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Sample records for dysfunction biological markers

  1. Markers of erectile dysfunction

    PubMed Central

    Davies, Kelvin P.; Melman, Arnold

    2008-01-01

    With the development and marketing of oral pharmacotherapy that is both noninvasive and successful in treating erectile dysfunction (ED), the quest to identify markers of organic ED lost ground. Indeed, the multi-factorial nature of ED may have led many researchers to conclude that searching for a universal marker of ED was futile. However, the realization that ED is strongly correlated with the overall health of men, and may act as a predictor for the development of cardiovascular disease (CVD) and diabetes, has stimulated interest in identifying genes that can distinguish organic ED. In addition, the potential ability to suggest to the patient that ED is reversible (i.e., psychogenic) with a simple test would be of significance to both the physician and patient, as well as for reimbursement issues for therapy by insurance companies. Such a marker may also act as a non-subjective measure of the degree of ED and the efficacy of treatment. This review discusses the importance of identifying such markers and recent work identifying potential markers in human patients. PMID:19468461

  2. [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.

  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

    García-Ortiz, Luis; Recio-Rodríguez, José I; Martín-Cantera, Carlos; Cabrejas-Sánchez, Alfredo; Gómez-Arranz, Amparo; González-Viejo, Natividad; Iturregui-San Nicolás, Eguskiñe; Patino-Alonso, Maria C; Gómez-Marcos, Manuel A

    2010-05-06

    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. A cross-sectional multicenter study with six research groups. 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. 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). 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. ClinicalTrials.gov Identifier: NCT01083082.

  4. 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

  5. Disease, dysfunction, and synthetic biology.

    PubMed

    Holm, Sune

    2014-08-01

    Theorists analyzing the concept of disease on the basis of the notion of dysfunction consider disease to be dysfunction requiring. More specifically, dysfunction-requiring theories of disease claim that for an individual to be diseased certain biological facts about it must be the case. Disease is not wholly a matter of evaluative attitudes. In this paper, I consider the dysfunction-requiring component of Wakefield's hybrid account of disease in light of the artifactual organisms envisioned by current research in synthetic biology. In particular, I argue that the possibility of artifactual organisms and the case of oncomice and other bred or genetically modified strains of organism constitute a significant objection to Wakefield's etiological account of the dysfunction requirement. I then develop a new alternative understanding of the dysfunction requirement that builds on the organizational theory of function. I conclude that my suggestion is superior to Wakefield's theory because it (a) can accommodate both artifactual and naturally evolved organisms, (b) avoids the possibility of there being a conflict between what an organismic part is supposed to do and the health of the organism, and (c) provides a nonarbitrary and practical way of determining whether dysfunction occurs.

  6. Microvesicles: potential markers and mediators of endothelial dysfunction.

    PubMed

    Liu, Ming-Lin; Williams, Kevin Jon

    2012-04-01

    Microvesicles (also known as microparticles) are small membranous structures that are released from platelets and cells upon activation or during apoptosis. Microvesicles have been found in blood, urine, synovial fluid, extracellular spaces of solid organs, atherosclerotic plaques, tumors, and elsewhere. Here, we focus on new clinical and basic work that implicates microvesicles as markers and mediators of endothelial dysfunction and hence novel contributors to cardiovascular and other diseases. Advances in the detection of microvesicles and the use of cell type-specific markers to determine their origin have allowed studies that associated plasma concentrations of specific microvesicles with major types of endothelial dysfunction - namely, inappropriate or maladaptive vascular tone, leukocyte recruitment, and thrombosis. Recent investigations have highlighted microvesicular transport of key biologically active molecules besides tissue factor, such as ligands for pattern-recognition receptors, elements of the inflammasome, and morphogens. Microvesicles generated from human cells under different pathologic circumstances, for example, during cholesterol loading or exposure to endotoxin, carry different subsets of these molecules and thereby alter endothelial function through several distinct, well characterized molecular pathways. Clinical and basic studies indicate that microvesicles may be novel markers and mediators of endothelial dysfunction. This work has advanced our understanding of the development of cardiovascular and other diseases. Opportunities and obstacles to clinical applications are discussed.

  7. Biologic markers of chronic GVHD.

    PubMed

    Pidala, J; Sarwal, M; Roedder, S; Lee, S J

    2014-03-01

    Biologic markers of chronic GVHD may provide insight into the pathogenesis of the syndrome, identify molecular targets for novel interventions, and facilitate advances in clinical management. Despite extensive work performed to date largely focused on prediction and diagnosis of the syndrome, little synthesis of findings and validation of promising candidate markers in independent populations has been performed. Studies suggest that risk for subsequent chronic GVHD development may be associated with donor-recipient genetic polymorphism, deficiency in regulatory immune cell populations (NK, Treg, DC2), and variation in inflammatory and immunoregulatory mediators post-HCT (increased TNFα, IL-10 and BAFF, and decreased TGFβ and IL-15). Established chronic GVHD is associated with alteration in immune cell populations (increased CD3(+) T cells, Th17, CD4(+) and CD8(+) effector memory cells, monocytes, CD86 expression, BAFF/B cell ratio, and deficiency of Treg, NK cells, and naïve CD8(+) T cells). Inflammatory and immunomodulatory factors (TNFα, IL-6, IL-1β, IL-8, sIL-2R, and IL-1Ra, BAFF, anti-dsDNA, sIL-2Rα, and sCD13) are also perturbed. Little is known about biologic markers of chronic GVHD phenotype and severity, response to therapy, and prognosis.

  8. Biological identification systems: genetic markers.

    PubMed

    Cunningham, E P; Meghen, C M

    2001-08-01

    Individual animals differ from each other on a number of biological levels. At the most basic level, the deoxyribonucleic acid (DNA) of each animal is different, and transcription of the DNA code yields variations at the protein level, which in turn give rise to individual diversity at the physical level. In recent years, accessing the primary genetic code of individual animals has become straightforward. The authors briefly review the development of biological identification technologies and then consider in more detail the application of current DNA testing technologies to issues of traceability of live animals and derived products. Although largely focused on cattle and beef traceability, the principles described are relevant to ovine, porcine and equine traceability. The accelerating pace of innovation and development within the field of molecular genetics suggests that the technologies described may soon be superseded. However, the principles of genetic identification will remain unchanged.

  9. Genetics and biological markers in urachal cancer

    PubMed Central

    van Rhijn, Bas W. G.

    2016-01-01

    Urachal cancer (UraC) is a rare tumor entity that usually develops at the basis of the remnant embryologic urachus. Consisting of mostly adenocarcinomas, most patients present with secondary symptoms due to an advanced stage with urinary bladder infiltration. One third of patients are already metastasized at presentation rendering them unsuitable for curative surgical treatment. In order to improve staging, treatment and follow-up, adequate knowledge about the genetic origin and potential markers is necessary. This paper reviews the English literature until December 2015. Pathologists argue for and against metaplasia or remnant enteric cells as origin for the adenomatous tissue found in UraC. Mutations in KRAS, BRAF, GNAS and Her2 have been associated with UraC. Immunohistochemical (IHC) markers like CEA, 34βE12, Claudin-18 and RegIV are indicative for mucous producing UraC. So far, IHC markers fail as prognosticators when matched to clinical data. Little is known about serum markers for UraC. CEA, CA19-9, CA125 and CA724 are mentioned as being elevated in UraC by some reports. Regarding the literature for biological markers in UraC, knowledge is mostly derived from case reports or cohort studies mentioning markers or predictors. More genetic research is needed to show whether UraC stems from progenitor cells of the cloaca or is due to metaplasia of transitional cells. Few IHC markers have shown indicative potential for UraC. A useful panel for differential diagnostics and clinicopathologic prognostication needs to be developed. Serum markers show very little potential for neither diagnosis nor follow-up in UraC. Further research on larger cohorts is necessary. PMID:27785422

  10. Comprehensive phenotyping and biological marker discovery

    PubMed Central

    Kantor, Aaron B.

    2002-01-01

    There is an enormous unmet need for biological markers to characterize disease type, status, progression, and response to therapy. We are developing and applying an integrated bioanalytical platform and clinical research program to facilitate comprehensive differential phenotyping of patient samples and enable the discovery of biomarkers. The platform employs high-throughput, quantitative analysis for the characterization of thousands of parameters including cell populations, cell-surface antigen density, soluble proteins and soluble low molecular weight biomolecules, from small-volume biological samples in a clinical research laboratory-like setting. PMID:12364815

  11. Biological (Molecular and Cellular) Markers of Toxicity.

    DTIC Science & Technology

    1991-12-15

    other mammals (Farber, 1987). Therefore, if we are to understand in any depth the processes by which environnental chemicals exhibit genotoxicity ... effectiveness to detect and quantitate biological responses at the molecular level to the action of genotoxic agenst. Particular emphasis was placed on the...Task 3. The short-term responses of the molecular markers as suitable biomarkers to estimate exposure and predict cellular effects to genotoxic

  12. Epithelia: Understanding the Cell Biology of Intestinal Barrier Dysfunction.

    PubMed

    Hu, Daniel J-K; Jasper, Heinrich

    2017-03-06

    Barrier dysfunction in the intestine is a common characteristic of aging organisms. A recent study provides new insight into the cell biology of this phenomenon. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. 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

  14. 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.

  15. Biological markers from Green River kerogen decomposition

    NASA Astrophysics Data System (ADS)

    Burnham, A. K.; Clarkson, J. E.; Singleton, M. F.; Wong, C. M.; Crawford, R. W.

    1982-07-01

    Isoprenoid and other carbon skeletons that are formed in living organisms and preserved essentially intact in ancient sediments are often called biological markers. The purpose of this paper is to develop improved methods of using isoprenoid hydrocarbons to relate petroleum or shale oil to its source rock. It is demonstrated that most, but not all, of the isoprenoid hydrocarbon structures are chemically bonded in kerogen (or to minerals) in Green River oil shale. The rate constant for thermally producing isoprenoid, cyclic, and aromatic hydrocarbons is substantially greater than for the bulk of shale oil. This may be related to the substantial quantity of CO 2 which is evolved coincident with the isoprenoid hydrocarbons but prior to substantial oil evolution. Although formation of isoprenoid alkenes is enhanced by rapid heating and high pyrolysis temperatures, the ratio of isoprenoid alkenes plus alkanes to normal alkenes plus alkanes is independent of heating rate. High-temperature laboratory pyrolysis experiments can thus be used to predict the distribution of aliphatic hydrocarbons in low temperature processes such as in situ shale oil production and perhaps petroleum formation. Finally, we demonstrate that significant variation in biological marker ratios occurs as a function of stratigraphy in the Green River formation. This information, combined with methods for measuring process yield from oil composition, enables one to relate time-dependent processing conditions to the corresponding time-dependent oil yield in a vertical modified- in situ retort even if there is a substantial and previously undetermined delay in drainage of shale oil from the retort.

  16. Auditory biological marker of concussion in children

    PubMed Central

    Kraus, Nina; Thompson, Elaine C.; Krizman, Jennifer; Cook, Katherine; White-Schwoch, Travis; LaBella, Cynthia R.

    2016-01-01

    Concussions carry devastating potential for cognitive, neurologic, and socio-emotional disease, but no objective test reliably identifies a concussion and its severity. A variety of neurological insults compromise sound processing, particularly in complex listening environments that place high demands on brain processing. The frequency-following response captures the high computational demands of sound processing with extreme granularity and reliably reveals individual differences. We hypothesize that concussions disrupt these auditory processes, and that the frequency-following response indicates concussion occurrence and severity. Specifically, we hypothesize that concussions disrupt the processing of the fundamental frequency, a key acoustic cue for identifying and tracking sounds and talkers, and, consequently, understanding speech in noise. Here we show that children who sustained a concussion exhibit a signature neural profile. They have worse representation of the fundamental frequency, and smaller and more sluggish neural responses. Neurophysiological responses to the fundamental frequency partially recover to control levels as concussion symptoms abate, suggesting a gain in biological processing following partial recovery. Neural processing of sound correctly identifies 90% of concussion cases and clears 95% of control cases, suggesting this approach has practical potential as a scalable biological marker for sports-related concussion and other types of mild traumatic brain injuries. PMID:28005070

  17. Auditory biological marker of concussion in children.

    PubMed

    Kraus, Nina; Thompson, Elaine C; Krizman, Jennifer; Cook, Katherine; White-Schwoch, Travis; LaBella, Cynthia R

    2016-12-22

    Concussions carry devastating potential for cognitive, neurologic, and socio-emotional disease, but no objective test reliably identifies a concussion and its severity. A variety of neurological insults compromise sound processing, particularly in complex listening environments that place high demands on brain processing. The frequency-following response captures the high computational demands of sound processing with extreme granularity and reliably reveals individual differences. We hypothesize that concussions disrupt these auditory processes, and that the frequency-following response indicates concussion occurrence and severity. Specifically, we hypothesize that concussions disrupt the processing of the fundamental frequency, a key acoustic cue for identifying and tracking sounds and talkers, and, consequently, understanding speech in noise. Here we show that children who sustained a concussion exhibit a signature neural profile. They have worse representation of the fundamental frequency, and smaller and more sluggish neural responses. Neurophysiological responses to the fundamental frequency partially recover to control levels as concussion symptoms abate, suggesting a gain in biological processing following partial recovery. Neural processing of sound correctly identifies 90% of concussion cases and clears 95% of control cases, suggesting this approach has practical potential as a scalable biological marker for sports-related concussion and other types of mild traumatic brain injuries.

  18. 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.

  19. 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. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2015-10-01

    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. 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. 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). The protein concentration in saliva and, to a lesser extent, the pH may be useful as glandular dysfunction indicators in DM2 patients. Saliva, type 2 diabetes mellitus, pH, protein concentration, xerostomia.

  1. 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

  2. Biological markers in older people at risk of mobility limitations.

    PubMed

    Lippi, Giuseppe; Sanchis-Gomar, Fabian; Montagnana, Martina

    2014-01-01

    Due to the progressive ageing of the worldwide population, prevention and treatment of late-life dysfunctions, including functional decline and mobility limitations, represent leading targets of scientists and clinicians, but are also receiving growing attention from governments and healthcare systems. The early identification of elderly patients more prone to physical decline represents a crucial step for establishing preventive measures. Although functional capacity can easily be assessed, the use of additional criteria that anticipate the onset of mobility limitations seems much more advantageous. The most challenging issues in the identification of biological markers for assessing the risk of functional decline in the elderly originates from the complex and multifaceted pathogenesis of sarcopenia and the resulting physiological decrement, so that bridging the gap between basic research and clinical practice may appear intricate. Nevertheless, several lines of evidence now confirm the existence of negative associations between functional mobility and values of hemoglobin, total and HDL-cholesterol, vitamin D, testosterone, adiponectin and antioxidants such carotenoids, vitamin C and E, selenium and magnesium, whereas positive associations have been reported with the values of uric acid, white blood cells, plasma and blood viscosity, erythrocyte sedimentation rate (ESR), triglycerides, homocysteine, plasma glucose, glycated hemoglobin (HbA1c), markers of renal functions (i.e., creatine and cystatin C), insulin-like growth factor-1 (IGF-1), as well as several inflammatory (e.g., C reactive protein, Intereleukin-6, Interleukin- 1 receptor antagonist), hemostatic (e.g., fibrinogen, Von Willebrand Factor, factors VIII and IX) and oxidative (oxidized lipoproteins, 8-oxo-7,8-2'-deoxyguanosine, protein carbonylation) biomarkers. In the foreseeable future, proteomic studies might predictably help identify novel associations between putative biomarkers and functional

  3. [Biological markers. Utility in the management of patients with pulmonary hypertension].

    PubMed

    Sánchez Román, Julio; Castillo Palma, María Jesús; García Hernández, Francisco J; González León, Rocío

    2011-01-01

    A biological marker can be defined as any substance that can be objectively measured and evaluated as an indicator of a normal biological process, a pathogenic process or pharmacological responses to a therapeutic intervention. In pulmonary hypertension (PH), in addition to routine markers (hemodynamic and functional), there are a growing number of biomarkers that allow an increasingly comprehensive approach to knowledge of susceptibility to this disease and to diagnosis, prognosis and treatment response. These markers can be both constitutive (genetic) and disease-related (related to right ventricular failure, such as BMP/NT-proBNP, endothelial dysfunction, such as endothelin-1, or inflammation, such as certain cytokines and chemokines). Novel insights in genomics and proteomics may allow major advances in this field.

  4. Medline search engine for finding genetic markers with biological significance.

    PubMed

    Xuan, Weijian; Wang, Pinglang; Watson, Stanley J; Meng, Fan

    2007-09-15

    Genome-wide high density SNP association studies are expected to identify various SNP alleles associated with different complex disorders. Understanding the biological significance of these SNP alleles in the context of existing literature is a major challenge since existing search engines are not designed to search literature for SNPs or other genetic markers. The literature mining of gene and protein functions has received significant attention and effort while similar work on genetic markers and their related diseases is still in its infancy. Our goal is to develop a web-based tool that facilitates the mining of Medline literature related to genetic studies and gene/protein function studies. Our solution consists of four main function modules for (1) identification of different types of genetic markers or genetic variations in Medline records (2) distinguishing positive versus negative linkage or association between genetic markers and diseases (3) integrating marker genomic location data from different databases to enable the retrieval of Medline records related to markers in the same linkage disequilibrium region (4) and a web interface called MarkerInfoFinder to search, display, sort and download Medline citation results. Tests using published data suggest MarkerInfoFinder can significantly increase the efficiency of finding genetic disorders and their underlying molecular mechanisms. The functions we developed will also be used to build a knowledge base for genetic markers and diseases. The MarkerInfoFinder is publicly available at: http://brainarray.mbni.med.umich.edu/brainarray/datamining/MarkerInfoFinder.

  5. Are there biological markers of wear?

    PubMed

    Bauer, Thomas W; Shanbhag, Arun S

    2008-01-01

    Potential systemic markers of implant wear include products of the wear process (particles and ions) and mediators of the inflammatory reaction that can be induced by wear. Ions from polymers used in arthroplasty are not specific, but high metal ion levels may help identify patients with unexpectedly high wear of metal-on-metal implants. The kinetics of ion production, transport, and excretion are complex, however, so it is currently difficult to interpret the significance of mild elevations in metal ions. Indices of bone turnover (eg, collagen fragments) and mediators involved in the inflammatory reaction to particles (eg, osteoprotegerin, RANKL, interleukins) may be associated with osteolysis, but systemic disorders (eg, osteoarthritis) and the use of medications that influence bone remodeling limit the predictive value of these analytes with respect to the consequences of implant wear. Using genomic and proteomic methods to measure multiple analytes offers promise, but the challenge is to identify markers specifically associated with wear that are not elevated by other conditions that often coexist in this patient population.

  6. New developments in biological markers of bone metabolism in osteoporosis.

    PubMed

    Garnero, Patrick

    2014-09-01

    Over the last 15 years several biological markers of bone turnover have been developed with increased specificity and sensitivity. In osteoporosis clinical studies, the IOF and IFCC organizations have recently recommended the measurements of serum type I collagen N-propeptide (PINP) and the crosslinked C-terminal telopeptide (serum CTX) as markers of bone formation and bone resorption, respectively. However these markers have some limitations including a lack of specificity for bone tissue, their inability to reflect osteocyte activity or periosteal apposition. In addition they do not allow the investigation of bone tissue quality an important determinant of skeletal fragility. To address these limitations, new developments in markers of bone metabolism have been recently achieved. These include assays for periostin, a matricellular protein preferentially localized in the periosteal tissue, sphingosine 1-phosphate, a lipid mediator which acts mainly on osteoclastogenesis and the osteocyte factors such as sclerostin and FGF-23. Recent studies have shown an association between the circulating levels of these biological markers and fracture risk in postmenopausal women or elderly men, although data require confirmation in additional prospective studies. Finally, recent studies suggest that the measurements of circulating microRNAs may represent a novel class of early biological markers in osteoporosis. It is foreseen that with the use of genomics and proteomics, new markers will be developed to ultimately improve the management of patients with osteoporosis.

  7. 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.

  8. Plasma myeloperoxidase in patients with erectile dysfunction of arteriogenic- and non-arteriogenic origin: association with markers of endothelial dysfunction.

    PubMed

    Dozio, E; Barassi, A; Marazzi, M G; Vianello, E; Colpi, G M; Solimene, U; Melzi D'Eril, G L; Corsi Romanelli, M M

    2013-01-01

    Endothelial dysfunction and the disruption of the nitric oxide-cyclic guanosine monophosphate (cGMP) pathway have been considered the early mechanisms for the development of erectile dysfunction (ED). Myeloperoxidase (MPO), a heme-containing enzyme mainly released by activated neutrophils and monocytes, may contribute to endothelial dysfunction by promoting oxidation of different substrates and thus may play a role in ED. MPO level and its correlation with different plasma biomarkers of endothelial dysfunction were studied in patient with ED of arteriogenic (A-ED) and non-arteriogenic (NA-ED) to assess potential differences between the two ED subgroups. Diagnosis of ED was based on the International Index of Erectile Function Score. Its etiology was classified with penile echo-color Doppler at baseline and after intracavernous injection of prostaglandin E1. MPO, soluble (s) cGMP, sICAM-1, sVCAM-1 and sP-Selectin were measured by enzyme-linked immunosorbent assay. MPO concentration in A-ED was significantly higher compared to control subjects and NA-ED patients. Plasmatic cGMP level resulted lower both in A-ED and in NA-ED patients, whereas no difference has been observed between the two ED groups. sICAM-1 concentration resulted higher in A-ED compared both to controls and NA-ED. sVCAM-1 level was the same in controls, A-ED and NA-ED patients. sP-Selectin concentration resulted higher both in A-ED and in NA-ED patients than in controls, whereas no difference has been observed between the two ED groups. Correlation analysis indicated a positive correlation between plasmatic MPO, sICAM-1 and sP-Selectin levels. MPO may represent an important link between oxidation, inflammation and cardiovascular diseases and may also represent a potential marker to distinguish between the two subgroups of ED patients. Moreover, in ED subjects circulating cGMP may reflect the local signaling dysfunction. The use cGMP as a potential marker for monitoring the disease needs further

  9. Assessing secondhand smoke using biological markers

    PubMed Central

    Al-Delaimy, Wael K; Ashley, David L; Benowitz, Neal; Bernert, John T; Kim, Sungroul; Samet, Jonathan M; Hecht, Stephen S

    2013-01-01

    Secondhand smoke exposure (SHSe) is a known cause of many adverse health effects in adults and children. Increasingly, SHSe assessment is an element of tobacco control research and implementation worldwide. In spite of decades of development of approaches to assess SHSe, there are still unresolved methodological issues; therefore, a multidisciplinary expert meeting was held to catalogue the approaches to assess SHSe and with the goal of providing a set of uniform methods for future use by investigators and thereby facilitate comparisons of findings across studies. The meeting, held at Johns Hopkins, in Baltimore, Maryland, USA, was supported by the Flight Attendant Medical Research Institute (FAMRI). A series of articles were developed to summarise what is known about self-reported, environmental and biological SHSe measurements. Non-smokers inhale toxicants in SHS, which are mainly products of combustion of organic materials and are not specific to tobacco smoke exposure. Biomarkers specific to SHSe are nicotine and its metabolites (eg, cotinine), and metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Cotinine is the preferred blood, saliva and urine biomarker for SHSe. Cotinine and nicotine can also be measured in hair and toenails. NNAL (4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol), a metabolite of NNK, can be determined in the urine of SHS-exposed non-smokers. The selection of a particular biomarker of SHSe and the analytic biological medium depends on the scientific or public health question of interest, study design and setting, subjects, and funding. This manuscript summarises the scientific evidence on the use of biomarkers to measure SHSe, analytical methods, biological matrices and their interpretation. PMID:22940677

  10. 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.

  11. An update on the biological markers of endometriosis.

    PubMed

    Socolov, Razvan; Socolov, Demetra; Sindilar, Allia; Pavaleanu, Ioana

    2017-10-01

    Endometriosis is a disease that affects 7-10% of reproductive-age women. When its diagnosis is delayed, its management becomes more difficult. Both for earlier detection and for therapeutic follow-up, discovering noninvasive biological markers with good specificity for this disease is a promising aspect of its research. We analyzed the recent data in the literature regarding these markers to determine which were worth following. This literature review focused on medical data reported in the last 6 years (2011-2016). After identifying articles in PubMed, an analysis of the type of data and level of evidence provided was performed. The selected articles were compared and conclusions regarding the specific markers addressed. Of the 255 articles identified that reported human studies, we had access to the full text for 169 of them. We selected 71 prospective studies to include in our analysis. The studies were divided based on the primary marker studied: 22 analyzed inflammatory and immunological markers, 9 adhesivity and migration markers, 18 genetic polymorphisms, 7 oxidative stress, 4 micro-RNA circulating fragments, and 11 other biological markers (hormonal receptors, leukocytes, and others). CA 125 remains the most recommended marker for suspicion of endometriosis and follow-up. Other markers, such as CA 19-9, CA 72-4, and endometrial cells in peripheral blood, have more value for differentiating endometriosis from other pathologies, while circulating micro-RNA could help clarify the endometrial stem cell's implication in its pathogeny. Finally, other new urinary markers could be used in early diagnostic and screening strategies.

  12. Environmental metabolomics: Biological markers for metal toxicity.

    PubMed

    García-Sevillano, Miguel Ángel; García-Barrera, Tamara; Gómez-Ariza, José Luis

    2015-07-14

    Environmental metabolomics is an emerging field referred to the application of metabolomics to characterize the interactions of living organisms with their environment. In this sense, the importance of monitoring the effects of toxic metals on living organisms has increased as a consequence of natural changes and anthropogenic activities that have led to an increase of toxic metals levels in terrestrial and aquatic ecosystems. For this purpose, the use of metabolomics based on mass spectrometry to study metal toxicity is gaining importance in recent years. Environmental metabolomics can be used to: discover the mode of action (MOA) of toxic metals through controlled laboratory experiments; evaluate toxicity (biological adverse response to a substance), that may be useful in risk assessment; and develop new biomarkers (based in metabolome shifts discovered through controlled laboratory experiments) that may be applied in environmental biomonitoring (environmental realistic scenario). In this review, it is discussed how metabolomics based on mass spectrometry can be applied to study metal toxicity, considering the most important hallmarks related to metabolomic experiments. This article is protected by copyright. All rights reserved.

  13. 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.

  14. Biological markers of generalized anxiety disorder

    PubMed Central

    Maron, Eduard; Nutt, David

    2017-01-01

    Generalized anxiety disorder (GAD) is a prevalent and highly disabling mental health condition; however, there is still much to learn with regard to pertinent biomarkers, as well as diagnosis, made more difficult by the marked and common overlap of GAD with affective and anxiety disorders. Recently, intensive research efforts have focused on GAD, applying neuroimaging, genetic, and blood-based approaches toward discovery of pathogenetic and treatment-related biomarkers. In this paper, we review the large amount of available data, and we focus in particular on evidence from neuroimaging, genetic, and neurochemical measurements in GAD in order to better understand potential biomarkers involved in its etiology and treatment. Overall, the majority of these studies have produced results that are solitary findings, sometimes inconsistent and not clearly replicable. For these reasons, they have not yet been translated into clinical practice. Therefore, further research efforts are needed to distinguish GAD from other mental disorders and to provide new biological insights into its pathogenesis and treatment. PMID:28867939

  15. 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.

  16. Discovery and development of integrative biological markers for schizophrenia.

    PubMed

    Oertel-Knöchel, Viola; Bittner, Robert A; Knöchel, Christian; Prvulovic, David; Hampel, Harald

    2011-12-01

    Schizophrenia is one of the most disabling forms of mental illness. One of the most important challenges is to establish biological markers which can accurately identify at-risk individuals in preclinical stages and thus improve the effects of early intervention strategies. Here, we review recent findings in the field of molecular genetics, CSF (cerebrospinal fluid) based markers as well as structural and functional neuroimaging in the light of their relevance for schizophrenia biomarker research. We also examine evidence supporting the hypothesis that schizophrenia and neurodegenerative disorders such as Alzheimer's disease may share certain pathophysiological features, e.g. chronic inflammation and oxidative stress, and discuss their possible role in schizophrenia. The heterogeneous, multifaceted and multifactorial nature of the traditionally clinically operationalized entity "schizophrenia" presents an enormous challenge towards the identification of single diagnostic or surrogate markers. We propose that abnormal neural coordination is a major point of convergence of a number of crucial pathophysiological pathways. Therefore, functional markers reflecting disturbed neural coordination might be particularly attractive biomarker candidates, because of their ability to integrate the influence of diverse pathophysiological mechanisms. Similarly, combinatorial and multimodal approaches may be a promising way to more accurately capture the complex biological underpinnings schizophrenia. We consider the development of such integrative biomarkers to be essential in order to facilitate a timely diagnosis of schizophrenia. They should also advance our understanding of the subtle and intricate biological nature of schizophrenia. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Biohumoral markers as predictor of right ventricular dysfunction in AL Amyloidosis.

    PubMed

    Cappelli, Francesco; Baldasseroni, Samuele; Bergesio, Franco; Padeletti, Luigi; Attanà, Paola; Pignone, Alberto Moggi; Grifoni, Elisa; Ciuti, Gabriele; Fabbri, Alessia; Tarantini, Francesca; Marchionni, Niccolò; Gensini, Gian Franco; Perfetto, Federico

    2014-06-01

    In AL amyloidosis, the importance of right ventricle (RV) involvement has recently been underlined and its role in predicting prognosis has been emphasized. Little is known about the relationship between RV involvement, N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin levels. Aim of our study was to clarify the relationship between NT-proBNP and troponin and RV involvement and analyze their independent value as predictors of RV dysfunction. We examined 76 consecutive patients with biopsy-proven AL amyloidosis. Each patient received complete clinical evaluation, troponin I, NT-proBNP assay and comprehensive echocardiographic evaluation. Considering a tricuspidal annulus plane systolic excursion (TAPSE) value <16 mm, 23 patients (30%) presented RV systolic dysfunction, whereas 53 (70%) did not. Patient with reduced TAPSE had thicker left ventricle (LV) walls and RV free walls, reduced LV fractional shortening, impaired LV diastolic function and worse LV and RV myocardial performance index. For RV dysfunction the best predictive value for NT-proBNP was identified as 2977 ng/l with sensitivity and specificity of 87% and 84%, respectively; best cut-off for troponin I was identified as 0.085 ng/l, with sensitivity and specificity of 85% and 90% respectively. At multivariable logistic regression analysis, both NT-proBNP and troponin I emerged as independent predictors of RV dysfunction presence but troponin appears to have a higher predictive power. Our study demonstrated that cut-off values of 2977 ng/ml for NT-proBNP and 0.085 ng/l for troponin were able to identify a subgroup of AL patients with RV dysfunction. Troponin I is more accurate and seems to be the best biohumoral marker of RV dysfunction.

  18. Chronic Kidney Disease Awareness Among Individuals with Clinical Markers of Kidney Dysfunction

    PubMed Central

    Plantinga, Laura C.; Hsu, Chi-yuan; Jordan, Regina; Burrows, Nilka Ríos; Hedgeman, Elizabeth; Yee, Jerry; Saran, Rajiv; Powe, Neil R.

    2011-01-01

    Summary Background and objectives Awareness of chronic kidney disease (CKD) among providers and patients is low. Whether clinical cues prompt recognition of CKD is unknown. We examined whether markers of kidney disease that should trigger CKD recognition among providers are associated with higher individual CKD awareness. Design, setting, participants, & measurements CKD awareness was assessed in 1852 adults with an estimated GFR <60 ml/min per 1.73 m2 using 1999 to 2008 National Health and Nutrition Examination Survey data. CKD awareness was a “yes” answer to “Have you ever been told you have weak or failing kidneys?” Participants were grouped by distribution of the following abnormal markers of CKD: hyperkalemia, acidosis, hyperphosphatemia, elevated blood urea nitrogen, anemia, albuminuria, and uncontrolled hypertension. Odds of CKD awareness associated with each abnormal marker and groupings of markers were estimated by multivariable logistic regression. Results Among individuals with kidney disease, only those with albuminuria had greater odds of CKD awareness (adjusted odds ratio, 4.0, P < 0.01) than those without. Odds of CKD awareness increased with each additional manifested clinical marker of CKD (adjusted odds ratio, 1.3, P = 0.05). Nonetheless, 90% of individuals with two to four markers of CKD and 84% of individuals with ≥5 markers of CKD were unaware of their disease. Conclusions Although individuals who manifest many markers of kidney dysfunction are more likely to be aware of their CKD, their CKD awareness remains low. A better understanding of mechanisms of awareness is required to facilitate earlier detection of CKD and implement therapy to minimize associated complications. PMID:21784832

  19. Toward an early marker of metabolic dysfunction: omentin-1 in prepubertal children.

    PubMed

    Prats-Puig, Anna; Bassols, Judit; Bargalló, Eva; Mas-Parareda, Marta; Ribot, Rosa; Soriano-Rodríguez, Pilar; Berengüí, Àngela; Díaz, Marta; de Zegher, Francis; Ibánez, Lourdes; López-Bermejo, Abel

    2011-09-01

    Omentin-1 is a recently recognized adipokine primarily originating in visceral adipose tissue. We posited that circulating omentin-1 could be an early marker of metabolic dysfunction. To this end, we examined the associations between circulating omentin-1, body fat (bioelectric impedance), an endocrine-metabolic profile (homeostasis model assessment for insulin resistance (HOMA(IR)), serum lipids, high-molecular-weight (HMW) adiponectin and blood pressure (BP)) and family history of obesity and diabetes in asymptomatic prepubertal children (n = 161; 77 boys and 84 girls; age 7 ± 1 year) with a normal distribution of height and weight. Increased circulating omentin-1 was associated with a poorer metabolic profile, with relatively higher HOMA(IR), fasting triacylglycerol, BP and familial prevalence of diabetes (all P < 0.005 to P < 0.0001), and relatively lower fraction of HMW adiponectin (P < 0.005), whereas no relationship was found with body weight or fat or with family history of obesity. All these associations were independent of age, gender and fat mass. In conclusion, circulating omentin-1 may become a marker of metabolic dysfunction integrating insulin sensitivity, markers of adipose-tissue metabolism and BP as early as in prepubertal childhood.

  20. Microparticles: markers and mediators of sepsis-induced microvascular dysfunction, immunosuppression, and AKI

    PubMed Central

    Souza, Ana Carolina P.; Yuen, Peter S. T.; Star, Robert A.

    2015-01-01

    Sepsis is a severe and complex syndrome that lacks effective prevention or therapeutics. The effects of sepsis on the microvasculature have become an attractive area for possible new targets and therapeutics. Microparticles (MPs) are cell membrane-derived particles that can promote coagulation, inflammation, and angiogenesis; and can participate in cell-to-cell communication. MPs retain cell membrane and cytoplasmic constituents of their parental cells, including two pro-coagulants: phosphatidylserine and tissue factor. We highlight the role of microparticles released by endothelial and circulating cells after sepsis-induced microvascular injury, and discuss possible mechanisms by which microparticles can contribute to endothelial dysfunction, immunosuppression, and multi-organ dysfunction--including sepsis-AKI. Once viewed as cellular byproducts, microparticles are emerging as a new class of markers and mediators in the pathogenesis of sepsis. PMID:25692956

  1. Genetics and biological markers of risk for alcoholism.

    PubMed Central

    Tabakoff, B; Hoffman, P L

    1988-01-01

    Substantial scientific evidence has accumulated that both genetic and environmental factors predispose the development of alcoholism in certain individuals. Evidence has accumulated to indicate that alcoholism is a heterogeneous entity arising from multiple etiologies. The demonstrated role of genetics in increasing the risk of alcoholism has promoted the search for biological markers that could objectively identify individuals who are genetically predisposed to alcoholism. Identifying such markers could allow for early diagnosis, focused prevention, and differential and type-specific treatment of alcoholism. Promising markers have been provided by research in electrophysiology, endocrinology, and biochemistry. Recent advances in molecular genetics are offering prospects for direct analysis of the human genome to determine elements that provide predisposition to, and protection from, alcoholism. Recent advances in research and new knowledge gained by the alcoholism treatment community and the lay public are helping to diminish the societal damage caused by alcohol abuse and alcoholism and to change prevailing attitudes about them. PMID:3141966

  2. Kidney Dysfunction and Markers of Inflammation in the Multicenter AIDS Cohort Study

    PubMed Central

    Abraham, Alison G.; Darilay, Annie; McKay, Heather; Margolick, Joseph B.; Estrella, Michelle M.; Palella, Frank J.; Bolan, Robert; Rinaldo, Charles R.; Jacobson, Lisa P.

    2015-01-01

    Background. Human immunodeficiency virus (HIV)–infected individuals are at higher risk for chronic kidney disease than HIV-uninfected individuals. We investigated whether the inflammation present in treated HIV infection contributes to kidney dysfunction among HIV-infected men receiving highly active antiretroviral therapy. Methods. The glomerular filtration rate (GFR) was directly measured (using iohexol) along with 12 markers of inflammation in Multicenter AIDS Cohort Study participants. Exploratory factor analysis was used to identify inflammatory processes related to kidney dysfunction. The estimated levels of these inflammatory processes were used in adjusted logistic regression analyses evaluating cross-sectional associations with kidney function outcomes. Results. There were 434 HIV-infected men receiving highly active antiretroviral therapy and 200 HIV-uninfected men. HIV-infected men were younger (median age, 51 vs 53 years) and had higher urine protein-creatinine ratios (median, 98 vs 66 mg/g) but comparable GFRs (median, 109 vs 106 mL/min|1.73 m2). We found an inflammatory process dominated by markers: soluble tumor necrosis factor receptor 2, soluble interleukin 2 receptor α, soluble gp130, soluble CD27, and soluble CD14. An increase of 1 standard deviation in that inflammatory process was associated with significantly greater odds of GFR ≤90 mL/min/1.73 m2 (odds ratio, 2.0) and urine protein >200 mg/g (odds ratio, 2.3). Conclusions. Higher circulating levels of immune activation markers among treated HIV-infected men may partially explain their higher burden of kidney dysfunction compared with uninfected men. PMID:25762788

  3. Saccade sequences as markers for cerebral dysfunction following mild closed head injury.

    PubMed

    Heitger, M H; Anderson, T J; Jones, R D

    2002-01-01

    Diffuse axonal injury caused by mild closed head injury (CHI) is likely to affect the neural networks concerned with the planning and execution of sequences of memory-guided saccades. Thirty subjects with mild CHI and thirty controls were tested on 2- and 3-step sequences of memory-guided saccades. CHI subjects showed more directional errors, larger position errors, and hypermetria of primary saccades and final eye position. No deficits were seen in temporal accuracy (timing and rhythm). These results suggest that computerized tests of saccade sequences can provide sensitive markers of cerebral dysfunction after mild CHI.

  4. [Association between biochemical markers and left ventricular dysfunction in the ST-elevation acute myocardial infarction].

    PubMed

    de Abreu, Maximiliano; Mariani, Javier; Guridi, Cristian; González-Villa-Monte, Gabriel; Gastaldello, Natalio; Potito, Mauricio; Reyes, Graciela; Antonietti, Laura; Tajer, Carlos

    2014-01-01

    The association between biochemical markers and left ventricular ejection fraction in patients with myocardial infarction was not completely studied. Our goal is to study the association between biochemical markers and left ventricular dysfunction in patients with ST-elevation acute myocardial infarction. With an observational and prospective design we included patients with less than 24h ST-elevation myocardial infarction. Leukocytes, glucose, B-type natriuretic peptide and T troponin were measured at admission, and creatine-phosphokinase and creatine-phosphokinase-MB were measured at admission and serially, and correlated with the ejection fraction estimated by echocardiography. A total of 108 patients were included. The median left ventricular ejection fraction was 48% (interquartile range 41-57). Simple linear regression analysis showed that B-type natriuretic peptide (P=.005), peak creatine-phosphokinase-MB (P=.01), leukocyte count (P=.001) and glucose (P=.033) were inversely and significantly associated with the left ventricular ejection fraction. The other parameters showed no association. B-type natriuretic peptide (P=.01) and peak creatine-phosphokinase-MB (P=.02) were the only two variables significantly associated with the left ventricular ejection fraction in the multiple linear regression analysis. Both markers were significantly associated with a left ventricular ejection fraction < 50%, independently of other clinical variables. B-type natriuretic peptide and peak creatine-phosphokinase-MB showed significant association with left ventricular ejection fraction in the acute phase of ST elevation acute myocardial infarction. This association was independent of the presence of other biochemical markers and clinical variables related to ventricular dysfunction. Copyright © 2013 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  5. [Reduction of exercise-mediated endothelial dysfunction markers in sedentary adults with chronic spinal cord injury].

    PubMed

    Rosety-Rodriguez, Manuel; Camacho-Molina, Alejandra; Rosety, Ignacio; Fornieles, Gabriel; Rosety, Miguel A; Ordoñez, Francisco Javier

    2015-01-20

    Recent studies have found increased markers of endothelial activation in men with chronic spinal cord injury. This study was conducted to determine the effects of arm-cranking exercise on endothelial dysfunction in male adults with chronic SCI. A prospective randomized study of 17 sedentary adult males with chronic SCI at or under T5 level. Nine performed a supervised exercise program at a moderate intensity (arm-cranking: 12 weeks, 3 sessions/week). Plasma levels of endothelin-1, soluble intercellular adhesion molecule type 1 (sICAM-1), and soluble vascular adhesion molecule type 1 (sVCAM-1) were assessed by ELISA. Outcome measurements also included physical fitness and total body fat mass percentage. We observed both in the randomized and in the before-after studies a significant reduction of the levels of endothelin-1 and sICAM-1. Furthermore, significant improvements of both physical fitness and body composition were also found. Arm-cranking exercise improved endothelial dysfunction in adult males with chronic SCI. Long-term studies are still required to determine whether the correction of endothelial dysfunction improves the clinical outcomes of adults with chronic SCI. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  6. Biologic markers of chronic graft vs. host disease

    PubMed Central

    Pidala, Joseph; Sarwal, Minnie; Roedder, Silke; Lee, Stephanie J.

    2014-01-01

    Biologic markers of chronic graft vs. host disease (GVHD) may provide insight into the pathogenesis of the syndrome, identify molecular targets for novel interventions, and facilitate advances in clinical management. Despite extensive work performed to date largely focused on prediction and diagnosis of the syndrome, little synthesis of findings and validation of promising candidate markers in independent populations has been performed. Studies suggest that risk for subsequent chronic GVHD development may be associated with donor-recipient genetic polymorphism, deficiency in regulatory immune cell populations (NK, Treg, DC2), and variation in inflammatory and immunoregulatory mediators post-HCT (increased TNFα, IL-10 and BAFF, and decreased TGFβ and IL-15). Established chronic GVHD is associated with alteration in immune cell populations (increased CD3+ T cells, Th17, CD4+ and CD8+ effector memory cells, monocytes, CD86 expression, BAFF/B cell ratio, and deficiency of Treg, NK cells, and naïve CD8+ T cells). Inflammatory and immunomodulatory factors (TNFα, IL-6, IL-1β, IL-8, sIL-2R, and IL-1Ra, BAFF, anti-dsDNA, sIL-2Rα, and sCD13) are also perturbed. Little is known about biologic markers of chronic GVHD phenotype and severity, response to therapy, and prognosis. PMID:23872737

  7. 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.

  8. Endothelial Dysfunction: An Early Cardiovascular Risk Marker in Asymptomatic Obese Individuals with Prediabetes

    PubMed Central

    Gupta, Alok K.; Ravussin, Eric; Johannsen, Darcy L.; Stull, April J.; Cefalu, William T.; Johnson, William D.

    2012-01-01

    Aims To elucidate if endothelial dysfunction is an early CV risk marker in obese men and women with prediabetes. Study Design Cross-sectional study. Place and Duration of Study Clinical Research Unit, Pennington Biomedical Research Center, Baton Rouge, LA. United States. Methodology Overweight and obese status denotes an increasing adipose tissue burden which spills over into ectopic locations, including the visceral compartment, muscle and liver. Associated co-morbidities enhance cardiovascular (CV) risk. Endothelium which is the largest receptor-effector end-organ in our bodies, while responding to numerous physical and chemical stimuli maintains vascular homeostasis. Endothelial dysfunction (ED) is the initial perturbation, which precedes fatty streak known to initiate atherosclerosis: insidious process which often culminates as sudden catastrophic CV adverse event. Asymptomatic men and women; [n=42] coming in after an overnight fast had demographic, anthropometric, clinical chemistry and resting endothelial function [EF: increased test finger peripheral arterial tone (PAT) relative to control; expressed as relative hyperemia index (RHI)] assessments. Results Adults with desirable weight [n=12] and overweight [n=8] state, had normal fasting plasma glucose [Mean(SD)]: FPG [91.1(4.5), 94.8(5.8) mg/dL], insulin [INS, 2.3(4.4), 3.1(4.8) μU/ml], insulin sensitivity by homeostasis model assessment [HOMA-IR, 0.62(1.2), 0.80(1.2)] and desirable resting clinic blood pressure [SBP/DBP, 118(12)/74(5), 118(13)/76(8) mmHg]. Obese adults [n=22] had prediabetes [FPG, 106.5(3.5) mg/dL], hyperinsulinemia [INS 18.0(5.2) μU/ml], insulin resistance [HOMA-IR 4.59(2.3)], prehypertension [PreHTN; SBP/DBP 127(13)/81(7) mmHg] and endothelial dysfunction [ED; reduced RHI 1.7(0.3) vs. 2.4(0.3); all p<0.05]. Age-adjusted RHI correlated with BMI [r=−0.53; p<0.001]; however, BMI-adjusted RHI was not correlated with age [r=−0.01; p=0.89]. Conclusion Endothelial dysfunction reflective of

  9. Prevalence, Prospective Risk Markers, and Prognosis Associated With the Presence of Left Ventricular Diastolic Dysfunction in Young Adults

    PubMed Central

    Desai, Chintan S.; Colangelo, Laura A.; Liu, Kiang; Jacobs,, David R.; Cook, Nakela L.; Lloyd-Jones, Donald M.; Ogunyankin, Kofo O.

    2013-01-01

    The authors sought to determine the prevalence, prospective risk markers, and prognosis associated with diastolic dysfunction in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. The CARDIA Study cohort includes approximately equal proportions of white and black men and women. The authors collected data on risk markers at year 0 (1985–1986), and echocardiography was done at year 5 when the participants were 23–35 years of age. Participants were followed for 20 years (through 2010) for a composite endpoint of all-cause mortality, myocardial infarction, heart failure, and stroke. Diastolic function was defined according to a validated hierarchical classification algorithm. In the 2,952 participants included in the primary analysis, severe diastolic dysfunction was present in 1.1% and abnormal relaxation was present in 9.3%. Systolic blood pressure at year 0 was associated with both severe diastolic dysfunction and abnormal relaxation 5 years later, whereas exercise capacity and pulmonary function abnormalities were associated only with abnormal relaxation 5 years later. After multivariate adjustment, the hazard ratios for the composite endpoint in participants with severe diastolic dysfunction and abnormal relaxation were 4.3 (95% confidence interval: 2.0, 9.3) and 1.6 (95% confidence interval: 1.1, 2.5), respectively. Diastolic dysfunction in young adults is associated with increased morbidity and mortality, and the identification of prospective risk markers associated with diastolic dysfunction could allow for targeted primary prevention efforts. PMID:23211639

  10. The prognostic value of biological markers in paediatric Hodgkin lymphoma.

    PubMed

    Farruggia, Piero; Puccio, Giuseppe; Sala, Alessandra; Todesco, Alessandra; Buffardi, Salvatore; Garaventa, Alberto; Bottigliero, Gaetano; Bianchi, Maurizio; Zecca, Marco; Locatelli, Franco; Pession, Andrea; Pillon, Marta; Favre, Claudio; D'Amico, Salvatore; Provenzi, Massimo; Trizzino, Angela; Zanazzo, Giulio Andrea; Sau, Antonella; Santoro, Nicola; Murgia, Giulio; Casini, Tommaso; Mascarin, Maurizio; Burnelli, Roberta

    2016-01-01

    Many biological and inflammatory markers have been proposed as having a prognostic value at diagnosis of Hodgkin lymphoma (HL), but very few have been validated in paediatric patients. We explored the significance of these markers in a large population of 769 affected children. By using the database of patients enrolled in A.I.E.O.P. (Associazione Italiana di Emato-Oncologia Pediatrica) trial LH2004 for paediatric HL, we identified 769 consecutive patients treated with curative intent from 1st June 2004 to 1st April 2014 with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), or hybrid COPP/ABV (cyclophosphamide, vincristine, prednisone, procarbazine, doxorubicin, bleomycin and vinblastine) regimens. On multivariate analysis with categorical forms, the 5-year freedom from progression survival was significantly lower in patients with stage IV or elevated value of platelets, eosinophils and ferritin at diagnosis. Furthermore, stage IV and eosinophils seem to maintain their predictive value independently of interim (after IV cycles of chemotherapy) positron emission tomography. Using the combination of four simple markers such as stage IV and elevated levels of platelets, ferritin and eosinophils, it is possible to classify the patients into subgroups with very different outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. The athlete's biological passport and indirect markers of blood doping.

    PubMed

    Sottas, Pierre-Edouard; Robinson, Neil; Saugy, Martial

    2010-01-01

    In the fight against doping, disciplinary sanctions have up to now been primarily based on the discovery of an exogenous substance in a biological fluid of the athlete. However, indirect markers of altered erythropoiesis can provide enough evidence to differentiate between natural variations and blood doping. Forensic techniques for the evaluation of the evidence, and more particularly Bayesian networks, allow antidoping authorities to take into account firstly the natural variations of indirect markers - through a mathematical formalism based on probabilities - and secondly the complexity due to the multiplicity of causes and confounding effects - through a distributed and flexible graphical representation. The information stored in an athlete's biological passport may be then sufficient to launch a disciplinary procedure against the athlete. The strength of the passport is that it relies on a statistical approach based on sound empirical testing on large populations and justifiable protocols. Interestingly, its introduction coincides with the paradigm shift that is materializing today in forensic identification science, from archaic assumptions of absolute certainty and perfection to a more defensible empirical and probabilistic foundation.

  12. Potential usefulness of biological markers in risk assessment

    SciTech Connect

    Perera, F.

    1987-12-01

    Substantial data have been generated during the last 5 years in experimental systems and human populations which shed light on the potential usefulness of biological markers in human cancer risk assessment. Following a brief review of overall progress to date in the biomonitoring of human populations, this paper turns to the growing body of data regarding carcinogen-DNA and protein adducts as illustrative markers of biologically effective dose of carcinogens. The data base illustrates considerable human interindividual variation in binding and the presence of significant background levels of adducts-both of which support the absence of human population thresholds for exposure to carcinogens. The contribution of adduct data to our understanding of the shape of low-dose-response curve and the reliability of interspecies extrapolation, as well as the relevance of adducts to cancer risk, are also discussed. Even though adducts can now be useful in hazard identification or qualitative risk assessment,more research is needed before they can serve as quantitative predictors of human cancer risk.

  13. Urinary nucleosides as biological markers for patients with colorectal cancer

    PubMed Central

    Zheng, Yu-Fang; Yang, Jun; Zhao, Xin-Jie; Feng, Bo; Kong, Hong-Wei; Chen, Ying-Jie; Lv, Shen; Zheng, Min-Hua; Xu, Guo-Wang

    2005-01-01

    AIM: Fourteen urinary nucleosides, primary degradation products of tRNA, were evaluated to know the potential as biological markers for patients with colorectal cancer. METHODS: The concentrations of 14 kinds of urinary nucleosides from 52 patients with colorectal cancer, 10 patients with intestinal villous adenoma and 60 healthy adults were determined by column switching high performance liquid chromatography method. RESULTS: The mean levels of 12 kinds of urinary nucleosides (except uridine and guanosine) in the patients with colorectal cancer were significantly higher than those in patients with intestinal villous adenoma or the healthy adults. Using the levels of 14 kinds of urinary nucleosides as the data vectors for principal component analysis, 71% (37/52) patients with colorectal cancer were correctly classified from healthy adults, in which the identification rate was much higher than that of CEA method (29%). Only 10% (1/10) of patients with intestinal villous adenoma were indistinguishable from patients with colorectal cancer. The levels of m1G, Pseu and m1A were positively related with tumor size and Duke’s stages of colorectal cancer. When monitoring the changes in urinary nucleoside concentrations of patients with colorectal cancer associated with surgery, it was found that the overall correlations with clinical assessment were 84% (27/32) and 91% (10/11) in response group and progressive group, respectively. CONCLUSION: These findings indicate that urinary nucleosides determined by column switching high performance liquid chromatography method may be useful as biological markers for colorectal cancer. PMID:15991285

  14. Utility of urinary markers in the assessment of renal dysfunction in canine babesiosis.

    PubMed

    Winiarczyk, Dagmara; Adaszek, Łukasz; Bartnicki, Michał; Abramowicz, Beata; Łyp, Paweł; Madany, Jacek; Winiarczyk, Stanisław

    2017-04-19

    Canine babesiosis is a common and clinically significant tick-borne disease caused by haemoprotozoan parasites of the genus Babesia. Acute renal failure is considered to be one of the most prevalent complications of canine babesiosis. This complication leads to a decrease in the glomerular filtration rate and in consequence causes azotemia and uremia. The objective of this study was to assess the localization and extent of renal damage in dogs infected with Babesia canis using an urinary marker for glomerular (urinary immunoglobulin G, uIgG), proximal tubular dysfunction (urinary retinol binding protein, uRBP) and distal tubular dysfunction (urinary Tamm-Horsfal protein, uTHP). Material und methods: In 10 dogs naturally infected with B. canis and 10 healthy control dogs the levels of urinary biomarkers were measured using commercially available ELISA tests. Higher concentrations of uIgG, uRBP and uTHP were found in the urine of all dogs with babesiosis than in those from the control group. This indicates that in the course of the disease, the glomeruli as well as the renal tubules become damaged. The study results allow a better understanding of the pathogenesis of canine babesiosis. However, in order to fully determine the extent and the nature of the damage to the kidneys of the infected dogs, it is advisable to conduct additional histopathological examinations of these organs.

  15. hSMR3A as a Marker for Patients With Erectile Dysfunction

    PubMed Central

    Tong, Yuehong; Tar, Moses; Monrose, Val; DiSanto, Michael; Melman, Arnold; Davies, Kelvin P.

    2007-01-01

    reported effects of intracorporeal injection of pVAX-Vcsa1 into the corpora of aging rats, establishing hSMR3A as a functional homologue of Vcsa1. More than 10-fold down-regulation in hSMR3A transcript expression was observed in the corpora of patients with vs without erectile dysfunction. In patients with diabetes associated and nondiabetes associated erectile dysfunction hSMR3A expression was found to be down-regulated. Conclusions These results suggest that hSMR3A can act as a marker for erectile dysfunction associated with diabetic and nondiabetic etiologies. Given that our previous studies demonstrated that gene transfer of the Vcsa1 gene and intracorporeal injection of its protein product in rats can restore erectile function, these results suggest that therapies that increase the hSMR3A gene and product expression could potentially have a positive impact on erectile function. PMID:17512016

  16. Synergy as a new and sensitive marker of basal ganglia dysfunction: A study of asymptomatic welders.

    PubMed

    Lewis, Mechelle M; Lee, Eun-Young; Jo, Hang Jin; Du, Guangwei; Park, Jaebum; Flynn, Michael R; Kong, Lan; Latash, Mark L; Huang, Xuemei

    2016-09-01

    pallidal index, R1, or R2* values in the basal ganglia. These data suggest that multi-digit synergy metrics may serve as preclinical markers for basal ganglia dysfunction in welders and other populations at risk for neurodegenerative diseases involving parkinsonian symptoms. This finding may have important clinical, scientific, and public/occupational health implications. Copyright © 2016 Elsevier B.V. All rights reserved.

  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.

  18. Significance of platelet distribution width as a severity marker of erectile dysfunction.

    PubMed

    Guo, L Q; Liu, Y Q; Sun, W D; Yuan, M Z; Xiao, Z Y; Song, H B; Zhao, S T; Zhang, X L; Ge, N

    2017-04-01

    Mean platelet volume (MPV) and Platelet distribution width (PDW) are potential markers in platelet activation. In present study, we aimed to evaluate MPV and PDW as potential severity markers for those patients who are complaining erectile dysfunction (ED). A total of 358 participants were enrolled in this study. The whole cohort was asked to complete the International Index of Erectile Function-5 (IIEF-5) questionnaire. The participants were classified into 3 groups: control group (n = 120), mild ED (n = 118) and severe ED (n = 120). We found in our cohort MPV and PDW were significantly higher in both mild ED group and severe ED group than control group (9.24 ± 0.70 and 9.71 ± 0.80 versus 8.56 ± 0.62 for MPV; 14.48 ± 1.29 and 14.98 ± 1.60 versus 12.86 ± 1.13 for PDW respectively). The MPV and PDW increased as the disease progressed. In the mild and severe ED groups, a significant inverse correlation was detected between the mean values of IIEF-5 score and PDW. Furthermore, in the receiver operating characteristic curve analysis, the area under the curve of the MPV and PDW to predict severe ED was 0.818 and 0.848 respectively. Our study establishes a dose-dependent association between the PDW and ED. Therefore, the PDW can serve as a potential marker for predicting the severity of ED.

  19. Endothelial dysfunction, inflammation, and oxidative stress in obese children and adolescents: markers and effect of lifestyle intervention.

    PubMed

    Montero, D; Walther, G; Perez-Martin, A; Roche, E; Vinet, A

    2012-05-01

    With an increasing prevalence, pediatric obesity is often a prelude to adulthood obesity, and represents a major public health issue. Comorbidities are very common and severe in obese adults, justifying the search for earlier markers or risk factors for cardiovascular diseases in obese children. Endothelial dysfunction has been found to be present in the early stages of atherosclerosis, and can be non-invasively assessed with widely accepted and well-standardized techniques at the macrocirculation level. Endothelial dysfunction at the microcirculation level is less documented in obese children. Obesity in children has been repeatedly and independently correlated to endothelial dysfunction, inflammation and oxidative stress markers, although the relationship between these factors remains to be investigated. However, this would not only allow substantial improvements in risk stratification, but also provide essential data regarding the evolution of endothelial dysfunction in childhood obesity, especially during puberty when pro-inflammatory and pro-oxidative changes, with relative insulin resistance, occur. Therapeutic strategies such as lifestyle interventions in early childhood obesity appear all the more necessary, optimally including both exercise and diet because of their known effects on inflammatory and oxidative stress markers, potentially reversing endothelial dysfunction.

  20. 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

  1. 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.

  2. 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

  3. Cardiac Dysfunction in Association with Increased Inflammatory Markers in Primary Aldosteronism

    PubMed Central

    Lim, Jung Soo; Park, Sungha; Park, Sung Il; Oh, Young Taik; Choi, Eunhee; Kim, Jang Young

    2016-01-01

    Background Oxidative stress in primary aldosteronism (PA) is thought to worsen aldosterone-induced damage by activating proinflammatory processes. Therefore, we investigated whether inflammatory markers associated with oxidative stress is increased with negative impacts on heart function as evaluated by echocardiography in patients with PA. Methods Thirty-two subjects (mean age, 50.3±11.0 years; 14 males, 18 females) whose aldosterone-renin ratio was more than 30 among patients who visited Severance Hospital since 2010 were enrolled. Interleukin-1β (IL-1β), IL-6, IL-8, monocyte chemoattractant protein 1, tumor necrosis factor α (TNF-α), and matrix metalloproteinase 2 (MMP-2), and MMP-9 were measured. All patients underwent adrenal venous sampling with complete access to both adrenal veins. Results Only MMP-2 level was significantly higher in the aldosterone-producing adenoma (APA) group than in the bilateral adrenal hyperplasia (BAH). Patients with APA had significantly higher left ventricular (LV) mass and A velocity, compared to those with BAH. IL-1β was positively correlated with left atrial volume index. Both TNF-α and MMP-2 also had positive linear correlation with A velocity. Furthermore, MMP-9 showed a positive correlation with LV mass, whereas it was negatively correlated with LV end-systolic diameter. Conclusion These results suggest the possibility that some of inflammatory markers related to oxidative stress may be involved in developing diastolic dysfunction accompanied by LV hypertrophy in PA. Further investigations are needed to clarify the role of oxidative stress in the course of cardiac remodeling. PMID:27834080

  4. Rosuvastatin and vascular dysfunction markers in pulmonary arterial hypertension: a placebo-controlled study.

    PubMed

    Barreto, A C; Maeda, N Y; Soares, R P S; Cícero, C; Lopes, A A

    2008-08-01

    We investigated whether chronic rosuvastatin administration could improve the abnormalities of the circulating levels of vascular dysfunction markers in pulmonary arterial hypertension (PAH). Sixty patients, aged 13 to 60 years, with idiopathic (N = 14) or congenital heart disease-associated PAH (N = 46) were equally but randomly assigned to rosuvastatin treatment (10 mg a day, orally) or placebo for 6 months in a blind fashion. Plasma levels of P-selectin, tissue-plasminogen activator and its inhibitor as well as von Willebrand factor antigen were measured by enzyme-linked immunoassay before and after 1, 3, and 6 months of treatment. Baseline levels of biomarkers were elevated (68, 16, 45 and 46% increase relative to controls, for P-selectin, von Willebrand factor antigen, tissue-plasminogen activator and its inhibitor, respectively; P < 0.001). P-selectin values at baseline, 1, 3, and 6 months were 39.9 +/- 18.5, 37.6 +/- 14.6, 34.8 +/- 14.6, and 35.4 +/- 13.9 ng/mL, respectively, for the rosuvastatin group and 45.7 +/- 26.8, 48.0 +/- 26.9, 48.1 +/- 25.7, and 45.7 +/- 25.6 ng/mL for the placebo group. The P-selectin level was lower in the rosuvastatin group compared with placebo throughout treatment (P = 0.037, general linear model). A trend was observed towards a decrease in tissue-plasminogen activator in the statin group (16% reduction, P = 0.094), with no significant changes in the other markers. Since P-selectin is crucial in inflammation and thrombosis, its reduction by rosuvastatin is potentially relevant in the pathophysiological scenario of PAH.

  5. 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

    2013-10-08

    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.

  6. Markers of endothelial dysfunction and evaluation of vascular reactivity tests in Behçet disease.

    PubMed

    Ozuguz, Pinar; Karabulut, Ayse Anil; Tulmac, Murat; Kisa, Ucler; Kocak, Mukadder; Gunduz, Ozgur

    2014-11-01

    We assessed endothelial dysfunction (ED) in patients with Behcet disease (BD; n=40) and healthy controls (n=20). Serum lipid, homocysteine, asymmetric dimethylarginine (ADMA) and high-sensitivity C-reactive protein (hsCRP) levels, erythrocyte sedimentation rates (ESRs), and ultrasonographic flow-mediated dilatation (FMD) were measured. Mean hsCRP, ESR, homocysteine, and ADMA were significantly higher in the BD group (P<.001 for all). Patients with active BD had higher serum levels of hsCRP, homocysteine, and ESR compared with those in remission (P<.001, P<.001, and P=.005, respectively). Flow-mediated dilatation was significantly lower in patients with BD than in controls (P=.001). Flow-mediated dilatation correlated negatively with BD duration and serum ADMA levels (P<.001, r=-.745 and P<.001, r=-.682); a positive correlation was seen between serum ADMA levels and BD duration (P<.001, r=.552). Only stepwise multivariate regression analysis revealed BD duration to have a significant effect on FMD. Flow-mediated dilatation, in conjunction with markers of inflammation, may evaluate ED in patients with BD.

  7. Prognostic factors in neuroendocrine carcinoma: biological markers are more useful than histomorphological markers

    PubMed Central

    Freis, Patricia; Graillot, Emmanuelle; Rousset, Pascal; Hervieu, Valérie; Chardon, Laurence; Lombard-Bohas, Catherine; Walter, Thomas

    2017-01-01

    Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are a very aggressive type of cancer, for which prognostic factors are lacking. We analysed clinical and histomorphological prognostic markers of overall survival (OS), completed with a record of biological and haematological data of patients diagnosed between December 2002 and December 2015. The median OS was 16 months (95% CI 13.9–18.1). After univariate analysis, performance status (PS) ≥ 2 and stage IV were associated with a worse outcome (9 months and 14 months, respectively), as well as patients with lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) levels ≥ 2 ULN (9 months and 8 months, respectively). After multivariate analysis, LDH and AST levels were the only factors that remained significantly associated with better survival: HR 0.36 (p = 0.04) and 0.31 (p = 0.03), respectively. When patients had elevated LDH and AST levels, OS was 20 months, when they had high LDH or AST levels, 13 months and 8 months in the group with low LDH and AST levels (p < 0.001). Therefore, biological data appeared to be more relevant prognostic factors than usual factors described in other studies (PS, stage, and Ki-67). Considering LDH and AST levels at diagnosis could help physicians to predict survival and to stratify patients for clinical trials. PMID:28074897

  8. Biological ageing and frailty markers in breast cancer patients

    PubMed Central

    Hatse, Sigrid; Laenen, Annouschka; Kenis, Cindy; Swerts, Evalien; Neven, Patrick; Smeets, Ann; Schöffski, Patrick; Wildiers, Hans

    2015-01-01

    Older cancer patients are a highly heterogeneous population in terms of global health and physiological reserves, and it is often difficult to determine the best treatment. Moreover, clinical tools currently used to assess global health require dedicated time and lack a standardized end score. Circulating markers of biological age and/or fitness could complement or partially substitute the existing screening tools. In this study we explored the relationship of potential ageing/frailty biomarkers with age and clinical frailty. On a population of 82 young and 162 older non-metastatic breast cancer patients, we measured mean leukocyte telomere length and plasma levels of interleukin-6 (IL-6), regulated upon activation, normal T cell expressed and secreted (RANTES), monocyte chemotactic protein 1 (MCP-1), insulin-like growth factor 1 (IGF-1). We also developed a new tool to summarize clinical frailty, designated Leuven Oncogeriatric Frailty Score (LOFS), by integrating GA results in a single, semi-continuous score. LOFS' median score was 8, on a scale from 0=frail to 10=fit. IL-6 levels were associated with chronological age in both groups and with clinical frailty in older breast cancer patients, whereas telomere length, IGF-1 and MCP-1 only correlated with age. Plasma IL-6 should be further explored as frailty biomarker in cancer patients. PMID:25989735

  9. Biologic markers of pain in the vulnerable infant.

    PubMed

    Goldman, Ran D; Koren, Gideon

    2002-09-01

    Detecting and quantifying pain in infants and young children is a complex task because young children cannot communicate this subjective phenomenon. In the 1950s, it was postulated that there might be "wound hormones" produced in injured tissues that activated the pituitary-adrenal axis. Research in adults demonstrated that plasma levels of different hormones, including corticosteroids, cathecholamines, growth hormone, and insulin, changed in response to emotionally and physically stressful stimuli. Stress response is the term given to those hormonal and metabolic changes that follow injury or trauma, but the debate as to whether increased stress response is a sign of pain or whether decreased stress response is a sign of diminished pain has not been resolved yet. Following the study of systemic response to surgery, the ability of anesthetic agents to substantially attenuate intraoperative and postoperative stress response has been reported. In newborns, a strong correlation between preoperative stress and postoperative complication rate was found. The full extent of the vulnerable infant's pain is still poorly understood, but further research of known biologic markers and newly discovered ones could promote our understanding of the pain response and increase our ability to prevent undesirable outcome.

  10. BNP and ANP as diagnostic and predictive markers in heart failure with left ventricular systolic dysfunction.

    PubMed

    Falcão, Luiz Menezes; Pinto, Fausto; Ravara, Luciano; van Zwieten, Peter Adriaan

    2004-09-01

    The prevalence of chronic heart failure (CHF) with systolic dysfunction is increasing. Plasma natriuretic peptides have been envisaged as diagnostic and predictive markers. To investigate the relationship between the levels of B-type natriuretic peptide (BNP) and A-type natriuretic peptide (ANP) and the clinical and functional parameters of CHF in outpatients with CHF at baseline, compared with normal healthy controls; to find out the differences in a randomised controlled trial between patients treated with an angiotensin-converting enzyme (ACE) inhibitor, captopril, or an angiotensin receptor blocker (ARB), irbesartan. These differences were assessed throughout the six-month treatment period and at the sixth month. Plasma BNP (pmol/L) and ANP (pmol/L) were determined in 68 hypertensive patients with dilated cardiomyopathy, NYHA class III-IV and ejection fraction (EF) < or = 40%, and in 26 normal controls. Statistical analysis for BNP and ANP was done by Students t-test. The patient group was randomly subdivided into two subgroups of 34 patients, each treated with either an ARB, irbesartan, or an ACE inhibitor (ACE-I), captopril. BNP and ANP were measured in both subsamples and correlated with clinical, functional and neurohormonal parameters throughout a follow-up period of six months and at the sixth month. The mean EF in the patient sample was 33.43+/-6.52% and in the controls was 61.96 +/-3.53% (p=0.000). The mean BNP (pmol/L) in patients was 44.78+/-54.36 and in the controls was 7.12+/-8.28 (p=0.000) and the mean ANP (pmol/L) was 30.32+/-25.97 in patients and 11.18+/-7.92 in controls (p=0.000). A statistically significant difference was found between patients and healthy controls. Significant correlations were found between natriuretic peptides and EF. Between the baseline phase and the sixth month, BNP and ANP decreased significantly in the ARB group. At the sixth month, both BNP and ANP were lower in the ARB group. Evidence of clinical benefit was found

  11. The effect of high altitude on endothelial and vascular dysfunction markers in preeclamptic patients.

    PubMed

    Bashir, S O; Suekit, H; Elkarib, A O; Dafaalla, M A; Abd Elrouf, M B; Morsy, M D; Eskandar, M

    2015-12-01

    Placental hypoxia, a major component of the pathophysiology of preeclampsia, is associated with various maternal vascular and endothelial dysfunctions. The higher incidence of preeclampsia at high altitude remains incompletely explained. The aim of the present study was to investigate the effect of high altitude on some endothelial and vascular dysfunction markers in normal and preeclamptic pregnancies. Eighty pregnant women (Paras 2-4) were enrolled in this study, which included four groups (each n = 20): normal pregnancies at low altitude (NL), normal pregnancies at high altitude (NH), preeclamptic pregnancies at low altitude (PL), and preeclamptic pregnancies at high altitude (PH). In normal pregnancies at high altitude serum ET-1, plasma TXA2, and serum TNF-α levels increased significantly with a significant reduction in plasma PGI2 (66.81 ± 7.36, 122.86 ± 13.37, 102.23 ± 13.31, 191.57 ± 19.68, respectively) compared with the NL group (48.92 ± 4.58, 89.03 ± 10.67, 69.86 ± 7.97, 238.01 ± 24.55, respectively). In preeclampsia at low altitude serum ET-1, plasma TXA2, and serum TNF-α levels increased significantly with a significant reduction in plasma PGI2 (88.39 ± 9.54, 162.73 ± 15.92, 142.39 ± 15.37, 149.155 ± 15.66, respectively) compared with both NL and NH groups. High altitude significantly augmented these changes in preeclamptic patients (117.75 ± 12.96, 211.01 ± 22.69, 196.86 ± 17.64, 111.92 ± 10.74) compared with PL, NH and NL groups. In conclusion hypoxia at high altitude aggravated the disturbances in the levels of ET-1, TXA2, PGI2 and TNF-α associated with preeclampsia. This may contribute to the higher risk of preeclampsia at high altitude.

  12. Bench-to-bedside review: Critical illness-associated cognitive dysfunction – mechanisms, markers, and emerging therapeutics

    PubMed Central

    Milbrandt, Eric B; Angus, Derek C

    2006-01-01

    Cognitive dysfunction is common in critically ill patients, not only during the acute illness but also long after its resolution. A large number of pathophysiologic mechanisms are thought to underlie critical illness-associated cognitive dysfunction, including neuro-transmitter abnormalities and occult diffuse brain injury. Markers that could be used to evaluate the influence of specific mechanisms in individual patients include serum anticholinergic activity, certain brain proteins, and tissue sodium concentration determination via high-resolution three-dimensional magnetic resonance imaging. Although recent therapeutic advances in this area are exciting, they are still too immature to influence patient care. Additional research is needed if we are to understand better the relative contributions of specific mechanisms to the development of critical illness-associated cognitive dysfunction and to determine whether these mechanisms might be amenable to treatment or prevention. PMID:17118217

  13. [Effects of mexidol and sulodexide on the level of specific markers of endothelial dysfunction in animals with experimental diabetes mellitus].

    PubMed

    Tiurenkov, I N; Voronkov, A V; Slietsans, A A; Snigur, G L

    2012-01-01

    Streptozotocin-induced diabetes leads to the development of endothelial dysfunction, as evidenced by decreased expression of endothelial nitric oxide synthase (eNOS) and increased expression of endothelin-1 as specific markers of endothelial disorders. All test substances showed endotelioprotective activity by increasing the concentration of eNOS and reducing the level of endothelin-1. With respect to the degree of impact on the eNOS and endothelin-1 levels, the compounds studied can be rated as follows: sulodexide > meksidol.

  14. Relationships between markers of vascular dysfunction and neurodevelopmental outcomes in perinatally HIV-infected youth.

    PubMed

    Kapetanovic, Suad; Leister, Erin; Nichols, Sharon; Miller, Tracie; Tassiopoulos, Katherine; Hazra, Rohan; Gelbard, Harris A; Malee, Kathleen M; Kammerer, Betsy; Mendez, Armando J; Williams, Paige L

    2010-06-19

    To examine the relationship between markers of vascular dysfunction and neurodevelopmental status in pediatric HIV disease. A cross-sectional design within a prospective, 15-site cohort study conducted in the United States. Nine vascular biomarkers were examined in 89 HIV-infected children: soluble P-selectin/sCD62P, fibrinogen, adiponectin, monocyte chemoattractant protein-1/CCL-2, interleukin-6, C-reactive protein, soluble vascular cell adhesion molecule-1/sCD106, sE-selectin/sCD62E, and soluble intercellular adhesion molecule-1/sCD54. The Wechsler Intelligence Scale for Children-Fourth edition (WISC-IV) was administered yielding indices for verbal comprehension, perceptual reasoning, working memory and processing speed, and overall composite Full-Scale IQ score. Linear regression models were used to evaluate neurodevelopmental status (measured by WISC-IV scores) as a function of each biomarker while adjusting for demographics, disease severity, and receipt of HAART. Biomarker levels were evaluated in quartiles to evaluate trends in WISC-IV responses. Among the 89 HIV-infected children (median age = 12 years), 56% were girls, 71% black, 16% Hispanic, and 43% had yearly household income below US $20,000. Log (soluble P-selectin) was significantly correlated with all WISC-IV scores; adjusted slopes showed 6-11-point average decrease in scores for each one log unit increase in soluble P-selectin. Final linear regression models for log (fibrinogen) adjusted for sociodemographic and disease characteristics also indicated a negative correlation with all WISC-IV scores (13-30-point decrease for each one log unit increase in fibrinogen); these decreases were significant in the verbal comprehension, perceptual reasoning, and Full-Scale IQ scores. Proinflammatory microvascular and immunologic mechanisms may be involved in neurodevelopmental impairment in children with perinatally acquired HIV disease.

  15. Biological markers in the diagnosis of tuberculous pleural effusion.

    PubMed

    Mollo, Bastien; Jouveshomme, Stéphane; Philippart, François; Pilmis, Benoît

    2017-02-01

    Tuberculosis is one of the main etiologies to evoke in the context of lymphocyte pleurisy. However, diagnosis is difficult and is based on mycobacteriology that is not enough sensitive and time-consuming, or on histology that requires invasive biopsy gesture. This literature review, carried out from Medline, summarizes the main meta-analyzes, reviews, and originator publications in English on biomarkers, classic and more innovative, studied for the diagnosis of tuberculous pleurisy. Among the immuno-biochemical markers, interferon-γ (IFN-γ), isoenzyme of adenosine deaminase 2 (ADA2) and total adenosine deaminase (ADA) seem the most relevant with respective sensitivities of 89% (87-91), 97.2% (95 to 98.7) and 92% (90-93) and specificities of 97% (96-98), 94.2% (91.8 to 96) and 90% (89-91). About molecular biology, PCR Xpert MTB/RIF has a sensitivity of 46.4% (26.3 to 67.8), which is much higher than the direct examination, while providing rapid diagnostic confirmation, with a specificity of 99.1% (95.2 to 99.8), and a resistance to rifampicin screening. The release assay of interferon-γ (IGRA) is less effective with a sensitivity of 75% (69-81) and a specificity of 82% (75-88) in blood and a sensitivity of 80% (74-86%) and a specificity of 72% (64-80) in pleural fluid. Other biomarkers (including several cytokines) might have an interest but are still under evaluation. These innovative methods, particularly the determination of ADA and the use of PCR Xpert MTB/RIF should find their place in the diagnostic algorithm of TB pleurisy.

  16. 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

  17. Endophenotypes and biological markers of schizophrenia: from biological signs of illness to novel treatment targets.

    PubMed

    Ferrarelli, Fabio

    2013-01-01

    Schizophrenia is a chronic, often disabling mental illness with a lifetime prevalence of ~1% worldwide, and 2-to-3 times higher mortality rates are reported in schizophrenia patients compared to the general population. Although research has been increasingly focusing on identifying novel diagnostic and treatment resources for this illness, the diagnosis of schizophrenia is still based on clinical criteria, which are subjectively assessed and tend to vary across the course of the illness. Endophenotypes are commonly described as molecular, neuropsychological, neuro-imaging, and electrophysiological parameters that are closely associated to the genetic underpinnings of a specific disorder. Putative endophenotypes for psychiatric disorders should: 1) be associated with a specific illness in the population, 2) be heritable, 3) be present regardless of the patients clinical status, 4) co-segregate with the illness within families, and 5) be detected in non-affected family members of psychiatric patients at higher rates than in the general population. Whenever a genetic association is not present, or has not been investigated, the term biomarker is usually preferred. Endophenotypes and biomarkers are stable over time and are largely symptom independent, thus enabling an objective diagnosis of schizophrenia. Furthermore, these measures could be utilized to assess the risk of developing this disorder, and to identify novel pharmacological targets for its treatment. In this article I will present some of the most promising endophenotypes and biological markers of schizophrenia. For each of them, I will briefly describe abnormal findings in schizophrenia patients and, whenever available, in their first-degree relatives. I will then review the ability of each of these measures to identify individuals with schizophrenia (diagnostic value) and to assess the risk for schizophrenia (predictive value). Finally, I will discuss how some of these endophenotypes and biological markers

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

    MedlinePlus

    ... U V W X Y Z Study Finds Association Between Biological Marker and Susceptibility to the Common ... published in the Journal of the American Medical Association . Funded in part by NCCAM, the study is ...

  19. 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.

  20. 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

  1. Interhemispheric electroencephalographic coherence as a biological marker in alcoholism.

    PubMed

    Michael, A; Mirza, K A; Mukundan, C R; Channabasavanna, S M

    1993-03-01

    Electroencephalographic coherence scores in 21 teetotaler first-degree relatives of alcoholics, 27 subjects with alcohol dependence and 21 healthy subjects without a family history of alcohol abuse were compared. The relatives had significantly higher coherence scores in the frontal and parietal leads than the alcoholics and in the frontal and centroparietal leads than in the healthy subjects. This might represent a trait marker of resilience in subjects at high risk for the development of alcoholism.

  2. Correlation of serum liver fibrosis markers with severity of liver dysfunction in liver cirrhosis: a retrospective cross-sectional study

    PubMed Central

    Zhu, Cuihong; Qi, Xingshun; Li, Hongyu; Peng, Ying; Dai, Junna; Chen, Jiang; Xia, Chunlian; Hou, Yue; Zhang, Wenwen; Guo, Xiaozhong

    2015-01-01

    Hyaluronic acid (HA), laminin (LN), amino-terminal pro-peptide of type III pro-collagen (PIIINP), and collagen IV (CIV) are four major serum markers of liver fibrosis. This retrospective cross-sectional study aimed to evaluate the correlations of the four serum markers with the severity of liver dysfunction in cirrhotic patients. Between January 2013 and June 2014, a total of 228 patients with a clinical diagnosis with liver cirrhosis and without malignancy underwent the tests of HA, LN, PIIINP, and CIV levels. Laboratory data were collected. Child-Pugh and model for the end-stage of liver diseases (MELD) scores were calculated. Of them, 32%, 40%, and 18% had Child-Pugh class A, B, and C, respectively. MELD score was 7.58±0.50. HA (coefficient r: 0.1612, P=0.0203), LN (coefficient r: 0.2445, P=0.0004), and CIV (coefficient r: 0.2361, P=0.0006) levels significantly correlated with Child-Pugh score, but not PIIINP level. Additionally, LN (coefficient r: 0.2588, P=0.0002) and CIV (coefficient r: 0.1795, P=0.0108) levels significantly correlated with MELD score, but not HA or PIIINP level. In conclusions, HA, LN, and CIV levels might be positively associated with the severity of liver dysfunction in cirrhotic patients. However, given a relatively weak correlation between them, our findings should be cautiously interpreted and further validated. PMID:26131195

  3. Urinary enzymes and low molecular weight proteins as markers of tubular dysfunction.

    PubMed

    Jung, K

    1994-11-01

    Reference intervals of different tubular markers, that is, low molecular weight proteins and urinary enzymes, show divergent data and wide ranges. The problems in establishing reference intervals for the tubular markers are caused by the necessarily different analytical methods. Also, the general rules of determining reference limits as well as the numerous physiological variables influencing tubular function are often not sufficiently taken into consideration. Compared to blood components, urinary tubular markers show a wide variability of values. This is due to the fact that the excretion of enzymes and proteins into urine represents an excretion into an open system. The influences of variables like age, sex, physical exercise, different urine flow rates, and biorhythms are immediately reflected by changed excretion rates of tubular markers. The problems occurring when the second morning urine sample is being used as a "standardized" collection method and the basis to characterize tubular function by analyte/creatinine ratios are discussed in this paper.

  4. Preoperative liver dysfunction influences blood product administration and alterations in circulating haemostatic markers following ventricular assist device implantation

    PubMed Central

    Woolley, Joshua R.; Kormos, Robert L.; Teuteberg, Jeffrey J.; Bermudez, Christian A.; Bhama, Jay K.; Lockard, Kathleen L.; Kunz, Nicole M.; Wagner, William R.

    2015-01-01

    OBJECTIVES Preoperative liver dysfunction may influence haemostasis following ventricular assist device (VAD) implantation. The Model for End-stage Liver Disease (MELD) score was assessed as a predictor of bleeding and levels of haemostatic markers in patients with currently utilized VADs. METHODS Sixty-three patients (31 HeartMate II, 15 HeartWare, 17 Thoratec paracorporeal ventricular assist device) implanted 2001–11 were analysed for preoperative liver dysfunction (MELD) and blood product administration. Of these patients, 21 had additional blood drawn to measure haemostatic marker levels. Cohorts were defined based on high (≥18.0, n = 7) and low (<18.0, n = 14) preoperative MELD scores. RESULTS MELD score was positively correlated with postoperative administration of red blood cell (RBC), platelet, plasma and total blood product units (TBPU) , as well as chest tube drainage and cardiopulmonary bypass time. Age and MELD were preoperative predictors of TBPU by multivariate analysis. The high-MELD cohort had higher administration of TBPU, RBC and platelet units and chest tube drainage postimplant. Similarly, patients who experienced at least one bleeding adverse event were more likely to have had a high preoperative MELD. The high-MELD group exhibited different temporal trends in F1 + 2 levels and platelet counts to postoperative day (POD) 55. D-dimer levels in high-MELD patients became elevated versus those for low-MELD patients on POD 55. CONCLUSIONS Preoperative MELD score predicts postoperative bleeding in contemporary VADs. Preoperative liver dysfunction may also alter postoperative subclinical haemostasis through different temporal trends of thrombin generation and platelet counts, as well as protracted fibrinolysis. PMID:24810756

  5. N-terminal proBNP--marker of cardiac dysfunction, fluid overload, or malnutrition in hemodialysis patients?

    PubMed

    Booth, John; Pinney, Jennifer; Davenport, Andrew

    2010-06-01

    N-terminal probrain type natriuretic peptide (NTproBNP) has been proven to be a valuable biomarker for predicting cardiac events and mortality in the hemodialysis population. However recent reports have suggested that NTproBNP is a marker of volume overload rather than one of cardiac dysfunction. Therefore this study investigated the effect of fluid volume status on NTproBNP. Volume status was determined pre- and postdialysis in 72 stable hemodialysis outpatients by multifrequency bioimpedance, and the relationship to NTproBNP values was examined. The mean and median NTproBNP values were 931.9 +/- 230 and 242 (90 to 688) pmol/L, respectively. On simple correlation, NTproBNP was associated with markers of volume overload and cardiac dysfunction. However, on logistical regression analysis, the strongest association was with the predialysis ratio of extracellular water/total body water (beta 26.6, F29.6, P = 0.000), followed by postdialysis mean arterial blood pressure (beta 0.14, F17.1, P = 0.000), dialysate calcium concentration (beta -1.19, F14.1, P = 0.002), and change in extracellular fluid volume with dialysis (beta 0.27, F7.4, P = 0.009) In this study, NTproBNP was not associated with cardiac dysfunction as assessed by transthoracic echo or nuclear medicine scintigraphy but was dependent on factors associated with volume overload. However, because bioimpedance results can also be affected by malnutrition with loss of cell mass, NTproBNP may be elevated not only in patients with volume overload, but also those with malnutrition.

  6. 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

  7. Minimal breast cancer: evaluation of histology and biological marker expression

    PubMed Central

    Dublin, E A; Millis, R R; Smith, P; Bobrow, L G

    1999-01-01

    Ninety-eight minimal breast cancers (MBCs) diagnosed between 1975 and 1990, and all originally considered to be invasive were found, on review, to form three groups: (a) 28 predominantly invasive carcinomas ≤10 mm (‘predominant invasive’); (b) 48 predominantly ductal carcinoma in situ (DCIS) lesions with definite foci of invasion each ≤10 mm (‘predominant DCIS’); and (c) 22 DCIS without evidence of invasion (‘pure DCIS’). Tumour histology and immunohistochemical expression of Ki-67, c-erbB2, p53, oestrogen receptor (ER), progesterone receptor (PR), and Bcl-2 were compared. The major finding was the contrasting features in the two invasive groups, with significant differences in their extent of invasion (P < 0.0001), tumour grade (P = 0.03), DCIS type (P = 0.008) and in marker expression. In the predominant invasive group, the infiltrative component was usually greater than 5 mm, low-grade and associated with well-differentiated DCIS. Expression of Ki-67, c-erbB2 and p53 was generally low, and that of ER, PR and Bcl-2 high. The predominant DCIS group in contrast had a much smaller, commonly high-grade, invasive component, usually with poorly differentiated DCIS and the reverse pattern of marker expression. Although not significant, survival of patients in the predominant invasive group was slightly better. These findings suggest that invasive MBCs should perhaps be treated as separate entities, in order to aid more appropriate selection of treatment. © 1999 Cancer Research Campaign PMID:10408407

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

    USDA-ARS?s Scientific Manuscript database

    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...

  9. Serum Markers of Endothelial Dysfunction and Inflammation Increase in Hypertension with Prediabetes Mellitus.

    PubMed

    Huang, Zhouqing; Chen, Chen; Li, Sheng; Kong, Fanqi; Shan, Peiren; Huang, Weijian

    2016-06-01

    The aim of this study was to examine endothelial dysfunction and inflammation in hypertension and prediabetes by studying adhesion molecules and inflammatory factors. This study included 133 outpatients. Participants were categorized into three groups based on the presence or absence of hypertension and prediabetes: control subjects without prediabetes and hypertension (N group, n = 39); patients with hypertension only (H group, n = 34); and patients with hypertension and prediabetes (HD group, n = 60). Hypertension was diagnosed according to JNC7 criteria. Prediabetes was defined according to 2010 American Diabetes Association criteria. Plasma was isolated from overnight fasting blood samples for enzyme-linked immunosorbent assay (ELISA) analysis of concentrations of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), P-selectin, and interleukin-6 (IL-6) as indicators of endothelial function and inflammation. We found that the H and HD groups showed significantly higher levels of all four biomarkers compared with the N group (all p < 0.01). The HD group also showed significantly higher levels of ICAM-1 (p = 0.042) and TNF-α (p < 0.01) compared with the H group; no significant differences in P-selectin (p = 0.59) and IL-6 (p = 0.70) levels were observed among these groups. Prediabetes and hypertension induce endothelial dysfunction and inflammation by elevating levels of soluble adhesion molecules and inflammatory cytokines. The comorbidity of these diseases may exacerbate inflammation and endothelial dysfunction by enhancing the expression of ICAM-1 and TNF-α.

  10. 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

  11. Prevalence, prospective risk markers, and prognosis associated with the presence of left ventricular diastolic dysfunction in young adults: the coronary artery risk development in young adults study.

    PubMed

    Desai, Chintan S; Colangelo, Laura A; Liu, Kiang; Jacobs, David R; Cook, Nakela L; Lloyd-Jones, Donald M; Ogunyankin, Kofo O

    2013-01-01

    The authors sought to determine the prevalence, prospective risk markers, and prognosis associated with diastolic dysfunction in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. The CARDIA Study cohort includes approximately equal proportions of white and black men and women. The authors collected data on risk markers at year 0 (1985-1986), and echocardiography was done at year 5 when the participants were 23-35 years of age. Participants were followed for 20 years (through 2010) for a composite endpoint of all-cause mortality, myocardial infarction, heart failure, and stroke. Diastolic function was defined according to a validated hierarchical classification algorithm. In the 2,952 participants included in the primary analysis, severe diastolic dysfunction was present in 1.1% and abnormal relaxation was present in 9.3%. Systolic blood pressure at year 0 was associated with both severe diastolic dysfunction and abnormal relaxation 5 years later, whereas exercise capacity and pulmonary function abnormalities were associated only with abnormal relaxation 5 years later. After multivariate adjustment, the hazard ratios for the composite endpoint in participants with severe diastolic dysfunction and abnormal relaxation were 4.3 (95% confidence interval: 2.0, 9.3) and 1.6 (95% confidence interval: 1.1, 2.5), respectively. Diastolic dysfunction in young adults is associated with increased morbidity and mortality, and the identification of prospective risk markers associated with diastolic dysfunction could allow for targeted primary prevention efforts.

  12. Erectile Dysfunction Severity as a Risk Marker for Cardiovascular Disease Hospitalisation and All-Cause Mortality: A Prospective Cohort Study

    PubMed Central

    Banks, Emily; Joshy, Grace; Abhayaratna, Walter P.; Kritharides, Leonard; Macdonald, Peter S.; Korda, Rosemary J.; Chalmers, John P.

    2013-01-01

    Background Erectile dysfunction is an emerging risk marker for future cardiovascular disease (CVD) events; however, evidence on dose response and specific CVD outcomes is limited. This study investigates the relationship between severity of erectile dysfunction and specific CVD outcomes. Methods and Findings We conducted a prospective population-based Australian study (the 45 and Up Study) linking questionnaire data from 2006–2009 with hospitalisation and death data to 30 June and 31 Dec 2010 respectively for 95,038 men aged ≥45 y. Cox proportional hazards models were used to examine the relationship of reported severity of erectile dysfunction to all-cause mortality and first CVD-related hospitalisation since baseline in men with and without previous CVD, adjusting for age, smoking, alcohol consumption, marital status, income, education, physical activity, body mass index, diabetes, and hypertension and/or hypercholesterolaemia treatment. There were 7,855 incident admissions for CVD and 2,304 deaths during follow-up (mean time from recruitment, 2.2 y for CVD admission and 2.8 y for mortality). Risks of CVD and death increased steadily with severity of erectile dysfunction. Among men without previous CVD, those with severe versus no erectile dysfunction had significantly increased risks of ischaemic heart disease (adjusted relative risk [RR] = 1.60, 95% CI 1.31–1.95), heart failure (8.00, 2.64–24.2), peripheral vascular disease (1.92, 1.12–3.29), “other” CVD (1.26, 1.05–1.51), all CVD combined (1.35, 1.19–1.53), and all-cause mortality (1.93, 1.52–2.44). For men with previous CVD, corresponding RRs (95% CI) were 1.70 (1.46–1.98), 4.40 (2.64–7.33), 2.46 (1.63–3.70), 1.40 (1.21–1.63), 1.64 (1.48–1.81), and 2.37 (1.87–3.01), respectively. Among men without previous CVD, RRs of more specific CVDs increased significantly with severe versus no erectile dysfunction, including acute myocardial infarction (1.66, 1.22–2

  13. Impaired heart rate variability as a marker of cardiovascular autonomic dysfunction in multiple sclerosis.

    PubMed

    Tombul, Temel; Anlar, Omer; Tuncer, Mustafa; Huseyinoglu, Nergis; Eryonucu, Beyhan

    2011-06-01

    Multiple sclerosis (MS) can cause alterations in autonomic cardiovascular functions. We aimed to investigate the correlation of disease activity and disability with heart rate variability (HRV) of cardiovascular autonomic dysfunction (CAD) demonstrated by 24-h Holter monitorization. Thirty-four patients with clinically active relapsing-remitting MS, age 33.8 +/- 7.6 years, were studied. Twenty healthy volunteers served as controls. The time domain long-term HRV parameters were recorded by a digicorder recorder calculated by ambulatory electrocardiograms. Variabilities in time domain were lower in the MS patients: SDNN (standard deviation of all R-R intervals, p = 0,019), SDANN (standard deviation of the averages of R-R intervals in all 5-minute segments of the entire recordings, p = 0,040), RMSSD (the square root of the mean of the sum of the squares of differences between adjacent R-R intervals, p = 0,026), HRVM (mean of the SDNN in all the 5-minute intervals, p = 0,029), HRVSD (standard deviation of the SDNN in all the 5-minute, p = 0,043). These results suggest that MS causes CAD manifesting as long-term HRV abnormalities. This illness seems to cause a dysfunction in parasympathetic cardiovascular tone. Depressed HRV parameters are independent from the clinicalfindings, but the illness progression partially seems to provoke a decrease in such parameters.

  14. Association of family history of type 2 diabetes mellitus with markers of endothelial dysfunction in South Indian population.

    PubMed

    Dhananjayan, R; Malati, T; Brindha, G; Kutala, Vijay Kumar

    2013-04-01

    Studies indicate that risk for type 2 diabetes mellitus (T2D) or cardiovascular disease is detectable in childhood, though these disorders may not emerge until adulthood. This study was aimed to assess the markers of endothelial dysfunction in patients with the family history of T2D from South Indian population. A total of 450 subjects were included in the study comprising Group I (n = 200) of T2D, Group II (n = 200) of age- and sex-matched healthy controls, Group III (n = 25) of children of T2D patients and Group IV (n = 25) of children of healthy controls. Results showed that intimal medial thickening (IMT) was significantly higher in T2D patients, compared with control subjects with no family history of diabetes. The fasting plasma glucose, glycated hemoglobin, serum total cholesterol, triglyceride, LDL-cholesterol, apolipoprotein B (ApoB) and high-sensitive C-reactive protein (hsCRP) levels were significantly increased, whereas HDL-cholesterol and serum nitrite levels were significantly decreased in T2D patients. However, children of T2D patients who were not diabetic did not show significant increase in the IMT, as compared to those of healthy controls. In conclusion, the present study demonstrate that IMT was significantly higher in the T2D patients and increased with age and family history. The increased levels of lipids, hsCRP, IMT and decreased nitrite levels might contribute to the risk of endothelial dysfunction in patients with T2D. However, further studies are warranted with other biomarkers of endothelial dysfunction in T2D patients with increased sample size.

  15. Biological Markers of Drug Use in the Club Setting*

    PubMed Central

    Miller, Brenda A.; Furr-Holden, Debra; Johnson, Mark B.; Holder, Harold; Voas, Robert; Keagy, Carolyn

    2009-01-01

    Objective: The prevalence of drug and alcohol use among patrons of clubs featuring electronic music dance events was determined by using biological assays at entrance and exit. Method: Using a portal methodology that randomly selects groups of patrons on arrival at clubs, oral assays for determining level and type of drug use and level of alcohol use were obtained anonymously. Patrons provided self-reported data on their personal characteristics. A total of 362 patrons were interviewed at entrance and provided oral assay data, and 277 provided data at both entrance and exit. Results: Overall, one quarter of all patrons surveyed at entrance were positive for some type of drug use. Based on our exit sample, one quarter of the sample was positive at exit. Individual drugs most prevalent at entrance or exit included cocaine, marijuana, and amphetamines/stimulants. Only the amphetamine/stimulant category increased significantly from entrance to exit. Drug-using patrons arrive at the club already using drugs; few patrons arrive with no drug use and leave with detectable levels of drug use. Clubs vary widely in drug-user prevalence at entrance and exit, suggesting that both events and club policies and practices may attract different types of patrons. Approximately one half of the total entrance sample arrived with detectable alcohol use, and nearly one fifth arrived with an estimated blood alcohol concentration of .08 or greater. Based on our exit sample data, one third of patrons were intoxicated, and slightly less than one fifth were using both drugs and alcohol at exit. Clubs attract a wide array of emerging adults, with both genders and all ethnicities well represented. Clubs also attract emerging adults who are not in college and who are working full time. Conclusions: At clubs featuring electronic music dance events, drug use and/or high levels of alcohol use were detected using biological assays from patrons at entrance and exit from the clubs. Thus, these clubs

  16. [Hair: a powerful biological marker for exposure to xenobiotics].

    PubMed

    Goullé, J P; Kintz, P

    1997-01-01

    Human hair analysis is now recognized for evaluating someone exposure to xenobiotics: drugs of abuse, pharmaceuticals and polluants. This paper describes analytical methods than can be used by biologists. For drugs of abuse after decontamination, hydrolysis of hair, selective extraction and derivatization, determinations are performed by gas chromatography-mass spectrometry (GC/MS). Calibration uses deuterated standards. The cut-off value is 0.5 ng/mg for 6-monoacetylmorphine (heroin) and amphetamines and a benzoylecgonine/cocaine ratio > 0.05 for cocaine. Measurement of metabolites from endogenous metabolism sign the exposure (6-monoacetylmorphine and morphine for heroin, benzoylecgonine for cocaine, delta 9-tetrahydrocannabinol carboxylic by-product for cannabis). For drugs, after selective extraction, determinations are performed by GC/MS or liquid chromatography coupled to a diode array detector. Main applications concern drug monitoring to complement blood determinations or when blood collection is missing, as evidence of hidden, illicit or criminal drug exposure. Finally it is a powerfull tool for clinical diagnosis especially when late biological investigations are performed.

  17. Markers of Endothelial Dysfunction, Coagulation and Tissue Fibrosis Independently Predict Venous Thromboembolism in HIV

    PubMed Central

    MUSSELWHITE, Laura W.; SHEIKH, Virginia; NORTON, Thomas D.; RUPERT, Adam; PORTER, Brian O.; PENZAK, Scott R.; SKINNER, Jeff; MICAN, JoAnn M.; HADIGAN, Colleen; SERETI, Irini

    2015-01-01

    Objective HIV infection is associated with coagulation abnormalities and significantly increased risk of venous thrombosis. It has been shown that higher plasma levels of coagulation and inflammatory biomarkers predicted mortality in HIV. We investigated the relationship between venous thrombosis and HIV-related characteristics, traditional risk factors of hypercoagulability and pre-event levels of biomarkers. Design A retrospective case-control study of 23 HIV-infected individuals who experienced an incident venous thromboembolic (VTE) event while enrolled in National Institutes of Health studies from 1995–2010 and 69 age and sex-matched HIV-infected individuals without known VTE. Methods Biomarkers of inflammation, endothelial dysfunction, coagulation, tissue fibrosis, and cytomegalovirus (CMV) reactivation were assessed by ELISA-based assays and PCR using plasma obtained prior to the event. Results VTE events were related to nadir CD4 count, lifetime history of multiple opportunistic infections, CMV disease, CMV viremia, immunological AIDS, active infection and provocation (i.e. recent hospitalization, surgery or trauma). VTE events were independently associated with increased plasma levels of P-selectin, P=0.002; D-dimer, P=0.01; and hyaluronic acid, P=0.009 in a multivariate analysis. No significant differences in antiretroviral or interleukin 2 exposures, plasma HIV viremia, or other traditional risk factors were observed. Conclusion Severe immunodeficiency, active infection and provocation are associated with venous thromboembolic disease in HIV. Biomarkers of endothelial dysfunction, coagulation and tissue fibrosis may help identify HIV-infected patients at elevated risk of VTE. PMID:21412059

  18. Cardiac dysfunction and ferritin as early markers of severity in pediatric sepsis.

    PubMed

    Tonial, Cristian T; Garcia, Pedro Celiny R; Schweitzer, Louise Cardoso; Costa, Caroline A D; Bruno, Francisco; Fiori, Humberto H; Einloft, Paulo R; Garcia, Ricardo Branco; Piva, Jefferson Pedro

    The aim of this study was to verify the association of echocardiogram, ferritin, C-reactive protein, and leukocyte count with unfavorable outcomes in pediatric sepsis. A prospective cohort study was carried out from March to December 2014, with pediatric critical care patients aged between 28 days and 18 years. Inclusion criteria were diagnosis of sepsis, need for mechanical ventilation for more than 48h, and vasoactive drugs. Serum levels of C-reactive protein, ferritin, and leukocyte count were collected on the first day (D0), 24h (D1), and 72h (D3) after recruitment. Patients underwent transthoracic echocardiography to determine the ejection fraction of the left ventricle on D1 and D3. The outcomes measured were length of hospital stay and in the pediatric intensive care unit, mechanical ventilation duration, free hours of VM, duration of use of inotropic agents, maximum inotropic score, and mortality. Twenty patients completed the study. Patients with elevated ferritin levels on D0 had also fewer ventilator-free hours (p=0.046) and higher maximum inotropic score (p=0.009). Patients with cardiac dysfunction by echocardiogram on D1 had longer hospital stay (p=0.047), pediatric intensive care unit stay (p=0.020), duration of mechanical ventilation (p=0.011), maximum inotropic score (p=0.001), and fewer ventilator-free hours (p=0.020). Cardiac dysfunction by echocardiography and serum ferritin value was significantly associated with unfavorable outcomes in pediatric patients with sepsis. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  19. Biological Markers for Pulpal Inflammation: A Systematic Review

    PubMed Central

    Galicia, Johnah C.; Peters, Ove A.

    2016-01-01

    Background and Objective Pulpitis is mainly caused by an opportunistic infection of the pulp space with commensal oral microorganisms. Depending on the state of inflammation, different treatment regimes are currently advocated. Predictable vital pulp therapy depends on accurate determination of the pulpal status that will allow repair to occur. The role of several players of the host response in pulpitis is well documented: cytokines, proteases, inflammatory mediators, growth factors, antimicrobial peptides and others contribute to pulpal defense mechanisms; these factors may serve as biomarkers that indicate the status of the pulp. Therefore, the aim of this systematic review was to evaluate the presence of biomarkers in pulpitis. Methods The electronic databases of MEDLINE, EMBASE, Scopus and other sources were searched for English and non-English articles published through February 2015. Two independent reviewers extracted information regarding study design, tissue or analyte used, outcome measures, results and conclusions for each article. The quality of the included studies was assessed using a modification of the Newcastle-Ottawa-Scale. Results and Conclusions From the initial 847 publications evaluated, a total of 57 articles were included in this review. In general, irreversible pulpitis was associated with different expression of various biomarkers compared to normal controls. These biomarkers were significantly expressed not only in pulp tissue, but also in gingival crevicular fluid that can be collected non-invasively, and in dentin fluid that can be analyzed without extirpating the entire pulpal tissue. Such data may then be used to accurately differentiate diseased from healthy pulp tissue. The interplay of pulpal biomarkers and their potential use for a more accurate and biologically based diagnostic tool in endodontics is envisaged. PMID:27898727

  20. Investigation of cerebral microbleeds in multiple sclerosis as a potential marker of blood-brain barrier dysfunction.

    PubMed

    Eisele, Philipp; Alonso, Angelika; Griebe, Martin; Szabo, Kristina; Hennerici, Michael G; Gass, Achim

    2016-05-01

    In multiple sclerosis (MS) lesions blood-brain-barrier (BBB) breakdown is a common phenomenon delineating the phase of focal inflammation in developing MS lesions. In other pathologies like cerebral amyloid angiopathy or arteriosclerotic cerebral small vessel disease permanent cerebral microbleeds (CMB) have been shown to be sensitive markers indicating BBB dysfunction. We were interested in the potential role of T(2)*-weighted MRI and CMBs as BBB integrity markers in MS. A large cohort of 189 MS patients (179 relapsing remitting MS and 10 secondary progressive MS) was investigated on a 3T MRI system with conventional and T(2)*-weighted gradient echo MRI (T(2)*w) sequences. T(2)*w images were analysed for CMBs by experienced raters. None of the MS patients showed a CMB. On T(2)*w MRI the prevalence of CMBs is not higher in MS patients than what is to be expected in young healthy people. In contrast to pathologies with structural vascular changes like small vessel disease or cerebral amyloid angiopathy, CMBs are not seen in MS where the immune reaction is causing a functional change in the BBB. Copyright © 2016. Published by Elsevier B.V.

  1. 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

  2. Increased RhoA/Rho-Kinase Activity and Markers of Endothelial Dysfunction in Young Adult Subjects with Metabolic Syndrome.

    PubMed

    Leguina-Ruzzi, Alberto; Pereira, Jaime; Pereira-Flores, Karla; Valderas, Juan P; Mezzano, Diego; Velarde, Victoria; Sáez, Claudia G

    2015-11-01

    Metabolic syndrome, a chronic condition associated with higher risk of cardiovascular diseases, is increasingly prevalent in young adults. Dyslipidemia, proinflammatory cytokines, endothelial dysfunction signs, and RhoA/Rho-kinase (ROCK) activation are considered risk factors of cardiovascular diseases. The occurrence of these factors in young patients with metabolic syndrome but without type 2 diabetes or hypertension has not been fully studied. The objective of this study was to evaluate young subjects with enlarged waist circumference and dyslipidemia but without type 2 diabetes or hypertension,for markers associated with a higher risk of cardiovascular diseases. Thirty-two male patients aged 31 ± 1.3 years diagnosed with metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III guide for enlarged waist circumference, elevated triglycerides, and low HDL levels, but with blood pressure and fasting glucose within normal ranges, were evaluated for RhoA/ROCK activity in leukocytes, serum fatty acid methyl esters profile, proinflammatory cytokines, and oxidative stress markers in addition to thrombin generation and biochemical analysis. Age- and gender-matched healthy subjects were equivalently evaluated. Patients showed higher RhoA/ROCK activity, elevated levels of interleukin-6, soluble CD40L, monocyte chemoattractant protein, and high-sensitivity C-reactive protein (P < 0.001) as well as parameters of endogenous thrombin generation potential (P < 0.05) compared with healthy subjects. Increased thiobarbituric acid reactive substances, advanced oxidation protein product, and insulin levels and low nitric oxide biodisponibility (P < 0.001) were also found in patients as compared with controls. Palmitic acid was one of the saturated fatty acids found to be significantly elevated in patients compared with control subjects (P = 0.0087). Increased markers of cardiovascular risk are already present in young

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

    USDA-ARS?s Scientific Manuscript database

    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...

  4. 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…

  5. 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…

  6. [Definitions destruction of endothelial cells as a marker of endothelial dysfunction in aging men].

    PubMed

    Пустовойт, Ганна Л; Ярмола, Тетяна І; Мохначов, Олександр В; Ткаченко, Лідія А; Супруненко, Сергій М

    Ukraine occupies the 143 place in the world in life expectancy and the first place in terms of mortality. The main cause of death - cardiovascular diseases - 58%. Recent studies show the important and independent role of endothelium in the development of cardiovascular disease. examination of the endothelium destruction in aging men by determining the level of surface specific antigens of endothelial microparticles. 88 men age from 45 to 76 years. 50 people of the main group had a history of the second type diabetes mellitus (DM-2) combined with arterial hypertension (AH). The control group included 38 men without aforementioned diseases. Also, men were divided into two groups by age: 45-59 years and over 60. in the main subgroup I endothelin level was higher than the control subgroup I: 2,07 ± 0,6 and 1,27 ± 0,25 (p <0.05). In main subgroup II endothelin level was also significantly higher compared with the specified index in control subgroup II: 3,91 ± 0,7 and 1,79 ± 0,27 (p <0.05). Among patients of the main subgroup II endothelin level (3,88 ± 0,7 and 2,04 ± 0,6 (p <0.05)), and triglycerides (2,77 ± 0,08 vs. 1.99 ± 0.05 (p <0.05)) was higher compared with the I subgroup. age androgen deficiency is accompanied by lipid metabolism, development of endothelial dysfunction, insulin resistance, diabetes and hypertension. Reduction of the cardiovascular risk includes measures aimed at normalizing hormonal balance and lipid metabolism in aging men with DM-2 and hypertension.

  7. [Definitions destruction of endothelial cells as a marker of endothelial dysfunction in aging men].

    PubMed

    Пустовойт, Ганна Л; Ярмола, Тетяна І; Мохначов, Олександр В; Ткаченко, Лідія А; Супруненко, Сергій М

    2016-01-01

    Ukraine occupies the 143 place in the world in life expectancy and the first place in terms of mortality. The main cause of death - cardiovascular diseases - 58%. Recent studies show the important and independent role of endothelium in the development of cardiovascular disease. examination of the endothelium destruction in aging men by determining the level of surface specific antigens of endothelial microparticles. 88 men age from 45 to 76 years. 50 people of the main group had a history of the second type diabetes mellitus (DM-2) combined with arterial hypertension (AH). The control group included 38 men without aforementioned diseases. Also, men were divided into two groups by age: 45-59 years and over 60. in the main subgroup I endothelin level was higher than the control subgroup I: 2,07 ± 0,6 and 1,27 ± 0,25 (p <0.05). In main subgroup II endothelin level was also significantly higher compared with the specified index in control subgroup II: 3,91 ± 0,7 and 1,79 ± 0,27 (p <0.05). Among patients of the main subgroup II endothelin level (3,88 ± 0,7 and 2,04 ± 0,6 (p <0.05)), and triglycerides (2,77 ± 0,08 vs. 1.99 ± 0.05 (p <0.05)) was higher compared with the I subgroup. age androgen deficiency is accompanied by lipid metabolism, development of endothelial dysfunction, insulin resistance, diabetes and hypertension. Reduction of the cardiovascular risk includes measures aimed at normalizing hormonal balance and lipid metabolism in aging men with DM-2 and hypertension.

  8. Evaluation Of Metabolic And Synaptic Dysfunction Hypotheses Of Alzheimer's Disease (Ad): A Meta-Analysis Of Csf Markers.

    PubMed

    Manyevitch, Roni; Protas, Matthew; Scarpiello, Sean; Deliso, Marisa; Bass, Brittany; Nanajian, Anthony; Chang, Matthew; Thompson, Stefani M; Khoury, Neil; Gonnella, Rachel; Trotz, Margit; Moore, D Blaine; Harms, Emily; Perry, George; Clunes, Lucy; Ortiz, Angélica; Friedrich, Jan O; Murray, Ian V J

    2017-09-21

    Alzheimer's disease (AD) is currently incurable and a majority of investigational drugs have failed clinical trials. One explanation for this failure may be the invalidity of hypotheses focusing on amyloid to explain AD pathogenesis. Recently, hypotheses which are centered on synaptic and metabolic dysfunction are increasingly implicated in AD. Evaluate AD hypotheses by comparing neurotransmitter and metabolite marker concentrations in normal versus AD CSF. Meta-analysis allows for statistical comparison of pooled, existing cerebrospinal fluid (CSF) marker data extracted from multiple publications, to obtain a more reliable estimate of concentrations. This method also provides a unique opportunity to rapidly validate AD hypotheses using the resulting CSF concentration data. Hubmed, Pubmed and Google Scholar were comprehensively searched for published English articles, without date restrictions, for the keywords "AD", "CSF", and "human" plus markers selected for synaptic and metabolic pathways. Synaptic markers were acetylcholine, gamma-aminobutyric acid (GABA), glutamine, and glycine. Metabolic markers were glutathione, glucose, lactate, pyruvate, and 8 other amino acids. Only studies that measured markers in AD and controls (Ctl), provided means, standard errors/deviation, and subject numbers were included. Data were extracted by six authors and reviewed by two others for accuracy. Data were pooled using ratio of means (RoM of AD/Ctl) random effects meta-analysis and the Cochrane Collaboration's Review Manager software. Of 435 identified publications, after exclusion and removal of duplicates, 35 articles were included comprising a total of 605 AD patients and 585 controls. The following markers of synaptic and metabolic pathways were significantly changed in AD/controls: acetylcholine (RoM 0.36, 95% CI 0.24-0.53, p<0.00001), GABA (0.74, 0.58-0.94, p<0.01), pyruvate (0.48, 0.24-0.94, p=0.03), glutathione (1.11, 1.01-1.21, p=0.03), alanine (1.10, 0.98-1.23, p=0

  9. Core biological marker candidates of Alzheimer's disease - perspectives for diagnosis, prediction of outcome and reflection of biological activity.

    PubMed

    Hampel, H; Mitchell, A; Blennow, K; Frank, R A; Brettschneider, S; Weller, L; Möller, H-J

    2004-03-01

    Alzheimer's disease (AD) is a complex neurodegenerative dementing illness. Over the past few years, however, remarkable advances have taken place in understanding both the genetic and molecular biology with the intracellular processing of amyloid and tau and the changes leading to the pathologic formation of extracellular amyloid plaques and the intraneuronal aggregation of hyperphosphorylated tau into neurofibrillary tangles. This progress in our understanding of the molecular pathology has set the stage for clinically meaningful advances in the development of biomarkers. Emerging diagnostic methods that are based on biochemical and imaging biomarkers of disease specific pathology hold the potential to provide effective measures of natural history (marker of disease that is predictive of outcome), biological activity (such as magnitude and frequency of response correlating with drug potency) and markers of surrogate endpoints (single or composite marker that accounts for clinical benefit of the therapy). Markers of biological activity should be also evaluated regarding their value to reflect disease progression, heterogeneity of the clinical population, for early decision making and characterization of new treatments. We focussed on the current status of core analytes which provide reasonable evidence for association with key mechanisms of pathogenesis or neurodegeneration in AD. In addition, feasibility was important, such as availability of a validated assay for the biological measure in question, with properties that included high precision and reliability of measurement, reagents and standards well described. On this basis we reviewed the body of literature that has examined CSF total tau (t-tau) and beta-amyloid 1-42 (Abeta(1-42)), phosphorylated tau (p-tau) and beta-amyloid-antibodies as diagnostic tests for AD versus clinically representative comparison groups. Measurement of t-tau and Abeta(1-42) in the CSF seems useful to discriminate early and incipient

  10. Developmental Programming of Obesity and Metabolic Dysfunction: Role of Prenatal Stress and Stress Biology

    PubMed Central

    Entringer, Sonja; Wadhwa, Pathik D.

    2014-01-01

    Epidemiological, clinical, physiological, cellular and molecular evidence suggests the origins of obesity and metabolic dysfunction can be traced back to intrauterine life and supports an important role for maternal nutrition prior to and during gestation in fetal programming. The elucidation of underlying mechanisms is an area of interest and intense investigation. We propose that in addition to maternal nutrition-related processes, it may be important to concurrently consider the potential role of intrauterine stress and stress biology. We frame our arguments in the larger context of an evolutionary-developmental perspective that supports roles for both nutrition and stress as key environmental conditions driving natural selection and developmental plasticity. We suggest that intrauterine stress exposure may interact with the nutritional milieu, and that stress biology may represent an underlying mechanism mediating the effects of diverse intrauterine perturbations, including but not limited to maternal nutritional insults (undernutrition and overnutrition), on brain and peripheral targets of programming of body composition, energy balance homeostasis and metabolic function. We discuss putative maternal-placental-fetal endocrine and immune/inflammatory candidate processes that may underlie the long-term effects of intrauterine stress. PMID:23887109

  11. 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…

  12. Oxidative Stress Markers Correlate with Renal Dysfunction and Thrombocytopenia in Severe Leptospirosis

    PubMed Central

    Araújo, Alan M.; Reis, Eliana A. G.; Athanazio, Daniel A.; Ribeiro, Guilherme S.; Hagan, José E.; Araujo, Guilherme C.; Damião, Alcineia O.; Couto, Nicolli S.; Ko, Albert I.; Noronha-Dutra, Alberto; Reis, Mitermayer G.

    2014-01-01

    Leptospirosis is a zoonotic disease that causes severe manifestations such as Weil's disease and pulmonary hemorrhage syndrome. The aim of this study was to evaluate whether reactive oxygen species (ROS) production and antioxidant reduced glutathione (GSH) levels are related to complications in patients hospitalized with leptospirosis. The ROS production and GSH levels were measured in blood samples of 12 patients and nine healthy controls using chemiluminescence and absorbance assays. We found that ROS production was higher and GSH levels were lower in leptospirosis patients compared with healthy individuals. Among patients, GSH depletion was correlated with thrombocytopenia and elevated serum creatinine, whereas a strong positive correlation was observed between ROS production and elevated serum potassium. Additional investigation of the biological significance of ROS production and GSH levels is warranted as they may guide the development of novel adjuvant therapies for leptospirosis targeting oxidative stress. PMID:24493675

  13. Interleukin-6 as inflammatory marker referring to multiple organ dysfunction syndrome in severely injured children

    PubMed Central

    2014-01-01

    Background Despite the suggestion that the inflammatory response in traumatized children is functionally unique, prognostic markers predicting pediatric multiple organ failure are lacking. We intended to verify whether Interleukin-6 (IL-6) displays a pivotal role in pediatric trauma similar to adults. Methods Traumatized children less than 18 years of age with an Injury Severity Score >9 points and consecutive admission to the hospital’s pediatric intensive care unit were included. Organ function was evaluated according to the score by Marshall et al. while IL-6 levels were measured repetitively every morning. Results 59 traumatized children were included (8.4 ± 4.4 years; 57.6% male gender). Incidence of MODS was 11.9%. No differences were found referring to age, gender, injury distribution or overall injury severity between children with and without MODS. Increased IL-6 levels during hospital admission were associated with injury severity (Spearman correlation: r = 0.522, p < 0.001), while an inconsistent association towards the development of MODS was proven at that time point (Spearman correlation: r = 0.180, p = 0.231; Pearson's correlation: r = 0.297, p = 0.045). However, increased IL-6 levels during the first two days were no longer associated with the injury severity but a significant correlation to MODS was measured. Conclusions The presented prospective study is the first providing evidence for a correlation of IL-6 levels with injury severity and the incidence of MODS in traumatized children. PMID:24589345

  14. Molecular and biologic markers of progression in monoclonal gammopathy of undetermined significance to multiple myeloma.

    PubMed

    Mailankody, Sham; Mena, Esther; Yuan, Constance M; Balakumaran, Arun; Kuehl, W Michael; Landgren, Ola

    2010-12-01

    Multiple myeloma (MM) is a malignant plasma cell dyscrasia localized in the bone marrow. Recent studies have shown that MM is preceded in virtually all cases by a premalignant state called monoclonal gammopathy of undetermined significance (MGUS). This review focuses on non-IgM MGUS and its progression to MM. Although certain clinical markers of MGUS progression have been identified, it currently is not possible to accurately determine individual risk of progression. This review focuses on the various biologic and molecular markers that could be used to determine the risk of MM progression. A better understanding of the pathogenesis will allow us to define the biological high-risk precursor disease and, ultimately, to develop early intervention strategies designed to delay and prevent full-blown MM.

  15. Covariance Association Test (CVAT) Identifies Genetic Markers Associated with Schizophrenia in Functionally Associated Biological Processes.

    PubMed

    Rohde, Palle Duun; Demontis, Ditte; Cuyabano, Beatriz Castro Dias; Børglum, Anders D; Sørensen, Peter

    2016-08-01

    Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited power to detect genetic markers with small effects. Instead, aggregating genetic markers based on biological information might increase the power to identify sets of genetic markers of etiological significance. Several set test methods have been proposed: Here we propose a new set test derived from genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT). We compared the performance of CVAT to other commonly used set tests. The comparison was conducted using a simulated study population having the same genetic parameters as for schizophrenia. We found that CVAT was among the top performers. When extending CVAT to utilize a mixture of SNP effects, we found an increase in power to detect the causal sets. Applying the methods to a Danish schizophrenia case-control data set, we found genomic evidence for association of schizophrenia with vitamin A metabolism and immunological responses, which previously have been implicated with schizophrenia based on experimental and observational studies. Copyright © 2016 by the Genetics Society of America.

  16. 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

  17. Markers of tubular dysfunction.

    PubMed

    Piscator, M

    1989-03-01

    Since the first description of tubular proteinuria in 1958, much progress has been made with regard to diagnostic means for detecting small changes in the function of the proximal tubule. Small increases in the excretion of low-molecular-weight proteins can now be determined with great accuracy. Determination of total protein is an economic way of screening large populations but does not give specific information on the type of damage. Determinations of glucose, phosphate and amino acids are relatively insensitive methods, since their excretion is also dependent on diet and nutritional status. Determination of high-molecular-weight enzymes released from damaged tubular cells may be of use for studies of acute as well as chronic effects of nephrotoxic agents, but more data are needed.

  18. Biological pathways, candidate genes and molecular markers associated with quality-of-life domains: an update

    PubMed Central

    Sprangers, Mirjam A.G.; Thong, Melissa S.Y.; Bartels, Meike; Barsevick, Andrea; Ordoñana, Juan; Shi, Qiuling; Wang, Xin Shelley; Klepstad, Pål; Wierenga, Eddy A.; Singh, Jasvinder A.; Sloan, Jeff A.

    2014-01-01

    Background There is compelling evidence of a genetic foundation of patient-reported QOL. Given the rapid development of substantial scientific advances in this area of research, the current paper updates and extends reviews published in 2010. Objectives The objective is to provide an updated overview of the biological pathways, candidate genes and molecular markers involved in fatigue, pain, negative (depressed mood) and positive (well-being/happiness) emotional functioning, social functioning, and overall QOL. Methods We followed a purposeful search algorithm of existing literature to capture empirical papers investigating the relationship between biological pathways and molecular markers and the identified QOL domains. Results Multiple major pathways are involved in each QOL domain. The inflammatory pathway has the strongest evidence as a controlling mechanism underlying fatigue. Inflammation and neurotransmission are key processes involved in pain perception and the COMT gene is associated with multiple sorts of pain. The neurotransmitter and neuroplasticity theories have the strongest evidence for their relationship with depression. Oxytocin-related genes and genes involved in the serotonergic and dopaminergic pathways play a role in social functioning. Inflammatory pathways, via cytokines, also play an important role in overall QOL. Conclusions Whereas the current findings need future experiments and replication efforts, they will provide researchers supportive background information when embarking on studies relating candidate genes and/or molecular markers to QOL domains. The ultimate goal of this area of research is to enhance patients’ QOL. PMID:24604075

  19. Pulmonary neuroendocrine cells and neuroepithelial bodies in sudden infant death syndrome: potential markers of airway chemoreceptor dysfunction.

    PubMed

    Cutz, Ernest; Perrin, Donald G; Pan, Jie; Haas, Elisabeth A; Krous, Henry F

    2007-01-01

    Pulmonary neuroendocrine cells (PNEC), including neuroepithelial bodies (NEB), are amine- and peptide (for example, bombesin)-producing cells that function as hypoxia/hypercapnia-sensitive chemoreceptors that could be involved in the pathophysiology of sudden infant death syndrome (SIDS). We assessed morphometrically the frequency and size of PNEC/NEB in lungs of infants who died of SIDS (n = 21) and compared them to an equal number PNEC/NEB in lungs of age-matched control infants who died of accidental death or homicide, with all cases obtained from the San Diego SIDS/SUDC Research Project database. As a marker for PNEC/NEB we used an antibody against chromogranin A (CGA), and computer-assisted morphometric analysis was employed to determine the relative frequency of PNEC per airway epithelial area (% immunostained area, %IMS), the size of NEB, the number of nuclei/NEB, and the size of the NEB cells. The lungs of SIDS infants showed significantly greater %IMS of airway epithelium (2.72 +/- 0.28 [standard error of the mean, SEM] versus 1.88 +/- 0.24; P < 0.05) and larger NEB (1557 +/- 153 microm(2) versus 1151 +/- 106 microm(2); P < 0.05) compared to control infants. The size of NEB cells was also significantly increased in SIDS cases compared to the controls (180 +/- 6.39 microm(2) versus 157 +/- 8.0 microm(2); P < 0.05), indicating the presence of hypertrophy in addition to hyperplasia. Our findings support previous studies demonstrating hyperplasia of PNEC/NEB in lungs of infants who died of SIDS. These changes could be secondary to chronic hypoxia and/or could be attributable to maturational delay. Morphometric assessment and/or measurement of the secretory products of these cells (for example, CGA, bombesin) could provide a potential biological marker for SIDS.

  20. Abacavir-based therapy does not affect biological mechanisms associated with cardiovascular dysfunction.

    PubMed

    Martínez, Esteban; Larrousse, María; Podzamczer, Daniel; Pérez, Ignacio; Gutiérrez, Félix; Loncá, Montserrat; Barragán, Patricia; Deulofeu, Ramón; Casamitjana, Roser; Mallolas, Josep; Pich, Judit; Gatell, José M

    2010-01-28

    To assess the effects of initiating abacavir-containing therapy on plasma lipids and cardiovascular biomarkers. Sub-study of the BICOMBO study in which participants were randomized to switch their nucleoside backbone to either abacavir/lamivudine or tenofovir/emtricitabine. We assessed 48-week changes in fasting lipids and several biomarkers including serum high-sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein-1 (MCP-1), osteoprotegerin, interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNF-alpha), intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), selectin E and P, adiponectin, insulin, and D-dimer in otherwise healthy, virologically suppressed HIV-infected patients randomly switched to abacavir/lamivudine or tenofovir/emtricitabine with no history of cardiovascular disease, no prior abacavir or tenofovir use, and no virological failure or AIDS during follow-up. Eighty (46 abacavir/lamivudine and 34 tenofovir/emtricitabine) patients were included. Baseline characteristics were similar between groups and between patients in the sub-study vs. those not. There were no significant differences in baseline lipids and markers between groups. Although total (6.5 vs. -6.7%, P < 0.0001) and low-density lipoprotein (LDL) (8.6 vs. -9.1%, P = 0.004) cholesterol increased significantly in the abacavir/lamivudine group relative to the tenofovir/emtricitabine group, we found no significant changes in the biomarkers: CRP (-3.9 vs. 0.0%), MCP-1 (5.9 vs. 4.0%), osteoprotegerin (5.1 vs. -2.8%), IL-6 (0.0 vs. 0.0%), IL-10 (0.0 vs. 0.0%), TNF-alpha (0.0 vs. 0.0%), ICAM-1 (6.6 vs. 5.2%), VCAM-1 (0.02 vs. -0.01%), selectin E (-0.4 vs. 7.8%), selectin P (4.6 vs. 12.6%), insulin (-2.5 vs. 8.8%), adiponectin (-2.2 vs. 15.4%), and D-dimer (0.0 vs. 0.0%) (P > or = 0.12 for all comparisons). Abacavir/lamivudine increased total and LDL cholesterol compared with tenofovir/emtricitabine, but it did not cause inflammation, endothelial

  1. Prognostic factors, predictive markers and cancer biology: the triad for successful oral cancer chemoprevention.

    PubMed

    Monteiro de Oliveira Novaes, Jose Augusto; William, William N

    2016-10-01

    Oral squamous cell carcinomas represent a significant cancer burden worldwide. Unfortunately, chemoprevention strategies investigated to date have failed to produce an agent considered standard of care to prevent oral cancers. Nonetheless, recent advances in clinical trial design may streamline drug development in this setting. In this manuscript, we review some of these improvements, including risk prediction tools based on molecular markers that help select patients most suitable for chemoprevention. We also discuss the opportunities that novel preclinical models and modern molecular profiling techniques will bring to the prevention field in the near future, and propose a clinical trials framework that incorporates molecular prognostic factors, predictive markers and cancer biology as a roadmap to improve chemoprevention strategies for oral cancers.

  2. Biological marker candidates of Alzheimer's disease in blood, plasma, and serum.

    PubMed

    Schneider, Philine; Hampel, Harald; Buerger, Katharina

    2009-01-01

    At the earliest clinical stages of Alzheimer's disease (AD), when first symptoms are mild, making a reliable and accurate diagnosis is difficult. AD related brain pathology and underlying molecular mechanisms precede symptoms. Biological markers can serve as supportive early screening and diagnostic tools as well as indicators of presymptomatic biochemical change. Moreover, biomarkers cover a variety of roles and functions such as disease prediction, indicating disease acuity and progression, and may ensure biological mapping of treatment outcome. Early screening, detection, and diagnosis of AD would permit earlier disease modifying intervention at potentially reversible stages. To date, most established biological markers from both cerebrospinal fluid neurochemistry and structural and functional neuroimaging have not reached widespread clinical application. Crucial remaining problems, such as easy acceptance and application of a test, cost-effectiveness, and noninvasiveness, need to be resolved. The development and validation of precise, reliable, and robust tests and biomarkers in blood, plasma, or serum has therefore been for a long time the ultimate focus of many research groups worldwide. Blood-based testing will most likely be the prerequisite to future sensitive screening of large populations at risk of AD and the baseline in a diagnostic flow approach to AD. The status and emerging perspectives on hypothesis and exploratory-based candidate biomarkers derived from blood, plasma, and serum are reviewed and discussed.

  3. Immune function parameters as markers of biological age and predictors of longevity

    PubMed Central

    de Toda, Irene Martínez; Maté, Ianire; Vida, Carmen; Cruces, Julia; De la Fuente, Mónica

    2016-01-01

    Chronological age is not a good indicator of how each individual ages and thus how to maintain good health. Due to the long lifespan in humans and the consequent difficulty of carrying out longitudinal studies, finding valid biomarkers of the biological age has been a challenge both for research and clinical studies. The aim was to identify and validate several immune cell function parameters as markers of biological age. Adult, mature, elderly and long-lived human volunteers were used. The chemotaxis, phagocytosis, natural killer activity and lymphoproliferation in neutrophils and lymphocytes of peripheral blood were analyzed. The same functions were measured in peritoneal immune cells from mice, at the corresponding ages (adult, mature, old and long lived) in a longitudinal study. The results showed that the evolution of these functions was similar in humans and mice, with a decrease in old subjects. However, the long-lived individuals maintained values similar to those in adults. In addition, the values of these functions in adult prematurely aging mice were similar to those in chronologically old animals, and they died before their non-prematurely aging mice counterparts. Thus, the parameters studied are good markers of the rate of aging, allowing the determination of biological age. PMID:27899767

  4. Bacterial glucuronidase as general marker for oncolytic virotherapy or other biological therapies

    PubMed Central

    2011-01-01

    Background Oncolytic viral tumor therapy is an emerging field in the fight against cancer with rising numbers of clinical trials and the first clinically approved product (Adenovirus for the treatment of Head and Neck Cancer in China) in this field. Yet, until recently no general (bio)marker or reporter gene was described that could be used to evaluate successful tumor colonization and/or transgene expression in other biological therapies. Methods Here, a bacterial glucuronidase (GusA) encoded by biological therapeutics (e.g. oncolytic viruses) was used as reporter system. Results Using fluorogenic probes that were specifically activated by glucuronidase we could show 1) preferential activation in tumors, 2) renal excretion of the activated fluorescent compounds and 3) reproducible detection of GusA in the serum of oncolytic vaccinia virus treated, tumor bearing mice in several tumor models. Time course studies revealed that reliable differentiation between tumor bearing and healthy mice can be done as early as 9 days post injection of the virus. Regarding the sensitivity of the newly developed assay system, we could show that a single infected tumor cell could be reliably detected in this assay. Conclusion GusA therefore has the potential to be used as a general marker in the preclinical and clinical evaluation of (novel) biological therapies as well as being useful for the detection of rare cells such as circulating tumor cells. PMID:21989091

  5. Assessment of MRI-Based Marker of Dopaminergic Integrity as a Biological Indicator of Gulf War Illness

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0622 TITLE: Assessment of MRI -Based Marker of Dopaminergic Integrity as a Biological Indicator of Gulf War...COVERED 29 Sep 2014 – 28 Sept 2015 4. TITLE AND SUBTITLE Illness 5a. CONTRACT NUMBER Assessment of MRI -Based Marker of Dopaminergic Integrity as a

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. The biology of equine mesenchymal stem cells: phenotypic characterization, cell surface markers and multilineage differentiation.

    PubMed

    Penny, Jasmine; Harris, Pat; Shakesheff, Kevin M; Mobasheri, Ali

    2012-01-01

    Mesenchymal stem cells (MSCs) are multipotent stem cells that can give rise to a range of connective tissue cells including osteoblasts, chondrocytes and adipocytes. MSCs have been isolated from humans and a variety of animal species including rodents, dogs, horses and rabbits. There is currently no consensus on how these cells are identified and characterized. This is partly due to the lack of standardized specific cell surface markers for MSCs. The aim of this review is to examine the literature on equine MSCs and establish whether there is a well-defined phenotype for these cells. Equine MSCs have been obtained from four main sources, bone marrow, adipose tissue, umbilical cord (blood and matrix) and peripheral blood. MSCs from these tissue sources have been shown to undergo chondrogenic, adipogenic and osteogenic differentiation. However the markers used to identify these cells vary significantly in the literature. Despite this, CD90 and CD34 seem to be reliable positive and negative markers respectively. Our understanding of the biology of equine MSCs will benefit from better reagents for their phenotypic characterization. The antibodies and molecular probes needed for the reliable identification of equine MSCs are not standardized and this is a high priority for future research.

  11. 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.

  12. Emotional management and biological markers of dietetic regimen in chronic kidney disease patients.

    PubMed

    Lai, Carlo; Aceto, Paola; Luciani, Massimiliano; Fazzari, Erika; Cesari, Valerio; Luciano, Stella; Fortini, Antonio; Berloco, Desiderata; Canulla, Francesco; Bruzzese, Vincenzo; Lai, Silvia

    2017-11-01

    The aim of the study was to investigate the association between psychological characteristics and biological markers of adherence in chronic kidney disease patients receiving conservative therapy, hemodialysis, peritoneal dialysis (PD), or kidney transplantation. Seventy-nine adult patients were asked to complete the following questionnaires: Toronto Alexithymia scale, Snaith-Hamilton Pleasure Scale, and Short Form Health Survey. Biological markers of adherence to treatment were measured. Peritoneal dialysis patients showed a lower capacity to feel pleasure from sensorial experience (p = .011) and a higher values of phosphorus compared to the other patients' groups (p = .0001). The inability to communicate emotions was negatively correlated with hemoglobin levels (r = -(0).69; p = .001) and positively correlated with phosphorus values in the PD patients (r = .45; p = .050). Findings showed higher psychological impairments and a lower adherence to the treatment in PD patients and suggest the implication of emotional competence in adherence to treatment.

  13. [Human papillomavirus infection, a possible biological marker of sexual behavior among university students].

    PubMed

    Sánchez-Alemán, Miguel A; Uribe-Salas, Felipe; Conde-González, Carlos J

    2002-01-01

    To estimate the prevalence of Human papillomavirus (HPV) among university students and to use it as a biological marker to assess sexual behavior. A cross-sectional study was carried out between 2000 and 2001 among 194 students at Universidad Autónoma del Estado de Morelos, Mexico. A data collection instrument was applied and genital samples were taken to detect oncogenic HPV DNA. Data were analyzed using the chi-squared test and odds ratios. Overall HPV prevalence was 14.4%. Women who had had two or more sexual partners during the previous year showed a greater risk of HPV infection (OR 6.0, 95% CI 1.7-21.1), as did women who had used oral contraceptives and spermicides at their latest intercourse (OR 3.0, 95% CI 1.0-8.7). Males who consumed cocaine were at a greater risk of HPV infection (OR 7.6, 95% CI 1.3-45.1). HPV prevalence is relatively high. HPV is a reliable biological marker of sexual behavior among females. A greater sample size may be needed to assess its reliability among men.

  14. [Evaluation of the concordance between biological markers and clinical activity in inflammatory bowel disease].

    PubMed

    Miranda García, Pablo; Chaparro, María; Gisbert, Javier P

    2015-01-06

    Endoscopy is the gold standard to assess disease severity in inflammatory bowel disease, although it is an invasive procedure. Clinical activity and biological markers have been routinely used to determine disease activity in a non-invasive manner. The aim of this study was to determine concordance between common biological markers (C reactive protein, orosomucoid, erythrocyte sedimentation rate, fibrinogen, platelets, leukocytes, neutrophils and haemoglobin) and clinical activity in inflammatory bowel disease. Consecutive patients with inflammatory bowel disease were included. Clinical activity was evaluated according to the Harvey-Bradshaw index in Crohn's disease and to the partial Mayo score in ulcerative colitis. Serum concentrations of the different biomarkers were analysed. Concordance between clinical activity and elevation of the serological biomarkers was determined using the kappa statistic. In total, 350 patients were included (median age 46 years, Crohn's disease 59%). Eleven percent of patients had clinical activity. Crohn's disease patients had mild clinical activity in 44% of cases, moderate disease in 44% and only 12% of patients had severe clinical activity. In ulcerative colitis, patients had mild, moderate and severe clinical activity in 50, 42 and 8% of cases, respectively. None of the biomarkers included had an acceptable concordance with clinical activity (kappa statistic ≤ 0.30). Concordance between serological biomarkers and clinical activity in inflammatory bowel disease is remarkably low. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  15. Endovascular treatment of chronic cerebro spinal venous insufficiency in patients with multiple sclerosis modifies circulating markers of endothelial dysfunction and coagulation activation: a prospective study.

    PubMed

    Napolitano, Mariasanta; Bruno, Aldo; Mastrangelo, Diego; De Vizia, Marcella; Bernardo, Benedetto; Rosa, Buonagura; De Lucia, Domenico

    2014-10-01

    We performed a monocentric observational prospective study to evaluate coagulation activation and endothelial dysfunction parameters in patients with multiple sclerosis undergoing endovascular treatment for cerebro-spinal-venous insufficiency. Between February 2011 and July 2012, 144 endovascular procedures in 110 patients with multiple sclerosis and chronical cerebro-spinal venous insufficiency were performed and they were prospectively analyzed. Each patient was included in the study according to previously published criteria, assessed by the investigators before enrollment. Endothelial dysfunction and coagulation activation parameters were determined before the procedure and during follow-up at 1, 3, 6, 9, 12, 15 and 18 months after treatment, respectively. After the endovascular procedure, patients were treated with standard therapies, with the addition of mesoglycan. Fifty-five percent of patients experienced a favorable outcome of multiple sclerosis within 1 month after treatment, 25% regressed in the following 3 months, 24.9% did not experience any benefit. In only 0.1% patients, acute recurrence was observed and it was treated with high-dose immunosuppressive therapy. No major complications were observed. Coagulation activation and endothelial dysfunction parameters were shown to be reduced at 1 month and stable up to 12-month follow-up, and they were furthermore associated with a good clinical outcome. Endovascular procedures performed by a qualified staff are well tolerated; they can be associated with other currently adopted treatments. Correlations between inflammation, coagulation activation and neurodegenerative disorders are here supported by the observed variations in plasma levels of markers of coagulation activation and endothelial dysfunction.

  16. The Relation of Markers of Inflammation and Endothelial Dysfunction to the Prevalence and Progression of Diabetic Retinopathy. Wisconsin Epidemiologic Study of Diabetic Retinopathy

    PubMed Central

    Klein, Barbara E.K.; Knudtson, Michael D.; Tsai, Michael Y.; Klein, Ronald

    2009-01-01

    Context Levels of glycemia, blood pressure, and serum total cholesterol are associated with prevalence and incidence of diabetic retinopathy. It has been reported the markers of systemic inflammation and endothelial dysfunction may be important additional risk factors. Objective To determine the association of several systemic markers of inflammation and endothelial dysfunction to prevalence and incidence of diabetic retinal outcomes in persons with long duration type 1 diabetes. Design Longitudinal population based study of persons with type 1 diabetes who were receiving care for their diabetes in south central Wisconsin in 1978-1979. Data for this investigation were from 1990-1992 through 2005-2007. Main Outcome Measures Severity of diabetic retinopathy and macular edema. Results In prevalence data from 1990-1992, soluble vascular cell adhesion molecule (sVCAM-1), tumor necrosis factor alpha (TNF-α) and homocysteine (Hcy) were associated with increased odds of more severe retinopathy (Odds ratios [highest versus lowest quartile] 2.43, 95% Confidence Interval 1.56, 3.78; 3.14 [1.98, 4.99]; 3.79 [2.33, 6.15], respectively) in those with kidney disease while controlling for relevant confounders. Similar odds were found for proliferative diabetic retinopathy. Only homocysteine was associated with increased odds of macular edema (4.68; 1.25-17.57) irrespective of kidney disease. None of the markers were associated with incidence of proliferative retinopathy, macular edema, or progression of retinopathy 15 years later. Conclusions A limited number of markers was associated with increased odds of prevalent retinal outcomes in persons with type 1 diabetes and kidney disease. Only Hcy was associated with macular edema in those with and without kidney disease. In the absence of kidney disease the markers do not add to the more conventional descriptors and predictors of diabetic retinopathy in persons with type 1 diabetes. This may reflect the close association of diabetic

  17. Circulating intercellular cell adhesion molecule-1, endothelin-1 and von Willebrand factor-markers of endothelial dysfunction in uncomplicated essential hypertension: the effect of treatment with ACE inhibitors.

    PubMed

    Hlubocká, Z; Umnerová, V; Heller, S; Peleska, J; Jindra, A; Jáchymová, M; Kvasnicka, J; Horký, K; Aschermann, M

    2002-08-01

    The aim of the study was to examine whether the circulating cell adhesion molecules, von Willebrand factor (vWf) and endothelin-1, are elevated in patients with essential hypertension with no other risk factors for atherosclerosis and thus may serve as a markers of endothelial dysfunction in uncomplicated hypertension. Furthermore, the effect of treatment with the ACE inhibitor, quinapril, on levels of endothelial dysfunction markers were studied. The levels of adhesion molecules (intercellular cell adhesion molecule-1 [ICAM-1], E-selectin, P-selectin), von Willebrand factor (vWf) and endothelin-1 were measured in patients with hypertension without any other risk factors of atherosclerosis before and after treatment with quinapril (n = 22) and in normotensive controls (n = 22). Compared with normotensive subjects, the hypertensive patients had significantly higher levels of ICAM-1 (238 vs 208 ng/ml, P = 0.02), vWf (119 vs 105 IU/dl, P < 0.05) and endothelin-1 (5.76 vs 5.14 fmol/ml, P < 0.05). Three-month treatment of hypertensive patients with quinapril led to a significant decrease in the levels of endothelin-1 (5.76 vs 5.28 fmol/ml, P < 0.01). We did not observe significant changes in the levels of adhesion molecules and vWf after ACE inhibitor treatment, although a trend toward a decrease was apparent with all these parameters. Patients with uncomplicated hypertension with no other risk factors of atherosclerosis had significantly elevated levels of ICAM-1, vWf, and endothelin-1. Our data suggest that these factors may serve as markers of endothelial damage even in uncomplicated hypertension. In hypertensive patients, treatment with the ACE inhibitor quinapril resulted in a significant decrease in endothelin-1 levels. These findings indicate a beneficial effect of ACE inhibitors on endothelial dysfunction in hypertensive patients.

  18. 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.

  19. An overview of biological markers of exposure to chemical warfare agents.

    PubMed

    Black, Robin M

    2008-01-01

    An overview is given of biological markers of exposure to chemical warfare agents. Metabolites, protein, and/or DNA adducts have been identified for most nerve agents and vesicants and validated in experimental animals or in a small number of human exposures. For several agents, metabolites derived from hydrolysis are unsatisfactory biomarkers of exposure because of background levels in the human population. These are assumed to result from environmental exposure to commercial products that contain these hydrolysis products or chemicals that are metabolized to them. In these cases, metabolites derived from glutathione pathways, or covalent adducts with proteins or DNA, provide more definitive biomarkers. Biomarkers for cyanide and phosgene are unsatisfactory as indicators of chemical warfare exposure because of other sources of these chemicals or their metabolites.

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

    PubMed

    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

    2009-03-01

    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.

  1. Matrix effect marker for multianalyte analysis by LC-MS/MS in biological samples.

    PubMed

    Tudela, Eva; Muñoz, Gloria; Muñoz-Guerra, Jesús A

    2012-07-15

    Matrix effects (ion suppression/enhancement) are a well-observed phenomenon in analyses of biological matrices by high-performance liquid chromatography-mass spectrometry (LC-MS). However, few simple solutions for detecting and minimizing these adverse effects have been described so far in multianalyte analysis, especially in the field of doping control. This study describes an exhaustive characterization of matrix effects in one hundred urine samples fortified with 41 analytes (glucocorticoids and diuretics). It introduces a novel marker to identify samples in which the reliability of the results is compromised because of acute ion suppression. This new strategy strengthens the rigor of the analysis for screening purposes. Once the matrix effect is identified, a selective sample preparation is introduced to minimize the adverse ion suppression effect. That selective extraction together with the use of a deuterated internal standard permits enhancing the ruggedness of the estimation of glucocorticoid concentration in urine.

  2. Minichromosome maintenance 7 protein is a reliable biological marker for human cervical progressive disease

    PubMed Central

    Lobato, Soraya; Tafuri, Alexandre; Fernandes, Paula Ávila; Caliari, Marcelo Vidigal; Silva, Marcos Xavier; Xavier, Marcelo Antônio Pascoal

    2012-01-01

    Objective This study focused on comparing the expression levels of p16, Ki-67, and minichromosome maintenance 7 (MCM7) protein in normal and affected cervical epithelium to ascertain the biological significance of these markers in detecting progressive cervical disease. Methods A quantitative and based on-scanning-microscopy analysis of the three markers expression was performed in normal and cervical intraepithelial neoplasia (CIN) I, II, and III tissues. p16 area as well as p16, Ki-67, and MCM7 positive cells or nuclei were evaluated according to their distribution and extent through the cervical epithelium. Results A clear p16 over-expression was observed in all the dysplastic epithelium tissue samples. The quantitative analysis of p16 area as well as the number of p16 positive cells was able to better discriminate the CIN lesions grades than the usual semi-quantitative analysis. The average Ki-67 labeling indexes for the normal epithelium, CIN I, CIN II, and CIN III groups were 19.8%, 27.3%, 32.8%, and 37.1%, respectively, whereas the mean MCM7 labeling indexes for the correspondent grades were 27.0%, 30.4%, 50.5%, and 67.2%. The Ki-67 and MCM7 labeling indexes were closely correlated with the CIN histological grade, with higher labeling indexe values obtained from the more severe lesions (p<0.05), being the MCM7 labeling indexes the highest values in all the CIN categories (p<0.05). Conclusion We observed a good correlation among the p16, Ki-67, and MCM7 data. In addition, MCM7 demonstrated to be a more efficient and sensitive marker to assess disease progression in the uterine cervix. PMID:22355461

  3. [VOLATILE FATTY ACIDS IN SALIVA--BIOLOGICAL MARKERS FOR ASSESSMENT OF DRINKING WATER POLLUTANTS ON CHILDREN].

    PubMed

    Akaizina, A E; Akaizin, E S; Starodumov, V L

    2015-01-01

    The use of modern methods of analysis is aimed to the search of ultimately novel biological markers. Volatile fatty acids in saliva were not used previously for the assessment of the effects of contaminating substances in the drinking water on the body of children. The aim of the study is to investigate the informative value of volatile fatty acids in saliva as biological markers of the impact for the assessment of the exposure to contaminating substances in the drinking water on the body of children. Hygienic assessment of drinking water quality was made according to data of the own research of drinking water from centralized supply system of the city of Ivanovo. For the comparison of indices there was investigated the drinking water from wells at the village Podvyaznovsky of the Ivanovo region. In the Ivanovo water from the distributing network of centralized drinking water supply system of the city of Ivanovo, there were identified indices of the permanganate oxidation and the total concentration of residual chlorine exceeding norms, and also chloroform and carbon tetrachloride were in concentrations not exceeding the norms. Studied by us the samples of drinking water from Podvyaznovsky village wells, the water met the standards for all investigated parameters. The was studied the informative value of volatile fatty acids in the saliva of children aged 9-14 years from the city of Ivanovo and the Podvyaznovsky village, Ivanovo region. There was established the fall in acetic, butyric, isovaleric acids and the total amount of volatile fatty acids in the saliva in children of the city of Ivanovo, consuming water treated with chlorine of Ivanovo centralized drinking water supply system. Indices of volatile fatty acids in saliva are informative for the assessment of the impact of organic pollutants, residual chlorine and organic chlorine compounds of drinking water on the body of children.

  4. Biological stress indicators as risk markers for increased alcohol use following traumatic experiences.

    PubMed

    Trautmann, Sebastian; Muehlhan, Markus; Kirschbaum, Clemens; Wittchen, Hans-Ulrich; Höfler, Michael; Stalder, Tobias; Steudte-Schmiedgen, Susann

    2017-01-20

    Alcohol misuse is a common sequela of traumatic event experiences causing considerable morbidity and mortality. Although biological stress indicators have been identified as useful risk markers for the development of trauma-related disorders, no such biological indicators exist for the risk of increased alcohol use after trauma exposure. This is the first study to prospectively investigate the predictive value of long-term cortisol levels and acute stress reactivity for the risk of increased alcohol use following traumatic events. Male soldiers were examined before and 12 months following deployment using a standardized diagnostic interview. We analyzed the moderating role of baseline hair cortisol concentrations (HCCs, n = 153) as well as baseline salivary cortisol and alpha-amylase stress reactivity in response to a laboratory stressor (n = 145) in the association between new-onset traumatic events (according to the DSM-IV A1 criterion) and subsequent daily alcohol use. No main effects of pre-traumatic HCC or salivary stress markers on subsequent change in alcohol use were observed. However, we found that with decreasing HCC, the number of new-onset traumatic events was more strongly associated with subsequent alcohol use independent from changes in posttraumatic stress disorder symptoms. No such relation was seen for the acute stress reactivity data. Taken together, this study provides first evidence suggesting that individual differences in long-term cortisol regulation are involved in the association between traumatic experiences and subsequent alcohol use. HCC may thus serve as a potential target in the early identification of individuals vulnerable for increased alcohol use following traumatic events. © 2017 Society for the Study of Addiction.

  5. Correlation of oils and source rock characteristics using biological markers, Cuyama Basin, California

    SciTech Connect

    Lillis, P.G.

    1988-03-01

    Biological marker data obtained from gas chromatography and gas chromatography/mass spectrometry were used to correlate the oils in the Cuyama basin and to characterize the potential source facies. Biological markers provide a wealth of information about petroleum and source rocks, including information on paleoecology, depositional environment, and thermal maturity. Pristane/phytane ratios and sterane and hopanoid distributions indicate the source facies was deposited in a restricted marine basin and the organic matter was derived primarily from marine phytoplankton with a significant contribution from land plants and bacteria. Previous studies have documented that the Miocene Monterey Formation is a major source rock for oils in several California basins. However, clear differences exist between the composition of Cuyama basin oils and typical Monterey oils. Cuyama basin oils have lower sulfur contents (< 0.5 wt. %), higher pristane/phytane ratios (1.7-1.9), and no 28,30-bisnorhopane, in comparison to Monterey oils, which have higher sulfur contents (1-6 wt %), lower pristane/phytane ratios (< 1), and significant amounts of 28,30-bisnorhopane. The low sulfur content of the Cuyama basin oils is probably due to precipitation of microbially reduced sulfur with iron from terrigenous clay input, this preventing sulfur incorporation into the kerogen. The higher clay content in the source facies is also indicated by higher diasterane content. Petroleum geochemistry studies indicate that the Cuyama basin oils share a common source. The source facies appears to be an atypical Monterey Formation deposited in an inboard basin, with significant terrigenous organic and clay mineral debris contributing to the autochthonous biogenous sediments.

  6. Circulating microRNAs Serve as Novel Biological Markers for Intracranial Aneurysms

    PubMed Central

    Li, Pengxiang; Zhang, Qunye; Wu, Xiao; Yang, Xinjian; Zhang, Yun; Li, Youxiang; Jiang, Fan

    2014-01-01

    Background Biological markers that can be used to predict the risk of intracranial aneurysms (IAs) are not available. Methods and Results To clarify whether circulating microRNAs could be used as biomarkers for IA, we carried out microarray assays in a screening cohort of 40 IA patients (20 unruptured and 20 ruptured) and 20 healthy volunteers. We identified 20 microRNAs that were unanimously changed in both ruptured and unruptured patients. We confirmed 60% of these changed microRNAs by a separate microarray test with an independent validation cohort (n=143 including 93 IA patients). To identify potential biomarkers, we combined the 2 cohorts and performed quantitative real‐time polymerase chain reactions for selected target microRNAs. Logistic regression analysis demonstrated that miR‐16 and miR‐25 were independent factors for IA occurrence (P<0.001). After controlling for age, sex, smoking, and history of hypertension, the contributions of miR‐16 and miR‐25 were still highly significant (P<0.001). The adjusted odds ratio values for miR‐16 and miR‐25 were 1.52 (95% CI 1.31 to 1.77) and 1.53 (1.30 to 1.79). Combining both miR‐16 and miR‐25 in a single model did not improve the performance of risk association. Conclusions Our data suggest that circulating miRNAs may be novel biological markers that are useful in assessing the likelihood of IA occurrence. PMID:25249297

  7. Genomic characterization of Alzheimer's disease and genotype-related phenotypic analysis of biological markers in dementia.

    PubMed

    Cacabelos, Ramón

    2004-12-01

    More than 180 genes distributed across the human genome are potentially involved in the pathogenesis of Alzheimer's disease (AD). The AD population shows a higher genetic variation rate than the control population. Significant differences in allelic distribution and frequency exist when AD-related polygenic clusters are compared with other forms of dementia, indicating that the genetic component in neurodegenerative dementia differs from that of other CNS disorders. The characterization of AD genotype-related phenotypic profiles reveals substantial differences in biological markers among AD clusters associated with different genes and/or allelic combinations. AD and dementia with vascular component (DVC) are the most prevalent forms of dementia. Both clinical entities share many similarities, but they differ in their major phenotypic and genotypic profiles, as revealed by structural and functional genomics studies. Comparative phenotypic studies have identified significant differences in 25% of more than 100 parametric variables, including anthropometric values, cardiovascular function, blood pressure, lipid metabolism, uric acid metabolism, peripheral calcium homeostasis, liver function, alkaline phosphatase, lactate dehydrogenase, red and white blood cells, regional brain atrophy, and brain blood flow velocity. Functional genomic studies incorporating apolipoprotein E (APOE)-related changes in biological markers extended the difference between AD and DVC by up to 57%. Structural genomic studies with AD-related genes, including APP, MAPT, APOE, PS1, PS2, A2M, ACE, AGT, cFOS, and PRNP, demonstrate different genetic profiles in AD and DVC, with an absolute genetic variation rate in the range of 30-80%, depending upon genes and genetic clusters. The relative polymorphic variation in genetic clusters integrated by two, three or four genes associated with AD ranges from 1 to 3%. The main phenotypic differences in AD are genotype dependent, indicating a powerful

  8. Can a score derived from the Critical Care Minimum Data Set be used as a marker of organ dysfunction? – a pilot study

    PubMed Central

    Felton, Tim W; Sander, Rebecca; Al-Aloul, Mo; Dark, Paul; Bentley, Andrew M

    2009-01-01

    Background The aim of this study was to develop a simple organ score derived from the Critical Care Minimum Data Set (CCMDS) to compare with the Sequential Organ Failure Assessment (SOFA) score, a previously validated score of organ dysfunction. Findings The CCMDS collects data regarding the support of seven organ systems. To create a CCMDS derived score each level of organ support was allocated a numerical value. SOFA scores were collected retrospectively from each patient in the study. Data was collected in 50 sequential admissions over the first 5 days of their admission. This generated a total of 147 pairs of data for comparison. Scatter plots and Spearman's rank correlation coefficient suggest a weak positive association between our CCMDS-derived score and the SOFA score. Daily Bland-Altman plots reveal minimal bias between the score but wide limits of agreement. Conclusion Our CCMDS-derived score cannot be regarded as an indicator of severity of organ dysfunction and cannot replace SOFA scores when a daily marker of organ dysfunction is required. PMID:19419551

  9. 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.

  10. Biological markers for anxiety disorders, OCD and PTSD - a consensus statement. Part I: Neuroimaging and genetics.

    PubMed

    Bandelow, Borwin; Baldwin, David; Abelli, Marianna; Altamura, Carlo; Dell'Osso, Bernardo; Domschke, Katharina; Fineberg, Naomi A; Grünblatt, Edna; Jarema, Marek; Maron, Eduard; Nutt, David; Pini, Stefano; Vaghi, Matilde M; Wichniak, Adam; Zai, Gwyneth; Riederer, Peter

    2016-08-01

    Biomarkers are defined as anatomical, biochemical or physiological traits that are specific to certain disorders or syndromes. The objective of this paper is to summarise the current knowledge of biomarkers for anxiety disorders, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). Findings in biomarker research were reviewed by a task force of international experts in the field, consisting of members of the World Federation of Societies for Biological Psychiatry Task Force on Biological Markers and of the European College of Neuropsychopharmacology Anxiety Disorders Research Network. The present article (Part I) summarises findings on potential biomarkers in neuroimaging studies, including structural brain morphology, functional magnetic resonance imaging and techniques for measuring metabolic changes, including positron emission tomography and others. Furthermore, this review reports on the clinical and molecular genetic findings of family, twin, linkage, association and genome-wide association studies. Part II of the review focuses on neurochemistry, neurophysiology and neurocognition. Although at present, none of the putative biomarkers is sufficient and specific as a diagnostic tool, an abundance of high-quality research has accumulated that will improve our understanding of the neurobiological causes of anxiety disorders, OCD and PTSD.

  11. Identification of biological markers for better characterization of older subjects with physical frailty and sarcopenia

    PubMed Central

    Fougère, Bertrand; Vellas, Bruno; van Kan, Gabor Abellan; Cesari, Matteo

    2015-01-01

    Population aging is rapidly accelerating worldwide; however, longer life expectancy is not the only public health goal. Indeed, extended lifetime involves maintaining function and the capacity of living independently. Sarcopenia and physical frailty are both highly relevant entities with regards to functionality and autonomy of older adults. The concepts and definitions of frailty and sarcopenia have largely been revised over the years. Sarcopenia is an age-related progressive and generalized loss of skeletal muscle mass and strength. On the other hand, frailty is a state of increased vulnerability to stressors, responsible for exposing the older person to enhanced risk of adverse outcomes. Physical frailty and sarcopenia substantially overlap and several adverse outcomes of frailty are likely mediated by sarcopenia. Indeed, the concepts of sarcopenia and physical frailty can be perceived as related to the same target organ (i.e., skeletal muscle) and it may be possible to combine them into a unique definition. The biological background of such a close relationship needs to be explored and clarified as it can potentially provide novel and pivotal insights for the assessment and treatment of these conditions in old age. The aim of this paper is to indicate and discuss possible biological markers to be considered in the framing of physical frailty and sarcopenia. PMID:28123793

  12. Markers of Islet Endothelial Dysfunction Occur in Male B6.BKS(D)-Leprdb/J Mice and May Contribute to Reduced Insulin Release.

    PubMed

    Hogan, Meghan F; Liu, Amy W; Peters, Michael J; Willard, Joshua R; Rabbani, Zaheen; Bartholomew, Erik C; Ottley, Adam; Hull, Rebecca L

    2017-02-01

    Islet endothelial cells produce paracrine factors that support β-cell function and growth. Endothelial dysfunction underlies diabetic microvascular complications; thus, we hypothesized that in diabetes, islet endothelial cells become dysfunctional, which may contribute to β-cell secretory dysfunction. Islets/islet endothelial cells were isolated from diabetic B6.BKS(D)-Leprdb/J male (db/db) mice, treated with or without the glucose-lowering agent phlorizin, or from C57BL/6J mice fed a high-fat diet for 18 weeks and appropriate controls. Messenger RNA (mRNA) and/or the protein levels of the cell adhesion molecule E-selectin (Sele), proinflammatory cytokine interleukin-6 (Il6), vasoconstrictor endothelin-1 (Edn1), and endothelial nitric oxide synthase (Nos3; Nos3) were evaluated, along with advanced glycation end product immunoreactivity. Furthermore, an islet endothelial cell line (MS-1) was exposed to diabetic factors (glucose, palmitate, insulin, and tumor necrosis factor-α) for six days. Conditioned media were collected from these cells, incubated with isolated islets, and glucose-stimulated insulin secretion and insulin content were assessed. Islet endothelial cells from db/db mice exhibited increased Sele, Il6, and Edn1 mRNA levels, decreased Nos3 protein, and accumulation of advanced glycation end products. Phlorizin treatment significantly increased Nos3 protein levels but did not alter expression of the other markers. High-fat feeding in C57BL/6J mice resulted in increased islet Sele, Il6, and Edn1 but no change in Nos3. Exposure of islets to conditioned media from MS-1 cells cultured in diabetic conditions resulted in a 50% decrease in glucose-stimulated insulin secretion and 30% decrease in insulin content. These findings demonstrate that, in diabetes, islet endothelial cells show evidence of a dysfunctional phenotype, which may contribute to loss of β-cell function. Copyright © 2017 by the Endocrine Society.

  13. 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

  14. 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

  15. 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.

  16. Metadiscourse markers in biological research articles and journal impact factor: Non-native writers vs. native writers.

    PubMed

    Gholami, Javad; Ilghami, Roghayeh

    2016-07-08

    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 frequency of these markers and Impact Factor (IF) of journals as an index of quality. Moreover, it aimed at finding out the difference(s) between two groups of authors (Iranian and American) in their use of these markers. Forty biological RAs published in years 2008-2011 written by Iranian non-native authors and published in four ISI journals with different IFs and 40 articles with the same characteristics published by American native authors were selected and examined for the use of the markers. The results showed that there was a strong positive correlation between the frequency of MDMs and IF of the journals. Regarding the frequency of MDMs, it was observed that Iranian authors employed interactive and interactional markers slightly more than their American counterparts. These results may provisionally confirm the considerable role of MDMs in enhancing the coherence and organization of articles for possible publication in high-impact journals. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):349-360, 2016.

  17. HMOX1 as a marker of iron excess-induced adipose tissue dysfunction, affecting glucose uptake and respiratory capacity in human adipocytes.

    PubMed

    Moreno-Navarrete, José María; Ortega, Francisco; Rodríguez, Amaia; Latorre, Jèssica; Becerril, Sara; Sabater-Masdeu, Mònica; Ricart, Wifredo; Frühbeck, Gema; Fernández-Real, José Manuel

    2017-05-01

    Iron excess in adipose tissue is known to promote adipose tissue dysfunction. Here, we aimed to investigate the possible role of haem oxygenase 1 (HMOX1) in iron excess-induced adipose tissue dysfunction. Cross-sectionally, HMOX1 gene expression in subcutaneous and visceral adipose tissue was analysed in two independent cohorts (n = 234 and 40) in relation to obesity. We also evaluated the impact of weight loss (n = 21), weight gain (in rats, n = 20) on HMOX1 mRNA; HMOX1 mRNA levels during human adipocyte differentiation; the effects of inflammation and iron on adipocyte HMOX1; and the effects of HMOX1-induced activity on adipocyte mitochondrial respiratory function, glucose uptake and adipogenesis. Adipose tissue HMOX1 was increased in obese participants (p = 0.01) and positively associated with obesity-related metabolic disturbances, and markers of iron accumulation, inflammation and oxidative stress (p < 0.01). HMOX1 was negatively correlated with mRNAs related to mitochondrial biogenesis, the insulin signalling pathway and adipogenesis (p < 0.01). These associations were replicated in an independent cohort. Bariatric surgery-induced weight loss led to reduced HMOX1 (0.024 ± 0.010 vs 0.010 ± 0.004 RU, p < 0.0001), whereas in rats, high-fat diet-induced weight gain resulted in increased Hmox1 mRNA levels (0.22 ± 0.15 vs 0.54 ± 0.22 RU, p = 0.005). These changes were in parallel with changes in BMI and adipose tissue markers of iron excess, adipogenesis and inflammation. In human adipocytes, iron excess and inflammation led to increased HMOX1 mRNA levels. HMOX1 induction (by haem arginate [hemin] administration), resulted in a significant reduction of mitochondrial respiratory capacity (including basal respiration and spare respiratory capacity), glucose uptake and adipogenesis in parallel with increased expression of inflammatory- and iron excess-related genes. HMOX1 is an important marker of iron excess

  18. Concurrent use of REM latency, dexamethasone suppression, clonidine, and apomorphine tests as biological markers of endogenous depression: a pilot study.

    PubMed

    Ansseau, M; Scheyvaerts, M; Doumont, A; Poirrier, R; Legros, J J; Franck, G

    1984-07-01

    In a sample of 12 major depressive inpatients, endogenous subtype (8 primary and 4 secondary) defined by Research Diagnostic Criteria, we compared the sensitivity of four potential biological markers: latency of rapid eye movement (REM) sleep (recorded during at least 4 consecutive nights), dexamethasone suppression, and the clonidine and apomorphine tests. Shortened REM latency (less than 50 minutes during at least 1 night) identified 67% of depressives (87% of primary and 25% of secondary); nonsuppression after dexamethasone identified 50% of depressives (62% of primary and 25% of secondary); blunted growth hormone (GH) response after clonidine identified 75% of depressives (100% of primary and 25% of secondary); and blunted GH response after apomorphine identified 42% of depressives (62% of primary and 0% of secondary). Ninety-two percent of patients were correctly identified by at least one biological marker (100% of primary and 75% of secondary depressives). Of 67% of patients positive on at least two biological markers, all were primary depressives (100%). These four biological markers do not necessarily identify the same population, suggesting that their concurrent use may yield the highest level of diagnostic sensitivity.

  19. 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…

  20. 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…

  1. N-Acetylaspartate, a marker of both cellular dysfunction and neuronal loss: its relevance to studies of acute brain injury.

    PubMed

    Demougeot, C; Garnier, P; Mossiat, C; Bertrand, N; Giroud, M; Beley, A; Marie, C

    2001-04-01

    To evaluate the contribution of cellular dysfunction and neuronal loss to brain N-acetylaspartate (NAA) depletion, NAA was measured in brain tissue by HPLC and UV detection in rats subjected to cerebral injury, associated or not with cell death. When lesion was induced by intracarotid injection of microspheres, the fall in NAA was related to the degree of embolization and to the severity of brain oedema. When striatal lesion was induced by local injection of malonate, the larger the lesion volume, the higher the NAA depletion. However, reduction of brain oedema and striatal lesion by treatment with the lipophilic iron chelator dipyridyl (20 mg/kg, 1 h before and every 8 h after embolization) and the inducible nitric oxide synthase inhibitor aminoguanidine (100 mg/kg given 1 h before malonate and then every 9 h), respectively, failed to ameliorate the fall in NAA. Moreover, after systemic administration of 3-nitropropionic acid, a marked reversible fall in NAA striatal content was observed despite the lack of tissue necrosis. Overall results show that cellular dysfunction can cause higher reductions in NAA level than neuronal loss, thus making of NAA quantification a potential tool for visualizing the penumbra area in stroke patients.

  2. Preservation of Biological Markers in Clasts Within Impact Melt Breccias from the Haughton Impact Structure, Devon Island

    NASA Astrophysics Data System (ADS)

    Lindgren, Paula; Parnell, John; Bowden, Stephen; Taylor, Colin; Osinski, Gordon R.; Lee, Pascal

    2009-05-01

    The 39±2 Ma Haughton impact structure on Devon Island comprises a thick target succession of sedimentary rocks, mainly carbonates. The carbonates contain pre-impact organic matter, including fossil biological markers. Haughton is located in an area where no major thermal event has affected the sedimentary succession after heating caused by impact. This makes Haughton uniquely suitable for studies concerning the preservation of fossil biological markers following an impact event. Melt breccia is the most common impactite at Haughton. It is composed of clasts of the target, mainly carbonates, embedded in a fine groundmass. The groundmass is composed of material that was melted during impact. In this study, fssil biological marker maturity p arameters (tricyclic terpane-hopane ratio and pregnane-sterane ratio) and an aromatic maturity parameter [methylphenanthrene ratio (MPR)] were used to c ompare the degree of thermal alteration in different size fractions of carbonate clasts (<0.5-4 cm in diameter) and between edges and centers of large carbonate clasts (15â-20 cm in diameter). The data show that fossil biological markers can be preserved and detected in isolated large and small fractions of carbonate clasts that are embedded in an impact melt. The results also indicate that there is a thermal gradient from the center of a clast to the edge of a clast, which suggests that biological markers are more likely to be found preserved in the center of a clast. The thermal maturity values point to a higher degree of thermal alteration in the melt breccia carbonate clasts than in the coherent carbonate bedrock.

  3. Do biologic markers predict cardiovascular end points in diabetic end-stage renal disease? A prospective longitudinal study

    PubMed Central

    Bayliss, George P.; Weinrauch, Larry A.; Gleason, Ray E.; Lee, Annette T.; D'Elia, John A.

    2013-01-01

    Background Diabetic patients on hemodialysis are at high risk of death from cardiovascular disease, and research has suggested that various biologic markers of inflammation, oxidative stress and hemostasis may give added value to clinical information for predicting cardiovascular event (CVE)-free survival. This information could be particularly important in evaluating this population for renal transplant, given the scarcity of organs. We hypothesized that in diabetic patients undergoing renal replacement therapy (RRT) these biologic markers would prove useful in predicting event-free follow-up in a prospective study. Methods One hundred and fifty diabetic (76 type 1, 74 type 2) and 27 non-diabetic stable RRT patients were followed for 0.04–13.69 years for CVE (myocardial infarction, coronary arterial intervention, peripheral arterial bypass or amputation, cerebrovascular accident or carotid artery intervention), cardiac and all-cause mortality. Measured biologic markers of inflammation included the following: Il-6, C reactive protein, fibrinogen; of hemostasis: fibrinogen, plasminogen activator inhibitor (PAI), fibrinolytic activity, von Willebrand factor VII (vWF), platelet-selectin, viscosity and of oxidative stress: advanced glycated end products and antibody to oxidized low-density lipoprotein. For each, upper versus lower tertiles were compared for duration of event-free follow-up. Results Cardiovascular events prior to study entry occurred in 51.3% of DM1, 54.0% of DM2 and 25.9% of DM0 patients. Subsequent cardiovascular events were noted in 31.6% of DM1, 45.9% of DM2 and 11.1% of DM0 patients. All mean levels of biologic markers at baseline were abnormal (P < 0.05). Conclusions In this RRT population, all biologic marker levels except PAI did not improve clinical prediction of events. PMID:26069829

  4. 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

  5. Total and Phosphorylated Tau Protein as Biological Markers of Alzheimer's Disease

    PubMed Central

    Hampel, Harald; Blennow, Kaj; Shaw, Leslie M.; Hoessler, Yvonne C.; Zetterberg, Henrik; Trojanowski, John Q.

    2009-01-01

    Advances in our understanding of tau-mediated neurodegeneration in Alzheimer's disease (AD) are moving this disease pathway to center stage for the development of biomarkers and disease modifying drug discovery efforts. Immunoassays were developed detecting total (ttau) and tau phosphorylated at specific epitopes (p-tauX) in cerebrospinal fluid (CSF), methods to analyse tau in blood are at the experimental beginning. Clinical research consistently demonstrated CSF t- and p-tau increased in AD compared to controls. Measuring these tau species proved informative for classifying AD from relevant differential diagnoses. Tau phosphorylated at threonine 231 (p-tau231) differentiated between AD and frontotemporal dementia, tau phosphorylated at serine 181 (p-tau181) enhanced classification between AD and dementia with Lewy bodies. T- and p-tau are considered “core” AD biomarkers that have been successfully validated by controlled large-scale multi-center studies. Tau biomarkers are implemented in clinical trials to reflect biological activity, mechanisms of action of compounds, support enrichment of target populations, provide endpoints for proof-of-concept and confirmatory trials on disease modification. World-wide quality control initiatives are underway to set required methodological and protocol standards. Discussions with regulatory authorities gain momentum defining the role of tau biomarkers for trial designs and how they may be further qualified for surrogate marker status. PMID:19853650

  6. [Biological markers reflecting peripheral effects of thyroid hormones in autonomous thyroid adenoma].

    PubMed

    Földes, J; Németh, J; Bános, C; Tarján, G; Büki, B

    1991-09-08

    In some patients with functioning thyroid autonomous nodules preclinical hyperthyroidism is detected. It is important to know, whether in this intermediate clinical state beside the suppression of pituitary TSH secretion other target organs are also affected by serum free-thyroxine and free-triiodothyronine levels still within the normal range. Determining some sensitive, but not specific biologic markers reflecting the impact of thyroid hormones at the peripheral tissue level, it was demonstrated that in the group of preclinical hyperthyroidism the mean level of plasma fibronectin exceeded that of the controls (mean +/- S. D.: 583.5 +/- 163.9 vs. 424.2 +/- 84.1 micrograms/ml, p less than 0.001), serum procollagen-III-peptide concentration was already significantly raised, though its value was still within the normal range (mean +/- S. D.: 0.73 +/- 0.17 vs. 0.57 +/- 0.16 U/ml, p less than 0.05), conversely, mean sex-hormone binding globulin level was the same as in euthyroid controls (mean +/- S. D. 47.4 +/- 18.2 vs. 48.3 +/- 16.3 nmol/l). The value of all three parameters was significantly elevated in patients with toxic nodular goiter. Based on the results of this study "tissue"-thyrotoxicosis is suspected in some patients with preclinical hyperthyroidism, which may have therapeutical implications.

  7. Beverage-specific effects of ethanol consumption on its biological markers.

    PubMed

    Sakutata, Hidenari; Suzuki, Takashi; Yasuda, Hiroko; Ito, Teizo

    2008-01-01

    Serum gamma-glutamyltransferase (GGT) and erythrocyte mean corpuscular volume (MCV) are well-known biological markers of excessive ethanol consumption. The beverage-specific effects of ethanol consumption on GGT level and MCV value were analyzed cross-sectionally and retrospectively among middle-aged Japanese men who underwent a retirement health checkup (n = 974). Both the consumption of distilled alcohol and that of fermented alcohol positively correlated with the logarithm of GGT [standard regression coefficient (beta) 0.261 and 0.174, respectively]. The prevalence rate of elevated GGT levels > or = 70 IU/L) was higher among heavy drinkers of distilled alcohol than among heavy drinkers of fermented alcohol (38.8% vs. 27.6%, p = 0.013). The MCV value correlated with distilled alcohol consumption (beta: 0.212, p < 0.0001) but not with fermented alcohol consumption (beta: 0.043, not significant). The prevalence rate of an elevated MCV (> or = 97 fL) was higher among heavy drinkers of distilled alcohol than among heavy drinkers of fermented alcohol (35.3% vs. 16.8%, p < 0.001). These results suggest that MCV is less sensitive for detecting heavy consumption of fermented alcohol than for detecting that of distilled alcohol in apparently healthy middle-aged men.

  8. Body mass index is associated with biological CSF markers of core brain pathology of Alzheimer's disease.

    PubMed

    Ewers, Michael; Schmitz, Susanne; Hansson, Oskar; Walsh, Cathal; Fitzpatrick, Annette; Bennett, David; Minthon, Lennart; Trojanowski, John Q; Shaw, Leslie M; Faluyi, Yetunde O; Vellas, Bruno; Dubois, Bruno; Blennow, Kaj; Buerger, Katharina; Teipel, Stefan J; Weiner, Michael; Hampel, Harald

    2012-08-01

    Weight changes are common in aging and Alzheimer's disease (AD) and postmortem findings suggest a relation between lower body mass index (BMI) and increased AD brain pathology. In the current multicenter study, we tested whether lower BMI is associated with higher core AD brain pathology as assessed by cerebrospinal fluid (CSF)-based biological markers of AD in 751 living subjects: 308 patients with AD, 296 subjects with amnestic mild cognitive impairment (MCI), and 147 elderly healthy controls (HC). Based upon a priori cutoff values on CSF concentration of total tau and beta-amyloid (Aβ(1-42)), subjects were binarized into a group with abnormal CSF biomarker signature (CSF+) and those without (CSF-). Results showed that BMI was significantly lower in the CSF+ when compared with the CSF- group (F = 27.7, df = 746, p < 0.001). There was no interaction between CSF signature and diagnosis or apolipoprotein E (ApoE) genotype. In conclusion, lower BMI is indicative of AD pathology as assessed with CSF-based biomarkers in demented and nondemented elderly subjects.

  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. Transesophageal Echocardiography, 3-Dimensional and Speckle Tracking Together as Sensitive Markers for Early Outcome in Patients With Left Ventricular Dysfunction Undergoing Cardiac Surgery.

    PubMed

    Kumar, Alok; Puri, Goverdhan Dutt; Bahl, Ajay

    2017-10-01

    Speckle tracking, when combined with 3-dimensional (3D) left ventricular ejection fraction, might prove to be a more sensitive marker for postoperative ventricular dysfunction. This study investigated early outcomes in a cohort of patients with left ventricular dysfunction undergoing cardiac surgery. Prospective, blinded, observational study. University hospital; single institution. The study comprised 73 adult patients with left ventricular ejection fraction <50% undergoing cardiac surgery using cardiopulmonary bypass. Routine transesophageal echocardiography before and after bypass. Global longitudinal strain using speckle tracking and 3D left ventricular ejection fraction were computed using transesophageal echocardiography. Mean prebypass global longitudinal strain and 3D left ventricle ejection fraction were significantly lower in patients with postoperative low-cardiac-output syndrome compared with patients who did not develop low cardiac output (global longitudinal strain -7.5% v -10.7% and 3D left ventricular ejection fraction 29% v 39%, respectively; p < 0.0001). The cut-off value of global longitudinal strain predicting postoperative low-cardiac-output syndrome was -6%, with 95% sensitivity and 68% specificity; and 3D left ventricular ejection fraction was 19% with 98% sensitivity and 81% specificity. Preoperative left ventricular global longitudinal strain (-6%) and 3D left ventricular ejection fraction (19%) together could act as predictor of postoperative low-cardiac-output states with high sensitivity (99.9%) in patients undergoing cardiac surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. 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.

  12. Infant Nutritional Status and Markers of Environmental Enteric Dysfunction are Associated with Midchildhood Anthropometry and Blood Pressure in Tanzania.

    PubMed

    Locks, Lindsey M; Mwiru, Ramadhani S; Mtisi, Expeditho; Manji, Karim P; McDonald, Christine M; Liu, Enju; Kupka, Roland; Kisenge, Rodrick; Aboud, Said; Gosselin, Kerri; Gillman, Matthew; Gewirtz, Andrew T; Fawzi, Wafaie W; Duggan, Christopher P

    2017-08-01

    To assess whether growth and biomarkers of environmental enteric dysfunction in infancy are related to health outcomes in midchildhood in Tanzania. Children who participated in 2 randomized trials of micronutrient supplements in infancy were followed up in midchildhood (4.6-9.8 years of age). Anthropometry was measured at age 6 and 52 weeks in both trials, and blood samples were available from children at 6 weeks and 6 months from 1 trial. Linear regression was used for height-for-age z-score, body mass index-for-age z-score, and weight for age z-score, and blood pressure analyses; log-binomial models were used to estimate risk of overweight, obesity, and stunting in midchildhood. One hundred thirteen children were followed-up. Length-for-age z-score at 6 weeks and delta length-for-age z-score from 6 to 52 weeks were associated independently and positively with height-for-age z-score and inversely associated with stunting in midchildhood. Delta weight-for-length and weight-for-age z-score were also positively associated with midchildhood height-for-age z-score. The 6-week and delta weight-for-length z-scores were associated independently and positively with midchildhood body mass index-for-age z-score and overweight, as was the 6-week and delta weight-for-age z-score. Delta length-for-age z-score was also associated with an increased risk of overweight in midchildhood. Body mass index-for-age z-score in midchildhood was associated positively with systolic blood pressure. Serum anti-flagellin IgA concentration at 6 weeks was also associated with increased blood pressure in midchildhood. Anthropometry at 6 weeks and growth in infancy independently predict size in midchildhood, while anti-flagellin IgA, a biomarker of environmental enteric dysfunction, in early infancy is associated with increased blood pressure in midchildhood. Interventions in early life should focus on optimizing linear growth while minimizing excess weight gain and environmental enteric

  13. Untethering the Nuclear Envelope and Cytoskeleton: Biologically Distinct Dystonias Arising from a Common Cellular Dysfunction

    PubMed Central

    Atai, Nadia A.; Ryan, Scott D.; Kothary, Rashmi; Breakefield, Xandra O.; Nery, Flávia C.

    2012-01-01

    Most cases of early onset DYT1 dystonia in humans are caused by a GAG deletion in the TOR1A gene leading to loss of a glutamic acid (ΔE) in the torsinA protein, which underlies a movement disorder associated with neuronal dysfunction without apparent neurodegeneration. Mutation/deletion of the gene (Dst) encoding dystonin in mice results in a dystonic movement disorder termed dystonia musculorum, which resembles aspects of dystonia in humans. While torsinA and dystonin proteins do not share modular domain architecture, they participate in a similar function by modulating a structural link between the nuclear envelope and the cytoskeleton in neuronal cells. We suggest that through a shared interaction with the nuclear envelope protein nesprin-3α, torsinA and the neuronal dystonin-a2 isoform comprise a bridge complex between the outer nuclear membrane and the cytoskeleton, which is critical for some aspects of neuronal development and function. Elucidation of the overlapping roles of torsinA and dystonin-a2 in nuclear/endoplasmic reticulum dynamics should provide insights into the cellular mechanisms underlying the dystonic phenotype. PMID:22611399

  14. Brain natriuretic peptide as a potential novel marker of salt-sensitivity in chronic kidney disease patients without cardiac dysfunction.

    PubMed

    Hayashi, Mutsuharu; Yasuda, Yoshinari; Suzuki, Susumu; Tagaya, Manaka; Ito, Takehiro; Kamada, Tomohito; Yoshinaga, Masataka; Sugishita, Yoshinori; Fujiwara, Wakaya; Yokoi, Hiroatsu; Ozaki, Yukio; Izawa, Hideo

    2017-03-01

    Although the renin-angiotensin system (RAS) is counter-balanced by a salt-sensitive mechanism in the hypertensive state, both are reported to be up-regulated in chronic kidney disease (CKD) patients. We conducted this study to evaluate the associations among the RAS, renal function, hypertension, and atherosclerosis, as well as to identify markers for salt-sensitivity. A total of 213 pre-dialysis CKD patients with preserved cardiac function (EF >50 %) were enrolled. Their renal and cardiac biochemical markers and plasma renin activity (PRA) were measured, and echocardiography and carotid artery ultrasound were performed. Their salt intake was estimated by the NaCl excretion from a 24-h collected urine sample. The PRA was higher in patients with hypertension (p = 0.018), and had a significant negative correlation with the eGFR (r = -0.23, p = 0.0067). Importantly, the PRA had a strong negative correlation with the brain natriuretic peptide (BNP) level (r = -0.28, p = 0.017) regardless of whether the patients were being treated with RAS inhibitors. The BNP level was related to the renal functions (eGFR: p = 0.001, ACR: p = 0.009). There was a significant positive correlation between the BNP level and carotid intima-media thickness (p < 0.001). A multivariate analysis revealed that older age and an excess of NaCl excretion were independent predictors of BNP elevation (p = 0.02 and 0.003, respectively). Our analysis revealed details of the counterbalance between BNP and PRA, as well as identifying that excess salt intake is a predictor of BNP elevation. These results indicate that the BNP could be a possible valuable marker for salt sensitivity, and that high salt sensitivity could facilitate atherosclerosis in CKD patients.

  15. Decreased high-density lipoprotein cholesterol level is an early prognostic marker for organ dysfunction and death in patients with suspected sepsis.

    PubMed

    Cirstea, Mihai; Walley, Keith R; Russell, James A; Brunham, Liam R; Genga, Kelly R; Boyd, John H

    2017-04-01

    We sought to determine whether an early high-density lipoprotein cholesterol (HDL-C) measurement at emergency department (ED) admission is prognostic of multiorgan dysfunction syndrome (MODS) and death in a suspected sepsis cohort. Two hundred patients with clinically suspected sepsis were recruited at admission to our tertiary care hospital's ED. Lipids were measured at the time of first ED blood draw. Clinical data were collected via chart review. Primary outcomes of interest were development of MODS and 28-day mortality. Secondary outcomes included need for critical care, single-organ failures, days alive and free of vasopressor and ventilator support, and 90-day mortality. High-density lipoprotein cholesterol was greatly decreased in patients who developed MODS and/or died and remained stable over the first week of admission. Receiver operator characteristic analysis demonstrated that HDL-C had superior predictive ability compared with all routine clinical markers for both development of MODS and 28-day mortality, and identified an HDL-C cutoff of 25.1 mg/dL below which patients were at significantly greater risk for development of all adverse outcomes. Plasma HDL-C level was characterized by early decrease and high stability, and was the best prognostic marker for adverse outcomes in a suspected sepsis cohort. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Disrupted Signaling through the Fanconi Anemia Pathway Leads to Dysfunctional Hematopoietic Stem Cell Biology: Underlying Mechanisms and Potential Therapeutic Strategies

    PubMed Central

    Geiselhart, Anja; Lier, Amelie; Walter, Dagmar; Milsom, Michael D.

    2012-01-01

    Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome. FA patients suffer to varying degrees from a heterogeneous range of developmental defects and, in addition, have an increased likelihood of developing cancer. Almost all FA patients develop a severe, progressive bone marrow failure syndrome, which impacts upon the production of all hematopoietic lineages and, hence, is thought to be driven by a defect at the level of the hematopoietic stem cell (HSC). This hypothesis would also correlate with the very high incidence of MDS and AML that is observed in FA patients. In this paper, we discuss the evidence that supports the role of dysfunctional HSC biology in driving the etiology of the disease. Furthermore, we consider the different model systems currently available to study the biology of cells defective in the FA signaling pathway and how they are informative in terms of identifying the physiologic mediators of HSC depletion and dissecting their putative mechanism of action. Finally, we ask whether the insights gained using such disease models can be translated into potential novel therapeutic strategies for the treatment of the hematologic disorders in FA patients. PMID:22675615

  17. Erectile dysfunction.

    PubMed

    Wylie, Kevan

    2008-01-01

    Erectile dysfunction is a common problem affecting sexual function in men. Approximately one in 10 men over the age of 40 is affected by this condition and the incidence is age related. Erectile dysfunction is a sentinel marker for several reversible conditions including peripheral and coronary vascular disease, hypertension and diabetes mellitus. Endothelial dysfunction is a common factor between the disease states. Concurrent conditions such as depression, late-onset hypogonadism, Peyronie's disease and lower urinary tract symptoms may significantly worsen erectile function, other sexual and relationship issues and penis dysmorphophobia. A focused physical examination and baseline laboratory investigations are mandatory. Management consists of initiating modifiable lifestyle changes, psychological and psychosexual/couples interventions and pharmacological and other interventions. In combination and with treatment of concurrent comorbid states, these interventions will often bring about successful resolution of symptoms and avoid the need for surgical interventions.

  18. Biologic markers in hospital workers exposed to low levels of ethylene oxide.

    PubMed

    Schulte, P A; Boeniger, M; Walker, J T; Schober, S E; Pereira, M A; Gulati, D K; Wojciechowski, J P; Garza, A; Froelich, R; Strauss, G

    1992-04-01

    Operators of hospital sterilizers that use ethylene oxide were studied to determine if there was a relationship between exposure and a battery of biological markers. A total of 73 workers from nine hospitals in the United States (U.S.) and one hospital in Mexico City was evaluated for ethylene oxide exposure during four months prior to collection of peripheral blood. The frequency of hemoglobin adducts (p = 0.0006) and sister-chromatid exchanges (SCEs) (p = 0.002) increased with cumulative exposure to ethylene oxide in U.S. subjects when controlling by regression analysis for various confounding factors, including cigarette smoking. Hemoglobin adducts, but not SCEs, were also increased in Mexican subjects (p = 0.0012). Chromosomal micronuclei showed no consistent relationship with exposure. The U.S. study participants were classified by four-month cumulative exposure levels of 10 ppm-h (n = 8), greater than 0 to 32 ppm-h (n = 32) and greater than 32 ppm-h (n = 11) of ethylene oxide exposure. The group with an exposure of greater than 32 ppm-h had an increased frequency of hemoglobin adducts (p = 0.002) and SCEs (p = 0.0001) compared to the nonexposed group. The estimated mean of the 8-h time-weighted average (8-h TWA) exposure levels for the highest U.S. exposure group (greater than 32 ppm-h) was 0.16 +/- 0.007 ppm (mean +/- SD). A similar exposure-related differential was observed in the Mexican subjects for hemoglobin adducts (p = 0.04) but not for SCEs. The latter finding may have been due to longer shipping times for the specimens in the cytogenetic assays. The estimated mean of the 8-h TWA exposure levels for the highest Mexican exposure group (greater than 32 ppm-h) was 0.48 +/- 0.08 ppm. This study is the third to suggest that exposures less than the U.S. OSHA standard of 1 ppm 8-h TWA result in biochemical and biologic changes. It is not known whether these changes may be indicative of increased risk of disease; however, they do appear to reflect exposure

  19. The serum zinc concentration as a potential biological marker in patients with major depressive disorder.

    PubMed

    Styczeń, Krzysztof; Sowa-Kućma, Magdalena; Siwek, Marcin; Dudek, Dominika; Reczyński, Witold; Szewczyk, Bernadeta; Misztak, Paulina; Topór-Mądry, Roman; Opoka, Włodzimierz; Nowak, Gabriel

    2017-02-01

    Despite many clinical trials assessing the role of zinc in major depressive disorder (MDD), the conclusions still remain ambiguous. The aim of the present clinical study was to determine and comparison the zinc concentration in the blood of MDD patients (active stage or remission) and healthy volunteers (controls), as well as to discuss its potential clinical usefulness as a biomarker of the disease. In this study 69 patients with current depressive episode, 45 patients in remission and 50 controls were enrolled. The zinc concentration was measured by electrothermal atomic absorption spectrometry (ET AAS). The obtained results revealed, that the zinc concentration in depressed phase were statistically lower than in the healthy volunteers [0.89 vs. 1.06 mg/L, respectively], while the zinc level in patients achieve remission was not significantly different from the controls [1.07 vs. 1.06 mg/L, respectively]. Additionally, among the patients achieve remission a significant differences in zinc concentration between group with and without presence of drug-resistance in the previous episode of depression were observed. Also, patients in remission demonstrated correlation between zinc level and the average number of depressive episodes in the last year. Serum zinc concentration was not dependent on atypical features of depression, presence of psychotic symptoms or melancholic syndrome, age, age of onset or duration of disease, number of episodes in the life time, duration of the episode/remission and severity of depression measured by the Hamilton Rating Scale for Depression (HDRS), and the Montgomery-Asberg Depression Rating Scale (MADRS). Concluding, our findings confirm the correlation between zinc deficit present in the depressive episode, and are consistent with the majority of previous studies. These results may also indicate that serum zinc concentration might be considered as a potential biological marker of MDD.

  20. Association of physical activity and sedentary behavior with biological markers among U.S. pregnant women.

    PubMed

    Loprinzi, Paul D; Fitzgerald, Elizabeth M; Woekel, Erica; Cardinal, Bradley J

    2013-11-01

    To examine the association between objectively measured light-intensity and moderate-to-vigorous-intensity physical activity (MVPA), sedentary behaviors, and biological markers in a national sample of U.S. pregnant women, as few studies have examined these relationships among this population. The sample of noninstitutionalized U.S. civilians was selected by a complex, multistage probability design. Data from the 2003-2006 National Health and Examination Survey were used. Two hundred six pregnant women were included in the data analysis. Physical activity and sedentary data were objectively measured via accelerometry (ActiGraph 7164). Biomarker data was obtained in the mobile examination center from urine, blood samples, blood pressure, and anthropometric measurements. Urine and blood samples were obtained to determine pregnancy status, C-reactive protein (CRP), high-density lipoprotein (HDL) cholesterol, total cholesterol, and cotinine as well as fasting glucose, fasting triglycerides, and fasting low-density lipoprotein (LDL) cholesterol data. Multivariable regression was employed to examine the association between physical activity, sedentary behavior, and biomarker levels. There was a positive association between sedentary behavior and CRP levels (beta coefficient [b]=0.001, p=0.02) and LDL cholesterol (b=0.12, p=0.02). There was an inverse association between light-intensity physical activity and CRP (b=-0.003; p=0.008) and diastolic blood pressure (b=-0.03; p=0.02), with those engaging in higher levels of MVPA having higher HDL cholesterol (b=6.7; p=0.01). Physical activity and sedentary behavior were favorably associated with various biomarkers among pregnant women, suggesting that healthcare providers should encourage pregnant women to participate in safe forms of physical activity behaviors while also reducing their amount of time spent in sedentary behaviors.

  1. Neuroglobin - a potential biological marker of retinal damage induced by LED light.

    PubMed

    Yu, Z-L; Qiu, S; Chen, X-C; Dai, Z-H; Huang, Y-C; Li, Y-N; Cai, R-H; Lei, H-T; Gu, H-Y

    2014-06-13

    Neuroglobin (NGB), a protein highly expressed in the retina, has been shown to be up-regulated to protect neurons from hypoxic and ischemic injuries. It exhibits neuroprotective functions and plays an important role in the survival of neurons. Recent studies show that light-emitting diode (LED) white light emitted significant amounts of blue light (short-wavelength), which may be harmful to retinal cells, but the studies about biomarkers for evaluating the damage from LED white light are still insufficient. In our study, we found that NGB levels in the retina showed a twofold increase and peaked at 1h after a 1-h exposure to blue light (453 nm) which did not cause damage to the retina. However, retinal damage was observed after 2h of blue-light irradiation, which induced an approximate sevenfold increase of NGB levels as confirmed by Western blot and RT-PCR analysis. Immunofluorescence study demonstrated that NGB was predominantly up-regulated in the ganglion cell layer (GCL), plexiform layer (PL) and photoreceptor layer (PRL). We also examined Ngb mRNA and protein expression in the damaged retina induced by light of other wavelengths given equal photon fluxes. The LED red light (625 nm), green light (527 nm) and blue light (453 nm) increased the expression of NGB and caused TdT-mediated dUTP nick-end labeling-positive cells, especially in the blue-light group. In addition, a negative correlation between NGB and rhodopsin was observed. These findings suggested that there was a correlation between NGB expression and the severity of the retinal damage, indicating NGB's potential function as a biological marker of retinal damage induced by LED light. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. 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

  3. Airway symptoms and biological markers in nasal lavage fluid in subjects exposed to metalworking fluids.

    PubMed

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

    2013-01-01

    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. 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. 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. 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.

  4. 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.

  5. THE IMPACT OF MODE OF ACQUISITION ON BIOLOGICAL MARKERS OF PAEDIATRIC HEPATITIS C VIRUS INFECTION

    PubMed Central

    England, Kirsty; Thorne, Claire; Harris, Helen; Ramsay, Mary; Newell, Marie-Louise

    2012-01-01

    Background Despite the introduction of blood donor screening, worldwide, children continue to become infected with HCV via un-sterile medical injections, receipt of unscreened blood and isolated hospital contamination outbreaks. It is plausible that the natural history and disease progression in these children might differ from that of their vertically infected counterparts. Materials and Methods Vertically and parenterally HCV infected children were prospectively followed within the European Paediatric HCV Network and the UK National HCV Register respectively. Biological profiles were compared. Results Vertically and parenterally HCV infected children differed in terms of some key characteristics including the male:female ratio and the proportion of children receiving therapy. Parenterally infected children were more likely to have at least one hepatomegaly event during follow-up, 20% vs. 10%. Parenteral infection did not significantly affect the odds of being consistently viraemic, AOR 1.14 p=0.703 and there was no significant difference in the odds of having consistently elevated ALT levels and mode of acquisition, AOR 0.83 p=0.748. The proportion of children with 2 or more markers of HCV infection did not differ significantly by mode of acquisition, χ21.13 p=0.288. Conclusions This analysis does not support substantial differences between vertically and parenterally infected groups but there are specific mechanisms identified requiring further investigation. Given the continued parenteral infection of children worldwide it is vital that knowledge of disease progression in this group is accurate and that the differences in comparison to vertically infected children are clarified to inform more accurate and individualised clinical management. PMID:21762285

  6. 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

  7. Markers of left ventricular dysfunction induced by exercise, dipyridamole or combined stress on ECG-gated myocardial perfusion scans.

    PubMed

    Hurwitz, G A; O'Donoghue, J P; MacDonald, A C; Laurin, N R; Powe, J E

    1993-04-01

    An index of left ventricular contraction can be extracted from the cavitary time-activity curve of electrocardiographic (ECG)-gated myocardial perfusion scans. To assess the induction of stress-induced myocardial depression, we compared contraction indexes derived from immediate poststress and delayed 201Tl images with indexes of ventricular dilation and lung uptake in the prediction of severe coronary artery disease (defined as two or more 90% stenoses). Stress procedures were performed in 93 patients with symptom-limited supine bicycle exercise alone, and in 227 with intravenous dipyridamole, combined where possible with exercise. The immediate and delayed contraction indexes reflected left ventricular dysfunction on ventriculography (P < 0.0001), but additionally the immediate index was reduced (P < 0.0001) in severe coronary disease. Stress-induced hypokinesis was seen frequently after each of the test modes. The relationship with angiographic findings was better defined for indexes of contraction than for lung uptake or ventricular dilation (P < 0.01). The prediction of severe coronary disease was optimized by combining the poststress contraction index and lung uptake. These data support the use of ECG-gated myocardial scans in evaluating the functional consequences of stress/imaging procedures.

  8. Increased response variability as a marker of executive dysfunction in veterans with post-traumatic stress disorder.

    PubMed

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

    2013-12-01

    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 (ICV) and ex-Gaussian analysis of RT distributions. Despite having mean RTs that were indistinguishable from controls, the PTSD patients had significantly greater RT variability as measured by ICV. More variable RTs were in turn associated with a greater number of false alarm errors in the patients, 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 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. © 2013 Published by Elsevier Ltd.

  9. 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.

  10. 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

  11. Social and Behavioral Risk Marker Clustering Associated with Biological Risk Factors for Coronary Heart Disease: NHANES 2001–2004

    PubMed Central

    Everage, Nicholas J.; Linkletter, Crystal D.; Gjelsvik, Annie; McGarvey, Stephen T.; Loucks, Eric B.

    2014-01-01

    Background. Social and behavioral risk markers (e.g., physical activity, diet, smoking, and socioeconomic position) cluster; however, little is known whether clustering is associated with coronary heart disease (CHD) risk. Objectives were to determine if sociobehavioral clustering is associated with biological CHD risk factors (total cholesterol, HDL cholesterol, systolic blood pressure, body mass index, waist circumference, and diabetes) and whether associations are independent of individual clustering components. Methods. Participants included 4,305 males and 4,673 females aged ≥20 years from NHANES 2001–2004. Sociobehavioral Risk Marker Index (SRI) included a summary score of physical activity, fruit/vegetable consumption, smoking, and educational attainment. Regression analyses evaluated associations of SRI with aforementioned biological CHD risk factors. Receiver operator curve analyses assessed independent predictive ability of SRI. Results. Healthful clustering (SRI = 0) was associated with improved biological CHD risk factor levels in 5 of 6 risk factors in females and 2 of 6 risk factors in males. Adding SRI to models containing age, race, and individual SRI components did not improve C-statistics. Conclusions. Findings suggest that healthful sociobehavioral risk marker clustering is associated with favorable CHD risk factor levels, particularly in females. These findings should inform social ecological interventions that consider health impacts of addressing social and behavioral risk factors. PMID:24719858

  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.

  13. Markers of endothelial dysfunction and inflammation predict progression of diabetic nephropathy in African Americans with type 1 diabetes.

    PubMed

    Roy, Monique S; Janal, Malvin N; Crosby, Juan; Donnelly, Robert

    2015-02-01

    African Americans with early-onset type 1 diabetes mellitus are at a high risk for severe diabetic nephropathy and end-stage renal disease. In order to determine whether baseline plasma levels of inflammatory markers predict incidence of overt proteinuria or renal failure in African Americans with type 1 diabetes mellitus, we re-examined data of 356 participants in our observational follow-up study of 725 New Jersey African Americans with type 1 diabetes. At baseline and 6-year follow-up, a detailed structured clinical interview was conducted to document medical history including kidney dialysis or transplant, other diabetic complications, and renal-specific mortality. Plasma levels of 28 inflammatory biomarkers were measured using a multiplex bead analysis system. After adjusting for baseline age, glycohemoglobin, and other confounders, the baseline plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) in the upper two quartiles were, respectively, associated with a three- to fivefold increase in the risk of progression from no albuminuria or microalbuminuria to overt proteinuria. Baseline plasma levels of the chemokine eotaxin in the upper quartile were significantly associated with a sevenfold increase in risk of incident renal failure. These associations were independent of traditional risk factors for progression of diabetic nephropathy. Thus, in type 1 diabetic African Americans, sICAM-1 predicted progression to overt proteinuria and eotaxin-predicted progression to renal failure.

  14. Cognitive control dysfunction and abnormal frontal cortex activation in stimulant drug users and their biological siblings

    PubMed Central

    Smith, D G; Jones, P S; Bullmore, E T; Robbins, T W; Ersche, K D

    2013-01-01

    Cognitive and neural abnormalities are known to accompany chronic drug abuse, with impairments in cognition and changes in cortical structure seen in stimulant-dependent individuals. However, premorbid differences have also been observed in the brains and behavior of individuals at risk for substance abuse, before they develop dependence. Endophenotype research has emerged as a useful method for assessing preclinical traits that may be risk factors for pathology by studying patient populations and their undiagnosed first-degree relatives. This study used the color-word Stroop task to assess executive functioning in stimulant-dependent individuals, their unaffected biological siblings and unrelated healthy control volunteers using a functional magnetic resonance imaging paradigm. Both the stimulant-dependent and sibling participants demonstrated impairments in cognitive control and processing speed on the task, registering significantly longer response latencies. However, the two groups generated very different neural responses, with the sibling participants exhibiting a significant decrease in activation in the inferior frontal gyrus compared with both stimulant-dependent individuals and control participants. Both target groups also demonstrated a decrease in hemispheric laterality throughout the task, exhibiting a disproportionate increase in right hemispheric activation, which was associated with their behavioral inefficiencies. These findings not only suggest a possible risk factor for stimulant abuse of poor inhibitory control and cortical inefficiency but they also demonstrate possible adaptations in the brains of stimulant users. PMID:23673468

  15. Sexual dysfunction is frequent in premenopausal women with diabetes, obesity, and hypothyroidism, and correlates with markers of increased cardiovascular risk. A preliminary report.

    PubMed

    Veronelli, Annamaria; Mauri, Chiara; Zecchini, Barbara; Peca, Maria Grazia; Turri, Olivia; Valitutti, Maria Teresa; dall'Asta, Chiara; Pontiroli, Antonio E

    2009-06-01

    Female sexual dysfunction (FSD) is characterized by reduced sexual appetite and altered psychologic and physiologic response to sexual intercourse; it is reported to be frequent in diabetes mellitus, but no data have been reported in thyroid disorders. To compare the prevalence of FSD in diabetic, in obese, and in hypothyroid women vs. healthy women, and to correlate FSD with endocrine and metabolic profiles. We evaluated, through a questionnaire (Female Sexual Function Index [FSFI]), the prevalence of FSD in 91 women affected by diabetes mellitus, obesity, or hypothyroidism, and in 36 healthy women, all aged 22-51 years and in premenopausal state. FSFI score, endocrine and metabolic parameters (triglycerides, high-density lipoprotein [HDL] and low-density lipoprotein [LDL] cholesterol, free-triiodothyronine (FT3), free-thyroxine (FT4), thyroid stimulating hormone [TSH], 17-beta-estradiol, testosterone, glycated hemoglobin 1c (HbA1c), thyroid autoantibodies, E-selectin, P-selectin, intercellular adhesion molecule-1 [ICAM-1], plasminogen-activator inhibitor-1 [PAI-1]), and anthropometric parameters (body mass index, waist, blood pressure [BP]). A reduced FSFI score was more frequent in diabetic, obese, and hypothyroid women vs. healthy women (P < 0.01). In the different groups of women, FSFI score was inversely correlated (pairwise correlation) with at least one of the following: HbA1c, TSH, LDL-cholesterol, PAI-1, diastolic BP, presence of thyroid Ab, and directly correlated with HDL-cholesterol (always P < 0.05 or less). At stepwise regression analysis, HDL-cholesterol (protective) and HbA1c, LDL-cholesterol, PAI-1, and diastolic BP (negatively) predicted reduced FSFI score. These data indicate an increased prevalence of sexual dysfunction in diabetic, in obese, and in hypothyroid women, associated with markers of cardiovascular risk.

  16. 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

  17. Search for biological/genetic markers in a long-term epidemiological and morbid risk study of affective disorders.

    PubMed

    Fieve, R R; Go, R; Dunner, D L; Elston, R

    1984-01-01

    A long-term epidemiological genetic study was conducted in which all new patients were evaluated prospectively at the Foundation for Depression and Manic Depression and two Lithium/Affective Disorders clinics at the Columbia-Presbyterian Medical Center between the years of 1972 and 1978. All patients met Feighner, RDC and DSM III criteria for Major Depressive Disorder after initial clinical screening interviews and were further subtyped using the Fieve-Dunner 7-point criteria. All 604 probands and 90% of 2711 first-degree relatives were interviewed blindly by diagnosticians trained in the use of the SADS structured interview. Cumulative morbid risk in parents, siblings and children of 490 bipolar probands was 15.6 +/- 3% and 14.0 +/- 1.7% in the first-degree relatives of 114 unipolar probands. A number of biological and genetic marker studies were simultaneously performed on samples of the overall population. The enzymes catechol O-methyltransferase and dopamine beta-hydroxylase, and the dexamethasone suppression test (SDT) did not show any biological marker value for outpatients even though both enzymes were determined to have hereditability. The HLA system, monoamine oxidase and acetylcholinesterase segregated differently from normal controls in samples of the patient population. The positive association findings with monoamine oxidase and the HLA system conflicted with the positive findings of other investigators, leaving doubtful their biological marker value. Red cell acetylcholinesterase was found to be significantly lower in affective disorder patients than in controls. This positive association finding was recently replicated by Mathews et al. (1982) but needs further confirmation. Using 28 blood group markers, a prior association study between the trait defining susceptibility to affective disorder and the genetic marker was positive for haptoglobin GC, and properdinfactor B, confirming earlier findings. Using the sib-pair method on the remaining 25 blood

  18. Effects of spinach nitrate on insulin resistance, endothelial dysfunction markers and inflammation in mice with high-fat and high-fructose consumption

    PubMed Central

    Li, Ting; Lu, Xinshan; Sun, Yanfei; Yang, Xingbin

    2016-01-01

    Background Insulin resistance, which is associated with an increased risk of cardiovascular morbidity and mortality, has become a leading nutrition problem. Inorganic nitrate enriched in spinach has been demonstrated to reverse the pathological features of insulin resistance and endothelial dysfunction. However, the effects of a direct intake of nitrate-enriched spinach on insulin resistance and endothelial dysfunction have not been studied. Objective To investigate the effects of spinach nitrate on insulin resistance, lipid metabolism, endothelial function, and inflammation in mice fed with a high-fat and high-fructose diet. Design A diet intervention of spinach with or without nitrate was performed in mice. A high-fat and high-fructose diet was used to cause insulin resistance, endothelial dysfunction, and inflammation in mice. The impacts of spinach nitrate on lipid profile, insulin resistance, markers of endothelial function, and inflammation were determined in mice. Results Spinach nitrate improved the vascular endothelial function of the mice with high-fat and high-fructose consumption, as evidenced by the elevated plasma nitrite level, increased serum nitric oxide (NO) level and decreased serum ET-1 level after spinach nitrate intervention. Spinach nitrate also reduced serum triglycerides, total cholesterol, and low-density lipoprotein-cholesterol levels and elevated serum high-density lipoprotein-cholesterol levels in the mice fed with a high-fat and high-fructose diet. Mice receiving spinach with 60 mg/kg of nitrate (1.02±0.34) showed a significantly low homeostasis model assessment-insulin resistance index as compared with the model mice (2.05±0.58), which is indicating that spinach nitrate could effectively improve the insulin resistance. In addition, spinach nitrate remarkably decreased the elevated serum C-reactive protein, tumor necrosis factor α, and interleukin-6 levels induced by a high-fat and high-fructose diet. Conclusions The intake of

  19. ABO blood group associations with markers of endothelial dysfunction in the Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Larson, Nicholas B.; Bell, Elizabeth J.; Decker, Paul A.; Pike, Mindy; Wassel, Christina L.; Tsai, Michael Y.; Pankow, James S.; Tang, Weihong; Hanson, Naomi Q.; Alexander, Kristine; Zakai, Neil; Cushman, Mary; Bielinski, Suzette J.

    2016-01-01

    Background and aims ABO blood type is associated with cardiovascular disease, although the underlying mechanisms are presumed to be complex. While the relationship between non-O blood types and von Willebrand Factor (vWF) is well-established, associations with cellular adhesion molecules (CAMs) across diverse populations are understudied. Methods We genetically inferred ABO alleles for N=6202 participants from the Multi-Ethnic Study of Atherosclerosis. Linear regression was used to evaluate associations between major ABO allele dosages and log-transformed measurements of vWF (N=924), soluble E-selectin (sE-selectin, N=925), soluble P-selectin (sP-selectin, N=2392), and soluble ICAM-1 (sICAM-1, N=2236) by race/ethnicity. Results For the selectins, the A1 allele was associated with significantly lower levels for all races/ethnicities, with each additional allele resulting in a 28-39% decrease in sE-selectin and 10-18% decrease in sP-selectin relative to Type O subjects. However, the A2 allele demonstrated effect heterogeneity across race/ethnicity for sE-selectin, with lower levels for non-Hispanic whites (p=0.0011) but higher levels for Hispanics (p=0.0021). We also identified elevated sP-selectin levels for B-allele carriers solely in Hispanic participants (p=1.0E-04). ABO-by-race/ethnicity interactions were significant for both selectins (p <0.0125). More modest associations were observed between A1 allele dosage and levels of sICAM-1, with ABO alleles explaining 0.8-1.1% of the total phenotypic variation within race/ethnicity. ABO associations with vWF activity were consistent across race/ethnicity, with B allele carriers corresponding to the highest vWF activity levels. Conclusions ABO blood type demonstrates complex associations with endothelial markers that are largely generalizable across diverse populations. PMID:27298014

  20. 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.

  1. Markers of endothelial dysfunction and leucocyte activation in Saudi and non-Saudi haplotypes of sickle cell disease.

    PubMed

    Al Najjar, Salwa; Adam, Soheir; Ahmed, Nessar; Qari, Mohamed

    2017-01-01

    Sickle cell disease (SCD) is an autosomal recessive inherited hemoglobinopathy, characterized by chronic hemolysis and recurrent vaso-occlusive crisis (VOC). This study investigates changes in leucocyte subsets and the relationship between cell adhesion molecule expression and disease manifestations in patients during steady state and acute VOC. We compared soluble E-selectin and P-selectin levels in 84 SCD patients, in steady state and during VOC to 84 healthy controls. Using immunophenotyping, we also compared lymphocyte subsets in these three groups. Further, we compared E-selectin and P-selectin levels in patients of Saudi ethnicity to non-Saudi patients, in all three groups. Lymphocyte subsets showed high percentages of total T lymphocytes, T helper and suppressor lymphocytes, B lymphocytes as well as NK cells in patients with SCD during steady state, while B lymphocytes and NK cells were significantly higher during acute VOC crisis. High levels of both soluble E-selectin (sE-selectin) and soluble P-selectin (sP-selectin) markers were demonstrated in the serum of patients with SCD during both steady state and acute VOC. Levels of selectins were significantly higher in acute VOC. The immunophenotypic expression of L-selectin, on leucocytes, was high in SCD both during steady state and during acute VOC in comparison to normal control subjects. There was no significant difference in all three study groups between Saudi and non-Saudi patients. These findings suggest that patients with SCD have increased expression of adhesion molecules: E-selectin and P-selectin, which play an important role in the pathogenesis of VOC. Despite the distinct phenotype of Saudi patients with SCD, there was no significant difference in levels of soluble E-selectin and soluble P-selectin between Saudi and non-Saudi patients in all three groups. While sickle cell disease is a well-recognized state of chronic inflammation, the role of specific adhesion molecules is steadily unraveling

  2. Iron overload correlates with serum liver fibrotic markers and liver dysfunction: Potential new methods to predict iron overload-related liver fibrosis in thalassemia patients

    PubMed Central

    Wang, Man; Liu, Rongrong; Liang, Yuzhen; Yang, Gaohui; Huang, Yumei; Yu, Chunlan; Sun, Kaiqi; Xia, Yang

    2016-01-01

    Background Early detection of liver fibrosis in thalassemia patients and rapid initiation of treatment to interfere with its progression are extremely important. Objective This study aimed to find a sensitive, easy-to-detect and noninvasive method other than liver biopsy for early detection of liver fibrosis in thalassemia patients. Methods A total of 244 Chinese Thalassemia patients with non-transfusion-dependent thalassemia (NTDT, n = 105) or thalassemia major (TM, n = 139) and 120 healthy individuals were recruited into the present study, and blood collagen type IV (C IV), precollagen type III (PIIINPC) and hyaluronic acid (HA), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and ferritin were measured. Liver iron concentration was determined by MRI. The correlation of serum markers with liver iron load and liver function was evaluated. Results Serum C IV, PIIINPC and HA were significantly elevated in Chinese patients with NTDT and further elevated in TM patients. Moreover, C IV, PIIINPC and HA were also positively correlated to serum ferritin and liver iron concentration and further elevated during the progression to multi-organ damage in NTDT patients. Finally, serum ferritin and liver iron concentration were significantly correlated with liver dysfunction determined by AST and ALT. Conclusion Taken together, our results indicate that monitoring serum C IV, PIIINPC and HA is a potentially sensitive method to predict the risks for iron overload-related liver fibrosis in Chinese thalassemia patients. PMID:28405327

  3. Potential anti-inflammatory effects of maraviroc in HIV-positive patients: a pilot study of inflammation, endothelial dysfunction, and coagulation markers.

    PubMed

    Francisci, Daniela; Falcinelli, Emanuela; Baroncelli, Silvia; Petito, Eleonora; Cecchini, Enisia; Weimer, Liliana Elena; Floridia, Marco; Gresele, Paolo; Baldelli, Franco

    2014-06-01

    Persistent immune activation and chronic inflammation significantly contribute to non-AIDS morbidity in HIV-infected patients. The HIV inhibitor maraviroc (MVC) targets the cellular chemokine CCR5 HIV co-receptor, which is involved in important inflammatory pathways. MVC could have significant anti-inflammatory and anti-atherosclerotic effects, also reducing immune activation. We designed a pilot study to determine which plasma biomarkers of inflammation, endothelial dysfunction, and hypercoagulability were modified by MVC in 2 groups of 10 patients starting MVC-free or MVC-containing regimens. Ten age- and gender-matched healthy controls were also included. We found higher levels of all inflammatory biomarkers in HIV-infected patients compared to healthy controls. Both groups showed decreasing levels of interleukin (IL)-17, IL-10, and macrophage inflammatory protein (MIP)-1a following the achievement of viral suppression. Vascular cell adhesion molecule (VCAM)-1 levels were decreased in the MVC group and increased in the MVC-free group. In conclusion, some inflammatory biomarkers tend to decrease with the salvage regimen; MVC was not associated with a better impact on these measured markers.

  4. Biological effect markers in exhaled breath condensate and biomonitoring in welders: impact of smoking and protection equipment.

    PubMed

    Gube, Monika; Ebel, Joachim; Brand, Peter; Göen, Thomas; Holzinger, Karl; Reisgen, Uwe; Kraus, Thomas

    2010-10-01

    The objective of this study was to investigate the effect of welding as well as the impact of smoking and protection measures on biological effect markers in exhaled breath condensate. Additionally, biomonitoring of chromium, aluminium and nickel in urine was performed to quantify internal exposure. Exhaled breath condensate (EBC) and urine samples of 45 male welders and 24 male non-exposed control subjects were collected on Friday pre-shift and after 8 h of work post-shift. In EBC, biological effect markers such as malondialdehyde, nitrite, nitrate, 3-nitrotyrosine, tyrosine, hydroxyproline, proline, H(2)O(2) and pH-value were measured while aluminium, nickel, and chromium were measured in the urine samples. Although internal exposure to aluminium, nickel and chromium in this study was low, welders showed significantly increased concentrations of all these parameters at baseline compared to non-exposed controls. Moreover, welders had higher nitrate concentrations in EBC at baseline and after shift. Nitrate concentration was considerably lower after shift if personal protection equipment was used. H(2)O(2) was increased only when subjects smoked during shift. It has been shown that welding-associated long-term and short-term health effects could be detected in a population of welders. The results also showed that using personal protection equipment is of high importance and H(2)O(2) may be an effect marker associated with smoking rather than with welding fumes, while nitrate in EBC seems to be sensitive to welding fume exposure.

  5. Levels of matrix metalloproteinases differ in plasma and serum - aspects regarding analysis of biological markers in cancer.

    PubMed

    Jonsson, Andreas; Hjalmarsson, Claes; Falk, Peter; Ivarsson, Marie-Lois

    2016-09-06

    There are inconsistencies in the use of serum or plasma when analysing the matrix metalloproteinases (MMPs) as diagnostic or prognostic markers. The purpose of this study was to compare the concentration of MMP-1, -2, -7, -8, -9 and -13 in serum vs plasma samples. Blood samples were obtained from sixty-five men and women. Samples were analysed for levels of MMPs in corresponding citrate plasma and serum. All MMPs expressed higher concentration in serum compared with plasma (P<0.01). There were no differences between genders. Present study demonstrated significant differences regarding concentrations of some MMPs using plasma vs serum. We conclude that future studies regarding MMPs as biological markers in cancer should consider the use of citrate plasma instead of serum.

  6. 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.

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

    PubMed

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

    2016-01-01

    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. 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. 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). 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 to be dependent on the degree of insulin resistance and

  8. Biological and clinical markers in colorectal cancer: state of the art.

    PubMed

    Cappellani, Alessandro; Di Vita, Maria; Zanghi, Antonio; Veroux, Pierfrancesco; Cavallaro, Andrea; Lo Menzo, Emanuele; Cacopardo, Bruno; Canzonieri, Vincenzo; Murabito, Paolo; Tirelli, Umberto; Berretta, Massimiliano

    2010-01-01

    Colorectal cancer (CRC) is the World's third most common cancer. Its prognosis is closely related to the disease stage at the time of diagnosis. Here we review the role of clinical biomarkers (tissue, serum, and faecal) in the management of CRC. Molecular studies have recently widened the opportunity for testing new possible markers, but actually, only few markers can be recommended for practical use in clinic. In the next future the hope is to have a complete panel of clinical biomarkers to use in every setting of CRC disease, and at the same time: 1) to receive information about prognostic significance by their expression and 2) to be oriented in the choice of the adequate treatment.

  9. 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

  10. Elevated reward-related neural activation as a unique biological marker of bipolar disorder: assessment and treatment implications.

    PubMed

    Nusslock, Robin; Young, Christina B; Damme, Katherine S F

    2014-11-01

    Growing evidence indicates that risk for bipolar disorder is characterized by elevated activation in a fronto-striatal reward neural circuit involving the ventral striatum and orbitofrontal cortex, among other regions. It is proposed that individuals with abnormally elevated reward-related neural activation are at risk for experiencing an excessive increase in approach-related motivation during life events involving rewards or goal striving and attainment. In the extreme, this increase in motivation is reflected in hypomanic/manic symptoms. By contrast, unipolar depression (without a history of hypomania/mania) is characterized by decreased reward responsivity and decreased reward-related neural activation. Collectively, this suggests that risk for bipolar disorder and unipolar depression are characterized by distinct and opposite profiles of reward processing and reward-related neural activation. The objective of the present paper is threefold. First, we review the literature on reward processing and reward-related neural activation in bipolar disorder, and in particular risk for hypomania/mania. Second, we propose that reward-related neural activation reflects a biological marker of differential risk for bipolar disorder versus unipolar depression that may help facilitate psychiatric assessment and differential diagnosis. We also discuss, however, the challenges to using neuroscience techniques and biological markers in a clinical setting for assessment and diagnostic purposes. Lastly, we address the pharmacological and psychosocial treatment implications of research on reward-related neural activation in bipolar disorder.

  11. Predictive biological markers for response of invasive breast cancer to anthracycline/cyclophosphamide-based primary (radio-)chemotherapy.

    PubMed

    Prisack, Hans-Bernd; Karreman, Christiaan; Modlich, Olga; Audretsch, Werner; Danae, Mahmoud; Rezai, Mahadi; Bojar, Hans

    2005-01-01

    The role of biological markers for the prediction of neoadjuvant chemotherapy and radio-chemotherapy may be evaluated using pathological complete response [pCR] in patients with invasive breast cancer. To investigate this, pre-treatment biopsies from 517 patients with locally advanced breast cancer were analyzed for expression of estrogen receptor [ER], progesterone receptor [PgR], Her-2/neu, epidermal growth factor receptor [EGF-R], p53, Bcl-2 and MIB-1 by immunohistochemistry [IHC], and these data were compared to the pathological response after preoperative epirubicine/cyclophosphamide [EC] chemotherapy (+/- radiotherapy). pCR was more frequent (28.30%, 56/198) in tumors that received radio-chemotherapy compared to chemotherapy alone (11.9%, 38/319, p < 0.0001). Patients with high grading, lower ER, PgR, Bcl-2 or a higher proliferation had a significantly greater benefit from chemotherapy. The overexpressions of Her2/neu or EGF-R were weakly correlated to pCR, while p53 staining did not have any predictive value. Younger patients, with negative PgR and high proliferation index, had the highest benefit from EC therapy (56% pCR). The different multivariate indices of binary regression, PLS-DA and SIMCA, had similar predictive quality and were slightly superior to univariate factors. This study emphasizes the value of traditional biological markers and Bcl-2 for use in the individual selection of a primary therapy regimen.

  12. 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.

  13. 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

  14. 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.

  15. 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, Jr, M. S.

    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.

  16. 4D-flow cardiac magnetic resonance-derived vorticity is sensitive marker of left ventricular diastolic dysfunction in patients with mild-to-moderate chronic obstructive pulmonary disease.

    PubMed

    Schäfer, Michal; Humphries, Stephen; Stenmark, Kurt R; Kheyfets, Vitaly O; Buckner, J Kern; Hunter, Kendall S; Fenster, Brett E

    2017-04-27

    To investigate the possibility that vorticity assessed by four-dimensional flow cardiac magnetic resonance (4D-Flow CMR) in the left ventricle of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is a potential marker of early LV diastolic dysfunction (LVDD) and more sensitive than standard echocardiography, and whether changes in vorticity are associated with quantitative computed tomography (CT) and clinical markers of COPD, and right ventricular (RV) echocardiographic markers indicative of ventricular interdependency. Sixteen COPD patients with presumptive LVDD and 10 controls underwent same-day 4D-Flow CMR and Doppler echocardiography to quantify early and late diastolic vorticity as well as standard evaluation for LVDD. Furthermore, all patients underwent detailed CT analysis for COPD markers including percent emphysema and air trapping. The 4D-Flow CMR derived diastolic vorticity measures were correlated with CT measures, standard clinical and CMR markers, and echocardiographic diastolic RV metrics. Early diastolic vorticity was significantly reduced in COPD patients (P < 0.0001) with normal left ventricular (LV) mass, geometry, systolic function, and no or mild signs of Doppler LVDD when compared with controls. Vorticity significantly differentiated COPD patients without echocardiographic signs of LVDD (n = 11) from controls (P < 0.0001), and from COPD patients with stage I LVDD (n = 5) (P < 0.0180). Vorticity markers significantly correlated with CT computed measures, CMR-derived RV ejection fraction, echocardiographic RV diastolic metrics, and 6-minute walk test. 4D-Flow CMR derived diastolic vorticity is reduced in patients with mild-to-moderate COPD and no or mild signs of LVDD, implying early perturbations in the LV flow domain preceding more obvious mechanical changes (i.e. stiffening and dilation). Furthermore, reduced LV vorticity appears to be driven by COPD induced changes in lung tissue and parallel RV

  17. 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, .

  18. Expression of CD90 and P75NTR stem cell markers in ameloblastomas: a possible role in their biological behavior.

    PubMed

    Silva, Fernanda Paula Yamamoto; Dias, Andrielle; Coelho, Carolinne Almeida; Guerra, Eliete Neves; Marques, Ana Elizia Mascarenhas; Decurcio, Daniel de Almeida; Mantesso, Andrea; Cury, Sérgio Elias Vieira; Silva, Brunno Santos de Freitas

    2016-10-10

    Multicystic and unicystic ameloblastomas are benign odontogenic tumors that present distinct biological behavior. The investigation of stem cells has become an important branch of tumor biology, with several studies addressing the possible role of these cells in tumor growth, angiogenesis, progression, infiltration and invasiveness. This study evaluated the immunohistochemical expression of CD90(Thy-1) and P75NTR stem cell markers in multicystic and unicystic ameloblastomas. Seventeen (17) samples of ameloblastomas (multicystic, n = 10; unicystic, n = 7) were submitted to immunohistochemical reactions and graded semi-quantitatively. The Kolmogorov-Smirnov test was used to verify possible differences in CD90 and P75NTR expressions between multicystic and unicystic ameloblastomas (p < 0.05). CD90 immunostaining was observed in all multicystic ameloblastoma specimens (n = 10), in the cytoplasm of the fibroblasts and vascular endothelial cells of the tumor stroma, near the neoplastic odontogenic epithelia. The staining of stromal CD90 was significantly higher in multicystic than in unicystic ameloblastomas (p = 0.003). Nuclear P75NTR immunostaining was observed in all ameloblastoma specimens. A significant difference was seen in the epithelial staining of P75NTR between multicystic and unicystic types (p = 0.007). The increased expression of CD90 and P75NTR found in multicystic ameloblastomas suggests a behavioral biological difference between multicystic and unicystic ameloblastomas, as well as a difference in ameloblastoma development.

  19. Elevations of inflammatory markers PTX3 and sST2 after resuscitation from cardiac arrest are associated with multiple organ dysfunction syndrome and early death.

    PubMed

    Ristagno, Giuseppe; Varpula, Tero; Masson, Serge; Greco, Marta; Bottazzi, Barbara; Milani, Valentina; Aleksova, Aneta; Sinagra, Gianfranco; Assandri, Roberto; Tiainen, Marjaana; Vaahersalo, Jukka; Kurola, Jouni; Barlera, Simona; Montanelli, Alessandro; Latini, Roberto; Pettilä, Ville; Bendel, Stepani; Skrifvars, Markus B

    2015-10-01

    A systemic inflammatory response is observed after cardiopulmonary resuscitation. We investigated two novel inflammatory markers, pentraxin 3 (PTX3) and soluble suppression of tumorigenicity 2 (sST2), in comparison with the classic high-sensitivity C-reactive protein (hsCRP), for prediction of early multiple organ dysfunction syndrome (MODS), early death, and long-term outcome after out-of-hospital cardiac arrest. PTX3, sST2, and hsCRP were assayed at ICU admission and 48 h later in 278 patients. MODS was defined as the 24 h non-neurological Sequential Organ Failure Assessment (SOFA) score ≥ 12. Intensive care unit (ICU) death and 12-month Cerebral Performance Category (CPC) were evaluated. In total, 82% of patients survived to ICU discharge and 48% had favorable neurological outcome at 1 year (CPC 1 or 2). At ICU admission, median plasma levels of hsCRP (2.8 mg/L) were normal, while levels of PTX3 (19.1 ng/mL) and sST2 (117 ng/mL) were markedly elevated. PTX3 and sST2 were higher in patients who developed MODS (p<0.0001). Admission levels of PTX3 and sST2 were also higher in patients who died in ICU and in those with an unfavorable 12-month neurological outcome (p<0.01). Admission levels of PTX3 and sST2 were independently associated with subsequent MODS [OR: 1.717 (1.221-2.414) and 1.340, (1.001-1.792), respectively] and with ICU death [OR: 1.536 (1.078-2.187) and 1.452 (1.064-1.981), respectively]. At 48 h, only sST2 and hsCRP were independently associated with ICU death. Higher plasma levels of PTX3 and sST2, but not of hsCRP, at ICU admission were associated with higher risk of MODS and early death.

  20. 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

  1. Serum Cardiac Troponin-I is Superior to Troponin-T as a Marker for Left Ventricular Dysfunction in Clinically Stable Patients with End-Stage Renal Disease

    PubMed Central

    Buiten, Maurits S.; de Bie, Mihály K.; Rotmans, Joris I.; Dekker, Friedo W.; van Buren, Marjolijn; Rabelink, Ton J.; Cobbaert, Christa M.; Schalij, Martin J.; van der Laarse, Arnoud; Jukema, J. Wouter

    2015-01-01

    Background Serum troponin assays, widely used to detect acute cardiac ischemia, might be useful biomarkers to detect chronic cardiovascular disease (CVD). Cardiac-specific troponin-I (cTnI) and troponin-T (cTnT) generally detect myocardial necrosis equally well. In dialysis patients however, serum cTnT levels are often elevated, unlike cTnI levels. The present study aims to elucidate the associations of cTnI and cTnT with CVD in clinically stable dialysis patients. Methods Troponin levels were measured using 5th generation hs-cTnT assays (Roche) and STAT hs-cTnI assays (Abbott) in a cohort of dialysis patients. Serum troponin levels were divided into tertiles with the lowest tertile as a reference value. Serum troponins were associated with indicators of CVD such as left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF) and the presence of coronary artery disease (CAD). Associations were explored using regression analysis. Results We included 154 consecutive patients, 68±7 years old, 77% male, 70% hemodialysis. Median serum cTnT was 51ng/L (exceeding the 99th percentile of the healthy population in 98%) and median serum cTnI was 13ng/L (elevated in 20%). A high cTnI (T3) was significantly associated with a higher LVMI (Beta 31.60; p=0.001) and LVEF (Beta -4.78; p=0.005) after adjusting for confounders whereas a high serum cTnT was not. CAD was significantly associated with a high cTnT (OR 4.70 p=0.02) but not with a high cTnI. Unlike cTnI, cTnT was associated with residual renal function (Beta:-0.09; p=0.006). Conclusion In the present cohort, serum cTnI levels showed a stronger association with LVMI and LVEF than cTnT. However, cTnT was significantly associated with CAD and residual renal function, unlike cTnI. Therefore, cTnI seems to be superior to cTnT as a marker of left ventricular dysfunction in asymptomatic dialysis patients, while cTnT might be better suited to detect CAD in these patients. PMID:26237313

  2. The proteasome: mechanisms of biology and markers of activity and response to treatment in multiple myeloma.

    PubMed

    Manasanch, Elisabet E; Korde, Neha; Zingone, Adriana; Tageja, Nishant; Fernandez de Larrea, Carlos; Bhutani, Manisha; Wu, Peter; Roschewski, Mark; Landgren, Ola

    2014-08-01

    Since the early 1990s, the synthesis and subsequent clinical application of small molecule inhibitors of the ubiquitin proteasome pathway (UPP) has revolutionized the treatment and prognosis of multiple myeloma. In this review, we summarize important aspects of the biology of the UPP with a focus on its structure and key upstream/downstream regulatory components. We then review current knowledge of plasma cell sensitivity to proteasome inhibition and highlight new proteasome inhibitors that have recently entered clinical development. Lastly, we address the putative role of circulating proteasomes as a novel biomarker in multiple myeloma and provide guidance for future clinical trials using proteasome inhibitors.

  3. Autoantibodies to GM1 and GQ1bα are not biological markers of Alzheimer's disease.

    PubMed

    Miura, Yumako; Miyaji, Kazuki; Chai, Yuek Ling; Chen, Christopher L H; Lai, Mitchell K P; Yuki, Nobuhiro

    2014-01-01

    A few studies have reported the association of autoantibodies to GM1 or GQ1bα with Alzheimer's disease (AD) or vascular dementia. Here we investigated whether patients with AD or vascular dementia had high titers of the anti-ganglioside antibodies. Sera were obtained from patients with AD (n = 22), vascular dementia (n = 14), Guillain-Barré syndrome, and multifocal motor neuropathy as well as normal controls. Enzyme-linked immunosorbent assay showed titers of IgG and IgM anti-GM1, anti-GQ1bα, and anti-GT1aα antibodies did not differ among AD, vascular dementia, and normal controls, and being remarkably lower than those in Guillain-Barré syndrome and multifocal motor neuropathy. The anti-ganglioside antibodies are not biological markers of AD.

  4. The impact of a prospective survey-based workplace intervention program on employee health, biologic stress markers, and organizational productivity.

    PubMed

    Anderzén, Ingrid; Arnetz, Bengt B

    2005-07-01

    To study whether knowledge about psychosocial work indicators and a structured method to implement changes based on such knowledge comprise an effective management tool for enhancing organizational as well as employee health and well-being. White- collar employees representing 22 different work units were assessed before and after a 1-year intervention program. Subjective ratings on health and work environment, biologic markers, absenteeism, and productivity were measured. Significant improvements in performance feedback, participatory management, employeeship, skills development, efficiency, leadership, employee well-being, and work-related exhaustion were identified. The restorative hormone testosterone increased during the intervention and changes correlated with increased overall organizational well-being. Absenteeism decreased and productivity improved. Fact-based psychosocial workplace interventions are suggested to be an important process for enhancing employee well-being as well as organizational performance.

  5. 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

  6. Diagnostic Capability of Biological Markers in Assessment of Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis

    PubMed Central

    De Luca Canto, Graziela; Pachêco-Pereira, Camila; Aydinoz, Secil; Major, Paul W.; Flores-Mir, Carlos; Gozal, David

    2015-01-01

    Objective: The purpose of this systematic review is to evaluate the diagnostic value of biological markers (exhaled breath condensate, blood, salivary and urinary) in the diagnosis of OSA in comparison to the gold standard of nocturnal PSG. Methods: Studies that differentiated OSA from controls based on PSG results, without age restriction, were eligible for inclusion. The sample of selected studies could include studies in obese patients and with known cardiac disease. A detailed individual search strategy for each of the following bibliographic databases was developed: Cochrane, EMBASE, MEDLINE, PubMed, and LILACS. The references cited in these articles were also crosschecked and a partial grey literature search was undertaken using Google Scholar. The methodology of selected studies was evaluated using the 14-item Quality Assessment Tool for Diagnostic Accuracy Studies. Results: After a two-step selection process, nine articles were identified and subjected to qualitative and quantitative analyses. Among them, only one study conducted in children and one in adults found biomarkers that exhibit sufficiently satisfactory diagnostic accuracy that enables application as a diagnostic method for OSA. Conclusion: Kallikrein-1, uromodulin, urocotin-3, and orosomucoid-1 when combined have enough accuracy to be an OSA diagnostic test in children. IL-6 and IL-10 plasma levels have potential to be good biomarkers in identifying or excluding the presence of OSA in adults. Citation: De Luca Canto G, Pachêco-Pereira C, Aydinoz S, Major PW, Flores-Mir C, Gozal D. Diagnostic capability of biological markers in assessment of obstructive sleep apnea: a systematic review and meta-analysis. J Clin Sleep Med 2015;11(1):27–36. PMID:25325575

  7. Serum levels of N-terminal-pro B-type natriuretic peptide as a diagnostic marker for left ventricular dysfunction in children with end-stage renal disease on hemodialysis.

    PubMed

    Zoair, Amr Mohamed; Abdel-Hafez, Maher Ahmed; Mawlana, Wegdan; Sweylam, Mohamed Abdel-Rahman

    2016-01-01

    The objective of this study was to determine the diagnostic cutoff value of N-terminal-pro B-type natriuretic peptide (NT-pro BNP) as a marker of left ventricular (LV) dysfunction in children with end-stage renal disease (ESRD) on regular hemodialysis (HD). The study was carried out on thirty children with ESRD on regular HD and thirty healthy controls. Echocardiographic studies were done, including a conventional mode for ejection fraction, fractional shortening, tissue Doppler imaging, and longitudinal global strain by speckle tracking. Serum levels of NT-pro BNP were measured in venous blood samples before and about 30 min after HD by ELISA. Volume status was assessed by calculating interdialytic weight gain %. There were significant higher serum NT-pro BNP levels before HD (mean: 702.3 ± 274.3 ng/L) compared to controls (mean: 365.55 ± 76.5 ng/L) (P <0.001) and these levels decreased significantly after the HD session (mean: 625.1 ± 117.69 ng/L) (P = 0.031). Echocardiographic studies showed a significant impairment of LV function of the patients compared to controls. Patients with LV dysfunction had significant higher serum concentrations of NT-pro BNP compared to patients without dysfunction both before (P = 0.003) and after dialysis (P <0.001). Receiver operating curve demonstrated better prediction of LV dysfunction by NT-pro BNP levels after HD compared to its levels before HD (area under the curve was 0.9 and 0.73, respectively). Using a cutoff value of 630 ng/L, serum NT-pro BNP levels after dialysis were a diagnostic predictor of LV dysfunction with a sensitivity of 86.6%, specificity of 93.3%, positive predictive value of 92.8%, and negative predictive value of 87.5%. Serum NT-pro BNP levels were strongly correlated with the parameters of LV dysfunction in children with ESRD on regular HD. A postdialysis cutoff value of 630 ng/L could serve as a biochemical marker of LV dysfunction in those children regardless of chronic fluid overload.

  8. Evaluation of 1-hydroxypyrene as a biological marker of industrial exposure to polycyclic aromatic hydrocarbons

    NASA Astrophysics Data System (ADS)

    Calderon, Francisco M.

    1993-03-01

    One hundred twenty-two workers (sixteen from a coke production plant and 106 from a graphite electrode manufacturing plant) agreed to participate in this study evaluating the relationship between exposure to polycyclic aromatic hydrocarbons (PAHs) and urinary excretion of 1-hydroxypyrene (1-HOP), the main metabolite of pyrene. The results show that the concentration of pyrene in air is highly correlated with total PAHs (r equals 0.83, P < 0.0001). The correlation coefficient between pyrene in air and 1-HOP is (r equals 0.69, P < 0.0001) and between 1-HOP and total PAHs is (r equals 0.77, P < 0.0001). The biological half life of the 1-HOP was determined (18 hrs) and the noninterference of smoking habits in relation to 1-HOP urinary excretion was established, concluding that 1-HOP is a suitable bioindicator of the occupational exposure to PAHs.

  9. Biologic markers of sun exposure and melanoma risk in women: pooled case-control analysis

    PubMed Central

    Olsen, Catherine M.; Zens, Michael S.; Green, Adele C.; Stukel, Therese A.; Holman, C. D’Arcy J.; Mack, Thomas; Elwood, J. Mark; Holly, Elizabeth A.; Sacerdote, Carlotta; Gallagher, Richard; Swerdlow, Anthony J.; Armstrong, Bruce K.; Rosso, Stefano; Kirkpatrick, Connie; Zanetti, Roberto; Bishop, Julia Newton; Bataille, Veronique; Chang, Yu-Mei; Mackie, Rona; Østerlind, Anne; Berwick, Marianne; Karagas, Margaret R.; Whiteman, David C.

    2010-01-01

    A model has been proposed whereby melanomas arise through two distinct pathways dependent upon the relative influence of host susceptibility and sun exposure. Such pathways may explain site-specific patterns of melanoma occurrence. To explore this model, we investigated the relationship between melanoma risk and general markers of acute (recalled sunburns) and chronic (prevalent solar keratoses) sun exposure, stratified by anatomic site and host phenotype. Our working hypothesis was that head and neck melanomas have stronger associations with solar keratoses and weaker associations with sunburn than trunk melanomas. We conducted a collaborative analysis using original data from women subjects of 11 case–control studies of melanoma (2575 cases, 3241 controls). We adjusted for potential confounding effects of sunlamp use and sunbathing. The magnitude of sunburn associations did not differ significantly by melanoma site, nevus count or histologic sub-type of melanoma. Across all sites, relative risk of melanoma increased with an increasing number of reported lifetime ‘painful’ sunburns, lifetime ‘severe’ sunburns and ‘severe’ sunburns in youth (ptrend<0.001), with pooled odds ratios for the highest category of sunburns vs no sunburns of 3.22 (95%CI 2.04–5.09) for lifetime ‘painful’ sunburns, 2.10 (95%CI 1.30–3.38) for lifetime ‘severe’ sunburns, and 2.43 (95%CI 1.61–3.65) for ‘severe’ sunburns in youth. Solar keratoses strongly increased the risk of head and neck melanoma (pOR 4.91, 95% CI 2.10–11.46), but data were insufficient to assess risk for other sites. Reported sunburn is strongly associated with melanoma on all major body sites. PMID:20857492

  10. 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

  11. Biological markers for anxiety disorders, OCD and PTSD: A consensus statement. Part II: Neurochemistry, neurophysiology and neurocognition

    PubMed Central

    Bandelow, Borwin; Baldwin, David; Abelli, Marianna; Bolea-Alamanac, Blanca; Bourin, Michel; Chamberlain, Samuel R.; Cinosi, Eduardo; Davies, Simon; Domschke, Katharina; Fineberg, Naomi; Grünblatt, Edna; Jarema, Marek; Kim, Yong-Ku; Maron, Eduard; Masdrakis, Vasileios; Mikova, Olya; Nutt, David; Pallanti, Stefano; Pini, Stefano; Ströhle, Andreas; Thibaut, Florence; Vaghix, Matilde M.; Won, Eunsoo; Wedekind, Dirk; Wichniak, Adam; Woolley, Jade; Zwanzger, Peter; Riederer, Peter

    2017-01-01

    Objective Biomarkers are defined as anatomical, biochemical or physiological traits that are specific to certain disorders or syndromes. The objective of this paper is to summarise the current knowledge of biomarkers for anxiety disorders, obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD). Methods Findings in biomarker research were reviewed by a task force of international experts in the field, consisting of members of the World Federation of Societies for Biological Psychiatry Task Force on Biological Markers and of the European College of Neuropsychopharmacology Anxiety Disorders Research Network. Results The present article (Part II) summarises findings on potential biomarkers in neurochemistry (neurotransmitters such as serotonin, norepinephrine, dopamine or GABA, neuropeptides such as cholecystokinin, neurokinins, atrial natriuretic peptide, or oxytocin, the HPA axis, neurotrophic factors such as NGF and BDNF, immunology and CO2 hypersensitivity), neurophysiology (EEG, heart rate variability) and neurocognition. The accompanying paper (Part I) focuses on neuroimaging and genetics. Conclusions Although at present, none of the putative biomarkers is sufficient and specific as a diagnostic tool, an abundance of high quality research has accumulated that should improve our understanding of the neurobiological causes of anxiety disorders, OCD and PTSD. PMID:27419272

  12. [Value of the sleep EEG as a biological marker of depressive states. Comparison with 3 neuroendocrine tests].

    PubMed

    Ansseau, M; Scheyvaerts, M; Doumont, A; Poirrier, R; Demonceau, G; Legros, J J; Franck, G

    1985-04-01

    In a sample of 12 endogenous depressive inpatients (8 primary and 4 secondary depressives), we compared the diagnostic usefulness of REM latency (recorded during at least 4 consecutive nights) with 3 neuroendocrine tests: dexamethasone suppression test and GH response after clonidine (a alpha-adrenergic agonist) and apomorphine (a dopaminergic agonist) challenges. Shortened REM latency (less than 50 min during at least 1 night) was present in 67% of depressives. However, REM latency presented a clear night to night intra-patient variability that makes it necessary to record at least 3 consecutive nights for the best sensitivity. Non-suppression after dexamethasone was present in 50% of depressives, blunted GH response after clonidine, in 75% and blunted response after apomorphine, in 42%. A total of 92% of patients exhibited at least one abnormal biological parameter (100% of primary and 75% of secondary depressives); 67% of patients exhibited at least two disturbed parameters and these patients constituted the whole primary depressive group (100%). These results show that these 4 potential biological markers of depression are not necessarily distributed in the same population. This suggests the potential usefulness of their concurrent use for improved accuracy of diagnosis.

  13. Bone lead as a biological marker in epidemiologic studies of chronic toxicity: conceptual paradigms.

    PubMed Central

    Hu, H; Rabinowitz, M; Smith, D

    1998-01-01

    The skeleton contains the majority of the body's lead burden in both children and adults. The half-life of lead in bone is in the range of years to decades, depending on bone type, metabolic state, and subject age, among other things. Measurement of skeletal lead has benefited greatly from the recent development of X-ray fluorescence (XRF) instruments that can make rapid, safe, accurate, and relatively precise measurements of lead in bone. Two types of XRF technologies exist, LXRF and KXRF; this paper focuses on KXRF, which has been the most widely validated and used. KXRF is proving to be a powerful analytical methodology for evaluating bone lead levels as a measure of time-integrated (i.e., cumulative) lead dose in epidemiologic studies of the effects of chronic lead exposure. However, insufficient attention has been given to conceptualizing the paradigms by which bone lead levels reflect lead exposure and by which the skeleton serves as an endogenous source of lead. Consideration of these paradigms, which rely on bone lead kinetics, is necessary for the proper development of a priori hypotheses involving bone lead accumulation and release, the selection of bone sites for measurement by KXRF, and the design of epidemiologic studies involving bone lead dynamics. We discuss and present supporting evidence for a conceptual model that distinguishes two major paradigms of skeletal lead, including 1) bone lead as an indicator of cumulative lead exposure (bone lead as repository), and 2) bone lead as a source of body lead burden that is mobilizable into the circulation (bone lead as source). These two roles are not mutually exclusive. Instead, they are components of the processes controlling lead accumulation into and release from bone over time. Developing successful strategies for distinguishing these two processes in epidemiologic studies will require separate measurements of lead in cortical and trabecular bone and additional measurement of specific markers of bone

  14. Occupational cosmic radiation exposure in Portuguese airline pilots: study of a possible correlation with oxidative biological markers.

    PubMed

    Silva, Rodrigo; Folgosa, Filipe; Soares, Paulo; Pereira, Alice S; Garcia, Raquel; Gestal-Otero, Juan Jesus; Tavares, Pedro; Gomes da Silva, Marco D R

    2013-05-01

    Several studies have sought to understand the health effects of occupational exposure to cosmic radiation. However, only few biologic markers or associations with disease outcomes have so far been identified. In the present study, 22 long- and 26 medium-haul male Portuguese airline pilots and 36 factory workers who did not fly regularly were investigated. The two groups were comparable in age and diet, were non-smokers, never treated with ionizing radiation and other factors. Cosmic radiation exposure in pilots was quantified based on direct monitoring of 51 flights within Europe, and from Europe to North and South America, and to Africa. Indirect dose estimates in pilots were performed based on the SIEVERT (Système informatisé d'évaluation par vol de l'exposition au rayonnement cosmique dans les transports aériens) software for 6,039 medium- and 1,366 long-haul flights. Medium-haul pilots had a higher cosmic radiation dose rate than long-haul pilots, that is, 3.3 ± 0.2 μSv/h and 2.7 ± 0.3 μSv/h, respectively. Biological tests for oxidative stress on blood and urine, as appropriate, at two time periods separated by 1 year, included measurements of antioxidant capacity, total protein, ferritin, hemoglobin, creatinine and 8-hydroxy-2-deoxyguanosine (8OHdG). Principal components analysis was used to discriminate between the exposed and unexposed groups based on all the biological tests. According to this analysis, creatinine and 8OHdG levels were different for the pilots and the unexposed group, but no distinctions could be made among the medium- and the long-haul pilots. While hemoglobin levels seem to be comparable between the studied groups, they were directly correlated with ferritin values, which were lower for the airline pilots.

  15. 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

  16. Rat sleep and eye movement density as biological markers of demyelinating disease.

    PubMed

    Anch, A M; Laposky, A D

    Myelin mutants provide an opportunity to study neurophysiological and behavioral effects of demyelination. The taiep rats are myelin mutants with progressive demyelination of the central nervous system (CNS), resulting in five neurological symptoms: tremor, ataxia, immobility, epilepsy, and paralysis. The demyelination affects the brainstem, an important area in the control of sleep. This study compared eye movement density (EMD) in taiep vs. normal control rats during paradoxical sleep (PS). It was hypothesized that taiep rats would have significantly reduced EMD during PS in comparison to normal controls due to their demyelinating disease. In addition, demyelination of brainstem structures would suggest possible changes in sleep-wake structure. Hence, we compared sleep-wake stages in taiep vs. normal, control rats. The results confirmed significantly reduced EMD during PS in taiep rats compared to normal rats during the 12-h (light) recording period. In addition, analysis of EMD values across the 12-h light period revealed significant differences in EMD values as a function of time of day in the taeip rats only. Comparison of waking and sleep values across the 12-h light phase revealed an "immobility episode" in three taiep rats, which was not present in normal controls. In addition, PS percentage was significantly lower and low-voltage sleep was significantly higher in taiep rats. These results suggest that EMD, immobility episodes, and sleep architecture may be useful as measurable biological events in the study of demyelinating disease. The results were discussed in terms of possible mechanisms underlying these differences, as well as possible implications for future studies.

  17. DHT and IGF-1 in peripheral blood lymphocytes: new markers for the biological passport of athletes.

    PubMed

    Mancini, A; Imperlini, E; Alfieri, A; Spaziani, S; Martone, D; Parisi, A; Orru, S; Buono, P

    2013-01-01

    We performed a pilot study using human peripheral blood lymphocytes (PBL) as a novel system to identify new biomarkers of dihydrotestosterone (DHT) and insulin-like growth factor-1 (IGF-1) abuse in sport. First, to obtain a gene signature, we treated cultures of lymphocytes from sedentary males with three doses of 0.237 microg/ml DHT, each of which is 80-fold the physiological concentration in young adult male serum, at days 0, 2 and 4, or with a single dose of 1.25 microg/ml IGF-1, which is 5-fold the physiological concentration in young adult male serum. We then used the Human Genome U133 Plus 2.0 microarray to identify a gene signature related to DHT or IGF-1 administration. Gene expression was evaluated after 7 and 21 days of DHT treatment, and after 24 h, 72 h and 7 days of IGF-1 treatment. Microarray analysis yielded a list of genes whose expression was altered after DHT or IGF-1 treatment. Among these we selected the genes that are most representative of the pathways associated with skeletal and muscular disorders using the IPA bioinformatics tool. We identified six (IDO1, CXCL13, CCL1, GZMB, VDR and IL2RA) and two (FN1 and RAB31) genes that were up-regulated in lymphocytes from sedentary subjects after 7 days of DHT and IGF-1 treatment, respectively. The expression of these genes in lymphocytes from differently trained athletes was either down-regulated or similar to that in lymphocytes from sedentary subjects. This finding suggests that up-regulation was due to the drug and not to physical exercise. In conclusion, we demonstrate that PBL can be useful in anti-doping checks, and we describe new biomarkers of DHT and IGF-1 abuse which can be included in the Athlete's Biological Passport.

  18. Relation of child birth and breast-feeding burden with cadmium and tubular dysfunction marker levels in urine of adult women in non-polluted areas in Japan.

    PubMed

    Ikeda, Masayuki; Moriguchi, Jiro; Sakuragi, Sonoko; Ohashi, Fumiko

    2013-08-01

    Cd absorption may be enhanced in association with iron (Fe) deficiency. Women have increased risks of Fe loss at the time of child birth as well as breast-feeding of children. Possible effects of these two factors were investigated in the present study. Data were drawn from previous publications from this group on Cd and tubular dysfunction markers (i.e., α1-microglobulin, β2-microglobulin, and N-acetyl-β-D-glucosaminidase) in urine of adult women in non-polluted areas in Japan. Information including age, smoking, number of children, and types of child feeding was obtained by self-administered questionnaires at the time of urine sampling. In practice, 17,468 cases were available, from which 12,869 cases were employed in the present analyses after exclusion of smokers, former or current patients of anemia or hypertension, and those with incomplete answers. Lactation burden was scored after coding of breast, mixed, and bottle feeding with 2, 1, and 0 for each child followed by summation for all children born to a mother. In order to exclude possible effect of aging, women were stratified by 5 years of age to randomly select equal numbers of cases and controls, followed by summation for all ages for comparison. The arithmetic mean age and the geometric mean Cd (as observed) were 49.7 years and 1.13 μg/l urine. The number of children was 0-7, and lactation burden score ranged from 0-12. Multiple regression analyses were conducted with age and either number of children or lactation burden scores as independent variables and Cd as a dependent variable. The results showed that age was an influential variable. Comparison after matching for age showed that having 1, 2, or 3 children or lactation burden score up to 2 were associated with a significant increase in Cd. Lactation burden score up to 2 was also associated with increased Cd in urine and such trend persisted up to the highest score of 5-12. The results of trend tests were generally in agreement with these

  19. Mitochondrial dysfunction, oxidative stress, and major depressive disorder

    PubMed Central

    Tobe, Edward H

    2013-01-01

    There is controversy about depression being a physical illness, in part because a reproducible, sensitive, and specific biologic marker is not available. However, there is evidence that mitochondrial dysfunction and oxidative stress may be associated with abnormal brain function and mood disorders, such as depression. This paper reviews selected human and animal studies providing evidence that intracellular mitochondrial metabolic dysfunction in specific brain regions is associated with major depressive disorder. This supports the hypothesis that chronic mitochondrial dysfunction in specific tissues may be associated with depression. Evaluation of mitochondrial dysfunction in specific tissues may broaden the perspective of depression beyond theories about neurotransmitters or receptor sites, and may explain the persistent signs and symptoms of depression. PMID:23650447

  20. 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. © The Author(s) 2015.

  1. Burden of Sexual Dysfunction.

    PubMed

    Balon, Richard

    2017-01-02

    Similar to the burden of other diseases, the burden of sexual dysfunction has not been systematically studied. However, there is growing evidence of various burdens (e.g., economic, symptomatic, humanistic) among patients suffering from sexual dysfunctions. The burden of sexual dysfunction has been studied a bit more often in men, namely the burden of erectile dysfunction (ED), premature ejaculation (PE) and testosterone deficiency syndrome (TDS). Erectile dysfunction is frequently associated with chronic conditions such as cardiovascular disease, diabetes, and depression. These conditions could go undiagnosed, and ED could be a marker of those diseases. The only available report from the United Kingdom estimated the total economic burden of ED at £53 million annually in terms of direct costs and lost productivity. The burden of PE includes significant psychological distress: anxiety, depression, lack of sexual confidence, poor self-esteem, impaired quality of life, and interpersonal difficulties. Some suggest that increase in female sexual dysfunction is associated with partner's PE, in addition to significant interpersonal difficulties. The burden of TDS includes depression, sexual dysfunction, mild cognitive impairment, and osteoporosis. One UK estimate of the economic burden of female sexual dysfunctions demonstrated that the average cost per patient was higher than the per annum cost of ED. There are no data on burden of paraphilic disorders. The burden of sexual dysfunctions is underappreciated and not well studied, yet it is significant for both the patients and the society.

  2. The Effects of Short-Term Propofol and Dexmedetomidine on Lung Mechanics, Histology, and Biological Markers in Experimental Obesity.

    PubMed

    Heil, Luciana Boavista Barros; Santos, Cíntia L; Santos, Raquel S; Samary, Cynthia S; Cavalcanti, Vinicius C M; Araújo, Mariana M P N; Poggio, Hananda; Maia, Lígia de A; Trevenzoli, Isis Hara; Pelosi, Paolo; Fernandes, Fatima C; Villela, Nivaldo R; Silva, Pedro L; Rocco, Patricia R M

    2016-04-01

    Administering anesthetics to the obese population requires caution because of a variety of reasons including possible interactions with the inflammatory process observed in obese patients. Propofol and dexmedetomidine have protective effects on pulmonary function and are widely used in short- and long-term sedation, particularly in intensive care unit settings in lean and obese subjects. However, the functional and biological effects of these drugs in obesity require further elucidation. In a model of diet-induced obesity, we compared the short-term effects of dexmedetomidine versus propofol on lung mechanics and histology, as well as biological markers of inflammation and oxidative stress modulation in obesity. Wistar rats (n = 56) were randomly fed a standard diet (lean) or experimental diet (obese) for 12 weeks. After this period, obese animals received sodium thiopental intraperitoneally and were randomly allocated into 4 subgroups: (1) nonventilated (n = 4) for molecular biology analysis only (control); (2) sodium thiopental (n = 8); (3) propofol (n = 8); and (4) dexmedetomidine (n = 8), which received continuous IV administration of the corresponding agents and were mechanically ventilated (tidal volume = 6 mL/kg body weight, fraction of inspired oxygen = 0.4, positive end-expiratory pressure = 3 cm H2O) for 1 hour. Compared with lean animals, obese rats did not present increased body weight but had higher total body and trunk fat percentages, airway resistance, and interleukin-6 levels in the lung tissue (P = 0.02, P = 0.0027, and P = 0.01, respectively). In obese rats, propofol, but not dexmedetomidine, yielded increased airway resistance, bronchoconstriction index (P = 0.016, P = 0.02, respectively), tumor necrosis factor-α, and interleukin-6 levels, as well as lower levels of nuclear factor-erythroid 2-related factor-2 and glutathione peroxidase (P = 0.001, Bonferroni-corrected t test). In this model of diet-induced obesity, a 1-hour propofol infusion

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. Geochemistry of biological marker compounds extracted from sediments and oils of the Bulge, northern Alaska and Yukon Territory

    SciTech Connect

    Banet, A.C. Jr. )

    1991-03-01

    The North Slope is a major petroleum province with production from sediments ranging in age from upper Mississippian through Cretaceous and noncommercial discoveries in sediments from Proterozoic( ) to Tertiary age. Many oils, seeps, and stains, and outcrops are heavily weathered in the Arctic, especially in the Bulge. This severely limits the familiar hydrocarbon-source rock correlations and interpretations based on total organic carbon, pyrolysis data, stable isotopes, and chromatograms of C-15+ extracts. Biological marker compounds such as steranes and triterpanes are present in these extracts in small quantities and are less affected by the severe weathering effects. Despite their horrendous names (both IUPAC and common), gas chromatography-mass spectrometric determined distributions and ratios of these compounds are useful in determining hydrocarbon-source rock relations. Ternary plots of C-27, -28, -29 steranes and rearranged steranes show affinities for depositional environments, possible maturity effects, and source rock-extract correlations. Triterpane analyses show similar correlations and compounds unique to certain stratigraphic units. Comparisons of data from the Arctic National Wildlife Refuge, Prudhoe, National Petroleum Reserve-Alaska, and the Yukon-Beaufort indicate the existence of multiple oil kitchens in the region generating oil and gas.

  8. 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.

  9. Upregulated plasma and urinary levels of nucleosides as biological markers in the diagnosis of primary gallbladder cancer.

    PubMed

    Jiao, Xingyuan; Mo, Yuxuan; Wu, Ying; He, Jinyun; Zhang, Peng; Hu, Ronglin; Luo, Canqiao; Du, Jun; Fu, Jian; Shi, Jinsen; Zhou, Liansuo; Li, Dongming

    2014-11-01

    We first detected aberrant nucleoside levels in the plasma, urine, bile, and tissues from cases and controls to explore them as biomarkers in the diagnosis of gallbladder cancer. Reversed-phase high-performance liquid chromatography was used to assess the levels of ten nucleosides in these samples from gallbladder cancer patients, gallstone patients, and healthy controls. Plasma and urine samples were collected from patients with gallbladder cancer (n = 202), patients with gallstones (n = 203), and healthy controls (n = 205); bile and tissue samples were collected from 91 gallbladder cancer patients, 93 gallstone patients; and 90 were donated after cardiac death. Of the ten nucleosides analyzed, eight urinary nucleosides, five plasma nucleosides, three bile nucleosides, and one tissue nucleoside were significantly upregulated in the gallbladder cancer patients compared to control groups (p < 0.05). Among these upregulated nucleosides, the sensitivity, specificity, and accuracy of urinary nucleosides in the diagnosis of gallbladder cancer patients were 89.4, 97.1, and 95.7%, respectively, those of plasma nucleosides were 91.2, 95.6, and 94.2%, respectively, those of bile nucleosides were 95.3, 96.4, and 95.1%, respectively, and those of tissue nucleosides were 86.2, 93.8, and 92.6%, respectively. These results suggest that nucleosides may be as useful as biological markers for gallbladder cancer. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Effects of neutral pH and low-glucose degradation product-containing peritoneal dialysis fluid on systemic markers of inflammation and endothelial dysfunction: a randomized controlled 1-year follow-up study.

    PubMed

    Park, Sun-Hee; Do, Jun-Young; Kim, Yeong Hoon; Lee, Ho Yung; Kim, Beom Seok; Shin, Sug-Kyun; Kim, Hyun Chul; Chang, Yoon-Kyung; Yang, Jong-Oh; Chung, Hyun-Chul; Kim, Chan-Duck; Lee, Won Kee; Kim, Jong-Yeon; Kim, Yong-Lim

    2012-03-01

    The local peritoneal effects of low-glucose degradation product (GDP)-containing peritoneal dialysis fluid (PDF) have been extensively described. However, the systemic effects of prolonged prescription of these solutions are unknown. This study aimed to evaluate the effects of neutral pH and low-GDP PDF on systemic inflammation and endothelial dysfunction markers in peritoneal dialysis (PD) patients. This is a multicenter, open labeled, randomized controlled trial including one hundred fifty-two patients initiating continuous ambulatory peritoneal dialysis for end-stage renal disease from seven centers in Korea. Participants were randomly allocated to conventional PDF (Stay safe®; Fresenius Medical Care, Bad Homburg, Germany) or low-GDP PDF (Balance®; Fresenius Medical Care) and were followed for 1 year. Primary outcome variable was the inflammation and endothelial dysfunction index (IEDI), a composite score derived from serum levels of soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cellular adhesion molecule (sVCAM)-1 and high-sensitivity C-reactive protein (hs-CRP). sICAM-1, sVCAM-1, residual renal function (RRF), peritoneal membrane transport characteristics, ultrafiltration volume and nutritional parameters were measured as secondary outcome variables. Of 152 patients randomized, 146 (low-GDP: conventional PDF, 79:67) patients entered the trial (46% male, 53% with diabetes mellitus). At 12-month follow-up, the low-GDP group had significantly lower levels of IEDI, sICAM-1 and sVCAM-1 compared to the conventional group; hs-CRP was not different between groups. Peritoneal transport characteristics, RRF, nutritional parameters, incidence of peritonitis and death-censored technique survival were not different between groups. Neutral pH and low-GDP PDF likely produce fewer changes in markers of endothelial dysfunction compared to conventional PDF in incident PD patients.

  11. 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

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

    PubMed

    Daiber, Andreas; Münzel, Thomas

    2015-10-10

    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.

  13. Functional, radiological and biological markers of alveolitis and infections of the lower respiratory tract in patients with systemic sclerosis.

    PubMed

    De Santis, Maria; Bosello, Silvia; La Torre, Giuseppe; Capuano, Anna; Tolusso, Barbara; Pagliari, Gabriella; Pistelli, Riccardo; Danza, Francesco Maria; Zoli, Angelo; Ferraccioli, Gianfranco

    2005-08-17

    A progressive lung disease and a worse survival have been observed in patients with systemic sclerosis and alveolitis. The objective of this study was to define the functional, radiological and biological markers of alveolitis in SSc patients. 100 SSc patients (76 with limited and 24 with diffuse disease) underwent a multistep assessment of cardiopulmonary system: pulmonary function tests (PFTs) every 6-12 months, echocardiography, high resolution computed tomography (HRCT) and bronchoalveolar lavage (BAL), if clinically advisable. Alveolar and interstitial scores on HRCT and IL-6 plasma levels were also assessed as lung disease activity indices. 90 SSc patients with abnormal PFTs and 3 with signs and/or symptoms of lung involvement and normal PFTs underwent HRCT and echocardiography. HRCT revealed evidence of fibrosis in 87 (93.5%) patients, with 55 (59.1%) showing both ground glass attenuation and fibrosis. In 42 patients who had exhibited ground glass on HRCT and consented to undergo BAL, 16 (38.1%) revealed alveolitis. 12 (75%) of these patients had restrictive lung disease (p < 0.0001) and presented diffuse skin involvement (p = 0.0009). IL-6 plasma levels were higher in patients with alveolitis than in patients without (p = 0.041). On logistic regression model the best independent predictors of alveolitis were diffuse skin involvement (OR(95%CIs):12.80(2.54-64.37)) and skin score > 14 (OR(95%CIs):7.03(1.40-34.33)). The alveolar score showed a significant correlation with IL-6 plasma levels (r = 0.36, p = 0.001) and with the skin score (r = 0.33, p = 0.001). Cultures of BAL fluid resulted positive in 10 (23.8%) of the 42 patients that underwent BAL and after one year a deterioration in PFTs occurred in 8 (80%) of these patients (p = 0.01). Pulmonary artery systolic pressure > or = 40 mmHg was found in 6 (37.5%) patients with alveolitis. We found alveolitis only in 38.1% of the patients who had exhibited ground glass on HRCT and then underwent BAL, probably

  14. Antral follicle count as a marker of ovarian biological age to reflect the background risk of fetal aneuploidy.

    PubMed

    Grande, Maribel; Borobio, Virginia; Jimenez, Jose Miguel; Bennasar, Mar; Stergiotou, Iosifina; Peñarrubia, Joana; Borrell, Antoni

    2014-06-01

    Can antral follicle count (AFC) measured during pregnancy be used as a marker of ovarian age to assess the background risk of fetal aneuploidy? AFC was lower than expected according to maternal chronological age in trisomic pregnancies; therefore ovarian age could potentially reflect a more precise background risk of fetal aneuploidy screening. The decline in a woman's reproductive function is determined by a decline in the ovarian follicle pool and the quality of oocytes. The quantitative status of ovarian reserve can be indirectly assessed by AFC, but the role of AFC as an aneuploidy risk marker in pregnant women has not been assessed yet. Our study comprised a prospective cohort including 1239 singleton pregnancies scanned before 14 weeks in our center during a 14-month period. Reference ranges for AFC were constructed using 812 spontaneously conceived, chromosomally normal singleton ongoing pregnancies using the Lambda-Mu-Sigma method. The study population (n = 934) included 19 pregnancies with viable autosomal trisomies (trisomies 21, 18 and 13), 17 non-viable autosomal trisomies (other than 21, 18 or 13), 7 monosomies X, 1 sex trisomy and 3 triploidies (total n = 47 with chromosomal abnormalities). AFC in chromosomally abnormal pregnancies was plotted against the reference ranges. AFC multiple of the median was calculated according to the median AFC obtained by each year of age. Sixty-eight percent of women carrying a pregnancy with viable trisomies and 65% with non-viable trisomies presented an AFC below the 50th percentile. The median ovarian age in viable trisomies and non-viable trisomies was estimated to be 3 and 6 years above than median maternal age, respectively. However, the median ovarian age in monosomies X and triploidies was not higher than median maternal age. We did not assess the intra- and inter-observer reliability, or use specific three-dimensional analysis which may have advantages over our two-dimensional study. In clinical practice, a

  15. Functional, radiological and biological markers of alveolitis and infections of the lower respiratory tract in patients with systemic sclerosis

    PubMed Central

    De Santis, Maria; Bosello, Silvia; La Torre, Giuseppe; Capuano, Anna; Tolusso, Barbara; Pagliari, Gabriella; Pistelli, Riccardo; Danza, Francesco Maria; Zoli, Angelo; Ferraccioli, Gianfranco

    2005-01-01

    Background A progressive lung disease and a worse survival have been observed in patients with systemic sclerosis and alveolitis. The objective of this study was to define the functional, radiological and biological markers of alveolitis in SSc patients. Methods 100 SSc patients (76 with limited and 24 with diffuse disease) underwent a multistep assessment of cardiopulmonary system: pulmonary function tests (PFTs) every 6–12 months, echocardiography, high resolution computed tomography (HRCT) and bronchoalveolar lavage (BAL), if clinically advisable. Alveolar and interstitial scores on HRCT and IL-6 plasma levels were also assessed as lung disease activity indices. Results 90 SSc patients with abnormal PFTs and 3 with signs and/or symptoms of lung involvement and normal PFTs underwent HRCT and echocardiography. HRCT revealed evidence of fibrosis in 87 (93.5%) patients, with 55 (59.1%) showing both ground glass attenuation and fibrosis. In 42 patients who had exhibited ground glass on HRCT and consented to undergo BAL, 16 (38.1%) revealed alveolitis. 12 (75%) of these patients had restrictive lung disease (p < 0.0001) and presented diffuse skin involvement (p = 0.0009). IL-6 plasma levels were higher in patients with alveolitis than in patients without (p = 0.041). On logistic regression model the best independent predictors of alveolitis were diffuse skin involvement (OR(95%CIs):12.80(2.54–64.37)) and skin score > 14 (OR(95%CIs):7.03(1.40–34.33)). The alveolar score showed a significant correlation with IL-6 plasma levels (r = 0.36, p = 0.001) and with the skin score (r = 0.33, p = 0.001). Cultures of BAL fluid resulted positive in 10 (23.8%) of the 42 patients that underwent BAL and after one year a deterioration in PFTs occurred in 8 (80%) of these patients (p = 0.01). Pulmonary artery systolic pressure ≥ 40 mmHg was found in 6 (37.5%) patients with alveolitis. Conclusion We found alveolitis only in 38.1% of the patients who had exhibited ground glass on

  16. Use of anti-tumor necrosis factor biologics in the treatment of rheumatoid arthritis does not change human T-lymphotropic virus type 1 markers: a case series.

    PubMed

    Umekita, Kunihiko; Umeki, Kazumi; Miyauchi, Shunichi; Ueno, Shiro; Kubo, Kazuyoshi; Kusumoto, Norio; Takajo, Ichiro; Nagatomo, Yasuhiro; Okayama, Akihiko

    2015-09-01

    Anti-tumor necrosis factor (anti-TNF) biologics are effective in the treatment of rheumatoid arthritis (RA); however, it is still not clear whether this treatment promotes the development of malignancies such as lymphoma. Human T-lymphotropic virus type 1 (HTLV-1), which is a causative agent of adult T-cell lymphoma (ATL), is prevalent in Japan. Many HTLV-1-positive patients with RA are assumed to exist; however, there have thus far been no reports on the effect of anti-TNF biologics on HTLV-1-positive patients. We analyzed the response to treatment with anti-TNF biologics and change of HTLV-1 markers in two cases of RA. The two cases showed no response based on the European League Against of Rheumatism response criteria 60-96 weeks after administration of anti-TNF biologics (infliximab and etanercept). No signs of ATL were observed and HTLV-1 markers, such as proviral load and clonality of HTLV-1-infected cells, showed no significant change in either of two cases. Therefore, treatment with anti-TNF biologics did not induce activation of HTLV-1, although the effect on RA was not as effective as in HTLV-1-negative patients in this limited study. Further long-term study with a greater number of patients is necessary to clarify the safety and efficacy of anti-TNF biologics in HTLV-1-positive patients with RA.

  17. Small Hepatocellular Carcinoma With Low Tumor Marker Expression Benefits More From Anatomical Resection Than Tumors With Aggressive Biology.

    PubMed

    Jung, Dong-Hwan; Hwang, Shin; Lee, Young-Joo; Kim, Ki-Hun; Song, Gi-Won; Ahn, Chul-Soo; Moon, Deok-Bog; Lee, Sung-Gyu

    2017-08-23

    We assessed prognostic advantage of anatomical resection (AR) over nonanatomical resection (NAR) for hepatocellular carcinoma (HCC) according to multiplication of α-fetoprotein, des-γ-carboxyprothrombin, and tumor volume (ADV) scores. Superiority of AR over NAR is debated. ADV score is surrogate marker of postresection prognosis for solitary HCC. This study included 1572 patients who underwent curative resection for solitary HCC of 2.0 to 5.0 cm between 2006 and 2014. Preoperative patient profiles were not statistically different between AR and NAR groups. In 1324 naïve patients without preoperative treatment, AR group showed lower recurrence rates (P = 0.003) and higher patient survival rates (P = 0.012) than NAR group. AR group showed lower recurrence rates in patients with ADV ≤5 log (P ≤ 0.046). ADV scores >4 log and >3 log were independent risk factors for tumor recurrence and patient survival in treatment-naïve patients, respectively. In treatment-naïve group with preserved hepatic functional reserve, AR group showed lower recurrence rates in patients with ADV ≤4 log (P = 0.026). Absence of microvascular invasion also showed lower recurrence rates (P = 0.007) in AR group. In 248 patients with preoperative treatment, AR group showed lower recurrence rates (P = 0.001) and higher patient survival rates (P = 0.006). AR group showed lower recurrence rates in patients with ADV ≤4 log (P < 0.001) and higher survival rates in patients with ADV ≤5 log (P ≤ 0.043). Prognostic benefit of AR was evident in patients with ADV score ≤4 log or absence of microvascular invasion. Patients with less aggressive tumor biology benefit more from AR than NAR, thus being reasonably indicated for AR.

  18. Orgasmic dysfunction

    MedlinePlus

    Inhibited sexual excitement; Sex - orgasmic dysfunction; Anorgasmia; Sexual dysfunction - orgasmic; Sexual problem - orgasmic ... of knowledge about sexual function Negative feelings about sex (often learned in childhood or teen years) Shyness ...

  19. Erectile Dysfunction

    MedlinePlus

    ... PCF? Featured Blue Jacket Fashion Show Contact Us Erectile Dysfunction Regardless of whether the nerves were spared during ... time returning to pre-treatment function. Management of Erectile Dysfunction When a man is sexually aroused, the erectile ...

  20. Diurnal variations of plasma homocysteine, total antioxidant status, and biological markers of muscle injury during repeated sprint: effect on performance and muscle fatigue--a pilot study.

    PubMed

    Hammouda, Omar; Chtourou, Hamdi; Chahed, Henda; Ferchichi, Salyma; Kallel, Choumous; Miled, Abdelhedi; Chamari, Karim; Souissi, Nizar

    2011-12-01

    The aim of this study was (i) to evaluate whether homocysteine (Hcy), total antioxidant status (TAS), and biological markers of muscle injury would be affected by time of day (TOD) in football players and (ii) to establish a relationship between diurnal variation of these biomarkers and the daytime rhythm of power and muscle fatigue during repeated sprint ability (RSA) exercise. In counterbalanced order, 12 football (soccer) players performed an RSA test (5 x[6 s of maximal cycling sprint + 24 s of rest]) on two different occasions: 07:00-08:30 h and 17:00-18:30 h. Fasting blood samples were collected from a forearm vein before and 3-5 min after each RSA test. Core temperature, rating of perceived exertion, and performances (i.e., Sprint 1, Sprint 2, and power decrease) during the RSA test were significantly higher at 17:00 than 07:00 h (p < .001, p < .05, and p < .05, respectively). The results also showed significant diurnal variation of resting Hcy levels and all biological markers of muscle injury with acrophases (peak times) observed at 17:00 h. These fluctuations persisted after the RSA test. However, biomarkers of antioxidant status' resting levels (i.e., total antioxidant status, uric acid, and total bilirubin) were higher in the morning. This TOD effect was suppressed after exercise for TAS and uric acid. In conclusion, the present study confirms diurnal variation of Hcy, selected biological markers of cellular damage, and antioxidant status in young football players. Also, the higher performances and muscle fatigue showed in the evening during RSA exercise might be due to higher levels of biological markers of muscle injury and lower antioxidant status at this TOD.

  1. 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

  2. Depressiveness, symptoms of anxiety and cognitive dysfunctions in patients with asthma and chronic obstructive pulmonary disease (COPD): possible associations with inflammation markers: a pilot study.

    PubMed

    Bratek, Agnieszka; Zawada, Karolina; Beil-Gawełczyk, Julia; Beil, Sonia; Sozańska, Ewa; Krysta, Krzysztof; Barczyk, Adam; Krupka-Matuszczyk, Irena; Pierzchała, Władysław

    2015-08-01

    Psychiatric symptoms of anxiety, depression and cognitive dysfunction often occur in patients suffering from somatic conditions such as asthma and chronic obstructive pulmonary disease (COPD) which constitute a major and growing public health problem. In the present study we therefore aimed at analyzing depressive symptoms as well as symptoms of anxiety and cognitive problems in patients with mild to moderate asthma and COPD. 59 participants-17 with asthma, 24 with COPD and 18 healthy controls were enrolled. Depressiveness was assessed with the beck depression inventory (BDI); anxiety symptoms were measured with the State-Trait Anxiety Inventory Part 1 and 2, and cognitive function levels were estimated with the Trail Making Test Part A and B. A score above the threshold indicative for depression was found by 33 % (n = 8) of COPD patients, 29 % (n = 5) of asthma patients compared to 0.05 % (n = 1) of the control group. Clinically relevant anxiety levels were found in 42 % (n = 10) of the COPD group, 41 % (n = 7) of the asthma patients and 17 % (n = 3) of the controls. Patients with COPD performed significantly worse on the TMT than other groups. Psychoemotional state and cognitive functions were found to be correlated with exposure to tobacco smoke (measured in pack-years) and airway obstruction (measured with FEV1). In conclusion, patients with mild to moderate asthma and COPD exhibit significantly higher levels of depressive and anxiety symptoms as well as cognitive dysfunctions than controls. The prevalence of these symptoms is related to the amount of exposure to tobacco smoke and the severity of airflow obstruction.

  3. 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

  4. Prognostic value of new-onset anemia as a marker of hemodilution in patients with acute decompensated heart failure and severe renal dysfunction.

    PubMed

    Hong, Namki; Youn, Jong-Chan; Oh, Jaewon; Lee, Hye Sun; Park, Sungha; Choi, Donghoon; Kang, Seok-Min

    2014-07-01

    In patients with acute decompensated heart failure (ADHF), the prognostic value of new-onset anemia with regard to renal function has not been investigated. Consecutive 299 ADHF patients (162 men, 62 ± 14 years) were enrolled. Cardiovascular (CV) events composite of CV mortality and rehospitalization occurred in 113 patients (37.8%) during 2 years of follow-up. Baseline anemia was prevalent (n = 124, 41.5%) and 43 patients (14.4%) had new-onset anemia at 1 month after discharge. Baseline anemia was strongly associated with CV events risk in overall [hazard ratio (HR): 1.79, 95% CI: 1.17-2.74, p = 0.006] and those with preserved renal function [estimated glomerular filtration rate (eGFR)≥ 45 mL/min/1.73 m(2)] (HR: 1.81, 95% CI: 1.05-3.12, p = 0.031). In patients with severe renal dysfunction (eGFR<45 mL/min/1.73 m(2)), new-onset anemia independently predicted CV events (HR: 2.72, 95% CI: 1.09-6.76, p = 0.031) whereas baseline anemia did not (HR: 1.28, 95% CI: 0.61-2.65, p = 0.505). New-onset anemia was significantly associated with hemodilution, which may reflect inadequate decongestion in ADHF patients. Baseline anemia was an independent prognostic factor in overall ADHF patients and those with preserved renal function. New-onset anemia as a surrogate for hemodilution better predicted CV events than baseline anemia in ADHF patients with severe renal dysfunction. Copyright © 2013. Published by Elsevier Ltd.

  5. Inflammatory markers are associated with left ventricular hypertrophy and diastolic dysfunction in a population-based sample of elderly men and women.

    PubMed

    Masiha, S; Sundström, J; Lind, L

    2013-01-01

    Markers of inflammation have previously been related to left ventricular (LV) hypertrophy (LVH) in uremic and hypertensive patients. The present study investigated inflammatory markers in relation to LV geometry and diastolic function in a population of elderly persons. In the population-based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (1016 men and women 70 years of age), echocardiograms to determine relative wall thickness (RWT), LV mass index (LVMI) and the E/A-ratio were obtained. Based on RWT and LVMI, four geometric subgroups were defined; normal, concentric remodeling, eccentric and concentric LVH. In all, 10 circulating inflammatory markers were measured. Higher levels of high sensitive C-reactive protein (hsCRP) and E-selectin were seen in the three abnormal geometry groups than in the normal group adjusting for gender, body mass index, systolic and diastolic blood pressure and use of antihypertensive medication. Higher level of inter-cellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1) and P-selectin were only seen in concentric LVH. Levels of tumor necrosis factor-alpha, interleukin-6, l-selectin, monocyte chemotactic protein-1 and leukocyte count did not differ between the LV groups. l-selectin and hsCRP were related to the E/A-ratio. The adhesion molecules; E-selectin, ICAM-1, VCAM-1, P-selectin and hsCRP were elevated in elderly persons with abnormal LV geometry, especially in concentric LVH, after adjusting for hypertension and obesity. l-selectin and hsCRP were related to LV diastolic function. Further studies are motivated to investigate a pathogenetic role of inflammation for abnormal LV geometry and function.

  6. Neutrophil Gelatinase-Associated Lipocalin in Kidney Transplantation Is an Early Marker of Graft Dysfunction and Is Associated with One-Year Renal Function

    PubMed Central

    Fonseca, Isabel; Oliveira, José Carlos; Almeida, Manuela; Cruz, Madalena; Malho, Anabela; Martins, La Salete; Dias, Leonídio; Santos, Josefina; Lobato, Luísa; Castro Henriques, António; Mendonça, Denisa

    2013-01-01

    Urinary neutrophil gelatinase-associated lipocalin (uNGAL) has been suggested as potential early marker of delayed graft function (DGF) following kidney transplantation (KTx). We conducted a prospective study in 40 consecutive KTx recipients to evaluate serial changes of uNGAL within the first week after KTx and assess its performance in predicting DGF (dialysis requirement during initial posttransplant week) and graft function throughout first year. Urine samples were collected on post-KTx days 0, 1, 2, 4, and 7. Linear mixed and multivariable regression models, receiver-operating characteristic (ROC), and areas under ROC curves were used. At all-time points, mean uNGAL levels were significantly higher in patients developing DGF (n = 18). Shortly after KTx (3–6 h), uNGAL values were higher in DGF recipients (on average +242 ng/mL, considering mean dialysis time of 4.1 years) and rose further in following days, contrasting with prompt function recipients. Day-1 uNGAL levels accurately predicted DGF (AUC-ROC = 0.93), with a performance higher than serum creatinine (AUC-ROC = 0.76), and similar to cystatin C (AUC-ROC = 0.95). Multivariable analyses revealed that uNGAL levels at days 4 and 7 were strongly associated with one-year serum creatinine. Urinary NGAL is an early marker of graft injury and is independently associated with dialysis requirement within one week after KTx and one-year graft function. PMID:24288591

  7. 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

  8. 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

    2016-08-03

    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.

  9. 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

  10. Composite Marker of Cognitive Dysfunction and Brain Atrophy is Highly Accurate in Discriminating Between Relapsing-Remitting and Secondary Progressive Multiple Sclerosis

    PubMed Central

    Kizlaitienandedot, Rasa; Kaubrys, Gintaras; Giedraitienandedot, Nataandscaron;a; Ramanauskas, Naglis; Dementaviandccaron;ienandedot;, Jūratandedot;

    2017-01-01

    Background With the advent of numerous new-generation disease-modifying drugs for multiple sclerosis (MS), the discrimination between relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) has become a problem of high importance. The aim of our study was to find a simple way to accurately discriminate between RRMS and SPMS that is applicable in clinical practice as a composite marker, using the linear measures of magnetic resonance imaging (MRI) and the results of cognitive tests. Material/Methods We included 88 MS patients in the study: 43 participants had RRMS and 45 had SPMS. A battery consisting of 11 tests was used to evaluate cognitive function. We used 11 linear MRI measures and 7 indexes to assess brain atrophy. Results Four cognitive tests and 3 linear MRI measures were able to distinguish RRMS from SPMS with the AUC >0.8 based on ROC analysis. Multiple logistic regression models were constructed to identify the best set of cognitive and MRI markers. The model, using the Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST), and Huckman Index, showed the highest predictive ability: AUC=0.921 (p<0.001). We constructed a simple remission-progression index from the same 3 variables, which discriminated well between RRMS and SPMS: AUC=0.920 (p<0.001), maximal Youden Index=0.702, cut-off=1.68, sensitivity=79.1%, and specificity=91.1%. Conclusions The composite remission-progression index, using the RAVLT test, DSST test, and MRI Huckman Index, is highly accurate in discriminating between RRMS and SPMS. PMID:28145395

  11. Composite Marker of Cognitive Dysfunction and Brain Atrophy is Highly Accurate in Discriminating Between Relapsing-Remitting and Secondary Progressive Multiple Sclerosis.

    PubMed

    Kizlaitienė, Rasa; Kaubrys, Gintaras; Giedraitienė, Nataša; Ramanauskas, Naglis; Dementavičienė, Jūratė

    2017-02-01

    BACKGROUND With the advent of numerous new-generation disease-modifying drugs for multiple sclerosis (MS), the discrimination between relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) has become a problem of high importance. The aim of our study was to find a simple way to accurately discriminate between RRMS and SPMS that is applicable in clinical practice as a composite marker, using the linear measures of magnetic resonance imaging (MRI) and the results of cognitive tests. MATERIAL AND METHODS We included 88 MS patients in the study: 43 participants had RRMS and 45 had SPMS. A battery consisting of 11 tests was used to evaluate cognitive function. We used 11 linear MRI measures and 7 indexes to assess brain atrophy. RESULTS Four cognitive tests and 3 linear MRI measures were able to distinguish RRMS from SPMS with the AUC >0.8 based on ROC analysis. Multiple logistic regression models were constructed to identify the best set of cognitive and MRI markers. The model, using the Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST), and Huckman Index, showed the highest predictive ability: AUC=0.921 (p<0.001). We constructed a simple remission-progression index from the same 3 variables, which discriminated well between RRMS and SPMS: AUC=0.920 (p<0.001), maximal Youden Index=0.702, cut-off=1.68, sensitivity=79.1%, and specificity=91.1%. CONCLUSIONS The composite remission-progression index, using the RAVLT test, DSST test, and MRI Huckman Index, is highly accurate in discriminating between RRMS and SPMS.

  12. 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.

  13. 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.

  14. Differing associations between Aβ accumulation, hypoperfusion, blood-brain barrier dysfunction and loss of PDGFRB pericyte marker in the precuneus and parietal white matter in Alzheimer's disease.

    PubMed

    Miners, J Scott; Schulz, Isabel; Love, Seth

    2017-01-01

    Recent studies implicate loss of pericytes in hypoperfusion and blood-brain barrier (BBB) leakage in Alzheimer's disease (AD). In this study, we have measured levels of the pericyte marker, platelet-derived growth factor receptor-β (PDGFRB), and fibrinogen (to assess blood-brain barrier leakage), and analyzed their relationship to indicators of microvessel density (von Willebrand factor level), ante-mortem oxygenation (myelin-associated glycoprotein:proteolipid protein-1 ratio and vascular endothelial growth factor level), Aβ level and plaque load, in precuneus and underlying white matter from 49 AD to 37 control brains. There was reduction in PDGFRB and increased fibrinogen in the precuneus in AD. These changes correlated with reduction in oxygenation and with plaque load. In the underlying white matter, increased fibrinogen correlated with reduced oxygenation, but PDGFRB level was unchanged. The level of platelet-derived growth factor-ββ (PDGF-BB), important for pericyte maintenance, was increased in AD but mainly in the insoluble tissue fraction, correlating with insoluble Aβ level. Loss of the PDGFRB within the precuneus in AD is associated with fibrinogen leakage and reduced oxygenation, and related to fibrillar Aβ accumulation. In contrast, fibrinogen leakage and reduced oxygenation of underlying white matter occur independently of loss of PDGFRB, perhaps secondary to reduced transcortical perfusion.

  15. Changes in bone biological markers after treatment of Iranian diabetic patients with pioglitazone: No relation to polymorphism of PPAR-γ (Pro12Ala).

    PubMed

    Namvaran, Fatemeh; Rahimi-Moghaddam, Parvaneh; Azarpira, Negar; Dabbaghmanesh, Mohammad Hossien; Bakhshayeshkaram, Marzieh; Namvaran, Mohamad Mahdi

    2013-04-01

    Thiazolidinediones (TZDs) improves insulin sensitivity by activating the peroxisome proliferator-activated receptor γ (PPAR-g). We aimed to study any association between variation in bone biochemical markers and single nucleotide polymorphism (SNP) in PPAR-γ (Pro12Ala) and investigate if these genetic variants affect bone turnover markers in Iranian diabetic population before and after treatment with pioglitazone. A total of 101 patients (type 2 diabetic (T2D) were treated for 12 weeks with pioglitazone (15 mg/day). Bone Biological markers, osteocalcin, and C-terminal telopeptide of type 1 collagen (CTx) were measured before and after pioglitazone therapy. We genotyped 128 nondiabetic controls and 101 T2D patients as well. Pro12Ala polymorphism in PPAR-γ was done by real-time polymerase chain reaction (RT-PCR) using TaqMan assay. There were statistically significant differences in allele frequencies of Pro12Ala while comparing the controls with T2D subjects. Ala frequency was 7 vs 3%, P = 0.036 and genotypic frequency of Pro/Ala was 5.94 vs 14.06%, P = 0.04. After treatment, the homeostasis model of assessment of insulin resistance (HOMA-IR) as a maker of insulin resistance was significantly decreased (P < 0.001). In respect of bone turnover markers, CTx values decreased and osteocalcin significantly increased. (P < 0.001). Our findings did not reveal a significant association between this polymorphism and bone turnover markers after pioglitazone treatment. The reduced insulin resistance might be the reason that CTx values decreased and osteocalcin increased significantly after short-term pioglitazone treatment. These findings suggest the need for further studies on the possible role of insulin in regulation of bone metabolism.

  16. Erectile dysfunction.

    PubMed

    Shamloul, Rany; Ghanem, Hussein

    2013-01-12

    Erectile dysfunction is a common clinical entity that affects mainly men older than 40 years. In addition to the classical causes of erectile dysfunction, such as diabetes mellitus and hypertension, several common lifestyle factors, such as obesity, limited or an absence of physical exercise, and lower urinary tract symptoms, have been linked to the development of erectile dysfunction. Substantial steps have been taken in the study of the association between erectile dysfunction and cardiovascular disease. Erectile dysfunction is a strong predictor for coronary artery disease, and cardiovascular assessment of a non-cardiac patient presenting with erectile dysfunction is now recommended. Substantial advances have occurred in the understanding of the pathophysiology of erectile dysfunction that ultimately led to the development of successful oral therapies, namely the phosphodiesterase type 5 inhibitors. However, oral phosphodiesterase type 5 inhibitors have limitations, and present research is thus investigating cutting-edge therapeutic strategies including gene and cell-based technologies with the aim of discovering a cure for erectile dysfunction.

  17. Socioeconomic status and biological markers of health: an examination of adults in the United States and Taiwan.

    PubMed

    Cornman, Jennifer C; Glei, Dana A; Goldman, Noreen; Ryff, Carol D; Weinstein, Maxine

    2015-02-01

    The study documents whether socioeconomic status (SES) differentials in biological risk are more widely observed and larger in the United States than Taiwan. 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. Physiological dysregulation is significantly, negatively related to SES in both the United States 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 United States and 11 of 24 are significant in Taiwan. Overall, SES differentials in biological risk do not appear to be more widely observed or larger in the United States than in Taiwan. © The Author(s) 2014.

  18. 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.

  19. 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.

  20. Elucidating the Biological Mechanisms Linking Depressive Symptoms With Type 2 Diabetes in Men: The Longitudinal Effects of Inflammation, Microvascular Dysfunction, and Testosterone.

    PubMed

    Tully, Phillip J; Baumeister, Harald; Martin, Sean; Atlantis, Evan; Jenkins, Alicia; Januszewski, Andrzej; OʼLoughlin, Peter; Taylor, Anne; Wittert, Gary A

    2016-01-01

    This prospective cohort study sought to examine key biological measures linking depressive symptoms with Type 2 diabetes, specifically inflammation, microvascular dysfunction, and androgens. A cohort of 688 men without diabetes who were 35 years or older were followed up for 5 years. Venous interleukin-6, high-sensitivity C-reactive protein, sE-selectin, endogenous total testosterone, fasting glucose, and glycated hemoglobin (HbA1c) were quantified at baseline and 5 years later. Depressive symptoms were assessed using the Beck Depression Inventory-I, and men were categorized into persistent, remitted, incident, and nondepressed groups (reference). Logistic regression was used to determine odds ratios (ORs) for diabetes adjusted for propensity score calculated from 18 established risk factors. Diabetes developed in 112 men (16.3% of sample). Persistent depressive symptoms were associated with diabetes (adjusted OR = 2.45, 95% confidence interval [CI] = 1.16-5.20, p = .019). Baseline testosterone (OR = 0.43, 95% CI = 0.22-0.81, p = .01) and follow-up testosterone (OR = 0.51, 95% CI = 0.31-0.84, p = .008) were inversely associated with Type 2 diabetes. Annualized HbA1c was positively associated with annualized change in cognitive Beck Depression Inventory symptoms (β = 0.14, p = .001) and inversely associated with annualized change in testosterone (β = -0.10, p = .014). Annualized change in fasting glucose was associated with sE-selectin (β = 0.12, p < .001) and somatic depressive symptoms (β = -0.12, p = .002). The findings suggest that lower endogenous total testosterone levels and persistent depressive symptoms were associated with Type 2 diabetes risk and HbA1c in men over a 5-year period.

  1. 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

  2. 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.

  3. Soluble endothelial protein C receptor and high sensitivity C reactive protein levels as markers of endothelial dysfunction in patients with type 1 and type 2 diabetes mellitus: their role in the prediction of vascular complications.

    PubMed

    Zaghloul, Amal; Al-Bukhari, T A M A; Al-Pakistani, H A; Shalaby, Maged; Halawani, Saeed H; Bajuaifer, Nada; Teama, Shirin H

    2014-12-01

    Endothelial dysfunction in diabetes mellitus (DM) is an important factor in the pathogenesis of micro and macrovascular complications. We aimed to measure soluble endothelial protein C receptor (sEPCR) and high sensitivity C reactive protein (hsCRP) levels as markers of endothelial damage in both types of diabetes mellitus and to determine if they can be used as predictors of vascular complications. Fifty patients with DM, 20 with type 1 and 30 with type 2 as well as 30 healthy subjects were included. All were subjected to measurement of sEPCR and hsCRP by enzyme linked immunosorbent assay. sEPCR and hsCRP were significantly increased when compared to the control group in both types of DM. sEPCR was a significant predictor of macrovascular complications and thrombosis in type 1 p=0.02, and p=0.015, respectively. hsCRP was a significant predictor of macrovascular complications in type 2 p=0.04. Patients with type 1 and type 2 DM exhibit higher sEPCR and hsCRP levels compared to healthy controls which suggesting endothelial damage. sEPCR could be used as a predictor of macrovascular complications and thrombosis in type 1 DM, whereas, hsCRP might be used as a predictor of macrovascular complications in type 2 DM. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed

    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. Copyright

  5. 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.

  6. Biologic markers of breast cancer in nipple aspirate fluid and nipple discharge are associated with clinical findings1

    PubMed Central

    Sauter, Edward R.; Wagner-Mann, Colette; Ehya, Hormoz; Klein-Szanto, Andres

    2007-01-01

    Background The aim of this prospective study was to assess predictive markers in nipple aspirate fluid (NAF) and pathologic nipple discharge (PND) collected prior to excisional breast biopsy, as well as clinical factors available prior to biopsy, with histopathologic results in women with a radiographically suspicious and/or palpable breast lesion. Methods 208 NAF samples from 191 women were evaluated for the following candidate predictive proteins and cellular markers: prostate-specific antigen (PSA), human glandular kallikrein 2 (hK2), basic fibroblast growth factor (bFGF), S phase fraction (SPF), DNA index, and cytology. Clinical factors included whether or not the lesion was palpable, menopausal status, history of pregnancy, history of birth control or hormone replacement use, and PND. Results Considering all women, bFGF (p=0.005) and SPF (0.031) were associated, and abnormal cytology approached an association (p=0.056) with the presence of breast cancer. Women with PND were less likely to have breast cancer (4 vs. 37%, p<0.001) or palpable lesions (10 vs.43%, p < 0.001), were younger, had lower PSA levels (p=0.046), and were more likely to have atypical NAF cytology (p=0.002). Excluding PND, increased age, postmenopause (both p<0.01), high bFGF (p=0.004) and low PSA (p=0.05) were associated with cancer. The best breast cancer predictive model included cytology, bFGF, and age (88% sensitive and 57% specific). When the data were divided by menopausal status, the optimal models, which included NAF hK2 or PSA and age, were 100% sensitive and 41% specific in pre- vs. 93% sensitive and 12% specific in predicting breast cancer in postmenopausal women. Conclusion NAF and clinical biomarkers are sensitive predictors of whether a breast contains cancer, and may ultimately help guide treatment. Future studies to determine the optimal combination of predictive markers are warranted. PMID:17317033

  7. Biochemistry, molecular biology, and pharmacology of fatty acid synthase, an emerging therapeutic target and diagnosis/prognosis marker

    PubMed Central

    Liu, Hailan; Liu, Jing-Yuan; Wu, Xi; Zhang, Jian-Ting

    2010-01-01

    Human fatty acid synthase (FASN) is a 270-kDa cytosolic dimeric enzyme that is responsible for palmitate synthesis. FASN is slowly emerging and rediscovered as a marker for diagnosis and prognosis of human cancers. Recent studies showed that FASN is an oncogene and inhibition of FASN effectively and selectively kill cancer cells. With recent publications of the FASN crystal structure and the new development of FASN inhibitors, targeting FASN opens a new window of opportunity for metabolically combating cancers. In this article, we will review critically the recent progresses in understanding the structure, function, and the role of FASN in cancers and pharmacologically targeting FASN for human cancer treatment. PMID:20706604

  8. Erectile Dysfunction

    MedlinePlus

    ... your erectile problems, such as drugs used to treat depression or high blood pressure. Making a change to your medications may help. Seek counseling. Anxiety and stress can worsen erectile dysfunction. A psychologist or other mental health provider can ...

  9. Erectile Dysfunction

    MedlinePlus

    ... can — over time — cause chronic health conditions that lead to erectile dysfunction Being overweight, especially if you're obese Certain medical treatments, such as prostate surgery or radiation treatment for cancer Injuries, particularly if they damage ...

  10. Genetic characterization of T-PLL reveals two major biologic subgroups and JAK3 mutations as prognostic marker.

    PubMed

    Stengel, Anna; Kern, Wolfgang; Zenger, Melanie; Perglerová, Karolína; Schnittger, Susanne; Haferlach, Torsten; Haferlach, Claudia

    2016-01-01

    T-cell prolymphocytic leukemia (T-PLL) is a rare post-thymic T-cell neoplasm with aggressive clinical course and short overall survival. So far, due to the rareness of this disease, genetic data are available only from individual cases or small cohorts. In our study, we aimed at performing a comprehensive cytogenetic and molecular genetic characterization of T-PLL comprising the largest cohort of patients with T-PLL analyzed so far, including correlations between the respective markers and their impact on prognosis. Genetic abnormalities were found in all 51 cases with T-PLL, most frequently involving the TCRA/D locus (86%). Deletions were detected for ATM (69%) and TP53 (31%), whereas i(8)(q10) was observed in 61% of cases. Mutations in ATM, TP53, JAK1, and JAK3 were detected in 73, 14, 6, and 21% of patients, respectively. Additionally, BCOR mutations were observed for the first time in a lymphoid malignancy (8%). Two distinct genetic subgroups of T-PLL were identified: A large subset (86% of patients) showed abnormalities involving the TCRA/D locus activating the proto-oncogenes TCL1 or MTCP1, while the second group was characterized by a high frequency of TP53 mutations (4/7 cases). Further, analyses of overall survival identified JAK3 mutations as important prognostic marker, showing a significant negative impact. © 2015 Wiley Periodicals, Inc.

  11. Quality Assessment of Panax notoginseng from Different Regions through the Analysis of Marker Chemicals, Biological Potency and Ecological Factors

    PubMed Central

    Zhang, Ding-kun; Wang, Yan-hui; Li, Gang; Yan, Gui-lin; Cao, Li-juan; Xiao, Xiao-he; Huang, Lu-qi; Wang, Jia-bo

    2016-01-01

    Panax notoginseng (Burk.) F.H. Chen, called Sanqi in China, is a perennial herb that has been used as a medicinal herb in traditional Chinese medicine for more than 400 years. Because notoginseng is included in many proprietary Chinese medicines, the quality of notoginseng directly affects its efficacy and safety. However, considering the complex and special growth environment requirements of notoginseng, it is insufficient to evaluate its quality based solely on the analysis of marker chemicals. Thus, in this study, we tried to evaluate the quality of notoginseng with integrated indicators: (1) the concentration of five marker chemicals, notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1 and ginsenoside Rd; (2) the anticoagulant activity (ACA); and (3) twenty-one ecological factors (e.g., longitude, latitude, elevation and soil data). Using these 27 parameters, notoginseng from different regions could be distinguished effectively, indicating a remarkable divergence of quality. A correlation analysis showed that variations of the ecological factors were closely associated with the saponins content and biopotency. For instance, the total nitrogen (TN), alkali hydrolysis nitrogen (AHN) and rapidly available potassium (RAPT) were significantly correlated with ACA, and RAPT was significantly correlated with the content of ginsenoside Rd and notoginsenoside R1. The results demonstrated that the high-quality notoginseng was produced from the emerging regions such as Kunming, Qujing and Honghe, which had higher ACA and saponin content than the notoginseng produced in traditional regions such as Wenshan and Baise. PMID:27723805

  12. Cutaneous lymphocyte-associated antigen as a novel predictive marker of TNF-alpha inhibitor biological therapy in psoriasis.

    PubMed

    Jókai, Hajnalka; Szakonyi, József; Kontár, Orsolya; Barna, Gábor; Inotai, Dóra; Kárpáti, Sarolta; Holló, Péter

    2013-03-01

    A considerable number of patients with psoriasis show secondary resistance during long-term TNF-alpha inhibitor therapy, necessitating the identification of reliable predictive markers. Predictive role of cutaneous lymphocyte-associated antigen (CLA) was investigated. Thirty-eight severe patients with psoriasis were treated for a 24-week-long study period. Clinical responsiveness (PASI) and changes in flow cytometry-measured peripheral lymphocyte CLA expression (week 0-2-6) were statistically analysed. Regarding 24-week-long treatment outcome patients were divided into two groups: During the first 6 weeks, mean CLA expression showed significant (P = 0.034604) increase among responders (32/38), while after a preliminary increase, it was significantly (P = 0.012539) decreasing in the relapsing group (6/38). Pearson's correlation analysis showed significant negative correlation between PASI and CLA changes. Responders showed (not significantly) lower initial CLA expression than relapsing patients. Our observations suggest change in CLA expression during the first 6 weeks of induction period to serve as a potential predictive marker of TNF-alpha inhibitor therapy in psoriasis.

  13. 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.

  14. 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

  15. The Report-AGE project: a permanent epidemiological observatory to identify clinical and biological markers of health outcomes in elderly hospitalized patients in Italy.

    PubMed

    Bustacchini, Silvia; Abbatecola, Angela Marie; Bonfigli, Anna Rita; Chiatti, Carlos; Corsonello, Andrea; Di Stefano, Giuseppina; Galeazzi, Roberta; Fabbietti, Paolo; Lisa, Rosamaria; Guffanti, Enrico E; Provinciali, Mauro; Lattanzio, Fabrizia

    2015-12-01

    Italy is expected to experience the largest growth in persons ≥65 years (>20% by 2020). This demographic shift allows for geriatric research on predictive clinical and biological markers of outcomes related to frailty, re-hospitalization and mortality. To describe rationale and methods of the Report-AGE study project of acute care patients in Italian National Research Center on Aging (INRCA) research hospitals. Report-AGE study is a large observational study on health conditions and outcomes of hospitalized elderly patients (≥65 years). The primary objective of the study is to create a high-level data resource of demographics, comprehensive geriatric assessments, clinical and diagnostic information, as well as biological and molecular markers in all older patients admitted to INRCA Hospitals. Assessments in physical and nutritional parameters, co-morbid health conditions, and associations with frailty parameters are ongoing in older hospitalized adults following an acute event. Study collection began in September 2011. Up to date, there are 3479 patients ≥65 years (mean age: 85 ± 7years) with 1543 men and 1936 women enrolled. Data have been recorded regarding functional and clinical parameters before, during hospital admission and at discharge. Data collection for primary outcome analyses related to re-hospitalization and mortality is estimated for September 2016. This study aims at collecting precise clinical data, comprehensive geriatric assessment, risk factors, and biological data from acute care patients. Data will also be used to identify mechanisms underlying frailty in this specific population. This study provides a descriptive epidemiological collection of the health conditions of older in-patients.

  16. Erectile dysfunction

    PubMed Central

    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

  17. Current status on behavioral and biological markers of PTSD: a search for clarity in a conflicting literature.

    PubMed

    Zoladz, Phillip R; Diamond, David M

    2013-06-01

    Extensive research has identified stereotypic behavioral and biological abnormalities in post-traumatic stress disorder (PTSD), such as heightened autonomic activity, an exaggerated startle response, reduced basal cortisol levels and cognitive impairments. We have reviewed primary research in this area, noting that factors involved in the susceptibility and expression of PTSD symptoms are more complex and heterogeneous than is commonly stated, with extensive findings which are inconsistent with the stereotypic behavioral and biological profile of the PTSD patient. A thorough assessment of the literature indicates that interactions among myriad susceptibility factors, including social support, early life stress, sex, age, peri- and post-traumatic dissociation, cognitive appraisal of trauma, neuroendocrine abnormalities and gene polymorphisms, in conjunction with the inconsistent expression of the disorder across studies, confounds attempts to characterize PTSD as a monolithic disorder. Overall, our assessment of the literature addresses the great challenge in developing a behavioral and biomarker-based diagnosis of PTSD. Published by Elsevier Ltd.

  18. Association of peripheral microvascular dysfunction and erectile dysfunction.

    PubMed

    Gerber, Rachael E; Vita, Joseph A; Ganz, Peter; Wager, Carrie G; Araujo, Andre B; Rosen, Raymond C; Kupelian, Varant

    2015-02-01

    Increasing evidence of a link between erectile dysfunction and cardiovascular disease suggests a shared vascular etiology with endothelial dysfunction as a plausible underlying biological mechanism. To our knowledge whether this association is different for large arterial endothelium compared to microvascular endothelium has not yet been established. We investigated the association of erectile dysfunction with macrovascular and microvascular endothelial function. A sample of 390 men with a mean age of 55.5 years was recruited from the BACH survey, a population based survey of urological symptoms. Erectile dysfunction was assessed using IIEF-5. The percent of brachial artery flow mediated dilatation, a measure of macrovascular function, and hyperemic flow velocity in cm per second, a measure of microvascular function, were assessed by ultrasound. Linear regression was used to assess the association of erectile dysfunction and endothelial function, and adjust for potential confounders. Reactive hyperemia was lower in men with vs without erectile dysfunction (mean ± SE 97.1 ± 2.5 vs 106.0 ± 1.6 cm per second, p = 0.003). However, the difference in flow mediated dilatation between men with vs without erectile dysfunction was statistically nonsignificant (mean 6.6% ± 0.33% vs 7.2% ± 0.24%, p = 0.147). The association of erectile dysfunction with reactive hyperemia was attenuated but it remained statistically significant in men with moderate to severe erectile dysfunction (IIEF-5 less than 12) after adjusting for traditional cardiovascular risk factors (p = 0.038). These results provide evidence of greater microvascular than macrovascular endothelial dysfunction as a potential contributor to erectile dysfunction and an underlying mechanism linking erectile dysfunction and cardiovascular disease. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  19. Preprocedural N-terminal pro-B-type natriuretic peptide as a useful marker for predicting periprocedural myocardial injury following percutaneous coronary intervention in diabetic patients without cardiac dysfunction.

    PubMed

    Zeng, Rui-Xiang; Li, Xiao-Lin; Zhang, Min-Zhou; Wang, Xiao-Wei; Guo, Yuan-Lin; Zhu, Cheng-Gang; Ren, Yi; Li, Sha; Zhang, Yan; Liu, Geng; Xu, Rui-Xia; Dong, Qian; Li, Jian-Jun

    2015-11-01

    Elevated preprocedural N-term pro-B-type natriuretic peptide (NT-pro-BNP) and postprocedural cardiac troponin I (cTnI) are related to a poor cardiac outcome in the non-diabetic population. We hypothesized that preprocedural NT-pro-BNP might be a useful marker in predicting periprocedural myocardial injury (PMI) following elective percutaneous coronary intervention (PCI) in type 2 diabetes (T2D). We prospectively enrolled 1194 consecutive diabetic patients with normal cardiac function and preprocedural cTnI who were successfully undergoing elective PCI. Preprocedural NT-pro-BNP levels were assessed at admission, and PMI was evaluated by analysis of cTnI within 24 hours. The relationship between preprocedural NT-pro-BNP levels and the peak values of cTnI after PCI was examined. Patients with high baseline NT-pro-BNP levels had higher postprocedural cTnI levels (β = 0.123, p < 0.001). In the multivariable model, NT-pro-BNP was associated with higher risk of postprocedural cTnI elevation above 1 × upper limit of normal (ULN, OR, 3.13; 95% CI, 1.51-6.50; p = 0.002), 3 × ULN (OR, 2.44; 95% CI, 1.17-5.08; p = 0.018), 5 × ULN (OR, 3.18; 95% CI, 1.44-7.0; p = 0.004), respectively. Moreover, the incidence of cTnI elevation was higher in patients with the upper tertile of NT-pro-BNP levels than that in ones with the lower tertile of NT-pro-BNP levels (> 1 × ULN: 63.1% vs. 50.0%, p < 0.001; > 3 × ULN: 39.2% vs. 31.9%, p = 0.032; > 5 × ULN: 30.4% vs. 21.9%, p < 0.006; respectively). Our data, for the first time, demonstrated that increased preprocedural NT-pro-BNP levels were strongly and independently associated with a higher risk of PMI, suggesting that baseline NT-pro-BNP level might be a useful marker for predicting PMI following PCI in diabetic patients without cardiac dysfunction.

  20. 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

  1. 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.

  2. 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

  3. Evaluation of stress response using psychological, biological, and electrophysiological markers during immersive simulation of life threatening events in multidisciplinary teams.

    PubMed

    Ghazali, D A; Darmian-Rafei, I; Nadolny, J; Sosner, P; Ragot, S; Oriot, D

    2017-07-27

    Stress might impair clinical performance in real life and in simulation-based education (SBE). Subjective or objective measures can be used to assess stress during SBE. This monocentric study aimed to evaluate the effects of simulation of life-threatening events on measurements of various stress parameters (psychological, biological, and electrophysiological parameters) in multidisciplinary teams (MDTs) during SBE. The effect of gender and status of participants on stress response was also investigated. Twelve emergency MDTs of 4 individuals were recruited for an immersive simulation session. Stress was assessed by: (1) self-reported stress; (2) Holter analysis, including heart rate and heart rate variability in the temporal and spectral domain (autonomic nervous system); (3) salivary cortisol (hypothalamic pituitary adrenal axis). Forty-eight participants (54.2% men, <7years of experience) were included. Measures were performed at baseline (T0), after simulation (T1), after debriefing (T2), and 30min after end of debriefing (T3). There was an increase in stress level at T1 (p<0.001) and a decrease at T2 (p<0.001). However, the variations of stress parameters induced by simulation (T0-T1 difference and T1-T2 difference) estimated by the three approaches were not correlated, while, as expected, Holter parameters were well-correlated to each other. Immersive SBE produced a change of stress level in all MDT members with no evidence for status effect but with gender difference. None developed a PTSD. These results support the hypothesis of a complementarity of the stress paths (collective reaction with increased stress level during simulation and a decrease during debriefing) but with relative independence of these paths (lack of correlation to each other). This study also suggests that because of the lack of correlation, stress response should be assessed by a combination of psychological, biological and electrophysiological parameters. Copyright © 2017 Australian

  4. 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.

  5. [Prognostic significance of leukemia-associated phenotype in correlation with other biologic markers in acute myeloid leukemia patients].

    PubMed

    Dăscălescu, Angela; Zlei, Mihaela; Grigore, Georgiana; Dănăila, C; Jitaru, Daniela; Carasevici, E

    2009-01-01

    Leukemic cells have unique aberrant phenotypes, which permit identification of this cells at diagnose and in evolution of the disease. Signaling molecules with other cells and bone marrow stroma are part of the leukemic cells phenotype. Genetic and molecular abnormalities have the main prognostic significance and confer the leukemic cell status. The main aim of the current study is to identify correlation between recognized prognostic factors in acute myeloid leukemia (AML) patients and other phenotypic markers. Imunophenotypic analysis (BDFACS CantoII, FACSDiva Software) was performed on peripheral blood/bone marrow aspirate samples of 56 patients diagnosed with AML (9 M0, 3 M1, 10 M2, 4 M3, 28 M4/M5, 1 M6, 1 M7) between 2007-2009 in Hematology Department of "Sf. Spiridon" Hospital Iaşi. We used an extended panel of monoclonal antibodies and we determined the level of expression of cytokines receptors (IL3Ra, IL7R) and chemokines (CXCR4, CKR5). In our study, IL7R expression on AML blasts was significant correlate with low WBC count at diagnosis (p = 0.04) and with multilinear displasia (p = 0.01), high CXCR4 expression was correlate (p = 0.05) with lack of response at first induction therapy and CD123 (IL3Ra) expression was correlate with M4 FAB phenotype. Survival was negative influenced by presence of IL3R on AML blasts, but flt3 mutations, CXCR4, IL7R expression on leukemic cells, other phenotypic aberrancies did not influenced treatment response and survival in our patients population. Complete investigation of leukemic cells phenotype extended with cytokines/chemokines receptors at diagnostic is useful for correct characterization of the disease, for discover new prognostic categories and for better identification of minimal residual disease.

  6. Impact of religiosity/spirituality on biological and preclinical markers related to cardiovascular disease. Results from the SPILI III study.

    PubMed

    Anyfantakis, Dimitrios; Symvoulakis, Emmanouil K; Panagiotakos, Demosthenes B; Tsetis, Dimitrios; Castanas, Elias; Shea, Sue; Venihaki, Maria; Lionis, Christos

    2013-01-01

    This study aimed at exploring to what extent psychosocial factors, such as religiosity/spirituality and sense of coherence, mediate the negative effects of stress on a variety of cardiometabolic indicators, i.e., hypertension, diabetes, cardiovascular and cerebrovascular disease, and atherosclerotic bio-clinical markers. A total of 220 subjects (66.2±16.0 years) of the SPILI III cohort (1988-2012) attending a primary care setting in Spili, a rural town in Crete, represented the target group for the present study. Of these, 195 (88.6%) participated in the re-examination (67.2±15.2 years). All participants underwent a standardized procedure including evaluation of anthropometric measurements, biochemical indicators of atherosclerosis, stress hormones, in parallel with ultrasound measurements of carotid intima media thickness (IMT). Religiosity, spirituality and sense of coherence were evaluated with the use of international questionnaires translated into the Greek language and linguistically validated. Participants with higher levels of religious and spiritual beliefs presented lower levels of carotid IMT (1.01±0.101 vs 1.53±0.502 mm, p<0.001). Patterns of inverse relationships were also observed between religiosity/spirituality and prevalence of diabetes (35.1% vs. 2%, p<0.001) with an estimated diabetes risk, fully adjusted odds ratio, 95% CI: 0.91 (0.87-0.94). Highly religious participants presented lower serum cortisol levels (12.3±5.8 vs. 18.2±5.1 μg/dl, p<0.001). Sense of coherence was positively associated with religiosity/spirituality [mean SOC (SD): 123±20 vs. 158±15) p<0.001]. These findings may be associated with a possible favourable effect of religiosity/spirituality on several cardio-metabolic determinants, therefore deserving further attention by healthcare practitioners and researchers.

  7. Microparticles: A new insight into lung primary graft dysfunction?

    PubMed

    Olland, Anne; Reeb, Jérémie; Leclerq, Alexandre; Renaud-Picard, Benjamin; Falcoz, Pierre-Emmanuel; Kessler, Romain; Schini-Kerth, Valérie; Kessler, Laurence; Toti, Florence; Massard, Gilbert

    2016-11-01

    Lung transplantation is the only life-saving treatment for end stage respiratory disease. The immediate outcome is still hampered by primary graft dysfunction. The latter is a form of acute lung injury occurring within the 30min following the unclamping of the pulmonary artery that prompts ischemia reperfusion injury. Severe forms may need prolonged mechanical ventilation and extra-corporeal membrane oxygenation. Overall, primary graft dysfunction accounts for at least one third of the deaths during the first post-operative month. Despite increasing experience and knowledge on the underlying cellular events, there is still a lack of an early marker of ischemia reperfusion graft injuries. Microparticles are plasma membrane vesicles that are released from damaged or stressed cells in biological fluids and remodeling tissues, among which the lung parenchyma during acute or chronic injury. We recently evidenced alveolar microparticles as surrogate markers of strong ischemia injury in ex-vivo reperfusion experimental models. We propose herein new insights on how microparticles may be helpful to evaluate the extent of lung ischemia reperfusion injuries and predict the occurrence of primary graft dysfunction.

  8. Erectile dysfunction in psoriasis patients.

    PubMed

    Cabete, Joana; Torres, Tiago; Vilarinho, Tiago; Ferreira, Ana; Selores, Manuela

    2014-01-01

    An association between psoriasis and sexual dysfunction has been explored. However, not much is known about the factors behind erectile dysfunction in these patients. To compare the prevalence and the severity of erectile dysfunction in patients with and without psoriasis and to determine potential associations between erectile dysfunction and psoriasis patients' characteristics. An observational cross-sectional study was conducted at two tertiary hospital-based Dermatology departments. Consecutive adult men with psoriasis or other skin conditions were recruited. Data were collected using an anonymous, self-completed, designed questionnaire, which included the Dermatology Life Quality Index and the 5-item version of the International Index of Erectile Function. A total of 135 psoriasis patients and 201 controls were included. Psoriasis patients had a higher prevalence of erectile dysfunction than controls (61.5% vs 43.8%, p = 0.001), and an increased risk of more severe forms of erectile dysfunction. Dermatology Life Quality Index, genital psoriasis and psoriasis duration were not associated with the presence of erectile dysfunction. In multivariate logistic regression, psoriasis and diabetes were found to be independent risk factors for erectile dysfunction with estimated odds ratios of 2.28 (CI 95%, 1.40-3.27) and 3.49 (CI 95%, 1.40-8.66), respectively. This study suggests psoriasis as a risk factor for erectile dysfunction. Atherosclerosis is a plausible connecting link, adding up to the already acknowledged effect of psychological factors in these patients. From a clinical standpoint, because erectile dysfunction may precede overt cardiovascular disease, it can be used as a precocious marker of cardiovascular risk in psoriatic men.

  9. Clinicopathological variables of sporadic schwannomas of peripheral nerve in 291 patients and expression of biologically relevant markers.

    PubMed

    Young, Eric D; Ingram, Davis; Metcalf-Doetsch, William; Khan, Dilshad; Al Sannaa, Ghadah; Le Loarer, Francois; Lazar, Alexander J F; Slopis, John; Torres, Keila E; Lev, Dina; Pollock, Raphael E; McCutcheon, Ian E

    2017-09-08

    OBJECTIVE While sporadic peripheral schwannomas (SPSs) are generally well treated with surgery, their biology is not well understood. Consequently, treatment options are limited. The aim of this study was to provide a comprehensive description of SPS. The authors describe clinicopathological features and treatment outcomes of patients harboring these tumors, and they assess expression of biomarkers using a clinically annotated tissue microarray. Together, these data give new insight into the biology and management of SPS. METHODS Patients presenting with a primary SPS between 1993 and 2011 (n = 291) were selected from an institutional registry to construct a clinical database. All patients underwent follow-up, and short- and long-term outcomes were assessed. Expression of relevant biomarkers was assessed using a new tissue microarray (n = 121). RESULTS SPSs were generally large (mean 5.5 cm) and frequently painful at presentation (55%). Most patients were treated with surgery (80%), the majority of whom experienced complete resolution (52%) or improvement (18%) of their symptoms. Tumors that were completely resected (85%) did not recur. Some patients experienced short-term (16%) and long-term (4%) complications postoperatively. Schwannomas expressed higher levels of platelet-derived growth factor receptor-β (2.1) than malignant peripheral nerve sheath tumors (MPNSTs) (1.5, p = 0.004) and neurofibromas (1.33, p = 0.007). Expression of human epidural growth factor receptor-2 was greater in SPSs (0.91) than in MPNSTs (0.33, p = 0.002) and neurofibromas (0.33, p = 0.026). Epidural growth factor receptor was expressed in far fewer SPS cells (10%) than in MPNSTs (58%, p < 0.0001) or neurofibromas (37%, p = 0.007). SPSs more frequently expressed cytoplasmic survivin (66% of tumor cells) than normal nerve (46% of cells), but SPS expressed nuclear survivin in fewer tumor cells than in MPNSTs (24% and 50%, respectively; p = 0.018). CONCLUSIONS Complete resection is curative

  10. Biological markers of interferon-beta therapy: comparison among interferon-stimulated genes MxA, TRAIL and XAF-1.

    PubMed

    Gilli, F; Marnetto, F; Caldano, M; Sala, A; Malucchi, S; Capobianco, M; Bertolotto, A

    2006-02-01

    Biological activity of interferon-beta (IFNbeta) can be assessed by measuring IFN-stimulated genes (ISGs). Among them, myxovirus resistance protein A (MxA) appears to have the highest specificity, but it has no role in the pathogenesis of multiple sclerosis (MS). To investigate the reliability of MxA as a biomarker, we compared its expression to that of two other ISGs: TNF-related apoptosis-inducing ligand (TRAIL) and X-linked inhibitor of apoptosis factor-1 (XAF-1). Both were shown to be involved in immunoregulatory mechanisms and might play a role in MS. Quantitative-PCR measurements were performed in peripheral blood mononuclear cells from 73 MS patients after short-term and long-term treatment with IFNbeta. A time-dependent response for multiple ISGs was observed in all patients after short-term treatment. In contrast, long-term treatment induced concurrent inhibition of ISGs in 12.3% (9/73) of patients, in whom neutralizing antibodies (NAbs) were detectable. Besides, 22% (16/73) of chronically treated patients showed a non-NAbs-related abrogation of TRAIL expression. In summary, 1) MxA expression was significantly higher than both TRAIL and XAF-1, and 2) MxA was the most sensitive gene to detect decreased bioavailability due to NAbs. These findings identify MxA as an appropriate biomarker for IFNbeta, although there is no evidence for a functional role of it in MS.

  11. The biological role of the unique molecule RCAS1: a bioactive marker that induces connective tissue remodeling and lymphocyte apoptosis.

    PubMed

    Sonoda, Kenzo; Miyamoto, Shingo; Nakashima, Manabu; Wake, Norio

    2008-01-01

    RCAS1 is a receptor-binding cancer antigen which is expressed on human uterine cervical adenocarcinoma cell line (SiSo). Finding a correlation between the expression of this gene and the overall survival of patients with 14 different types of cancer points to the clinical significance of this gene. Moreover, the expression RCAS1 correlates with other clinicopathological parameters including the histological type of cancer, its differentiation, tumor size, clinical stage, the depth of invasion, lymphovascular space involvement, lymph node metastasis, and positive peritoneal cytological results. RCAS1 can induce apoptosis in peripheral lymphocytes in vitro as well as in an increased number of apoptotic tumor-infiltrating lymphocytes. RCAS1 is also believed to contribute to the escape of tumor cells from immune surveillance. RCAS1 is secreted via ectodomain shedding, and its expression is related to changes in the characteristics of the extracellular matrix and to a reduced number of vimentin-positive tumor stromal cells, findings that suggest that RCAS1 may induce connective tissue remodeling. The concentration of RCAS1 in serum or pleural effusions has been found to be significantly higher in patients with several different types of cancer as compared to normal controls. Together, the available data shows that RCAS1 may have value as a biomarker for monitoring therapeutic efficacy. Further exploration of the biological function of RCAS1 should help in the development of new therapeutic strategies against human malignancies.

  12. High biological variation of serum hyaluronic acid and Hepascore, a biochemical marker model for the prediction of liver fibrosis.

    PubMed

    Rossi, Enrico; Adams, Leon A; Ching, Helena L; Bulsara, Max; MacQuillan, Gerry C; Jeffrey, Gary P

    2013-05-01

    Serum hyaluronic acid and biochemical models which require hyaluronic acid analysis are commonly used as predictors of liver fibrosis in patients with chronic liver disease, however biological variation data for hyaluronic acid are deficient. Four serial serum samples were obtained at weekly intervals from healthy volunteers and patients with chronic hepatitis B, chronic hepatitis C and non- alcoholic fatty liver disease (NAFLD; 20 in each group). The within-individual week-to-week variation (CVI) and reference change values for hyaluronic acid, α₂-macroglobulin and Hepascore were obtained. Hepascore is calculated from hyaluronic acid, α2-macroglobulin, bilirubin and γ-glutamyltransferase activity. Hyaluronic acid displayed large within-individual variation, the CVI values were 62% in healthy subjects, 38% in hepatitis C, 37% in hepatitis B and 36% in NAFLD patients. Hepascore CVIs were 43% in healthy subjects, 24% in hepatitis C, 28% in hepatitis B and 39% in NAFLD patients. α₂-Macroglobulin was much less variable with CVIs ranging from 4.4% to 7.6%. Bland-Altman plots of week-to-week variations showed rates of significant disagreement for samples collected in any 2 successive weeks varied from 5% in NAFLD patients to 8.3% in healthy subjects. When using non-fasting serum samples, hyaluronic acid and to a lesser extent, the Hepascore model display large within-individual variations in both health and chronic liver disease. This information is critical for interpreting the significance of both single measurements and changes in serial measurements.

  13. 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

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

    PubMed

    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.

  15. Keratin 15, transcobalamin I and homeobox gene Hox-B13 expression in breast phyllodes tumors: novel markers in biological classification.

    PubMed

    Chong, Luke Yong-Zheng; Cheok, Poh Yian; Tan, Wai-Jin; Thike, Aye Aye; Allen, George; Ang, Mei Kim; Ooi, Aik Seng; Tan, Patrick; Teh, Bin Tean; Tan, Puay Hoon

    2012-02-01

    Breast phyllodes tumors are rare neoplasms which present challenges for histological classification. Microscopic features are not always predictive of clinical behavior, and scarce data exist on the prognostic role of biological markers. Our study evaluated a series of 145 phyllodes tumors diagnosed at the Department of Pathology, Singapore General Hospital between 2006 and 2009, incorporating 91 (62.8%) benign, 40 (27.6%) borderline, and 14 (9.7%) malignant phyllodes tumors. Antibodies to keratin 15 (KRT15), transcobalamin I (TCN1), and homeobox gene Hox-B13 (HOXB13) were applied to sections cut from tissue microarray blocks. KRT15 and TCN1 positivity was defined when there was reactivity of 1% or more stromal cells, while HOXB13 positivity was defined using a H-score of 100 and above. Positive immunohistochemical expression for KRT15, TCN1, and HOXB13 was seen in 21 (14.5%), 96 (66.2%), and 66 (45.5%) of tumors, respectively. Stromal expression of KRT15, TCN1, and HOXB13 was significantly correlated with tumor grade (P < 0.001, P < 0.001, P = 0.012), stromal hypercellularity (P = 0.005, P < 0.001, P = 0.023), mitotic activity (P < 0.001), and microscopic borders (P = 0.006, P < 0.001, P = 0.011). Co-expression of TCN1 and HOXB13 was seen in 21 of 91 (23.1%) benign, 18 of 40 (45.0%) borderline, and 11 of 14 (78.6%) malignant tumors, suggesting that the dual-marker panels of TCN1 and HOXB13 might be helpful in classifying borderline and malignant tumors. Although expression of TCN1 alone was present in all malignant and 34 of 40 (85.0%) borderline tumors, a combined panel with HOXB13 excluded some benign cases and was a better discriminant for a significant proportion of borderline and malignant tumors.

  16. The degree of premature hair graying as an independent risk marker for coronary artery disease: a predictor of biological age rather than chronological age.

    PubMed

    Kocaman, Sinan Altan; Çetin, Mustafa; Durakoğlugil, Murtaza Emre; Erdoğan, Turan; Çanga, Aytun; Çiçek, Yüksel; Doğan, Sıtkı; Şahin, Ismail; Şatıroğlu, Omer; Bostan, Mehmet

    2012-09-01

    Age is the most important and uncorrectable coronary risk factor at the moment. The concept of measuring aging biologically rather than only chronologically may be of importance in clinical practice. Hair graying is the most apparent sign of biological aging in humans, yet its mechanism is largely unknown. Today, it is known that cardiovascular risk factors (CVRFs), especially in combination, cause premature atherosclerosis. In our opinion, premature hair graying or whitening may represent early atherosclerotic changes as a surrogate of host response to the CVRFs. In this study, we planned to investigate the relationship of hair graying with CVRFs and coronary atherosclerotic burden in order to determine whether it is an independent marker for coronary artery disease (CAD). The current study has a cross-sectional observational design. Two hundred and thirteen men who underwent coronary angiography with a suspicion of CAD were enrolled in the study. The patients were evaluated in terms of age, demographical properties and the CVRFs. Hair whitening score (HWS) was defined according to extent of gray/white hairs (1: pure black; 2: black>white; 3: black=white; 4: white>black; 5: pure white). Coronary atherosclerotic burden was assessed by the Gensini score. Analyses were performed in age-matched normal coronary arteries (NCA) and CAD groups. Linear and logistic regression analyses were used for the multivariate analyses of independent variables associated with hair greying. The CVRFs were higher in CAD group. Hair whitening score (2.7 ± 1.3 vs. 3.3 ± 1.2, p=0.002), hair losing score (1.2 ± 0.9 vs. 1.5 ± 1.0, p=0.038) and xanthelasma rate (24% vs. 45%, p=0.013) were also significantly different between NCA and CAD groups. Age (p<0001), Gensini score (p<0.001) and coronary severity score (p=0.001) were higher in the categories of increased HWS. In multiple logistic regression analysis, only diabetes mellitus (OR: 3.240, 95% CI: [1.017-10.319], p=0.047), low

  17. ECIL recommendations for the use of biological markers for the diagnosis of invasive fungal diseases in leukemic patients and hematopoietic SCT recipients.

    PubMed

    Marchetti, O; Lamoth, F; Mikulska, M; Viscoli, C; Verweij, P; Bretagne, S

    2012-06-01

    As culture-based methods for the diagnosis of invasive fungal diseases (IFD) in leukemia and hematopoietic SCT patients have limited performance, non-culture methods are increasingly being used. The third European Conference on Infections in Leukemia (ECIL-3) meeting aimed at establishing evidence-based recommendations for the use of biological tests in adult patients, based on the grading system of the Infectious Diseases Society of America. The following biomarkers were investigated as screening tests: galactomannan (GM) for invasive aspergillosis (IA); β-glucan (BG) for invasive candidiasis (IC) and IA; Cryptococcus Ag for cryptococcosis; mannan (Mn) Ag/anti-mannan (A-Mn) Ab for IC, and PCR for IA. Testing for GM, Cryptococcus Ag and BG are included in the revised EORTC/MSG (European Organization for Research and Treatment of Cancer/Mycoses Study Group) consensus definitions for IFD. Strong evidence supports the use of GM in serum (A II), and Cryptococcus Ag in serum and cerebrospinal fluid (CSF) (A II). Evidence is moderate for BG detection in serum (B II), and the combined Mn/A-Mn testing in serum for hepatosplenic candidiasis (B III) and candidemia (C II). No recommendations were formulated for the use of PCR owing to a lack of standardization and clinical validation. Clinical utility of these markers for the early management of IFD should be further assessed in prospective randomized interventional studies.

  18. Survivin, Survivin-2B, and Survivin-deItaEx3 expression in medulloblastoma: biologic markers of tumour morphology and clinical outcome.

    PubMed

    Fangusaro, J R; Jiang, Y; Holloway, M P; Caldas, H; Singh, V; Boué, D R; Hayes, J; Altura, R A

    2005-01-31

    Survivin is an apoptotic inhibitor that is expressed at high levels in a variety of malignancies. Survivin has four known alternative splice forms (Survivin, Survivin-2B, Survivin-deltaEx3, and Survivin-3B), and the recent literature suggests that these splice variants have unique functions and subcellular localisation patterns. We evaluated 19 fresh-frozen paediatric medulloblastomas for the expression of three Survivin isoforms by quantitative PCR. Survivin was most highly expressed when compared with normal cerebellar tissue. We also investigated Survivin protein expression in 40 paraffin-embedded paediatric medulloblastoma tumours by immunohistochemistry. We found a statistically significant association between the percentage of Survivin-positive cells and histologic subtype, with the large-cell-anaplastic variant expressing Survivin at higher levels than the classic subtype. We also found a statistically significant relationship between the percent of Survivin-positive cells in the tumours and clinical outcome, with higher levels of Survivin correlating with a worse prognosis. In summary, our study demonstrates a role for Survivin as a marker of tumour morphology and clinical outcome in medulloblastoma. Survivin may be a promising future prognostic tool and potential biologic target in this malignancy.

  19. A systematic review of the psychobiological burden of informal caregiving for patients with dementia: Focus on cognitive and biological markers of chronic stress.

    PubMed

    Allen, Andrew P; Curran, Eileen A; Duggan, Áine; Cryan, John F; Chorcoráin, Aoife Ní; Dinan, Timothy G; Molloy, D William; Kearney, Patricia M; Clarke, Gerard

    2017-02-01

    As the physiological impact of chronic stress is difficult to study in humans, naturalistic stressors are invaluable sources of information in this area. This review systematically evaluates the research literature examining biomarkers of chronic stress, including neurocognition, in informal dementia caregivers. We identified 151 papers for inclusion in the final review, including papers examining differences between caregivers and controls as well as interventions aimed at counteracting the biological burden of chronic caregiving stress. Results indicate that cortisol was increased in caregivers in a majority of studies examining this biomarker. There was mixed evidence for differences in epinephrine, norepinephrine and other cardiovascular markers. There was a high level of heterogeneity in immune system measures. Caregivers performed more poorly on attention and executive functioning tests. There was mixed evidence for memory performance. Interventions to reduce stress improved cognition but had mixed effects on cortisol. Risk of bias was generally low to moderate. Given the rising need for family caregivers worldwide, the implications of these findings can no longer be neglected.

  20. T cell immunoglobulin and mucin domain-containing molecule 3 on CD14(+) monocytes serves as a novel biological marker for diabetes duration in type 2 diabetes mellitus.

    PubMed

    Yan, Wen-Jiang; Sun, Peng; Wei, Dan-Dan; Wang, Shuang-Xi; Yang, Jing-Jing; Li, Yi-Hui; Zhang, Cheng

    2016-11-01

    Type 2 diabetes is a worldwide disease that is associated with increased rates of obesity and reduced physical activity. Obesity-associated insulin resistance in type 2 diabetes is a disorder in the balance between pro-inflammatory and anti-inflammatory signals. T cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) has been reported as an important regulatory inflammation molecule, and plays a pivotal role in several inflammation-related diseases. Peripheral blood mononuclear cells were obtained from type 2 diabetes patients (n = 31) and healthy donors (n = 18), and Tim-3 expression on peripheral blood mononuclear cells was evaluated by flow cytometry. We showed the downregulated expression of Tim-3 on CD14(+) monocytes from type 2 diabetes patients. In addition, the upregulated expression of Tim-3 on peripheral CD4(+) T cells and CD8(+) T cells was observed in the present study. The correlation analysis between Tim-3 expression on CD14(+) monocytes and diabetes duration showed the longer diabetes duration time, the lower Tim-3 expression on CD14 monocytes. The present results suggest that Tim-3 might participate in the progression of type 2 diabetes by its negative regulation on these immune cells, and Tim-3 on CD14(+) monocytes serves as a novel biological marker for diabetes duration in type 2 diabetes patients. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  1. 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

  2. Memory Dysfunction

    PubMed Central

    Matthews, Brandy R.

    2015-01-01

    Purpose of Review: This article highlights the dissociable human memory systems of episodic, semantic, and procedural memory in the context of neurologic illnesses known to adversely affect specific neuroanatomic structures relevant to each memory system. Recent Findings: Advances in functional neuroimaging and refinement of neuropsychological and bedside assessment tools continue to support a model of multiple memory systems that are distinct yet complementary and to support the potential for one system to be engaged as a compensatory strategy when a counterpart system fails. Summary: Episodic memory, the ability to recall personal episodes, is the subtype of memory most often perceived as dysfunctional by patients and informants. Medial temporal lobe structures, especially the hippocampal formation and associated cortical and subcortical structures, are most often associated with episodic memory loss. Episodic memory dysfunction may present acutely, as in concussion; transiently, as in transient global amnesia (TGA); subacutely, as in thiamine deficiency; or chronically, as in Alzheimer disease. Semantic memory refers to acquired knowledge about the world. Anterior and inferior temporal lobe structures are most often associated with semantic memory loss. The semantic variant of primary progressive aphasia (svPPA) is the paradigmatic disorder resulting in predominant semantic memory dysfunction. Working memory, associated with frontal lobe function, is the active maintenance of information in the mind that can be potentially manipulated to complete goal-directed tasks. Procedural memory, the ability to learn skills that become automatic, involves the basal ganglia, cerebellum, and supplementary motor cortex. Parkinson disease and related disorders result in procedural memory deficits. Most memory concerns warrant bedside cognitive or neuropsychological evaluation and neuroimaging to assess for specific neuropathologies and guide treatment. PMID:26039844

  3. Erectile dysfunction.

    PubMed

    McMahon, C G

    2014-01-01

    In the past 30 years, advances in basic science have been instrumental in the evolution of the male sexual health treatment paradigm from a psychosexual model to a new model, which includes oral and intracavernosal injection pharmacotherapy, vacuum constriction devices and penile prostheses for the treatment of erectile dysfunction. This progress has coincided with an increased understanding of the nature of male sexual health problems, and epidemiological data that confirm that these problems are widely prevalent and the source of considerable morbidity, both for individuals and within relationships.

  4. Executive Dysfunction

    PubMed Central

    Rabinovici, Gil D.; Stephens, Melanie L.; Possin, Katherine L.

    2015-01-01

    Purpose of Review: Executive functions represent a constellation of cognitive abilities that drive goal-oriented behavior and are critical to the ability to adapt to an ever-changing world. This article provides a clinically oriented approach to classifying, localizing, diagnosing, and treating disorders of executive function, which are pervasive in clinical practice. Recent Findings: Executive functions can be split into four distinct components: working memory, inhibition, set shifting, and fluency. These components may be differentially affected in individual patients and act together to guide higher-order cognitive constructs such as planning and organization. Specific bedside and neuropsychological tests can be applied to evaluate components of executive function. While dysexecutive syndromes were first described in patients with frontal lesions, intact executive functioning relies on distributed neural networks that include not only the prefrontal cortex, but also the parietal cortex, basal ganglia, thalamus, and cerebellum. Executive dysfunction arises from injury to any of these regions, their white matter connections, or neurotransmitter systems. Dysexecutive symptoms therefore occur in most neurodegenerative diseases and in many other neurologic, psychiatric, and systemic illnesses. Management approaches are patient specific and should focus on treatment of the underlying cause in parallel with maximizing patient function and safety via occupational therapy and rehabilitation. Summary: Executive dysfunction is extremely common in patients with neurologic disorders. Diagnosis and treatment hinge on familiarity with the clinical components and neuroanatomic correlates of these complex, high-order cognitive processes. PMID:26039846

  5. Early detection of tubular dysfunction.

    PubMed

    Piscator, M

    1991-11-01

    The determination of low-molecular-weight proteins in urine as a tool for early detection of damage to the proximal tubules is briefly discussed. Beta 2-microglobulin, retinol-binding protein and alpha 1-microglobulin are at present the most widely used markers for tubular dysfunction. The determination of beta 2-microglobulin has earlier been the method of choice, but due to its instability at low pH there are certain disadvantages. Available data indicate that alpha 1-microglobulin may replace beta 2-microglobulin for screening purposes. The low-molecular-weight proteins are at present the best markers for early detection of tubular dysfunction; other constituents are not as well suited for this, even if the determination of urine enzymes has its supporters.

  6. Erectile dysfunction and cardiovascular disease

    PubMed Central

    Jackson, Graham

    2013-01-01

    The link between erectile dysfunction (ED) and cardiovascular disease (CVD) is reviewed by assessing original papers, current consensus, previous reviews and meta-analyses. The link between these conditions is confirmed, and the evaluation and assessment summarised with a new evidence-based algorithm. ED, especially in younger men, is a marker of an increased risk of CVD, and ED needs to be incorporated into all risk-screening programmes. PMID:26558084

  7. 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.

  8. Overweight and Obesity in Southern Italy: their association with social and life-style characteristics and their effect on levels of biologic markers.

    PubMed

    Osella, Alberto R; Díaz, María Del Pilar; Cozzolongo, Rafaelle; Bonfiglio, Caterina; Franco, Isabella; Abrescia, Daniela Isabel; Bianco, Antonella; Giampiero, Elba Silvana; Petruzzi, José; Elsa, Lanzilota; Mario, Correale; Mastrosimni, Anna María; Giocchino, Leandro

    2014-01-01

    In the last decades, overweight and obesity have been transformed from minor public health issues to a major threat to public health affecting the most affluent societies and also the less developed ones. To estimate overweight-obesity prevalence in adults, their association with some social determinants and to assess the effect of these two conditions on levels of biologic and biochemical characteristics, by means of a population-based study. A random sample of the general population of Putignano was drawn. All participants completed a general pre-coded and a Food Frequency questionnaire; anthropometric measures were taken and a venous blood sample was drawn. All subjects underwent liver ultra-sonography. Data description was done by means of tables and then Quantile Regression was performed. Overall prevalence of overweight and obesity were 34.5% and 16.1% respectively. Both overweight and obesity were more frequent among male, married and low socio-economic position subjects. There were increasing frequencies of normal weight with higher levels of education. Overweight and obese subjects had more frequently Nonalcoholic Fatty Liver Disease, Hypertension and altered biochemical markers. Quantile regression showed a statistically significant association of age with overweight and obesity (maximum about 64.8 yo), gender (female) and low levels of education in both overweight and obesity. More than 10 gr/day of wine intake was associated with overweight. The prevention and treatment of overweight/obesity on a population wide basis are needed. Population-based strategies should also improve social and physical environmental contexts for healthful lifestyles.

  9. Spatial navigation in complex and radial mazes in APP23 animals and neurotrophin signaling as a biological marker of early impairment.

    PubMed

    Hellweg, Rainer; Lohmann, Peter; Huber, Roman; Kühl, Alexander; Riepe, Matthias W

    2006-01-01

    Impairment of hippocampal function precedes frontal and parietal cortex impairment in human Alzheimer's disease (AD). Neurotrophins are critical for behavioral performance and neuronal survival in AD. We used complex and radial mazes to assess spatial orientation and learning in wild-type and B6-Tg(ThylAPP)23Sdz (APP23) animals, a transgenic mouse model of AD. We also assessed brain content of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3). Performance was alike in wild-type and APP23 animals in the radial maze. In contrast, performance in the complex maze was better in wild-type than APP23 animals. Contrary to the wild-type, hippocampal BDNF levels decreased on training in APP23 animals. Hippocampal and frontal cortex NGF levels in APP23 animals correlated with the time to solve the complex maze, but correlated inversely with escape time in wild-type animals. NT-3 levels were alike in wild-type and APP23 animals and were unchanged even after training. Both types of mazes depend on hippocampal integrity to some extent. However, according to the cognitive mapping theory of spatial learning, the complex maze because of the increased complexity of the environment most likely depends more strongly on preserved hippocampal function than the radial maze in the working memory configuration applied here. Greater impairment in complex maze performance than in radial maze performance thus resembles the predominant affliction of the loss of hippocampal function in human AD. NGF and BDNF levels on maze learning are different in wild-type and transgenic animals, indicating that biological markers of AD may be altered on challenge even though equilibrium levels are alike.

  10. Interleukin 6, soluble tumor necrosis factor receptor I and red blood cell distribution width as biological markers of functional dependence in an elderly population: a translational approach.

    PubMed

    de Gonzalo-Calvo, David; de Luxán-Delgado, Beatriz; Rodríguez-González, Susana; García-Macia, Marina; Suárez, Francisco Manuel; Solano, Juan José; Rodríguez-Colunga, María Josefa; Coto-Montes, Ana

    2012-05-01

    In the present investigation we have analyzed the association between functional dependence and inflammatory biomarkers using the Barthel Index (BI) and the Katz Index (KI). This analysis may contribute to translational medicine by incorporating the clinical and laboratory data to better understand the relationship between chronic inflammation and functional dependence in the elderly population. The ultimate goal of this study was to identify possible useful biomarkers of functional dependence in the elderly. Participants in this study consisted of 120 older subjects (90 women and 30 men; range 68-105 years) who were selected from the Santa Teresa nursing home (Oviedo, Spain). We studied functional status using the following tools to diagnose the functional dependence by clinicians: BI and KI for activities of daily living. We analyzed morbidity, sociodemographic characteristics and a panel of inflammatory and inflammatory-related markers. In linear regression models adjusted by age, sex, anti-inflammatory drug use and morbid conditions high levels of interleukin 6 (IL-6) and soluble TNF receptor-I (sTNF-RI) were associated with functional dependence as measured using BI and KI. Elevated levels of red blood cell distribution width (RDW) were also associated with functional dependence measured using the KI after adjusting for the same potential confounders. The current results suggest that high IL-6, sTNF-RI and RDW levels are associated with the functional dependence in the elderly population. The results are consistent with the presumed underlying biological mechanism, in which the up-regulation of inflammatory mediators is associated with functional dependence in elderly subjects.

  11. 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

  12. Biological markers of mesenchymal stromal cells as predictors of response to autologous stem cell transplantation in patients with amyotrophic lateral sclerosis: an investigator-initiated trial and in vivo study.

    PubMed

    Kim, Hyun Young; Kim, Heejaung; Oh, Ki-Wook; Oh, Seong-Il; Koh, Seong-Ho; Baik, Wonki; Noh, Min Young; Kim, Kyung Suk; Kim, Seung Hyun

    2014-10-01

    Bone marrow mesenchymal stromal cells (MSCs) can modify disease progression in amyotrophic lateral sclerosis (ALS) model. However, there are currently no accurate biological markers for predicting the efficacy of autologous MSC transplants in ALS patients. This open-label, single-arm, investigator-initiated clinical study was designed to identify markers of MSCs that could be used as potential predictors of response to autologous MSC therapy in patients with ALS. We enrolled 37 patients with ALS who received autologous MSCs via intrathecal injection in two monthly doses. After a 6-month follow-up period, the patients were categorized as responders and non-responders based on their scores on the revised ALS Functional Rating Scale (ALSFRS-R). Biological markers including β-fibroblast growth factor-2, stromal cell-derived factor-1α, vascular endothelial growth factor (VEGF), insulin-like growth factor-1, brain-derived neurotrophic factor, angiogenin (ANG), interleukin (IL)-4, IL-10, and transforming growth factor-β (TGF-β) were measured in the MSC cultures and their levels were compared between the responders and nonresponders. To confirm the markers' predictive ability, MSCs isolated from one patient in each group were transplanted into the cisterna magna of mutant SOD1(G93A) transgenic mice to measure their lifespans, locomotor activity, and motor neuron numbers. The levels of VEGF, ANG, and TGF-β were significantly higher in responders than in nonresponders. In the mouse model, the recipients of responder MSCs had a significantly slower onset of symptoms and a significantly longer lifespan than the recipients of nonresponders or controls. Our data suggest that VEGF, ANG, and TGF-β levels in MSCs could be used as potential biological markers to predict the effectiveness of autologous MSC therapy and to identify those patients who could optimally benefit from MSC treatment. © 2014 AlphaMed Press.

  13. Erectile dysfunction and coronary heart disease.

    PubMed

    Katsiki, Niki; Wierzbicki, Anthony S; Mikhailidis, Dimitri P

    2015-07-01

    This narrative review discusses the associations of erectile dysfunction with coronary heart disease (CHD) morbidity and mortality, all-cause death and CHD risk factors. Treatment strategies for erectile dysfunction are also mentioned. Erectile dysfunction shares common pathways and risk factors with vascular diseases. Erectile dysfunction has been reported to independently predict CHD events, thus highlighting its role as a marker of early atherosclerosis. Erectile dysfunction prevalence may be followed by the presentation of CHD symptoms in 2-3 years, and a CHD event may occur in 3-5 years. Furthermore, erectile dysfunction has been associated with stroke, peripheral artery disease, diabetes and chronic kidney disease as well as with several CHD risk factors including hypertension, dyslipidaemia, smoking, obesity, metabolic syndrome, hyperuricaemia, arterial stiffness and obstructive sleep apnea syndrome. On the basis of these data, erectile dysfunction may be regarded as a part of polyvascular disease. Patients with erectile dysfunction are at an increased risk for CHD morbidity and/or mortality as well as for all-cause death. Clinicians should monitor patients with erectile dysfunction by assessing their vascular risk and preventing or adequately treating CHD risk factors. In this context, lifestyle interventions should be recommended in addition to drug treatment to attain better outcomes.

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

    PubMed Central

    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

    2016-01-01

    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

  15. Mitochondrial dysfunction in autism.

    PubMed

    Legido, Agustín; Jethva, Reena; Goldenthal, Michael J

    2013-09-01

    Using data of the current prevalence of autism as 200:10,000 and a 1:2000 incidence of definite mitochondrial (mt) disease, if there was no linkage of autism spectrum disorder (ASD) and mt disease, it would be expected that 1 in 110 subjects with mt disease would have ASD and 1 in 2000 individuals with ASD would have mt disease. The co-occurrence of autism and mt disease is much higher than these figures, suggesting a possible pathogenetic relationship. Such hypothesis was initially suggested by the presence of biochemical markers of abnormal mt metabolic function in patients with ASD, including elevation of lactate, pyruvate, or alanine levels in blood, cerebrospinal fluid, or brain; carnitine level in plasma; and level of organic acids in urine, and by demonstrating impaired mt fatty acid β-oxidation. More recently, mtDNA genetic mutations or deletions or mutations of nuclear genes regulating mt function have been associated with ASD in patients or in neuropathologic studies on the brains of patients with autism. In addition, the presence of dysfunction of the complexes of the mt respiratory chain or electron transport chain, indicating abnormal oxidative phosphorylation, has been reported in patients with ASD and in the autopsy samples of brains. Possible pathogenetic mechanisms linking mt dysfunction and ASD include mt activation of the immune system, abnormal mt Ca(2+) handling, and mt-induced oxidative stress. Genetic and epigenetic regulation of brain development may also be disrupted by mt dysfunction, including mt-induced oxidative stress. The role of the purinergic system linking mt dysfunction and ASD is currently under investigation. In summary, there is genetic and biochemical evidence for a mitochondria (mt) role in the pathogenesis of ASD in a subset of children. To determine the prevalence and type of genetic and biochemical mt defects in ASD, there is a need for further research using the latest genetic technology such as next

  16. Family dysfunction

    PubMed Central

    Hayaki, Chie; Anno, Kozo; Shibata, Mao; Iwaki, Rie; Kawata, Hiroshi; Sudo, Nobuyuki; Hosoi, Masako

    2016-01-01

    Abstract Previous studies have shown differences in the psychosocial factors related to chronic localized pain (CLP) and chronic widespread pain (CWP). However, no studies have done an evaluation of differences between CLP and CWP from the viewpoint of family functioning. We did a cross-sectional study in a tertiary care setting to investigate possible differences in the relation of CWP and CLP to family functioning. Patients with CLP (N = 126) or CWP (N = 75) were assessed for family functioning by the Family Assessment Device (FAD) and a comparison was done. Logistic regression analysis was used to estimate associations of family functioning subscales with pain status (CWP vs CLP), controlling for demographic variables, pain variables; pain duration, pain ratings, pain disability, and psychological factors; depression, anxiety, and catastrophizing. The odds ratios (ORs) for the presence of CWP were calculated. Compared to patients with CLP, patients with CWP showed a lower functional status for Roles and Affective Involvement. The ORs for CWP were significantly higher in lower functioning Roles (OR: 2.38, 95% CI: 1.21–4.65) and Affective Involvement (OR: 2.86, 95% CI: 1.56–5.24) after adjusting for demographic variables. The significant association of CWP to Roles and Affective Involvement remained after controlling for the pain variables and psychological factors. This study shows that the families of patients with CWP have poorer family functioning than those with CLP. Our findings suggest that early identification and interventions for the family dysfunction of chronic pain patients are important to the treatment and prevention of CWP. PMID:27930535

  17. Triglycerides as a biological marker of repeated re-hospitalization resulting from deliberate self-harm in acute psychiatry patients: a prospective observational study

    PubMed Central

    2014-01-01

    Background Biological factors have been associated with deliberate self-harm (DSH) but have not been integrated with clinical factors in routine risk assessments. This study aimed to examine the incremental validity of lipid levels and platelet serotonin when combined with psychosocial factors in risk assessments for repeated admissions due to DSH. Methods In this prospective observational study of 196 acutely admitted patients, results of blood tests performed upon admission and the MINI Suicidal Scale and psychosocial DSH risk factor assessments performed at discharge were compared with the incidence of DSH recorded during the first 3 and 12 months after discharge. Results High triglyceride levels were found to be a significant marker for patients admitted 3 or more times due to DSH (repeated DSH, DSH-R) when tested against other significant risk factors. When all (9) significant univariate factors associated with 12-month post-discharge DSH-R were analyzed in a multivariate logistic regression, the MINI Suicidal Scale (p = 0.043), a lack of insight (p = 0.040), and triglyceride level (p = 0.020) remained significant. The estimated 12-month area under the curve of the receiver operator characteristic (ROC-AUC) for DSH-R was 0.74 for triglycerides, 0.81 for the MINI, 0.89 for the MINI + psychosocial factors, and 0.91 for the MINI + psychosocial factors + triglycerides. The applied multifaceted approach also significantly discriminated between 12-month post-discharge DSH-R patients and other DSH patients, and a lack of insight (p = 0.047) and triglycerides (p = 0.046) remained significant for DSH-R patients in a multivariate analysis in which other DSH patients served as the reference group (rather than non-DSH patients). Conclusion The triglyceride values provided incremental validity to the MINI Suicidal Scale and psychosocial risk factors in the assessment of the risk of repeated DSH. Therefore, a bio-psychosocial approach appears promising, but further

  18. Triglycerides as a biological marker of repeated re-hospitalization resulting from deliberate self-harm in acute psychiatry patients: a prospective observational study.

    PubMed

    Roaldset, John O; Linaker, Olav M; Bjørkly, Stål

    2014-02-25

    Biological factors have been associated with deliberate self-harm (DSH) but have not been integrated with clinical factors in routine risk assessments.This study aimed to examine the incremental validity of lipid levels and platelet serotonin when combined with psychosocial factors in risk assessments for repeated admissions due to DSH. In this prospective observational study of 196 acutely admitted patients, results of blood tests performed upon admission and the MINI Suicidal Scale and psychosocial DSH risk factor assessments performed at discharge were compared with the incidence of DSH recorded during the first 3 and 12 months after discharge. High triglyceride levels were found to be a significant marker for patients admitted 3 or more times due to DSH (repeated DSH, DSH-R) when tested against other significant risk factors. When all (9) significant univariate factors associated with 12-month post-discharge DSH-R were analyzed in a multivariate logistic regression, the MINI Suicidal Scale (p = 0.043), a lack of insight (p = 0.040), and triglyceride level (p = 0.020) remained significant. The estimated 12-month area under the curve of the receiver operator characteristic (ROC-AUC) for DSH-R was 0.74 for triglycerides, 0.81 for the MINI, 0.89 for the MINI + psychosocial factors, and 0.91 for the MINI + psychosocial factors + triglycerides. The applied multifaceted approach also significantly discriminated between 12-month post-discharge DSH-R patients and other DSH patients, and a lack of insight (p = 0.047) and triglycerides (p = 0.046) remained significant for DSH-R patients in a multivariate analysis in which other DSH patients served as the reference group (rather than non-DSH patients). The triglyceride values provided incremental validity to the MINI Suicidal Scale and psychosocial risk factors in the assessment of the risk of repeated DSH. Therefore, a bio-psychosocial approach appears promising, but further research is necessary to refine and validate

  19. 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

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

    2016-04-22

    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. 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. 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. Published by the BMJ Publishing Group Limited. For permission to use

  20. 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.

  1. Marker chromosomes.

    PubMed

    Rao, Kiran Prabhaker; Belogolovkin, Victoria

    2013-04-01

    Marker chromosomes are a morphologically heterogeneous group of structurally abnormal chromosomes that pose a significant challenge in prenatal diagnosis. Phenotypes associated with marker chromosomes are highly variable and range from normal to severely abnormal. Clinical outcomes are very difficult to predict when marker chromosomes are detected prenatally. In this review, we outline the classification, etiology, cytogenetic characterization, and clinical consequences of marker chromosomes, as well as practical approaches to prenatal diagnosis and genetic counseling.

  2. Tim-3 is a Marker of Plasmacytoid Dendritic Cell Dysfunction during HIV Infection and Is Associated with the Recruitment of IRF7 and p85 into Lysosomes and with the Submembrane Displacement of TLR9.

    PubMed

    Schwartz, Jordan Ari; Clayton, Kiera L; Mujib, Shariq; Zhang, Hongliang; Rahman, A K M Nur-Ur; Liu, Jun; Yue, Feng Yun; Benko, Erika; Kovacs, Colin; Ostrowski, Mario A

    2017-03-06

    In chronic diseases, such as HIV infection, plasmacytoid dendritic cells (pDCs) are rendered dysfunctional, as measured by their decreased capacity to produce IFN-α. In this study, we identified elevated levels of T cell Ig and mucin-domain containing molecule-3 (Tim-3)-expressing pDCs in the blood of HIV-infected donors. The frequency of Tim-3-expressing pDCs correlated inversely with CD4 T cell counts and positively with HIV viral loads. A lower frequency of pDCs expressing Tim-3 produced IFN-α or TNF-α in response to the TLR7 agonists imiquimod and Sendai virus and to the TLR9 agonist CpG. Thus, Tim-3 may serve as a biomarker of pDC dysfunction in HIV infection. The source and function of Tim-3 was investigated on enriched pDC populations from donors not infected with HIV. Tim-3 induction was achieved in response to viral and artificial stimuli, as well as exogenous IFN-α, and was PI3K dependent. Potent pDC-activating stimuli, such as CpG, imiquimod, and Sendai virus, induced the most Tim-3 expression and subsequent dysfunction. Small interfering RNA knockdown of Tim-3 increased IFN-α secretion in response to activation. Intracellular Tim-3, as measured by confocal microscopy, was dispersed throughout the cytoplasm prior to activation. Postactivation, Tim-3 accumulated at the plasma membrane and associated with disrupted TLR9 at the submembrane. Tim-3-expressing pDCs had reduced IRF7 levels. Furthermore, intracellular Tim-3 colocalized with p85 and IRF7 within LAMP1(+) lysosomes, suggestive of a role in degradation. We conclude that Tim-3 is a biomarker of dysfunctional pDCs and may negatively regulate IFN-α, possibly through interference with TLR signaling and recruitment of IRF7 and p85 into lysosomes, enhancing their degradation.

  3. 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

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

    PubMed

    Meza, J Salvador; Schetelig, Marc F; Zepeda-Cisneros, C Silvia; Handler, Alfred M

    2014-01-01

    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. 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. A Y-linked insertion of the pBXL{PUbnlsEGFP, Asβ2tub-DsRed.T3} transformation vector in A. ludens resulted in male-specific expression of the EGFP fluorescent protein marker, and was

  5. 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.

  6. Cardiovascular Mitochondrial Dysfunction Induced by Cocaine: Biomarkers and Possible Beneficial Effects of Modulators of Oxidative Stress

    PubMed Central

    Magnifico, Maria Chiara

    2017-01-01

    Cocaine abuse has long been known to cause morbidity and mortality due to its cardiovascular toxic effects. The pathogenesis of the cardiovascular toxicity of cocaine use has been largely reviewed, and the most recent data indicate a fundamental role of oxidative stress in cocaine-induced cardiovascular toxicity, indicating that mitochondrial dysfunction is involved in the mechanisms of oxidative stress. The comprehension of the mechanisms involving mitochondrial dysfunction could help in selecting the most appropriate mitochondria injury biological marker, such as superoxide dismutase-2 activity and glutathionylated hemoglobin. The potential use of modulators of oxidative stress (mitoubiquinone, the short-chain quinone idebenone, and allopurinol) in the treatment of cocaine cardiotoxic effects is also suggested to promote further investigations on these potential mitochondria-targeted antioxidant strategies. PMID:28593024

  7. 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

  8. Prospective validation of a risk score based on biological markers for predicting progression free survival in Binet stage A chronic lymphocytic leukemia patients: results of the multicenter O-CLL1-GISL study.

    PubMed

    Gentile, Massimo; Cutrona, Giovanna; Mosca, Laura; Matis, Serena; Fabris, Sonia; Lionetti, Marta; Ilariucci, Fiorella; Zupo, Simona; Musolino, Caterina; Levato, Luciano; Molica, Stefano; Di Raimondo, Francesco; Vincelli, Iolanda; Di Rienzo, Nicola; Pesce, Emanuela Anna; Angrilli, Francesco; Federico, Massimo; Neri, Antonino; Ferrarini, Manlio; Morabito, Fortunato

    2014-07-01

    A risk score based on three biological features (CD38, ZAP-70, and IGHV mutational status) was previously developed to predict progression-free survival (PFS) in untreated Binet A CLL patients. Here we perform a score validation analysis in a prospective and independent cohort of patients. Biological markers (CD38, ZAP-70, and IGHV mutational status) and gene expression profiles (GEP) of leukemic cells from CLL patients included in a prospective multicenter observational study (O-CLL1-GISL protocol, clinicaltrial.gov ID:NCT00917549) were used to assess the value and reproducibility of this score. To date, 468 Binet A patients were classified as low- (0 positive marker), intermediate- (1 positive marker), or high-risk (2 or 3 positive markers) using the progression risk score. The 3-year PFS probability was 91.7%, 82.9%, and 57.4% for low-, intermediate-, and high-risk (P < 0.0001) cases, respectively. These values were similar to those found in the original cohort. At Cox multivariate analysis, Rai stage, absolute lymphocyte count, progression risk score, and β-2 microglobulin maintained an independent prognostic impact on PFS. This score remained a predictor of progression when analysis was limited to 371 Rai 0 cases (P < 0.0001). Finally, the cells from the different CLL risk groups showed differences in their gene expression patterns. These results confirm the ability of this progression risk score to predict PFS among Binet A patients. The utility of the score was also extended by demonstrating that it retains prognostic value when applied exclusively to Rai 0 patients. Specific transcriptional patterns were significantly associated with risk groups.

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

    USDA-ARS?s Scientific Manuscript database

    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,...

  10. Genetics and biology of human ovarian teratomas. II. Molecular analysis of origin of nondisjunction and gene-centromere mapping of chromosome I markers.

    PubMed Central

    Deka, R; Chakravarti, A; Surti, U; Hauselman, E; Reefer, J; Majumder, P P; Ferrell, R E

    1990-01-01

    Chromosomal heteromorphisms and DNA polymorphisms have been utilized to identify the mechanisms that lead to formation of human ovarian teratomas and to construct a gene-centromere map of chromosome 1 by using those teratomas that arise by meiotic nondisjunction. Of 61 genetically informative ovarian teratomas, 21.3% arose by nondisjunction at meiosis I, and 39.3% arose by meiosis II nondisjunction. Eight polymorphic marker loci on chromosome 1p and one marker on 1q were used to estimate a gene-centromere map. The results show clear linkage of the most proximal 1p marker (NRAS) and the most proximal 1q marker (D1S61) to the centromere at a distance of 14 cM and 20 cM, respectively. Estimated gene-centromere distances suggest that, while recombination occurs normally in ovarian teratomas arising by meiosis II errors, ovarian teratomas arising by meiosis I nondisjunction have altered patterns of recombination. Furthermore, the estimated map demonstrates clear evidence of chiasma interference. Our results suggest that ovarian teratomas can provide a rapid method for mapping genes relative to the centromere. Images Figure 1 Figure 2 PMID:1977308

  11. Application of proteomic marker ensembles to subcellular organelle identification.

    PubMed

    Andreyev, Alexander Y; Shen, Zhouxin; Guan, Ziqiang; Ryan, Andrea; Fahy, Eoin; Subramaniam, Shankar; Raetz, Christian R H; Briggs, Steven; Dennis, Edward A

    2010-02-01

    Compartmentalization of biological processes and the associated cellular components is crucial for cell function. Typically, the location of a component is revealed through a co-localization and/or co-purification with an organelle marker. Therefore, the identification of reliable markers is critical for a thorough understanding of cellular function and dysfunction. We fractionated macrophage-like RAW264.7 cells, both in the resting and endotoxin-activated states, into six fractions representing the major organelles/compartments: nuclei, mitochondria, cytoplasm, endoplasmic reticulum, and plasma membrane as well as an additional dense microsomal fraction. The identity of the first five of these fractions was confirmed via the distribution of conventional enzymatic markers. Through a quantitative liquid chromatography/mass spectrometry-based proteomics analysis of the fractions, we identified 50-member ensembles of marker proteins ("marker ensembles") specific for each of the corresponding organelles/compartments. Our analysis attributed 206 of the 250 marker proteins ( approximately 82%) to organelles that are consistent with the location annotations in the public domain (obtained using DAVID 2008, EntrezGene, Swiss-Prot, and references therein). Moreover, we were able to correct locations for a subset of the remaining proteins, thus proving the superior power of analysis using multiple organelles as compared with an analysis using one specific organelle. The marker ensembles were used to calculate the organelle composition of the six above mentioned subcellular fractions. Knowledge of the precise composition of these fractions can be used to calculate the levels of metabolites in the pure organelles. As a proof of principle, we applied these calculations to known mitochondria-specific lipids (cardiolipins and ubiquinones) and demonstrated their exclusive mitochondrial location. We speculate that the organelle-specific protein ensembles may be used to

  12. Using the Ubiquitin-modified Proteome to Monitor Distinct and Spatially Restricted Protein Homeostasis Dysfunction.

    PubMed

    Gendron, Joshua M; Webb, Kristofor; Yang, Bing; Rising, Lisa; Zuzow, Nathan; Bennett, Eric J

    2016-08-01

    Protein homeostasis dysfunction has been implicated in the development and progression of aging related human pathologies. There is a need for the establishment of quantitative methods to evaluate global protein homoeostasis function. As the ubiquitin (ub) proteasome system plays a key role in regulating protein homeostasis, we applied quantitative proteomic methods to evaluate the sensitivity of site-specific ubiquitylation events as markers for protein homeostasis dysfunction. Here, we demonstrate that the ub-modified proteome can exceed the sensitivity of engineered fluorescent reporters as a marker for proteasome dysfunction and can provide unique signatures for distinct proteome challenges which is not possible with engineered reporters. We demonstrate that combining ub-proteomics with subcellular fractionation can effectively separate degradative and regulatory ubiquitylation events on distinct protein populations. Using a recently developed potent inhibitor of the critical protein homeostasis factor p97/VCP, we demonstrate that distinct insults to protein homeostasis function can elicit robust and largely unique alterations to the ub-modified proteome. Taken together, we demonstrate that proteomic approaches to monitor the ub-modified proteome can be used to evaluate global protein homeostasis and can be used to monitor distinct functional outcomes for spatially separated protein populations. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. [Hypothalamic dysfunction in obesity].

    PubMed

    van de Sande-Lee, Simone; Velloso, Licio A

    2012-08-01

    Obesity, defined as abnormal or excessive fat accumulation that may impair life quality, is one of the major public health problems worldwide. It results from an imbalance between food intake and energy expenditure. The control of energy balance in animals and humans is performed by the central nervous system (CNS) by means of neuroendocrine connections, in which circulating peripheral hormones, such as leptin and insulin, provide signals to specialized neurons of the hypothalamus reflecting body fat stores, and induce appropriate responses to maintain the stability of these stores. The majority of obesity cases are associated with central resistance to both leptin and insulin actions. In experimental animals, high-fat diets can induce an inflammatory process in the hypothalamus, which impairs leptin and insulin intracellular signaling pathways, and results in hyperphagia, decreased energy expenditure and, ultimately, obesity. Recent evidence obtained from neuroimaging studies and assessment of inflammatory markers in the cerebrospinal fluid of obese subjects suggests that similar alterations may be also present in humans. In this review, we briefly present the mechanisms involved with the loss of homeostatic control of energy balance in animal models of obesity, and the current evidence of hypothalamic dysfunction in obese humans.

  14. In juvenile dermatomyositis, heart rate variability is reduced, and associated with both cardiac dysfunction and markers of inflammation: a cross-sectional study median 13.5 years after symptom onset.

    PubMed

    Barth, Zoltan; Nomeland Witczak, Birgit; Schwartz, Thomas; Gjesdal, Knut; Flatø, Berit; Koller, Akos; Sanner, Helga; Sjaastad, Ivar

    2016-03-01

    Low heart rate variability (HRV) is a well-established predictor of cardiac death. The aim of this study was to investigate arrhythmias and HRV in patients with JDM, and associations between HRV and inflammatory markers, echocardiographic measurements and disease parameters. Fifty-five patients with JDM were examined 2-34 years (median 13.5 years) after disease onset, and compared with 55 age and sex matched controls. Holter ECG monitoring and echocardiography were analysed blinded to patient information. Arrhythmia and HRV (six parameters) were analysed by standard software, finally adjudicated by an experienced cardiologist. Markers of inflammation (ESR, high sensitivity (hs)CRP and cytokines) were analysed. Disease activity and organ damage were assessed by clinical examination at follow-up and retrospectively by chart review. In two out of six HRV parameters, JDM patients had lower values than controls. No difference in arrhythmias was found between the groups. In patients, but not in controls, there were significant negative correlations between five out of six HRV parameters, and ESR and hsCRP (Spearman correlation coefficient, -0.306 to -0.470; P, 0.023 to <0.001). Also, in patients, negative correlations were found between three out of six HRV parameters and systolic and diastolic function. Active disease and low HRV were associated. Patients with hsCRP in the highest quartile (Q4) had lower HRV in all parameters compared with those in pooled Q1-3 (P < 0.001). JDM patients had reduced HRV, which was associated with elevated inflammatory markers, active disease and reduced myocardial function. This suggests reduced vagal control of the heart; further studies are needed to determine whether this is also associated with cardiac morbidity or mortality. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Reviewe: Genetics and genomics in equine exercise physiology: an overview of the new applications of molecular biology as positive and negative markers of performance and health.

    PubMed

    Barrey, E

    2010-11-01

    Equine breeding selection has been developed by applying quantitative genetic methods for calculating the heritability of the complex traits such as performance in racing or sport competitions. With the great development of biotechnologies, equine molecular genetics has come of age. The recent sequencing of the equine genome by an international consortium was a major advance that will impact equine genomics in the near future. With the rapid progress in equine genetics, new applications in early performance evaluation and the detection of disease markers become available. Many new biomolecular tools will change management of horse selection, disease diagnosis and treatment. The purpose of this review is to present new developments in equine genetics and genomics for performance evaluation and health markers after a short summary of the previous knowledge about the genetic components of the exercise performance traits.

  16. 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

  17. Obesity-induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury.

    PubMed

    Shah, Dilip; Romero, Freddy; Guo, Zhi; Sun, Jianxin; Li, Jonathan; Kallen, Caleb B; Naik, Ulhas P; Summer, Ross

    2017-03-09

    Obesity is a significant risk factor for the acute respiratory distress syndrome (ARDS). The mechanisms underlying this association are unknown. We recently showed that diet-induced obese (DIO) mice exhibit pulmonary vascular endothelial dysfunction which is associated with enhanced susceptibility to lipopolysaccharide (LPS)-induced lung injury. Here, we demonstrate that lung endothelial dysfunction in DIO mice coincides with increased endoplasmic reticulum (ER) stress. Specifically, we observed enhanced expression of the major sensors of misfolded proteins including PERK, IREα and ATF6, in whole lung and in lung endothelial cells isolated from DIO mice. Further, we found that lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of DIO mice. Similar changes were observed in lung endothelial cells and in whole lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation; indicating that ER stress causes endothelial dysfunction in the lung. Treatment with 4-PBA, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in DIO mice. Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium leading to pulmonary endothelial cell dysfunction. Our work suggests that reducing protein load in the endoplasmic reticulum of pulmonary endothelial cells might protect against ARDS in obese individuals.

  18. 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.

  19. Grave Markers.

    ERIC Educational Resources Information Center

    DeMuro, Ted

    1985-01-01

    Junior high school students studied the cultural uses, symbolic meanings, and general physical forms of tombs and tombstones and then used basic slab building techniques to construct large clay grave markers. (RM)

  20. Bone Markers

    MedlinePlus

    ... from the amino terminal end of the protein matrix; another marker used to monitor therapy. Deoxypyridinoline (DPD) – a collagen breakdown product with a ring structure. Pyridinium Crosslinks – a group of collagen breakdown products ...

  1. Classification of tumor markers.

    PubMed

    Suresh, M R

    1996-01-01

    Since the discovery of the first tumor markers more than a century ago (Bence-Jones proteins), a vast array of molecules have been described as being associated with cancer. These are generally naturally occurring biomolecules with the exception of neo-antigens expressed in certain tumors induced by viruses. Tumor markers can be broadly classified into tumor specific antigens and tumor-associated markers. Most tumor markers were often heralded as highly tumor specific but subsequent studies demonstrated their presence in normal tissues of the adult or in various stages of ontogeny. As a result, very few tumor-specific antigens can be recognized. The idiotypes of immunoglobulins of B cell tumors and certain neo-antigens of virus induced tumors are two examples that are strictly tumor specific. The vast majority of tumor markers are in reality tumor-associated antigens and can be classified into two types based on their size. The low-molecular weight tumor markers (approximately < 1000 Daltons) include some nucleosides, lipid associated sialic acid, polyamines, pseudouridine, pigment derivatives, and other metabolites. The macromolecular tumor antigens are the most important sub-type useful in the clinical management of cancer patients. The large cancer antigens are either enzymes, growth factors, hormones, receptors, biological response modifiers, oncogenes and their products, or glycoconjugates which include glycoproteins and glycolipids. Collectively all the commercial tumor marker assays available to the oncologist for cancer patient management amount to an annual sales of > $1 billion world wide. The demonstrated clinical usefulness and commercial success of tumor markers have continued to fuel exciting research into the discovery and novel uses of new analytes.

  2. Diagnosis of erectile dysfunction.

    PubMed

    Glina, Sidney; Cohen, David J; Vieira, Marcelo

    2014-11-01

    Erectile dysfunction is a very prevalent condition and impairs quality of life of men and their partners. The diagnosis strategy of erectile dysfunction has changed, and it is important for every health professional to learn how to deal with erectile dysfunction. Although very prevalent, the sexual dysfunctions, including erectile dysfunction, continue to be underdiagnosed. Patients often expect physicians to initiate the conversation and ask about their troubles having sex. The routine to identify erectile dysfunction causes has undergone significant changes over the last decade. Identification of erectile dysfunction can be made through questionnaires or a complete medical and sexual history. Anamnesis and laboratory tests are sufficient in most cases to identify erectile dysfunction and to manage the treatment. Supplementary tests are used in special cases or when there is a need for an etiological diagnosis. Sexual function must be a part of every medical consultation, as any other body function. Erectile dysfunction diagnosis is not a complex task and can be accomplished by any physician. Even when the professional does not feel secure to treat erectile dysfunction, he or she can just identify the dysfunction and refer the patient to an expert.

  3. 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.

  4. Motor neuron dysfunction in frontotemporal dementia.

    PubMed

    Burrell, James R; Kiernan, Matthew C; Vucic, Steve; Hodges, John R

    2011-09-01

    Frontotemporal dementia and motor neuron disease share clinical, genetic and pathological characteristics. Motor neuron disease develops in a proportion of patients with frontotemporal dementia, but the incidence, severity and functional significance of motor system dysfunction in patients with frontotemporal dementia has not been determined. Neurophysiological biomarkers have been developed to document motor system dysfunction including: short-interval intracortical inhibition, a marker of corticospinal motor neuron dysfunction and the neurophysiological index, a marker of lower motor neuron dysfunction. The present study performed detailed clinical and neurophysiological assessments on 108 participants including 40 consecutive patients with frontotemporal dementia, 42 age- and gender-matched patients with motor neuron disease and 26 control subjects. Of the 40 patients with frontotemporal dementia, 12.5% had concomitant motor neuron disease. A further 27.3% of the patients with frontotemporal dementia had clinical evidence of minor motor system dysfunction such as occasional fasciculations, mild wasting or weakness. Biomarkers of motor system function were abnormal in frontotemporal dementia. Average short-interval intracortical inhibition was reduced in frontotemporal dementia (4.3 ± 1.7%) compared with controls (9.1 ± 1.1%, P < 0.05). Short-interval intracortical inhibition was particularly reduced in the progressive non-fluent aphasia subgroup, but was normal in patients with behavioural variant frontotemporal dementia and semantic dementia. The neurophysiological index was reduced in frontotemporal dementia (1.1) compared with controls (1.9, P < 0.001), indicating a degree of lower motor neuron dysfunction, although remained relatively preserved when compared with motor neuron disease (0.7, P < 0.05). Motor system dysfunction in frontotemporal dementia may result from pathological involvement of the primary motor cortex, with secondary

  5. Dysfunctional Reward Processing in Depression

    PubMed Central

    Admon, Roee; Pizzagalli, Diego A.

    2015-01-01

    Anhedonia - diminished pleasure and/or decreased reactivity to pleasurable stimuli - is a core feature of depression that frequently persists after treatment. As a result, extensive effort has been directed towards characterizing the psychological and biological processes that mediate dysfunctional reward processing in depression. Reward processing can be parsed into sub-components that include motivation, reinforcement learning, and hedonic capacity, which, according to preclinical and neuroimaging evidence, involve partially dissociable brain systems. In line with this, recent findings indicate that behavioral impairments and neural abnormalities in depression vary across distinct reward-related constructs. Ultimately, improved understanding of precise reward-related dysfunctions in depression promises to improve diagnostic and therapeutic efforts in depression. PMID:26258159

  6. Telomere length attrition, a marker of biological senescence, is inversely correlated with triglycerides and cholesterol in South Asian males with type 2 diabetes mellitus.

    PubMed

    Harte, Alison L; da Silva, Nancy F; Miller, Michelle A; Cappuccio, Francesco P; Kelly, Ann; O'Hare, Joseph P; Barnett, Anthony H; Al-Daghri, Nasser M; Al-Attas, Omar; Alokail, Majed; Sabico, Shaun; Tripathi, Gyanendra; Bellary, Srikanth; Kumar, Sudhesh; McTernan, Philip G

    2012-01-01

    South Asians have a higher risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) than white Caucasians, for a given BMI. Premature biological ageing, assessed by reduction in telomere length (TL), may be mediated by factors resulting from altered metabolic profiles associated with obesity. We hypothesise that ethnicity and metabolic status represent detrimental factors contributing to premature biological ageing. Therefore we assessed TL in two South Asian, age and BMI-matched cohorts [T2DM (n = 142) versus non-T2DM (n = 76)] to determine the effects of BMI, gender, lipid and CVD profile on biological ageing. Genomic DNA was obtained from the UKADS cohort; biochemical and anthropometric data was collected and TL was measured by quantitative real-time PCR. Our findings indicated a gender-specific effect with reduced TL in T2DM men compared with non-T2DM men (P = 0.006). Additionally, in T2DM men, TL was inversely correlated with triglycerides and total cholesterol (r = -0.419, P < 0.01; r = -0.443, P < 0.01). In summary, TL was reduced amongst South Asian T2DM men and correlated with triglycerides and total cholesterol. This study highlights enhanced biological ageing among South Asian, T2DM men, which appears to be tracked by changes in lipids and BMI, suggesting that raised lipids and BMI may directly contribute to premature ageing.

  7. Telomere Length Attrition, a Marker of Biological Senescence, Is Inversely Correlated with Triglycerides and Cholesterol in South Asian Males with Type 2 Diabetes Mellitus

    PubMed Central

    Harte, Alison L.; da Silva, Nancy F.; Miller, Michelle A.; Cappuccio, Francesco P.; Kelly, Ann; O'Hare, Joseph P.; Barnett, Anthony H.; Al-Daghri, Nasser M.; Al-Attas, Omar; Alokail, Majed; Sabico, Shaun; Tripathi, Gyanendra; Bellary, Srikanth; Kumar, Sudhesh; McTernan, Philip G.

    2012-01-01

    South Asians have a higher risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) than white Caucasians, for a given BMI. Premature biological ageing, assessed by reduction in telomere length (TL), may be mediated by factors resulting from altered metabolic profiles associated with obesity. We hypothesise that ethnicity and metabolic status represent detrimental factors contributing to premature biological ageing. Therefore we assessed TL in two South Asian, age and BMI-matched cohorts [T2DM (n = 142) versus non-T2DM (n = 76)] to determine the effects of BMI, gender, lipid and CVD profile on biological ageing. Genomic DNA was obtained from the UKADS cohort; biochemical and anthropometric data was collected and TL was measured by quantitative real-time PCR. Our findings indicated a gender-specific effect with reduced TL in T2DM men compared with non-T2DM men (P = 0.006). Additionally, in T2DM men, TL was inversely correlated with triglycerides and total cholesterol (r = −0.419, P < 0.01; r = −0.443, P < 0.01). In summary, TL was reduced amongst South Asian T2DM men and correlated with triglycerides and total cholesterol. This study highlights enhanced biological ageing among South Asian, T2DM men, which appears to be tracked by changes in lipids and BMI, suggesting that raised lipids and BMI may directly contribute to premature ageing. PMID:22474429

  8. Serotonin, neural markers, and memory.

    PubMed

    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.

  9. 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

  10. 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

  11. Echocardiographic Markers of Elevated Pulmonary Pressure and Left Ventricular Diastolic Dysfunction are Associated with Exercise Intolerance in Adults and Adolescents with Homozygous Sickle Cell Anemia in the US and UK

    PubMed Central

    Sachdev, Vandana; Kato, Gregory J.; Gibbs, J. Simon R.; Barst, Robyn J.; Machado, Roberto F.; Nouraie, Mehdi; Hassell, Kathryn L.; Little, Jane A.; Schraufnagel, Dean E.; Krishnamurti, Lakshmanan; Girgis, Reda E.; Morris, Claudia R.; Rosenzweig, Erika Berman; Badesch, David B.; Lanzkron, Sophie; Castro, Oswaldo L.; Taylor, James G.; Hannoush, Hwaida; Goldsmith, Jonathan C.; Gladwin, Mark T.; Gordeuk, Victor R.

    2011-01-01

    Background Non-invasively assessed pulmonary pressure elevations and left ventricular diastolic dysfunction (LVDD) are associated with increased mortality in adults with sickle cell disease (SCD), but their relationship to exercise intolerance has not been evaluated prospectively. Methods and Results Echocardiography, six-minute walk distance, hemolytic rate, and serum concentrations of ferritin and erythropoietin were evaluated in a cohort of 483 subjects with homozygous hemoglobin S in the US and UK Walk-PHaSST study. Tricuspid regurgitation velocity (TRV), which reflects systolic pulmonary artery pressure, was 2.7 to <3.0 m/sec (mean±SD 2.8±0.1) in 26% of the subjects and ≥3.0 m/sec (3.4±0.4) in 11%. LV lateral E/e′ ratio, which has been shown to reflect LV filling pressure in other conditions but has not been studied in SCD, was significantly higher in the groups with TRV ≥2.7 m/sec. Increased hemolysis (P<0.0001), LV lateral E/e′ ratio (P=0.0001), BUN (P=0.0002) and erythropoietin (P=0.002) were independently associated with an increased TRV. Further, female gender (P<0.0001), older age (P<0.0001), LV lateral E/e′ ratio (P=0.014), and TRV (P=0.019) were independent predictors of a shorter six-minute walk distance. Conclusions Echocardiography-estimated elevated pulmonary artery systolic pressure and LV lateral E/e′ ratio were independently associated with poor exercise capacity in a large cohort of patients with sickle cell anemia. Controlled trials investigating whether strategies to prevent or delay pulmonary hypertension and/or LVDD will improve exercise capacity and long-term outcomes in sickle cell anemia should be considered. PMID:21900080

  12. Biological markers of liver fibrosis and activity as non-invasive alternatives to liver biopsy in patients with chronic hepatitis C and associated mixed cryoglobulinemia vasculitis.

    PubMed

    Sène, Damien; Limal, Nicholas; Messous, Djamila; Ghillani-Dalbin, Pascale; Charlotte, Frédéric; Thiollière, Jean-Marie; Piette, Jean-Charles; Imbert-Bismut, Françoise; Halfon, Philippe; Poynard, Thierry; Cacoub, Patrice

    2006-07-01

    We assessed the reliability of non-invasive biological scoring indexes (Fibrotest-Actitest [FT-AT], Forns, APRI, age-platelet, platelet, hyaluronic acid) as non-invasive alternatives to liver biopsy (LB) in 138 HCV-infected patients. Thirty-six of 138 (26%) patients had systemic vasculitis, 27% significant serum inflammation, 47% fibrosis (F2F3F4) on LB. The diagnostic value of FT (F2F3F4 vs. F0F1) was assessed by an AUC of 0.83, without difference regarding to systemic vasculitis or serum inflammation. A discordance between FT-AT and the Metavir scoring indexes, present in 29% of patients, was associated with serum hemolysis and male but not with systemic vasculitis or serum inflammation. The other non-invasive biological tests were not influenced by serum inflammation or systemic vasculitis but were less reliable than FT (P biological indexes.

  13. Uric acid levels may be a biological marker for the differentiation of unipolar and bipolar disorder: the role of affective temperament.

    PubMed

    Kesebir, Sermin; Tatlıdil Yaylacı, Elif; Süner, Ozgür; Gültekin, Bülent Kadri

    2014-08-01

    The aim of this study was to investigate whether uric acid levels are different between patients with remission period of bipolar disorder type I (BD) and patients with remission period of major depressive disorder (MDD). For this aim 41 patients diagnosed with BD and 30 patients diagnosed with recurrent MDD according to DSM-IV who were in remission period for at least 8 weeks were evaluated consecutively. The median age and gender distribution of the two groups were similar. Subjects with comorbid psychiatric diagnosis and/or severe medical illnesses were excluded. Affective temperament was evaluated with TEMPS-A (Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire). Plasma uric acid levels were recorded in mg/dl. The uric acid levels of BD patients were found higher than patients with MDD and healthy controls. Additionally uric acid levels of MDD patients were lower than patients with BD and healthy subjects (F=4.183, p=0.039). A moderate correlation between hyperthymic and irritable temperament scores and uric acid levels was detected in both patient groups and in healthy controls. A negative correlation was observed between depressive temperament and uric acid levels only in MDD group. The measurements of temperament were estimated depending on the patient׳s statement. The medications that patients used were not controlled. There is a purinergic dysfunction not only in BD but also in MDD patients. High uric acid levels are associated with hyperthymic and irritable temperament scores whereas low uric acid levels are associated with depressive temperament scores. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Chromatin states define tumour-specific T cell dysfunction and reprogramming.

    PubMed

    Philip, Mary; Fairchild, Lauren; Sun, Liping; Horste, Ellen L; Camara, Steven; Shakiba, Mojdeh; Scott, Andrew C; Viale, Agnes; Lauer, Peter; Merghoub, Taha; Hellmann, Matthew D; Wolchok, Jedd D; Leslie, Christina S; Schietinger, Andrea

    2017-05-25

    Tumour-specific CD8 T cells in solid tumours are dysfunctional, allowing tumours to progress. The epigenetic regulation of T cell dysfunction and therapeutic reprogrammability (for example, to immune checkpoint blockade) is not well understood. Here we show that T cells in mouse tumours differentiate through two discrete chromatin states: a plastic dysfunctional state from which T cells can be rescued, and a fixed dysfunctional state in which the cells are resistant to reprogramming. We identified surface markers associated with each chromatin state that distinguished reprogrammable from non-reprogrammable PD1(hi) dysfunctional T cells within heterogeneous T cell populations from tumours in mice; these surface markers were also expressed on human PD1(hi) tumour-infiltrating CD8 T cells. Our study has important implications for cancer immunotherapy as we define key transcription factors and epigenetic programs underlying T cell dysfunction and surface markers that predict therapeutic reprogrammability.

  15. Erectile Dysfunction and Undiagnosed Diabetes, Hypertension, and Hypercholesterolemia.

    PubMed

    Skeldon, Sean C; Detsky, Allan S; Goldenberg, S Larry; Law, Michael R

    2015-01-01

    We investigated whether erectile dysfunction, a marker for future cardiovascular disease, is associated with undiagnosed cardiometabolic risk factors among US men. Identifying the presence of these risk factors could lead to earlier initiation of treatment for primary prevention of cardiovascular disease. We analyzed cross-sectional data from men aged 20 years and older who participated in the National Health and Nutrition Examination Survey during 2001-2004. Erectile dysfunction was determined by a single, validated survey question. We used logistic regression analyses to investigate the relationship between erectile dysfunction and undiagnosed hypertension, hypercholesterolemia, and diabetes. After multivariate adjustment, men with erectile dysfunction had more than double the odds of having undiagnosed diabetes (odds ratio = 2.20; 95% CI, 1.10-4.37), whereas no association was seen for undiagnosed hypertension or undiagnosed hypercholesterolemia. For the average man aged 40 to 59 years, the predicted probability of having undiagnosed diabetes increased from 1 in 50 in the absence of erectile dysfunction to 1 in 10 in the presence of erectile dysfunction. Our results underscore the importance of erectile dysfunction as a marker of undiagnosed diabetes. Erectile dysfunction should be a trigger to initiate diabetes screening, particularly among middle-aged men. © 2015 Annals of Family Medicine, Inc.

  16. 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

  17. Mitochondrial Dysfunction in Airway Disease.

    PubMed

    Prakash, Y S; Pabelick, Christina M; Sieck, Gary C

    2017-09-01

    There is increasing appreciation that mitochondria serve cellular functions beyond oxygen sensing and energy production. Accordingly, it has become important to explore noncanonical roles of mitochondria in normal and pathophysiological processes that influence airway structure and function in the context of diseases such as asthma and COPD. Mitochondria can sense upstream processes such as inflammation, infection, tobacco smoke, and environmental insults important in these diseases and in turn can respond to such stimuli through altered mitochondrial protein expression, structure, and resultant dysfunction. Conversely, mitochondrial dysfunction has downstream influences on cytosolic and mitochondrial calcium regulation, airway contractility, gene and protein housekeeping, responses to oxidative stress, proliferation, apoptosis, fibrosis, and certainly metabolism, which are all key aspects of airway disease pathophysiology. Indeed, mitochondrial dysfunction is thought to play a role even in normal processes such as aging and senescence and in conditions such as obesity, which impact airway diseases. Thus, understanding how mitochondrial structure and function play central roles in airway disease may be critical for the development of novel therapeutic avenues targeting dysfunctional mitochondria. In this case, it is likely that mitochondria of airway epithelium, smooth muscle, and fibroblasts play differential roles, consistent with their contributions to disease biology, underlining the challenge of targeting a ubiquitous cellular element of existential importance. This translational review summarizes the current state of understanding of mitochondrial processes that play a role in airway disease pathophysiology and identifying areas of unmet research need and opportunities for novel therapeutic strategies. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  18. 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

  19. Telomere shortening in Ph-negative chronic myeloproliferative neoplasms: a biological marker of polycythemia vera and myelofibrosis, regardless of hydroxycarbamide therapy.

    PubMed

    Ruella, Marco; Salmoiraghi, Silvia; Risso, Alessandra; Carobbio, Alessandra; Buttiglieri, Stefano; Spatola, Tiziana; Sivera, Piera; Ricca, Irene; Barbui, Tiziano; Tarella, Corrado; Rambaldi, Alessandro

    2013-07-01

    The purpose of this study was to investigate telomere length (TL) in Ph-negative chronic myeloproliferative neoplasms (Ph-neg-CMNs), and the possible association of TL with disease progression and hydroxycarbamide (HU) treatment. TL was analyzed in peripheral blood samples from 239 patients with Ph-neg-CMNs, including polycythemia vera (PV), essential thrombocythemia and myelofibrosis (MF), and compared with age-matched healthy control subjects (CTR), along with some cases of secondary erythrocytosis (SE). More than half of the patients with CMN received at least 1 year of cytoreduction, mainly HU, before TL analysis. JAK2 mutation analysis was performed as well. TL was significantly shortened in patients with CMN compared with CTR (p < 0.0001). PV and MF showed the most pronounced decrease (p < 0.0001), whereas both essential thrombocythemia and SE showed no significant difference in TL compared with CTR. A short TL correlated with JAK2-V617F allele burden greater than 50% (p = 0.0025), age (p = 0.0132) and diagnosis of PV (p = 0.0122). No correlation was found with disease duration, history of thrombosis, cytoreductive treatment, antiaggregation agents, adverse cytogenetics, phlebotomies, or time to evolution to MF. In summary, TL is distinctly shortened in PV and MF, and it inversely correlates with JAK2V617F allele burden. In addition, HU is unlikely to contribute to telomere erosion. Lastly, PV and SE significantly differ in TL. Therefore, TL could be an additional diagnostic marker to identify and monitor Ph-neg-CMN patients.

  20. Resting-state regional homogeneity as a biological marker for patients with Internet gaming disorder: A comparison with patients with alcohol use disorder and healthy controls.

    PubMed

    Kim, Heejung; Kim, Yu Kyeong; Gwak, Ah Reum; Lim, Jae-A; Lee, Jun-Young; Jung, Hee Yeon; Sohn, Bo Kyung; Choi, Sam-Wook; Kim, Dai Jin; Choi, Jung-Seok

    2015-07-03

    Internet gaming disorder (IGD) shares core clinical features with other addictive disorders, such as gambling disorder and substance use disorder. Designation of IGD as a formal disorder requires elucidation of its neurobiological features and comparison of these with those of other addictive disorders. The aims of the present study were to identify the neurobiological features of the resting-state brain of patients with IGD, alcohol use disorder (AUD), and healthy controls, and to examine brain regions related to the clinical characteristics of IGD. Functional magnetic resonance imaging was performed on 16 subjects with IGD, 14 subjects with AUD, and 15 healthy controls during the resting-state. We computed regional homogeneity (ReHo) measures to identify intrinsic local connectivity and to explore associations with clinical status and impulsivity. We found significantly increased ReHo in the posterior cingulate cortex (PCC) of the IGD and AUD groups, and decreased ReHo in the right superior temporal gyrus (STG) of those with IGD, compared with the AUD and HC groups. We also found decreased ReHo in the anterior cingulate cortex of patients with AUD. Scores on Internet addiction severity were positively correlated with ReHo in the medial frontal cortex, precuneus/PCC, and left inferior temporal cortex (ITC) among those with IGD. Furthermore, impulsivity scores were negatively correlated with that in the left ITC in individuals with IGD. Our results provide evidence of distinctive functional changes in the resting-state of patients with IGD and demonstrate that increased ReHo in the PCC may be a common neurobiological feature of IGD and AUD and that reduced ReHo in the STG may be a candidate neurobiological marker for IGD, differentiating individuals with this disorder from those with AUD and healthy controls. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Erectile dysfunction: management update

    PubMed Central

    Fazio, Luke; Brock, Gerald

    2004-01-01

    DRAMATIC ADVANCES IN THE MANAGEMENT of erectile dysfunction have occurred over the past decade. Oral therapy with vasoactive agents has emerged as first-line treatment and has transformed both the manner in which the public views erectile dysfunction and the way health care providers deliver care. Whereas an extensive investigation was previously common in the management of erectile dysfunction, recent treatment guidelines promote a more minimalist, goal-oriented approach. In this article, we review the physiology of erection, and the pathophysiology, diagnosis and clinical management of erectile dysfunction. We also present the existing evidence for the efficacy of 3 phosphodiesterase inhibitors, the most widely used class of agents for erectile dysfunction. PMID:15111479

  2. Telomere dysfunction induces metabolic and mitochondrial compromise

    PubMed Central

    Sahin, Ergün; Colla, Simona; Liesa, Marc; Moslehi, Javid; Müller, Florian L.; Guo, Mira; Cooper, Marcus; Kotton, Darrell; Fabian, Attila J.; Walkey, Carl; Maser, Richard S.; Tonon, Giovanni; Foerster, Friedrich; Xiong, Robert; Wang, Y. Alan; Shukla, Sachet A.; Jaskelioff, Mariela; Martin, Eric S.; Heffernan, Timothy P.; Protopopov, Alexei; Ivanova, Elena; Mahoney, John E.; Kost-Alimova, Maria; Perry, Samuel R.; Bronson, Roderick; Liao, Ronglih; Mulligan, Richard; Shirihai, Orian S.; Chin, Lynda; DePinho, Ronald A.

    2013-01-01

    Telomere dysfunction activates p53-mediated cellular growth arrest, senescence and apoptosis to drive progressive atrophy and functional decline in high-turnover tissues. The broader adverse impact of telomere dysfunction across many tissues including more quiescent systems prompted transcriptomic network analyses to identify common mechanisms operative in haematopoietic stem cells, heart and liver. These unbiased studies revealed profound repression of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha and beta (PGC-1α and PGC-1β, also known as Ppargc1a and Ppargc1b, respectively) and the downstream network in mice null for either telomerase reverse transcriptase (Tert) or telomerase RNA component (Terc) genes. Consistent with PGCs as master regulators of mitochondrial physiology and metabolism, telomere dysfunction is associated with impaired mitochondrial biogenesis and function, decreased gluconeogenesis, cardiomyopathy, and increased reactive oxygen species. In the setting of telomere dysfunction, enforced Tert or PGC-1α expression or germline deletion of p53 (also known as Trp53) substantially restores PGC network expression, mitochondrial respiration, cardiac function and gluconeogenesis. We demonstrate that telomere dysfunction activates p53 which in turn binds and represses PGC-1α and PGC-1β promoters, thereby forging a direct link between telomere and mitochondrial biology. We propose that this telomere–p53–PGC axis contributes to organ and metabolic failure and to diminishing organismal fitness in the setting of telomere dysfunction. PMID:21307849

  3. FSL Constructs: A Simple Method for Modifying Cell/Virion Surfaces with a Range of Biological Markers Without Affecting their Viability

    PubMed Central

    Blake, Deborah A.; Bovin, Nicolai V.; Bess, Dan; Henry, Stephen M.

    2011-01-01

    The ability to modify/visualize biological surfaces, and then study the modified cell/virion in a range of in vitro and in vivo environments is essential to gaining further insight into the function of specific molecules or the entire entity. Studies of biological surface modification are generally limited to genetic engineering of the organism or the covalent attachment of chemical moieties to the cell surface1,2. However these traditional techniques expose the cell to chemical reactants, or they require significant manipulation to achieve the desired outcome, making them cumbersome, and they may also inadvertently affect the viability/functionality of the modified cell. A simple method to harmlessly modify the surface of cells is required. Recently a new technology, KODE Technology has introduced a range of novel constructs consisting of three components: a functional head group (F), a spacer (S) and a lipid tail (L) and are known as Function-Spacer-Lipid or FSL constructs3. The spacer (S) is selected to provide a construct that is dispersible in water, yet will spontaneously and stably incorporate into a membrane. FSL construct functional moieties (F) so far include a range of saccharides including blood group-related determinants, sialic acids, hyaluronan polysaccharides, fluorophores, biotin, radiolabels, and a range of peptides3-12. FSL constructs have been used in modifying embryos, spermatozoa, zebrafish, epithelial/endometrial cells, red blood cells, and virions to create quality controls systems and diagnostic panels, to modify cell adhesion/ interaction/ separation/ immobilization, and for in vitro and in vivo imaging of cells/virions3-12. The process of modifying cells/virions is generic and extremely simple. The most common procedure is incubation of cells (in lipid free media) with a solution for FSL constructs for 1-2 hours at 37°C4-10. During the incubation the FSL constructs spontaneously incorporate into the membrane, and the process is complete

  4. Cardiovascular Implications of Erectile Dysfunction

    MedlinePlus

    ... Heart Association Cardiology Patient Page Cardiovascular Implications of Erectile Dysfunction Bryan G. Schwartz , Robert A. Kloner Download PDF ... if you think you have ED. What Is Erectile Dysfunction? Erectile dysfunction means that a man is not ...

  5. [Blood amylase: a biological marker in irradiation accidents? Preliminary results obtained at the Gustave-Roussy Institut (GRI) and a literature review].

    PubMed

    Hennequin, C; Cosset, J M; Cailleux, P E; Girinsky, T; Ganem, G; Hubert, D; Comoy, E; Dutreix, J

    1989-01-01

    The retrospective evaluation of the dose after an irradiation accident is of paramount importance; it allows an adequate selection of patients and the most appropriate treatment can then be proposed. Classical physical dosimetry often lacks precision for dose assessment in such accidents. Cytogenetics, usually more reliable, is not 100% accurate and cannot be used in some particular instances. At the Institut Gustave-Roussy, we studied amylasemia in 15 patients who received a total body irradiation (TBI) for bone marrow grafting, at various dose levels (10, 2 and 1.35 Gy). Hyperamylasemia was found to be constant and dose-dependent. Ten additional patients given a localized irradiation of 2 Gy in the Waldeyer ring had a similar rise in amylasemia as did TBI patients who had received the same dose. In contrast, 13 patients given a pancreatic irradiation (as part of a localized abdominal irradiation) did not show any increase in amylasemia. This study seems to confirm reported data, which suggested that post-TBI hyperamylasemia is almost only related to salivary gland irradiation. Amylasemia could possibly be used as a "biological dosimeter"; however, the dose-effect relationship should be more precisely defined, as well as individual variations. Moreover, the definition of a "threshold-dose" below which hyperamylasemia can never be detected, would be of interest for radioprotection.

  6. PTSD and Sexual Dysfunction in Men and Women.

    PubMed

    Yehuda, Rachel; Lehrner, Amy; Rosenbaum, Talli Y

    2015-05-01

    Difficulties in sexual desire and function often occur in persons with posttraumatic stress disorder (PTSD), but many questions remain regarding the mechanisms underlying the occurrence of sexual problems in PTSD. The aim of this review was to present a model of sexual dysfunction in PTSD underpinned by an inability to regulate and redirect the physiological arousal needed for healthy sexual function away from aversive hyperarousal and intrusive memories. A literature review pertaining to PTSD and sexual function was conducted. Evidence for the comorbidity of sexual dysfunction and PTSD is presented, and biological and psychological mechanisms that may underlie this co-occurrence are proposed. This manuscript presents evidence of sexual dysfunction in conjunction with PTSD, and of the neurobiology and neuroendocrinology of PTSD and sexual function. Sexual dysfunction following trauma exposure may be mediated by PTSD-related biological, cognitive, and affective processes. The treatment of PTSD must include attention to sexual dysfunction and vice versa. © 2015 International Society for Sexual Medicine.

  7. [Circadian markers and genes in bipolar disorder].

    PubMed

    Yeim, S; Boudebesse, C; Etain, B; Belliviera, F

    2015-09-01

    Bipolar disorder is a severe and complex multifactorial disease, characterized by alternance of acute episodes of depression and mania/hypomania, interspaced by euthymic periods. The etiological determinants of bipolar disorder yet, are still poorly understood. For the last 30 years, chronobiology is an important field of investigation to better understand the pathophysiology of bipolar disorder. We conducted a review using Medline, ISI Database, EMBase, PsyInfo up to January 2015, using the following keywords combinations: "mood disorder", "bipolar disorder", "depression", "unipolar disorder", "major depressive disorder", "affective disorder", for psychiatric conditions; and "circadian rhythms", "circadian markers", "circadian gene", "clock gene", "melatonin" for circadian rhythms. The search critera was presence of word in any field of the article. Quantitative and qualitative circadian abnormalities are associated with bipolar disorders both during acute episodes and euthymic periods, suggesting that these altered circadian rhythms may represent biological trait markers of the disorder. These circadian dysfunctions were assessed by various validated tools including polysomnography, actigraphy, sleep diaries, chronotype assessments and blood melatonin/cortisol measures. Other altered endogenous circadian activities have also been reported in bipolar patients, such as hormones secretion, core body temperature or fibroblasts activity. Moreover, these markers were also altered in healthy relatives of bipolar patients, suggesting a degree of heritability. Several genetic association studies have also showed associations between multiple circadian genes and bipolar disorder, such as CLOCK, ARTNL1, GSK3β, PER3, NPAS2, NR1D1, TIMELESS, RORA, RORB, and CSNK1ε. Thus, these circadian gene variants may contribute to the genetic susceptibility of the disease. Furthermore, the study of the clock system may help to better understand some phenotypic aspects like the

  8. 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.

  9. Connecting heart failure with preserved ejection fraction and renal dysfunction: the role of endothelial dysfunction and inflammation.

    PubMed

    Ter Maaten, Jozine M; Damman, Kevin; Verhaar, Marianne C; Paulus, Walter J; Duncker, Dirk J; Cheng, Caroline; van Heerebeek, Loek; Hillege, Hans L; Lam, Carolyn S P; Navis, Gerjan; Voors, Adriaan A

    2016-06-01

    Renal dysfunction in heart failure with preserved ejection fraction (HFpEF) is common and is associated with increased mortality. Impaired renal function is also a risk factor for developing HFpEF. A new paradigm for HFpEF, proposing a sequence of events leading to myocardial remodelling and dysfunction in HFpEF, was recently introduced, involving inflammatory, microvascular, and cardiac components. The kidney might play a key role in this systemic process. Renal impairment causes metabolic and systemic derangements in circulating factors, causing an activated systemic inflammatory state and endothelial dysfunction, which may lead to cardiomyocyte stiffening, hypertrophy, and interstitial fibrosis via cross-talk between the endothelium and cardiomyocyte compartments. Here, we review the role of endothelial dysfunction and inflammation to explain the link between renal dysfunction and HFpEF, which allows for identification of new early risk markers, prognostic factors, and unique targets for intervention.

  10. Neural activity, memory, and dementias: serotonergic markers.

    PubMed

    Meneses, Alfredo

    2017-04-01

    Dysfunctional memory seems to be a key component of diverse dementias and other neuropsychiatric disorders; unfortunately, no effective treatment exists for this, probably because of the absence of neural biomarkers accompanying it. Diverse neurotransmission systems have been implicated in memory, including serotonin or 5-hydroxytryptamine (5-HT). There are multiple serotonergic pharmacological tools, well-characterized downstream signaling in mammals' species and neural markers providing new insights into memory functions and dysfunctions. Serotonin in mammal species has multiple neural markers, including receptors (5-HT1-7), serotonin transporter, and volume transmission, which are present in brain areas involved in memory. Memory, amnesia, and forgetting modify serotonergic markers; this influence is bidirectional. Evidence shows insights and therapeutic targets and diverse approaches support the translatability of using neural markers and cerebral functions and dysfunctions, including memory formation and amnesia. For instance, 5-HT2A/2B/2C, 5-HT4, and 5-HT6 receptors are involved in tau protein hyperphosphorylation in Alzheimer's disease. In addition, at least, 5-HT1A, 5-HT4, 5-HT6, and 5-HT7 receptors as well as serotonin transporter seem to be useful neural markers and therapeutic targets. Hence, available evidence supports the notion that several mechanisms cooperate to achieve synaptic plasticity or memory, including changes in the number of neurotransmitter receptors and transporters. Considering that memory is a key component of dementias, hence reversing or reducing memory deficits might positively affect them?

  11. 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

  12. Sexual Dysfunction in Women

    MedlinePlus

    ... pressure), excessive alcohol use or vaginal infections can cause sexual problems. Depression, relationship problems or abuse (current or past abuse) can also cause sexual dysfunction.You may have less sexual desire ...

  13. Distal median nerve dysfunction

    MedlinePlus

    ... Distal median nerve dysfunction is a form of peripheral neuropathy that affects the movement of or sensation in ... and the A.D.A.M. Editorial team. Peripheral Nerve Disorders Read more Latest Health News Read more Health ...

  14. 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 ...

  15. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. 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

  17. Mitochondrial Dysfunction in Depression

    PubMed Central

    Bansal, Yashika; Kuhad, Anurag

    2016-01-01

    Abstract: Background Depression is the most debilitating neuropsychiatric disorder with significant impact on socio-occupational and well being of individual. The exact pathophysiology of depression is still enigmatic though various theories have been put forwarded. There are evidences showing that mitochondrial dysfunction in various brain regions is associated with depression. Recent findings have sparked renewed appreciation for the role of mitochondria in many intracellular processes coupled to synaptic plasticity and cellular resilience. New insights in depression pathophysiology are revolving around the impairment of neuroplasticity. Mitochondria have potential role in ATP production, intracellular Ca2+ signalling to establish membrane stability, reactive oxygen species (ROS) balance and to execute the complex processes of neurotransmission and plasticity. So understanding the various concepts of mitochondrial dysfunction in pathogenesis of depression indubitably helps to generate novel and more targeted therapeutic approaches for depression treatment. Objective The review was aimed to give a comprehensive insight on role of mitochondrial dysfunction in depression. Result Targeting mitochondrial dysfunction and enhancing the mitochondrial functions might act as potential target for the treatment of depression. Conclusion Literature cited in this review highly supports the role of mitochondrial dysfunction in depression. As impairment in the mitochondrial functions lead to the generation of various insults that exaggerate the pathogenesis of depression. So, it is useful to study mitochondrial dysfunction in relation to mood disorders, synaptic plasticity, neurogenesis and enhancing the functions of mitochondria might show promiscuous effects in the treatment of depressed patients. PMID:26923778

  18. Neutrophil Dysfunction in Sepsis

    PubMed Central

    Zhang, Fang; Liu, An-Lei; Gao, Shuang; Ma, Shui; Guo, Shu-Bin

    2016-01-01

    Objective: Sepsis is defined as life-threatening organ dysfunction due to a dysregulated host response to infection. In this article, we reviewed the correlation between neutrophil dysfunction and sepsis. Data Sources: Articles published up to May 31, 2016, were selected from the PubMed databases, with the keywords of “neutrophil function”, “neutrophil dysfunction”, and “sepsis”. Study Selection: Articles were obtained and reviewed to analyze the neutrophil function in infection and neutrophil dysfunction in sepsis. Results: We emphasized the diagnosis of sepsis and its limitations. Pathophysiological mechanisms involve a generalized circulatory, immune, coagulopathic, and/or neuroendocrine response to infection. Many studies focused on neutrophil burst or cytokines. Complement activation, impairment of neutrophil migration, and endothelial lesions are involved in this progress. Alterations of cytokines, chemokines, and other mediators contribute to neutrophil dysfunction in sepsis. Conclusions: Sepsis represents a severe derangement of the immune response to infection, resulting in neutrophil dysfunction. Neutrophil dysfunction promotes sepsis and even leads to organ failure. Mechanism studies, clinical practice, and strategies to interrupt dysregulated neutrophil function in sepsis are desperately needed. PMID:27824008

  19. Renal dysfunction in cirrhosis

    PubMed Central

    Urrunaga, Nathalie H.; Mindikoglu, Ayse L.; Rockey, Don C.

    2015-01-01

    Purpose of review Renal dysfunction causes significant morbidity in cirrhotic patients. Diagnosis is challenging because it is based on serum creatinine, which is used to calculate estimated glomerular filtration rate, which itself is not an ideal measure of renal function in patients with cirrhosis. Finding the exact cause of renal injury in patients with cirrhosis remains problematic due to the limitations of the current diagnostic tests. The purpose of this review is to highlight studies used to diagnose renal dysfunction in patients with renal dysfunction and review current treatments. Recent findings New diagnostic criteria and classification of renal dysfunction, especially for acute kidney injury (AKI), have been proposed in hopes of optimizing treatment and improving outcomes. New biomarkers that help to differentiate structural from functional AKI in cirrhotic patients have been developed, but require further investigation. Vasoconstrictors are the most commonly recommended treatment of hepatorenal syndrome (HRS). Given the high mortality in patients with type 1 HRS, all patients with HRS should be evaluated for liver transplantation. When renal dysfunction is considered irreversible, combined liver–kidney transplantation is advised. Summary Development of new biomarkers to differentiate the different types of AKI in cirrhosis holds promise. Early intervention in cirrhotic patients with renal dysfunction offers the best hope of improving outcomes. PMID:25763790

  20. Bubble-Induced Endothelial Microparticles Promote Endothelial Dysfunction

    PubMed Central

    Huang, Guoyang; Zhang, Kun; Qing, Long; Liu, Wenwu; Xu, Weigang

    2017-01-01

    Decompression sickness is a systemic pathophysiological process caused by bubbles and endothelial microparticles (EMPs) are established markers reflecting competency of endothelial function and vascular biology. Here, we investigated the effects of bubble-induced EMPs on endothelial cells in vitro and vivo. Rat pulmonary microvascular endothelial cells (PMVECs) were isolated and stimulated by bubbles and bubble-induced EMPs were collected and incubated with normal PMVECs in vitro. Cell viability and apoptosis were detected using Cell Counting Kit-8 assay and Annexin V FITC/PI double staining, respectively. Cell permeability and pro-inflammatory cytokines were determined by electric cell substrate impedance sensing and enzyme-linked immunosorbent assay, respectively. Intracellular nitric oxide and reactive oxygen species production were analyzed microscopically. In vivo study, bubble-induced EMPs were intravenously injected to the rats and soluble thrombomodulin, intercellular adhesion molecule 1, and vascullar adhesion molecule 1 were involved in evaluating endothelial dysfunction. In our study, bubble stimulus resulted in a significant increase of EMPs release by 3 fold. Bubble-induced EMPs significantly decreased cell viability and increased cell apoptosis. Moreover, bubble-induced EMPs induced abnormal increase of cell permeability and over-expression of pro-inflammatory cytokines. Intracellular ROS production increased while NO production decreased. These negative effects caused by bubble-induced EMPs were remarkably suppressed when EMPs pretreated with surfactant FSN-100. Finally, intravenous injection of bubble-induced EMPs caused elevations of soluble thrombomodulin and pro-inflammatory cytokines in the circulation. Altogether, our results demonstrated that bubble-induced EMPs can mediate endothelial dysfunction in vitro and vivo, which can be attenuated by EMPs abatement strategy. These data expanded our horizon of the detrimental effects of bubble

  1. 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

    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.

  2. Characterization of Relationships Between Sleep, Inflammation, and Psychiatric Dysfunction in Depressed Youth with Crohn’s Disease

    PubMed Central

    Benhayon, David; Youk, Ada; McCarthy, F. Nicole; Davis, Stephanie; Keljo, David J.; Bousvaros, Athos; Fairclough, Diane; Kupfer, David; Buysse, Daniel J.; Szigethy, Eva M.

    2013-01-01

    Objectives Recent reports demonstrate a link between Inflammatory Bowel Disease (IBD) and sleep disturbance. Increased psychiatric dysfunction is consistently reported in patients with IBD. Our objective is to examine relationships among sleep disturbance, inflammation, and psychiatric dysfunction in a pediatric population with Crohn’s disease (CD) and depression. Methods Pediatric CD patients with depression (n = 96) and healthy controls (n = 19) completed measures of sleep (Pittsburgh Sleep Quality Index [PSQI]), depression, anxiety, and abdominal pain, and provided blood for inflammatory markers. CD activity was determined by Pediatric Crohn’s Disease Activity Index (PCDAI). Factor analysis was performed on subscales of the PSQI in order to derive measures of sleep disturbance. Univariate and multivariate regression analyses assessed relationships between sleep disturbance, psychosocial, and biological measures of CD and psychiatric dysfunction. Results Sleep disturbance in depressed youth with CD was significantly greater than healthy controls, and was significantly related to measures of abdominal pain, depression, and anxiety, but not biomarkers of inflammation. Factor analysis of the PSQI demonstrated a two-factor solution. The first factor, termed ‘Qualitative,’ included Subjective Sleep Quality, Daytime Dysfunction, Sleep Disturbance, and Sleep Latency, whereas the second, ‘Quantitative,’ factor consisted of Habitual Sleep Efficiency and Sleep Duration. This factor showed a significant relationship with inflammatory markers. Multivariate modeling suggested Qualitative sleep disturbance was predicted by disease activity, pain, and anxiety whereas Quantitative sleep disturbance was predicted by disease activity. Conclusions These results indicate that sleep disturbance in depressed CD sufferers differs depending upon illness activity. Patients may require different interventions depending upon the sleep disturbance exhibited. PMID:23591911

  3. Circulating endothelial cells: a new biomarker of endothelial dysfunction in hematological diseases.

    PubMed

    Gendron, Nicolas; Smadja, David M

    2016-08-01

    The endothelium and its integrity are in the center of numerous cardiovascular, pulmonary and tumoral diseases. Several studies identified different circulating cellular sub-populations, which allow a noninvasive exploration of endothelial dysfunction. Furthermore, angiogenesis plays a major role in the biology of benign and malignant hematologic diseases. Among these biomarkers, circulating endothelial cells could be considered as a marker of endothelial injury and/or endothelial activation as well as vascular remodeling, whereas circulating endothelial progenitor cells would be only involved in the vascular regeneration. In the future, the quantification of circulating endothelial cells in many diseases could be a noninvasive biomarker used in diagnosis, prognostic and therapeutic follow-up of lung vasculopathy and/or residual disease of hematological malignancies.

  4. New and Emerging Biomarkers in Left Ventricular Systolic Dysfunction - Insight into Dilated Cardiomyopathy

    PubMed Central

    Gopal, Deepa M.; Sam, Flora

    2013-01-01

    Background Dilated cardiomyopathy (DCM) is characterized by deteriorating cardiac performance and impaired contraction and dilation of the left (or both) ventricles. Blood markers – known as “biomarkers” allow insight into underlying pathophysiologic mechanisms and biologic pathways, while predicting outcomes and guiding heart failure management and/or therapies. Content In this review, we provide an alternative approach to conceptualize heart failure biomarkers: the cardiomyocyte, its surrounding microenvironment, and the macroenvironment with clear interaction between these entities which may impact cellular processes involved in the pathogenesis and/or propagation of DCM. Newer biomarkers of left ventricular systolic dysfunction can be categorized under: (a) myocyte stress and stretch, (b) myocyte apoptosis, (c) cardiac interstitium, (d) inflammation, (e) oxidative stress, (f) cardiac energetics, (g) neurohormones and (h) renal biomarkers. Summary Biomarkers provide insight into the pathogenesis of DCM while predicting and potentially providing prognostic information in these patients with heart failure. PMID:23609585

  5. Neurogenic voiding dysfunction.

    PubMed

    Georgopoulos, Petros; Apostolidis, Apostolos

    2017-05-01

    This review aims to analyze and discuss all recently published articles associated with neurogenic voiding discussion providing readers with the most updated knowledge and trigger for further research. They include the proposal of a novel classification system for the pathophysiology of neurogenic lower urinary tract dysfunction (NLUTD) which combines neurological defect in a distinct anatomic location, and data on bowel dysfunction, autonomic dysreflexia and urine biomarkers; review of patient-reported outcome measures in NLUTD; review of the criteria for the diagnosis of clinically significant urinary infections; novel research findings on the pathophysiology of NLUTD; and review of data on minimally and more invasive treatments. Despite the extended evidence base on NLUTD, there is a paucity of high-quality new research concerning voiding dysfunction as opposed to storage problems. The update aims to inform clinicians about new developments in clinical practice, as well as ignite discussion for further clinical and basic research in the aforementioned areas of NLUTD.

  6. Diastolic dysfunction in hypertension.

    PubMed

    Nazário Leão, R; Marques da Silva, P

    2017-03-03

    Hypertension and coronary heart disease, often coexisting, are the most common risk factors for heart failure. The progression of hypertensive heart disease involves myocardial fibrosis and alterations in the left ventricular geometry that precede the functional change, initially asymptomatic. The left ventricular diastolic dysfunction is part of this continuum being defined by the presence of left ventricular diastolic dysfunction without signs or symptoms of heart failure or poor left ventricular systolic function. It is highly prevalent in hypertensive patients and is associated with increased cardiovascular morbidity and mortality. Despite its growing importance in clinical practice it remains poorly understood. This review aims to present the epidemiological fundamentals and the latest developments in the pathophysiology, diagnosis and treatment of left ventricular diastolic dysfunction.

  7. Immune dysfunction in cirrhosis

    PubMed Central

    Sipeki, Nora; Antal-Szalmas, Peter; Lakatos, Peter L; Papp, Maria

    2014-01-01

    Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific complications, comprise distinct clinical entities with different immunopathology mechanisms. Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations. Acute and chronic exposure to bacteria and/or their products, however, can result in variable clinical consequences. The immune status of patients is not constant during the illness; consequently, alterations of the balance between pro- and anti-inflammatory processes result in very different dynamic courses. In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis. We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms. Moreover, we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease. Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications, delaying progression and reducing mortality. PMID:24627592

  8. Twinning: A Marker for Biological Insults

    ERIC Educational Resources Information Center

    Howard, Robert G.; Brown, Anne M.

    1970-01-01

    Analysis of various statistics from birth records of 317 consecutive births revealed that twins are nonrepresentative of newborns with respect to birth weight and gestation, with male pairs to same-sex pairs the least representative. Differences between Negro and Caucasian twins were also found. (MH)

  9. Biological (molecular and cellular) markers of toxicity

    SciTech Connect

    McCarthy, J.F.

    1990-04-01

    The overall objective of this study is to evaluate the use of the small aquarium fish, Japanese Medaka, 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). 11 refs., 1 fig., 1 tab.

  10. 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

  11. Male endocrine dysfunction.

    PubMed

    Hotaling, James M; Patel, Zamip

    2014-02-01

    Evaluation for endocrine function is a pivotal part of the male infertility workup. Endocrine dysfunction may result from endogenous and exogenous sources. This article describes the traditional roles that the hypothalamic-pituitary-gonadal endocrine axis plays in spermatogenesis and testicular dysfunction, as well as other insults that may contribute to hypospermatogenesis. Recent research into the role alternative hormonal axes play in spermatogenesis and promising new technologies that may correct inborn or acquired endocrinopathies leading to impaired sperm growth and maturation are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Renal dysfunction in cirrhosis: pathophysiology, diagnosis, and management.

    PubMed

    Sourianarayanane, Achuthan; Thandassery, Ragesh B

    2016-06-01

    The development of decompensation in patients with cirrhosis is associated with increased mortality. Renal function gradually deteriorates with significant hemodynamic changes associated with decompensated liver disease, but may also rapidly decrease in response to precipitating events. Newer definitions of renal dysfunction may result in early diagnosis, this along with the use of sensitive markers helps in accurate determination of renal function in cirrhosis. Although renal dysfunction progresses slowly in cirrhotic patients, it is associated with increased mortality. Prompt intervention with appropriate management reduces the risk of renal dysfunction, as well as improving survival and quality of life. Appropriate management may include the removal of precipitating causes and use of pharmacological agents supporting circulatory dysfunction. Outcomes following treatment of this condition remain a major concern, especially in patients who develop hepatorenal syndrome. Transplantation of the liver or kidney and liver may be the only option when other modalities of treatment fail. Early transplantation may benefit these patients.

  13. Female sexual dysfunction: Assessment.

    PubMed

    Sharma, J B; Kalra, Bharti

    2016-05-01

    Female sexual dysfunction (FSD) is a common complex clinical condition, with multiple etiologies, association and pathophysiologic correlations. This review includes the definition, etiology, and diagnosis of FSD. It calls for a bio psychosocial approach to FSD management, which incorporates, but is not limited to, only the psychological aspects of FSD.

  14. 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…

  15. Immune Dysfunction in Cirrhosis

    PubMed Central

    Noor, Mohd Talha; Manoria, Piyush

    2017-01-01

    Abstract Cirrhosis due to any etiology disrupts the homeostatic role of liver in the body. Cirrhosis-associated immune dysfunction leads to alterations in both innate and acquired immunity, due to defects in the local immunity of liver as well as in systemic immunity. Cirrhosis-associated immune dysfunction is a dynamic phenomenon, comprised of both increased systemic inflammation and immunodeficiency, and is responsible for 30% mortality. It also plays an important role in acute as well as chronic decompensation. Immune paralysis can accompany it, which is characterized by increase in anti-inflammatory cytokines and suppression of proinflammatory cytokines. There is also presence of increased gut permeability, reduced gut motility and altered gut flora, all of which leads to increased bacterial translocation. This increased bacterial translocation and consequent endotoxemia leads to increased blood stream bacterial infections that cause systemic inflammatory response syndrome, sepsis, multiorgan failure and death. The gut microbiota of cirrhotic patients has more pathogenic microbes than that of non-cirrhotic individuals, and this disturbs the homeostasis and favors gut translocation. Prompt diagnosis and treatment of such infections are necessary for better survival. We have reviewed the various mechanisms of immune dysfunction and its consequences in cirrhosis. Recognizing the exact pathophysiology of immune dysfunction will help treating clinicians in avoiding its complications in their patients and can lead to newer therapeutic interventions and reducing the morbidity and mortality rates. PMID:28507927

  16. Multiple organ dysfunction syndrome.

    PubMed

    Parke, A L; Liu, P T; Parke, D V

    2003-01-01

    Multiple organ dysfunction syndrome, including acute respiratory distress syndrome (ARDS) and renal failure, is described, its clinical features outlined, its origins in tissue oxidative stress following severe infections, surgical trauma, ionizing radiation, high-dosage drugs and chemicals, severe hemorrhage, etc., are defined, and its prevention and treatment prescribed.

  17. 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…

  18. Adipocytokines in Thyroid Dysfunction

    PubMed Central

    Aydogan, Berna İmge; Sahin, Mustafa

    2013-01-01

    Adipocytokines are important mediators of interorgan crosstalk in metabolic regulation. Thyroid diseases have effects on metabolism and inflammation. The mechanism of these effects is not clear. Recently, there are several reports suggesting this interrelation between adipocytokines and thyroid dysfunction. In this review, we summarize this relation according to the literature. PMID:24049662

  19. Diastolic dysfunction in arterial hypertension.

    PubMed

    de Simone, G; Palmieri, V

    2001-01-01

    Left ventricular diastolic properties are important markers of pump function and are frequently abnormal when myocardial insults alter tissue structure. Alterations can be limited to the early diastolic phase (early active relaxation) or to late diastolic filling (late ventricular compliance), but more often involve regulation of both phases of diastole. In asymptomatic patients with arterial hypertension, left ventricular relaxation is often prolonged, independently, at least in part, of cardiac loading conditions and left ventricular geometry, but this abnormality is associated with early signs of systolic dysfunction. Uncontrolled hypertension, diabetes, and obesity are most often associated with ischemic heart disease and impaired diastolic function. Reducing blood pressure with antihypertension therapy will reduce myocardial afterload, regress LVH, and improve systolic and diastolic function. In patients with symptoms of CHF with a normal ejection fraction, however, changes in therapy may be indicated. Greater emphasis should be placed on using medications that decrease myocardial load, but also reduce the effects of neurohormonal activation. (c)2001 by Le Jacq Communications, Inc.

  20. [Minimal cerebral dysfunctions and ADHD in adulthood].

    PubMed

    Linden, M; Weddigen, J

    2016-11-01

    Attention deficit hyperactivity disorder (ADHD) is of great importance not only in children but also in adults; however, despite extensive research there are still many unsolved questions with respect to the diagnosis. Patients not only suffer from attention deficits and hyperactivity but also a variety of other problems, such as dyspraxia, problems with stimulus discrimination, dysgrammatism, legasthenia, or motor coordination problems. Furthermore, there are also psychopathological disorders, such as problems with memory, formal thinking, emotional modulation, drive and vegetative stability, in the sense of a psycho-organic syndrome. Such syndromes have long been known in psychiatry under terms, such as complex capacity disorders, minimal cerebral dysfunction (MCD), minimal brain dysfunction (MBD), mild psycho-organic syndrome, psycho-organic axis syndrome, mild cognitive impairment, developmental disorder and developmental biological syndrome. Etiological data with respect to genetics and early childhood brain trauma support the notion of a psychobiological disorder for complex cerebral dysfunction in the sense of a psycho-organic syndrome. Depending on the individual life and work situation, these additional symptoms of ADHD are in many cases of greater relevance for life adjustment than the core symptoms, depending on the individual life and work situations. The concept of minimal cerebral dysfunction describes the ADHD problem better and has a direct bearing on the diagnosis, therapy and sociomedical care of the patients.

  1. Evidence of Mild Liver Dysfunction Identifies Stable Heart Failure Outpatients with Reversible Renal Dysfunction

    PubMed Central

    Brisco, Meredith A.; Cheng, Susan J.; Laur, Olga; Kula, Alexander J.; Testani, Jeffrey M.

    2015-01-01

    Background In decompensated heart failure (HF), reversible renal dysfunction (RD) is more frequently observed in patients with mild liver dysfunction likely due to the shared pathophysiologic factors involved. The objective of this study was to determine if these findings also apply to stable HF outpatients. Methods Patients in the Beta-Blocker Evaluation of Survival Trial (BEST) were studied. Improvement in renal function (IRF) was defined as a 20% improvement in the estimated glomerular filtration rate from baseline to 3 months. Results Elevated bilirubin (BIL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were significantly associated with signs of congestion or poor perfusion. IRF occurred in 12.0% of all patients and was more common in those with elevated BIL (OR = 1.5, p = 0.003), ALT (OR = 1.4, p = 0.01), and AST (OR = 1.4, p = 0.01). In a model containing all 3 liver parameters and baseline characteristics, including markers of congestion/poor perfusion, BIL (OR = 1.6, p = 0.001) and ALT (OR = 1.7, p < 0.001) were independently associated with IRF. Conclusions Biochemical evidence of mild liver dysfunction is significantly associated with IRF in stable HF outpatients. Given the widespread availability and low cost of these markers, additional research is necessary to determine the utility of these parameters in identifying patients with reversible RD who may benefit from cardiorenal interventions. PMID:26195975

  2. What Is a Dysfunctional School?

    ERIC Educational Resources Information Center

    Bergman, M. M.

    2013-01-01

    Whether or not a school is dysfunctional depends largely on how dysfunctionality in schools is defined and measured. Dysfunctionality, as any construct, is subject to definition and interpretation, and it is thus always marked by perspectivism. But regardless of the definition games occasionally played by academics, some form of reality takes…

  3. What Is a Dysfunctional School?

    ERIC Educational Resources Information Center

    Bergman, M. M.

    2013-01-01

    Whether or not a school is dysfunctional depends largely on how dysfunctionality in schools is defined and measured. Dysfunctionality, as any construct, is subject to definition and interpretation, and it is thus always marked by perspectivism. But regardless of the definition games occasionally played by academics, some form of reality takes…

  4. Risk factors for asymptomatic ventricular dysfunction in rheumatoid arthritis patients.

    PubMed

    Garza-García, Carlos; Rocío, Sánchez-Santillán; Orea-Tejeda, Arturo; Castillo-Martínez, Lilia; Eduardo, Canseco; López-Campos, José Luis; Keirns-Davis, Candace

    2013-01-01

    Objective. The aim of the study was to describe echocardiographic abnormalities in patients with rheumatoid arthritis, concurrent systemic comorbidities, rheumatologic clinical activity, serologic markers of rheumatoid arthritis, and inflammatory activity. Methods. In an observational, cross-sectional study, rheumatoid arthritis outpatients were included (n = 105). Conventional transthoracic echocardiographic variables were compared between patients with arthritis and non-RA controls (n = 41). For rheumatoid arthritis patients, articular activity and rheumatologic and inflammatory markers were obtained. Results. Ventricular dysfunction was found in 54.3% of the population: systolic (18.1%), diastolic (32.4%), and/or right (24.8%), with lower ejection fraction (P < 0.0001). Pulmonary hypertension was found in 46.9%. Other echocardiographic findings included increased left atrial diameter (P = 0.01), aortic diameter (P = 0.01), ventricular septum (P = 0.01), left ventricular posterior wall (P = 0.013), and right ventricular (P = 0.01) and atrial diameters compared to control subjects. Rheumatoid factor and anti-CCP antibodies levels were significantly elevated in cases with ventricular dysfunction. Angina and myocardial infarction, diabetes, and dyslipidemia were the main risk factors for ventricular dysfunction. Conclusions. Ventricular dysfunction is common in rheumatoid arthritis and associated with longer disease duration and increased serologic markers of rheumatoid arthritis. Screening for cardiac abnormalities should be considered in this kind of patients.

  5. Risk Factors for Asymptomatic Ventricular Dysfunction in Rheumatoid Arthritis Patients

    PubMed Central

    Garza-García, Carlos; Rocío, Sánchez-Santillán; Orea-Tejeda, Arturo; Castillo-Martínez, Lilia; Eduardo, Canseco; López-Campos, José Luis; Keirns-Davis, Candace

    2013-01-01

    Objective. The aim of the study was to describe echocardiographic abnormalities in patients with rheumatoid arthritis, concurrent systemic comorbidities, rheumatologic clinical activity, serologic markers of rheumatoid arthritis, and inflammatory activity. Methods. In an observational, cross-sectional study, rheumatoid arthritis outpatients were included (n = 105). Conventional transthoracic echocardiographic variables were compared between patients with arthritis and non-RA controls (n = 41). For rheumatoid arthritis patients, articular activity and rheumatologic and inflammatory markers were obtained. Results. Ventricular dysfunction was found in 54.3% of the population: systolic (18.1%), diastolic (32.4%), and/or right (24.8%), with lower ejection fraction (P < 0.0001). Pulmonary hypertension was found in 46.9%. Other echocardiographic findings included increased left atrial diameter (P = 0.01), aortic diameter (P = 0.01), ventricular septum (P = 0.01), left ventricular posterior wall (P = 0.013), and right ventricular (P = 0.01) and atrial diameters compared to control subjects. Rheumatoid factor and anti-CCP antibodies levels were significantly elevated in cases with ventricular dysfunction. Angina and myocardial infarction, diabetes, and dyslipidemia were the main risk factors for ventricular dysfunction. Conclusions. Ventricular dysfunction is common in rheumatoid arthritis and associated with longer disease duration and increased serologic markers of rheumatoid arthritis. Screening for cardiac abnormalities should be considered in this kind of patients. PMID:24368945

  6. Early markers of Fabry disease revealed by proteomics.

    PubMed

    Matafora, V; Cuccurullo, M; Beneduci, A; Petrazzuolo, O; Simeone, A; Anastasio, P; Mignani, R; Feriozzi, S; Pisani, A; Comotti, C; Bachi, A; Capasso, G

    2015-06-01

    Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal hydrolase α-galactosidase A (α-GalA) that leads to the intra-lysosomal accumulation of globotriaosylceramide (Gb3) in various organ systems. As a consequence, a multisystems disorder develops, culminating in stroke, progressive renal and cardiac dysfunction. Enzyme replacement therapy (ERT) offers a specific treatment for patients affected by FD, though the monitoring of treatment is hindered by a lack of surrogate markers of response. Remarkably, due to the high heterogeneity of the Fabry phenotype, both diagnostic testing and treatment decisions are more challenging in females than in males; thus, reliable biomarkers for Fabry disease are needed, particularly for female patients. Here, we use a proteomic approach for the identification of disease-associated markers that can be used for the early diagnosis of FD as well as for monitoring the effectiveness of ERT. Our data show that the urinary proteome of Fabry naïve patients is different from that of normal subjects. In addition, biological pathways mainly affected by FD are related to immune response, inflammation, and energetic metabolism. In particular, the up-regulation of uromodulin, prostaglandin H2 d-isomerase and prosaposin in the urine of FD patients was demonstrated; these proteins might be involved in kidney damage at the tubular level, inflammation and immune response. Furthermore, comparing the expression of these proteins in Fabry patients before and after ERT treatment, a decrease of their concentration was observed, thus demonstrating the correlation between the identified markers and the effectiveness of the pharmacological treatment.

  7. The cone dysfunction syndromes

    PubMed Central

    Aboshiha, Jonathan; Dubis, Adam M; Hardcastle, Alison J; Michaelides, Michel

    2016-01-01

    The cone dysfunction syndromes are a heterogeneous group of inherited, predominantly stationary retinal disorders characterised by reduced central vision and varying degrees of colour vision abnormalities, nystagmus and photophobia. This review details the following conditions: complete and incomplete achromatopsia, blue-cone monochromatism, oligocone trichromacy, bradyopsia and Bornholm eye disease. We describe the clinical, psychophysical, electrophysiological and imaging findings that are characteristic to each condition in order to aid their accurate diagnosis, as well as highlight some classically held notions about these diseases that have come to be challenged over the recent years. The latest data regarding the genetic aetiology and pathological changes observed in the cone dysfunction syndromes are discussed, and, where relevant, translational avenues of research, including completed and anticipated interventional clinical trials, for some of the diseases described herein will be presented. Finally, we briefly review the current management of these disorders. PMID:25770143

  8. Prevalence of Sexual Dysfunctions

    PubMed Central

    Simons, Jeffrey; Carey, Michael P.

    2008-01-01

    Ten years of research that has provided data regarding the prevalence of sexual dysfunctions is reviewed. A thorough review of the literature identified 52 studies that have been published in the 10 years since an earlier review by Spector and Carey (1990). Community samples indicate a current prevalence of 0 - 3% for male orgasmic disorder, 0 - 5% for erectile disorder, and 0 - 3% for male hypoactive sexual desire disorder. Pooling current and 1-year figures provides community prevalence estimates of 7 - 10% for female orgasmic disorder and 4 - 5% for premature ejaculation. Stable community estimates of the current prevalence for the other sexual dysfunctions remain unavailable. Prevalence estimates obtained from primary care and sexuality clinic samples are characteristically higher. Although a relatively large number of studies have been conducted since Spector and Carey’s (1990) review, the lack of methodological rigor of many studies limits the confidence that can be placed in these findings. PMID:11329727

  9. Molecular biology of atherosclerosis

    PubMed Central

    Mannarino, Elmo; Pirro, Matteo

    2008-01-01

    The traditional view of atherosclerosis as a pathological lipid deposition within the artery wall has been redefined by a more complex concept of an ongoing inflammatory disease. The atherosclerotic process is initiated when cardiovascular risk factors, through a chemical, mechanical or immunological insult, activate and/or injury the endothelium, thus contributing to endothelial dysfunction and fragmentation. This triggers a cascade of inflammatory reactions, in which monocytes, macrophages, T lymphocytes, vascular smooth muscle cells actively participate. Particularly, atherosclerotic lesions have been seen to have increased expression of T helper-1 cells together with increased levels of the T helper-1 related pro-inflammatory cytokines. Along with pro-inflammatory cytokines, other molecular factors involved in atherosclerosis appearance, progression and complication include chemokines, growth factors, vasoactive substances, enzymes, apoptosis signals and many others. Many of these molecular factors are both involved as possible markers of the atherosclerotic disease activity and burden, but may also play a crucial role in the pathogenesis of the disease. In recent years, the discovery of progenitor cells of myeloid origin has offered the prospect of merging the most recent theories on the pathogenesis of atherosclerosis with the evolving concept of a role of these progenitor cells in the repair of the injured vessel wall and the neovascularisation of ischemic tissues. This review summarizes current knowledge about the biology of atherosclerosis with emphasis on the mechanisms of endothelial damage and repair and on the concept that the turnover and replacement of endothelial cells is a major determinant in the maintenance of vascular integrity. PMID:22460847

  10. Sexual dysfunction in diabetes.

    PubMed

    Tamás, Várkonyi; Kempler, Peter

    2014-01-01

    We aimed to summarize the etiology, clinical characteristics, diagnosis, and possible treatment options of sexual dysfunction in diabetic patients of both sexes. Details of dysfunction in diabetic women are less conclusive than in men due to the lack of standardized evaluation of sexual function in women. Male sexual dysfunction is a common complication of diabetes, including abnormalities of orgasmic/ejaculatory function and desire/libido in addition to penile erection. The prevalence of erectile dysfunction (ED) among diabetic men varies from 35% to 75%. Diabetes-induced ED has a multifactorial etiology including metabolic, neurologic, vascular, hormonal, and psychological components. ED should be regarded as the first sign of cardiovascular disease because it can be present before development of symptomatic coronary artery disease, as larger coronary vessels better tolerate the same amount of plaque compared to smaller penile arteries. The diagnosis of ED is based on validated questionnaires and determination of functional and organic abnormalities. First-, second- and third-line therapy may be applied. Phosphodiesterase-5 (PDE-5) inhibitor treatment from the first-line options leads to smooth muscle relaxation in the corpus cavernosum and enhancement in blood flow, resulting in erection during sexual stimulus. The use of PDE-5 inhibitors in the presence of oral nitrates is strictly contraindicated in diabetic men, as in nondiabetic subjects. All PDE-5 inhibitors have been evaluated for ED in diabetic patients with convincing efficacy data. Second-line therapy includes intracavernosal, trans- or intraurethral administration of vasoactive drugs or application of a vacuum device. Third-line therapies are the implantation of penile prosthesis and penile revascularization.

  11. Sexual Dysfunction After Urethroplasty.

    PubMed

    Dogra, Prem Nath; Singh, Prabhjot; Nayyar, Rishi; Yadav, Siddharth

    2017-02-01

    Posturethroplasty sexual dysfunction (SD) is multifactorial and its true incidence is unknown. Even with the current evidence suggesting that it is uncommon, de novo SD causes dissatisfaction even after a successful surgery. Posterior urethroplasty carries the highest chance of SD, mostly attributable to the pelvic fracture itself rather than the urethroplasty. With anterior urethroplasty, transecting bulbar urethroplasty leads to greater SD compared with penile or nontransecting bulbar urethroplasty. Most patients with posturethroplasty SD recover within 6 months after surgery.

  12. Thyroid dysfunction and subfertility.

    PubMed

    Cho, Moon Kyoung

    2015-12-01

    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.

  13. Diastolic dysfunction in hypertension.

    PubMed

    Slama, Michel; Susic, Dinko; Varagic, Jasmina; Frohlich, Edward D

    2002-07-01

    Heart failure is one of the most common causes of cardiovascular morbidity and mortality, and hypertension is the most common cause of cardiac failure. Recent studies have shown that isolated diastolic dysfunction very often accompanies hypertensive heart disease. Ventricular diastolic function may be divided into an active relaxation phase and a passive compliance period. These two components have been investigated invasively, and they remain the gold standards for the study of diastolic function. However, in the routine clinical setting, echocardiographic and Doppler techniques are most useful for evaluating ventricular filling. Thus, analysis of E and A waves of mitral flow have provided important and useful information. Unfortunately, these indices depend on too many factors. Newer indices obtained from ventricular time intervals, tissue Doppler imaging, and color M-mode echocardiography have enhanced the means to assess diastolic function. In addition, new methods including MRI and cine CT have also provided better understanding of left ventricular filling in hypertension. Using these techniques, diastolic dysfunction has been found to be common in patients with hypertension, even before left ventricular hypertrophy is demonstrable and before hypertension in young, normotensive male offspring of hypertensive parents has developed. Furthermore, it has been made clear recently that myocardial ischemia and fibrosis are two important factors associated with diastolic dysfunction in hypertension.

  14. 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

  15. Fullerenol Cytotoxicity in Kidney Cells is Associated with Cytoskeleton Disruption, Autophagic Vacuole Accumulation, and Mitochondrial Dysfunction

    PubMed Central

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

    2010-01-01

    Water soluble fullerenes, such as the hydroxylated fullerene, fullerenol (C60OHx), 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. PMID:20713077

  16. 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.

  17. Sexual dysfunction with antihypertensive drugs.

    PubMed

    Prisant, L M; Carr, A A; Bottini, P B; Solursh, D S; Solursh, L P

    1994-04-11

    The relationship of antihypertensive drugs have a long history of association with sexual dysfunction; however, this relationship is poorly documented. There appears to be a higher rate of sexual dysfunction in untreated hypertensive men compared with normotensive men. Sexual dysfunction increases with age and is associated with physical and emotional symptoms. There are few studies assessing sexual dysfunction with female and African-American hypertensive patients. Sexual dysfunction is associated with impairment of quality of life and noncompliance. Since group data may hide individual drug effects, baseline data should be collected on all patients before initiating therapy with any antihypertensive agent. Although questionnaires may not provide objective information on sexual dysfunction, the response rate to direct questioning may be less than the response rate on a questionnaire and may be affected by the gender or race of the interviewer. Research protocols using a double-blind, placebo-controlled design should assess sexual dysfunction in men and women in a standardized fashion.

  18. Erectile dysfunction in young patients is a proxy of overall men's health status.

    PubMed

    Capogrosso, Paolo; Montorsi, Francesco; Salonia, Andrea

    2016-03-01

    This article summarizes current findings supporting the role of erectile dysfunction as a proxy of general health status, with a focus on the young population. Erectile dysfunction has been historically associated to increased cardiovascular risk and mortality. Several studies supported the role of erectile dysfunction as a predictive factor of subsequent cardiovascular events, acquiring significant importance even in young men. Similarly, erectile dysfunction emerged as a potential marker for metabolic alterations including diabetes mellitus and metabolic syndrome, eventually presenting as the initial manifestation of a dysmetabolic condition in young patients. Moreover, current epidemiologic data demonstrated a significant association of erectile dysfunction with several conditions including vascular, respiratory, gastrointestinal disorders, and endocrine with chronic-sustained inflammation representing the common pathophysiological link between erectile dysfunction and comorbidities. Interestingly, longitudinal studies demonstrated a higher risk of overall mortality in patients complaining of erectile dysfunction, even irrespective of cardiovascular risk. Erectile dysfunction does not represent an uncommon condition among young men. Considering the amount of data demonstrating a strong correlation between several life-risky comorbidities and erectile dysfunction, a careful and comprehensive general health assessment of patients complaining of erectile dysfunction should be carried out, regardless of patient's age. The identification of erectile dysfunction as an early sign of a major comorbidity would allow the implementation of therapeutic measures aimed at improving the overall health status and life expectancy across the entire aging process.

  19. [Beyond immunopathogenesis. Insulin resistance and "epidermal dysfunction"].

    PubMed

    Boehncke, W-H; Boehncke, S; Buerger, C

    2012-03-01

    Insulin is a central player in the regulation of metabolic as well as non-metabolic cells: inefficient signal transduction (insulin resistance) not only represents the cornerstone in the pathogenesis of type 2 diabetes mellitus, but also drives atherosclerosis through inducing endothelial dysfunction. Last but not least epidermal homeostasis depends on insulin. We summarize the effects of insulin on proliferation and differentiation of human keratinocytes as well as the relevance of cytokine-induced insulin resistance for alterations in epidermal homeostasis characteristic for psoriasis. Kinases involved in both insulin- as well as cytokine-receptor signaling represent potential targets for innovative therapeutics. Such small molecules would primarily normalize "epidermal dysfunction", thus complementing the immunomodulatory strategies of today's biologics.

  20. [Genomic markers and anticancer chemotherapy].

    PubMed

    Nishiyama, Masahiko

    2008-02-01

    Worldwide research on the human genome exerts a major impact on medical science. The growing evidence that genetic polymorphisms in the metabolism, the disposition, and the targets of drugs can have an even greater influence on the efficacy and the toxicity led to the creation of a novel chemotherapeutic strategy, personalized medicine. Much effort has been directed toward identifying the indicators of individual response to drugs, and these studies have provided a variety of potent predictive markers of individual drug response, which include some significant markers in clinical practice with sufficient evidence. Personalized medicine based on the response prediction using genomic marker is increasingly being recognized as a practical treatment approach in cancer chemotherapy, and to be indispensable when molecular targeted drugs are involved in the therapy. Even so, the ingenious and intricate mechanism of individual drug response creates obstacles in predicting chemotherapeutic response: Multiple factors are involved in the mechanisms, and key factors for drug response vary significantly among individuals. DNA chip technology enables us to overview a huge number of gene expressions simultaneously, but gene expression profiles of drug sensitivity vary considerably even for the same drug, which shows the limited value of a static microarray-expression profile as a marker aimed at individualizing patient therapy. Selection of a set of truly significant genomic markers and understanding of their interplay are of key importance in prediction of individual response to drug therapies. Challenges to such biological complexity are now started to identify a better genomic marker. The contribution of genomic marker research to anticancer chemotherapy and problems of the day were reviewed.

  1. WIPP marker development

    SciTech Connect

    1994-04-01

    This article discusses the development of permanent, passive markers for the Waste Isolation Pilot Plant (WIPP) and presents some preliminary concepts in drawings and a table of components for the markers. The panel, convened by Sandia National Laboratories, was charged with developing design characteristics for permanent markers and judging the efficacy of markers in deterring inadvertent human intrusion. 6 figs., 2 tabs.

  2. Stereotactic core needle breast biopsy marker migration: An analysis of factors contributing to immediate marker migration.

    PubMed

    Jain, Ashali; Khalid, Maria; Qureshi, Muhammad M; Georgian-Smith, Dianne; Kaplan, Jonah A; Buch, Karen; Grinstaff, Mark W; Hirsch, Ariel E; Hines, Neely L; Anderson, Stephan W; Gallagher, Katherine M; Bates, David D B; Bloch, B Nicolas

    2017-05-19

    To evaluate breast biopsy marker migration in stereotactic core needle biopsy procedures and identify contributing factors. This retrospective study analyzed 268 stereotactic biopsy markers placed in 263 consecutive patients undergoing stereotactic biopsies using 9G vacuum-assisted devices from August 2010-July 2013. Mammograms were reviewed and factors contributing to marker migration were evaluated. Basic descriptive statistics were calculated and comparisons were performed based on radiographically-confirmed marker migration. Of the 268 placed stereotactic biopsy markers, 35 (13.1%) migrated ≥1 cm from their biopsy cavity. Range: 1-6 cm; mean (± SD): 2.35 ± 1.22 cm. Of the 35 migrated biopsy markers, 9 (25.7%) migrated ≥3.5 cm. Patient age, biopsy pathology, number of cores, and left versus right breast were not associated with migration status (P> 0.10). Global fatty breast density (P= 0.025) and biopsy in the inner region of breast (P = 0.031) were associated with marker migration. Superior biopsy approach (P= 0.025), locally heterogeneous breast density, and t-shaped biopsy markers (P= 0.035) were significant for no marker migration. Multiple factors were found to influence marker migration. An overall migration rate of 13% supports endeavors of research groups actively developing new biopsy marker designs for improved resistance to migration. • Breast biopsy marker migration is documented in 13% of 268 procedures. • Marker migration is affected by physical, biological, and pathological factors. • Breast density, marker shape, needle approach etc. affect migration. • Study demonstrates marker migration prevalence; marker design improvements are needed.

  3. 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.

  4. 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.

  5. Depression and erectile dysfunction.

    PubMed

    Makhlouf, Antoine; Kparker, Ashay; Niederberger, Craig S

    2007-11-01

    Depression and erectile dysfunction (ED) clearly are associated. Although urologists and psychiatrists have long recognized that antidepressant medications affect erectile function negatively, the interplay between the two conditions remains underappreciated. Psychiatrists may be reluctant to question a patient in detail about ED, and urologists seldom perform a formal assessment of the presence of depression in patients who have ED. This article gives a quick overview of the relationship between these two conditions and provides the clinician with the knowledge required to effectively manage ED with comorbid depression.

  6. Dysfunctional voiding in adults.

    PubMed

    Haifler, Miki; Stav, Kobi

    2013-05-01

    Dysfunctional voiding is characterized by an intermittent and/or fluctuating flow rate due to involuntary intermittent contractions of the periurethral striated or levator muscles during voiding in neurologically normal women (International Continence Society definition). Due to the variable etiology, the diagnosis and treatment of DV is problematic. Frequently, the diagnosis is done at a late stage mainly due to non-specific symptoms and lack of awareness. The objectives of treatment are to normalize micturition patterns and prevent complications such as renal failure and recurrent infections. Treatment should be started as early as possible and a multidisciplinary approach is beneficial.

  7. [Thyroid dysfunctions and pregnancy].

    PubMed

    Caron, Philippe

    2011-12-01

    Advances in understanding the physiology of the thyroid function in normal pregnancy have highlighted the importance of the consequences of abnormal thyroid function on mother and fetal outcomes. Thyroid diseases are common in young women of childbearing age while management of thyroid diseases is relatively straightforward. For each thyroid dysfunction (hypothyroxinemia, hypothyroidism, hyperthyroidism, postpartum thyroiditis), the issues with the obstetric complications of the mother and the fetus are considered. Indeed, early recognition of thyroid diseases during pregnancy and appropriate management has the potential to improve outcome for the mother and the fetus.

  8. DNA marker technology for wildlife conservation.

    PubMed

    Arif, Ibrahim A; Khan, Haseeb A; Bahkali, Ali H; Al Homaidan, Ali A; Al Farhan, Ahmad H; Al Sadoon, Mohammad; Shobrak, Mohammad

    2011-07-01

    Use of molecular markers for identification of protected species offers a greater p