méndez, Jorge A; Arcega-Cabrera, Flor E; Fargher, Lane F; Moo-Puc, Rosa E

    2016-02-01

    Mercury (Hg) is a global pollutant that is released into the environment from geologic and anthropogenic sources. Once it enters an organism, it generates several toxicity mechanisms and oxidative stress has been proposed as the main one. Metal susceptibility is greater in children, which is a result of their physiology and behavior. In Yucatan, Mexico, burning of unregulated garbage dumps and household trash, ingestion of top marine predators, and pottery manufacturing are among the conditions that could promote Hg exposure. However, for Yucatan, there are no published studies that report Hg levels and associated oxidative stress status in children. Therefore, this study aimed to assess Hg levels in blood and urine and oxidative stress biomarkers levels in a sample of 107 healthy children from three localities in Yucatan, Mexico, as well as investigate the relationship between these parameters. Hg was detected in 11 (10.28%) of blood samples and 38 (35.51%) of urine samples collected from the participating children. Fourteen subjects showed Hg above recommended levels. The oxidative stress biomarkers were slightly elevated in comparison with other studies and were statistically different between the sampling sites. No linear correlation between Hg levels and oxidative stress biomarkers was found. Nevertheless, exploratory univariate and multivariate analysis showed non-linear relations among the measured variables. Globally, the study provides, for the first time, information regarding Hg levels and their relationship with oxidative stress biomarkers in a juvenile population from Mexico's southeast (Yucatan) region. In agreement with worldwide concern about Hg, this study should stimulate studies on metal monitoring in humans (especially children) among scientists working in Mexico, the establishment of polices for its regulation, and the reduction of human health risks.

  7. Bladder cancer biomarker array to detect aberrant levels of proteins in urine.

    PubMed

    Gogalic, S; Sauer, U; Doppler, S; Preininger, C

    2015-02-07

    Bladder cancer (BCa) is a serious malignancy of the urinary tract worldwide and also prominent for its high rate of recurrence incorporating 50% of all treated patients. To reduce relapse of BCa, lifelong surveillance of patients is essential leading to high treatment costs. The gold standard for the diagnosis of bladder cancer is cystoscopy. It is very sensitive, but due to high costs and its invasive nature this method for routine diagnosis of bladder cancer remains questionable. Because of this and the required surveillance of patients suffering from bladder cancer, urine based markers represent a new potential field of investigation. Literature at the National Center of Biological Information (NCBI) was retrieved for a potential marker panel offering specific protein signatures and used to develop a sensitive and accurate chip assay to monitor BCa. Discovery of possible bladder cancer protein markers is compiled by extensive literature search including 1077 recently (15.01.2008-20.03.2014) published research articles. Validation of this literature is done by selection based on prior defined inclusion and exclusion criteria. A set of six putative biomarkers (VEGF, IL-8, MMP-9, MMP-7, survivin and Cyfra 21.1) was identified and a non-invasive microarray developed to be used for further clinical validation. Investigation regarding optimized urine preparation and assay development, to enhance assay sensitivity for the marker panel, was carried out. This protein based BCa chip enables the fast (within 5 h), simultaneous, easy to operate, cheap, early and non-invasive determination of BCa and is ready for clinical evaluation.

  8. Calcium montmorillonite clay reduces urinary biomarkers of fumonisin B1 exposure in rats and humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Fumonisin B1 (FB1) is often a co-contaminant with aflatoxin (AF) in grains and may enhance AF’s carcinogenicity by acting as a cancer promoter. An oral dose of calcium montmorillonite clay (i.e. NovaSil, NS) was able to reduce aflatoxin exposure in a Ghanaian population at risk. In vitro...

  9. Plasma Levels of Soluble Interleukin 1 Receptor Accessory Protein Are Reduced in Obesity

    PubMed Central

    Attard, Chantal; Kulkarni, Hemant; Cummings, Nik; Diego, Vincent P.; Carless, Melanie A.; Shields, Katherine A.; Johnson, Matthew P.; Kowlessur, Sudhir; Dyer, Thomas D.; Comuzzie, Anthony G.; Almasy, Laura; Zimmet, Paul; Moses, Eric K.; Göring, Harald H. H.; Curran, Joanne E.; Blangero, John; Jowett, Jeremy B. M.

    2014-01-01

    Context: Adipokines actuate chronic, low-grade inflammation through a complex network of immune markers, but the current understanding of these networks is incomplete. The soluble isoform of the IL-1 receptor accessory protein (sIL1RAP) occupies an important position in the inflammatory pathways involved in obesity. The pathogenetic and clinical influences of sIL1RAP are unknown. Objective: The objective of the study was to elucidate whether plasma levels of sIL1RAP are reduced in obesity, using affluent clinical, biochemical, and genetic data from two diverse cohorts. Design, Setting, and Participants: The study was conducted in two cohorts: the San Antonio Family Heart Study (n = 1397 individuals from 42 families) and South Asians living in Mauritius, n = 230). Main Outcome Measures: Plasma sIL1RAP levels were measured using an ELISA. The genetic basis of sIL1RAP levels were investigated using both a large-scale gene expression profiling study and a genome-wide association study. Results: A significant decrease in plasma sIL1RAP levels were observed in obese subjects, even after adjustment for age and sex. The sIL1RAP levels demonstrated a strong inverse association with obesity measures in both populations. All associations were more significant in females. Plasma sIL1RAP levels were significantly heritable, correlated with IL1RAP transcript levels (NM_134470), showed evidence for shared genetic influences with obesity measures and were significantly associated with the rs2885373 single-nucleotide polymorphism (P = 6.7 × 10−23) within the IL1RAP gene. Conclusions: Plasma sIL1RAP levels are reduced in obesity and can potentially act as biomarkers of obesity. Mechanistic studies are required to understand the exact contribution of sIL1RAP to the pathogenesis of obesity. PMID:24915116

  10. Low level laser therapy reduces inflammation in activated Achilles tendinitis

    NASA Astrophysics Data System (ADS)

    Bjordal, Jan M.; Iversen, Vegard; Lopes-Martins, Rodrigo Alvaro B.

    2006-02-01

    Objective: Low level laser therapy (LLLT) has been forwarded as therapy for osteoarthritis and tendinopathy. Results in animal and cell studies suggest that LLLT may act through a biological mechanism of inflammatory modulation. The current study was designed to investigate if LLLT has an anti-inflammatory effect on activated tendinitis of the Achilles tendon. Methods: Seven patients with bilateral Achilles tendonitis (14 tendons) who had aggravated symptoms by pain-inducing activity immediately prior to the study. LLLT (1.8 Joules for each of three points along the Achilles tendon with 904nm infrared laser) and placebo LLLT were administered to either Achilles tendons in a random order to which patients and therapist were blinded. Inflammation was examined by 1) mini-invasive microdialysis for measuring the concentration of inflammatory marker PGE II in the peritendinous tissue, 2) ultrasound with Doppler measurement of peri- and intratendinous blood flow, 3) pressure pain algometry and 4) single hop test. Results: PGE 2- levels were significantly reduced at 75, 90 and 105 minutes after active LLLT compared both to pre-treatment levels (p=0.026) and to placebo LLLT (p=0.009). Changes in pressure pain threshold (PPT) were significantly different (P=0.012) between groups. PPT increased by a mean value of 0.19 kg/cm2 [95%CI:0.04 to 0.34] after treatment in the active LLLT group, while pressure pain threshold was reduced by -0.20 kg/cm2 [95%CI:-0.45 to 0.05] after placebo LLLT. Conclusion: LLLT can be used to reduce inflammatory musculskeletal pain as it reduces inflammation and increases pressure pain threshold levels in activity-induced pain episodes of Achilles tendinopathy.

  11. Total bilirubin level may be a biomarker of nephropathy in type 2 diabetes mellitus

    PubMed Central

    Zhang, Dan; Zhu, Bo; Zhang, Wei; Wang, Wei; Guo, Dan; Yang, Ligang; Wang, Lu

    2017-01-01

    Abstract Recently, the number of the studies on the relationship between the total bilirubin level (TBL) and diabetic nephropathy (DN) is increasing, but their results were not consistent. Therefore, we performed a meta-analysis to analyze the relationship between TBL and the risk of DN. We searched 5 databases before October 31, 2016, and reviewed the reference list of relevant articles. The fixed or random-effects model was used to pool risk estimates. We conducted the dose–response meta-analysis to evaluate the relationship between TBL and the risk of DN. Our meta-analysis showed that TBL in the DN group was lower than that in diabetes without the kidney disease (NDN) group (standard mean difference [SMD]: −0.63, 95% CI: −0.80, −0.46). The result of each subgroup also showed that TBL in the DN group was lower than that in the NDN group. The result of meta-regression indicated that duration of diabetes mellitus might be the source of heterogeneity. Our meta-analysis also showed that there was a significant negative relationship between TBL and the risk of DN (OR: 0.86, 95%CI: 0.82, 0.90). The results of subgroup analysis were similar to those of SMD; no sources of heterogeneity were detected by meta-regression. Sensitivity analysis indicated that the results were robust. We observed a linear association between TBL and the risk of DN, and there was a negative dose–response association between TBL and the risk of DN. In conclusion, bilirubin may be used as a biomarker of DN. It helps early diagnosis and effective therapeutic strategies on DN. PMID:28072721

  12. [Phytosterols: another way to reduce LDL cholesterol levels].

    PubMed

    Bitzur, Rafael; Cohen, Hofit; Kamari, Yehuda; Harats, Dror

    2013-12-01

    Phytosterols are sterols found naturally in various oils from plants. Phytosterols compete with cholesterol for a place in the mixed micelles, needed for cholesterol absorption by the small intestine. As a result, cholesterol absorption, either from food or from bile salts is lowered by about 50%, leading to a towering of about 10% of blood cholesterol level, despite an increase in hepatic cholesterol synthesis. This reduction is achieved when phytosterols are given both as monotherapy, and in addition to statin therapy. The average Western diet contains about 400-800 mg of phytosterols per day, while the dose needed for lowering the blood cholesterol level is about 2-3 grams per day. Therefore, for the purpose of reducing blood cholesterol, they should be given either as phytosterol-enriched food or as supplements. The reduction in the level of LDL-choLesterol achieved with phytosterols may reduce the risk of coronary disease by about 25%. Hence, the American Heart Association recommended the consumption of phytosterols, as part of a balanced diet, for towering blood cholesterol levels.

  13. Low stimulus environments: reducing noise levels in continuing care

    PubMed Central

    Brown, Juliette; Fawzi, Waleed; Shah, Amar; Joyce, Margaret; Holt, Genevieve; McCarthy, Cathy; Stevenson, Carmel; Marange, Rosca; Shakes, Joy; Solomon-Ayeh, Kwesi

    2016-01-01

    In the low stimulus environment project, we aimed to reduce the levels of intrusive background noise on an older adult mental health ward, combining a very straightforward measure on decibel levels with a downstream measure of reduced distress and agitation as expressed in incidents of violence. This project on reducing background noise levels on older adult wards stemmed from work the team had done on reducing levels of violence and aggression. We approached the problem using quality improvement methods. Reducing harm to patients and staff is a strategic aim of our Trust and in our efforts we were supported by the Trust's extensive programme of quality improvement, including training and support provided by the Institute for Healthcare Improvement and the trust's own Quality Improvement team. Prior to the project we were running a weekly multi-disciplinary quality improvement group on the ward. We established from this a sub-group to address the specific problem of noise levels and invited carers of people with dementia on our ward to the group. The project was led by nursing staff. We used a noise meter app readily downloadable from the internet to monitor background noise levels on the ward and establish a baseline measure. As a group we used a driver diagram to identify an overall aim and a clear understanding of the major factors that would drive improvements. We also used a staff and carer survey to identify further areas to work on. Change ideas that came from staff and carers included the use of the noise meter to track and report back on noise levels, the use of posters to remind staff about noise levels, the introduction of a visual indication of current noise levels (the Yacker Tracker), the addition of relaxing background music, and adaptations to furniture and environment. We tested many of these over the course of nine months in 2015, using the iterative learning gained from multiple PDSA cycles. The specific aim was a decrease from above 60dB to

  14. Reduced striatal adenosine A2A receptor levels define a molecular subgroup in schizophrenia.

    PubMed

    Villar-Menéndez, Izaskun; Díaz-Sánchez, Sara; Blanch, Marta; Albasanz, José Luis; Pereira-Veiga, Thais; Monje, Alfonso; Planchat, Luis Maria; Ferrer, Isidre; Martín, Mairena; Barrachina, Marta

    2014-04-01

    Schizophrenia (SZ) is a mental disorder of unknown origin. Some scientific evidence seems to indicate that SZ is not a single disease entity, since there are patient groups with clear symptomatic, course and biomarker differences. SZ is characterized by a hyperdopaminergic state related to high dopamine D2 receptor activity. It has also been proposed that there is a hypoadenosynergic state. Adenosine is a nucleoside widely distributed in the organism with neuromodulative and neuroprotective activity in the central nervous system. In the brain, the most abundant adenosine receptors are A1R and A2AR. In the present report, we characterize the presence of both receptors in human postmortem putamens of patients suffering SZ with real time TaqMan PCR, western blotting and radioligand binding assay. We show that A1R levels remain unchanged with respect to age-matched controls, whereas nearly fifty percent of patients have reduced A2AR, at the transcriptional and translational levels. Moreover, we describe how DNA methylation plays a role in the pathological A2AR levels with the bisulfite-sequencing technique. In fact, an increase in 5-methylcytosine percentage in the 5' UTR region of ADORA2A was found in those SZ patients with reduced A2AR levels. Interestingly, there was a relationship between the A2A/β-actin ratio and motor disturbances as assessed with some items of the PANSS, AIMS and SAS scales. Therefore, there may be a subgroup of SZ patients with reduced striatal A2AR levels accompanied by an altered motor phenotype.

  15. Biomarkers and transcription levels of cancer-related genes in cockles Cerastoderma edule from Galicia (NW Spain) with disseminated neoplasia.

    PubMed

    Ruiz, Pamela; Díaz, Seila; Orbea, Amaia; Carballal, Maria J; Villalba, Antonio; Cajaraville, Miren P

    2013-07-15

    Disseminated neoplasia (DN) is a pathological condition reported for several species of marine bivalves throughout the world, but its aetiology has not yet been satisfactorily explained. It has been suggested that chemical contamination could be a factor contributing to neoplasia. The aim of the present study was to compare cell and tissue biomarkers and the transcription level of cancer-related genes in cockles (Cerastoderma edule) affected by DN with those of healthy cockles in relation to chemical contaminant burdens. For this, cockles were collected from a natural bed in Cambados (Ria de Arousa, Galicia) in May 2009. The prevalence of DN was 12.36% and 3 degrees of DN severity were distinguished. No significant differences in metal accumulation, non-specific inflammatory responses and parasites were observed between healthy and DN-affected cockles. Lysosomal membrane stability was significantly reduced in cockles affected by DN, which indicates a poorer health condition. Very low frequencies of micronuclei were recorded and no significant differences were detected between DN severity groups. Haemolymph analyses showed a higher frequency of mitotic figures and binucleated cells in cockles affected by moderate and heavy DN than in healthy ones. Neoplastic animals showed significantly higher transcription levels of p53 and ras than healthy cockles and mutational alterations in ras gene sequence were detected. Low concentrations of metals, polycyclic aromatic hydrocarbons, polychlorinated biphenyls and phthalate esters were measured in cockles from Cambados. In conclusion, cockles affected by DN suffer a general stress situation and have altered patterns of cancer-related gene transcription. Further studies are in progress to elucidate mechanisms of carcinogenesis in this species.

  16. Ultratrace Level Determination and Quantitative Analysis of Kidney Injury Biomarkers in Patient Samples Attained by Zinc Oxide Nanorods

    PubMed Central

    Singh, Manpreet; Alabanza, Anginelle; Gonzalez, Lorelis E.; Wang, Weiwei; Reeves, W. Brian; Hahm, Jong-in

    2016-01-01

    Determining ultratrace amounts of protein biomarkers in patient samples in a straightforward and quantitative manner is extremely important for early disease diagnosis and treatment. Here, we successfully demonstrate the novel use of zinc oxide nanorods (ZnO NRs) in the ultrasensitive and quantitative detection of two acute kidney injury (AKI)-related protein biomarkers, tumor necrosis factor (TNF)-α and interleukin (IL)-8, directly from patient samples. We first validate the ZnO NRs-based IL-8 results via comparison with those obtained from using a conventional enzyme-linked immunosorbent method in samples from 38 individuals. We further assess the full detection capability of the ZnO NRs-based technique by quantifying TNF-α, whose levels in human urine are often below the detection limits of conventional methods. Using the ZnO NR platforms, we determine the TNF-α concentrations of all 46 patient samples tested, down to the fg/mL level. Subsequently, we screen for TNF-α levels in approximately 50 additional samples collected from different patient groups in order to demonstrate a potential use of the ZnO NRs-based assay in assessing cytokine levels useful for further clinical monitoring. Our research efforts demonstrate that ZnO NRs can be straightforwardly employed in the rapid, ultrasensitive, quantitative, and simultaneous detection of multiple AKI-related biomarkers directly in patient urine samples, providing an unparalleled detection capability beyond those of conventional analysis methods. Additional key advantages of the ZnO NRs-based approach include a fast detection speed, low-volume assay condition, multiplexing ability, and easy automation/integration capability to existing fluorescence instrumentation. Therefore, we anticipate that our ZnO NRs-based detection method will be highly beneficial for overcoming the frequent challenges in early biomarker development and treatment assessment, pertaining to the facile and ultrasensitive quantification of

  17. Is the hair nicotine level a more accurate biomarker of environmental tobacco smoke exposure than urine cotinine?

    PubMed Central

    Al-Delaimy, W; Crane, J; Woodward, A

    2002-01-01

    Study objective: The aim of this study was to compare the two biomarkers of exposure to environmental tobacco smoke (ETS); urine cotinine and hair nicotine, using questionnaires as the standard. Design: A cross sectional study of children consecutively admitted to hospital for lower respiratory illnesses during the period of the study. Settings: Three regional hospitals in the larger Wellington area, New Zealand. Participants: Children aged 3–27 months and admitted to the above hospitals during August 1997 to October 1998. A total of 322 children provided 297 hair samples and 158 urine samples. Main results: Hair nicotine levels were better able to discriminate the groups of children according to their household's smoking habits at home (no smokers, smoke only outside the home, smoke inside the house) than urine cotinine (Kruskall-Wallis; χ2=142.14, and χ2=49.5, respectively (p<0.0001)). Furthermore, hair nicotine levels were more strongly correlated with number of smokers in the house, and the number of cigarettes smoked by parents and other members of the child's households. Hair nicotine was better related to the questionnaire variables of smoking in a multivariate regression model (r2=0.55) than urine cotinine (r2=0.31). Conclusions: In this group of young children, hair nicotine was a more precise biomarker of exposure to ETS than urine cotinine levels, using questionnaire reports as the reference. Both biomarkers indicate that smoking outside the house limits ETS exposure of children but does not eliminate it. PMID:11801622

  18. Brassica vegetable consumption reduces urinary F2-isoprostane levels independent of micronutrient intake.

    PubMed

    Fowke, Jay H; Morrow, Jason D; Motley, Saundra; Bostick, Roberd M; Ness, Reid M

    2006-10-01

    Isothiocyanates and indoles (e.g. indole-3-carbinol) from Brassica vegetables (e.g. broccoli) induce Phase I and Phase II enzymes responsible for the oxidation, reduction and metabolism of endogenous and exogenous carcinogens. Brassica vegetables also contain micronutrients that may provide additional DNA protection from reactive oxygen species. This randomized crossover trial (n = 20) compares the effects of a Brassica Vegetable (BV) intervention against a Micronutrient and Fiber Supplementation (M+F) intervention on urinary F2-isoprostane levels (F2-iP), a stable biomarker of systemic oxidative stress. Brassica intake was monitored by repeated 24 h recalls, urinary ITC levels and questionnaire. Urinary F2-iP levels were measured by mass spectrometry from first-morning urine samples collected at Baseline and after each intervention, and change in natural log transformed urinary F2-iP levels were analyzed using repeated measures regression. Brassica consumption increased from 2 grams/day (g/d) during the Baseline or M+F intervention periods to 218 g/d during the BV intervention, whereas exposure to most antioxidant vitamins and minerals was greatest during the M+F intervention. F2-iP levels significantly decreased by 22.0 or 21.8% during the BV intervention compared with Baseline or the M+F intervention (P = 0.05, P = 0.05, respectively). Urinary F2-iP levels did not significantly differ between Baseline and the M+F intervention (difference = 0.2%; P = 0.98). Brassica intake has been associated with reduced risk of colon, lung, bladder, breast, prostate and other cancers. Our results suggest that Brassica consumption reduces systemic oxidative stress independent of the vitamin and mineral content of these vegetables.

  19. Correlation of serum levo-fucose levels as a biomarker with tumor node metastasis staging in oral cancer patients

    PubMed Central

    Manchil, P. Redwin Dhas; Joy, E. Tatu; Kiran, M. Shashi; Sherubin, J. Eugenia; Khan, M. Farakath; Aravind, B. S.

    2016-01-01

    Background: oral cancer is a result of disordered cellular behavior initiated by various stimuli which is characterized by the alteration of serum glycoproteins consisting of different monosaccharides. One of these is levo-fucose (L-fucose), a methyl pentose. Elevated levels of protein-bound fucose have been reported in various malignancies. Aim: The present study attempted to correlate levels of serum L-fucose as a biomarker with the various tumor node metastasis (TNM) stages of oral cancer. Methodology: The study was carried out on 90 subjects consisting of 30 healthy controls and 60 histopathologically proven oral squamous cell carcinoma (OSCC) cases. The serum fucose level estimation was done based on the method adopted by Winzler. Statistical analysis included independent sample's t-test, one-way ANOVA test, Karl–Pearson correlation test, and Tukey's HSD post hoc test to evaluate the significance and variability of values between groups. Results: Significant elevation in serum fucose levels was noticed among OSCC patients when compared with the controls and a progressive ascent of L-fucose levels were noted as the stage of severity increased. Serum fucose levels were independent of histopathological grading, age, and sex. Conclusion: Serum L-fucose levels were increased in OSCC patients, and a positive correlation was observed between serum L-fucose levels and TNM staging of OSCC. Thus, serum L-fucose can be used as an effective diagnostic and prognostic biomarker in OSCC patients. PMID:27829767

  20. Serum Levels of Toxic AGEs (TAGE) May Be a Promising Novel Biomarker for the Onset/Progression of Lifestyle-Related Diseases

    PubMed Central

    Takeuchi, Masayoshi

    2016-01-01

    Advanced glycation end-products (AGEs) generated with aging or in the presence of diabetes mellitus, particularly AGEs derived from the glucose/fructose metabolism intermediate glyceraldehyde (Glycer-AGEs; termed toxic AGEs (TAGE)), were recently shown to be closely involved in the onset/progression of diabetic vascular complications via the receptor for AGEs (RAGE). TAGE also contribute to various diseases, such as cardiovascular disease; nonalcoholic steatohepatitis; cancer; Alzheimer’s disease, and; infertility. This suggests the necessity of minimizing the influence of the TAGE-RAGE axis in order to prevent the onset/progression of lifestyle-related diseases (LSRD) and establish therapeutic strategies. Changes in serum TAGE levels are closely associated with LSRD related to overeating, a lack of exercise, or excessive ingestion of sugars/dietary AGEs. We also showed that serum TAGE levels, but not those of hemoglobin A1c, glucose-derived AGEs, or Nε-(carboxymethyl)lysine, have potential as a biomarker for predicting the progression of atherosclerosis and future cardiovascular events. We herein introduce the usefulness of serum TAGE levels as a biomarker for the prevention/early diagnosis of LSRD and the evaluation of the efficacy of treatments; we discuss whether dietary AGE/sugar intake restrictions reduce the generation/accumulation of TAGE, thereby preventing the onset/progression of LSRD. PMID:27338481

  1. Bisphenol A alters transcript levels of biomarker genes for Major Depressive Disorder in vascular endothelial cells and colon cancer cells.

    PubMed

    Ribeiro-Varandas, Edna; Pereira, H Sofia; Viegas, Wanda; Delgado, Margarida

    2016-06-01

    Bisphenol A (BPA) is capable of mimicking endogenous hormones with potential consequences for human health and BPA exposure has been associated with several human diseases including neuropsychiatric disorders. Here, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) results show that BPA at low concentrations (10 ng/mL and 1 μg/mL) induces differential transcript levels of four biomarker genes for Major Depressive Disorder (MDD) in HT29 human colon adenocarcinona cell line and Human Umbilical Vein Endothelial Cells (HUVEC). These results substantiate increasing concerns of BPA exposure in levels currently detected in humans.

  2. Reduced levels of vasopressin and reduced behavioral modulation of oxytocin in psychotic disorders.

    PubMed

    Rubin, Leah H; Carter, C Sue; Bishop, Jeffrey R; Pournajafi-Nazarloo, Hossein; Drogos, Lauren L; Hill, S Kristian; Ruocco, Anthony C; Keedy, Sarah K; Reilly, James L; Keshavan, Matcheri S; Pearlson, Godfrey D; Tamminga, Carol A; Gershon, Elliot S; Sweeney, John A

    2014-11-01

    Oxytocin (OT) and arginine vasopressin (AVP) exert robust influence on social affiliation and specific cognitive processes in healthy individuals. Abnormalities in these neuroendocrine systems have been observed in psychotic disorders, but their relation to impairments in behavioral domains that these endocrines modulate is not well understood. We compared abnormalities of OT and AVP serum concentrations in probands with schizophrenia (n = 57), schizoaffective disorder (n = 34), and psychotic bipolar disorder (n = 75); their first-degree relatives without a history of psychosis (n = 61, 43, 91, respectively); and healthy controls (n = 66) and examined their association with emotion processing and cognition. AVP levels were lower in schizophrenia (P = .002) and bipolar probands (P = .03) and in relatives of schizophrenia probands (P = .002) compared with controls. OT levels did not differ between groups. Familiality estimates were robust for OT (h(2) = 0.79, P = 3.97e-15) and AVP (h(2) = 0.78, P = 3.93e-11). Higher levels of OT were associated with better emotion recognition (β = 0.40, P < .001) and general neuropsychological function (β = 0.26, P = .04) in healthy controls as expected but not in any proband or relative group. In schizophrenia, higher OT levels were related to greater positive symptom severity. The dissociation of OT levels and behavioral function in all proband and relative groups suggests that risk and illness factors associated with psychotic disorders are not related to reduced OT levels but to a disruption in the ability of physiological levels of OT to modulate social cognition and neuropsychological function. Decreased AVP levels may be a marker of biological vulnerability in schizophrenia because alterations were seen in probands and relatives, and familiality was high.

  3. Biomarker Profile Does Not Predict Weight Loss Success in Successful and Unsuccessful Diet-Reduced Obese Individuals: A Prospective Study

    PubMed Central

    Ogden, Lorraine Garratt; MacLean, Paul Scown; Giles, Erin Danielle; Wyatt, Holly Roxanna

    2013-01-01

    Background. Individuals attempting weight reduction have varying success when participating in the same intervention. Identifying physiological factors associated with greater weight loss could improve outcomes. Methods. Sixty-one adults (BMI 27–30 kg/m2) participated in a 16-week group-based, cognitive-behavioral control weight loss program. Concentrations of 12 fasting hormones and cytokines related to adiposity, satiety/hunger, and inflammation were measured using the Milliplex human metabolic human panel before and after weight loss. Participants were grouped based on ≥8% (successful group, SG) or <8% weight loss (less successful group, LSG). Results. The SG had 46 subjects (75.4%), while the LSG had 15 (24.6%). There were no differences in baseline sex distribution, age, weight, BMI, and body composition between groups. In the SG, baseline to the 16-week levels decreased significantly for c-peptide (1,030 versus 891 pg/mL, P = 0.002), insulin (665 versus 541 pg/mL, P = 0.001), and leptin (0.83 versus 0.58 ng/mL/kg fat, P < 0.001). None of the baseline analytes predicted greater weight loss. Conclusions. Successful weight loss was associated with changes in adiposity (less fat mass) and unfavorable hunger signals. No baseline biomarker profile was associated with weight loss success. Behavioral factors may have outweighed physiological signals for determining successful weight loss. This trial is registered with Clinicaltrials.gov NCT00429650. PMID:24363955

  4. Levels of biomarkers correlate with magnetic resonance imaging progression of knee cartilage degeneration: a study on canine.

    PubMed

    Qi, Chang; Changlin, Huang

    2007-07-01

    To examine the association between levers of cartilage oligomeric matrix protein (COMP), matrix metalloproteinases-1 (MMP-1), matrix metalloproteinases-3 (MMP-3), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in serum and synovial fluid, and MR imaging of cartilage degeneration in knee joint, and to understand the effects of movement training with different intensity on cartilage of knee joint. 20 adult canines were randomly divided into three groups (8 in the light training group; 8 in the intensive training group; 4 in the control group), and canines of the two training groups were trained daily at different intensity. The training lasted for 10 weeks in all. Magnetic resonance imaging (MRI) examinations were performed regularly (2, 4, 6, 8, 10 week) to investigate the changes of articular cartilage in the canine knee, while concentrations of COMP, MMP-1, MMP-3, TIMP-1 in serum and synovial fluid were measured by ELISA assays. We could find imaging changes of cartilage degeneration in both the training groups by MRI examination during training period, compared with the control group. However, there was no significant difference between these two training groups. Elevations of levels of COMP, MMP-1, MMP-3, TIMP-1, MMP-3/TIMP-1 were seen in serum and synovial fluid after training, and their levels had obvious association with knee MRI grades of cartilage lesion. Furthermore, there were statistically significant associations between biomarkers levels in serum and in synovial fluid. Long-time and high-intensity movement training induces cartilage degeneration in knee joint. Within the intensity extent applied in this study, knee cartilage degeneration caused by light training or intensive training has no difference in MR imaging, but has a comparatively obvious difference in biomarkers level. To detect articular cartilage degeneration in early stage and monitor pathological process, the associated application of several biomarkers has a very good practical

  5. Serum miR-21 level: a potential diagnostic and prognostic biomarker for non-small cell lung cancer.

    PubMed

    Zhao, Wei; Zhao, Jun-Jie; Zhang, Long; Xu, Qin-Fu; Zhao, Yu-Miao; Shi, Xiao-Ya; Xu, Ai-Guo

    2015-01-01

    Because lung cancer is the most common cause of cancer death among both men and women, focused efforts are necessary to identify and develop biomarkers that aid in the detection and treatment of this serious disease. Recent research has been aimed at understanding the roles of microRNAs (miRNAs) in tumorigenesis and their utility as cancer biomarkers. Here, miR-21 was investigated as a potential serum biomarker for non-small cell lung cancer (NSCLC). The relative expression level of miR-21 was detected by real-time PCR in the sera of 80 NSCLC patients; sera were also collected from 60 healthy people as a control. The most suitable cut-off value and the prognostic value of serum miR-21 levels were analyzed using a receiver-operating curve. The relative serum miR-21 level in NSCLC patients was significantly higher than that in healthy people (P<0.05). For relative miR-21 expression, the area under the ROC curve was 0.812 (95% CI: 0.736-0.888) with a sensitivity of 73.8% and a specificity of 71.7%, based on a cut-off value of 1.22. NSCLC patients were divided into two groups based on miR-21 expression; those with higher relative expression (≥1.22) had significantly lower survival time than those in the lower expression group (P<0.05). Further, serum miR-21 level and survival time were negatively correlated in NSCLC patients (P<0.05). Thus, miR-21 may be useful as a diagnostic and prognostic indicator of NSCLC.

  6. Calcium Deficiency Reduces Circulating Levels of FGF23

    PubMed Central

    Rodriguez-Ortiz, María E.; Lopez, Ignacio; Muñoz-Castañeda, Juan R.; Martinez-Moreno, Julio M.; Ramírez, Alan Peralta; Pineda, Carmen; Canalejo, Antonio; Jaeger, Philippe; Aguilera-Tejero, Escolastico; Felsenfeld, Arnold; Almaden, Yolanda

    2012-01-01

    Fibroblast growth factor (FGF) 23 inhibits calcitriol production, which could exacerbate calcium deficiency or hypocalcemia unless calcium itself modulates FGF23 in this setting. In Wistar rats with normal renal function fed a diet low in both calcium and vitamin D, the resulting hypocalcemia was associated with low FGF23 despite high parathyroid hormone (PTH) and high calcitriol levels. FGF23 correlated positively with calcium and negatively with PTH. Addition of high dietary phosphorus to this diet increased FGF23 except in rats with hypocalcemia despite high PTH levels. In parathyroidectomized rats, an increase in dietary calcium for 10 days increased serum calcium, with an associated increase in FGF23, decrease in calcitriol, and no change in phosphorus. Also in parathyroidectomized rats, FGF23 increased significantly 6 hours after administration of calcium gluconate. Taken together, these results suggest that hypocalcemia reduces the circulating concentrations of FGF23. This decrease in FGF23 could be a response to avoid a subsequent reduction in calcitriol, which could exacerbate hypocalcemia. PMID:22581996

  7. Population Characteristics May Reduce the Levels of Individual Call Identity

    PubMed Central

    Delgado, María del Mar; Caferri, Eleonora; Méndez, Maria; Godoy, José A.; Campioni, Letizia; Penteriani, Vincenzo

    2013-01-01

    Individual variability influences the demographic and evolutionary dynamics of spatially structured populations, and conversely ecological and evolutionary dynamics provide the context under which variations at the individual level occur. Therefore, it is essential to identify and characterize the importance of the different factors that may promote or hinder individual variability. Animal signaling is a prime example of a type of behavior that is largely dependent on both the features of individuals and the characteristics of the population to which they belong. After 10 years studying the dynamics of a population of a long-lived species, the eagle owl (Bubo bubo), we investigated the emergence and maintenance of traits that reveal individual identity by focusing on vocal features. We found that individuals inhabiting a high density population characterized by a relative lack of heterogeneity (in terms of prey availability and breeding success) among breeding sites might be selected for reducing the levels of identity. Two non-mutually exclusive hypotheses may explain the structural call patterns we detected: (1) similarity in calls may be principally a consequence of the particular characteristics of the population; and (2) high density may encourage individuals to mimic each other’s vocalizations in a cascade effect, leading to a widespread and unique communication network. PMID:24204869

  8. Reducing ethylene levels along the food supply chain: a key to reducing food waste?

    PubMed

    Blanke, Michael M

    2014-09-01

    Excessive waste along the food supply chain of 71 (UK, Netherlands) to 82 (Germany) kg per head per year sparked widespread criticism of the agricultural food business and provides a great challenge and task for all its players and stakeholders. Origins of this food waste include private households, restaurants and canteens, as well as supermarkets, and indicate that 59-65% of this food waste can be avoided. Since ∼50% of the food waste is fruit and vegetables, monitoring and control of their natural ripening gas - ethylene - is suggested here as one possible key to reducing food waste. Ethylene accelerates ripening of climacteric fruits, and accumulation of ethylene in the supply chain can lead to fruit decay and waste. While ethylene was determined using a stationary gas chromatograph with gas cylinders, the new generation of portable sensor-based instruments now enables continuous in situ determination of ethylene along the food chain, a prerequisite to managing and maintaining the quality and ripeness of fruits and identifying hot spots of ethylene accumulation along the supply chain. Ethylene levels were measured in a first trial, along the supply chain of apple fruit from harvest to the consumer, and ranged from 10 ppb in the CA fruit store with an ethylene scrubber, 70 ppb in the fruit bin, to 500 ppb on the sorting belt in the grading facility, to ppm levels in perforated plastic bags of apples. This paper also takes into account exogenous ethylene originating from sources other than the fruit itself. Countermeasures are discussed, such as the potential of breeding for low-ethylene fruit, applications of ethylene inhibitors (e.g. 1-MCP) and absorber strips (e.g. 'It's Fresh', Ryan'), packages (e.g. 'Peakfresh'), both at the wholesale and retail level, vents and cooling for the supply chain, sale of class II produce ('Wunderlinge'), collection (rather than waste) of produce on the 'sell by' date ('Die Tafel') and whole crop purchase (WCP) to aid reducing

  9. Increased levels of the oxidative stress biomarker 8-iso-prostaglandin F2α in wastewater associated with tobacco use

    NASA Astrophysics Data System (ADS)

    Ryu, Yeonsuk; Gracia-Lor, Emma; Bade, Richard; Baz-Lomba, J. A.; Bramness, Jørgen G.; Castiglioni, Sara; Castrignanò, Erika; Causanilles, Ana; Covaci, Adrian; de Voogt, Pim; Hernandez, Felix; Kasprzyk-Hordern, Barbara; Kinyua, Juliet; McCall, Ann-Kathrin; Ort, Christoph; Plósz, Benedek G.; Ramin, Pedram; Rousis, Nikolaos I.; Reid, Malcolm J.; Thomas, Kevin V.

    2016-12-01

    Wastewater analysis has been demonstrated to be a complementary approach for assessing the overall patterns of drug use by a population while the full potential of wastewater-based epidemiology has yet to be explored. F2-isoprostanes are a prototype wastewater biomarker to study the cumulative oxidative stress at a community level. In this work, 8-iso-prostaglandin F2α (8-iso-PGF2α) was analysed in raw 24 h-composite wastewater samples collected from 4 Norwegian and 7 other European cities in 2014 and 2015. Using the same samples, biomarkers of alcohol (ethyl sulfate) and tobacco (trans-3‧-hydroxycotinine) use were also analysed to investigate any possible correlation between 8-iso-PGF2α and the consumption of the two drugs. The estimated per capita daily loads of 8-iso-PGF2α in the 11 cities ranged between 2.5 and 9.9 mg/day/1000 inhabitants with a population-weighted mean of 4.8 mg/day/1000 inhabitants. There were no temporal trends observed in the levels of 8-iso-PGF2α, however, spatial differences were found at the inter-city level correlating to the degree of urbanisation. The 8-iso-PGF2α mass load was found to be strongly associated with that of trans-3‧-hydroxycotinine while it showed no correlation with ethyl sulfate. The present study shows the potential for 8-iso-PGF2α as a wastewater biomarker for the assessment of community public health.

  10. Polycyclic aromatic hydrocarbon sources related to biomarker levels in fish from Prince William Sound and the Gulf of Alaska.

    PubMed

    Page, David S; Huggett, Robert J; Stegeman, John J; Parker, Keith R; Woodin, Bruce; Brown, John S; Bence, A Edward

    2004-10-01

    Seafloor sediments in Prince William Sound (PWS) and the eastern Gulf of Alaska (GOA) have a substantial regional hydrocarbon background from natural sources including oil seeps and eroding sedimentary rocks along the eastern GOA coast. Polycyclic aromatic hydrocarbons (PAH) from that background appear to be bioavailable to fish. Fish collected from PWS and the GOA in a 1999--2000 biomarker study (bile fluorescent aromatic contaminants and liver ethoxyresorufin O-deethylase) show evidence of exposure to low levels of PAH at all categories of sites sampled. Seafloor sediments at fish sampling sites in the GOA east of PWS and at three PWS site categories (nonspill path, spill path oiled, and spill path not oiled) contain hydrocarbons from four principal sources: regional background, combustion products, residues from the 1989 Exxon Valdez oil spill (EVOS), and Monterey (CA) petroleum residues. GOA sediments between PWS and Yakutat Bay, approximately 350 km to the east, are dominated by regional petrogenic background hydrocarbons (total PAH (TPAH) range approximately 60-3400 ng/g) that are the probable cause of low biomarker levels measured in halibut from this area. PWS sediments contain varying proportions of regional background, combustion products, Monterey residues, and EVOS residues at some spill path sites. Rockfish caught in PWS embayments in 1999 have liver EROD activities that correlate positively with the pyrogenic PAH indicator ratio (FI+Py)/C24Ph. Although traces (<5-100 ng/g TPAH) of EVOS residues were detected in seafloor sediments at some nearshore spill path sites, biomarker levels in fish from those sites are not elevated relative to other sites in PWS.

  11. Increased levels of the oxidative stress biomarker 8-iso-prostaglandin F2α in wastewater associated with tobacco use.

    PubMed

    Ryu, Yeonsuk; Gracia-Lor, Emma; Bade, Richard; Baz-Lomba, J A; Bramness, Jørgen G; Castiglioni, Sara; Castrignanò, Erika; Causanilles, Ana; Covaci, Adrian; de Voogt, Pim; Hernandez, Felix; Kasprzyk-Hordern, Barbara; Kinyua, Juliet; McCall, Ann-Kathrin; Ort, Christoph; Plósz, Benedek G; Ramin, Pedram; Rousis, Nikolaos I; Reid, Malcolm J; Thomas, Kevin V

    2016-12-15

    Wastewater analysis has been demonstrated to be a complementary approach for assessing the overall patterns of drug use by a population while the full potential of wastewater-based epidemiology has yet to be explored. F2-isoprostanes are a prototype wastewater biomarker to study the cumulative oxidative stress at a community level. In this work, 8-iso-prostaglandin F2α (8-iso-PGF2α) was analysed in raw 24 h-composite wastewater samples collected from 4 Norwegian and 7 other European cities in 2014 and 2015. Using the same samples, biomarkers of alcohol (ethyl sulfate) and tobacco (trans-3'-hydroxycotinine) use were also analysed to investigate any possible correlation between 8-iso-PGF2α and the consumption of the two drugs. The estimated per capita daily loads of 8-iso-PGF2α in the 11 cities ranged between 2.5 and 9.9 mg/day/1000 inhabitants with a population-weighted mean of 4.8 mg/day/1000 inhabitants. There were no temporal trends observed in the levels of 8-iso-PGF2α, however, spatial differences were found at the inter-city level correlating to the degree of urbanisation. The 8-iso-PGF2α mass load was found to be strongly associated with that of trans-3'-hydroxycotinine while it showed no correlation with ethyl sulfate. The present study shows the potential for 8-iso-PGF2α as a wastewater biomarker for the assessment of community public health.

  12. Increased levels of the oxidative stress biomarker 8-iso-prostaglandin F2α in wastewater associated with tobacco use

    PubMed Central

    Ryu, Yeonsuk; Gracia-Lor, Emma; Bade, Richard; Baz-Lomba, J. A.; Bramness, Jørgen G.; Castiglioni, Sara; Castrignanò, Erika; Causanilles, Ana; Covaci, Adrian; de Voogt, Pim; Hernandez, Felix; Kasprzyk-Hordern, Barbara; Kinyua, Juliet; McCall, Ann-Kathrin; Ort, Christoph; Plósz, Benedek G.; Ramin, Pedram; Rousis, Nikolaos I.; Reid, Malcolm J.; Thomas, Kevin V.

    2016-01-01

    Wastewater analysis has been demonstrated to be a complementary approach for assessing the overall patterns of drug use by a population while the full potential of wastewater-based epidemiology has yet to be explored. F2-isoprostanes are a prototype wastewater biomarker to study the cumulative oxidative stress at a community level. In this work, 8-iso-prostaglandin F2α (8-iso-PGF2α) was analysed in raw 24 h-composite wastewater samples collected from 4 Norwegian and 7 other European cities in 2014 and 2015. Using the same samples, biomarkers of alcohol (ethyl sulfate) and tobacco (trans-3′-hydroxycotinine) use were also analysed to investigate any possible correlation between 8-iso-PGF2α and the consumption of the two drugs. The estimated per capita daily loads of 8-iso-PGF2α in the 11 cities ranged between 2.5 and 9.9 mg/day/1000 inhabitants with a population-weighted mean of 4.8 mg/day/1000 inhabitants. There were no temporal trends observed in the levels of 8-iso-PGF2α, however, spatial differences were found at the inter-city level correlating to the degree of urbanisation. The 8-iso-PGF2α mass load was found to be strongly associated with that of trans-3′-hydroxycotinine while it showed no correlation with ethyl sulfate. The present study shows the potential for 8-iso-PGF2α as a wastewater biomarker for the assessment of community public health. PMID:27976726

  13. Cocoa, Hazelnuts, Sterols and Soluble Fiber Cream Reduces Lipids and Inflammation Biomarkers in Hypertensive Patients: A Randomized Controlled Trial

    PubMed Central

    Solà, Rosa; Valls, Rosa M.; Godàs, Gemma; Perez-Busquets, Gloria; Ribalta, Josep; Girona, Josefa; Heras, Mercedes; Cabré, Anna; Castro, Antoni; Domenech, Gema; Torres, Ferran; Masana, Lluís; Anglés, Neus; Reguant, Jordi; Ramírez, Bartolomé; Barriach, Joaquim M.

    2012-01-01

    Background Cocoa, mixed with other food ingredients, intake can have beneficial effects on cardiovascular disease (CVD) biomarkers. We compared the effects of 4 cocoa cream products on some of these biomarkers. Methods and Findings In this multi-centered, randomized, controlled, double-blind, parallel trial, volunteers (n = 113; age range: 43–65 years) who were pre-hypertensive, stage-1 hypertensive and hypercholesterolemic received one of 4 cocoa cream products (13 g/unit; 1 g cocoa/unit, 6 units/d; 465 Kcal/d) added to a low saturated fat diet for 4 weeks. The groups were: A) (n = 28), cocoa cream considered as control; B) (n = 28), cocoa+hazelnut cream (30 g/d hazelnuts); C) (n = 30), cocoa+hazelnuts+phytosterols (2 g/d); and D) (n = 27), cocoa+hazelnuts+phytosterols+soluble fiber (20 g/d) the patented “LMN product”. Primary outcome measures were BP, LDL-c, apolipoprotein B-100 (Apo B), ApoB/ApoA ratio, oxidized LDL (oxLDL) and high-sensitive C-reactive protein (hsCRP) determined at baseline and post-cocoa cream product intake. Statistical analysis used was ANCOVA or mixed models (in case of repeated measurements), with baseline observation included as a covariate. After 4 weeks, compared to product A, product C reduced LDL-c by 11.2%, Apo B by 8.1% and ApoB/ApoA ratio by 7.8% (P = 0.01). LMN decreased LDL-c by 9.2%, Apo B-100 by 8.5%, ApoB/ApoA ratio by 10.5%, hsCRP by 33.4% and oxLDL by 5.9% (P = 0.01). Surprisingly, even “control” product A reduced systolic BP (−7.89 mmHg; 95%CI: −11.45 to −4.3) and diastolic BP (−5.54 mmHg; 95%CI: −7.79 to −3.29). The BP reductions were similar with the other 3 products. Limitations of the study are that the trial period was relatively short and that a better “BP control” product would have been preferable. Conclusion The creams (particularly the LMN) have anti-inflammatory and antioxidant effects in addition to lowering LDL-c, Apo B and ApoB/ApoA ratio. Thus, the soluble

  14. LINE-1 and inflammatory gene methylation levels are early biomarkers of metabolic changes: association with adiposity.

    PubMed

    Carraro, Júlia Cristina Cardoso; Mansego, Maria Luisa; Milagro, Fermin Ignacio; Chaves, Larissa Oliveira; Vidigal, Fernanda Carvalho; Bressan, Josefina; Martínez, J Alfredo

    2016-11-01

    We analyzed whether global and inflammatory genes methylation can be early predictors of metabolic changes and their associations with the diet, in a cross-sectional study (n = 40). Higher global methylation was associated to adiposity, insulin resistance, and lower quality of the diet. Methylation of IL-6, SERPINE1 and CRP genes was related to adiposity traits and macronutrients intake. SERPINE1 hypermethylation was also related to some metabolic alterations. CRP methylation was a better predictor of insulin resistance than CRP plasma concentrations. Global and inflammatory gene promoter hypermethylation can be good early biomarkers of adiposity and metabolic changes and are associated to the quality of the diet.

  15. Acid retention with reduced glomerular filtration rate increases urine biomarkers of kidney and bone injury.

    PubMed

    Wesson, Donald E; Pruszynski, Jessica; Cai, Wendy; Simoni, Jan

    2017-04-01

    Diets high in acid of developed societies that do not cause metabolic acidosis in patients with chronic kidney disease nevertheless appear to cause acid retention with associated morbidity, particularly in those with reduced glomerular filtration rate. Here we used a rat 2/3 nephrectomy model of chronic kidney disease to study induction and maintenance of acid retention and its consequences on indicators of kidney and bone injury. Dietary acid was increased in animals eating base-producing soy protein with acid-producing casein and in casein-eating animals with added ammonium chloride. Using microdialysis to measure the kidney cortical acid content, we found that nephrectomized animals had greater acid retention than sham-operated animals when both ate the soy diet. Each increment in dietary acid further increased acid retention more in nephrectomized than in sham rats. Nephrectomized and sham animals achieved similar steady-state daily urine net acid excretion in response to increments in dietary acid but nephrectomized animals took longer to do so, contributing to greater acid retention that was maintained until the increased dietary acid was stopped. Acid retention was associated with increased urine excretion of both N-acetyl-β-D-glucosaminidase and deoxypyridinoline, greater in nephrectomized than control rats, consistent with kidney tubulointerstitial and bone matrix injury, respectively. Greater acid retention in nephrectomized than control animals was induced by a slower increase in urinary net acid excretion rate in response to the increment in dietary acid and also maintained until the dietary acid increment was stopped. Thus, acid retention increased biomarkers of kidney and bone injury in the urine, supporting untoward consequences to these two tissues.

  16. Ultratrace level determination and quantitative analysis of kidney injury biomarkers in patient samples attained by zinc oxide nanorods

    NASA Astrophysics Data System (ADS)

    Singh, Manpreet; Alabanza, Anginelle; Gonzalez, Lorelis E.; Wang, Weiwei; Reeves, W. Brian; Hahm, Jong-In

    2016-02-01

    Determining ultratrace amounts of protein biomarkers in patient samples in a straightforward and quantitative manner is extremely important for early disease diagnosis and treatment. Here, we successfully demonstrate the novel use of zinc oxide nanorods (ZnO NRs) in the ultrasensitive and quantitative detection of two acute kidney injury (AKI)-related protein biomarkers, tumor necrosis factor (TNF)-α and interleukin (IL)-8, directly from patient samples. We first validate the ZnO NRs-based IL-8 results via comparison with those obtained from using a conventional enzyme-linked immunosorbent method in samples from 38 individuals. We further assess the full detection capability of the ZnO NRs-based technique by quantifying TNF-α, whose levels in human urine are often below the detection limits of conventional methods. Using the ZnO NR platforms, we determine the TNF-α concentrations of all 46 patient samples tested, down to the fg per mL level. Subsequently, we screen for TNF-α levels in approximately 50 additional samples collected from different patient groups in order to demonstrate a potential use of the ZnO NRs-based assay in assessing cytokine levels useful for further clinical monitoring. Our research efforts demonstrate that ZnO NRs can be straightforwardly employed in the rapid, ultrasensitive, quantitative, and simultaneous detection of multiple AKI-related biomarkers directly in patient urine samples, providing an unparalleled detection capability beyond those of conventional analysis methods. Additional key advantages of the ZnO NRs-based approach include a fast detection speed, low-volume assay condition, multiplexing ability, and easy automation/integration capability to existing fluorescence instrumentation. Therefore, we anticipate that our ZnO NRs-based detection method will be highly beneficial for overcoming the frequent challenges in early biomarker development and treatment assessment, pertaining to the facile and ultrasensitive quantification

  17. Dynamic changes in lymphocyte GRK2 levels in cardiac transplant patients: a biomarker for left ventricular function.

    PubMed

    Bonita, Raphael E; Raake, Philip W; Otis, Nicholas J; Chuprun, J Kurt; Spivack, Talya; Dasgupta, Abhijit; Whellan, David J; Mather, Paul J; Koch, Walter J

    2010-02-01

    G protein-coupled receptor kinase 2 (GRK2), which is upregulated in the failing human myocardium, appears to have a role in heart failure (HF) pathogenesis. In peripheral lymphocytes, GRK2 expression has been shown to reflect myocardial levels. This study represents an attempt to define the role for GRK2 as a potential biomarker of left ventricular function in HF patients. We obtained blood from 24 HF patients before and after heart transplantation and followed them for up to 1 year, also recording hemodynamic data and histological results from endomyocardial biopsies. We determined blood GRK2 protein by Western blotting and enzyme-linked immunosorbent assay. GRK2 levels were obtained before transplant and at first posttransplant biopsy. GRK2 levels significantly declined after transplant and remained low over the course of the study period. After transplantation, we found that blood GRK2 significantly dropped and remained low consistent with improved cardiac function in the transplanted heart. Blood GRK2 has potential as a biomarker for myocardial function in end-stage HF.

  18. Dynamic Changes in Lymphocyte GRK2 Levels in Cardiac Transplant Patients: A Biomarker for Left Ventricular Function

    PubMed Central

    Bonita, Raphael E.; Raake, Philip W.; Otis, Nicholas J.; Chuprun, J. Kurt; Spivack, Talya; Dasgupta, Abhijit; Whellan, David J.; Mather, Paul J.; Koch, Walter J.

    2010-01-01

    G protein-coupled receptor kinase 2 (GRK2), which is upregulated in the failing human myocardium, appears to have a role in heart failure (HF) pathogenesis. In peripheral lymphocytes, GRK2 expression has been shown to reflect myocardial levels. This study represents an attempt to define the role for GRK2 as a potential biomarker of left ventricular function in HF patients. We obtained blood from 24 HF patients before and after heart transplantation and followed them for up to 1 year, also recording hemodynamic data and histological results from endomyocardial biopsies. We determined blood GRK2 protein by Western blotting and enzyme-linked immunosorbent assay. GRK2 levels were obtained before transplant and at first posttransplant biopsy. GRK2 levels significantly declined after transplant and remained low over the course of the study period. After transplantation, we found that blood GRK2 significantly dropped and remained low consistent with improved cardiac function in the transplanted heart. Blood GRK2 has potential as a biomarker for myocardial function in end-stage HF. PMID:20443948

  19. Estimation and inference on correlations between biomarkers with repeated measures and left-censoring due to minimum detection levels

    PubMed Central

    Xie, Xianhong; Xue, Xiaonan; Gange, Stephen J.; Strickler, Howard D.; Kim, Mimi Y.

    2013-01-01

    Statistical approaches for estimating and drawing inference on the correlation between two biomarkers which are repeatedly assessed over time and subject to left-censoring due to minimum detection levels are lacking. We propose a linear mixed-effects model and estimate the parameters with the Monte Carlo Expectation Maximization (MCEM) method. Inferences regarding the model parameters and the correlation between the biomarkers are performed by applying Louis’s method and the delta method. Simulation studies were conducted to compare the proposed MCEM method with existing methods including the MLE method, the multiple imputation (MI) method, and two widely used ad hoc approaches: replacing the censored values with the detection limit (DL) or with half of the detection limit (HDL). The results show that the performance of the MCEM with respect to relative bias and coverage probability for the 95% confidence interval is superior to the DL and HDL approaches and exceeds that of the MI method at medium to high levels of censoring, and the standard error estimates from the MCEM method are close to ideal. The MLE method can estimate the parameters accurately; however, a non-positive definite information matrix can occur so that the variances are not estimable. These five methods are illustrated with data from a longitudinal HIV study to estimate and draw inference on the correlation between HIV RNA levels measured in plasma and in cervical secretions at multiple time points. PMID:22714546

  20. Elevated morning cortisol is a stratified population-level biomarker for major depression in boys only with high depressive symptoms.

    PubMed

    Owens, Matthew; Herbert, Joe; Jones, Peter B; Sahakian, Barbara J; Wilkinson, Paul O; Dunn, Valerie J; Croudace, Timothy J; Goodyer, Ian M

    2014-03-04

    Major depressive disorder (MD) is a debilitating public mental health problem with severe societal and personal costs attached. Around one in six people will suffer from this complex disorder at some point in their lives, which has shown considerable etiological and clinical heterogeneity. Overall there remain no validated biomarkers in the youth population at large that can aid the detection of at-risk groups for depression in general and for boys and young men in particular. Using repeated measurements of two well-known correlates of MD (self-reported current depressive symptoms and early-morning cortisol), we undertook a population-based investigation to ascertain subtypes of adolescents that represent separate longitudinal phenotypes. Subsequently, we tested for differential risks for MD and other mental illnesses and cognitive differences between subtypes. Through the use of latent class analysis, we revealed a high-risk subtype (17% of the sample) demarcated by both high depressive symptoms and elevated cortisol levels. Membership of this class of individuals was associated with increased levels of impaired autobiographical memory recall in both sexes and the greatest likelihood of experiencing MD in boys only. These previously unidentified findings demonstrate at the population level a class of adolescents with a common physiological biomarker specifically for MD in boys and for a mnemonic vulnerability in both sexes. We suggest that the biobehavioral combination of high depressive symptoms and elevated morning cortisol is particularly hazardous for adolescent boys.

  1. Earth Mover’s Distance (EMD): A True Metric for Comparing Biomarker Expression Levels in Cell Populations

    PubMed Central

    Orlova, Darya Y.; Zimmerman, Noah; Meehan, Stephen; Meehan, Connor; Waters, Jeffrey; Ghosn, Eliver E. B.; Filatenkov, Alexander; Kolyagin, Gleb A.; Gernez, Yael; Tsuda, Shanel; Moore, Wayne; Moss, Richard B.; Herzenberg, Leonore A.; Walther, Guenther

    2016-01-01

    Changes in the frequencies of cell subsets that (co)express characteristic biomarkers, or levels of the biomarkers on the subsets, are widely used as indices of drug response, disease prognosis, stem cell reconstitution, etc. However, although the currently available computational “gating” tools accurately reveal subset frequencies and marker expression levels, they fail to enable statistically reliable judgements as to whether these frequencies and expression levels differ significantly between/among subject groups. Here we introduce flow cytometry data analysis pipeline which includes the Earth Mover’s Distance (EMD) metric as solution to this problem. Well known as an informative quantitative measure of differences between distributions, we present three exemplary studies showing that EMD 1) reveals clinically-relevant shifts in two markers on blood basophils responding to an offending allergen; 2) shows that ablative tumor radiation induces significant changes in the murine colon cancer tumor microenvironment; and, 3) ranks immunological differences in mouse peritoneal cavity cells harvested from three genetically distinct mouse strains. PMID:27008164

  2. Elevated morning cortisol is a stratified population-level biomarker for major depression in boys only with high depressive symptoms

    PubMed Central

    Owens, Matthew; Herbert, Joe; Jones, Peter B.; Sahakian, Barbara J.; Wilkinson, Paul O.; Dunn, Valerie J.; Croudace, Timothy J.; Goodyer, Ian M.

    2014-01-01

    Major depressive disorder (MD) is a debilitating public mental health problem with severe societal and personal costs attached. Around one in six people will suffer from this complex disorder at some point in their lives, which has shown considerable etiological and clinical heterogeneity. Overall there remain no validated biomarkers in the youth population at large that can aid the detection of at-risk groups for depression in general and for boys and young men in particular. Using repeated measurements of two well-known correlates of MD (self-reported current depressive symptoms and early-morning cortisol), we undertook a population-based investigation to ascertain subtypes of adolescents that represent separate longitudinal phenotypes. Subsequently, we tested for differential risks for MD and other mental illnesses and cognitive differences between subtypes. Through the use of latent class analysis, we revealed a high-risk subtype (17% of the sample) demarcated by both high depressive symptoms and elevated cortisol levels. Membership of this class of individuals was associated with increased levels of impaired autobiographical memory recall in both sexes and the greatest likelihood of experiencing MD in boys only. These previously unidentified findings demonstrate at the population level a class of adolescents with a common physiological biomarker specifically for MD in boys and for a mnemonic vulnerability in both sexes. We suggest that the biobehavioral combination of high depressive symptoms and elevated morning cortisol is particularly hazardous for adolescent boys. PMID:24550453

  3. Measurements of biomarker levels in flounder (Platichthys flesus) and blue mussel (Mytilus trossulus) from the Gulf of Gdańsk (southern Baltic).

    PubMed

    Kopecka, Justyna; Lehtonen, Kari K; Barsiene, Janina; Broeg, Katja; Vuorinen, Pekka J; Gercken, Jens; Pempkowiak, Janusz

    2006-01-01

    In the framework of the EU funded BEEP project a set of biomarkers, gross morphometric indices and tissue concentrations of selected organic pollutants were measured in flounder (Platichthys flesus) and mussels (Mytilus trossulus) collected twice a year (April and October) from three sites in the inner Gulf of Gdańsk between autumn 2001 and spring 2003. In flounder, seasonal differences in most biomarkers were observed, but no correlations with tissue pollutant levels could be found. In mussels, highly variable levels in biomarker responses were seen, but no clear seasonal or spatial trends, directly related to tissue concentrations, could be established. The observed biomarkers distribution the study sites are probably mostly caused by interannual, seasonal and individual variability and, in case of flounder, possibly by exchange of stocks between the sampling sites.

  4. Serum levels of toxic AGEs (TAGE) may be a promising novel biomarker in development and progression of NASH.

    PubMed

    Takeuchi, M; Sakasai-Sakai, A; Takata, T; Ueda, T; Takino, J; Tsutsumi, M; Hyogo, H; Yamagishi, S

    2015-05-01

    Nonalcoholic fatty liver disease (NAFLD) ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), leads to fibrosis and potentially cirrhosis, liver failure, and hepatocellular carcinoma, and is one of the most common causes of liver disease worldwide. NAFLD has also been implicated in other medical conditions such as insulin resistance, obesity, metabolic syndrome, hyperlipemia, hypertension, cardiovascular disease, and diabetes. Continuous hyperglycemia has been implicated in the pathogenesis of diabetic micro- and macro-vascular complications via various metabolic pathways, and numerous hyperglycemia-induced metabolic and hemodynamic conditions exist, including the increased generation of various types of advanced glycation end-products (AGEs). We recently demonstrated that glyceraldehyde-derived AGEs (Glycer-AGEs), the predominant components of toxic AGEs (TAGE), played an important role in the pathogenesis of angiopathy in diabetic patients. Moreover, a growing body of evidence suggests that the interaction between TAGE and the receptor for AGEs may alter intracellular signaling, gene expression, and the release of pro-inflammatory molecules and also elicits the generation of oxidative stress in numerous types of cells including hepatocytes and hepatic stellate cells. Serum levels of TAGE were significantly higher in NASH patients than in those with simple steatosis and healthy controls. Moreover, serum levels of TAGE inversely correlated with adiponectin (adiponectin is produced by adipose tissue and is an anti-inflammatory adipokine that can increase insulin sensitivity). Furthermore, immunohistochemical staining of TAGE showed intense staining in the livers of patients with NASH. Serum levels of TAGE may be a useful biomarker for discriminating NASH from simple steatosis. The administration of atorvastatin (10 mg daily) for 12 months significantly improved NASH-related metabolic parameters and significantly decreased serum levels of TAGE. The

  5. Reduced serum hepcidin levels in patients with chronic hepatitis C

    PubMed Central

    Girelli, Domenico; Pasino, Michela; Goodnough, Julia B.; Nemeth, Elizabeta; Guido, Maria; Castagna, Annalisa; Busti, Fabiana; Campostrini, Natascia; Martinelli, Nicola; Vantini, Italo; Corrocher, Roberto; Ganz, Tomas; Fattovich, Giovanna

    2009-01-01

    Background/Aims Patients with chronic hepatitis C (CHC) often have increased liver iron, a condition associated with reduced sustained response to antiviral therapy, more rapid progression to cirrhosis, and development of hepatocellular carcinoma. The hepatic hormone hepcidin is the major regulator of iron metabolism and inhibits iron absorption and recycling from erythrophagocytosis. Hepcidin decrease is a possible pathophysiological mechanism of iron overload in CHC, but studies in humans have been hampered so far by the lack of reliable quantitative assays for the 25-amino acid bioactive peptide in serum (s-hepcidin). Methods Using a recently validated immunoassay, we measured s-hepcidin levels in 81 untreated CHC patients and 57 controls with rigorous definition of normal iron status. All CHC patients underwent liver biopsy with histological iron score. Results S-hepcidin was significantly lower in CHC patients than in controls (geometric means with 95% confidence intervals: 33.7, 21.5–52.9 vs. 90.9, 76.1–108.4 ng/mL, respectively; p < 0.001). In CHC patients, s-hepcidin significantly correlated with serum ferritin and histological total iron score, but not with s-interleukin-6. After stratification for ferritin quartiles, s-hepcidin increased significantly across quartiles in both controls and CHC patients (chi for trend, p < 0.001). However, in CHC patients, s-hepcidin was significantly lower than in controls for each corresponding quartile (analysis of variance, p < 0.001). Conclusions These results, together with very recent studies in animal and cellular models, indicate that although hepcidin regulation by iron stores is maintained in CHC, the suppression of this hormone by hepatitis C virus is likely an important factor in liver iron accumulation in this condition. PMID:19729219

  6. The use of biomarkers in biomonitoring: a 2-tier approach assessing the level of pollutant-induced stress syndrome in sentinel organisms.

    PubMed

    Viarengo, A; Lowe, D; Bolognesi, C; Fabbri, E; Koehler, A

    2007-09-01

    The paper outlines a 2-tier approach for wide-scale biomonitoring programmes. To obtain a high level of standardization, we suggest the use of caged organisms (mussels or fish). An "early warning", highly sensitive, low-cost biomarker is employed in tier 1 (i.e. lysosomal membrane stability (LMS) and survival rate, a marker for highly polluted sites). Tier 2 is used only for animals sampled at sites in which LMS changes are evident and there is no mortality, with a complete battery of biomarkers assessing the levels of pollutant-induced stress syndrome. Possible approaches for integrating biomarker data in a synthetic index are discussed, along with our proposal to use a recently developed Expert System. The latter system allows a correct selection of biomarkers at different levels of biological organisation (molecular/cellular/tissue/organism) taking into account trends in pollutant-induced biomarker changes (increasing, decreasing, bell-shape). A selection of biomarkers of stress, genotoxicity and exposure usually employed in biomonitoring programmes is presented, together with a brief overview of new biomolecular approaches.

  7. Gene expression levels in normal human lymphoblasts with variable sensitivities to arsenite: Identification of GGT1 and NFKBIE expression levels as possible biomarkers of susceptibility

    SciTech Connect

    Komissarova, Elena V.; Li Ping; Uddin, Ahmed N.; Chen, Xuyan; Nadas, Arthur; Rossman, Toby G.

    2008-01-15

    Drinking arsenic-contaminated water is associated with increased risk of neoplasias of the skin, lung, bladder and possibly other sites, as well as other diseases. Earlier, we showed that human lymphoblast lines from different normal unexposed donors showed variable sensitivities to the toxic effects of arsenite. In the present study, we used microarray analysis to compare the basal gene expression profiles between two arsenite-resistant (GM02707, GM00893) and two arsenite-sensitive lymphoblast lines (GM00546, GM00607). A number of genes were differentially expressed in arsenite-sensitive and arsenite-resistant cells. Among these, {gamma}-glutamyltranspeptidase 1 (GGT1) and NF{kappa}B inhibitor-epsilon (NFKBIE) showed higher expression levels in arsenite-resistant cells. RT-PCR analysis with gene-specific primers confirmed these results. Reduction of GGT1 expression level in arsenite-resistant lymphoblasts with GGT1-specific siRNA resulted in increased cell sensitivity to arsenite. In conclusion, we have demonstrated for the first time that expression levels of GGT1 and possibly NFKBIE might be useful as biomarkers of genetic susceptibility to arsenite. Expression microarrays can thus be exploited for identifying additional biomarkers of susceptibility to arsenite and to other toxicants.

  8. A Potential VEP Biomarker for Mild Cognitive Impairment: Evidence from Selective Visual Deficit of Higher-Level Dorsal Pathway.

    PubMed

    Yamasaki, Takao; Horie, Shizuka; Ohyagi, Yasumasa; Tanaka, Eri; Nakamura, Norimichi; Goto, Yoshinobu; Kanba, Shigenobu; Kira, Jun-Ichi; Tobimatsu, Shozo

    2016-05-23

    Visual dysfunctions are common in Alzheimer's disease (AD). Our aim was to establish a neurophysiological biomarker for amnestic mild cognitive impairment (aMCI). Visual evoked potentials (VEPs) were recorded in aMCI patients who later developed AD (n = 15) and in healthy older (n = 15) and younger controls (n = 15). Visual stimuli were optimized to separately activate lower and higher levels of the ventral and dorsal streams. We compared VEP parameters across the three groups of participants and conducted a linear correlation analysis between VEPs and data from neuropsychological tests. We then used a receiver operating characteristic (ROC) analysis to discriminate those with aMCI from those who were healthy older adults. The latency and phase of VEPs to lower-level stimuli (chromatic and achromatic gratings) were significantly affected by age but not by cognitive decline. Conversely, VEP latencies for higher-ventral (faces and kanji-words) and dorsal (kana-words and optic flow motion) stimuli were not affected by age, but they were significantly prolonged in aMCI patients. Interestingly, VEPs for higher-dorsal stimuli were related to outcomes of neuropsychological tests. Furthermore, the ROC analysis showed that the highest areas under the curve were obtained for VEP latencies in response to higher-dorsal stimuli. These results suggest aMCI-related functional impairment specific to higher-level visual processing. Further, dysfunction in the higher-level of the dorsal stream could be an early indicator of cognitive decline. Therefore, we conclude that VEPs associated with higher-level dorsal stream activity can be a sensitive biomarker for early detection of aMCI.

  9. Elevated Levels of Volatile Organic Carcinogen and Toxicant Biomarkers in Chinese Women Who Regularly Cook at Home

    PubMed Central

    Hecht, Stephen S.; Seow, Adeline; Wang, Mingyao; Wang, Renwei; Meng, Lei; Koh, Woon-Puay; Carmella, Steven G.; Chen, Menglan; Han, Shaomei; Yu, Mimi C.; Yuan, Jian-Min

    2010-01-01

    Background Epidemiologic studies associate lung cancer in non-smoking Chinese women with Chinese-style wok cooking. Our goal was to quantify carcinogen and toxicant biomarkers in Chinese women who reported regularly doing home cooking compared to women randomly selected from the Singapore Chinese Health Study as controls. Methods Biomarkers were quantified by high performance liquid chromatography-mass spectrometry (HPLC-MS), HPLC-with fluorescence detection, and gas chromatography-mass spectrometry. Results Compared with controls, women who engaged in regular home cooking had significantly higher levels of mercapturic acids of acrolein [geometric mean 1959 pmol/mg creatinine (95% CI 1554–2467) vs.1370 (95% CI 1077–1742), P = 0.038], crotonaldehyde [geometric mean 232 pmol/mg creatinine (95% CI 193–277) vs. 142 (95% CI 118–171) P = 0.0004], and benzene [geometric mean 0.58 pmol/mg creatinine (95% CI 0.44–0.78) vs. 0.18 (95% CI 0.14–0.24) P < 0.0001]. No significant differences were found in levels of mercapturic acids of 1,3-butadiene, pyrene and phenanthrene metabolites, or acetaldehyde-leukocyte DNA adduct levels between the groups. Levels of the ethylene oxide mercapturic acid were significantly higher in the controls. Conclusions The higher levels of the mercapturic acid of benzene, a multi-organ carcinogen, in the women who cooked are particularly notable. Overall, the results showing increased exposure to the volatile toxicants and carcinogens acrolein, crotonaldehyde, and benzene in Chinese women who regularly cook provide a plausible lead for further investigating the role of volatile compounds generated during high temperature cooking with oils as causes of lung cancer. Impact A new direction for research on lung cancer etiology is suggested. PMID:20406956

  10. Risk Factors Associated with Serum Levels of the Inflammatory Biomarker Soluble Urokinase Plasminogen Activator Receptor in a General Population

    PubMed Central

    Haupt, Thomas H; Kallemose, Thomas; Ladelund, Steen; Rasmussen, Line JH; Thorball, Christian W; Andersen, Ove; Pisinger, Charlotta; Eugen-Olsen, Jesper

    2014-01-01

    The soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of mortality risk in various patient populations. However, little is known about the implications of lifestyle for suPAR levels in the general population. Lifestyle, demographic, and cardiovascular disease (CVD) risk factor data were collected from 5,538 participants in the Danish population-based Inter99 study. Their suPAR levels were measured using a sandwich enzyme-linked immunosorbent assay. In the final adjusted model, smoking and morbid obesity were strongly associated with higher suPAR levels (P < 0.001). An unhealthy diet and alcohol abstinence in men were also associated with higher suPAR levels. Physical activity in leisure time had a modest impact on suPAR levels in univariate analysis, but not in the final adjusted model. In conclusion, smoking and morbid obesity were strongly associated with higher serum suPAR levels in this general population. Diet and alcohol consumption also seemed to impact suPAR levels. Lifestyle changes are likely to affect suPAR since ex-smokers had suPAR levels comparable to those of never-smokers. PMID:25574132

  11. Cardioembolic Stroke Diagnosis Using Blood Biomarkers

    PubMed Central

    Llombart, VÍctor; GarcÍa-Berrocoso, Teresa; Bustamante, Alejandro; Fernández-Cadenas, Israel; Montaner, Joan

    2013-01-01

    Stroke is one of the main causes of death and disability in the world. Cardioembolic etiology accounts for approximately one fifth of all ischemic strokes whereas 25-30% remains undetermined even after an advanced diagnostic workup. Despite there is not any biomarker currently approved to distinguish cardioembolic stroke among other etiologies in clinical practice the use of biomarkers represents a promising valuable complement to determine stroke etiology reducing the number of cryptogenic strokes and aiding in the prescription of the most appropriated primary and secondary treatments in order to minimize therapeutic risks and to avoid recurrences. In this review we present an update about specific cardioembolic stroke-related biomarkers at a protein, transcriptomic and genetic level. Finally, we also focused on reported biomarkers associated with atrial fibrillation (a cardiac illness strongly related with cardioembolic stroke subtype) thus with a potential to become biomarkers to detect cardioembolic stroke in the future. PMID:24527683

  12. Increased levels of urinary biomarkers of lipid peroxidation products among workers occupationally exposed to diesel engine exhaust.

    PubMed

    Bin, Ping; Shen, Meili; Li, Haibin; Sun, Xin; Niu, Yong; Meng, Tao; Yu, Tao; Zhang, Xiao; Dai, Yufei; Gao, Weimin; Gu, Guizhen; Yu, Shanfa; Zheng, Yuxin

    2016-08-01

    Diesel engine exhaust (DEE) was found to induce lipid peroxidation (LPO) in animal exposure studies. LPO is a class of oxidative stress and can be reflected by detecting the levels of its production, such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), and etheno-DNA adducts including 1,N(6)-etheno-2'-deoxyadenosine (ɛdA) and 3,N(4)-etheno-2'-deoxycytidine (ɛdC). However, the impact of DEE exposure on LPO has not been explored in humans. In this study, we evaluated urinary MDA, 4-HNE, ɛdA, and ɛdC levels as biomarkers of LPO among 108 workers with exclusive exposure to DEE and 109 non-DEE-exposed workers. Results showed that increased levels of urinary MDA and ɛdA were observed in subjects occupationally exposed to DEE before and after age, body mass index (BMI), smoking status, and alcohol use were adjusted (all p < 0.001). There was a statistically significant relationship between the internal exposure dose (urinary ΣOH-PAHs) and MDA, 4-HNE, and ɛdA (all p < 0.001). Furthermore, significant increased relations between urinary etheno-DNA adduct and MDA, 4-HNE were observed (all p < 0.05). The findings of this study suggested that the level of LPO products (MDA and ɛdA) was increased in DEE-exposed workers, and urinary MDA and ɛdA might be feasible biomarkers for DEE exposure. LPO induced DNA damage might be involved and further motivated the genomic instability could be one of the pathogeneses of cancer induced by DEE-exposure. However, additional investigations should be performed to understand these observations.

  13. Education, gender, and state-level disparities in the health of older Indians: Evidence from biomarker data.

    PubMed

    Lee, Jinkook; McGovern, Mark E; Bloom, David E; Arokiasamy, P; Risbud, Arun; O'Brien, Jennifer; Kale, Varsha; Hu, Peifeng

    2015-12-01

    Using new biomarker data from the 2010 pilot round of the Longitudinal Aging Study in India (LASI), we investigate education, gender, and state-level disparities in health. We find that hemoglobin level, a marker for anemia, is lower for respondents with no schooling (0.7g/dL less in the adjusted model) compared to those with some formal education and is also lower for females than for males (2.0g/dL less in the adjusted model). In addition, we find that about one third of respondents in our sample aged 45 or older have high C-reaction protein (CRP) levels (>3mg/L), an indicator of inflammation and a risk factor for cardiovascular disease. We find no evidence of educational or gender differences in CRP, but there are significant state-level disparities, with Kerala residents exhibiting the lowest CRP levels (a mean of 1.96mg/L compared to 3.28mg/L in Rajasthan, the state with the highest CRP). We use the Blinder-Oaxaca decomposition approach to explain group-level differences, and find that state-level disparities in CRP are mainly due to heterogeneity in the association of the observed characteristics of respondents with CRP, rather than differences in the distribution of endowments across the sampled state populations.

  14. Education, Gender, and State-Level Disparities in the Health of Older Indians: Evidence from Biomarker Data

    PubMed Central

    Lee, Jinkook; McGovern, Mark E.; Bloom, David E.; Arokiasamy, P.; Risbud, Arun; O’Brien, Jennifer; Kale, Varsha; Hu, Peifeng

    2015-01-01

    Using new biomarker data from the 2010 pilot round of the Longitudinal Aging Study in India (LASI), we investigate education, gender, and state-level disparities in health. We find that hemoglobin level, a marker for anemia, is lower for respondents with no schooling (0.7 g/dL less in the adjusted model) compared to those with some formal education and is also lower for females than for males (2.0 g/dL less in the adjusted model). In addition, we find that about one third of respondents in our sample aged 45 or older have high C-reaction protein (CRP) levels (>3 mg/L), an indicator of inflammation and a risk factor for cardiovascular disease. We find no evidence of educational or gender differences in CRP, but there are significant state-level disparities, with Kerala residents exhibiting the lowest CRP levels (a mean of 1.96 mg/L compared to 3.28 mg/L in Rajasthan, the state with the highest CRP). We use the Blinder-Oaxaca decomposition approach to explain group-level differences, and find that state-level disparities in CRP are mainly due to heterogeneity in the association of the observed characteristics of respondents with CRP, rather than differences in the distribution of endowments across the sampled state populations. PMID:26398850

  15. Potential utility of soluble p3-alcadein α plasma levels as a biomarker for sporadic Alzheimer's disease.

    PubMed

    Kamogawa, Kenji; Kohara, Katsuhiko; Tabara, Yasuharu; Takita, Rie; Miki, Tetsuro; Konno, Tomoko; Hata, Saori; Suzuki, Toshiharu

    2012-01-01

    Alcadeins (Alcs) constitute a family of neuronal type I membrane proteins (α, β, γ) that share identical localization and function to the amyloid-β protein precursor (AβPP) in the brain. Alcs are proteolyzed in neurons through successive cleavages via secretases, resulting in non-aggregative p3-Alc, where p3 corresponds to the AβPP-fragment. We found p3-Alcα detected in human plasma reflected the pathological process of amyloid-β accumulation in Alzheimer's disease (AD) patients and therefore investigated the utility of p3-Alcα as a plasma biomarker in AD. We measured p3-Alcα plasma levels in 83 sporadic-AD, 18 mild cognitive impaired (MCI), and 24 control subjects using the sandwich-ELISA system. Pooled samples with previously published data (171 AD and 45 controls) were also analyzed. The plasma p3-Alcα concentrations in patients with AD and MCI were significantly higher compared with control subjects (224.7 ± 40.4, 223.3 ± 53.9, and 189.1 ± 32.9 pg/ml, respectively; p = 0.0012). In AD patients, the plasma p3-Alcα concentration significantly correlated with age (r = 0.23, p = 0.037) and serum creatinine levels (r = 0.23, p = 0.0012). Even after adjusting for confounding factors of age, gender, renal function, and ApoE-ε4, high plasma p3-Alcα levels were correlated with significant AD risk, with an odds ratio 1.47 (95% confidence interval: 1.18-1.93, p = 0.0019) for every 10 pg/ml increase. Pooled analysis further confirmed these findings. Increased plasma p3-Alcα, evident in the early stages of cognitive impairment, suggests that Alc metabolites are useful plasma biomarkers of AD.

  16. Investigating relationships between biomarkers of exposure and environmental copper and manganese levels in house dusts from a Portuguese industrial city.

    PubMed

    Reis, A P; Costa, S; Santos, I; Patinha, C; Noack, Y; Wragg, J; Cave, M; Sousa, A J

    2015-08-01

    This study reports on data obtained from a pilot survey focusing on house dust and toenail metal(loids) concentrations in residents living in the industrial city of Estarreja. The study design hereby described aims at investigating relationships between human toenails and both copper and manganese levels in settled house dusts. A total of 21 households and 30 individuals were recruited for the pilot study: 19 households corresponding to 27 residents living near the industrial complex, forming the exposed group, plus 2 households and 3 residents from residential areas with no anticipated environmental contaminants that were used for comparison. Factorial analysis was used for source identification purposes. Investigation on the potential influence of environmental factors over copper and manganese levels in the toenails was carried out via questionnaire data and multiple correspondence analysis. The results show that copper concentrations are more elevated in the indoor dusts, while manganese concentrations are more elevated in the outdoor dust samples. The geometrical relationships in the datasets suggest that the backyard soil is a probable source of manganese to the indoor dust. Copper and manganese contents in the toenail clippings are more elevated in children than in adults, but the difference between the two age groups is not statistically significant (p > 0.05). Investigation of environmental factors influencing the exposure-biomarker association indicates a probable relationship between manganese contents in indoor dust and manganese levels in toenail clippings, a result that is partially supported by the bioaccessibility estimates. However, for copper, no relationship was found between indoor dusts and the biomarkers of exposure.

  17. Plasma levels of the tissue inhibitor matrix metalloproteinase-3 as a potential biomarker in oral cancer progression

    PubMed Central

    Su, Chun-Wen; Su, Bo-Feng; Chiang, Whei-Ling; Yang, Shun-Fa; Chen, Mu-Kuan; Lin, Chiao-Wen

    2017-01-01

    Oral cancer is the most common malignancy with poor prognosis and is the fourth most common cancer in men in Taiwan. The tissue inhibitor of metalloproteinase-3 (TIMP3) acts as a tumor suppressor gene by inhibiting the growth, angiogenesis, migration, and invasion of cancer cells. However, few studies have examined the association of plasma TIMP3 levels with oral squamous cell carcinoma (OSCC), and the role of plasma TIMP3 levels in OSCC progression is still unclear. We measured the plasma TIMP3 levels of 450 OSCC patients and 64 healthy controls by using a commercial enzyme-linked immunosorbent assay. We also analyzed TIMP3 mRNA levels of 328 OSCC patients and 32 normal tissues from The Cancer Genome Atlas (TCGA) dataset. Our results revealed that plasma TIMP3 levels were significantly lower in patients with OSCC than in healthy controls (p < 0.001). Moreover, plasma TIMP3 levels in patients with OSCC were significantly associated with the tumor stage and tumor status but not with the lymph node status, metastasis, and cell differentiation. To verify our findings, we also examined TCGA bioinformatics database and discovered similar results for the association with the pathological stage of OSCC. In conclusion, our results suggest that plasma TIMP3 is a potential biomarker for predicting the tumor stage and T status in patients with OSCC. PMID:28138307

  18. Reduced ING1 levels in breast cancer promotes metastasis

    PubMed Central

    Chen, Jie; Tran, Uyen; Yang, Yang; Salazar, Carolina; Magliocco, Anthony; Klimowicz, Alexander; Jirik, Frank R.; Riabowol, Karl

    2014-01-01

    INhibitor of Growth 1 (ING1) expression is repressed in breast carcinomas, but its role in breast cancer development and metastasis is unknown. ING1 levels were quantified in >500 patient samples using automated quantitative fluorescence immunohistochemistry, and data were analysed for correlations to patient outcome. Effects of altering ING levels were examined in microarrays and metastasis assays in vitro, and in a mouse metastasis model in vivo. ING1 levels were lower in tumors compared to adjacent normal breast tissue and correlated with tumor size (p=0.019) and distant recurrence (p=0.001) in ER- or Her2+ patients. In these patients ING1 predicted disease-specific and distant metastasis-free survival. Transcriptome analysis showed that the pathway most affected by ING1 was breast cancer (p = 0.0008). Decreasing levels of ING1 increased, and increasing levels decreased, migration and invasion of MDA-MB231 cells in vitro. ING1 overexpression also blocked cancer cell metastasis in vivo and eliminated tumor-induced mortality in mouse models. Our data show that ING1 protein levels are downregulated in breast cancer and for the first time, we show that altering their levels regulates metastasis in vitro and in vivo, which indicates that ING1 may have a therapeutic role for inhibiting metastasis of breast cancer. PMID:24962136

  19. Techniques for Reducing Gun Blast Noise Levels: An Experimental Study

    DTIC Science & Technology

    1981-04-01

    gun muzzle blast noise level were in- vestigated experimentally to determine potential effectiveness and utility for existing major-caliber guns...impact on training and testing operations was to be minimized. Most of the noise reduction techniques that were investigated involve the use of some type ...shock noise level at the earth’s surface varies according to a complicated dependence upon projectile trajectory, projectile speed along the trajectory

  20. Cytokine levels as biomarkers of radiation fibrosis in patients treated with breast radiotherapy

    PubMed Central

    2014-01-01

    Background Radiation fibrosis is not easily measurable although clinical scores have been developed for this purpose. Biomarkers present an alternative more objective approach to quantification, and estimation in blood provides accessible samples. We investigated if blood cytokines could be used to measure established fibrosis in patients who have undergone radiotherapy for breast cancer. Methods We studied two cohorts treated by breast-conserving surgery and radiotherapy in the UK START Trial A, one with breast fibrosis (cases) and one with no or minimal fibrosis (controls). Two candidate cytokines, plasma connective tissue growth factor (CTGF) and serum interleukin-6 (IL6) were estimated by ELISA. Comparisons between cases and controls used the t-test or Mann–Whitney test and associations between blood concentration and clinical factors were assessed using the Spearman rank correlation coefficient. Results Seventy patients were included (26 cases, 44 controls). Mean time since radiotherapy was 9.9 years (range 8.3-12.0). No statistically significant differences between cases and controls in serum IL6 (median (IQR) 0.84 pg/ml (0.57-1.14), 0.75 pg/ml (0.41-1.43) respectively) or plasma CTGF (331.4 pg/ml (234.8-602.9), 334.5 pg/ml (270.0-452.8) were identified. There were no significant associations between blood cytokine concentration and age, fibrosis severity, breast size or time since radiotherapy. Conclusions No significant difference in IL6 or CTGF concentrations was detected between patients with breast fibrosis and controls with minimal or no fibrosis. PMID:24885397

  1. Procalcitonin Biomarker Algorithm Reduces Antibiotic Prescriptions, Duration of Therapy, and Costs in Chronic Obstructive Pulmonary Disease: A Comparison in the Netherlands, Germany, and the United Kingdom.

    PubMed

    van der Maas, Marloes E; Mantjes, Gertjan; Steuten, Lotte M G

    2017-04-01

    Antibiotics are often recommended as treatment for patients with chronic obstructive pulmonary disease (COPD) exacerbations. However, not all COPD exacerbations are caused by bacterial infections and there is consequently considerable misuse and overuse of antibiotics among patients with COPD. This poses a severe burden on healthcare resources such as increased risk of developing antibiotic resistance. The biomarker procalcitonin (PCT) displays specificity to distinguish bacterial inflammations from nonbacterial inflammations and may therefore help to rationalize antibiotic prescriptions. We report in this study, a three-country comparison of the health and economic consequences of a PCT biomarker-guided prescription and clinical decision-making strategy compared to current practice in hospitalized patients with COPD exacerbations. A decision tree was developed, comparing the expected costs and effects of the PCT algorithm to current practice in the Netherlands, Germany, and the United Kingdom. The time horizon of the model captured the length of hospital stay and a societal perspective was also adopted. The primary health outcome was the duration of antibiotic therapy. The incremental cost-effectiveness ratio was defined as the incremental costs per antibiotic day avoided. The incremental cost savings per day on antibiotic therapy avoided were (in Euros) €90 in the Netherlands, €125 in Germany, and €52 in the United Kingdom. Probabilistic sensitivity analyses showed that in the majority of simulations, the PCT biomarker strategy was superior to current practice (the Netherlands: 58%, Germany: 58%, and the United Kingdom: 57%). In conclusion, the PCT biomarker algorithm to optimize antibiotic prescriptions in COPD is likely to be cost-effective compared to current practice. Both the percentage of patients who start with antibiotic treatment as well as the duration of antibiotic therapy are reduced with the PCT decision algorithm, leading to a decrease in

  2. Evaluation of Ki-67 Staining Levels as an Independent Biomarker of Biochemical Recurrence After Salvage Radiation Therapy for Prostate Cancer

    SciTech Connect

    Parker, Alexander S.; Heckman, Michael G.; Wu, Kevin J.; Crook, Julia E.; Hilton, Tracy W.; Pisansky, Thomas M.; Bernard, Johnny R.; Schild, Steven E.; Khor, Li Yan; Hammond, Elizabeth H.; Pollack, Alan; Buskirk, Steven J.

    2009-12-01

    Purpose: We recently published a scoring algorithm to predict biochemical recurrence (BCR) after salvage radiation therapy (SRT) for prostate cancer. Currently, this algorithm is based on clinicopathologic features and does not incorporate information from tumor-based biomarkers. Herein, we evaluate the ability of Ki-67 staining in primary prostate cancer to independently aid in the prediction of BCR among men undergoing SRT. Methods and Materials: We identified 147 patients who were treated with SRT between July 1987 and July 2003 at Mayo Clinic (Rochester, MN; Jacksonville, FL; Scottsdale, AZ). Staining levels of Ki-67 in primary tumor samples were detected by use of a monoclonal antibody and quantified by use of a computer-assisted method. We used Cox proportional hazards models to examine the association of Ki-67 staining and BCR in single-variable models and after multivariable adjustment. Results: The risk of BCR for men with tumors in the highest tertile of Ki-67 staining is approximately two times that for men with tumors in the lower two tertiles (relative risk, 2.02; 95% confidence interval, 1.23-3.32; p = 0.005) after adjustment for the features in our original scoring algorithm. Further adjustment for additional covariates did not attenuate this association. Evidence from concordance index values supports that Ki-67 staining adds to the predictive ability of our existing scoring algorithm. Conclusions: Our data suggest that higher levels of Ki-67 staining are associated with increased risk of BCR after SRT, independent of existing clinicopathologic covariates. Future studies involving larger numbers of patients are required to validate these results and also explore possible means of combining this biomarker with existing prognostic tools.

  3. Health Promotion to Reduce Blood Pressure Level among Older Blacks.

    ERIC Educational Resources Information Center

    Haber, David

    1986-01-01

    Low-income Black elders completed a 10-week health promotion program for the purpose of lowering or stabilizing blood pressure levels. Comparisons were made between classes that met weekly versus three times a week, and between yoga and aerobics formats. A peer-led program was developed that continued for 10 months after the professionally-led…

  4. PMP22 messenger RNA levels in skin biopsies: testing the effectiveness of a Charcot-Marie-Tooth 1A biomarker.

    PubMed

    Nobbio, Lucilla; Visigalli, Davide; Radice, Davide; Fiorina, Elisabetta; Solari, Alessandra; Lauria, Giuseppe; Reilly, Mary M; Santoro, Lucio; Schenone, Angelo; Pareyson, Davide

    2014-06-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with increased gene dosage for PMP22. Therapeutic approaches are currently aiming at correcting PMP22 over-expression. It is unknown whether PMP22 can be used as a biological marker of disease progression and therapy efficacy. We performed quantitative real-time polymerase chain reaction on skin biopsies of 45 patients with CMT1A, obtained at study entry and after 24-months of treatment either with ascorbic acid or placebo. Data of a subgroup of patients were also compared with matched healthy subjects. Finally, we analysed PMP22 messenger RNA levels in sural nerve biopsies. We did not find significant differences in the levels of any known PMP22 transcripts in treated or untreated patients with CMT1A, thus confirming that ascorbic acid does not impact on the molecular features of CMT1A. Most importantly, we did not observe any correlation between PMP22 messenger RNA levels and the different clinical and electrophysiological outcome measures, underscoring the weakness of PMP22 to mirror the phenotypic variability of patients with CMT1A. We did not find increased PMP22 messenger RNA levels in skin and sural nerve biopsies of patients with CMT1A compared with relative controls. In conclusion, this study shows that ascorbic acid does not impact on PMP22 transcriptional regulation and PMP22 is not a suitable biomarker for CMT1A.

  5. Green tea consumption is associated with reduced incident CHD and improved CHD-related biomarkers in the Dongfeng-Tongji cohort

    PubMed Central

    Tian, Chong; Huang, Qiao; Yang, Liangle; Légaré, Sébastien; Angileri, Francesca; Yang, Handong; Li, Xiulou; Min, Xinwen; Zhang, Ce; Xu, Chengwei; Yuan, Jing; Miao, Xiaoping; He, Mei-an; Wu, Tangchun; Zhang, Xiaomin

    2016-01-01

    Prospective studies on the association of green tea with risk of coronary heart disease (CHD) incidence were scarce. This study examined whether green tea can reduce CHD incidence and have a beneficial effect on CHD-related risk markers in middle-aged and older Chinese population. We included 19 471 participants who were free of CHD, stroke or cancer at baseline from September 2008 to June 2010, and were followed until October 2013. Cox proportional hazard models were used to examine the hazard ratios (HR) of CHD incidence in relation to green tea consumption. Linear regression models were used to evaluate the effect of green tea on 5-year changes of CHD-related biomarkers. Compared with non-green tea consumers, the multivariable-adjusted HR for CHD was 0.89 (95% CI, 0.81-0.98) in green tea consumers. Particularly, the reduced risk of CHD incidence with green tea consumption was more evident among participants who were male, more than 60 years old, overweight, or with diabetes mellitus. In addition, green tea consumption improved multiple CHD-related risk markers including total cholesterol, HDL-cholesterol, triglycerides, mean platelet volume, and uric acid. In conclusion, green tea consumption was associated with a reduced risk of CHD incidence in the middle-aged and older Chinese populations, and the association might be partly due to altered CHD-related biomarkers. PMID:27072746

  6. Time-dependent changes in serum biomarker levels after blast traumatic brain injury.

    PubMed

    Gyorgy, Andrea; Ling, Geoffrey; Wingo, Daniel; Walker, John; Tong, Lawrence; Parks, Steve; Januszkiewicz, Adolph; Baumann, Richard; Agoston, Denes V

    2011-06-01

    Neuronal and glial proteins detected in the peripheral circulating blood after injury can reflect the extent of the damage caused by blast traumatic brain injury (bTBI). The temporal pattern of their serum levels can further predict the severity and outcome of the injury. As part of characterizing a large-animal model of bTBI, we determined the changes in the serum levels of S100B, neuron-specific enolase (NSE), myelin basic protein (MBP), and neurofilament heavy chain (NF-H). Blood samples were obtained prior to injury and at 6, 24, 72 h, and 2 weeks post-injury from animals with different severities of bTBI; protein levels were determined using reverse phase protein microarray (RPPM) technology. Serum levels of S100B, MBP, and NF-H, but not NSE, showed a time-dependent increase following injury. The detected changes in S100B and MBP levels showed no correlation with the severity of the injury. However, serum NF-H levels increased in a unique, rapid manner, peaking at 6 h post-injury only in animals exposed to severe blast with poor clinical and pathological outcomes. We conclude that the sudden increase in serum NF-H levels following bTBI may be a useful indicator of injury severity. If additional studies verify our findings, the observed early peak of serum NF-H levels can be developed into a useful diagnostic tool for predicting the extent of damage following bTBI.

  7. Temporal overlap and repeatability of feather corticosterone levels: practical considerations for use as a biomarker

    PubMed Central

    Harris, Christopher M.; Madliger, Christine L.; Love, Oliver P.

    2016-01-01

    The measurement of corticosterone (CORT) levels in feathers has recently become an appealing tool for the conservation toolbox, potentially providing a non-invasive, integrated measure of stress activity throughout the time of feather growth. However, because the mechanism of CORT deposition, storage and stability in feathers is not fully understood, it is unclear how reliable this measure may be, especially when there is an extended interval between growth and feather collection. We compared CORT levels of naturally grown feathers from tree swallows (Tachycineta bicolor) that were moulted and regrown concurrently and therefore expected to have similar CORT levels. Specifically, we compared the same feather from the left and right wing (moulted symmetrically) and different types of feathers (wing, back and tail) expected to have been moulted within the same time period. We found that larger, heavier feathers held more CORT per unit length. In addition, we found a lack of concordance in CORT levels both within the same feather type and between different feather types, even after taking into account differences in feather density. Our results indicate that naturally grown feathers may not consistently provide an indication of stress status. Additionally, conflict in results may arise depending on the feather assayed, and total feather volume may be an important consideration when interpreting feather CORT levels. Future work is necessary to determine explicitly the mechanisms of CORT deposition, the effects of environmental exposure and feather wear on the permanence of the feather CORT signal, and the influence of responses to wild stressors on feather CORT levels, before feather CORT can be implemented effectively as a tool for ecological and conservation applications. PMID:27933163

  8. Temporal overlap and repeatability of feather corticosterone levels: practical considerations for use as a biomarker.

    PubMed

    Harris, Christopher M; Madliger, Christine L; Love, Oliver P

    2016-01-01

    The measurement of corticosterone (CORT) levels in feathers has recently become an appealing tool for the conservation toolbox, potentially providing a non-invasive, integrated measure of stress activity throughout the time of feather growth. However, because the mechanism of CORT deposition, storage and stability in feathers is not fully understood, it is unclear how reliable this measure may be, especially when there is an extended interval between growth and feather collection. We compared CORT levels of naturally grown feathers from tree swallows (Tachycineta bicolor) that were moulted and regrown concurrently and therefore expected to have similar CORT levels. Specifically, we compared the same feather from the left and right wing (moulted symmetrically) and different types of feathers (wing, back and tail) expected to have been moulted within the same time period. We found that larger, heavier feathers held more CORT per unit length. In addition, we found a lack of concordance in CORT levels both within the same feather type and between different feather types, even after taking into account differences in feather density. Our results indicate that naturally grown feathers may not consistently provide an indication of stress status. Additionally, conflict in results may arise depending on the feather assayed, and total feather volume may be an important consideration when interpreting feather CORT levels. Future work is necessary to determine explicitly the mechanisms of CORT deposition, the effects of environmental exposure and feather wear on the permanence of the feather CORT signal, and the influence of responses to wild stressors on feather CORT levels, before feather CORT can be implemented effectively as a tool for ecological and conservation applications.

  9. Salivary Biomarker Levels and Diurnal Variation: Associations with Medications Prescribed to Control Children's Problem Behavior

    ERIC Educational Resources Information Center

    Hibel, Leah C.; Granger, Douglas A.; Cicchetti, Dante; Rogosch, Fred

    2007-01-01

    This study examined associations between medications prescribed to control children's problem behaviors and levels of, and diurnal variation in, salivary cortisol (C), testosterone (T), and dehydroepiandrosterone (DHEA). Saliva was collected in the morning, midday, and afternoon from 432 children ages 6-13 years. Relative to a no-medication…

  10. Association of Dietary Intake and Biomarker Levels of Arsenic, Cadmium, Lead, and Mercury among Asian Populations in the United States: NHANES 2011–2012

    PubMed Central

    Awata, Hiroshi; Linder, Stephen; Mitchell, Laura E.; Delclos, George L.

    2016-01-01

    Background: We have recently shown that biomarker levels of selected metals are higher in Asians than in other U.S. ethnic groups, with important differences within selected Asian subgroups. Much of this difference may be dietary in origin; however, this is not well established. Objective: We evaluated dietary intake of toxic metals as a source of increased biomarker levels of metals among U.S. Asians. Methods: We estimated daily food consumption and dietary intake of arsenic, cadmium, lead, and mercury by combining 24-hr dietary intake recall data from the 2011–2012 National Health and Nutrition Examination Survey (NHANES) with data from the USDA Food Composition Intake Database and FDA Total Dietary Study. We analyzed associations between dietary metal intake and biomarker levels of the metals using linear regression. Further, estimated food consumption and metal intake levels were compared between Asians and other racial/ethnic groups (white, black, Mexican American, and other Hispanic) and within three Asian subgroups (Chinese, Indian Asian, and other Asians). Results: Significant associations (p < 0.05) were found between biomarker levels and estimated dietary metal intake for total and inorganic arsenic and mercury among Asians. Asians had the highest daily fish and rice consumption across the racial/ethnic groups. Fish was the major contributor to dietary mercury and total arsenic intake, whereas rice was the major contributor to inorganic arsenic dietary intake. Fish consumption across the Asian subgroups varied, with Asian Indians having lower fish consumption than the other Asian subgroups. Rice consumption was similar across the Asian subgroups. Conclusions: We confirmed that estimated dietary intake of arsenic (total and inorganic) and mercury is significantly associated with their corresponding biomarkers in U.S. Asians, using nationally representative data. In contrast, estimated dietary intake of cadmium and lead were not significantly associated

  11. Whole blood lead levels are associated with biomarkers of joint tissue metabolism in African American and White men and women: The Johnston County Osteoarthritis Project

    PubMed Central

    Nelson, Amanda E.; Chaudhary, Sanjay; Kraus, Virginia B.; Fang, Fang; Chen, Jiu-Chiuan; Schwartz, Todd A.; Shi, Xiaoyan A.; Renner, Jordan B.; Stabler, Thomas V.; Helmick, Charles G.; Caldwell, Kathleen; Poole, A. Robin; Jordan, Joanne M.

    2011-01-01

    Purpose To examine associations between biomarkers of joint tissue metabolism and whole blood lead (Pb), separately for men and women in an African American and Caucasian population, which may reflect an underlying pathology. Methods Participants in the Johnston County Osteoarthritis Project Metals Exposure Sub-study (329 men and 342 women) underwent assessment of whole blood Pb and biochemical biomarkers of joint tissue metabolism. Urinary cross-linked N telopeptide of type I collagen (uNTX-I) and C-telopeptide fragments of type II collagen (uCTX-II), and serum cleavage neoepitope of type II collagen (C2C), serum type II procollagen synthesis C-propeptide (CPII), and serum hyaluronic acid (HA) were measured using commercially available kits; the ratio of [C2C:CPII] was calculated. Serum cartilage oligomeric matrix protein (COMP) was measured by an in-house assay. Multiple linear regression models were used to examine associations between continuous blood Pb and biomarker outcomes, adjusted for age, race, current smoking status, and body mass index. Results are reported as estimated change in biomarker level for a 5-unit change in Pb level. Results The median Pb level among men and women was 2.2 and 1.9 µg/dL, respectively. Correlations were noted between Pb levels and the biomarkers uNTX-I, uCTX-II, and COMP in women, and between Pb and uCTX-II, COMP, CPII, and the ratio [C2C:CPII] in men. In adjusted models among women, a 5-unit increase in blood Pb level was associated with a 28% increase in uCTX-II and a 45% increase in uNTX-I levels (uCTX-II: 1.28 [95%CI: 1.04–1.58], uNTX-I: 1.45 [95%CI:1.21–1.74]). Among men, levels of Pb and COMP showed a borderline positive association (8% increase in COMP for a 5-unit change in Pb: 1.08 [95% CI: 1.00–1.18])); no other associations were significant after adjustment. Conclusions Based upon known biomarker origins, the novel associations between blood Pb and biomarkers appear to be primarily reflective of relationships

  12. Relevance of angiopoietin-2 and soluble P-selectin levels in patients with pulmonary arterial hypertension receiving combination therapy with oral treprostinil: a FREEDOM-C2 biomarker substudy

    PubMed Central

    Schermuly, Ralph; Seeger, Werner; Rao, Youlan; Ghofrani, Hossein A.; Gall, Henning

    2016-01-01

    Abstract Studies have suggested roles for angiopoietin-2 (Ang-2) and soluble P-selectin (sP-selectin) as biomarkers of disease severity and treatment response in pulmonary arterial hypertension (PAH), but additional data are required for validation. We evaluated these biomarkers using data from FREEDOM-C2, in which patients with PAH receiving stable monotherapy or combination therapy were randomized to receive additional treatment with oral treprostinil (up-titrated from 0.25 mg twice daily) or placebo for 16 weeks. Biomarker analysis was optional in FREEDOM-C2. We measured plasma Ang-2 and sP-selectin levels at baseline and at week 16, and we assessed their association with predefined outcomes (6-minute walk distance [6MWD] change from baseline >40 m, 6MWD >380 m, functional class I/II, and/or N-terminal pro-brain natriuretic peptide [NT-proBNP] <1,800 pg/mL at week 16) using Spearman correlation, receiver operating characteristics, and logistic regression. Biomarker data were available for 83 of 157 and 95 of 153 patients in the oral treprostinil and placebo groups, respectively. In the oral treprostinil group, baseline Ang-2 levels correlated with week 16 NT-proBNP levels (P < 0.0001). Baseline Ang-2 ≥12 ng/mL was associated with a reduced likelihood of having NT-proBNP <1,800 pg/mL at week 16 (multivariate odds ratio: 0.08; 95% confidence interval: 0.02–0.32). However, Ang-2 showed no significant association with the other assessed outcomes, and sP-selectin was not associated or correlated with any of the outcomes. These data suggest that Ang-2 and sP-selectin are not associated with response to oral treprostinil in patients already receiving stable PAH therapy. Trial registration: Clinicaltrials.gov identifier NCT00887978. PMID:28090293

  13. Extreme Mountain Ultra-Marathon Leads to Acute but Transient Increase in Cerebral Water Diffusivity and Plasma Biomarkers Levels Changes.

    PubMed

    Zanchi, Davide; Viallon, Magalie; Le Goff, Caroline; Millet, Grégoire P; Giardini, Guido; Croisille, Pierre; Haller, Sven

    2016-01-01

    Background: Pioneer studies demonstrate the impact of extreme sport load on the human brain, leading to threatening conditions for athlete's health such as cerebral edema. The investigation of brain water diffusivity, allowing the measurement of the intercellular water and the assessment of cerebral edema, can give a great contribution to the investigation of the effects of extreme sports on the brain. We therefore assessed the effect of supra-physiological effort (extreme distance and elevation changes) in mountain ultra-marathons (MUMs) athletes combining for the first time brain magnetic resonance imaging (MRI) and blood parameters. Methods:This longitudinal study included 19 volunteers (44.2 ± 9.5 years) finishing a MUM (330 km, elevation + 24000 m). Quantitative measurements of brain diffusion-weighted images (DWI) were performed at 3 time-points: Before the race, upon arrival and after 48 h. Multiple blood biomarkers were simultaneously investigated. Data analyses included brain apparent diffusion coefficient (ADC) and physiological data comparisons between three time-points. Results:The whole brain ADC significantly increased from baseline to arrival (p = 0.005) and then significantly decreased at recovery (p = 0.005) to lower values than at baseline (p = 0.005). While sodium, potassium, calcium, and chloride as well as hematocrit (HCT) changed over time, the serum osmolality remained constant. Significant correlations were found between whole brain ADC changes and osmolality (p = 0.01), cholesterol (p = 0.009), c-reactive protein (p = 0.04), sodium (p = 0.01), and chloride (p = 0.002) plasma level variations. Conclusions:These results suggest the relative increase of the inter-cellular volume upon arrival, and subsequently its reduction to lower values than at baseline, indicating that even after 48 h the brain has not fully recovered to its equilibrium state. Even though serum electrolytes may only indirectly indicate modifications at the brain level due

  14. Extreme Mountain Ultra-Marathon Leads to Acute but Transient Increase in Cerebral Water Diffusivity and Plasma Biomarkers Levels Changes

    PubMed Central

    Zanchi, Davide; Viallon, Magalie; Le Goff, Caroline; Millet, Grégoire P.; Giardini, Guido; Croisille, Pierre; Haller, Sven

    2017-01-01

    Background: Pioneer studies demonstrate the impact of extreme sport load on the human brain, leading to threatening conditions for athlete's health such as cerebral edema. The investigation of brain water diffusivity, allowing the measurement of the intercellular water and the assessment of cerebral edema, can give a great contribution to the investigation of the effects of extreme sports on the brain. We therefore assessed the effect of supra-physiological effort (extreme distance and elevation changes) in mountain ultra-marathons (MUMs) athletes combining for the first time brain magnetic resonance imaging (MRI) and blood parameters. Methods:This longitudinal study included 19 volunteers (44.2 ± 9.5 years) finishing a MUM (330 km, elevation + 24000 m). Quantitative measurements of brain diffusion-weighted images (DWI) were performed at 3 time-points: Before the race, upon arrival and after 48 h. Multiple blood biomarkers were simultaneously investigated. Data analyses included brain apparent diffusion coefficient (ADC) and physiological data comparisons between three time-points. Results:The whole brain ADC significantly increased from baseline to arrival (p = 0.005) and then significantly decreased at recovery (p = 0.005) to lower values than at baseline (p = 0.005). While sodium, potassium, calcium, and chloride as well as hematocrit (HCT) changed over time, the serum osmolality remained constant. Significant correlations were found between whole brain ADC changes and osmolality (p = 0.01), cholesterol (p = 0.009), c-reactive protein (p = 0.04), sodium (p = 0.01), and chloride (p = 0.002) plasma level variations. Conclusions:These results suggest the relative increase of the inter-cellular volume upon arrival, and subsequently its reduction to lower values than at baseline, indicating that even after 48 h the brain has not fully recovered to its equilibrium state. Even though serum electrolytes may only indirectly indicate modifications at the brain level due

  15. Clinical neuropathology practice guide 3-2013: levels of evidence and clinical utility of prognostic and predictive candidate brain tumor biomarkers.

    PubMed

    Berghoff, Anna S; Stefanits, Harald; Woehrer, Adelheid; Heinzl, Harald; Preusser, Matthias; Hainfellner, Johannes A

    2013-01-01

    A large number of potential tissue biomarkers has been proposed for brain tumors. However, hardly any have been adopted for routine clinical use, so far. For most candidate biomarkers substantial controversy exists with regard to their usefulness in clinical practice. The multidisciplinary neurooncology taskforce of the Vienna Comprehensive Cancer Center Central Nervous System Unit (CCC-CNS) addressed this issue and elaborated a four-tiered levels-of-evidence system for assessing analytical performance (reliability of test result) and clinical performance (prognostic or predictive) based on consensually defined criteria. The taskforce also consensually agreed that only biomarker candidates should be considered as ready for clinical use, which meet defined quality standards for both, analytical and clinical performance. Applying this levels-of-evidence system to MGMT, IDH1, 1p19q, Ki67, MYCC, MYCN and β-catenin, only immunohistochemical IDH1 mutation testing in patients with diffuse gliomas is supported by sufficient evidence in order to be unequivocally qualified for clinical use. For the other candidate biomarkers lack of published evidence of sufficiently high analytical test performance and, in some cases, also of clinical performance limits evidence-based confirmation of their clinical utility. For most of the markers, no common standard of laboratory testing exists. We conclude that, at present, there is a strong need for studies that specifically address the analytical performance of candidate brain tumor biomarkers. In addition, standardization of laboratory testing is needed. We aim to regularly challenge and update the present classification in order to systematically clarify the current translational status of candidate brain tumor biomarkers and to identify specific research needs for accelerating the translational pace.

  16. Impact of Chronic Periodontitis on Levels of Glucoregulatory Biomarkers in Gingival Crevicular Fluid of Adults with and without Type 2 Diabetes

    PubMed Central

    Mohamed, Hasaan G.; Idris, Shaza B.; Mustafa, Manal; Ahmed, Mutaz F.; Åstrøm, Anne N.; Mustafa, Kamal; Ibrahim, Salah O.

    2015-01-01

    The relationship between diabetes and periodontal disease is bidirectional, but information about the effect of chronic periodontitis on the levels of the glucoregulatory biomarkers locally in gingival crevicular fluid (GCF) is limited. The aim of this study was to compare the levels of 10 glucoregulatory biomarkers in GCF, firstly in subjects with type 2 diabetes (T2DM) presenting with and without chronic periodontitis and secondly, in subjects without diabetes, with and without chronic periodontitis. The material comprised a total of 152 subjects, stratified as: 54 with T2DM and chronic periodontitis (G1), 24 with T2DM (G2), 30 with chronic periodontitis (G3) and 44 without T2DM or periodontitis (G4). The levels of the biomarkers were measured using multiplex biometric immunoassays. Periodontal pocket depths were recorded in mm. Subsets G1 and G2 and subsets G3 and G4 were compared independently. Among T2DM subjects, GIP, GLP-1 and glucagon were significantly up-regulated in G1 compared to G2. Moreover, there were no statistical differences between the two groups regarding C-peptide, insulin, ghrelin, leptin and PAI-1. Comparisons among individuals without T2DM revealed significantly lower amounts of C-peptide and ghrelin in G3 than in G4. The number of sites with pocket depth ≥ 4mm correlated negatively with C-peptide (Spearman’s correlation co-efficient: -0.240, P < 0.01) and positively with GIP and visfatin (Spearman’s correlation co-efficient: 0.255 and 0.241, respectively, P < 0.01). The results demonstrate that chronic periodontitis adversely influences the GCF levels of glucoregulatory biomarkers, as it is associated with disturbed levels of biomarkers related to the onset of T2DM and its medical complications. PMID:25993052

  17. Impact of Chronic Periodontitis on Levels of Glucoregulatory Biomarkers in Gingival Crevicular Fluid of Adults with and without Type 2 Diabetes.

    PubMed

    Mohamed, Hasaan G; Idris, Shaza B; Mustafa, Manal; Ahmed, Mutaz F; Åstrøm, Anne N; Mustafa, Kamal; Ibrahim, Salah O

    2015-01-01

    The relationship between diabetes and periodontal disease is bidirectional, but information about the effect of chronic periodontitis on the levels of the glucoregulatory biomarkers locally in gingival crevicular fluid (GCF) is limited. The aim of this study was to compare the levels of 10 glucoregulatory biomarkers in GCF, firstly in subjects with type 2 diabetes (T2DM) presenting with and without chronic periodontitis and secondly, in subjects without diabetes, with and without chronic periodontitis. The material comprised a total of 152 subjects, stratified as: 54 with T2DM and chronic periodontitis (G1), 24 with T2DM (G2), 30 with chronic periodontitis (G3) and 44 without T2DM or periodontitis (G4). The levels of the biomarkers were measured using multiplex biometric immunoassays. Periodontal pocket depths were recorded in mm. Subsets G1 and G2 and subsets G3 and G4 were compared independently. Among T2DM subjects, GIP, GLP-1 and glucagon were significantly up-regulated in G1 compared to G2. Moreover, there were no statistical differences between the two groups regarding C-peptide, insulin, ghrelin, leptin and PAI-1. Comparisons among individuals without T2DM revealed significantly lower amounts of C-peptide and ghrelin in G3 than in G4. The number of sites with pocket depth ≥ 4mm correlated negatively with C-peptide (Spearman's correlation co-efficient: -0.240, P < 0.01) and positively with GIP and visfatin (Spearman's correlation co-efficient: 0.255 and 0.241, respectively, P < 0.01). The results demonstrate that chronic periodontitis adversely influences the GCF levels of glucoregulatory biomarkers, as it is associated with disturbed levels of biomarkers related to the onset of T2DM and its medical complications.

  18. Histopathological alterations, biochemical responses and acetylcholinesterase levels in Clarias gariepinus as biomarkers of exposure to organophosphates pesticides.

    PubMed

    Doherty, V F; Ladipo, M K; Aneyo, I A; Adeola, A; Odulele, W Y

    2016-05-01

    Organophosphate pesticides, commonly used in large scale farming, have been found to be major contaminants in aquatic environment. Clarias gariepinus was exposed to acute and sublethal concentrations of phostoxin and DD Force to evaluate single and joint action toxicity of the organophosphates. Effects of phostoxin and DD force on antioxidant enzymes, fish organs and acetylcholinesterase levels in fingerlings and juveniles of C. gariepinus were also investigated. The lethal concentrations (96 h LC50) for phostoxin and DD Force were 0.631 and 1.759 mg/l, respectively. The results obtained from the bioassay showed that phostoxin was 2.8× more toxic than DD Force after exposure of C. gariepinus. Joint action toxicity evaluations of phostoxin and DD Force showed that the interaction between the chemicals was synergistic (RTU >1). The biochemical responses in the exposed fish differed significantly (P < 0.05) from the control fish. The result of acetylcholinesterase study revealed significant difference between acetylcholinesterase levels in the exposed fish and control, with reduction in the acetylcholineterase level in fish exposed to sublethal concentrations of phostoxin and DD Force. Haematological studies revealed an increase in WBC, RBC, PCV and platelets in the exposed fish. Histopathology of the gills showed shortened primary lamellae, loss of secondary lamellae and loss of ceratobrachial bones. In the acute toxicity studies, respiratory stress, erratic swimming and instant death of fish were observed in the exposed fish. This study reveals that changes in histopathology and acetylcholinesterase level are good biomarkers and can be successfully used to detect exposure to organophosphates pesticides in fish.

  19. Increased Zn/Glutathione Levels and Higher Superoxide Dismutase-1 Activity as Biomarkers of Oxidative Stress in Women with Long-Term Dental Amalgam Fillings: Correlation between Mercury/Aluminium Levels (in Hair) and Antioxidant Systems in Plasma

    PubMed Central

    Cabaña-Muñoz, María Eugenia; Parmigiani-Izquierdo, José María; Bravo-González, Luis Alberto; Kyung, Hee-Moon; Merino, José Joaquín

    2015-01-01

    Background The induction of oxidative stress by Hg can affect antioxidant enzymes. However, epidemiological studies have failed to establish clear association between dental fillings presence and health problems. Objectives To determine whether heavy metals (in hair), antioxidant enzymes (SOD-1) and glutathione levels could be affected by the chronic presence of heavy metals in women who had dental amalgam fillings. Materials and Methods 55 hair samples (42 females with amalgam fillings and 13 female control subjects) were obtained. All subjects (mean age 44 years) who had dental amalgam filling for more than 10 years (average 15 years). Certain metals were quantified by ICP-MS (Mass Spectrophotometry) in hair (μg/g: Al, Hg, Ba, Ag, Sb, As, Be, Bi, Cd, Pb, Pt, Tl, Th, U, Ni, Sn, Ti) and SOD-1 and Glutathione (reduced form) levels in plasma. Data were compared with controls without amalgams, and analyzed to identify any significant relation between metals and the total number of amalgam fillings, comparing those with four or less (n = 27) with those with more than four (n = 15). As no significant differences were detected, the two groups were pooled (Amlgam; n = 42). Findings Hg, Ag, Al and Ba were higher in the amalgam group but without significant differences for most of the heavy metals analyzed. Increased SOD-1 activity and glutathione levels (reduced form) were observed in the amalgam group. Aluminum (Al) correlated with glutathione levels while Hg levels correlated with SOD-1. The observed Al/glutathione and Hg/SOD-1 correlation could be adaptive responses against the chronic presence of mercury. Conclusions Hg, Ag, Al and Ba levels increased in women who had dental amalgam fillings for long periods. Al correlated with glutathione, and Hg with SOD-1. SOD-1 may be a possible biomarker for assessing chronic Hg toxicity. PMID:26076368

  20. Detection of cord blood hepcidin levels as a biomarker for early-onset neonatal sepsis.

    PubMed

    Cizmeci, Mehmet Nevzat; Kara, Semra; Kanburoglu, Mehmet Kenan; Simavli, Serap; Duvan, Candan Iltemur; Tatli, Mustafa Mansur

    2014-03-01

    Early-onset neonatal sepsis (EONS) continues to be a severe condition associated with a high mortality and morbidity. However, symptoms and laboratory markers of this serious condition are nonspecific and currently there are no available standard tests to provide perfect diagnostic accuracy. An early recognition and initiation of antimicrobial therapy are essential in order to prevent morbidity and mortality. Hepcidin, the key regulator of iron homeostasis, is also an acute-phase reactant, which has a critical role in inflammation and contributes to host defense by interfering with microorganism's access to iron. Since hepcidin expression is induced by interleukin-6 (IL-6), it also plays role in the innate immune system. Recently, endogenous expression of hepcidin by macrophages and neutrophils in response to bacterial pathogens confirmed its role in innate immunity. The clear link between the hepcidin molecule and innate immunity may be used for the detection of EONS. We hypothesized that an increased level of hepcidin in cord blood may be used as a reliable biological marker of EONS and designed a prospective cohort study to test this hypothesis and collected pilot data. Cord blood samples of all infants born between January 2009 and December 2010 at our university hospital were collected after parental consent and a total of 38 infants were enrolled in the study who fulfilled the sepsis criteria. The range of cord blood hepcidin was found to be significantly increased in newborns with EONS (min-max: 118.1-8400 ng/mL). To the best of our knowledge, this is the first study to investigate the pathophysiologic relevance of hepcidin in EONS and demonstrate increased levels of hepcidin in cord blood as an acute-phase reactant in response to sepsis.

  1. Biomarkers in clinical medicine.

    PubMed

    Chen, Xiao-He; Huang, Shuwen; Kerr, David

    2011-01-01

    Biomarkers have been used in clinical medicine for decades. With the rise of genomics and other advances in molecular biology, biomarker studies have entered a whole new era and hold promise for early diagnosis and effective treatment of many diseases. A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacologic responses to a therapeutic intervention (1). They can be classified into five categories based on their application in different disease stages: 1) antecedent biomarkers to identify the risk of developing an illness, 2) screening biomarkers to screen for subclinical disease, 3) diagnostic biomarkers to recognize overt disease, 4) staging biomarkers to categorise disease severity, and 5) prognostic biomarkers to predict future disease course, including recurrence, response to therapy, and monitoring efficacy of therapy (1). Biomarkers can indicate a variety of health or disease characteristics, including the level or type of exposure to an environmental factor, genetic susceptibility, genetic responses to environmental exposures, markers of subclinical or clinical disease, or indicators of response to therapy. This chapter will focus on how these biomarkers have been used in preventive medicine, diagnostics, therapeutics and prognostics, as well as public health and their current status in clinical practice.

  2. Pro-Apoptotic Kinase Levels in Cerebrospinal Fluid as Potential Future Biomarkers in Alzheimer’s Disease

    PubMed Central

    Paquet, Claire; Dumurgier, Julien; Hugon, Jacques

    2015-01-01

    Alzheimer’s disease (AD) is characterized by the accumulation of Aβ peptides, hyperphosphorylated tau proteins, and neuronal loss in the brain of affected patients. The causes of neurodegeneration in AD are not clear, but apoptosis could be one of the cell death mechanisms. According to the amyloid hypothesis, abnormal aggregation of Aβ leads to altered kinase activities inducing tau phosphorylation and neuronal degeneration. Several studies have shown that pro-apoptotic kinases could be a link between Aβ and tau anomalies. Here, we present recent evidences from AD experimental models and human studies that three pro-apoptotic kinases (double-stranded RNA kinase (PKR), glycogen synthase kinase-3β, and C-Jun terminal kinase (JNK) could be implicated in AD physiopathology. These kinases are detectable in human fluids and the analysis of their levels could be used as potential surrogate markers to evaluate cell death and clinical prognosis. In addition to current biomarkers (Aβ1–42, tau, and phosphorylated tau), these new evaluations could bring about valuable information on potential innovative therapeutic targets to alter the clinical evolution. PMID:26300842

  3. Molecular Tools for the Selective Detection of Nine Diatom Species Biomarkers of Various Water Quality Levels

    PubMed Central

    Cimarelli, Lucia; Singh, Kumar Saurabh; Mai, Nguyen Thi Nhu; Dhar, Bidhan Chandra; Brandi, Anna; Brandi, Letizia; Spurio, Roberto

    2015-01-01

    Our understanding of the composition of diatom communities and their response to environmental changes is currently limited by laborious taxonomic identification procedures. Advances in molecular technologies are expected to contribute more efficient, robust and sensitive tools for the detection of these ecologically relevant microorganisms. There is a need to explore and test phylogenetic markers as an alternative to the use of rRNA genes, whose limited sequence divergence does not allow the accurate discrimination of diatoms at the species level. In this work, nine diatom species belonging to eight genera, isolated from epylithic environmental samples collected in central Italy, were chosen to implement a panel of diatoms covering the full range of ecological status of freshwaters. The procedure described in this work relies on the PCR amplification of specific regions in two conserved diatom genes, elongation factor 1-a (eEF1-a) and silicic acid transporter (SIT), as a first step to narrow down the complexity of the targets, followed by microarray hybridization experiments. Oligonucleotide probes with the potential to discriminate closely related species were designed taking into account the genetic polymorphisms found in target genes. These probes were tested, refined and validated on a small-scale prototype DNA chip. Overall, we obtained 17 highly specific probes targeting eEF1-a and SIT, along with 19 probes having lower discriminatory power recognizing at the same time two or three species. This basic array was validated in a laboratory setting and is ready for tests with crude environmental samples eventually to be scaled-up to include a larger panel of diatoms. Its possible use for the simultaneous detection of diatoms selected from the classes of water quality identified by the European Water Framework Directive is discussed. PMID:26006124

  4. Molecular tools for the selective detection of nine diatom species biomarkers of various water quality levels.

    PubMed

    Cimarelli, Lucia; Singh, Kumar Saurabh; Mai, Nguyen Thi Nhu; Dhar, Bidhan Chandra; Brandi, Anna; Brandi, Letizia; Spurio, Roberto

    2015-05-22

    Our understanding of the composition of diatom communities and their response to environmental changes is currently limited by laborious taxonomic identification procedures. Advances in molecular technologies are expected to contribute more efficient, robust and sensitive tools for the detection of these ecologically relevant microorganisms. There is a need to explore and test phylogenetic markers as an alternative to the use of rRNA genes, whose limited sequence divergence does not allow the accurate discrimination of diatoms at the species level. In this work, nine diatom species belonging to eight genera, isolated from epylithic environmental samples collected in central Italy, were chosen to implement a panel of diatoms covering the full range of ecological status of freshwaters. The procedure described in this work relies on the PCR amplification of specific regions in two conserved diatom genes, elongation factor 1-a (eEF1-a) and silicic acid transporter (SIT), as a first step to narrow down the complexity of the targets, followed by microarray hybridization experiments. Oligonucleotide probes with the potential to discriminate closely related species were designed taking into account the genetic polymorphisms found in target genes. These probes were tested, refined and validated on a small-scale prototype DNA chip. Overall, we obtained 17 highly specific probes targeting eEF1-a and SIT, along with 19 probes having lower discriminatory power recognizing at the same time two or three species. This basic array was validated in a laboratory setting and is ready for tests with crude environmental samples eventually to be scaled-up to include a larger panel of diatoms. Its possible use for the simultaneous detection of diatoms selected from the classes of water quality identified by the European Water Framework Directive is discussed.

  5. Association Between Changes in Air Pollution Levels During the Beijing Olympics and Biomarkers of Inflammation and Thrombosis in Healthy Young Adults

    PubMed Central

    Rich, David Q.; Kipen, Howard M.; Huang, Wei; Wang, Guangfa; Wang, Yuedan; Zhu, Ping; Ohman-Strickland, Pamela; Hu, Min; Philipp, Claire; Diehl, Scott R.; Lu, Shou-En; Tong, Jian; Gong, Jicheng; Thomas, Duncan; Zhu, Tong; Zhang, Junfeng (Jim)

    2014-01-01

    . The fraction of above-detection-limit values for CRP (percentage ≥0.3 mg/L) was reduced from 55% in the pre-Olympic period to 46% in the during-Olympic period and reduced further to 36% in the post-Olympic period. Interquartile range increases in pollutant concentrations were consistently associated with statistically significant increases in fibrinogen, von Wille-brand factor, heart rate, sCD62P, and sCD40L concentrations. Conclusions Changes in air pollution levels during the Beijing Olympics were associated with acute changes in biomarkers of inflammation and thrombosis and measures of cardiovascular physiology in healthy young persons. These findings are of uncertain clinical significance. PMID:22665106

  6. Salivary Cortisol Levels: The Importance of Clown Doctors to Reduce Stress

    PubMed Central

    Saliba, Flávia G.; Adiwardana, Natanael S.; Uehara, Eliane U.; Silvestre, Renata N.; Leite, Victor V.; Faleiros, Francisca T.V.; Padovani, Flávia H.P.; De Gobbi, Juliana I.F.

    2016-01-01

    This study was designed to correlate entertainment of clown-doctors (CD) activities on hospitalized children and aphysiological bio-marker. For this purpose we collected saliva samples and verified children satisfaction with these activities by using a visual analog scale (VAS). Children from 6 to 7 years-old, with diagnosis of any acute pathology, interned in the Pediatric Ward of the Botucatu Medical School Hospital (São Paulo, Brazil) were interviewed. Two groups were taken into consideration: lunchCD and dinnerCD. The following protocol was applied in each group (lunch and dinner): collection of the first saliva sample and presentation of VAS prior to CD activities, followed by collection of a second saliva sample and another VAS assessment after CD activities. The salivary cortisol was reduced in both groups comparing the first saliva sample. The satisfaction of the intervention was evident for lunchCD. The CD intervention is effective in decreasing an important physiological biomarker of stress factor, cortisol, in hospitalized children, been effective for the healing process. PMID:27114816

  7. Salivary Cortisol Levels: The Importance of Clown Doctors to Reduce Stress.

    PubMed

    Saliba, Flávia G; Adiwardana, Natanael S; Uehara, Eliane U; Silvestre, Renata N; Leite, Victor V; Faleiros, Francisca T V; Padovani, Flávia H P; De Gobbi, Juliana I F

    2016-03-31

    This study was designed to correlate entertainment of clown-doctors (CD) activities on hospitalized children and aphysiological bio-marker. For this purpose we collected saliva samples and verified children satisfaction with these activities by using a visual analog scale (VAS). Children from 6 to 7 years-old, with diagnosis of any acute pathology, interned in the Pediatric Ward of the Botucatu Medical School Hospital (São Paulo, Brazil) were interviewed. Two groups were taken into consideration: lunchCD and dinnerCD. The following protocol was applied in each group (lunch and dinner): collection of the first saliva sample and presentation of VAS prior to CD activities, followed by collection of a second saliva sample and another VAS assessment after CD activities. The salivary cortisol was reduced in both groups comparing the first saliva sample. The satisfaction of the intervention was evident for lunchCD. The CD intervention is effective in decreasing an important physiological biomarker of stress factor, cortisol, in hospitalized children, been effective for the healing process.

  8. Metal-based superoxide dismutase and catalase mimics reduce oxidative stress biomarkers and extend life span of Saccharomyces cerevisiae.

    PubMed

    Ribeiro, Thales de P; Fonseca, Fernanda L; de Carvalho, Mariana D C; Godinho, Rodrigo M da C; de Almeida, Fernando Pereira; Saint'Pierre, Tatiana D; Rey, Nicolás A; Fernandes, Christiane; Horn, Adolfo; Pereira, Marcos D

    2017-01-15

    Aging is a natural process characterized by several biological changes. In this context, oxidative stress appears as a key factor that leads cells and organisms to severe dysfunctions and diseases. To cope with reactive oxygen species and oxidative-related damage, there has been increased use of superoxide dismutase (SOD)/catalase (CAT) biomimetic compounds. Recently, we have shown that three metal-based compounds {[Fe(HPClNOL)Cl2]NO3, [Cu(HPClNOL)(CH3CN)](ClO4)2 and Mn(HPClNOL)(Cl)2}, harboring in vitro SOD and/or CAT activities, were critical for protection of yeast cells against oxidative stress. In this work, treating Saccharomyces cerevisiae with these SOD/CAT mimics (25.0 µM/1 h), we highlight the pivotal role of these compounds to extend the life span of yeast during chronological aging. Evaluating lipid and protein oxidation of aged cells, it becomes evident that these mimics extend the life expectancy of yeast mainly due to the reduction in oxidative stress biomarkers. In addition, the treatment of yeast cells with these mimics regulated the amounts of lipid droplet occurrence, consistent with the requirement and protection of lipids for cell integrity during aging. Concerning SOD/CAT mimics uptake, using inductively coupled plasma mass spectrometry, we add new evidence that these complexes, besides being bioabsorbed by S. cerevisiae cells, can also affect metal homeostasis. Finally, our work presents a new application for these SOD/CAT mimics, which demonstrate a great potential to be employed as antiaging agents. Taken together, these promising results prompt future studies concerning the relevance of administration of these molecules against the emerging aging-related diseases such as Parkinson's, Alzheimer's and Huntington's.

  9. Selenoprotein Transcript Level and Enzyme Activity as Biomarkers for Selenium Status and Selenium Requirements of Chickens (Gallus gallus)

    PubMed Central

    Li, Jin-Long; Sunde, Roger A.

    2016-01-01

    The NRC selenium (Se) requirement for broiler chicks is 0.15 μg Se/g diet, based primarily on weight gain and feed intake studies reported in 1986. To determine Se requirements in today’s rapidly growing broiler chick, day-old male chicks were fed Se-deficient basal diets supplemented with graded levels of Se (0, 0.025, 0.05, 0.075, 0.1, 0.2, 0.3, 0.5, 0.75, and 1.0 μg Se/g) as Na2SeO3 (5/treatment). Diets contained 15X the vitamin E requirement, and there were no gross signs of Se-deficiency. At 29 d, Se-deficient chicks weighed 62% of Se-supplemented chicks; 0.025 μg Se/g reversed this effect, indicating a minimum Se requirement of 0.025 μg Se/g diet for growth for male broiler chicks. Enzyme activities in Se-deficient chicks for plasma GPX3, liver and gizzard GPX1, and liver and gizzard GPX4 decreased dramatically to 3, 2, 5, 10 and 5%, respectively, of Se-adequate levels, with minimum Se requirements of 0.10–0.13 μg Se/g, and with defined plateaus above these levels. Pancreas GPX1 and GPX4 activities, however, lacked defined plateaus, with breakpoints at 0.3 μg Se/g. qPCR measurement of all 24 chicken selenoprotein transcripts, plus SEPHS1, found that SEPP1 in liver, GPX3 in gizzard, and SEPP1, GPX3 and SELK in pancreas were expressed at levels comparable to housekeeping transcripts. Only 33%, 25% and 50% of selenoprotein transcripts were down-regulated significantly by Se deficiency in liver, gizzard and pancreas, respectively. No transcripts could be used as biomarkers for supernutritional Se status. For export selenoproteins SEPP1 and GPX3, tissue distribution, high expression and Se-regulation clearly indicate unique Se metabolism, which may underlie tissues targeted by Se deficiency. Based on enzyme activities in liver, gizzard, and plasma, the minimum Se requirement in today’s broiler chick is 0.15 μg Se/g diet; pancreas data indicate that the Se requirement should be raised to 0.2 μg Se/g diet to provide a margin of safety. PMID:27045754

  10. Prognostic usefulness of insulin-like growth factor-binding protein 7 in heart failure with reduced ejection fraction: a novel biomarker of myocardial diastolic function?

    PubMed

    Gandhi, Parul U; Gaggin, Hanna K; Sheftel, Alex D; Belcher, Arianna M; Weiner, Rory B; Baggish, Aaron L; Motiwala, Shweta R; Liu, Peter P; Januzzi, James L

    2014-11-15

    Insulin-like growth factor-binding protein 7 (IGFBP7) is a biomarker that has recently been associated with heart failure and cardiac hypertrophy. The aim of this study was to examine IGFBP7 relative to echocardiographic abnormalities reflecting diastolic dysfunction. One hundred twenty-four patients with ambulatory heart failure with reduced ejection fraction and baseline detailed 2-dimensional echocardiograms were followed for a mean of 10 months. IGFBP7 was measured serially at each office visit; 108 patients underwent follow-up echocardiography. Echocardiographic parameters of diastolic function were compared at baseline and over time. IGFBP7 concentrations were not linked to left ventricular size or systolic function. In contrast, those with elevated baseline IGFBP7 concentrations were more likely to have abnormalities of parameters describing diastolic function, such as higher left atrial volume index, transmitral E/A ratio, E/E' ratio, and right ventricular systolic pressure. IGFBP7 was correlated with left atrial volume index (ρ = 0.237, p = 0.008), transmitral E/A ratio (ρ = 0.304, p = 0.001), E/E' ratio (ρ = 0.257, p = 0.005), and right ventricular systolic pressure (ρ = 0.316, p = 0.001). Furthermore, each was found to be independently predictive of IGFBP7 in adjusted analysis. In subjects with baseline and final echocardiograms, more time spent with elevated IGFBP7 concentrations in serial measurement was associated with worsening diastolic function and increasing left atrial volume index or right ventricular systolic pressure. IGFBP7 concentrations were predictive of an increased risk for cardiovascular events independent of echocardiographic measures of diastolic function (p = 0.006). In conclusion, IGFBP7 is a novel prognostic biomarker for heart failure with reduced ejection fraction and shows significant links to the presence and severity of echocardiographic parameters of abnormal diastolic function.

  11. Cost of reducing aromatics and sulfur levels in motor-vehicle fuels. Volume 2. Final report

    SciTech Connect

    Felten, J.R.; McCarthy, K.M.

    1988-08-01

    Linear-programming (LP) models were developed for five refineries representative of the California refining industry and validated against historic operation. Process options to reduce gasoline and diesel contaminants were selected and represented in the LP models. Costs were estimated to separately reduce aromatics levels in automotive gasoline, aromatics in diesel, and sulfur in diesel for 1991 and 1995. Cost impacts were scaled up to obtain the overall cost impact in California. Estimates were made of total aromatics and benzene levels in gasoline and of sulfur, aromatics, and cetane levels in diesel. Estimates were made of the impact on refinery emissions, automotive emissions, and automotive performance. The cost to reduce diesel sulfur level to .05% was 6.3 cents/gallon. The cost to reduce diesel aromatics level to 10% was 27.6 cents/gallon. The cost to reduce gasoline aromatics levels by 18% was 7.0 cents/gallon.

  12. The Temporal Pattern of Changes in Serum Biomarker Levels Reveals Complex and Dynamically Changing Pathologies after Exposure to a Single Low-Intensity Blast in Mice

    PubMed Central

    Ahmed, Farid; Plantman, Stefan; Cernak, Ibolja; Agoston, Denes V.

    2015-01-01

    Time-dependent changes in blood-based protein biomarkers can help identify the ­pathological processes in blast-induced traumatic brain injury (bTBI), assess injury severity, and monitor disease progression. We obtained blood from control and injured mice (exposed to a single, low-intensity blast) at 2-h, 1-day, 1–week, and 1-month post-injury. We then determined the serum levels of biomarkers related to metabolism (4-HNE, HIF-1α, ceruloplasmin), vascular function (AQP1, AQP4, VEGF, vWF, Flk-1), inflammation (OPN, CINC1, fibrinogen, MIP-1a, OX-44, p38, MMP-8, MCP-1 CCR5, CRP, galectin-1), cell adhesion and the extracellular matrix (integrin α6, TIMP1, TIMP4, Ncad, connexin-43), and axonal (NF-H, Tau), neuronal (NSE, CK-BB) and glial damage (GFAP, S100β, MBP) at various post-injury time points. Our findings indicate that the exposure to a single, low-intensity blast results in metabolic and vascular changes, altered cell adhesion, and axonal and neuronal injury in the mouse model of bTBI. Interestingly, serum levels of several inflammatory and astroglial markers were either unchanged or elevated only during the acute and subacute phases of injury. Conversely, serum levels of the majority of biomarkers related to metabolic and vascular functions, cell adhesion, as well as neuronal and axonal damage remained elevated at the termination of the experiment (1 month), indicating long-term systemic and cerebral alterations due to blast. Our findings show that the exposure to a single, low-intensity blast induces complex pathological processes with distinct temporal profiles. Hence, monitoring serum biomarker levels at various post-injury time points may provide enhanced diagnostics in blast-related neurological and multi-system deficits. PMID:26124743

  13. Sputum biomarkers in IPF: Evidence for raised gene expression and protein level of IGFBP-2, IL-8 and MMP-7

    PubMed Central

    Henket, M.; Corhay, J. L.; Moermans, C.; Louis, R.

    2017-01-01

    Background Idiopathic pulmonary fibrosis (IPF) is a rare lung disease of unknown origin leading rapidly to death. This paper addresses the issue of whether sputum induction is a suitable tool to study respiratory tract inflammation and potential biomarkers in IPF compared to COPD, a fibrosing airway wall disease. Methods In a cross-sectional analysis, 15 IPF patients, 32 COPD and 30 healthy subjects underwent sputum induction. Total sputum cell counts and the amount of TGF- β, IGF-1, IGF-2, IGFBP-1, IGFBP-2, IGFBP-3, IL-8, IL-13, MMP-7, MMP-9, YKL-40, TNF-α and KL-6 in sputum supernatant were analysed. We also profiled gene expression of cells in the induced sputum for TGF-β, MMP-7, YKL-40, IGFBP-2, IL-6, IL-8 and TNF-α. Results IPF patients, like COPD, had increased sputum absolute number of neutrophils, eosinophils, macrophages and epithelial cells compared to HS. IPF sputum supernatants had increased concentrations of IGFBP-2, IL-8, TGF-β, MMP-7, MMP-9 and KL-6 (p<0.05, p<0.0001, p<0.05, p<0.05, p<0.0001, p<0.05 respectively) when compared to healthy subjects where COPD had higher IL-6 and TNF-α levels than IPF (p<0.05 and p<0.05 respectively) and HS (p<0.0001 and p<0.001 respectively) and higher IL-8 and MMP-9 than HS (p<0.0001 and p<0.001 respectively). Conversely to IL-6 and TNF-α, MMP-7 was increased in IPF compared to COPD (p<0.05). The KL-6 and MMP-7 protein levels in sputum were inversely correlated with total lung capacity (TLC, % of predicted) in IPF patients (r = -0.73 and r = -0.53 respectively). Sputum gene expression analysis identified a significant increase for IGFBP-2, IL-6, IL-8 and MMP-7 in IPF compared to HS (p<0.05, p<0.01, p<0.05 and p<0.0001 respectively) and for IGFBP-2, YKL-40, IL-6, IL-8 and MMP-7 compared to COPD (p<0.01, p<0.01, p<0.05, p<0.01 and p<0.0001 respectively). Furthermore, gene expression of TGF-β was increased in IPF compared to COPD (p<0.001) but not to HS. Conclusion Our data show clear increase in expression and

  14. Biomarkers for exposure to ambient air pollution--comparison of carcinogen-DNA adduct levels with other exposure markers and markers for oxidative stress.

    PubMed

    Autrup, H; Daneshvar, B; Dragsted, L O; Gamborg, M; Hansen, M; Loft, S; Okkels, H; Nielsen, F; Nielsen, P S; Raffn, E; Wallin, H; Knudsen, L E

    1999-03-01

    Human exposure to genotoxic compounds present in ambient air has been studied using selected biomarkers in nonsmoking Danish bus drivers and postal workers. A large interindividual variation in biomarker levels was observed. Significantly higher levels of bulky carcinogen-DNA adducts (75.42 adducts/10(8) nucleotides) and of 2-amino-apidic semialdehyde (AAS) in plasma proteins (56.7 pmol/mg protein) were observed in bus drivers working in the central part of Copenhagen, Denmark. In contrast, significantly higher levels of AAS in hemoglobin (55.8 pmol/mg protein), malondialdehyde in plasma (0. 96 nmol/ml plasma), and polycyclic aromatic hydrocarbon (PAH)-albumin adduct (3.38 fmol/ microg albumin) were observed in the suburban group. The biomarker levels in postal workers were similar to the levels in suburban bus drivers. In the combined group of bus drivers and postal workers, negative correlations were observed between bulky carcinogen-DNA adduct and PAH-albumin levels (p = 0.005), and between DNA adduct and [gamma]-glutamyl semialdehyde (GGS) in hemoglobin (p = 0.11). Highly significant correlations were found between PAH-albumin adducts and AAS in plasma (p = 0.001) and GGS in hemoglobin (p = 0.001). Significant correlations were also observed between urinary 8-oxo-7, 8-dihydro-2'-deoxyguanosine and AAS in plasma (p = 0.001) and PAH-albumin adducts (p = 0.002). The influence of the glutatione S-transferase (GST) M1 deletion on the correlation between the biomarkers was studied in the combined group. A significant negative correlation was only observed between bulky carcinogen-DNA adducts and PAH-albumin adducts (p = 0.02) and between DNA adduct and urinary mutagenic activity (p = 0.02) in the GSTM1 null group, but not in the workers who were homozygotes or heterozygotes for GSTM1. Our results indicate that some of the selected biomarkers can be used to distinguish between high and low exposure to environmental genotoxins.

  15. Vaccination induced changes in pro-inflammatory cytokine levels as an early putative biomarker for cognitive improvement in a transgenic mouse model for Alzheimer disease.

    PubMed

    Lin, Xiaoyang; Bai, Ge; Lin, Linda; Wu, Hengyi; Cai, Jianfeng; Ugen, Kenneth E; Cao, Chuanhai

    2014-01-01

    Several pieces of experimental evidence suggest that administration of anti-β amyloid (Aβ) vaccines, passive anti-Aβ antibodies or anti-inflammatory drugs can reduce Aβ deposition as well as associated cognitive/behavioral deficits in an Alzheimer disease (AD) transgenic (Tg) mouse model and, as such, may have some efficacy in human AD patients as well. In the investigation reported here an Aβ 1-42 peptide vaccine was administered to 16-month old APP+PS1 transgenic (Tg) mice in which Aβ deposition, cognitive memory deficits as well as levels of several pro-inflammatory cytokines were measured in response to the vaccination regimen. After vaccination, the anti-Aβ 1-42 antibody-producing mice demonstrated a significant reduction in the sera levels of 4 pro-inflammatory cytokines (TNF-α, IL-6, IL-1 α, and IL-12). Importantly, reductions in the cytokine levels of TNF-α and IL-6 were correlated with cognitive/behavioral improvement in the Tg mice. However, no differences in cerebral Aβ deposition in these mice were noted among the different control and experimental groups, i.e., Aβ 1-42 peptide vaccinated, control peptide vaccinated, or non-vaccinated mice. However, decreased levels of pro-inflammatory cytokines as well as improved cognitive performance were noted in mice vaccinated with the control peptide as well as those immunized with the Aβ 1-42 peptide. These findings suggest that reduction in pro-inflammatory cytokine levels in these mice may be utilized as an early biomarker for vaccination/treatment induced amelioration of cognitive deficits and are independent of Aβ deposition and, interestingly, antigen specific Aβ 1-42 vaccination. Since cytokine changes are typically related to T cell activation, the results imply that T cell regulation may have an important role in vaccination or other immunotherapeutic strategies in an AD mouse model and potentially in AD patients. Overall, these cytokine changes may serve as a predictive marker for AD

  16. Comparison of plasma levels of obesity-related biomarkers among Japanese populations in Tokyo, Japan, São Paulo, Brazil, and Hawaii, USA.

    PubMed

    Iwasaki, Motoki; Le Marchand, Loïc; Franke, Adrian A; Hamada, Gerson Shigeaki; Miyajima, Nelson Tomio; Sharma, Sangita; Yamaji, Taiki; Tsugane, Shoichiro

    2016-01-01

    Although Japanese in Japan and the USA are high-risk populations for colorectal cancer, the prevalence of obesity, one of the established risk factors for this disease, is low in these populations compared with other high-risk populations. To understand this inconsistency, we compared plasma obesity-related biomarkers in cross-sectional studies carried out in Tokyo, São Paulo, and Hawaii. We measured plasma levels of insulin-like growth factor-I (IGF-I), insulin-like growth factor-binding protein (IGFBP)-1, IGFBP-3, C-peptide, adiponectin, leptin, tumor necrosis factor-α, and interleukin-6 by immunoassay and total C-reactive protein, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides using a clinical chemistry autoanalyzer. A total of 299 participants were included in the present analysis, comprising 142 Japanese in Tokyo, 79 Japanese Brazilians in São Paulo, and 78 Japanese Americans in Hawaii. We found significantly lower plasma levels of C-peptide and IGF-I in Japanese in Tokyo than in Japanese Americans, and lower levels of leptin and triglycerides and higher levels of adiponectin, IGFBP-3, and high-density lipoprotein cholesterol in Japanese in Tokyo than in the other two populations. We also observed a significantly higher plasma IGFBP-1 level in Japanese Brazilians, and lower plasma levels of total cholesterol and low-density lipoprotein in Japanese Americans than in the other two populations. We observed significant differences in obesity-related biomarkers between the three Japanese populations. If our results are confirmed, the risk of colorectal cancer predicted on the basis of these biomarkers would be lowest for Japanese in Tokyo, followed by Japanese Brazilians and Japanese Americans.

  17. Blood glutathione peroxidase-1 mRNA levels can be used as molecular biomarkers to determine dietary selenium requirements in rats.

    PubMed

    Sunde, Roger A; Thompson, Kevin M; Evenson, Jacqueline K; Thompson, Britta M

    2009-11-01

    Transcript (mRNA) levels are increasingly being used in medicine as molecular biomarkers for disease and disease risk, including use of whole blood as a target tissue for analysis. Development of blood molecular biomarkers for nutritional status, too, has potential application that parallels opportunities in medicine, including providing solid data for individualized nutrition. We previously reported that blood glutathione peroxidase-1 (Gpx1) mRNA was expressed at levels comparable to major tissues in rats and humans. To determine the efficacy of using blood Gpx1 mRNA to assess selenium (Se) status and requirements, we fed graded levels of Se (0-0.3 microg Se/g as selenite) to weanling male rats. Se status was determined by liver Se concentration and selenoenzyme activity, and selenoprotein mRNA abundance in liver and blood was determined by ribonuclease protection analysis. Liver Se and plasma glutathione peroxidase-3 and liver Gpx1 activities indicated that minimal Se requirements were at 0.08 microg Se/g diet. When total RNA was isolated from whole blood, Gpx1 mRNA in Se-deficient rats decreased to 10% of levels in Se-adequate (0.2 microg Se/g diet) rats. With Se supplementation, blood Gpx1 mRNA levels increased sigmoidally to a plateau with a minimum Se requirement of 0.08 microg Se/g diet, whereas glutathione peroxidase-4 mRNA levels were unaffected. Similarly, Gpx1 mRNA in RNA isolated from fractionated red blood cells decreased in Se-deficient rats to 23% of Se-adequate levels, with a minimum Se requirement of 0.09 microg Se/g diet. Additional studies showed that the preponderance of whole blood Gpx1 mRNA arises from erythroid cells, most likely reticulocytes and young erythrocytes. In summary, whole blood selenoprotein mRNA levels can be used as molecular biomarkers for assessing Se requirements, illustrating that whole blood has potential as a target tissue in development of molecular biomarkers for use in nutrition as well as in medicine.

  18. A School-Level Proxy Measure for Individual-level Poverty Using School-Level Eligibility for Free and Reduced-Price Meals

    ERIC Educational Resources Information Center

    Day, Sophia E.; Hinterland, Kinjia; Myers, Christa; Gupta, Leena; Harris, Tiffany G.; Konty, Kevin J.

    2016-01-01

    Background: Socioeconomic status (SES) impacts health outcomes. The Youth Risk Behavior Survey (YRBS), like many school-based data sources, lacks individual-level poverty information. We propose using school-level percentages of student eligibility for free/reduced-price meals (%FRPM) as a proxy for individual-level poverty. Methods: Using the New…

  19. Dexamethasone-poly(dimethylamino)ethyl methacrylate (pDMAEMA) conjugates reduce inflammatory biomarkers in human intestinal epithelial monolayers

    PubMed Central

    Keely, Simon; Ryan, Sinead; Haddleton, David M.; Limer, Adam; Murphy, Evelyn P.; Colgan, Sean P.; Brayden, David J.

    2014-01-01

    The mucoadhesive polymer, poly(dimethylamino)ethyl methacrylate (pDMAEMA) was synthesised by living radical polymerisation and subsequently conjugated by esterification to the anti-inflammatory corticosteroid, dexamethasone, to separately yield two concentrations of conjugates with ratios of 10:1 and 20:1 active:polymer. The hypothesis was to test whether the active agent maintained in vitro bioactivity when exposed to the apical side of human intestinal epithelial monolayers, Caco-2 and mucous-covered HT29-MTX-E12 (E12). HPLC analysis showed that 80% of the dexamethasone in both conjugates was attached to pDMAEMA. Similar to pDMAEMA, fluorescently-labelled dexamethasone-pDMAEMA conjugates were bioadhesive to Caco-2 and mucoadhesive to E12. Apical addition of conjugates suppressed mRNA expression of the inflammatory markers, NURR1 and ICAM-1 in E12 following stimulation by PGE2 and TNF-α, respectively. Conjugates also suppressed TNF-α stimulated cytokine secretion to the basolateral side of Caco-2 monolayers. pDMAEMA was inactive in these assays. Measurement of dexamethasone permeability from conjugates across monolayers suggested that conjugation reduced permeability compared to free dexamethasone. LDH assay indicated that conjugates were not cytotoxic to monolayers at high concentrations. Anti-inflammatory agents can therefore be successfully conjugated to polymers and they retain adhesion and bioactivity to enable formulation for topical administration. PMID:19110018

  20. Dietary arsenic exposure with low level of arsenic in drinking water and biomarker: a study in West Bengal.

    PubMed

    Mazumder, Debendra Nath Guha; Deb, Debasree; Biswas, Anirban; Saha, Chandan; Nandy, Ashoke; Das, Arabinda; Ghose, Aloke; Bhattacharya, Kallol; Mazumdar, Kunal Kanti

    2014-01-01

    The authors investigated association of arsenic intake through water and diet and arsenic level in urine in people living in arsenic endemic region in West Bengal supplied with arsenic-safe water (<50 μg L(-1)). Out of 94 (Group-1A) study participants using water with arsenic level <50 μg L(-1), 72 participants (Group-1B) were taking water with arsenic level <10 μg L(-1). Multiple regressions analysis conducted on the Group-1A participants showed that daily arsenic dose from water and diet were found to be significantly positively associated with urinary arsenic level. However, daily arsenic dose from diet was found to be significantly positively associated with urinary arsenic level in Group-1B participants only, but no significant association was found with arsenic dose from water in this group. In a separate analysis, out of 68 participants with arsenic exposure through diet only, urinary arsenic concentration was found to correlate positively (r = 0.573) with dietary arsenic in 45 participants with skin lesion while this correlation was insignificant (r = 0.007) in 23 participants without skin lesion. Our study suggested that dietary arsenic intake was a potential pathway of arsenic exposure even where arsenic intake through water was reduced significantly in arsenic endemic region in West Bengal. Observation of variation in urinary arsenic excretion in arsenic-exposed subjects with and without skin lesion needed further study.

  1. Ghrelin O-acyltransferase (GOAT) enzyme is overexpressed in prostate cancer, and its levels are associated with patient's metabolic status: Potential value as a non-invasive biomarker.

    PubMed

    Hormaechea-Agulla, Daniel; Gómez-Gómez, Enrique; Ibáñez-Costa, Alejandro; Carrasco-Valiente, Julia; Rivero-Cortés, Esther; L-López, Fernando; Pedraza-Arevalo, Sergio; Valero-Rosa, José; Sánchez-Sánchez, Rafael; Ortega-Salas, Rosa; Moreno, María M; Gahete, Manuel D; López-Miranda, José; Requena, María J; Castaño, Justo P; Luque, Raúl M

    2016-12-01

    Ghrelin-O-acyltransferase (GOAT) is the key enzyme regulating ghrelin activity, and has been proposed as a potential therapeutic target for obesity/diabetes and as a biomarker in some endocrine-related cancers. However, GOAT presence and putative role in prostate-cancer (PCa) is largely unknown. Here, we demonstrate, for the first time, that GOAT is overexpressed (mRNA/protein-level) in prostatic tissues (n = 52) and plasma/urine-samples (n = 85) of PCa-patients, compared with matched controls [healthy prostate tissues (n = 12) and plasma/urine-samples from BMI-matched controls (n = 28), respectively]. Interestingly, GOAT levels in PCa-patients correlated with aggressiveness and metabolic conditions (i.e. diabetes). Actually, GOAT expression was regulated by metabolic inputs (i.e. In1-ghrelin, insulin/IGF-I) in cultured normal prostate cells and PCa-cell lines. Importantly, ROC-curve analysis unveiled a valuable diagnostic potential for GOAT to discriminate PCa at the tissue/plasma/urine-level with high sensitivity/specificity, particularly in non-diabetic individuals. Moreover, we discovered that GOAT is secreted by PCa-cells, and that its levels are higher in urine samples from a stimulated post-massage vs. pre-massage prostate-test. In conclusion, plasmatic GOAT levels exhibit high specificity/sensitivity to predict PCa-presence compared with other PCa-biomarkers, especially in non-diabetic individuals, suggesting that GOAT holds potential as a novel non-invasive PCa-biomarker.

  2. Biomarkers of respiratory syncytial virus (RSV) infection: specific neutrophil and cytokine levels provide increased accuracy in predicting disease severity.

    PubMed

    Brown, Paul M; Schneeberger, Dana L; Piedimonte, Giovanni

    2015-09-01

    Despite fundamental advances in the research on respiratory syncytial virus (RSV) since its initial identification almost 60 years ago, recurring failures in developing vaccines and pharmacologic strategies effective in controlling the infection have allowed RSV to become a leading cause of global infant morbidity and mortality. Indeed, the burden of this infection on families and health care organizations worldwide continues to escalate and its financial costs are growing. Furthermore, strong epidemiologic evidence indicates that early-life lower respiratory tract infections caused by RSV lead to the development of recurrent wheezing and childhood asthma. While some progress has been made in the identification of reliable biomarkers for RSV bronchiolitis, a "one size fits all" biomarker capable of accurately and consistently predicting disease severity and post-acute outcomes has yet to be discovered. Therefore, it is of great importance on a global scale to identify useful biomarkers for this infection that will allow pediatricians to cost-effectively predict the clinical course of the disease, as well as monitor the efficacy of new therapeutic strategies.

  3. Creating a Culture of Safety by Reducing Noise Levels in the OR.

    PubMed

    Hogan, Lisa J; Harvey, Renee L

    2015-10-01

    We implemented a quality improvement project to reduce noise levels in the OR in response to complaints from the anesthesia staff members at two community hospitals. Excessive noise has been shown to increase staff member stress, fatigue, distraction, and ineffective communication, which can lead to medical errors. We measured noise levels during anesthesia induction and emergence for 118 different surgical procedures and compared noise levels before and after the improvement project intervention. Staff member education and noise reduction strategies, which included signage, prominent noise meters, and specific suggestions to staff members, helped to significantly reduce the noise level during the anesthetic induction and emergence phases of OR procedures.

  4. Impact of dredged urban river sediment on a Saronikos Gulf dumping site (Eastern Mediterranean): sediment toxicity, contaminant levels, and biomarkers in caged mussels.

    PubMed

    Tsangaris, Catherine; Strogyloudi, Evangelia; Hatzianestis, Ioannis; Catsiki, Vassiliki-Angelique; Panagiotopoulos, Ioannis; Kapsimalis, Vasilios

    2014-05-01

    Impacts of chemical contaminants associated with dumping of dredged urban river sediments at a coastal disposal area in Saronikos Gulf (Eastern Mediterranean) were investigated through a combined approach of sediment toxicity testing and active biomonitoring with caged mussels. Chemical analyses of aliphatic hydrocarbons (AHs), polycyclic aromatic hydrocarbons (PAHs), Cu, and Zn in combination with the solid phase Microtox® test were performed on sediments. Concentrations of PAHs, AHs, Cu, and Zn as well as multiple biomarkers of contaminant exposure and/or effects were measured in caged mussels. Sediments in the disposal and neighboring area showed elevated PAHs and AHs concentrations and were characterized as toxic by the solid-phase Microtox® test during and after dumping operations. Biomarker results in the caged mussels indicated sublethal effects mainly during dumping operations, concomitantly with high concentrations of PAHs and AHs in the caged mussel tissues. Cu and Zn concentrations in sediments and caged mussels were generally not elevated except for sediments at the site in the disposal area that received the major amount of dredges. High PAHs and AHs levels as well as sublethal effects in the caged mussels were not persistent after termination of operations. The combined bioassay-biomarker approach proved useful for detecting toxicological impacts of dredged river sediment disposal in sediments and the water column. Nevertheless, further research is needed to evaluate whether sediment toxicity will have long-term effects on benthic communities of the disposal area.

  5. Intersite variations of a battery of biomarkers at different levels of biological organisation in the estuarine endobenthic worm Nereis diversicolor (Polychaeta, Nereididae).

    PubMed

    Fossi Tankoua, O; Buffet, P E; Amiard, J C; Amiard-Triquet, C; Méléder, V; Gillet, P; Mouneyrac, C; Berthet, B

    2012-06-15

    The ragworm Nereis diversicolor has been proposed as a sentinel species for the assessment of estuarine sediment quality. The aim of this study was to test the responsiveness of the worms using a battery of biomarkers in specimens from a moderately contaminated site (Loire estuary, Fr.) and a comparatively cleaner site (Bay of Bourgneuf, Fr.) as a reference site. Ragworms were collected on 7 occasions from April 2008 to October 2009 for the determination of biochemical (GST, AChE, digestive enzymes), physiological (energy reserves (glycogen, lipids and proteins), relationship between length and weight), and behavioural (feeding and burrowing) biomarkers. The biomarker responses were tentatively interpreted in terms of the concept of cascading events potentially responsible for local depletion/extinction of populations submitted to chemical stress. Impairments of AChE and amylase activities, feeding rate, energy reserve concentrations (glycogen and lipids), and the relationship between length and weight showed up differences between the reference site and the Loire estuary despite the latter being far from the most contaminated estuary in France or internationally. However, no links could be established in the Loire estuary ragworms between effects at infra-individual and individual levels, nor with worm population density, even though a small oil spill had occurred in the Loire estuary only one month before the beginning of sampling.

  6. Linking molecular biomarkers with higher level condition indicators to identify effects of copper exposures on the endangered delta smelt (Hypomesus transpacificus).

    PubMed

    Connon, Richard E; Beggel, Sebastian; D'Abronzo, Leandro S; Geist, Juergen P; Pfeiff, Janice; Loguinov, Alexander V; Vulpe, Christopher D; Werner, Inge

    2011-02-01

    The delta smelt (Hypomesus transpacificus) is an endangered pelagic fish species endemic to the Sacramento-San Joaquin estuary (CA, USA), and considered an indicator of ecosystem health. Copper is a contaminant of concern in Californian waterways that may affect the development and survival of this endangered species. The experimental combination of molecular biomarkers with higher level effects may allow for interpretation of responses in a functional context that can be used to predict detrimental outcomes caused by exposure. A delta smelt microarray was developed and applied to screen for candidate molecular biomarkers that may be used in monitoring programs. Functional classifications of microarray responses were used along with quantitative polymerase chain reaction determining effects upon neuromuscular, digestive, and immune responses in Cu-exposed delta smelt. Differences in sensitivity were measured between juveniles and larvae (median lethal concentration = 25.2 and 80.4 µg/L Cu(2+), respectively). Swimming velocity declined with higher exposure concentrations in a dose-dependent manner (r =  -0.911, p < 0.05), though was not statistically significant to controls. Genes encoding for aspartoacylase, hemopexin, α-actin, and calcium regulation proteins were significantly affected by exposure and were functionally interpreted with measured swimming responses. Effects on digestion were measured by upregulation of chitinase and downregulation of amylase, whereas downregulation of tumor necrosis factor indicated a probable compromised immune system. Results from this study, and many others, support the use of functionally characterized molecular biomarkers to assess effects of contaminants in field scenarios. We thus propose that to attribute environmental relevance to molecular biomarkers, research should concentrate on their application in field studies with the aim of assisting monitoring programs.

  7. Potential Biomarkers of Fat Loss as a Feature of Cancer Cachexia

    PubMed Central

    Ebadi, Maryam; Mazurak, Vera C.

    2015-01-01

    Fat loss is associated with shorter survival and reduced quality of life in cancer patients. Effective intervention for fat loss in cachexia requires identification of the condition using prognostic biomarkers for early detection and prevention of further depletion. No biomarkers of fat mass alterations have been defined for application to the neoplastic state. Several inflammatory cytokines have been implicated in mediating fat loss associated with cachexia; however, plasma levels may not relate to adipose atrophy. Zinc-α2-glycoprotein may be a local catabolic mediator within adipose tissue rather than serving as a plasma biomarker of fat loss. Plasma glycerol and leptin associate with adipose tissue atrophy and mass, respectively; however, no study has evaluated their potential as a prognostic biomarker of cachexia-associated fat loss. This review confirms the need for further studies to identify valid prognostic biomarkers to identify loss of fat based on changes in plasma levels of biomarkers. PMID:26508820

  8. Electrochemical immunosensor for detecting typical bladder cancer biomarker based on reduced graphene oxide-tetraethylene pentamine and trimetallic AuPdPt nanoparticles.

    PubMed

    Ma, Hongmin; Zhang, Xiaoyue; Li, Xiaojian; Li, Rongxia; Du, Bin; Wei, Qin

    2015-10-01

    A highly sensitive electrochemical immunosensor for detection of typical bladder cancer biomarker-nuclear matrix protein 22 (NMP22) was developed by using reduced graphene oxide-tetraethylene pentamine (rGO-TEPA) and trimetallic AuPdPt nanoparticles (NPs). rGO-TEPA was used as the ideal material for signal amplification and AuPdPt NPs immobilization due to its excellent conductivity and large surface area. An effective platform was constructed for antibodies anchoring by using AuPdPt NPs, which kept the antibodies' high stability and bioactivity. Moreover, AuPdPt NPs could accelerate the electron transfer and enhance the signal response, which assisted by the synergistic effect of the three different metals (Au, Pd and Pt). The proposed immunosensor showed satisfied performance such as simple fabrication, low detection limits (0.01 U/mL), wide linear range (from 0.040 to 20 U/mL), short analysis time (2 min), high stability and selectivity in the detection of NMP22. Furthermore, the proposed immunosensor was employed to test real urine samples with satisfactory results.

  9. The mRNA level of MLH1 in peripheral blood is a biomarker for the diagnosis of hereditary nonpolyposis colorectal cancer

    PubMed Central

    Yu, Hong; Li, Hui; Cui, Yongan; Xiao, Wei; Dai, Guihong; Huang, Junxing; Wang, Chaofu

    2016-01-01

    Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by functional defects in mismatch repair (MMR) genes, including mutL homolog 1 (MLH1) and mutS homolog 2 (MSH2). This study aimed to assess whether the mRNA expression of MLH1 in peripheral blood could be used as a biomarkers for the diagnosis of HNPCC. The mRNA level of MLH1 was determined in 19 HNPCC families (46 members) using real-time quantitative polymerase chain reaction (qPCR). The mRNA levels of MLH1 in HNPCC were significantly lower than controls (P < 0.001). Receiver operating characteristic (ROC) curve showed a high diagnostic value of the mRNA level of MLH1 for the diagnosis of HNPCC with the area under curve of 0.858. At an optimal cut-off value (0.511), the mRNA level of MLH1 had a sensitivity of 81.3% and a specificity of 86.7% for distinguishing HNPCC from controls. In conclusion, the mRNA expression of MLH1 in peripheral blood may serve as a biomarker for the diagnosis of HNPCC. PMID:27294005

  10. Blood lead levels and enzymatic biomarkers of environmental lead exposure in children in Cordoba, Argentina, after the ban of leaded gasoline.

    PubMed

    Martínez, S A; Simonella, L; Hansen, C; Rivolta, S; Cancela, L M; Virgolini, M B

    2013-05-01

    Lead (Pb) is a developmental neurotoxicant found in industrial activities, many of them already prohibited worldwide. This study aimed to evaluate current blood Pb (PbB) levels in children in Cordoba, Argentina, and to compare these with similar studies performed before Pb was banned in gasoline in 1996. We also sought to identify mechanistically relevant biomarkers by measuring δ-aminolevulinic acid dehydratase (δ-ALAD), superoxide dismutase (SOD), and catalase (CAT) activities. We finally aimed to determine whether sociodemographic characteristics are associated with Pb toxicity. Blood samples collected from 161 healthy children between September 2009 and February 2010 revealed mean PbB levels of 2.58 ± 0.30 µg/dl. Enzymatic δ-ALAD, CAT, and SOD activities showed no significant variations when plotted against PbB levels. Finally, children living in the suburbs have higher PbB levels than their city counterparts, while low socioeconomic status increased δ-ALAD inhibition compared with that of middle-income children. Overall, these results evidenced a substantial reduction in exposure to Pb in this pediatric population over a decade after Pb was restricted in gasoline and reveal the importance of pursuing novel biomarkers of toxicity along with the sociodemographic profile to complement Pb diagnosis.

  11. New alleles of FATB-1A to reduce palmitic acid levels in soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In wild-type soybeans, palmitic acid typically constitutes 10% of the total seed oil. Palmitic acid is a saturated fat linked to increased cholesterol levels, and reducing levels of saturated fats in soybean oil has been a breeding target. To identify novel and useful variation that could help in re...

  12. Interactive Effects of Indigestible Carbohydrates, Protein Type, and Protein Level on Biomarkers of Large Intestine Health in Rats

    PubMed Central

    Taciak, Marcin; Barszcz, Marcin; Tuśnio, Anna; Pastuszewska, Barbara

    2015-01-01

    The effects of indigestible carbohydrates, protein type, and protein level on large intestine health were examined in rats. For 21 days, 12 groups of six 12-week-old male Wistar rats were fed diets with casein (CAS), or potato protein concentrate (PPC), providing 14% (lower protein level; LP), or 20% (higher protein level; HP) protein, and containing cellulose, resistant potato starch, or pectin. Fermentation end-products, pH, and β-glucuronidase levels in cecal digesta, and ammonia levels in colonic digesta were determined. Cecal digesta, tissue weights, cecal and colon morphology, and colonocyte DNA damage were also analyzed. Digesta pH was lower, whereas relative mass of cecal tissue and digesta were higher in rats fed pectin diets than in those fed cellulose. Cecal parameters were greater in rats fed PPC and HP diets than in those fed CAS and LP diets, respectively. Short-chain fatty acid (SCFA) concentrations were unaffected by protein or carbohydrate type. Total SCFA, acetic acid, and propionic acid concentrations were greater in rats fed LP diets than in those fed HP. Cecal pool of isobutyric and isovaleric acids was greater in rats fed PPC than in those fed CAS diets. PPC diets decreased phenol concentration and increased ammonia concentration in cecal and colonic digesta, respectively. Cecal crypt depth was greater in rats fed PPC and HP diets, and was unaffected by carbohydrates; whereas colonic crypt depth was greater in rats fed cellulose. Myenteron thickness in the cecum was unaffected by nutrition, but was greater in the colon of rats fed cellulose. Colonocyte DNA damage was greater in rats fed LP diets than in those fed HP diets, and was unaffected by carbohydrate or protein type. It was found that nutritional factors decreasing cecal digesta weight contribute to greater phenol production, increased DNA damage, and reduced ammonia concentration in the colon. PMID:26536028

  13. Tension between reducing sea-level rise and global warming through solar-radiation management

    NASA Astrophysics Data System (ADS)

    Irvine, P. J.; Sriver, R. L.; Keller, K.

    2012-02-01

    Geoengineering using solar-radiation management (SRM) is gaining interest as a potential strategy to reduce future climate change impacts. Basic physics and past observations suggest that reducing insolation will, on average, cool the Earth. It is uncertain, however, whether SRM can reduce climate change stressors such as sea-level rise or rates of surface air temperature change. Here we use an Earth system model of intermediate complexity to quantify the possible response of sea levels and surface air temperatures to projected climate forcings and SRM strategies. We find that SRM strategies introduce a potentially strong tension between the objectives to reduce (1) the rate of temperature change and (2) sea-level rise. This tension arises primarily because surface air temperatures respond faster to radiative forcings than sea levels. Our results show that the forcing required to stop sea-level rise could cause a rapid cooling with a rate similar to the peak business-as-usual warming rate. Furthermore, termination of SRM was found to produce warming rates up to five times greater than the maximum rates under the business-as-usual CO2 scenario, whereas sea-level rise rates were only 30% higher. Reducing these risks requires a slow phase-out of many decades and thus commits future generations.

  14. PEG-b-AGE Polymer Coated Magnetic Nanoparticle Probes with Facile Functionalization and Anti-fouling Properties for Reducing Non-specific Uptake and Improving Biomarker Targeting

    PubMed Central

    Wang, Liya; Huang, Jing; Wu, Hui; Cheng, Guojun; Zhou, Zhengyang; MacDonald, Tobey; Yang, Lily; Mao, Hui

    2015-01-01

    Non-specific surface adsorption of bio-macromolecules (e.g. proteins) on nanoparticles, known as biofouling, and the uptake of nanoparticles by the mononuclear phagocyte system (MPS) and reticuloendothelial system (RES) lead to substantial reduction in the efficiency of target-directed imaging and delivery in biomedical applications of engineered nanomaterials in vitro and in vivo. In this work, a novel copolymer consisting of blocks of poly ethylene glycol and allyl glycidyl ether (PEG-b-AGE) was developed for coating magnetic iron oxide nanoparticles (IONPs) to reduce non-specific protein adhesion that leads to formation of “protein corona” and uptake by macrophages. The facile surface functionalization was demonstrated by using targeting ligands of a small peptide of RGD or a whole protein of transferrin (Tf). The PEG-b-AGE coated IONPs exhibited anti-biofouling properties with significantly reduced protein corona formation and non-specific uptake by macrophages before and after the surface functionalization, thus improving targeting of RGD-conjugated PEG-b-AGE coated IONPs to integrins in U87MG glioblastoma and MDA-MB-231 breast cancer cells that overexpress αvβ3 integrins, and Tf-conjugated PEG-b-AGE coated IONPs to transferrin receptor (TfR) in D556 and Daoy medulloblastoma cancer cells with high overexpression of transferrin receptor, compared to respective control cell lines. Magnetic resonance imaging (MRI) of cancer cells treated with targeted IONPs with or without anti-biofouling PEG-b-AGE coating polymers demonstrated the target specific MRI contrast change using anti-biofouling PEG-b-AGE coated IONP with minimal off-targeted background compared to the IONPs without anti-biofouling coating, promising the highly efficient active targeting of nanoparticle imaging probes and drug delivery systems and potential applications of imaging quantification of targeted biomarkers. PMID:26594360

  15. PEG-b-AGE Polymer Coated Magnetic Nanoparticle Probes with Facile Functionalization and Anti-fouling Properties for Reducing Non-specific Uptake and Improving Biomarker Targeting.

    PubMed

    Li, Yuancheng; Lin, Run; Wang, Liya; Huang, Jing; Wu, Hui; Cheng, Guojun; Zhou, Zhengyang; MacDonald, Tobey; Yang, Lily; Mao, Hui

    2015-05-07

    Non-specific surface adsorption of bio-macromolecules (e.g. proteins) on nanoparticles, known as biofouling, and the uptake of nanoparticles by the mononuclear phagocyte system (MPS) and reticuloendothelial system (RES) lead to substantial reduction in the efficiency of target-directed imaging and delivery in biomedical applications of engineered nanomaterials in vitro and in vivo. In this work, a novel copolymer consisting of blocks of poly ethylene glycol and allyl glycidyl ether (PEG-b-AGE) was developed for coating magnetic iron oxide nanoparticles (IONPs) to reduce non-specific protein adhesion that leads to formation of "protein corona" and uptake by macrophages. The facile surface functionalization was demonstrated by using targeting ligands of a small peptide of RGD or a whole protein of transferrin (Tf). The PEG-b-AGE coated IONPs exhibited anti-biofouling properties with significantly reduced protein corona formation and non-specific uptake by macrophages before and after the surface functionalization, thus improving targeting of RGD-conjugated PEG-b-AGE coated IONPs to integrins in U87MG glioblastoma and MDA-MB-231 breast cancer cells that overexpress αvβ3 integrins, and Tf-conjugated PEG-b-AGE coated IONPs to transferrin receptor (TfR) in D556 and Daoy medulloblastoma cancer cells with high overexpression of transferrin receptor, compared to respective control cell lines. Magnetic resonance imaging (MRI) of cancer cells treated with targeted IONPs with or without anti-biofouling PEG-b-AGE coating polymers demonstrated the target specific MRI contrast change using anti-biofouling PEG-b-AGE coated IONP with minimal off-targeted background compared to the IONPs without anti-biofouling coating, promising the highly efficient active targeting of nanoparticle imaging probes and drug delivery systems and potential applications of imaging quantification of targeted biomarkers.

  16. Potentials of the elevated circulating miR-185 level as a biomarker for early diagnosis of HBV-related liver fibrosis

    PubMed Central

    Li, Bin-bin; Li, Dong-liang; Chen, Chao; Liu, Bao-hai; Xia, Chun-yan; Wu, Han-jun; Wu, Chao-qun; Ji, Guo-qin; Liu, Su; Ni, Wu; Yao, Ding-kang; Zeng, Zhi-yu; Chen, Da-gui; Qin, Bao-dong; Xin, Xuan; Yan, Gang-li; Dan Tang; Liu, Hui-min; He, Jin; Yan, Hongli; Zhu, Wei-Jian; Yu, Hong-yu; Zhu, Liang

    2016-01-01

    Early diagnosis of liver fibrosis is critical for early intervention and prognosis of various chronic liver diseases. Conventional repeated histological assessment is impractical due to the associated invasiveness. In the current study, we evaluated circulating miR-185 as a potential biomarker to predict initiation and progression of liver fibrosis. We found that miR-185 was significantly up-regulated in blood specimens from patients with HBV-liver fibrosis and rats with liver fibrosis, the miR-185 levels were correlated with liver fibrosis progression, but not with the different viral loads in HBV-infected patients. miR-185 was observed in collagen deposition regions during advanced liver fibrosis. We found that differences in miR-185 levels facilitated the discrimination between early-staged or advanced-staged liver fibrosis and the healthy controls with high specificity, sensitivity, and likelihood ratio using receiver-operator characteristic analysis. miR-185 targeted SREBF1, and increased expression of COL1A1 and a-SMA genes that are hallmarks of liver fibrosis. Our data supported that circulating miR-185 levels could be used as potential biomarkers for the early diagnosis of liver fibrosis. PMID:27677421

  17. CHURCHILL COUNTY, NEVADA ARSENIC STUDY: WATER CONSUMPTION AND EXPOSURE BIOMARKERS

    EPA Science Inventory

    The US Environmental Protection Agency is required to reevaluate the Maximum Contaminant Level (MCL) for arsenic in 2006. To provide data for reducing uncertainties in assessing health risks associated with exposure to low levels (<200 g/l) of arsenic, a large scale biomarker st...

  18. Reduced levels of maternal progesterone during pregnancy increase the risk for allergic airway diseases in females only.

    PubMed

    Hartwig, Isabel R V; Bruenahl, Christian A; Ramisch, Katherina; Keil, Thomas; Inman, Mark; Arck, Petra C; Pincus, Maike

    2014-10-01

    Observational as well as experimental studies support that prenatal challenges seemed to be associated with an increased risk for allergic airway diseases in the offspring. However, insights into biomarkers involved in mediating this risk are largely elusive. We here aimed to test the association between endogenous and exogenous factors documented in pregnant women, including psychosocial, endocrine, and life style parameters, and the risk for allergic airway diseases in the children later in life. We further pursued to functionally test identified factors in a mouse model of an allergic airway response. In a prospectively designed pregnancy cohort (n = 409 families), women were recruited between the 4th and 12th week of pregnancy. To investigate an association between exposures during pregnancy and the incidence of allergic airway disease in children between 3 and 5 years of age, multiple logistic regression analyses were applied. Further, in prenatally stressed adult offspring of BALB/c-mated BALB/c female mice, asthma was experimentally induced by ovalbumin (OVA) sensitization. In addition to the prenatal stress challenge, some pregnant females were treated with the progesterone derivative dihydrodydrogesterone (DHD). In humans, we observed that high levels of maternal progesterone in early human pregnancies were associated with a decreased risk for an allergic airway disease (asthma or allergic rhinitis) in daughters (adjusted OR 0.92; 95% confidence interval [CI] 0.84 to 1.00) but not sons (aOR 1.02, 95% CI 0.94-1.10). In mice, prenatal DHD supplementation of stress-challenged dams attenuated prenatal stress-induced airway hyperresponsiveness exclusively in female offspring. Reduced levels of maternal progesterone during pregnancy-which can result from high stress perception-increase the risk for allergic airway diseases in females but not in males. Key messages: Lower maternal progesterone during pregnancy increases the risk for allergic airway disease

  19. Differential metallothionein, reduced glutathione and metal levels in Perna perna mussels in two environmentally impacted tropical bays in southeastern Brazil.

    PubMed

    Lavradas, Raquel T; Rocha, Rafael C C; Bordon, Isabella C A C; Saint'Pierre, Tatiana D; Godoy, José M; Hauser-Davis, Rachel A

    2016-07-01

    Mussel farming is an important economic activity in Brazil, and these organisms are consumed by the majority of the population in most coastal zones in the country. However, despite the increasing pollution of aquatic ecosystems in Brazil, little is known about the biochemical activity in mussels in response to metal exposure. In this context, the aim of the present study was to investigate metal and metalloid exposure effects in Perna perna mussels, by determining metal levels, the induction of metallothionein (MT) synthesis, and oxidative stress, in the form of reduced glutathione (GSH) in 3 contaminated areas from the Guanabara Bay in comparison to a reference site, Ilha Grande Bay, both in summer and winter. Metal and metalloid concentrations were also compared to Brazilian and international guidelines, to verify potential health risks to human consumers. Mussels from all sampling sites were shown to be improper for human consumption due to metal contamination, including Ilha Grande Bay, which has previously been considered a reference site. Several statistically significant correlations and seasonal differences were observed between MT, GSH and metals and metalloids in both analyzed tissues. A Discriminant Canonical Analysis indicated that the digestive gland is a better bioindicator for environmental contamination by metals and metalloids in this species and offers further proof that MT variations observed are due to metal exposure and not oxidative stress, since GSH influence for both muscle tissue and the digestive glands was non-significant in this analysis. These results show that P. perna mussels are an adequate sentinel species for metal contamination with significant effects on oxidative stress and metal exposure biomarkers. To the best of our knowledge, this is the first study to report metals, metalloids, MT and GSH levels in the muscle tissue of this species.

  20. Levels of Cotinine in Dried Blood Specimens from Newborns as a Biomarker of Maternal Smoking Close to the Time of Delivery

    PubMed Central

    Yang, Juan; Pearl, Michelle; Jacob, Peyton; DeLorenze, Gerald N.; Benowitz, Neal L.; Yu, Lisa; Havel, Christopher; Kharrazi, Martin

    2013-01-01

    The precise quantitation of smoking during pregnancy is difficult in retrospective studies. Routinely collected blood specimens from newborns, stored as dried blood spots, may provide a low-cost method to objectively measure maternal smoking close to the time of delivery. This article compares cotinine levels in dried blood spots to those in umbilical cord blood to assess cotinine in dried blood spots as a biomarker of maternal smoking close to the time of delivery. The California Genetic Disease Screening Program provided dried blood spots from 428 newborns delivered in 2001–2003 with known umbilical cord blood cotinine levels. Cotinine in dried blood spots was measured in 6.35­-mm punches by using liquid chromatography­–tandem mass spectrometry (quantitation limit, 3.1 ng/mL). Repeated measures of cotinine in dried blood spots were highly correlated (R2 = 0.99, P < 0.001) among 100 dried blood spots with cotinine quantitated in 2 separate punches. Linear regression revealed that cotinine levels in dried blood spots were slightly lower than those in umbilical cord blood and predicted umbilical cord blood cotinine levels well (β = 0.95, R2 = 0.80, and P < 0.001 for both cotinine levels in log10 scale). When defining active smoking as a cotinine level of 10 ng/mL or more and using umbilical cord blood cotinine as the criterion standard, we found that measurements of cotinine in dried blood spots had high sensitivity (92.3%) and specificity (99.7%) in the prediction of maternal active smoking. Cotinine levels in dried blood spots are an accurate biomarker of maternal smoking close to the time of delivery. PMID:24068198

  1. Reduced maternal and cord nerve growth factor levels in preterm deliveries.

    PubMed

    Dhobale, Madhavi; Mehendale, Savita; Pisal, Hemlata; Nimbargi, Vandana; Joshi, Sadhana

    2012-04-01

    Nerve growth factor (NGF) is a neurotrophin, which exerts an important role in the development and function of the central and peripheral nervous system. There is limited information regarding the levels of NGF during pregnancy and its role in fetal development. We have earlier reported increased oxidative stress in pregnancy complications. The present study examines the levels of NGF in maternal and cord samples in preterm deliveries and its association with oxidative stress marker. A total number of 96 women delivering preterm (<37 weeks gestation) and 94 women delivering at term (control group) (≥37 weeks gestation) were recruited. Plasma NGF levels were measured in both mother and cord plasma using the Emax Immuno Assay System Promega kit. Maternal and cord plasma NGF levels were significantly reduced (p<0.05 for both) in women delivering preterm as compared to term. There was a positive association between maternal and cord plasma NGF levels (p=0.022). Maternal NGF levels were negatively (p=0.017) associated with maternal malondialdehyde (MDA) levels. Reduced cord NGF levels may affect fetal growth in preterm deliveries which may have implications for the neurodevelopmental pathologies in later life. Circulating maternal NGF levels in preterm pregnancies may be a useful marker to predict NGF levels in the neonate.

  2. Dietary fiber stabilizes blood glucose and insulin levels and reduces physical activity in sows (Sus scrofa).

    PubMed

    de Leeuw, John A; Jongbloed, Age W; Verstegen, Martin W A

    2004-06-01

    The aim of this study was to test whether a diet with a high level of fermentable dietary fiber can stabilize interprandial blood glucose and insulin levels, prevent declines below basal levels, and reduce physical activity in limited-fed breeding sows. Stable levels of glucose and insulin may prevent interprandial feelings of hunger and, consequently, increased activity. Catheterized sows (n = 10) were fed twice daily (0700 and 1900 h) 900 g of a diet with either a low (L-sows) or a high level of fermentable dietary fiber (H-sows; sugarbeet pulp). Blood samples, taken between feeding times, were analyzed for glucose and insulin levels (basal and area under the curve) and stability of levels (variance and sum of absolute differences between levels in consecutive samples). The main focus was on samples taken after the postprandial peak. Behavior was videotaped for analysis of postures and posture changes. Basal glucose and insulin levels did not differ between treatments. H-sows had more stable levels than L-sows. Interprandial levels of H-sows were higher than or equal to basal levels. L-sows showed a decline in glucose below basal levels at 1400 h (P < 0.05). Before 1400 h, no difference in the frequency of posture changes was observed between treatments. After 1400 h, the frequency of posture changes increased more in L-sows than in H-sows. We concluded that sugarbeet pulp as a source of fermentable dietary fiber stabilizes glucose and insulin levels and reduces physical activity in limited-fed sows several hours after feeding. This may indicate a prolonged feeling of satiety.

  3. Effect of physical activity level on biomarkers of inflammation and insulin resistance over 5 years in outpatients with coronary heart disease (from the Heart and Soul Study).

    PubMed

    Jarvie, Jennifer L; Whooley, Mary A; Regan, Mathilda C; Sin, Nancy L; Cohen, Beth E

    2014-10-15

    Higher levels of physical activity are associated with lower rates of coronary heart disease (CHD). Previous studies have suggested that this is due partly to lower levels of inflammation and insulin resistance. The aim of this study was to determine whether physical activity level was associated with inflammation or insulin resistance during a 5-year period in outpatients with known CHD. A total of 656 participants from the Heart and Soul Study, a prospective cohort study of outpatients with documented CHD, were evaluated. Self-reported physical activity frequency was assessed at baseline and after 5 years of follow-up. Participants were classified as low versus high activity at each visit, yielding 4 physical activity groups: stable low activity, decreasing activity (high at baseline to low at year 5), increasing activity (low at baseline to high at year 5), and stable high activity. Year 5 markers of inflammation (C-reactive protein [CRP], interleukin-6, and fibrinogen) and insulin resistance (insulin, glucose, and glycated hemoglobin) were compared across the 4 activity groups. After 5 years of follow-up, higher activity was associated with lower mean levels of all biomarkers. In the fully adjusted regression models, CRP, interleukin-6, and glucose remained independently associated with physical activity frequency (log CRP, p for trend across activity groups = 0.03; log interleukin-6, p for trend = 0.01; log glucose, p for trend = 0.003). Subjects with stable high activity typically had the lowest levels of biomarkers. In conclusion, in this novel population of outpatients with known CHD followed for 5 years, higher physical activity frequency was independently associated with lower levels of CRP, interleukin-6, and glucose.

  4. Investigation of MicroRNA-21 Expression Levels in Serum and Stool as a Potential Non-Invasive Biomarker for Diagnosis of Colorectal Cancer

    PubMed Central

    Bastaminejad, Saiyad; Taherikalani, Morovat; Ghanbari, Reza; Akbari, Akbar; Shabab, Nooshin; Saidijam, Massoud

    2017-01-01

    Background: Most cancer studies focus on exploring non-invasive biomarkers for cancer detection. In the present study, we sought to investigate the expression level of microRNA-21 (miR-21), as a potential diagnostic marker, in serum and stool samples from 40 patients with colorectal cancer (CRC) and 40 healthy controls. Methods: Quantitative real-time RT-PCR was applied to determine the relative expression level of miR-21 in serum and stool. At the same time, the sensitivity and specificity of this marker was evaluated by receiver operating characteristic (ROC) curve analysis. Results: miR-21 expression levels of serum and stool were up-regulated 12.1 (P<0.05, 95% CI: 5.774-34.045) and 10.0 (P<0.05, 95% CI: 0.351-16.260) times in CRC patients, respectively, when compared to the control group. The sensitivity and specificity of miR-21 was found to be 86.05% and 72.97%, respectively (an area under the ROC curve [AUC] of 0.783). The stool miR-21 level in CRC patients was much higher than that in the healthy controls, showing a sensitivity of 86.05% and a specificity of 81.08% (AUC: 0.829). The expression level of miR-21 in stool was able to significantly distinguish CRC tumor, node, metastasis stages III-IV from stages I-II, with a sensitivity and specificity of 88.1% and 81.6%, respectively (AUC: 0.872). Conclusion: The results of this study indicated that miR-21 expression levels in serum and stool can be considered as a potential diagnostic biomarker for the diagnosis of CRC patients. However, more studies are required to confirm the validity of miR-21 as a valuable non-invasive diagnostic tool for CRC. PMID:27432735

  5. Postprandial ghrelin response is reduced in patients with Parkinson's disease and idiopathic REM sleep behaviour disorder: a peripheral biomarker for early Parkinson's disease?

    PubMed

    Unger, Marcus M; Möller, Jens C; Mankel, Katharina; Eggert, Karla M; Bohne, Katharina; Bodden, Maren; Stiasny-Kolster, Karin; Kann, Peter H; Mayer, Geert; Tebbe, Johannes J; Oertel, Wolfgang H

    2011-06-01

    Ghrelin, an orexigenic peptide, has multiple functions, which include promoting gastrointestinal motility and influencing higher brain functions. Experimental data suggest that ghrelin has neuroprotective potential in the MPTP mouse model of Parkinson's disease (PD). PD patients show delayed gastric emptying and other symptoms that may relate to disturbed excretion of ghrelin. No data are available on postprandial ghrelin response in patients with PD and idiopathic REM sleep behaviour disorder (iRBD)--a condition considered a putative preclinical stage of PD. We measured fasting and postprandial ghrelin serum concentrations in 20 healthy controls, 39 (including 19 drug-naïve) PD patients and 11 iRBD patients using a commercial radioimmunoassay for total ghrelin. For statistical analysis we employed ANCOVA and post-hoc testing with Bonferroni's method. Controls showed a decrease of mean fasting ghrelin serum concentrations in the early postprandial phase, followed by a recuperation starting 60 min after the test meal and reaching a maximum at 300 min. This recuperation was less pronounced in PD and iRBD; the slope of relative postprandial ghrelin recovery was different between the investigated groups (p = 0.007). Post-hoc testing showed a difference between controls and PD patients (p = 0.002) and between controls and iRBD patients (p = 0.037). The dynamic regulation of ghrelin in response to food intake is partially impaired in subjects at putative preclinical (iRBD) and clinical stages of PD. Reduced ghrelin excretion might increase the vulnerability of nigrostriatal dopaminergic neurons as suggested by animal studies. The impaired ghrelin excretion might qualify as a peripheral biomarker and be of diagnostic or therapeutic value.

  6. Antioxidant Biomarkers from Vanda coerulea Stems Reduce Irradiated HaCaT PGE-2 Production as a Result of COX-2 Inhibition

    PubMed Central

    Simmler, Charlotte; Antheaume, Cyril; Lobstein, Annelise

    2010-01-01

    Background In our investigations towards the isolation of potentially biologically active constituents from Orchidaceae, we carried out phytochemical and biological analyses of Vanda species. A preliminary biological screening revealed that Vanda coerulea (Griff. ex. Lindl) crude hydro-alcoholic stem extract displayed the best DPPH /•OH radical scavenging activity and in vitro inhibition of type 2 prostaglandin (PGE-2) release from UVB (60 mJ/cm2) irradiated HaCaT keratinocytes. Principal Findings Bio-guided fractionation and phytochemical analysis led to the isolation of five stilbenoids: imbricatin (1) methoxycoelonin (2) gigantol (3) flavidin (4) and coelonin (5). Stilbenoids (1–3) were the most concentrated in crude hydro-alcoholic stem extract and were considered as Vanda coerulea stem biomarkers. Dihydro-phenanthropyran (1) and dihydro-phenanthrene (2) displayed the best DPPH/•OH radical scavenging activities as well as HaCaT intracellular antioxidant properties (using DCFH-DA probe: IC50 8.8 µM and 9.4 µM, respectively) compared to bibenzyle (3) (IC50 20.6 µM). In turn, the latter showed a constant inhibition of PGE-2 production, stronger than stilbenoids (1) and (2) (IC50 12.2 µM and 19.3 µM, respectively). Western blot analysis revealed that stilbenoids (1–3) inhibited COX-2 expression at 23 µM. Interestingly, stilbenoids (1) and (2) but not (3) were able to inhibit human recombinant COX-2 activity. Conclusions Major antioxidant stilbenoids (1–3) from Vanda coerulea stems displayed an inhibition of UVB-induced COX-2 expression. Imbricatin (1) and methoxycoelonin (2) were also able to inhibit COX-2 activity in a concentration-dependent manner thereby reducing PGE-2 production from irradiated HaCaT cells. Our studies suggest that stilbenoids (1–3) could be potentially used for skin protection against the damage caused by UVB exposure. PMID:21060890

  7. Low-level laser therapy (LLLT) associated with aerobic plus resistance training to improve inflammatory biomarkers in obese adults.

    PubMed

    da Silveira Campos, Raquel Munhoz; Dâmaso, Ana Raimunda; Masquio, Deborah Cristina Landi; Aquino, Antonio Eduardo; Sene-Fiorese, Marcela; Duarte, Fernanda Oliveira; Tock, Lian; Parizotto, Nivaldo Antonio; Bagnato, Vanderlei Salvador

    2015-07-01

    Recently, investigations suggest the benefits of low-level laser (light) therapy (LLLT) in noninvasive treatment of cellulite, improvement of body countering, and control of lipid profile. However, the underlying key mechanism for such potential effects associated to aerobic plus resistance training to reduce body fat and inflammatory process, related to obesity in women still unclear. The purpose of the present investigation was to evaluate the effects of combined therapy of LLLT and aerobic plus resistance training in inflammatory profile and body composition of obese women. For this study, it involved 40 obese women with age of 20-40 years. Inclusion criteria were primary obesity and body mass index (BMI) greater than 30 kg/m(2) and less than 40 kg/m(2). The voluntaries were allocated in two different groups: phototherapy group and SHAM group. The interventions consisted on physical exercise training and application of phototherapy (808 nm), immediately after the physical exercise, with special designed device. Proinflammatory/anti-inflammatory adipokines were measured. It was showed that LLLT associated to physical exercise is more effective than physical exercise alone to increase adiponectin concentration, an anti-inflammatory adipokine. Also, it showed reduced values of neck circumference (cm), insulin concentration (μU/ml), and interleukin-6 (pg/ml) in LLLT group. In conclusion, phototherapy can be an important tool in the obesity, mostly considering its potential effects associated to exercise training in attenuating inflammation in women, being these results applicable in the clinical practices to control related risk associated to obesity.

  8. Sound-Level Measurements of a Light Airplane Modified to Reduce Noise Reaching the Ground

    NASA Technical Reports Server (NTRS)

    Vogeley, A W

    1949-01-01

    An Army liaison-type airplane, representative of personal airplanes in the 150 to 200 horsepower class, has been modified to reduce propeller and engine noise according to known principles of airplane-noise reduction. Noise-level measurements demonstrate that, with reference to an observer on the ground, a noisy airplane of this class can be made quiet -- perhaps more quiet than necessary. In order to avoid extreme and unnecessary modifications, acceptable noise levels must be determined.

  9. Ubiquitin Carboxy-Terminal Hydrolase-L1 as a Serum Neurotrauma Biomarker for Exposure to Occupational Low-Level Blast

    PubMed Central

    Carr, Walter; Yarnell, Angela M.; Ong, Ricardo; Walilko, Timothy; Kamimori, Gary H.; da Silva, Uade; McCarron, Richard M.; LoPresti, Matthew L.

    2015-01-01

    Repeated exposure to low-level blast is a characteristic of a few select occupations and there is concern that such occupational exposures present risk for traumatic brain injury. These occupations include specialized military and law enforcement units that employ controlled detonation of explosive charges for the purpose of tactical entry into secured structures. The concern for negative effects from blast exposure is based on rates of operator self-reported headache, sleep disturbance, working memory impairment, and other concussion-like symptoms. A challenge in research on this topic has been the need for improved assessment tools to empirically evaluate the risk associated with repeated exposure to blast overpressure levels commonly considered to be too low in magnitude to cause acute injury. Evaluation of serum-based neurotrauma biomarkers provides an objective measure that is logistically feasible for use in field training environments. Among candidate biomarkers, ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) has some empirical support and was evaluated in this study. We used daily blood draws to examine acute change in UCH-L1 among 108 healthy military personnel who were exposed to repeated low-level blast across a 2-week period. These research volunteers also wore pressure sensors to record blast exposures, wrist actigraphs to monitor sleep patterns, and completed daily behavioral assessments of symptomology, postural stability, and neurocognitive function. UCH-L1 levels were elevated as a function of participating in the 2-week training with explosives, but the correlation of UCH-L1 elevation and blast magnitude was weak and inconsistent. Also, UCH-L1 elevations did not correlate with deficits in behavioral measures. These results provide some support for including UCH-L1 as a measure of central nervous system effects from exposure to low-level blast. However, the weak relation observed suggests that additional indicators of blast effect are needed

  10. Ubiquitin carboxy-terminal hydrolase-l1 as a serum neurotrauma biomarker for exposure to occupational low-level blast.

    PubMed

    Carr, Walter; Yarnell, Angela M; Ong, Ricardo; Walilko, Timothy; Kamimori, Gary H; da Silva, Uade; McCarron, Richard M; LoPresti, Matthew L

    2015-01-01

    Repeated exposure to low-level blast is a characteristic of a few select occupations and there is concern that such occupational exposures present risk for traumatic brain injury. These occupations include specialized military and law enforcement units that employ controlled detonation of explosive charges for the purpose of tactical entry into secured structures. The concern for negative effects from blast exposure is based on rates of operator self-reported headache, sleep disturbance, working memory impairment, and other concussion-like symptoms. A challenge in research on this topic has been the need for improved assessment tools to empirically evaluate the risk associated with repeated exposure to blast overpressure levels commonly considered to be too low in magnitude to cause acute injury. Evaluation of serum-based neurotrauma biomarkers provides an objective measure that is logistically feasible for use in field training environments. Among candidate biomarkers, ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) has some empirical support and was evaluated in this study. We used daily blood draws to examine acute change in UCH-L1 among 108 healthy military personnel who were exposed to repeated low-level blast across a 2-week period. These research volunteers also wore pressure sensors to record blast exposures, wrist actigraphs to monitor sleep patterns, and completed daily behavioral assessments of symptomology, postural stability, and neurocognitive function. UCH-L1 levels were elevated as a function of participating in the 2-week training with explosives, but the correlation of UCH-L1 elevation and blast magnitude was weak and inconsistent. Also, UCH-L1 elevations did not correlate with deficits in behavioral measures. These results provide some support for including UCH-L1 as a measure of central nervous system effects from exposure to low-level blast. However, the weak relation observed suggests that additional indicators of blast effect are needed.

  11. Employing individual measures of baseline glucocorticoids as population-level conservation biomarkers: considering within-individual variation in a breeding passerine

    PubMed Central

    Madliger, Christine L.; Love, Oliver P.

    2016-01-01

    Labile physiological variables, such as stress hormones [i.e. glucocorticoids (GCs)], allow individuals to react to perturbations in their environment and may therefore reflect the effect of disturbances or positive conservation initiatives in advance of population-level demographic measures. Although the application of GCs as conservation biomarkers has been of extensive interest, few studies have explicitly investigated whether baseline GC concentrations respond to disturbances consistently across individuals. However, confirmation of consistent responses is of paramount importance to assessing the ease of use of GCs in natural systems and to making valid interpretations regarding population-level change (or lack of change) in GC concentrations. We investigated whether free-ranging female tree swallows (Tachycineta bicolor) display individually specific changes in baseline glucocorticoid concentrations naturally over the breeding season (from incubation to offspring provisioning) and in response to a manipulation of foraging profitability (representing a decrease in access to food resources). We show that baseline GC concentrations are repeatable within individuals over reproduction in natural conditions. However, in response to a reduction in foraging ability, baseline GC concentrations increase at the population level but are not repeatable within individuals, indicating a high level of within-individual variation. Overall, we suggest that baseline GCs measured on a subset of individuals may not provide a representative indication of responses to environmental change at the population level, and multiple within-individual measures may be necessary to determine the fitness correlates of GC concentrations. Further validation should be completed across a variety of taxa and life-history stages. Moving beyond a traditional cross-sectional approach by incorporating repeated-measures methods will be necessary to assess the suitability of baseline GCs as biomarkers of

  12. Diagnostic and Prognostic Value of Plasma Levels of Cardiac Myosin Binding Protein-C as a Novel Biomarker in Heart Failure.

    PubMed

    El Amrousy, Doaa; Hodeib, Hossam; Suliman, Ghada; Hablas, Nahed; Salama, Eman Ramadan; Esam, Ahmed

    2017-02-01

    Heart failure (HF) has high morbidity and mortality in children. This study aimed to investigate the value of cardiac myosin binding protein-C (cMyBP-C) as a diagnostic and prognostic biomarker in children with heart failure. This study was a prospective case-control study that involved 50 children with acute HF and 25 healthy children of matched age and sex as a control group. cMyBP-C plasma levels were measured in patients with HF at the time of admission and 1 month after treatment. Echocardiographic assessment was done for all children. All patients were followed up for a period of 3 months. There was a significant increase in plasma levels of cMyBP-C (ng/ml) in patients with HF at admission (122.44 ± 41.01) as compared to patients after treatment (71.38 ± 49.68) and to control group (24.40 ± 9.83). This increase was associated with increased severity of HF according to pediatric Ross classification of HF. Significant increase in plasma levels of cMyBP-C at admission and its persistent increase after treatment were associated with adverse outcome of mortality and readmission. Plasma levels of cMyBP-C were significantly correlated with echocardiographic and clinical assessment of heart failure. Plasma levels of cMyBP-C were a good biomarker for diagnosis of HF with sensitivity 100% and specificity 96% at cutoff point of 45 ng/ml. Its value in predicting adverse outcome in HF patients was obtained by ROC curve with sensitivity of 90% and specificity 93% at a cutoff point of 152 ng/ml cMyBP-C at admission. cMyBP-C may be a novel useful diagnostic and prognostic biomarker in children with heart failure and determination of severity of HF in these patients.

  13. Effects of Parsley (Petroselinum crispum) and its Flavonol Constituents, Kaempferol and Quercetin, on Serum Uric Acid Levels, Biomarkers of Oxidative Stress and Liver Xanthine Oxidoreductase Aactivity inOxonate-Induced Hyperuricemic Rats.

    PubMed

    Haidari, Fatemeh; Keshavarz, Seid Ali; Mohammad Shahi, Majid; Mahboob, Soltan-Ali; Rashidi, Mohammad-Reza

    2011-01-01

    Increased serum uric acid is known to be a major risk related to the development of several oxidative stress diseases. The aim of this study was to investigate the effect of parsley, quercetin and kaempferol on serum uric acid levels, liver xanthine oxidoreductase activity and two non-invasive biomarkers of oxidative stress (total antioxidant capacity and malondialdehyde concentration) in normal and oxonate-induced hyperuricemic rats. A total of 60 male Wistar rats were randomly divided into ten equal groups; including 5 normal groups (vehicle, parsley, quercetin, kaempferol and allopurinol) and 5 hyperuricemic groups (vehicle, parsley, quercetin, kaempferol and allopurinol). Parsley (5 g/Kg), quercetin (5 mg/Kg), kaempferol (5 mg/Kg) and allopurinol (5 mg/Kg) were administrated to the corresponding groups by oral gavage once a day for 2 weeks. The results showed that parsley and its flavonol did not cause any significant reduction in the serum uric acid levels in normal rats, but significantly reduced the serum uric acid levels of hyperuricemic rats in a time-dependent manner. All treatments significantly inhibited liver xanthine oxidoreductase activity. Parsley, kaempferol and quercetin treatment led also to a significant increase in total antioxidant capacity and decrease in malondialdehyde concentration in hyperuricemic rats. Although the hypouricemic effect of allopurinol was much higher than that of parsley and its flavonol constituents, it could not significantly change oxidative stress biomarkers. These features of parsley and its flavonols make them as a possible alternative for allopurinol, or at least in combination therapy to minimize the side effects of allopurinol to treat hyperuricemia and oxidative stress diseases.

  14. Circulating Level of Neutrophil Extracellular Traps Is Not a Useful Biomarker for Assessing Disease Activity in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

    PubMed Central

    Ma, Tian-Tian; Zhang, Lu-Xia; Chen, Min; Zhao, Ming-Hui

    2016-01-01

    Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of life-threatening disorders, and frequently affects the kidneys. This study investigated whether the circulating neutrophil extracellular traps (NETs) levels were associated with disease activity of AAV. We collected serum samples from 34 patients with AAV in active stage and 62 patients with AAV in remission. Cell free DNA in serum was quantified using the Quant-iT PicoGreen assay. NETs associated MPO-DNA complexes, citrullinated-histone H3-DNA (cit-H3-DNA) complexes and the concentration of deoxyribonuclease I (DNase I) were quantified using ELISA. The activity of DNase I was quantified using radial enzyme-diffusion method. Associations between circulating levels of NETs with clinico-pathological parameters were analyzed. Serum levels of NETs in active AAV patients were significantly higher than those in healthy controls, and the level of cell free DNA correlated with C-reactive protein (CRP). However, no correlation was found between MPO-DNA complexes or cit-H3-DNA complexes level and CRP. Also there was no significant correlation between NETs level and initial serum creatinine, estimated glomerular filtration rate (eGFR), crescents formation or Birmingham Vasculitis Activity Score (BVAS). Furthermore, there was no significant difference of serum levels of cell free DNA or MPO-DNA complexes between active stage and remission of AAV. In conclusion, circulating levels of NETs cannot be used as a biomarker to assess disease activity in AAV patients. PMID:26840412

  15. Reduced heme levels underlie the exponential growth defect of the Shewanella oneidensis hfq mutant.

    PubMed

    Brennan, Christopher M; Mazzucca, Nicholas Q; Mezoian, Taylor; Hunt, Taylor M; Keane, Meaghan L; Leonard, Jessica N; Scola, Shelby E; Beer, Emma N; Perdue, Sarah; Pellock, Brett J

    2014-01-01

    The RNA chaperone Hfq fulfills important roles in small regulatory RNA (sRNA) function in many bacteria. Loss of Hfq in the dissimilatory metal reducing bacterium Shewanella oneidensis strain MR-1 results in slow exponential phase growth and a reduced terminal cell density at stationary phase. We have found that the exponential phase growth defect of the hfq mutant in LB is the result of reduced heme levels. Both heme levels and exponential phase growth of the hfq mutant can be completely restored by supplementing LB medium with 5-aminolevulinic acid (5-ALA), the first committed intermediate synthesized during heme synthesis. Increasing expression of gtrA, which encodes the enzyme that catalyzes the first step in heme biosynthesis, also restores heme levels and exponential phase growth of the hfq mutant. Taken together, our data indicate that reduced heme levels are responsible for the exponential growth defect of the S. oneidensis hfq mutant in LB medium and suggest that the S. oneidensis hfq mutant is deficient in heme production at the 5-ALA synthesis step.

  16. Schoolwide Intervention to Reduce Chronic Tardiness at the Middle and High School Levels

    ERIC Educational Resources Information Center

    Tyre, Ashli; Feuerborn, Laura; Pierce, Jennifer

    2011-01-01

    When many students are tardy at the secondary level, teachers must continually restart instruction or delay beginning instructional periods throughout the school day. To address the considerable amount of instructional time lost caused by high rates of tardiness, the authors investigated the results of schoolwide intervention to reduce student…

  17. An Action Science Research Approach to Reducing Student Tardiness at the High School Level

    ERIC Educational Resources Information Center

    Gile, Curtis S.

    2013-01-01

    The purpose of this action research study was to design, implement, analyze, and evaluate a series of interventions to reduce student tardiness at the high school level. Another purpose of the study was to determine the underlying values, beliefs, and behaviors associated with student tardiness from a faculty and staff perspective. The study…

  18. Reduced Heme Levels Underlie the Exponential Growth Defect of the Shewanella oneidensis hfq Mutant

    PubMed Central

    Mezoian, Taylor; Hunt, Taylor M.; Keane, Meaghan L.; Leonard, Jessica N.; Scola, Shelby E.; Beer, Emma N.; Perdue, Sarah; Pellock, Brett J.

    2014-01-01

    The RNA chaperone Hfq fulfills important roles in small regulatory RNA (sRNA) function in many bacteria. Loss of Hfq in the dissimilatory metal reducing bacterium Shewanella oneidensis strain MR-1 results in slow exponential phase growth and a reduced terminal cell density at stationary phase. We have found that the exponential phase growth defect of the hfq mutant in LB is the result of reduced heme levels. Both heme levels and exponential phase growth of the hfq mutant can be completely restored by supplementing LB medium with 5-aminolevulinic acid (5-ALA), the first committed intermediate synthesized during heme synthesis. Increasing expression of gtrA, which encodes the enzyme that catalyzes the first step in heme biosynthesis, also restores heme levels and exponential phase growth of the hfq mutant. Taken together, our data indicate that reduced heme levels are responsible for the exponential growth defect of the S. oneidensis hfq mutant in LB medium and suggest that the S. oneidensis hfq mutant is deficient in heme production at the 5-ALA synthesis step. PMID:25356668

  19. Biomarkers of sepsis.

    PubMed

    Faix, James D

    2013-01-01

    Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate's effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high.

  20. Predicting bone remodeling around tissue- and bone-level dental implants used in reduced bone width.

    PubMed

    Eser, Atilim; Tonuk, Ergin; Akca, Kivanc; Dard, Michel M; Cehreli, Murat Cavit

    2013-09-03

    The objective of this study was to predict time-dependent bone remodeling around tissue- and bone-level dental implants used in patients with reduced bone width. The remodeling of bone around titanium tissue-level, and titanium and titanium-zirconium alloy bone-level implants was studied under 100 N oblique load for one month by implementing the Stanford theory into three-dimensional finite element models. Maximum principal stress, minimum principal stress, and strain energy density in peri-implant bone and displacement in x- and y- axes of the implant were evaluated. Maximum and minimum principal stresses around tissue-level implant were higher than bone-level implants and both bone-level implants experienced comparable stresses. Total strain energy density in bone around titanium implants slightly decreased during the first two weeks of loading followed by a recovery, and the titanium-zirconium implant showed minor changes in the axial plane. Total strain energy density changes in the loading and contralateral sides were higher in tissue-level implant than other implants in the cortical bone at the horizontal plane. The displacement values of the implants were almost constant over time. Tissue-level implants were associated with higher stresses than bone-level implants. The time-dependent biomechanical outcome of titanium-zirconium alloy bone-level implant was comparable to the titanium implant.

  1. Effect of self-glazing on reducing the radioactivity levels of red mud based ceramic materials.

    PubMed

    Qin, Shuo; Wu, Bolin

    2011-12-30

    Self-glazing red mud based ceramic materials (RMCM) were produced by normal pressure sintering process using the main raw materials of red mud. The properties of the RMCM samples were investigated by the measurements of mechanical properties, radiation measurement, X-ray diffraction (XRD) and scanning electron microscopy (SEM). The results show that the self-glazing RMCM have good mechanical properties (water absorption and apparent porosity approached zero; bulk density, 2.94 g/cm(3); compressive strength, 78.12 MPa). The radiation level has clear change regularity that the radioactivity levels of red mud (6360 Bq) is obvious declined, and can be reduced to that of the natural radioactive background of Guilin Karst landform, China (3600 Bq). It will not only consume large quantities of red mud, but also decrease the production cost of self-glazing RMCM. And the statement of this paper will offer effective ways to reduce the radioactivity level of red mud.

  2. Restricted cell elongation in Arabidopsis hypocotyls is associated with a reduced average pectin esterification level

    PubMed Central

    Derbyshire, Paul; McCann, Maureen C; Roberts, Keith

    2007-01-01

    Background Cell elongation is mainly limited by the extensibility of the cell wall. Dicotyledonous primary (growing) cell walls contain cellulose, xyloglucan, pectin and proteins, but little is known about how each polymer class contributes to the cell wall mechanical properties that control extensibility. Results We present evidence that the degree of pectin methyl-esterification (DE%) limits cell growth, and that a minimum level of about 60% DE is required for normal cell elongation in Arabidopsis hypocotyls. When the average DE% falls below this level, as in two gibberellic acid (GA) mutants ga1-3 and gai, and plants expressing pectin methyl-esterase (PME1) from Aspergillus aculeatus, then hypocotyl elongation is reduced. Conclusion Low average levels of pectin DE% are associated with reduced cell elongation, implicating PMEs, the enzymes that regulate DE%, in the cell elongation process and in responses to GA. At high average DE% other components of the cell wall limit GA-induced growth. PMID:17572910

  3. Increasing the maximally random jammed density with electric field to reduce the fat level in chocolate

    NASA Astrophysics Data System (ADS)

    Tao, R.; Tang, H.

    Chocolate is one of the most popular food types and flavors in the world. Unfortunately, at present, chocolate products contain too much fat, leading to obesity. For example, a typical molding chocolate has various fat up to 40% in total and chocolate for covering ice cream has fat 50 -60%. Especially, as children are the leading chocolate consumers, reducing the fat level in chocolate products to make them healthier is important and urgent. While this issue was called into attention and elaborated in articles and books decades ago and led to some patent applications, no actual solution was found unfortunately. Why is reducing fat in chocolate so difficult? What is the underlying physical mechanism? We have found that this issue is deeply related to the basic science of soft matters, especially to their viscosity and maximally random jammed (MRJ) density φx. All chocolate productions are handling liquid chocolate, a suspension with cocoa solid particles in melted fat, mainly cocoa butter. The fat level cannot be lower than 1-φxin order to have liquid chocolate to flow. Here we show that that with application of an electric field to liquid chocolate, we can aggregate the suspended particles into prolate spheroids. This microstructure change reduces liquid chocolate's viscosity along the flow direction and increases its MRJ density significantly. Hence the fat level in chocolate can be effectively reduced. We are looking forward to a new class of healthier and tasteful chocolate coming to the market soon. Dept. of Physics, Temple Univ, Philadelphia, PA 19122.

  4. Anabolic androgenic steroid nandrolone decanoate reduces hypothalamic proopiomelanocortin mRNA levels.

    PubMed

    Lindblom, Jonas; Kindlundh, Anna M S; Nyberg, Fred; Bergström, Lena; Wikberg, Jarl E S

    2003-10-03

    Supratherapeutical doses of anabolic androgenic steroids (AASs) have dramatic effects on metabolism in humans, and also inhibit feeding and reduce the rate of body weight gain in rats. In order to test the hypothesis that the AAS metabolic syndrome is accompanied by alterations in the central melanocortin system, we evaluated body weight, food intake and hypothalamic agouti-related protein (AgRP) and proopiomelanocortin (POMC) mRNA levels following administration of different doses of the anabolic androgenic steroid nandrolone decanoate. In order to distinguish changes induced by the steroid treatment per se from those resulting from the reduced food intake and growth rate, we also compared the effect of nandrolone decanoate on AgRP and POMC mRNA expression with both normally fed, and food restricted control groups. We here report that administration of nandrolone specifically reduces arcuate nucleus POMC mRNA levels while not affecting the expression level of AgRP. The effect on POMC expression was not observed in the food restricted controls, excluding the possibility that the observed effect was a mere response to the reduced food intake and body weight. These results raise the possibility that some of the metabolic and behavioural consequences of AAS abuse may be the result of alterations in the melanocortin system.

  5. Linkage of biomarkers along levels of biological complexity in juvenile and adult diazinon fed terrestrial isopod (Porcellio scaber, Isopoda, Crustacea).

    PubMed

    Stanek, Katja; Drobne, Damjana; Trebse, Polonca

    2006-09-01

    In parallel laboratory experiments, we determined the effect of a typical representative of organophosphorous pesticides, diazinon, on AChE activity, lipid, protein and glycogen content, weight change, feeding activity and mortality of juvenile and adult terrestrial isopods Porcellio scaber (Isopoda, Crustacea). Organophosphorous pesticides (OP) are among the most extensively used pesticides, which have replaced organochlorine pesticides. OPs inhibit the enzyme acetylcholinesterase (AChE), resulting in neurotoxicity. They have more widespread effects on non-target organisms than do organochlorine pesticides. The aim of this study was to link effect of diazinon on target enzyme to energy reserves and to integrated biomarker responses in juvenile and adult P. scaber. The non-observed effect concentration (NOEC) for AChE activity after diazinon exposure in two weeks toxicity study with isopods was below 5 microg/g diazinon. There was a good agreement between concentrations at which AChE and survival were affected (10 microg/g diazinon in juveniles, 100 microg/g diazinon in adults). We revealed a link among AChE activity, protein content and mortality. Glycogen and lipid content, feeding activity and weight change were not affected in two weeks diazinon exposure up to 100 microg/g diazinon. Juveniles were affected at concentrations that were an order of magnitude lower than those provoking similar effects on adults. Recommendations are made for future toxicity studies with terrestrial isopods.

  6. The EFFECT trial: evaluating exacerbations, biomarkers, and safety outcomes with two dose levels of fluticasone propionate/formoterol in COPD

    PubMed Central

    Papi, Alberto; Jones, Paul W; Dalvi, Prashant S; McAulay, Kirsten; McIver, Tammy; Dissanayake, Sanjeeva

    2015-01-01

    Inhaled corticosteroid/long-acting β2-agonist combination therapy is recommended in chronic obstructive pulmonary disease (COPD) patients at high risk of exacerbations. The EFFECT (Efficacy of Fluticasone propionate/FormotErol in COPD Treatment) trial is a Phase III, 52-week, randomized, double-blind study to evaluate the efficacy and safety of two doses of fluticasone propionate/formoterol compared to formoterol monotherapy in COPD patients with FEV1 ≥50% predicted and a history of exacerbations. The primary endpoint is the annualized rate of moderate and severe exacerbations. Secondary endpoints include pre-dose FEV1, EXACT-PRO (EXAcerbations of Chronic pulmonary disease Tool – Patient-Reported Outcome)-defined exacerbations, St George’s Respiratory Questionnaire for COPD, COPD Assessment Test, and EXACT-Respiratory Symptoms total score. Lung-specific biomarkers (surfactant protein D and CC chemokine ligand-18) will be measured in a subset of patients to explore their relationship to other clinical indices in COPD and their predictive utility. Pneumonia will be diagnosed per criteria defined by the British Thoracic Society community acquired pneumonia guideline, primarily by radiological confirmation and, additionally, using clinical criteria when a chest radiograph cannot be obtained. Serial measurements of serum potassium, vital signs and electrocardiograms, 24-hour Holter monitoring, and 24-hour urinary cortisol measurement will be performed in a subset of patients in addition to conventional safety assessments. PMID:26648706

  7. Usefulness of DNA Methylation Levels in COASY and SPINT1 Gene Promoter Regions as Biomarkers in Diagnosis of Alzheimer’s Disease and Amnestic Mild Cognitive Impairment

    PubMed Central

    Shinagawa, Shunichiro; Nagata, Tomoyuki; Shimada, Kazuya; Shibata, Nobuto; Ohnuma, Tohru; Kasanuki, Koji; Arai, Heii; Yamada, Hisashi; Nakayama, Kazuhiko; Kondo, Kazuhiro

    2016-01-01

    In order to conduct early therapeutic interventions for Alzheimer’s disease (AD), convenient, early diagnosis markers are required. We previously reported that changes in DNA methylation levels were associated with amnestic mild cognitive impairment (aMCI) and AD. As the results suggested changes in DNA methylation levels in the COASY and SPINT1 gene promoter regions, in the present study we examined DNA methylation in these regions in normal controls (NCs, n = 30), aMCI subjects (n = 28) and AD subjects (n = 30) using methylation-sensitive high resolution melting (MS-HRM) analysis. The results indicated that DNA methylation in the two regions was significantly increased in AD and aMCI as compared to NCs (P < 0.0001, P < 0.0001, ANOVA). Further analysis suggested that DNA methylation in the COASY gene promoter region in particular could be a high sensitivity, high specificity diagnosis biomarker (COASY: sensitivity 96.6%, specificity 96.7%; SPINT1: sensitivity 63.8%, specificity 83.3%). DNA methylation in the COASY promoter region was associated with CDR Scale Sum of Boxes (CDR-SB), an indicator of dementia severity. In the SPINT1 promoter region, DNA methylation was negatively associated with age in NCs and elevated in aMCI and AD subjects positive for antibodies to Herpes simplex virus type 1 (HSV-1). These findings suggested that changes in DNA methylation in the COASY and SPINT1 promoter regions are influenced by various factors. In conclusion, DNA methylation levels in the COASY and SPINT1 promoter regions were considered to potentially be a convenient and useful biomarker for diagnosis of AD and aMCI. PMID:27992572

  8. Elevated serum microRNA-122/222 levels are potential diagnostic biomarkers in Egyptian patients with chronic hepatitis C but not hepatic cancer.

    PubMed

    Motawi, Tarek M K; Sadik, Nermin A H; Shaker, Olfat G; Ghaleb, Maggy H

    2016-07-01

    MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that regulate gene expression at the post-transcriptional level. Because of their size, specificity, and relative stability in plasma, miRNAs can be used as diagnostic and prognostic biomarkers to monitor liver injury, such as that caused by hepatitis C virus (HCV) and liver cancer. In this study, we investigated miRNA expression patterns from the serum of Egyptian patients with HCV and liver cancer compared with matched healthy controls. Using microarray-based expression profiling followed by real-time quantitative polymerase chain reaction validation, we compared the levels of circulating miRNA-122 and miRNA-222 in serum from patients with hepatitis C virus (n = 40) and liver cancer (n = 60) to matched healthy controls (n = 30). MiRNA SNORD68 was the housekeeping endogenous control. We found that the serum levels of miR-122 and miR-222 were significantly elevated in HCV patients, but not in liver cancer patients, compared with controls. Receiver operating characteristic analysis revealed that miR-122 and miR-222 have a high diagnostic potential in discriminating patients with HCV from controls. Serum miR-222 was significantly higher in HCV patients compared to liver cancer patients. Our results indicate that serum miR-122 and miR-222 are elevated in Egyptian patients with chronic HCV, and these miRNAs have a strong potential to serve as novel biomarkers for liver injury but not specifically for liver cancer.

  9. Oxidative stress reduces levels of dysbindin-1A via its PEST domain.

    PubMed

    Yap, Mei-Yi Alicia; Lo, Yew-Long; Talbot, Konrad; Ong, Wei-Yi

    2014-12-01

    Oxidative stress resulting from the generation of reactive oxygen species has been proposed as an etiological factor in schizophrenia. The present study tests the hypothesis that oxidative stress can affect levels of dysbindin-1A, encoded by Dtnbp1, a genetic risk factor for schizophrenia, via its PEST domain. In vitro studies on SH-SY5Y cells indicate that oxidative stress triggers proteasomal degradation of dysbindin-1A, and that this requires interactions with its PEST domain, which may be a TRIM32 target. We specifically found (a) that oxidative stress induced in SH-SY5Y cells by 500 µM hydrogen peroxide reduced levels of full-length dysbindin-1, but did not reduce levels of that protein lacking its PEST domain and (b) that levels of full-length dysbindin-1, but not dysbindin-1 lacking its PEST domain, were higher in cells treated with the proteasome inhibitor MG132. Oxidative stress thus emerges as the first known cellular factor regulating dysbindin-1 isoforms with PEST domains. These findings are consistent with the previously noted fact that phosphorylation of PEST domains often marks proteins for proteasomal degradation, and raises the possibility that treatments reducing oxidative stress in the brain, especially during development, may lower schizophrenia risk.

  10. Mouth-level intake of benzo[a]pyrene from reduced nicotine cigarettes.

    PubMed

    Ding, Yan S; Ward, Jennye; Hammond, David; Watson, Clifford H

    2014-11-18

    Cigarette smoke is a known source of exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs), especially benzo[a]pyrene (BaP). Exposure to BaP in cigarette smoke is influenced by how a person smokes and factors, such as tobacco blend. To determine whether sustained use of reduced-nicotine cigarettes is associated with changes in exposure to nicotine and BaP, levels of BaP in spent cigarette filter butts were correlated with levels of BaP in cigarette smoke to estimate mouth-level intake (MLI) of BaP for 72 daily smokers given three progressively reduced nicotine content cigarettes. Urinary cotinine, a marker of nicotine exposure, and urinary 1-hydroxypyrene (1-HOP), a marker of PAH exposure, were measured throughout the study. Median daily BaP MLI and urine cotinine decreased in a similar manner as smokers switched to progressively lower nicotine cigarettes, despite relatively constant daily cigarette consumption. 1-HOP levels were less responsive to the use of reduced nicotine content cigarettes. We demonstrate that spent cigarette filter butt analysis is a promising tool to estimate MLI of harmful chemicals on a per cigarette or per-day basis, which partially addresses the concerns of the temporal influence of smoking behavior or differences in cigarette design on exposure.

  11. Mouth-Level Intake of Benzo[a]pyrene from Reduced Nicotine Cigarettes

    PubMed Central

    Ding, Yan S.; Ward, Jennye; Hammond, David; Watson, Clifford H.

    2014-01-01

    Cigarette smoke is a known source of exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs), especially benzo[a]pyrene (BaP). Exposure to BaP in cigarette smoke is influenced by how a person smokes and factors, such as tobacco blend. To determine whether sustained use of reduced-nicotine cigarettes is associated with changes in exposure to nicotine and BaP, levels of BaP in spent cigarette filter butts were correlated with levels of BaP in cigarette smoke to estimate mouth-level intake (MLI) of BaP for 72 daily smokers given three progressively reduced nicotine content cigarettes. Urinary cotinine, a marker of nicotine exposure, and urinary 1-hydroxypyrene (1-HOP), a marker of PAH exposure, were measured throughout the study. Median daily BaP MLI and urine cotinine decreased in a similar manner as smokers switched to progressively lower nicotine cigarettes, despite relatively constant daily cigarette consumption. 1-HOP levels were less responsive to the use of reduced nicotine content cigarettes. We demonstrate that spent cigarette filter butt analysis is a promising tool to estimate MLI of harmful chemicals on a per cigarette or per-day basis, which partially addresses the concerns of the temporal influence of smoking behavior or differences in cigarette design on exposure. PMID:25411724

  12. Relevance of Post-Stroke Circulating BDNF Levels as a Prognostic Biomarker of Stroke Outcome. Impact of rt-PA Treatment.

    PubMed

    Rodier, Marion; Quirié, Aurore; Prigent-Tessier, Anne; Béjot, Yannick; Jacquin, Agnès; Mossiat, Claude; Marie, Christine; Garnier, Philippe

    2015-01-01

    The recombinant form of tissue plasminogen activator (rt-PA) is the only curative treatment for ischemic stroke. Recently, t-PA has been linked to the metabolism of brain-derived neurotrophic factor (BDNF), a major neurotrophin involved in post-stroke neuroplasticity. Thus, the objective of our study was to investigate the impact of rt-PA treatment on post-stroke circulating BDNF levels in humans and in animals. Serum BDNF levels and t-PA/plasmin activity were measured at hospital admission and at up to 90 days in stroke patients receiving (n = 24) or not (n = 14) rt-PA perfusion. We investigated the relationships between serum BDNF with concurrent t-PA/plasmin activity, neurological outcomes and cardiovascular scores at admission. In parallel, serum BDNF levels and t-PA/plasmin activity were assessed before and after (1, 4 and 24h) the induction of ischemic stroke in rats. Our study revealed higher serum BDNF levels and better neurological outcome in rt-PA-treated than non-treated patients. However, serum BDNF levels did not predict stroke outcome when the whole cohort of stroke patients was analyzed. By contrast, serum BDNF levels when measured at admission and at day 90 correlated with cardiovascular scores, and those at day 1 correlated with serum t-PA/plasmin activity in the whole cohort of patients whereas no association could be found in the rt-PA-treated group. In rats devoid of cardiovascular risk, no difference in post-stroke serum BDNF levels was detected between rt-PA- and vehicle-treated animals and no correlation was found between serum BDNF levels and t-PA/plasmin activity. Overall, the data suggest that serum BDNF levels may not be useful as a prognostic biomarker of stroke outcome and that endothelial dysfunction could be a confounding factor when serum BDNF levels after stroke are used to reflect of brain BDNF levels.

  13. Relevance of Post-Stroke Circulating BDNF Levels as a Prognostic Biomarker of Stroke Outcome. Impact of rt-PA Treatment

    PubMed Central

    Rodier, Marion; Quirié, Aurore; Prigent-Tessier, Anne; Béjot, Yannick; Jacquin, Agnès; Mossiat, Claude; Marie, Christine; Garnier, Philippe

    2015-01-01

    The recombinant form of tissue plasminogen activator (rt-PA) is the only curative treatment for ischemic stroke. Recently, t-PA has been linked to the metabolism of brain-derived neurotrophic factor (BDNF), a major neurotrophin involved in post-stroke neuroplasticity. Thus, the objective of our study was to investigate the impact of rt-PA treatment on post-stroke circulating BDNF levels in humans and in animals. Serum BDNF levels and t-PA/plasmin activity were measured at hospital admission and at up to 90 days in stroke patients receiving (n = 24) or not (n = 14) rt-PA perfusion. We investigated the relationships between serum BDNF with concurrent t-PA/plasmin activity, neurological outcomes and cardiovascular scores at admission. In parallel, serum BDNF levels and t-PA/plasmin activity were assessed before and after (1, 4 and 24h) the induction of ischemic stroke in rats. Our study revealed higher serum BDNF levels and better neurological outcome in rt-PA-treated than non-treated patients. However, serum BDNF levels did not predict stroke outcome when the whole cohort of stroke patients was analyzed. By contrast, serum BDNF levels when measured at admission and at day 90 correlated with cardiovascular scores, and those at day 1 correlated with serum t-PA/plasmin activity in the whole cohort of patients whereas no association could be found in the rt-PA-treated group. In rats devoid of cardiovascular risk, no difference in post-stroke serum BDNF levels was detected between rt-PA- and vehicle-treated animals and no correlation was found between serum BDNF levels and t-PA/plasmin activity. Overall, the data suggest that serum BDNF levels may not be useful as a prognostic biomarker of stroke outcome and that endothelial dysfunction could be a confounding factor when serum BDNF levels after stroke are used to reflect of brain BDNF levels. PMID:26469350

  14. Inhibition of Hyaluronan Synthesis Reduces Versican and Fibronectin Levels in Trabecular Meshwork Cells

    PubMed Central

    Keller, Kate E.; Sun, Ying Ying; Vranka, Janice A.; Hayashi, Lauren; Acott, Ted S.

    2012-01-01

    Hyaluronan (HA) is a major component of the extracellular matrix (ECM) and is synthesized by three HA synthases (HAS). Similarities between the HAS2 knockout mouse and the hdf mutant mouse, which has a mutation in the versican gene, suggest that HA and versican expression may be linked. In this study, the relationship between HA synthesis and levels of versican, fibronectin and several other ECM components in trabecular meshwork cells from the anterior segment of the eye was investigated. HA synthesis was inhibited using 4-methylumbelliferone (4MU), or reduced by RNAi silencing of each individual HAS gene. Quantitative RT-PCR and immunoblotting demonstrated a reduction in mRNA and protein levels of versican and fibronectin. Hyaluronidase treatment also reduced versican and fibronectin levels. These effects could not be reversed by addition of excess glucose or glucosamine or exogenous HA to the culture medium. CD44, tenascin C and fibrillin-1 mRNA levels were reduced by 4MU treatment, but SPARC and CSPG6 mRNA levels were unaffected. Immunostaining of trabecular meshwork tissue after exposure to 4MU showed an altered localization pattern of HA-binding protein, versican and fibronectin. Reduction of versican by RNAi silencing did not affect HA concentration as assessed by ELISA. Together, these data imply that HA concentration affects synthesis of certain ECM components. Since precise regulation of the trabecular meshwork ECM composition and organization is required to maintain the aqueous humor outflow resistance and intraocular pressure homeostasis in the eye, coordinated coupling of HA levels and several of its ECM binding partners should facilitate this process. PMID:23139787

  15. Chronic treatment with krill powder reduces plasma triglyceride and anandamide levels in mildly obese men.

    PubMed

    Berge, Kjetil; Piscitelli, Fabiana; Hoem, Nils; Silvestri, Cristoforo; Meyer, Ingo; Banni, Sebastiano; Di Marzo, Vincenzo

    2013-05-27

    We have previously shown that treatment of Zucker rats and mice with diet-induced obesity with dietary docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids in the form of krill oil reduces peripheral levels of endocannabinoids, ectopic fat formation and hyperglycemia. We reported that such treatment reduces plasma endocannabinoid levels also in overweight and obese human individuals, in whom high triglycerides may correlate with high circulating endocannabinoid levels. In this study, we report the effects of krill powder, which contains proteins (34%) in addition to krill oil (61.8%), on these two parameters. We submitted 11 obese men (average BMI of 32.3 kg/m², age of 42.6 years and plasma triglycerides of 192.5 ± 96.3 mg/dl) to a 24 week dietary supplementation with krill powder (4 g/day per os) and measured anthropometric and metabolic parameters, as well as blood endocannabinoid (anandamide and 2-arachidonoylglycerol) and esterified DHA and EPA levels. Six subjects were included as control subjects and not given any supplements. The treatment produced, after 12 and 24 weeks, a significant increase in DHA and EPA in total plasma, a 59 and 84% decrease in anandamide plasma levels, and a 22.5 and 20.6% decrease in triglyceride levels, respectively. There was also a significant decrease in waist/hip ratio and visceral fat/skeletal muscle mass ratio at 24 weeks, but no change in body weight. These data confirm that dietary krill powder reduces peripheral endocannabinoid overactivity in obese subjects, and might ameliorate some parameters of the metabolic syndrome.

  16. Chronic corticosterone exposure reduces hippocampal glycogen level and induces depression-like behavior in mice.

    PubMed

    Zhang, Hui-yu; Zhao, Yu-nan; Wang, Zhong-li; Huang, Yu-fang

    2015-01-01

    Long-term exposure to stress or high glucocorticoid levels leads to depression-like behavior in rodents; however, the cause remains unknown. Increasing evidence shows that astrocytes, the most abundant cells in the central nervous system (CNS), are important to the nervous system. Astrocytes nourish and protect the neurons, and serve as glycogen repositories for the brain. The metabolic process of glycogen, which is closely linked to neuronal activity, can supply sufficient energy substrates for neurons. The research team probed into the effects of chronic corticosterone (CORT) exposure on the glycogen level of astrocytes in the hippocampal tissues of male C57BL/6N mice in this study. The results showed that chronic CORT injection reduced hippocampal neurofilament light protein (NF-L) and synaptophysin (SYP) levels, induced depression-like behavior in male mice, reduced hippocampal glycogen level and glycogen synthase activity, and increased glycogen phosphorylase activity. The results suggested that the reduction of the hippocampal glycogen level may be the mechanism by which chronic CORT treatment damages hippocampal neurons and induces depression-like behavior in male mice.

  17. Chronic corticosterone exposure reduces hippocampal glycogen level and induces depression-like behavior in mice*

    PubMed Central

    Zhang, Hui-yu; Zhao, Yu-nan; Wang, Zhong-li; Huang, Yu-fang

    2015-01-01

    Long-term exposure to stress or high glucocorticoid levels leads to depression-like behavior in rodents; however, the cause remains unknown. Increasing evidence shows that astrocytes, the most abundant cells in the central nervous system (CNS), are important to the nervous system. Astrocytes nourish and protect the neurons, and serve as glycogen repositories for the brain. The metabolic process of glycogen, which is closely linked to neuronal activity, can supply sufficient energy substrates for neurons. The research team probed into the effects of chronic corticosterone (CORT) exposure on the glycogen level of astrocytes in the hippocampal tissues of male C57BL/6N mice in this study. The results showed that chronic CORT injection reduced hippocampal neurofilament light protein (NF-L) and synaptophysin (SYP) levels, induced depression-like behavior in male mice, reduced hippocampal glycogen level and glycogen synthase activity, and increased glycogen phosphorylase activity. The results suggested that the reduction of the hippocampal glycogen level may be the mechanism by which chronic CORT treatment damages hippocampal neurons and induces depression-like behavior in male mice. PMID:25559957

  18. Reducing bullying and victimization: student- and classroom-level mechanisms of change.

    PubMed

    Saarento, Silja; Boulton, Aaron J; Salmivalli, Christina

    2015-01-01

    This longitudinal study examines the mediating mechanisms by which the KiVa antibullying program, based on the Participant Role approach, reduces bullying and victimization among elementary school students. Both student-level mechanisms leading to reduced perpetration of bullying and classroom-level mechanisms leading to reductions in bullying and victimization are considered. Analyses are based on a sample of 7,491 students (49.5% boys) nested within 421 classrooms within 77 schools. At the beginning of program implementation, the children were in Grades 4, 5, and 6 (mean age 11.3 years). Multilevel structural equation modeling was used to analyze whether changes in the hypothesized mediators accounted for later reductions in the outcomes. At the student level, antibullying attitudes and perceptions regarding peers' defending behaviors and teacher attitudes toward bullying mediated the effects of KiVa on self-reported bullying perpetration. The effects on peer-reported bullying were only mediated by antibullying attitudes. At the classroom level, the program effects on both self- and peer-reported bullying were mediated by students' collective perceptions of teacher attitudes toward bullying. Also, perceived reinforcing behaviors predicted bullying but did not emerge as a significant mediator. Finally, bullying mediated the effects of the classroom-level factors on victimization. These findings enhance knowledge of the psychosocial developmental processes contributing to bullying and victimization and shed light on the key mechanisms by which school bullying can successfully be counteracted.

  19. High intensity and reduced volume training attenuates stress and recovery levels in elite swimmers.

    PubMed

    Elbe, Anne-Marie; Rasmussen, Camilla P; Nielsen, Glen; Nordsborg, Nikolai B

    2016-01-01

    This study investigated the effect of increased high-intensity interval training (HIT) at the expense of total training volume on the stress and recovery levels of elite swimmers. Forty-one elite swimmers participated in the study and were randomly assigned to either a HIT or a control group (CON). Eleven swimmers did not complete the questionnaires. For 12 weeks both groups trained ~12 h per week. The amount of HIT was ~5 h vs. 1 h, and total distance was ~17 km vs. ~35 km per week for HIT and CON, respectively. HIT was performed as 6-10 × 10-30 s maximal effort interspersed by 2-4 min of rest. The Recovery Stress Questionnaire - Sport was used to measure the swimmers' stress and recovery levels. After the 12 week intervention, the general stress level was 16.6% (2.6-30.7%; mean and 95% CI) lower and the general recovery level was 6.5% (0.7-12.4%) higher in HIT compared to the CON, after adjusting for baseline values. No significant effects could be observed in sports-specific stress or sports-specific recovery. The results indicate that increasing training intensity and reducing training volume for 12 weeks can reduce general stress and increase general recovery levels in competitive swimmers.

  20. Induction of early meconium evacuation: is it effective in reducing the level of neonatal hyperbilirubinemia?

    PubMed

    Bader, David; Yanir, Yoav; Kugelman, Amir; Wilhelm-Kafil, Mira; Riskin, Arieh

    2005-08-01

    This prospective randomized trial evaluated the effect of induction of early meconium evacuation on neonatal jaundice in healthy term neonates. The study group was given glycerin suppository immediately after birth and every 4 hours thereafter, until evacuation of first stool. Glycerin suppository caused faster meconium evacuation but had no effect on mean bilirubin levels at 48 hours. However, males had significantly lower mean bilirubin levels, especially if they also had type A blood group. Glycerin suppository cannot be routinely recommended as a means for reducing the severity of neonatal jaundice. Nonetheless, male newborn with type A blood group may benefit from such a therapy.

  1. Membrane of Functionalized Reduced Graphene Oxide Nanoplates with Angstrom-Level Channels

    PubMed Central

    Lee, Byeongho; Li, Kunzhou; Yoon, Hong Sik; Yoon, Jeyong; Mok, Yeongbong; Lee, Yan; Lee, Hong H.; Kim, Yong Hyup

    2016-01-01

    Membranes with atomic level pores or constrictions are valuable for separation and catalysis. We report a graphene-based membrane with an interlayer spacing of 3.7 angstrom (Å). When graphene oxide nanoplates are functionalized and then reduced, the laminated reduced graphene oxide (rGO) nanoplates or functionalized rGO membrane is little affected by an intercalated fluid, and the interlayer spacing of 3.7 Å increases only to 4.4 Å in wetted state, in contrast to the graphene oxide (GO) membrane whose interlayer spacing increases from 9 Å to 13 Å in wetted state. When applied to ion separation, this membrane reduced the permeation rate of small ions such as K+ and Na+ by three orders of magnitude compared to the GO membrane. PMID:27306853

  2. Low Level Laser Therapy Reduces the Development of Lung Inflammation Induced by Formaldehyde Exposure

    PubMed Central

    Miranda da Silva, Cristiane; Peres Leal, Mayara; Brochetti, Robson Alexandre; Braga, Tárcio; Vitoretti, Luana Beatriz; Saraiva Câmara, Niels Olsen; Damazo, Amílcar Sabino; Ligeiro-de-Oliveira, Ana Paula; Chavantes, Maria Cristina; Lino-dos-Santos-Franco, Adriana

    2015-01-01

    Lung diseases constitute an important public health problem and its growing level of concern has led to efforts for the development of new therapies, particularly for the control of lung inflammation. Low Level Laser Therapy (LLLT) has been highlighted as a non-invasive therapy with few side effects, but its mechanisms need to be better understood and explored. Considering that pollution causes several harmful effects on human health, including lung inflammation, in this study, we have used formaldehyde (FA), an environmental and occupational pollutant, for the induction of neutrophilic lung inflammation. Our objective was to investigate the local and systemic effects of LLLT after FA exposure. Male Wistar rats were exposed to FA (1%) or vehicle (distillated water) during 3 consecutive days and treated or not with LLLT (1 and 5 hours after each FA exposure). Non-manipulated rats were used as control. 24 h after the last FA exposure, we analyzed the local and systemic effects of LLLT. The treatment with LLLT reduced the development of neutrophilic lung inflammation induced by FA, as observed by the reduced number of leukocytes, mast cells degranulated, and a decreased myeloperoxidase activity in the lung. Moreover, LLLT also reduced the microvascular lung permeability in the parenchyma and the intrapulmonary bronchi. Alterations on the profile of inflammatory cytokines were evidenced by the reduced levels of IL-6 and TNF-α and the elevated levels of IL-10 in the lung. Together, our results showed that LLLT abolishes FA-induced neutrophilic lung inflammation by a reduction of the inflammatory cytokines and mast cell degranulation. This study may provide important information about the mechanisms of LLLT in lung inflammation induced by a pollutant. PMID:26569396

  3. Reducing Benzene and Cresol Levels in National Renewable Energy Laboratory's Pilot-Scale Biorefinergy Scrubber Water

    SciTech Connect

    Buzek, M.L.; Phillips, S.

    2004-01-01

    The Thermochemical Process Development Unit at the National Renewable Energy Laboratory converts biomass into energy by gasification or pyrolysis. The aqueous effluent generated in these processes must be disposed of as hazardous waste according to the Resource Conservation and Recovery Act because certain components exceed the regulatory concentration limit. Gas stripping of the scrubber water was investigated as a method of reducing benzene and cresol levels. A custom-designed packed-bed column was built and a half-factorial experimental design was implemented to determine the effects of gas flow rate, liquid flow rate, and column packing height on the final benzene concentration in the liquid. The experimental results show that packing height had a significant effect on final benzene concentration; gas flow rate and liquid flow rate had little effect. The effects of each design variable on final cresol concentration were not determined. Although the current column design did significantly reduce the benzene and cresol levels in the scrubber water, it did not reduce the concentrations below the regulatory limits. A full-factorial experimental design will be implemented with an increased packing height. Other variables, including column diameter and packing type, will be investigated to determine their effects on final benzene and cresol concentrations. Once the packed-bed column is determined to be effective in reducing contaminant concentrations below the regulatory limit, photocatalytic oxidation will be explored for remediating the benzene and cresol from the gas stream.

  4. Is it possible to reduce the knee joint compression force during level walking with hiking poles?

    PubMed

    Jensen, S B; Henriksen, M; Aaboe, J; Hansen, L; Simonsen, E B; Alkjaer, T

    2011-12-01

    Walking with hiking poles has become a popular way of exercising. Walking with poles is advocated as a physical activity that significantly reduces the loading of the hip, knee and ankle joints. We have previously observed that pole walking does not lead to a reduction of the load on the knee joint. However, it is unclear whether an increased force transmitted through the poles can reduce the load on the knee joint. Thus, the purpose of the present study was to investigate if an increased load transmitted through the arms to the poles could reduce the knee joint compression force during level walking with poles. We hypothesized that an increased pole force would result in a reduction of the knee joint compression force. Gait analyses from 10 healthy subjects walking with poles were obtained. The pole force was measured simultaneously during the gait analyses. The knee joint compression forces were estimated by using a biomechanical knee joint model. The results showed that the subjects were able to increase the pole force by 2.4 times the normal pole force. However, this did not lead to a reduction in the knee joint compressive force and we rejected our hypothesis. In conclusion, the use of poles during level walking does not seem to reduce knee joint compressive loads. However, it is possible that the use of poles in other populations (e.g. osteoarthritis patients) and in terrain would unload the knee joint. This should be investigated in the future.

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

    PubMed Central

    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

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

    PubMed

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

    2016-06-06

    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.

  7. Hydrogen gas alleviates oxygen toxicity by reducing hydroxyl radical levels in PC12 cells

    PubMed Central

    Yu, Junchao; Yu, Qiuhong; Liu, Yaling; Zhang, Ruiyun; Xue, Lianbi

    2017-01-01

    Hyperbaric oxygen (HBO) therapy through breathing oxygen at the pressure of above 1 atmosphere absolute (ATA) is useful for varieties of clinical conditions, especially hypoxic-ischemic diseases. Because of generation of reactive oxygen species (ROS), breathing oxygen gas at high pressures can cause oxygen toxicity in the central nervous system, leading to multiple neurological dysfunction, which limits the use of HBO therapy. Studies have shown that Hydrogen gas (H2) can diminish oxidative stress and effectively reduce active ROS associated with diseases. However, the effect of H2 on ROS generated from HBO therapy remains unclear. In this study, we investigated the effect of H2 on ROS during HBO therapy using PC12 cells. PC12 cells cultured in medium were exposed to oxygen gas or mixed oxygen gas and H2 at 1 ATA or 5 ATA. Cells viability and oxidation products and ROS were determined. The data showed that H2 promoted the cell viability and inhibited the damage in the cell and mitochondria membrane, reduced the levels of lipid peroxidation and DNA oxidation, and selectively decreased the levels of •OH but not disturbing the levels of O2•-, H2O2, or NO• in PC12 cells during HBO therapy. These results indicated that H2 effectively reduced •OH, protected cells against oxygen toxicity resulting from HBO therapy, and had no effect on other ROS. Our data supported that H2 could be potentially used as an antioxidant during HBO therapy. PMID:28362819

  8. Reduced Activity-Dependent Protein Levels in a Mouse Model of the Fragile X Premutation

    PubMed Central

    von Leden, Ramona E.; Curley, Lindsey C.; Greenberg, Gian D.; Hunsaker, Michael R.; Willemsen, Rob; Berman, Robert F.

    2014-01-01

    Environmental enrichment results in increased levels of Fmrp in brain and increased dendritic complexity. The present experiment evaluated activity-dependent increases in Fmrp levels in the motor cortex in response to training on a skilled forelimb reaching task in the CGG KI mouse model of the fragile X premutation. Fmrp, Arc, and c-Fos protein levels were quantified by Western blot in the contralateral motor cortex of mice following training to reach for sucrose pellets with a non-preferred paw and compared to levels in the ipsilateral motor cortex. After training, all mice showed increases in Fmrp, Arc, and c-Fos protein levels in the contralateral compared to the ipsilateral hemisphere; however, the increase in CGG KI mice was less than wildtype mice. Increases in Fmrp and Arc proteins scaled with learning, whereas this relationship was not observed with the c-Fos levels. These data suggest the possibility that reduced levels of activity-dependent proteins associated with synaptic plasticity such as Fmrp and Arc may contribute to the neurocognitive phenotype reported in the CGG KI mice and the fragile X premutation. PMID:24462720

  9. Methoxychlor reduces estradiol levels by altering steroidogenesis and metabolism in mouse antral follicles in vitro.

    PubMed

    Basavarajappa, Mallikarjuna S; Craig, Zelieann R; Hernández-Ochoa, Isabel; Paulose, Tessie; Leslie, Traci C; Flaws, Jodi A

    2011-06-15

    The organochlorine pesticide methoxychlor (MXC) is a known endocrine disruptor that affects adult rodent females by causing reduced fertility, persistent estrus, and ovarian atrophy. Since MXC is also known to target antral follicles, the major producer of sex steroids in the ovary, the present study was designed to test the hypothesis that MXC decreases estradiol (E₂) levels by altering steroidogenic and metabolic enzymes in the antral follicles. To test this hypothesis, antral follicles were isolated from CD-1 mouse ovaries and cultured with either dimethylsulfoxide (DMSO) or MXC. Follicle growth was measured every 24 h for 96 h. In addition, sex steroid hormone levels were measured using enzyme-linked immunosorbent assays (ELISA) and mRNA expression levels of steroidogenic enzymes as well as the E₂ metabolic enzyme Cyp1b1 were measured using qPCR. The results indicate that MXC decreased E₂, testosterone, androstenedione, and progesterone (P₄) levels compared to DMSO. In addition, MXC decreased expression of aromatase (Cyp19a1), 17β-hydroxysteroid dehydrogenase 1 (Hsd17b1), 17α-hydroxylase/17,20-lyase (Cyp17a1), 3β hydroxysteroid dehydrogenase 1 (Hsd3b1), cholesterol side-chain cleavage (Cyp11a1), steroid acute regulatory protein (Star), and increased expression of Cyp1b1 enzyme levels. Thus, these data suggest that MXC decreases steroidogenic enzyme levels, increases metabolic enzyme expression and this in turn leads to decreased sex steroid hormone levels.

  10. Reduced activity-dependent protein levels in a mouse model of the fragile X premutation.

    PubMed

    von Leden, Ramona E; Curley, Lindsey C; Greenberg, Gian D; Hunsaker, Michael R; Willemsen, Rob; Berman, Robert F

    2014-03-01

    Environmental enrichment results in increased levels of Fmrp in brain and increased dendritic complexity. The present experiment evaluated activity-dependent increases in Fmrp levels in the motor cortex in response to training on a skilled forelimb reaching task in the CGG KI mouse model of the fragile X premutation. Fmrp, Arc, and c-Fos protein levels were quantified by Western blot in the contralateral motor cortex of mice following training to reach for sucrose pellets with a non-preferred paw and compared to levels in the ipsilateral motor cortex. After training, all mice showed increases in Fmrp, Arc, and c-Fos protein levels in the contralateral compared to the ipsilateral hemisphere; however, the increase in CGG KI mice was less than wildtype mice. Increases in Fmrp and Arc proteins scaled with learning, whereas this relationship was not observed with the c-Fos levels. These data suggest the possibility that reduced levels of activity-dependent proteins associated with synaptic plasticity such as Fmrp and Arc may contribute to the neurocognitive phenotype reported in the CGG KI mice and the fragile X premutation.

  11. High plasma levels of vitamin E forms and reduced Alzheimer's disease risk in advanced age.

    PubMed

    Mangialasche, Francesca; Kivipelto, Miia; Mecocci, Patrizia; Rizzuto, Debora; Palmer, Katie; Winblad, Bengt; Fratiglioni, Laura

    2010-01-01

    In this study we investigated the association between plasma levels of eight forms of vitamin E and incidence of Alzheimer's disease (AD) among oldest-old individuals in a population-based setting. A dementia-free sample of 232 subjects aged 80+ years, derived from the Kungsholmen Project, was followed-up to 6 years to detect incident AD. Plasma levels of vitamin E (alpha-, beta-, gamma, and delta-tocopherol; alpha-, beta-, gamma-, and delta-tocotrienol) were measured at baseline. Vitamin E forms-AD association was analyzed with Cox proportional hazard model after adjustment for several potential confounders. Subjects with plasma levels of total tocopherols, total tocotrienols, or total vitamin E in the highest tertile had a reduced risk of developing AD in comparison to persons in the lowest tertile. Multi-adjusted hazard ratios (HRs) and 95% confidence interval (CI) were 0.55 (0.32-0.94) for total tocopherols, 0.46 (0.23-0.92) for total tocotrienols, and 0.55 (0.32-0.94) for total vitamin E. When considering each vitamin E form, the risk of developing AD was reduced only in association with high plasma levels of beta-tocopherol (HR: 0.62, 95% CI 0.39-0.99), whereas alpha-tocopherol, alpha- tocotrienol, and beta-tocotrienol showed only a marginally significant effect in the multiadjusted model [HR (95% CI): alpha-tocopherol: 0.72 (0.48-1.09); alpha-tocotrienol: 0.70 (0.44-1.11); beta-tocotrienol: 0.69 (0.45-1.06)]. In conclusion, high plasma levels of vitamin E are associated with a reduced risk of AD in advanced age. The neuroprotective effect of vitamin E seems to be related to the combination of different forms, rather than to alpha-tocopherol alone, whose efficacy in interventions against AD is currently debated.

  12. Biomarkers for antipsychotic therapies.

    PubMed

    Pich, Emilio Merlo; Vargas, Gabriel; Domenici, Enrico

    2012-01-01

    Molecular biomarkers for antipsychotic treatments have been conceptually linked to the measurements of dopamine functions, mostly D(2) receptor occupancy, either by imaging using selective PET/SPECT radioactive tracers or by assessing plasma prolactin levels. A quest for novel biomarkers was recently proposed by various academic, health service, and industrial institutions driven by the need for better treatments of psychoses. In this review we conceptualize biomarkers within the Translational Medicine paradigm whose goal was to provide support to critical decision-making in drug discovery. At first we focused on biomarkers as outcome measure of clinical studies by searching into the database clinicaltrial.gov. The results were somewhat disappointing, showing that out of 1,659 antipsychotic trials only 18 used a biomarker as an outcome measure. Several of these trials targeted plasma lipids as sentinel marker for metabolic adverse effects associated with the use of atypical antipsychotics, while only few studies were aimed to new disease specific biological markers. As an example of a mechanistic biomarker, we described the work done to progress the novel class of glycine transporter inhibitors as putative treatment for negative symptoms of schizophrenia. We also review how large-scale multiplex biological assays were applied to samples from tissues of psychiatric patients, so to learn from changes of numerous analytes (metabolic products, lipids, proteins, RNA transcripts) about the substrates involved in the disease. We concluded that a stringent implementation of these techniques could contribute to the endophenotypic characterization of patients, helping in the identification of key biomarkers to drive personalized medicine and new treatment development.

  13. Reduced Hepatic Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Level in Obesity

    PubMed Central

    Heinrich, Garrett; Muturi, Harrison T.; Rezaei, Khadijeh; Al-Share, Qusai Y.; DeAngelis, Anthony M.; Bowman, Thomas A.; Ghadieh, Hilda E.; Ghanem, Simona S.; Zhang, Deqiang; Garofalo, Robert S.; Yin, Lei; Najjar, Sonia M.

    2017-01-01

    Impairment of insulin clearance is being increasingly recognized as a critical step in the development of insulin resistance and metabolic disease. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes insulin clearance. Null deletion or liver-specific inactivation of Ceacam1 in mice causes a defect in insulin clearance, insulin resistance, steatohepatitis, and visceral obesity. Immunohistological analysis revealed reduction of hepatic CEACAM1 in obese subjects with fatty liver disease. Thus, we aimed to determine whether this occurs at the hepatocyte level in response to systemic extrahepatic factors and whether this holds across species. Northern and Western blot analyses demonstrate that CEACAM1 mRNA and protein levels are reduced in liver tissues of obese individuals compared to their lean age-matched counterparts. Furthermore, Western analysis reveals a comparable reduction of CEACAM1 protein in primary hepatocytes derived from the same obese subjects. Similar to humans, Ceacam1 mRNA level, assessed by quantitative RT-PCR analysis, is significantly reduced in the livers of obese Zucker (fa/fa, ZDF) and Koletsky (f/f) rats relative to their age-matched lean counterparts. These studies demonstrate that the reduction of hepatic CEACAM1 in obesity occurs at the level of hepatocytes and identify the reduction of hepatic CEACAM1 as a common denominator of obesity across multiple species.

  14. Apathy and APOE4 are associated with reduced BDNF levels in Alzheimer's disease.

    PubMed

    Alvarez, Antón; Aleixandre, Manuel; Linares, Carlos; Masliah, Eliezer; Moessler, Herbert

    2014-01-01

    Reduced brain-derived neurotrophic factor (BDNF) signaling is considered as a pathogenic event in early Alzheimer's disease (AD), but the influence of apathy and apolipoprotein E ε4 allele (APOE4) on serum BDNF values was not previously investigated in AD. We evaluated serum BDNF levels in AD, amnestic mild cognitive impairment (MCI), and control subjects. Baseline BDNF levels were similar in AD, MCI, and controls. AD patients having apathy showed lower BDNF values than patients without apathy (p < 0.05). After correction for the influence of apathy, APOE4 carriers showed lower BDNF levels (p < 0.01) and MMSE scores (p < 0.01) than non-APOE4 carriers in the subgroup of AD females, but not in males. Significant (p < 0.05) positive correlations between BDNF values and MMSE scores were only observed in subgroups of AD males and of AD patients without apathy. These results are showing the association of apathy and APOE4 with reduced serum BDNF levels in AD, and are suggesting that BDNF reductions might contribute to the worse cognitive performance exhibited by AD apathetic patients and female APOE4 carriers.

  15. Oxidative DNA damage levels and catalase activity in the clam Ruditapes decussatus as pollution biomarkers of Tunisian marine environment.

    PubMed

    Jebali, Jamel; Banni, Mohamed; de Almeida, Eduardo Alves; Boussetta, Hamadi

    2007-01-01

    Levels of the oxidative DNA damage 7, 8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG) and catalase (CAT) activity were measured in the digestive gland and gills of clams Ruditapes decussatus, related to the presence of pollutants along Tunisian marine environment. Increased levels of CAT were observed in tissues of clams from all the sites studied, compared to control values, and elevated 8-oxodG levels were observed at specific sites. Results obtained in this work indicate that the measurement of 8-oxodG levels and CAT activity in tissues of R. decussatus is promising in pollution monitoring studies of the Tunisian marine environment.

  16. Instructions, feedback, and reinforcement in reducing activity levels in the classroom.

    PubMed

    Schulman, J L; Suran, B G; Stevens, T M; Kupst, M J

    1979-01-01

    The biomotometer, an electronic device which simultaneously measures motor activity and provides auditory feedback, was used in combination with material reinforcers in an experiment to reduce children's activity level in a classroom setting. Subjects were nine boys and two girls, aged 9--13, from a day hospital program for emotionally disturbed children. After five baseline trials, each child had five contingent reinforcement trials in which he/she received feedback "beeps" from the biomotometer and was given toy or candy rewards after each trial in which activity fell at least 20% below mean baseline level. Then five noncontingent reinforcement trials were run in which children received rewards for wearing the apparatus without the feedback attachment. Results indicated that the intervention "package," including instructions, feedback, and contingent reinforcement, was successful in all five trials for 8 of 11 children. Activity levels increased during the final noncontingent phase.

  17. Dual-Level LVDS Technique for Reducing Data Transmission Lines by Half in LCD Driver IC's

    NASA Astrophysics Data System (ADS)

    Kim, Doo-Hwan; Yang, Sung-Hyun; Cho, Kyoung-Rok

    This paper proposes a dual-level low voltage differential signaling (DLVDS) circuit aimed at low power consumption and reducing transmission lines for LCD driver IC's. We apply two-bit binary data to the DLVDS circuit as inputs, and then the circuit converts these two inputs into two kinds of fully differential signal levels. In the DLVDS circuit, two transmission lines are sufficient to transfer two-bit binary inputs while keeping the conventional LVDS features. The receiver recovers the original two-bit binary data through a level decoding circuit. The proposed circuit was fabricated using a commercial 0.25μm CMOS technology. Under a 2.5V supply voltage, the circuit shows a data rate of 1-Gbps/2-line and power consumption of 35mW.

  18. Sulforaphane restores cellular glutathione levels and reduces chronic periodontitis neutrophil hyperactivity in vitro.

    PubMed

    Dias, Irundika H K; Chapple, Ian L C; Milward, Mike; Grant, Melissa M; Hill, Eric; Brown, James; Griffiths, Helen R

    2013-01-01

    The production of high levels of reactive oxygen species by neutrophils is associated with the local and systemic destructive phenotype found in the chronic inflammatory disease periodontitis. In the present study, we investigated the ability of sulforaphane (SFN) to restore cellular glutathione levels and reduce the hyperactivity of circulating neutrophils associated with chronic periodontitis. Using differentiated HL60 cells as a neutrophil model, here we show that generation of extracellular O2 (. -) by the nicotinamide adenine dinucleotide (NADPH) oxidase complex is increased by intracellular glutathione depletion. This may be attributed to the upregulation of thiol regulated acid sphingomyelinase driven lipid raft formation. Intracellular glutathione was also lower in primary neutrophils from periodontitis patients and, consistent with our previous findings, patients neutrophils were hyper-reactive to stimuli. The activity of nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of the antioxidant response, is impaired in circulating neutrophils from chronic periodontitis patients. Although patients' neutrophils exhibit a low reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio and a higher total Nrf2 level, the DNA-binding activity of nuclear Nrf2 remained unchanged relative to healthy controls and had reduced expression of glutamate cysteine ligase catalytic (GCLC), and modifier (GCLM) subunit mRNAs, compared to periodontally healthy subjects neutrophils. Pre-treatment with SFN increased expression of GCLC and GCM, improved intracellular GSH/GSSG ratios and reduced agonist-activated extracellular O2 (. -) production in both dHL60 and primary neutrophils from patients with periodontitis and controls. These findings suggest that a deficiency in Nrf2-dependent pathways may underpin susceptibility to hyper-reactivity in circulating primary neutrophils during chronic periodontitis.

  19. Reduced ubiquitin C-terminal hydrolase-1 expression levels in dementia with Lewy bodies.

    PubMed

    Barrachina, Marta; Castaño, Esther; Dalfó, Esther; Maes, Tamara; Buesa, Carlos; Ferrer, Isidro

    2006-05-01

    Parkinson disease (PD) and dementia with Lewy bodies (DLB) are characterized by the accumulation of abnormal alpha-synuclein and ubiquitin in protein aggregates conforming Lewy bodies and Lewy neurites. Ubiquitin C-terminal hydrolase-1 (UCHL-1) disassembles polyubiquitin chains to increase the availability of free monomeric ubiquitin to the ubiquitin proteasome system (UPS) thus favoring protein degradation. Since mutations in the UCHL-1 gene, reducing UPS activity by 50%, have been reported in autosomal dominant PD, and UCHL-1 inhibition results in the formation of alpha-synuclein aggregates in mesencephalic cultured neurons, the present study was initiated to test UCHL-1 mRNA and protein levels in post-mortem frontal cortex (area 8) of PD and DLB cases, compared with age-matched controls. TaqMan PCR assays, and Western blots demonstrated down-regulation of UCHL-1 mRNA and UCHL-1 protein in the cerebral cortex in DLB (either in pure forms, not associated with Alzheimer disease: AD, and in common forms, with accompanying AD changes), but not in PD, when compared with age-matched controls. Interestingly, UCHL-1 mRNA and protein expressions were reduced in the medulla oblongata in the same PD cases. Moreover, UCHL-1 protein was decreased in the substantia nigra in cases with Lewy body pathology. UCHL-1 down-regulation was not associated with reduced protein levels of several proteasomal subunits, including 20SX, 20SY, 19S and 11Salpha. Yet UCHL-3 expression was reduced in the cerebral cortex of PD and DLB patients. Together, these observations show reduced UCHL-1 expression as a contributory factor in the abnormal protein aggregation in DLB, and points UCHL-1 as a putative therapeutic target in the treatment of DLB.

  20. Oral midazolam reduces cortisol levels during local anaesthesia in children: a randomised controlled trial.

    PubMed

    Gomes, Heloisa Sousa; Corrêa-Faria, Patrícia; Silva, Tarcília Aparecida; Paiva, Saul Martins; Costa, Paulo Sérgio Sucasas; Batista, Aline Carvalho; Costa, Luciane Rezende

    2015-01-01

    Little is known about whether midazolam sedation can reduce salivary cortisol levels and consequently influence children's behaviour during dental treatment. The aim of this study was to evaluate the effect of midazolam sedation on salivary cortisol and its correlation with children's behaviour during restorative dental treatment. Eighteen healthy children, aged two to five years, were randomly assigned to two dental treatment appointments, both with physical restraint: oral midazolam 1 mg/kg (MS) and placebo (PS). An observer assessed the children's behaviour (videos) using the Ohio State University Behavioral Rating Scale (OSUBRS). The children's saliva was collected just after waking up, on arrival at the dental school, 25 minutes after local anaesthesia, and 25 minutes after the end of the procedure. Salivary cortisol levels were determined using the enzyme-linked immunoabsorbent assay. The data were analysed by bivariate tests and multivariate analysis of variance (5% level). Salivary cortisol levels were lower in the MS group than in the PS group at the time of anaesthesia (p = 0.004), but did not vary during the appointment within sedation (p = 0.319) or placebo (p = 0.080) groups. Children's behaviour was negative most of the time and did not differ between MS and PS; however, the behaviour (OSUBRS) did not correlate with salivary cortisol levels. Oral midazolam is able to control salivary cortisol levels during dental treatment of pre-schoolers, which might not lead to better clinical behaviour.

  1. Two-Level Incremental Checkpoint Recovery Scheme for Reducing System Total Overheads

    PubMed Central

    Li, Huixian; Pang, Liaojun; Wang, Zhangquan

    2014-01-01

    Long-running applications are often subject to failures. Once failures occur, it will lead to unacceptable system overheads. The checkpoint technology is used to reduce the losses in the event of a failure. For the two-level checkpoint recovery scheme used in the long-running tasks, it is unavoidable for the system to periodically transfer huge memory context to a remote stable storage. Therefore, the overheads of setting checkpoints and the re-computing time become a critical issue which directly impacts the system total overheads. Motivated by these concerns, this paper presents a new model by introducing i-checkpoints into the existing two-level checkpoint recovery scheme to deal with the more probable failures with the smaller cost and the faster speed. The proposed scheme is independent of the specific failure distribution type and can be applied to different failure distribution types. We respectively make analyses between the two-level incremental and two-level checkpoint recovery schemes with the Weibull distribution and exponential distribution, both of which fit with the actual failure distribution best. The comparison results show that the total overheads of setting checkpoints, the total re-computing time and the system total overheads in the two-level incremental checkpoint recovery scheme are all significantly smaller than those in the two-level checkpoint recovery scheme. At last, limitations of our study are discussed, and at the same time, open questions and possible future work are given. PMID:25111048

  2. Mice lacking Mrp1 have reduced testicular steroid hormone levels and alterations in steroid biosynthetic enzymes

    PubMed Central

    SIVILS, JEFFREY C.; GONZALEZ, IVEN; BAIN, LISA J.

    2010-01-01

    The multidrug resistance-associated protein 1 (MRP1/ABCC1) is a member of the ABC active transporter family that can transport several steroid hormone conjugates, including 17β-estradiol glucuronide, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate. The present study investigated the role that MRP1 plays in maintaining proper hormone levels in the serum and testes. Serum and testicular steroid hormone levels were examined in both wild-type mice and Mrp1 null mice. Serum testosterone levels were reduced 5-fold in mice lacking Mrp1, while testicular androstenedione, testosterone, estradiol, and dehydroepiandrosterone (DHEA) were significantly reduced by 1.7- to 4.5-fold in Mrp1 knockout mice. Investigating the mechanisms responsible for the reduction in steroid hormones in Mrp1-/- mice revealed no differences in the expression or activity of enzymes that inactivate steroids, the sulfotransferases or glucuronosyltransferases. However, steroid biosynthetic enzyme levels in the testes were altered. Cyp17 protein levels were increased by 1.6-fold, while Cyp17 activity using progesterone as a substrate was also increased by 1.4-2.0-fold in mice lacking Mrp1. Additionally, the ratio of 17β-hydroxysteroid dehydrogenase to 3β-hydroxysteroid dehydrogenase, and steroidogenic factor 1 to 3βhydroxysteroid dehydrogenase were significantly increased in the testes of Mrp1-/- mice. These results indicate that Mrp1-/- mice have lowered steroid hormones levels, and suggests that upregulation of steroid biosynthetic enzymes may be an attempt to maintain proper steroid hormone homeostasis. PMID:20178799

  3. Maintain levels of nicotine but reduce other smoke constituents: a formula for ''less-hazardous'' cigarettes

    SciTech Connect

    Robinson, J.C.; Young, J.C.; Rickert, W.S.

    1984-09-01

    Twenty-two volunteers who smoked more than 20 cigarettes with ''high'' nicotine yields (0.8 to 1.2 mg) per day participated in an 8-week study designed to test the hypothesis that smoking cigarettes with a constant level of nicotine but reduced deliveries of tar, carbon monoxide, and hydrogen cyanide leads to a decrease in smoke absorption. All subjects smoked their usual high-nicotine brand for the first 3 weeks (P1), and the absorption of smoke constituents was determined from levels of thiocyanate and cotinine in saliva and serum, levels of carbon monoxide in expired air, and levels of carboxyhemoglobin in the blood. During the final 5 weeks (P2), the treatment group (16 subjects) switched to the ''light'' version of their usual brands (similar yields of nicotine but with reduced yields of tar, carbon monoxide, and hydrogen cyanide); the control group (6 subjects) smoked their usual brands for the duration of the study. Average levels of cotinine for the subjects who switched during P2 were not significantly different from those of the control group as was expected. Slight reductions were noted in average expired-air carbon monoxide levels, blood carboxyhemoglobin, and saliva thiocyanate, but these reductions were smaller than anticipated based on brand characteristics. The results suggest that the ratio of smoke constituents is different when individuals, rather than machines, smoke cigarettes. Yields determined under subject-defined conditions are necessary in order to properly evaluate the role of nicotine in the design of ''less-hazardous'' cigarettes.

  4. Biomarkers in pediatrics: children as biomarker orphans.

    PubMed

    Savage, William J; Everett, Allen D

    2010-12-01

    Biomarkers have enormous potential to improve patient care by establishing tests of diagnosis, prognosis, and treatment effects. Successfully translating a biomarker from discovery to clinical application demands high-quality discovery research and high-quality clinical studies for biomarker validation; however, there are additional challenges that face biomarker research in pediatrics. There are also additional characteristics of pediatric medicine that make biomarker research especially needed. This review focuses on the fundamentals of biomarkers, the additional considerations needed for applying biomarker research to children, and recommendations for advancing pediatric biomarker research.

  5. Enterovirus 71 Disrupts Interferon Signaling by Reducing the Level of Interferon Receptor 1

    PubMed Central

    Lu, Jing; Yi, Lina; Zhao, Jin; Yu, Jun; Chen, Ying; Lin, Marie C.; Kung, Hsiang-Fu

    2012-01-01

    The recent outbreak of enterovirus 71 (EV71) infected millions of children and caused over 1,000 deaths. To date, neither an effective vaccine nor antiviral treatment is available for EV71 infection. Interferons (IFNs) have been successfully applied to treat patients with hepatitis B and C viral infections for decades but have failed to treat EV71 infections. Here, we provide the evidence that EV71 antagonizes type I IFN signaling by reducing the level of interferon receptor 1 (IFNAR1). We show that the host cells could sense EV71 infection and stimulate IFN-β production. However, the induction of downstream IFN-stimulated genes is inhibited by EV71. Also, only a slight interferon response and antiviral effects could be detected in cells treated with recombinant type I IFNs after EV71 infection. Further studies reveal that EV71 blocks the IFN-mediated phosphorylation of STAT1, STAT2, Jak1, and Tyk2 by reducing IFNAR1. Finally, we identified the 2A protease encoded by EV71 as an antagonist of IFNs and show that the protease activity is required for reducing IFNAR1 levels. Taken together, our study for the first time uncovers a mechanism used by EV71 to antagonize type I IFN signaling and provides new targets for future antiviral strategies. PMID:22258259

  6. Serum anti-Helicobacter pylori immunoglobulin G titer correlates with grade of histological gastritis, mucosal bacterial density, and levels of serum biomarkers.

    PubMed

    Tu, Huakang; Sun, Liping; Dong, Xiao; Gong, Yuehua; Xu, Qian; Jing, Jingjing; Yuan, Yuan

    2014-03-01

    OBJECTIVE. Clinical implications of serum anti-Helicobacter pylori immunoglobulin G (IgG) titer were unclear. This study investigated the associations of serum anti-H. pylori IgG titer with grade of histological gastritis, mucosal bacterial density and levels of serum biomarkers, including pepsinogen (PG) I, PGII, PGI/II ratio and gastrin-17. MATERIAL AND METHODS. Study participants were from a screening program in northern China. Serum anti-H. pylori IgG measurements were available for 5922 patients with superficial gastritis. Serum anti-H. pylori IgG titer and serum biomarkers were measured using ELISA, and gastric biopsies were evaluated using standardized criteria. RESULTS. In patients with mild, moderate or severe superficial gastritis, the mean serum anti-H. pylori IgG titers were 17.3, 33.4 and 54.4 EIU (p for trend < 0.0001), respectively. As mucosal H. pylori density score increased from 0 to 3, the mean serum anti-H. pylori IgG titers also increased from 24.7 to 44.8 EIU (p for trend < 0.0001). Serum anti-H. pylori IgG titer was associated positively with serum PGI, PGII and gastrin-17 concentrations and negatively with PGI/II ratio, and the association was the strongest for PGII. The mean PGII concentration of the patients in the highest quartile of IgG titer was twice the mean concentration of the patients in the lowest quartile (17.2 vs. 8.6 EIU, p < 0.0001). CONCLUSIONS. Our results suggest that serum anti-H. pylori IgG titer was associated positively with grade of histological gastritis, mucosal bacterial density and concentrations of serum PGI, PGII and gastrin-17, and negatively with PGI/II ratio.

  7. Global 5-Hydroxymethylcytosine Levels Are Profoundly Reduced in Multiple Genitourinary Malignancies

    PubMed Central

    Munari, Enrico; Chaux, Alcides; Vaghasia, Ajay M.; Taheri, Diana; Karram, Sarah; Bezerra, Stephania M.; Gonzalez Roibon, Nilda; Nelson, William G.; Yegnasubramanian, Srinivasan; Netto, George J.; Haffner, Michael C.

    2016-01-01

    Solid tumors are characterized by a plethora of epigenetic changes. In particular, patterns methylation of cytosines at the 5-position (5mC) in the context of CpGs are frequently altered in tumors. Recent evidence suggests that 5mC can get converted to 5-hydroxylmethylcytosine (5hmC) in an enzymatic process involving ten eleven translocation (TET) protein family members, and this process appears to be important in facilitating plasticity of cytosine methylation. Here we evaluated the global levels of 5hmC using a validated immunohistochemical staining method in a large series of clear cell renal cell carcinoma (n = 111), urothelial cell carcinoma (n = 55) and testicular germ cell tumors (n = 84) and matched adjacent benign tissues. Whereas tumor-adjacent benign tissues were mostly characterized by high levels of 5hmC, renal cell carcinoma and urothelial cell carcinoma showed dramatically reduced staining for 5hmC. 5hmC levels were low in both primary tumors and metastases of clear cell renal cell carcinoma and showed no association with disease outcomes. In normal testis, robust 5hmC staining was only observed in stroma and Sertoli cells. Seminoma showed greatly reduced 5hmC immunolabeling, whereas differentiated teratoma, embryonal and yolk sack tumors exhibited high 5hmC levels. The substantial tumor specific loss of 5hmC, particularly in clear cell renal cell carcinoma and urothelial cell carcinoma, suggests that alterations in pathways involved in establishing and maintaining 5hmC levels might be very common in cancer and could potentially be exploited for diagnosis and treatment. PMID:26785262

  8. Global 5-Hydroxymethylcytosine Levels Are Profoundly Reduced in Multiple Genitourinary Malignancies.

    PubMed

    Munari, Enrico; Chaux, Alcides; Vaghasia, Ajay M; Taheri, Diana; Karram, Sarah; Bezerra, Stephania M; Gonzalez Roibon, Nilda; Nelson, William G; Yegnasubramanian, Srinivasan; Netto, George J; Haffner, Michael C

    2016-01-01

    Solid tumors are characterized by a plethora of epigenetic changes. In particular, patterns methylation of cytosines at the 5-position (5mC) in the context of CpGs are frequently altered in tumors. Recent evidence suggests that 5mC can get converted to 5-hydroxylmethylcytosine (5hmC) in an enzymatic process involving ten eleven translocation (TET) protein family members, and this process appears to be important in facilitating plasticity of cytosine methylation. Here we evaluated the global levels of 5hmC using a validated immunohistochemical staining method in a large series of clear cell renal cell carcinoma (n = 111), urothelial cell carcinoma (n = 55) and testicular germ cell tumors (n = 84) and matched adjacent benign tissues. Whereas tumor-adjacent benign tissues were mostly characterized by high levels of 5hmC, renal cell carcinoma and urothelial cell carcinoma showed dramatically reduced staining for 5hmC. 5hmC levels were low in both primary tumors and metastases of clear cell renal cell carcinoma and showed no association with disease outcomes. In normal testis, robust 5hmC staining was only observed in stroma and Sertoli cells. Seminoma showed greatly reduced 5hmC immunolabeling, whereas differentiated teratoma, embryonal and yolk sack tumors exhibited high 5hmC levels. The substantial tumor specific loss of 5hmC, particularly in clear cell renal cell carcinoma and urothelial cell carcinoma, suggests that alterations in pathways involved in establishing and maintaining 5hmC levels might be very common in cancer and could potentially be exploited for diagnosis and treatment.

  9. Reducing the Level of Undecaprenyl Pyrophosphate Synthase Has Complex Effects on Susceptibility to Cell Wall Antibiotics.

    PubMed

    Lee, Yong Heon; Helmann, John D

    2013-06-24

    Undecaprenyl pyrophosphate synthase (UppS) catalyzes the formation of the C55 lipid carrier (UPP) that is essential for bacterial peptidoglycan biosynthesis. Here we selected a vancomycin (VAN)-resistant derivative of Bacillus subtilis W168 which contains a single-point mutation in the ribosome-binding site (RBS) of the uppS gene designated uppS1. Genetic reconstruction experiments demonstrate that the uppS1 allele is sufficient to confer low-level VAN resistance and causes reduced UppS translation. The decreased level of UppS renders B. subtilis slightly more susceptible to many late-acting cell wall antibiotics including β-lactams, but significantly more resistant to fosfomycin and D-cycloserine, antibiotics that interfere with the very early steps of cell wall synthesis. We further show that the uppS1 allele leads to slightly elevated expression of the σ(M) regulon, possibly helping to compensate for the stress caused by a decrease in UPP levels. Notably, the uppS1 mutation increases resistance to VAN, fosfomycin, and D-cycloserine in wild-type cells, but this effect is greatly reduced or eliminated in a sigM mutant background. Our findings suggest that, although UppS is an attractive antibacterial target, incomplete inhibition of UppS function may lead to increased resistance to some cell wall-active antibiotics.

  10. Imaging Biomarkers or Biomarker Imaging?

    PubMed Central

    Mitterhauser, Markus; Wadsak, Wolfgang

    2014-01-01

    Since biomarker imaging is traditionally understood as imaging of molecular probes, we highly recommend to avoid any confusion with the previously defined term “imaging biomarkers” and, therefore, only use “molecular probe imaging (MPI)” in that context. Molecular probes (MPs) comprise all kinds of molecules administered to an organism which inherently carry a signalling moiety. This review highlights the basic concepts and differences of molecular probe imaging using specific biomarkers. In particular, PET radiopharmaceuticals are discussed in more detail. Specific radiochemical and radiopharmacological aspects as well as some legal issues are presented. PMID:24967536

  11. Reduced Levels of Hspa9 Attenuates Stat5 Activation in Mouse B-cells

    PubMed Central

    Krysiak, Kilannin; Tibbitts, Justin F.; Shao, Jin; Liu, Tuoen; Ndonwi, Matthew; Walter, Matthew J.

    2014-01-01

    HSPA9 is located on chromosome 5q31.2 in humans, a region that is commonly deleted in patients with myeloid malignancies [del(5q)], including myelodysplastic syndromes (MDS). HSPA9 expression is reduced by 50% in patients with del(5q)-associated MDS, consistent with haploinsufficient levels. Zebrafish mutants and knockdown studies in human and mouse cells have implicated a role for HSPA9 in hematopoiesis. To comprehensively evaluate the effects of Hspa9 haploinsufficiency on hematopoiesis, we generated an Hspa9 knockout mouse model. While homozygous knockout of Hspa9 is embryonic lethal, mice with heterozygous deletion of Hspa9 (Hspa9+/−) are viable and have a 50% reduction in Hspa9 expression. Hspa9+/− mice have normal basal hematopoiesis and do not develop MDS. However, Hspa9+/− mice have a cell- intrinsic reduction in bone marrow CFU-PreB colony formation without alterations in the number of B-cell progenitors in vivo, consistent with a functional defect in Hspa9+/− B-cell progenitors. We further reduced Hspa9 expression (<50%) using RNAi and observe reduced B-cell progenitors in vivo, indicating that appropriate levels (≥50%) of Hspa9 are required for normal B- lymphopoiesis in vivo. Knockdown of Hspa9 in an IL-7 dependent mouse B-cell line reduced Stat5 phosphorylation following IL-7 receptor stimulation, supporting a role for Hspa9 in Stat5 signaling in B-cells. Collectively, these data implicate a role for Hspa9 in B-lymphopoiesis and Stat5 activation downstream of IL-7 signaling. PMID:25550197

  12. Latrepirdine (Dimebon™) enhances autophagy and reduces intracellular GFP-Aβ42 levels in yeast

    PubMed Central

    Bharadwaj, Prashant R.; Verdile, Giuseppe; Barr, Renae K.; Gupta, Veer; Steele, John W.; Lachenmayer, M. Lenard; Yue, Zhenyu; Ehrlich, Michelle E.; Petsko, Gregory; Ju, Shulin; Ringe, Dagmar; Sankovich, Sonia E.; Caine, Joanne M.; Macreadie, Ian G.; Gandy, Sam; Martins, Ralph N.

    2012-01-01

    Latrepirdine (Dimebon™), an anti-histamine, has shown some benefits in trials of neurodegenerative diseases characterized by accumulation of aggregated or misfolded protein such as Alzheimer’s disease (AD) and has been shown to promote the removal of α-synuclein protein aggregates in vivo. An important pathway for removal of aggregated or misfolded proteins is the autophagy-lysosomal pathway, which has been implicated in AD pathogenesis, and enhancing this pathway has been shown to have therapeutic potential in AD and other proteinopathies. Here we use a yeast model Saccharomyces cerevisiae, to investigate whether latrepirdine can enhance autophagy and reduce levels of Aβ42 aggregates. Latrepirdine was shown to up-regulate yeast vacuolar (lysosomal) activity and promote transport of the autophagic marker (Atg8) to the vacuole. Using an in vitro GFP tagged Aβ yeast expression system, we investigated whether latrepirdine-enhanced autophagy was associated with a reduction in levels of intracellular GFP-Aβ42. GFP-Aβ42 was localized into punctate patterns compared to the diffuse cytosolic pattern of GFP and the GFP-Aβ42 (19:34), which does not aggregate. In the autophagy deficient mutant (Atg8Δ), GFP-Aβ42 showed a more diffuse cytosolic localization, reflecting the inability of this mutant to sequester GFP-Aβ42. Similar to rapamycin, we observed that latrepirdine significantly reduced GFP-Aβ42 in wild-type compared to the Atg8Δ mutant. Further, latrepirdine treatment attenuated Aβ42-induced toxicity in wild-type cells but not in the Atg8Δ mutant. Together, our findings provide evidence for a novel mechanism of action for latrepirdine in inducing autophagy and reducing intracellular levels of GFP-Aβ42. PMID:22903131

  13. Methoxychlor reduces estradiol levels by altering steroidogenesis and metabolism in mouse antral follicles in vitro

    SciTech Connect

    Basavarajappa, Mallikarjuna S. Craig, Zelieann R. Hernandez-Ochoa, Isabel Paulose, Tessie Leslie, Traci C. Flaws, Jodi A.

    2011-06-15

    The organochlorine pesticide methoxychlor (MXC) is a known endocrine disruptor that affects adult rodent females by causing reduced fertility, persistent estrus, and ovarian atrophy. Since MXC is also known to target antral follicles, the major producer of sex steroids in the ovary, the present study was designed to test the hypothesis that MXC decreases estradiol (E{sub 2}) levels by altering steroidogenic and metabolic enzymes in the antral follicles. To test this hypothesis, antral follicles were isolated from CD-1 mouse ovaries and cultured with either dimethylsulfoxide (DMSO) or MXC. Follicle growth was measured every 24 h for 96 h. In addition, sex steroid hormone levels were measured using enzyme-linked immunosorbent assays (ELISA) and mRNA expression levels of steroidogenic enzymes as well as the E{sub 2} metabolic enzyme Cyp1b1 were measured using qPCR. The results indicate that MXC decreased E{sub 2}, testosterone, androstenedione, and progesterone (P{sub 4}) levels compared to DMSO. In addition, MXC decreased expression of aromatase (Cyp19a1), 17{beta}-hydroxysteroid dehydrogenase 1 (Hsd17b1), 17{alpha}-hydroxylase/17,20-lyase (Cyp17a1), 3{beta} hydroxysteroid dehydrogenase 1 (Hsd3b1), cholesterol side-chain cleavage (Cyp11a1), steroid acute regulatory protein (Star), and increased expression of Cyp1b1 enzyme levels. Thus, these data suggest that MXC decreases steroidogenic enzyme levels, increases metabolic enzyme expression and this in turn leads to decreased sex steroid hormone levels. - Highlights: > MXC inhibits steroidogenesis > MXC inhibits steroidogenic enzymes > MXC induces metabolic enzymes

  14. Longitudinal Floating Ice Control Structures: A New Concept for Reducing Ice Jam Flood Levels

    DTIC Science & Technology

    1990-09-01

    friction factor is taken as 1.25 based on data from several ice jams I % . ( Beltaos 1983), and the ice properties g = 1.2 and S , = 0.92 are held...as much as Beltaos , S . (1983) River ice jams: Theory, case 8 studies, and applications. Journal of the Hydraulics sign. Journal of Waterway, Port...DOTIC S NOV 15 1990O. 0’~’FL P Longitudinal Floating Ice Control Structures A New Concept for Reducing Ice Jam Flood Levels 00NDarryl J. Calkins

  15. Improving patients' sleep: reducing light and noise levels on wards at night.

    PubMed

    Hewart, Carol; Fethney, Loveday

    2016-02-01

    There is much research concerning the psychological and physical effects of sleep deprivation on patients in healthcare systems, yet interrupted sleep on hospital wards at night remains a problem. Staff at Plymouth Hospitals NHS Trust, Devon, wanted to identify the factors that prevent patients from sleeping well at night. Two audits were carried out, between April and August 2015, to assess noise and light levels on wards at night, and to engage nurses in ways of reducing these. A number of recommendations were made based on the audit findings, many of which have been put into practice.

  16. Synbiotic food consumption reduces levels of triacylglycerols and VLDL, but not cholesterol, LDL, or HDL in plasma from pregnant women.

    PubMed

    Taghizadeh, Mohsen; Hashemi, Teibeh; Shakeri, Hossein; Abedi, Fatemeh; Sabihi, Sima-Sadat; Alizadeh, Sabihe-Alsadat; Asemi, Zatolla

    2014-02-01

    To our knowledge, no reports are available indicating the effects of synbiotic food consumption on blood lipid profiles and biomarkers of oxidative stress among pregnant women. This study was conducted to evaluate the effects of daily consumption of a synbiotic food on blood lipid profiles and biomarkers of oxidative stress in pregnant women. This randomized, double-blind, controlled clinical trial was performed among 52 primigravida pregnant women, aged 18 to 35-year-old at their third trimester. After a 2-week run-in period, subjects were randomly assigned to consume either a synbiotic (n = 26) or control food (n = 26) for 9 weeks. The synbiotic food consisted of a probiotic viable and heat-resistant Lactobacillus sporogenes (1 × 10⁷ CFU) and 0.04 g inulin (HPX)/g as the prebiotic. Patients were asked to consume the synbiotic and control foods two times a day. Biochemical measurements including blood lipid profiles, plasma total antioxidant capacity (TAC) and total glutathione (GSH) were conducted before and after 9 weeks of intervention. Consumption of a synbiotic food for 9 weeks resulted in a significant reduction in serum TAG (P = 0.04), VLDL (P = 0.04) and a significant rise in plasma GSH levels (P = 0.004) compared to the control food. No significant effects of the synbiotic food consumption on serum TC, LDL, HDL and plasma TAC levels (P > 0.05) were observed. Trial registry code: http://www.irct.ir . IRCT201212105623N3.

  17. Can enhanced autophagy be associated with human longevity? Serum levels of the autophagy biomarker beclin-1 are increased in healthy centenarians.

    PubMed

    Emanuele, Enzo; Minoretti, Piercarlo; Sanchis-Gomar, Fabian; Pareja-Galeano, Helios; Yilmaz, Yusuf; Garatachea, Nuria; Lucia, Alejandro

    2014-12-01

    Autophagy is a major clearance mechanism that degrades organelles and large protein aggregates to maintain cell survival and protein homeostasis. Although induction of autophagy can promote longevity in experimental models, the question as to whether increased basal levels of autophagy can be associated with human longevity remains open. In this pilot study, we investigated the association between serum concentrations of beclin-1, a key regulator of autophagy, and human exceptional longevity (EL). Serum beclin-1 was measured in three study groups: 79 healthy centenarians (39 males, aged 100-104 years); 178 non-diabetic patients who had experienced an acute myocardial infarction at a young age (101 males, 28-39 years); and 180 age- and sex-matched healthy young volunteers (103 males, 27-39 years) using an enzyme-linked immunosorbent assay. Healthy centenarians had significantly higher beclin-1 levels (2.2±0.8 ng/mL) compared with both young patients with myocardial infarction (1.5±0.7 ng/mL; p<0.001) and healthy controls (1.4±0.9 ng/mL; p<0.001), whereas no significant difference was observed between the two groups of young subjects. The multivariate-adjusted odds ratio for having serum beclin-1 levels >1.5 ng/mL (i.e., 75th percentile of the young controls' levels) was 3.4 (95% confidence interval 1.8-5.7; p<0.001) for healthy centenarians. Our preliminary data suggest that elevated basal levels of autophagy as reflected by high serum beclin-1 levels may be a biomarker of healthy human EL.

  18. Phosphorus speciation by coupled HPLC-ICPMS: low level determination of reduced phosphorus in natural materials

    NASA Astrophysics Data System (ADS)

    Atlas, Zachary; Pasek, Matthew; Sampson, Jacqueline

    2015-04-01

    Phosphorus is a geologically important minor element in the Earth's crust commonly found as relatively insoluble apatite. This constraint causes phosphorus to be a key limiting nutrient in biologic processes. Despite this, phosphorus plays a direct role in the formation of DNA, RNA and other cellular materials. Recent works suggest that since reduced phosphorus is considerably more soluble than oxidized phosphorus that it was integrally involved in the development of life on the early Earth and may continue to play a role in biologic productivity to this day. This work examines a new method for quantification and identification of reduced phosphorus as well as applications to the speciation of organo-phosphates separated by coupled HPLC - ICP-MS. We show that reduced phosphorus species (P1+, P3+ and P5+) are cleanly separated in the HPLC and coupled with the ICPMS reaction cell, using oxygen as a reaction gas to effectively convert elemental P to P-O. Analysis at M/Z= 47 producing lower background and flatter baseline chromatography than analyses performed at M/Z = 31. Results suggest very low detection limits (0.05 μM) for P species analyzed as P-O. Additionally we show that this technique has potential to speciate at least 5 other forms of phosphorus compounds. We verified the efficacy of method on numerous materials including leached Archean rocks, suburban retention pond waters, blood and urine samples and most samples show small but detectible levels of reduced phosphorus and or organo-phaospates. This finding in nearly all substances analyzed supports the assumption that the redox processing of phosphorus has played a significant role throughout the history of the Earth and it's presence in the present environment is nearly ubiquitous with the reduced oxidation state phosphorus compounds, phosphite and hypophosphite, potentially acting as significant constituents in the anaerobic environment.

  19. Reducing greenhouse gas emissions, water use, and grain arsenic levels in rice systems.

    PubMed

    Linquist, Bruce A; Anders, Merle M; Adviento-Borbe, Maria Arlene A; Chaney, Rufus L; Nalley, L Lanier; da Rosa, Eliete F F; van Kessel, Chris

    2015-01-01

    Agriculture is faced with the challenge of providing healthy food for a growing population at minimal environmental cost. Rice (Oryza sativa), the staple crop for the largest number of people on earth, is grown under flooded soil conditions and uses more water and has higher greenhouse gas (GHG) emissions than most crops. The objective of this study was to test the hypothesis that alternate wetting and drying (AWD--flooding the soil and then allowing to dry down before being reflooded) water management practices will maintain grain yields and concurrently reduce water use, greenhouse gas emissions and arsenic (As) levels in rice. Various treatments ranging in frequency and duration of AWD practices were evaluated at three locations over 2 years. Relative to the flooded control treatment and depending on the AWD treatment, yields were reduced by <1-13%; water-use efficiency was improved by 18-63%, global warming potential (GWP of CH4 and N2 O emissions) reduced by 45-90%, and grain As concentrations reduced by up to 64%. In general, as the severity of AWD increased by allowing the soil to dry out more between flood events, yields declined while the other benefits increased. The reduction in GWP was mostly attributed to a reduction in CH4 emissions as changes in N2 O emissions were minimal among treatments. When AWD was practiced early in the growing season followed by flooding for remainder of season, similar yields as the flooded control were obtained but reduced water use (18%), GWP (45%) and yield-scaled GWP (45%); although grain As concentrations were similar or higher. This highlights that multiple environmental benefits can be realized without sacrificing yield but there may be trade-offs to consider. Importantly, adoption of these practices will require that they are economically attractive and can be adapted to field scales.

  20. Rising sea levels will reduce extreme temperature variations in tide-dominated reef habitats

    PubMed Central

    Lowe, Ryan Joseph; Pivan, Xavier; Falter, James; Symonds, Graham; Gruber, Renee

    2016-01-01

    Temperatures within shallow reefs often differ substantially from those in the surrounding ocean; therefore, predicting future patterns of thermal stresses and bleaching at the scale of reefs depends on accurately predicting reef heat budgets. We present a new framework for quantifying how tidal and solar heating cycles interact with reef morphology to control diurnal temperature extremes within shallow, tidally forced reefs. Using data from northwestern Australia, we construct a heat budget model to investigate how frequency differences between the dominant lunar semidiurnal tide and diurnal solar cycle drive ~15-day modulations in diurnal temperature extremes. The model is extended to show how reefs with tidal amplitudes comparable to their depth, relative to mean sea level, tend to experience the largest temperature extremes globally. As a consequence, we reveal how even a modest sea level rise can substantially reduce temperature extremes within tide-dominated reefs, thereby partially offsetting the local effects of future ocean warming. PMID:27540589

  1. Heavy metals chromium and neodymium reduced phosphorylation level of heat shock protein 27 in human keratinocytes.

    PubMed

    Zhang, Qihao; Zhang, Lei; Xiao, Xue; Su, Zhijian; Zou, Ping; Hu, Hao; Huang, Yadong; He, Qing-Yu

    2010-06-01

    Heavy metals may exert their acute and chronic effects on the human skin through stress signals. In the present study, 2DE-based proteomics was used to analyze the protein expression in human keratinocytes exposed to heavy metals, chromium and neodymium, and 10 proteins with altered expression were identified. Among these proteins, small heat shock protein 27 (HSP27) was up-regulated significantly and the up-regulation was validated by Western blot and immunofluorescence. In addition, the mRNA expression level of HSP27 markedly increased as detected by quantitative PCR. More interestingly, the ratio of phosphorylated HSP27 and total HSP27 significantly decreased in keratinocytes treated with the heavy metals. These findings suggested that heavy metals reduced the phosphorylation level of HSP27, and that the ratio of p-HSP27 and HSP27 may represent a potential marker or additional endpoint for the hazard assessment of skin irritation caused by chemical products.

  2. Rising sea levels will reduce extreme temperature variations in tide-dominated reef habitats.

    PubMed

    Lowe, Ryan Joseph; Pivan, Xavier; Falter, James; Symonds, Graham; Gruber, Renee

    2016-08-01

    Temperatures within shallow reefs often differ substantially from those in the surrounding ocean; therefore, predicting future patterns of thermal stresses and bleaching at the scale of reefs depends on accurately predicting reef heat budgets. We present a new framework for quantifying how tidal and solar heating cycles interact with reef morphology to control diurnal temperature extremes within shallow, tidally forced reefs. Using data from northwestern Australia, we construct a heat budget model to investigate how frequency differences between the dominant lunar semidiurnal tide and diurnal solar cycle drive ~15-day modulations in diurnal temperature extremes. The model is extended to show how reefs with tidal amplitudes comparable to their depth, relative to mean sea level, tend to experience the largest temperature extremes globally. As a consequence, we reveal how even a modest sea level rise can substantially reduce temperature extremes within tide-dominated reefs, thereby partially offsetting the local effects of future ocean warming.

  3. High-fat diet transition reduces brain DHA levels associated with altered brain plasticity and behaviour.

    PubMed

    Sharma, Sandeep; Zhuang, Yumei; Gomez-Pinilla, Fernando

    2012-01-01

    To assess how the shift from a healthy diet rich in omega-3 fatty acids to a diet rich in saturated fatty acid affects the substrates for brain plasticity and function, we used pregnant rats fed with omega-3 supplemented diet from their 2nd day of gestation period as well as their male pups for 12 weeks. Afterwards, the animals were randomly assigned to either a group fed on the same diet or a group fed on a high-fat diet (HFD) rich in saturated fats for 3 weeks. We found that the HFD increased vulnerability for anxiety-like behavior, and that these modifications harmonized with changes in the anxiety-related NPY1 receptor and the reduced levels of BDNF, and its signalling receptor pTrkB, as well as the CREB protein. Brain DHA contents were significantly associated with the levels of anxiety-like behavior in these rats.

  4. Low level exposure to the flame retardant BDE-209 reduces thyroid hormone levels and disrupts thyroid signaling in fathead minnows.

    PubMed

    Noyes, Pamela D; Lema, Sean C; Macaulay, Laura J; Douglas, Nora K; Stapleton, Heather M

    2013-09-03

    Polybrominated diphenyl ether (PBDE) flame retardants have been shown to disrupt thyroid hormone regulation, neurodevelopment, and reproduction in some animals. However, effects of the most heavily used PBDE, decabromodiphenyl ether (BDE-209), on thyroid functioning remain unclear. This study examined low-dose effects of BDE-209 on thyroid hormone levels and signaling in fathead minnows. Adult males received dietary exposures of BDE-209 at a low dose (∼3 ng/g bw-day) and high dose (∼300 ng/g bw-day) for 28 days followed by a 14-day depuration to evaluate recovery. Compared to controls, fish exposed to the low dose for 28 days experienced a 53% and 46% decline in circulating total thyroxine (TT4) and 3,5,3'-triiodothyronine (TT3), respectively, while TT4 and TT3 deficits at the high dose were 59% and 62%. Brain deiodinase activity (T4-ORD) was reduced by ∼65% at both doses. BDE-209 elevated the relative mRNA expression of genes encoding deiodinases, nuclear thyroid receptors, and membrane transporters in the brain and liver in patterns that varied with time and dose, likely in compensation to hypothyroidism. Declines in the gonadal-somatic index (GSI) and increased mortality were also measured. Effects at the low dose were consistent with the high dose, suggesting nonlinear relationships between BDE-209 exposures and thyroid dysfunction.

  5. Maternal Highly Active Antiretroviral Therapy Reduces Vertical Cytomegalovirus Transmission But Does Not Reduce Breast Milk Cytomegalovirus Levels.

    PubMed

    Slyker, Jennifer A; Richardson, Barbra; Chung, Michael H; Atkinson, Claire; Ásbjörnsdóttir, Kristjana H; Lehman, Dara A; Boeckh, Michael; Emery, Vincent; Kiarie, James; John-Stewart, Grace

    2017-04-01

    To evaluate the impact of highly active antiretroviral therapy (HAART) on CMV transmission and breast milk level in the context of maternal HIV. Specimens from a randomized trial conducted in Nairobi, Kenya between 2003-2005 were used to compare CMV transmission and breast milk levels between mother-infant pairs randomized to HAART versus short-course antenatal zidovudine plus single-dose nevirapine (ZDV/sdNVP) for prevention of mother-to-child HIV transmission (PMTCT). Fifty-one antiretroviral-naïve women ≤32 weeks gestation, and CD4 between 200-500 cells/mm(3) were randomized at 34 weeks to begin either antenatal ZDV/sdNVP, or HAART through 6 months postpartum. Mean breast milk CMV levels and transmission were compared between arms. Age, sociodemographics, CD4%, and HIV plasma RNA viral load were similar between arms at baseline. CMV viral loads were measured from 243 infant plasma and 185 breast milk specimens during the first year postpartum. The probability of infant CMV infection at 12 months was 19% lower in the HAART arm compared to ZDV/sdNVP (75% vs. 94%, p = .04). All women had CMV detected in breast milk, with 72%, 98%, and 97% testing positive during the first, second, and third weeks postpartum, respectively. There was a trend for early higher mean breast milk CMV level in the HAART arm at 1 week (p = .08), and there was significantly slower decline in breast milk CMV levels (area under the curve, p = .01). HAART started during the third trimester may decrease infant CMV infections, by mechanisms independent of breast milk CMV levels.

  6. Effectiveness of ionizing radiation in reducing furan and acrylamide levels in foods.

    PubMed

    Fan, Xuetong; Mastovska, Katerina

    2006-10-18

    Furan and acrylamide are two possible carcinogens commonly found in many thermally processed foods. The possibility of using ionizing radiation to reduce the levels of thermally induced furan and acrylamide in water and selected foods was investigated. Aqueous furan solutions, and foods (frankfurters, sausages, infant sweet potatoes) that contained furan were irradiated to various doses of gamma-rays. Water and oil spiked with acrylamide and potato chips (a known acrylamide-containing food) were also irradiated. In addition, possible irradiation-induced formation of acrylamide in glucose and asparagine solutions was analyzed. Results showed that irradiation at 1.0 kGy destroyed almost all furan in water. In frankfurters, sausages, and infant sweet potatoes, the rate of irradiation-induced destruction of furan was much lower than the rate in water, although significant reductions in furan levels were observed in all foods. Irradiation at 2.5-3.5 kGy, doses that can inactivate 5-log of most common pathogens, reduced furan levels in the food samples by 25-40%. Similarly to furan, acrylamide in water was also sensitive to irradiation. After 1.5 kGy of irradiation, most of the acrylamide was degraded. Irradiation, however, had a very limited effect on acrylamide levels in oil and in potato chips, even at a dose of 10 kGy. No detectable acrylamide was formed in the mixture of asparagine and glucose upon irradiation. These results suggest that a low dose of irradiation easily destroys furan and acrylamide in water. In real foods, however, the reduction of furan was less effective than in water, whereas the reduction in acrylamide was minimal.

  7. Sulforaphane reduces the alterations induced by quinolinic acid: modulation of glutathione levels.

    PubMed

    Santana-Martínez, R A; Galván-Arzáte, S; Hernández-Pando, R; Chánez-Cárdenas, M E; Avila-Chávez, E; López-Acosta, G; Pedraza-Chaverrí, J; Santamaría, A; Maldonado, P D

    2014-07-11

    Glutamate-induced excitotoxicity involves a state of acute oxidative stress, which is a crucial event during neuronal degeneration and is part of the physiopathology of neurodegenerative diseases. In this work, we evaluated the ability of sulforaphane (SULF), a natural dietary isothiocyanate, to induce the activation of transcription factor Nrf2 (a master regulator of redox state in the cell) in a model of striatal degeneration in rats infused with quinolinic acid (QUIN). Male Wistar rats received SULF (5mg/kg, i.p.) 24h and 5min before the intrastriatal infusion of QUIN. SULF increased the reduced glutathione (GSH) levels 4h after QUIN infusion, which was associated with its ability to increase the activity of glutathione reductase (GR), an antioxidant enzyme capable to regenerate GSH levels at 24h. Moreover, SULF treatment increased glutathione peroxidase (GPx) activity, while no changes were observed in γ-glutamyl cysteine ligase (GCL) activity. SULF treatment also prevented QUIN-induced oxidative stress (measured by oxidized proteins levels), the histological damage and the circling behavior. These results suggest that the protective effect of SULF could be related to its ability to preserve GSH levels and increase GPx and GR activities.

  8. Leveling coatings for reducing the atomic oxygen defect density in protected graphite fiber epoxy composites

    NASA Technical Reports Server (NTRS)

    Jaworske, D. A.; Degroh, K. K.; Podojil, G.; Mccollum, T.; Anzic, J.

    1992-01-01

    Pinholes or other defect sites in a protective oxide coating provide pathways for atomic oxygen in low Earth orbit to reach underlying material. One concept for enhancing the lifetime of materials in low Earth orbits is to apply a leveling coating to the material prior to applying any reflective and protective coatings. Using a surface tension leveling coating concept, a low viscosity epoxy was applied to the surface of several composite coupons. A protective layer of 1000 A of SiO2 was deposited on top of the leveling coating, and the coupons were exposed to an atomic oxygen environment in a plasma asher. Pinhole populations per unit area were estimated by counting the number of undercut sites observed by scanning electron microscopy. Defect density values of 180,000 defects/sq cm were reduced to about 1000 defects/sq cm as a result of the applied leveling coating. These improvements occur at a mass penalty of about 2.5 mg/sq cm.

  9. Leveling coatings for reducing the atomic oxygen defect density in protected graphite fiber epoxy composites

    NASA Technical Reports Server (NTRS)

    Jaworske, D. A.; Degroh, Kim K.; Podojil, G.; Mccollum, T.; Anzic, J.

    1992-01-01

    Pinholes or other defect sites in a protective oxide coating provide pathways for atomic oxygen in low Earth orbit to reach underlying material. One concept of enhancing the lifetime of materials in low Earth orbit is to apply a leveling coating to the material prior to applying any reflective and protective coatings. Using a surface tension leveling coating concept, a low viscosity epoxy was applied to the surface of several composite coupons. A protective layer of 1000 A of SiO2 was deposited on top of the leveling coating, and the coupons were exposed to an atomic oxygen environment in a plasma asher. Pinhole populations per unit area were estimated by counting the number of undercut sites observed by scanning electron microscopy. Defect density values of 180,000 defects/sq cm were reduced to about 1000 defects/sq cm as a result of the applied leveling coating. These improvements occur at a mass penalty of about 2.5 mg/sq cm.

  10. Probiotic treatment reduces appetite and glucose level in the zebrafish model

    PubMed Central

    Falcinelli, Silvia; Rodiles, Ana; Unniappan, Suraj; Picchietti, Simona; Gioacchini, Giorgia; Merrifield, Daniel Lee; Carnevali, Oliana

    2016-01-01

    The gut microbiota regulates metabolic pathways that modulate the physiological state of hunger or satiety. Nutrients in the gut stimulate the release of several appetite modulators acting at central and peripheral levels to mediate appetite and glucose metabolism. After an eight-day exposure of zebrafish larvae to probiotic Lactobacillus rhamnosus, high-throughput sequence analysis evidenced the ability of the probiotic to modulate the microbial composition of the gastrointestinal tract. These changes were associated with a down-regulation and up-regulation of larval orexigenic and anorexigenic genes, respectively, an up-regulation of genes related to glucose level reduction and concomitantly reduced appetite and body glucose level. BODIPY-FL-pentanoic-acid staining revealed higher short chain fatty acids levels in the intestine of treated larvae. These results underline the capability of the probiotic to modulate the gut microbiota community and provides insight into how the probiotic interacts to regulate a novel gene network involved in glucose metabolism and appetite control, suggesting a possible role for L. rhamnosus in the treatment of impaired glucose tolerance and food intake disorders by gut microbiota manipulation. PMID:26727958

  11. Probiotic treatment reduces appetite and glucose level in the zebrafish model.

    PubMed

    Falcinelli, Silvia; Rodiles, Ana; Unniappan, Suraj; Picchietti, Simona; Gioacchini, Giorgia; Merrifield, Daniel Lee; Carnevali, Oliana

    2016-01-05

    The gut microbiota regulates metabolic pathways that modulate the physiological state of hunger or satiety. Nutrients in the gut stimulate the release of several appetite modulators acting at central and peripheral levels to mediate appetite and glucose metabolism. After an eight-day exposure of zebrafish larvae to probiotic Lactobacillus rhamnosus, high-throughput sequence analysis evidenced the ability of the probiotic to modulate the microbial composition of the gastrointestinal tract. These changes were associated with a down-regulation and up-regulation of larval orexigenic and anorexigenic genes, respectively, an up-regulation of genes related to glucose level reduction and concomitantly reduced appetite and body glucose level. BODIPY-FL-pentanoic-acid staining revealed higher short chain fatty acids levels in the intestine of treated larvae. These results underline the capability of the probiotic to modulate the gut microbiota community and provides insight into how the probiotic interacts to regulate a novel gene network involved in glucose metabolism and appetite control, suggesting a possible role for L. rhamnosus in the treatment of impaired glucose tolerance and food intake disorders by gut microbiota manipulation.

  12. Fermented soy permeate reduces cytokine level and oxidative stress in streptozotocin-induced diabetic rats.

    PubMed

    Malardé, Ludivine; Groussard, Carole; Lefeuvre-Orfila, Luz; Vincent, Sophie; Efstathiou, Théo; Gratas-Delamarche, Arlette

    2015-01-01

    Oxidative stress and inflammation are involved in the development of type 1 diabetes and its complications. Because two compounds found in soy, that is, isoflavones and alpha-galactooligosaccharides, have been shown to exert antioxidant and anti-inflammatory effects, this study aimed to assess the effects of a dietary supplement containing these two active compounds, the fermented soy permeate (FSP). We hypothesized that FSP would be able to reduce in vivo oxidative stress and inflammation in streptozotocin (STZ)-induced type 1 diabetic rats. Thirty male Wistar rats were divided into the control placebo, diabetic placebo, and diabetic FSP-supplemented groups. They received daily, by oral gavage, water (placebo groups) or diluted FSP (0.1 g/day; FSP-supplemented group). After 3 weeks, glycemic regulation (glycemia and fructosamine level); the plasma level of carboxymethyllysine (CML), a marker of systemic oxidative stress in diabetes; and the plasma levels of inflammatory markers (CRP, IL-1β, IL-6, and uric acid) were evaluated. Markers of oxidative damage (isoprostanes and GSH/GSSG), antioxidant enzymatic activity (SOD and GPX), and Mn-SOD content were determined in skeletal muscle (gastrocnemius). Diabetic placebo rats exhibited higher CML levels, lower SOD and GPX activities, and decreased Mn-SOD contents. FSP supplementation in diabetic animals normalized the CML and antioxidant enzymatic activity levels and tended to increase Mn-SOD expression. The markers of inflammation whose levels were increased in the diabetic placebo group were markedly decreased by FSP (IL-1β: -75%, IL-6: -46%, and uric acid: -17%), except for CRP. Our results demonstrate that FSP exhibited antioxidant and anti-inflammatory properties in vivo in STZ-induced diabetic rats.

  13. Prospective evaluation of serum biomarker levels and cartilage repair by autologous chondrocyte transplantation and subchondral drilling in a canine model

    PubMed Central

    Nganvongpanit, Korakot; Pothacharoen, Peraphan; Chaochird, Patama; Klunklin, Kasisin; Warrit, Kanawee; Settakorn, Jongkolnee; Pattamapaspong, Nuttaya; Luevitoonvechkij, Sirichai; Arpornchayanon, Olarn; Kongtawelert, Prachya; Pruksakorn, Dumnoensun

    2009-01-01

    Introduction The purpose of this study was to evaluate serum chondroitin sulfate (CS) and hyaluronic acid (HA) levels and the capability of cartilage repair of full-thickness cartilage defects after treatment with two different fundamental surgical techniques: autologous chondrocyte transplantation (AC) and subchondral drilling (SD). Methods A 4-mm-diameter full-thickness cartilage defect was created in each of 10 skeletally mature male outbred dogs. The dogs were randomly separated into two groups. Groups A and B were treated with AC and SD, respectively. An evaluation was made at the 24th week of the experiment. Serum was analyzed prospectively – preoperatively and at 6-week intervals – for CS and HA levels by enzyme-linked immunosorbent assay (ELISA) and ELISA-based assays, respectively. Results The cartilage repair assessment score (median ± standard deviation) of group A (9.5 ± 2.5) was significantly higher than that of group B (2.5 ± 1.3) (P < 0.05). Group A also demonstrated a better quality of hyaline-like cartilage repair. Prospective analysis of serum WF6 and HA levels between the two groups did not show any significant difference. Serum WF6 levels at the 24th week of the experiment had a negative correlation (r = -0.69, P < 0.05) with the cartilage repair assessment score, whereas serum HA levels tended to correlate positively (r = 0.46, 0.1

    levels. AC treatment demonstrated a smoother surface, less fissure, better border integration, and a more reliable outcome of repairing cartilage. Moreover, a decreasing level of serum WF6, which correlated with good quality of the repairing tissue at the end of the follow-up period, was found predominantly in the AC group. Serum WF6 therefore should be further explored as a sensitive marker for the noninvasive therapeutic evaluation of cartilage repair procedures. PMID

  14. Butyrylcholinesterase as a Blood Biomarker in Neuroblastoma.

    PubMed

    Coulter, Don W; Boettner, Angela D; Kortylewicz, Zbigniew P; Enke, Stephen P; Luther, Jake A; Verma, Vivek; Baranowska-Kortylewicz, Janina

    2017-04-03

    Blood-based biomarkers are important in the detection of the disease and in the assessment of responses to therapy. In this study, butyrylcholinesterase was evaluated as a potential biomarker in newly diagnosed neuroblastoma (NB) patients at diagnosis and longitudinally during treatment. Plasma butyrylcholinesterase activities in age-matched and sex-matched children were used as controls. Pretreatment butyrylcholinesterase levels in NB subjects are on an average 2 times lower than butyrylcholinesterase levels in healthy subjects. Significantly, butyrylcholinesterase activities are ∼40% lower in MYCN-amplified as compared with nonamplified disease. As the course of chemotherapy progresses, butyrylcholinesterase activities recover and normalize to control values. The evident response to treatment indicates that plasma butyrylcholinesterase is a good biomarker of tumor response to therapy. Depressed butyrylcholinesterase levels in NB subjects are not caused by hepatic deficits suggesting a specific role for butyrylcholinesterase in NB. Further examination of the mechanism of altered butyrylcholinesterase production require an animal model that best approximates human condition. Studies in mice show that murine NB allografts significantly reduce butyrylcholinesterase activity in plasma. This finding correlates with changes observed in NB patients. In contrast, human NB xenografts produce the opposite effect, that is, butyrylcholinesterase plasma levels rise as the xenograft size increases. In the absence of any liver damage, dissimilarities between butyrylcholinesterase production in murine and human NB models suggest species-specific signaling pathways. This disparity also suggests that human NB xenograft mouse models do not approximate the human disease.

  15. Alpha-fetoprotein level as a biomarker of liver fibrosis status: a cross-sectional study of 619 consecutive patients with chronic hepatitis B

    PubMed Central

    2014-01-01

    a predictive mathematical model by which AFP levels with other biomarkers. PMID:25128299

  16. Ultraviolet-ozone treatment reduces levels of disease-associated prion protein and prion infectivity

    USGS Publications Warehouse

    Johnson, C.J.; Gilbert, P.; McKenzie, D.; Pedersen, J.A.; Aiken, Judd M.

    2009-01-01

    Background. Transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative diseases caused by novel infectious agents referred to as prions. Prions appear to be composed primarily, if not exclusively, of a misfolded isoform of the cellular prion protein. TSE infectivity is remarkably stable and can resist many aggressive decontamination procedures, increasing human, livestock and wildlife exposure to TSEs. Findings. We tested the hypothesis that UV-ozone treatment reduces levels of the pathogenic prion protein and inactivates the infectious agent. We found that UV-ozone treatment decreased the carbon and prion protein content in infected brain homogenate to levels undetectable by dry-ashing carbon analysis or immunoblotting, respectively. After 8 weeks of ashing, UV-ozone treatment reduced the infectious titer of treated material by a factor of at least 105. A small amount of infectivity, however, persisted despite UV-ozone treatment. When bound to either montmorillonite clay or quartz surfaces, PrPTSE was still susceptible to degradation by UV-ozone. Conclusion. Our findings strongly suggest that UV-ozone treatment can degrade pathogenic prion protein and inactivate prions, even when the agent is associated with surfaces. Using larger UV-ozone doses or combining UV-ozone treatment with other decontaminant methods may allow the sterilization of TSE-contaminated materials. ?? 2009 Aiken et al; licensee BioMed Central Ltd.

  17. Biomarkers for PTSD

    DTIC Science & Technology

    2012-07-01

    smaller dentate/ CA3 hippocampal subfield volumes, lower ambient cortisol levels, and greater cortisol suppression following dexamethasone...administration. It is also predicted that lower neuropeptide Y levels will be associated with smaller Dentate/ CA3 volumes, and that APO E4 polymorphisms will be...associated with smaller Dentate/ CA3 volumes. 5 BODY: The Biomarkers for PTSD study is in the implementation phase. In year 2 of the grant

  18. Evaluation of household sanitizers for reducing levels of Escherichia coli on iceberg lettuce.

    PubMed

    Vijayakumar, Chitra; Wolf-Hall, Charlene E

    2002-10-01

    Diluted solutions of various household sanitizers (apple cider vinegar, white vinegar, bleach, and a reconstituted lemon juice product) were tested for their effectiveness in reducing counts of inoculated Escherichia coli and naturally present aerobic, mesophilic bacteria on lettuce. Sanitization treatments were carried out at 4 degrees C and at room temperature (ca. 21 degrees C) with and without agitation and at different exposure times (0, 1, 5, and 10 min). Of the sanitizers tested, 35% white vinegar (1.9% acetic acid) was the most effective in reducing E. coli levels (with a 5-log10 reduction after 5 min with agitation and after 10 min without agitation) and in reducing aerobic plate counts (with a >2-log10 reduction after 10 min with agitation). Lettuce samples treated with diluted household sanitizers were analyzed for consumer acceptability by sensory evaluation using a 9-point hedonic scale. The sanitized samples did not differ in acceptability (P > 0.05), except for samples treated with white vinegar. Samples treated with the white vinegar for 10 min were noticeably sour and slightly wilted in appearance. Consumer acceptability was maintained with all sanitization treatments, including those involving 35% white vinegar.

  19. Vitellogenin, sex steroid levels and gonadal biomarkers in wild Solea solea and Solea senegalensis from NW Mediterranean fishing grounds.

    PubMed

    Solé, M; Mañanós, E; Blázquez, M

    2016-06-01

    Specimens of Solea solea and Solea senegalenesis at different developmental stages were obtained from seven fishing grounds along the NW Mediterranean. Gonad development in males was classified into five stages, from early spermatogenesis to recovery, while four stages were considered in females, from growth to maturation. Vitellogenin (VTG) and sex steroid levels including an estrogen (estradiol, E2), two androgens (testosterone, T and 11-ketotestosterone, 11KT) and a progestin (17,20β-dihydroxy pregn-4-en-3-one, 17,20β-P or maturation inducing steroid, MIS) were analysed in plasma. Their levels were more clearly related to the developmental stage of the gonads than to the sampling site characteristics. In addition, enzyme activities in gonads, such as acetylcholinesterase (AChE) and carboxylesterase (CbE) were gender-dependent and higher in males than in females. Gonadal glutathione S-transferase (GST) activity was enhanced in the most anthropogenic impacted sites. VTG was absent in males and very low or undetectable in immature females, while mature females exhibited high VTG levels, clearly related to the gonado-somatic index. Sex steroid levels (ng/ml) varied in males and females regardless of the species. E2 levels in females ranged from 0.22 to 6.98 while in males ranged from 0.11 to 0.27. T varied from 0.12 to 0.93 in females and from 0.56 to 1.36 in males, while 11KT in females fluctuated from 0.03 to 0.57 and from 0.26 to 6.42 in males. Similarly, MIS in females ranged from 0.75 to 3.71 and from 1.12 to 5.61 in males. The lack of endocrine disturbances was confirmed by histological examination of the gonads. This study informs on basal sex hormone levels and enzyme activities during gonadal maturation of wild Solea spp. that can be useful in the identification and further remediation of possible pollution events.

  20. A heuristic re-mapping algorithm reducing inter-level communication in SAMR applications.

    SciTech Connect

    Steensland, Johan; Ray, Jaideep

    2003-07-01

    This paper aims at decreasing execution time for large-scale structured adaptive mesh refinement (SAMR) applications by proposing a new heuristic re-mapping algorithm and experimentally showing its effectiveness in reducing inter-level communication. Tests were done for five different SAMR applications. The overall goal is to engineer a dynamically adaptive meta-partitioner capable of selecting and configuring the most appropriate partitioning strategy at run-time based on current system and application state. Such a metapartitioner can significantly reduce execution times for general SAMR applications. Computer simulations of physical phenomena are becoming increasingly popular as they constitute an important complement to real-life testing. In many cases, such simulations are based on solving partial differential equations by numerical methods. Adaptive methods are crucial to efficiently utilize computer resources such as memory and CPU. But even with adaption, the simulations are computationally demanding and yield huge data sets. Thus parallelization and the efficient partitioning of data become issues of utmost importance. Adaption causes the workload to change dynamically, calling for dynamic (re-) partitioning to maintain efficient resource utilization. The proposed heuristic algorithm reduced inter-level communication substantially. Since the complexity of the proposed algorithm is low, this decrease comes at a relatively low cost. As a consequence, we draw the conclusion that the proposed re-mapping algorithm would be useful to lower overall execution times for many large SAMR applications. Due to its usefulness and its parameterization, the proposed algorithm would constitute a natural and important component of the meta-partitioner.

  1. Analysis on the serum levels of the biomarker CTX-II in professional indoor soccer players over the course of one season☆

    PubMed Central

    Severino, Rodrigo Miziara; Jorge, Pedro Baches; Martinelli, Mauro Olivo; de Lima, Marcos Vaz; Severino, Nilson Roberto; Duarte Junior, Aires

    2015-01-01

    Objective The aim of this study was to analyze the blood serum levels of CTX-II in professional indoor soccer players, at three different times during one season: at the start of the pre-season, four months later (a time that marks the middle of the season) and at the end of the season. Methods Fourteen male soccer players of mean age 19 years were included. Blood samples of 3 mL were collected from each individual. The samples were analyzed by means of Elisa tests. Results There was a significant increase in the serum level of CTX-II in the indoor soccer players, from the beginning to the end of the season (p < 0.01). Conclusion These data suggest that joint degradation had occurred in these soccer players, by the end of this period. It is evident that further studies are needed, with methodological rigor, so as to make an effective contribution toward precise elucidation of the etiology of this osteoarthritis and its relationship with the biomarkers, as a tool for early diagnosis. PMID:26229939

  2. Selenium Levels in Serum, Red Blood Cells, and Cerebrospinal Fluid of Alzheimer's Disease Patients: A Report from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL).

    PubMed

    Cardoso, Bárbara R; Hare, Dominic J; Bush, Ashley I; Li, Qiao-Xin; Fowler, Christopher J; Masters, Colin L; Martins, Ralph N; Ganio, Katherine; Lothian, Amber; Mukherjee, Soumya; Kapp, Eugene A; Roberts, Blaine R

    2017-01-01

    Selenium (Se) protects cells against oxidative stress damage through a range of bioactive selenoproteins. Increased oxidative stress is a prominent feature of Alzheimer's disease (AD), and previous studies have shown that Se deficiency is associated with age-related cognitive decline. In this study, we assessed Se status in different biofluids from a subgroup of participants in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing. As Se in humans can either be an active component of selenoproteins or inactive via non-specific incorporation into other proteins, we used both size exclusion chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP-MS) and tandem mass spectrometry to characterize selenoproteins in serum. We observed no differences in total Se concentration in serum or cerebrospinal fluid of AD subjects compared to mildly cognitively impairment patients and healthy controls. However, Se levels in erythrocytes were decreased in AD compared to controls. SEC-ICP-MS analysis revealed a dominant Se-containing fraction. This fraction was subjected to standard protein purification and a bottom-up proteomics approach to confirm that the abundant Se in the fraction was due, in part, to selenoprotein P. The lack of change in the Se level is at odds with our previous observations in a Brazilian population deficient in Se, and we attribute this to the Australian cohort being Se-replete.

  3. Serum Levels of Cytokines, and Biomarkers for Inflammation and Immune Activation, and HIV-Associated Non-Hodgkin B cell Lymphoma Risk

    PubMed Central

    Vendrame, Elena; Hussain, Shehnaz K.; Breen, Elizabeth Crabb; Magpantay, Larry; Widney, Daniel P.; Jacobson, Lisa P.; Variakojis, Daina; Knowlton, Emilee R.; Bream, Jay H.; Ambinder, Richard F.; Detels, Roger; Martínez-Maza, Otoniel

    2013-01-01

    Background: HIV infection is associated with a marked increase in risk for non-Hodgkin lymphoma (AIDS-NHL). However, the mechanisms that promote the development of AIDS-NHL are not fully understood. Methods: In this study serum levels of several cytokines and other molecules associated with immune activation were measured in specimens collected longitudinally during 1-to-5 years preceding AIDS-NHL diagnosis, in 176 AIDS-NHL cases and 176 HIV+ controls from the Multicenter AIDS Cohort Study (MACS). Results: Multivariate analyses revealed that serum levels of immunoglobulin free light chains (FLC), IL-6, IL-10, IP-10/CXCL10, neopterin, and TNFα were elevated in those HIV+ individuals who went on to develop AIDS-NHL. Additionally, the fraction of specimens with detectable IL-2 was increased, and the fraction with detectable IL-4 was decreased, in these subjects. Conclusions: These results suggest that long term, chronic immune activation, possibly driven by macrophage-produced cytokines, precedes development of NHL in HIV+ individuals. Impact: FLC, IL-6, IL-10, IP-10/CXCL10, neopterin, and TNFα may serve as biomarkers for AIDS-NHL. PMID:24220912

  4. Evaluation of copper-induced stress on eggplant (Solanum melongena L.) seedlings at the molecular and population levels by use of various biomarkers.

    PubMed

    Körpe, Didem Aksoy; Aras, Sümer

    2011-02-03

    Heavy-metal contamination is an important environmental problem in the world. It is known that high concentrations of heavy metals cause toxic damage to cells and tissues. In this study the effects of copper (Cu(2+)) contamination were determined at the molecular and population levels in eggplant (Solanum melongena L.) seedlings exposed to various concentrations of the metal ion. Inhibition of root growth, reduction in dry weight and total soluble protein content in the roots of eggplant seedlings were observed with increasing Cu(2+) concentrations. In ecotoxicology, analysis by random amplification of polymorphic DNA (RAPD) has been applied as a suitable biomarker assay for plants. For the RAPD analyses, nine RAPD primers were found to produce unique polymorphic band patterns and were subsequently used to produce a total of 80 and 168 bands in the roots of untreated and treated eggplant seedlings, respectively. The changes in RAPD profiles after Cu(2+) contamination were considered as variations, i.e. as gain and/or loss of bands compared with control seedlings. These results suggest that changes in genomic template stability could be detected with RAPD profiles and this result could be compared with the growth, dry weight and total soluble protein content of the seedlings grown at various Cu(2+) concentrations. The measurements of parameters at the molecular and population levels are fundamental to accumulate valuable information and to understand clearly the effect of a contaminant on an organism in ecotoxicology.

  5. Correlations between the Memory-Related Behavior and the Level of Oxidative Stress Biomarkers in the Mice Brain, Provoked by an Acute Administration of CB Receptor Ligands.

    PubMed

    Kruk-Slomka, Marta; Boguszewska-Czubara, Anna; Slomka, Tomasz; Budzynska, Barbara; Biala, Grazyna

    2016-01-01

    The endocannabinoid system, through cannabinoid (CB) receptors, is involved in memory-related responses, as well as in processes that may affect cognition, like oxidative stress processes. The purpose of the experiments was to investigate the impact of CB1 and CB2 receptor ligands on the long-term memory stages in male Swiss mice, using the passive avoidance (PA) test, as well as the influence of these compounds on the level of oxidative stress biomarkers in the mice brain. A single injection of a selective CB1 receptor antagonist, AM 251, improved long-term memory acquisition and consolidation in the PA test in mice, while a mixed CB1/CB2 receptor agonist WIN 55,212-2 impaired both stages of cognition. Additionally, JWH 133, a selective CB2 receptor agonist, and AM 630, a competitive CB2 receptor antagonist, significantly improved memory. Additionally, an acute administration of the highest used doses of JWH 133, WIN 55,212-2, and AM 630, but not AM 251, increased total antioxidant capacity (TAC) in the brain. In turn, the processes of lipids peroxidation, expressed as the concentration of malondialdehyde (MDA), were more advanced in case of AM 251. Thus, some changes in the PA performance may be connected with the level of oxidative stress in the brain.

  6. Activity levels of cathepsins B and L in tumor cells are a biomarker for efficacy of reovirus-mediated tumor cell killing.

    PubMed

    Terasawa, Y; Hotani, T; Katayama, Y; Tachibana, M; Mizuguchi, H; Sakurai, F

    2015-03-01

    Reovirus has gained much attention as an anticancer agent; however, the mechanism of the tumor cell-specific replication of reovirus is not fully understood. Although Ras activation is known to be crucial for tumor cell-specific replication of reovirus, it remains controversial which cellular factors are required for the reovirus-mediated tumor cell killing. In this study, we systematically investigated which cellular factors determined the efficiencies of reovirus-mediated tumor cell killing in various human cultured cell lines. The efficiency of reovirus-mediated cell killing varied widely among the cell lines. Junction adhesion molecule-A, a reovirus receptor, was highly expressed in almost all cell lines examined. Ras activation levels were largely different between the cell lines; however, there were no apparent correlations among the reovirus-mediated cell killing efficiencies and Ras activation status. On the other hand, activity levels of the cysteine proteases cathepsins B and L, which are crucial for proteolytic disassembly of the outer capsid proteins of reovirus, showed a tendency to be correlated with the efficiency of reovirus-mediated cell killing. These results indicate that the activity of cathepsins B and L is the most suitable as a biomarker for the efficacy of reovirus-mediated oncolysis among the factors examined in this study.

  7. Correlations between the Memory-Related Behavior and the Level of Oxidative Stress Biomarkers in the Mice Brain, Provoked by an Acute Administration of CB Receptor Ligands

    PubMed Central

    Kruk-Slomka, Marta; Boguszewska-Czubara, Anna; Slomka, Tomasz; Budzynska, Barbara; Biala, Grazyna

    2016-01-01

    The endocannabinoid system, through cannabinoid (CB) receptors, is involved in memory-related responses, as well as in processes that may affect cognition, like oxidative stress processes. The purpose of the experiments was to investigate the impact of CB1 and CB2 receptor ligands on the long-term memory stages in male Swiss mice, using the passive avoidance (PA) test, as well as the influence of these compounds on the level of oxidative stress biomarkers in the mice brain. A single injection of a selective CB1 receptor antagonist, AM 251, improved long-term memory acquisition and consolidation in the PA test in mice, while a mixed CB1/CB2 receptor agonist WIN 55,212-2 impaired both stages of cognition. Additionally, JWH 133, a selective CB2 receptor agonist, and AM 630, a competitive CB2 receptor antagonist, significantly improved memory. Additionally, an acute administration of the highest used doses of JWH 133, WIN 55,212-2, and AM 630, but not AM 251, increased total antioxidant capacity (TAC) in the brain. In turn, the processes of lipids peroxidation, expressed as the concentration of malondialdehyde (MDA), were more advanced in case of AM 251. Thus, some changes in the PA performance may be connected with the level of oxidative stress in the brain. PMID:26839719

  8. Relationship between sunlight exposure, housing condition, and serum vitamin D and related physiologic biomarker levels in captive chimpanzees (Pan troglodytes).

    PubMed

    Videan, Elaine N; Heward, Christopher B; Fritz, Jo; Murphy, James; Cortez, Czarina; Su, Yali

    2007-08-01

    In primates, the primary source of vitamin D is synthesis in the skin through sun exposure. Decreased sun exposure may lead to vitamin D deficiency and consequently other health issues. In laboratory, sanctuary, and zoo settings, chimpanzees (Pan troglodytes) may be housed indoors for prolonged periods of time without regular exposure to unfiltered sunlight. However, little research has examined the relationship between housing conditions and vitamin D serum levels in captive chimpanzees. In this study, we retrospectively compared serum levels of total vitamin D, calcium, ionic calcium, phosphorous, albumin, and alkaline phosphatase in 18 female and 12 male chimpanzees as they cycled between indoor-only and indoor-outdoor enclosures. Total vitamin D was significantly lower and alkaline phosphatase significantly higher when subjects were in the indoor-only enclosures compared with when they had regular access to outdoor enclosures. A vitamin D effect occurred only in young and prime-adult animals. Changes were significant in female but not in male chimpanzees. Calcium, ionic calcium, phosphorus, and albumin did not differ between indoor-only and indoor-outdoor enclosures. However, female chimpanzees exhibited significantly lower calcium and phosphorous levels while in the indoor-only enclosures. These results suggest that adult captive chimpanzees experience vitamin D deficiency when housed without regular access to unfiltered sunlight and that these effects may be more acute for adult female animals.

  9. Increased iron level in phytase-supplemented diets reduce performance and nutrient utilisation in broiler chickens.

    PubMed

    Akter, M; Iji, P A; Graham, H

    2017-04-11

    1. The effect of different levels of dietary iron on phytase activity and its subsequent effect on broiler performance was investigated in a 3 x 2 factorial arrangement. A total of 360 day-old Ross 308 male broiler chicks were distributed to 6 experimental diets, formulated with three levels of Fe (60, 80 and 100 mg/kg) and two levels of phytase (0, 500 FTU/kg). 2. Phytase supplemented to mid-Fe diets increased feed consumption more than the non-supplemented diet at d 24. From hatch to d 35, Fe x phytase interaction significantly influenced the FI, BWG and FCR. The high-Fe diet supplemented with phytase significantly reduced FI and BWG of broilers than those supplemented with low or mid-Fe diets. The overall FCR was significantly better in birds fed on the mid-Fe diets with phytase supplementation. 3. A significant improvement in ileal digestibility of N, P, Mg and Fe was observed in birds feed diets containing 60 mg Fe/kg, with significant interaction between Fe and phytase. 4. Phytase improved the bone breaking strength when supplemented to low or mid-Fe diets, compared to the non-supplemented diets. There was a significant Fe x phytase interaction effect. Tibia Fe content was higher in birds fed on phytase-free diets with high Fe but the reverse was the case when phytase was added and their interaction was significant. High dietary Fe significantly increased the accumulation of Fe in liver. 5. Phytase improved Ca-Mg-ATPase, Ca-ATPase and Mg-ATPase activities in jejunum when supplemented to the diet containing 80 mg Fe/kg. 6. This study indicates that high (100 mg/kg) dietary Fe inhibited phytase efficacy and subsequently reduced the overall performance and nutrient utilisation of broilers.

  10. Reduced CSF turnover and decreased ventricular Aβ42 levels are related

    PubMed Central

    2011-01-01

    Background The appearance of Aβ42 peptide deposits is admitted to be a key event in the pathogenesis of Alzheimer's disease, although amyloid deposits also occur in aged non-demented subjects. Aβ42 is a degradation product of the amyloid protein precursor (APP). It can be catabolized by several enzymes, reabsorbed by capillaries or cleared into cerebrospinal fluid (CSF). The possible involvement of a decrease in CSF turnover in A4β2 deposit formation is up to now poorly known. We therefore investigated a possible relationship between a reduced CSF turnover and the CSF levels of the A4β2 peptide. To this aim, CSF of 31 patients with decreased CSF turnover were studied. These patients presented chronic hydrocephalus communicating or obstructive, which required surgery (ventriculostomy or ventriculo-peritoneal shunt). Nine subjects had idiopathic normal pressure hydrocephalus (iNPH), and the other 22 chronic hydrocephalus from other origins (oCH). The Aβ42 peptide concentration was measured by an ELISA test in 31 ventricular CSF samples and in 5 lumbar CSF samples from patients with communicating hydrocephalus. Results The 5 patients with lumbar CSF analysis had similar levels of lumbar and ventricular Aβ42. A significant reduction in Aβ42 ventricular levels was observed in 24 / 31 patients with hydrocephalus. The values were lower than 300 pg/ml in 5 out of 9 subjects with iNPH, and in 15 out of 22 subjects with oCH. Conclusion The decrease of CSF Aβ42 seems to occur independently of the surgical hydrocephalus aetiology. This suggests that a CSF reduced turnover may play an important role in the decrease of CSF Aβ42 concentration. PMID:21569454

  11. Increasing Level of Leisure Physical Activity Could Reduce the Risk of Hip Fracture in Older Women

    PubMed Central

    Rong, Ke; Liu, Xiao-yu; Wu, Xu-hua; Li, Xiao-liu; Xia, Qing-quan; Chen, Jiong; Yin, Xiao-fan

    2016-01-01

    Abstract We carried out the study to investigate and quantitatively assess the potential association between current level of physical activity and the risk of osteoporosis hip fracture in older women. Relevant publications before October 2015 were identified using the PubMed and Ovid searching tools. A dose–response meta-analysis was carried out to combine and analysis results. Fourteen prospective studies were included in the meta-analysis. A general analysis of 9 studies showed a significant inverse relationship between increasing level of physical activity and risk of hip fracture in older women [relative risk (RR) = 0.93, 95% confidence interval (95% CI): 0.91–0.96]. The result of a sensitivity analysis was consistent with the general analysis (RR = 0.94, 95% CI: 0.93–0.96). The association between increasing level of physical activity and risk of wrist fracture was not statistically significant in a general analysis of three studies (RR = 1.004, 95% CI: 0.98–1.03). A potential direct association between increasing level of physical activity and risk of wrist fracture was observed after removing 1 study with the greatest weight (RR = 1.01, 95% CI: 1.00–1.03). No significant publication bias was observed in our analysis. Our results show that increasing level of physical activity within an appropriate range may reduce the risk of hip fracture but not the risk of wrist fracture in older women. PMID:26986111

  12. Diagnostic accuracy at several reduced radiation dose levels for CT imaging in the diagnosis of appendicitis

    NASA Astrophysics Data System (ADS)

    Zhang, Di; Khatonabadi, Maryam; Kim, Hyun; Jude, Matilda; Zaragoza, Edward; Lee, Margaret; Patel, Maitraya; Poon, Cheryce; Douek, Michael; Andrews-Tang, Denise; Doepke, Laura; McNitt-Gray, Shawn; Cagnon, Chris; DeMarco, John; McNitt-Gray, Michael

    2012-03-01

    Purpose: While several studies have investigated the tradeoffs between radiation dose and image quality (noise) in CT imaging, the purpose of this study was to take this analysis a step further by investigating the tradeoffs between patient radiation dose (including organ dose) and diagnostic accuracy in diagnosis of appendicitis using CT. Methods: This study was IRB approved and utilized data from 20 patients who underwent clinical CT exams for indications of appendicitis. Medical record review established true diagnosis of appendicitis, with 10 positives and 10 negatives. A validated software tool used raw projection data from each scan to create simulated images at lower dose levels (70%, 50%, 30%, 20% of original). An observer study was performed with 6 radiologists reviewing each case at each dose level in random order over several sessions. Readers assessed image quality and provided confidence in their diagnosis of appendicitis, each on a 5 point scale. Liver doses at each case and each dose level were estimated using Monte Carlo simulation based methods. Results: Overall diagnostic accuracy varies across dose levels: 92%, 93%, 91%, 90% and 90% across the 100%, 70%, 50%, 30% and 20% dose levels respectively. And it is 93%, 95%, 88%, 90% and 90% across the 13.5-22mGy, 9.6-13.5mGy, 6.4-9.6mGy, 4-6.4mGy, and 2-4mGy liver dose ranges respectively. Only 4 out of 600 observations were rated "unacceptable" for image quality. Conclusion: The results from this pilot study indicate that the diagnostic accuracy does not change dramatically even at significantly reduced radiation dose.

  13. High level methicillin resistance correlates with reduced Staphylococcus aureus endothelial cell damage.

    PubMed

    Seidl, Kati; Leemann, Michèle; Palheiros Marques, Miguel; Rachmühl, Carole; Leimer, Nadja; Andreoni, Federica; Achermann, Yvonne; Zinkernagel, Annelies S

    2017-01-01

    There has been controversy about the intrinsic virulence of methicillin-resistant Staphylococcus aureus (MRSA) as compared to methicillin-susceptible S. aureus (MSSA). To address this discrepancy, the intrinsic virulence of 42 MRSA and 40 MSSA clinical isolates was assessed by testing endothelial cell (EC) damage, a surrogate marker for virulence in blood stream infections. Since these clinical isolates represent a heterogeneous group, well characterized S. aureus laboratory strains with SCCmec loss- and gain-of-function mutations were used in addition. The clinical MRSA isolates carrying typical hospital acquired SCCmec types (I, II or III) induced significantly less damage (47.8%) as compared to isolates with other SCCmec types (62.3%, p=0.03) and MSSA isolates (64.2%, p<0.01). There was a strong inverse correlation between high-level oxacillin resistance and low EC damage induction (R(2)=0.4464, p<0.001). High-level oxacillin resistant strains (MIC >32μ/ml) grew significantly slower as compared to isolates with low-level resistance (p=0.047). The level of EC damage positively correlated with α- and δ-toxin production (p<0.0001 and p<0.05, respectively) but not with β-toxin production. Invasive MRSA isolates (n=21, 56.3%) were significantly less cytotoxic as compared to invasive MSSA isolates (n=20, 68.0%, p<0.05). There was no difference between EC damage induced by superficial versus invasive isolates in either MRSA or MSSA strains. Our data suggest that the intrinsic virulence of MRSA is similar or even reduced as compared to MSSA strains but is linked to the level of methicillin resistance.

  14. Loop Current variability due to wind stress and reduced sea level during the Last Glacial Maximum

    NASA Astrophysics Data System (ADS)

    Mildner, T. C.; Eden, C.; Nuernberg, D.; Schoenfeld, J.

    2011-12-01

    One of the most prominent features of the circulation in the Gulf of Mexico is the Loop Current (LC). It is of special interest as it influences not only the climate in the Gulf of Mexico. Although causation is not well understood yet, dynamical relationships between LC retraction and extension, seasonal migrations of the Intertropical Convergence Zone (ITCZ) and the related wind stress curl over the subtropical North Atlantic, and changes in the thermohaline circulation are indicated by model simulations. A characteristic feature of the LC is the shedding of anticyclonic eddies. These eddies can have depth signatures of up to 1000 m and are of special interest as they supply heat and moisture into the western and northern Gulf. The eddies are generated aperiodically every 3 to 21 months, with an average shedding time of 9.5 months. Eddy shedding appears to be related to a suite of oceanographic forcing fields such as the Yucatan Channel throughflow, the Florida Current and North Brazil Current variability, as well as synoptic meteorological forcing variability. By combining state-of-the-art paleoceanographic and meso-scale eddy-resolving numerical modeling techniques, we examined the Loop Current dynamics and hydrographic changes in the Gulf going back in time up to ~21,000 years. To assess the impact of Last Glacial Maximum (LGM) wind stress and reduced sea level we have re-configured an existing hierarchy of models of the North Atlantic Ocean (FLAME) with a horizontal grid resolution of ca. 30 km (wind stress was taken from the PMIP-II database). The sea level was lowered compared to the CONTROL run by 110 m and 67 m. These sea level changes have been chosen according to the cold-deglacial periods Heinrich I and Younger Dryas. The result of our model simulations is a continuous increase in eddy shedding from the LGM to the Holocene. This increase is predominantly controlled by the continuous deglacial sea level rise. Changes in wind stress curl related to the

  15. Changes in ovarian gene expression profiles and plasma hormone levels in maturing European eel (Anguilla anguilla); Biomarkers for broodstock selection.

    PubMed

    Burgerhout, Erik; Minegishi, Yuki; Brittijn, Sebastiaan A; de Wijze, Danielle L; Henkel, Christiaan V; Jansen, Hans J; Spaink, Herman P; Dirks, Ron P; van den Thillart, Guido E E J M

    2016-01-01

    Complete sexual maturation of European eels (Anguilla anguilla) in captivity can only be achieved via injections with gonadotropins. For female eels this procedure takes 4-6months and the response ranges from "unresponsive" to final maturation and ovulation. Reproductive success could be significantly increased via early selection of responders based on predictive markers and minimally invasive sampling methods. To get a better understanding of the genetic background of ovarian maturation of the European eel we performed a pilot deep-sequencing transcriptome analysis of ovarian tissue derived from a yellow eel, a prepubertal silver eel and a post-spawning matured eel. Two key players in steroidogenesis were strongly correlated with advanced sexual maturation, namely P450c17 and liver receptor homolog-1, suggesting that blood plasma steroids might qualify as minimally invasive markers for early detection of responders. Since the predictive value of plasma sex steroid levels for final maturation of the European eel had not yet been carefully examined, we performed an extensive artificial maturation trial. Farmed silver eels were treated with pituitary extracts and sampled at multiple time intervals. Expression of steroidogenesis-related genes in ovarian tissue of responding and non-responding eels after four weekly injections with pituitary extract was compared using a custom-built microarray and RNAseq. Increased expression of 17β-hsd1 was strongly linked to sexual maturation. Blood plasma levels of sex steroids were measured using ELISAs. We show that a 2.5-fold increase in blood-plasma estradiol level after 4 weekly pituitary extract injections is a strong predictor of final sexual maturation of female European eel.

  16. IL-10 Reduces Levels of Apoptosis in Toxoplasma gondii-Infected Trophoblasts

    PubMed Central

    Liu, Yang; Zhang, Haixia; Zhai, Xiaoyu; Hu, Xuemei

    2013-01-01

    Background To analyze the effects of IL-10 on the HLA-G expression and the apoptosis of trophoblasts infected with Toxoplasma gondii. Methods T. gondii-infected or uninfected human trophoblasts and immortalized human placental BeWo cells were cultured with or without human IL-10. Uninfected and infected cells without IL-10 cells served as controls. HLA-G expression was measured by real-time PCR and flow cytometry, respectively. Cells apoptosis were analyzed by flow cytometry. Apoptosis associated moleculars were measured by real-time PCR and Western bolt. Results HLA-G expression was increased in the infected trophoblasts and BeWo cells compared to uninfected cells. Treatment of infected cells with IL-10 decreased HLA-G expression compared to infected cells while no change in treatment of uninfected cells compared with uninfected cells. Levels of apoptosis and apoptosis associated caspase-3 and caspase-8 decreased and c-FLIP levels increased in treated infected cells with IL-10 compared to infected cells and no difference in IL-10 treated uninfected cells compared to uninfected cells. Conclusions IL-10 regulates HLA-G expression in T. gondii-infected trophoblasts. IL-10 treatment of infected trophoblasts reduced levels of apoptosis. This may contribute to the improvement in pregnancy outcomes when women infected with T. gondii treated with IL-10. PMID:23418570

  17. Syzygium cumini inhibits adenosine deaminase activity and reduces glucose levels in hyperglycemic patients.

    PubMed

    Bopp, A; De Bona, K S; Bellé, L P; Moresco, R N; Moretto, M B

    2009-08-01

    Syzigium cumini (L.) Skeels from the Myrtaceae family is among the most common medicinal plants used to treat diabetes in Brazil. Leaves, fruits, and barks of S. cumini have been used for their hypoglycemic activity. Adenosine deaminase (ADA) is an important enzyme that plays a relevant role in purine and DNA metabolism, immune responses, and peptidase activity. ADA is suggested to be an important enzyme for modulating the bioactivity of insulin, but its clinical significance in diabetes mellitus (DM) has not yet been proven. In this study, we examined the effect of aqueous leaf extracts of S. cumini (L.) (ASC) on ADA activity of hyperglycemic subjects and the activity of total ADA, and its isoenzymes in serum and erythrocytes. The present study indicates that: (i) the ADA activity in hyperglycemic serum was higher than normoglycemic serum and ADA activity was higher when the blood glucose level was more elevated; (ii) ASC (60-1000 microg/mL) in vitro caused a concentration-dependent inhibition of total ADA activity and a decrease in the blood glucose level in serum; (iii) ADA1 and 2 were reduced both in erythrocytes and in hyperglycemic serum. These results suggest that the decrease of ADA activity provoked by ASC may contribute to control adenosine levels and the antioxidant defense system of red cells and could be related to the complex ADA/DPP-IV-CD26 and the properties of dipeptidyl peptidase IV (DPP-IV) inhibitors which serve as important regulators of blood glucose.

  18. Predicting preferred coring level to reduce toner scatter in electrophotographic printing

    NASA Astrophysics Data System (ADS)

    Park, Hyung Jun; Allebach, Jan P.

    2011-01-01

    The electrophotographic process depends on a complex interplay between electrostatically charged toner particles, the developer roller, and the organic photoconductor during development; and between the toner particles, the organic photoconductor, and the paper during transfer. The task of controlling the imaging process is made even more challenging by the fact that colorant planes are developed independently and in succession. At high colorant levels, toner particles for a given colorant plane may be strongly repelled by toner that has already been deposited for previously developed colorant planes. The result is scattering of toner away from the edges of thin lines and character strokes. In previous work, we have proposed a coring method to reduce the occurrence of the toner scatter, and conducted psychophysical experiments to determine the preferred level of coring as a function of line width and colorant level. In this paper, we apply the edge transition width (ETW) metric to physically measure the impact of toner scatter on the sharpness of edges of lines and character strokes. We consider ETW both with and without coring, and compare it to the results from our earlier psychophysical experiments.

  19. Lacosamide reduces HDAC levels in the brain and improves memory: Potential for treatment of Alzheimer's disease.

    PubMed

    Bang, Shraddha R; Ambavade, Shirishkumar D; Jagdale, Priti G; Adkar, Prafulla P; Waghmare, Arun B; Ambavade, Prashant D

    2015-07-01

    Lacosamide, a histone deacetylase (HDAC) inhibitor, has been approved for the treatment of epilepsy. Some HDAC inhibitors have been proven effective for the treatment of memory disorders. The present investigation was designed to evaluate the effect of lacosamide on memory and brain HDAC levels. The effect on memory was evaluated in animals with scopolamine-induced amnesia using the elevated plus maze, object recognition test, and radial arm maze. The levels of acetylcholinesterase and HDAC in the cerebral cortex were evaluated. Lacosamide at doses of 10 and 30mg/kg significantly reduced the transfer latency in the elevated plus maze. Lacosamide at a dose of 30mg/kg significantly increased the time spent with a familiar object in the object recognition test at the 24h interval and decreased the time spent in the baited arm. Moreover, at this dose, the number of errors in the radial arm maze at 3 and 24h intervals was minimized and a reduction in the level of HDAC1, but not acetylcholinesterase, was observed in the cerebral cortex. These effects of lacosamide are equivalent to those of piracetam at a dose of 300mg/kg. These results suggest that lacosamide at a 30mg/kg dose improves disrupted memory, possibly by inhibiting HDAC, and could be used to treat amnesic symptoms of Alzheimer's disease.

  20. Stress Biomarkers, Mood States, and Sleep during a Major Competition: “Success” and “Failure” Athlete's Profile of High-Level Swimmers

    PubMed Central

    Chennaoui, Mounir; Bougard, Clément; Drogou, Catherine; Langrume, Christophe; Miller, Christian; Gomez-Merino, Danielle; Vergnoux, Frédéric

    2016-01-01

    The aim of this study was to evaluate stress markers, mood states, and sleep indicators in high-level swimmers during a major 7-days competition according to the outcomes. Nine swimmers [six men and three women (age: 22 ± 2 and 22 ± 4 years, respectively)] were examined. Before (PRE) and after (POST) each race (series, semi-finals, and finals), salivary concentrations of cortisol, α-amylase (sAA), and chromogranin-A (CgA) were determined. Mood states were assessed by the profile of mood state (POMS) questionnaire completed before and after the 7-days, and self-reported sleep diaries were completed daily. In the “failure” group, cortisol and sAA significantly increased between PRE-POST measurements (p < 0.05), while sCgA was not changed. Significant overall decrease of cortisol (-52.6%) and increase of sAA (+68.7%) was shown in the “failure group.” In this group, fatigue, confusion and depression scores, and sleep duration before the finals increased. The results in the “success” group show tendencies for increased cortisol and sCgA concentrations in response to competition, while sAA was not changed. Cortisol levels before the semi-finals and finals and sCgA levels before the finals were positively correlated to the fatigue score in the “failure” group only (r = 0.89). sAA levels before and after the semi-finals were negatively correlated to sleep duration measured in the subsequent night (r = −0.90). In conclusion, the stress of the competition could trigger a negative mood profile and sleep disturbance which correspond to different responses of biomarkers related to the hypothalamo-pituitary-adrenal axis and the sympathetic nervous system (SNS) activity, cortisol, sAA, and CgA. PMID:27014092

  1. Biomarkers of oxidative stress to nucleic acids: background levels and effects of body mass index and life-style factors in an urban paediatric population.

    PubMed

    Protano, Carmela; Andreoli, Roberta; Mutti, Antonio; Petti, Stefano; Vitali, Matteo

    2014-12-01

    The aims of the present study were to establish the background levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), 8-oxo-7,8-dihydroguanine (8-oxoGua) among a group of healthy Italian children, and to evaluate the contribution of some potential interfering/confounding factors to the urinary (u) levels of these biomarkers of oxidised guanine derivatives. The levels of 8-oxodGuo, 8-oxoGuo, 8-oxoGua, and u-cotinine in urine samples from 159 healthy children (5-11years) recruited in a cross-sectional study were measured via liquid chromatography-tandem mass spectrometry. Data regarding the anthropometric and life-style characteristics of the participants were obtained from questionnaires. The 5th-95th percentiles of the levels of 8-oxodGuo, 8-oxoGuo, and 8-oxoGua for all children were 2.4-13.9, 3.8-19.9 and 5.4-79.5μg/L and 2.9-12.6, 4.8-15.2, and 5.1-93.4μg/g creatinine, respectively. Significant correlations were found between the level of 8-oxoGuo and that of 8-oxoGua and 8-oxodGuo but not between the level of 8-oxoGua and that of 8-oxodGuo in all children and in both the male and female subgroups. Multiple linear regression analyses revealed the independent effect of the investigated variables on 8-oxodGuo, 8-oxoGuo, and 8-oxoGua. u-Creatinine was the most significant predictor of the urinary excretion of both 8-oxoGuo and 8-oxodGuo, age displayed a significant positive independent effect on the level of 8-oxoGuo, whereas the weight status according to the BMI was negatively associated with the level of 8-oxodGuo. None of the chosen independent variables influenced the levels of 8-oxoGua.

  2. Associations of serum insulin-like growth factor-I and insulin-like growth factor-binding protein 3 levels with biomarker-calibrated protein, dairy product and milk intake in the Women's Health Initiative.

    PubMed

    Beasley, Jeannette M; Gunter, Marc J; LaCroix, Andrea Z; Prentice, Ross L; Neuhouser, Marian L; Tinker, Lesley F; Vitolins, Mara Z; Strickler, Howard D

    2014-03-14

    It is well established that protein-energy malnutrition decreases serum insulin-like growth factor (IGF)-I levels, and supplementation of 30 g of whey protein daily has been shown to increase serum IGF-I levels by 8 % after 2 years in a clinical trial. Cohort studies provide the opportunity to assess associations between dietary protein intake and IGF axis protein levels under more typical eating conditions. In the present study, we assessed the associations of circulating IGF axis protein levels (ELISA, Diagnostic Systems Laboratories) with total biomarker-calibrated protein intake, as well as with dairy product and milk intake, among postmenopausal women enrolled in the Women's Health Initiative (n 747). Analyses were carried out using multivariate linear regression models that adjusted for age, BMI, race/ethnicity, education, biomarker-calibrated energy intake, alcohol intake, smoking, physical activity and hormone therapy use. There was a positive association between milk intake and free IGF-I levels. A three-serving increase in milk intake per d (approximately 30 g of protein) was associated with an estimated average 18·6 % higher increase in free IGF-I levels (95 % CI 0·9, 39·3 %). However, total IGF-I and insulin-like growth factor-binding protein 3 (IGFBP-3) levels were not associated with milk consumption and nor were there associations between biomarker-calibrated protein intake, biomarker-calibrated energy intake, and free IGF-I, total IGF-I or IGFBP-3 levels. The findings of the present study carried out in postmenopausal women are consistent with clinical trial data suggesting a specific relationship between milk consumption and serum IGF-I levels, although in the present study this association was only statistically significant for free, but not total, IGF-I or IGFBP-3 levels.

  3. Application of a battery of biomarkers in mussel digestive gland to assess long-term effects of the Prestige oil spill in Galicia and Bay of Biscay: tissue-level biomarkers and histopathology.

    PubMed

    Garmendia, Larraitz; Soto, Manu; Vicario, Unai; Kim, Yungkul; Cajaraville, Miren P; Marigómez, Ionan

    2011-04-01

    In order to assess the biological effects of the Prestige oil spill (POS), mussels, Mytilus galloprovincialis, were collected in 22 localities along the North coast of the Iberian Peninsula over 3 years (April 2003-April 2006). Different tissue-level biomarkers including cell type composition (volume density of basophilic cells, Vv(BAS)) in digestive gland epithelium, structural changes of digestive alveoli (mean luminal radius to mean epithelial thickness, MLR/MET) and histopathological alterations (prevalence and intensity) of the digestive gland were analysed. Severe alterations in the general condition of the digestive gland tissue were observed all over the study area up to 2004-2005. High Vv(BAS) values were recorded mainly in Galicia but also to a lesser extent in the Bay of Biscay in 2003-2004. Atrophy of the digestive alveoli, measured in terms of MLR/MET, was detected all along the studied area up to 2006. Inflammatory responses cannot be related to pollution due to the POS: (a) prevalence and intensity of focal hemocytic infiltration were higher in the Bay of Biscay than in Galicia but they did not show a clear temporal trend; (b) high intensities of brown cell aggregates were only sporadically recorded; and (c) granulocytomas were more frequently recorded in the Bay of Biscay than in Galicia and especially in localities (i.e. Arrigunaga) subjected to chronic pollution. Likewise, Marteilia, trematodes, intracellular ciliates, unidentified eosinophilic bodies, R/CLO and Mytilicola did not follow any recognisable pattern that could be associated to the POS. In contrast, high Nematopsis intensities recorded in several localities in 2003 might suggest some response of local interest after the POS (i.e., in combination with particular factors/conditions). More data at a regional scale are needed before histopathology may provide a reliable ecosystem health assessment but the present results suggest that the approach is worthwhile. Overall, although Vv

  4. Cost of reducing aromatics and sulfur levels in motor-vehicle fuels. Volume 3. Appendices. Final report

    SciTech Connect

    Felten, J.R.; McCarthy, K.M.

    1988-08-01

    Linear-programming (LP) models were developed for five refineries representative of the California refining industry and validated against historic operation. Process options to reduce gasoline and diesel contaminants were selected and represented in the LP models. Costs were estimated to separately reduce aromatics levels in automotive gasoline, aromatics in diesel, and sulfur in diesel for 1991 and 1995. Cost impacts were scaled up to obtain the overall cost impact in California. Estimates were made of total aromatics and benzene levels in gasoline and of sulfur, aromatics, and cetane levels in diesel. Estimates were made of the impact on refinery emissions, automotive emissions and automotive performance. The cost to reduce diesel sulfur level to .05% was 6.3 cents/gallon. The cost to reduce diesel aromatics level to 10% was 27.6 cents/gallon. The cost to reduce gasoline aromatics levels by 18% was 7.0 cents/gallon.

  5. Comparison of serum concentrations of symmetric dimethylarginine and creatinine as kidney function biomarkers in healthy geriatric cats fed reduced protein foods enriched with fish oil, L-carnitine, and medium-chain triglycerides.

    PubMed

    Hall, J A; Yerramilli, M; Obare, E; Yerramilli, M; Yu, S; Jewell, D E

    2014-12-01

    The purpose of this study was to determine whether feeding cats reduced protein and phosphorus foods with added fish oil, L-carnitine, and medium-chain triglycerides (MCT) altered serum biomarkers of renal function. Thirty-two healthy cats, mean age 14.0 (8.3-19.6) years, were fed control food or one of two experimental foods for 6 months. All foods had similar concentrations of moisture, protein, and fat (approximately 8.0%, 26.5%, and 20.0%, respectively). Both experimental foods contained added fish oil (1.5%) and L-carnitine (500 mg/kg). Experimental-food 2 also contained increased MCT (10.5% from coconut oil), 1.5% added corn oil, and reduced animal fat. Glomerular filtration rate (GFR), serum biochemistries, renal function biomarkers including serum creatinine (sCr) and symmetrical dimethylarginine (SDMA), and plasma metabolomic profiles were measured at baseline, and at 1.5, 3, and 6 months. Body composition was determined by dual-energy X-ray absorptiometry. Although both experimental foods altered plasma fatty acids, carnitine and related metabolites, and lysophospholipid concentrations, there were no changes in renal function biomarkers. There was, however, a benefit in using SDMA versus sCr to assess renal function in older cats with less total lean mass. Compared with cats <12 years, those >15 years had lower total lean mass (P < 0.01), lower GFR (P = 0.04), and lower sCr concentrations (P < 0.01). However, SDMA concentrations (P < 0.01) were higher in older cats. This study shows that in cats, serum SDMA concentration is more highly correlated with GFR than sCr concentration, and, unlike sCr, which declines with age because of muscle wasting, SDMA increases as GFR declines with age.

  6. Electroencephalography-driven approach to prodromal Alzheimer's disease diagnosis: from biomarker integration to network-level comprehension.

    PubMed

    Moretti, Davide Vito

    2016-01-01

    Decay of the temporoparietal cortex is associated with prodromal Alzheimer's disease (AD). Additionally, shrinkage of the temporoparietal cerebral area has been connected with an increase in α3/α2 electroencephalogram (EEG) power ratio in prodromal AD. Furthermore, a lower regional blood perfusion has been exhibited in patients with a higher α3/α2 proportion when contrasted with low α3/α2 proportion. Furthermore, a lower regional blood perfusion and reduced hippocampal volume has been exhibited in patients with higher α3/α2 when contrasted with lower α3/α2 EEG power ratio. Neuropsychological evaluation, EEG recording, and magnetic resonance imaging were conducted in 74 patients with mild cognitive impairment (MCI). Estimation of cortical thickness and α3/α2 frequency power ratio was conducted for each patient. A subgroup of 27 patients also underwent single-photon emission computed tomography evaluation. In view of α3/α2 power ratio, the patients were divided into three groups. The connections among cortical decay, cerebral perfusion, and memory loss were evaluated by Pearson's r coefficient. Results demonstrated that higher α3/α2 frequency power ratio group was identified with brain shrinkage and cutdown perfusion inside the temporoparietal projections. In addition, decay and cutdown perfusion rate were connected with memory shortfalls in patients with MCI. MCI subgroup with higher α3/α2 EEG power ratio are at a greater risk to develop AD dementia.

  7. Electroencephalography-driven approach to prodromal Alzheimer’s disease diagnosis: from biomarker integration to network-level comprehension

    PubMed Central

    Moretti, Davide Vito

    2016-01-01

    Decay of the temporoparietal cortex is associated with prodromal Alzheimer’s disease (AD). Additionally, shrinkage of the temporoparietal cerebral area has been connected with an increase in α3/α2 electroencephalogram (EEG) power ratio in prodromal AD. Furthermore, a lower regional blood perfusion has been exhibited in patients with a higher α3/α2 proportion when contrasted with low α3/α2 proportion. Furthermore, a lower regional blood perfusion and reduced hippocampal volume has been exhibited in patients with higher α3/α2 when contrasted with lower α3/α2 EEG power ratio. Neuropsychological evaluation, EEG recording, and magnetic resonance imaging were conducted in 74 patients with mild cognitive impairment (MCI). Estimation of cortical thickness and α3/α2 frequency power ratio was conducted for each patient. A subgroup of 27 patients also underwent single-photon emission computed tomography evaluation. In view of α3/α2 power ratio, the patients were divided into three groups. The connections among cortical decay, cerebral perfusion, and memory loss were evaluated by Pearson’s r coefficient. Results demonstrated that higher α3/α2 frequency power ratio group was identified with brain shrinkage and cutdown perfusion inside the temporoparietal projections. In addition, decay and cutdown perfusion rate were connected with memory shortfalls in patients with MCI. MCI subgroup with higher α3/α2 EEG power ratio are at a greater risk to develop AD dementia. PMID:27462146

  8. Postmenopausal vegetarians' low serum ferritin level may reduce the risk for metabolic syndrome.

    PubMed

    Kim, Mi-Hyun; Bae, Yun Jung

    2012-10-01

    The present study was conducted to compare the serum ferritin status between the postmenopausal vegetarians and non-vegetarians and to identify the relation of serum ferritin with metabolic syndrome (MetS) risk factors in postmenopausal women. The two study groups consisted of postmenopausal vegetarians (n=59) who maintained a vegetarian diet for over 20 years and age-matched non-vegetarian controls (n=48). Anthropometric measurements, dietary intakes, serum metabolic syndrome-related parameters, and serum ferritin level between the two groups were compared. The vegetarians exhibited significantly lower weight (p<0.01), body mass index (BMI) (p<0.001), percentage of body fat (p<0.001), waist circumference (p<0.01), SBP (p<0.001), DBP (p<0.001), and fasting glucose (p<0.05). According to the National Cholesterol Education Program (NCEP)-Adult Treatment Panel III criteria for MetS applying Korean guidelines for waist circumference, the prevalence of MetS was lower in vegetarians (33.9 %) than in non-vegetarians (47.9 %). Vegetarians had significantly lower serum level of ferritin (p<0.01) than non-vegetarians. In the correlation analysis, serum ferritin was positively related to fasting glucose (r=0.264, p<0.01), triglycerides (r=0.232, p<0.05), and the NCEP score (r=0.214, p<0.05) and negatively related to high-density lipoprotein-cholesterol (r=-0.225, p<0.05) after adjusting for BMI, lifestyle, and dietary factors (animal protein, animal fat, and dietary fiber intake). In conclusion, postmenopausal vegetarians had lower MetS presence and a lower serum ferritin level compared to non-vegetarians. Furthermore, vegetarians' low serum ferritin level may reduce the risk of MetS in postmenopausal women.

  9. Targeted mutation of plasma phospholipid transfer protein gene markedly reduces high-density lipoprotein levels

    PubMed Central

    Jiang, Xian-cheng; Bruce, Can; Mar, Jefferson; Lin, Min; Ji, Yong; Francone, Omar L.; Tall, Alan R.

    1999-01-01

    It has been proposed that the plasma phospholipid transfer protein (PLTP) facilitates the transfer of phospholipids and cholesterol from triglyceride-rich lipoproteins (TRL) into high-density lipoproteins (HDL). To evaluate the in vivo role of PLTP in lipoprotein metabolism, we used homologous recombination in embryonic stem cells and produced mice with no PLTP gene expression. Analysis of plasma of F2 homozygous PLTP–/– mice showed complete loss of phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, sphingomyelin, and partial loss of free cholesterol transfer activities. Moreover, the in vivo transfer of [3H]phosphatidylcholine ether from very-low-density proteins (VLDL) to HDL was abolished in PLTP–/– mice. On a chow diet, PLTP–/– mice showed marked decreases in HDL phospholipid (60%), cholesterol (65%), and apo AI (85%), but no significant change in non-HDL lipid or apo B levels, compared with wild-type littermates. On a high-fat diet, HDL levels were similarly decreased, but there was also an increase in VLDL and LDL phospholipids (210%), free cholesterol (60%), and cholesteryl ester (40%) without change in apo B levels, suggesting accumulation of surface components of TRL. Vesicular lipoproteins were shown by negative-stain electron microscopy of the free cholesterol– and phospholipid-enriched IDL/LDL fraction. Thus, PLTP is the major factor facilitating transfer of VLDL phospholipid into HDL. Reduced plasma PLTP activity causes markedly decreased HDL lipid and apoprotein, demonstrating the importance of transfer of surface components of TRL in the maintenance of HDL levels. Vesicular lipoproteins accumulating in PLTP–/– mice on a high-fat diet could influence the development of atherosclerosis. PMID:10079112

  10. Systematic review of effect of community-level interventions to reduce maternal mortality

    PubMed Central

    Kidney, Elaine; Winter, Heather R; Khan, Khalid S; Gülmezoglu, A Metin; Meads, Catherine A; Deeks, Jonathan J; MacArthur, Christine

    2009-01-01

    Background The objective was to provide a systematic review of the effectiveness of community-level interventions to reduce maternal mortality. Methods We searched published papers using Medline, Embase, Cochrane library, CINAHL, BNI, CAB ABSTRACTS, IBSS, Web of Science, LILACS and African Index Medicus from inception or at least 1982 to June 2006; searched unpublished works using National Research Register website, metaRegister and the WHO International Trial Registry portal. We hand searched major references. Selection criteria were maternity or childbearing age women, comparative study designs with concurrent controls, community-level interventions and maternal death as an outcome. We carried out study selection, data abstraction and quality assessment independently in duplicate. Results We found five cluster randomised controlled trials (RCT) and eight cohort studies of community-level interventions. We summarised results as odds ratios (OR) and confidence intervals (CI), combined using the Peto method for meta-analysis. Two high quality cluster RCTs, aimed at improving perinatal care practices, showed a reduction in maternal mortality reaching statistical significance (OR 0.62, 95% CI 0.39 to 0.98). Three equivalence RCTs of minimal goal-oriented versus usual antenatal care showed no difference in maternal mortality (1.09, 95% CI 0.53 to 2.25). The cohort studies were of low quality and did not contribute further evidence. Conclusion Community-level interventions of improved perinatal care practices can bring about a reduction in maternal mortality. This challenges the view that investment in such interventions is not worthwhile. Programmes to improve maternal mortality should be evaluated using randomised controlled techniques to generate further evidence. PMID:19154588

  11. A new system to reduce formaldehyde levels improves safety conditions during gross veterinary anatomy learning.

    PubMed

    Nacher, Víctor; Llombart, Cristina; Carretero, Ana; Navarro, Marc; Ysern, Pere; Calero, Sebastián; Fígols, Enric; Ruberte, Jesús

    2007-01-01

    Dissection is a very useful method of learning veterinary anatomy. However, formaldehyde, which is widely used to preserve cadavers, is an irritant, and it has recently been classified as a carcinogen. In 1997, the Instituto Nacional de Seguridad e Higiene en el Trabajo [National Institute of Workplace Security and Hygiene] found that the levels of formaldehyde in our dissection room were above the threshold limit values. Unfortunately, no optimal substitute for formaldehyde is currently available. Therefore, we designed a new ventilation system that combines slow propulsion of fresh air from above the dissection table and rapid aspiration of polluted air from the perimeter. Formaldehyde measurements performed in 2004, after the introduction of this new system into our dissection laboratory, showed a dramatic reduction (about tenfold, or 0.03 ppm). A suitable propelling/aspirating air system successfully reduces the concentration of formaldehyde in the dissection room, significantly improving safety conditions for students, instructors, and technical staff during gross anatomy learning.

  12. Blood circulation in rat lungs under conditions of reduced oxygen level in inhaled air.

    PubMed

    Ivanov, K P; Mel'nikova, N N

    2012-12-01

    According to some authors, reduction in oxygen level in the lung alveoli results in constriction of afferent vessels, while others observed no vessel constriction. The issue is of principle importance in relation to the lung involvement in body adaptation to hypoxia. Conventional methods are inefficient to solve it, therefore we used a contact microscope allowing observation of lung circulatory system structure and condition of the lung circulatory system in whole, virtually intact animal, on whole undamaged lungs in situ, at normal physiological lung position in the thorax. We found that large vessels carrying blood to the alveoli do not constrict or dilate at reduced Po(2)in lung alveoli. These vessels with a diameter of 15 to 40 μ and more are the only blood source for alveoli.

  13. Background levels of carbon-13 reduced in breath and stool by new infant formula.

    PubMed

    Boutton, T W; Hopkinson, J M; Benton, D A; Klein, P D

    1988-01-01

    Studies of the absorption and bioavailability of nutrients naturally enriched with 13C require accurate measurements of small increases of 13C in respiratory CO2 and stool carbon. The sensitivity of these measurements would be increased if the natural background of 13C in these excreta were reduced. We have developed a 13C-depleted infant formula based on lactose, whey, and casein from New Zealand cows that consume only C3 vegetation naturally low in 13C. This formula, designated CNRC3, was produced by a commercial infant formula manufacturer and was comparable with a 60:40 whey/casein product. To test the ability of the formula to reduce baseline levels of 13C in infant excreta, 10 formula-fed infants 28-60 days old and free of metabolic disorders were enrolled in the 9-day study. Two stool samples were collected daily. Infants received their usual formula on days 1 and 2 and were switched to CNRC3 formula for days 3-9. On days 2 and 9, seven breath samples were collected at 30-min intervals with a face mask. Breath and stool samples were analyzed for 13C content by gas isotope ratio mass spectrometry. Infants consuming their commercial formula had breath delta 13C values of -21.1 +/- 0.6% over the 3-h collection period; stool values were -22.9 +/- 0.4%. After 7 days on the CNRC3 formula, delta 13C values of breath declined by 5.6% to -26.7 +/- 0.7%; stool values declined by 3.0% to -25.6 +/- 0.5%. The reduced background of 13C achieved by the CNRC3 formula can improve resolution of excess 13C from naturally enriched substrates in infant breath by approximately 50% and in stool by approximately 30%.

  14. CAV1 siRNA Reduces Membrane Estrogen Receptor-α Levels and Attenuates Sexual Receptivity

    PubMed Central

    Christensen, Amy

    2012-01-01

    Although classic estrogen receptors (ER) have been proposed to mediate estradiol signaling, it has been relatively recently that mechanisms of trafficking these receptors have been elucidated. ERα is palmitoylated and associates with caveolin proteins to be targeted to the cell membrane. Caveolins are scaffold proteins that not only traffic ERα to the membrane but also are involved in establishing metabotropic glutamate receptor interactions that are necessary for activating G protein signaling. To demonstrate the role of caveolin proteins in regulating an estradiol-dependent behavior, sexual receptivity, we used small interfering RNA to knock down caveolin-1 (CAV1) expression in the arcuate nucleus of the hypothalamus. In CAV1 knockdown rats, membrane, but not intracellular levels of ERα, were significantly reduced. As expected, estrogenic stimulation of the arcuate nucleus of the hypothalamus to medial preoptic nucleus projection was abrogated in CAV1 knockdown rats, indicating that the membrane-initiated activation of this circuit was compromised. Moreover, estradiol-induced lordosis behavior that is dependent on activation of μ-opioid receptors in the medial preoptic nucleus was also significantly reduced. Thus, CAV1-mediated ERα trafficking to the cell membrane is required for estradiol activation of circuits underlying female sexual receptivity. PMID:22669893

  15. Neurotensin increases mortality and mast cells reduce neurotensin levels in a mouse model of sepsis.

    PubMed

    Piliponsky, Adrian M; Chen, Ching-Cheng; Nishimura, Toshihiko; Metz, Martin; Rios, Eon J; Dobner, Paul R; Wada, Etsuko; Wada, Keiji; Zacharias, Sherma; Mohanasundaram, Uma M; Faix, James D; Abrink, Magnus; Pejler, Gunnar; Pearl, Ronald G; Tsai, Mindy; Galli, Stephen J

    2008-04-01

    Sepsis is a complex, incompletely understood and often fatal disorder, typically accompanied by hypotension, that is considered to represent a dysregulated host response to infection. Neurotensin (NT) is a 13-amino-acid peptide that, among its multiple effects, induces hypotension. We find that intraperitoneal and plasma concentrations of NT are increased in mice after severe cecal ligation and puncture (CLP), a model of sepsis, and that mice treated with a pharmacological antagonist of NT, or NT-deficient mice, show reduced mortality during severe CLP. In mice, mast cells can degrade NT and reduce NT-induced hypotension and CLP-associated mortality, and optimal expression of these effects requires mast cell expression of neurotensin receptor 1 and neurolysin. These findings show that NT contributes to sepsis-related mortality in mice during severe CLP and that mast cells can lower NT concentrations, and suggest that mast cell-dependent reduction in NT levels contributes to the ability of mast cells to enhance survival after CLP.

  16. Bacteriophages of wastewater foaming-associated filamentous Gordonia reduce host levels in raw activated sludge.

    PubMed

    Liu, Mei; Gill, Jason J; Young, Ry; Summer, Elizabeth J

    2015-09-09

    Filamentous bacteria are a normal and necessary component of the activated sludge wastewater treatment process, but the overgrowth of filamentous bacteria results in foaming and bulking associated disruptions. Bacteriophages, or phages, were investigated for their potential to reduce the titer of foaming bacteria in a mixed-microbial activated sludge matrix. Foaming-associated filamentous bacteria were isolated from activated sludge of a commercial wastewater treatment plan and identified as Gordonia species by 16S rDNA sequencing. Four representative phages were isolated that target G. malaquae and two un-named Gordonia species isolates. Electron microscopy revealed the phages to be siphophages with long tails. Three of the phages--GordTnk2, Gmala1, and GordDuk1--had very similar ~76 kb genomes, with >93% DNA identity. These genomes shared limited synteny with Rhodococcus equi phage ReqiDocB7 and Gordonia phage GTE7. In contrast, the genome of phage Gsput1 was smaller (43 kb) and was not similar enough to any known phage to be placed within an established phage type. Application of these four phages at MOIs of 5-15 significantly reduced Gordonia host levels in a wastewater sludge model by approximately 10-fold as compared to non-phage treated reactors. Phage control was observed for nine days after treatment.

  17. Bacteriophages of wastewater foaming-associated filamentous Gordonia reduce host levels in raw activated sludge

    PubMed Central

    Liu, Mei; Gill, Jason J.; Young, Ry; Summer, Elizabeth J.

    2015-01-01

    Filamentous bacteria are a normal and necessary component of the activated sludge wastewater treatment process, but the overgrowth of filamentous bacteria results in foaming and bulking associated disruptions. Bacteriophages, or phages, were investigated for their potential to reduce the titer of foaming bacteria in a mixed-microbial activated sludge matrix. Foaming-associated filamentous bacteria were isolated from activated sludge of a commercial wastewater treatment plan and identified as Gordonia species by 16S rDNA sequencing. Four representative phages were isolated that target G. malaquae and two un-named Gordonia species isolates. Electron microscopy revealed the phages to be siphophages with long tails. Three of the phages - GordTnk2, Gmala1, and GordDuk1 - had very similar ~76 kb genomes, with >93% DNA identity. These genomes shared limited synteny with Rhodococcus equi phage ReqiDocB7 and Gordonia phage GTE7. In contrast, the genome of phage Gsput1 was smaller (43 kb) and was not similar enough to any known phage to be placed within an established phage type. Application of these four phages at MOIs of 5–15 significantly reduced Gordonia host levels in a wastewater sludge model by approximately 10-fold as compared to non-phage treated reactors. Phage control was observed for nine days after treatment. PMID:26349678

  18. Usefulness of serum bilirubin levels as a biomarker for long-term clinical outcomes after percutaneous coronary intervention.

    PubMed

    Kim, Hyun-Wook; Choi, Dong-Hyun; Lim, Leejin; Lee, Young-Min; Kang, Joon Tae; Chae, Seung Seok; Ki, Young-Jae; Song, Heesang; Koh, Young-Youp

    2015-11-01

    The aim of this study was to evaluate the prognostic value of serum total bilirubin on the development of adverse outcomes after percutaneous coronary intervention (PCI) besides high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B type natriuretic peptide (NT-proBNP). Serum total bilirubin, hs-cTnT, and NT-proBNP were analyzed in 372 patients who underwent PCI. The primary endpoint was cardiac death. There were 21 events of cardiac death during a mean of 25.8 months of follow-up. When the serum total bilirubin cut-off level (median value) was set to 0.58 mg/dL using the receiver operating characteristic curve, the sensitivity was 95.2 % and the specificity was 51.0 % for differentiating between the group with cardiac death and the group without cardiac death. Kaplan-Meier analysis revealed that the lower serum total bilirubin group (<0.58 mg/dL) had a significantly higher cardiac death rate than the higher serum total bilirubin group (≥0.58 mg/dL) (10.4 vs. 0.6 %, log-rank: P = 0.0001). In conclusion, low serum total bilirubin is a predictive marker for cardiac death after PCI.

  19. Postpartum levels of 8-iso-prostaglandin F2α in plasma and milk phospholipid fractions as biomarker of oxidative stress in first-lactating dairy cows.

    PubMed

    Vernunft, A; Viergutz, T; Plinski, C; Weitzel, J M

    2014-08-01

    F2-isoprostanes such as 8-iso-prostaglandin F2 (8-iso-PGF2α) are formed by free radical-catalyzed mechanisms from membrane phospholipids and from low density lipoproteins through peroxidation of arachidonic acid. Esterified 8-iso-PGF2α is cleaved by phospholipases, circulates in blood and is excreted as putatively harmful oxidatively modified lipid via the kidney into urine. In this study we demonstrate that 8-iso-PGF2α concentrations in plasma samples from heifers are higher (p<0.005) compared to those from first-lactating dairy cows at 71 days postpartum. Furthermore, plasma 8-iso-PGF2α concentrations vary with ovarian activity and differ in response to luteolytic initiation as well as activation of the hypothalamic-pituitary-gonadal axis between heifers and first-lactating cows. Sustainable concentrations of 8-iso-PGF2α (50-150 pg/ml) are detectable in the phospholipid fraction of milk, suggesting milk as an additional excretion route for 8-isoprostanes. Plasma levels largely paralleled levels in milk (p<0.001). Plasma phospholipid 8-iso-PGF2α concentrations in cyclic cows decreased (p<0.05) from day 38 to day 71 postpartum, whereas milk phospholipid 8-iso-PGF2α rather increased (p<0.05). Cyclic cows tend to have higher 8-isoprostane levels compared to acyclic animals. In contrast to lipohydroperoxides, concentration of 8-iso-PGF2α were not correlated with milk yield (p>0.05). Our data indicate 8-iso-PGF2α may be a novel biomarker of oxidative stress in dairy cow, which is detectable in blood as well as in milk.

  20. Differential blood-based diagnosis between benign prostatic hyperplasia and prostate cancer: miRNA as source for biomarkers independent of PSA level, Gleason score, or TNM status.

    PubMed

    Leidinger, Petra; Hart, Martin; Backes, Christina; Rheinheimer, Stefanie; Keck, Bastian; Wullich, Bernd; Keller, Andreas; Meese, Eckart

    2016-08-01

    Since the benefit of prostate-specific antigen (PSA) screening remains controversial, new non-invasive biomarkers for prostate carcinoma (PCa) are still required. There is evidence that microRNAs (miRNAs) in whole peripheral blood can separate patients with localized prostate cancer from healthy individuals. However, the potential of blood-based miRNAs for the differential diagnosis of PCa and benign prostatic hyperplasia (BPH) has not been tested. We compared the miRNome from blood of PCa and BPH patients and further investigated the influence of the tumor volume, tumor-node-metastasis (TNM) classification, Gleason score, pretreatment risk status, and the pretreatment PSA value on the miRNA pattern. By microarray approach, we identified seven miRNAs that were significantly deregulated in PCa patients compared to BPH patients. Using quantitative real time PCR (qRT-PCR), we confirmed downregulation of hsa-miR-221* (now hsa-miR-221-5p) and hsa-miR-708* (now hsa-miR-708-3p) in PCa compared to BPH. Clinical parameters like PSA level, Gleason score, or TNM status seem to have only limited impact on the overall abundance of miRNAs in patients' blood, suggesting a no influence of these factors on the expression of deregulated miRNAs.

  1. Plasma Acylcarnitines and Amino Acid Levels As an Early Complex Biomarker of Propensity to High-Fat Diet-Induced Obesity in Mice

    PubMed Central

    Bardova, Kristina; Gardlo, Alzbeta; Rombaldova, Martina; Kuda, Ondrej; Rossmeisl, Martin; Kopecky, Jan

    2016-01-01

    Obesity is associated with insulin resistance and impaired glucose tolerance, which represent characteristic features of the metabolic syndrome. Development of obesity is also linked to changes in fatty acid and amino acid metabolism observed in animal models of obesity as well as in humans. The aim of this study was to explore whether plasma metabolome, namely the levels of various acylcarnitines and amino acids, could serve as a biomarker of propensity to obesity and impaired glucose metabolism. Taking advantage of a high phenotypic variation in diet-induced obesity in C57BL/6J mice, 12-week-old male and female mice (n = 155) were fed a high-fat diet (lipids ~32 wt%) for a period of 10 weeks, while body weight gain (BWG) and changes in insulin sensitivity (ΔHOMA-IR) were assessed. Plasma samples were collected before (week 4) and after (week 22) high-fat feeding. Both univariate and multivariate statistical analyses were then used to examine the relationships between plasma metabolome and selected phenotypes including BWG and ΔHOMA-IR. Partial least squares-discrimination analysis was able to distinguish between animals selected either for their low or high BWG (or ΔHOMA-IR) in male but not female mice. Among the metabolites that differentiated male mice with low and high BWG, and which also belonged to the major discriminating metabolites when analyzed in plasma collected before and after high-fat feeding, were amino acids Tyr and Orn, as well as acylcarnitines C16-DC and C18:1-OH. In general, the separation of groups selected for their low or high ΔHOMA-IR was less evident and the outcomes of a corresponding multivariate analysis were much weaker than in case of BWG. Thus, our results document that plasma acylcarnitines and amino acids could serve as a gender-specific complex biomarker of propensity to obesity, however with a limited predictive value in case of the associated impairment of insulin sensitivity. PMID:27183228

  2. Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor protein NDP52

    NASA Astrophysics Data System (ADS)

    Jo, Chulman; Gundemir, Soner; Pritchard, Susanne; Jin, Youngnam N.; Rahman, Irfan; Johnson, Gail V. W.

    2014-03-01

    Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal transcription factor in the defence against oxidative stress. Here we provide evidence that activation of the Nrf2 pathway reduces the levels of phosphorylated tau by induction of an autophagy adaptor protein NDP52 (also known as CALCOCO2) in neurons. The expression of NDP52, which we show has three antioxidant response elements (AREs) in its promoter region, is strongly induced by Nrf2, and its overexpression facilitates clearance of phosphorylated tau in the presence of an autophagy stimulator. In Nrf2-knockout mice, phosphorylated and sarkosyl-insoluble tau accumulates in the brains concurrent with decreased levels of NDP52. Moreover, NDP52 associates with phosphorylated tau from brain cortical samples of Alzheimer disease cases, and the amount of phosphorylated tau in sarkosyl-insoluble fractions is inversely proportional to that of NDP52. These results suggest that NDP52 plays a key role in autophagy-mediated degradation of phosphorylated tau in vivo.

  3. Paeonol Oxime Inhibits bFGF-Induced Angiogenesis and Reduces VEGF Levels in Fibrosarcoma Cells

    PubMed Central

    Han, Ihn; Jung, Ji Hoon; Lee, Eun-Ok; Zhu, Shudong; Chen, Chang-Yan; Kim, Sung-Hoon

    2010-01-01

    Background We previously reported the anti-angiogenic activity of paeonol isolated from Moutan Cortex. In the present study, we investigated the negative effect of paeonol oxime (PO, a paeonol derivative) on basic fibroblast growth factor (bFGF)-mediated angiogenesis in human umbilical vein endothelial cells (HUVECs) (including tumor angiogenesis) and pro-survival activity in HT-1080 fibrosarcoma cell line. Methodology/Principal Findings We showed that PO (IC50  = 17.3 µg/ml) significantly inhibited bFGF-induced cell proliferation, which was achieved with higher concentrations of paeonol (IC50 over 200 µg). The treatment with PO blocked bFGF-stimulated migration and in vitro capillary differentiation (tube formation) in a dose-dependent manner. Furthermore, PO was able to disrupt neovascularization in vivo. Interestingly, PO (25 µg/ml) decreased the cell viability of HT-1080 fibrosarcoma cells but not that of HUVECs. The treatment with PO at 12.5 µg/ml reduced the levels of phosphorylated AKT and VEGF expression (intracellular and extracelluar) in HT-1080 cells. Consistently, immunefluorescence imaging analysis revealed that PO treatment attenuated AKT phosphorylation in HT-1080 cells. Conclusions/Significance Taken together, these results suggest that PO inhibits bFGF-induced angiogenesis in HUVECs and decreased the levels of PI3K, phospho-AKT and VEGF in HT-1080 cells. PMID:20808805

  4. Reducing the likelihood of future human activities that could affect geologic high-level waste repositories

    SciTech Connect

    Not Available

    1984-05-01

    The disposal of radioactive wastes in deep geologic formations provides a means of isolating the waste from people until the radioactivity has decayed to safe levels. However, isolating people from the wastes is a different problem, since we do not know what the future condition of society will be. The Human Interference Task Force was convened by the US Department of Energy to determine whether reasonable means exist (or could be developed) to reduce the likelihood of future human unintentionally intruding on radioactive waste isolation systems. The task force concluded that significant reductions in the likelihood of human interference could be achieved, for perhaps thousands of years into the future, if appropriate steps are taken to communicate the existence of the repository. Consequently, for two years the task force directed most of its study toward the area of long-term communication. Methods are discussed for achieving long-term communication by using permanent markers and widely disseminated records, with various steps taken to provide multiple levels of protection against loss, destruction, and major language/societal changes. Also developed is the concept of a universal symbol to denote Caution - Biohazardous Waste Buried Here. If used for the thousands of non-radioactive biohazardous waste sites in this country alone, a symbol could transcend generations and language changes, thereby vastly improving the likelihood of successful isolation of all buried biohazardous wastes.

  5. Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid

    PubMed Central

    Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E.; Redhi, Godfrey H.; Panlilio, Leigh V.; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D.; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R.

    2013-01-01

    In the reward circuitry of the brain, alpha-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of delta-9-tetrahydrocannabinol (THC), marijuana’s main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by re-exposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are currently no medications approved for treatment of marijuana dependence. Modulation of KYNA provides a novel pharmacological strategy for achieving abstinence from marijuana and preventing relapse. PMID:24121737

  6. Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid.

    PubMed

    Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E; Redhi, Godfrey H; Panlilio, Leigh V; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R

    2013-11-01

    In the reward circuitry of the brain, α-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of Δ(9)-tetrahydrocannabinol (THC), marijuana's main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by reexposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are no medications approved for treatment of marijuana dependence. Modulation of KYNA offers a pharmacological strategy for achieving abstinence from marijuana and preventing relapse.

  7. COPE Method Implementation Program to Reduce Communication Apprehension Level in Full Day Yunior High School Students

    NASA Astrophysics Data System (ADS)

    Prasetyo, A. R.

    2017-02-01

    This study was aimed to explore the effect of COPE method to reduce communication apprehension level of students in Early Adolescence who become Full Day Junior High School students. Full Day Junior High School students, especially in Surabaya coastal area, have more demands to develop the communication aspects such as group discussions and presentations and extracurricular activities. Higher demands to develop such aspects of communication may cause them to experience communication apprehension. The subject was Full Day School students totaling 31 students. The design of the research was experimental design. The experimental method used was a non-randomized pretest posttest control group design and purposive sampling was also used. COPE method is a process that consists of four main stages where people are trying to deal with and control of stressful situations as a result of the problem being faced by conducting cognitive and behavioral changes. Four main stages COPE method is Calming the nervous system, Originating an imaginative plan, Persisting in the face of obstacles and failure, and Evaluating and adjusting the plan. Results of quantitative analysis based on U-Mann Whitney Test shows significant effect on the COPE Method to decrease anxiety levels of communication (0.000 <0.005).

  8. Highly charged swelling mica reduces free and extractable Cu levels in Cu-contaminated soils.

    PubMed

    Stuckey, Jason W; Neaman, Alexander; Ravella, Ramesh; Komarneni, Sridhar; Martínez, Carmen Enid

    2008-12-15

    Smelting of copper (Cu) results in the atmospheric deposition of Cu onto surrounding soils. Excess concentrations of Cu in soils can be absorbed by soil biota to toxic levels or leached into the groundwater, threatening the entire ecosystem. A means to restrict Cu mobility and uptake by plants is to remove it from the aqueous phase by applying an adsorptive material. A synthetic clay (highly charged swelling mica) was tested for its ability to decrease the levels of free and 0.1 M KNO3-extractable Cu in 15 surface soils from three different Cu mining areas in central Chile. The soils contained excessive total Cu levels (112-2790 mg Cu (kg soil)(-1)), while extractable Cu ranged from 0.3 to 22.9 mg Cu L(-1). The mica was applied to each soil at rates of 0.1%, 1%, and 2% (w/w). A 2% sodium-montmorillonite treatment and the nonamended soil served as controls. The order of treatment efficacy in reducing extractable Cu and free Cu2+ for low pH soils ( 1% mica > 2% montmorillonite > 0.1% mica. At 120 days, the 2% mica treatment maintained reductions of up to 93% in the free Cu2+ activity and up to 75% in the extractable Cu concentration upon acidification to the original soil pH value. In addition, Cu retention in mica-treated soils was more resistant to acidification than in lime-treated soils. This mica has promise for the remediation of acidic soils with metal contamination at the surface.

  9. Oxidative DNA damage and repair in children exposed to low levels of arsenic in utero and during early childhood: Application of salivary and urinary biomarkers

    SciTech Connect

    Hinhumpatch, Pantip; Navasumrit, Panida; Chaisatra, Krittinee; Promvijit, Jeerawan; Mahidol, Chulabhorn; Ruchirawat, Mathuros

    2013-12-15

    The present study aimed to assess arsenic exposure and its effect on oxidative DNA damage and repair in young children exposed in utero and continued to live in arsenic-contaminated areas. To address the need for biological specimens that can be acquired with minimal discomfort to children, we used non-invasive urinary and salivary-based assays for assessing arsenic exposure and early biological effects that have potentially serious health implications. Levels of arsenic in nails showed the greatest magnitude of difference between exposed and control groups, followed by arsenic concentrations in saliva and urine. Arsenic levels in saliva showed significant positive correlations with other biomarkers of arsenic exposure, including arsenic accumulation in nails (r = 0.56, P < 0.001) and arsenic concentration in urine (r = 0.50, P < 0.05). Exposed children had a significant reduction in arsenic methylation capacity indicated by decreased primary methylation index and secondary methylation index in both urine and saliva samples. Levels of salivary 8-OHdG in exposed children were significantly higher (∼ 4-fold, P < 0.01), whereas levels of urinary 8-OHdG excretion and salivary hOGG1 expression were significantly lower in exposed children (∼ 3-fold, P < 0.05), suggesting a defect in hOGG1 that resulted in ineffective cleavage of 8-OHdG. Multiple regression analysis results showed that levels of inorganic arsenic (iAs) in saliva and urine had a significant positive association with salivary 8-OHdG and a significant negative association with salivary hOGG1 expression. - Highlights: • The effects of arsenic exposure in utero and through early childhood were studied. • Arsenic-exposed children had a reduction in arsenic methylation capacity. • Exposed children had more DNA damage, observed as elevated salivary 8-OHdG. • Lower salivary hOGG1 in exposed children indicated impairment of 8-OHdG repair. • Salivary and urinary 8-OHdG levels were discordant.

  10. Plasma Elaidic Acid Level as Biomarker of Industrial Trans Fatty Acids and Risk of Weight Change: Report from the EPIC Study

    PubMed Central

    Chajès, Véronique; Biessy, Carine; Ferrari, Pietro; Romieu, Isabelle; Freisling, Heinz; Huybrechts, Inge; Scalbert, Augustin; Bueno de Mesquita, Bas; Romaguera, Dora; Gunter, Marc J.; Vineis, Paolo; Hansen, Camilla Plambeck; Jakobsen, Marianne Uhre; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine; Katzke, Verana; Neamat-Allah, Jasmine; Boeing, Heiner; Bachlechner, Ursula; Trichopoulou, Antonia; Naska, Androniki; Orfanos, Philippos; Pala, Valeria; Masala, Giovanna; Mattiello, Amalia; Skeie, Guri; Weiderpass, Elisabete; Agudo, Antonio; Huerta, Jose Maria; Ardanaz, Eva; Sánchez, Maria Jose; Dorronsoro, Miren; Quirós, Jose Ramon; Johansson, Ingegerd; Winkvist, Anna; Sonested, Emily; Key, Tim; Khaw, Kay-Tee; Wareham, Nicolas J.; Peeters, Petra H.M.; Slimani, Nadia

    2015-01-01

    Background Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods Baseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow-up, age, energy, alcohol, smoking status, physical activity, and region. Results In women, doubling elaidic acid was associated with a decreased risk of weight loss (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.55-0.88, p = 0.002) and a trend was observed with an increased risk of weight gain during the 5-year follow-up (OR = 1.23, 95% CI = 0.97-1.56, p = 0.082) (p-trend<.0001). In men, a trend was observed for doubling elaidic acid level and risk of weight loss (OR = 0.82, 95% CI = 0.66-1.01, p = 0.062) while no significant association was found with risk of weight gain during the 5-year follow-up (OR = 1.08, 95% CI = 0.88-1.33, p = 0.454). No association was found for saturated and cis-monounsaturated fatty acids. Conclusions These data suggest that a high intake of industrial trans fatty acids may decrease the risk of weight loss, particularly in women. Prevention of obesity should consider limiting the consumption of highly processed foods, the main source of industrially-produced trans fatty acids. PMID:25675445

  11. High dose trans-10,cis-12 CLA increases lean body mass in hamsters, but elevates levels of plasma lipids and liver enzyme biomarkers.

    PubMed

    Liu, Xiaoran; Joseph, Shama V; Wakefield, Andrew P; Aukema, Harold M; Jones, Peter J H

    2012-01-01

    The current study examined the efficacy of graded doses of c9,t11 and t10,c12 CLA isomers on body composition, energy expenditure, hepatic and serum lipid liver biomarkers in hamsters. Animals (n = 105) were randomized to seven treatments (control, 1, 2, 3% of c9,t11; 1, 2, 3% of t10,c12) for 28 days. After 28 days treatment, 1-3% of t10,c12 lowered (p < 0.05) body fat mass compared to the control group. The 1-3% t10,c12 and 3% c9,t11 fed groups showed higher (p < 0.05) lean mass compared to other groups. We observed unfavorable changes in plasma total cholesterol and non-HDL cholesterol levels in animals fed with 3% t10,c12 CLA isomers. The 2%, 3% t10,c12 groups presented elevated (p < 0.05) ALT levels. The present data suggest that a diet enriched with more than 2% t10, c12 led to liver malfunction and poses unfavorable changes on plasma lipid profiles. The 1% t10,c12 CLA lowered (p < 0.05) body fat mass and increased (p < 0.05) lean body mass. The c9,t11 CLA has less potent actions than t10,c12 CLA. We conclude that the actions of CLA on energy and lipid metabolism are form and dose dependent in the hamster model.

  12. Body size, nuptial pad size and hormone levels: potential non-destructive biomarkers of reproductive health in wild toads (Bufo bufo).

    PubMed

    Orton, Frances; Baynes, Alice; Clare, Frances; Duffus, Amanda L J; Larroze, Severine; Scholze, Martin; Garner, Trenton W J

    2014-09-01

    Amphibians are declining and fertility/fecundity are major drivers of population stability. The development of non-destructive methods to assess reproductive health are needed as destructive measures are fundamentally at odds with conservation goals for declining species. We investigated the utility of body size, nuptial pad size and forelimb width as non-destructive biomarkers of internal reproductive physiology, by analysing correlations with commonly used destructive methods in adult male toads (Bufo bufo) from a low human impact and a high human impact site. Principal component analyses revealed that size was the most important variable for explaining inter-individual differences in other measured endpoints, both non-destructive and destructive, except for hormone levels and nuptial pad, which were independent of size. Toads from the LI and the HI site differed in almost all of the measured endpoints; this was largely driven by the significantly smaller size of toads from the HI site. Correlational analyses within sites revealed that size was correlated with several reproductive endpoints in toads from the HI site but not the LI site, indicating a possible limiting effect of size on reproductive physiology. Intersex was observed in 33% of toads from the HI site and incidence was not related to any other measured endpoint. In conclusion, we provide evidence that size is associated with reproductive physiology and that nuptial pad/hormone levels have potential as additional markers due to their independence from size. We also show that human activities can have a negative effect on reproductive physiology of the common toad.

  13. Reduced plasma homocysteine levels in levodopa/entacapone treated Parkinson patients.

    PubMed

    Valkovic, Peter; Benetin, Ján; Blazícek, Pavol; Valkovicová, L'udmila; Gmitterová, Karin; Kukumberg, Peter

    2005-06-01

    Hyperhomocysteinemia is not only a major risk factor for atherothrombotic disease, but is also strongly associated with an increased risk of dementia and cognitive impairment, both of which are common in the course of Parkinson's disease (PD). Previous work has found that levodopa increases plasma homocysteine concentrations. Animal studies have indicated that the catechol-O-methyltransferase (COMT) inhibitors can prevent levodopa-induced elevation of homocysteine concentrations by reducing the O-methylation of levodopa. The objective of our study was to assess the impact of entacapone, a COMT inhibitor, on plasma levels of homocysteine, serum folate, and vitamin B12 in levodopa-treated PD patients. Nineteen PD patients receiving only levodopa and 21 PD patients on a combination of levodopa and entacapone participated in the cross-sectional study. The control group consisted of 17 subjects on dopamine agonists. The mean plasma homocysteine concentration in the subjects on only levodopa was higher than that in the subjects on a combination of levodopa and entacapone (P=0.001) or in the control group (P=0.0001). Concentrations of serum vitamin B12 and serum folate were on average normal in all groups, but levodopa-treated subjects (with or without entacapone therapy) were more prone to have hypovitaminosis B12 (45%) than controls on dopamine agonists (6%). We suggest that the COMT inhibition may play a promising role in successfully controlling levodopa-induced hyperhomocysteinemia and in reducing the risk of pathologies probably linked to it. These preliminary findings and postulated hypotheses must now be confirmed in prospective studies.

  14. Application of neutral electrolyzed water spray for reducing dust levels in a layer breeding house.

    PubMed

    Zheng, Weichao; Li, Baoming; Cao, Wei; Zhang, Guoqiang; Yang, Zhanyong

    2012-11-01

    Reducing airborne dust is an essential process for improving hen housing environment. Dust reduction effects of neutral electrolyzed water (pH 8.2) spray were investigated in a commercial tunnel-ventilated layer breeding house during production in northern China. A multipoint sampler was used to measure airborne dust concentration to study the dust reduction effects and distribution in the house. Compared with the control treatment (without spray), airborne dust level was reduced 34% in the 3 hr after spraying 216 mL m(-2) neutral electrolyzed water in the breeding house. The dust concentration was significantly higher during the periods of feed distribution (1.13 +/- 0.13 mg m(-3)) and artificial insemination (0.72 +/- 0.13 mg m(-3)) compared with after spray (0.47 +/- 0.09 mg m(-3)) and during lights-off period (0.29 +/- 0.08 mg m(-3)) in the three consecutive testing days (P <0.05). The experimental cage area was divided into four zones along the length of the house, with zone 1 nearest to the evaporative cooling pad and zone 4 nearest to the fans. The air temperature, relative humidity, airflow rate, and dust concentration were measured at the sampling points of the four zones in 3 consecutive days and mortality of the birds for the duration of a month were investigated. The results showed that the air temperature, airflow rate, dust concentration, and number of dead birds increase from zone 1 to zone 4 in the tunnel-ventilated layer breeding house.

  15. Oral Fluids that Detect Cardiovascular Disease Biomarkers

    PubMed Central

    Foley, Joseph D.; Sneed, J. Darrell; Steinhubl, Steven R; Kolasa, Justin; Ebersole, Jeffrey L.; Lin, Yushun; Kryscio, Richard J.; McDevitt, John T.; Campbell, Charles L.; Miller, Craig S.

    2013-01-01

    Objective To determine the utility of oral fluids for assessment of coronary and cardiovascular (CVD) health. Study Design Twenty-nine patients with pre-existing CVD disease underwent an invasive cardiac procedure (alcohol septal ablation or percutaneous coronary intervention) and provided unstimulated whole saliva (UWS), sublingual swabs (LS), gingival swabs (GS) and serum at 0, 8, 16, 24, 48 hr. Concentrations of 13 relevant biomarkers were determined and correlated with levels in serum and the oral fluids. Results Concentrations of the majority of biomarkers were higher in UWS than LS and GS. Coronary and CVD disease biomarkers in UWS correlated better with serum than LS and GS based on group status and measures of time effect. Seven biomarkers demonstrated time effect changes consistent with serum biomarkers, including C-reactive protein and troponin I. Conclusions Changes in serum biomarker profiles are reflected in oral fluids suggesting that oral fluid biomarkers could aid in the assessment of cardiac ischemia/necrosis. PMID:22769406

  16. N-Terminal Pro-B-Type Natriuretic Peptide Plasma Levels as a Potential Biomarker for Cardiac Damage After Radiotherapy in Patients With Left-Sided Breast Cancer

    SciTech Connect

    D'Errico, Maria P.; Grimaldi, Luca; Petruzzelli, Maria F.; Gianicolo, Emilio A.L.; Tramacere, Francesco; Monetti, Antonio; Placella, Roberto; Pili, Giorgio; Andreassi, Maria Grazia; Sicari, Rosa; Picano, Eugenio; Portaluri, Maurizio

    2012-02-01

    Purpose: Adjuvant radiotherapy (RT) after breast-conserving surgery has been associated with increased cardiovascular mortality. Cardiac biomarkers may aid in identifying patients with radiation-mediated cardiac dysfunction. We evaluated the correlation between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin (TnI) and the dose of radiation to the heart in patients with left-sided breast cancer. Methods and Materials: NT-proBNP and TnI plasma concentrations were measured in 30 left-sided breast cancer patients (median age, 55.0 years) 5 to 22 months after RT (Group I) and in 30 left-sided breast cancer patients (median age, 57.0 years) before RT as control group (Group II). Dosimetric and geometric parameters of heart and left ventricle were determined in all patients of Group I. Seventeen patients underwent complete two-dimensional echocardiography. Results: NT-proBNP levels were significantly higher (p = 0.03) in Group I (median, 90.0 pg/ml; range, 16.7-333.1 pg/ml) than in Group II (median, 63.2 pg/ml; range, 11.0-172.5 pg/ml). TnI levels remained below the cutoff threshold of 0.07 ng/ml in both groups. In patients with NT-proBNP values above the upper limit of 125 pg/ml, there were significant correlations between plasma levels and V{sub 3Gy}(%) (p = 0.001), the ratios D{sub 15cm{sup 3}}(Gy)/D{sub mean}(Gy) (p = 0.01), the ratios D{sub 15cm}{sup 3}/D{sub 50%} (Gy) (p = 0.008) for the heart and correlations between plasma levels and V{sub 2Gy} (%) (p = 0.002), the ratios D{sub 1cm{sup 3}}(Gy)/D{sub mean}(Gy) (p = 0.03), and the ratios D{sub 0.5cm{sup 3}}(Gy)/D{sub 50%}(Gy) (p = 0.05) for the ventricle. Conclusions: Patients with left-sided breast cancer show higher values of NT-pro BNP after RT when compared with non-RT-treated matched patients, increasing in correlation with high doses in small volumes of heart and ventricle. The findings of this study show that the most important parameters are not the mean doses but instead the small

  17. Increasing Safety and Reducing Environmental Damage Risk from Aging High-Level Radioactive Waste Tanks

    SciTech Connect

    Steffler, Eric D.; McClintock, Frank A.; Lam, Poh-Sang; Williamson, Richard L.; Lloyd, W. R.; Rashid, Mark M.

    2003-06-01

    There exists a paramount need for improved understanding the behavior of high-level nuclear waste containers and the impact on structural integrity in terms of leak tightness and mechanical stability. The current program aims to develop and verify models of crack growth in high level waste tanks under accidental overloads such as ground settlement, earthquakes and airplane crashes based on extending current fracture mechanics methods. While studies in fracture have advanced, the mechanics have not included extensive crack growth. For problems at the INEEL, Savannah River Site and Hanford there are serious limitations to current theories regarding growth of surface cracks through the thickness and the extension of through-thickness cracks. We propose to further develop and extend slip line fracture mechanics (SLFM, a ductile fracture modeling methodology) and, if need be, other ductile fracture characterizing approaches with the goal of predicting growth of surface cracks to the point o f penetration of the opposing surface. Ultimately we aim to also quantify the stress and displacement fields surrounding a growing crack front (slanted and tunneled) using generalized plane stress and fully plastic, three-dimensional finite element analyses. Finally, we will investigate the fracture processes associated with the previously observed transition of stable ductile crack growth to unstable cleavage fracture to include estimates of event probability. These objectives will build the groundwork for a reliable predictive model of fracture in the HLW storage tanks that will also be applicable to standardized spent nuclear fuel storage canisters. This predictive capability will not only reduce the potential for severe environmental damage, but will also serve to guide safe retrieval of waste. This program was initiated in November of 2001.

  18. Increasing Safety and Reducing Environmental Damage Risk from Aging High-Level Radioactive Waste Tanks

    SciTech Connect

    Steffler, Eric D.; McClintock, Frank A.; Lam, Poh-Sang; Lloyd, W. R.

    2002-06-01

    There exists a paramount need for improved understanding the behavior of high-level nuclear waste containers and the impact on structural integrity in terms of leak tightness and mechanical stability. The current program, which at the time of this writing is in its early stages, aims to develop and verify models of crack growth in high level waste tanks under accidental overloads such as ground settlement, earthquakes and airplane crashes based on extending current fracture mechanics methods. While studies in fracture have advanced, the mechanics have not included extensive crack growth. For problems at the INEEL, Savannah River Site and Hanford there are serious limitations to current theories regarding growth of surface cracks through the thickness and the extension of through-thickness cracks. We propose to further develop and extend slip line fracture mechanics (SLFM, a ductile fracture modeling methodology) and, if need be, other ductile fracture characterizing approaches with the goal of predicting growth of surface cracks to the point of penetration of the opposing surface. We also aim to quantify the stress and displacement fields surrounding a growing crack front (slanted and tunneled) using generalized plane stress and fully plastic, three-dimensional finite element analyses. Finally, we will quantify the fracture processes associated with the previously observed transition of stable ductile crack growth to unstable cleavage fracture to include estimates of event probability. These objectives will build the groundwork for a reliable predictive model of fracture in the HLW storage tanks that will also be applicable to standardized spent nuclear fuel storage canisters. This predictive capability will not only reduce the potential for severe environmental damage, but will also serve to justify life extension through retrieval of waste. This program was initiated in November of 2001.

  19. Developing Community-Level Policy and Practice to Reduce Traffic-Related Air Pollution Exposure

    PubMed Central

    Brugge, Doug; Patton, Allison P.; Bob, Alex; Reisner, Ellin; Lowe, Lydia; Bright, Oliver-John M.; Durant, John L.; Newman, Jim; Zamore, Wig

    2016-01-01

    The literature consistently shows associations of adverse cardiovascular and pulmonary outcomes with residential proximity to highways and major roadways. Air monitoring shows that traffic-related pollutants (TRAP) are elevated within 200–400 m of these roads. Community-level tactics for reducing exposure include the following: 1) HEPA filtration; 2) Appropriate air-intake locations; 3) Sound proofing, insulation and other features; 4) Land-use buffers; 5) Vegetation or wall barriers; 6) Street-side trees, hedges and vegetation; 7) Decking over highways; 8) Urban design including placement of buildings; 9) Garden and park locations; and 10) Active travel locations, including bicycling and walking paths. A multidisciplinary design charrette was held to test the feasibility of incorporating these tactics into near-highway housing and school developments that were in the planning stages. The resulting designs successfully utilized many of the protective tactics and also led to engagement with the designers and developers of the sites. There is a need to increase awareness of TRAP in terms of building design and urban planning. PMID:27413416

  20. Chemical genoprotection: reducing biological damage to as low as reasonably achievable levels

    PubMed Central

    Alcaraz, M; Armero, D; Martínez-Beneyto, Y; Castillo, J; Benavente-García, O; Fernandez, H; Alcaraz-Saura, M; Canteras, M

    2011-01-01

    Objectives The aim of this study was to evaluate the antioxidant substances present in the human diet with an antimutagenic protective capacity against genotoxic damage induced by exposure to X-rays in an attempt to reduce biological damage to as low a level as reasonably possible. Methods Ten compounds were assessed using the lymphocyte cytokinesis-block micronucleus (MN) cytome test. The compounds studied were added to human blood at 25 μM 5 min before exposure to irradiation by 2 Gy of X-rays. Results The protective capacity of the antioxidant substances assessed was from highest to lowest according to the frequency of the MN generated by X-ray exposure: rosmarinic acid = carnosic acid = δ-tocopherol = l-acid ascorbic = apigenin = amifostine (P < 0.001) > green tea extract = diosmine = rutin = dimetylsulfoxide (P < 0.05) > irradiated control. The reduction in genotoxic damage with the radiation doses administered reached 58%, which represents a significant reduction in X-ray-induced chromosomal damage (P < 0.001). This degree of protection is greater than that obtained with amifostine, a radioprotective compound used in radiotherapy and which is characterised by its high toxicity. Conclusion Several antioxidant substances, common components of the human diet and lacking toxicity, offer protection from the biological harm induced by ionizing radiation. Administering these protective substances to patients before radiological exploration should be considered, even in the case of small radiation doses and regardless of the biological damage expected. PMID:21697157

  1. Developing Community-Level Policy and Practice to Reduce Traffic-Related Air Pollution Exposure.

    PubMed

    Brugge, Doug; Patton, Allison P; Bob, Alex; Reisner, Ellin; Lowe, Lydia; Bright, Oliver-John M; Durant, John L; Newman, Jim; Zamore, Wig

    2015-06-01

    The literature consistently shows associations of adverse cardiovascular and pulmonary outcomes with residential proximity to highways and major roadways. Air monitoring shows that traffic-related pollutants (TRAP) are elevated within 200-400 m of these roads. Community-level tactics for reducing exposure include the following: 1) HEPA filtration; 2) Appropriate air-intake locations; 3) Sound proofing, insulation and other features; 4) Land-use buffers; 5) Vegetation or wall barriers; 6) Street-side trees, hedges and vegetation; 7) Decking over highways; 8) Urban design including placement of buildings; 9) Garden and park locations; and 10) Active travel locations, including bicycling and walking paths. A multidisciplinary design charrette was held to test the feasibility of incorporating these tactics into near-highway housing and school developments that were in the planning stages. The resulting designs successfully utilized many of the protective tactics and also led to engagement with the designers and developers of the sites. There is a need to increase awareness of TRAP in terms of building design and urban planning.

  2. Human ribosomes from cells with reduced dyskerin levels are intrinsically altered in translation.

    PubMed

    Penzo, Marianna; Rocchi, Laura; Brugiere, Sabine; Carnicelli, Domenica; Onofrillo, Carmine; Couté, Yohann; Brigotti, Maurizio; Montanaro, Lorenzo

    2015-08-01

    Dyskerin is a pseudouridine (ψ) synthase involved in fundamental cellular processes including uridine modification in rRNA and small nuclear RNA and telomere stabilization. Dyskerin functions are altered in X-linked dyskeratosis congenita (X-DC) and cancer. Dyskerin's role in rRNA pseudouridylation has been suggested to underlie the alterations in mRNA translation described in cells lacking dyskerin function, although relevant direct evidences are currently lacking. Our purpose was to establish definitely whether defective dyskerin function might determine an intrinsic ribosomal defect leading to an altered synthetic activity. Therefore, ribosomes from dyskerin-depleted human cells were purified and 1) added to a controlled reticulocyte cell-free system devoid of ribosomes to study mRNA translation; 2) analyzed for protein contamination and composition by mass spectrometry, 3) analyzed for global pseudouridylation levels. Ribosomes purified from dyskerin-depleted cells showed altered translational fidelity and internal ribosome entry site (IRES)-mediated translation. These ribosomes displayed reduced uridine modification, whereas they were not different in terms of protein contamination or ribosomal protein composition with respect to ribosomes from matched control cells with full dyskerin activity. In conclusion, lack of dyskerin function in human cells induces a defect in rRNA uridine modification, which is sufficient to alter ribosome activity.

  3. Biomarkers of Selenium Status

    PubMed Central

    Combs, Gerald F.

    2015-01-01

    The essential trace element, selenium (Se), has multiple biological activities, which depend on the level of Se intake. Relatively low Se intakes determine the expression of selenoenzymes in which it serves as an essential constituent. Higher intakes have been shown to have anti-tumorigenic potential; and very high Se intakes can produce adverse effects. This hierarchy of biological activities calls for biomarkers informative at different levels of Se exposure. Some Se-biomarkers, such as the selenoproteins and particularly GPX3 and SEPP1, provide information about function directly and are of value in identifying nutritional Se deficiency and tracking responses of deficient individuals to Se-treatment. They are useful under conditions of Se intake within the range of regulated selenoprotein expression, e.g., for humans <55 μg/day and for animals <20 μg/kg diet. Other Se-biomarkers provide information indirectly through inferences based on Se levels of foods, tissues, urine or feces. They can indicate the likelihood of deficiency or adverse effects, but they do not provide direct evidence of either condition. Their value is in providing information about Se status over a wide range of Se intake, particularly from food forms. There is need for additional Se biomarkers particularly for assessing Se status in non-deficient individuals for whom the prospects of cancer risk reduction and adverse effects risk are the primary health considerations. This would include determining whether supranutritional intakes of Se may be required for maximal selenoprotein expression in immune surveillance cells. It would also include developing methods to determine low molecular weight Se-metabolites, i.e., selenoamino acids and methylated Se-metabolites, which to date have not been detectable in biological specimens. Recent analytical advances using tandem liquid chromatography-mass spectrometry suggest prospects for detecting these metabolites. PMID:25835046

  4. Biomarkers of Oxidative Stress and Heavy Metal Levels as Indicators of Environmental Pollution in African Cat Fish (Clarias gariepinus) from Nigeria Ogun River

    PubMed Central

    Farombi, E. O.; Adelowo, O. A.; Ajimoko, Y. R.

    2007-01-01

    Levels of Zn, Cu, Cd, As, and Pb in the kidney, Liver, Gills and Heart of African cat fish (Clarias gariepinus) from the Ogun River in Ogun State located close to six major industries in the South Western part of Nigeria, were determined using Bulk Scientific Atomic Absorption Spectrophotometer. Fishes were also collected from Government owned fish farm in Agodi, Ibadan which was considered a reference site. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione (GSH) concentration and malondialdehyde (MDA) formation were also determined. The trend of accumulation of the metals in the organs is as follows: Heart - Zn > Cu > Pb > As > Cd; Gills - Zn > Cu > Pb > Cd > As; Kidney - Zn > Cu > Pb > As > Cd; Liver -Zn > Cu > Pb > As > Cd. The order of concentration of the metals in the organs is as follows: Arsenite - Kidney > Liver > Gills > Heart; Zinc - Gills > Liver > Kidney > Heart; Lead- Liver > Kidney > Gills > Heart; Copper- Kidney > Liver > Gills > Heart; Cadmium > Liver > Gills > Kidney > Heart. The levels of heavy metals ranged between 0.25–8.96 ppm in the heart, 0.69– 19.05 ppm in the kidneys, 2.10–19.75 ppm in the liver and 1.95–20.35 ppm in the gills. SOD activity increased by 61% in the liver, 50% in the kidney and in the heart by 28 % while a significant decrease (44%) was observed in the gill of Clarias gariepinus from Ogun river compared to that Agodi fish farm (P<0.001). On the contrary there was 46%, 41%, 50% and 19% decrease in CAT activity in the liver, kidney, gills and heart respectively. The levels of GST activities in the liver, kidney and heart of Clarias gariepinus from Ogun river increased by 62%, 72% and 37% respectively (P<0.001) whereas there was a significant decrease (41%) in the gills (P<0.05) compared to that from the Agodi fish farm. GSH concentration increased by 81%, 83% and 53% in the liver, kidney and heart respectively but decreased by 44% in the gills. MDA levels of

  5. Highly specific changes in antioxidant levels and lipid peroxidation in Parkinson's disease and its progression: Disease and staging biomarkers and new drug targets.

    PubMed

    de Farias, Carine Coneglian; Maes, Michael; Bonifácio, Kamila Landucci; Bortolasci, Chiara Cristina; de Souza Nogueira, André; Brinholi, Francis Fregonesi; Matsumoto, Andressa Keiko; do Nascimento, Matheus Amarante; de Melo, Lúcio Baena; Nixdorf, Suzana Lucy; Lavado, Edson Lopes; Moreira, Estefânia Gastaldello; Barbosa, Décio Sabbatini

    2016-03-23

    There is evidence that immune-inflammatory, stress of reactive oxygen and nitrogen species (IO&NS) processes play a role in the neurodegenerative processes observed in Parkinson's disease (PD). The aim of the present study was to investigate peripheral IO&NS biomarkers in PD. We included 56 healthy individuals and 56 PD patients divided in two groups: early PD stage and late PD stage. Plasma lipid hydroperoxides (LOOH), malondialdehyde (MDA), nitric oxide metabolites (NOx), sulfhydryl (SH) groups, catalase (CAT) activity, superoxide dismutase (SOD) activity, paraoxonase (PON)1 activity, total radical trapping antioxidant parameter (TRAP) and C-reactive protein (CRP) were measured. PD is characterized by increased LOOH, MDA and SOD activity and lowered CAT activity. A combination of five O&NS biomarkers highly significantly predicts PD with a sensitivity of 94.5% and a specificity of 86.8% (i.e., MDA, SOD activity, TRAP, SH-groups and CAT activity). The single best biomarker of PD is MDA, while LOOH and SOD activity are significantly associated with late PD stage, but not early PD stage. Antiparkinson drugs did not affect O&NS biomarkers, but levodopa+carbidopa significantly increased CRP. It is suggested that MDA may serve as a disease biomarker, while LOOH and SOD activity are associated with late PD stage characteristic. New treatments for PD should not only target dopamine but also lipid peroxidation.

  6. Decreased vitellogenin inducibility and 17β-estradiol levels correlated with reduced egg production in killifish (Fundulus heteroclitus) from Newark Bay, NJ

    PubMed Central

    Bugel, Sean M.; White, Lori A.; Cooper, Keith R.

    2016-01-01

    Aquatic species inhabiting polluted estuaries are exposed to complex mixtures of xenobiotics which can alter normal reproduction. We previously reported that female Atlantic killifish (Fundulus heteroclitus) from the highly contaminated Newark Bay, NJ (USA) exhibited an inhibition of oocyte development due to reduced vitellogenin (egg-yolk precursor) levels. Our hypothesis was that the inhibition of oocyte development in Newark Bay killifish is due to (1) deficient levels of circulating 17β-estradiol, and (2) a decreased sensitivity of the vitellogenin pathway to physiological doses of 17β-estradiol. In the first study, adult naïve killifish from Tuckerton, NJ (reference) were caged at Tuckerton and Newark Bay. After 1 month, males caged at Newark Bay exhibited inductions of hepatic vitellogenin and estrogen receptor α, which were transient and returned to basal levels after 2 months (p ≤ 0.05). In the second study, fecundity and 17β-estradiol levels were measured in reproductively active adult females from Tuckerton and Newark Bay. Tuckerton females produced 140 eggs per female and Newark Bay females produced 11 eggs per female. Embryos from Newark Bay had 34% greater mortality and 28% less hatch, relative to Tuckerton. In addition, embryo mass and yolk-volume of Newark Bay embryos compared to Tuckerton embryos was 16% and 25% lower, respectively. Circulating 17β-estradiol levels in Newark Bay females (0.26 ng/mL) were measured to be 8-fold lower than Tuckerton females (2.25 ng/mL). In the third study, adult killifish from both sites were dosed with 17β-estradiol to assess the sensitivity of the vitellogenin pathway. At doses of 0.01, 0.1, 1 and 10 ng/g body weight, induction levels of circulating vitellogenin in Newark Bay males were significantly inhibited by 97, 99, 98 and 44%, respectively, compared to Tuckerton males. At doses of 0.01, 0.1, 1, 10 and 100 ng/g body weight, induction levels of circulating vitellogenin in Newark Bay females were

  7. Decreased vitellogenin inducibility and 17β-estradiol levels correlated with reduced egg production in killifish (Fundulus heteroclitus) from Newark Bay, NJ.

    PubMed

    Bugel, Sean M; White, Lori A; Cooper, Keith R

    2011-09-01

    Aquatic species inhabiting polluted estuaries are exposed to complex mixtures of xenobiotics which can alter normal reproduction. We previously reported that female Atlantic killifish (Fundulus heteroclitus) from the highly contaminated Newark Bay, NJ (USA) exhibited an inhibition of oocyte development due to reduced vitellogenin (egg-yolk precursor) levels. Our hypothesis was that the inhibition of oocyte development in Newark Bay killifish is due to (1) deficient levels of circulating 17β-estradiol, and (2) a decreased sensitivity of the vitellogenin pathway to physiological doses of 17β-estradiol. In the first study, adult naïve killifish from Tuckerton, NJ (reference) were caged at Tuckerton and Newark Bay. After 1 month, males caged at Newark Bay exhibited inductions of hepatic vitellogenin and estrogen receptor α, which were transient and returned to basal levels after 2 months (p≤0.05). In the second study, fecundity and 17β-estradiol levels were measured in reproductively active adult females from Tuckerton and Newark Bay. Tuckerton females produced 140 eggs per female and Newark Bay females produced 11 eggs per female. Embryos from Newark Bay had 34% greater mortality and 28% less hatch, relative to Tuckerton. In addition, embryo mass and yolk-volume of Newark Bay embryos compared to Tuckerton embryos was 16% and 25% lower, respectively. Circulating 17β-estradiol levels in Newark Bay females (0.26 ng/mL) were measured to be 8-fold lower than Tuckerton females (2.25 ng/mL). In the third study, adult killifish from both sites were dosed with 17β-estradiol to assess the sensitivity of the vitellogenin pathway. At doses of 0.01, 0.1, 1 and 10 ng/g body weight, induction levels of circulating vitellogenin in Newark Bay males were significantly inhibited by 97, 99, 98 and 44%, respectively, compared to Tuckerton males. At doses of 0.01, 0.1, 1, 10 and 100 ng/g body weight, induction levels of circulating vitellogenin in Newark Bay females were inhibited

  8. Biochemical assessment of red blood cells during storage by 1H nuclear magnetic resonance spectroscopy. Identification of a biomarker of their level of protection against oxidative stress

    PubMed Central

    Pertinhez, Thelma A.; Casali, Emanuela; Lindner, Luisa; Spisni, Alberto; Baricchi, Roberto; Berni, Pamela

    2014-01-01

    Background Blood transfusion is an established therapeutic practice. The characteristics of blood components at different storage times are expected to affect the efficacy of transfusion therapy. Metabolic profiling by nuclear magnetic resonance (NMR) spectroscopy requires little or no sample treatment and allows identification of more than 50 soluble metabolites in a single experiment. The aim of this study was to assess the metabolic behaviour of red blood cells during 42 days of storage in blood bank conditions. Materials and methods Red blood cells (RBC), collected from eight healthy male donors, aged 25–50 years, were prepared as prestorage leukoreduced erythrocyte concentrates and stored under standard blood bank conditions. Samples taken at various storage times were separated in two fractions: the supernatant, recovered after centrifugation, and the red blood cell lysate obtained after protein depletion by ultrafiltration. The metabolic profile of the red blood cells was determined from analysis of 1H-NMR spectra. Results The red blood cell supernatant was studied to track the consumption of the preservative additives and to detect and quantify up to 30 metabolites excreted by the erythrocytes. The NMR spectra of the RBC lysate provided complementary information on some biochemical pathways and set the basis for building a time-dependent red blood cell metabolic profile. Discussion We proved the analytical power of 1H-NMR spectroscopy to study red blood cell metabolism under blood bank conditions. A potential biomarker able to provide information on the level of cellular oxidative stress protection was identified. Our data support the hypothesis that a more detailed knowledge of metabolic modifications during storage opens the way to the development of new and more effective protocols for red blood cell conservation and patient-oriented transfusion therapy. PMID:24960643

  9. Biological Networks for Cancer Candidate Biomarkers Discovery

    PubMed Central

    Yan, Wenying; Xue, Wenjin; Chen, Jiajia; Hu, Guang

    2016-01-01

    Due to its extraordinary heterogeneity and complexity, cancer is often proposed as a model case of a systems biology disease or network disease. There is a critical need of effective biomarkers for cancer diagnosis and/or outcome prediction from system level analyses. Methods based on integrating omics data into networks have the potential to revolutionize the identification of cancer biomarkers. Deciphering the biological networks underlying cancer is undoubtedly important for understanding the molecular mechanisms of the disease and identifying effective biomarkers. In this review, the networks constructed for cancer biomarker discovery based on different omics level data are described and illustrated from recent advances in the field. PMID:27625573

  10. BACE-1, PS-1 and sAPPβ Levels Are Increased in Plasma from Sporadic Inclusion Body Myositis Patients: Surrogate Biomarkers among Inflammatory Myopathies

    PubMed Central

    Catalán-García, Marc; Garrabou, Glòria; Morén, Constanza; Guitart-Mampel, Mariona; Gonzalez-Casacuberta, Ingrid; Hernando, Adriana; Gallego-Escuredo, Jose Miquel; Yubero, Dèlia; Villarroya, Francesc; Montero, Raquel; O-Callaghan, Albert Selva; Cardellach, Francesc; Grau, Josep Maria

    2015-01-01

    Sporadic inclusion body myositis (sIBM) is a rare disease that is difficult to diagnose. Muscle biopsy provides three prominent pathological findings: inflammation, mitochondrial abnormalities and fibber degeneration, represented by the accumulation of protein depots constituted by β-amyloid peptide, among others. We aim to perform a screening in plasma of circulating molecules related to the putative etiopathogenesis of sIBM to determine potential surrogate biomarkers for diagnosis. Plasma from 21 sIBM patients and 20 age- and gender-paired healthy controls were collected and stored at −80°C. An additional population of patients with non-sIBM inflammatory myopathies was also included (nine patients with dermatomyositis and five with polymyositis). Circulating levels of inflammatory cytokines (interleukin [IL]-6 and tumor necrosis factor [TNF]-α), mitochondrial-related molecules (free plasmatic mitochondrial DNA [mtDNA], fibroblast growth factor-21 [FGF-21] and coenzyme-Q10 [CoQ]) and amyloidogenic-related molecules (beta-secretase-1 [BACE-1], presenilin-1 [PS-1], and soluble Aβ precursor protein [sAPPβ]) were assessed with magnetic bead–based assays, real-time polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA) and high-pressure liquid chromatography (HPLC). Despite remarkable trends toward altered plasmatic expression of inflammatory and mitochondrial molecules (increased IL-6, TNF-α, circulating mtDNA and FGF-21 levels and decreased content in CoQ), only amyloidogenic degenerative markers including BACE-1, PS-1 and sAPPβ levels were significantly increased in plasma from sIBM patients compared with controls and other patients with non-sIBM inflammatory myopathies (p < 0.05). Inflammatory, mitochondrial and amyloidogenic degeneration markers are altered in plasma of sIBM patients confirming their etiopathological implication in the disease. Sensitivity and specificity analysis show that BACE-1, PS-1 and sAPPβ represent a good

  11. Gamma-magnetic normalization - new effect to reduce flux-gate magnetometer noise level

    NASA Astrophysics Data System (ADS)

    Korepanov, V.

    2012-04-01

    It is the author's opinion confirmed by numerous experiments, that the FGM noise level (NL) is determined not by Barkhausen jumps during the core remagnetization from positive to negative state as the majority of designers believe, but by non-repeatability of the magnetic domains transition from negative to positive states and back. This shows the way how to reduce the magnetic noise: to manufacture the magnetic material with a structure which will create conditions for magnetic domain walls to glide easily and uniformly when changing their orientation leading to minimal efforts at cyclic remagnetization. Ideally, such a material may be represented as a solid "liquid" with freely floating uniform magnetic domains without walls friction. To reduce the specific NL of the materials, several post-melting processing technologies were developed. A set of experiments made by many investigators has shown that the best results gives the magnetic materials annealing in vacuum or in any inert gas applying by this during all annealing time the alternative magnetic field, imitating core excitation field during FGM operation. If to accept the "solid liquid" model, this mechanism of NL decreasing has clear physical explanation: permanent re-magnetization of domains leads to the structural improvements favorable namely for the homogenization of transitions, rise of temperature gives necessary energy for the impurities liquidation. Probably, M. Acuna was the first who reported that during FGM operation in space its NL is decreasing with time and attributed this to the relaxation of mechanical stresses in the core material in weightlessness conditions [1]. We studied in details the conditions in which the core material is in space: weightlessness, vacuum and radiation. Mechanical stresses relaxation hypothesis was rejected because the internal forces in any solid body are much stronger as those to which a gravity force might have influence. Also the tests of FGM sensor in vacuum

  12. Combining enhanced biomass density with reduced lignin level for improved forage quality.

    PubMed

    Gallego-Giraldo, Lina; Shadle, Gail; Shen, Hui; Barros-Rios, Jaime; Fresquet Corrales, Sandra; Wang, Huanzhong; Dixon, Richard A

    2016-03-01

    To generate a forage crop with increased biomass density that retains forage quality, we have genetically transformed lines of alfalfa (Medicago sativa L.) expressing antisense constructs targeting two different lignin pathway biosynthetic genes with a construct for down-regulation of a WRKY family transcription factor that acts as a repressor of secondary cell wall formation in pith tissues. Plants with low-level expression of the WRKY dominant repressor construct produced lignified cell walls in pith tissues and exhibited enhanced biomass and biomass density, with an increase in total sugars in the cell wall fraction; however, lines with high expression of the WRKY dominant repressor construct exhibited a very different phenotype, with loss of interfascicular fibres associated with repression of the NST1 transcription factor. This latter phenotype was not observed in transgenic lines in which the WRKY transcription factor was down-regulated by RNA interference. Enhanced and/or ectopic deposition of secondary cell walls was also seen in corn and switchgrass expressing WRKY dominant repressor constructs, with enhanced biomass in corn but reduced biomass in switchgrass. Neutral detergent fibre digestibility was not impacted by WRKY expression in corn. Cell walls from WRKY-DR-expressing alfalfa plants with enhanced secondary cell wall formation exhibited increased sugar release efficiency, and WRKY dominant repressor expression further increased sugar release in alfalfa down-regulated in the COMT, but not the HCT, genes of lignin biosynthesis. These results suggest that significant enhancements in forage biomass and quality can be achieved through engineering WRKY transcription factors in both monocots and dicots.

  13. Ecological feedbacks can reduce population-level efficacy of wildlife fertility control

    USGS Publications Warehouse

    Ransom, Jason I.; Powers, Jenny G.; Hobbs, N. Thompson; Baker, Dan L.

    2014-01-01

    1. Anthropogenic stress on natural systems, particularly the fragmentation of landscapes and the extirpation of predators from food webs, has intensified the need to regulate abundance of wildlife populations with management. Controlling population growth using fertility control has been considered for almost four decades, but nearly all research has focused on understanding effects of fertility control agents on individual animals. Questions about the efficacy of fertility control as a way to control populations remain largely unanswered. 2. Collateral consequences of contraception can produce unexpected changes in birth rates, survival, immigration and emigration that may reduce the effectiveness of regulating animal abundance. The magnitude and frequency of such effects vary with species-specific social and reproductive systems, as well as connectivity of populations. Developing models that incorporate static demographic parameters from populations not controlled by contraception may bias predictions of fertility control efficacy. 3. Many population-level studies demonstrate that changes in survival and immigration induced by fertility control can compensate for the reduction in births caused by contraception. The most successful cases of regulating populations using fertility control come from applications of contraceptives to small, closed populations of gregarious and easily accessed species. 4. Fertility control can result in artificial selection pressures on the population and may lead to long-term unintentional genetic consequences. The magnitude of such selection is dependent on individual heritability and behavioural traits, as well as environmental variation. 5. Synthesis and applications. Understanding species' life-history strategies, biology, behavioural ecology and ecological context is critical to developing realistic expectations of regulating populations using fertility control. Before time, effort and funding are invested in wildlife

  14. Phytochemicals from Tradescantia albiflora Kunth Extracts Reduce Serum Uric Acid Levels in Oxonate-induced Rats

    PubMed Central

    Wang, Wen-Ling; Sheu, Shi-Yuan; Huang, Wen-Dar; Chuang, Ya-Ling; Tseng, Han-Chun; Hwang, Tzann-Shun; Fu, Yuan-Tsung; Kuo, Yueh-Hsiung; Yao, Chun-Hsu; Kuo, Tzong-Fu

    2016-01-01

    Background: Tradescantia albiflora (TA) Kunth (Commelinaceae) has been used for treating gout and hyperuricemia as folklore remedies in Taiwan. Therefore, it is worthwhile to study the effect of TA extracts on lowering uric acid activity. The hypouricemic effects of TA extracts on potassium oxonate (PO)-induced acute hyperuricemia were investigated for the first time. Materials and Methods: All treatments at the same volume (1 ml) were orally administered to the abdominal cavity of PO-induced hyperuricemic rats. One milliliter of TA extract in n-hexane (HE), ethyl acetate (EA), n-butanol (BuOH), and water fractions has 0.28, 0.21, 0.28, and 1.03 mg TA, respectively; and the plasma uric acid (PUA) level was measured for a consecutive 4 h after administration. Results: All four fractions' extracts derived from TA were observed to significantly reduce PUA compared with the PO group. The EA-soluble fraction (TA-EA) exhibited the best xanthine oxidase (XO) inhibitory activity. Following column chromatography, 12 phytochemicals were isolated and identified from the EA fraction. The IC50 values of isolated phytochemicals indicated that bracteanolide A (AR11) showed the remarkable XO inhibitory effect (IC50 value of 76.4 μg/ml). These findings showed that the in vivo hypouricemic effect in hyperuricemic rats was consistent with in vitro XO inhibitory activity, indicating that TA extracts and derived phytochemicals could be potential candidates as hypouricemic agents. SUMMARY Tradescantia albiflora extracts possess in vivo hypouricemic action in hyperuricemic ratsT. albiflora extracts exhibited strong inhibitory activity against xanthine oxidase (XO)Butenolide may play an important role in XO inhibitionThe extract bracteanolide A was demonstrated potent XO inhibitory activity in vitro. Abbreviations used: TA: Tradescantia albiflora, PO: potassium oxonate, HE: n-hexane, EA: ethyl acetate, BuOH: n-butanol, PUA: plasma uric acid, XO: xanthine oxidase, MeOH: methanol, IP

  15. Ecological feedbacks can reduce population-level efficacy of wildlife fertility control.

    PubMed

    Ransom, Jason I; Powers, Jenny G; Thompson Hobbs, N; Baker, Dan L

    2014-02-01

    Anthropogenic stress on natural systems, particularly the fragmentation of landscapes and the extirpation of predators from food webs, has intensified the need to regulate abundance of wildlife populations with management. Controlling population growth using fertility control has been considered for almost four decades, but nearly all research has focused on understanding effects of fertility control agents on individual animals. Questions about the efficacy of fertility control as a way to control populations remain largely unanswered.Collateral consequences of contraception can produce unexpected changes in birth rates, survival, immigration and emigration that may reduce the effectiveness of regulating animal abundance. The magnitude and frequency of such effects vary with species-specific social and reproductive systems, as well as connectivity of populations. Developing models that incorporate static demographic parameters from populations not controlled by contraception may bias predictions of fertility control efficacy.Many population-level studies demonstrate that changes in survival and immigration induced by fertility control can compensate for the reduction in births caused by contraception. The most successful cases of regulating populations using fertility control come from applications of contraceptives to small, closed populations of gregarious and easily accessed species.Fertility control can result in artificial selection pressures on the population and may lead to long-term unintentional genetic consequences. The magnitude of such selection is dependent on individual heritability and behavioural traits, as well as environmental variation.Synthesis and applications. Understanding species' life-history strategies, biology, behavioural ecology and ecological context is critical to developing realistic expectations of regulating populations using fertility control. Before time, effort and funding are invested in wildlife contraception, managers may

  16. Tuberculosis Biomarkers: From Diagnosis to Protection

    PubMed Central

    Goletti, Delia; Petruccioli, Elisa; Joosten, Simone A.; Ottenhoff, Tom H.M.

    2016-01-01

    New approaches to control tuberculosis (TB) worldwide are needed. In particular, new tools for diagnosis and new biomarkers are required to evaluate both pathogen and host key elements of the response to infection. Non-sputum based diagnostic tests, biomarkers predictive of adequate responsiveness to treatment, and biomarkers of risk of developing active TB disease are major goals. Here, we review the current state of the field. Although reports on new candidate biomarkers are numerous, validation and independent confirmation are rare. Efforts are needed to reduce the gap between the exploratory up-stream identification of candidate biomarkers, and the validation of biomarkers against clear clinical endpoints in different populations. This will need a major commitment from both scientists and funding bodies. PMID:27403267

  17. Cardiovascular disease biomarkers across autoimmune diseases.

    PubMed

    Ahearn, Joseph; Shields, Kelly J; Liu, Chau-Ching; Manzi, Susan

    2015-11-01

    Cardiovascular disease is increasingly recognized as a major cause of premature mortality among those with autoimmune disorders. There is an urgent need to identify those patients with autoimmune disease who are at risk for CVD so as to optimize therapeutic intervention and ultimately prevention. Accurate identification, monitoring and stratification of such patients will depend upon a panel of biomarkers of cardiovascular disease. This review will discuss some of the most recent biomarkers of cardiovascular diseases in autoimmune disease, including lipid oxidation, imaging biomarkers to characterize coronary calcium, plaque, and intima media thickness, biomarkers of inflammation and activated complement, genetic markers, endothelial biomarkers, and antiphospholipid antibodies. Clinical implementation of these biomarkers will not only enhance patient care but also likely accelerate the pharmaceutical pipeline for targeted intervention to reduce or eliminate cardiovascular disease in the setting of autoimmunity.

  18. High Serum Lipopolysaccharide-Binding Protein Level in Chronic Hepatitis C Viral Infection Is Reduced by Anti-Viral Treatments

    PubMed Central

    Nien, Hsiao-Ching; Hsu, Shih-Jer; Su, Tung-Hung; Yang, Po-Jen; Sheu, Jin-Chuan; Wang, Jin-Town; Chow, Lu-Ping; Chen, Chi-Ling

    2017-01-01

    Background Lipopolysaccharide-binding protein (LBP) has been reported to associate with metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease. Since chronic hepatitis C virus (HCV) infection is associated with metabolic derangements, the relationship between LBP and HCV deserves additional studies. This study aimed to determine the serum LBP level in subjects with or without HCV infection and investigate the change of its level after anti-viral treatments with or without interferon. Methods and Findings We recruited 120 non-HCV subjects, 42 and 17 HCV-infected subjects respectively treated with peginterferon α-2a/ribavirin and direct-acting antiviral drugs. Basic information, clinical data, serum LBP level and abdominal ultrasonography were collected. All the subjects provided written informed consent before being enrolled approved by the Research Ethics Committee of the National Taiwan University Hospital. Serum LBP level was significantly higher in HCV-infected subjects than non-HCV subjects (31.0 ± 8.8 versus 20.0 ± 6.4 μg/mL; p-value < 0.001). After multivariate analyses, LBP at baseline was independently associated with body mass index, hemoglobin A1c, alanine aminotransferase (ALT) and HCV infection. Moreover, the baseline LBP was only significantly positively associated with ALT and inversely with fatty liver in HCV-infected subjects. The LBP level significantly decreased at sustained virologic response (27.4 ± 6.6 versus 34.6 ± 7.3 μg/mL, p-value < 0.001; 15.9 ± 4.4 versus 22.2 ± 5.7 μg/mL, p-value = 0.001), regardless of interferon-based or -free therapy. Conclusions LBP, an endotoxemia associated protein might be used as an inflammatory biomarker of both infectious and non-infectious origins in HCV-infected subjects. PMID:28107471

  19. Effect of smoking reduction and cessation on the plasma levels of the oxidative stress biomarker glutathione--Post-hoc analysis of data from a smoking cessation trial.

    PubMed

    Mons, Ute; Muscat, Joshua E; Modesto, Jennifer; Richie, John P; Brenner, Hermann

    2016-02-01

    Cigarette smoke contains high concentrations of free radical components that induce oxidative stress. Smoking-induced oxidative stress is thought to contribute to chronic obstructive pulmonary disease, cardiovascular disease and lung cancer through degenerative processes in the lung and other tissues. It is uncertain however whether smoking cessation lowers the burden of oxidative stress. We used data from a randomized controlled cessation trial of 434 current smokers for a post-hoc examination of the effects of smoking cessation on blood plasma levels of total glutathione (tGSH), the most abundant endogenous antioxidant in cells, and total cysteine (tCys), an amino acid and constituent of glutathione. Smoking status was validated based on serum cotinine levels. Multivariate linear mixed models were fitted to examine the association of smoking cessation and change in cigarette consumption with tGSH and tCys. After 12 months follow-up, quitters (n=55) had significantly increased levels of tGSH compared to subjects who continued to smoke (P<0.01). No significant change in tGSH was found for subjects who continued to smoke but reduced their intensity of smoking. No significant effect of smoking cessation or reduction was observed on levels of tCys. These results suggest that smoking cessation but not smoking reduction reduces levels of oxidative stress.

  20. Transmural heterogeneity of cellular level power output is reduced in human heart failure

    PubMed Central

    Haynes, Premi; Nava, Kristofer E.; Lawson, Benjamin A.; Chung, Charles S.; Mitov, Mihail I.; Campbell, Stuart G.; Stromberg, Arnold J.; Sadayappan, Sakthivel; Bonnell, Mark R.; Hoopes, Charles W.; Campbell, Kenneth S.

    2014-01-01

    Heart failure is associated with pump dysfunction and remodeling but it is not yet known if the condition affects different transmural regions of the heart in the same way. We tested the hypotheses that the left ventricles of non-failing human hearts exhibit transmural heterogeneity of cellular level contractile properties, and that heart failure produces transmural region-specific changes in contractile function. Permeabilized samples were prepared from the sub-epicardial, mid-myocardial, and sub-endocardial regions of the left ventricular free wall of non-failing (n=6) and failing (n=10) human hearts. Power, an in vitro index of systolic function, was higher in non-failing mid-myocardial samples (0.59±0.06 μW mg−1) than in samples from the sub-epicardium (p=0.021) and the sub-endocardium (p=0.015). Non-failing mid-myocardial samples also produced more isometric force (14.3±1.33 kN m−2) than samples from the sub-epicardium (p=0.008) and the sub-endocardium (p=0.026). Heart failure reduced power (p=0.009) and force (p=0.042) but affected the mid-myocardium more than the other transmural regions. Fibrosis increased with heart failure (p=0.021) and mid-myocardial tissue from failing hearts contained more collagen than matched sub-epicardial (p<0.001) and sub-endocardial (p=0.043) samples. Power output was correlated with the relative content of actin and troponin I, and was also statistically linked to the relative content and phosphorylation of desmin and myosin light chain- 1. Non-failing human hearts exhibit transmural heterogeneity of contractile properties. In failing organs, region-specific fibrosis produces the greatest contractile deficits in the mid-myocardium. Targeting fibrosis and sarcomeric proteins in the mid-myocardium may be particularly effective therapies for heart failure. PMID:24560668

  1. Dried distillers grains with solubles with reduced corn silage levels in beef finishing diets.

    PubMed

    May, M L; Quinn, M J; Depenbusch, B E; Reinhardt, C D; Gibson, M L; Karges, K K; Cole, N A; Drouillard, J S

    2010-07-01

    Two finishing experiments were conducted to evaluate the use of 25% dried corn distillers grains with solubles (DDG) in beef cattle finishing diets by partially replacing a portion of the grain and soybean meal in the control diets. In Exp.1, crossbred heifers (n = 377; BW 378 +/- 4.1 kg) were fed diets consisting of steam-flaked corn (SFC) with a control diet containing 0% DDG and 15% corn silage (CS), 25% DDG and 15% CS, or 25% DDG and 5% CS. Compared with the control treatment, heifers fed DDG and 15% CS had a greater proportion of USDA yield grade 4 and 5 carcasses (P = 0.04; 5.68 vs. 14.12), and smaller LM area (P = 0.04; 86.09 vs. 82.48 cm(2)). In Exp. 2, crossbred heifers (n = 582; BW = 377 +/- 27.09 kg) were fed diets similar to Exp. 1 except dry-rolled corn (DRC) and SFC were compared as the basal grain sources. Treatments included DRC or SFC: with control diets containing 0% DDG and 15% CS, 25% DDG and 15% CS, or 25% DDG and 5% CS. Feeding SFC decreased DMI (P < 0.01), improved G:F (P < 0.01) and final shrunk BW (P = 0.05) compared with DRC. Average USDA yield grade was greater for cattle fed DRC than for those fed SFC (P = 0.02), but calculated yield grade was not different among treatments (P = 0.71). Feeding DDG and 5% CS, regardless of grain source, led to decreased DMI and greater G:F than feeding DDG and 15% CS (P = 0.02). When comparing the control treatments with the diets containing 25% DDG and 15% CS shrunk final BW, ADG, and G:F were decreased (P < or = 0.05); however, carcass-adjusted measurements were not different (P > 0.52). Results indicate that roughage levels can be reduced in feedlot diets containing 25% DDG with no adverse effects on BW gain, feed efficiency, or carcass quality.

  2. Biomarkers of satiation and satiety.

    PubMed

    de Graaf, Cees; Blom, Wendy A M; Smeets, Paul A M; Stafleu, Annette; Hendriks, Henk F J

    2004-06-01

    This review's objective is to give a critical summary of studies that focused on physiologic measures relating to subjectively rated appetite, actual food intake, or both. Biomarkers of satiation and satiety may be used as a tool for assessing the satiating efficiency of foods and for understanding the regulation of food intake and energy balance. We made a distinction between biomarkers of satiation or meal termination and those of meal initiation related to satiety and between markers in the brain [central nervous system (CNS)] and those related to signals from the periphery to the CNS. Various studies showed that physicochemical measures related to stomach distension and blood concentrations of cholecystokinin and glucagon-like peptide 1 are peripheral biomarkers associated with meal termination. CNS biomarkers related to meal termination identified by functional magnetic resonance imaging and positron emission tomography are indicators of neural activity related to sensory-specific satiety. These measures cannot yet serve as a tool for assessing the satiating effect of foods, because they are not yet feasible. CNS biomarkers related to satiety are not yet specific enough to serve as biomarkers, although they can distinguish between extreme hunger and fullness. Three currently available biomarkers for satiety are decreases in blood glucose in the short term (<5 min), which have been shown to be involved in meal initiation; leptin changes during longer-term (>2-4 d) negative energy balance; and ghrelin concentrations, which have been implicated in both short-term and long-term energy balance. The next challenge in this research area is to identify food ingredients that have an effect on biomarkers of satiation, satiety, or both. These ingredients may help consumers to maintain their energy intake at a level consistent with a healthy body weight.

  3. Environment biomarkers: Fiction, fantasy, or functional?

    SciTech Connect

    McCarty, L.S.; Munkittrick, K.R.

    1995-12-31

    The first biomarkers used in ecotoxicology were biochemical in nature. Subsequently, this approach was extended to other levels of biological organization. Although popular biomarkers can be problematic. They can be viewed as a ``short-cut`` methodology which must ultimately be based on a clear understanding of an established biological indicator. Thus, a biomarker should be a quantitative or semi-quantitative surrogate measurement for either cause or effect (i.e., dose or response). If the biomarker-biological indicator relationship is established a biomarker can be a useful, practical, scientifically valid tool. Unfortunately, validation is not common and some current biochemical biomarker approaches are critically examined in this regard under the categories of exposure (dose), effect (response), and causality. Observations include: (1) Most popular biochemical biomarkers provide only qualitative estimates of exposure which are of underwhelming value as some exposure can essentially be assumed at many sites of concern. (2) At the same site different biomarkers can suggest exactly opposite trends and conclusions. (3) Correlation between a biomarker and an effect does NOT prove causality. Biomarkers, biochemical or otherwise, represent a ``short-cut`` that should be used only after both a general validation of the concept and a site specific confirmation of applicability.

  4. Reducing Ambulance Diversion at Hospital and Regional Levels: Systemic Review of Insights from Simulation Models

    PubMed Central

    Delgado, M. Kit; Meng, Lesley J.; Mercer, Mary P.; Pines, Jesse M.; Owens, Douglas K.; Zaric, Gregory S.

    2013-01-01

    Introduction: Optimal solutions for reducing diversion without worsening emergency department (ED) crowding are unclear. We performed a systematic review of published simulation studies to identify: 1) the tradeoff between ambulance diversion and ED wait times; 2) the predicted impact of patient flow interventions on reducing diversion; and 3) the optimal regional strategy for reducing diversion. Methods: Data Sources: Systematic review of articles using MEDLINE, Inspec, Scopus. Additional studies identified through bibliography review, Google Scholar, and scientific conference proceedings. Study Selection: Only simulations modeling ambulance diversion as a result of ED crowding or inpatient capacity problems were included. Data extraction: Independent extraction by two authors using predefined data fields. Results: We identified 5,116 potentially relevant records; 10 studies met inclusion criteria. In models that quantified the relationship between ED throughput times and diversion, diversion was found to only minimally improve ED waiting room times. Adding holding units for inpatient boarders and ED-based fast tracks, improving lab turnaround times, and smoothing elective surgery caseloads were found to reduce diversion considerably. While two models found a cooperative agreement between hospitals is necessary to prevent defensive diversion behavior by a hospital when a nearby hospital goes on diversion, one model found there may be more optimal solutions for reducing region wide wait times than a regional ban on diversion. Conclusion: Smoothing elective surgery caseloads, adding ED fast tracks as well as holding units for inpatient boarders, improving ED lab turnaround times, and implementing regional cooperative agreements among hospitals are promising avenues for reducing diversion. PMID:24106548

  5. Biomarkers for lymphoma

    DOEpatents

    Zangar, Richard C.; Varnum, Susan M.

    2014-09-02

    A biomarker, method, test kit, and diagnostic system for detecting the presence of lymphoma in a person are disclosed. The lymphoma may be Hodgkin's lymphoma or non-Hodgkin's lymphoma. The person may be a high-risk subject. In one embodiment, a plasma sample from a person is obtained. The level of at least one protein listed in Table S3 in the plasma sample is measured. The level of at least one protein in the plasma sample is compared with the level in a normal or healthy subject. The lymphoma is diagnosed based upon the level of the at least one protein in the plasma sample in comparison to the normal or healthy level.

  6. Application of the urinary S-phenylmercapturic acid test as a biomarker for low levels of exposure to benzene in industry.

    PubMed Central

    van Sittert, N J; Boogaard, P J; Beulink, G D

    1993-01-01

    Recently, the determination of S-phenylmercapturic acid (S-PMA) in urine has been proposed as a suitable biomarker for the monitoring of low level exposures to benzene. In the study reported here, the test has been validated in 12 separate studies in chemical manufacturing plants, oil refineries, and natural gas production plants. Parameters studied were the urinary excretion characteristics of S-PMA, the specificity and the sensitivity of the assay, and the relations between exposures to airborne benzene and urinary S-PMA concentrations and between urinary phenol and S-PMA concentrations. The range of exposures to benzene was highest in workers in chemical manufacturing plants and in workers cleaning tanks or installations containing benzene as a component of natural gas condensate. Urinary S-PMA concentrations were measured up to 543 micrograms/g creatinine. Workers' exposures to benzene were lowest in oil refineries and S-PMA concentrations were comparable with those in smoking or nonsmoking control persons (most below the detection limit of 1 to 5 micrograms/g creatinine). In most workers S-PMA was excreted in a single phase and the highest S-PMA concentrations were at the end of an eight hour shift. The average half life of elimination was 9.0 (SD 4.5) hours (31 workers). Tentatively, in five workers a second phase of elimination was found with an average half life of 45 (SD 4) hours. A strong correlation was found between eight hour exposure to airborne benzene of 1 mg/m3 (0.3 ppm) and higher and urinary S-PMA concentrations in end of shift samples. It was calculated that an eight hour benzene exposure of 3.25 mg/m3 (1 ppm) corresponds to an average S-PMA concentration of 46 micrograms/g creatinine (95% confidence interval 41-50 micrograms/g creatinine). A strong correlation was also found between urinary phenol and S-PMA concentrations. At a urinary phenol concentration of 50 mg/g creatinine, corresponding to an eight hour benzene exposure of 32.5 mg/m3 (10

  7. Alzheimer's disease dementia as the diagnosis best supported by the cerebrospinal fluid biomarkers: difference in cut-off levels from thai experience.

    PubMed

    Senanarong, V; Siwasariyanon, N; Washirutmangkur, L; Poungvarin, N; Ratanabunakit, C; Aoonkaew, N; Udomphanthurak, S

    2012-01-01

    Objectives. To determine how beta-amyloid 1-42 (Aβ 1-42), total tau (tTau), and phosphorylated tau (pTau) levels in CSF behave in a cohort of Thai patients from the Memory Clinic in Bangkok, Thailand. Methods. During 2009-2011, twenty eight subjects from the memory clinic at Siriraj Hospital had CSF analysis for AD biomarkers. Aβ 1-42, tTau, and pTau (at amino acid 181) were measured in CSF by ELISA technique. Results. Mean of Thai mental state examination (TMSE) of 28 Thai cohort was 16.48 (6.63). Fourteen had AD, ten had non-AD dementia, and four non-cases were those with subjective memory complaint (SMC) without dementia. Mean CSF Aβ 1-42, tTau, ptau (181), and pTau/Aβ 1-42 in the AD group were 241.36 (60.14) pg/mL, 222.79 (212.24) pg/mL, 40.79 (27.84) pg/mL, and 0.18 (0.12) accordingly. Mean CSF Aβ 1-42, tTau, pTau (181), and pTau/Aβ 1-42 in the non-AD dementia group were 430.40 (125.18) pg/mL, 349.30 (692.16) pg/mL, 36.80 (14.90) pg/mL, and 0.09 (0.04) accordingly. Mean CSF Aβ 1-42, tTau, pTau (181), and pTau/Aβ 1-42 in the non-cases with SMC without dementia were 499.75 (93.44) pg/mL, 137.25 (62.74) pg/mL, 31.75 (17.48) pg/mL, and 0.06 (0.02). There is significant difference (P < 0.05) among the 3 groups in CSF Aβ 1-42 and pTau/Aβ 1-42. We propose mean + 1.5 SD of CSF Aβ 1-42 in AD group (331.57 pg/mL) to be the cut-off point in Thai subjects. Conclusion. There are significant different in CSF Aβ 1-42 and CSF p-tau/Aβ 1-42 among those with AD, non-AD dementia and non cases with SMC without dementia in Thai cohort. Cut-off point of CSF Aβ 1-42 of 331.57 pg/mL is suggested in Thai study.

  8. Understanding the degradation of ascorbic acid and glutathione in relation to the levels of oxidative stress biomarkers in broccoli (Brassica oleracea L. italica cv. Bellstar) during storage and mechanical processing.

    PubMed

    Raseetha, Siva; Leong, Sze Ying; Burritt, David John; Oey, Indrawati

    2013-06-01

    The purpose of this research was to understand the degradation of ascorbic acid and glutathione content in broccoli florets (Brassica oleracea L. italica cv. Bellstar) during prolonged storage and subsequent mechanical processing. The initial content of total ascorbic acid and glutathione in broccoli florets averaged at 5.18 ± 0.23 and 0.70 ± 0.03 μmol/g fresh weight, respectively. Results showed that the content of ascorbic acid and glutathione in broccoli degraded during storage at 23°C, for at least 4.5-fold after 6 days of storage. On each day of storage, broccoli florets were mechanically processed, but the content of total ascorbic acid and glutathione was not significantly affected. When the mechanically processed broccoli florets were further incubated for up to 6h, the amount of ascorbic acid was greatly reduced as compared to glutathione. To obtain an in-depth understanding on the degradation of ascorbic acid and glutathione, the activity of enzymes involved in plant antioxidative system via ascorbate-glutathione cycle, as a response towards oxidative stress that took place during storage was determined in this study. The content of total ascorbic acid and glutathione in broccoli florets before and after mechanical processing were found to decrease concurrently with the activity of ascorbic acid peroxidase and glutathione reductase over the experimental storage duration. Meanwhile, the effect of oxidative stress on the content of ascorbic acid and glutathione was apparent during the 6h of incubation after mechanical processing. This phenomenon was demonstrated by the level of oxidative stress biomarkers examined, in which the formation of lipid peroxides, protein carbonyls and DNA oxidised products was positively associated with the degradation of total ascorbic acid and glutathione.

  9. Nutrient Plasma Levels Achieved During Treatment that Reduces Noise-Induced Hearing Loss

    PubMed Central

    Le Prell, C. G.; Dolan, D. F.; Bennett, D. C.; Boxer, P. A.

    2011-01-01

    Hearing loss encompasses both temporary and permanent deficits. If temporary threshold shift (TTS) and permanent threshold shift (PTS) share common pathological mechanisms, then agents that reduce PTS should also reduce TTS. Several antioxidant agents have reduced PTS in rodent models; however, reductions in TTS have been inconsistent. This study first determined whether dietary antioxidants (beta-carotene, and vitamins C and E) delivered in combination with magnesium (Mg) reliably increase plasma concentrations of the active agents. Then, additional manipulations tested the hypothesis that these nutrients reduce acute TTS insult in the first 24 hours following loud sound, as well as longer lasting changes in hearing measured up to 7 days post-noise. Saline or nutrients were administered to guinea pigs prior to and after noise exposure. Sound-evoked electrophysiological responses were measured before noise, with tests repeated 1-hour post-noise, as well as 1-, 3-, 5-, and 7-days post-noise. All subjects showed significant functional recovery; subjects treated with nutrients recovered more rapidly, and had better hearing outcomes at early post-noise times as well as the final test time. Thus, this combination of nutrients, which produced significant increases in plasma concentrations of vitamins C and E and Mg, effectively reduced hearing loss at multiple post-noise times. These data suggest free radical formation contributes to TTS as well as PTS insults, and suggest a potential opportunity to prevent TTS in human populations. PMID:21708356

  10. The use of asparaginase to reduce acrylamide levels in cooked food.

    PubMed

    Xu, Fei; Oruna-Concha, Maria-Jose; Elmore, J Stephen

    2016-11-01

    Strategies proposed for reducing the formation of the suspected carcinogen acrylamide in cooked foods often rely on a reduction in the extent of the Maillard reaction, in which acrylamide is formed from the reaction between asparagine and reducing sugars. However, the Maillard reaction also provides desirable sensory attributes of cooked foods. Mitigation procedures that modify the Maillard reaction may negatively affect flavour and colour. The use of asparaginase to convert asparagine to aspartic acid may provide a means to reduce acrylamide formation, while maintaining sensory quality. This review collates research on the use of enzymes, asparaginase in particular, to mitigate acrylamide formation. Asparaginase is a powerful tool for the food industry and it is likely that its use will increase. However, the potential adverse effects of asparaginase treatment on sensory properties of cooked foods and the need to achieve sufficient enzyme-substrate contact remain areas for future research.

  11. Prolonged fasting and cortisol reduce myostatin mRNA levels in tilapia larvae; short-term fasting elevates.

    PubMed

    Rodgers, Buel D; Weber, Gregory M; Kelley, Kevin M; Levine, Michael A

    2003-05-01

    Myostatin negatively regulates muscle growth and development and has recently been characterized in several fishes. We measured fasting myostatin mRNA levels in adult tilapia skeletal muscle and in whole larvae. Although fasting reduced some growth indexes in adults, skeletal muscle myostatin mRNA levels were unaffected. By contrast, larval myostatin mRNA levels were sometimes elevated after a short-term fast and were consistently reduced with prolonged fasting. These effects were specific for myostatin, as mRNA levels of glyceraldehyde-3-phosphate dehydrogenase and glucose-6-phosphatase were unchanged. Cortisol levels were elevated in fasted larvae with reduced myostatin mRNA, whereas in addition immersion of larvae in 1 ppm (2.8 microM) cortisol reduced myostatin mRNA in a time-dependent fashion. These results suggest that larval myostatin mRNA levels may initially rise but ultimately fall during a prolonged fast. The reduction is likely mediated by fasting-induced hypercortisolemia, indicating divergent evolutionary mechanisms of glucocorticoid regulation of myostatin mRNA, since these steroids upregulate myostatin gene expression in mammals.

  12. Instructions, Feedback, and Reinforcement in Reducing Activity Levels in the Classroom.

    ERIC Educational Resources Information Center

    Schulman, Jerome L.; And Others

    1979-01-01

    Results indicated that the intervention package--including instructions, feedback from an electronic device that measures motor activity, and contingent reinforcement--was successful in reducing activity in the classroom for 8 of the 11 emotionally disturbed Ss (ages 9 to 13 years). (Author/DLS)

  13. Challenges for red blood cell biomarker discovery through proteomics.

    PubMed

    Barasa, Benjamin; Slijper, Monique

    2014-05-01

    Red blood cells are rather unique body cells, since they have lost all organelles when mature, which results in lack of potential to replace proteins that have lost their function. They maintain only a few pathways for obtaining energy and reducing power for the key functions they need to fulfill. This makes RBCs highly sensitive to any aberration. If so, these RBCs are quickly removed from circulation, but if the RBC levels reduce extremely fast, this results in hemolytic anemia. Several causes of HA exist, and proteome analysis is the most straightforward way to obtain deeper insight into RBC functioning under the stress of disease. This should result in discovery of biomarkers, typical for each source of anemia. In this review, several challenges to generate in-depth RBC proteomes are described, like to obtain pure RBCs, to overcome the wide dynamic range in protein expression, and to establish which of the identified/quantified proteins are active in RBCs. The final challenge is to acquire and validate suited biomarkers unique for the changes that occur for each of the clinical questions; in red blood cell aging (also important for transfusion medicine), for thalassemias or sickle cell disease. Biomarkers for other hemolytic anemias that are caused by dysfunction of RBC membrane proteins (the RBC membrane defects) or RBC cytosolic proteins (the enzymopathies) are sometimes even harder to discover, in particular for the patients with RBC rare diseases with unknown cause. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.

  14. The toc132toc120 heterozygote mutant of Arabidopsis thaliana accumulates reduced levels of hexadecatrienoic acid.

    PubMed

    Afitlhile, Meshack; Duffield-Duncan, Kayla; Fry, Morgan; Workman, Samantha; Hum-Musser, Sue; Hildebrand, David

    2015-11-01

    A null and heterozygous mutant for the Arabidopsis thaliana TOC132 and TOC120 genes accumulates increased levels of 16:0 and decreased 16:3, suggesting altered homeostasis in fatty acid synthesis. The FAD5 gene encodes a plastid desaturase that catalyzes the first step in the synthesis of 16:3 in monogalactosyldiacylglycerol (MGDG). In non-acclimated toc132toc120+/- mutant plants, the FAD5 gene was repressed and this correlated with decreased levels of 16:3. In cold-acclimated mutant however, the FAD5 gene was upregulated and there was a small increase in 16:3 levels relative to the non-acclimated mutant plants. The MGD1 gene was expressed at control levels and the mutant accumulated levels of MGDG that were similar to the wild type. In the mutant however, MGDG had decreased 16:3 levels, suggesting that the activity of FAD5 desaturase was compromised. In the mutant, the FAD2 and FAD3 genes were downregulated but levels of 18:3-PC were increased, suggesting posttranscriptional regulation for the ER-localized fatty acid desaturases. The Toc120 or Toc159 receptor is likely to compensate for a defective Toc132 receptor. In the cold-acclimated mutant, the TOC159 gene was repressed ca. 300-fold, whereas the TOC120 gene was repressed 7-fold relative to the non-acclimated wild type. Thus, the TOC159 gene is more sensitive to cold-stress and might not compensate for defect in the TOC132 gene under these conditions. Overall, these data show that a mutation in the TOC132 gene results in decreased 16:3 levels, indicating the need for an intact Toc132/Toc120 receptor, presumably to facilitate the import of the FAD5 preprotein into chloroplasts.

  15. Use of cationic polymers to reduce pathogen levels during dairy manure separation.

    PubMed

    Liu, Zong; Carroll, Zachary S; Long, Sharon C; Gunasekaran, Sundaram; Runge, Troy

    2016-01-15

    Various separation technologies are used to deal with the enormous amounts of animal waste that large livestock operations generate. When the recycled waste stream is land applied, it is essential to lower the pathogen load to safeguard the health of livestock and humans. We investigated whether cationic polymers, used as a flocculent in the solid/liquid separation process, could reduce the pathogen indicator load in the animal waste stream. The effects of low charge density cationic polyacrylamide (CPAM) and high charge density cationic polydicyandiamide (PDCD) were investigated. Results demonstrated that CPAM was more effective than PDCD for manure coagulation and flocculation, while PDCD was more effective than CPAM in reducing the pathogen indicator loads. However, their combined use, CPAM followed by PDCD, resulted in both improved solids separation and pathogen indicator reduction.

  16. Analysis of high-level radioactive slurries as a method to reduce DWPF turnaround times

    SciTech Connect

    Coleman, C.J.; Bibler, N.E.; Ferrara, D.M.; Hay, M.S.

    1996-06-01

    Analysis of Defense Waste Processing Facility (DWPF) samples as slurries rather than as dried or vitrified samples is an effective way to reduce sample turnaround times. Slurries can be dissolved with a mixture of concentrated acids to yield solutions for elemental analysis by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). Slurry analyses can be performed in eight hours, whereas analyses of vitrified samples require up to 40 hours to complete. Analyses of melter feed samples consisting of the DWPF borosilicate frit and either simulated or actual DWPF radioactive sludge were typically within a range of 3--5% of the predicted value based on the relative amounts of sludge and frit added to the slurry. The results indicate that the slurry analysis approach yields analytical accuracy and precision competitive with those obtained from analyses of vitrified samples. Slurry analyses offer a viable alternative to analyses of solid samples as a simple way to reduce analytical turnaround times.

  17. Reduced cortical neurotransmitter receptor complex levels in fetal Down syndrome brain.

    PubMed

    Falsafi, Soheil Keihan; Dierssen, Mara; Ghafari, Maryam; Pollak, Arnold; Lubec, Gert

    2016-01-01

    In this study, cortical receptor complex levels were determined in fetal Down syndrome (DS, trisomy 21) brain. Frontal cortices were obtained from individuals with DS (19th-22nd week of gestation) and controls. Membrane proteins were extracted, assayed on blue native gels and immunoblotted with brain receptor antibodies. Levels of a D1R-containing complex were markedly decreased in male and female cortices of DS individuals. Females with DS had significant reductions of nicotinic acetylcholine receptors α4 and α7, NMDA receptor GluN1 and AMPA receptor GluA1- and GluA3-containing receptor complexes. Levels of other brain receptor complexes (5-hydroxytryptamine 1A, GluA2 and GluR4 receptor-containing complexes) were comparable between the groups of females. Levels of GluA2- and GluA3-containing complexes were significantly increased in males. Decreased levels of D1R complexes in both sexes, along with the significant reduction of α4, α7-containing receptor complexes observed in females, may explain the brain deficits and impaired cognition observed in DS.

  18. Persimmon fruit tannin-rich fiber reduces cholesterol levels in humans.

    PubMed

    Gato, Nobuki; Kadowaki, Akio; Hashimoto, Natsumi; Yokoyama, Shin-ichiro; Matsumoto, Kenji

    2013-01-01

    Bile acid-binding agents are known to lower blood cholesterol levels and have been clinically used for the treatment of hypercholesterolemia. We previously showed that tannin-rich fiber from young persimmon (Diospyros kaki) fruits had bile acid-binding properties. In this study, we performed a randomized, double-blind, placebo-controlled trial to investigate the hypocholesterolemic effects of tannin-rich fiber in humans. The subjects (n = 40, plasma total cholesterol levels 180-259 mg/dl) were divided into 3 groups and ingested cookie bars containing 0 g (placebo group, n = 14), 3 g (low-dose group, n = 13), or 5 g (high-dose group, n = 13) of tannin-rich fiber 3 times daily before meals for 12 weeks. Plasma total cholesterol levels decreased significantly in the low-dose (12 weeks, p < 0.005) and high-dose (6 weeks, p < 0.05; 12 weeks, p < 0.001) groups. In addition, plasma low-density lipoprotein cholesterol levels decreased significantly in the high-dose group (6 weeks, p < 0.05; 12 weeks, p < 0.001). These improvements were not accompanied by changes in plasma high-density lipoprotein cholesterol or plasma triglyceride levels. Our findings indicate that tannin-rich fiber from young persimmon fruits is a useful food material for treating hypercholesterolemia.

  19. Hydrogen water reduces NSE, IL-6, and TNF-α levels in hypoxic-ischemic encephalopathy

    PubMed Central

    Yang, Lin

    2016-01-01

    Abstract This study retrospectively analyzed the efficacy of hydrogen water in the treatment of neonatal hypoxic-ischemic encephalopathy (HIE) and its effect on serum neuron-specific enolase (NSE), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels. Forty newborns with HIE who received treatment from April 2014 to April 2015 were divided into a conventional care group and a hydrogen water group according to the different treatment methods applied. Twenty healthy full-term newborns comprised the control group. In the hydrogen water group, 5-mL/kg hydrogen water was orally administered two days after birth daily for 10 days in addition to conventional treatment. After 10 days, efficacy indicators were examined in the HIE groups. The NSE, IL-6, and TNF-α levels were compared among all three groups. The efficacy indicators were significantly lower in the hydrogen water group compared with the conventional group. Before treatment, the serum NSE, IL-6, and TNF-α levels in the HIE groups were higher than those in the control group. After treatment, these levels in the hydrogen water group were lower than those in the conventional group. Hydrogen water lowers serum NSE, IL-6, and TNF-α levels in HIE newborns, thereby exerting a protective effect. PMID:28352827

  20. Vitamin E-coated dialysis membranes reduce the levels of oxidative genetic damage in hemodialysis patients.

    PubMed

    Rodríguez-Ribera, Lara; Corredor, Zuray; Silva, Irene; Díaz, Juan Manuel; Ballarín, José; Marcos, Ricard; Pastor, Susana; Coll, Elisabet

    2017-03-01

    End-stage renal disease patients present oxidative stress status that increases when they are submitted to hemodialysis (HD). This increase in oxidative stress can affect their genetic material, among other targets. The objective of this study was to evaluate the effect of using polysulfone membranes coated with vitamin E, during the HD sessions, on the levels of genetic damage of HD patients. Forty-six patients were followed for 6 months, of whom 29 changed from conventional HD to the use of membranes coated with vitamin E. The level of genetic damage was measured using the micronucleus and the comet assays, both before and after the follow-up period. Serum vitamin E concentration was also checked. The obtained results showed that 24% of our patients presented vitamin E deficiency, and this was normalized in those patients treated with vitamin E-coated membranes. Patients with vitamin E deficiency showed higher levels of oxidative DNA damage. After the use of vitamin E-coated membranes we detected a significant decrease in the levels of oxidative damage. Additionally, hemoglobin values increased significantly with the use of vitamin E-coated membranes. In conclusion, the use of vitamin E-coated membranes supposes a decrease on the levels of oxidative DNA damage, and improves the uremic anemia status. Furthermore, the use of this type of membrane was also effective in correcting vitamin E deficiency.

  1. Cerebrospinal Fluid Levels of Amyloid Beta 1-43 Mirror 1-42 in Relation to Imaging Biomarkers of Alzheimer’s Disease

    PubMed Central

    Almdahl, Ina S.; Lauridsen, Camilla; Selnes, Per; Kalheim, Lisa F.; Coello, Christopher; Gajdzik, Beata; Møller, Ina; Wettergreen, Marianne; Grambaite, Ramune; Bjørnerud, Atle; Bråthen, Geir; Sando, Sigrid B.; White, Linda R.; Fladby, Tormod

    2017-01-01

    Introduction: Amyloid beta 1-43 (Aβ43), with its additional C-terminal threonine residue, is hypothesized to play a role in early Alzheimer’s disease pathology possibly different from that of amyloid beta 1-42 (Aβ42). Cerebrospinal fluid (CSF) Aβ43 has been suggested as a potential novel biomarker for predicting conversion from mild cognitive impairment (MCI) to dementia in Alzheimer’s disease. However, the relationship between CSF Aβ43 and established imaging biomarkers of Alzheimer’s disease has never been assessed. Materials and Methods: In this observational study, CSF Aβ43 was measured with ELISA in 89 subjects; 34 with subjective cognitive decline (SCD), 51 with MCI, and four with resolution of previous cognitive complaints. All subjects underwent structural MRI; 40 subjects on a 3T and 50 on a 1.5T scanner. Forty subjects, including 24 with SCD and 12 with MCI, underwent 18F-Flutemetamol PET. Seventy-eight subjects were assessed with 18F-fluorodeoxyglucose PET (21 SCD/7 MCI and 11 SCD/39 MCI on two different scanners). Ten subjects with SCD and 39 with MCI also underwent diffusion tensor imaging. Results: Cerebrospinal fluid Aβ43 was both alone and together with p-tau a significant predictor of the distinction between SCD and MCI. There was a marked difference in CSF Aβ43 between subjects with 18F-Flutemetamol PET scans visually interpreted as negative (37 pg/ml, n = 27) and positive (15 pg/ml, n = 9), p < 0.001. Both CSF Aβ43 and Aβ42 were negatively correlated with standardized uptake value ratios for all analyzed regions; CSF Aβ43 average rho -0.73, Aβ42 -0.74. Both CSF Aβ peptides correlated significantly with hippocampal volume, inferior parietal and frontal cortical thickness and axial diffusivity in the corticospinal tract. There was a trend toward CSF Aβ42 being better correlated with cortical glucose metabolism. None of the studied correlations between CSF Aβ43/42 and imaging biomarkers were significantly different for the two A

  2. Effectiveness of flushing on reducing lead and copper levels in school drinking water.

    PubMed

    Murphy, E A

    1993-08-01

    Samples from drinking water fountains in 50 schools in New Jersey were collected at specific times during a typical school day and analyzed for lead, copper, pH, alkalinity, and hardness. First-draw lead and copper levels (medians 0.010 mg/l and 0.26 mg/l, respectively) decreased significantly after 10 min of flushing in the morning (medians 0.005 mg/l lead and 0.068 mg/l copper), but levels increased significantly by lunchtime (medians 0.007 mg/l lead and 0.12 mg/l copper) after normal use of fountains in the morning by students. Corrosive water, as defined by the aggressive index, contained significantly higher levels of lead and copper (medians 0.012 mg/l and 0.605 mg/l, respectively) than noncorrosive water (medians 0.005 mg/l and 0.03 mg/l, respectively).

  3. Hypersaline Microbial Mat Lipid Biomarkers

    NASA Technical Reports Server (NTRS)

    Jahnke, Linda L.; Embaye, Tsegereda; Turk, Kendra A.; Summons, Roger E.

    2002-01-01

    Lipid biomarkers and compound specific isotopic abundances are powerful tools for studies of contemporary microbial ecosystems. Knowledge of the relationship of biomarkers to microbial physiology and community structure creates important links for understanding the nature of early organisms and paleoenvironments. Our recent work has focused on the hypersaline microbial mats in evaporation ponds at Guerrero Negro, Baja California Sur, Mexico. Specific biomarkers for diatoms, cyanobacteria, archaea, green nonsulfur (GNS), sulfate reducing, sulfur oxidizing and methanotrophic bacteria have been identified. Analyses of the ester-bound fatty acids indicate a highly diverse microbial community, dominated by photosynthetic organisms at the surface. The delta C-13 of cyanobacterial biomarkers such as the monomethylalkanes and hopanoids are consistent with the delta C-13 measured for bulk mat (-10%o), while a GNS biomarker, wax esters (WXE), suggests a more depleted delta C-13 for GNS biomass (-16%o). This isotopic relationship is different than that observed in mats at Octopus Spring, Yellowstone National Park (YSNP) where GNS appear to grow photoheterotrophic ally. WXE abundance, while relatively low, is most pronounced in an anaerobic zone just below the cyanobacterial layer. The WXE isotope composition at GN suggests that these bacteria utilize photoautotrophy incorporating dissolved inorganic carbon (DIC) via the 3-hydroxypropionate pathway using H2S or H2.

  4. Feeding Jerusalem artichoke reduced skatole level and changed intestinal microbiota in the gut of entire male pigs.

    PubMed

    Vhile, S G; Kjos, N P; Sørum, H; Overland, M

    2012-05-01

    Different levels of dried Jerusalem artichoke were fed to entire male pigs 1 week before slaughter. The objective was to investigate the effect on skatole level in the hindgut and in adipose tissue, as well as the effect on microflora and short-chain fatty acids (SCFA) in the hindgut. Five experimental groups (n = 11) were given different dietary treatments 7 days before slaughtering: negative control (basal diet), positive control (basal diet + 9% chicory-inulin), basal diet + 4.1% Jerusalem artichoke, basal diet + 8.1% Jerusalem artichoke and basal diet + 12.2% Jerusalem artichoke. Samples from colon, rectum, faeces and adipose tissue were collected. Effect of dietary treatment on skatole, indole and androstenone levels in adipose tissue and on skatole, indole, pH, dry matter (DM), microbiota and SCFA in the hindgut was evaluated. Feeding increasing levels of Jerusalem artichoke to entire male pigs reduced skatole in digesta from colon and in faeces (linear, P < 0.01). There was also a tendency towards a decreased level of skatole in adipose tissue (linear, P = 0.06). Feeding Jerusalem artichoke decreased DM content in colon and faeces and pH in colon (linear, P < 0.01). Increasing levels of Jerusalem artichoke resulted in a reduced level of Clostridium perfringens in both colon and rectum (linear, P < 0.05) and a tendency towards decreased levels of enterobacteria in colon (linear, P = 0.05). Further, there was an increase in total amount of SCFA (linear, P < 0.05), acetic acid (linear, P < 0.05) and valerianic acid (linear, P < 0.01) in faeces. In conclusion, adding dried Jerusalem artichoke to diets for entire male pigs 1 week before slaughter resulted in a dose-dependent decrease in skatole levels in the hindgut and adipose tissue. The reduced skatole levels might be related to the decrease in C. perfringens and the increase in SCFA with subsequent reduction in pH.

  5. Ursolic acid reduces prostate size and dihydrotestosterone level in a rat model of benign prostatic hyperplasia.

    PubMed

    Shin, In-Sik; Lee, Mee-Young; Jung, Da-Young; Seo, Chang-Seob; Ha, Hye-Kyung; Shin, Hyeun-Kyoo

    2012-03-01

    Benign prostatic hyperplasia (BPH) is characterized by hyperplasia of prostatic stromal and epithelial cells, which can lead to lower urinary tract symptoms. The prevalence of BPH increases in an age-dependent manner. We investigated the protective effect of ursolic acid in BPH development using a testosterone-induced BPH rat model. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate (TP), for a period of four weeks. Ursolic acid was administrated daily by oral gavage at a dose level of 5mg/kg during the four weeks of TP injections. Animals were sacrificed on the scheduled termination, before prostates were weighed and subjected to histopathological examination. TP and dihydrotestosterone (DHT) levels in the serum and prostate were also measured. BPH-induced animals displayed an increase in prostate weight with increased testosterone and DHT levels in both the serum and prostate. However, ursolic acid treatment resulted in significant reductions in prostate weight and testosterone and DHT levels in both the serum and prostate, compared with BPH-induced animals. Histopathological examination also showed that ursolic acid treatment suppressed TP-induced prostatic hyperplasia. These findings indicate that ursolic acid may effectively inhibit the development of BPH and it may be a useful agent in BPH treatment.

  6. Exposure to Organic Solvents Used in Dry Cleaning Reduces Low and High Level Visual Function

    PubMed Central

    Jiménez Barbosa, Ingrid Astrid

    2015-01-01

    Purpose To investigate whether exposure to occupational levels of organic solvents in the dry cleaning industry is associated with neurotoxic symptoms and visual deficits in the perception of basic visual features such as luminance contrast and colour, higher level processing of global motion and form (Experiment 1), and cognitive function as measured in a visual search task (Experiment 2). Methods The Q16 neurotoxic questionnaire, a commonly used measure of neurotoxicity (by the World Health Organization), was administered to assess the neurotoxic status of a group of 33 dry cleaners exposed to occupational levels of organic solvents (OS) and 35 age-matched non dry-cleaners who had never worked in the dry cleaning industry. In Experiment 1, to assess visual function, contrast sensitivity, colour/hue discrimination (Munsell Hue 100 test), global motion and form thresholds were assessed using computerised psychophysical tests. Sensitivity to global motion or form structure was quantified by varying the pattern coherence of global dot motion (GDM) and Glass pattern (oriented dot pairs) respectively (i.e., the percentage of dots/dot pairs that contribute to the perception of global structure). In Experiment 2, a letter visual-search task was used to measure reaction times (as a function of the number of elements: 4, 8, 16, 32, 64 and 100) in both parallel and serial search conditions. Results Dry cleaners exposed to organic solvents had significantly higher scores on the Q16 compared to non dry-cleaners indicating that dry cleaners experienced more neurotoxic symptoms on average. The contrast sensitivity function for dry cleaners was significantly lower at all spatial frequencies relative to non dry-cleaners, which is consistent with previous studies. Poorer colour discrimination performance was also noted in dry cleaners than non dry-cleaners, particularly along the blue/yellow axis. In a new finding, we report that global form and motion thresholds for dry cleaners

  7. Short term exposure to elevated levels of leptin reduces proximal tubule cell metabolic activity.

    PubMed

    Briffa, Jessica F; Grinfeld, Esther; McAinch, Andrew J; Poronnik, Philip; Hryciw, Deanne H

    2014-01-25

    Leptin plays a pathophysiological role in the kidney, however, its acute effects on the proximal tubule cells (PTCs) are unknown. In opossum kidney (OK) cells in vitro, Western blot analysis identified that exposure to leptin increases the phosphorylation of the mitogen-activated protein kinase (MAPK) p44/42 and the mammalian target of rapamycin (mTOR). Importantly leptin (0.05, 0.10, 0.25 and 0.50 μg/ml) significantly reduced the metabolic activity of PTCs, and significantly decreased protein content per cell. Investigation of the role of p44/42 and mTOR on metabolic activity and protein content per cell, demonstrated that in the presence of MAPK inhibitor U0126 and mTOR inhibitor Ku-63794, that the mTOR pathway is responsible for the reduction in PTC metabolic activity in response to leptin. However, p44/42 and mTOR play no role the reduced protein content per cell in OKs exposed to leptin. Therefore, leptin modulates metabolic activity in PTCs via an mTOR regulated pathway.

  8. Reducing Jagged 1 and 2 levels prevents cerebral arteriovenous malformations in matrix Gla protein deficiency.

    PubMed

    Yao, Yucheng; Yao, Jiayi; Radparvar, Melina; Blazquez-Medela, Ana M; Guihard, Pierre J; Jumabay, Medet; Boström, Kristina I

    2013-11-19

    Cerebral arteriovenous malformations (AVMs) are common vascular malformations, which may result in hemorrhagic strokes and neurological deficits. Bone morphogenetic protein (BMP) and Notch signaling are both involved in the development of cerebral AVMs, but the cross-talk between the two signaling pathways is poorly understood. Here, we show that deficiency of matrix Gla protein (MGP), a BMP inhibitor, causes induction of Notch ligands, dysregulation of endothelial differentiation, and the development of cerebral AVMs in MGP null (Mgp(-/-)) mice. Increased BMP activity due to the lack of MGP induces expression of the activin receptor-like kinase 1, a BMP type I receptor, in cerebrovascular endothelium. Subsequent activation of activin receptor-like kinase 1 enhances expression of Notch ligands Jagged 1 and 2, which increases Notch activity and alters the expression of Ephrin B2 and Ephrin receptor B4, arterial and venous endothelial markers, respectively. Reducing the expression of Jagged 1 and 2 in the Mgp(-/-) mice by crossing them with Jagged 1 or 2 deficient mice reduces Notch activity, normalizes endothelial differentiation, and prevents cerebral AVMs, but not pulmonary or renal AVMs. Our results suggest that Notch signaling mediates and can modulate changes in BMP signaling that lead to cerebral AVMs.

  9. Reducing indoor radon levels in a UK test house using different ventilation strategies

    SciTech Connect

    Welsh, P.A.

    1995-12-31

    This paper reports on some of the most recent tests involving a number of studies in an unoccupied radon test house. The house has a suspended timber floor and naturally elevated indoor radon levels, peaking at times above 6000 Bqm{sup -3}. Various sensors monitor how different ventilation strategies affect indoor radon levels and the building environment. Data from five different scenarios is presented. Initially the house was monitored as purchased with poor natural underfloor ventilation. This was followed by testing whole house pressurisation, improved natural underfloor ventilation, and two types of mechanical underfloor ventilation. The results from these and future studies may be used to make a more informed choice of remedy, based on a whole number of aspects, not only radon reduction as is frequently the case.

  10. Regional growth management policies: Toward reducing global warming at state and local levels

    SciTech Connect

    Purdie, J.

    1995-09-01

    State and local governments in the United States are accepting mandates to coordinate legislated land use and growth management planning with vigorous environmental protection and resource conservation. These mandates, implemented or planned in states with populations totaling over 100 million, will directly impact growth patterns and ultimately affect the level of atmospheric gases and particulates generated within their borders. This paper addresses the issues of growth management and land use planning at the local, state and regional levels and identifies areas impacting global warming. A review of existing systems will be presented, and recommendations will be made to improve monitoring of growth management mechanisms and organizational structures with the goal of global atmospheric improvement. The issues discussed include urban sprawl, transportation, and growth patterns as managed by policies also designed to protect environments and provide for sustainable growth. Areas for improved coordination between jurisdictions to ease global warming will also be examined.

  11. Metformin reduces thyrotropin levels in obese, diabetic women with primary hypothyroidism on thyroxine replacement therapy.

    PubMed

    Isidro, M Luisa; Penín, Manuel A; Nemiña, Rosa; Cordido, Fernando

    2007-08-01

    Context It has been reported that metformin might modify thyroid hormone economy. In two retrospective studies, initiation of treatment with metformin caused suppression of TSH to subnormal levels. Objective To prospectively evaluate if administration of metformin to obese, diabetic patients with primary hypothyroidism on stable thyroxine replacement doses modifies TSH levels. Patients and methods Eight obese, diabetic postmenopausal women with primary hypothyroidism participated in the study. They received 1,700 mg of metformin daily for 3 months. Weight, TSH, free T4, and free T3 levels were measured at baseline, 3 months after metformin initiation and 3 months after its withdrawal. Results After 3 months of on metformin, mean TSH was significantly lower than basal TSH (3.11 +/- 0.50 microUI/ml vs. 1.18 +/- 0.36 microUI/ml; P = 0.01). Mean TSH 3 months after metformin withdrawal was 2.21 +/- 0.37 microUI/ml, significantly higher than TSH after metformin (P = 0.05), but not different from basal TSH. Mean fT4 level increased during metformin administration (basal fT4: 1.23 +/- 0.06 ng/dl, fT4 after metformin: 1.32 +/- 0.04 ng/dl; P = ns), and decreased after its withdrawal (fT4 3 months after metformin withdrawal: 1.15 +/- 0.05 ng/dl; vs. 3 months after metformin, P = 0.04; vs. basal; P = ns). Conclusions In obese, diabetic patients with primary hypothyroidism on thyroxine replacement treatment, short-term metformin administration is associated with a significant fall in TSH.

  12. Use of Aqueous Foam to Reduce Shoulder-Launched Rocket Noise Level: Feasibility Investigation.

    DTIC Science & Technology

    1981-07-01

    1 tj~ * UNCLASSIFIED SECUflITY CLASSIFICATION OF THIS PAGE (**en Dese Entered) REPORT DOCUMENTATION PAGE BEFORE COOTRUTIONS I. REPORT NUMBER 2. GOVT...assistance and cooperation of Mr. Jerry Arszman of U.S. Army MIRADCOM (Missile Research and Development Command) and Mr. Charles Carter and Mr. George...REFERENCES 1. A. Clark, et al., The Reduction of Noise Levels from Explosive Test Facilities Using Aqueous Foan, Royal Armament Research and Development

  13. Both physiological and pharmacological levels of melatonin reduce DNA adduct formation induced by the carcinogen safrole.

    PubMed

    Tan, D; Reiter, R J; Chen, L D; Poeggeler, B; Manchester, L C; Barlow-Walden, L R

    1994-02-01

    Hepatic DNA adduct formation induced by the chemical carcinogen, safrole, was suppressed by both endogenous pineal melatonin release and by the exogenous administration of melatonin to rats. DNA damage after administration of of melatonin to rats. DNA damage after administration of 100 mg/kg safrole (i.p.) was measured by the P1 enhanced 32P-postlabeling analysis method. The RAL (relative adduct labeling) x 10(7) of carcinogen modified DNA in the liver of untreated controls and in safrole treated animals killed during the day, at night, after pinealectomy and pinealectomy plus melatonin injection (0.15 mg/kg x 4 or a total of 0.6 mg/kg) was 0, 12.6 +/- 0.75, 10.9 +/- 0.72, 13.6 +/- 1.12 and 5.7 +/- 0.53 respectively. For the same groups of animals, circulating melatonin levels at the termination of the study were 31 +/- 3, 29 +/- 2, 276 +/- 31, 24 +/- 1 and 13,950 +/- 1016 pg/ml serum respectively. The higher the melatonin concentration in the serum the lower was DNA adduct formation in the rat liver. Thus, high nocturnal levels of melatonin were protective against safrole-induced DNA damage. These findings indicate that the functional pineal gland plays an important role in oncostatic actions of carcinogens such as safrole. At physiological levels, melatonin seemed to prevent especially the formation of what was referred to as the N1 DNA adduct. Melatonin's ability to suppress DNA adduct formation may relate to its inhibitory effect on a mixed function oxidase, cytochrome p-450, and on the recently identified hydroxyl radical scavenging capacity of the indole. The oncostatic action of melatonin is also suggested by its nuclear accumulation and DNA stabilization characteristics. At pharmacological levels melatonin is extremely potent in preventing DNA modification induced by the chemical carcinogen, safrole.

  14. Targeting CAG repeat RNAs reduces Huntington's disease phenotype independently of huntingtin levels.

    PubMed

    Rué, Laura; Bañez-Coronel, Mónica; Creus-Muncunill, Jordi; Giralt, Albert; Alcalá-Vida, Rafael; Mentxaka, Gartze; Kagerbauer, Birgit; Zomeño-Abellán, M Teresa; Aranda, Zeus; Venturi, Veronica; Pérez-Navarro, Esther; Estivill, Xavier; Martí, Eulàlia

    2016-11-01

    Huntington's disease (HD) is a polyglutamine disorder caused by a CAG expansion in the Huntingtin (HTT) gene exon 1. This expansion encodes a mutant protein whose abnormal function is traditionally associated with HD pathogenesis; however, recent evidence has also linked HD pathogenesis to RNA stable hairpins formed by the mutant HTT expansion. Here, we have shown that a locked nucleic acid-modified antisense oligonucleotide complementary to the CAG repeat (LNA-CTG) preferentially binds to mutant HTT without affecting HTT mRNA or protein levels. LNA-CTGs produced rapid and sustained improvement of motor deficits in an R6/2 mouse HD model that was paralleled by persistent binding of LNA-CTG to the expanded HTT exon 1 transgene. Motor improvement was accompanied by a pronounced recovery in the levels of several striatal neuronal markers severely impaired in R6/2 mice. Furthermore, in R6/2 mice, LNA-CTG blocked several pathogenic mechanisms caused by expanded CAG RNA, including small RNA toxicity and decreased Rn45s expression levels. These results suggest that LNA-CTGs promote neuroprotection by blocking the detrimental activity of CAG repeats within HTT mRNA. The present data emphasize the relevance of expanded CAG RNA to HD pathogenesis, indicate that inhibition of HTT expression is not required to reverse motor deficits, and further suggest a therapeutic potential for LNA-CTG in polyglutamine disorders.

  15. Reduced beta 2-microglobulin mRNA levels in transgenic mice expressing a designed hammerhead ribozyme.

    PubMed Central

    Larsson, S; Hotchkiss, G; Andäng, M; Nyholm, T; Inzunza, J; Jansson, I; Ahrlund-Richter, L

    1994-01-01

    We have generated three artificial hammerhead ribozymes, denoted 'Rz-b', 'Rz-c' and 'Rz-d', with different specificities for exon II of the mouse beta-2-microglobulin (beta 2M) mRNA. In this study we tested for ribozyme mediated reduction of beta 2M mRNA in a cell line and in transgenic mice. Transfections of either of the Rz-b, Rz-c or Rz-d plasmids into a mouse cell-line (NIH/3T3) revealed reductions of beta 2M mRNA substrate in each case. Ribozyme expression in individual transfected clones was accompanied with an up to 80% reduction of beta 2M mRNA levels. Rz-c was selected for a transgenic study. Seven Rz-c transgenic founder animals were identified from which three ribozyme expressing families were established and analysed. Expression of the ribozyme transgene was tested for and detected in lung, kidney and spleen. Expression was accompanied with reduction of the beta 2M mRNA levels of heterozygous (Rz+/-) animals compared to non-transgenic litter mates. The effect was most pronounced in lung with more than 90% beta 2M mRNA reduction in individual mice. In summary, expression of our ribozymes in a cell free system, in a cell-line and in transgenic mice were all accompanied with reductions of beta 2M mRNA levels. Images PMID:8036151

  16. Bilateral native nephrectomy reduces systemic oxalate level after combined liver-kidney transplant: A case report.

    PubMed

    Villani, Vincenzo; Gupta, Neena; Elias, Nahel; Vagefi, Parsia A; Markmann, James F; Paul, Elahna; Traum, Avram Z; Yeh, Heidi

    2017-03-05

    Primary hyperoxaluria type 1 (PH1) is a rare liver enzymatic defect that causes overproduction of plasma oxalate. Accumulation of oxalate in the kidney and subsequent renal failure are fatal to PH1 patients often in pediatric age. Combined liver and kidney transplantation is the therapy of choice for end-stage renal disease due to PH1. Levels of plasma oxalate remain elevated for several months after liver transplantation, as the residual body oxalate is slowly excreted. Patients with persistent hyperoxaluria after transplant often require hemodialysis, and accumulation of residual oxalate in the kidney can induce graft dysfunction. As the native kidneys are the main target of calcium oxalate accumulation, we postulated that removal of native kidneys could drastically decrease total body oxalate levels after transplantation. Here, we report a case of bilateral nephrectomy at the time of combined liver-kidney transplantation in a pediatric PH1 patient. Bilateral nephrectomy induced a rapid decrease in plasma oxalate to normal levels in less than 20 days, compared to the several months reported in the literature. Our results suggest that removal of native kidneys could be an effective strategy to decrease the need for hemodialysis and the risk of renal dysfunction after combined liver-kidney transplantation in patients with PH1.

  17. Targeting CAG repeat RNAs reduces Huntington’s disease phenotype independently of huntingtin levels

    PubMed Central

    Rué, Laura; Bañez-Coronel, Mónica; Creus-Muncunill, Jordi; Giralt, Albert; Alcalá-Vida, Rafael; Mentxaka, Gartze; Kagerbauer, Birgit; Aranda, Zeus; Venturi, Veronica; Pérez-Navarro, Esther; Estivill, Xavier

    2016-01-01

    Huntington’s disease (HD) is a polyglutamine disorder caused by a CAG expansion in the Huntingtin (HTT) gene exon 1. This expansion encodes a mutant protein whose abnormal function is traditionally associated with HD pathogenesis; however, recent evidence has also linked HD pathogenesis to RNA stable hairpins formed by the mutant HTT expansion. Here, we have shown that a locked nucleic acid–modified antisense oligonucleotide complementary to the CAG repeat (LNA-CTG) preferentially binds to mutant HTT without affecting HTT mRNA or protein levels. LNA-CTGs produced rapid and sustained improvement of motor deficits in an R6/2 mouse HD model that was paralleled by persistent binding of LNA-CTG to the expanded HTT exon 1 transgene. Motor improvement was accompanied by a pronounced recovery in the levels of several striatal neuronal markers severely impaired in R6/2 mice. Furthermore, in R6/2 mice, LNA-CTG blocked several pathogenic mechanisms caused by expanded CAG RNA, including small RNA toxicity and decreased Rn45s expression levels. These results suggest that LNA-CTGs promote neuroprotection by blocking the detrimental activity of CAG repeats within HTT mRNA. The present data emphasize the relevance of expanded CAG RNA to HD pathogenesis, indicate that inhibition of HTT expression is not required to reverse motor deficits, and further suggest a therapeutic potential for LNA-CTG in polyglutamine disorders. PMID:27721240

  18. Reduced levels of protein recoding by A-to-I RNA editing in Alzheimer's disease

    PubMed Central

    Khermesh, Khen; D'Erchia, Anna Maria; Barak, Michal; Annese, Anita; Wachtel, Chaim; Levanon, Erez Y.; Picardi, Ernesto; Eisenberg, Eli

    2016-01-01

    Adenosine to inosine (A-to-I) RNA editing, catalyzed by the ADAR enzyme family, acts on dsRNA structures within pre-mRNA molecules. Editing of the coding part of the mRNA may lead to recoding, amino acid substitution in the resulting protein, possibly modifying its biochemical and biophysical properties. Altered RNA editing patterns have been observed in various neurological pathologies. Here, we present a comprehensive study of recoding by RNA editing in Alzheimer's disease (AD), the most common cause of irreversible dementia. We have used a targeted resequencing approach supplemented by a microfluidic-based high-throughput PCR coupled with next-generation sequencing to accurately quantify A-to-I RNA editing levels in a preselected set of target sites, mostly located within the coding sequence of synaptic genes. Overall, editing levels decreased in AD patients’ brain tissues, mainly in the hippocampus and to a lesser degree in the temporal and frontal lobes. Differential RNA editing levels were observed in 35 target sites within 22 genes. These results may shed light on a possible association between the neurodegenerative processes typical for AD and deficient RNA editing. PMID:26655226

  19. Low level laser therapy reduces oxidative stress in cortical neurons in vitro

    NASA Astrophysics Data System (ADS)

    Huang, Ying-Ying; Tedford, Clark E.; McCarthy, Thomas; Hamblin, Michael R.

    2012-03-01

    It is accepted that the mechanisms of low level laser therapy (LLLT) involves photons that are absorbed in the mitochondria of cells and lead to increase of mitochondrial metabolism resulting in more electron transport, increase of mitochondrial membrane potential, and more ATP production. Intracellular calcium changes are seen that correlate with mitochondrial stimulation. The situation with two other intermediates is more complex however: reactive oxygen species (ROS) and nitric oxide (NO). Evidence exists that low levels of ROS are produced by LLLT in normal cells that can be beneficial by (for instance) activating NF-kB. However high fluences of light can produce large amounts of ROS that can damage the cells. In oxidatively stressed cells the situation may be different. We exposed primary cultured cortical neurons to hydrogen peroxide (H2O2) or cobalt chloride (CoCl2) oxidative insults in the presence or absence of LLLT (810-nm laser at 0.3 or 3 J/cm2). Cell viability of cortical neurons was determined by lactate dehydrogenase assay. ROS in neurons was detected using an ROS probe, MitoRox with confocal microscopy. Results showed that LLLT dose-dependently reversed ROS production and protected cortical neurons against H2O2 or CoCl2 induced oxidative injury in cultured cortical neurons. Conclusion: LLLT can protect cortical neurons against oxidative stress by reversing the levels of ROS.

  20. Optical Mass Gauging System for Measuring Liquid Levels in a Reduced Gravity Environment

    NASA Technical Reports Server (NTRS)

    Sullenberger, Ryan M.; Munoz, Wesley M.; Lyon, Matt P.; Vogel, Kenny; Yalin, Azer P.; Korman, Valentin; Polzin, Kurt A.

    2010-01-01

    A compact and rugged fiber-coupled liquid volume sensor designed for flight on a sounding rocket platform is presented. The sensor consists of a Mach-Zehnder interferometer capable of measuring the amount of liquid contained in a tank under any gravitational conditions, including a microgravity environment, by detecting small changes in the index of refraction of the gas contained within a sensing region. By monitoring changes in the interference fringe pattern as the system undergoes a small compression provided by a piston, the ullage volume of a tank can be directly measured allowing for a determination of the liquid volume. To demonstrate the technique, data are acquired using two tanks containing different volumes of liquid, which are representative of the levels of liquid in a tank at different time periods during a mission. The two tanks are independently exposed to the measurement apparatus, allowing for a determination of the liquid level in each. In a controlled, laboratory test of the unit, the system demonstrated a capability of measuring a liquid level in an individual tank of 10.53 mL with a 2% error. The overall random uncertainty for the flight system is higher than that one test, at +/- 1.5 mL.

  1. Triclosan exposure reduces thyroxine levels in pregnant and lactating rat dams and in directly exposed offspring.

    PubMed

    Axelstad, Marta; Boberg, Julie; Vinggaard, Anne Marie; Christiansen, Sofie; Hass, Ulla

    2013-09-01

    Thyroid disrupting chemicals can potentially disrupt brain development. Two studies investigating the effect of the antibacterial compound triclosan on thyroxine (T₄) levels in rats are reported. In the first, Wistar rat dams were gavaged with 75, 150 or 300 mg triclosan/kg bw/day throughout gestation and lactation. Total T₄ serum levels were measured in dams and offspring, and all doses of triclosan significantly lowered T₄ in dams, but no significant effects on T₄ levels were seen in the offspring at the end of the lactation period. Since this lack of effect could be due to minimal exposure through maternal milk, a second study using direct per oral pup exposure from postnatal day 3-16 to 50 or 150 mg triclosan/kg bw/day was performed. This exposure pointed to significant T₄ reductions in 16 day old offspring in both dose groups. These results corroborate previous studies showing that in rats lactational transfer of triclosan seems limited. Since an optimal study design for testing potential developmental neurotoxicants in rats, should include exposure during both the pre- and postnatal periods of brain development, we suggest that in the case of triclosan, direct dosing of pups may be the best way to obtain that goal.

  2. Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats.

    PubMed

    Kawabata, Fuminori; Mizushige, Takafumi; Uozumi, Keisuke; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kishida, Taro

    2015-01-01

    In our previous study, fish protein was proven to reduce serum lipids and body fat accumulation by skeletal muscle hypertrophy and enhancing basal energy expenditure in rats. In the present study, we examined the precise effects of fish protein intake on different skeletal muscle fiber types and metabolic gene expression of the muscle. Fish protein increased fast-twitch muscle weight, reduced liver triglycerides and serum glucose levels, compared with the casein diet after 6 or 8 weeks of feeding. Furthermore, fish protein upregulated the gene expressions of a fast-twitch muscle-type marker and a glucose transporter in the muscle. These results suggest that fish protein induces fast-muscle hypertrophy, and the enhancement of basal energy expenditure by muscle hypertrophy and the increase in muscle glucose uptake reduced liver lipids and serum glucose levels. The present results also imply that fish protein intake causes a slow-to-fast shift in muscle fiber type.

  3. Esculetin reduces leukotriene B4 level in plasma of rats with adjuvant-induced arthritis

    PubMed Central

    Gąsińska, Emilia; Gajewski, Michał; Bujalska-Zadrożny, Magdalena; Szukiewicz, Dariusz; Maśliński, Sławomir

    2016-01-01

    Objectives Esculetin (6,7-dihydroxycoumarin) is a natural coumarin with anti-oxidant, anti-inflammatory and anti-nociceptive activity. It acts as a potent inhibitor of lipoxygenases (5-LOX and 12-LOX) and decreases the production of matrix metalloproteinases (MMP-1, MMP-3 and MMP-9). Because both inhibition of lipoxygenases and inhibition of matrix metalloproteinases are effective strategies in the treatment of rheumatoid arthritis, we investigated whether esculetin may be effective in adjuvant-induced arthritis in rats. Material and methods The study was performed on male Lewis rats, in the adjuvant-induced arthritis model. Rats were divided into two groups: control (treated with 1% methylcellulose) and experimental (treated with esculetin – 10 mg/kg ip.). The tested compound was administered for 5 consecutive days starting on the 21st day after induction of arthritis. Each group consisted of 7 animals. After 5 days of treatment, rats were anesthetized. The concentration of leukotriene B4 (LTB4) in plasma was determined by a competitive enzyme immunoassay. Results The LTB4 level in plasma of rats with adjuvant-induced arthritis is increased in comparison to rats without inflammation (362 ±34 vs. 274 ±15 pg/ml, p < 0.01, respectively). Five-day treatment with esculetin in adjuvant-induced arthritis rats decreases the LTB4 level to a level comparable with rats without inflammation (284 ±23 pg/ml, p < 0.01). Conclusions LTB4 is the most potent chemotactic agent influencing neutrophil migration into the joint. It is known that its level in serum of patients with active rheumatoid arthritis is increased and correlates with disease severity. Some other lipoxygenase inhibitors have already been tested as potential drug candidates in clinical and preclinical trials for rheumatoid arthritis (Zileuton, PF-4191834). Because esculetin decreases the LTB4 level in plasma of rats in adjuvant-induced arthritis, it may also be considered as an attractive drug candidate for

  4. Defining Pesticide Biomarkers

    EPA Pesticide Factsheets

    Biomarkers are measurable substances or characteristics in the human body that can be used to monitor the presence of a chemical in the body, biological responses or harm to health. This Web page describes categories of biomarkers and provides examples.

  5. BIOMARKERS OF REPRODUCTIVE TOXICITY

    EPA Science Inventory

    Identification and verification of anatomical, endocrine, cellular and molecular biomarkers is crucial for successful clinical diagnosis and treatment of toxicity and disease, as well as basic toxicological, epidemiological and other research. Various in situ biomarkers of repro...

  6. Biomarkers in Computational Toxicology

    EPA Science Inventory

    Biomarkers are a means to evaluate chemical exposure and/or the subsequent impacts on toxicity pathways that lead to adverse health outcomes. Computational toxicology can integrate biomarker data with knowledge of exposure, chemistry, biology, pharmacokinetics, toxicology, and e...

  7. Prolonged fermentation of whole wheat sourdough reduces phytate level and increases soluble magnesium.

    PubMed

    Lopez, H W; Krespine, V; Guy, C; Messager, A; Demigne, C; Remesy, C

    2001-05-01

    This work was designed to compare the effects of different leavens (yeast, sourdough, and a mixture of both) on phytic acid (PA) degradation and to assess the repercussions of PA breakdown on phosphorus and magnesium solubility during bread-making. Sourdough fermentation was more efficient than yeast fermentation in reducing the phytate content in whole wheat bread (-62 and -38%, respectively). Furthermore, lactic acid bacteria present in sourdough enhanced acidification, leading to increased magnesium and phosphorus solubility. To intensify phytate breakdown, bran was incubated with microorganisms (yeast or sourdough) before bread-making. Using this new method, the percentage of phytate breakdown was near 90%, whereas 40% of phytate remained in traditional French bread. In conclusion, a prolonged fermentation with sourdough still leads to improved Mg and P solubility by decreasing phytate content and through acidification.

  8. Pilot-scale continuous ultrasonic cleaning equipment reduces Listeria monocytogenes levels on conveyor belts.

    PubMed

    Tolvanen, Riina; Lundén, Janne; Hörman, Ari; Korkeala, Hannu

    2009-02-01

    Ultrasonic cleaning of a conveyor belt was studied by building a pilot-scale conveyor with an ultrasonic cleaning bath. A piece of the stainless steel conveyor belt was contaminated with meat-based soil and Listeria monocytogenes strains (V1, V3, and B9) and incubated for 72 h to allow bacteria to attach to the conveyor belt surfaces. The effect of ultrasound with a potassium hydroxide-based cleaning detergent was determined by using the cleaning bath at 45 and 50 degrees C for 30 s with and without ultrasound. The detachment of L. monocytogenes from the conveyor belt caused by the ultrasonic treatment was significantly greater at 45 degrees C (independent samples t test, P < 0.001) and at 50 degrees C (independent samples t test, P = 0.04) than without ultrasound. Ultrasonic cleaning efficiency was tested with different cleaning durations (10, 15, 20, and 30 s) and temperatures (30, 45, and 50 degrees C). The differences in the log reduction between cleaning treatments were analyzed by analysis of variance with Tamhane's T2 posthoc test using SPSS (Chicago, IL). The lengthening of the treatment time from 10 to 30 s did not significantly increase the detachment of L. monocytogenes (ANOVA 0.633). At 30 degrees C and at the longest time tested (30 s), the treatment reduced L. monocytogenes counts by only 2.68 log units. However, an increase in temperature from 30 to 50 degrees C improved the effect of the ultrasonic treatment significantly (P < 0.01). Ultrasonic cleaning for 10 s at 50 degrees C reduced L. monocytogenes counts by more than 5 log units. These results indicate that ultrasonic cleaning of a conveyor belt is effective even with short treatment times.

  9. Higher levels of serum lycopene are associated with reduced mortality in individuals with metabolic syndrome.

    PubMed

    Han, Guang-Ming; Meza, Jane L; Soliman, Ghada A; Islam, K M Monirul; Watanabe-Galloway, Shinobu

    2016-05-01

    Metabolic syndrome increases the risk of mortality. Increased oxidative stress and inflammation may play an important role in the high mortality of individuals with metabolic syndrome. Previous studies have suggested that lycopene intake might be related to the reduced oxidative stress and decreased inflammation. Using data from the National Health and Nutrition Examination Survey, we examined the hypothesis that lycopene is associated with mortality among individuals with metabolic syndrome. A total of 2499 participants 20 years and older with metabolic syndrome were divided into 3 groups based on their serum concentration of lycopene using the tertile rank method. The National Health and Nutrition Examination Survey from years 2001 to 2006 was linked to the mortality file for mortality follow-up data through December 31, 2011, to determine the mortality rate and hazard ratios (HR) for the 3 serum lycopene concentration groups. The mean survival time was significantly higher in the group with the highest serum lycopene concentration (120.6 months; 95% confidence interval [CI], 118.8-122.3) and the medium group (116.3 months; 95% CI, 115.2-117.4), compared with the group with lowest serum lycopene concentration (107.4 months; 95% CI, 106.5-108.3). After adjusting for possible confounding factors, participants in the highest (HR, 0.61; P = .0113) and in the second highest (HR, 0.67; P = .0497) serum lycopene concentration groups showed significantly lower HRs of mortality when compared with participants in the lower serum lycopene concentration. The data suggest that higher serum lycopene concentration has a significant association with the reduced risk of mortality among individuals with metabolic syndrome.

  10. Public acceptability of population-level interventions to reduce alcohol consumption: a discrete choice experiment.

    PubMed

    Pechey, Rachel; Burge, Peter; Mentzakis, Emmanouil; Suhrcke, Marc; Marteau, Theresa M

    2014-07-01

    Public acceptability influences policy action, but the most acceptable policies are not always the most effective. This discrete choice experiment provides a novel investigation of the acceptability of different interventions to reduce alcohol consumption and the effect of information on expected effectiveness, using a UK general population sample of 1202 adults. Policy options included high, medium and low intensity versions of: Minimum Unit Pricing (MUP) for alcohol; reducing numbers of alcohol retail outlets; and regulating alcohol advertising. Outcomes of interventions were predicted for: alcohol-related crimes; alcohol-related hospital admissions; and heavy drinkers. First, the models obtained were used to predict preferences if expected outcomes of interventions were not taken into account. In such models around half of participants or more were predicted to prefer the status quo over implementing outlet reductions or higher intensity MUP. Second, preferences were predicted when information on expected outcomes was considered, with most participants now choosing any given intervention over the status quo. Acceptability of MUP interventions increased by the greatest extent: from 43% to 63% preferring MUP of £1 to the status quo. Respondents' own drinking behaviour also influenced preferences, with around 90% of non-drinkers being predicted to choose all interventions over the status quo, and with more moderate than heavy drinkers favouring a given policy over the status quo. Importantly, the study findings suggest public acceptability of alcohol interventions is dependent on both the nature of the policy and its expected effectiveness. Policy-makers struggling to mobilise support for hitherto unpopular but promising policies should consider giving greater prominence to their expected outcomes.

  11. Allopregnanolone Levels are Reduced in Temporal Cortex in Patients with Alzheimer’s Disease Compared to Cognitively Intact Control Subjects

    PubMed Central

    Naylor, Jennifer C.; Kilts, Jason D.; Hulette, Christine M.; Steffens, David C.; Blazer, Dan G.; Ervin, John F.; Strauss, Jennifer L.; Allen, Trina B.; Massing, Mark W.; Payne, Victoria M.; Youssef, Nagy A.; Shampine, Lawrence J.; Marx, Christine E.

    2010-01-01

    Background The neurosteroid allopregnanolone has pronounced neuroprotective actions, increases myelination, and enhances neurogenesis. Evidence suggests that allopregnanolone dysregulation may play a role in the pathophysiology of Alzheimer’s disease (AD) and other neurodegenerative disorders. Our prior data demonstrate that allopregnanolone is reduced in prefrontal cortex in male patients with AD compared to male cognitively intact control subjects, and inversely correlated with neuropathological disease stage (Braak and Braak). We therefore determined if allopregnanolone levels are also reduced in AD patients compared to control subjects in temporal cortex, utilizing a larger set of samples from both male and female patients. In addition, we investigated if neurosteroids are altered in subjects who are APOE4 allele carriers. Methods Allopregnanolone, dehydroepiandrosterone (DHEA), and pregnenolone levels were determined in temporal cortex postmortem samples by gas chromatography/mass spectrometry, preceded by high performance liquid chromatography (40 subjects with AD/41 cognitively intact control subjects). Results Allopregnanolone levels are reduced in temporal cortex in patients with AD (median 2.68 ng/g, n= 40) compared to control subjects (median 5.64 ng/g, n=41), Mann-Whitney p=0.0002, and inversely correlated with Braak and Braak neuropathological disease stage (Spearman r= −0.38, p=0.0004). DHEA and pregnenolone are increased in patients with AD compared to control subjects. Patients carrying an APOE4 allele demonstrate reduced allopregnanolone levels in temporal cortex (Mann-Whitney p=0.04). Conclusions Neurosteroids are altered in temporal cortex in patients with AD and related to neuropathological disease stage. The APOE4 allele is associated with reduced allopregnanolone levels. Neurosteroids may be relevant to the neurobiology and therapeutics of AD. PMID:20488256

  12. Exercise training reduces PGE2 levels and induces recovery from steatosis in tumor-bearing rats.

    PubMed

    Lira, F S; Yamashita, A; Carnevali, L C; Gonçalves, D C; Lima, W P; Rosa, J C; Caperuto, E C; Rosa, L F C; Seelaender, M

    2010-12-01

    The effects of endurance training on PGE (2) levels and upon the maximal activity of hepatic carnitine palmitoyltransferase (CPT) system were studied in rats bearing the Walker 256 carciosarcoma. Animals were randomly assigned to a sedentary control (SC), sedentary tumor-bearing (ST), exercised control (EC), and as an exercised tumor-bearing (ET) group. Trained rats ran on a treadmill (60% VO (2) max) for 60 min/day, 5 days/week, for 8 weeks. We examined the mRNA expression (RT-PCR) and maximal activity (radioassay) of the carnitine palmitoyltransferase system enzymes (CPT I and CPT II), as well as the gene expression of fatty-acid-binding protein (L-FABP) in the liver. PGE (2) content was measured in the serum, in tumor cells, and in the liver (ELISA). CPT I and CPT II maximal activity were decreased (p<0.01) in ST when compared with SC. In contrast, serum PGE (2) was increased (p<0.05) in cachectic animals as compared with SC. In the liver, PGE (2) content was also increased (p<0.05) when compared with SC. Endurance training restored maximal CPT I and CPT II activity in the tumor-bearing animals (p<0.0001). Exercise training induced PGE (2) levels to return to control values in the liver of tumor-bearing training rats (p<0.05) and decreased the eicosanoid content in the tumor (p<0.01). In conclusion, endurance training was capable of reestablishing liver carnitine palmitoyltransferase (CPT) system activity associated with decreased PGE (2) levels in cachectic tumor-bearing animals, preventing steatosis.

  13. Reiki brief report: using Reiki to reduce stress levels in a nine-year-old child.

    PubMed

    Bukowski, Elaine L; Berardi, Diana

    2014-01-01

    A nine-year-old female with a history of perinatal stroke, seizures, and type-I diabetes was seen for six weeks of Reiki to determine the effects of Reiki on relaxation, and in turn, the prevention of future seizures. The secondary and tertiary aims were to determine the effects of Reiki on sleep patterns and the stress levels of the mother. There was a decrease in stress in both the child and the mother, as measured by a modified Perceived Stress Scale and a Perceived Stress Scale, respectively. There was no change in the child's overall sense of well-being, as measured by a global questionnaire. There was a positive change in sleep patterns on 33.3% of the nights during which the study occurred, as reported on a sleep log kept by the mother. The child and the Reiki Master (a Reiki practitioner who has completed all three levels of Reiki certification training and trains and certifies individuals in the practice of Reiki as well as provides Reiki to individuals) experienced warmth and tingling sensations on the same area of the child during the Reiki sessions. The child relaxed within the first five to seven minutes of each session as reported by the Reiki Master. There were no reports of seizures during this study. Reiki may be a useful adjunct for children with increased stress levels and sleep disturbances secondary to their medical condition. Further research is warranted to evaluate the use of Reiki in children, particularly with a large sample size, and to evaluate the long-term use of Reiki and its effects on adequate sleep.

  14. (Reduce uncertainty in projection of future sea-level change due to ice wastage)

    SciTech Connect

    Meier, M.F.

    1991-01-01

    Three basic goals were stated in the original proposal. These were: (1) develop an understanding of the heat and mass flow into subfreezing snow and firn, in order to model the evolution of the temperature distribution and the infiltration rates through the firn; (2) relate changes in climate, as given by general circulation model predictions, to changes in the surface mass and energy balances of glaciers; and (3) use the above results to analyze the effects of changed surface mass and energy balances on the flow of meltwater through snow and firn, and on the runoff from these glaciers, in a CO{sub 2}-affected climate. This final report summarizes our progress toward these goals. The primary product of this research program has been the communication of this progress in the form of publications in the scientific literature and presentations at scientific meetings. Our research activities in the past three years have provided a new basis for modeling of multiphase flow in subfreezing snow, new field data on the structural properties of arctic firn pertinent to hydrological modeling, and estimates of sea level change in response to changing patterns of runoff from the Greenland Ice Sheet. We conclude that forecasts of future sea level changes from all glacier runoff sources may be in error by amounts on the order of +8 cm over the next 150 years, due to the lag in generating runoff to the sea. Our specific research products include two distributed-parameter models of water flow through snow with melting and freezing, a theoretical model of wetting-front advance into subfreezing snow for inclusion in a future model, and a simple large-scale model of the response of Greenland runoff in a changing climate which provides estimates of the effect of melt water refreezing phenomena on sea level changes in response to a range of possible future climates.

  15. Reduced levels of skeletal muscle Na+K+ -ATPase in McArdle disease

    NASA Technical Reports Server (NTRS)

    Haller, R. G.; Clausen, T.; Vissing, J.; Blomqvist, C. G. (Principal Investigator)

    1998-01-01

    We evaluated the hypothesis that impaired sarcolemmal function associated with exaggerated potassium release, impaired potassium uptake, or both may contribute to exertional fatigue and abnormal circulatory responses to exercise in McArdle disease (MD). The cellular mechanism of exertional fatigue and muscle injury in MD is unknown but likely involves impaired function of the ATPases that couple ATP hydrolysis to cellular work, including the muscle sodium potassium pump (Na+K+-ATPase). However, the concentration of muscle Na+K+ pumps in MD is not known, and no studies have related exercise increases in blood potassium concentrations to muscle Na+K+ pump levels. We measured muscle Na+K+ pumps (3H-ouabain binding) and plasma K+ in response to 20 minutes of cycle exercise in six patients with MD and in six sex-, age-, and weight-matched sedentary individuals. MD patients had lower levels of 3H-ouabain binding (231 +/- 18 pmol/g w.w., mean +/- SD, range, 210 to 251) than control subjects (317 +/- 37, range, 266 to 371, p < 0.0004), higher peak increases in plasma potassium in response to 45 +/- 7 W cycle exercise (MD, 1.00 +/- 0.15 mmol/L; control subjects, 0.48 +/- 0.09; p < 0.0001), and mean exercise heart rate responses to exercise that were 45 +/- 12 bpm greater than control subjects. Our results indicate that Na+K+ pump levels are low in MD patients compared with healthy subjects and identify a limitation of potassium reuptake that could result in sarcolemmal failure during peak rates of membrane activation and may promote exaggerated potassium-activated circulatory responses to submaximal exercise. The mechanism of the low Na+K+ pump concentrations in MD is unknown but may relate to deconditioning or to disruption of a close functional relationship between membrane ion transport and glycolysis.

  16. Low Level Laser Therapy to Reduce Recurrent Oral Ulcers in Behçet's Disease

    PubMed Central

    Babu, D. B. Gandhi; Chavva, Sunanda; Waghray, Shefali

    2016-01-01

    Behçet's disease (BD) is a chronic, relapsing multisystemic vascular condition. Behçet's disease was described by Hulusi Behçet in 1937. This rare multisystem relapsing-remitting inflammatory disease is poorly understood but is thought to be an autoimmune inflammatory vasculitic process in a genetically predisposed population. Diagnosis of Behçet's disease is based on International Criteria of Behçet's Disease (ICBD). The present paper describes a case report of Behçet's syndrome where aphthous stomatitis was treated with low level laser therapy. PMID:27555969

  17. Increasing Safety and Reducing Environmental Damage Risk from Aging High-Level Radioactive Waste Tanks

    SciTech Connect

    Steffler, Eric D.; McClintock, Frank A.; Lloyd, W. Randolph; Rashid, Mark M.; Williamson, Richard L.

    2005-06-01

    Cracks of various shapes and sizes exist in large high-level waste (HLW) tanks at several DOE sites. There is justifiable concern that these cracks could grow to become unstable causing a substantial release of liquid contaminants to the environment. Accurate prediction of crack growth behavior in the tanks, especially during accident scenarios, is not possible with existing analysis methodologies. This research project responds to this problem by developing an improved ability to predict crack growth in material structure combinations that are ductile (Fig. 1). This new model not only addresses the problem for these tanks, but also has applicability to any crack in any ductile structure.

  18. Opportunities for state-level action to reduce firearm violence: proceeding from the evidence.

    PubMed

    Wintemute, Garen J; Braga, Anthony A

    2011-09-01

    Firearm violence remains an important problem, and a large body of evidence shows that guns used in crime follow generally predictable paths from manufacturer to criminal end user. Policy initiatives based on that evidence have been shown to be effective. A recently published study conducted by a leading policy organization presents new evidence and makes specific recommendations for action by state-level policymakers. Unfortunately, the study's analysis is overly simplified, and the recommendations are therefore misleading. We suggest alternatives that are evidence based.

  19. Biomarkers in Veterinary Medicine.

    PubMed

    Myers, Michael J; Smith, Emily R; Turfle, Phillip G

    2017-02-08

    This article summarizes the relevant definitions related to biomarkers; reviews the general processes related to biomarker discovery and ultimate acceptance and use; and finally summarizes and reviews, to the extent possible, examples of the types of biomarkers used in animal species within veterinary clinical practice and human and veterinary drug development. We highlight opportunities for collaboration and coordination of research within the veterinary community and leveraging of resources from human medicine to support biomarker discovery and validation efforts for veterinary medicine.

  20. Reduced genetic distance and high replication levels increase the RNA recombination rate of hepatitis delta virus.

    PubMed

    Lin, Chia-Chi; Yang, Zhi-Wei; Iang, Shan-Bei; Chao, Mei

    2015-01-02

    Hepatitis delta virus (HDV) replication is carried out by host RNA polymerases. Since homologous inter-genotypic RNA recombination is known to occur in HDV, possibly via a replication-dependent process, we hypothesized that the degree of sequence homology and the replication level should be related to the recombination frequency in cells co-expressing two HDV sequences. To confirm this, we separately co-transfected cells with three different pairs of HDV genomic RNAs and analyzed the obtained recombinants by RT-PCR followed by restriction fragment length polymorphism and sequencing analyses. The sequence divergence between the clones ranged from 24% to less than 0.1%, and the difference in replication levels was as high as 100-fold. As expected, significant differences were observed in the recombination frequencies, which ranged from 0.5% to 47.5%. Furthermore, varying the relative amounts of parental RNA altered the dominant recombinant species produced, suggesting that template switching occurs frequently during the synthesis of genomic HDV RNA. Taken together, these data suggest that during the host RNA polymerase-driven RNA recombination of HDV, both inter- and intra-genotypic recombination events are important in shaping the genetic diversity of HDV.

  1. Depletion of host cell riboflavin reduces Wolbachia levels in cultured mosquito cells.

    PubMed

    Fallon, Ann M; Baldridge, Gerald D; Carroll, Elissa M; Kurtz, Cassandra M

    2014-09-01

    Wolbachia is an obligate intracellular alphaproteobacterium that occurs in arthropod and nematode hosts. Wolbachia presumably provides a fitness benefit to its hosts, but the basis for its retention and spread in host populations remains unclear. Wolbachia genomes retain biosynthetic pathways for some vitamins, and the possibility that these vitamins benefit host cells provides a potential means of selecting for Wolbachia-infected cell lines. To explore whether riboflavin produced by Wolbachia is available to its host cell, we established that growth of uninfected C7-10 mosquito cells decreases in riboflavin-depleted culture medium. A well-studied inhibitor of riboflavin uptake, lumiflavin, further inhibits growth of uninfected C7-10 cells with an LC50 of approximately 12 μg/ml. Growth of C/wStr1 mosquito cells, infected with Wolbachia from the planthopper, Laodelphax striatellus, was enhanced in medium containing low levels of lumiflavin, but Wolbachia levels decreased. Lumiflavin-enhanced growth thus resembled the improved growth that accompanies treatment with antibiotics that deplete Wolbachia, rather than a metabolic advantage provided by the Wolbachia infection. We used the polymerase chain reaction to validate the decrease in Wolbachia abundance and evaluated our results in the context of a proteomic analysis in which we detected nearly 800 wStr proteins. Our data indicate that Wolbachia converts riboflavin to FMN and FAD for its own metabolic needs, and does not provide a source of riboflavin for its host cell.

  2. Arginine vasotocin reduces levels of cooperative behaviour in a cleaner fish.

    PubMed

    Cardoso, Sónia C; Paitio, José R; Oliveira, Rui F; Bshary, Redouan; Soares, Marta C

    2015-02-01

    Cooperation between unrelated individuals usually involves investments that often mean a decrease in immediate payoffs, but ensure future benefits. Here we investigated the potential role of the neuropeptides Arginine-vasotocin (AVT) and Isotocin (IT) as proximate agents affecting individuals' cooperative levels in the Indo-pacific bluestreak cleaner wrasse Labroides dimidiatus. Their 'client' reef fish partners only benefit from interacting if cleaners eat ectoparasites and refrain from gleaning preferred client mucus. Thus, cleaners must control their impulse to eat according to their preference, and eat less preferred items to maintain ongoing interactions and avoid clients' leaving or punishing. We found that solely the experimental transient higher dosage of AVT led to a decrease of cleaners' willingness to feed against their preference, while IT and AVT antagonists had no significant effects. The sole effect of AVT on cleaner's performance may imply a link between AVT's influence and a potential activation of a stress response. Our results confirm the importance of the AVT/AVP system as an agent affecting levels of cooperation, offering a potential mechanistic pathway for the reported flexible service quality that cleaners provide their clients.

  3. Serum brain-derived neurotrophic factor levels were reduced during methamphetamine early withdrawal.

    PubMed

    Chen, Pao-Huan; Huang, Ming-Chi; Lai, Ying-Ching; Chen, Po-Yu; Liu, Hsing-Cheng

    2014-05-01

    Methamphetamine (METH) abuse is an increasing public health problem worldwide. Many of the METH-induced physical and mental problems are associate