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Sample records for dysfunction biological markers

  1. Elevated Cell-Specific Microparticles Are a Biological Marker for Cerebral Dysfunctions in Human Severe Malaria

    PubMed Central

    Pankoui Mfonkeu, Joël Bertrand; Gouado, Inocent; Fotso Kuaté, Honoré; Zambou, Odile; Amvam Zollo, Paul Henri; Grau, Georges Emile Raymond; Combes, Valéry

    2010-01-01

    Cerebral malaria (CM) and severe anemia (SA) are the most severe complications of Plasmodium falciparum infections. Although increased release of endothelial microparticles (MP) correlates with malaria severity, the full extent of vascular cell vesiculation remains unknown. Here, we characterize the pattern of cell-specific MP in patients with severe malaria. We tested the hypothesis that systemic vascular activation contributes to CM by examining origins and levels of plasma MP in relation to clinical syndromes, disease severity and outcome. Patients recruited in Douala, Cameroon, were assigned to clinical groups following WHO criteria. MP quantitation and phenotyping were carried out using cell-specific markers by flow cytometry using antibodies recognizing cell-specific surface markers. Platelet, erythrocytic, endothelial and leukocytic MP levels were elevated in patients with cerebral dysfunctions and returned to normal by discharge. In CM patients, platelet MP were the most abundant and their levels significantly correlated with coma depth and thrombocytopenia. This study shows for the first time a widespread enhancement of vesiculation in the vascular compartment appears to be a feature of CM but not of SA. Our data underpin the role of MP as a biomarker of neurological involvement in severe malaria. Therefore, intervention to block MP production in severe malaria may provide a new therapeutic pathway. PMID:20976232

  2. Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review.

    PubMed

    Poggesi, Anna; Pasi, Marco; Pescini, Francesca; Pantoni, Leonardo; Inzitari, Domenico

    2016-01-01

    The term cerebral small vessel disease (SVD) refers to a group of pathologic processes with various etiologies that affect small arteries, arterioles, venules, and capillaries of the brain. Magnetic resonance imaging (MRI) correlates of SVD are lacunes, recent small subcortical infarcts, white-matter hyperintensities, enlarged perivascular spaces, microbleeds, and brain atrophy. Endothelial dysfunction is thought to have a role in the mechanisms leading to SVD-related brain changes, and the study of endothelial dysfunction has been proposed as an important step for a better comprehension of cerebral SVD. Among available methods to assess endothelial function in vivo, measurement of molecules of endothelial origin in peripheral blood is currently receiving selective attention. These molecules include products of endothelial cells that change when the endothelium is activated, as well as molecules that reflect endothelial damage and repair. This review examines the main molecular factors involved in both endothelial function and dysfunction, and the evidence linking endothelial dysfunction with cerebral SVD, and gives an overview of clinical studies that have investigated the possible association between endothelial circulating biomarkers and SVD-related brain changes. PMID:26058695

  3. Physical exercise, fitness and dietary pattern and their relationship with circadian blood pressure pattern, augmentation index and endothelial dysfunction biological markers: EVIDENT study protocol

    PubMed Central

    2010-01-01

    Background Healthy lifestyles may help to delay arterial aging. The purpose of this study is to analyze the relationship of physical activity and dietary pattern to the circadian pattern of blood pressure, central and peripheral blood pressure, pulse wave velocity, carotid intima-media thickness and biological markers of endothelial dysfunction in active and sedentary individuals without arteriosclerotic disease. Methods/Design Design: A cross-sectional multicenter study with six research groups. Subjects: From subjects of the PEPAF project cohort, in which 1,163 who were sedentary became active, 1,942 were sedentary and 2,346 were active. By stratified random sampling, 1,500 subjects will be included, 250 in each group. Primary measurements: We will evaluate height, weight, abdominal circumference, clinical and ambulatory blood pressure with the Radial Pulse Wave Acquisition Device (BPro), central blood pressure and augmentation index with Pulse Wave Application Software (A-Pulse) and SphymgoCor System Px (Pulse Wave Analysis), pulse wave velocity (PWV) with SphymgoCor System Px (Pulse Wave Velocity), nutritional pattern with a food intake frequency questionnaire, physical activity with the 7-day PAR questionnaire and accelerometer (Actigraph GT3X), physical fitness with the cycle ergometer (PWC-170), carotid intima-media thickness by ultrasound (Micromax), and endothelial dysfunction biological markers (endoglin and osteoprotegerin). Discussion Determining that sustained physical activity and the change from sedentary to active as well as a healthy diet improve circadian pattern, arterial elasticity and carotid intima-media thickness may help to propose lifestyle intervention programs. These interventions could improve the cardiovascular risk profile in some parameters not routinely assessed with traditional risk scales. From the results of this study, interventional approaches could be obtained to delay vascular aging that combine physical exercise and diet

  4. [Biological markers of alcoholism].

    PubMed

    Marcos Martín, M; Pastor Encinas, I; Laso Guzmán, F J

    2005-09-01

    Diagnosis of alcoholism is very important, given its high prevalence and possibility of influencing the disease course. For this reason, the so-called biological markers of alcoholism are useful. These are analytic parameters that alter in the presence of excessive alcohol consumption. The two most relevant markers are the gamma-glutamyltranspeptidase and carbohydrate deficient transferrin. With this clinical comment, we aim to contribute to the knowledge of these tests and promote its use in the clinical practice. PMID:16194480

  5. [THE LEVEL OF LACTATE DEHYDROGENASE AS A MARKER OF RENAL DYSFUNCTION IN NEONATES WITH ASPHYXIA].

    PubMed

    Loboda, A M

    2015-01-01

    The article examines the possibility of determining the level of lactate dehydrogenase (LD) in biological fluids as a marker of renal dysfunction and energy supply in neonates with asphyxia. Investigation included 200 full-term newborns with disturbance kidney function: 100 infants who had severe asphyxia, and 100--with moderate asphyxia. LD activity was determined by kinetic spectrophotometric method. Determination of the activity of LD in the urine in the early neonatal period it is advisable to use as a non-invasive marker for the diagnosis of renal dysfunction in neonates with asphyxia. The content of LD in the blood serum can be used as one of the early markers of kidney damage in newborns with asphyxia. PMID:27491157

  6. [Biology and markers of preeclampsia].

    PubMed

    Guibourdenche, Jean; Leguy, Marie-Clémence; Tsatsaris, Vassilis

    2013-11-01

    Preeclampsia is a syndrome specific of pregnancy and placenta diagnosed after 20 WG on the association of an hypertension and a proteinuria. It is responsible for significant maternal-fetal morbidity and mortality which justify the development of markers for screening, diagnosis and prognosis. These markers are actors or witnesses to the various stages and mechanisms of the disease : the initial defect of trophoblast invasion and remodeling of uterine arteries (proteases [PAPP-A, ADAM-12, uPA, MMPs], their inhibitors, and angiogenic factors [PlGF, sflt-1, s-eng]) which induces hydrostatic abnormalities (uterine doppler) and placental hypoperfusion with dysoxia (HIF-1α) and oxidative stress (free radicals, peroxynitrites, oxidized LDL). This results in impaired placental functions including endocrine and metabolic functions (hCG, leptin) with increase in placental apoptosis and necrosis with the release of exosomes and toxic placental fragments (STBM) and their content (RNA, DNA and proteins). This fragments amplify the gestational inflammation (IL6, TNFα ; activation of leukocytes and macrophages [elastase, neopterin] and complement) and lead to a deterioration of the maternal endothelium (vasoconstriction [ET2, TxA2]; platelet adhesion [sVCAM -1α), aggregation and activation; impaired vascular permeability) generating edema, hypertension, atherosclerosis and glomerular nephropathy (proteinuria, hyperuricemia). Other markers such as PP13 and PTX3 seem of interest even if their functions are poorly understood. Preeclampsia develops on a predisposed maternal environment (genetic, epigenetic infectious, and endocrine factors) characterized by a maternal inadequacy to pregnancy. PMID:24235331

  7. Markers of Cardiac Dysfunction in Cognitive Impairment and Dementia

    PubMed Central

    Hilal, Saima; Chai, Yuek Ling; Ikram, Mohammad Kamran; Elangovan, Sakktivel; Yeow, Tan Boon; Xin, Xu; Chong, Jun Yi; Venketasubramanian, Narayanaswamy; Richards, Arthur Mark; Chong, Jenny P.C.; Lai, Mitchell Kim Peng; Chen, Christopher

    2015-01-01

    Abstract Markers of cardiac dysfunction such as amino terminal pro-brain natriuretic peptide (NTpro-BNP) and high sensitivity cardiac troponin T (hs-cTnT) may be associated with dementia. However, limited data exist on their association with either pre-dementia stages, that is, cognitive impairment no dementia (CIND), or the burden of cerebrovascular diseases (CeVD). We therefore, examined the association of these biomarkers of cardiac dysfunction with CeVD in both CIND and dementia. A case–control study, with cases recruited from memory clinics and controls from memory clinics and community. All subjects underwent collection of blood samples, neuropsychological assessment, and neuroimaging. Subjects were classified as CIND and dementia based on clinical criteria whilst significant CeVD was defined as the presence of cortical infarcts and/or more than 2 lacunes and/or confluent white matter lesions in two regions of brain on Age-Related White Matter Changes Scale. We included a total of 35 controls (mean age: 65.9 years), 78 CIND (mean age: 70.2 years) and 80 cases with dementia (mean age: 75.6 years). Plasma concentrations of hs-cTnT were associated significantly with CeVD in both CIND (odds ratios [OR]: 9.05; 95% confidence interval [CI]: 1.64–49.79) and dementia (OR: 16.89; 95%CI: 2.02–142.67). In addition, NTpro-BNP was associated with dementia with CeVD (OR: 7.74; 95%CI: 1.23–48.58). These associations were independent of other vascular risk factors. In this study, we showed that plasma NTproBNP and hs-cTnT are associated with dementia and CIND, only when accompanied by presence of CeVD. PMID:25569645

  8. Hepatic Steatosis as a Marker of Metabolic Dysfunction

    PubMed Central

    Fabbrini, Elisa; Magkos, Faidon

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the liver manifestation of the complex metabolic derangements associated with obesity. NAFLD is characterized by excessive deposition of fat in the liver (steatosis) and develops when hepatic fatty acid availability from plasma and de novo synthesis exceeds hepatic fatty acid disposal by oxidation and triglyceride export. Hepatic steatosis is therefore the biochemical result of an imbalance between complex pathways of lipid metabolism, and is associated with an array of adverse changes in glucose, fatty acid, and lipoprotein metabolism across all tissues of the body. Intrahepatic triglyceride (IHTG) content is therefore a very good marker (and in some cases may be the cause) of the presence and the degree of multiple-organ metabolic dysfunction. These metabolic abnormalities are likely responsible for many cardiometabolic risk factors associated with NAFLD, such as insulin resistance, type 2 diabetes mellitus, and dyslipidemia. Understanding the factors involved in the pathogenesis and pathophysiology of NAFLD will lead to a better understanding of the mechanisms responsible for the metabolic complications of obesity, and hopefully to the discovery of novel effective treatments for their reversal. PMID:26102213

  9. Vorticity is a marker of right ventricular diastolic dysfunction.

    PubMed

    Fenster, Brett E; Browning, James; Schroeder, Joyce D; Schafer, Michal; Podgorski, Chris A; Smyser, Jamie; Silveira, Lori J; Buckner, J Kern; Hertzberg, Jean R

    2015-09-15

    Right ventricular diastolic dysfunction (RVDD) is an important prognostic indicator in pulmonary arterial hypertension (PAH). RV vortex rings have been observed in healthy subjects, but their significance in RVDD is unknown. Vorticity, the local spinning motion of an element of fluid, may be a sensitive measure of RV vortex dynamics. Using four-dimensional (4D) flow cardiac magnetic resonance imaging (CMR), we investigated the relationship between right heart vorticity with echocardiographic indexes of RVDD. Thirteen (13) PAH subjects and 10 controls underwent same-day 4D flow CMR and echocardiography. RV diastolic function was assessed using trans-tricuspid valve (TV) early (E) and late (A) velocities, E/A ratio, and e' and a' tissue Doppler velocities. RV and right atrial (RA) integrated mean vorticity was calculated for E and A-wave filling periods using 4D datasets. Compared with controls, A-wave vorticity was significantly increased in RVDD subjects in both the RV [2343 (1,559-3,295) vs. 492 (267-2,649) 1/s, P = 0.028] and RA [30 (27-44) vs. 9 (5-27) 1/s, P = 0.005]. RA E vorticity was significantly decreased [13 (7-22) vs. 28 (15-31) 1/s, P = 0.038] in RVDD. E-wave vorticity correlated TV e', E-,and TV E/A (P < 0.05), and A-wave vorticity associated with both TV A and E/A (P < 0.02). RVDD is associated with alterations in E- and A-wave vorticity, and vorticity correlates with multiple echocardiographic markers of RVDD. Vorticity may be a robust noninvasive research tool for the investigation of RV fluid and tissue mechanical interactions in PAH. PMID:26254331

  10. DIET QUALITY SCORES AND PLASMA CONCENTRATIONS OF MARKERS OF INFLAMMATION AND ENDOTHELIAL DYSFUNCTION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endothelial dysfunction is one of the mechanisms linked to an increased risk of cardiovascular disease. We assessed the association between several diet-quality scores and plasma concentrations of markers of inflammation and endothelial dysfunction. Diet-quality scores on the Healthy Eating Index (H...

  11. Biologic Markers for Odontogenic Periradicular Periodontitis

    PubMed Central

    Burgener, Bruna; Ford, Angelique R.; Situ, Hongsa; Fayad, Mohamed I.; Hao, Jian Jun; Wenckus, Christopher S.; Johnson, Bradford R.; BeGole, Ellen A.; George, Anne

    2011-01-01

    Introduction The diagnosis and assessment of apical periodontitis by traditional periapical radiographs can be challenging and might yield false-negative results. The aim of this study was to determine whether interleukin-1beta (IL-1β) and dentin sialoprotein (DSP) in gingival crevicular fluid (GCF) can be used as biological markers for apical periodontitis. Methods Forty healthy patients with teeth diagnosed with apical periodontitis of pulpal origin were included in the study. GCF samples were obtained from the diseased tooth and from a healthy contralateral control tooth. Total protein concentration in each sample was determined by using the Bio-Rad protein assay. Enzyme-linked immunosorbent assay was used to analyze the concentration of IL-1β and DSP in the samples. Results Protein content of the GCF was statistically significantly higher in the disease group compared with the control group. The levels of IL-1β and DSP were not statistically different between disease and control groups. Conclusions Although this study was unable to demonstrate a significantly higher level of IL-1β or DSP in the GCF of teeth with apical periodontitis, the observed presence of a significantly higher level of total protein in the GCF of diseased teeth suggests the possible role of total protein level as a marker for periapical disease. PMID:20647085

  12. Assessment of renal dysfunction using urinary markers in canine babesiosis caused by Babesia rossi.

    PubMed

    Defauw, P; Schoeman, J P; Smets, P; Goddard, A; Meyer, E; Liebenberg, C; Daminet, S

    2012-12-21

    Renal damage is deemed a common, yet poorly documented, complication in canine babesiosis. Serum urea and creatinine are insensitive and non-specific markers of early renal dysfunction and their measurements are influenced by hemolysis caused by babesiosis. Therefore, the aim of this study was to use urinary markers to assess the localization and degree of renal dysfunction in dogs with Babesia rossi infection. Urinary immunoglobulin G (uIgG) and urinary C-reactive protein (uCRP) were measured as markers for glomerular dysfunction, while urinary retinol-binding protein (uRBP) was used as a marker for tubular dysfunction. Eighteen dogs presenting with uncomplicated babesiosis were included and compared with eight clinically healthy dogs. Previously validated commercial ELISA kits were used for the measurement of uIgG, uCRP, and uRBP. Results were related to urinary creatinine concentrations (c). Dogs with babesiosis had significantly higher concentrations of all three measured urinary markers compared to healthy dogs. Except for urinary protein/c ratio (UPC), routine urinary and serum markers for renal function (urine specific gravity (USG), serum urea and creatinine (sCr)) were not significantly different between dogs with babesiosis and healthy dogs. All three urinary markers were positively correlated with each other and with UPC. The data supports the presence of both glomerular and tubular dysfunction in dogs suffering from uncomplicated B. rossi infection. Urinary markers were superior to USG, serum urea and creatinine concentrations for the early detection of renal dysfunction in dogs with babesiosis. PMID:22884913

  13. Prediction of Post-Operative Liver Dysfunction by Serum Markers of Liver Fibrosis in Hepatocellular Carcinoma

    PubMed Central

    Shen, Yinghao; Shi, Guoming; Huang, Cheng; Zhu, Xiaodong; Chen, Si; Sun, Huichuan; Zhou, Jian; Fan, Jia

    2015-01-01

    Aim To investigate the role of biomarkers in predicting postoperative liver dysfunction in patients with hepatocellular carcinoma (HCC). Methods A total of 200 patients operated from July 2009 to June 2010 at Zhongshan Hospital, Fudan University for pathologically confirmed HCC were retrospectively analyzed for clinical data, HBD DNA level and serum biochemical markers for liver fibrosis. The patients were followed up to observersation end point. Correlation of the monitored parameters with postoperative liver dysfunction and patient survival was statistically analyzed. Results Preoperative hepatitis B virus (HBV) DNA level, serum prealbumin (PA) hyaluronic acid (HA), and laminin (LN) levels correlated with postoperative liver dysfunction. A predictive model was generated using these 4 parameters and validated in 89 HCC patients with sensitivity and specificity of 0.625 and 0.912, respectively. However, no correlation was identified between postoperative liver function and overall survival. Conclusion Liver fibrosis markers could be preoperatively used in predicting postoperative liver dysfunction in HCC patients. PMID:26501145

  14. Genetic and biological markers in drug abuse and alcoholism

    SciTech Connect

    Braude, M.C.; Chao, H.M.

    1986-01-01

    This book contains 11 selections. Some of the titles are: Polymorphic Gene Marker Studies; Pharmacogenetic Approaches to the Prediction of Drug Response; Genetic Markers of Drug Abuse in Mouse Models; Genetics as a Tool for Identifying Biological Markers of Drug Abuse; and Studies of an Animal Model of Alcoholism.

  15. Salivary gland dysfunction markers in type 2 diabetes mellitus patients

    PubMed Central

    Aitken-Saavedra, Juan; Rojas-Alcayaga, Gonzalo; Maturana-Ramírez, Andrea; Escobar-Álvarez, Alejandro; Cortes-Coloma, Andrea; Reyes-Rojas, Montserrat; Viera -Sapiain, Valentina; Villablanca-Martínez, Claudia

    2015-01-01

    Background Diabetes mellitus (DM) is a chronic disease of the carbohydrate metabolism that, when not rigorously controlled, compromises systemic and organ integrity, thereby causing renal diseases, blindness, neuropathy, arteriosclerosis, infections, and glandular dysfunction, including the salivary glands. The aim of this study was to determine the relationship between the qualitative and quantitative parameters of salivary alteration, which are indicators of salivary gland dysfunction, and the level of metabolic control of type 2 diabetes patients. Material and Methods A convenience sample of 74 voluntary patients with type 2 DM was selected, each of whom donated a sample of unstimulated saliva. Salivary parameters such as salivary flow rate, protein concentration, pH, and xerostomia were studied. Results There is a positive relationship between the level of metabolic control measured with HbA1 and the protein concentration in saliva (Spearman rho = 0.329 and p = 0.004). The same assay showed an inverse correlation between HbA1 and pH (Spearman rho = -0.225 and p = 0.05). Conclusions The protein concentration in saliva and, to a lesser extent, the pH may be useful as glandular dysfunction indicators in DM2 patients. Key words:Saliva, type 2 diabetes mellitus, pH, protein concentration, xerostomia. PMID:26535097

  16. Biological markers in reproductive epidemiology: prospects and precautions

    SciTech Connect

    Stein, Z.; Hatch, M.

    1987-10-01

    We begin by defining ''biological markers'' for the purposes of the present review, distinguishing markers from other types of information, such as subject reports or conventional clinical data. We find the distinctions to be hazy. Next, from the standpoint of epidemiologists, we set out circumstances in which exposure markers might be needed, suggesting requirements for useful markers. We give two instances (lead, PCB), drawn from studies of female reproduction, where the use of exposure markers is compared to environmental or anamnestic data. Effect markers are considered in turn. It is argued that their usefulness (if they are to be more informative than exposure markers) depends on their sensitivity and specificity in relation to the disease outcome. Also, their timeliness, and the use that can be made of the gain in time, for individuals and populations is discussed. In this context, we consider markers of events before and around fertilization; more specifically, we consider those events that precede the clinical marker of the first missed period. In returning to the potential uses of biological markers in discovering or interpreting female reproductive disorders that might be owed to environmental causes, we compare markers of the pre- and peri-implantation phases with markers of the postimplantation phase, drawing on experience with studies of chromosome anomaly in spontaneous abortion. Finally, we suggest other sensitive reproductive processes for which biological markers might usefully be developed. 30 references.

  17. Biological markers of invasive breast cancer.

    PubMed

    Matsumoto, Akiko; Jinno, Hiromitsu; Ando, Tomofumi; Fujii, Taku; Nakamura, Tetsuya; Saito, Junichi; Takahashi, Maiko; Hayashida, Tetsu; Kitagawa, Yuko

    2016-02-01

    Biological markers for breast cancer are biomolecules that result from cancer-related processes and are associated with particular clinical outcomes; they thus help predict responses to therapy. In recent years, gene expression profiling has made the molecular classification of breast cancer possible. Classification of breast cancer by immunohistochemical expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 and Ki-67 is standard practice for clinical decision-making. Assessments of hormone receptor expression and human epidermal growth factor receptor 2 overexpression help estimate benefits from targeted therapies and have greatly improved prognoses for women with these breast cancer types. Although Ki-67 positivity is associated with an adverse outcome, its clear identification is an aid to optimal disease management. Standardization of testing methodology to minimize inter-laboratory measurement variations is a remaining issue. Multi-gene assays provide prognostic information and identify those most likely to benefit from systemic chemotherapy. Incorporating molecular profiles with conventional pathological classification would be more precise, and could enhance the clinical development of personalized therapy in breast cancer. PMID:26486826

  18. Identification of a biochemical marker for endothelial dysfunction using Raman spectroscopy.

    PubMed

    Rygula, A; Pacia, M Z; Mateuszuk, L; Kaczor, A; Kostogrys, R B; Chlopicki, S; Baranska, M

    2015-04-01

    In the present work, we propose the spectroscopic approach to identify biochemical alterations in endothelial dysfunction. The method is based on the quantification of the ratio of phenylalanine (Phe) to tyrosine (Tyr) contents in the endothelium. The synthesis of Tyr from Phe requires the presence of tetrahydrobiopterin (BH4) as a cofactor of phenylalanine hydroxylase (PAH). Limitation of BH4 availability in the endothelium is a hallmark endothelial nitric oxide synthase (eNOS) dysfunction that may also lead to PAH dysfunction and a fall in Tyr contents. Using Raman spectra, the ratio of marker bands of Tyr to Phe was calculated and the pathological state of the endothelium was detected. We provide evidence that Phe/Tyr ratio analysis by Raman spectroscopy discriminate endothelial dysfunction in ApoE/LDLR(-/-) mice as compared to control mice. PMID:25664353

  19. Searching for disease-modifying drugs in AD: can we combine neuropsychological tools with biological markers?

    PubMed

    Caraci, Filippo; Castellano, Sabrina; Salomone, Salvatore; Drago, Filippo; Bosco, Paolo; Di Nuovo, Santo

    2014-02-01

    Drug discovery efforts in Alzheimer's disease (AD) have been directed in the last ten years to develop "disease-modifying drugs" able to exert neuroprotective effects in an early phase of AD pathogenesis. Unfortunately several candidate disease-modifying drugs have failed in Phase III clinical trials conducted in mild to moderate AD for different methodological difficulties, such as the time course of treatment in relation to development of disease as well as the appropriate use of validated biological and neuropsychological markers. Mild cognitive impairment (MCI) has been considered a precursor of AD. Much effort is now directed to identify the most appropriate and sensitive markers which can predict the progression from MCI to AD, such as neuroimaging markers (e.g. hippocampal atrophy and amyloid positron emission tomography imaging), cerebrospinal fluid markers (i.e. association of elevated tau with low levels of amyloid β -peptide(1-42) and neuropsychological markers (i.e. episodic memory deficits and executive dysfunction). Recent studies demonstrate that the combination of these different biomarkers significantly increases the chance to predict the conversion into AD within 24 months. These biomarkers will be essential in the future to analyze clinical efficacy of disease-modifying drugs in MCI patients at high risk to develop AD. In the present review we analyze recent evidence on the combination of neuropsychological and biological markers in AD as a new tool to track disease progression in early AD as well as the response to disease-modifying drugs. PMID:24040795

  20. Validation of biological markers for quantitative risk assessment.

    PubMed Central

    Schulte, P; Mazzuckelli, L F

    1991-01-01

    The evaluation of biological markers is recognized as necessary to the future of toxicology, epidemiology, and quantitative risk assessment. For biological markers to become widely accepted, their validity must be ascertained. This paper explores the range of considerations that compose the concept of validity as it applies to the evaluation of biological markers. Three broad categories of validity (measurement, internal study, and external) are discussed in the context of evaluating data for use in quantitative risk assessment. Particular attention is given to the importance of measurement validity in the consideration of whether to use biological markers in epidemiologic studies. The concepts developed in this presentation are applied to examples derived from the occupational environment. In the first example, measurement of bromine release as a marker of ethylene dibromide toxicity is shown to be of limited use in constructing an accurate quantitative assessment of the risk of developing cancer as a result of long-term, low-level exposure. This example is compared to data obtained from studies of ethylene oxide, in which hemoglobin alkylation is shown to be a valid marker of both exposure and effect. PMID:2050067

  1. Biological (molecular and cellular) markers of toxicity

    SciTech Connect

    Shugart, L.R.; D'Surney, S.J.; Gettys-Hull, C.; Greeley, M.S. Jr.

    1991-12-15

    Several molecular and cellular markers of genotoxicity were adapted for measurement in the Medaka (Oryzias latipes), and were used to describe the effects of treatment of the organism with diethylnitrosamine (DEN). NO{sup 6}-ethyl guanine adducts were detected, and a slight statistically significant, increase in DNA strand breaks was observed. These results are consistent with the hypothesis that prolonged exposure to high levels of DEN induced alkyltransferase activity which enzymatically removes any O{sup 6}-ethyl guanine adducts but does not result in strand breaks or hypomethylation of the DNA such as might be expected from excision repair of chemically modified DNA. Following a five week continuous DEN exposure with 100 percent renewal of DEN-water every third day, the F values (DNA double strandedness) increased considerably and to similar extent in fish exposed to 25, 50, and 100 ppM DEN. This has been observed also in medaka exposed to BaP.

  2. Biological (molecular and cellular) markers of toxicity

    SciTech Connect

    Shugart, L.R.

    1990-10-01

    The overall objective of this study is to evaluate the use of the small aquarium fish, Japanese Medaka (Oryzias latipes), as a predictor of potential genotoxicity following exposure to carcinogens. This will be accomplished by quantitatively investigating the early molecular events associated with genotoxicity of various tissues of Medaka subsequent to exposure of the organism to several known carcinogens, such as diethylnitrosamine (DEN) and benzo(a)pyrene (BaP). Because of the often long latent period between initial contact with certain chemical and physical agents in our environment and subsequent expression of deleterious health or ecological impact, the development of sensitive methods for detecting and estimating early exposure is needed so that necessary interventions can ensue. A promising biological endpoint for detecting early exposure to damaging chemicals is the interaction of these compounds with cellular macromolecules such as Deoxyribonucleic acids (DNA). This biological endpoint assumes significance because it can be one of the critical early events leading eventually to adverse effects (neoplasia) in the exposed organism.

  3. Biological markers of male reproductive toxicology

    SciTech Connect

    Ewing, L.L.; Mattison, D.R.

    1987-10-01

    Reproduction is a complex, stepwise series of processes that begins with gametogenesis, continues through gamete interaction, implantation, embryonic development, growth, parturition, and postnatal adaptation, and is completed with the development and sexual maturation of the newly formed organism. These reproductive processes do not take place in a chemically pristine environment, but rather in an environment increasingly contaminated with the products and by-products of the chemical age in which we live. Some environmental pollutants are known to be carcinogenic, mutagenic, or toxic to the reproductive system, but most have not been adequately tested for reproductive toxicity. Just as reproduction is complex, biological mechanisms underlying toxicology are similarly complex and involve absorption, distribution, metabolism (toxification and/or detoxification), excretion, and repair. The synthesis of these sciences into the relatively nascent science of reproductive toxicology includes teratology, pharmacology, epidemiology, and occupational and environmental health. Female reproductive function (especially pregnancy outcome) has historically been the focus of attention, but there is increasing interest in the effects of chemical exposure on male reproductive function. Several reports have documented the physiology, biochemistry, and toxicology of male mammalian reproduction, and evaluated susceptibility of the male to the effects of exogenous chemicals.

  4. [Uric acid and purine plasma levels as plausible markers for placental dysfunction in pre-eclampsia].

    PubMed

    Escudero, Carlos; Bertoglia, Patricio; Muñoz, Felipe; Roberts, James M

    2013-07-01

    Uric acid is the final metabolite of purine break down, such as ATP, ADP, AMP, adenosine, inosine and hypoxanthine. The metabolite has been used broadly as a renal failure marker, as well as a risk factor for maternal and neonatal morbidity during pre-eclamptic pregnancies. High purine levels are observed in pre-eclamptic pregnancies, but the sources of these purines are unknown. However, there is evidence that pre-eclampsia (mainly severe pre-eclampsia) is associated with an increased release of cellular fragments (or microparticles) from the placenta to the maternal circulation. These in fact could be the substrate for purine metabolism. Considering this background, we propose that purines and uric acid are part of the same physiopathological phenomenon in pre-eclampsia (i.e., placental dysfunction) and could become biomarkers for placental dysfunction and postnatal adverse events. PMID:24356738

  5. Strategies for use of biological markers of exposure

    SciTech Connect

    Henderson, R.F.

    1995-09-01

    A major public health concern is the degree to which environmental or occupational exposures to exogenous chemicals result in adverse health effects. Biological markers have the potential for helping to answer this important question by providing links between markers of exposures and markers of early stages of the development of disease. However, that potential requires in-depth, mechanistic research to be fully realized. Biological markers of exposure have been extensively investigated, and mathematical models of the toxicokinetics of agents have been developed to relate exposures to internal doses. The field of clinical medicine has long used clinical signs and symptoms to detect disease. However, the critical area of research needed to improve the application of biomarkers to environmental health research is mechanistic research to link dose to critical tissues to the development of early, pre-clinical signs of developing disease. Only if the mechanism of disease induction is known can one determine the ``biologically effective`` dose and the earliest biological changes leading to disease.

  6. The Effect of Experimental Thyroid Dysfunction on Markers of Oxidative Stress in Rat Pancreas.

    PubMed

    Sajadian, Mojtaba; Hashemi, Mohammad; Salimi, Saeedeh; Nakhaee, Alireza

    2016-06-01

    Preclinical Research The aim of the present study was to evaluate the effects of thyroid dysfunction on markers of oxidative stress in rat pancreas. Hypothyroidism and hyperthyroidism were, respectively, induced in rats via administration of propylthiouracil (PTU) and L-thyroxine sodium salt in drinking water for 45 days. The activities of superoxide dismutase (SOD), catalase (CAT), glutathioen peroxidase (GPx), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD), xanthine oxidase (XO), and nonenzymatic markers of oxidative stress including malondialdehyde (MDA), protein carbonyl (PC), reduced glutathione (GSH), and total thiols (T-SH) were determined in the rat pancreas. In hyperthyroid rats, pancreatic CAT, SOD, GPx, GR, XO, G6PD activities were increased compared with those in hypothyroid and control groups. There were no differences in activities of antioxidant enzymes between hypothyroid and control rats. Pancreatic MDA and PC in hyperthyroid rats increased compared with hypothyroid and the control animals. Whereas, hyperthyroid rats had decreased levels of tissue GSH and T-SH compared with hypothyroid and the control groups. The findings showed that only GSH level has decreased significantly in the hypothyroid group compared with control groups. In conclusion, our results showed that experimental hyperthyroidism induces oxidative stress in pancreas of rats, but hypothyroidism has no major impact on oxidative stress markers. Drug Dev Res 77 : 199-205, 2016.   © 2016 Wiley Periodicals, Inc. PMID:27241437

  7. Study Finds Association between Biological Marker and Susceptibility to the Common Cold

    MedlinePlus

    ... W X Y Z Study Finds Association Between Biological Marker and Susceptibility to the Common Cold Share: © ... a cold caused by a particular rhinovirus. The biological marker identified in the study was the length ...

  8. Biological plausibility linking sleep apnoea and metabolic dysfunction.

    PubMed

    Gileles-Hillel, Alex; Kheirandish-Gozal, Leila; Gozal, David

    2016-05-01

    Obstructive sleep apnoea (OSA) is a very common disorder that affects 10-25% of the general population. In the past two decades, OSA has emerged as a cardiometabolic risk factor in both paediatric and adult populations. OSA-induced metabolic perturbations include dyslipidaemia, atherogenesis, liver dysfunction and abnormal glucose metabolism. The mainstay of treatment for OSA is adenotonsillectomy in children and continuous positive airway pressure therapy in adults. Although these therapies are effective at resolving the sleep-disordered breathing component of OSA, they do not always produce beneficial effects on metabolic function. Thus, a deeper understanding of the underlying mechanisms by which OSA influences metabolic dysfunction might yield improved therapeutic approaches and outcomes. In this Review, we summarize the evidence obtained from animal models and studies of patients with OSA of potential mechanistic pathways linking the hallmarks of OSA (intermittent hypoxia and sleep fragmentation) with metabolic dysfunction. Special emphasis is given to adipose tissue dysfunction induced by sleep apnoea, which bears a striking resemblance to adipose dysfunction resulting from obesity. In addition, important gaps in current knowledge and promising lines of future investigation are identified. PMID:26939978

  9. Role of Peripheral Inflammatory Markers in Postoperative Cognitive Dysfunction (POCD): A Meta-Analysis

    PubMed Central

    Ouyang, Wen

    2013-01-01

    Background Postoperative cognitive dysfunction (POCD) is common following cardiac and non-cardiac surgery, but the pathogenic mechanisms remain unknown. Many studies suggest that an inflammatory response is a key contributor to POCD. The current meta-analysis shows that the levels of peripheral inflammatory markers are associated with POCD. Methods An online search was performed to identify peer-reviewed studies without language restriction that measured peripheral inflammatory markers of patients with and without POCD, using PubMed, ScienceDirect, SinoMed and the National Knowledge Infrastructure database. Extracted data were analyzed with STATA (version 12).The standardized mean difference (SMD) and the 95% confidence interval (95%CI) were calculated for each outcome using a random effect model. Tests of heterogeneity assessment of bias, and meta-regression were performed in the meta-analysis. Results A total of 13 studies that measured the concentrations of peripheral inflammatory markers were included. The current meta-analysis found significantly higher concentrations of S-100β(SMD[95%CI]) (1.377 [0.423, 2.331], p-value < 0.001, N [POCD/non-POCD] =178/391, 7 studies), and interleukin(IL)-6 (SMD[95%CI]) (1.614 [0.603,2.624], p-value < 0.001, N[POCD/non-POCD] = 91/99, 5 studies), but not of neuron specific enolase, interleukin-1β, or tumor necrosis factor-α , in POCD compared with patients without POCD. In meta-regression analyses, a significant positive association was found between the SMD and the preoperative interleukin-6 peripheral blood concentration in patients with POCD (Coef.= 0.0587, p-value=0.038, 5 studies). Conclusions This study shows that POCD is indeed correlated with the concentrations of peripheral inflammatory markers, particularly interleukin-6 and S-100β. PMID:24236147

  10. Physiological and biochemical markers of alveolar epithelial barrier dysfunction in perfused human lungs

    PubMed Central

    Frank, James A.; Briot, Raphael; Lee, Jae Woo; Ishizaka, Akitoshi; Uchida, Tokujiro; Matthay, Michael A.

    2009-01-01

    To study air space fluid clearance (AFC) under conditions that resemble the clinical setting of pulmonary edema in patients, we developed a new perfused human lung preparation. We measured AFC in 20 human lungs rejected for transplantation and determined the contribution of AFC to lung fluid balance. AFC was then compared with air space and perfusate levels of a biological marker of epithelial injury. The majority of human lungs rejected for transplant had intact basal (75%) and β2-adrenergic agonist-stimulated (70%) AFC. For lungs with both basal and stimulated AFC, the basal AFC rate was 19 ± 10%/h, and the β2-adrenergic-stimulated AFC rate was 43 ± 13%/h. Higher rates of AFC were associated with less lung weight gain (Pearson coefficient −0.90, P < 0.0001). Air space and perfusate levels of the type I pneumocyte marker receptor for advanced glycation end products (RAGE) were threefold and sixfold higher, respectively, in lungs without basal AFC compared with lungs with AFC (P < 0.05). These data show that preserved AFC is a critical determinant of favorable lung fluid balance in the perfused human lung, raising the possibility that β2-agonist therapy to increase edema fluid clearance may be of value for patients with acute lung injury and pulmonary edema. Also, although additional studies are needed, a biological marker of alveolar epithelial injury may be useful clinically in predicting preserved AFC. PMID:17351061

  11. Testing systems for biologic markers of genotoxic exposure and effect

    SciTech Connect

    Mendelsohn, M.L.

    1986-11-19

    Societal interest in genotoxicity stems from two concerns: the fear of carcinogenesis secondary to somatic mutation; and the fear of birth defects and decreasing genetic fitness secondary to heritable mutation. There is a pressing need to identify agents that can cause these effects, to understand the underlying dose-response relationships, to identify exposed populations, and to estimate both the magnitude of exposure and the risk of adverse health effects in such populations. Biologic markers refer either to evidence in surrogate organisms, or to the expressions of exposure and effect in human populations. 21 refs.

  12. Biological markers of macrophage activation: applications for fish phagocytes.

    PubMed Central

    Enane, N A; Frenkel, K; O'Connor, J M; Squibb, K S; Zelikoff, J T

    1993-01-01

    The immune defence mechanisms of fish seem to be related and similarly competent to those of mammals. Because of this, there is an increased interest in the immune responses of fish as models for higher vertebrates in immunological/immunotoxicological studies. Macrophages (M phi), phagocytic cells of the mammalian and teleost immune system which reside in tissues, represent a quiescent population of cells. However, upon stimulation, alterations in the physiology of these resident M phi occur which can be defined in terms of activation. This study was undertaken to determine whether biological markers used to assess mammalian M phi activation are applicable for use with fish M phi. Cells were recovered from the peritoneal cavity of non-injected and Aeromonas salmonicida-injected fish, and differences between resident and elicited M phi were evaluated with respect to protein content, phagocytic competence, enzyme activities and hydrogen peroxide production. Results demonstrate that biological markers used to assess mammalian M phi activation, with the exception of acid phosphatase activity, can be used to characterize the activation state of trout M phi, and that the activation process in both fish and mammals may occur by similar mechanism(s). PMID:8244466

  13. Endothelial cell markers reflecting endothelial cell dysfunction in patients with mixed connective tissue disease

    PubMed Central

    2010-01-01

    Introduction The aim of the present study was to investigate the association between cardiovascular risk factors and endothelial dysfunction in patients with mixed connective tissue disease (MCTD) and to determine which biomarkers are associated with atherosclerotic complications, such as cardiovascular disease. Methods Fifty MCTD patients and 38 healthy age-matched and sex-matched controls were enrolled in this study. In order to describe endothelial dysfunction, we assessed flow-mediated dilation (FMD), nitrate-mediated dilation (NMD) and carotid artery intima-media thickness (IMT). We investigated FMD of the brachial artery after reactive hyperemia and NMD after sublingual nitroglycerin administration, while the IMT of the common carotid artery was determined by ultrasound. Anti-U1 ribonucleoprotein (anti-U1RNP) antibodies, anti-cardiolipin (anti-CL) antibodies, anti-endothelial cell antibody (AECA) and endothelial cell markers, such as soluble thrombomodulin (TM) and von Willebrand factor antigen (vWFAg), were assessed. Results The endothelium-dependent vasodilation (FMD) was significantly impaired in patients with MCTD, as compared with controls (%FMD: 4.7 ± 4.2% vs. 8.7 ± 5.0%; P < 0.001), while the percentage NMD did not differ (%NMD: 14.3 ± 6.6% vs. 17.1 ± 6.7%; P = 0.073). Mean carotid IMT values were higher in patients than in controls (IMT: MCTD, 0.64 ± 0.13 mm vs. controls, 0.53 ± 0.14 mm; P < 0.001). FMD negatively correlated with disease duration, the levels of apolipoprotein A1, the paraoxonase-1 activity, and systolic blood pressure in MCTD patients. The percentage FMD was significantly lower in MCTD patients with cardiovascular diseases (CVD), than in those without CVD (%FMD: 3.5 ± 2.9 vs. 5.8 ± 4.8, P < 0.0002), while percentage NMD did not differ between patients with and without CVDs. Serum levels of autoantibodies (anti-U1RNP, AECA and anti-CL) were significantly higher in MCTD patients and differed between MCTD patients with and

  14. Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia?

    PubMed

    Castro-Marrero, Jesús; Cordero, Mario D; Sáez-Francas, Naia; Jimenez-Gutierrez, Conxita; Aguilar-Montilla, Francisco J; Aliste, Luisa; Alegre-Martin, José

    2013-11-20

    Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are complex and serious illnesses that affect approximately 2.5% and 5% of the general population worldwide, respectively. The etiology is unknown; however, recent studies suggest that mitochondrial dysfunction has been involved in the pathophysiology of both conditions. We have investigated the possible association between mitochondrial biogenesis and oxidative stress in patients with CFS and FM. We studied 23 CFS patients, 20 FM patients, and 15 healthy controls. Peripheral blood mononuclear cell showed decreased levels of Coenzyme Q10 from CFS patients (p<0.001 compared with controls) and from FM subjects (p<0.001 compared with controls) and ATP levels for CFS patients (p<0.001 compared with controls) and for FM subjects (p<0.001 compared with controls). On the contrary, CFS/FM patients had significantly increased levels of lipid peroxidation, respectively (p<0.001 for both CFS and FM patients with regard to controls) that were indicative of oxidative stress-induced damage. Mitochondrial citrate synthase activity was significantly lower in FM patients (p<0.001) and, however, in CFS, it resulted in similar levels than controls. Mitochondrial DNA content (mtDNA/gDNA ratio) was normal in CFS and reduced in FM patients versus healthy controls, respectively (p<0.001). Expression levels of peroxisome proliferator-activated receptor gamma-coactivator 1-alpha and transcription factor A, mitochondrial by immunoblotting were significantly lower in FM patients (p<0.001) and were normal in CFS subjects compared with healthy controls. These data lead to the hypothesis that mitochondrial dysfunction-dependent events could be a marker of differentiation between CFS and FM, indicating the mitochondria as a new potential therapeutic target for these conditions. PMID:23600892

  15. Urinary Strong Ion Difference as a Marker of Renal Dysfunction. A Retrospective Analysis

    PubMed Central

    2016-01-01

    Introduction The kidneys play a crucial role in the regulation of electrolytes and acid-base homeostasis. Urinary Strong Ion Difference (SIDu = NaU + KU—ClU) represents an important aspect of renal acid-base regulation. We evaluated the role of SIDu as a marker of renal dysfunction in critically ill patients. Materials and Methods Patients admitted to the Medical Intensive Care Unit with a diagnosis of AKI for whom concomitant urinary samples available for SIDu calculation were retrospectively reviewed and staged according to KDIGO criteria for 3 days from inclusion. Patients were classified as Recovered (R-AKI) or Persistent-AKI (P-AKI) whether they exited KDIGO criteria within the 3-day observation period or not. A control group with normal renal function and normal serum acid-base and electrolytes was prospectively recruited in order to identify reference SIDu values. Results One-hundred-and-forty-three patients with a diagnosis of AKI were included: 77 with R-AKI, and 66 with P-AKI. Thirty-six controls were recruited. Patients with P-AKI had more severe renal dysfunction and higher mortality than patients with R-AKI (SCr 2.23(IQR:1.68–3.45) and 1.81(IQR1.5–2.5) mg/dl respectively, p<0.001; 24-h UO 1297(950) and 2100(1094) ml respectively, p = 0.003); 30-d mortality, 39% and 13% respectively; p<0.001). SIDu significantly differed between groups, with rising values from controls to P-AKI groups (16.4(12), 30(24) and 47.3(21.5) mEq/l respectively, p<0.001). Discussion SIDu may be a simple and inexpensive tool in AKI patients’ evaluation. Further research is needed to evaluate the ability of SIDu to identify patients with renal dysfunction before derangements in serum creatinine or urine output are observed. PMID:27258049

  16. Can Erectile Dysfunction in Young Patients Serve as a Surrogate Marker for Coronary Artery Disease?

    PubMed Central

    Dattatrya, Kaje Yogesh; Gorakhnath, Wagaska Vinayak; kiran, Patwardhan Sujata

    2015-01-01

    Introduction Early diagnosis and expeditious management of coronary artery disease (CAD) has a rewarding survival benefit. Aim To study whether erectile dysfunction (ED) serves as a surrogate marker for CAD in a young patient. Settings and Design Males (n=207) between ages 20-60 years with ED were evaluated prospectively for risk factors for CAD. Materials and Methods Blood Glucose Levels (BGL) fasting and post meal), lipid profile (LP) and 12 lead electrocardiogram (ECG) was done in all of them. International Index of Erectile Function-5 (IEF-5) was used for the evaluation of ED. Those with abnormal parameters were assessed by cardiologists by echocardiography, stress test and if necessary coronary angiography (Non-Invasive or Invasive). Statistical Analysis All the data were analysed using SPSS. 16 statistical software (SPSS Inc., Chicago, IL, USA). All data are expressed as mean and standard deviation. The Student’s t-test was used to compare means between groups, and the chi-square test was used to compare proportions between the groups. P-value <0.05 was considered statistically significant. All confidence intervals (CIs) are two tailed and calculated at the 0.05 level. Results Out of 207, 149 patients had at least one abnormal screening parameter. All underwent cardiology consultation and 2D ECHO and Stress test. Thirty six patients underwent coronary angiography. CAD was found in 22 patients. Of these, 19 patients had severe ED. Nine patients were between 20-40 years of age (13.23%). All 9 young patients had deranged LP; severe ED. Six patients were smokers while nobody was hypertensive. Conclusion ED serves as a surrogate marker for CAD in young patients (p=0.001). Presence of risk factors and lab abnormalities in young patients with ED warrants a cardiology referral to detect CAD. PMID:26674799

  17. Impact of chronic lead exposure on selected biological markers.

    PubMed

    Jangid, Ambica P; John, P J; Yadav, D; Mishra, Sandhya; Sharma, Praveen

    2012-01-01

    Lead poisoning remains a major problem in India due to the lack of awareness of its ill effects among the clinical community. Blood lead, δ-aminolevulinic acid dehydratase (δ-ALAD) and zinc protoporphyrin (ZPP) concentrations are widely used as biomarkers for lead toxicity The present study was designed to determine the impact of chronic lead exposure on selected biological markers. A total of 250 subjects, of both sexes, ranging in age from 20 to 70 years, were recruited. On the basis of BLLs, the subjects were categorized into four groups: Group A (BLL: 0-10 μg/dl), Group B (BLL: 10-20 μg/dl). Group C (BLL: 20-30 μg/dl) and Group D (BLL: 30-40 μg/dl) having BLLs of 3.60 ± 2.71 μg/dl, 15.21 ± 2.65 μg/dl, 26.82 ± 2.53 μg/dl and 36.38 ± 2.83 μg/dl, respectively. Significant changes in biological markers due to elevated BLLs were noted. The relation of BLL and biological markers to demographic characteristics such as sex, habits, diet and substances abuse (smoking effect) were also studied in the present investigation. Males, urban population, non-vegetarians, and smokers had higher blood lead levels. δ-ALAD activity was found to be significantly lower with increased BLL (P < 0.001), while the ZPP level was significantly higher with increased BLL (P < 0.001). Further, BLL showed a negative correlation with δ-ALAD (r = -0.425, P < 0.001, N = 250) and a positive correlations with ZPP (r = 0.669, P < 0.001, N = 250). Chronic lead exposure affects the prooxidant-antioxidant equilibrium leading to cellular oxidative stress. PMID:23277717

  18. Histomorphometry of feline chronic kidney disease and correlation with markers of renal dysfunction.

    PubMed

    Chakrabarti, S; Syme, H M; Brown, C A; Elliott, J

    2013-01-01

    Chronic kidney disease is common in geriatric cats, but most cases have nonspecific renal lesions, and few studies have correlated these lesions with clinicopathological markers of renal dysfunction. The aim of this study was to identify the lesions best correlated with renal function and likely mediators of disease progression in cats with chronic kidney disease. Cats were recruited through 2 first-opinion practices between 1992 and 2010. When postmortem examinations were authorized, renal tissues were preserved in formalin. Sections were evaluated by a pathologist masked to all clinicopathological data. They were scored semiquantitatively for the severity of glomerulosclerosis, interstitial inflammation, and fibrosis. Glomerular volume was measured using image analysis; the percentage of glomeruli that were obsolescent was recorded. Sections were assessed for hyperplastic arteriolosclerosis and tubular mineralization. Kidneys from 80 cats with plasma biochemical data from the last 2 months of life were included in the study. Multivariable linear regression (P < .05) was used to assess the association of lesions with clinicopathological data obtained close to death. Interstitial fibrosis was the lesion best correlated with the severity of azotemia, hyperphosphatemia, and anemia. Proteinuria was associated with interstitial fibrosis and glomerular hypertrophy, whereas higher time-averaged systolic blood pressure was associated with glomerulosclerosis and hyperplastic arteriolosclerosis. PMID:22773469

  19. Hydrocarbon biological markers in Carboniferous coals of different maturities from the Ruhr area (northwest Germany)

    SciTech Connect

    ten Haven, H.L.; Littke, R.; Rullkoetter, J. , Juelich )

    1989-03-01

    A great variety of biological markers has been found in Carboniferous coal samples. Changes in the paleo-depositional environment are reflected by the distribution of bacterial derived hydrocarbons. These biological markers contribute to a significant extent to the aliphatic hydrocarbon fraction of low-maturity coal samples; their absolute contribution to total organic matter has yet not been estimated. Biological markers for gymnosperm were observed, which is in accordance with the phylogenetic evolution of the plant kingdom during the Carboniferous.

  20. Biological markers of oxidative stress: Applications to cardiovascular research and practice.

    PubMed

    Ho, Edwin; Karimi Galougahi, Keyvan; Liu, Chia-Chi; Bhindi, Ravi; Figtree, Gemma A

    2013-01-01

    Oxidative stress is a common mediator in pathogenicity of established cardiovascular risk factors. Furthermore, it likely mediates effects of emerging, less well-defined variables that contribute to residual risk not explained by traditional factors. Functional oxidative modifications of cellular proteins, both reversible and irreversible, are a causal step in cellular dysfunction. Identifying markers of oxidative stress has been the focus of many researchers as they have the potential to act as an "integrator" of a multitude of processes that drive cardiovascular pathobiology. One of the major challenges is the accurate quantification of reactive oxygen species with very short half-life. Redox-sensitive proteins with important cellular functions are confined to signalling microdomains in cardiovascular cells and are not readily available for quantification. A popular approach is the measurement of stable by-products modified under conditions of oxidative stress that have entered the circulation. However, these may not accurately reflect redox stress at the cell/tissue level. Many of these modifications are "functionally silent". Functional significance of the oxidative modifications enhances their validity as a proposed biological marker of cardiovascular disease, and is the strength of the redox cysteine modifications such as glutathionylation. We review selected biomarkers of oxidative stress that show promise in cardiovascular medicine, as well as new methodologies for high-throughput measurement in research and clinical settings. Although associated with disease severity, further studies are required to examine the utility of the most promising oxidative biomarkers to predict prognosis or response to treatment. PMID:24251116

  1. Biological markers of Pseudomonas aeruginosa epidemic high-risk clones.

    PubMed

    Mulet, Xavier; Cabot, Gabriel; Ocampo-Sosa, Alain A; Domínguez, M Angeles; Zamorano, Laura; Juan, Carlos; Tubau, Fe; Rodríguez, Cristina; Moyà, Bartolomé; Peña, Carmen; Martínez-Martínez, Luis; Oliver, Antonio

    2013-11-01

    A limited number of Pseudomonas aeruginosa genotypes (mainly ST-111, ST-175, and ST-235), known as high-risk clones, are responsible for epidemics of nosocomial infections by multidrug-resistant (MDR) or extensively drug-resistant (XDR) strains worldwide. We explored the potential biological parameters that may explain the success of these clones. A total of 20 isolates from each of 4 resistance groups (XDR, MDR, ModR [resistant to 1 or 2 classes], and MultiS [susceptible to all antipseudomonals]), recovered from a multicenter study of P. aeruginosa bloodstream infections performed in 10 Spanish hospitals, were analyzed. A further set of 20 XDR isolates belonging to epidemic high-risk clones (ST-175 [n = 6], ST-111 [n = 7], and ST-235 [n = 7]) recovered from different geographical locations was also studied. When unknown, genotypes were documented through multilocus sequence typing. The biological parameters evaluated included twitching, swimming, and swarming motility, biofilm formation, production of pyoverdine and pyocyanin, spontaneous mutant frequencies, and the in vitro competition index (CI) obtained with a flow cytometry assay. All 20 (100%) XDR, 8 (40%) MDR, and 1 (5%) ModR bloodstream isolate from the multicenter study belonged to high-risk clones. No significant differences were observed between clonally diverse ModR and MultiS isolates for any of the parameters. In contrast, MDR/XDR high-risk clones showed significantly increased biofilm formation and mutant frequencies but significantly reduced motility (twitching, swimming, and swarming), production of pyoverdine and pyocyanin, and fitness. The defined biological markers of high-risk clones, which resemble those resulting from adaptation to chronic infections, could be useful for the design of specific treatment and infection control strategies. PMID:23979744

  2. Biological Markers of Pseudomonas aeruginosa Epidemic High-Risk Clones

    PubMed Central

    Mulet, Xavier; Cabot, Gabriel; Ocampo-Sosa, Alain A.; Domínguez, M. Angeles; Zamorano, Laura; Juan, Carlos; Tubau, Fe; Rodríguez, Cristina; Moyà, Bartolomé; Peña, Carmen; Martínez-Martínez, Luis

    2013-01-01

    A limited number of Pseudomonas aeruginosa genotypes (mainly ST-111, ST-175, and ST-235), known as high-risk clones, are responsible for epidemics of nosocomial infections by multidrug-resistant (MDR) or extensively drug-resistant (XDR) strains worldwide. We explored the potential biological parameters that may explain the success of these clones. A total of 20 isolates from each of 4 resistance groups (XDR, MDR, ModR [resistant to 1 or 2 classes], and MultiS [susceptible to all antipseudomonals]), recovered from a multicenter study of P. aeruginosa bloodstream infections performed in 10 Spanish hospitals, were analyzed. A further set of 20 XDR isolates belonging to epidemic high-risk clones (ST-175 [n = 6], ST-111 [n = 7], and ST-235 [n = 7]) recovered from different geographical locations was also studied. When unknown, genotypes were documented through multilocus sequence typing. The biological parameters evaluated included twitching, swimming, and swarming motility, biofilm formation, production of pyoverdine and pyocyanin, spontaneous mutant frequencies, and the in vitro competition index (CI) obtained with a flow cytometry assay. All 20 (100%) XDR, 8 (40%) MDR, and 1 (5%) ModR bloodstream isolate from the multicenter study belonged to high-risk clones. No significant differences were observed between clonally diverse ModR and MultiS isolates for any of the parameters. In contrast, MDR/XDR high-risk clones showed significantly increased biofilm formation and mutant frequencies but significantly reduced motility (twitching, swimming, and swarming), production of pyoverdine and pyocyanin, and fitness. The defined biological markers of high-risk clones, which resemble those resulting from adaptation to chronic infections, could be useful for the design of specific treatment and infection control strategies. PMID:23979744

  3. Sinus computed tomography scan and markers of inflammation in vocal cord dysfunction and asthma

    PubMed Central

    Peters, Edward J.; Hatley, Tina K.; Crater, Scott E.; Phillips, C. Douglas; Platts-Mills, Thomas A. E.; Borish, Larry

    2005-01-01

    Background: The inappropriate closure of the vocal cords is characteristic of vocal cord dysfunction (VCD). These patients present with wheezing and frequently receive a misdiagnosis of asthma. Objective: To demonstrate the ability of computed tomography (CT) scored for the presence and extent of sinus disease and markers of inflammation to distinguish patients with VCD from patients with asthma. Methods: Comparisons of 13 patients with VCD were made to 77 patients presenting to the emergency room with acute asthma, 31 non-acute asthmatic patients, and 65 nonasthmatic controls. Evaluation consisted of exhaled nitric oxide gas (eNO), circulating eosinophils, and total serum immunoglobulin (Ig)E, as well as the sinus CT scan. Results: Extensive sinus CT changes were present in 23 of 74 acute asthmatic patients, 5 of 29 non-acute asthmatic patients, and 2 of 59 nonasthmatic controls. In addition, absolute eosinophil counts, eNO, and total IgE were significantly elevated among the asthmatic patients. Sinus symptoms reported by questionnaire did not predict sinus CT findings. Among the patients with VCD, none had extensive sinus disease. They also had normal eNO, low IgE, and normal eosinophil count. Five of the patients presenting to the emergency room who were identified as acute asthmatic were identified with VCD by laryngoscopy and were all characterized by the absence of significant inflammation on their sinus CT scan, low IgE, and normal eosinophil count. Conclusions: Among patients presenting with intermittent or reversible airway obstruction, patients with VCD can be distinguished from asthma by minimum or absence of inflammation in their sinuses as shown by CT scan. Clinical symptom scores are not predictive of presence or extent of sinus disease in most cases. PMID:12669895

  4. Molecular and biological pathways of skeletal muscle dysfunction in chronic obstructive pulmonary disease.

    PubMed

    Barreiro, Esther; Gea, Joaquim

    2016-08-01

    Chronic obstructive pulmonary disease (COPD) will be a major leading cause of death worldwide in the near future. Weakness and atrophy of the quadriceps are associated with a significantly poorer prognosis and increased mortality in COPD. Despite that skeletal muscle dysfunction may affect both respiratory and limb muscle groups in COPD, the latter are frequently more severely affected. Therefore, muscle dysfunction in COPD is a common systemic manifestation that should be evaluated on routine basis in clinical settings. In the present review, several aspects of COPD muscle dysfunction are being reviewed, with special emphasis on the underlying biological mechanisms. Figures on the prevalence of COPD muscle dysfunction and the most relevant etiologic contributors are also provided. Despite that ongoing research will shed light into the contribution of additional mechanisms to COPD muscle dysfunction, current knowledge points toward the involvement of a wide spectrum of cellular and molecular events that are differentially expressed in respiratory and limb muscles. Such mechanisms are thoroughly described in the article. The contribution of epigenetic events on COPD muscle dysfunction is also reviewed. We conclude that in view of the latest discoveries, from now, on new avenues of research should be designed to specifically target cellular mechanisms and pathways that impair muscle mass and function in COPD using pharmacological strategies and/or exercise training modalities. PMID:27056059

  5. Monitoring of biological markers indicative of doping: the athlete biological passport.

    PubMed

    Saugy, Martial; Lundby, Carsten; Robinson, Neil

    2014-05-01

    The athlete biological passport (ABP) was recently implemented in anti-doping work and is based on the individual and longitudinal monitoring of haematological or urine markers. These may be influenced by illicit procedures performed by some athletes with the intent to improve exercise performance. Hence the ABP is a valuable tool in the fight against doping. Actually, the passport has been defined as an individual and longitudinal observation of markers. These markers need to belong to the biological cascade influenced by the application of forbidden hormones or more generally, affected by biological manipulations which can improve the performance of the athlete. So far, the haematological and steroid profile modules of the ABP have been implemented in major sport organisations, and a further module is under development. The individual and longitudinal monitoring of some blood and urine markers are of interest, because the intraindividual variability is lower than the corresponding interindividual variability. Among the key prerequisites for the implementation of the ABP is its prospect to resist to the legal and scientific challenges. The ABP should be implemented in the most transparent way and with the necessary independence between planning, interpretation and result management of the passport. To ensure this, the Athlete Passport Management Unit (APMU) was developed and the WADA implemented different technical documents associated to the passport. This was carried out to ensure the correct implementation of a profile which can also stand the challenge of any scientific or legal criticism. This goal can be reached only by following strictly important steps in the chain of production of the results and in the management of the interpretation of the passport. Various technical documents have been then associated to the guidelines which correspond to the requirements for passport operation. The ABP has been completed very recently by the steroid profile module

  6. [Pre-psychotic states--contemporary diagnostic and therapeutic issues. Part II. The biological markers of the risk of schizophrenia. Therapy of pre-psychotic states].

    PubMed

    Szulc, Agata; Czernikiewicz, Andrzej

    2007-01-01

    The authors review the literature on the topic of early identification and intervention in "pre-psychotic" and "pre-schizophrenic" persons. Most of the early intervention programmes include more or less "false positive results". There is still no classic biological marker of schizophrenia available. Authors review the possible markers of schizophrenia, including some neurophysiological and neurocognitive disorders (eye-tracking dysfunction, sensory motor gating dysfunction, working memory and other neurocognitive dysfunctions) and also structural, neurochemical and functional brain abnormalities. Unfortunately, the marker of transition to psychosis is still unknown. Only the complex analysis of all possible factors: family, social, clinical and biological can be helpful in identification of the future schizophrenic persons. The authors also review the research on the treatment of "pre-psychotic" persons. The most frequent methods used in these cases are the generation antipsychotics in low doses and psychotherapy. The results are promising, but need further confirmation, both in every day practice and in randomized controlled trials. PMID:17494411

  7. Muscle dysfunction in chronic obstructive pulmonary disease: update on causes and biological findings

    PubMed Central

    Pascual, Sergi; Casadevall, Carme; Orozco-Levi, Mauricio; Barreiro, Esther

    2015-01-01

    Respiratory and/or limb muscle dysfunction, which are frequently observed in chronic obstructive pulmonary disease (COPD) patients, contribute to their disease prognosis irrespective of the lung function. Muscle dysfunction is caused by the interaction of local and systemic factors. The key deleterious etiologic factors are pulmonary hyperinflation for the respiratory muscles and deconditioning secondary to reduced physical activity for limb muscles. Nonetheless, cigarette smoke, systemic inflammation, nutritional abnormalities, exercise, exacerbations, anabolic insufficiency, drugs and comorbidities also seem to play a relevant role. All these factors modify the phenotype of the muscles, through the induction of several biological phenomena in patients with COPD. While respiratory muscles improve their aerobic phenotype (percentage of oxidative fibers, capillarization, mitochondrial density, enzyme activity in the aerobic pathways, etc.), limb muscles exhibit the opposite phenotype. In addition, both muscle groups show oxidative stress, signs of damage and epigenetic changes. However, fiber atrophy, increased number of inflammatory cells, altered regenerative capacity; signs of apoptosis and autophagy, and an imbalance between protein synthesis and breakdown are rather characteristic features of the limb muscles, mostly in patients with reduced body weight. Despite that significant progress has been achieved in the last decades, full elucidation of the specific roles of the target biological mechanisms involved in COPD muscle dysfunction is still required. Such an achievement will be crucial to adequately tackle with this relevant clinical problem of COPD patients in the near-future. PMID:26623119

  8. Muscle dysfunction in chronic obstructive pulmonary disease: update on causes and biological findings.

    PubMed

    Gea, Joaquim; Pascual, Sergi; Casadevall, Carme; Orozco-Levi, Mauricio; Barreiro, Esther

    2015-10-01

    Respiratory and/or limb muscle dysfunction, which are frequently observed in chronic obstructive pulmonary disease (COPD) patients, contribute to their disease prognosis irrespective of the lung function. Muscle dysfunction is caused by the interaction of local and systemic factors. The key deleterious etiologic factors are pulmonary hyperinflation for the respiratory muscles and deconditioning secondary to reduced physical activity for limb muscles. Nonetheless, cigarette smoke, systemic inflammation, nutritional abnormalities, exercise, exacerbations, anabolic insufficiency, drugs and comorbidities also seem to play a relevant role. All these factors modify the phenotype of the muscles, through the induction of several biological phenomena in patients with COPD. While respiratory muscles improve their aerobic phenotype (percentage of oxidative fibers, capillarization, mitochondrial density, enzyme activity in the aerobic pathways, etc.), limb muscles exhibit the opposite phenotype. In addition, both muscle groups show oxidative stress, signs of damage and epigenetic changes. However, fiber atrophy, increased number of inflammatory cells, altered regenerative capacity; signs of apoptosis and autophagy, and an imbalance between protein synthesis and breakdown are rather characteristic features of the limb muscles, mostly in patients with reduced body weight. Despite that significant progress has been achieved in the last decades, full elucidation of the specific roles of the target biological mechanisms involved in COPD muscle dysfunction is still required. Such an achievement will be crucial to adequately tackle with this relevant clinical problem of COPD patients in the near-future. PMID:26623119

  9. Effects of a Physical Activity Program on Markers of Endothelial Dysfunction, Oxidative Stress, and Metabolic Status in Adolescents with Metabolic Syndrome

    PubMed Central

    Camarillo-Romero, Eneida; Dominguez-Garcia, Ma Victoria; Amaya-Chavez, Araceli; Camarillo-Romero, Maria del Socorro; Talavera-Piña, Juan; Huitron-Bravo, Gerardo; Majluf-Cruz, Abraham

    2012-01-01

    The metabolic syndrome (MetS) is a precursor of diabetes. Physical activity (PA) improves endothelial dysfunction and may benefit patients with MetS. Aims. To evaluate the effect of a physical activity (PA) program on markers of endothelial dysfunction and oxidative stress in adolescents with (MetS). Methods. We carried out a cohort study of 38 adolescents with and without MetS (18 females and 20 males). All participants completed a 3-month PA program. All variables of the MetS as well as markers of endothelial dysfunction and oxidative stress tests were evaluated. Results. Females with and without MetS showed significant differences for almost all components of the MetS, whereas males were significantly different in half of the components. After the PA program, components of the MetS were not different from baseline values except for HDL-C levels. Some baseline endothelial dysfunction markers were significantly different among adolescents with and without MetS; however, after the PA program, most of these markers significantly improved in subjects with and without MetS. Conclusion. PA improves the markers of endothelial dysfunction in adolescents with MetS although other changes in the components of the MetS were not observed. Perhaps the benefits of PA on all components of MetS would appear after a PA program with a longer duration. PMID:22888450

  10. Impact of OSA on Biological Markers in Morbid Obesity and Metabolic Syndrome

    PubMed Central

    Salord, Neus; Gasa, Mercè; Mayos, Mercedes; Fortuna-Gutierrez, Ana Maria; Montserrat, Josep Maria; Sánchez-de-la-Torre, Manuel; Barceló, Antonia; Barbé, Ferran; Vilarrasa, Núria; Monasterio, Carmen

    2014-01-01

    Background and Objective: There is compelling evidence that obstructive sleep apnoea (OSA) can affect metabolic syndrome (MetS) and cardiovascular risk, but the intermediate mechanisms through which it occurs have not been well defined. We explored the impact of OSA in morbidly obese patients with MetS on adipokines, pro-inflammatory markers, endothelial dysfunction, and atherosclerosis markers. Methods: We included 52 morbidly obese patients in an observational study matched for age, gender and central obesity in 3 groups (OSA-MetS, Non-OSA-MetS, and Non OSA-non-MetS). Anthropometrical, blood pressure, and fasting blood measurements were obtained the morning after an overnight polysomnography. VEGF, soluble CD40 ligand (sCD40L), TNF-α, IL-6, leptin, adiponectin, and chemerin were determined in serum by ELISA. OSA was defined as apnea/ hypopnea index ≥ 15 and MetS by NCEP-ATP III. Results: Cases and control subjects did not differ in age, BMI, waist circumference, and gender (43 ± 10 years, 46 ± 5 kg/m2, 128 ± 10 cm, 71% females). The cases had severe OSA with 47 (32-66) events/h, time spent < 90% SpO2 7% (5%-31%). All groups presented similar serum cytokines, adipokines, VEGF, and sCD40L levels. Conclusions: In a morbidly obese population with established MetS, the presence of OSA did not determine any differences in the studied mediators when matched by central obesity. Morbidly obese NonOSA-NonMetS had a similar inflammatory, adipokine VEGF, and sCD40L profile as those with established MetS, with or without OSA. Obesity itself could overwhelm the effect of sleep apnea and MetS in the studied biomarkers. Citation: Salord N; Gasa M; Mayos M; Fortuna-Gutierrez AM; Montserrat JM; Sánchez-de-la-Torre M; Barceló A; Barbé F; Vilarrasa N; Monasterio C. Impact of OSA on biological markers in morbid obesity and metabolic syndrome. J Clin Sleep Med 2014;10(3):263-270. PMID:24634623

  11. Age correlation of petroleum of unknown source using biological markers

    SciTech Connect

    Moldowan, J.M.; Jacobson, S.R.; Lee, C.Y. ); Huizinga, B.J. )

    1990-05-01

    Determination of age constraints on petroleums from unknown sources provides a means of choosing among possible source rock candidates, predicting migration scenarios for oil, and determining the timing of its emplacement in the reservoir. A number of parameters used to assign such age constraints to petroleum have been suggested by geochemists. However, any constraining marker, regardless of age, may not be found in a particular facies because the parent organisms are absent in those sediments. Thus, the presence of a specific age correlation marker may be significant whereas its absence may not. The authors have investigated two markers for their age-correlation significance. Oleanane, a marker related to pentacyclic triterpanes in flowering plants (angiosperms) occurs in many Late Cretaceous or younger rocks and oils, even though angiosperm fossils are known in older rocks. A survey of a sequence of middle to upper Cretaceous rocks from Wyoming provides an example of a Late Cretaceous age for the onset of oleanane. However, a level of uncertainty exists for older Cretaceous rocks where a trace component with many similarities to oleanane (which could in fact be oleanane) can occur. C{sub 30}-steranes (24-n-propylcholestanes) have been used as a widely occurring marker for marine organic input to petroleum. A recent report postulates the origin of C{sub 30}-steranes from marine Sarcinochrysidales order of Chrysophycase (golden brown algae). Although the fossil record of these algae has not been recorded, their sample base indicates that C{sub 30} steranes, and therefore their parent organisms, originate in the Middle Ordovician.

  12. Urine albumin to creatinine ratio: A marker of early endothelial dysfunction in youth

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The urine albumin-to-creatinine ratio (UACR) is a useful predictor of cardiovascular (CV) events in adults. Its relationship to vascular function in children is not clear. We investigated whether UACR was related to insulin resistance and endothelial function, a marker of subclinical atherosclerosis...

  13. AB006. Erectile dysfunction (ED) as a marker for cardiovascular diseases (CVD)

    PubMed Central

    Torres, Luiz Otavio

    2015-01-01

    In 1973 V. Michal, a vascular surgeon said “Erectile dysfunction (ED) is related to diseases of the vascular bed”. And this makes sense since ED and cardiovascular diseases (CVD) share many risk factors like aging, obesity, inactivity, smoking, depression, dyslipidemia, hypertension, diabetes/insuline resistance. These conditions may lead to an oxidative stress which ultimately can promote vasoconstriction, thrombosis, atherosclerosis and finally ED and CVD. One of the most accepted Idea is that small vessels plug earlier, it means, small arteries when have for example 50% of obstruction will probably have a clinical manifestation before bigger arteries!

  14. Traveled distance is a sensitive and accurate marker of motor dysfunction in a mouse model of multiple sclerosis.

    PubMed

    Takemiya, Takako; Takeuchi, Chisen

    2013-01-01

    Multiple sclerosis (MS) is a common central nervous system disease associated with progressive physical impairment. To study the mechanisms of the disease, we used experimental autoimmune encephalomyelitis (EAE), an animal model of MS. EAE is induced by myelin oligodendrocyte glycoprotein35-55 peptide, and the severity of paralysis in the disease is generally measured using the EAE score. Here, we compared EAE scores and traveled distance using the open-field test for an assessment of EAE progression. EAE scores were obtained with a 6-step observational scoring system for paralysis, and the traveled distance was obtained by automatic trajectory analysis of natural exploratory behaviors detected by a computer. The traveled distance of the EAE mice started to decrease significantly at day 7 of the EAE process, when the EAE score still did not reflect a change. Moreover, in the relationship between the traveled distance and paralysis as measured by the EAE score after day 14, there was a high coefficient of determination between the distance and the score. The results suggest that traveled distance is a sensitive marker of motor dysfunction in the early phases of EAE progression and that it reflects the degree of motor dysfunction after the onset of paralysis in EAE. PMID:24967302

  15. Cocaine Abstinence and Reduced Use Associated With Lowered Marker of Endothelial Dysfunction in African Americans: A Preliminary Study

    PubMed Central

    Lai, Hong; Stitzer, Maxine; Treisman, Glenn; Moore, Richard; Brinker, Jeffrey; Gerstenblith, Gary; Kickler, Thomas S.; Li, Ji; Chen, Shaoguang; Fishman, Elliot; Lai, Shenghan

    2016-01-01

    Objectives Clinical and epidemiological evidence suggests that cocaine use is associated with an increased risk of premature atherosclerosis. The objectives of this study were to explore (1) whether cocaine abstinence is associated with a reduced marker of endothelial dysfunction, (2) whether cocaine abstinence is associated with a slower coronary plaque progression, and (3) whether reduction in cocaine use is associated with a reduced marker of endothelial dysfunction in African American chronic cocaine users with contrast-enhanced coronary CT angiography-confirmed less than 50% coronary stenosis. Methods Between March and June 2014, a total of 57 African American cocaine users with contrast-enhanced CT angiography-confirmed less than 50% coronary stenosis in Baltimore, Maryland, were enrolled in a 6-month follow-up study to investigate whether cocaine abstinence or reduction in cocaine use is associated with decreased endothelin-1 (ET-1) levels and coronary plaque progression at the 6-month follow-up. A voucher-based incentive approach was used to systematically reinforce cocaine abstinence, and urine benzoylecgonine test was implemented to confirm cocaine use. Results Among the 57 participants, 44 were HIV-infected. The median of duration of cocaine use was 18 (interquartile range, 7–30) years. According to generalized estimating equation analyses, both cocaine abstinence and reduction in cocaine use in the 6 months were independently associated with decreased ET-1. The incidence of coronary plaque progression was 7.4/100 person-years and 23.1/100 person-years in those who were totally abstinent from cocaine and those who continued to use cocaine, respectively. However, the difference in the incidence between these 2 groups was not significant (exact P = 0.30). Conclusions The findings of this study revealed a possible association of cocaine abstinence/reduction with lowered ET levels, which suggests that such changes in cocaine use might be beneficial for

  16. Brief Report: High Frequency of Biochemical Markers for Mitochondrial Dysfunction in Autism: No Association with the Mitochondrial Aspartate/Glutamate Carrier "SLC25A12" Gene

    ERIC Educational Resources Information Center

    Correia, Catarina; Coutinho, Ana M.; Diogo, Luisa; Grazina, Manuela; Marques, Carla; Miguel, Teresa; Ataide, Assuncao; Almeida, Joana; Borges, Luis; Oliveira, Catarina; Oliveira, Guiomar; Vicente, Astrid M.

    2006-01-01

    In the present study we confirm the previously reported high frequency of biochemical markers of mitochondrial dysfunction, namely hyperlactacidemia and increased lactate/pyruvate ratio, in a significant fraction of 210 autistic patients. We further examine the involvement of the mitochondrial aspartate/glutamate carrier gene ("SLC25A12") in…

  17. Effects of Complementary Creatine Monohydrate and Physical Training on Inflammatory and Endothelial Dysfunction Markers Among Heart Failure Patients

    PubMed Central

    Hemati, Farajollah; Rahmani, Asghar; Asadollahi, Khairollah; Soleimannejad, Koroush; Khalighi, Zahra

    2016-01-01

    Background: Previous studies have reported endothelial dysfunction and inflammatory cytokine in heart failure patients (HF). Objectives: The purpose of this study was to determine the effects of creatine monohydrate and exercise on inflammatory and endothelial dysfunction markers among HF patients. Patients and Methods: One hundred patients were prospectively randomized into two groups: Intervention group which received 5 grams/day creatine monohydrate and exercised for 8 weeks; and control group which did not receive any interventions. Interleukine-6 (IL-6), high sensitivity C reactive protein (hs-CRP), P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were measured at the start and end of the study for both groups. Results: In total, 100 patients including 50 controls and 50 intervention group (54% male, mean EF of 34.2 ± 10.5% and 52% male, mean EF of 35.6 ± 12.7%, respectively) were analyzed. The serum levels of hs-CRP and IL-6 increased at the end of the study in the control group compared to the baseline, (7.5 ± 1.5 mg/L vs. 6.9 ± 1.3 mg/L, P < 0.05 and 3.0 ± 0.75 ng/L vs. 2.55 ± 0.9 ng/L, P < 0.05, respectively). However, compared to the baseline, the level of both markers decreased at the end of the study in the intervention group (6.3 ± 1.6 mg/L vs.7.5 ± 1.5 mg/L, P < 0.05 and 2.1 ± 0.8 ng/L vs.2.5 ± 0.5 ng/L, P < 0.05). Also, P-selectin and ICAM-1 levels increased at the end of study (56.9 ± 1.8 ng/L vs. 51.9 ± 1.5 ng/L, P < 0.05 and 368.1 ± 25.4 µg/L vs. 353.1 ± 10.4 µg/L, P < 0.05 respectively). Inversely, the levels of these markers decreased in the intervention group, at the end of study (49.7 ± 1.9 ng/l vs. 51.4 ± 2.1 ng/l, P < 0.05 and 342.7 ± 16.5 µg/l vs. 350.4 ± 14.7 µg/l, P < 0.05, respectively). VCAM-1 level was not decreased significantly at the end of the study in the intervention group (570.5 ± 78.4 µg/L vs. 575.3 ± 86.5 µg/L, P > 0.05). Conclusions: Combination

  18. Surrogate biochemical markers: precise measurement for strategic drug and biologics development.

    PubMed

    Lee, J W; Hulse, J D; Colburn, W A

    1995-05-01

    More efficient drug and biologics development is necessary for future success of pharmaceutical and biotechnology companies. One way to achieve this objective is to use rationally selected surrogate markers to improve the early decision-making process. Using typical clinical chemistry methods to measure biochemical markers may not ensure adequate precision and reproducibility. In contrast, using analytical methods that meet good laboratory practices along with rational selection and validation of biochemical markers can give those who use them a competitive advantage over those who do not by providing meaningful data for earlier decision making. PMID:7657845

  19. Major Histocompatibility Complex (MHC) Markers in Conservation Biology

    PubMed Central

    Ujvari, Beata; Belov, Katherine

    2011-01-01

    Human impacts through habitat destruction, introduction of invasive species and climate change are increasing the number of species threatened with extinction. Decreases in population size simultaneously lead to reductions in genetic diversity, ultimately reducing the ability of populations to adapt to a changing environment. In this way, loss of genetic polymorphism is linked with extinction risk. Recent advances in sequencing technologies mean that obtaining measures of genetic diversity at functionally important genes is within reach for conservation programs. A key region of the genome that should be targeted for population genetic studies is the Major Histocompatibility Complex (MHC). MHC genes, found in all jawed vertebrates, are the most polymorphic genes in vertebrate genomes. They play key roles in immune function via immune-recognition and -surveillance and host-parasite interaction. Therefore, measuring levels of polymorphism at these genes can provide indirect measures of the immunological fitness of populations. The MHC has also been linked with mate-choice and pregnancy outcomes and has application for improving mating success in captive breeding programs. The recent discovery that genetic diversity at MHC genes may protect against the spread of contagious cancers provides an added impetus for managing and protecting MHC diversity in wild populations. Here we review the field and focus on the successful applications of MHC-typing for conservation management. We emphasize the importance of using MHC markers when planning and executing wildlife rescue and conservation programs but stress that this should not be done to the detriment of genome-wide diversity. PMID:21954351

  20. Major Histocompatibility Complex (MHC) markers in conservation biology.

    PubMed

    Ujvari, Beata; Belov, Katherine

    2011-01-01

    Human impacts through habitat destruction, introduction of invasive species and climate change are increasing the number of species threatened with extinction. Decreases in population size simultaneously lead to reductions in genetic diversity, ultimately reducing the ability of populations to adapt to a changing environment. In this way, loss of genetic polymorphism is linked with extinction risk. Recent advances in sequencing technologies mean that obtaining measures of genetic diversity at functionally important genes is within reach for conservation programs. A key region of the genome that should be targeted for population genetic studies is the Major Histocompatibility Complex (MHC). MHC genes, found in all jawed vertebrates, are the most polymorphic genes in vertebrate genomes. They play key roles in immune function via immune-recognition and -surveillance and host-parasite interaction. Therefore, measuring levels of polymorphism at these genes can provide indirect measures of the immunological fitness of populations. The MHC has also been linked with mate-choice and pregnancy outcomes and has application for improving mating success in captive breeding programs. The recent discovery that genetic diversity at MHC genes may protect against the spread of contagious cancers provides an added impetus for managing and protecting MHC diversity in wild populations. Here we review the field and focus on the successful applications of MHC-typing for conservation management. We emphasize the importance of using MHC markers when planning and executing wildlife rescue and conservation programs but stress that this should not be done to the detriment of genome-wide diversity. PMID:21954351

  1. Is there convincing biological or behavioral evidence linking vitamin D deficiency to brain dysfunction?

    PubMed

    McCann, Joyce C; Ames, Bruce N

    2008-04-01

    Vitamin D insufficiency is common in the United States; the elderly and African-Americans are at particularly high risk of deficiency. This review, written for a broad scientific readership, presents a critical overview of scientific evidence relevant to a possible causal relationship between vitamin D deficiency and adverse cognitive or behavioral effects. Topics discussed are 1) biological functions of vitamin D relevant to cognition and behavior; 2) studies in humans and rodents that directly examine effects of vitamin D inadequacy on cognition or behavior; and 3) immunomodulatory activity of vitamin D relative to the proinflammatory cytokine theory of cognitive/behavioral dysfunction. We conclude there is ample biological evidence to suggest an important role for vitamin D in brain development and function. However, direct effects of vitamin D inadequacy on cognition/behavior in human or rodent systems appear to be subtle, and in our opinion, the current experimental evidence base does not yet fully satisfy causal criteria. Possible explanations for the apparent inconsistency between results of biological and cognitive/behavioral experiments, as well as suggested areas for further research are discussed. Despite residual uncertainty, recommendations for vitamin D supplementation of at-risk groups, including nursing infants, the elderly, and African-Americans appear warranted to ensure adequacy. PMID:18056830

  2. Fine particles, genetic pathways, and markers of inflammation and endothelial dysfunction: Analysis on particulate species and sources.

    PubMed

    Dai, Lingzhen; Bind, Marie-Abele; Koutrakis, Petros; Coull, Brent A; Sparrow, David; Vokonas, Pantel S; Schwartz, Joel D

    2016-06-01

    Studies have found associations between PM2.5 and cardiovascular events. The role of different components of PM2.5 is not well understood. We used linear mixed-effects models with the adaptive LASSO penalty to select PM2.5 species and source(s), separately, that may be associated with markers of inflammation and endothelial dysfunction, with adjustment for age, obesity, smoking, statin use, diabetes mellitus, temperature, and season as fixed effects in a large longitudinal cohort of elderly men. We also analyzed these associations with source apportionment models and examined genetic pathway-air pollution interactions within three relevant pathways (oxidative stress, metal processing, and endothelial function). We found that independent of PM2.5 mass vanadium (V) was associated with intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). An IQR increase (3.2 ng/m(3)) in 2-day moving average V was associated with a 2.5% (95% CI: 1.2-3.8%) change in ICAM-1 and a 3.9% (95% CI: 2.2-5.7%) change in VCAM-1, respectively. In addition, an oil combustion source rich in V was linked to these adhesion molecules. People with higher allelic risk profiles related to oxidative stress may have greater associations (P-value of interaction=0.11). Our findings suggest that particles derived from oil combustion may be associated with inflammation and endothelial dysfunction, and it is likely that oxidative stress plays a role in the associations. PMID:26732377

  3. Biological marker of furfural, chemicals without administrative control level.

    PubMed

    Morimoto, Yasuo; Hori, Hajime; Higashi, Toshiaki; Nagatomo, Hiroko; Hino, Yoshiyuki; Ohsato, Atsushi; Uchino, Bungo

    2007-06-01

    Furfural, a colorless liquid used in solvent-extraction processes, petroleum refining and as a rubber additive, has been assigned an occupational exposure limit of 2.5 ppm by the Japan Society for Occupational Health, but an administrative control level for furfural has not been established. In order to conduct effective occupational health management in workplaces where furfural is used, we measured furfural concentrations in working environments and collected urine samples to measure furoic acid levels (one of the principal metabolites), which act as a biomarker of exposure to furfural. The measurements of airborne concentrations in a working environment where furfural or a solution containing furfural was handled were made in 2004. Workers answered a questionnaire on working conditions, urine samples were collected at the end of the workshift, and furoic acid in the urine was measured by gas chromatography/flame ionization detector (GC/FID). The ambient concentrations of furfural during the period were 2.1 ppm in a mixer room and 1.6 ppm in a filling room. The mean concentrations of furoic acid in the workers' urine were 7.7 +/- 7.8 mg/g-creatinine in summer and winter, respectively (normal range: 3 - 60 mg/g-creatinine). The average exposure to furfural per month calculated by multiplying the concentration in the working environment by working hours for a month was 86.4 +/- 108.6 ppm hours/months (mean +/- standard deviation) (range; 0 - 336 ppm hours/month). The relationship between average exposure to furfural and furoic acid in the urine was analyzed by simple linear regression analysis and a positive correlation was found. These findings suggest that furoic acid in urine is useful for biological monitoring of exposure to furfural, and that the measurement of both furfural in the environment and furoic acid in the urine are beneficial in occupational health management of furfural. PMID:17582986

  4. Systems Biology in Animal Breeding: Identifying relationships among markers, genes, and phenotypes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Breeding and Genetics Symposium titled “Systems Biology in Animal Breeding: Identifying relationships among markers, genes, and phenotypes” was held at the Joint Annual Meeting of the American Dairy Science Association and the American Society of Animal Science in Phoenix, AZ, July 15 to 19, 201...

  5. Use of biological markers and pharmacokinetics in human health risk assessment.

    PubMed Central

    Hattis, D

    1991-01-01

    There are two reasons to connect discussions of biological markers and pharmacokinetics. First, both tend to open up the black box between exposure and effect. Doing this promises more complete scientific understanding than simple input-output analysis, the possibility of better mechanism-based projection of risk beyond the range of possible direct observations, and the possibility of greater sensitivity of analysis, in some cases going from the organism to the cell as the unit of analysis. Second, pharmacokinetic (or similar pharmacodynamic) analysis will often be essential for appropriate interpretation of biological marker information. One needs some sort of dynamic model of the generation and loss of the marker in relation to exposure in order to use a biological marker, either to form a better measure of dosage (either accumulated past dose, or biologically relevant dose), or to make an improved prediction of effect. (For example, the use of a blood cadmium level alone to predict kidney effects might be inferior to predictions based on aggregate past accumulation of cadmium in the kidney, based on the past history of cadmium blood levels x time). Several examples will be discussed of the use of biomarkers and pharmacokinetics in risk assessments for both carcinogenesis and other effects. PMID:2050066

  6. Markers

    ERIC Educational Resources Information Center

    Healthy Schools Network, Inc., 2011

    2011-01-01

    Dry erase whiteboards come with toxic dry erase markers and toxic cleaning products. Dry erase markers labeled "nontoxic" are not free of toxic chemicals and can cause health problems. Children are especially vulnerable to environmental health hazards; moreover, schools commonly have problems with indoor air pollution, as they are more densely…

  7. Implications of comorbidity for genetic studies of bipolar disorder: P300 and eye tracking as biological markers for illness.

    PubMed

    Blackwood, D H; Sharp, C W; Walker, M T; Doody, G A; Glabus, M F; Muir, W J

    1996-06-01

    In large families with affective illness, identification of a biological variable is needed that reflects brain dysfunction at an earlier point than symptom development. Eye movement disorder, a possible vulnerability marker in schizophrenia, is less clearly associated with affective illness, although a subgroup of affective disorders shows smooth-pursuit eye movement disorder. The auditory P300 event-related potential may be a useful marker for risk to schizophrenia, but a role in bipolar illness is less certain. The distribution of these two biological variables and their association with symptoms in two multiply affected bipolar families is described. In a single, five-generation family identified for linkage studies through two bipolar I (BPI) probands, 128 members (including 20 spouses) were interviewed. The 108 related individuals had diagnoses of BPI (7), bipolar II (2), cyclothymia (3), or major depressive disorder (19). Eight others had generalised anxiety (1), minor depression (5), intermittent depression (1), or alcoholism (1). Sixty-nine subjects had no psychiatric diagnosis. P300 latency (81) and eye tracking (71) were recorded from a subgroup of relatives within the pedigree. Eye tracking was abnormal in 11 of 71 relatives (15.5%) and was bimodally distributed. In these 11 relatives, clinical diagnoses included minor depression (1), alcoholism (1) and generalised anxiety disorder (1). P300 latency was normally distributed and did not differ from controls. In a second family in which five of seven siblings have BPI illness, P300 latency and eye movement disorder were found in affected relatives and in some unaffected offspring. In these large families, clinical diagnoses of general anxiety, alcoholism and minor depression, when associated with eye tracking abnormality, may be considered alternative clinical manifestations of the same trait that in other relatives is expressed as bipolar illness. PMID:8864153

  8. "Biological markers" and psychiatric diagnosis: risk-benefit balancing using ROC analysis.

    PubMed

    Somoza, E; Mossman, D

    1991-04-15

    Although the clinical interview retains a central role in psychiatric diagnosis, recent research has suggested that "biological markers" may ultimately increase the precision of clinicians' nosologic and therapeutic decisions. Evaluating and operationalizing diagnostic tests require mathematical techniques that reflect the tests' essential features and limitations, and that guide clinicians in particular clinical situations. In this article we describe a technique that combines signal detection theory and utility-based decision theory, and apply the technique to published data in which sleep architecture was used as a biological marker for depression. We show how outcome utilities influence the optimum REM latency cut-off and show how this relationship is influenced by the prevalence of depression in the population being tested. We also make specific calculations of the practical limits that must be imposed on uncertainties in utilities to operationalize a diagnostic test for a specific clinical situation. PMID:2054454

  9. Physical Activity, Physical Performance, and Biological Markers of Health among Sedentary Older Latinos.

    PubMed

    Moreno, Gerardo; Mangione, Carol M; Wang, Pin-Chieh; Trejo, Laura; Butch, Anthony; Tseng, Chi-Hong; Sarkisian, Catherine A

    2014-01-01

    Background. Physical activity is associated with better physical health, possibly by changing biological markers of health such as waist circumference and inflammation, but these relationships are unclear and even less understood among older Latinos-a group with high rates of sedentary lifestyle. Methods. Participants were 120 sedentary older Latino adults from senior centers. Community-partnered research methods were used to recruit participants. Inflammatory (C-reactive protein) and metabolic markers of health (waist circumference, HDL-cholesterol, triglycerides, insulin, and glucose), physical activity (Yale physical activity survey), and physical performance (short physical performance NIA battery) were measured at baseline and 6-month followup. Results. Eighty percent of the sample was female. In final adjusted cross-sectional models, better physical activity indices were associated with faster gait speed (P < 0.05). In adjusted longitudinal analyses, change in self-reported physical activity level correlated inversely with change in CRP (β = -0.05; P = 0.03) and change in waist circumference (β = -0.16; P = 0.02). Biological markers of health did not mediate the relationship between physical activity and physical performance. Conclusion. In this community-partnered study, higher physical activity was associated with better physical performance in cross-sectional analyses. In longitudinal analysis, increased physical activity was associated with improvements in some metabolic and inflammatory markers of health. PMID:25136359

  10. The Promise of Biological Markers for Treatment Response in First-Episode Psychosis: A Systematic Review

    PubMed Central

    Fond, Guillaume; d’Albis, Marc-Antoine; Jamain, Stéphane; Tamouza, Ryad; Arango, Celso; Fleischhacker, W. Wolfgang; Glenthøj, Birte; Leweke, Markus; Lewis, Shôn; McGuire, Phillip; Meyer-Lindenberg, Andreas; Sommer, Iris E.; Winter-van Rossum, Inge; Kapur, Shitij; Kahn, René S.; Rujescu, Dan; Leboyer, Marion

    2015-01-01

    Successful treatment of first-episode psychosis is one of the major factors that impacts long-term prognosis. Currently, there are no satisfactory biological markers (biomarkers) to predict which patients with a first-episode psychosis will respond to which treatment. In addition, a non-negligible rate of patients does not respond to any treatment or may develop side effects that affect adherence to the treatments as well as negatively impact physical health. Thus, there clearly is a pressing need for defining biomarkers that may be helpful to predict response to treatment and sensitivity to side effects in first-episode psychosis. The present systematic review provides (1) trials that assessed biological markers associated with antipsychotic response or side effects in first-episode psychosis and (2) potential biomarkers associated with biological disturbances that may guide the choice of conventional treatments or the prescription of innovative treatments. Trials including first-episode psychoses are few in number. Most of the available data focused on pharmacogenetics markers with so far only preliminary results. To date, these studies yielded—beside markers for metabolism of antipsychotics—no or only a few biomarkers for response or side effects, none of which have been implemented in daily clinical practice. Other biomarkers exploring immunoinflammatory, oxidative, and hormonal disturbances emerged as biomarkers of first-episode psychoses in the last decades, and some of them have been associated with treatment response. In addition to pharmacogenetics, further efforts should focus on the association of emergent biomarkers with conventional treatments or with innovative therapies efficacy, where some preliminary data suggest promising results. PMID:25759473

  11. Sequence-related amplified polymorphism (SRAP) markers: A potential resource for studies in plant molecular biology1

    PubMed Central

    Robarts, Daniel W. H.; Wolfe, Andrea D.

    2014-01-01

    In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR), random-amplified polymorphic DNA (RAPD), and amplified fragment length polymorphism (AFLP) to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP) markers have been developed, which are used to amplify coding regions of DNA with primers targeting open reading frames. These markers have proven to be robust and highly variable, on par with AFLP, and are attained through a significantly less technically demanding process. SRAP markers have been used primarily for agronomic and horticultural purposes, developing quantitative trait loci in advanced hybrids and assessing genetic diversity of large germplasm collections. Here, we suggest that SRAP markers should be employed for research addressing hypotheses in plant systematics, biogeography, conservation, ecology, and beyond. We provide an overview of the SRAP literature to date, review descriptive statistics of SRAP markers in a subset of 171 publications, and present relevant case studies to demonstrate the applicability of SRAP markers to the diverse field of plant biology. Results of these selected works indicate that SRAP markers have the potential to enhance the current suite of molecular tools in a diversity of fields by providing an easy-to-use, highly variable marker with inherent biological significance. PMID:25202637

  12. Prognostic Cell Biological Markers in Cervical Cancer Patients Primarily Treated With (Chemo)radiation: A Systematic Review

    SciTech Connect

    Noordhuis, Maartje G.; Eijsink, Jasper J.H.; Roossink, Frank; Graeff, Pauline de; Pras, Elisabeth; Schuuring, Ed; Wisman, G. Bea A.; Bock, Geertruida H. de; Zee, Ate G.J. van der

    2011-02-01

    The aim of this study was to systematically review the prognostic and predictive significance of cell biological markers in cervical cancer patients primarily treated with (chemo)radiation. A PubMed, Embase, and Cochrane literature search was performed. Studies describing a relation between a cell biological marker and survival in {>=}50 cervical cancer patients primarily treated with (chemo)radiation were selected. Study quality was assessed, and studies with a quality score of 4 or lower were excluded. Cell biological markers were clustered on biological function, and the prognostic and predictive significance of these markers was described. In total, 42 studies concerning 82 cell biological markers were included in this systematic review. In addition to cyclooxygenase-2 (COX-2) and serum squamous cell carcinoma antigen (SCC-ag) levels, markers associated with poor prognosis were involved in epidermal growth factor receptor (EGFR) signaling (EGFR and C-erbB-2) and in angiogenesis and hypoxia (carbonic anhydrase 9 and hypoxia-inducible factor-1{alpha}). Epidermal growth factor receptor and C-erbB-2 were also associated with poor response to (chemo)radiation. In conclusion, EGFR signaling is associated with poor prognosis and response to therapy in cervical cancer patients primarily treated with (chemo)radiation, whereas markers involved in angiogenesis and hypoxia, COX-2, and serum SCC-ag levels are associated with a poor prognosis. Therefore, targeting these pathways in combination with chemoradiation may improve survival in advanced-stage cervical cancer patients.

  13. Pollutional haze and COPD: etiology, epidemiology, pathogenesis, pathology, biological markers and therapy

    PubMed Central

    Wang, Fei; Ni, Song-Shi

    2016-01-01

    In recent years, serious pollutional haze occurs in the mainland of China thanks to the development of urbanization and industrialization. There is a close relationship between air pollution and the occurrence and development of chronic obstructive pulmonary disease (COPD), but there are some new characteristics in some aspects of COPD associated with pollutional haze compared with COPD induced by traditional physical and chemical factors. This article attempts to summarize the new progress from these new features of COPD related to pollutional haze, focus on etiology, epidemiology, pathogenesis, pathology, biological markers and therapy. PMID:26904250

  14. Biological markers in animals can provide information on exposure and bioavailability of environmental contaminants

    SciTech Connect

    Shugart, L.R.; Adams, S.M.; Jimenez, B.D.; Talmage, S.S.; McCarthy, J.F.

    1987-01-01

    Epidemiologic studies of agents present in the environment seek to identify the extent to which they contribute to the causation of a specific toxic, clinical, or pathological endpoint. The multifactorial nature of disease etiology, long latency periods and the complexity of exposure, all contribute to the difficulty of establishing associations and casual relationships between a specific exposure and an adverse outcome. These barriers to studies of exposures and subsequent risk assessment cannot generally be changed. However, the appropriate use of biological markers in animal species living in a contaminated habitat can provide a measure of potential damage from that exposure and, in some instances, act as a surrogate for human environmental exposures. Quantitative predictivity of the effect of exposure to environmental pollutants is being approached by employing an appropriate array of biological end points. 34 refs., 1 fig., 6 tabs.

  15. Emergence of biological markers of musicianship with school-based music instruction.

    PubMed

    Kraus, Nina; Strait, Dana L

    2015-03-01

    Musician children and adults demonstrate biological distinctions in auditory processing relative to nonmusicians. For example, musician children and adults have more robust neural encoding of speech harmonics, more adaptive sound processing, and more precise neural encoding of acoustically similar sounds; these enhancements may contribute to musicians' linguistic advantages, such as for hearing speech in noise and reading. Such findings have inspired proposals that the auditory and cognitive stimulation induced by musical practice renders musicians enhanced according to biological metrics germane to communication. Cross-sectional methodologies comparing musicians with nonmusicians, however, are limited by the inability to disentangle training-related effects from demographic and innate qualities that may predistinguish musicians. Over the past several years, our laboratory has addressed this problem by examining the emergence of neural markers of musicianship in children and adolescents using longitudinal approaches to track the development of biological indices of speech processing. This work was conducted in partnership with successful community-based music programs, thus avoiding reliance on a synthetic program for the purposes of laboratory study. Outcomes indicate that many of musicians' auditory-related biological enhancements emerge with training and may promote the acquisition of language skills, including in at-risk populations. PMID:25773631

  16. Effects of exercise on knee joints with osteoarthritis: a pilot study of biologic markers

    NASA Technical Reports Server (NTRS)

    Bautch, J. C.; Malone, D. G.; Vailas, A. C.

    1997-01-01

    OBJECTIVE: To determine the effects of low intensity weight-bearing exercise on osteoarthritis (OA) of the knee. METHODS: Synovial fluid keratan sulfate (KS) and hydroxyproline were measured as markers of cartilage degradation. The Arthritis Impact Measurement Scales (AIMS) were used to measure health status, and a visual analog scale for pain assessment was used before and after intervention. An exercise (EX) group (n = 15) received a thrice-weekly 12-week low intensity exercise program and a weekly educational program, and a minimal treatment (Min RX) group (n = 15) received only the education program. RESULTS: Pain levels declined in the EX group, and the Min RX group showed improvement on the AIMS. Synovial fluid was obtained in 11 subjects before and after the intervention. Levels of KS and hydroxyproline did not change. CONCLUSION: Further study of exercise effects should include both clinical and biologic parameters to examine the outcome of exercise as a therapeutic intervention in OA of the knee.

  17. Tauopathies with parkinsonism: clinical spectrum, neuropathologic basis, biological markers, and treatment options

    PubMed Central

    Ludolph, A. C.; Kassubek, J.; Landwehrmeyer, B. G.; Mandelkow, E.; Mandelkow, E.-M.; Burn, D. J.; Caparros-Lefebvre, D.; Frey, K. A.; de Yebenes, J. G.; Gasser, T.; Heutink, P.; Höglinger, G.; Jamrozik, Z.; Jellinger, K. A.; Kazantsev, A.; Kretzschmar, H.; Lang, A. E.; Litvan, I.; Lucas, J. J.; McGeer, P. L.; Melquist, S.; Oertel, W.; Otto, M.; Paviour, D.; Reum, T.; Saint-Raymond, A.; Steele, J. C.; Tolnay, M.; Tumani, H.; van Swieten, J. C.; Vanier, M. T.; Vonsattel, J.-P.; Wagner, S.; Wszolek, Z. K.

    2009-01-01

    Tauopathies with parkinsonism represent a spectrum of disease entities unified by the pathologic accumulation of hyperphosphorylated tau protein fragments within the central nervous system. These pathologic characteristics suggest shared pathogenetic pathways and possible molecular targets for disease-modifying therapeutic interventions. Natural history studies, for instance, in progressive supranuclear palsy, frontotemporal dementia with parkinsonism linked to chromosome 17, corticobasal degeneration, and Niemann-Pick disease type C as well as in amyotrophic lateral sclerosis/Parkinson–dementia complex permit clinical characterization of the disease phenotypes and are crucial to the development and validation of biological markers for differential diagnostics and disease monitoring, for example, by use of neuroimaging or proteomic approaches. The wide pathologic and clinical spectrum of the tauopathies with parkinsonism is reviewed in this article, and perspectives on future advances in the understanding of the pathogenesis are given, together with potential therapeutic strategies. PMID:19364361

  18. DNA damage as a biological marker in aquatic organisms exposed to benzo(a)pyrene

    SciTech Connect

    Shugart, L.R.; Jimenez, B.D.; McCarthy, J.F.

    1987-01-01

    We show that minute quantities of BaPDE-DNA adducts in the liver of bluegill sunfish can be detected and quantitated using a simple analytical technique whose sensitivity depends upon the intrinsic fluorescence of the specific adduct being analyzed. These adducts represent damage to DNA of the organism, which, if left uncorrected, could trigger a sequence of events that culminate in the appearance of an overt malignancy. We believe that the data reported here demonstrate that the covalent interaction of genotoxic chemicals with cellular macromolecules such as DNA is, potentially, a sensitive biological marker which could be of early predictive value in assessing exposure and its significance. 13 refs., 1 fig., 1 tab.

  19. Is the Alzheimer's disease cortical thickness signature a biological marker for memory?

    PubMed

    Busovaca, Edgar; Zimmerman, Molly E; Meier, Irene B; Griffith, Erica Y; Grieve, Stuart M; Korgaonkar, Mayuresh S; Williams, Leanne M; Brickman, Adam M

    2016-06-01

    Recent work suggests that analysis of the cortical thickness in key brain regions can be used to identify individuals at greatest risk for development of Alzheimer's disease (AD). It is unclear to what extent this "signature" is a biological marker of normal memory function - the primary cognitive domain affected by AD. We examined the relationship between the AD signature biomarker and memory functioning in a group of neurologically healthy young and older adults. Cortical thickness measurements and neuropsychological evaluations were obtained in 110 adults (age range 21-78, mean = 46) drawn from the Brain Resource International Database. The cohort was divided into young adult (n = 64, age 21-50) and older adult (n = 46, age 51-78) groups. Cortical thickness analysis was performed with FreeSurfer, and the average cortical thickness extracted from the eight regions that comprise the AD signature. Mean AD-signature cortical thickness was positively associated with performance on the delayed free recall trial of a list learning task and this relationship did not differ between younger and older adults. Mean AD-signature cortical thickness was not associated with performance on a test of psychomotor speed, as a control task, in either group. The results suggest that the AD signature cortical thickness is a marker for memory functioning across the adult lifespan. PMID:26040979

  20. Quantitative changes in sets of proteins as markers of biological response

    SciTech Connect

    Giometti, C.S.; Taylor, J.; Gemmell, M.A.; Tollaksen, S.L. ); Lalwani, N.D.; Reddy, J.K. )

    1990-01-01

    Exposure to either physical or chemical insults triggers a cascade of bio-chemical events within the target cell. This response requires adjustment within the protein population of the cell, some proteins becoming more abundant (those involved in the cellular response), others less abundant (those not required or counterproductive to the response). Thus, quantitative changes in the global protein population of an exposed biological system may well serve as an indicator of exposure, provided the alterations observed are selective and dose-dependent. In this paper we present results from a study in which liver protein changes induced by exposure of mice to chemicals known to cause peroxisome proliferation and subsequent hepatocellular carcinoma where monitored. Clofibrate, and its chemical analog ciprofibrate, are hypolipidemic drugs. Di-(ethylhexyl)phthalate (DEHP) is a plasticizer used widely in disposable containers for blood products. WY-14643 is a chemical shown to cause hypolipidemic and peroxisome proliferation, similar to clofibrate, ciprofibrate and DEHP, but structurally different from these three chemicals. Thus, two of the four chemicals are structurally similar while the remaining two are very distinct, although all four chemicals cause the same gross biological response. Our results show that although common protein effects are observed in mice exposed to these chemicals, each chemical also causes specific alterations in selective subsets of proteins that could serve as markers of a particular exposure. 13 refs., 4 figs., 1 tab.

  1. Galectin-3 is a marker of favorable prognosis and a biologically relevant molecule in neuroblastic tumors

    PubMed Central

    Veschi, V; Petroni, M; Bartolazzi, A; Altavista, P; Dominici, C; Capalbo, C; Boldrini, R; Castellano, A; McDowell, H P; Pizer, B; Frati, L; Screpanti, I; Gulino, A; Giannini, G

    2014-01-01

    Childhood neuroblastic tumors are characterized by heterogeneous clinical courses, ranging from benign ganglioneuroma (GN) to highly lethal neuroblastoma (NB). Although a refined prognostic evaluation and risk stratification of each tumor patient is becoming increasingly essential to personalize treatment options, currently only few biomolecular markers (essentially MYCN amplification, chromosome 11q status and DNA ploidy) are validated for this purpose in neuroblastic tumors. Here we report that Galectin-3 (Gal-3), a β-galactoside-binding lectin involved in multiple biological functions that has already acquired diagnostic relevance in specific clinical settings, is variably expressed in most differentiated and less aggressive neuroblastic tumors, such as GN and ganglioneuroblastoma, as well as in a subset of NB cases. Gal-3 expression is associated with the INPC histopathological categorization (P<0.001) and Shimada favorable phenotype (P=0.001), but not with other prognostically relevant features. Importantly, Gal-3 expression was associated with a better 5-year overall survival (P=0.003), and with improved cumulative survival in patient subsets at worse prognosis, such as older age at diagnosis, advanced stages or NB histopathological classification. In vitro, Gal-3 expression and nuclear accumulation accompanied retinoic acid-induced cell differentiation in NB cell lines. Forced Gal-3 overexpression increased phenotypic differentiation and substrate adherence, while inhibiting proliferation. Altogether, these findings suggest that Gal-3 is a biologically relevant player for neuroblastic tumors, whose determination by conventional immunohistochemistry might be used for outcome assessment and patient's risk stratification in the clinical setting. PMID:24603328

  2. S-Allylcysteine prevents the rat from 3-nitropropionic acid-induced hyperactivity, early markers of oxidative stress and mitochondrial dysfunction.

    PubMed

    Herrera-Mundo, María N; Silva-Adaya, Daniela; Maldonado, Perla D; Galván-Arzate, Sonia; Andrés-Martínez, Leticia; Pérez-De La Cruz, Verónica; Pedraza-Chaverrí, José; Santamaría, Abel

    2006-09-01

    We investigated the effects of S-allylcysteine (SAC) on early behavioral alterations, striatal changes in superoxide dismutase (SOD) activity, lipid peroxidation (LP) and mitochondrial dysfunction induced by the systemic infusion of 3-nitropropionic acid (3-NPA) to rats. SAC (300 mg/kg, i.p.), given to animals 30 min before 3-NPA (30 mg/kg, i.p.), prevented the hyperkinetic pattern evoked by the toxin. In addition, 3-NPA alone produced decreased activities of manganese- (Mn-SOD) and copper/zinc-dependent superoxide dismutase (Cu,Zn-SOD), increased LP (evaluated as the formation of lipid fluorescent products) and produced mitochondrial dysfunction in the striatum (measured as decreased 3-(3,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction). In contrast, pretreatment of 3-NPA-injected rats with SAC resulted in a significant prevention of all these markers. Our findings suggest that the protective actions of SAC are related with its antioxidant properties, which in turn may be accounting for the preservation of SOD activity and primary mitochondrial tasks. PMID:16806549

  3. Review: domestic animal forensic genetics - biological evidence, genetic markers, analytical approaches and challenges.

    PubMed

    Kanthaswamy, S

    2015-10-01

    This review highlights the importance of domestic animal genetic evidence sources, genetic testing, markers and analytical approaches as well as the challenges this field is facing in view of the de facto 'gold standard' human DNA identification. Because of the genetic similarity between humans and domestic animals, genetic analysis of domestic animal hair, saliva, urine, blood and other biological material has generated vital investigative leads that have been admitted into a variety of court proceedings, including criminal and civil litigation. Information on validated short tandem repeat, single nucleotide polymorphism and mitochondrial DNA markers and public access to genetic databases for forensic DNA analysis is becoming readily available. Although the fundamental aspects of animal forensic genetic testing may be reliable and acceptable, animal forensic testing still lacks the standardized testing protocols that human genetic profiling requires, probably because of the absence of monetary support from government agencies and the difficulty in promoting cooperation among competing laboratories. Moreover, there is a lack in consensus about how to best present the results and expert opinion to comply with court standards and bear judicial scrutiny. This has been the single most persistent challenge ever since the earliest use of domestic animal forensic genetic testing in a criminal case in the mid-1990s. Crime laboratory accreditation ensures that genetic test results have the courts' confidence. Because accreditation requires significant commitments of effort, time and resources, the vast majority of animal forensic genetic laboratories are not accredited nor are their analysts certified forensic examiners. The relevance of domestic animal forensic genetics in the criminal justice system is undeniable. However, further improvements are needed in a wide range of supporting resources, including standardized quality assurance and control protocols for sample

  4. Biological markers in non-invasive brain stimulation trials in major depressive disorder: a systematic review

    PubMed Central

    Fidalgo, TM; Morales-Quezada, L; Muzy, GSC; Chiavetta, NM; Mendonça, ME; Santana, MVB; Gonçalves, OF; Brunoni, AR; Fregni, F

    2014-01-01

    Objectives The therapeutic effects of Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) in patients with major depression have shown promising results; however, there is a lack of mechanistic studies using biological markers (BM) as an outcome. Therefore, our aim was to review non-invasive brain stimulation trials in depression using BM. Method The following databases were used for our systematic review: MEDLINE, Web of Science, Cochrane, and SCIELO. We examined articles published before November 2012 that used TMS and tDCS as an intervention for depression and had BM as an outcome measure. The search was limited to human studies written in English. Results Of 1234 potential articles, 52 papers were included. Only studies using TMS were found. BM included immune and endocrine serum markers, neuroimaging techniques and electrophysiological outcomes. In 12 articles (21.4%) endpoint BM measurements were not significantly associated with clinical outcomes. All studies reached significant results in the main clinical rating scales. BM outcomes were used as predictors of response, to understand mechanisms of TMS, and as a surrogate of safety. Conclusions fMRI, SPECT, PET, MRS, cortical excitability and BDNF consistently showed positive results. BDNF was the best predictor of patients’ likeliness to respond. These initial results are promising; however, all studies investigating BM are small, used heterogeneous samples, and did not take into account confounders such as age, gender or family history. Based on our findings we recommend further studies to validate BM in non-invasive brain stimulation trials in MDD. PMID:23845938

  5. The habitat of petroleum in the Brazilian marginal and west African basins: A biological marker investigation

    SciTech Connect

    Mello, M.R.; Soldan, A.L. ); Maxwell, J.R. ); Figueira, J. )

    1990-05-01

    A geochemical and biological marker investigation of a variety of oils from offshore Brazil and west Africa, ranging in age from Lower Cretaceous to Tertiary, has been done, with the following aims: (1) assessing the depositional environment of source rocks, (2) correlating the reservoired oils, (3) comparing the Brazilian oils with their west African counterparts. The approach was based in stable isotope data; bulk, elemental, and hydrous pyrolysis results; and molecular studies involving quantitative geological marker investigations of alkanes using GC-MS and GC-MS-MS. The results reveal similarities between groups of oils from each side of the Atlantic and suggest an origin from source rocks deposited in five types of depositional environment: lacustrine fresh water, lacustrine saline water, marine evaporitic/carbonate, restricted marine anoxic, and marine deltaic. In west Africa, the Upper Cretaceous marine anoxic succession (Cenomanian-Santonian) appears to be a major oil producer, but in Brazil it is generally immature. The Brazilian offshore oils have arisen mainly from the pre-salt sequence, whereas the African oils show a balance between origins from the pre-salt and marine sequences. The integration of the geochemical and geological data indicate that new frontiers of hydrocarbon exploration in the west African basins must consider the Tertiary reservoirs in the offshore area of Niger Delta, the reservoirs of the rift sequences in the shallow-water areas of south Gabon, Congo, and Cuanza basins, and the reservoirs from the drift sequences (post-salt) in the deep-water areas of Gabon, Congo Cabinda, and Cuanza basins.

  6. Metadiscourse Markers in Biological Research Articles and Journal Impact Factor: Non-Native Writers vs. Native Writers

    ERIC Educational Resources Information Center

    Gholami, Javad; Ilghami, Roghayeh

    2016-01-01

    Metadiscourse markers (MDMs) are lexical resources that writers employ to organize their discourse and state their stance towards the content or the reader. This study investigated the frequency with which interactive and interactional MDMs were employed in biological research articles (RAs). It also explored the possible relationship between the…

  7. Increased Response Variability as a Marker of Executive Dysfunction in Veterans with Post-Traumatic Stress Disorder

    PubMed Central

    Swick, Diane; Honzel, Nikki; Larsen, Jary; Ashley, Victoria

    2015-01-01

    The stability of cognitive control processes over time can be indexed by trial-to-trial variability in reaction time (RT). Greater RT variability has been interpreted as an indicator of executive dysfunction, inhibitory inefficiency, and excessive mental noise. Previous studies have demonstrated that combat veterans with post-traumatic stress disorder (PTSD) show substantial impairments in inhibitory control, but no studies have examined response variability in this population. In the current experiment, RT variability in the Go/NoGo response inhibition task was assessed for 45 veterans with PTSD and 34 control veterans using the intra-individual coefficient of variation and ex-Gaussian analysis of RT distributions. Despite having mean RTs that were indistinguishable from controls, the PTSD patients had significantly greater RT variability, which was not solely due to attentional lapses. More variable RTs were in turn associated with a greater number of false alarm errors, suggesting that less consistent performers were less successful at inhibiting inappropriate responses. RT variability was also highly correlated with self-reported symptoms of PTSD, depression, and attentional impulsiveness. Furthermore, response variability predicted diagnosis even when controlling for PTSD symptom severity. In turn, PTSD severity was correlated with self-rated attentional impulsiveness. Deficits in the sustained attention and top-down cognitive control processes that cause greater response variability might contribute to the maintenance of PTSD symptomology. Thus, the distractibility issues that cause more variable reaction times might also result in greater distress related to the trauma. PMID:24157540

  8. Seawater Incursion Events in a Cretaceous Paleo-lake Revealed by Specific Marine Biological Markers

    PubMed Central

    Hu, J. F.; Peng, P. A.; Liu, M. Y.; Xi, D. P.; Song, J. Z.; Wan, X. Q.; Wang, C. S.

    2015-01-01

    Many large paleo-lakes in North China were formed after the Triassic Era. Seawater incursion events (SWIEs) in these lakes have been extensively discussed in the literature, yet lack reliable methodology and solid evidence, which are essential for reconstructing and confirming SWIEs. The present study employs specific marine biological markers (24-n-propyl and 24-isopropyl cholestanes) to trace SWIEs in a dated core taken from the Songliao Basin (SLB). Two SWIEs were identified. The first SWIE from 91.37 to 89.00 Ma, was continuous and variable but not strong, while the second SWIE from 84.72 to 83.72 Ma was episodic and strong. SWIEs caused high total organic carbon (TOC) and negative δ13Corg values in the sediments, which were interpreted as an indication of high productivity in the lake, due to the enhancement of nutrient supplies as well as high levels of aqueous CO2, due to the mixing of alkaline seawater and acidic lake water. The SWIEs in SLB were controlled by regional tectonic activity and eustatic variation. Movement direction changes of the Izanagi/Kula Plate in 90 Ma and 84 Ma created faults and triggered SWIEs. A high sea level, from 90 to 84 Ma, also facilitated the occurrence of SWIEs in SLB. PMID:25946976

  9. Biological marker distribution in coexisting kerogen, bitumen and asphaltenes in Monterey Formation diatomite, California

    NASA Technical Reports Server (NTRS)

    Tannenbaum, E.; Ruth, E.; Huizinga, B. J.; Kaplan, I. R.

    1986-01-01

    Organic-rich (18.2%) Monterey Formation diatomite from California was studied. The organic matter consist of 94% bitumen and 6% kerogen. Biological markers from the bitumen and from pyrolysates of the coexisting asphaltenes and kerogen were analyzed in order to elucidate the relationship between the various fractions of the organic matter. While 17 alpha(H), 18 alpha(H), 21 alpha(H)-28,30-bisnorhopane was present in the bitumen and in the pryolysate of the asphaltenes, it was not detected in the pyrolysates of the kerogen. A C40-isoprenoid with "head to head" linkage, however, was present in pyrolysates of both kerogen and asphaltenes, but not in the bitumen from the diatomite. The maturation level of the bitumen, based on the extent of isomerization of steranes and hopanes, was that of a mature oil, whereas the pyrolysate from the kerogen showed a considerably lower maturation level. These relationships indicate that the bitumen may not be indigenous to the diatomite and that it is a mature oil that migrated into the rock. We consider the possibility, however, that some of the 28,30-bisnorhopane-rich Monterey Formation oils have not been generated through thermal degradation of kerogen, but have been expelled from the source rock at an early stage of diagenesis.

  10. Seawater Incursion Events in a Cretaceous Paleo-lake Revealed by Specific Marine Biological Markers

    NASA Astrophysics Data System (ADS)

    Hu, J. F.; Peng, P. A.; Liu, M. Y.; Xi, D. P.; Song, J. Z.; Wan, X. Q.; Wang, C. S.

    2015-05-01

    Many large paleo-lakes in North China were formed after the Triassic Era. Seawater incursion events (SWIEs) in these lakes have been extensively discussed in the literature, yet lack reliable methodology and solid evidence, which are essential for reconstructing and confirming SWIEs. The present study employs specific marine biological markers (24-n-propyl and 24-isopropyl cholestanes) to trace SWIEs in a dated core taken from the Songliao Basin (SLB). Two SWIEs were identified. The first SWIE from 91.37 to 89.00 Ma, was continuous and variable but not strong, while the second SWIE from 84.72 to 83.72 Ma was episodic and strong. SWIEs caused high total organic carbon (TOC) and negative δ13Corg values in the sediments, which were interpreted as an indication of high productivity in the lake, due to the enhancement of nutrient supplies as well as high levels of aqueous CO2, due to the mixing of alkaline seawater and acidic lake water. The SWIEs in SLB were controlled by regional tectonic activity and eustatic variation. Movement direction changes of the Izanagi/Kula Plate in 90 Ma and 84 Ma created faults and triggered SWIEs. A high sea level, from 90 to 84 Ma, also facilitated the occurrence of SWIEs in SLB.

  11. Markers of Inflammation, Oxidative Stress, and Endothelial Dysfunction and the 20-year Cumulative Incidence of Early Age-related Macular Degeneration: The Beaver Dam Eye Study

    PubMed Central

    Klein, Ronald; Myers, Chelsea E.; Cruickshanks, Karen J.; Gangnon, Ronald E.; Danforth, Lorraine G.; Sivakumaran, Theru A.; Iyengar, Sudha K.; Tsai, Michael Y.; Klein, Barbara E. K.

    2014-01-01

    Importance Modifying levels of factors associated with age-related macular degeneration (AMD) may decrease risk of visual impairment in older persons. Objective To examine the relationships of markers of inflammation, oxidative stress, and endothelial dysfunction to the 20-year cumulative incidence of early AMD. Design Longitudinal population-based cohort study. Setting Beaver Dam, Wisconsin. Participants A random sample of 975 persons in the Beaver Dam Eye Study without signs of AMD who participated in the baseline examination in 1988-1990 and up to four follow-up examinations in 1993-1995, 1998-2000, 2003-2005, and 2008-2010. Exposures Serum markers of inflammation (high sensitivity C-reactive protein [hsCRP], tumor necrosis factor-α receptor 2 [TNF-αR2], interleukin-6 [IL-6], and white blood cell count), oxidative stress (8-isoprostane and total carbonyl content), and endothelial dysfunction (soluble vascular cell adhesion molecule-1 [sVCAM-1] and soluble intercellular adhesion molecule-1) were measured. Interactions with Complement Factor H (rs1061170) and Age-Related Maculopathy Susceptibility 2 (rs10490924), C3 (rs2230199) and C2/CFB (rs4151667) were examined using multiplicative models. AMD was assessed from fundus photographs. Main Outcome Measure Early AMD defined by the presence of any size drusen and the presence of pigmentary abnormalities, or by the presence of large-sized drusen (≥125 μm diameter), in the absence of late AMD. Results The 20-year cumulative incidence of early AMD was 23.0%. Adjusting for age, sex, and other risk factors, hsCRP (odds ratio [OR] comparing 4th to 1st quartile 2.18, P=0.005), TNF-αR2 (1.78, P=0.04), and IL-6 (1.78, P=0.03) were associated with the incidence of early AMD. Increased incidence of early AMD was associated with sVCAM-1 (OR per standard deviation on the log ng/mL scale 1.21, P=0.04). Conclusions and Relevance We found modest evidence of relationships of serum hsCRP, TNF-αR2, and IL-6 and sVCAM-1 to the 20

  12. Aberrant self-grooming as early marker of motor dysfunction in a rat model of Huntington's disease.

    PubMed

    Tartaglione, Anna Maria; Armida, Monica; Potenza, Rosa Luisa; Pezzola, Antonella; Popoli, Patrizia; Calamandrei, Gemma

    2016-10-15

    In the study of neurodegenerative diseases, rodent models provide experimentally accessible systems to study multiple pathogenetic aspects. The identification of early and robust behavioural changes is crucial to monitoring disease progression and testing potential therapeutic strategies in animals. Consistent experimental data support the translational value of rodent self-grooming as index of disturbed motor functions and perseverative behaviour patterns in different rodent models of brain disorders. Huntington's disease (HD) is a progressive neurodegenerative disorder, characterized by severe degeneration of basal ganglia, cognitive and psychiatric impairments and motor abnormalities. In the rat species, intrastriatal injection of the excitotoxin quinolinic acid (QA) mimics some of the neuroanatomical and behavioural changes found in HD, including the loss of GABAergic neurons and the appearance of motor and cognitive deficits. We show here that striatal damage induced by unilateral QA injection in dorsal striatum of rats triggers aberrant grooming behaviour as early as three weeks post-lesion in absence of other motor impairments: specifically, both quantitative (frequency and duration) and qualitative (the sequential pattern of movements) features of self-grooming behaviour were significantly altered in QA-lesioned rats placed in either the elevated plus-maze and the open-field. The consistent abnormalities in self-grooming recorded in two different experimental contexts support the use of this behavioural marker in rodent models of striatal damage such as HD, to assess the potential effects of drug and cell replacement therapy in the early stage of disease. PMID:27374158

  13. Does age difference really matter? Facial markers of biological quality and age difference between husband and wife.

    PubMed

    Danel, D P; Dziedzic-Danel, A; Kleisner, K

    2016-08-01

    Information conveyed by facial attractiveness markers such as averageness, bilateral symmetry, and secondary sexual characteristics may play an important adaptive role in human sexual selection. Nonetheless, mate choice also relies on other non-physical characteristics such as, for instance, an individual's age. Women prefer and enter in relationships with older partners, whereas in men the inverse relation is observed. Surprisingly, the link between facial morphological markers of biological quality on the one hand and age disparity between partners on the other hand has been as yet subject of very little research. This study aims to fill this gap. We had used facial photographs and demographic data of heterosexual marriages. Facial cues of biological quality, such as averageness, bilateral symmetry, and sexual dimorphism, were digitally measured using geometric morphometric methods and then associated with spouses' age difference. It turned out that a greater age disparity between spouses correlates, in both partners, with higher scores in facial measures which indicate partners' biological quality. One exception is female facial masculinity - generally regarded as an unattractive marker of a low biological quality - which, too, is associated with higher spouse age disparity. In general, our results show that facial symmetry, averageness, and secondary sexual characteristics may play a role in age-dependent mate choice. We suggest that in marriages where the wife is considerably younger than the husband, wife's greater facial masculinity may increase her perceived age and with it, her perceived maturity. PMID:27238548

  14. Subsensitive melatonin suppression by dim white light: possible biological marker of panic disorder.

    PubMed

    Nathan, Pradeep J.; Burrows, Graham D.; Norman, Trevor R.

    1998-12-01

    Light is involved in providing entrainment of circadian rhythms and the suppression of the pineal hormone melatonin. In patients with affective disorders, there have been indications of circadian as well as seasonal variation in illness, which may be reflected in melatonin production. Varying sensitivity to light has been noted within healthy individuals as well as in some patients with affective disorders. Recent evidence suggests that patients with panic disorder may have an altered and phase-delayed melatonin rhythm. The present study examined the nocturnal plasma melatonin rhythm in patients with panic disorder, and also examined their melatonin sensitivity to dim light. The melatonin rhythm was examined in 6 patients with panic disorder and 8 controls. The melatonin sensitivity to dim white light (200 lx) was examined in 8 patients with panic disorder and 63 controls and was compared to that of a group of 7 patients with other anxiety disorders. Patients with panic disorder demonstrated a trend towards higher and delayed peak melatonin levels compared to controls. Patients with panic disorder also had a subsensitive melatonin suppression by dim white light, compared to controls and patients with other anxiety disorders (p<0.005). The phase-delayed circadian rhythm observed in patients with panic disorder may be secondary to the subsensitivity of the melatonin response to light. It is hypothesized that the subsensitivity may be due to abnormal neurotransmitter/receptor systems involved in regulation of melatonin suppression and circadian rhythmicity, and may lead to phase- delayed circadian rhythms. The melatonin subsensitivity to light may be used as a biological marker of panic disorder. PMID:11281954

  15. Genetic Markers in Biological Fluids for Aging-Related Major Neurocognitive Disorder

    PubMed Central

    Castro-Chavira, S.A.; Fernández, T.; Nicolini, H.; Diaz-Cintra, S.; Prado-Alcalá, R.A.

    2015-01-01

    Aging-related major neurocognitive disorder (NCD), formerly named dementia, comprises of the different acquired diseases whose primary deficit is impairment in cognitive functions such as complex attention, executive function, learning and memory, language, perceptual/motor skills, and social cognition, and that are related to specific brain regions and/or networks. According to its etiology, the most common subtypes of major NCDs are due to Alzheimer’s disease (AD), vascular disease (VaD), Lewy body disease (LBD), and frontotemporal lobar degeneration (FTLD). These pathologies are frequently present in mixed forms, i.e., AD plus VaD or AD plus LBD, thus diagnosed as due to multiple etiologies. In this paper, the definitions, criteria, pathologies, subtypes and genetic markers for the most common age-related major NCD subtypes are summarized. The current diagnostic criteria consider cognitive decline leading to major NCD or dementia as a progressive degenerative process with an underlying neuropathology that begins before the manifestation of symptoms. Biomarkers associated with this asymptomatic phase are being developed as accurate risk factor and biomarker assessments are fundamental to provide timely treatment since no treatments to prevent or cure NCD yet exist. Biological fluid assessment represents a safer, cheaper and less invasive method compared to contrast imaging studies to predict NCD appearance. Genetic factors particularly have a key role not only in predicting development of the disease but also the age of onset as well as the presentation of comorbidities that may contribute to the disease pathology and trigger synergistic mechanisms which may, in turn, accelerate the neurodegenerative process and its resultant behavioral and functional disorders. PMID:25731625

  16. Airway Symptoms and Biological Markers in Nasal Lavage Fluid in Subjects Exposed to Metalworking Fluids

    PubMed Central

    Fornander, Louise; Graff, Pål; Wåhlén, Karin; Ydreborg, Kjell; Flodin, Ulf; Leanderson, Per; Lindahl, Mats; Ghafouri, Bijar

    2013-01-01

    Backgrounds Occurrence of airway irritation among industrial metal workers was investigated. The aims were to study the association between exposures from water-based metal working fluids (MWF) and the health outcome among the personnel, to assess potential effects on the proteome in nasal mucous membranes, and evaluate preventive actions. Methods The prevalence of airway symptoms related to work were examined among 271 metalworkers exposed to MWF and 24 metal workers not exposed to MWF at the same factory. At the same time, air levels of potentially harmful substances (oil mist, morpholine, monoethanolamine, formaldehyde) generated from MWF was measured. Nasal lavage fluid was collected from 13 workers and 15 controls and protein profiles were determined by a proteomic approach. Results Airway symptoms were reported in 39% of the workers exposed to MWF although the measured levels of MWF substances in the work place air were low. Highest prevalence was found among workers handling the MWF machines but also those working in the same hall were affected. Improvement of the ventilation to reduce MWF exposure lowered the prevalence of airway problems. Protein profiling showed significantly higher levels of S100-A9 and lower levels of SPLUNC1, cystatin SN, Ig J and β2-microglobulin among workers with airway symptoms. Conclusions This study confirms that upper airway symptoms among metal workers are a common problem and despite low levels of MWF-generated substances, effects on airway immune proteins are found. Further studies to clarify the role of specific MWF components in connection to airway inflammation and the identified biological markers are warranted. PMID:24391738

  17. Genetic markers in biological fluids for aging-related major neurocognitive disorder.

    PubMed

    Castro-Chavira, S A; Fernandez, T; Nicolini, H; Diaz-Cintra, S; Prado-Alcala, R A

    2015-01-01

    Aging-related major neurocognitive disorder (NCD), formerly named dementia, comprises of the different acquired diseases whose primary deficit is impairment in cognitive functions such as complex attention, executive function, learning and memory, language, perceptual/motor skills, and social cognition, and that are related to specific brain regions and/or networks. According to its etiology, the most common subtypes of major NCDs are due to Alzheimer' s disease (AD), vascular disease (VaD), Lewy body disease (LBD), and frontotemporal lobar degeneration (FTLD). These pathologies are frequently present in mixed forms, i.e., AD plus VaD or AD plus LBD, thus diagnosed as due to multiple etiologies. In this paper, the definitions, criteria, pathologies, subtypes and genetic markers for the most common age-related major NCD subtypes are summarized. The current diagnostic criteria consider cognitive decline leading to major NCD or dementia as a progressive degenerative process with an underlying neuropathology that begins before the manifestation of symptoms. Biomarkers associated with this asymptomatic phase are being developed as accurate risk factor and biomarker assessments are fundamental to provide timely treatment since no treatments to prevent or cure NCD yet exist. Biological fluid assessment represents a safer, cheaper and less invasive method compared to contrast imaging studies to predict NCD appearance. Genetic factors particularly have a key role not only in predicting development of the disease but also the age of onset as well as the presentation of comorbidities that may contribute to the disease pathology and trigger synergistic mechanisms which may, in turn, accelerate the neurodegenerative process and its resultant behavioral and functional disorders. PMID:25731625

  18. Effects of weathering on biological marker and aromatic hydrocarbon composition of organic matter in Phosphoria shale outcrop

    USGS Publications Warehouse

    Clayton, J.L.; King, J.D.

    1987-01-01

    GC-MS analyses were performed on core samples collected from a shale outcrop of the Permian Phosphoria Formation in Utah, U.S.A., to study effects of weathering on selected biological marker and aromatic (phenanthrene) hydrocarbon compounds. Among the biological markers, the most important weathering effects are a decrease in the 20S 20R diastereomer ratio of the C29 steranes and loss of low molecular weight triaromatic steroids. A decrease in the C19 through C22 tricylcic terpanes occurs relative to the total C19-C26 tricyclic fraction. Pronounced loss of methyl-substituted phenanthrenes occurs relative to phenanthrene. No major effect on the overall distribution of pentacyclic terpanes is evident. ?? 1987.

  19. Treatment of non-muscle invasive bladder cancer with Bacillus Calmette–Guerin (BCG): Biological markers and simulation studies

    PubMed Central

    Kiselyov, Alex; Bunimovich-Mendrazitsky, Svetlana; Startsev, Vladimir

    2015-01-01

    Intravesical Bacillus Calmette–Guerin (BCG) vaccine is the preferred first line treatment for non-muscle invasive bladder carcinoma (NMIBC) in order to prevent recurrence and progression of cancer. There is ongoing need for the rational selection of i) BCG dose, ii) frequency of BCG administration along with iii) synergistic adjuvant therapy and iv) a reliable set of biochemical markers relevant to tumor response. In this review we evaluate cellular and molecular markers pertinent to the immunological response triggered by the BCG instillation and respective mathematical models of the treatment. Specific examples of markers include diverse immune cells, genetic polymorphisms, miRNAs, epigenetics, immunohistochemistry and molecular biology ‘beacons’ as exemplified by cell surface proteins, cytokines, signaling proteins and enzymes. We identified tumor associated macrophages (TAMs), human leukocyte antigen (HLA) class I, a combination of Ki-67/CK20, IL-2, IL-8 and IL-6/IL-10 ratio as the most promising markers for both pre-BCG and post-BCG treatment suitable for the simulation studies. The intricate and patient-specific nature of these data warrants the use of powerful multi-parametral mathematical methods in combination with molecular/cellular biology insight and clinical input. PMID:26673853

  20. [THE CHARACTER OF EXPRESSION AND THE ROLE OF APOPTOSIS MARKERS IN THE DEVELOPMENT OF PLACENTAL DYSFUNCTION IN PREGNANT WITH UROGENITAL INFECTIONS].

    PubMed

    Shcherbuna, N; Vygovskaya, L; Kapustnik, N

    2016-02-01

    The aim of the current study was to examine the expression level and possibilities of apoptotic markers in realization of placental insufficiency in pregnant women with urogenital infections. The study was conducted on 250 pregnant women with urogenital infections (1-st group - 50 pregnant women with bacterial infections (Chlamydia, ureaplasma, mycoplasma), 2-nd group - 50 pregnant women with viral infections (CMV and herpes simplex virus), 3-rd group - 150 patients with mixed viral and bacterial infections) and 50 pregnant women with normal pregnancy. The content of apoptosis inducers: sFasL and TNF-α in blood serum of pregnant women was determined; the level of caspase-3 in placental sample was analyzed; sonographic examination of the placenta was performed. Maximal indices of apoptosis inducers were observed in the 3-rd group (with mixed viral and bacterial infections). Changes in the placenta according to ultrasound data were determined in all pregnant women with urogenital infections. It was suggested that increased placental cell death in apoptosis might be one of the key points, triggering the development of placental dysfunction. PMID:27001779

  1. The role of psychological and biological factors in postinfective gut dysfunction

    PubMed Central

    Gwee, K; Leong, Y; Graham, C; McKendrick, M; Collins, S; Walters, S; Underwood, J; Read, N

    1999-01-01

    BACKGROUND—Both psychological and physiological disturbances have been implicated in the aetiopathogenesis of irritable bowel syndrome (IBS). 
AIMS—To investigate how the psychological factors act, and the involvement of infective and physiological factors. 
METHODS—Consecutive patients hospitalised for gastroenteritis reported life events for the previous 12 months, and past illness experiences on standardised questionnaires. They also completed psychometric questionnaires for anxiety, neuroticism, somatisation, and hypochondriasis. In some patients, rectal biopsy specimens were obtained during the acute illness and at three months postinfection. 
RESULTS—Ninety four patients completed all questionnaires: 22 patients were diagnosed with IBS after their gastroenteritis (IBS+), and 72 patients returned to normal bowel habits (IBS−). IBS+ patients reported more life events and had higher hypochondriasis scores than IBS− patients. The predictive value of the life event and hypochondriasis measures was highly significant and independent of anxiety, neuroticism, and somatisation scores, which were also elevated in IBS+ patients. Rectal biopsy specimens from 29 patients showed a chronic inflammatory response in both IBS+ and IBS− patients. Three months later, specimens from IBS+ patients continued to show increased chronic inflammatory cell counts but those from IBS− patients had returned to normal levels. IBS+ and IBS− patients exhibited rectal hypersensitivity and hyper-reactivity and rapid colonic transit compared with normal controls, but there were no significant differences between IBS+ and IBS− patients for these physiological measurements. 
CONCLUSION—Psychological factors most clearly predict the development of IBS symptoms after gastroenteritis but biological mechanisms also contribute towards the expression of symptoms. 

 Keywords: irritable bowel syndrome; gastroenteritis; chronic inflammation; rectal sensitivity; intestinal

  2. A stable carbon isotope and biological marker study of Polish bituminous coals and carbonaceous shales

    USGS Publications Warehouse

    Kotarba, M.J.; Clayton, J.L.

    2003-01-01

    Biological marker and carbon isotopic compositions of coals and carbonaceous shales from the Upper Carboniferous strata of the Upper Silesian (USCB), Lower Silesian (LSCB), and Lublin (LCB) coal basins were determined to assess depositional conditions and sources of the organic matter. n-Alkane, sterane, and isoprenoid distribution, and carbon isotope ratios are consistent with an origin from higher plants. In some cases, pristane/phytane (Pr/Ph) ratios of carbonaceous shales (roof and floor shales) are < 1.0, while the associated coals have high ratios (??? 1.0). This suggests that reducing conditions prevailed during deposition of the shales, but a period of oxidizing conditions accompanied deposition of the coals. Steranes present in coal extracts are dominated by the 14??(H)17??(H)20R C29 stereoisomers, typical, but not conclusive, of higher plant origin. Carbonaceous shales exhibit a wider range of sterane composition, suggesting local, significant input of algal organic matter. Significant amounts of benzohopanes and gammacerane are present in some coals. Although benzohopanes are present at least in small amounts in samples from many different environments, they have been reported to occur most commonly in marine environments. The present study seems to provide the first example where benzohopanes have been reported in significant amounts in terrestrial organic matter. Gammacerane is abundant in rocks or sediments deposited in carbonate or highly saline marine environments. The finding of high gammacerane concentrations in the coals expands the depositional settings in which it has been observed and questions its utility as an independent indicator of hypersaline carbonate environments. Stable carbon isotope composition of coals, and type III kerogen in carbonaceous shales as well as correlation of stable carbon isotope composition of saturated and aromatic hydrocarbons in carbonaceous shales from both the USCB and the LSCB indicate terrigenous origin

  3. Biologic markers determine both the risk and the timing of recurrence in breast cancer

    PubMed Central

    Moore, Dan H.; Tsing, Pamela J.; Chu, Philip W.; Yau, Christina; Ozanne, Elissa; Chung, Robert E.; Tandon, Vickram J.; Park, John W.; Baehner, Frederick L.; Kreps, Stig; Tutt, Andrew N. J.; Gillett, Cheryl E.; Benz, Christopher C.

    2015-01-01

    Breast cancer has a long natural history. Established and emerging biologic markers address overall risk but not necessarily timing of recurrence. 346 adjuvant naïve breast cancer cases from Guy’s Hospital with 23 years minimum follow-up and archival blocks were recut and reassessed for hormone-receptors (HR), HER2-receptor and grade. Disease-specific survival (DSS) was analyzed by recursive partitioning. To validate insights from this analysis, gene-signatures (proliferative and HR-negative) were evaluated for their ability to predict early versus late metastatic risk in 683 node-negative, adjuvant naïve breast cancers annotated with expression microarray data. Risk partitioning showed that adjuvant naïve node-negative outcome risk was primarily partitioned by tumor receptor status and grade but not tumor size. HR-positive and HER2-negative (HRpos) risk was partitioned by tumor grade; low grade cases have very low early risk but a 20% fall-off in DSS 10 or more years after diagnosis. Higher grade HRpos cases have risk over >20 years. Triple-negative (Tneg) and HER2-positive (HER2pos) cases DSS events occurred primarily within the first 5 years. Among node-positive cases, only low grade conferred late risk, suggesting that proliferative gene signatures that identify proliferation would be important for predicting early but not late recurrence. Using pooled data from four publicly available data sets for node-negative tumors annotated with gene expression and outcome data, we evaluated four prognostic gene signatures: two proliferation-based and two immune function-based. Tumor proliferative capacity predicted early but not late metastatic risk for HRpos cases. The immune function or HRneg specific signatures predicted only early metastatic risk in Tneg and HER2pos cases. Breast cancer prognostic signatures need to inform both risk and timing of metastatic events and may best be applied within subsets. Current signatures predict for outcome risk within 5 years

  4. Correlation between iodine-131 MIBG imaging and biological markers in advanced neuroblastoma

    SciTech Connect

    Yeh, S.D.; Helson, L.; Benua, R.S.

    1988-01-01

    I-131 metaiodobenzylguanidine (MIBG) imaging was performed in 38 patients with advanced neuroblastoma. Abnormal images were found in patients with elevations of urinary vanillylmandelic acid and dopamine and high serum neuron-specific enolase levels. Normal or minimal elevation of markers was seen in patients with negative images. In follow-up studies after chemotherapy, the disappearance of abnormal uptake was noted in those patients with normal marker values. A persistently abnormal uptake occurred in patients with high marker values. Conversion from a normal image to an abnormal image also occurred in patients whose markers became elevated. I-131 MIBG imaging is sensitive in detecting active foci of a neuroblastoma and is useful in monitoring chemotherapy in these patients.

  5. Interdependencies among Selected Pro-Inflammatory Markers of Endothelial Dysfunction, C-Peptide, Anti-Inflammatory Interleukin-10 and Glucose Metabolism Disturbance in Obese Women

    PubMed Central

    Janowska, Joanna; Chudek, Jerzy; Olszanecka-Glinianowicz, Magdalena; Semik-Grabarczyk, Elżbieta; Zahorska-Markiewicz, Barbara

    2016-01-01

    Background: Currently increasing importance is attributed to the inflammatory process as a crucial factor responsible for the progressive damage to vascular walls and progression of atherosclerosis in obese people. We have studied the relationship between clinical and biochemical parameters and C-peptide and anti-inflammatory IL-10, as well as selected markers of inflammation and endothelial dysfunction such as: CCL2, CRP, sICAM-1, sVCAM-1 and E-selectin in obese women with various degree of glucose metabolism disturbance. Material and methods: The studied group consisted of 61 obese women, and 20 normal weight, healthy volunteers. Obese patients were spited in subgroups based on the degree of glucose metabolism disorder. Serum samples were analyzed using ELISA kits. Results: Increased concentrations of sICAM-1, sVCAM-1, E-selectin, CCL2 and CRP were found in all obese groups compared to the normal weight subjects. In patients with Type 2 diabetes mellitus (T2DM) parameters characterizing the degree of obesity significantly positively correlated with levels of CRP and CCL2. Significant relationships were found between levels of glucose and sICAM-1and also E-selectin and HOMA-IR. C-peptide levels are positively associated with CCL2, E-selectin, triglycerides levels, and inversely with IL-10 levels in newly diagnosed T2DM group (p<0.05). Concentrations of IL-10 correlated negatively with E-selectin, CCL2, C-peptide levels, and HOMA-IR in T2DM group (p<0.05). Conclusion: Disturbed lipid and carbohydrate metabolism are manifested by enhanced inflammation and endothelial dysfunction in patients with simply obesity. These disturbances are associates with an increase of adhesion molecules. The results suggest the probable active participation of higher concentrations of C-peptide in the intensification of inflammatory and atherogenic processes in obese patients with type 2 diabetes. In patients with obesity and type 2 diabetes, altered serum concentrations of Il-10 seems

  6. Evaluation of biochemical and clinical markers of endothelial dysfunction and their correlation with urinary albumin excretion in patients with type 1 diabetes mellitus.

    PubMed

    Polat, Sefika Burcak; Ugurlu, Nagihan; Aslan, Nabi; Cuhaci, Neslihan; Ersoy, Reyhan; Cakir, Bekir

    2016-04-01

    Objective Endothelial dysfunction (ED) plays an important role in the pathogenesis of diabetic nephropathy. The purpose of the study was to determine flow mediated endothelial dependent vasodilatation (FMD) measurements and serum soluble (s) endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) levels in patients with type 1 diabetes mellitus (T1DM) with or without increased urinary albumin excretion (UAE) and compare them with the healthy controls. Subjects and methods Seventy three patients with T1DM were enrolled. Patients were divided into two subgroups according to microalbumin measurements in 24-hr urine collections. The diabetic patients without microalbuminuria (41 patients) were defined as Group I and those with microalbuminuria (32 patients) were defined as group II. A hundred age and sex matched healthy subjects participated as the control group (Group III). Serum sET-1, sICAM-1, sVCAM-1 levels and FMD measurements were determined in all participants. Results Median FMD measurement was significantly lower in the diabetic groups compared with the control group (6.6, 6.4 and 7.8% in Group I, II and III, respectively) (p < 0.05). FMD was negatively correlated with age (p = 0.042). Median serum sICAM-1 level was higher in the patient groups compared to the control group (p < 0.05). Median serum sVCAM-1 level was higher in the group of patients with increased albuminuria compared to the normoalbuinuric and the control group (p < 0.05). Serum sVCAM-1 level was found to be positively correlated with degree of urinary albumin excretion (p < 0.001). Conclusion We assume that sVCAM-1 may be used as a predictive marker for risk stratification for nephropathy development and progression. PMID:26886090

  7. Urinary Dysfunction

    MedlinePlus

    ... PCF Spotlight Glossary African American Men Living with Prostate Cancer Urinary Dysfunction Side Effects Urinary Dysfunction Bowel Dysfunction ... dysfunction is normal following initial therapy for localized prostate cancer. But it’s important to realize that not all ...

  8. [Biological properties of the mumps virus. Behavior using the T50 marker].

    PubMed

    Glathe, H; Nöbel, B

    1977-01-01

    The authors studied the behaviour of 11 mumps virus strains or variants including the thermolabile standard Jeryl Lynn strain under thermal charge (50 degrees C/30 min). Varants were obtained from the Soviet vaccinal strains Leningrad-3 by cultivation under various conditions. Incubation temperature and cellular substrate played an important role therein. Variants with various behaviour in the marker T50 resulted. It was found that passages at 32 degrees C at limited dilutions as well as those on chick embryos or in cultures of chicken fibroblasts increased their thermolability. Possible correlations between their behaviour in the marker T50 and the degree of di attenuation are discussed. (Ta) PMID:562370

  9. Biological markers during early pregnancy: trophoblastic signals of the peri-implantation period

    SciTech Connect

    Glasser, S.R.; Julian, J.; Munir, M.I.; Soares, M.J.

    1987-10-01

    The peri-implantation period extends from the time the blastocyst is free in the uterus, through the processes of recognition and attachment, to the beginning of trophoblast differentiation and the interactions between the embryo and the uterine endometrium which initiate establishment of the hemochorial placenta. It is during the peri-implantation period that the embryo and hormonally regulated endometrial cells appear to be most sensitive to factors which introduce risk into the intrauterine environment. There are no markers which can be used practically to assess pregnancy risk during the peri-implantation period of either human or laboratory rodents. Experimental studies, using in vitro laboratory models of differentiating trophoblasst cells, have identified peptide hormone markers of pivotal developmental processes. Exposure of trophoblast during the expression of these processes could have severe and far-reaching effects individually and societally. Human chorionic gonadotropin (hCG) has been used extensively as a marker to assess risk during the early stages of pregnancy. Extrapolation of experimental data indicates how hCG could be used more effectively in analyses of possible cause and effect relationships. The limitations of hCG as a marker for risk during the human peri-implantation period are discussed. Peptide hormones which could serve to assess risk during this critical period of extraordinary sensitivity to toxic factors are introduced.

  10. Biological markers during early pregnancy: trophoblastic signals of the peri-implantation period.

    PubMed Central

    Glasser, S R; Julian, J; Munir, M I; Soares, M J

    1987-01-01

    The peri-implantation period extends from the time the blastocyst is free in the uterus, through the processes of recognition and attachment, to the beginning of trophoblast differentiation and the interactions between the embryo and the uterine endometrium which initiate establishment of the hemochorial placenta. It is during the peri-implantation period that the embryo and hormonally regulated endometrial cells appear to be most sensitive to factors which introduce risk into the intrauterine environment. There are no markers which can be used practically to assess pregnancy risk during the peri-implantation period of either human or laboratory rodents. Experimental studies, using in vitro laboratory models of differentiating trophoblast cells, have identified peptide hormone markers of pivotal developmental processes. Exposure of trophoblast during the expression of these processes could have severe and far-reaching effects individually and societally. While these trophoblast signals are limited in their utility with respect to health monitoring extrapolation of these findings to human pregnancy, the signals could serve to identify more practical and sensitive markers to assess risk in early gestation. Human chorionic gonadotropin (hCG) has been used extensively as a marker to assess risk during the early stages of pregnancy. Extrapolation of experimental data indicates how hCG could be used more effectively in analyses of possible cause and effect relationships. The limitations of hCG as a marker for risk during the human peri-implantation period are discussed. Peptide hormones which could serve to assess risk during this critical period of extraordinary sensitivity to toxic factors are introduced. PMID:3319548

  11. Environmental DNA Marker Development with Sparse Biological Information: A Case Study on Opossum Shrimp (Mysis diluviana)

    PubMed Central

    Carim, Kellie J.; Christianson, Kyle R.; McKelvey, Kevin M.; Pate, William M.; Silver, Douglas B.; Johnson, Brett M.; Galloway, Bill T.; Young, Michael K.; Schwartz, Michael K.

    2016-01-01

    The spread of Mysis diluviana, a small glacial relict crustacean, outside its native range has led to unintended shifts in the composition of native fish communities throughout western North America. As a result, biologists seek accurate methods of determining the presence of M. diluviana, especially at low densities or during the initial stages of an invasion. Environmental DNA (eDNA) provides one solution for detecting M. diluviana, but building eDNA markers that are both sensitive and species-specific is challenging when the distribution and taxonomy of closely related non-target taxa are poorly understood, published genetic data are sparse, and tissue samples are difficult to obtain. To address these issues, we developed a pair of independent eDNA markers to increase the likelihood of a positive detection of M. diluviana when present and reduce the probability of false positive detections from closely related non-target species. Because tissue samples of closely-related and possibly sympatric, non-target taxa could not be obtained, we used synthetic DNA sequences of closely related non-target species to test the specificity of eDNA markers. Both eDNA markers yielded positive detections from five waterbodies where M. diluviana was known to be present, and no detections in five others where this species was thought to be absent. Daytime samples from varying depths in one waterbody occupied by M. diluviana demonstrated that samples near the lake bottom produced 5 to more than 300 times as many eDNA copies as samples taken at other depths, but all samples tested positive regardless of depth. PMID:27551919

  12. Environmental DNA Marker Development with Sparse Biological Information: A Case Study on Opossum Shrimp (Mysis diluviana).

    PubMed

    Carim, Kellie J; Christianson, Kyle R; McKelvey, Kevin M; Pate, William M; Silver, Douglas B; Johnson, Brett M; Galloway, Bill T; Young, Michael K; Schwartz, Michael K

    2016-01-01

    The spread of Mysis diluviana, a small glacial relict crustacean, outside its native range has led to unintended shifts in the composition of native fish communities throughout western North America. As a result, biologists seek accurate methods of determining the presence of M. diluviana, especially at low densities or during the initial stages of an invasion. Environmental DNA (eDNA) provides one solution for detecting M. diluviana, but building eDNA markers that are both sensitive and species-specific is challenging when the distribution and taxonomy of closely related non-target taxa are poorly understood, published genetic data are sparse, and tissue samples are difficult to obtain. To address these issues, we developed a pair of independent eDNA markers to increase the likelihood of a positive detection of M. diluviana when present and reduce the probability of false positive detections from closely related non-target species. Because tissue samples of closely-related and possibly sympatric, non-target taxa could not be obtained, we used synthetic DNA sequences of closely related non-target species to test the specificity of eDNA markers. Both eDNA markers yielded positive detections from five waterbodies where M. diluviana was known to be present, and no detections in five others where this species was thought to be absent. Daytime samples from varying depths in one waterbody occupied by M. diluviana demonstrated that samples near the lake bottom produced 5 to more than 300 times as many eDNA copies as samples taken at other depths, but all samples tested positive regardless of depth. PMID:27551919

  13. Micro-RNAs Let7e and 126 in Plasma as Markers of Metabolic Dysfunction in 10 to 12 Years Old Children

    PubMed Central

    Krause, Bernardo J.; Carrasco-Wong, Ivo; Dominguez, Angélica; Arnaiz, Pilar; Farías, Marcelo; Barja, Salesa; Mardones, Francisco; Casanello, Paola

    2015-01-01

    Background Growing evidence shows that metabolic syndrome (MetS) is already starting in childhood however there is no consensus regarding how to diagnose this condition in pediatric population. Studies in adults show that altered levels of specific micro-RNAs are related with components of the MetS. Objective We determined the plasma levels of four MetS-associated micro-RNAs (miR-126, miR-132, mir-145 and Let-7e) in 10 to 12 years old children with or without MetS traits. Design Pediatric subjects were selected from a cohort of 3325 school-age children, and clustered by the absence (control, n = 30), or the presence of 1 (n = 50), 2 (n = 41) or 3 (n = 35) MetS traits according to Cook´s criteria. Micro-RNAs were isolated from plasma, and levels of miR-126, miR-132, miR-145 and Let-7e were determined by Taqman qPCR. Results Regression analysis of the different MetS traits regarding the different miRNAs analyzed showed that Let-7e presented a negative association with HDL-C levels, but a positive correlation with the number of MetS traits. Levels of miR-126 presented a positive correlation with waist circumference, waist to hip ratio, BMI, and plasma triglycerides and VLDL-C. Levels of miR-132 showed a positive correlation with waist to hip ratio. Plasma levels of Let-7e were increased (~3.4 fold) in subjects with 3 MetS traits, and showed significant AUC (0.681; 95%CI = [0.58, 0.78]; p < 0.001) in the ROC analysis which were improved when miR-126 was included in the analysis (AUC 0.729; p < 0.001). In silico analysis of the interaction of proteins derived from mRNAs targeted by Let7 and miR-126 showed an important effect of both Let-7e and miR-126 regulating the insulin signaling pathway. Conclusions These results suggest that changes in the plasma levels of Let-7e and miR-126 could represent early markers of metabolic dysfunction in children with MetS traits. PMID:26046362

  14. Biological and Chemical Removal of Primary Cilia Affects Mechanical Activation of Chondrogenesis Markers in Chondroprogenitors and Hypertrophic Chondrocytes

    PubMed Central

    Deren, Matthew E.; Yang, Xu; Guan, Yingjie; Chen, Qian

    2016-01-01

    Chondroprogenitors and hypertrophic chondrocytes, which are the first and last stages of the chondrocyte differentiation process, respectively, are sensitive to mechanical signals. We hypothesize that the mechanical sensitivity of these cells depends on the cell surface primary cilia. To test this hypothesis, we removed the primary cilia by biological means with transfection with intraflagellar transport protein 88 (IFT88) siRNA or by chemical means with chloral hydrate treatment. Transfection of IFT88 siRNA significantly reduced the percentage of ciliated cells in both chondroprogenitor ATDC5 cells as well as primary hypertrophic chondrocytes. Cyclic loading (1 Hz, 10% matrix deformation) of ATDC5 cells in three-dimensional (3D) culture stimulates the mRNA levels of chondrogenesis marker Type II collagen (Col II), hypertrophic chondrocyte marker Type X collagen (Col X), and a molecular regulator of chondrogenesis and chondrocyte hypertrophy bone morphogenetic protein 2 (BMP-2). The reduction of ciliated chondroprogenitors abolishes mechanical stimulation of Col II, Col X, and BMP-2. In contrast, cyclic loading stimulates Col X mRNA levels in hypertrophic chondrocytes, but not those of Col II and BMP-2. Both biological and chemical reduction of ciliated hypertrophic chondrocytes reduced but failed to abolish mechanical stimulation of Col X mRNA levels. Thus, primary cilia play a major role in mechanical stimulation of chondrogenesis and chondrocyte hypertrophy in chondroprogenitor cells and at least a partial role in hypertrophic chondrocytes. PMID:26861287

  15. Perspective Biological Markers for Autism Spectrum Disorders: Advantages of the Use of Receiver Operating Characteristic Curves in Evaluating Marker Sensitivity and Specificity

    PubMed Central

    2015-01-01

    Autism Spectrum Disorders (ASD) are a heterogeneous group of neurodevelopmental disorders. Recognized causes of ASD include genetic factors, metabolic diseases, toxic and environmental factors, and a combination of these. Available tests fail to recognize genetic abnormalities in about 70% of ASD children, where diagnosis is solely based on behavioral signs and symptoms, which are difficult to evaluate in very young children. Although it is advisable that specific psychotherapeutic and pedagogic interventions are initiated as early as possible, early diagnosis is hampered by the lack of nongenetic specific biological markers. In the past ten years, the scientific literature has reported dozens of neurophysiological and biochemical alterations in ASD children; however no real biomarker has emerged. Such literature is here reviewed in the light of Receiver Operating Characteristic (ROC) analysis, a very valuable statistical tool, which evaluates the sensitivity and the specificity of biomarkers to be used in diagnostic decision making. We also apply ROC analysis to some of our previously published data and discuss the increased diagnostic value of combining more variables in one ROC curve analysis. We also discuss the use of biomarkers as a tool for advancing our understanding of nonsyndromic ASD. PMID:26648598

  16. High intensity exercise affects diurnal variation of some biological markers in trained subjects.

    PubMed

    Hammouda, O; Chtourou, H; Chahed, H; Ferchichi, S; Chaouachi, A; Kallel, C; Miled, A; Chamari, K; Souissi, N

    2012-11-01

    The study investigated if markers of muscle injury and antioxidant status were affected by a Wingate test performed at 2 different times of day. 15 young male footballers performed 2 tests (randomized) at 07:00-h and 17:00-h. Fasting blood samples were collected before and 3 min after each test for assessment of markers of muscle injury and antioxidant status. Resting oral temperature was recorded during each session. Peak power (10.76 ± 1.05 vs. 11.15 ± 0.83 W.kg( - 1)) and fatigue index (0.41 ± 0.04 vs. 0.49 ± 0.13%) during the Wingate test, and core temperature, were significantly higher (all p<0.05) in the evening. Markers of muscle injury were significantly higher in the evening before and after exercise (e. g., 148.7 ± 67.05 vs. 195 ± 74.6 and 191.6 ± 79.52 vs. 263.6 ± 96.06 IU.L (- 1), respectively, for creatine kinase; both p<0.001). Antioxidant parameters increased after the Wingate test but only resting values were significantly higher in the morning (e. g., 1.33 ± 0.19 vs. 1.19 ± 0.14 µmol.L (- 1) for total antioxidant status; p<0.05). The results indicate that muscle injury and antioxidant activity after the Wingate test were higher in the evening, suggesting a possible link between the biochemical measures and the diurnal fluctuation of anaerobic performance. However, repetition of this study after prescribed rather than self-selected exercise intensity is recommended. PMID:22791622

  17. Bowel Dysfunction

    MedlinePlus

    ... PCF Spotlight Glossary African American Men Living with Prostate Cancer Bowel Dysfunction Side Effects Urinary Dysfunction Bowel Dysfunction ... rectal worse. Back to Side Effects Print | Understanding Prostate Cancer Research Faces of Prostate Cancer About PCF Take ...

  18. Eye Blink Rate as a biological marker of Mild Cognitive Impairment.

    PubMed

    Ladas, Aristea; Frantzidis, Christos; Bamidis, Panagiotis; Vivas, Ana B

    2014-07-01

    We investigated the relationship between dopamine activity (DA), as measured by Eye Blink Rate (EBR), and cognitive function in old adults with Mild Cognitive Impairment (MCI) and healthy controls. Research has been inconclusive so far about the factors responsible for the transition from MCI to dementia. However, some studies suggest that cortical hyperexcitability in very early stages of pathological aging may progressively lead to cell death, and thus to Alzheimer's disease. Hence, we speculated that a dysfunction of DA activity, as measured by EBR, may characterize people with MCI, and account for their poor cognitive function. Thirty three (33) healthy and thirty six (36) old adults with MCI (Mean age = 67.52 y.o.) participated in this study. The EBR was recorded under resting conditions, using two gold skin electrodes above and below the left eye. Cognitive function was assessed with a battery of neuropsychological tests. Participants with MCI showed significantly higher EBR than the healthy controls. Also, EBR was negatively related to scores on the Montreal Cognitive Assessment test (MoCA) test. We propose that abnormally increased dopamine activity, as indexed by relatively high EBR, may be partially responsible for the neurotransmitter imbalance in the central nervous system of people with MCI, and the overall impaired cognitive performance. In addition, this finding suggests that an abnormally high EBR may be a potential biomarker of the transition from healthy aging to dementia. PMID:23912068

  19. A multimodal imaging workflow to visualize metal mixtures in the human placenta and explore colocalization with biological response markers.

    PubMed

    Niedzwiecki, Megan M; Austin, Christine; Remark, Romain; Merad, Miriam; Gnjatic, Sacha; Estrada-Gutierrez, Guadalupe; Espejel-Nuñez, Aurora; Borboa-Olivares, Hector; Guzman-Huerta, Mario; Wright, Rosalind J; Wright, Robert O; Arora, Manish

    2016-04-01

    Fetal exposure to essential and toxic metals can influence life-long health trajectories. The placenta regulates chemical transmission from maternal circulation to the fetus and itself exhibits a complex response to environmental stressors. The placenta can thus be a useful matrix to monitor metal exposures and stress responses in utero, but strategies to explore the biologic effects of metal mixtures in this organ are not well-developed. In this proof-of-concept study, we used laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to measure the distributions of multiple metals in placental tissue from a low-birth-weight pregnancy, and we developed an approach to identify the components of metal mixtures that colocalized with biological response markers. Our novel workflow, which includes custom-developed software tools and algorithms for spatial outlier identification and background subtraction in multidimensional elemental image stacks, enables rapid image processing and seamless integration of data from elemental imaging and immunohistochemistry. Using quantitative spatial statistics, we identified distinct patterns of metal accumulation at sites of inflammation. Broadly, our multiplexed approach can be used to explore the mechanisms mediating complex metal exposures and biologic responses within placentae and other tissue types. Our LA-ICP-MS image processing workflow can be accessed through our interactive R Shiny application 'shinyImaging', which is available at or through our laboratory's website, . PMID:26987553

  20. Biological (molecular and cellular) markers of toxicity. Final report, September 15, 1988--September 14, 1991

    SciTech Connect

    Shugart, L.R.; D`Surney, S.J.; Gettys-Hull, C.; Greeley, M.S. Jr.

    1991-12-15

    Several molecular and cellular markers of genotoxicity were adapted for measurement in the Medaka (Oryzias latipes), and were used to describe the effects of treatment of the organism with diethylnitrosamine (DEN). NO{sup 6}-ethyl guanine adducts were detected, and a slight statistically significant, increase in DNA strand breaks was observed. These results are consistent with the hypothesis that prolonged exposure to high levels of DEN induced alkyltransferase activity which enzymatically removes any O{sup 6}-ethyl guanine adducts but does not result in strand breaks or hypomethylation of the DNA such as might be expected from excision repair of chemically modified DNA. Following a five week continuous DEN exposure with 100 percent renewal of DEN-water every third day, the F values (DNA double strandedness) increased considerably and to similar extent in fish exposed to 25, 50, and 100 ppM DEN. This has been observed also in medaka exposed to BaP.

  1. A systematic review of secondhand smoke exposure in a car: Attributable changes in atmospheric and biological markers.

    PubMed

    Raoof, Sana A; Agaku, Israel T; Vardavas, Constantine I

    2015-05-01

    Exposure to secondhand smoke (SHS) has been linked to disease, disability, and premature death. While several countries have enacted smoke-free legislations, exposure to SHS may still occur in unregulated private environments, such as in the family car. We performed a systematic review of peer-reviewed literature in PubMed and Web of Science up to May 2013. Articles were selected if they provided a quantitative measure of SHS exposure (biological or atmospheric markers); the study was conducted inside a car; and the assessed exposure was attributable to cigarette combustion. From 202 articles identified, 12 met the inclusion criteria. Among all studies that assessed smoking in cars with at least one window partially open, the particulate matter 2.5 μm or less in diameter (PM2.5) concentrations ranged from 47 μg/m(3) to 12,150 μg/m(3). For studies with all windows closed, PM2.5 ranged from 203.6 μg/m(3) to 13,150 μg/m(3). SHS concentration in a car was mediated by air-conditioning status, extent of airflow, and driving speed. Smoking in cars leads to extremely high exposure to SHS and increased concentration of atmospheric markers of exposure-even in the presence of air-conditioning or increased airflow from open windows. This clearly shows that the only way to protect nonsmokers, especially children, from SHS within cars is by eliminating tobacco smoking. PMID:25758677

  2. A life course approach to explore the biological embedding of socioeconomic position and social mobility through circulating inflammatory markers

    PubMed Central

    Castagné, Raphaële; Delpierre, Cyrille; Kelly-Irving, Michelle; Campanella, Gianluca; Guida, Florence; Krogh, Vittorio; Palli, Domenico; Panico, Salvatore; Sacerdote, Carlotta; Tumino, Rosario; Kyrtopoulos, Soterios; Hosnijeh, Fatemeh Saberi; Lang, Thierry; Vermeulen, Roel; Vineis, Paolo; Stringhini, Silvia; Chadeau-Hyam, Marc

    2016-01-01

    Lower socioeconomic position (SEP) has consistently been associated with poorer health. To explore potential biological embedding and the consequences of SEP experiences from early life to adulthood, we investigate how SEP indicators at different points across the life course may be related to a combination of 28 inflammation markers. Using blood-derived inflammation profiles measured by a multiplex array in 268 participants from the Italian component of the European Prospective Investigation into Cancer and Nutrition cohort, we evaluate the association between early life, young adulthood and later adulthood SEP with each inflammatory markers separately, or by combining them into an inflammatory score. We identified an increased inflammatory burden in participants whose father had a manual occupation, through increased plasma levels of CSF3 (G-CSF; β = 0.29; P = 0.002), and an increased inflammatory score (β = 1.96; P = 0.029). Social mobility was subsequently modelled by the interaction between father’s occupation and the highest household occupation, revealing a significant difference between “stable Non-manual” profiles over the life course versus “Manual to Non-manual” profiles (β = 2.38, P = 0.023). Low SEP in childhood is associated with modest increase in adult inflammatory burden; however, the analysis of social mobility suggests a stronger effect of an upward social mobility over the life course. PMID:27117519

  3. Evolving Evidence for the Value of Neuroimaging Methods and Biological Markers in Subjects Categorized with Subjective Cognitive Decline.

    PubMed

    Lista, Simone; Molinuevo, Jose L; Cavedo, Enrica; Rami, Lorena; Amouyel, Philippe; Teipel, Stefan J; Garaci, Francesco; Toschi, Nicola; Habert, Marie-Odile; Blennow, Kaj; Zetterberg, Henrik; O'Bryant, Sid E; Johnson, Leigh; Galluzzi, Samantha; Bokde, Arun L W; Broich, Karl; Herholz, Karl; Bakardjian, Hovagim; Dubois, Bruno; Jessen, Frank; Carrillo, Maria C; Aisen, Paul S; Hampel, Harald

    2015-09-24

    There is evolving evidence that individuals categorized with subjective cognitive decline (SCD) are potentially at higher risk for developing objective and progressive cognitive impairment compared to cognitively healthy individuals without apparent subjective complaints. Interestingly, SCD, during advancing preclinical Alzheimer's disease (AD), may denote very early, subtle cognitive decline that cannot be identified using established standardized tests of cognitive performance. The substantial heterogeneity of existing SCD-related research data has led the Subjective Cognitive Decline Initiative (SCD-I) to accomplish an international consensus on the definition of a conceptual research framework on SCD in preclinical AD. In the area of biological markers, the cerebrospinal fluid signature of AD has been reported to be more prevalent in subjects with SCD compared to healthy controls; moreover, there is a pronounced atrophy, as demonstrated by magnetic resonance imaging, and an increased hypometabolism, as revealed by positron emission tomography, in characteristic brain regions affected by AD. In addition, SCD individuals carrying an apolipoprotein ɛ4 allele are more likely to display AD-phenotypic alterations. The urgent requirement to detect and diagnose AD as early as possible has led to the critical examination of the diagnostic power of biological markers, neurophysiology, and neuroimaging methods for AD-related risk and clinical progression in individuals defined with SCD. Observational studies on the predictive value of SCD for developing AD may potentially be of practical value, and an evidence-based, validated, qualified, and fully operationalized concept may inform clinical diagnostic practice and guide earlier designs in future therapy trials. PMID:26402088

  4. Biological effect of dose distortion by fiducial markers in spot-scanning proton therapy with a limited number of fields: A simulation study

    SciTech Connect

    Matsuura, Taeko; Maeda, Kenichiro; Sutherland, Kenneth; Takayanagi, Taisuke; Shimizu, Shinichi; Takao, Seishin; Miyamoto, Naoki; Nihongi, Hideaki; Toramatsu, Chie; Nagamine, Yoshihiko; Fujimoto, Rintaro; Suzuki, Ryusuke; Ishikawa, Masayori; Umegaki, Kikuo; Shirato, Hiroki

    2012-09-15

    Purpose: In accurate proton spot-scanning therapy, continuous target tracking by fluoroscopic x ray during irradiation is beneficial not only for respiratory moving tumors of lung and liver but also for relatively stationary tumors of prostate. Implanted gold markers have been used with great effect for positioning the target volume by a fluoroscopy, especially for the cases of liver and prostate with the targets surrounded by water-equivalent tissues. However, recent studies have revealed that gold markers can cause a significant underdose in proton therapy. This paper focuses on prostate cancer and explores the possibility that multiple-field irradiation improves the underdose effect by markers on tumor-control probability (TCP). Methods: A Monte Carlo simulation was performed to evaluate the dose distortion effect. A spherical gold marker was placed at several characteristic points in a water phantom. The markers were with two different diameters of 2 and 1.5 mm, both visible on fluoroscopy. Three beam arrangements of single-field uniform dose (SFUD) were examined: one lateral field, two opposite lateral fields, and three fields (two opposite lateral fields + anterior field). The relative biological effectiveness (RBE) was set to 1.1 and a dose of 74 Gy (RBE) was delivered to the target of a typical prostate size in 37 fractions. The ratios of TCP to that without the marker (TCP{sub r}) were compared with the parameters of the marker sizes, number of fields, and marker positions. To take into account the dependence of biological parameters in TCP model, {alpha}/{beta} values of 1.5, 3, and 10 Gy (RBE) were considered. Results: It was found that the marker of 1.5 mm diameter does not affect the TCPs with all {alpha}/{beta} values when two or more fields are used. On the other hand, if the marker diameter is 2 mm, more than two irradiation fields are required to suppress the decrease in TCP from TCP{sub r} by less than 3%. This is especially true when multiple

  5. SPR imaging biosensor for determination of laminin-5 as a potential cancer marker in biological material.

    PubMed

    Sankiewicz, A; Romanowicz, L; Laudanski, P; Zelazowska-Rutkowska, B; Puzan, B; Cylwik, B; Gorodkiewicz, E

    2016-07-01

    A new method for the selective determination of laminin-5 concentration using a biosensor and surface plasmon resonance imaging (SPRI) technique is presented. A biosensor based on the specific interaction of laminin-5 with rabbit polyclonal antibody was constructed. The analytically useful dynamic response range of the biosensor is between 0.014 and 0.1 ng mL(-1). The detection limit is 4 pg mL(-1). The potential influence of interferences on the SPRI signal was investigated, and the high selectivity of the biosensor was confirmed. In order to demonstrate the potential application of the biosensor, laminin-5 concentration in blood plasma was determined. The results were compared with the laminin-5 concentration obtained by the commercial enzyme-linked immunosorbent assay (ELISA) kit. A comparison of results from healthy donors obtained by SPRI measurement and ELISA indicates that they are close and shows good agreement with the data reported in the literature. The plasma samples of bladder cancer patients gave higher concentration measured with specific biosensor than by ELISA assay. The study shows the clear difference in concentration of laminin-5 in healthy humans and patients with bladder cancer. Extensive clinical studies using the newly developed method can result in an increase in the use of laminin-5 as a potential cancer marker. PMID:27209594

  6. Extended morphological processing: a practical method for automatic spot detection of biological markers from microscopic images

    PubMed Central

    2010-01-01

    Background A reliable extraction technique for resolving multiple spots in light or electron microscopic images is essential in investigations of the spatial distribution and dynamics of specific proteins inside cells and tissues. Currently, automatic spot extraction and characterization in complex microscopic images poses many challenges to conventional image processing methods. Results A new method to extract closely located, small target spots from biological images is proposed. This method starts with a simple but practical operation based on the extended morphological top-hat transformation to subtract an uneven background. The core of our novel approach is the following: first, the original image is rotated in an arbitrary direction and each rotated image is opened with a single straight line-segment structuring element. Second, the opened images are unified and then subtracted from the original image. To evaluate these procedures, model images of simulated spots with closely located targets were created and the efficacy of our method was compared to that of conventional morphological filtering methods. The results showed the better performance of our method. The spots of real microscope images can be quantified to confirm that the method is applicable in a given practice. Conclusions Our method achieved effective spot extraction under various image conditions, including aggregated target spots, poor signal-to-noise ratio, and large variations in the background intensity. Furthermore, it has no restrictions with respect to the shape of the extracted spots. The features of our method allow its broad application in biological and biomedical image information analysis. PMID:20615231

  7. CD66b Overexpression and Loss of C5a Receptors as Surface Markers for Staphylococcus aureus-Induced Neutrophil Dysfunction

    PubMed Central

    Schnitzler, Norbert; Grüger, Thomas; Brandenburg, Kerstin; Zinserling, Jörg; Zündorf, Josef

    2015-01-01

    Neutrophil granulocytes constitute the main component of innate immunity in the clearance of bacterial infections. However, during systemic inflammation, immunoparalysis may occur resulting in neutrophil dysfunction. This study presents a new in vitro model for analyzing the dysfunction of human peripheral blood neutrophils resulting from the interaction with Staphylococcus aureus components in whole blood. After induction of a massive complement activation by S. aureus supernatant, the neutrophils exhibit a reduced phagocytic capacity resulting in a dramatic reduction of the antibacterial activity similar to that of neutrophils isolated from septic patients. The number of phagocytozing neutrophils is drastically reduced as well as the phagocytic capacity designated by a significantly lower number of ingested microbes. This dysfunction correlates with the loss of complement component 5a receptor 1 from the neutrophil cell surface and can be further characterized by a C5a-induced CD66b overexpression. The presented in vitro model offers a new platform for preclinical testing of immunosuppressive drugs and delivers new information for the understanding of neutrophil dysfunctions under the conditions described. PMID:26176669

  8. Chronic mental stress is a cause of essential hypertension: presence of biological markers of stress.

    PubMed

    Esler, Murray; Eikelis, Nina; Schlaich, Markus; Lambert, Gavin; Alvarenga, Marlies; Dawood, Tye; Kaye, David; Barton, David; Pier, Ciaran; Guo, Ling; Brenchley, Celia; Jennings, Garry; Lambert, Elisabeth

    2008-04-01

    1. In searching for biological evidence that essential hypertension is caused by chronic mental stress, a disputed proposition, parallels are noted with panic disorder, which provides an explicit clinical model of recurring stress responses. 2. There is clinical comorbidity; panic disorder prevalence is increased threefold in essential hypertension. Plasma cortisol is elevated in both. 3. In panic disorder and essential hypertension, but not in health, single sympathetic nerve fibres commonly fire repeatedly within an individual cardiac cycle; this appears to be a signature of stress exposure. For both conditions, adrenaline cotransmission is present in sympathetic nerves. 4. Tissue nerve growth factor is increased in both (nerve growth factor is a stress reactant). There is induction of the adrenaline synthesizing enzyme, phenylethanolamine-N-methyltransferase, in sympathetic nerves, an explicit indicator of mental stress exposure. 5. The question of whether chronic mental stress causes high blood pressure, still hotly debated, has been reviewed by an Australian Government body, the Specialist Medical Review Council. Despite the challenging medicolegal implications, the Council determined that stress is one proven cause of hypertension, this ruling being published in the 27 March 2002 Australian Government Gazette. This judgement was reached after consideration of the epidemiological evidence, but in particular after review of the specific elements of the neural pathophysiology of essential hypertension, described above. PMID:18307749

  9. Identification of Molecular Markers of Delayed Graft Function Based on the Regulation of Biological Ageing

    PubMed Central

    McGuinness, Dagmara; Leierer, Johannes; Shapter, Olivier; Mohammed, Suhaib; Gingell-Littlejohn, Marc; Kingsmore, David B.; Little, Ann-Margaret; Kerschbaum, Julia; Schneeberger, Stefan; Maglione, Manuel; Nadalin, Silvio; Wagner, Sylvia; Königsrainer, Alfred; Aitken, Emma; Whalen, Henry; Clancy, Marc; McConnachie, Alex; Koppelstaetter, Christian; Stevenson, Karen S.; Shiels, Paul G.

    2016-01-01

    Introduction Delayed graft function is a prevalent clinical problem in renal transplantation for which there is no objective system to predict occurrence in advance. It can result in a significant increase in the necessity for hospitalisation post-transplant and is a significant risk factor for other post-transplant complications. Methodology The importance of microRNAs (miRNAs), a specific subclass of small RNA, have been clearly demonstrated to influence many pathways in health and disease. To investigate the influence of miRNAs on renal allograft performance post-transplant, the expression of a panel of miRNAs in pre-transplant renal biopsies was measured using qPCR. Expression was then related to clinical parameters and outcomes in two independent renal transplant cohorts. Results Here we demonstrate, in two independent cohorts of pre-implantation human renal allograft biopsies, that a novel pre-transplant renal performance scoring system (GRPSS), can determine the occurrence of DGF with a high sensitivity (>90%) and specificity (>60%) for donor allografts pre-transplant, using just three senescence associated microRNAs combined with donor age and type of organ donation. Conclusion These results demonstrate a relationship between pre-transplant microRNA expression levels, cellular biological ageing pathways and clinical outcomes for renal transplantation. They provide for a simple, rapid quantitative molecular pre-transplant assay to determine post-transplant allograft function and scope for future intervention. Furthermore, these results demonstrate the involvement of senescence pathways in ischaemic injury during the organ transplantation process and an indication of accelerated bio-ageing as a consequence of both warm and cold ischaemia. PMID:26734715

  10. Disordered porphyrin metabolism: a potential biological marker for autism risk assessment.

    PubMed

    Heyer, Nicholas J; Echeverria, Diana; Woods, James S

    2012-04-01

    Autism (AUT) is a complex neurodevelopmental disorder that, together with Asperger's syndrome and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS), comprises the expanded classification of autistic spectrum disorder (ASD). The heterogeneity of ASD underlies the need to identify biomarkers or clinical features that can be employed to identify meaningful subtypes of ASD, define specific etiologies, and inform intervention and treatment options. Previous studies have shown that disordered porphyrin metabolism, manifested principally as significantly elevated urinary concentrations of pentacarboxyl (penta) and coproporphyrins, is commonly observed among some children with ASD. Here, we extend these observations by specifically evaluating penta and coproporphyrins as biological indicators of ASD among 76 male children comprising 30 with validated AUT, 14 with PDD-NOS, and 32 neurotypical (NT) controls. ASD children (AUT and PDD-NOS) had higher mean urinary penta (P < 0.006) and copro (P < 0.006) concentrations compared with same-aged NT children, each characterized by a number of extreme values. Using Receiver Operating Characteristic curve analysis, we evaluated the sensitivity and specificity of penta, copro, and their combined Z-scores in ASD detection. The penta sensitivity was 30% for AUT and 36% for PDD-NOS, with 94% specificity. The copro sensitivity was 33% and 14%, respectively, with 94% specificity. The combined Z-score measure had 33% and 21% sensitivity for AUT and PDD-NOS, respectively, with 100% specificity. These findings demonstrate that porphyrin measures are strong predictors of both AUT and PDD-NOS, and support the potential clinical utility of urinary porphyrin measures for identifying a subgroup of ASD subjects in whom disordered porphyrin metabolism may be a salient characteristic. PMID:22298513

  11. Levels of biological markers of nitric oxide in serum of patients with squamous cell carcinoma of the oral cavity

    PubMed Central

    Ratajczak-Wrona, Wioletta; Jablonska, Ewa; Antonowicz, Bozena; Dziemianczyk, Dorota; Grabowska, Stanislawa Zyta

    2013-01-01

    The aim of the study was a determination of the levels of nitric oxide (NO) and its biological markers such as malonyldialdehyde (MDA) and nitrotyrosine in the serum of patients with squamous cell carcinoma (SCC) of the oral cavity and identification of the relationships between NO and those markers. These studies were performed on patients with SCC of the oral cavity before and after treatment. Griess reaction was used for the estimation of the total concentration of NO in serum. The nitrotyrosine level in serum was assessed with an enzyme-linked immunosorbent assay (ELISA) kit, and MDA level using a spectrophotometric assay. Higher concentrations of NO in blood serum were determined in patients with stage IV of the disease before treatment in comparison to the control group and patients with stages II and III of the disease. Moreover, higher concentrations of MDA and nitrotyrosine were determined in the serum of patients in all stages of the disease in comparison to healthy people. After treatment, lower concentrations of NO in the serum of patients with stage IV of the disease were observed in comparison to the amounts obtained prior to treatment. In addition, lower levels of nitrotyrosine in the serum of patients with all stages of the disease were recorded, whereas higher concentrations of MDA were determined in these patients in comparison to results obtained before treatment. The compounds formed with the contribution of NO, such as MDA and nitrotyrosine, may lead to cancer progression in patients with SCC of the oral cavity, and contribute to formation of resistance to therapy in these patients as well. Moreover, the lack of a relationship between concentrations of NO and MDA, and between NO and nitrotyrosine in serum suggests that the process of lipid peroxidation and nitration in patients with SCC does not just depend on NO. PMID:23970140

  12. Cystatin C as a predictive marker of renal dysfunction and mid-term outcomes following off-pump coronary artery bypass grafting

    PubMed Central

    Lee, Seung Hyun; Youn, Young-Nam; Choo, Hyun Chel; Lee, Sak; Yoo, Kyung-Jong

    2015-01-01

    Objective To determine whether plasma cystatin C and creatinine levels after isolated off-pump coronary artery bypass grafting (OPCAB) are predictive of postoperative renal dysfunction and clinical outcomes. Methods Between January 2008 and December 2013, 1033 who underwent isolated OPCAB were recruited. The patients were divided into three groups according to the preoperative level of cystatin C: low (0.83 mg/L>), mid (0.83–1.13 mg/L) and high (1.13 mg/L<). The endpoints of all-cause mortality and major adverse cerebrovascular and cardiovascular events were compared among three groups using the Kaplan–Meier method. The predictive power of cystatin C was compared with creatinine using receiver operating curves. Results Follow-up was complete in all of the included patients at a mean of 2.9±1.5 years. Within the follow-up period, 9 early (30-day mortality) and 46 late deaths occurred. The 30-day mortality was zero, four (44%), and five (56%) cases in low, mid and high groups, respectively (p=0.03). The cut-off value of cystatin C for renal dysfunction prediction was approximately 1.04 (mg/L, p<0.001), and cystatin C showed greater predictive power than creatinine for renal dysfunction (area under the curve=0.73 vs 0.65; p=0.01). One-year and five-year overall survival in low, mid and high groups were 99.2%, 98.9% and 94.3%, and 97.9%, 97.3% and 86.3%, respectively (low vs high, p=0.01). Conclusions Cystatin C is a stronger predictor of postoperative renal dysfunction than serum creatinine, and its level is directly correlated with mid-term OPCAB adverse results. PMID:26215986

  13. Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress

    PubMed Central

    2015-01-01

    Abstract Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3′,-5′-monophosphate (cGMP) levels lead to an activation of the cGMP-dependent kinase I, thereby causing the relaxation of the vascular smooth muscle by decreasing intracellular calcium concentrations. The hemodynamic and anti-ischemic effects of organic nitrates are rapidly lost upon long-term (low-dose) administration due to the rapid development of tolerance and endothelial dysfunction, which is in most cases linked to increased intracellular oxidative stress. Enzymatic sources of reactive oxygen species under nitrate therapy include mitochondria, NADPH oxidases, and an uncoupled •NO synthase. Acute high-dose challenges with organic nitrates cause a similar loss of potency (tachyphylaxis), but with distinct pathomechanism. The differences among organic nitrates are highlighted regarding their potency to induce oxidative stress and subsequent tolerance and endothelial dysfunction. We also address pleiotropic effects of organic nitrates, for example, their capacity to stimulate antioxidant pathways like those demonstrated for PETN, all of which may prevent adverse effects in response to long-term therapy. Based on these considerations, we will discuss and present some preclinical data on how the nitrate of the future should be designed. Antioxid. Redox Signal. 23, 899–942. PMID:26261901

  14. The Stanley Neuropathology Consortium Integrative Database: a Novel, Web-Based Tool for Exploring Neuropathological Markers in Psychiatric Disorders and the Biological Processes Associated with Abnormalities of Those Markers

    PubMed Central

    Kim, Sanghyeon; Webster, Maree J

    2010-01-01

    An integrative database, Stanley Neuropathology Consortium Integrative Database (SNCID) (http://sncid.stanleyresearch.org), has been developed to facilitate psychiatric research. The SNCID includes 1749 neuropathological markers measured in 12 different brain regions in 60 human subjects (15 each schizophrenia, bipolar disorder, depression, and unaffected controls). Genome-wide expression microarray datasets from three independent studies are also included. Statistical analysis tools such as variance analysis, correlation analysis, and functional annotation tools have been integrated into the database. In this report, we first replicate an earlier correlation analysis between genome-wide expression profiles and an abnormal cytoarchitectural marker using the SNCID. We then show the potential for identifying neuropathological markers that are abnormal in subjects with psychiatric disorders. We also identify biological pathways associated with several abnormal neuropathological markers, including those in the dopamine, glutamate, Reelin, and γ-aminobutyric acid (GABA)ergic systems. Data exploration using the SNCID may provide insights into the biological pathways associated with the neurotransmitter abnormalities identified in subjects with major psychiatric disorders. PMID:19829293

  15. Olfactory dysfunction in Alzheimer's disease.

    PubMed

    Zou, Yong-Ming; Lu, Da; Liu, Li-Ping; Zhang, Hui-Hong; Zhou, Yu-Ying

    2016-01-01

    Alzheimer's disease (AD) is a common neurodegenerative disorder with the earliest clinical symptom of olfactory dysfunction, which is a potential clinical marker for AD severity and progression. However, many questions remain unanswered. This article reviews relevant research on olfactory dysfunction in AD and evaluates the predictive value of olfactory dysfunction for the epidemiological, pathophysiological, and clinical features of AD, as well as for the conversion of cognitive impairment to AD. We summarize problems of existing studies and provide a useful reference for further studies in AD olfactory dysfunction and for clinical applications of olfactory testing. PMID:27143888

  16. Chronic Inflammatory Diseases and Endothelial Dysfunction

    PubMed Central

    Castellon, Xavier; Bogdanova, Vera

    2016-01-01

    Chronic inflammatory diseases are associated with increases in cardiovascular diseases (CVD) and subclinical atherosclerosis as well as early-stage endothelial dysfunction screening using the FMD method (Flow Mediated Dilation). This phenomenon, referred to as accelerated pathological remodeling of arterial wall, could be attributed to traditional risk factors associated with atherosclerosis. Several new non-invasive techniques have been used to study arterial wall’s structural and functional alterations. These techniques (based of Radio Frequency, RF) allow for an assessment of artery age through calculations of intima-media thickness (RF- QIMT), pulse wave rate (RF- QAS) and endothelial dysfunction degree (FMD). The inflammatory and autoimmune diseases should now be considered as new cardiovascular risk factors, result of the major consequences of oxidative stress and RAS (Renin Angiotensin System) imbalance associated with the deleterious effect of known risk factors that lead to the alteration of the arterial wall. Inflammation plays a key role in all stages of the formation of vascular lesions maintained and exacerbated by the risk factors. The consequence of chronic inflammation is endothelial dysfunction that sets in and we can define it as an integrated marker of the damage to arterial walls by classic risk factors. The atherosclerosis, which develops among these patients, is the main cause for cardiovascular morbi-mortality and uncontrolled chronic biological inflammation, which quickly favors endothelial dysfunction. These inflammatory and autoimmune diseases should now be considered as new cardiovascular risk factors. PMID:26815098

  17. Proteomic analysis as a means to approach limbal stem cell biology in a search for stem cell markers.

    PubMed

    Honoré, Bent; Vorum, Henrik

    2014-04-01

    The cornea consists of three main layers: an outer surface epithelium, the stroma, and the endothelium. A clear cornea is necessary for optimal vision and is maintained and repaired from limbal epithelial stem cells located in the limbus between the cornea and the sclera. Diseases and injury may result in deficiency of the stem cells impairing their ability to renew the corneal epithelium. Patients with limbal stem cell deficiency experience chronic pain and ultimately blindness. Attempts to treat the disease are based on replacement of the stem cells by transplantation or by culturing the stem cells. We here review the proteomic techniques that so far have been used to approach characterization of limbal stem cells and markers to identify them. It is apparent that the field is in a rather inchoate state due to the scarcity and relative inaccessibility of the stem cells. However, the importance of revealing limbal stem cell biology and identifying stem cell biomarkers calls for greater use of emerging methodology. Strategies for future studies are discussed. PMID:24497450

  18. Organic geochemical studies of a Messinian evaporitic basin, northern Apennines (Italy) I: Hydrocarbon biological markers for a hypersaline environment

    NASA Astrophysics Data System (ADS)

    Ten Haven, H. L.; De Leeuw, J. W.; Schenck, P. A.

    1985-10-01

    This paper describes the occurrence and significance of hydrocarbons present in two bituminous marl layers and one distinct gypsum layer from a Messinian sedimentary basin, where hypersaline conditions prevailed. Several new compounds were detected and tentatively identified: of these 20R and 20S 4α, 24-dimethyl-5α(H),14β(H),17β(H) and 20R and 20S 4β,24-dimethyI-5α(H),14β(H),17β(H) cholestanes; 4-methylspirosterenes; 4,4-dimethyl-5α(H),14β(H),17β(H) pregnanes and homopregnanes are discussed in this paper. Several of these compounds might be considered as biological markers for a (hyper)saline environment. The short side chain 4-desmethylsteranes, 5α(H),14β(H),17β(H), 5α(H),14β(H),17α(H) and 5α(H),14α(H), 17α(H) pregnanes and homopregnanes, are the most abundant compounds in the extract from the gypsum sample. It is suggested that in this case these compounds do not reflect the stage of diagenesis but are related to certain organisms exclusively occurring in hypersaline environments. In addition the very low pristane/phytane ratio, often considered as an indicator for anoxicity, could also be interpreted as a useful indicator for hypersalinity.

  19. The A3 adenosine receptor (A3AR): therapeutic target and predictive biological marker in rheumatoid arthritis.

    PubMed

    Fishman, Pnina; Cohen, Shira

    2016-09-01

    The Gi protein-associated A3 adenosine receptor (A3AR) is over-expressed in inflammatory cells, and this high expression is also reflected in the peripheral blood mononuclear cells of patients with autoimmune inflammatory diseases such as rheumatoid arthritis, psoriasis, and Crohn's disease. CF101, a selective agonist with high affinity to the A3AR, is known to induce robust anti-inflammatory effect in experimental animal models of adjuvant-, collagen-, and tropomyosin-induced arthritis. The effect is mediated via a definitive molecular mechanism entailing deregulation of the nuclear factor-κB (NF-κB) and the Wnt signal transduction pathways resulting in apoptosis of inflammatory cells. CF101 was found to be safe and well tolerated in all preclinical, phase I, and phase II human clinical studies. In two phase II clinical studies where CF101 was administered to rheumatoid arthritis (RA) patients as a stand-alone drug, a significant anti-rheumatic effect and a direct significant correlation were found between receptor expression at baseline and patients' response to the drug, suggesting that A3AR may be utilized as a predictive biomarker. The A3AR is a promising therapeutic target in rheumatoid arthritis and can be used also as a biological marker to predict patients' response to CF101. This is a unique type of a personalized medicine approach which may pave the way for a safe and efficacious treatment for this patient population. PMID:26886128

  20. Impact of different welding techniques on biological effect markers in exhaled breath condensate of 58 mild steel welders.

    PubMed

    Hoffmeyer, Frank; Raulf-Heimsoth, Monika; Lehnert, Martin; Kendzia, Benjamin; Bernard, Sabine; Berresheim, Hans; Düser, Maria; Henry, Jana; Weiss, Tobias; Koch, Holger M; Pesch, Beate; Brüning, Thomas

    2012-01-01

    Total mass and composition of welding fumes are predominantly dependent on the welding technique and welding wire applied. The objective of this study was to investigate the impact of welding techniques on biological effect markers in exhaled breath condensate (EBC) of 58 healthy welders. The welding techniques applied were gas metal arc welding with solid wire (GMAW) (n=29) or flux cored wire (FCAW) (n=29). Welding fume particles were collected with personal samplers in the breathing zone inside the helmets. Levels of leukotriene B(4) (LTB(4)), prostaglandin E(2) (PGE(2)), and 8-isoprostane (8-iso-PGF(2α)) were measured with immunoassay kits and the EBC pH was measured after deaeration. Significantly higher 8-iso-PGF(2α) concentrations and a less acid pH were detected in EBC of welders using the FCAW than in EBC of welders using the GMAW technique. The lowest LTB(4) concentrations were measured in nonsmoking welders applying a solid wire. No significant influences were found in EBC concentrations of PGE(2) based upon smoking status or type of welding technique. This study suggests an enhanced irritative effect in the lower airways of mild steel welders due to the application of FCAW compared to GMAW, most likely associated with a higher emission of welding fumes. PMID:22686312

  1. Effects of short-term propofol and dexmedetomidine on pulmonary morphofunction and biological markers in experimental mild acute lung injury.

    PubMed

    Cavalcanti, Vinícius; Santos, Cintia Lourenço; Samary, Cynthia Santos; Araújo, Mariana Neves; Heil, Luciana Boavista Barros; Morales, Marcelo Marcos; Silva, Pedro Leme; Pelosi, Paolo; Fernandes, Fatima Carneiro; Villela, Nivaldo; Rocco, Patricia Rieken Macedo

    2014-11-01

    We evaluated whether the short-term use of dexmedetomidine and propofol may attenuate inflammatory response and improve lung morphofunction in experimental acute lung injury (ALI). Thirty-six Wistar rats were randomly divided into five groups. Control (C) and ALI animals received sterile saline solution and Escherichia coli lipopolysaccharide by intraperitoneal injection respectively. After 24h, ALI animals were randomly treated with dexmedetomidine, propofol, or thiopental sodium for 1h. Propofol reduced static lung elastance and resistive pressure and was associated with less alveolar collapse compared to thiopental sodium and dexmedetomidine. Dexmedetomidine improved oxygenation, but did not modify lung mechanics or histology. Propofol was associated with lower IL (interleukin)-6 and IL-1β expression, whereas dexmedetomidine led to reduced inducible nitric oxide (iNOS) and increased nuclear factor erythroid 2-related factor 2 (Nrf2) expression in lung tissue compared to thiopental sodium. In conclusion, in this model of mild ALI, short-term use of dexmedetomidine and propofol led to different functional effects and activation of biological markers associated with pulmonary inflammation. PMID:25149586

  2. Markers of early endothelial dysfunction in intrauterine growth restriction-derived human umbilical vein endothelial cells revealed by 2D-DIGE and mass spectrometry analyses.

    PubMed

    Caniuguir, Andres; Krause, Bernardo J; Hernandez, Cherie; Uauy, Ricardo; Casanello, Paola

    2016-05-01

    Intrauterine growth restriction (IUGR) associates with fetal and placental vascular dysfunction, and increased cardiovascular risk later on life. We hypothesize that endothelial cells derived from IUGR umbilical veins present significant changes in the proteome which could be involved in the endothelial dysfunction associated to this conditions. To address this the proteome profile of human umbilical endothelial cells (HUVEC) isolated from control and IUGR pregnancies was compared by 2D-Differential In Gel Electrophoresis (DIGE) and further protein identification by MALDI-TOF MS. Using 2D-DIGE 124 spots were identified as differentially expressed between control and IUGR HUVEC, considering a cut-off of 2 fold change, which represented ∼10% of the total spots detected. Further identification by MALDI-TOF MS and in silico clustering of the proteins showed that those differentially expressed proteins between control and IUGR HUVEC were mainly related with cytoskeleton organization, proteasome degradation, oxidative stress response, mRNA processing, chaperones and vascular function. Finally Principal Component analysis of the identified proteins showed that differentially expressed proteins allow distinguishing between control and IUGR HUVEC based on their proteomic profile. This study demonstrates for the first time that IUGR-derived HUVEC maintained in primary culture conditions present an altered proteome profile, which could reflect an abnormal programming of endothelial function in this fetal condition. PMID:27208404

  3. Relationships of Circulating Carotenoid Concentrations with Several Markers of Inflammation, Oxidative Stress, and Endothelial Dysfunction: The Coronary Artery Risk Development in Young Adults (CARDIA)/Young Adult Longitudinal Trends in Antioxidants (YALTA) Study

    PubMed Central

    Hozawa, Atsushi; Jacobs, David R.; Steffes, Michael W.; Gross, Myron D.; Steffen, Lyn M.; Lee, Duk-Hee

    2008-01-01

    Background Serum carotenoid concentrations relate inversely to cardiovascular disease incidence. To clarify the effect of carotenoids on atherosclerotic risk factors, we examined the association of circulating carotenoids with inflammation, oxidative stress, endothelial dysfunction, and smoking. Methods Black and white men and women in the Coronary Artery Risk Development in Young Adults study, ages 18 to 30 years at recruitment (1985–1986) from 4 US cities, were investigated over 15 years. We included 2048 to 4580 participants in analyses of the sum of serum α-carotene, β-carotene, zeaxanthin/lutein, and β-cryptoxanthin concentrations and of lycopene at year 0 and at year 7. Results The year 0 sum of 4 carotenoids was inversely associated (all P <0.05) with year 0 leukocyte count (slope per sum carotenoid SD, −0.17); year 7 fibrinogen (slope, −0.10); year 7 and year 15 C-reactive protein (slope, −0.12 and −0.09); and year 15 F2-isoprostanes (slope, −13.0), soluble P-selectin (slope, −0.48), and soluble intercellular adhesion molecule-1 (sICAM1; slope, −5.1). Leukocyte counts and sICAM1 and F2-isoprostane concentrations had stronger associations in smokers than in nonsmokers, and sICAM1 concentrations were higher in the highest carotenoid quartile in smokers than in the lowest carotenoid quartile in nonsmokers. Superoxide dismutase was positively associated with the sum of 4 carotenoids (slope, 0.12; P <0.01). Lycopene was inversely associated only with sICAM1. The year 7 carotenoid associations with these markers were mostly similar to those at year 0. Conclusions Circulating serum carotenoids were associated, some interactively with smoking, in apparently beneficial directions with markers of inflammation, oxidative stress, and endothelial dysfunction. PMID:17234732

  4. CD4:CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV-positive patients

    PubMed Central

    Lu, Wei; Mehraj, Vikram; Vyboh, Kishanda; Cao, Wei; Li, Taisheng; Routy, Jean-Pierre

    2015-01-01

    Introduction Absolute CD4 T cell count and plasma viral load have been established as predictors of HIV disease progression, and CD4 T cell count is used as an indicator for initiation of antiretroviral therapy. Following long-term therapy, patients generally present with significant CD4 T cell recovery contrasting with persistently elevated CD8 T cell counts, which leads to a partial restoration of CD4:CD8 ratio. This review focuses on the relevance of the CD4:CD8 ratio on clinical outcomes, immune dysfunction and HIV reservoir size in long-term treated patients. Method We conducted a comprehensive literature review of publications in English language using major electronic databases. Our search was focused on factors contributing to CD4:CD8 T cell ratio and clinical outcome in adult HIV-positive patients in the context of treated infection. Discussion Low CD4:CD8 ratio has been linked to ageing and acts as a predictor of mortality in the general population. This ratio may represent the combined effects of inflammation and immunological changes called “inflammaging.” Although the mechanisms underlying partial correction of the CD4:CD8 ratio and persistently elevated CD8 T cell count in long-term treated patients remain poorly understood, it has been recently indicated that patients with optimal CD4 T cell recovery and low CD4:CD8 ratio still harbour increased immune activation, an immune senescent phenotype and have a higher risk of non-AIDS morbidity and mortality. This review reconsiders CD4:CD8 ratio in the light of advances in the understanding of immune dysfunction and examines its pathophysiological features and implications on clinical outcome and HIV reservoir size in long-term treated HIV-positive adults. Conclusion The CD4:CD8 ratio can contribute to the immunological evaluation of treated patients in a long-term follow-up and may be applied for monitoring both immune dysfunction and viral reservoir size in immune-based clinical trials. PMID:26130226

  5. Association of Mitochondrial Dysfunction and Fatigue: A Review of the Literature.

    PubMed

    Filler, Kristin; Lyon, Debra; Bennett, James; McCain, Nancy; Elswick, Ronald; Lukkahatai, Nada; Saligan, Leorey N

    2014-06-01

    Fatigue is often described by patients as a lack of energy, mental or physical tiredness, diminished endurance, and prolonged recovery after physical activity. Etiologic mechanisms underlying fatigue are not well understood; however, fatigue is a hallmark symptom of mitochondrial disease, making mitochondrial dysfunction a putative biological mechanism for fatigue. Therefore, this review examined studies that investigated the association of markers of mitochondrial dysfunction with fatigue and proposes possible research directions to enhance understanding of the role of mitochondrial dysfunction in fatigue. A thorough search using PubMed, Scopus, Web of Science, and Embase databases returned 1,220 articles. After application of inclusion and exclusion criteria, a total of 25 articles meeting eligibility criteria were selected for full review. Dysfunctions in the mitochondrial structure, mitochondrial function (mitochondrial enzymes and oxidative/nitrosative stress), mitochondrial energy metabolism (ATP production and fatty acid metabolism), immune response, and genetics were investigated as potential contributors to fatigue. Carnitine was the most investigated mitochondrial function marker. Dysfunctional levels were reported in all the studies investigating carnitine; however, the specific type of carnitine that was dysfunctional varied. Genetic profiles were the second most studied mitochondrial parameter. Six common pathways were proposed: metabolism, energy production, protein transport, mitochondrial morphology, central nervous system dysfunction and post-viral infection. Coenzyme Q10 was the most commonly investigated mitochondrial enzyme. Low levels of Coenzyme Q10 were consistently associated with fatigue. Potential targets for further investigation were identified as well as gaps in the current literature. PMID:25147756

  6. Association of mitochondrial dysfunction and fatigue: A review of the literature

    PubMed Central

    Filler, Kristin; Lyon, Debra; Bennett, James; McCain, Nancy; Elswick, Ronald; Lukkahatai, Nada; Saligan, Leorey N.

    2014-01-01

    Fatigue is often described by patients as a lack of energy, mental or physical tiredness, diminished endurance, and prolonged recovery after physical activity. Etiologic mechanisms underlying fatigue are not well understood; however, fatigue is a hallmark symptom of mitochondrial disease, making mitochondrial dysfunction a putative biological mechanism for fatigue. Therefore, this review examined studies that investigated the association of markers of mitochondrial dysfunction with fatigue and proposes possible research directions to enhance understanding of the role of mitochondrial dysfunction in fatigue. A thorough search using PubMed, Scopus, Web of Science, and Embase databases returned 1220 articles. After the application of inclusion and exclusion criteria, a total of 25 articles meeting eligibility criteria were selected for full review. Dysfunctions in the mitochondrial structure, mitochondrial function (mitochondrial enzymes and oxidative/nitrosative stress), mitochondrial energy metabolism (ATP production and fatty acid metabolism), immune response, and genetics were investigated as potential contributors to fatigue. Carnitine was the most investigated mitochondrial function marker. Dysfunctional levels were reported in all the studies investigating carnitine; however, the specific type of carnitine that was dysfunctional varied. Genetic profiles were the second most studied mitochondrial parameter. Six common pathways were proposed: metabolism, energy production, protein transport, mitochondrial morphology, central nervous system dysfunction and post-viral infection. Coenzyme Q10 was the most commonly investigated mitochondrial enzyme. Low levels of Coenzyme Q10 were consistently associated with fatigue. Potential targets for further investigation were identified as well as gaps in the current literature. PMID:25147756

  7. Bone lead as a new biologic marker of lead dose: recent findings and implications for public health.

    PubMed Central

    Hu, H

    1998-01-01

    Measurements of lead in bone have recently become the focus of research because a) bone lead levels serve as a cumulative dosimeter of lead exposure over many years (because of lead's long residence time in bone), and cumulative exposure may be more predictive of chronic toxicity than recent exposure, which is what blood lead levels mostly reflect; b) there is suspicion that heightened bone turnover (e.g. during pregnancy, lactation, and aging) may liberate enough stored lead to pose a significant threat of delayed toxicity; and c) although lead exposure has largely declined in the United States over the past 10 to 15 years, decades of heavy environmental pollution have resulted in significant accumulation of lead in bone among most members of the general U.S. population. Epidemiologic research on the impact of lead stored in bone is now possible with the development of 109Cd K-X-ray fluorescence (KXRF) instruments for the in vivo measurement of lead in bone. In this paper, the KXRF method will be briefly reviewed, followed by a summary of several Superfund-supported studies (and others) of blood lead and KXRF-measured bone lead in which these measures are compared as biologic markers of lead dose. Measurement of bone lead in epidemiologic studies has proved useful in exposure assessment studies, i.e., in identifying factors that contribute most to retained body lead burden, and in investigating cumulative lead exposure as a risk factor for poor health outcomes such as hypertension, kidney impairment, cognitive impairment, behavioral disturbances, and adverse reproductive outcomes. Images Figure 1 PMID:9703479

  8. Assessing the Value of BMI and Aerobic Capacity as Surrogate Markers for the Severity of Left Ventricular Diastolic Dysfunction in Patients with Type 2 Diabetes Who Are Obese.

    PubMed

    Smith, Cassandra; Asrar Ul Haq, Muhammad; Jerums, George; Hanson, Erik; Hayes, Alan; Allen, Jason D; Sbaraglia, Melissa; Selig, Steve; Wong, Chiew; Hare, David L; Levinger, Itamar

    2016-01-01

    Left ventricular diastolic dysfunction (LVDD) is one of the earliest signs for abnormal cardiac function in patients with type 2 diabetes (T2DM). It is important to explore the risk factors that will assist in identifying the severity of the LVDD in this population. We examined the influences of fitness and fatness on the level of left ventricular (LV) impairment in patients with T2DM. Twenty-five patients (age: 64.0 ± 2.5 years, body mass index [BMI] = 36.0 ± 1.5 kg/m(2), mean ± standard error of measurement) with T2DM and preserved systolic function, but impaired diastolic function, mitral valve (MV) E/e', participated in the study. LV function was assessed using a stress echocardiograph, aerobic power was assessed with a sign- and symptom-limited graded exercise test, and the fatness level was assessed using Dual-energy X-ray absorptiometry and BMI. Patients in the higher 50% of BMI had higher lateral and septal MV E/e' (∼34% and ∼25%, respectively, both P < 0.001), compared to those in the lower 50% of BMI, with no difference in LV ejection fraction (LVEF) (P > 0.05). In addition, a higher BMI correlated with a higher lateral (r = 0.62, P < 0.001) and septal (r = 0.56, P < 0.01) E/e'. There was no such relationship for VO2peak. BMI and VO2peak were not correlated with LV systolic function (ejection fraction). In individuals with T2DM and diastolic dysfunction, a higher BMI was associated with worsening diastolic function independent of their aerobic capacity. The data provide a simple and practical approach for clinicians to assist in the early identification and diagnostics of functional changes in the heart diastolic function in this population. PMID:27199576

  9. The non-invasive 13C-methionine breath test detects hepatic mitochondrial dysfunction as a marker of disease activity in non-alcoholic steatohepatitis

    PubMed Central

    2011-01-01

    Introduction Mitochondrial dysfunction plays a central role in the general pathogenesis of non-alcoholic fatty liver disease (NAFLD), increasing the risk of developing steatosis and subsequent hepatocellular inflammation. We aimed to assess hepatic mitochondrial function by a non-invasive 13C-methionine breath test (MeBT) in patients with histologically proven NAFLD. Methods 118 NAFLD-patients and 18 healthy controls were examined by MeBT. Liver biopsy specimens were evaluated according to the NASH scoring system. Results Higher grades of NASH activity and fibrosis were independently associated with a significant decrease in cumulative 13C-exhalation (expressed as cPDR(%)). cPDR1.5h was markedly declined in patients with NASH and NASH cirrhosis compared to patients with simple steatosis or borderline diagnosis (cPDR1.5h: 3.24 ± 1.12% and 1.32 ± 0.94% vs. 6.36 ± 0.56% and 4.80 ± 0.88% respectively; p < 0.001). 13C-exhalation further declined in the presence of advanced fibrosis which was correlated with NASH activity (r = 0.36). The area under the ROC curve (AUROC) for NASH diagnosis was estimated to be 0.87 in the total cohort and 0.83 in patients with no or mild fibrosis (F0-1). Conclusion The 13C-methionine breath test indicates mitochondrial dysfunction in non-alcoholic fatty liver disease and predicts higher stages of disease activity. It may, therefore, be a valuable diagnostic addition for longitudinal monitoring of hepatic (mitochondrial) function in non-alcoholic fatty liver disease. PMID:21810560

  10. Assessing the Value of BMI and Aerobic Capacity as Surrogate Markers for the Severity of Left Ventricular Diastolic Dysfunction in Patients with Type 2 Diabetes Who Are Obese

    PubMed Central

    Smith, Cassandra; Asrar ul Haq, Muhammad; Jerums, George; Hanson, Erik; Hayes, Alan; Allen, Jason D; Sbaraglia, Melissa; Selig, Steve; Wong, Chiew; Hare, David L; Levinger, Itamar

    2016-01-01

    Left ventricular diastolic dysfunction (LVDD) is one of the earliest signs for abnormal cardiac function in patients with type 2 diabetes (T2DM). It is important to explore the risk factors that will assist in identifying the severity of the LVDD in this population. We examined the influences of fitness and fatness on the level of left ventricular (LV) impairment in patients with T2DM. Twenty-five patients (age: 64.0 ± 2.5 years, body mass index [BMI] = 36.0 ± 1.5 kg/m2, mean ± standard error of measurement) with T2DM and preserved systolic function, but impaired diastolic function, mitral valve (MV) E/e′, participated in the study. LV function was assessed using a stress echocardiograph, aerobic power was assessed with a sign- and symptom-limited graded exercise test, and the fatness level was assessed using Dual-energy X-ray absorptiometry and BMI. Patients in the higher 50% of BMI had higher lateral and septal MV E/e′ (∼34% and ∼25%, respectively, both P < 0.001), compared to those in the lower 50% of BMI, with no difference in LV ejection fraction (LVEF) (P > 0.05). In addition, a higher BMI correlated with a higher lateral (r = 0.62, P < 0.001) and septal (r = 0.56, P < 0.01) E/e′. There was no such relationship for VO2peak. BMI and VO2peak were not correlated with LV systolic function (ejection fraction). In individuals with T2DM and diastolic dysfunction, a higher BMI was associated with worsening diastolic function independent of their aerobic capacity. The data provide a simple and practical approach for clinicians to assist in the early identification and diagnostics of functional changes in the heart diastolic function in this population. PMID:27199576

  11. Undaria pinnatifida and Fucoxanthin Ameliorate Lipogenesis and Markers of Both Inflammation and Cardiovascular Dysfunction in an Animal Model of Diet-Induced Obesity.

    PubMed

    Grasa-López, Ameyalli; Miliar-García, Ángel; Quevedo-Corona, Lucía; Paniagua-Castro, Norma; Escalona-Cardoso, Gerardo; Reyes-Maldonado, Elba; Jaramillo-Flores, María-Eugenia

    2016-01-01

    Brown algae and its carotenoids have been shown to have a positive influence on obesity and its comorbidities. This study evaluated the effect of Undaria pinnatifida and fucoxanthin on biochemical, physiological and inflammation markers related to obesity and on the expression of genes engaged on white adipose tissue lipid metabolism in a murine model of diet-induced obesity. The treatments improved energy expenditure, β-oxidation and adipogenesis by upregulating PPARα, PGC1α, PPARγ and UCP-1. Adipogenesis was also confirmed by image analysis of the retroperitoneal adipose tissue, by measuring cell area, perimeter and cellular density. Additionally, the treatments, ameliorated adipose tissue accumulation, insulin resistance, blood pressure, cholesterol and triglycerides concentration in serum, and reduced lipogenesis and inflammation by downregulating acetyl-CoA carboxylase (ACC) gene expression, increasing serum concentration and expression of adiponectin as well as downregulating IL-6 expression. Both fucoxanthin and Undaria pinnatifida may be considered for treating obesity and other diseases related. PMID:27527189

  12. Undaria pinnatifida and Fucoxanthin Ameliorate Lipogenesis and Markers of Both Inflammation and Cardiovascular Dysfunction in an Animal Model of Diet-Induced Obesity

    PubMed Central

    Grasa-López, Ameyalli; Miliar-García, Ángel; Quevedo-Corona, Lucía; Paniagua-Castro, Norma; Escalona-Cardoso, Gerardo; Reyes-Maldonado, Elba; Jaramillo-Flores, María-Eugenia

    2016-01-01

    Brown algae and its carotenoids have been shown to have a positive influence on obesity and its comorbidities. This study evaluated the effect of Undaria pinnatifida and fucoxanthin on biochemical, physiological and inflammation markers related to obesity and on the expression of genes engaged on white adipose tissue lipid metabolism in a murine model of diet-induced obesity. The treatments improved energy expenditure, β-oxidation and adipogenesis by upregulating PPARα, PGC1α, PPARγ and UCP-1. Adipogenesis was also confirmed by image analysis of the retroperitoneal adipose tissue, by measuring cell area, perimeter and cellular density. Additionally, the treatments, ameliorated adipose tissue accumulation, insulin resistance, blood pressure, cholesterol and triglycerides concentration in serum, and reduced lipogenesis and inflammation by downregulating acetyl-CoA carboxylase (ACC) gene expression, increasing serum concentration and expression of adiponectin as well as downregulating IL-6 expression. Both fucoxanthin and Undaria pinnatifida may be considered for treating obesity and other diseases related. PMID:27527189

  13. Predictable factors for lymph node metastasis in early gastric cancer analysis of clinicopathologic factors and biological markers.

    PubMed

    Wang, Yi-Wei; Zhu, Mei-Ling; Wang, Rui-Fen; Xue, Wen-Ji; Zhu, Xue-Ru; Wang, Li-Feng; Zheng, Lei-Zhen

    2016-07-01

    Predicting lymph node metastasis (LNM) accurately is very important to decide treatment strategies preoperatively. The aim of this study was to explore risk factors that predict the presence of LNM in early gastric cancer (EGC). A total of 230 patients with EGC who underwent curative gastrectomy with lymph adenectomy at Xinhua Hospital from January 2006 to July 2014 were retrospectively reviewed. We studied the relationship between clinicopathological factors, biological markers (p53, ki67, nm23, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), E-cadherin (E-cad), beta-catenin (b-catenin), glutathione S-transferase (GST), and topoisomerase II (Topo II)), and LNM of EGC patients by chi-square test and logistic regression analysis. Meta-analyses were further conducted to review the effects of the proteins (P53, ki67, E-cad, and b-catenin) on LNM in ECG patients. LNM was detected in 42 (18.3 %) of 230 patients. Incidences of LNM was distinct in different tumor size (p = 0.044), depth of submucosal invasion (p < 0.0001), and P53 overexpression (p = 0.004). Multivariate analysis further indentified that large tumor size (≥20 mm, odds ratio (OR) = 2.168, p = 0.041), submucosa (OR = 4.000, p = 0.0005), and P53 overexpression (OR = 3.010, p = 0.022) were independent risk factors of LNM in EGC patients. The meta-analysis revealed a significantly statistical association of P53, ki67, and b-catenin with an increased risk of LNM in EGC patients (P53, OR = 1.81, p = 0.017; ki67, OR = 2.53, p = 0.0003; b-catenin, OR = 0.53, p = 0.01). Tumor size (≥20 mm), the depth of invasion (submucosa), and P53 overexpression may be helpful predictors of LNM in EGC patients. Furthermore, the results of meta-analysis revealed that P53, ki67 overexpression, and abnormal expression of b-catenin may be associated with LNM in EGC. The results need further validation in single large studies. PMID

  14. Reaction between peroxynitrite and triphenylphosphonium-substituted arylboronic acid isomers: identification of diagnostic marker products and biological implications.

    PubMed

    Sikora, Adam; Zielonka, Jacek; Adamus, Jan; Debski, Dawid; Dybala-Defratyka, Agnieszka; Michalowski, Bartosz; Joseph, Joy; Hartley, Richard C; Murphy, Michael P; Kalyanaraman, Balaraman

    2013-06-17

    Aromatic boronic acids react rapidly with peroxynitrite (ONOO(-)) to yield phenols as major products. This reaction was used to monitor ONOO(-) formation in cellular systems. Previously, we proposed that the reaction between ONOO(-) and arylboronates (PhB(OH)2) yields a phenolic product (major pathway) and a radical pair PhB(OH)2O(•-)···(•)NO2 (minor pathway). [Sikora, A. et al. (2011) Chem. Res. Toxicol. 24, 687-697]. In this study, we investigated the influence of a bulky triphenylphosphonium (TPP) group on the reaction between ONOO(-) and mitochondria-targeted arylboronate isomers (o-, m-, and p-MitoPhB(OH)2). Results from the electron paramagnetic resonance (EPR) spin-trapping experiments unequivocally showed the presence of a phenyl radical intermediate from meta and para isomers, and not from the ortho isomer. The yield of o-MitoPhNO2 formed from the reaction between o-MitoPhB(OH)2 and ONOO(-) was not diminished by phenyl radical scavengers, suggesting a rapid fragmentation of the o-MitoPhB(OH)2O(•-) radical anion with subsequent reaction of the resulting phenyl radical with (•)NO2 in the solvent cage. The DFT quantum mechanical calculations showed that the energy barrier for the dissociation of the o-MitoPhB(OH)2O(•-) radical anion is significantly lower than that of m-MitoPhB(OH)2O(•-) and p-MitoPhB(OH)2O(•-) radical anions. The nitrated product, o-MitoPhNO2, is not formed by the nitrogen dioxide radical generated by myeloperoxidase in the presence of the nitrite anion and hydrogen peroxide, indicating that this specific nitrated product may be used as a diagnostic marker product for ONOO(-). Incubation of o-MitoPhB(OH)2 with RAW 264.7 macrophages activated to produce ONOO(-) yielded the corresponding phenol o-MitoPhOH as well as the diagnostic nitrated product, o-MitoPhNO2. We conclude that the ortho isomer probe reported here is most suitable for specific detection of ONOO(-) in biological systems. PMID:23611338

  15. Reaction between peroxynitrite and triphenylphosphonium-substituted arylboronic acid isomers–Identification of diagnostic marker products and biological implications

    PubMed Central

    Sikora, Adam; Zielonka, Jacek; Adamus, Jan; Debski, Dawid; Dybala-Defratyka, Agnieszka; Michalowski, Bartosz; Joseph, Joy; Hartley, Richard C.; Murphy, Michael P.; Kalyanaraman, Balaraman

    2013-01-01

    Aromatic boronic acids react rapidly with peroxynitrite (ONOO−) to yield phenols as major products. This reaction was used to monitor ONOO− formation in cellular systems. Previously, we proposed that the reaction between ONOO− and arylboronates (PhB(OH)2) yields a phenolic product (major pathway) and a radical pair PhB(OH)2O•−…•NO2 (minor pathway). [Sikora A. et al., Chem Res Toxicol 24, 687-97, 2011]. In this study, we investigated the influence of a bulky triphenylphosphonium (TPP) group on the reaction between ONOO− and mitochondria-targeted arylboronate isomers (o-, m-, and p-MitoPhB(OH)2). Results from the electron paramagnetic resonance (EPR) spin-trapping experiments unequivocally showed the presence of a phenyl radical intermediate from meta and para isomers, and not from the ortho isomer. The yield of o-MitoPhNO2 formed from the reaction between o-MitoPhB(OH)2 and ONOO− was not diminished by phenyl radical scavengers, suggesting a rapid fragmentation of the o-MitoPhB(OH)2O•− radical anion with subsequent reaction of the resulting phenyl radical with •NO2 in the solvent cage. The DFT quantum mechanical calculations showed that the energy barrier for the dissociation of o-MitoPhB(OH)2O•− radical anion is significantly lower than that of m-MitoPhB(OH)2O•− and p-MitoPhB(OH)2O•− radical anions. The nitrated product, o-MitoPhNO2, is not formed by nitrogen dioxide radical generated by myeloperoxidase in the presence of nitrite anion and hydrogen peroxide, indicating that this specific nitrated product may be used as a diagnostic marker product for ONOO−. Incubation of o-MitoPhB(OH)2 with RAW 264.7 macrophages activated to produce ONOO− yielded the corresponding phenol o-MitoPhOH as well as the diagnostic nitrated product, o-MitoPhNO2. We conclude that the ortho isomer probe reported here is most suitable for specific detection of ONOO− in biological systems. PMID:23611338

  16. Adequate Intake levels of choline are sufficient for preventing elevations in serum markers of liver dysfunction in Mexican American men but are not optimal for minimizing plasma total homocysteine increases after a methionine load2

    PubMed Central

    Veenema, Kristin; Solis, Claudia; Li, Rui; Wang, Wei; Maletz, Charles V; Abratte, Christian M; Caudill, Marie A

    2009-01-01

    Background An adequate intake of 550 mg choline/d was established for the prevention of liver dysfunction in men, as assessed by measuring serum alanine aminotransferase concentrations. Objective This controlled feeding study investigated the influence of choline intakes ranging from 300 to 2200 mg/d on biomarkers of choline status. The effect of the methylenetetrahydrofolate reductase (MTHFR) C677T genotype on choline status was also examined. Design Mexican American men (n = 60) with different MTHFR C677T genotypes (29 677TT, 31 677CC) consumed a diet providing 300 mg choline/d plus supplemental choline intakes of 0, 250, 800, or 1900 mg/d for total choline intakes of 300, 550, 1100, or 2200 mg/d, respectively, for 12 wk; 400 μg/d as dietary folate equivalents and 173 mg betaine/d were consumed throughout the study. Results Choline intake affected the response of plasma free choline and betaine (time × choline, P < 0.001); the highest concentrations were observed in the 2200 mg/d group. Phosphatidylcholine (P = 0.026) and total cholesterol (P = 0.002) were also influenced by choline intake; diminished concentrations were observed in the 300 mg/d group. Phosphatidylcholine was modified by MTHFR genotype (P = 0.035; 677TT < 677CC). After a methionine load (100 mg/kg body wt), choline intakes of 1100 and 2200 mg/d attenuated (P = 0.016) the rise in plasma homocysteine, as did the MTHFR 677TT genotype (P < 0.001). Serum alanine aminotransferase was not influenced by the choline intakes administered in this study. Conclusions These data suggest that 550 mg choline/d is sufficient for preventing elevations in serum markers of liver dysfunction in this population under the conditions of this study; higher intakes may be needed to optimize other endpoints. PMID:18779284

  17. Diastolic Dysfunction

    PubMed Central

    Jeong, Euy-Myoung; Dudley, Samuel C.

    2016-01-01

    Despite the growing number of patients affected, the understanding of diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF) is still poor. Clinical trials, largely based on successful treatments for systolic heart failure, have been disappointing, suggesting that HFpEF has a different pathology to that of systolic dysfunction. In this review, general concepts, epidemiology, diagnosis, and treatment of diastolic dysfunction are summarized, with an emphasis on new experiments suggesting that oxidative stress plays a crucial role in the pathogenesis of at least some forms of the disease. This observation has lead to potential new diagnostics and therapeutics for diastolic dysfunction and heart failure caused by diastolic dysfunction. PMID:25746522

  18. Biological Marker Analysis as Part of the CIBERES-RTIC Cancer-SEPAR Strategic Project on Lung Cancer.

    PubMed

    Monsó, Eduard; Montuenga, Luis M; Sánchez de Cos, Julio; Villena, Cristina

    2015-09-01

    The aim of the Clinical and Molecular Staging of Stage I-IIp Lung Cancer Project is to identify molecular variables that improve the prognostic and predictive accuracy of TMN classification in stage I/IIp non-small cell lung cancer (NSCLC). Clinical data and lung tissue, tumor and blood samples will be collected from 3 patient cohorts created for this purpose. The prognostic protein signature will be validated from these samples, and micro-RNA, ALK, Ros1, Pdl-1, and TKT, TKTL1 y G6PD expression will be analyzed. Tissue inflammatory markers and stromal cell markers will also be analyzed. Methylation of p16, DAPK, RASSF1a, APC and CDH13 genes in the tissue samples will be determined, and inflammatory markers in peripheral blood will also be analyzed. Variables that improve the prognostic and predictive accuracy of TNM in NSCLC by molecular staging may be identified from this extensive analytical panel. PMID:25614375

  19. Infrared Structural Biology of Proteins: Development of Vibrational Structural Markers for Probing the Structural Dynamics of COO- of Asp/Glu in Proteins

    NASA Astrophysics Data System (ADS)

    Kang, Zhouyang; Xie, Aihua

    2013-03-01

    Asp and Glu often play critical roles in the active sites of proteins. Probing the structural dynamics of functionally important Asp and/or Glu provides crucial information for protein functionality. Time-resolved infrared structural biology offers strong advantages for its high structural sensitivity and broad dynamic range (ps to ks). In order to connect the vibrational frequencies to specific structures of COO- groups, such as the number, type, and geometry of hydrogen bond interactions, we develop two vibrational structural markers (VSM), built on the symmetric and asymmetric COO- stretching frequencies. Extensive quantum physics (density functional theory) based computational studies, combined with 13C isotopic editing of Asp/Glu and experimental FTIR data on Asp/Glu in proteins, are used to establish a unique correlation between the symmetric and asymmetric COO- vibrations with more than 10 types of hydrogen bonding interactions. Development of the COO- VSM markers enhances the power of time-resolved infrared structural biology for the study of functionally important structural dynamics of COO- in proteins, including rhodopsin for biological signaling, bacteriorhodopsin for proton transfer, photosystem II for energy transformation, and HIV protease for enzymatic catalysis.

  20. Polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs and related environmental compounds: biological markers of exposure and effects.

    PubMed Central

    Talaska, G; Underwood, P; Maier, A; Lewtas, J; Rothman, N; Jaeger, M

    1996-01-01

    Lung cancer caused by polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs and related environmental agents is a major problem in industrialized nations. The high case-fatality rate of the disease, even with the best supportive treatment, underscores the importance of primary lung cancer prevention. Development of biomarkers of exposure and effects to PAHs and related compounds is now underway and includes measurement of urinary metabolites of specific PAHs as well as detection of protein and DNA adducts as indicators of effective dose. Validation of these markers in terms of total environmental dose requires that concurrent measures of air levels and potential dermal exposure be made. In addition, the interrelationships between PAH biomarkers must be determined, particularly when levels of the marker in surrogate molecules (e.g., protein) or markers from surrogate tissues (e.g., lymphocyte DNA) are used to assess the risk to the target organ, the lung. Two approaches to biomarker studies will be reviewed in this article: the progress made using blood lymphocytes as surrogates for lung tissues and the progress made developing noninvasive markers of carcinogen-DNA adduct levels in lung-derived cells available in bronchial-alveolar lavage and in sputum. Data are presented from studies in which exfoliated urothelial cells were used as a surrogate tissue to assess exposure to human urinary bladder carcinogens in occupational groups. PMID:8933032

  1. Erectile dysfunction.

    PubMed

    Yafi, Faysal A; Jenkins, Lawrence; Albersen, Maarten; Corona, Giovanni; Isidori, Andrea M; Goldfarb, Shari; Maggi, Mario; Nelson, Christian J; Parish, Sharon; Salonia, Andrea; Tan, Ronny; Mulhall, John P; Hellstrom, Wayne J G

    2016-01-01

    Erectile dysfunction is a multidimensional but common male sexual dysfunction that involves an alteration in any of the components of the erectile response, including organic, relational and psychological. Roles for nonendocrine (neurogenic, vasculogenic and iatrogenic) and endocrine pathways have been proposed. Owing to its strong association with metabolic syndrome and cardiovascular disease, cardiac assessment may be warranted in men with symptoms of erectile dysfunction. Minimally invasive interventions to relieve the symptoms of erectile dysfunction include lifestyle modifications, oral drugs, injected vasodilator agents and vacuum erection devices. Surgical therapies are reserved for the subset of patients who have contraindications to these nonsurgical interventions, those who experience adverse effects from (or are refractory to) medical therapy and those who also have penile fibrosis or penile vascular insufficiency. Erectile dysfunction can have deleterious effects on a man's quality of life; most patients have symptoms of depression and anxiety related to sexual performance. These symptoms, in turn, affect his partner's sexual experience and the couple's quality of life. This Primer highlights numerous aspects of erectile dysfunction, summarizes new treatment targets and ongoing preclinical studies that evaluate new pharmacotherapies, and covers the topic of regenerative medicine, which represents the future of sexual medicine. PMID:27188339

  2. Biological findings from the PheWAS catalog: focus on connective tissue-related disorders (pelvic floor dysfunction, abdominal hernia, varicose veins and hemorrhoids).

    PubMed

    Salnikova, Lyubov E; Khadzhieva, Maryam B; Kolobkov, Dmitry S

    2016-07-01

    Pelvic floor dysfunction, specifically genital prolapse (GP) and stress urinary inconsistency (SUI) presumably co-occur with other connective tissue disorders such as hernia, hemorrhoids, and varicose veins. Observations on non-random coexistence of these disorders have never been summarized in a meta-analysis. The performed meta-analysis demonstrated that varicose veins and hernia are associated with GP. Disease connections on the molecular level may be partially based on shared genetic susceptibility. A unique opportunity to estimate shared genetic susceptibility to disorders is provided by a PheWAS (phenome-wide association study) designed to utilize GWAS data concurrently to many phenotypes. We searched the PheWAS Catalog, which includes the results of the PheWAS study with P value < 0.05, for genes associated with GP, SUI, abdominal hernia, varicose veins and hemorrhoids. We found pronounced signals for the associations of the SLC2A9 gene with SUI (P = 6.0e-05) and the MYH9 gene with varicose veins of lower extremity (P = 0.0001) and hemorrhoids (P = 0.0007). The comparison of the PheWAS Catalog and the NHGRI Catalog data revealed enrichment of genes associated with bone mineral density in GP and with activated partial thromboplastin time in varicose veins of lower extremity. In cross-phenotype associations, genes responsible for peripheral nerve functions seem to predominate. This study not only established novel biologically plausible associations that may warrant further studies but also exemplified an effective use of the PheWAS Catalog data. PMID:27126235

  3. Intra individual variability in markers of proteinuria for normal subjects and those with cadmium induced renal dysfunction: interpretation of results from untimed, random urine samples.

    PubMed

    Howard J Mason Alison J Stevenson Nerys Williams Michael Morgan

    1999-01-01

    The project aimed to help interpretation of urinary protein measurements, namely -2-microglobulin, retinol-binding protein, albumin and total protein in untimed, random urine samples as indicating significant changes in renal tubular reabsorption and glomerular permeability in an individual. A standard methodology used in clinical laboratory medicine was applied to calculate the intra-individual biological variation for these analytes. This parameter in conjunction with a laboratory's analytical variation allows definition of uncertainty about a single urine protein measurement, significant changes above normal variation in serial measurements within an individual and a defined level of maximum acceptable analytical imprecision. Repeat urine samples were obtained over a period of one week from a group of cadmium-exposed workers, 90% of whom had long-term tubular proteinuria, and a group of five unexposed volunteers with normal renal function. Dilute samples defined as having creatinines less than 3 mmol l-1 were excluded, as were urines with pH less than 5.5 for -2-microglobulin. Samples were analysed twice after randomisation in large batches. There was no evidence of any diurnal variation in the four protein measurements from samples collected between early morning and 16:00 hours. Creatinine or specific gravity correction of urine results for all four proteins only marginally reduced the uncertainty associated with an individual measurement asreflecting the true excretion value. For those subjects with defined tubular proteinuria, variability in retinol-binding protein excretion was less than that for -2- microglobulin. About 30% of the samples had urine pHs of 5.5 or less where -2- microglobulin degradation occurs. Using our laboratory analytical precision the minimum changes between serial creatinine-corrected measurements that are needed to be considered statistically significant (p < 0.05) is 110% for retinol-binding protein, 177% for -2-microglobulin, 70

  4. Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for biomarkers and endophenotypes of schizophrenia part I: Neurophysiology.

    PubMed

    Thibaut, Florence; Boutros, Nash N; Jarema, Marek; Oranje, Bob; Hasan, Alkomiet; Daskalakis, Zafiris Jeffrey; Wichniak, Adam; Schmitt, Andrea; Riederer, Peter; Falkai, Peter

    2015-01-01

    The neurophysiological components that have been proposed as biomarkers or as endophenotypes for schizophrenia can be measured through electroencephalography (EEG) and magnetoencephalography (MEG), transcranial magnetic stimulation (TMS), polysomnography (PSG), registration of event-related potentials (ERPs), assessment of smooth pursuit eye movements (SPEM) and antisaccade paradigms. Most of them demonstrate deficits in schizophrenia, show at least moderate stability over time and do not depend on clinical status, which means that they fulfil the criteria as valid endophenotypes for genetic studies. Deficits in cortical inhibition and plasticity measured using non-invasive brain stimulation techniques seem promising markers of outcome and prognosis. However the utility of these markers as biomarkers for predicting conversion to psychosis, response to treatments, or for tracking disease progression needs to be further studied. PMID:26213111

  5. Surgically resected human tumors reveal the biological significance of the gastric cancer stem cell markers CD44 and CD26

    PubMed Central

    NISHIKAWA, SHIMPEI; KONNO, MASAMITSU; HAMABE, ATSUSHI; HASEGAWA, SHINICHIRO; KANO, YOSHIHIRO; FUKUSUMI, TAKAHITO; SATOH, TAROH; TAKIGUCHI, SHUJI; MORI, MASAKI; DOKI, YUICHIRO; ISHII, HIDESHI

    2015-01-01

    Cancer tissue is maintained by relatively small populations of cancer stem cells (CSCs), which are involved in chemotherapy resistance, recurrence and metastasis. As tumor tissues are comprised of various cells, studies of human clinical samples are important for the characterization of CSCs. In the present study, an expression profiling study was performed in which an anti-cell surface marker antibody-based array platform, a flow cytometry-based cell separation technique and a tumorigenicity analysis in immunodeficient animals were utilized. These approaches revealed that the markers cluster of differentiation (CD)44 and CD26 facilitated the fractionation of surgically resected human gastric cancer (GC) cells into the following subset populations with distinct tumorigenic potentials: Highly tumorigenic CD26+CD44+ cells (6/6 mice formed tumors), moderately tumorigenic CD26+CD44− cells (5/6 mice formed tumors), and weakly or non-tumorigenic CD26−CD44− cells (2/6 mice formed tumors). Furthermore, exposure to 5-fluorouracil significantly increased the proportion of CD26+ cells in vitro. The present study demonstrated that the combined expression of CD26 and CD44 presents a potential marker of human GC stem cells. PMID:26137071

  6. Socioeconomic Status and Biological Markers of Health: An Examination of Adults in the United States and Taiwan

    PubMed Central

    Glei, Dana A.; Goldman, Noreen; Ryff, Carol D.; Weinstein, Maxine

    2014-01-01

    Objective The study documents whether socioeconomic status (SES) differentials in biological risk are more widely observed and larger in the United States than Taiwan. Method Data come from the Social Environment and Biomarkers of Aging Study in Taiwan and the Midlife in the United States study. We use regression analyses to test whether four summary measures of biological risk are significantly related to categorical measures of education, income, and subjective social status among four country-sex specific subgroups. Results Physiological dysregulation is significantly, negatively related to SES in both the US and Taiwan, especially for males. The prevalence and magnitude of the relationships are similar in the two countries:12 of 24 possible SES-biological summary score relationships are significant in the US and 11 of 24 are significant in Taiwan. Discussion Overall, SES differentials in biological risk do not appear to be more widely observed or larger in the US than in Taiwan. PMID:24972822

  7. Parasites as Biological Tags for Stock Discrimination of Beaked Redfish (Sebastes mentella): Parasite Infra-Communities vs. Limited Resolution of Cytochrome Markers

    PubMed Central

    Klapper, Regina; Kochmann, Judith; O’Hara, Robert B.; Karl, Horst; Kuhn, Thomas

    2016-01-01

    The use of parasites as biological tags for discrimination of fish stocks has become a commonly used approach in fisheries management. Metazoan parasite community analysis and anisakid nematode population genetics based on a mitochondrial cytochrome marker were applied in order to assess the usefulness of the two parasitological methods for stock discrimination of beaked redfish Sebastes mentella of three fishing grounds in the North East Atlantic. Multivariate, model-based approaches demonstrated that the metazoan parasite fauna of beaked redfish from East Greenland differed from Tampen, northern North Sea, and Bear Island, Barents Sea. A joint model (latent variable model) was used to estimate the effects of covariates on parasite species and identified four parasite species as main source of differences among fishing grounds; namely Chondracanthus nodosus, Anisakis simplex s.s., Hysterothylacium aduncum, and Bothriocephalus scorpii. Due to its high abundance and differences between fishing grounds, Anisakis simplex s.s. was considered as a major biological tag for host stock differentiation. Whilst the sole examination of Anisakis simplex s.s. on a population genetic level is only of limited use, anisakid nematodes (in particular, A. simplex s.s.) can serve as biological tags on a parasite community level. This study confirmed the use of multivariate analyses as a tool to evaluate parasite infra-communities and to identify parasite species that might serve as biological tags. The present study suggests that S. mentella in the northern North Sea and Barents Sea is not sub-structured. PMID:27104735

  8. Parasites as Biological Tags for Stock Discrimination of Beaked Redfish (Sebastes mentella): Parasite Infra-Communities vs. Limited Resolution of Cytochrome Markers.

    PubMed

    Klapper, Regina; Kochmann, Judith; O'Hara, Robert B; Karl, Horst; Kuhn, Thomas

    2016-01-01

    The use of parasites as biological tags for discrimination of fish stocks has become a commonly used approach in fisheries management. Metazoan parasite community analysis and anisakid nematode population genetics based on a mitochondrial cytochrome marker were applied in order to assess the usefulness of the two parasitological methods for stock discrimination of beaked redfish Sebastes mentella of three fishing grounds in the North East Atlantic. Multivariate, model-based approaches demonstrated that the metazoan parasite fauna of beaked redfish from East Greenland differed from Tampen, northern North Sea, and Bear Island, Barents Sea. A joint model (latent variable model) was used to estimate the effects of covariates on parasite species and identified four parasite species as main source of differences among fishing grounds; namely Chondracanthus nodosus, Anisakis simplex s.s., Hysterothylacium aduncum, and Bothriocephalus scorpii. Due to its high abundance and differences between fishing grounds, Anisakis simplex s.s. was considered as a major biological tag for host stock differentiation. Whilst the sole examination of Anisakis simplex s.s. on a population genetic level is only of limited use, anisakid nematodes (in particular, A. simplex s.s.) can serve as biological tags on a parasite community level. This study confirmed the use of multivariate analyses as a tool to evaluate parasite infra-communities and to identify parasite species that might serve as biological tags. The present study suggests that S. mentella in the northern North Sea and Barents Sea is not sub-structured. PMID:27104735

  9. Gustatory dysfunction

    PubMed Central

    Maheswaran, T.; Abikshyeet, P.; Sitra, G.; Gokulanathan, S.; Vaithiyanadane, V.; Jeelani, S.

    2014-01-01

    Tastes in humans provide a vital tool for screening soluble chemicals for food evaluation, selection, and avoidance of potentially toxic substances. Taste or gustatory dysfunctions are implicated in loss of appetite, unintended weight loss, malnutrition, and reduced quality of life. Dental practitioners are often the first clinicians to be presented with complaints about taste dysfunction. This brief review provides a summary of the common causes of taste disorders, problems associated with assessing taste function in a clinical setting and management options available to the dental practitioner. PMID:25210380

  10. Constitutive expression of tdTomato protein as a cytotoxicity and proliferation marker for space radiation biology

    NASA Astrophysics Data System (ADS)

    Chishti, Arif A.; Hellweg, Christine E.; Berger, Thomas; Baumstark-Khan, Christa; Feles, Sebastian; Kätzel, Thorben; Reitz, Günther

    2015-01-01

    The radiation risk assessment for long-term space missions requires knowledge on the biological effectiveness of different space radiation components, e.g. heavy ions, on the interaction of radiation and other space environmental factors such as microgravity, and on the physical and biological dose distribution in the human body. Space experiments and ground-based experiments at heavy ion accelerators require fast and reliable test systems with an easy readout for different endpoints. In order to determine the effect of different radiation qualities on cellular proliferation and the biological depth dose distribution after heavy ion exposure, a stable human cell line expressing a novel fluorescent protein was established and characterized. tdTomato, a red fluorescent protein of the new generation with fast maturation and high fluorescence intensity, was selected as reporter of cell proliferation. Human embryonic kidney (HEK/293) cells were stably transfected with a plasmid encoding tdTomato under the control of the constitutively active cytomegalovirus (CMV) promoter (ptdTomato-N1). The stably transfected cell line was named HEK-ptdTomato-N1 8. This cytotoxicity biosensor was tested by ionizing radiation (X-rays and accelerated heavy ions) exposure. As biological endpoints, the proliferation kinetics and the cell density reached 100 h after irradiation reflected by constitutive expression of the tdTomato were investigated. Both were reduced dose-dependently after radiation exposure. Finally, the cell line was used for biological weighting of heavy ions of different linear energy transfer (LET) as space-relevant radiation quality. The relative biological effectiveness of accelerated heavy ions in reducing cellular proliferation peaked at an LET of 91 keV/μm. The results of this study demonstrate that the HEK-ptdTomato-N1 reporter cell line can be used as a fast and reliable biosensor system for detection of cytotoxic damage caused by ionizing radiation.

  11. A Novel Malaria Pf/Pv Ab Rapid Diagnostic Test Using a Differential Diagnostic Marker Identified by Network Biology.

    PubMed

    Cho, Sung Jin; Lee, Jihoo; Lee, Hyun Jae; Jo, Hyun-Young; Sinniah, Mangalam; Kim, Hak-Yong; Chong, Chom-Kyu; Song, Hyun-Ok

    2016-01-01

    Rapid diagnostic tests (RDTs) can detect anti-malaria antibodies in human blood. As they can detect parasite infection at the low parasite density, they are useful in endemic areas where light infection and/or re-infection of parasites are common. Thus, malaria antibody tests can be used for screening bloods in blood banks to prevent transfusion-transmitted malaria (TTM), an emerging problem in malaria endemic areas. However, only a few malaria antibody tests are available in the microwell-based assay format and these are not suitable for field application. A novel malaria antibody (Ab)-based RDT using a differential diagnostic marker for falciparum and vivax malaria was developed as a suitable high-throughput assay that is sensitive and practical for blood screening. The marker, merozoite surface protein 1 (MSP1) was discovered by generation of a Plasmodium-specific network and the hierarchical organization of modularity in the network. Clinical evaluation revealed that the novel Malaria Pf/Pv Ab RDT shows improved sensitivity (98%) and specificity (99.7%) compared with the performance of a commercial kit, SD BioLine Malaria P.f/P.v (95.1% sensitivity and 99.1% specificity). The novel Malaria Pf/Pv Ab RDT has potential for use as a cost-effective blood-screening tool for malaria and in turn, reduces TTM risk in endemic areas. PMID:27313496

  12. A Novel Malaria Pf/Pv Ab Rapid Diagnostic Test Using a Differential Diagnostic Marker Identified by Network Biology

    PubMed Central

    Cho, Sung Jin; Lee, Jihoo; Lee, Hyun Jae; Jo, Hyun-Young; Sinniah, Mangalam; Kim, Hak-Yong; Chong, Chom-Kyu; Song, Hyun-Ok

    2016-01-01

    Rapid diagnostic tests (RDTs) can detect anti-malaria antibodies in human blood. As they can detect parasite infection at the low parasite density, they are useful in endemic areas where light infection and/or re-infection of parasites are common. Thus, malaria antibody tests can be used for screening bloods in blood banks to prevent transfusion-transmitted malaria (TTM), an emerging problem in malaria endemic areas. However, only a few malaria antibody tests are available in the microwell-based assay format and these are not suitable for field application. A novel malaria antibody (Ab)-based RDT using a differential diagnostic marker for falciparum and vivax malaria was developed as a suitable high-throughput assay that is sensitive and practical for blood screening. The marker, merozoite surface protein 1 (MSP1) was discovered by generation of a Plasmodium-specific network and the hierarchical organization of modularity in the network. Clinical evaluation revealed that the novel Malaria Pf/Pv Ab RDT shows improved sensitivity (98%) and specificity (99.7%) compared with the performance of a commercial kit, SD BioLine Malaria P.f/P.v (95.1% sensitivity and 99.1% specificity). The novel Malaria Pf/Pv Ab RDT has potential for use as a cost-effective blood-screening tool for malaria and in turn, reduces TTM risk in endemic areas. PMID:27313496

  13. Ejaculatory dysfunction.

    PubMed

    Phillips, Elizabeth; Carpenter, Christina; Oates, Robert D

    2014-02-01

    Ejaculatory dysfunction may occur after many different disorders ranging from traumatic spinal cord injury to diabetes mellitus. With an understanding of the many facets and nuances of the ejaculatory apparatus, both anatomic and neurologic, the well-versed clinician can proceed along a safe, efficient, and appropriate treatment algorithm to help affected men and their partners achieve parenthood. PMID:24286771

  14. Erectile Dysfunction

    MedlinePlus

    ... or vascular problems, will have a more difficult time returning to pre-treatment function. Management of Erectile Dysfunction When a man is sexually aroused, the erectile nerves running alongside the penis stimulate the ... blood to rush in. At the same time, tiny valves at the base of the penis ...

  15. Memory dysfunction.

    PubMed

    Amici, Serena

    2012-01-01

    Memory is the cognitive ability that allows to acquire, store and recall information; its dysfunction is called amnesia and can be a presentation of unilateral ischemic stroke in the territory of the posterior cerebral and anterior choroidal artery as well as subarachnoid hemorrhage. PMID:22377863

  16. Sensory Dysfunction

    MedlinePlus

    ... to Web version Sensory Dysfunction Overview Why are smell and taste important? Your senses of smell and taste let you fully enjoy the scents ... bitter and sour. Flavor involves both taste and smell. For example, because a person is able to ...

  17. Olfactory dysfunction in Alzheimer’s disease

    PubMed Central

    Zou, Yong-ming; Lu, Da; Liu, Li-ping; Zhang, Hui-hong; Zhou, Yu-ying

    2016-01-01

    Alzheimer’s disease (AD) is a common neurodegenerative disorder with the earliest clinical symptom of olfactory dysfunction, which is a potential clinical marker for AD severity and progression. However, many questions remain unanswered. This article reviews relevant research on olfactory dysfunction in AD and evaluates the predictive value of olfactory dysfunction for the epidemiological, pathophysiological, and clinical features of AD, as well as for the conversion of cognitive impairment to AD. We summarize problems of existing studies and provide a useful reference for further studies in AD olfactory dysfunction and for clinical applications of olfactory testing. PMID:27143888

  18. Integrated analysis of pediatric glioblastoma reveals a subset of biologically favorable tumors with associated molecular prognostic markers.

    PubMed

    Korshunov, Andrey; Ryzhova, Marina; Hovestadt, Volker; Bender, Sebastian; Sturm, Dominik; Capper, David; Meyer, Jochen; Schrimpf, Daniel; Kool, Marcel; Northcott, Paul A; Zheludkova, Olga; Milde, Till; Witt, Olaf; Kulozik, Andreas E; Reifenberger, Guido; Jabado, Nada; Perry, Arie; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M; Jones, David T W

    2015-05-01

    Pediatric glioblastoma (pedGBM) is amongst the most common malignant brain tumors of childhood and carries a dismal prognosis. In contrast to adult GBM, few molecular prognostic markers for the pediatric counterpart have been established. We, therefore, investigated the prognostic significance of genomic and epigenetic alterations through molecular analysis of 202 pedGBM (1-18 years) with comprehensive clinical annotation. Routinely prepared formalin-fixed paraffin-embedded tumor samples were assessed for genome-wide DNA methylation profiles, with known candidate genes screened for alterations via direct sequencing or FISH. Unexpectedly, a subset of histologically diagnosed GBM (n = 40, 20 %) displayed methylation profiles similar to those of either low-grade gliomas or pleomorphic xanthoastrocytomas (PXA). These tumors showed a markedly better prognosis, with molecularly PXA-like tumors frequently harboring BRAF V600E mutations and 9p21 (CDKN2A) homozygous deletion. The remaining 162 tumors with pedGBM molecular signatures comprised four subgroups: H3.3 G34-mutant (15 %), H3.3/H3.1 K27-mutant (43 %), IDH1-mutant (6 %), and H3/IDH wild-type (wt) GBM (36 %). These subgroups were associated with specific cytogenetic aberrations, MGMT methylation patterns and clinical outcomes. Analysis of follow-up data identified a set of biomarkers feasible for use in risk stratification: pedGBM with any oncogene amplification and/or K27M mutation (n = 124) represents a particularly unfavorable group, with 3-year overall survival (OS) of 5 %, whereas tumors without these markers (n = 38) define a more favorable group (3-year OS ~70 %).Combined with the lower grade-like lesions, almost 40 % of pedGBM cases had distinct molecular features associated with a more favorable outcome. This refined prognostication method for pedGBM using a molecular risk algorithm may allow for improved therapeutic choices and better planning of clinical trial stratification for this otherwise devastating

  19. Conditional independence relations among biological markers may improve clinical decision as in the case of triple negative breast cancers

    PubMed Central

    Stefanini, Federico M; Coradini, Danila; Biganzoli, Elia

    2009-01-01

    The associations existing among different biomarkers are important in clinical settings because they contribute to the characterisation of specific pathways related to the natural history of the disease, genetic and environmental determinants. Despite the availability of binary/linear (or at least monotonic) correlation indices, the full exploitation of molecular information depends on the knowledge of direct/indirect conditional independence (and eventually causal) relationships among biomarkers, and with target variables in the population of interest. In other words, that depends on inferences which are performed on the joint multivariate distribution of markers and target variables. Graphical models, such as Bayesian Networks, are well suited to this purpose. Therefore, we reconsidered a previously published case study on classical biomarkers in breast cancer, namely estrogen receptor (ER), progesterone receptor (PR), a proliferative index (Ki67/MIB-1) and to protein HER2/neu (NEU) and p53, to infer conditional independence relations existing in the joint distribution by inferring (learning) the structure of graphs entailing those relations of independence. We also examined the conditional distribution of a special molecular phenotype, called triple-negative, in which ER, PR and NEU were absent. We confirmed that ER is a key marker and we found that it was able to define subpopulations of patients characterized by different conditional independence relations among biomarkers. We also found a preliminary evidence that, given a triple-negative profile, the distribution of p53 protein is mostly supported in 'zero' and 'high' states providing useful information in selecting patients that could benefit from an adjuvant anthracyclines/alkylating agent-based chemotherapy. PMID:19828073

  20. Radiosynthesis of [131I]IAZGP via nucleophilic substitution and its biological evaluation as a hypoxia marker — is specific activity a factor influencing hypoxia-mapping ability of a hypoxia marker?

    PubMed Central

    Suehiro, Makiko; Burgman, Paul; Carlin, Sean; Burke, Sean; Yang, Guangbin; Ouerfelli, Ouathek; Oehler-Janne, Christoph; O’Donoghue, Joseph; Ling, Clifton; Humm, John

    2010-01-01

    Introduction The hypoxia marker IAZGP, 1-(6-deoxy-6-iodo-β-D-galactopyranosyl)-2-nitroimidazole, has been labeled with 123I/124I/125I/131I via iodine–radioiodine exchange, which gives the radiotracer in a specific activity of 10–90 MBq/μmol. We synthesized the same radiotracer possessing several hundred to thousand times higher specific activity (high-SA IAZGP) via nucleophilic substitution and compared its biological behavior with that of conventionally produced IAZGP (low-SA IAZGP) to determine if specific activity is a factor influencing cell uptake kinetics, biodistribution and intratumor microregional localization of the radiotracer. Methods High-SA [131I]IAZGP was prepared by substitution of the tosyl functionality with [131I]iodide. In vitro uptake of high- and low-SA [131I]IAZGP by HCT8 and HT29 cells was assessed in normoxic and hypoxic conditions. Biodistribution and intratumor localization of high- and low-SA [131I]IAZGP were determined by injection into HT29 tumor-bearing mice. Results The nucleophilic substitution reaction proceeded efficiently in acetonitrile at 150°C, giving the final product in an average yield of 42% and an average specific activity of 30 GBq/μmol. In vitro, high-SA [131I]IAZGP was incorporated into the tumor cells with similar kinetics and oxygen dependence to low-SA [131I]IAZGP. In HT29 tumor-bearing mice, biodistributions of high- and low-SA [131I]IAZGP were equivalent. Ex vivo autoradiography revealed heterogeneous intratumor localization of high-SA [131I]IAZGP corresponding closely to distributions of other exogenous and endogenous hypoxia markers. Comparable microregional distribution patterns were observed with low-SA [131I]IAZGP. Conclusions Radiolabeled IAZGP produced via nucleophilic substitution is validated as an exogenous hypoxia marker. Specific activity does not appear to influence the in vivo hypoxia-mapping ability of the radiotracer. PMID:19520288

  1. Telomere Dysfunction Induced Foci (TIF) Analysis

    PubMed Central

    Mender, Ilgen; Shay, Jerry W.

    2016-01-01

    Telomerase maintains telomeric DNA in eukaryotes during early developments, ~90% of cancer cells and some proliferative stem like cells. Telomeric repeats at the end of chromosomes are associated with the shelterin complex. This complex consists of TRF1, TRF2, Rap1, TIN2, TPP1, POT1 which protect DNA from being recognized as DNA double-stranded breaks. Critically short telomeres or impaired shelterin proteins can cause telomere dysfunction, which eventually induces DNA damage responses at the telomeres. DNA damage responses can be identified by antibodies to 53BP1, gammaH2AX, Rad17, ATM, and Mre11. DNA damage foci at uncapped telomeres are referred to as Telomere dysfunction-Induced Foci (TIFs) (de Lange, 2005; Takai et al., 2003). The TIF assay is based on the co-localization detection of DNA damage by an antibody against DNA damage markers, such as gamma-H2AX, and telomeres using an antibody against one of the shelterin proteins such as TRF2 (Takai et al., 2003; de Lange, 2002; Karlseder et al., 1999). The method we describe here can be used in normal human and cancer cells. Other commonly used methods-Telomere Restriction Fragment (TRF) Analysis (Mender and Shay, 2015b) and Telomere Repeat Amplification Protocol (TRAP) (Mender and Shay, 2015a)- in telomere biology can be found by clicking on the indicated links.

  2. Utility of OCT3/4, TSPY and β-Catenin as Biological Markers for Gonadoblastoma Formation and Malignant Germ Cell Tumor Development in Dysgenetic Gonads

    PubMed Central

    Palma, Icela; Garibay, Nayely; Pena-Yolanda, Rocio; Contreras, Alejandra; Raya, Atlantida; Dominguez, Carolina; Romero, Mirna; Aristi, Gerardo; Queipo, Gloria

    2013-01-01

    BACKGROUND: Gonadoblastoma (GB) is regarded as an in situ form of germ cell tumor in dysgenetic gonads, and 30% of patients with GB develop a dysgerminoma/seminoma tumor. OBJECTIVE: Determine whether OCT3/4 and β-catenin are expressed in dysgenetic gonads before GB development and whether TSPY participates in the OCT3/4-β-catenin pathways in the malignant invasive behavior. METHODS: dysgenetic gonads of Disorders of sex differentiation (DSD) patients with mixed gonadal dysgenesis were analyzed by immunohistochemistry and immunofluorescence for comparison with GB and dysgerminoma/seminoma. RESULTS: Our results suggest that the development of GB is secondary to the interaction of OCT3/4 and TSPY, that β-catenin does not participate in this process. CONCLUSIONS: The use of this biological markers detects the potential high risk gonads. PMID:23396295

  3. Genetic investigation of biological materials from patients after stem cell transplantation based on autosomal as well as Y-chromosomal markers.

    PubMed

    Jacewicz, Renata; Lewandowski, Krzysztof; Rupa-Matysek, Joanna; Jedrzejczyk, Maciej; Komarnicki, Mieczysław; Berent, Jarosław

    2013-03-01

    The authors presented the results of DNA polymorphism investigation of blood, buccal swabs and hair follicles originating from patients after allogeneic hematopoietic stem cell transplantation. The real-time and multiplex assays based on polymerase chain reaction within the range of autosomal as well as Y-chromosomal markers were applied to assess the possible dangers arising from investigation of these materials in forensic genetics. The results revealed that not only post-transplant blood and buccal swab, but also recipient hair, up to now regarded as devoid of any donor's cells, do not constitute entirely safe material for forensic purposes. Their analysis can lead to the false identification of gender or male haplotype. The investigation of sex-determining region Y and Y-chromosome short tandem repeats performed in female recipients with male donors resulted in the designation of donor's DNA in hair cells as well as in blood and buccal swabs. Therefore, biological stains gathered from crime scenes should not be analysed exclusively based on the investigation of male-specific markers. PMID:23052441

  4. Multiple facets of histone variant H2AX: a DNA double-strand-break marker with several biological functions

    PubMed Central

    Turinetto, Valentina; Giachino, Claudia

    2015-01-01

    In the last decade, many papers highlighted that the histone variant H2AX and its phosphorylation on Ser 139 (γH2AX) cannot be simply considered a specific DNA double-strand-break (DSB) marker with a role restricted to the DNA damage response, but rather as a ‘protagonist’ in different scenarios. This review will present and discuss an up-to-date view regarding the ‘non-canonical’ H2AX roles, focusing in particular on possible functional and structural parts in contexts different from the canonical DNA DSB response. We will present aspects concerning sex chromosome inactivation in male germ cells, X inactivation in female somatic cells and mitosis, but will also focus on the more recent studies regarding embryonic and neural stem cell development, asymmetric sister chromosome segregation in stem cells and cellular senescence maintenance. We will discuss whether in these new contexts there might be a relation with the canonical DNA DSB signalling function that could justify γH2AX formation. The authors will emphasize that, just as H2AX phosphorylation signals chromatin alteration and serves the canonical function of recruiting DSB repair factors, so the modification of H2AX in contexts other than the DNA damage response may contribute towards creating a specific chromatin structure frame allowing ‘non-canonical’ functions to be carried out in different cell types. PMID:25712102

  5. Biological markers of asexuality: Handedness, birth order, and finger length ratios in self-identified asexual men and women.

    PubMed

    Yule, Morag A; Brotto, Lori A; Gorzalka, Boris B

    2014-02-01

    Human asexuality is defined as a lack of sexual attraction to anyone or anything and it has been suggested that it may be best conceptualized as a sexual orientation. Non-right-handedness, fraternal birth order, and finger length ratio (2D:4D) are early neurodevelopmental markers associated with sexual orientation. We conducted an Internet study investigating the relationship between self-identification as asexual, handedness, number of older siblings, and self-measured finger-lengths in comparison to individuals of other sexual orientation groups. A total of 325 asexuals (60 men and 265 women; M age, 24.8 years), 690 heterosexuals (190 men and 500 women; M age, 23.5 years), and 268 non-heterosexuals (homosexual and bisexual; 64 men and 204 women; M age, 29.0 years) completed online questionnaires. Asexual men and women were 2.4 and 2.5 times, respectively, more likely to be non-right-handed than their heterosexual counterparts and there were significant differences between sexual orientation groups in number of older brothers and older sisters, and this depended on handedness. Asexual and non-heterosexual men were more likely to be later-born than heterosexual men, and asexual women were more likely to be earlier-born than non-heterosexual women. We found no significant differences between sexual orientation groups on measurements of 2D:4D ratio. This is one of the first studies to test and provide preliminary empirical support for an underlying neurodevelopmental basis to account for the lack of sexual attraction characteristic of asexuality. PMID:24045903

  6. Intra-specific biodiversity of Italian myrtle (Myrtus communis) through chemical markers profile and biological activities of leaf methanolic extracts.

    PubMed

    Sacchetti, G; Muzzoli, M; Statti, G A; Conforti, F; Bianchi, A; Agrimonti, C; Ballero, M; Poli, F

    2007-02-01

    Methanolic extracts of Myrtus communis leaves from two Italian regions (Calabria and Sardinia) were processed to determine the content of myrtenol, linalool and eucalyptol. Among the Calabrian and Sardinian myrtle samples, linalool and eucalyptol chemotypes were prevalent. The extracts were also tested for antioxidant, antibacterial and antifungal activities. Myrtle leaves samples were dried and extracted through maceration. Partition chromatography was adopted to separate myrtenol, linalool and eucalyptol fractions. Analyses were performed through GC and GC-MS. Some of the samples showed a good scavenger activity evidenced by DPPH radical scavenging assay and beta-carotene bleaching test. Antibacterial and antifungal activities were generally weak. The phytochemical and biological characterization of all the extracts were determined with an aim to characterize the intra-specific biodiversity of myrtle populations. PMID:17365705

  7. The power and promise of identifying autism early: Insights from the search for clinical and biological markers

    PubMed Central

    Pierce, Karen; Glatt, Stephen J.; Liptak, Gregory S.; Lee McIntyre, Laura

    2016-01-01

    BACKGROUND The biological changes that lead to autism likely occur during prenatal life. Although earlier identification of the disorder has occurred within the past decade, the mean age of diagnosis is still not made before a mean age of 3 years. This is because autism remains a behaviorally defined disorder, placing limits on the age at which a confident diagnosis can be made. The study of the biological basis of autism prior to age 3 is essential and can most directly be achieved with prospective research designs. METHODS The literature on the early identification of autism is discussed, including the timescale for the onset of social symptoms. Also discussed is a new method for the prospective study of autism called the “1-Year Well-Baby Check-Up Approach,” which allows for the prospective study of the disorder in simplex families with infants as young as 12 months of age. RESULTS Although likely present at subtle, subclinical levels, early social abnormalities are not clearly detectable prior to 12 months in age in infants later diagnosed as having autism spectrum disorder. CONCLUSIONS Using the 1-Year Well-Baby Check-Up Approach or other prospective design, examining early biomarkers related to early brain overgrowth, cerebellar development, gene expression patterns and immune system function may be key to early diagnosis efforts under 3 years. We also note the importance of comparing and contrasting the early “signature” of autism in children from singleton versus multiplex families, which may be etiologically distinct. PMID:19758535

  8. Dysfunctional voiding.

    PubMed

    Chiozza, M L

    2002-01-01

    Wetting may be considered the Cinderella of paediatric medicine. Before discussing dysfunctional voiding, the milestones of the normal development of continence in the child and the definitions used to describe this topic are presented. Bladder storage requires (1): accommodation of increasing volumes of urine at low intravesical pressure and with appropriate sensation; (2): a bladder outlet that is closed and not modified during increase in intra-abdominal pressure; (3): absence of involuntary bladder contractions. Development of continence in the child involves three independent factors maturing concomitantly: (1) development of normal bladder capacity; (2) maturation of urethral sphincter function; (3) development of neural control over bladder-sphincter function. All these processes are discussed. Abnormalities of any of these maturational sequences, which run parallel and overlapping, may result in clinically evident abnormalities of bladder sphincter control. Although dysfunctional voiding (DV) in children is very common its prevalence has not been well studied and, to date, and its origin is not well known. In a correct evaluation of functional voiding we must take into account different elements: the bladder capacity (that increases during the first 8 years of life roughly 30 ml per year), the micturition frequency, post-void residual volumes, bladder dynamics, urinary flow rates. Thus the correct assessment of children with lower urinary tract dysfunction should include a detailed history. Signs of DV range from urge syndrome to complex incontinence patterns during the day and the night. In addition to incontinence problems, children may have frequency, urgency, straining to void, weak or interrupted urinary stream, urinary tract infections (UTIs) and chronic constipation with or without encopresis. DV are also referred in enuretic children who wet the bed more than one time per night and have a functional bladder capacity lower than attended for age

  9. Prognostic value of histological and biological markers in pharyngeal squamous cell carcinoma: a case-control study.

    PubMed Central

    Guerry, M.; Vabre, L.; Talbot, M.; Mamelle, G.; Leridant, A. M.; Hill, C.; Bosq, J.; Luboinski, B.; Janot, F.

    1998-01-01

    Between 1980 and 1985, 914 patients with head and neck squamous cell carcinoma underwent lymph node dissection in our institution. The prognostic value of clinical factors has already been reported (Mamelle et al, 1994, Am J Surg 168: 494-498). We present here a comparison of biological characteristics of pharyngeal tumours in patients who developed distant metastasis and in patients without metastasis, matched on tumour site, node site and size, and year of diagnosis. Tumour differentiation, keratinization, vascular emboli, immunohistochemical expression of p53, c-erb-B2, Rb and bcl2 were first assessed in 31 pairs of patients. Factors of potential interest were then determined in 32 additional pairs of patients. Statistical analysis showed that the risk of distant metastasis was halved in patients with tumours expressing c-erb-B2 compared with patients with c-erb-B2-negative tumours (P = 0.05). The significance of c-erb-B2 expression and its potential value as a prognostic factor is discussed. PMID:9667670

  10. A functional biological network centered on XRCC3: a new possible marker of chemoradiotherapy resistance in rectal cancer patients

    PubMed Central

    Agostini, Marco; Zangrando, Andrea; Pastrello, Chiara; D'Angelo, Edoardo; Romano, Gabriele; Giovannoni, Roberto; Giordan, Marco; Maretto, Isacco; Bedin, Chiara; Zanon, Carlo; Digito, Maura; Esposito, Giovanni; Mescoli, Claudia; Lavitrano, Marialuisa; Rizzolio, Flavio; Jurisica, Igor; Giordano, Antonio; Pucciarelli, Salvatore; Nitti, Donato

    2015-01-01

    Preoperative chemoradiotherapy is widely used to improve local control of disease, sphincter preservation and to improve survival in patients with locally advanced rectal cancer. Patients enrolled in the present study underwent preoperative chemoradiotherapy, followed by surgical excision. Response to chemoradiotherapy was evaluated according to Mandard's Tumor Regression Grade (TRG). TRG 3, 4 and 5 were considered as partial or no response while TRG 1 and 2 as complete response. From pretherapeutic biopsies of 84 locally advanced rectal carcinomas available for the analysis, only 42 of them showed 70% cancer cellularity at least. By determining gene expression profiles, responders and non-responders showed significantly different expression levels for 19 genes (P < 0.001). We fitted a logistic model selected with a stepwise procedure optimizing the Akaike Information Criterion (AIC) and then validated by means of leave one out cross validation (LOOCV, accuracy = 95%). Four genes were retained in the achieved model: ZNF160, XRCC3, HFM1 and ASXL2. Real time PCR confirmed that XRCC3 is overexpressed in responders group and HFM1 and ASXL2 showed a positive trend. In vitro test on colon cancer resistant/susceptible to chemoradioterapy cells, finally prove that XRCC3 deregulation is extensively involved in the chemoresistance mechanisms. Protein-protein interactions (PPI) analysis involving the predictive classifier revealed a network of 45 interacting nodes (proteins) with TRAF6 gene playing a keystone role in the network. The present study confirmed the possibility that gene expression profiling combined with integrative computational biology is useful to predict complete responses to preoperative chemoradiotherapy in patients with advanced rectal cancer. PMID:26023803

  11. Marker development

    SciTech Connect

    Adams, M.R.

    1987-05-01

    This report is to discuss the marker development for radioactive waste disposal sites. The markers must be designed to last 10,000 years, and place no undue burdens on the future generations. Barriers cannot be constructed that preclude human intrusion. Design specifications for surface markers will be discussed, also marker pictograms will also be covered.

  12. All men with vasculogenic erectile dysfunction require a cardiovascular workup.

    PubMed

    Miner, Martin; Nehra, Ajay; Jackson, Graham; Bhasin, Shalender; Billups, Kevin; Burnett, Arthur L; Buvat, Jacques; Carson, Culley; Cunningham, Glenn; Ganz, Peter; Goldstein, Irwin; Guay, Andre; Hackett, Geoff; Kloner, Robert A; Kostis, John B; LaFlamme, K Elizabeth; Montorsi, Piero; Ramsey, Melinda; Rosen, Raymond; Sadovsky, Richard; Seftel, Allen; Shabsigh, Ridwan; Vlachopoulos, Charalambos; Wu, Frederick

    2014-03-01

    An association between erectile dysfunction and cardiovascular disease has long been recognized, and studies suggest that erectile dysfunction is an independent marker of cardiovascular disease risk. Therefore, assessment and management of erectile dysfunction may help identify and reduce the risk of future cardiovascular events, particularly in younger men. The initial erectile dysfunction evaluation should distinguish between predominantly vasculogenic erectile dysfunction and erectile dysfunction of other etiologies. For men believed to have predominantly vasculogenic erectile dysfunction, we recommend that initial cardiovascular risk stratification be based on the Framingham Risk Score. Management of men with erectile dysfunction who are at low risk for cardiovascular disease should focus on risk-factor control; men at high risk, including those with cardiovascular symptoms, should be referred to a cardiologist. Intermediate-risk men should undergo noninvasive evaluation for subclinical atherosclerosis. A growing body of evidence supports the use of emerging prognostic markers to further understand cardiovascular risk in men with erectile dysfunction, but few markers have been prospectively evaluated in this population. In conclusion, we support cardiovascular risk stratification and risk-factor management in all men with vasculogenic erectile dysfunction. PMID:24423973

  13. Preoperative Volume-Based PET Parameter, MTV2.5, as a Potential Surrogate Marker for Tumor Biology and Recurrence in Resected Pancreatic Cancer.

    PubMed

    Kang, Chang Moo; Lee, Sung Hwan; Hwang, Ho Kyoung; Yun, Mijin; Lee, Woo Jung

    2016-03-01

    neoadjuvant treatment attenuated adverse oncologic impact of high preoperative MTV2.5 (P = 0.210). Preoperatively determined volume-based PET parameter, MTV2.5, can potentially be used as a surrogate marker to estimate tumor biology and tumor recurrence. Individual treatment strategies for pancreatic cancer can be suggested based on patients' preoperative MTV2.5. PMID:26945350

  14. Preoperative Volume-Based PET Parameter, MTV2.5, as a Potential Surrogate Marker for Tumor Biology and Recurrence in Resected Pancreatic Cancer

    PubMed Central

    Kang, Chang Moo; Lee, Sung Hwan; Hwang, Ho Kyoung; Yun, Mijin; Lee, Woo Jung

    2016-01-01

    neoadjuvant treatment attenuated adverse oncologic impact of high preoperative MTV2.5 (P = 0.210). Preoperatively determined volume-based PET parameter, MTV2.5, can potentially be used as a surrogate marker to estimate tumor biology and tumor recurrence. Individual treatment strategies for pancreatic cancer can be suggested based on patients’ preoperative MTV2.5. PMID:26945350

  15. Recreational drug use in the Oslo nightlife setting: study protocol for a cross-sectional time series using biological markers, self-reported and qualitative data

    PubMed Central

    Nordfjærn, Trond; Edland-Gryt, Marit; Bretteville-Jensen, Anne Line; Buvik, Kristin; Gripenberg, Johanna

    2016-01-01

    Introduction Recreational drug use in the nightlife setting carries the risk of many negative consequences, such as violence, injuries, aberrant driving and sexual risk-taking. The aim of this study is to investigate recreational drug use and user characteristics among people visiting licensed premises, for example, nightclubs and bars, by using self-reports and biological markers. Staff of licensed premises will be asked to report drug use observations. Further, by using qualitative data, we will examine the motives, consequences and culture associated with recreational drug use. An additional aim is to compare self-reported drug use with oral fluid test (OFT) results in order to validate the different measurement methods in this context. Methods and analyses Data collection will be conducted among patrons (n=1000) outside licensed premises. On consent, patrons will be asked to anonymously complete a questionnaire, a breath alcohol concentration test and an OFT. Patrons who report use of recreational drugs in the previous 12 months will be asked to leave their contact information for a subsequent qualitative in-depth interview (n=30–40). Staff from licensed premises (n=500) will be invited during Responsible Beverage Service Training to participate in an anonymous survey. Survey data will be analysed by univariate and multivariate statistical methods and the oral fluids will be analysed for a large number of drugs using biochemical methods. Cohen's κ will be used as a measure of agreement between self-reported drug use and OFT. In-depth interviews will be coded in HyperRESEARCH and analysed using an inductive approach. Data collection will be repeated on a biannual basis until at least 2020, allowing for examination of trends in recreational drug use. Ethics and dissemination This study has been approved by the Regional Committee for Medical and Health Research Ethics. Results will be disseminated in research journals, conferences and the media. PMID:27105710

  16. Prognostic significance of clinical parameters and biological markers in patients with squamous cell carcinoma of the head and neck treated with concurrent chemoradiotherapy.

    PubMed

    Homma, A; Furuta, Y; Oridate, N; Nakano, Y; Kohashi, G; Yagi, K; Nagahashi, T; Yagi, K; Nagahashi, T; Fukuda, S; Inoue, K; Inuyama, Y

    1999-04-01

    Concurrent chemoradiotherapy is reported to have a fair clinical outcome with organ preservation for patients with squamous cell carcinoma of the head and neck (SCCHN). The aim of this study was to determine whether biological markers are related to proliferative activity or apoptosis of tumor cells and whether clinical factors are associated with a clinical outcome in SCCHN patients treated with concurrent chemoradiotherapy. Immunostaining with antibodies specific for p53, bcl-2, bax, and MIB-1 was performed to evaluate expression of these proteins in formalin-fixed, paraffin-embedded specimens of 111 SCCHN patients treated with concurrent chemoradiotherapy (carboplatin, 100 mg/m2, four to six times every week; total radiation therapy dose of 40-65 Gy over 4-6.5 weeks). Multivariate analysis indicated that nodal status was a significant indicator of overall survival (OS; P = 0.001) and locoregional control (LRC; P = 0.002). In a univariate analysis, patients with a low MIB-1-positive index (< 40%) had better OS than those with a high MIB-1-positive index (> or = 40%; P = 0.013), although the difference was not statistically significant in a multivariate analysis (P = 0.060). Patients with bcl-2-positive tumors had better LRC than those with bcl-2-negative tumors, based on a multivariate analysis (P = 0.017). No statistically significant association was found between p53 or bax expression and clinical outcome. These results indicate that nodal status is the major prognostic factor in SCCHN patients treated with concurrent chemoradiotherapy. In addition, our findings suggest that bcl-2 positivity is associated with better LRC and that the proliferative activity of tumor cells might be prognostic for OS. PMID:10213215

  17. Biological and biophysics aspects of metformin-induced effects: cortex mitochondrial dysfunction and promotion of toxic amyloid pre-fibrillar aggregates.

    PubMed

    Picone, Pasquale; Vilasi, Silvia; Librizzi, Fabio; Contardi, Marco; Nuzzo, Domenico; Caruana, Luca; Baldassano, Sara; Amato, Antonella; Mulè, Flavia; San Biagio, Pier Luigi; Giacomazza, Daniela; Di Carlo, Marta

    2016-08-01

    The onset of Alzheimer disease (AD) is influenced by several risk factors comprising diabetes. Within this context, antidiabetic drugs, including metformin, are investigated for their effect on AD. We report that in the C57B6/J mice, metformin is delivered to the brain where activates AMP-activated kinase (AMPK), its molecular target. This drug affects the levels of β-secretase (BACE1) and β-amyloid precursor protein (APP), promoting processing and aggregation of β-amyloid (Aβ), mainly in the cortex region. Moreover, metformin induces mitochondrial dysfunction and cell death by affecting the level and conformation of Translocase of the Outer Membrane 40 (TOM40), voltage-dependent anion-selective channels 1 (VDAC1) and hexokinase I (HKI), proteins involved in mitochondrial transport of molecules, including Aβ. By using biophysical techniques we found that metformin is able to directly interact with Aβ influencing its aggregation kinetics and features. These findings indicate that metformin induces different adverse effects, leading to an overall increase of the risk of AD onset. PMID:27509335

  18. Photobiomodulation on alcohol induced dysfunction

    NASA Astrophysics Data System (ADS)

    Yang, Zheng-Ping; Liu, Timon C.; Zhang, Yan; Wang, Yan-Fang

    2007-05-01

    Alcohol, which is ubiquitous today, is a major health concern. Its use was already relatively high among the youngest respondents, peaked among young adults, and declined in older age groups. Alcohol is causally related to more than 60 different medical conditions. Overall, 4% of the global burden of disease is attributable to alcohol, which accounts for about as much death and disability globally as tobacco and hypertension. Alcohol also promotes the generation of reactive oxygen species (ROS) and/or interferes with the body's normal defense mechanisms against these compounds through numerous processes, particularly in the liver. Photobiomodulation (PBM) is a cell-specific effect of low intensity monochromatic light or low intensity laser irradiation (LIL) on biological systems. The cellular effects of both alcohol and LIL are ligand-independent so that PBM might rehabilitate alcohol induced dysfunction. The PBM on alcohol induced human neutrophil dysfunction and rat chronic atrophic gastritis, the laser acupuncture on alcohol addiction, and intravascular PBM on alcoholic coma of patients and rats have been observed. The endonasal PBM (EPBM) mediated by Yangming channel, autonomic nervous systems and blood cells is suggested to treat alcohol induced dysfunction in terms of EPBM phenomena, the mechanism of alcohol induced dysfunction and our biological information model of PBM. In our opinion, the therapeutic effects of PBM might also be achieved on alcoholic myopathy.

  19. Bone Markers

    MedlinePlus

    ... Alkaline Phosphatase; Osteocalcin; P1NP; Procollagen Type 1 N-Terminal Propeptide Formal name: Biochemical Markers of Bone Remodeling ... tests for evaluating bone turnover: C-telopeptide (C-terminal telopeptide of type 1 collagen (CTx)) – a marker ...

  20. Post-genomics of bone metabolic dysfunctions and neoplasias.

    PubMed

    Bernardini, Giulia; Braconi, Daniela; Spreafico, Adriano; Santucci, Annalisa

    2012-02-01

    Post-genomic research on osteoblastic and osteoclastic cells, in contrast to that on many other cell types, has only been undertaken recently. Nevertheless, important information has been gained from these investigations on the mechanisms involved in osteoblast differentiation and on markers relevant for tissue regeneration and therapeutic validation of drugs, hormones and growth factors. These protein indicators may also have a diagnostic and prognostic value for bone dysfunctions and tumors. Some reviews have already focused on the application of transcriptomics and/or proteomics for exploring skeletal biology and related disorders. The main goal of the present review is to systematically summarize the most relevant post-genomic studies on various metabolic bone diseases (osteoporosis, Paget's disease and osteonecrosis), neoplasias (osteosarcoma) and metabolic conditions that indirectly affect bone tissue, such as alkaptonuria. PMID:22246652

  1. Endothelial Dysfunction in Type 2 Diabetes Mellitus.

    PubMed

    Dhananjayan, R; Koundinya, K S Srivani; Malati, T; Kutala, Vijay Kumar

    2016-10-01

    Endothelial dysfunction is an imbalance in the production of vasodilator factors and when this balance is disrupted, it predisposes the vasculature towards pro-thrombotic and pro-atherogenic effects. This results in vasoconstriction, leukocyte adherence, platelet activation, mitogenesis, pro-oxidation, impaired coagulation and nitric oxide production, vascular inflammation, atherosclerosis and thrombosis. Endothelial dysfunction is focussed as it is a potential contributor to the pathogenesis of vascular disease in diabetes mellitus. Under physiological conditions, there is a balanced release of endothelial-derived relaxing and contracting factors, but this delicate balance is altered in diabetes mellitus and atherosclerosis, thereby contributing to further progression of vascular and end-organ damage. This review focuses on endothelial dysfunction in atherosclerosis, insulin resistance, metabolic syndrome, oxidative stress associated with diabetes mellitus, markers and genetics that are implicated in endothelial dysfunction. PMID:27605734

  2. The Road Ahead to Cure Alzheimer’s Disease: Development of Biological Markers and Neuroimaging Methods for Prevention Trials Across all Stages and Target Populations

    PubMed Central

    Cavedo, E.; Lista, S.; Khachaturian, Z.; Aisen, P.; Amouyel, P.; Herholz, K.; Jack, C.R.; Sperling, R.; Cummings, J.; Blennow, K.; O’Bryant, S.; Frisoni, G.B.; Khachaturian, A.; Kivipelto, M.; Klunk, W.; Broich, K.; Andrieu, S.; de Schotten, M. Thiebaut; Mangin, J.-F.; Lammertsma, A.A.; Johnson, K.; Teipel, S.; Drzezga, A.; Bokde, A.; Colliot, O.; Bakardjian, H.; Zetterberg, H.; Dubois, B.; Vellas, B.; Schneider, L.S.; Hampel, H.

    2015-01-01

    Alzheimer’s disease (AD) is a slowly progressing non-linear dynamic brain disease in which pathophysiological abnormalities, detectable in vivo by biological markers, precede overt clinical symptoms by many years to decades. Use of these biomarkers for the detection of early and preclinical AD has become of central importance following publication of two international expert working group’s revised criteria for the diagnosis of AD dementia, mild cognitive impairment (MCI) due to AD, prodromal AD and preclinical AD. As a consequence of matured research evidence six AD biomarkers are sufficiently validated and partly qualified to be incorporated into operationalized clinical diagnostic criteria and use in primary and secondary prevention trials. These biomarkers fall into two molecular categories: biomarkers of amyloid-beta (Aβ) deposition and plaque formation as well as of tau-protein related hyperphosphorylation and neurodegeneration. Three of the six gold-standard (“core feasible) biomarkers are neuroimaging measures and three are cerebrospinal fluid (CSF) analytes. CSF Aβ1-42 (Aβ1-42), also expressed as Aβ1-42 : Aβ1-40 ratio, T-tau, and P-tau Thr181 & Thr231 proteins have proven diagnostic accuracy and risk enhancement in prodromal MCI and AD dementia. Conversely, having all three biomarkers in the normal range rules out AD. Intermediate conditions require further patient follow-up. Magnetic resonance imaging (MRI) at increasing field strength and resolution allows detecting the evolution of distinct types of structural and functional abnormality pattern throughout early to late AD stages. Anatomical or volumetric MRI is the most widely used technique and provides local and global measures of atrophy. The revised diagnostic criteria for “prodromal AD” and “mild cognitive impairment due to AD” include hippocampal atrophy (as the fourth validated biomarker), which is considered an indicator of regional neuronal injury. Advanced image analysis

  3. Asymmetric Dimethylarginine, Endothelial Dysfunction and Renal Disease

    PubMed Central

    Aldámiz-Echevarría, Luis; Andrade, Fernando

    2012-01-01

    l-Arginine (Arg) is oxidized to l-citrulline and nitric oxide (NO) by the action of endothelial nitric oxide synthase (NOS). In contrast, protein-incorporated Arg residues can be methylated with subsequent proteolysis giving rise to methylarginine compounds, such as asymmetric dimethylarginine (ADMA) that competes with Arg for binding to NOS. Most ADMA is degraded by dimethylarginine dimethyaminohydrolase (DDAH), distributed widely throughout the body and regulates ADMA levels and, therefore, NO synthesis. In recent years, several studies have suggested that increased ADMA levels are a marker of atherosclerotic change, and can be used to assess cardiovascular risk, consistent with ADMA being predominantly absorbed by endothelial cells. NO is an important messenger molecule involved in numerous biological processes, and its activity is essential to understand both pathogenic and therapeutic mechanisms in kidney disease and renal transplantation. NO production is reduced in renal patients because of their elevated ADMA levels with associated reduced DDAH activity. These factors contribute to endothelial dysfunction, oxidative stress and the progression of renal damage, but there are treatments that may effectively reduce ADMA levels in patients with kidney disease. Available data on ADMA levels in controls and renal patients, both in adults and children, also are summarized in this review. PMID:23109853

  4. Male-specific Y-linked transgene markers to enhance biologically-based control of the Mexican fruit fly, Anastrepha ludens (Diptera: Tephritidae)

    PubMed Central

    2014-01-01

    Background Reliable marking systems are critical to the prospective field release of transgenic insect strains. This is to unambiguously distinguish released insects from wild insects in the field that are collected in field traps, and tissue-specific markers, such as those that are sperm-specific, have particular uses such as identifying wild females that have mated with released males. For tephritid fruit flies such as the Mexican fruit fly, Anastrepha ludens, polyubiquitin-regulated fluorescent protein body markers allow transgenic fly identification, and fluorescent protein genes regulated by the spermatocyte-specific β2-tubulin promoter effectively mark sperm. For sterile male release programs, both marking systems can be made male-specific by linkage to the Y chromosome. Results An A. ludens wild type strain was genetically transformed with a piggyBac vector, pBXL{PUbnlsEGFP, Asβ2tub-DsRed.T3}, having the polyubiquitin-regulated EGFP body marker, and the β2-tubulin-regulated DsRed.T3 sperm-specific marker. Autosomal insertion lines effectively expressed both markers, but a single Y-linked insertion (YEGFP strain) expressed only PUbnlsEGFP. This insertion was remobilized by transposase helper injection, which resulted in three new autosomal insertion lines that expressed both markers. This indicated that the original Y-linked Asβ2tub-DsRed.T3 marker was functional, but specifically suppressed on the Y chromosome. The PUbnlsEGFP marker remained effective however, and the YEGFP strain was used to create a sexing strain by translocating the wild type allele of the black pupae (bp+) gene onto the Y, which was then introduced into the bp- mutant strain. This allows the mechanical separation of mutant female black pupae from male brown pupae, that can be identified as adults by EGFP fluorescence. Conclusions A Y-linked insertion of the pBXL{PUbnlsEGFP, Asβ2tub-DsRed.T3} transformation vector in A. ludens resulted in male-specific expression of the EGFP

  5. Sexual Dysfunction and Infertility

    MedlinePlus

    ... American Society for Reproductive Medicine Sexual dysfunction and infertility What is sexual dysfunction and how common is ... and 40% of women. For couples dealing with infertility, it is even more common. Often, people ignore ...

  6. Evaluation of molecular markers for discriminating Gonaterocerus morrilli: A biological control agent imported from the origin of the glassy-winged sharpshooter

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We examined the utility of molecular markers for discriminating between two very closely related species, Gonatocerus morrilli (Howard) (imported from Texas) and G. walkerjonesi S. Triapitsyn (native to California), to determine whether post-release G. morrilli specimens could be detected and discri...

  7. Male-specific Y-linked transgene markers to enhance biologically-based control of the Mexican fruit fly, Anastrepha ludens (Diptera: Tephritidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Reliable marking systems are critical to the prospective field release of transgenic insect strains. This is to unambiguously distinguish released insects from wild insects in the field that are collected in field traps, and tissue-specific markers, such as those that are sperm-specific,...

  8. Serotonin, neural markers, and memory

    PubMed Central

    Meneses, Alfredo

    2015-01-01

    Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly understood. Hence, neural markers and cerebral functions and dysfunctions are revised. To our knowledge no previous systematic works have been published addressing these issues. The interactions among behavioral tasks, control groups and molecular changes and/or pharmacological effects are mentioned. Neurotransmitter receptors and signaling pathways, during normal and abnormally functioning memory with an emphasis on the behavioral aspects of memory are revised. With focus on serotonin, since as it is a well characterized neurotransmitter, with multiple pharmacological tools, and well characterized downstream signaling in mammals' species. 5-HT1A, 5-HT4, 5-HT5, 5-HT6, and 5-HT7 receptors as well as SERT (serotonin transporter) seem to be useful neural markers and/or therapeutic targets. Certainly, if the mentioned evidence is replicated, then the translatability from preclinical and clinical studies to neural changes might be confirmed. Hypothesis and theories might provide appropriate limits and perspectives of evidence. PMID:26257650

  9. [Evaluation of autonomic dysfunction by novel methods].

    PubMed

    Ando, Yukio; Obayashi, Konen

    2004-07-01

    The autonomic nervous system innervates every organ in the body. Since autonomic disturbances affect patient survival, an understanding and recognition of these disturbances are important. We adopted several new methods to evaluate autonomic function accurately. 123I-metaiodobenzylguanidine scintigraphy can assess the cardiac autonomic function even in the presence of cardiac arrhythmia. Laser-Doppler flowmetry, ultrasonographic study in the vessels and near-infrared spectrophotoscopy techniques serve as useful markers for screening the dysfunction of vasomotor neurons and blood circulation. Electrogastrography and the circadian rhythms of protein C secretion could be markers of the visceromotor nerves in the abdomen. Electrogastrography is a particularly useful tool for reflecting on functional changes in gastrointestinal motility. The evaluation of anemia could be a marker of autonomic dysfunction in the kidney and bone marrow in patients with familial amyloidotic polyneuropathy, pandysautonomia, and multiple system atrophy. Normocytic and normochromic anemia correlated with the severity of autonomic dysfunction were shown in these patients. We also evaluated the dysfunction of the neuroendocrine system and sudomotor neuron using our new autonomic function tests. The glucose-tolerance test could become one of the most useful clinical tools for detecting autonomic dysfunction in the endocrine system. Microhydrography and thermography could be useful tools for diagnosing the lesion site of dyshidrosis. Moreover, it is clinically important to check the systemic circulation and autonomic function in patients treated with sildenafil citrate and organ transplantation to save their lives. Our new autonomic function tests, such as laser-Doppler flowmetry and 123I-metaiodobenzylguanidine scintigraphy, are crucial tools in supplying the best symptomatic treatment for such patients. PMID:15344558

  10. Synthesis and Characterization of 8-O-Carboxymethylpyranine (CM-Pyranine) as a Bright, Violet-Emitting, Fluid-Phase Fluorescent Marker in Cell Biology

    PubMed Central

    Legenzov, Eric A.; Dirda, Nathaniel D. A.; Hagen, Brian M.; Kao, Joseph P. Y.

    2015-01-01

    To avoid spectral interference with common fluorophores in multicolor fluorescence microscopy, a fluid-phase tracer with excitation and emission in the violet end of the visible spectrum is desirable. CM-pyranine is easily synthesized and purified. Its excitation and emission maxima at 401.5 nm and 428.5 nm, respectively, are well suited for excitation by 405-nm diode lasers now commonly available on laser-scanning microscopes. High fluorescence quantum efficiency (Q = 0.96) and strong light absorption (ε405 > 25,000 M-1cm-1) together make CM-pyranine the brightest violet aqueous tracer. The fluorescence spectrum of CM-pyranine is invariant above pH 4, which makes it a good fluid-phase marker in all cellular compartments. CM-pyranine is very photostable, is retained for long periods by cells, does not self-quench, and has negligible excimer emission. The sum of its properties make CM-pyranine an ideal fluorescent tracer. The use of CM-pyranine as a fluid-phase marker is demonstrated by multicolor confocal microscopy of cells that are also labeled with lipid and nuclear markers that have green and red fluorescence emission, respectively. PMID:26186650

  11. Novel markers of endothelial dysfunction and inflammation in Behçet's disease patients with ocular involvement: epicardial fat thickness, carotid intima media thickness, serum ADMA level, and neutrophil-to-lymphocyte ratio.

    PubMed

    Yuksel, Murat; Yildiz, Abdulkadir; Oylumlu, Mustafa; Turkcu, Fatih Mehmet; Bilik, Mehmet Zihni; Ekinci, Aysun; Elbey, Bilal; Tekbas, Ebru; Alan, Sait

    2016-03-01

    The etiology of Behçet's disease (BD) has not been fully elucidated. However, immunological and environmental factors, endothelial dysfunction (ED), and genetic susceptibility have been proposed to play a role. In this study, we aimed to evaluate epicardial fat thickness (EFT) together with serum asymmetric dimethylarginine (ADMA), carotid intima media thickness (CIMT), and neutrophil-to-lymphocyte ratio (NLR) in BD patients with ocular involvement. Thirty-six ocular BD patients (17 active and 19 inactive ocular involvement), and 35 age and sex-matched healthy controls were enrolled to this cross-sectional study. All patients underwent examinations with transthoracic echocardiography and carotid Doppler ultrasound. Serum ADMA levels, CIMT, EFT, and NLR were compared between groups, and their association with disease activity was evaluated. Behçet's disease patients had higher WBC counts, neutrophil counts, NLR, CIMT, EFT values, and serum ADMA levels than do healthy controls. The other biochemical, hematological, and echocardiographic parameters were comparable between the two groups. Behçet's disease duration was positively correlated with EFT and CIMT. Multivariate logistic regression analysis revealed that increased serum ADMA concentration and CIMT are independently associated with BD. Neutrophil counts, NLR, and serum ADMA level were higher, and lymphocyte count was lower in patients with active ocular BD compared to those of inactive ocular BD group. Carotid intima media thickness, serum ADMA level, EFT, and NLR were increased in ocular BD patients compared to healthy subjects. In addition, both serum ADMA level and NLR were associated with disease activity of ocular involvement. Increase in disease duration was associated with increase in CIMT and EFT which suggests that anatomical changes occur in time during the disease course. Increased CIMT, serum ADMA level, EFT, and NLR may provide new clues about the role of ED and inflammation in the

  12. Planar optical waveguide based sandwich assay sensors and processes for the detection of biological targets including protein markers, pathogens and cellular debris

    DOEpatents

    Martinez, Jennifer S.; Swanson, Basil I.; Grace, Karen M.; Grace, Wynne K.; Shreve, Andrew P.

    2009-06-02

    An assay element is described including recognition ligands bound to a film on a single mode planar optical waveguide, the film from the group of a membrane, a polymerized bilayer membrane, and a self-assembled monolayer containing polyethylene glycol or polypropylene glycol groups therein and an assay process for detecting the presence of a biological target is described including injecting a biological target-containing sample into a sensor cell including the assay element, with the recognition ligands adapted for binding to selected biological targets, maintaining the sample within the sensor cell for time sufficient for binding to occur between selected biological targets within the sample and the recognition ligands, injecting a solution including a reporter ligand into the sensor cell; and, interrogating the sample within the sensor cell with excitation light from the waveguide, the excitation light provided by an evanescent field of the single mode penetrating into the biological target-containing sample to a distance of less than about 200 nanometers from the waveguide thereby exciting the fluorescent-label in any bound reporter ligand within a distance of less than about 200 nanometers from the waveguide and resulting in a detectable signal.

  13. Distribution and localization of microsatellites in the Perigord black truffle genome and identification of new molecular markers (2010) Fungal Genetics and Biology

    SciTech Connect

    Murat, Claude; Riccioni, C; Belfiori, B; Cichocki, N; Labbe, Jessy L; Morin, Emmanuelle; Tisserant, Emilie; Paolocci, F; Rubini, A; Martin, Francis

    2011-01-01

    The level of genetic diversity and genetic structure in the Perigord black truffle (Tuber melanosporum Vittad.) has been debated for several years, mainly due to the lack of appropriate genetic markers. Microsatellites or simple sequence repeats (SSRs) are important for the genome organisation, phenotypic diversity and are one of the most popular molecular markers. In this study, we surveyed the T. melanosporum genome (1) to characterise its SSR pattern; (2) to compare it with SSR patterns found in 48 other fungal and three oomycetes genomes and (3) to identify new polymorphic SSR markers for population genetics. The T. melanosporum genome is rich in SSRs with 22,425 SSRs with mono-nucleotides being the most frequent motifs. SSRs were found in all genomic regions although they are more frequent in non-coding regions (introns and intergenic regions). Sixty out of 135 PCR-amplified mono-, di-, tri-, tetra, penta, and hexanucleotides were polymorphic (44%) within black truffle populations and 27 were randomly selected and analysed on 139 T. melanosporum isolates from France, Italy and Spain. The number of alleles varied from 2 to 18 and the expected heterozygosity from 0.124 to 0.815. One hundred and thirty-two different multilocus genotypes out of the 139 T. melanosporum isolates were identified and the genotypic diversity was high (0.999). Polymorphic SSRs were found in UTR regulatory regions of fruiting bodies and ectomycorrhiza regulated genes, suggesting that they may play a role in phenotypic variation. In conclusion, SSRs developed in this study were highly polymorphic and our results showed that T. melanosporum is a species with an important genetic diversity, which is in agreement with its recently uncovered heterothallic mating system.

  14. Coronary microvascular dysfunction: an update

    PubMed Central

    Crea, Filippo; Camici, Paolo G.; Bairey Merz, Cathleen Noel

    2014-01-01

    Many patients undergoing coronary angiography because of chest pain syndromes, believed to be indicative of obstructive atherosclerosis of the epicardial coronary arteries, are found to have normal angiograms. In the past two decades, a number of studies have reported that abnormalities in the function and structure of the coronary microcirculation may occur in patients without obstructive atherosclerosis, but with risk factors or with myocardial diseases as well as in patients with obstructive atherosclerosis; furthermore, coronary microvascular dysfunction (CMD) can be iatrogenic. In some instances, CMD represents an epiphenomenon, whereas in others it is an important marker of risk or may even contribute to the pathogenesis of cardiovascular and myocardial diseases, thus becoming a therapeutic target. This review article provides an update on the clinical relevance of CMD in different clinical settings and also the implications for therapy. PMID:24366916

  15. [Neurogenic erectile dysfunction].

    PubMed

    Ramos, Antonio Sánchez; Durán, Juan Antonio Godino; Oliviero, Antonio

    2010-10-01

    Neurogenic erectile dysfunction is a consequence of alterations in neural pathways, autonomic, somatic, the combination of both or brain components that induce erection. This review aims to explain the physiopathological mechanisms of the most frequent neurological alterations causing erectile dysfunction and sexual disorders. PMID:20978292

  16. Insulin dysfunction and Tau pathology

    PubMed Central

    El Khoury, Noura B.; Gratuze, Maud; Papon, Marie-Amélie; Bretteville, Alexis; Planel, Emmanuel

    2013-01-01

    The neuropathological hallmarks of Alzheimer's disease (AD) include senile plaques of β-amyloid (Aβ) peptides (a cleavage product of the Amyloid Precursor Protein, or APP) and neurofibrillary tangles (NFT) of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF). NFT pathology is important since it correlates with the degree of cognitive impairment in AD. Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99%) is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease. Insulin dysfunction, manifested by diabetes mellitus (DM) might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since Tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment. Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia. PMID:24574966

  17. Clinical Significance of Endothelial Dysfunction in Essential Hypertension.

    PubMed

    Gkaliagkousi, Eugenia; Gavriilaki, Eleni; Triantafyllou, Areti; Douma, Stella

    2015-11-01

    The endothelium is recognized as a major determinant of vascular physiology and pathophysiology. Over the last few decades, a plethora of studies have implicated endothelial dysfunction in the progression of atherosclerosis and the subclinical target organ damage observed in essential hypertension. However, the clinical significance of diagnosing endothelial dysfunction in patients with essential hypertension remains under investigation. Although a number of vascular and non-vascular markers of endothelial dysfunction have been proposed, there is an ongoing quest for a marker in the clinical setting that is optimal, inexpensive, and reproducible. In addition, endothelial dysfunction emerges as a promising therapeutic target of agents that are readily available in clinical practice. In this context, a better understanding of its role in essential hypertension becomes of great importance. Here, we aim to investigate the clinical significance of endothelial dysfunction in essential hypertension by accumulating novel data on (a) early diagnosis using robust markers with prognostic value in cardiovascular risk prediction, (b) the association of endothelial dysfunction with subclinical vascular organ damage, and (c) potential therapeutic targets. PMID:26371063

  18. [Pharmacotherapy of erectile dysfunction].

    PubMed

    Kovalev, V A; Koroleva, S V; Kamalov, A A

    2000-01-01

    Among the drugs used to treat erectile dysfunction most common are prostaglandins El, viagra, iochimbin, vasodilators and desaggregants, vitamins, biogenic stimulators, etc. The comparative analysis of their efficacy was made in 360 patients with erectile dysfunction, primarily at subcompensated stage, aged 17-83 years. Organic and psychogenic erectile dysfunctions were diagnosed in 69 and 31% of the patients, respectively. Intracavernous injections of prostaglandin El (Caverject) were effective in 74%, transurethral alprostadil (MUSE) when adjusting the dose--in 38.7% of the patients. Iochimbin in patients with organic and psychogenic forms of erectile dysfunctions was effective in 25 and 40% of patients, respectively. In 26.3 and 19% of such patients the response was obtained after use of the combination including xantinol, nicotinate, trental, biogenic stimulators and adaptogens. Viagra was effective in 60 and 77.3% of patients with psychogenic and organic erectile dysfunctions, respectively. PMID:16856460

  19. Meibomian Gland Dysfunction: Endocrine Aspects

    PubMed Central

    Sahin, Ozlem G.; Kartal, Elçin; Taheri, Nusret

    2011-01-01

    Purpose. To compare the hormone levels of patients with seborrheic meibomian gland dysfunction with controls. Procedures. This is a retrospective case-control study involving 50 patients and 50 controls. Blood workup for hormones was studied in both groups by using macroELISA (enzyme-linked immunosorbent assay). Statistical evaluation was done by using SPSS 15.0 independent samples t-test. Results. There were statistically significant differences of serum testosterone and dehydroepiandrosterone sulphate levels between patients and controls (P = 0.000). Female gender showed statistically significant differences of serum thyroid-stimulating hormone and prolactin levels between patients and controls (P = 0.014 and P = 0.043), in addition to serum testosterone and dehydroepiandrosterone sulphate levels (P = 0.000 and P = 0.001). However, male gender showed statistically significant differences of only serum testosterone and dehydroepiandrosterone sulphate levels between patients and controls. (P = 0.003 and P = 0.003 resp.). Conclusions. Increased serum levels of testosterone and dehydroepiandrosterone sulphate in both genders should be considered as diagnostic markers for seborrheic meibomian gland dysfunction. PMID:24533183

  20. NHEXAS PHASE I REGION 5 STUDY--STANDARD OPERATING PROCEDURE--HUMAN BIOLOGICAL MARKERS:BLOOD AND URINE SAMPLE COLLECTION AND ANALYSES (EOHSI-AP-209-040)

    EPA Science Inventory

    This procedure describes the process for collecting and analyzing blood and urine samples. The presence of chemical contaminants in biological specimens such as blood, urine, and hair represent a measure of the internal dose or body burden for a given individual derived from the ...

  1. Genetics Home Reference: surfactant dysfunction

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions surfactant dysfunction surfactant dysfunction Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Surfactant dysfunction is a lung disorder that causes breathing ...

  2. Radial nerve dysfunction (image)

    MedlinePlus

    The radial nerve travels down the arm and supplies movement to the triceps muscle at the back of the upper arm. ... the wrist and hand. The usual causes of nerve dysfunction are direct trauma, prolonged pressure on the ...

  3. Chronic pelvic floor dysfunction.

    PubMed

    Hartmann, Dee; Sarton, Julie

    2014-10-01

    The successful treatment of women with vestibulodynia and its associated chronic pelvic floor dysfunctions requires interventions that address a broad field of possible pain contributors. Pelvic floor muscle hypertonicity was implicated in the mid-1990s as a trigger of major chronic vulvar pain. Painful bladder syndrome, irritable bowel syndrome, fibromyalgia, and temporomandibular jaw disorder are known common comorbidities that can cause a host of associated muscular, visceral, bony, and fascial dysfunctions. It appears that normalizing all of those disorders plays a pivotal role in reducing complaints of chronic vulvar pain and sexual dysfunction. Though the studies have yet to prove a specific protocol, physical therapists trained in pelvic dysfunction are reporting success with restoring tissue normalcy and reducing vulvar and sexual pain. A review of pelvic anatomy and common findings are presented along with suggested physical therapy management. PMID:25108498

  4. Eustachian Tube Dysfunction

    MedlinePlus

    ... flying (because of altitude changes). Riding in elevators, driving through mountains or diving may also make your symptoms worse. Causes & Risk Factors What causes eustachian tube dysfunction? The most common ...

  5. Tibial nerve dysfunction

    MedlinePlus

    ... a loss of movement or sensation in the foot from damage to the tibial nerve. ... Tibial nerve dysfunction is an unusual form of peripheral ... the calf and foot muscles. A problem in function with a single ...

  6. Temporomandibular Joint Dysfunction

    MedlinePlus

    The temporomandibular joint (TMJ) connects your jaw to the side of your head. When it works well, it enables you to ... For people with TMJ dysfunction, problems with the joint and muscles around it may cause Pain that ...

  7. Sexual Dysfunction in Women

    PubMed Central

    Brown, Pamela

    1989-01-01

    Sexual dysfunction takes place in the context of women's lives and affects their sexuality and self-esteem. Awareness of these influences are vital to the management of the dysfunction and the promotion of positive sexuality. The family physician's contribution to both the prevention and management of sexual concerns includes an awareness of societal influences and facilitation of a woman's sense of her own power and control over her life. PMID:21248971

  8. Cellular dysfunction in sepsis.

    PubMed

    Singer, Mervyn

    2008-12-01

    Cellular dysfunction is a commonplace sequelum of sepsis and other systemic inflammatory conditions. Impaired energy production (related to mitochondrial inhibition, damage, and reduced protein turnover) appears to be a core mechanism underlying the development of organ dysfunction. The reduction in energy availability appears to trigger a metabolic shutdown that impairs normal functioning of the cell. This may well represent an adaptive mechanism analogous to hibernation that prevents a massive degree of cell death and thus enables eventual recovery in survivors. PMID:18954700

  9. An occupational hygiene investigation of exposure to acrylamide and the role for urinary S-carboxyethyl-cysteine (CEC) as a biological marker.

    PubMed

    Bull, Peter J; Brooke, Richard K; Cocker, John; Jones, Katharine; Warren, Nicholas

    2005-11-01

    Acrylamide has a range of toxicological hazards including neurotoxicity and reproductive toxicity; however, occupational risk management is driven by its genotoxic and carcinogenic potential (it is classified within the EU as a Category 2 carcinogen, R45 and Category 2 mutagen, R46). Since there is the potential for skin absorption and systemic toxicity, biological monitoring may be a useful aid for the assessment of exposure via inhalation, ingestion and dermal absorption. However, there are currently no biological monitoring guidance values (BMGVs). This study describes an extensive survey of potential workplace exposure to acrylamide at the Ciba (Bradford) site to gather data suitable for a BMGV. This manufacturing site is typical within the industry as a whole and includes a cross section of activities and tasks representative of acrylamide exposure. Acrylamide is used in the manufacture of polyacrylamide based products for applications in water treatment; oil and mineral extraction; paper, paint and textile processes. Workers (62 plus 6 controls) with varying potential exposures provided a total of 275 pre shift and 247 post-shift urine samples along with 260 personal air samples. A small non-exposed control group was similarly monitored. Urine samples were analysed for S-carboxyethyl-cysteine (CEC). Airborne, surface and glove samples were analysed for acrylamide. Inhalation exposures were well controlled with values consistently below one-tenth of the UK Workplace Exposure Limit. Engineering controls, personal protective equipment and work practice, all contributed to good control of occupational exposure. CEC was found in urine samples from both exposed workers and non-occupationally exposed controls. At the low levels of exposure found, smoking made a significant contribution to urinary CEC levels. Nevertheless a correlation between urinary CEC and airborne acrylamide was found. A mixed effects model incorporating inhalation concentrations of acrylamide

  10. Endothelial Dysfunction in Chronic Inflammatory Diseases

    PubMed Central

    Steyers, Curtis M.; Miller, Francis J.

    2014-01-01

    Chronic inflammatory diseases are associated with accelerated atherosclerosis and increased risk of cardiovascular diseases (CVD). As the pathogenesis of atherosclerosis is increasingly recognized as an inflammatory process, similarities between atherosclerosis and systemic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel diseases, lupus, psoriasis, spondyloarthritis and others have become a topic of interest. Endothelial dysfunction represents a key step in the initiation and maintenance of atherosclerosis and may serve as a marker for future risk of cardiovascular events. Patients with chronic inflammatory diseases manifest endothelial dysfunction, often early in the course of the disease. Therefore, mechanisms linking systemic inflammatory diseases and atherosclerosis may be best understood at the level of the endothelium. Multiple factors, including circulating inflammatory cytokines, TNF-α (tumor necrosis factor-α), reactive oxygen species, oxidized LDL (low density lipoprotein), autoantibodies and traditional risk factors directly and indirectly activate endothelial cells, leading to impaired vascular relaxation, increased leukocyte adhesion, increased endothelial permeability and generation of a pro-thrombotic state. Pharmacologic agents directed against TNF-α-mediated inflammation may decrease the risk of endothelial dysfunction and cardiovascular disease in these patients. Understanding the precise mechanisms driving endothelial dysfunction in patients with systemic inflammatory diseases may help elucidate the pathogenesis of atherosclerosis in the general population. PMID:24968272

  11. Genitourinary dysfunction in Parkinson's disease.

    PubMed

    Sakakibara, Ryuji; Uchiyama, Tomoyuki; Yamanishi, Tomonori; Kishi, Masahiko

    2010-01-15

    Bladder dysfunction (urinary urgency/frequency) and sexual dysfunction (erectile dysfunction) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, genitourinary autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the genitourinary dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life. PMID:20077468

  12. Rescue of dysfunctional autophagy attenuates hyperinflammatory responses from cystic fibrosis cells.

    PubMed

    Mayer, Matthew L; Blohmke, Christoph J; Falsafi, Reza; Fjell, Chris D; Madera, Laurence; Turvey, Stuart E; Hancock, Robert E W

    2013-02-01

    A hallmark feature of cystic fibrosis (CF) is progressive pulmonary obstruction arising from exaggerated host proinflammatory responses to chronic bacterial airway colonization. The mechanisms for these heightened inflammatory responses have been only partially characterized, hampering development of effective anti-inflammatory therapies. The aim of this study was to identify and validate novel dysfunctional processes or pathways driving the hyperinflammatory phenotype of CF cells using systems biology and network analysis to examine transcriptional changes induced by innate defense regulator (IDR)-1018, an anti-inflammatory peptide. IDR-1018 selectively attenuated hyperinflammatory cytokine production from CF airway cells and PBMCs stimulated with multiple bacterial ligands, including flagellin (FliC). Network analysis of CF cell transcriptional responses to FliC and IDR-1018 identified dysfunctional autophagy as the target of the peptide via modulation of upstream adenosine monophosphate-activated protein kinase (AMPK)-Akt signaling. After treatment with FliC, CF cells were found to have elevated levels of the autophagosome marker LC3-II, and GFP-LC3-transfected CF airway cells showed abnormal perinuclear accumulation of GFP(+) structures. In both instances, treatment of CF cells with IDR-1018 abolished the accumulation of LC3 induced by FliC. Furthermore, inhibition of autophagosome-lysosome fusion with bafilomycinA1 attenuated the anti-inflammatory and autophagosome-clearing effects of IDR-1018, as did a chemical inhibitor of Akt and an activator of AMPK. These findings were consistent with hypotheses generated in silico, demonstrating the utility of systems biology and network analysis approaches for providing pathway-level insights into CF-associated inflammation. Collectively, these data suggest that dysfunctional autophagosome clearance contributes to heightened inflammatory responses from CF transmembrane receptor mutant cells and highlight autophagy and

  13. Identification of characteristic mass spectrometric markers for primary biological aerosol particles and comparison with field data from submicron pristine aerosol particles

    NASA Astrophysics Data System (ADS)

    Freutel, F.; Schneider, J.; Zorn, S. R.; Drewnick, F.; Borrmann, S.; Hoffmann, T.; Martin, S. T.

    2009-04-01

    The contribution of primary biological aerosol (PBA) to the total aerosol particle concentration is estimated to range between 25 and 80%, depending on location and season. Especially in the tropical rain forest it is expected that PBA is a major source of particles in the supermicron range, and is also an important fraction of the submicron aerosol. PBA particles like plant fragments, pollen, spores, fungi, viruses etc. contain chemical compounds as proteins, sugars, amino acids, chlorophyll, and cellular material as cellulose. For this reason we have performed mass spectrometric laboratory measurements (Aerodyne C-ToF and W-ToF AMS, single particle laser ablation instrument SPLAT) on pure submicron aerosol particles containing typical PBA compounds in order to identify typical mass spectral patterns of these compounds and to explain the observed fragmentation patterns on the basis of molecular structures. These laboratory data were compared to submicron particle mass spectra obtained during AMAZE-08 (Amazonian Aerosol CharacteriZation Experiment, Brazil, February/March 2008). The results indicate that characteristic m/z ratios for carbohydrates (e.g., glucose, saccharose, levoglucosan, mannitol) can be identified, for example m/z = 60(C2H4O2+) or m/z = 61(C2H5O2+). Certain characteristic peaks for amino acids were also identified in the laboratory experiments. In the field data from AMAZE-08, these characteristic peaks for carbohydrates and amino acids were found, and their contribution to the total organic mass was estimated to about 5%. Fragment ions from peptides and small proteins were also identified in laboratory experiments. Larger proteins, however, seem to become oxidized to CO2+ to a large extend in the vaporizing process of the AMS. Thus, detection of proteins in atmospheric aerosol particles with the AMS appears to be difficult.

  14. Dysfunctional Uterine Bleeding

    PubMed Central

    Casper, Robert F.

    1983-01-01

    Dysfunctional uterine bleeding is most commonly associated with chronic anovulation. Early diagnosis of anovulation is important; the induction of regular withdrawal periods using a progestin such as Provera prevents the development of endometrial hyperplasia with the subsequent inevitable occurrence of a heavy, frightening vaginal bleed. The etiology of dysfunctional uterine bleeding occurring during ovulatory cycles is unknown and all medical therapies at present are necessarily experimental. Hysterectomy is probably the treatment of choice for women who have finished their childbearing career and in whom persisting menorrhagia during ovulatory cycles results in anemia. PMID:21283453

  15. Assessment of fetal inflammatory syndrome by "classical" markers in the management of preterm labor: a possible lesson from metabolomics and system biology.

    PubMed

    Ferrazzi, Enrico; Muggiasca, Maria Luisa; Fabbri, Elisa; Fontana, Paola; Castoldi, Francesco; Lista, Gianluca; Primerano, Liviana; Livio, Stefania; Di Francesco, Stefania

    2012-10-01

    There exists a huge gap between protocols issued by scientific bodies and evidence derived by system biology studies on the multifactorial origin of threatened preterm delivery and their different associations with neonatal outcome. The objective of this prospective study was the analysis obstetrical and neonatal outcome in a cohort of pregnant patients treated for the risk of preterm delivery according to maternal and fetal assessment determined by amniotic fluid samples. Methods. Threatened preterm delivery and premature rupture of membranes between 24 + 1 and 32 + 6 weeks of gestation were treated by prolonged tocolytic regimens and if necessary by antibiotics for maternal infections when intra-amniotic inflammation (IAI) was excluded on the basis of negative white blood cell count in the amniotic fluid, or opposite, by delivery after a course of betamethasone and 48 hours maintenance tocolysis. Twenty-three cases were compared with 22 historical controls treated by the same teams according to the 48 hours treat and wait criteria. In addition to this, cases with normal and abnormal amniotic fluid white blood cell were compared. Results. Maternal and fetal conditions at admission were not significantly different between the study and control cohort for all maternal and fetal variables. Clinical indices were significantly improved as regard to latency from admission to delivery, number of newborns admitted to neonatal intensive care unit and length of stay in neonatal intensive care unit. Not any perinatal death or sepsis occurred in the study cohort. Overall, improved neonatal outcomes were observed in the study cohort. Composite major neonatal eventful outcomes occurred in 26% of cases vs. 50% in controls. The limited number of cases was not powered enough to reach a statistical significance for these variables. Continued tocolysis on demand and full regimen of mono or combined antibiotic regimen for maternal infection achieved significantly longer delay between

  16. Cystatin C: a new renal marker and its potential use in small animal medicine.

    PubMed

    Ghys, L; Paepe, D; Smets, P; Lefebvre, H; Delanghe, J; Daminet, S

    2014-01-01

    The occurrence of chronic kidney disease is underestimated in both human and veterinary medicine. Glomerular filtration rate (GFR) is considered the gold standard for evaluating kidney function. However, GFR assessment is time-consuming and labor-intensive and therefore not routinely used in practice. The commonly used indirect GFR markers, serum creatinine (sCr) and urea, are not sufficiently sensitive or specific to detect early renal dysfunction. Serum cystatin C (sCysC), a proteinase inhibitor, has most of the properties required for an endogenous GFR marker. In human medicine, numerous studies have evaluated its potential use as a GFR marker in several populations. In veterinary medicine, this marker is gaining interest. The measurement is easy, which makes it an interesting parameter for clinical use. This review summarizes current knowledge about cystatin C (CysC) in humans, dogs, and cats, including its history, assays, relationship with GFR, and biological and clinical variations in both human and veterinary medicine. PMID:24814357

  17. Endothelin and endothelial dysfunction.

    PubMed

    Masaki, Tomoh; Sawamura, Tatsuya

    2006-03-01

    Nitric oxide (NO) and endothelin (ET) produced in endothelial cells are leading molecules which regulate vascular function. Failure of the physiological balance between these two molecules is usually referred to as endothelial dysfunction. ET was initially identified as a potent vasoconstrictive peptide. Three ET isoforms and two ET receptors have been identified. One of the isoforms, ET-1, plays a significant role in many cardiovascular diseases. On the other hand, oxidized low-density lipoprotein (oxLDL) is known to induce endothelial dysfunction. The endothelial receptor for oxLDL was cloned, and named lectin-like oxidized receptor-1 (LOX-1). Activation of LOX-1 generates reactive oxygen species (ROS), and acivates a transcriptional factor, nuclear factor κB (NFκB), resulting in down-regulation of NO and up-regulation of ET-1. LOX-1 might be a key molecule in the generation of endothelial dysfunction. In endothelial dysfunction, ET-1 is an aggravating factor of cardiovascular diseases. PMID:25792766

  18. Mitochondrial Dysfunction in Cancer

    PubMed Central

    Boland, Michelle L.; Chourasia, Aparajita H.; Macleod, Kay F.

    2013-01-01

    A mechanistic understanding of how mitochondrial dysfunction contributes to cell growth and tumorigenesis is emerging beyond Warburg as an area of research that is under-explored in terms of its significance for clinical management of cancer. Work discussed in this review focuses less on the Warburg effect and more on mitochondria and how dysfunctional mitochondria modulate cell cycle, gene expression, metabolism, cell viability, and other established aspects of cell growth and stress responses. There is increasing evidence that key oncogenes and tumor suppressors modulate mitochondrial dynamics through important signaling pathways and that mitochondrial mass and function vary between tumors and individuals but the significance of these events for cancer are not fully appreciated. We explore the interplay between key molecules involved in mitochondrial fission and fusion and in apoptosis, as well as in mitophagy, biogenesis, and spatial dynamics of mitochondria and consider how these distinct mechanisms are coordinated in response to physiological stresses such as hypoxia and nutrient deprivation. Importantly, we examine how deregulation of these processes in cancer has knock on effects for cell proliferation and growth. We define major forms of mitochondrial dysfunction and address the extent to which the functional consequences of such dysfunction can be determined and exploited for cancer diagnosis and treatment. PMID:24350057

  19. Perceptual-Motor Dysfunction.

    ERIC Educational Resources Information Center

    Pyfer, Jean L.

    Discussed are theoretical and treatment aspects of perceptual motor dysfunction and rehabilitation in 4- to 12-year-old academically failing children involved in a 3-year investigation at the University of Kansas. The program is said to stress increasing the amount of stimulation received by sensory receptors of the vestibular, reflex, and haptic…

  20. Shared Parenting Dysfunction.

    ERIC Educational Resources Information Center

    Turkat, Ira Daniel

    2002-01-01

    Joint custody of children is the most prevalent court ordered arrangement for families of divorce. A growing body of literature indicates that many parents engage in behaviors that are incompatible with shared parenting. This article provides specific criteria for a definition of the Shared Parenting Dysfunction. Clinical aspects of the phenomenon…

  1. Kidney Dysfunction and Left Ventricular Assist Device Support: A Comprehensive Perioperative Review

    PubMed Central

    Coffin, Samuel T.; Waguespack, Dia R.; Haglund, Nicholas A.; Maltais, Simon; Dwyer, Jamie P.; Keebler, Mary E.

    2015-01-01

    Left ventricular assist devices (LVADs) are used increasingly as a bridge to transplantation or as destination therapy in end-stage heart failure patients who do not respond to optimal medical therapy. Many of these patients have end-organ dysfunction, including advanced kidney dysfunction, before and after LVAD implantation. Kidney dysfunction is a marker of adverse outcomes, such as increased morbidity and mortality. This review discusses kidney dysfunction and associated management strategies during the dynamic perioperative time period of LVAD implantation. Furthermore, we suggest potential future research directions to better understand the complex relationship between renal pathophysiology and mechanical circulatory support. PMID:25759700

  2. Large-Scale Fusion of Gray Matter and Resting-State Functional MRI Reveals Common and Distinct Biological Markers across the Psychosis Spectrum in the B-SNIP Cohort

    PubMed Central

    Wang, Zheng; Meda, Shashwath A.; Keshavan, Matcheri S.; Tamminga, Carol A.; Sweeney, John A.; Clementz, Brett A.; Schretlen, David J.; Calhoun, Vince D.; Lui, Su; Pearlson, Godfrey D.

    2015-01-01

    To investigate whether aberrant interactions between brain structure and function present similarly or differently across probands with psychotic illnesses [schizophrenia (SZ), schizoaffective disorder (SAD), and bipolar I disorder with psychosis (BP)] and whether these deficits are shared with their first-degree non-psychotic relatives. A total of 1199 subjects were assessed, including 220 SZ, 147 SAD, 180 psychotic BP, 150 first-degree relatives of SZ, 126 SAD relatives, 134 BP relatives, and 242 healthy controls (1). All subjects underwent structural MRI (sMRI) and resting-state functional MRI (rs-fMRI) scanning. Joint-independent component analysis (jICA) was used to fuse sMRI gray matter and rs-fMRI amplitude of low-frequency fluctuations data to identify the relationship between the two modalities. jICA revealed two significantly fused components. The association between functional brain alteration in a prefrontal–striatal–thalamic–cerebellar network and structural abnormalities in the default mode network was found to be common across psychotic diagnoses and correlated with cognitive function, social function, and schizo-bipolar scale scores. The fused alteration in the temporal lobe was unique to SZ and SAD. The above effects were not seen in any relative group (including those with cluster-A personality). Using a multivariate-fused approach involving two widely used imaging markers, we demonstrate both shared and distinct biological traits across the psychosis spectrum. Furthermore, our results suggest that the above traits are psychosis biomarkers rather than endophenotypes. PMID:26732139

  3. Clinical tumour markers in ovarian cancer.

    PubMed

    Mazurek, A; Nikliński, J; Laudański, T; Pluygers, E

    1998-02-01

    Within past few years, the measurement of serological, histochemical and molecular genetic markers has had an increasing influence on clinical decisions about initial treatment and follow-up. This review presents data concerning the most studied and interesting markers in ovarian cancer. CA 125, CA 19.9, TATI, CASA, CEA, TPA, TPS and CYFRA21-1 are now the most widely used serological tumour markers for management of ovarian cancer patients. Ras oncogenes, C-erb2 proto-oncogene, p53 suppressor gene and Bcl-2 oncogene are examples of currently used molecular genetic markers. As histochemical markers-proliferation markers, flow cytometric analysis, thymidine labelling index, Ki-67 nuclear antigen or differentiation markers are nowadays the ones most often determined. Some of these markers might be useful adjuncts for monitoring response to therapy, including early detection of tumour reactivation to allow curative therapy and rapid detection of treatment failure. The study of these markers may also lead to a better understanding of the biological characteristics of ovarian cancer. Numerous tumour markers characterized in this paper have been recognized as promising prognostic factors. The information derived from studies of these markers also represents the most promising avenue towards new treatment strategies; nevertheless to validate these factors, prospective studies of a large patient population are needed. PMID:9511849

  4. Fullerenol cytotoxicity in kidney cells is associated with cytoskeleton disruption, autophagic vacuole accumulation, and mitochondrial dysfunction

    SciTech Connect

    Johnson-Lyles, Denise N.; Peifley, Kimberly; Lockett, Stephen; Neun, Barry W.; Hansen, Matthew; Clogston, Jeffrey; Stern, Stephan T.; McNeil, Scott E.

    2010-11-01

    Water soluble fullerenes, such as the hydroxylated fullerene, fullerenol (C{sub 60}OH{sub x}), are currently under development for diagnostic and therapeutic biomedical applications in the field of nanotechnology. These molecules have been shown to undergo urinary clearance, yet there is limited data available on their renal biocompatibility. Here we examine the biological responses of renal proximal tubule cells (LLC-PK1) exposed to fullerenol. Fullerenol was found to be cytotoxic in the millimolar range, with viability assessed by the sulforhodamine B and trypan blue assays. Fullerenol-induced cell death was associated with cytoskeleton disruption and autophagic vacuole accumulation. Interaction with the autophagy pathway was evaluated in vitro by Lysotracker Red dye uptake, LC3-II marker expression and TEM. Fullerenol treatment also resulted in coincident loss of cellular mitochondrial membrane potential and ATP depletion, as measured by the Mitotracker Red dye and the luciferin-luciferase assays, respectively. Fullerenol-induced ATP depletion and loss of mitochondrial potential were partially ameliorated by co-treatment with the autophagy inhibitor, 3-methyladenine. In vitro fullerenol treatment did not result in appreciable oxidative stress, as measured by lipid peroxide and glutathione content. Based on these data, it is hypothesized that cytoskeleton disruption may be an initiating event in fullerenol cytotoxicity, leading to subsequent autophagy dysfunction and loss of mitochondrial capacity. As nanoparticle-induced cytoskeleton disruption, autophagic vacuole accumulation and mitochondrial dysfunction are commonly reported in the literature, the proposed mechanism may be relevant for a variety of nanomaterials.

  5. [Erectile and Ejaculatory Dysfunction].

    PubMed

    Gross, Oliver; Sulser, Tullio; Eberli, Daniel

    2015-11-25

    The inability to achieve an erection of the penis sufficient for sexual activity is called erectile dysfunction (ED). In most cases, the diagnosis can be made by medical history. The prevalence of ED in men at the age of 65 has been reported to be up to 50%. Premature ejaculation has a prevalence, up to 20% and is the most frequent ejaculatory dysfunction. The etiology of ED can involve psychological, vascular, neurogenic, hormonal or urogenital pathologies. The main pathophysiological mechanisms of ED are vascular disorders such as diabetes mellitus and atherosclerosis. Because of the common pathophysiology, patients diagnosed with ED should have a diagnostic work-up for systemic vascular pathologies to prevent concomitant cardiac events. Treatment options include invasive and non-invasive procedures. PMID:26602851

  6. Thyroid dysfunction and subfertility

    PubMed Central

    2015-01-01

    The thyroid hormones act on nearly every cell in the body. Moreover, the thyroid gland continuously interacts with the ovaries, and the thyroid hormones are involved in almost all phases of reproduction. Thyroid dysfunctions are relatively common among women of reproductive age, and can affect fertility in various ways, resulting in anovulatory cycles, high prolactin levels, and sex hormone imbalances. Undiagnosed and untreated thyroid disease can be a cause of subfertility. Subclinical hypothyroidism (SCH), also known as mild thyroid failure, is diagnosed when peripheral thyroid hormone levels are within the normal reference laboratory range, but serum thyroid-stimulating hormone levels are mildly elevated. Thyroid autoimmunity (TAI) is characterized by the presence of anti-thyroid antibodies, which include anti-thyroperoxidase and anti-thyroglobulin antibodies. SCH and TAI may remain latent, asymptomatic, or even undiagnosed for an extended period. It has also been demonstrated that controlled ovarian hyperstimulation has a significant impact on thyroid function, particularly in women with TAI. In the current review, we describe the interactions between thyroid dysfunctions and subfertility, as well as the proper work-up and management of thyroid dysfunctions in subfertile women. PMID:26816871

  7. Preclinical Diastolic Dysfunction

    PubMed Central

    Wan, Siu-Hin; Vogel, Mark W.; Chen, Horng H

    2014-01-01

    Preclinical Diastolic Dysfunction (PDD) has been broadly defined as subjects with left ventricular diastolic dysfunction, without the diagnosis of congestive heart failure (HF), and with normal systolic function. PDD is an entity which remains poorly understood, yet has definite clinical significance. Although few original studies have focused on PDD, it has been shown that PDD is prevalent, and that there is a clear progression from PDD to symptomatic heart failure including dyspnea, edema, and fatigue. In diabetic patients and patients with coronary artery disease or hypertension, it has been shown that patients with PDD have a significantly higher risk of progression to heart failure and death compared to patients without PDD. Because of these findings and the increasing prevalence of the heart failure epidemic, it is clear that an understanding of PDD is essential to decreasing patients’ morbidity and mortality. This review will focus on what is known concerning preclinical diastolic dysfunction, including definitions, staging, epidemiology, pathophysiology, and the natural history of the disease. In addition, given the paucity of trials focused on PDD treatment, studies targeting risk factors associated with the development of PDD and therapeutic trials for heart failure with preserved ejection fraction will be reviewed. PMID:24291270

  8. [Endothelial dysfunction and nonspecific immune reactions in development and progression of osteoarthrosis in women engaged into manual work].

    PubMed

    Maliutina, N N; Nevzorova, M S

    2015-01-01

    The article considers mechanisms of development and progression of osteoarthrosis as an occupationally conditioned disease in women of manual work. Women working in physical overstrain conditions are under occupational risk with dysfunction of many body systems. The authors set a hypothesis on association of endothelial dysfunction markers dysbalance and structural remodelling of cartilage matrix as a proof of degenerative changes. PMID:26596115

  9. Management of ejaculatory dysfunction.

    PubMed

    McMahon, C G

    2014-02-01

    Ejaculatory dysfunction is a common complaint and is often associated with a reduced quality of life for sufferer and partner. The spectrum of ejaculatory dysfunction extends from premature ejaculation (PE) to delayed ejaculation (DE) and anejaculation. Over the past 20-30 years, the PE treatment paradigm, previously limited to behavioural psychotherapy, has expanded to include drug treatment. Multiple well-controlled, evidence-based studies have demonstrated the efficacy and safety of selective serotonin re-uptake inhibitors in delaying ejaculation, confirming their role as first-line agents for the treatment of lifelong and acquired PE. More recently, there has been increased attention to the psychosocial consequences of PE, its epidemiology, its aetiology and its pathophysiology by both clinicians and the pharmaceutical industry. DE and anejaculation are probably the least common, least studied and least understood of the male sexual dysfunctions. However, their impact is significant as they may result in a lack of sexual fulfilment for both the man and his partner, an effect further compounded when procreation is among the couple's goals of sexual intercourse. The causes of DE, anejaculation and anorgasmia are manifold. Numerous psychotherapeutic treatments are described for the management of delayed or anejaculation. Although some appear to be effective, none has been properly evaluated in large-scale samples. Treatment of DE or anejaculation with pharmacotherapy has met with limited success. No drugs have been approved by regulatory agencies for this purpose, and most drugs that have been identified for potential use have limited efficacy, impart significant side-effects or are yet considered experimental in nature. PMID:24528812

  10. Posttraumatic olfactory dysfunction.

    PubMed

    Coelho, Daniel H; Costanzo, Richard M

    2016-04-01

    Impairment of smell may occur following injury to any portion of the olfactory tract, from nasal cavity to brain. A thorough understanding of the anatomy and pathophysiology combined with comprehensively obtained history, physical exam, olfactory testing, and neuroimaging may help to identify the mechanism of dysfunction and suggest possible treatments. Although most olfactory deficits are neuronal mediated and therefore currently unable to be corrected, promising technology may provide novel treatment options for those most affected. Until that day, patient counseling with compensatory strategies and reassurance is essential for the maintenance of safety and QoL in this unique and challenging patient population. PMID:26441369