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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. 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

  3. [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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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

  13. [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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  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. 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

  5. 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

  6. 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

  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, 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.

  9. 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.

  10. 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.

  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. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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

  2. [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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  14. 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.

  15. 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.

  16. Connection between telomerase activity in PBMC and markers of inflammation and endothelial dysfunction in patients with metabolic syndrome.

    PubMed

    Rentoukas, Elias; Tsarouhas, Konstantinos; Kaplanis, Ioannis; Korou, Eleni; Nikolaou, Maria; Marathonitis, George; Kokkinou, Stavroula; Haliassos, Alexander; Mamalaki, Avgi; Kouretas, Demetrios; Tsitsimpikou, Christina

    2012-01-01

    Metabolic syndrome (MS) is a constellation of metabolic derangements associated with vascular endothelial dysfunction and oxidative stress and is widely regarded as an inflammatory condition, accompanied by an increased risk for cardiovascular disease. The present study tried to investigate the implications of telomerase activity with inflammation and impaired endothelial function in patients with metabolic syndrome. Telomerase activity in circulating peripheral blood mononuclear cells (PBMC), TNF-α, IL-6 and ADMA were monitored in 39 patients with MS and 20 age and sex-matched healthy volunteers. Telomerase activity in PBMC, TNF-α, IL-6 and ADMA were all significantly elevated in patients with MS compared to healthy volunteers. PBMC telomerase was negatively correlated with HDL and positively correlated with ADMA, while no association between TNF-α and IL-6 was observed. IL-6 was increasing with increasing systolic pressure both in the patients with MS and in the healthy volunteers, while smoking and diabetes were positively correlated with IL-6 only in the patients' group. In conclusion, in patients with MS characterised by a strong dyslipidemic profile and low diabetes prevalence, significant telomerase activity was detected in circulating PBMC, along with elevated markers of inflammation and endothelial dysfunction. These findings suggest a prolonged activity of inflammatory cells in the studied state of this metabolic disorder that could represent a contributory pathway in the pathogenesis of atherosclerosis.

  17. 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

  18. 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

  19. 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

  20. 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…

  1. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  3. 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…

  4. Developmental programming of obesity and metabolic dysfunction: role of prenatal stress and stress biology.

    PubMed

    Entringer, Sonja; Wadhwa, Pathik D

    2013-01-01

    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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. Identification and Development of Biological Markers of Human Exposure to the Insecticide Permethrin

    DTIC Science & Technology

    2008-04-01

    Davis, CA 95616-8671 REPORT DATE : April 2008 TYPE OF REPORT: Final PREPARED FOR: U.S. Army Medical Research and Materiel...display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE 1 Apri 2008 2. REPORT TYPE...Final 3. DATES COVERED 24 Sep 2001 – 23 Mar 2008 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Identification and Development of Biological Markers

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  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. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. [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.

  9. 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

  10. 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.

  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. 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.

  13. 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.

  14. 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.

  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. 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

  17. 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

  18. 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…

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. [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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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

  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. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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, .

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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

  18. [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.

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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 ...

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Erectile Dysfunction

    MedlinePlus

    ... or other heart problems take medications that contain nitrates to help the blood flow better to the ... erectile dysfunction can affect the way that the nitrates work—and cause blood pressure to drop to ...

  9. 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

  10. Long-term validity of biological markers of psychopathy and criminal recidivism: follow-up 6-8 years after forensic psychiatric investigation.

    PubMed

    Stalenheim, E Gunilla

    2004-01-01

    This study is a follow-up investigation of a forensic psychiatric sub-population 6-8 years after forensic psychiatric evaluation. The aim was to examine the long-term validity of biological markers of psychopathy and antisocial behavior over time. Data on criminal records were obtained at follow-up from the National Council for Crime Prevention. Basic data included findings of psychiatric and psychological assessments, as well as values for serum triiodothyronine (T3) and free thyroxin (FT4), and platelet monoamine oxidase (MAO) activity, all obtained during the forensic psychiatric examination. Criminal recidivists at follow-up had higher serum T3 levels than non-recidivists, and much higher values than normal controls, while their levels of free T4 were lower. The T3 levels in criminal recidivists correlated to psychopathy- and aggression-related personality traits as measured by the Karolinska Scale of Personality. In violent recidivists, a remarkably high correlation was noted between T3 levels and Irritability and Detachment, traits that have previously been linked to the dopaminergic system. Stepwise multiple regression analyses confirmed the relationships of T3 levels and platelet MAO activity with personality traits in criminal recidivists. The predictive validity of biological markers of psychopathy, T3 and platelet MAO, measured during forensic psychiatric investigation, is stable over time. The results indicate chronic alterations of the hypothalamic-pituitary-thyroid axis in this group of subjects.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  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. 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.

  2. Erectile dysfunction

    PubMed Central

    2011-01-01

    Introduction Erectile dysfunction may affect 30% to 50% of men aged 40 to 70 years, with age, smoking, and obesity being the main risk factors, although 20% of cases have psychological causes. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of phosphodiesterase inhibitors in men with erectile dysfunction of any cause? What are the effects of phosphodiesterase inhibitors on erectile dysfunction in men with diabetes, with cardiovascular disease, with spinal cord injury, and with prostate cancer or undergoing prostatectomy? What are the effects of drug treatments other than phosphodiesterase inhibitors in men with erectile dysfunction of any cause? What are the effects of devices, psychological/behavioural treatments, and alternative treatments in men with erectile dysfunction of any cause? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 81 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: alprostadil (intracavernosal, intraurethral, topical), cognitive behavioural therapy, ginseng, papaverine, papaverine plus phentolamine (bimix), papaverine plus phentolamine plus alprostadil (trimix), penile prostheses, phosphodiesterase inhibitors (sildenafil, tadalafil, vardenafil), psychosexual counselling, vacuum devices, and yohimbine. PMID:21711956

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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?

  9. Axillary nerve dysfunction

    MedlinePlus

    ... Causes Axillary nerve dysfunction is a form of peripheral neuropathy . It occurs when there is damage to the ... Multiple mononeuropathy Muscle function loss Numbness and tingling Peripheral neuropathy Systemic Review Date 2/3/2015 Updated by: ...

  10. Tibial nerve dysfunction

    MedlinePlus

    ... Tibial nerve dysfunction is an unusual form of peripheral neuropathy . It occurs when there is damage to the ... PA: Elsevier Saunders; 2012:chap 76. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman-Cecil ...

  11. 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.

  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. 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 ...

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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

  19. Multiple sclerosis and sexual dysfunction

    PubMed Central

    Guo, Zhen-Ni; He, Si-Yuan; Zhang, Hong-Liang; Wu, Jiang; Yang, Yi

    2012-01-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system characterized by episodic and progressive neurologic dysfunction resulting from inflammatory and autoimmune reactions. The underlying pathogenesis of MS remains largely unclear. However, it is currently accepted as a T cell-mediated autoimmune disease. Among other clinical manifestations, sexual dysfunction (SD) is a painful but still underreported and underdiagnosed symptom of the disorder. SD in MS patients may result from a complex set of conditions and may be associated with multiple anatomic, physiologic, biologic, medical and psychological factors. SD arises primarily from lesions affecting the neural pathways involved in physiologic function. In addition, psychological factors, the side effects of medications and physical symptoms such as fatigue, muscular weakness, menstrual changes, pain and concerns about bladder and bowel incontinence may also be involved. Since MS primarily affects young people, SD secondary to MS may have a great impact on quality of life. Thus, maintaining a healthy sexual life with MS is an important priority. The treatment of SD requires multidisciplinary teamwork and cooperation among specialists, individual patients, partners and the society. PMID:22447199

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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.

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

    PubMed Central

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

    2015-01-01

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

  6. 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

  7. 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…

  8. 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.

  9. 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.

  10. Female Sexual Dysfunction

    MedlinePlus

    ... on women with certain sexual dysfunctions, but more study is needed. Yoga. During yoga, you perform a series of postures and controlled breathing exercises to promote a flexible body and a calm mind. Certain subsets of yoga aim to channel the ...

  11. 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…

  12. 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

  13. 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…

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

    DTIC Science & Technology

    1991-12-15

    Mayer , 1974) and expressed as pmoles of resorufin mirr I mg’J of microsomal and homogenate protein respectively. Concentrations of cytochrome P450 in...measured fluorometrically at 30*C (Burke and 25 Mayer , 1974) and expressed as pmoles of resorufin min-I mg-I of microsomal and homogenate protein...alkyl deoxynucleosides in the DNA of mammalian cells by monoclonal antibodies. Environ. Health Persuec. 62:49-55. Burke, M. D.; Mayer , R. T. (1974

  15. 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.

  16. 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)

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. [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.

  8. Andropause: endocrinology, erectile dysfunction, and prostate pathophysiology.

    PubMed

    Hafez, B; Hafez, E S E

    2004-01-01

    This review summarizes major biological aspects of andrology of andropause, deficiency in androgens/growth hormones, and molecular parameters; erectile dysfunction (ED), the use of malleable, mechanical, inflatable devices as well as the application of Viagra (Sildenafil), alprotadil (Caverject), Yohimbine, and other drugs not yet approved by FDA, such as Papaverine, phentolamine (Vasomax), and apormorphine (Uprima); osteopenia/osteoporosis: testosterone/osteoporesis; supplementation during andropause: administration of andiogens, possible risk factors of androgens, calcium supplement and muscle mass; prostate pathophysiology: consequences of prostatectomy, prostate cancer, benign prostatic hyperplasia (BPH), hormone-dependent cancers; bladder and urethral dysfunction: neurological parameter, urodynamics technology; models on aging in male animals: comparative physiology of prostate of laboratory animals/farm animals; future research: functional anatomy of male reproductive organs, pharmacokinetics of osteoporosis, endocrinology/neuroendocrinology/chromosome anomalies supplementation during andropause, experimental animal models and future multicenter multidisciplinary research.

  9. [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.

  10. 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.

  11. 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.

  12. [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.

  13. 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.

  14. 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.

  15. 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.

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

    PubMed

    Maliutina, N N; Nevzorova, M S

    2015-01-01

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

  17. 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

  18. Managing female sexual dysfunction.

    PubMed

    Buster, John E

    2013-10-01

    Female sexual dysfunctions (FSDs) range from short-term aggravations to major emotional disturbances adversely affecting family and workplace. This review highlights diagnosis and management of the four most widely diagnosed FSDs. It initially focuses on hypoactive sexual desire disorder (HSDD) as a driving force at the heart of all other FSDs; nothing happens without sexual desire. Successful resolution of HSDD frequently facilitates resolution of other disorders. Central to understanding HSDD is the impact of aging female sexual endocrinology and its effect on both prevalence and expression patterns of FSD. Advances in this field have enabled introduction of some the most effective treatments yet described for HSDD. Sexual arousal disorder, though commonly affected by the same factors as HSDD, is heavily associated with psychotropic drugs and mood elevators. Orgasmic disorder is frequently the downstream result of other sexual dysfunctions, particularly HSDD, or the result of a major psychosexual trauma. Successful management of the underlying disorder often resolves orgasmic disorder. Sexual pain disorder is frequently the result of a gynecologic disorder, such as endometriosis, that can be substantially managed through successful treatment of that disorder. This article ends with the article's most important note: how to initiate the conversation.

  19. Multiple organ dysfunction syndrome.

    PubMed Central

    Murray, M. J.; Coursin, D. B.

    1993-01-01

    The multiple organ dysfunction syndrome (MODS), though newly described, has manifested itself in intensive care unit (ICU) patients for several decades. As the name implies, it is a syndrome in which more than one organ system fails. Failure of these multiple organ systems may or may not be related to the initial injury or disease process for which the patient was admitted to the ICU. MODS is the leading cause of morbidity and mortality in current ICU practice. While the pathophysiology of MODS is not completely known, much evidence indicates that, during the initial injury which precipitates ICU admission, a chain of events is initiated which results in activation of several endogenous metabolic pathways. These pathways release compounds which, in and of themselves, are usually cytoprotective. However, an over exuberant activation of these endogenous systems results in an inflammatory response which can lead to development of failure in distant organs. As these organs fail, they activate and propagate the systemic inflammatory response. No therapy has proven entirely efficacious at modulating this inflammatory response and the incidence and severity of MODS. In current ICU practice, treatment is focused on prevention and treating individual organ dysfunction as it develops. With increased understanding of the pathophysiology of MODS therapy will come newer modalities which inhibit or interfere with the propagation of the endogenous systemic inflammatory response. These newer therapies hold great promise and already some are undergoing clinical investigation. PMID:7825351

  20. [Multiple organ dysfunction syndrome].

    PubMed

    Cuenca Solanas, M

    1999-01-01

    Multiple organ dysfunction syndrome (MODS) is a clinical situation that has been described as a result of the rapid progress and advances that have been made in recent decades in the physiology, diagnosis, and therapeutic support of critically ill patients. In 1991, in view of the confusing terminology used to characterize processes coursing with systemic inflammatory response syndrome (SIRS), a consensus conference was held. A series of basic definitions were established and the term "multiple organ failure" was replace by MODS. In response to outside aggression, the organism tries to defend itself with two mechanisms: a non-specific humoral and cellular response called inflammation, and a specific antigenic response that modifies the genetic codes of cells of the defense system and constitutes an immunological response. At present it is thought that the inflammatory response is activated (SIRS) in response to an uncontrolled aggression, but an antiinflammatory response syndrome (ARS) exists as well. An exaggerated SIRS can lead to MODS. MODS usually debuts with pulmonary dysfunction. If the aggression persists, cardiovascular, renal, hepatic, coagulation, central nervous system, gastrointestinal metabolism, neuroendocrine and musculoskeletal failure follow. A series of causes often trigger this syndrome and certain factors favor it. Prevention of these causes and factors in fundamental for controlling the occurrence of MODS. At present, there is no clear treatment for MODS, although numerous studies designed to block the release of certain proinflammatory mediators or to neutralize antiinflammatory responses are being carried out.

  1. Animal models of erectile dysfunction.

    PubMed

    Kapoor, Mandeep Singh; Khan, Samsroz Ahmad; Gupta, Sanjay Kumar; Choudhary, Rajesh; Bodakhe, Surendra H

    2015-01-01

    Erectile dysfunction (ED) is a prevalent male sexual dysfunction with profound adverse effects on the physical and the psychosocial health of men and, subsequently, on their partners. The expanded use of various types of rodent models has produced some advances in the study of ED, and neurophysiological studies using various animal models have provided important insights into human sexual dysfunction. At present, animal models play a key role in exploring and screening novel drugs designed to treat ED.

  2. Identification of dysfunctional modules and disease genes in congenital heart disease by a network-based approach

    PubMed Central

    2011-01-01

    Background The incidence of congenital heart disease (CHD) is continuously increasing among infants born alive nowadays, making it one of the leading causes of infant morbidity worldwide. Various studies suggest that both genetic and environmental factors lead to CHD, and therefore identifying its candidate genes and disease-markers has been one of the central topics in CHD research. By using the high-throughput genomic data of CHD which are available recently, network-based methods provide powerful alternatives of systematic analysis of complex diseases and identification of dysfunctional modules and candidate disease genes. Results In this paper, by modeling the information flow from source disease genes to targets of differentially expressed genes via a context-specific protein-protein interaction network, we extracted dysfunctional modules which were then validated by various types of measurements and independent datasets. Network topology analysis of these modules revealed major and auxiliary pathways and cellular processes in CHD, demonstrating the biological usefulness of the identified modules. We also prioritized a list of candidate CHD genes from these modules using a guilt-by-association approach, which are well supported by various kinds of literature and experimental evidence. Conclusions We provided a network-based analysis to detect dysfunctional modules and disease genes of CHD by modeling the information transmission from source disease genes to targets of differentially expressed genes. Our method resulted in 12 modules from the constructed CHD subnetwork. We further identified and prioritized candidate disease genes of CHD from these dysfunctional modules. In conclusion, module analysis not only revealed several important findings with regard to the underlying molecular mechanisms of CHD, but also suggested the distinct network properties of causal disease genes which lead to identification of candidate CHD genes. PMID:22136190

  3. Prognostic markers in acute pancreatitis.

    PubMed

    Gomatos, Ilias P; Xiaodong, Xu; Ghaneh, Paula; Halloran, Christopher; Raraty, Michael; Lane, Brian; Sutton, Robert; Neoptolemos, John P

    2014-04-01

    Acute pancreatitis has a mortality rate of 5-10%. Early deaths are mainly due to multiorgan failure and late deaths are due to septic complications from pancreatic necrosis. The recently described 2012 Revised Atlanta Classification and the Determinant Classification both provide a more accurate description of edematous and necrotizing pancreatitis and local complications. The 2012 Revised Atlanta Classification uses the modified Marshall scoring system for assessing organ dysfunction. The Determinant Classification uses the sepsis-related organ failure assessment scoring system for organ dysfunction and, unlike the 2012 Revised Atlanta Classification, includes infected necrosis as a criterion of severity. These scoring systems are used to assess systemic complications requiring intensive therapy unit support and intra-abdominal complications requiring minimally invasive interventions. Numerous prognostic systems and markers have been evaluated but only the Glasgow system and serum CRP levels provide pragmatic prognostic accuracy early on. Novel concepts using genetic, transcriptomic and proteomic profiling and also functional imaging for the identification of specific disease patterns are now required.

  4. Autonomic dysfunction in multiple sclerosis.

    PubMed

    Racosta, Juan Manuel; Kimpinski, Kurt; Morrow, Sarah Anne; Kremenchutzky, Marcelo

    2015-12-01

    Autonomic dysfunction is a prevalent and significant cause of disability among patients with multiple sclerosis. Autonomic dysfunction in multiple sclerosis is usually explained by lesions within central nervous system regions responsible for autonomic regulation, but novel evidence suggests that other factors may be involved as well. Additionally, the interactions between the autonomic nervous system and the immune system have generated increased interest about the role of autonomic dysfunction in the pathogenesis of multiple sclerosis. In this paper we analyze systematically the most relevant signs and symptoms of autonomic dysfunction in MS, considering separately their potential causes and implications.

  5. 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 promise in the field of conservation biology. The information on genetic diversity of wildlife is necessary to ascertain the genetically deteriorated populations so that better management plans can be established for their conservation. Accurate classification of these threatened species allows understanding of the species biology and identification of distinct populations that should be managed with utmost care. Molecular markers are versatile tools for identification of populations with genetic crisis by comparing genetic diversities that in turn helps to resolve taxonomic uncertainties and to establish management units within species. The genetic marker analysis also provides sensitive and useful tools for prevention of illegal hunting and poaching and for more effective implementation of the laws for protection of the endangered species. This review summarizes various tools of DNA markers technology for application in molecular diversity analysis with special emphasis on wildlife conservation.

  6. DNA marker technology for wildlife conservation

    PubMed Central

    Arif, Ibrahim A.; Khan, Haseeb A.; Bahkali, Ali H.; Al Homaidan, Ali A.; Al Farhan, Ahmad H.; Al Sadoon, Mohammad; Shobrak, Mohammad

    2011-01-01

    Use of molecular markers for identification of protected species offers a greater promise in the field of conservation biology. The information on genetic diversity of wildlife is necessary to ascertain the genetically deteriorated populations so that better management plans can be established for their conservation. Accurate classification of these threatened species allows understanding of the species biology and identification of distinct populations that should be managed with utmost care. Molecular markers are versatile tools for identification of populations with genetic crisis by comparing genetic diversities that in turn helps to resolve taxonomic uncertainties and to establish management units within species. The genetic marker analysis also provides sensitive and useful tools for prevention of illegal hunting and poaching and for more effective implementation of the laws for protection of the endangered species. This review summarizes various tools of DNA markers technology for application in molecular diversity analysis with special emphasis on wildlife conservation. PMID:23961128

  7. Compensatory and maladaptive responses to cardiac dysfunction.

    PubMed

    Francis, G S; Chu, C

    1994-05-01

    The past few years have witnessed an extraordinary number of important developments in the study of compensatory and maladaptive responses to cardiac dysfunction. It now seems clear that the process whereby the heart remodels in response to left ventricular injury is of paramount importance in the expression of clinical heart failure. There have been parallel attempts by basic scientists and clinical investigators to understand better the fundamental biologic processes that underlie remodeling and to assess numerous new treatments--especially angiotensin-converting enzyme inhibitors. A general consensus seems to be emerging that holds that the response of the heart to acute injury includes a number of highly compensatory and adaptive mechanisms that ultimately become maladaptive and contribute to cardiomegaly and severe congestive heart failure. Such mechanisms undoubtedly include local and systemic release of cytokines, peptides, and neurohormones, and altered loading conditions leading to unusual mechanical forces on cardiac myocytes and other cells of the heart. At the organ level there is hypertrophy, dilatation and growth of the interstitium. Preliminary evidence also suggests there may be some "remodeling" at the cardiac myocyte level. Reduction in peripheral vasodilator reserve is seen in experimental animal models of heart failure. Patients with heart failure also develop an endothelial-dependent form of peripheral vascular dysfunction expressed clinically as an attenuated ability to dilate in response to such stimuli as acetylcholine. The transition point whereby these myocardial and peripheral vascular abnormalities become clearly dysfunctional and contribute toward the full clinical expression of heart failure remains to be further investigated.

  8. MicroRNA Expression Profiles as Biomarkers of Minor Salivary Gland Inflammation and Dysfunction in Sjögren's Syndrome

    PubMed Central

    Alevizos, Ilias; Alexander, Stefanie; Turner, R. James; Illei, Gabor G.

    2013-01-01

    Objective MicroRNA reflect physiologic and pathologic processes and may be used as biomarkers of concurrent pathophysiologic events in complex settings such as autoimmune diseases. We generated microRNA microarray profiles from the minor salivary glands of control subjects without Sjögren's syndrome (SS) and patients with SS who had low-grade or high-grade inflammation and impaired or normal saliva production, to identify microRNA patterns specific to salivary gland inflammation or dysfunction. Methods MicroRNA expression profiles were generated by Agilent microRNA arrays. We developed a novel method for data normalization by identifying housekeeping microRNA. MicroRNA profiles were compared by unsupervised mathematical methods to test how well they distinguish between control subjects and various subsets of patients with SS. Several bioinformatics methods were used to predict the messenger RNA targets of the differentially expressed microRNA. Results MicroRNA expression patterns accurately distinguished salivary glands from control subjects and patients with SS who had low-degree or high-degree inflammation. Using real-time quantitative polymerase chain reaction, we validated 2 microRNA as markers of inflammation in an independent cohort. Comparing microRNA from patients with preserved or low salivary flow identified a set of differentially expressed microRNA, most of which were up-regulated in the group with decreased salivary gland function, suggesting that the targets of microRNA may have a protective effect on epithelial cells. The predicted biologic targets of microRNA associated with inflammation or salivary gland dysfunction identified both overlapping and distinct biologic pathways and processes. Conclusion Distinct microRNA expression patterns are associated with salivary gland inflammation and dysfunction in patients with SS, and microRNA represent a novel group of potential biomarkers. PMID:21280008

  9. Recognition of immunogold markers in electron micrographs.

    PubMed

    Wang, Ruixuan; Pokhariya, Himanshu; McKenna, Stephen J; Lucocq, John

    2011-11-01

    Immunoelectron microscopy is used in cell biological research to study the spatial distribution of intracellular macromolecules at the ultrastructural level. Colloidal gold particles (immunogold markers) are commonly used to localise molecules of interest on ultrathin sections and can be visualised in transmission electron micrographs as dark spots. Quantitative analysis involves detection of the immunogold markers, and is often performed manually or interactively as part of a stereological estimation technique. The method presented in this paper automatically detects and counts immunogold markers, estimating the location, size and type of each marker. It was evaluated on single-labelled as well as double-labelled images showing markers of two different sizes. This is a first step towards automatic analysis of immunoelectron micrographs, enabling a rapid and more complete quantitative analysis than is currently practicable.

  10. Psychotropics and sexual dysfunction

    PubMed Central

    Bella, Anthony J.

    2013-01-01

    Introduction Sexual dysfunction (SD) is common in patients taking antipsychotics, and is the most bothersome symptom and adverse drug effect compromising treatment compliance. Mechanisms involved in psychotropics–induced SD are either largely unknown or poorly understood. The aim of this review is to present an updated analysis of SD associated with the use of psychotropic drugs in psychiatric patients. Results Contemporary evidence from available studies demonstrates that SD rates are drug–related rather than drug–class specific, and that these rates vary widely. Mechanisms involved in psychotropics–induced SD are either largely unknown or poorly understood. Our understanding of psychotropics–induced SD is limited by the inability to differentiate whether these effects are really drug–induced or due to different inclusion criteria. Conclusions Rigorous research, basic and clinical, is needed to understand the exact incidence, severity and mechanisms involved in the development of SD induced by various psychotropic treatment regimens. PMID:24757547

  11. Telomere dysfunction and chromothripsis.

    PubMed

    Ernst, Aurélie; Jones, David T W; Maass, Kendra K; Rode, Agata; Deeg, Katharina I; Jebaraj, Billy Michael Chelliah; Korshunov, Andrey; Hovestadt, Volker; Tainsky, Michael A; Pajtler, Kristian W; Bender, Sebastian; Brabetz, Sebastian; Gröbner, Susanne; Kool, Marcel; Devens, Frauke; Edelmann, Jennifer; Zhang, Cindy; Castelo-Branco, Pedro; Tabori, Uri; Malkin, David; Rippe, Karsten; Stilgenbauer, Stephan; Pfister, Stefan M; Zapatka, Marc; Lichter, Peter

    2016-06-15

    Chromothripsis is a recently discovered form of genomic instability, characterized by tens to hundreds of clustered DNA rearrangements resulting from a single dramatic event. Telomere dysfunction has been suggested to play a role in the initiation of this phenomenon, which occurs in a large number of tumor entities. Here, we show that telomere attrition can indeed lead to catastrophic genomic events, and that telomere patterns differ between cells analyzed before and after such genomic catastrophes. Telomere length and telomere stabilization mechanisms diverge between samples with and without chromothripsis in a given tumor subtype. Longitudinal analyses of the evolution of chromothriptic patterns identify either stable patterns between matched primary and relapsed tumors, or loss of the chromothriptic clone in the relapsed specimen. The absence of additional chromothriptic events occurring between the initial tumor and the relapsed tumor sample points to telomere stabilization after the initial chromothriptic event which prevents further shattering of the genome.

  12. The heart as an extravascular target of endothelin-1 in particulate matter-induced cardiac dysfunction

    EPA Science Inventory

    Exposure to particulate matter air pollution has been causally linked to cardiovascular disease in humans. Several broad and overlapping hypotheses describing the biological mechanisms by which particulate matter exposure leads to cardiovascular disease and cardiac dysfunction ha...

  13. Pulmonary Hypertension Secondary to Left Ventricular Systolic Dysfunction: Contemporary Diagnosis and Management

    PubMed Central

    Shah, Ravi V.; Semigran, Marc J.

    2011-01-01

    Pulmonary hypertension secondary to left ventricular systolic dysfunction is often a poor prognostic marker in chronic heart failure. In this article, we review evidence supporting modern strategies addressing pulmonary hypertension in patients with left ventricular systolic dysfunction, including right-sided heart catheterization with vasoreactivity testing and subsequent parenteral, oral, and inhaled therapy. We delineate a diagnostic approach to secondary pulmonary hypertension and outline evidence-based therapeutic strategies for management in acute and chronic heart failure. PMID:19032918

  14. Ceramic subsurface marker prototypes

    SciTech Connect

    Lukens, C.E.

    1985-05-02

    The client submitted 5 sets of porcelain and stoneware subsurface (radioactive site) marker prototypes (31 markers each set). The following were determined: compressive strength, thermal shock resistance, thermal crazing resistance, alkali resistance, color retention, and chemical resistance.

  15. Ghrelin Attenuates Intestinal Barrier Dysfunction Following Intracerebral Hemorrhage in Mice

    PubMed Central

    Cheng, Yijun; Wei, Yongxu; Yang, Wenlei; Cai, Yu; Chen, Bin; Yang, Guoyuan; Shang, Hanbing; Zhao, Weiguo

    2016-01-01

    Intestinal barrier dysfunction remains a critical problem in patients with intracerebral hemorrhage (ICH) and is associated with poor prognosis. Ghrelin, a brain-gut peptide, has been shown to exert protection in animal models of gastrointestinal injury. However, the effect of ghrelin on intestinal barrier dysfunction post-ICH and its possible underlying mechanisms are still unknown. This study was designed to investigate whether ghrelin administration attenuates intestinal barrier dysfunction in experimental ICH using an intrastriatal autologous blood infusion mouse model. Our data showed that treatment with ghrelin markedly attenuated intestinal mucosal injury at both histomorphometric and ultrastructural levels post-ICH. Ghrelin reduced ICH-induced intestinal permeability according to fluorescein isothiocyanate conjugated-dextran (FITC-D) and Evans blue extravasation assays. Concomitantly, the intestinal tight junction-related protein markers, Zonula occludens-1 (ZO-1) and claudin-5 were upregulated by ghrelin post-ICH. Additionally, ghrelin reduced intestinal intercellular adhesion molecule-1 (ICAM-1) expression at the mRNA and protein levels following ICH. Furthermore, ghrelin suppressed the translocation of intestinal endotoxin post-ICH. These changes were accompanied by improved survival rates and an attenuation of body weight loss post-ICH. In conclusion, our results suggest that ghrelin reduced intestinal barrier dysfunction, thereby reducing mortality and weight loss, indicating that ghrelin is a potential therapeutic agent in ICH-induced intestinal barrier dysfunction therapy. PMID:27929421

  16. Endothelial dysfunction and tendinopathy: how far have we come?

    PubMed

    Papalia, R; Moro, L; Franceschi, F; Albo, E; D'Adamio, S; Di Martino, A; Vadalà, G; Faldini, C; Denaro, V

    2013-12-01

    Symptomatic tendon tears are one of the most important causes of pain and joint dysfunction. Among the intrinsic causes, vascularization recently gained a major role. Endothelial function is indeed a key factor, as well as vascular tone and thrombotic factors, in the regulation of vascular homeostasis and the composition of vascular wall. In this review, we studied systematically whether there is a relationship between endothelial dysfunction and tendinopathy. A literature search was performed using the isolated or combined keywords endothelial dysfunction and tendon,' 'nitric oxide (NO) and tendinopathy,' and 'endothelial dysfunction in tendon healing.' We identified 21 published studies. Of the selected studies, 9 were in vivo studies, 2 focusing on animals and 7 on humans, while 12 reported about in vitro evaluations, where 7 were carried out on humans and 5 on animals. The evidence about a direct relationship between tendinopathy and endothelial dysfunction is still poor. As recent studies have shown, there is no significant improvement in clinical and functional assessments after treatment with NO in patients suffering from tendinopathy in different locations. No significant differences were identified in the outcomes reported for experiment group when compared with controls treated with conventional surgical procedures or rehabilitation programs. Nitric oxide could be a marker to quantify the response of the endothelium to mechanical stress or hypoxia indicating the final balance between vasodilatating and vasoconstricting factors and their effects, but more ad stronger evidence is still needed to fully support this practice.

  17. Methylglyoxal promotes oxidative stress and endothelial dysfunction.

    PubMed

    Sena, Cristina M; Matafome, Paulo; Crisóstomo, Joana; Rodrigues, Lisa; Fernandes, Rosa; Pereira, Paulo; Seiça, Raquel M

    2012-05-01

    Modern diets can cause modern diseases. Research has linked a metabolite of sugar, methylglyoxal (MG), to the development of diabetic complications, but the exact mechanism has not been fully elucidated. The present study was designed to investigate whether MG could directly influence endothelial function, oxidative stress and inflammation in Wistar and Goto-Kakizaki (GK) rats, an animal model of type 2 diabetes. Wistar and GK rats treated with MG in the drinking water for 3 months were compared with the respective control rats. The effects of MG were investigated on NO-dependent vasorelaxation in isolated rat aortic arteries from the different groups. Insulin resistance, NO bioavailability, glycation, a pro-inflammatory biomarker monocyte chemoattractant protein-1 (MCP-1) and vascular oxidative stress were also evaluated. Methylglyoxal treated Wistar rats significantly reduced the efficacy of NO-dependent vasorelaxation (p<0.001). This impairment was accompanied by a three fold increase in the oxidative stress marker nitrotyrosine. Advanced glycation endproducts (AGEs) formation was significantly increased as well as MCP-1 and the expression of the receptor for AGEs (RAGE). NO bioavailability was significantly attenuated and accompanied by an increase in superoxide anion immunofluorescence. Methylglyoxal treated GK rats significantly aggravated endothelial dysfunction, oxidative stress, AGEs accumulation and diminished NO bioavailability when compared with control GK rats. These results indicate that methylglyoxal induced endothelial dysfunction in normal Wistar rats and aggravated the endothelial dysfunction present in GK rats. The mechanism is at least in part by increasing oxidative stress and/or AGEs formation with a concomitant increment of inflammation and a decrement in NO bioavailability. The present study provides further evidence for methylglyoxal as one of the causative factors in the pathogenesis of atherosclerosis and development of macrovascular

  18. Evaluating retinal ganglion cell loss and dysfunction.

    PubMed

    Mead, Ben; Tomarev, Stanislav

    2016-10-01

    Retinal ganglion cells (RGC) bear the sole responsibility of propagating visual stimuli to the brain. Their axons, which make up the optic nerve, project from the retina to the brain through the lamina cribrosa and in rodents, decussate almost entirely at the optic chiasm before synapsing at the superior colliculus. For many traumatic and degenerative ocular conditions, the dysfunction and/or loss of RGC is the primary determinant of visual loss and are the measurable endpoints in current research into experimental therapies. To actually measure these endpoints in rodent models, techniques must ascertain both the quantity of surviving RGC and their functional capacity. Quantification techniques include phenotypic markers of RGC, retrogradely transported fluorophores and morphological measurements of retinal thickness whereas functional assessments include electroretinography (flash and pattern) and visual evoked potential. The importance of the accuracy and reliability of these techniques cannot be understated, nor can the relationship between RGC death and dysfunction. The existence of up to 30 types of RGC complicates the measuring process, particularly as these may respond differently to disease and treatment. Since the above techniques may selectively identify and ignore particular subpopulations, their appropriateness as measures of RGC survival and function may be further limited. This review discusses the above techniques in the context of their subtype specificity.

  19. Mitochondrial Dysfunction in Autism Spectrum Disorders

    PubMed Central

    Siddiqui, Maheen F; Elwell, Clare; Johnson, Mark H

    2016-01-01

    Autism spectrum disorders (ASD) are classified as neurodevelopmental disorders characterised by diminished social communication and interaction. Recently, evidence has accrued that a significant proportion of individuals with autism have concomitant diseases such as mitochondrial disease and abnormalities of energy generation. This has therefore led to the hypothesis that autism may be linked to mitochondrial dysfunction. We review such studies reporting decreased activity of mitochondrial electron transport chain (ETC) complexes and reduced gene expression of mitochondrial genes, in particular genes of respiratory chain complexes, in individuals with autism. Overall, the findings support the hypothesis that there is an association of ASD with impaired mitochondrial function; however, many of the studies have small sample sizes and there is variability in the techniques utilised. There is therefore a vital need to utilise novel imaging techniques, such as near-infrared spectroscopy, that will allow non-invasive measurement of metabolic markers for neuronal activity such as cytochrome c oxidase, in order to better establish the link between autism and mitochondrial dysfunction. PMID:27928515

  20. Renal dysfunction after total body irradiation: Dose-effect relationship

    SciTech Connect

    Kal, Henk B. . E-mail: H.B.Kal@UMCUtrecht.nl; Kempen-Harteveld, M. Loes van

    2006-07-15

    Purpose: Late complications related to total body irradiation (TBI) as part of the conditioning regimen for hematopoietic stem cell transplantation have been increasingly noted. We reviewed and compared the results of treatments with various TBI regimens and tried to derive a dose-effect relationship for the endpoint of late renal dysfunction. The aim was to find the tolerance dose for the kidney when TBI is performed. Methods and Materials: A literature search was performed using PubMed for articles reporting late renal dysfunction. For intercomparison, the various TBI regimens were normalized using the linear-quadratic model, and biologically effective doses (BEDs) were calculated. Results: Eleven reports were found describing the frequency of renal dysfunction after TBI. The frequency of renal dysfunction as a function of the BED was obtained. For BED >16 Gy an increase in the frequency of dysfunction was observed. Conclusions: The tolerance BED for kidney tissue undergoing TBI is about 16 Gy. This BED can be realized with highly fractionated TBI (e.g., 6 x 1.7 Gy or 9 x 1.2 Gy at dose rates >5 cGy/min). To prevent late renal dysfunction, the TBI regimens with BED values >16 Gy (almost all found in published reports) should be applied with appropriate shielding of the kidneys.

  1. The biostatistical theory versus the harmful dysfunction analysis, part 1: is part-dysfunction a sufficient condition for medical disorder?

    PubMed

    Wakefield, Jerome C

    2014-12-01

    Christopher Boorse's biostatistical theory of medical disorder claims that biological part-dysfunction (i.e., failure of an internal mechanism to perform its biological function), a factual criterion, is both necessary and sufficient for disorder. Jerome Wakefield's harmful dysfunction analysis of medical disorder agrees that part-dysfunction is necessary but rejects the sufficiency claim, maintaining that disorder also requires that the part-dysfunction causes harm to the individual, a value criterion. In this paper, I present two considerations against the sufficiency claim. First, I analyze Boorse's central argument for the sufficiency claim, the "pathologist argument," which takes pathologists' intuitions about pathology as determinative of medical disorder and conclude that it begs the question and fails to support the sufficiency claim. Second, I present four counterexamples from the medical literature in which salient part-dysfunctions are considered nondisorders, including healthy disease carriers, HIV-positive status, benign mutations, and situs inversus totalis, thus falsifying the sufficiency claim and supporting the harm criterion.

  2. Understanding brain dysfunction in sepsis

    PubMed Central

    2013-01-01

    Sepsis often is characterized by an acute brain dysfunction, which is associated with increased morbidity and mortality. Its pathophysiology is highly complex, resulting from both inflammatory and noninflammatory processes, which may induce significant alterations in vulnerable areas of the brain. Important mechanisms include excessive microglial activation, impaired cerebral perfusion, blood–brain-barrier dysfunction, and altered neurotransmission. Systemic insults, such as prolonged inflammation, severe hypoxemia, and persistent hyperglycemia also may contribute to aggravate sepsis-induced brain dysfunction or injury. The diagnosis of brain dysfunction in sepsis relies essentially on neurological examination and neurological tests, such as EEG and neuroimaging. A brain MRI should be considered in case of persistent brain dysfunction after control of sepsis and exclusion of major confounding factors. Recent MRI studies suggest that septic shock can be associated with acute cerebrovascular lesions and white matter abnormalities. Currently, the management of brain dysfunction mainly consists of control of sepsis and prevention of all aggravating factors, including metabolic disturbances, drug overdoses, anticholinergic medications, withdrawal syndromes, and Wernicke’s encephalopathy. Modulation of microglial activation, prevention of blood–brain-barrier alterations, and use of antioxidants represent relevant therapeutic targets that may impact significantly on neurologic outcomes. In the future, investigations in patients with sepsis should be undertaken to reduce the duration of brain dysfunction and to study the impact of this reduction on important health outcomes, including functional and cognitive status in survivors. PMID:23718252

  3. Review: quantifying mitochondrial dysfunction in complex diseases of aging.

    PubMed

    Horan, Martin P; Pichaud, Nicolas; Ballard, J William O

    2012-10-01

    There is accumulating evidence that mitochondrial respiratory malfunction is associated with aging-associated complex diseases. However, progress in our understanding of these diseases has been hampered by the sensitivity and throughput of systems employed to quantify dysfunction and inherent limitations of the biological systems studied. In this review, we describe and contrast two methodologies that have been developed for measuring mitochondrial function to address the need for improved sensitivity and increased throughput. We then consider the utility of each methodology in studying three biological systems: isolated mitochondria, cultured cells, and cell fibers and tissues. Finally, we discuss the application of each methodology in the study of mitochondrial dysfunction in Alzheimer's disease, type 2 diabetes mellitus, and aging-associated autophagy impairment and mitochondrial malfunction. We conclude that the methodologies are complementary, and researchers may need to examine multiple biological systems to unravel complex diseases of aging.

  4. Psychoanalysis: a dysfunctional family?

    PubMed

    Grosskurth, P

    1998-01-01

    The discussion opens with an account of the author's mother's bizarre family in which a strong, charismatic grandmother maintained absolute control over her large family by encouraging a neurotic dependence in them through daily reports of their complaints. Getting interested in psychoanalysis in an effort to understand the dynamics of this dysfunctional family, the author, a biographer, turned to the study of Melanie Klein, becoming entranced by her ideas. Her research also revealed how Klein had discouraged her followers from developing ideas that diverged in any way from her own. Her portrait of the pioneer analyst provoked intense indignation. A similar pattern of absolute loyalty to his person and theories was to be found in Freud's Secret Committee, formed primarily as a means of getting rid of Jung who had been showing disturbing signs of independence. When Ferenczi and Rank began to pursue independent lines of enquiry in their work, they too were though to be undermining the foundations of classical psychoanalysis. Finally, the author concludes that though there have been sorry incidents in psychoanalysis, we should be mature enough to accept both the contributions of the early pioneers and the realizations that new ideas must be permitted to evolve.

  5. [Thyroid dysfunction during pregnancy].

    PubMed

    Díez, Juan J; Iglesias, Pedro; Donnay, Sergio

    2015-10-21

    Recent clinical practice guidelines on thyroid dysfunction and pregnancy have changed health care provided to pregnant women, although their recommendations are under constant revision. Trimester- and area-specific reference ranges for serum thyroid-stimulating hormone are required for proper diagnosis of hypothyroidism and hyperthyroidism. There is no doubt on the need of therapy for overt hypothyroidism, while therapy for subclinical hypothyroidism is controversial. Further research is needed to settle adverse effects of isolated hypothyroxinemia and thyroid autoimmunity. Differentiation between hyperthyroidism due to Graves' disease and the usually self-limited gestational transient thyrotoxicosis is critical. It is also important to recognize risk factors for postpartum thyroiditis. Supplementation with iodine is recommended to maintain adequate iodine nutrition during pregnancy and avoid serious consequences in offspring. Controversy remains about universal screening for thyroid disease during pregnancy or case-finding in high-risk women. Opinions of some scientific societies and recent cost-benefit studies favour universal screening. Randomized controlled studies currently under development should reduce the uncertainties that still remain in this area.

  6. [Female sexual dysfunction].

    PubMed

    Luria, Mijal

    2009-09-01

    Female sexual problems are common, frequently overlooked and have a significant impact on the lives of women. Research in the last decade has brought to the understanding and recognition of a number of standpoints, mainly the broad range of normative function. In 2003, the American Urological Association Foundation convened an international committee of experts in the field of women's sexuality, to reconsider the existing definitions of women's sexual dysfunction. Based on the circular response cycle developed by Basson, the group emphasized motivations that might move a woman from being sexually "neutral" to making a decision to be sexual with her partner, as a normative alternative to the need for spontaneous sexual desire as the trigger for sexual behavior. Etiology may stem from medical as well as psychological factors, thus assessment must include a complete evaluation. Treatment includes psycho-education, improvement of interpersonal communication, cognitive behavioral treatment and elucidation and treatment of medical problems, if necessary. Several pharmacological treatments are under investigation, with modest results and uncertainties about their long term safety. This review presents the female sexual response as it is understood today and the current diagnostic and therapeutic understandings and directions.

  7. CGMD: An integrated database of cancer genes and markers.

    PubMed

    Pradeepkiran, Jangampalli Adi; Sainath, Sri Bhashyam; Kumar, Konidala Kramthi; Balasubramanyam, Lokanada; Prabhakar, Kodali Vidya; Bhaskar, Matcha

    2015-07-10

    Integrating cancer genes and markers with experimental evidence might provide valuable information for the further investigation of crosstalk between tumor genes and markers in cancer biology. To achieve this objective, we developed a database known as the Cancer Gene Marker Database (CGMD), which integrates data on tumor genes and markers based on experimental evidence. The major goal of CGMD is to provide the following: 1) current systematic treatment approaches and recent advances in different cancer treatments; 2) the aggregation of different genes and markers by their molecular characteristics and pathway associations; and 3) free access to the data compiled by CGMD at http://cgmd.in/. The database consists of 309 genes and 206 markers, as well as a list of 40 different human cancers, with detailed descriptions of all characterized markers. CGMD provides complete cancer annotations and molecular descriptions of cancer genes and markers such as CpG islands, promoters, exons, PDB structures, active sites and domains.

  8. CGMD: An integrated database of cancer genes and markers

    PubMed Central

    Pradeepkiran, Jangampalli Adi; Sainath, Sri Bhashyam; Kramthi Kumar, Konidala; Balasubramanyam, Lokanada; Vidya Prabhakar, Kodali; Bhaskar, Matcha

    2015-01-01

    Integrating cancer genes and markers with experimental evidence might provide valuable information for the further investigation of crosstalk between tumor genes and markers in cancer biology. To achieve this objective, we developed a database known as the Cancer Gene Marker Database (CGMD), which integrates data on tumor genes and markers based on experimental evidence. The major goal of CGMD is to provide the following: 1) current systematic treatment approaches and recent advances in different cancer treatments; 2) the aggregation of different genes and markers by their molecular characteristics and pathway associations; and 3) free access to the data compiled by CGMD at http://cgmd.in/. The database consists of 309 genes and 206 markers, as well as a list of 40 different human cancers, with detailed descriptions of all characterized markers. CGMD provides complete cancer annotations and molecular descriptions of cancer genes and markers such as CpG islands, promoters, exons, PDB structures, active sites and domains. PMID:26160459

  9. Strapping for temporomandibular joint dysfunction.

    PubMed

    Babu, Abraham Samuel; John, Sandhya Mary; Unni, Amith

    2008-01-01

    Temporomandibular joint dysfunction (TMJD) is a common problem seen in many of the dental clinics. Management of this depends on an accurate diagnosis of the cause for the TMJD. Physical therapy and rehabilitation play a vital role in the management of these dysfunctions. Physical therapy is useful in treating post-traumatic stiffness of the TMJ while strapping of the TMJ for a dysfunction along with conventional physical therapy is of benefit in terms of reduction in click, decrease in pain, and an improvement in function.

  10. Sacroiliac joint dysfunction in athletes.

    PubMed

    Brolinson, P Gunnar; Kozar, Albert J; Cibor, Greg

    2003-02-01

    The sacroiliac (SI) joint is a common source of low back pain in the general population. Because it is the link between the lower extremities and the spine, it sustains even higher loads during athletic activity, predisposing athletes to a greater probability of joint dysfunction and pain. The diagnosis and treatment of SI joint dysfunction remains controversial, due to complex anatomy and biomechanics, and a lack of universally accepted nomenclature and terminology, consistently reliable clinical tests and imaging studies, and consistently effective treatments. This article clarifies these issues by presenting a model of SI joint anatomy and function, a systematic approach to the diagnosis of dysfunction, and a comprehensive treatment plan.

  11. Dysfunction of brain pericytes in chronic neuroinflammation.

    PubMed

    Persidsky, Yuri; Hill, Jeremy; Zhang, Ming; Dykstra, Holly; Winfield, Malika; Reichenbach, Nancy L; Potula, Raghava; Mukherjee, Abir; Ramirez, Servio H; Rom, Slava

    2016-04-01

    Brain pericytes are uniquely positioned within the neurovascular unit to provide support to blood brain barrier (BBB) maintenance. Neurologic conditions, such as HIV-1-associated neurocognitive disorder, are associated with BBB compromise due to chronic inflammation. Little is known about pericyte dysfunction during HIV-1 infection. We found decreased expression of pericyte markers in human brains from HIV-1-infected patients (even those on antiretroviral therapy). Using primary human brain pericytes, we assessed expression of pericyte markers (α1-integrin, α-smooth muscle actin, platelet-derived growth factor-B receptor β, CX-43) and found their downregulation after treatment with tumor necrosis factor-α (TNFα) or interleukin-1 β (IL-1β). Pericyte exposure to virus or cytokines resulted in decreased secretion of factors promoting BBB formation (angiopoietin-1, transforming growth factor-β1) and mRNA for basement membrane components. TNFα and IL-1β enhanced expression of adhesion molecules in pericytes paralleling increased monocyte adhesion to pericytes. Monocyte migration across BBB models composed of human brain endothelial cells and pericytes demonstrated a diminished rate in baseline migration compared to constructs composed only of brain endothelial cells. However, exposure to the relevant chemokine, CCL2, enhanced the magnitude of monocyte migration when compared to BBB models composed of brain endothelial cells only. These data suggest an important role of pericytes in BBB regulation in neuroinflammation.

  12. Genetic markers as instrumental variables

    PubMed Central

    von Hinke, Stephanie; Davey Smith, George; Lawlor, Debbie A.; Propper, Carol; Windmeijer, Frank

    2016-01-01

    The use of genetic markers as instrumental variables (IV) is receiving increasing attention from economists, statisticians, epidemiologists and social scientists. Although IV is commonly used in economics, the appropriate conditions for the use of genetic variants as instruments have not been well defined. The increasing availability of biomedical data, however, makes understanding of these conditions crucial to the successful use of genotypes as instruments. We combine the econometric IV literature with that from genetic epidemiology, and discuss the biological conditions and IV assumptions within the statistical potential outcomes framework. We review this in the context of two illustrative applications. PMID:26614692

  13. The Dysfunctions of Bureaucratic Structure.

    ERIC Educational Resources Information Center

    Duttweiler, Patricia Cloud

    1988-01-01

    Numerous dysfunctions result from bureaucratic school organization, including an overemphasis on specialized tasks, routine operating rules, and formal procedures for managing teaching and learning. Such schools are characterized by numerous regulations; formal communications; centralized decision making; and sharp distinctions among…

  14. Nivolumab-induced thyroid dysfunction.

    PubMed

    Tanaka, Ryota; Fujisawa, Yasuhiro; Maruyama, Hiroshi; Nakamura, Yasuhiro; Yoshino, Koji; Ohtsuka, Mikio; Fujimoto, Manabu

    2016-06-01

    Nivolumab (ONO-4538) is an anti-programmed death-1 specific monoclonal antibody, which has become a standard treatment for metastatic malignant melanoma. Nivolumab induces autoimmune adverse events, defined as immune-related adverse events. Herein, we report a case of nivolumab-induced thyroid dysfunction in the clinical setting. Fourteen patients were treated with nivolumab at our institute, of which three developed thyroid dysfunction, an incidence higher than previously reported in the initial clinical trials. Interestingly, one patient achieved complete remission; suggesting that in some patients, the occurrence of immune-related adverse events, including thyroid dysfunction, might reflect the drug's antitumour efficacy. No patient died or discontinued nivolumab treatment owing to thyroid dysfunction. Although thyroid dysfunction first appeared to be asymptomatic, two of the three patients developed symptoms related to hypothyroidism soon after, requiring hormone replacement therapy. Another patient developed hyperthyroidism that was initially asymptomatic; the patient subsequently developed myalgia with fever >39.5°C after two additional courses of nivolumab. Treatment with nivolumab was therefore discontinued, and treatment with prednisolone was initiated. Symptoms resolved within a few days, and thyroid function normalized. Thyroid dysfunction is sometimes difficult to diagnose because its symptoms similar to those of many other diseases. In addition, thyroid-related immune-related adverse events may present with unique symptoms such as myalgia with high fever, abruptly worsening patients' quality of life. Consequently, thyroid dysfunction should be considered as a possible immune-related adverse event. Thus, it is important to test for thyroid dysfunction at baseline and before the administration of each nivolumab dose if possible.

  15. Obesity, inflammation and endothelial dysfunction.

    PubMed

    Iantorno, M; Campia, U; Di Daniele, N; Nistico, S; Forleo, G B; Cardillo, C; Tesauro, M

    2014-01-01

    Cardiovascular disease is the leading cause of morbidity and mortality in obese individuals. Obesity dramatically increases the risk of development of metabolic and cardiovascular disease. This risk appears to originate from disruption in adipose tissue function leading to a chronic inflammatory state and to dysregulation of the endocrine and paracrine actions of adipocyte-derived factors. These, in turn, impair vascular homeostasis and lead to endothelial dysfunction. An altered endothelial cell phenotype and endothelial dysfunction are common among all obesity-related complications. A crucial aspect of endothelial dysfunction is reduced nitric oxide (NO) bioavailability. A systemic pro-inflammatory state in combination with hyperglycemia, insulin resistance, oxidative stress and activation of the renin angiotensin system are systemic disturbances in obese individuals that contribute independently and synergistically to decreasing NO bioavailability. On the other hand, pro-inflammatory cytokines are locally produced by perivascular fat and act through a paracrine mechanism to independently contribute to endothelial dysfunction and smooth muscle cell dysfunction and to the pathogenesis of vascular disease in obese individuals. The promising discovery that obesity-induced vascular dysfunction is, at least in part, reversible, with weight loss strategies and drugs that promote vascular health, has not been sufficiently proved to prevent the cardiovascular complication of obesity on a large scale. In this review we discuss the pathophysiological mechanisms underlying inflammation and vascular damage in obese patients.

  16. Monitoring of the Immune Dysfunction in Cancer Patients.

    PubMed

    Santegoets, Saskia J A M; Welters, Marij J P; van der Burg, Sjoerd H

    2016-09-02

    Immunotherapy shows promising clinical results in patients with different types of cancer, but its full potential is not reached due to immune dysfunction as a result of several suppressive mechanisms that play a role in cancer development and progression. Monitoring of immune dysfunction is a prerequisite for the development of strategies aiming to alleviate cancer-induced immune suppression. At this point, the level at which immune dysfunction occurs has to be established, the underlying mechanism(s) need to be known, as well as the techniques to assess this. While it is relatively easy to measure general signs of immune suppression, it turns out that accurate monitoring of the frequency and function of immune-suppressive cells is still difficult. A lack of truly specific markers, the phenotypic complexity among suppressive cells of the same lineage, but potentially with different functions and functional assays that may not cover every mechanistic aspect of immune suppression are among the reasons complicating proper assessments. Technical innovations in flow and mass cytometry will allow for more complete sets of markers to precisely determine phenotype and associated function. There is, however, a clear need for functional assays that recapitulate more of the mechanisms employed to suppress the immune system.

  17. Monitoring of the Immune Dysfunction in Cancer Patients

    PubMed Central

    Santegoets, Saskia J. A. M.; Welters, Marij J. P.; van der Burg, Sjoerd H.

    2016-01-01

    Immunotherapy shows promising clinical results in patients with different types of cancer, but its full potential is not reached due to immune dysfunction as a result of several suppressive mechanisms that play a role in cancer development and progression. Monitoring of immune dysfunction is a prerequisite for the development of strategies aiming to alleviate cancer-induced immune suppression. At this point, the level at which immune dysfunction occurs has to be established, the underlying mechanism(s) need to be known, as well as the techniques to assess this. While it is relatively easy to measure general signs of immune suppression, it turns out that accurate monitoring of the frequency and function of immune-suppressive cells is still difficult. A lack of truly specific markers, the phenotypic complexity among suppressive cells of the same lineage, but potentially with different functions and functional assays that may not cover every mechanistic aspect of immune suppression are among the reasons complicating proper assessments. Technical innovations in flow and mass cytometry will allow for more complete sets of markers to precisely determine phenotype and associated function. There is, however, a clear need for functional assays that recapitulate more of the mechanisms employed to suppress the immune system. PMID:27598210

  18. Endothelial dysfunction in morbid obesity.

    PubMed

    Mauricio, Maria Dolores; Aldasoro, Martin; Ortega, Joaquin; Vila, José María

    2013-01-01

    Morbid obesity is a chronic multifunctional disease characterized by an accumulation of fat. Epidemiological studies have shown that obesity is associated with cardiovascular and metabolic disorders. Endothelial dysfunction, as defined by an imbalance between relaxing and contractile endothelial factors, plays a central role in the pathogenesis of these cardiometabolic diseases. Diminished bioavailability of nitric oxide (NO) contributes to endothelial dysfunction and impairs endothelium- dependent vasodilatation. But this is not the only mechanism that drives to endothelial dysfunction. Obesity has been associated with a chronic inflammatory process, atherosclerosis, and oxidative stress. Moreover levels of asymmetrical dimethyl-L-arginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (eNOS), are elevated in obesity. On the other hand, increasing prostanoid-dependent vasoconstriction and decreasing vasodilator prostanoids also lead to endothelial dysfunction in obesity. Other mechanisms related to endothelin-1 (ET-1) or endothelium derived hyperpolarizing factor (EDHF) have been proposed. Bariatric surgery (BS) is a safe and effective means to achieve significant weight loss, but its use is limited only to patients with severe obesity including morbid obesity. BS also proved efficient in endothelial dysfunction reduction improving cardiovascular and metabolic comorbidities associated with morbid obesity such as diabetes, coronary artery disease, nonalcoholic fatty liver disease and cancer. This review will provide a brief overview of the mechanisms that link obesity with endothelial dysfunction, and how weight loss is a cornerstone treatment for cardiovascular comorbidities obesity-related. A better understanding of the mechanisms of obesity-induced endothelial dysfunction may help develop new therapeutic strategies to reduce cardiovascular morbidity and mortality.

  19. Laryngeal Dysfunction: Assessment and Management for the Clinician.

    PubMed

    Hull, James H; Backer, Vibeke; Gibson, Peter G; Fowler, Stephen J

    2016-11-01

    The larynx is one of the most highly innervated organs in humans and serves a number of vitally important, complex, and highly evolved biological functions. On a day-to-day basis, the larynx functions autonomously, addressing several roles including airway protection, swallowing, and phonation. In some situations the larynx appears to adopt a functional state that could be considered maladaptive or "dysfunctional." This laryngeal dysfunction can underpin and account for a number of respiratory symptoms that otherwise appear incongruous with a clinical disease state and/or contribute to the development of symptoms that appear "refractory" to treatment. These include conditions associated with a heightened tendency for inappropriate laryngeal closure (e.g., inducible laryngeal obstruction), voice disturbance, and chronic cough. Recognition of laryngeal dysfunction is important to deliver targeted treatment and failure to recognize the condition can lead to repeated use of inappropriate treatment. Diagnosis is not straightforward, however, and many patients appear to present with symptoms attributable to laryngeal dysfunction, but in whom the diagnosis has been overlooked in clinical work-up for some time. This review provides an overview of the current state of knowledge in the field of laryngeal dysfunction, with a focus on pragmatic clinical assessment and management.

  20. [Female sexual dysfunction].

    PubMed

    Bitzer, Johannes; Alder, Judith

    2010-03-01

    Sexual medicine has become an integrated part of womens' health care. Physicians need therefore communication skills to talk about sexuality with their female patients and a knowledge about models of human sexuality, about classification systems, and diagnostic and therapeutic concepts and processes. The diagnostic reaches from a clear description of the sexual problem to an exploration of the conditioning factors. These can be differentiated into biological factors, intraindividual and interpersonal psychological factors and sociocultural factors. These factors can become effective as predisposing, precipitating and maintaining factors. The therapeutic process is based on several steps. The basic step consists in psychoeducation and basic counselling. Therapy usually includes the combination of pharmacologic intervention (hormones, PDE5) and specific psychotherapeutic techniques (sensate focus, cognitive techniques, couple counselling).

  1. Endothelial Dysfunction and Inflammation: Immunity in Rheumatoid Arthritis

    PubMed Central

    Yang, XueZhi; Chang, Yan; Wei, Wei

    2016-01-01

    Inflammation, as a feature of rheumatoid arthritis (RA), leads to the activation of endothelial cells (ECs). Activated ECs induce atherosclerosis through an increased expression of leukocyte adhesion molecules. Endothelial dysfunction (ED) is recognized as a failure of endothelial repair mechanisms. It is also an early preclinical marker of atherosclerosis and is commonly found in RA patients. RA is now established as an independent cardiovascular risk factor, while mechanistic determinants of ED in RA are still poorly understood. An expanding body of study has shown that EC at a site of RA is both active participant and regulator of inflammatory process. Over the last decade, a role for endothelial dysfunction in RA associated with cardiovascular disease (CVD) has been hypothesized. At the same time, several maintenance drugs targeting this phenomenon have been tested, which has promising results. Assessment of endothelial function may be a useful tool to identify and monitor RA patients. PMID:27122657

  2. Biomarkers of endothelial activation/dysfunction in infectious diseases

    PubMed Central

    Page, Andrea V; Liles, W Conrad

    2013-01-01

    Endothelial dysfunction contributes to the pathogenesis of a variety of potentially serious infectious diseases and syndromes, including sepsis and septic shock, hemolytic-uremic syndrome, severe malaria, and dengue hemorrhagic fever. Because endothelial activation often precedes overt endothelial dysfunction, biomarkers of the activated endothelium in serum and/or plasma may be detectable before classically recognized markers of disease, and therefore, may be clinically useful as biomarkers of disease severity or prognosis in systemic infectious diseases. In this review, the current status of mediators of endothelial cell function (angiopoietins-1 and -2), components of the coagulation pathway (von Willebrand Factor, ADAMTS13, and thrombomodulin), soluble cell-surface adhesion molecules (soluble E-selectin, sICAM-1, and sVCAM-1), and regulators of vascular tone and permeability (VEGF and sFlt-1) as biomarkers in severe infectious diseases is discussed in the context of sepsis, E. coli O157:H7 infection, malaria, and dengue virus infection. PMID:23669075

  3. Sumoylation in Synaptic Function and Dysfunction.

    PubMed

    Schorova, Lenka; Martin, Stéphane

    2016-01-01

    Sumoylation has recently emerged as a key post-translational modification involved in many, if not all, biological processes. Small Ubiquitin-like Modifier (SUMO) polypeptides are covalently attached to specific lysine residues of target proteins through a dedicated enzymatic pathway. Disruption of the SUMO enzymatic pathway in the developing brain leads to lethality indicating that this process exerts a central role during embryonic and post-natal development. However, little is still known regarding how this highly dynamic protein modification is regulated in the mammalian brain despite an increasing number of data implicating sumoylated substrates in synapse formation, synaptic communication and plasticity. The aim of this review is therefore to briefly describe the enzymatic SUMO pathway and to give an overview of our current knowledge on the function and dysfunction of protein sumoylation at the mammalian synapse.

  4. Sumoylation in Synaptic Function and Dysfunction

    PubMed Central

    Schorova, Lenka; Martin, Stéphane

    2016-01-01

    Sumoylation has recently emerged as a key post-translational modification involved in many, if not all, biological processes. Small Ubiquitin-like Modifier (SUMO) polypeptides are covalently attached to specific lysine residues of target proteins through a dedicated enzymatic pathway. Disruption of the SUMO enzymatic pathway in the developing brain leads to lethality indicating that this process exerts a central role during embryonic and post-natal development. However, little is still known regarding how this highly dynamic protein modification is regulated in the mammalian brain despite an increasing number of data implicating sumoylated substrates in synapse formation, synaptic communication and plasticity. The aim of this review is therefore to briefly describe the enzymatic SUMO pathway and to give an overview of our current knowledge on the function and dysfunction of protein sumoylation at the mammalian synapse. PMID:27199730

  5. Platelets: A possible glance into brain biological processes in schizophrenia

    PubMed Central

    Asor, Eyal; Ben-Shachar, Dorit

    2012-01-01

    Schizophrenia is a severe mental disorder, characterized by behavioral, emotional and cognitive disturbances, which commonly follows a chronic course. Diagnostic accuracy, management plans, treatment evaluation and prognosis are dependent on relatively subjective assessments. Despite extensive research and improvement in imaging technology, as well as modern genetic and molecular methodologies, the biological basis of this disease is still unclear. Therefore, there is a need for objective and valid biological markers. Platelets have often been used as a model in neurobiological research. The accessibility of platelets and their similarities with neurons turns them into an attractive candidate to search for biological markers for diagnosis and for unraveling pathophysiological processes relevant to the etiology of brain disorders, including schizophrenia. The present review addresses the main changes in platelet physiology observed in schizophrenia and its response to antipsychotic medication. We summarize numerous studies demonstrating impaired metabolism, uptake and receptor kinetics of schizophrenia-relevant neurotransmitters, abnormalities in membrane derived phospholipids and polyunsaturated fatty acids, as well as dysfunctions in the mitochondria. These changes fit with the various hypotheses raised for the etiology of schizophrenia, including the dopamine-glutamate hypothesis, the autoimmune hypothesis, the polyunsaturated fatty acid hypothesis and the impaired energy metabolism hypothesis. Despite extensive research in platelets, no conclusive reliable biomarker has been identified yet. This review suggests that the clinical heterogeneity and the biological complexity of schizophrenia lead to the inevitable conclusion that biomarkers will be identified only for subgroups characterized according to the different diagnostic criteria. Moreover, any biomarker would have to be an array of interrelated factors or even a set of several such arrays. PMID:24175178

  6. Mitochondrial dysfunction in migraine.

    PubMed

    Yorns, William R; Hardison, H Huntley

    2013-09-01

    Migraine is the most frequent type of headache in children. In the 1980s, scientists first hypothesized a connection between migraine and mitochondrial (mt) disorders. More recent studies have suggested that at least some subtypes of migraine may be related to a mt defect. Different types of evidence support a relationship between mitochondria (mt) and migraine: (1) Biochemical evidence: Abnormal mt function translates into high intracellular penetration of Ca(2+), excessive production of free radicals, and deficient oxidative phosphorylation, which ultimately causes energy failure in neurons and astrocytes, thus triggering migraine mechanisms, including spreading depression. The mt markers of these events are low activity of superoxide dismutase, activation of cytochrome-c oxidase and nitric oxide, high levels of lactate and pyruvate, and low ratios of phosphocreatine-inorganic phosphate and N-acetylaspartate-choline. (2) Morphologic evidence: mt abnormalities have been shown in migraine sufferers, the most characteristic ones being direct observation in muscle biopsy of ragged red and cytochrome-c oxidase-negative fibers, accumulation of subsarcolemmal mt, and demonstration of giant mt with paracrystalline inclusions. (3) Genetic evidence: Recent studies have identified specific mutations responsible for migraine susceptibility. However, the investigation of the mtDNA mutations found in classic mt disorders (mt encephalomyopathy with lactic acidosis and stroke-like episodes, myoclonus epilepsy with ragged red fibers, Kearns-Sayre syndrome, and Leber hereditary optic neuropathy) has not demonstrated any association. Recently, 2 common mtDNA polymorphisms (16519C→T and 3010G→A) have been associated with pediatric cyclic vomiting syndrome and migraine. Also, POLG mutations (eg, p.T851 A, p.N468D, p.Y831C, p.G517V, and p.P163S) can cause disease through impaired replication of mtDNA, including migraine. Further studies to investigate the relationship between mt

  7. Obesity and pelvic floor dysfunction.

    PubMed

    Ramalingam, Kalaivani; Monga, Ash

    2015-05-01

    Obesity is associated with a high prevalence of pelvic floor disorders. Patients with obesity present with a range of urinary, bowel and sexual dysfunction problems as well as uterovaginal prolapse. Urinary incontinence, faecal incontinence and sexual dysfunction are more prevalent in patients with obesity. Uterovaginal prolapse is also more common than in the non-obese population. Weight loss by surgical and non-surgical methods plays a major role in the improvement of these symptoms in such patients. The treatment of symptoms leads to an improvement in their quality of life. However, surgical treatment of these symptoms may be accompanied by an increased risk of complications in obese patients. A better understanding of the mechanism of obesity-associated pelvic floor dysfunction is essential.

  8. [Sexual dysfunctions in selected endocrinopathies].

    PubMed

    Skrzypulec, Violetta; Nowosielski, Krzysztof; Drosdzol, Agnieszka; Kowalaczyk, Robert

    2005-01-01

    According to the socio-sexological reports approximately 40-45% of women and up to 30% of males may suffer from different sexual dysfunctions. The prevalence of those disorders is gradually increasing with age. Multiply numbers of endocrinopathies may influence the human sexual life. In diabetic patients all phases of the sexual responses cycle, especially orgasm, might be affected. Women diagnosed with PCOS have decreased adaptation to the sexual life, low self-esteem and perception of self sexual attractiveness. The intimacy of infertile couples has not been well described and the characteristic of particular dysfunction in sex life has not been established yet. Interdisciplinary approach, understood as treatment of the endocrinopathy accompanied with psychological and sexological counseling, seems to be the fundamental issue in the therapy of sexual dysfunctions in patients with endocrinological disorders.

  9. Mitochondrial Dysfunction in Cardiac Ageing

    PubMed Central

    Tocchi, Autumn; Quarles, Ellen K.; Basisty, Nathan; Gitari, Lemuel; Rabinovitch, Peter S.

    2015-01-01

    Cardiovascular diseases are the leading cause of death in most developed nations. While it has received the least public attention, aging is the dominant risk factor for developing cardiovascular diseases, as the prevalence of cardiovascular diseases increases dramatically with increasing age. Cardiac aging is an intrinsic process that results in impaired cardiac function, along with cellular and molecular changes. Mitochondria play a great role in these processes, as cardiac function is an energetically demanding process. In this review, we examine mitochondrial dysfunction in cardiac aging. Recent research has demonstrated that mitochondrial dysfunction can disrupt morphology, signaling pathways, and protein interactions; conversely, mitochondrial homeostasis is maintained by mechanisms that include fission/fusion, autophagy, and unfolded protein responses. Finally, we describe some of the recent findings in mitochondrial targeted treatments to help meet the challenges of mitochondrial dysfunction in aging. PMID:26191650

  10. Metabolic profiles of biological aging in American Indians: the Strong Heart Family Study.

    PubMed

    Zhao, Jinying; Zhu, Yun; Uppal, Karan; Tran, ViLinh T; Yu, Tianwei; Lin, Jue; Matsuguchi, Tet; Blackburn, Elizabeth; Jones, Dean; Lee, Elisa T; Howard, Barbara V

    2014-03-01

    Short telomere length, a marker of biological aging, has been associated with age-related metabolic disorders. Telomere attrition induces profound metabolic dysfunction in animal models, but no study has examined the metabolome of telomeric aging in human. Here we studied 423 apparently healthy American Indians participating in the Strong Family Heart Study. Leukocyte telomere length (LTL) was measured by qPCR. Metabolites in fasting plasma were detected by untargeted LC/MS. Associations of LTL with each metabolite and their combined effects were examined using generalized estimating equation adjusting for chronological age and other aging-related factors. Multiple testing was corrected using the q-value method (q<0.05). Of the 1,364 distinct m/z features detected, nineteen metabolites in the classes of glycerophosphoethanolamines, glycerophosphocholines, glycerolipids, bile acids, isoprenoids, fatty amides, or L-carnitine ester were significantly associated with LTL, independent of chronological age and other aging-related factors. Participants with longer (top tertile) and shorter (bottom tertile) LTL were clearly separated into distinct groups using a multi-marker score comprising of all these metabolites, suggesting that these newly detected metabolites could be novel metabolic markers of biological aging. This is the first study to interrogate the human metabolome of telomeric aging. Our results provide initial evidence for a metabolic control of LTL and may reveal previously undescribed new roles of various lipids in the aging process.

  11. Molecular basis of telomere dysfunction in human genetic diseases.

    PubMed

    Sarek, Grzegorz; Marzec, Paulina; Margalef, Pol; Boulton, Simon J

    2015-11-01

    Mutations in genes encoding proteins required for telomere structure, replication, repair and length maintenance are associated with several debilitating human genetic disorders. These complex telomere biology disorders (TBDs) give rise to critically short telomeres that affect the homeostasis of multiple organs. Furthermore, genome instability is often a hallmark of telomere syndromes, which are associated with increased cancer risk. Here, we summarize the molecular causes and cellular consequences of disease-causing mutations associated with telomere dysfunction.

  12. Autonomic Dysfunctions in Parkinsonian Disorders

    PubMed Central

    Bae, Hyo-Jin; Cheon, Sang-Myung; Kim, Jae Woo

    2009-01-01

    Background and Purpose: Symptoms of autonomic dysfunctions are common in the patients with parkinsonian disorders. Because clinical features of autonomic dysfunctions are diverse, the comprehensive evaluation is essential for the appropriate management. For the appreciation of autonomic dysfunctions and the identification of differences, patients with degenerative parkinsonisms are evaluated using structured questionnaire for autonomic dysfunction (ADQ). Methods: Total 259 patients, including 192 patients with [idiopathic Parkinson’s disease (IPD, age 64.6 ± 9.6 years)], 37 with [multiple system atrophy (MSA, 62.8 ± 9.1)], 9 with [dementia with Lewy body (DLB, 73.9 ± 4.3)], and 21 with [progressive supranuclear palsy (PSP, 69.4 ± 9.6)]. The ADQ was structured for evaluation of the presence of symptoms and its severity due to autonomic dysfunction, covering gastrointestinal, urinary, sexual, cardiovascular and thermoregulatory domains. Patients were also evaluated for the orthostatic hypotension. Results: Although dementia with Lewy body (DLB) patients were oldest and duration of disease was longest in IPD, total ADQ scores of MSA and PSP (23.9 ± 12.6 and 21.1 ± 7.8) were significantly increased than that of IPD (15.1 ± 10.6). Urinary and cardiovascular symptom scores of MSA and gastrointestinal symptom score of PSP were significantly worse than those of IPD. The ratio of patient with orthostatic hypotension in IPD was 31.2% and not differed between groups (35.1% in MSA, 33.3% in DLB and 33.3% in PSP). But the systolic blood pressure dropped drastically after standing in patients with MSA and DLB than in patients with IPD and PSP. Conclusions: Patients with degenerative parkinsonism showed widespread symptoms of autonomic dysfunctions. The severity of those symptoms in patients with PSP were comparing to that of MSA patients and worse than that of IPD. PMID:24868361

  13. Ligophorus species (Monogenea: Ancyrocephalidae) from Mugil cephalus (Teleostei: Mugilidae) off Morocco with the description of a new species and remarks about the use of Ligophorus spp. as biological markers of host populations.

    PubMed

    El Hafidi, Fouzia; Rkhami, Ouafae Berrada; de Buron, Isaure; Durand, Jean-Dominique; Pariselle, Antoine

    2013-11-01

    Gill monogenean species of Ligophorus Euzet et Suriano, 1977 were studied from the teleost Mugil cephalus Linneaus (Mugilidae) from the Mediterranean and Atlantic coasts of Morocco. We report the presence of L. mediterraneus from both the Mediterranean and Atlantic coast and L. cephali and L. maroccanus sp. n. from the Atlantic coast only. The latter species, which is described herein as new, resembles L. guanduensis but differs from this species mainly in having a shorter penis compared to the accessory piece, a proportionally longer extremity of the accessory piece and a less developed heel. The utility of Ligophorus spp. as markers of cryptic species of the complex M. cephalus is discussed in the context of species diversity and geographical distribution of these monogeneans on this host around the world. Presence of different species of Ligophorus on M. cephalus sensu stricto from the Atlantic and Mediterranean coast of Morocco demonstrates the usefulness of these species as fine resolution markers of genetic populations of their host, which are known to inhabit those coasts.

  14. Strain-specific SCAR markers for the detection of Trichoderma harzianum AS12-2, a biological control agent against Rhizoctonia solani, the causal agent of rice sheath blight.

    PubMed

    Naeimi, S; Kocsubé, S; Antal, Zsuzsanna; Okhovvat, S M; Javan-Nikkhah, M; Vágvölgyi, C; Kredics, L

    2011-03-01

    In order to identify a specific marker for T. harzianum AS12-2, a strain capable of controlling rice sheath blight caused by Rhizoctonia solani, UP-PCR was performed using five universal primers (UP) both separately and in pairwise combinations. The application of two UP primers resulted in the amplification of unique fragments from the genomic DNA of T. harzianum AS12-2, clearly distinguishing it from other Trichoderma strains. The unique fragments had no significant sequence homology with any other known sequence available in databases. Based on the sequences of the unique fragments, 14 oligonucleotide primers were designed. Two primer sets amplified a fragment of expected size from the DNA of strain T. harzianum AS12-2 but not from any other examined strains belonging to T. harzianum, to other Trichoderma species assayed, or to other common fungi present in paddy fields of Mazandaran province, Iran. In conclusion, SCAR (sequence characterized amplified regions) markers were successfully identified and rapid, reliable tools were provided for the detection of an effective biocontrol Trichoderma strain, which can facilitate studies of its population dynamics and establishment after release into the natural environment.

  15. Herbs and spices: characterization and quantitation of biologically-active markers for routine quality control by multiple headspace solid-phase microextraction combined with separative or non-separative analysis.

    PubMed

    Sgorbini, Barbara; Bicchi, Carlo; Cagliero, Cecilia; Cordero, Chiara; Liberto, Erica; Rubiolo, Patrizia

    2015-01-09

    Herbs and spices are used worldwide as food flavoring, thus determination of their identity, origin, and quality is mandatory for safe human consumption. An analysis strategy based on separative (HS-SPME-GC-MS) and non-separative (HS-SPME-MS) approaches is proposed for the volatile fraction of herbs and spices, for quality control and to quantify the aromatic markers with a single analysis directly on the plant material as such. Eight-to-ten lots of each of the following herbs/spices were considered: cloves (Syzygium aromaticum (L.) Merr. & Perry), American peppertree (Schinus molle L.), black pepper and white pepper (Piper nigrum L.), rosemary (Rosmarinus officinalis L.), sage (Salvia officinalis L.) and thyme (Thymus vulgaris L.). Homogeneity, origin, and chemotypes of the investigated lots of each herb/spice were defined by fingerprinting, through statistical elaboration with principal component analysis (PCA). Characterizing aromatic markers were directly quantified on the solid matrix through multiple headspace extraction-HS-SPME (MHS-SPME). Reliable results were obtained with both separative and non-separative methods (where the latter were applicable); the two were in full agreement, RSD% ranging from 1.8 to 7.7% for eugenol in cloves, 2.2-18.4% for carvacrol+thymol in thyme, and 3.1-16.8% for thujones in sage.

  16. Novel diagnostics of metabolic dysfunction detected in breath and plasma by selective isotope-assisted labeling.

    PubMed

    Haviland, Julia A; Tonelli, Marco; Haughey, Dermot T; Porter, Warren P; Assadi-Porter, Fariba M

    2012-08-01

    Metabolomics is the study of a unique fingerprint of small molecules present in biological systems under healthy and disease conditions. One of the major challenges in metabolomics is validation of fingerprint molecules to identify specifically perturbed pathways in metabolic aberrations. This step is crucial to the understanding of budding metabolic pathologies and the ability to identify early indicators of common diseases such as obesity, type 2 diabetes mellitus, metabolic syndrome, polycystic ovary syndrome, and cancer. We present a novel approach to diagnosing aberrations in glucose utilization including metabolic pathway switching in a disease state. We used a well-defined prenatally exposed glucocorticoid mouse model that results in adult females with metabolic dysfunction. We applied the complementary technologies of nuclear magnetic resonance spectroscopy and cavity ring-down spectroscopy to analyze serial plasma samples and real-time breath measurements following selective (13)C-isotope-assisted labeling. These platforms allowed us to trace metabolic markers in whole animals and identify key metabolic pathway switching in prenatally glucocorticoid-treated animals. Total glucose flux is significantly proportionally increased through the major oxidative pathways of glycolysis and the pentose phosphate pathway in the prenatally glucocorticoid-treated animals relative to the control animals. This novel diagnostics approach is fast, noninvasive, and sensitive for determining specific pathway utilization, and provides a direct translational application in the health care field.

  17. Noninvasive Staging of Kidney Dysfunction Enabled by Renal Clearable Luminescent Gold Nanoparticles

    PubMed Central

    Yu, Mengxiao; Zhou, Jiancheng; Du, Bujie; Ning, Xuhui; Authement, Craig; Gandee, Leah; Kapur, Payal; Hsieh, Jer-Tsong; Zheng, Jie

    2016-01-01

    As a “silent killer”, kidney disease is often hardly detected at its early stage but can cause the lethal kidney failure in its late stage. Thus, a preclinical imaging technique that can readily differentiate the stages of kidney dysfunction is highly desired for fundamental understanding of kidney disease progression. Herein, we reported that in vivo fluorescence imaging, enabled by renal clearable near infrared-emitting gold nanoparticles, can noninvasively detect kidney dysfunction, report the dysfunctional stages and even reveal adaptive function in mouse model of unilateral obstructive nephropathy that cannot be diagnosed with routine kidney function markers. These results demonstrated that low-cost florescence kidney functional imaging is highly sensitive for longitudinal, noninvasive monitoring of kidney dysfunction progression in the preclinical research. PMID:26800513

  18. Noninvasive Staging of Kidney Dysfunction Enabled by Renal-Clearable Luminescent Gold Nanoparticles.

    PubMed

    Yu, Mengxiao; Zhou, Jiancheng; Du, Bujie; Ning, Xuhui; Authement, Craig; Gandee, Leah; Kapur, Payal; Hsieh, Jer-Tsong; Zheng, Jie

    2016-02-18

    As a "silent killer", kidney disease is often hardly detected at an early stage but can cause lethal kidney failure later on. Thus, a preclinical imaging technique that can readily differentiate between the stages of kidney dysfunction is highly desired for improving our fundamental understanding of kidney disease progression. Herein, we report that in vivo fluorescence imaging, enabled by renal-clearable near-infrared-emitting gold nanoparticles, can noninvasively detect kidney dysfunction, report on the dysfunctional stages, and even reveal adaptive function in a mouse model of unilateral obstructive nephropathy, which cannot be diagnosed with routine kidney function markers. These results demonstrate that low-cost fluorescence kidney functional imaging is highly sensitive and useful for the longitudinal, noninvasive monitoring of kidney dysfunction progression in preclinical research.

  19. Novel Identity and Functional Markers for Human Corneal Endothelial Cells

    PubMed Central

    Bartakova, Alena; Alvarez-Delfin, Karen; Weisman, Alejandra D.; Salero, Enrique; Raffa, Gabriella A.; Merkhofer, Richard M.; Kunzevitzky, Noelia J.; Goldberg, Jeffrey L.

    2016-01-01

    Purpose Human corneal endothelial cell (HCEC) density decreases with age, surgical complications, or disease, leading to vision impairment. Such endothelial dysfunction is an indication for corneal transplantation, although there is a worldwide shortage of transplant-grade tissue. To overcome the current poor donor availability, here we isolate, expand, and characterize HCECs in vitro as a step toward cell therapy. Methods Human corneal endothelial cells were isolated from cadaveric corneas and expanded in vitro. Cell identity was evaluated based on morphology and immunocytochemistry, and gene expression analysis and flow cytometry were used to identify novel HCEC-specific markers. The functional ability of HCEC to form barriers was assessed by transendothelial electrical resistance (TEER) assays. Results Cultured HCECs demonstrated canonical morphology for up to four passages and later underwent endothelial-to-mesenchymal transition (EnMT). Quality of donor tissue influenced cell measures in culture including proliferation rate. Cultured HCECs expressed identity markers, and microarray analysis revealed novel endothelial-specific markers that were validated by flow cytometry. Finally, canonical HCECs expressed higher levels of CD56, which correlated with higher TEER than fibroblastic HCECs. Conclusions In vitro expansion of HCECs from cadaveric donor corneas yields functional cells identifiable by morphology and a panel of novel markers. Markers described correlated with function in culture, suggesting a basis for cell therapy for corneal endothelial dysfunction. PMID:27196322

  20. Fiducial marker for correlating images

    DOEpatents

    Miller, Lisa Marie; Smith, Randy J.; Warren, John B.; Elliott, Donald

    2011-06-21

    The invention relates to a fiducial marker having a marking grid that is used to correlate and view images produced by different imaging modalities or different imaging and viewing modalities. More specifically, the invention relates to the fiducial marking grid that has a grid pattern for producing either a viewing image and/or a first analytical image that can be overlaid with at least one other second analytical image in order to view a light path or to image different imaging modalities. Depending on the analysis, the grid pattern has a single layer of a certain thickness or at least two layers of certain thicknesses. In either case, the grid pattern is imageable by each imaging or viewing modality used in the analysis. Further, when viewing a light path, the light path of the analytical modality cannot be visualized by viewing modality (e.g., a light microscope objective). By correlating these images, the ability to analyze a thin sample that is, for example, biological in nature but yet contains trace metal ions is enhanced. Specifically, it is desired to analyze both the organic matter of the biological sample and the trace metal ions contained within the biological sample without adding or using extrinsic labels or stains.

  1. Sexual dysfunction in infertile women

    PubMed Central

    Zare, Zahra; Amirian, Malihe; Golmakani, Nahid; Mazlom, Reza; Laal Ahangar, Mojtaba

    2016-01-01

    Background: Sexual problems have different effects on the life of people by influencing their interpersonal and marital relationships and satisfaction. Relationship between sexual dysfunctions and infertility can be mutual. Sexual dysfunction may cause difficulty conceiving but also attempts to conceive, may cause sexual dysfunction. Objective: This paper compares sexual dysfunction in fertile and infertile women. Materials and Methods: In this cross-sectional study, 110 infertile couples referring to Montasarieh Infertility Clinic and 110 fertile couples referring to five healthcare centers in Mashhad were selected by class cluster sampling method. Data collection tools included demographic questionnaire and Glombok-Rust Inventory of Sexual Satisfaction. Data were analyzed through descriptive and analytical statistical methods by SPSS. Results: There was no significant difference in total score of sexual problems and other dimensions of sexual problems (except infrequency) in fertile 28.9 (15.5) and infertile 29.0 (15.4) women. Fertile women had more infrequency than infertile women (p=0.002). Conclusion: There was no significant difference between fertile and infertile women in terms of sexual problems. Paying attention to sexual aspects of infertility and presence of programs for training of sexual skills seems necessary for couples. PMID:27200422

  2. Assessing mitochondrial dysfunction in cells

    PubMed Central

    Brand, Martin D.; Nicholls, David G.

    2011-01-01

    Assessing mitochondrial dysfunction requires definition of the dysfunction to be investigated. Usually, it is the ability of the mitochondria to make ATP appropriately in response to energy demands. Where other functions are of interest, tailored solutions are required. Dysfunction can be assessed in isolated mitochondria, in cells or in vivo, with different balances between precise experimental control and physiological relevance. There are many methods to measure mitochondrial function and dysfunction in these systems. Generally, measurements of fluxes give more information about the ability to make ATP than do measurements of intermediates and potentials. For isolated mitochondria, the best assay is mitochondrial respiratory control: the increase in respiration rate in response to ADP. For intact cells, the best assay is the equivalent measurement of cell respiratory control, which reports the rate of ATP production, the proton leak rate, the coupling efficiency, the maximum respiratory rate, the respiratory control ratio and the spare respiratory capacity. Measurements of membrane potential provide useful additional information. Measurement of both respiration and potential during appropriate titrations enables the identification of the primary sites of effectors and the distribution of control, allowing deeper quantitative analyses. Many other measurements in current use can be more problematic, as discussed in the present review. PMID:21726199

  3. Pathophysiology of diabetic sexual dysfunction.

    PubMed

    Morano, S

    2003-01-01

    Sexual dysfunction is common in patients with diabetes mellitus. Vascular, neurological and hormonal alterations are involved in this complication. Many studies showed altered endothelium-dependent and neurogenic relaxations in corpus cavernosum from diabetic patients with erectile dysfunction (ED). This finding has been associated with a lack of nitric oxyde (NO) production and a significant increase in NO synthase (NOS) binding sites in penile tissues, induced by diabetes. Advanced glycation endproducts (AGEs) concur to diabetic vascular complications by quenching NO activity and by increasing the expression of mediators of vascular damage such as vascular endothelial growth factor (VEGF), possessing permeabilizing and neoangiogenic effects, and endothelin-1 (ET-1), with vaso-constricting and mitogenic action. Moreover, the differential gene expression for various growth factors in penile tissues may be involved in the pathophysiology of ED associated with diabetes. Neuropathy is also likely to be an important cause of diabetic ED: morphological alterations of autonomic nerve fibers in cavernosal tissue of patients with diabetic ED have been demonstrated. Finally, androgens enhance nNOS gene expression in the penile corpus cavernosum of rats, suggesting that they play a role in maintaining NOS activity. However, sexual dysfunctions in women with diabetes has received less attention in clinical research. Several studies suggest an increased prevalence of deficient vaginal lubrication, making sexual intercourse unpleasant. Sexual dysfunction is associated with lower overall quality of marital relation and more depressive symptoms in diabetic women.

  4. [Biomarkers of iron metabolism and inflammation in patients with chronic heart failure and various types of left ventricular dysfunction].

    PubMed

    Kazymyrko, V K; Kutovyĭ, V V; Ivanyts'ka, L M; Dubkova, A G; Silant'ieva, T S

    2013-09-01

    Study the level of some of the indicators of iron metabolism and inflammatory markers in patients with chronic heart failure due to hypertension and coronary heart disease. The results of the study in systolic and diastolic dysfunction of the left ventricle, the varying degrees of severity of heart failure. The level of the studied parameters determined by the severity of heart failure and does not depend on the nature of left ventricular dysfunction.

  5. Fiducial Marker Placement

    MedlinePlus

    ... Media Computed Tomography (CT) - Body General Ultrasound Ultrasound - Prostate Introduction to Cancer Therapy (Radiation Oncology) Proton Therapy Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiotherapy (SBRT) Images related to Fiducial Marker Placement Sponsored by ...

  6. Alcoholism: Current Marker Research

    DTIC Science & Technology

    1984-03-01

    genetically determined characteristics such as color blindness and blood type . GENETIC MARKER STUDIES In 1966 Dr. Cruz-Coke and Dr. Varela reported that...and recovery from severe alcoholism symptoms. ■󈧒:584-587) Blood - typing marker studies have produced similar mixed results. One study published in...1959 showed a high correlation among 939 alcoholics and blood type A. (20:4 60-4 61) A similar study in 1973 reported no blood type distribution

  7. Cellular glutathione peroxidase deficiency and endothelial dysfunction.

    PubMed

    Forgione, Marc A; Weiss, Norbert; Heydrick, Stanley; Cap, André; Klings, Elizabeth S; Bierl, Charlene; Eberhardt, Robert T; Farber, Harrison W; Loscalzo, Joseph

    2002-04-01

    Cellular glutathione peroxidase (GPx-1) is the most abundant intracellular isoform of the GPx antioxidant enzyme family. In this study, we hypothesized that GPx-1 deficiency directly induces an increase in vascular oxidant stress, with resulting endothelial dysfunction. We studied vascular function in a murine model of homozygous deficiency of GPx-1 (GPx-1(-/-)). Mesenteric arterioles of GPx-1(-/-) mice demonstrated paradoxical vasoconstriction to beta-methacholine and bradykinin, whereas wild-type (WT) mice showed dose-dependent vasodilation in response to both agonists. One week of treatment of GPx-1(-/-) mice with L-2-oxothiazolidine-4-carboxylic acid (OTC), which increases intracellular thiol pools, resulted in restoration of normal vascular reactivity in the mesenteric bed of GPx-1(-/-) mice. We observed an increase of the isoprostane iPF(2alpha)-III, a marker of oxidant stress, in the plasma and aortas of GPx-1(-/-) mice compared with WT mice, which returned toward normal after OTC treatment. Aortic sections from GPx-1(-/-) mice showed increased binding of an anti-3-nitrotyrosine antibody in the absence of frank vascular lesions. These findings demonstrate that homozygous deficiency of GPx-1 leads to impaired endothelium-dependent vasodilator function presumably due to a decrease in bioavailable nitric oxide and to increased vascular oxidant stress. These vascular abnormalities can be attenuated by increasing bioavailable intracellular thiol pools.

  8. [New approved markers of bone turnover for osteoporosis in Japan].

    PubMed

    Miki, Takami; Masaki, Hideki

    2012-06-01

    Various markers of bone turnover are already under clinical use in Japan, and mostly for clinical investigation in some countries. Standard values including ranges and variations are summarized in the previous edition of the guideline. The information of additional new markers adapted by government is summarized including clinical features in the new edition 2012. Among the new markers, the methods for measurement for TRACP-5b and ucOC are developed in Japan. As P1NP and TRACP-5b levels are not affected by meals, biological variations are smaller compared with other markers. ucOC is unique because it is to evaluate vitamin K insufficiency for bone. New bone markers adapted in the Japanese guideline 2012 will facilitate clinicians to utilize of metabolic markers of bone for osteoporosis treatment.

  9. Association between markers of emphysema and more severe chronic obstructive pulmonary disease

    PubMed Central

    Boschetto, P; Quintavalle, S; Zeni, E; Leprotti, S; Potena, A; Ballerin, L; Papi, A; Palladini, G; Luisetti, M; Annovazzi, L; Iadarola, P; De Rosa, E; Fabbri, L M; Mapp, C E

    2006-01-01

    Background The predominant emphysema phenotype is associated with more severe airflow limitation in patients with chronic obstructive pulmonary disease (COPD). A study was undertaken to investigate whether COPD patients, with or without emphysema quantitatively confirmed by high resolution computed tomography (HRCT), have different COPD severity as assessed by the BODE index (body mass index, airflow obstruction, dyspnoea, exercise performance) and inspiratory capacity to total lung capacity ratio (IC/TLC), and by different biological markers of lung parenchymal destruction. Methods Twenty six outpatients with COPD and eight healthy non‐smokers were examined. Each subject underwent HRCT scanning, pulmonary function tests, cell counts, and measurements of neutrophil elastase, matrix metalloproteinase (MMP)‐9 and tissue inhibitor of metalloproteinase (TIMP)‐1 in induced sputum, as well as measurement of desmosine, a marker of elastin degradation in urine, plasma and sputum. Results Patients with HRCT confirmed emphysema had a higher BODE index and lower IC/TLC ratio than subjects without HRCT confirmed emphysema and controls. Forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity ratio, and carbon monoxide transfer coefficient were lower, whereas the number of eosinophils, MMP‐9, and the MMP‐9/TIMP‐1 ratio in sputum were higher in patients with emphysema. In COPD patients the number of sputum eosinophils was the biological variable that correlated positively with the HRCT score of emphysema (p = 0.04). Conclusions These results suggest that COPD associated with HRCT confirmed emphysema is characterised by more severe lung function impairment, more intense airway inflammation and, possibly, more serious systemic dysfunction than COPD not associated with HRCT confirmed emphysema. PMID:16769715

  10. Dobzhansky-Muller model of hybrid dysfunction supported by poor burst-speed performance in hybrid tiger salamanders.

    PubMed

    Fitzpatrick, B M

    2008-01-01

    Speciation may result from 'complementary' genetic differences that cause dysfunction when brought together in hybrids despite having no deleterious effects within pure species genomes. The theory of complementary genes, independently proposed by Dobzhansky and Muller, yields specific predictions about the genetics of hybrid fitness. Here, I show how alternative models of hybrid dysfunction can be compared using a simple multivariate analysis of hybrid indices calculated from molecular markers. I use the approach to fit models of hybrid dysfunction to swimming performance in hybrid tiger salamander larvae. Poor burst-speed performance is a dysfunction suggesting low vigour and could translate directly into low survival. My analyses show that the Dobzhansky-Muller model fits these data better than heterozygote disadvantage. The approach demonstrated here can be applied to a broad array of nonmodel species, potentially leading to important generalizations about the genetics of hybrid dysfunction.

  11. Epigenetics and muscle dysfunction in chronic obstructive pulmonary disease.

    PubMed

    Barreiro, Esther; Gea, Joaquim

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable disease and a major leading cause of morbidity and mortality worldwide. In COPD, comorbidities, acute exacerbations, and systemic manifestations negatively influence disease severity and progression regardless of the respiratory condition. Skeletal muscle dysfunction, which is one of the commonest systemic manifestations in patients with COPD, has a tremendous impact on their exercise capacity and quality of life. Several pathophysiological and molecular underlying mechanisms including epigenetics (the process whereby gene expression is regulated by heritable mechanisms that do not affect DNA sequence) have been shown to participate in the etiology of COPD muscle dysfunction. The epigenetic modifications identified so far in cells include DNA methylation, histone acetylation and methylation, and noncoding RNAs such as microRNAs. Herein, we first review the role of epigenetic mechanisms in muscle development and adaptation to environmental factors in several models. Moreover, the epigenetic events reported so far to be potentially involved in muscle dysfunction and mass loss of patients with COPD are also discussed. Furthermore, the different expression profile of several muscle-enriched microRNAs in the diaphragm and vastus lateralis muscles of patients with COPD are also reviewed from results recently obtained in our group. The role of protein hyperacetylation in enhanced muscle protein catabolism of limb muscles is also discussed. Future research should focus on the full elucidation of the triggers of epigenetic mechanisms and their specific downstream biological pathways in COPD muscle dysfunction and wasting.

  12. [Mirror neuron system dysfunction in schizophrenia and its clinical implication].

    PubMed

    Kato, Motoichiro; Kato, Yutaka

    2014-06-01

    Since the discovery of mirror neuron system, several neurophysiological and neuroimaging studies showed that the mirror neuron system might have a role in understanding other people's actions and intentions with automatic simulation of their actions. Moreover, some studies suggested that mirror neurons have a broader role in social cognition including understanding others' emotions and empathy. It has not been proved, however, whether the mirror neuron system is necessarily involved in empathy processes. In the domain of social cognition deficits, it is important to investigate the involvement of mirror neuron system dysfunction in psychosis such as schizophrenia. Using magnetoencephalography, we examined whether antipsychotic-free schizophrenia patients displayed mirror neuron system dysfunction during observation of biological motion (jaw movement). Compared with normal controls, the patients with schizophrenia had fewer components of both the waveform and equivalent current dipole, suggesting aberrant brain activity resulting from dysfunction of the right inferior parietal cortex. They also lacked the changes of alpha band and gamma band oscillation seen in normal controls, and had weaker phase locking factors and gamma-synchronization predominantly in right parietal cortex. This finding demonstrated that untreated patients with schizophrenia exhibited aberrant mirror neuron system function based on the right inferior parietal cortex, which is characterized by dysfunction of gamma-synchronization.

  13. Genetic markers in alcoholic liver cirrhosis.

    PubMed

    Lareu, M V; Alvarez-Prechous, A; Pardiñas, C; Concheiro, L; Carracedo, A

    1992-01-01

    11 genetic markers were typed in 157 individuals suffering from alcoholic cirrhosis, and compared with a random sample of healthy individuals. No significant differences were found for transferrin, specific group component, orosomucoid, esterase D, phosphogluconate dehydrogenase and adenylate kinase. Strong associations between alcoholic cirrhosis and alpha-1-antitrypsin PI*Z allele, haptoglobin HP*1 allele and acid phosphatase ACP AC phenotype were observed. The biological significance of these associations and their relationships with the development of alcoholic cirrhosis are also discussed.

  14. Chronic Glucocorticoid-Rich Milieu and Liver Dysfunction

    PubMed Central

    Castro, María Cecilia

    2016-01-01

    We investigated the impact of chronic hypercorticosteronemia (due to neonatal monosodium L-glutamate, MSG, and treatment) on liver oxidative stress (OS), inflammation, and carbohydrate/lipid metabolism in adult male rats. We evaluated the peripheral concentrations of several metabolic and OS markers and insulin resistance indexes. In liver we assessed (a) OS (GSH and protein carbonyl groups) and inflammatory (IL-1b, TNFa, and PAI-1) biomarkers and (b) carbohydrate and lipid metabolisms. MSG rats displayed degenerated optic nerves, hypophagia, low body and liver weights, and enlarged adipose tissue mass; higher peripheral levels of glucose, triglycerides, insulin, uric acid, leptin, corticosterone, transaminases and TBARS, and peripheral and liver insulin resistance; elevated liver OS, inflammation markers, and glucokinase (mRNA/activity) and fructokinase (mRNA). Additionally, MSG liver phosphofructokinase-2, glucose-6-phosphatase (mRNA and activity) and glucose-6-phosphate dehydrogenase, Chrebp, Srebp1c, fatty acid synthase, and glycerol-3-phosphate (mRNAs) were increased. In conclusion adult MSG rats developed an insulin-resistant state and increased OS and serious hepatic dysfunction characterized by inflammation and metabolic signs suggesting increased lipogenesis. These features, shared by both metabolic and Cushing's syndrome human phenotypes, support that a chronic glucocorticoid-rich endogenous environment mainly impacts on hepatic glucose cycle, displacing local metabolism to lipogenesis. Whether correcting the glucocorticoid-rich environment ameliorates such dysfunctions requires further investigation. PMID:27597864

  15. Chronic Glucocorticoid-Rich Milieu and Liver Dysfunction.

    PubMed

    Villagarcía, Hernán Gonzalo; Sabugo, Vanesa; Castro, María Cecilia; Schinella, Guillermo; Castrogiovanni, Daniel; Spinedi, Eduardo; Massa, María Laura; Francini, Flavio

    2016-01-01

    We investigated the impact of chronic hypercorticosteronemia (due to neonatal monosodium L-glutamate, MSG, and treatment) on liver oxidative stress (OS), inflammation, and carbohydrate/lipid metabolism in adult male rats. We evaluated the peripheral concentrations of several metabolic and OS markers and insulin resistance indexes. In liver we assessed (a) OS (GSH and protein carbonyl groups) and inflammatory (IL-1b, TNFa, and PAI-1) biomarkers and (b) carbohydrate and lipid metabolisms. MSG rats displayed degenerated optic nerves, hypophagia, low body and liver weights, and enlarged adipose tissue mass; higher peripheral levels of glucose, triglycerides, insulin, uric acid, leptin, corticosterone, transaminases and TBARS, and peripheral and liver insulin resistance; elevated liver OS, inflammation markers, and glucokinase (mRNA/activity) and fructokinase (mRNA). Additionally, MSG liver phosphofructokinase-2, glucose-6-phosphatase (mRNA and activity) and glucose-6-phosphate dehydrogenase, Chrebp, Srebp1c, fatty acid synthase, and glycerol-3-phosphate (mRNAs) were increased. In conclusion adult MSG rats developed an insulin-resistant state and increased OS and serious hepatic dysfunction characterized by inflammation and metabolic signs suggesting increased lipogenesis. These features, shared by both metabolic and Cushing's syndrome human phenotypes, support that a chronic glucocorticoid-rich endogenous environment mainly impacts on hepatic glucose cycle, displacing local metabolism to lipogenesis. Whether correcting the glucocorticoid-rich environment ameliorates such dysfunctions requires further investigation.

  16. Assessment of Endothelial Dysfunction in Childhood Obesity and Clinical Use

    PubMed Central

    Hoymans, Vicky Y.; Van Craenenbroeck, Amaryllis H.; Vissers, Dirk K.; Vrints, Christiaan J.; Conraads, Viviane M.

    2013-01-01

    The association of obesity with noncommunicable diseases, such as cardiovascular complications and diabetes, is considered a major threat to the management of health care worldwide. Epidemiological findings show that childhood obesity is rapidly rising in Western society, as well as in developing countries. This pandemic is not without consequences and can affect the risk of future cardiovascular disease in these children. Childhood obesity is associated with endothelial dysfunction, the first yet still reversible step towards atherosclerosis. Advanced research techniques have added further insight on how childhood obesity and associated comorbidities lead to endothelial dysfunction. Techniques used to measure endothelial function were further brought to perfection, and novel biomarkers, including endothelial progenitor cells, were discovered. The aim of this paper is to provide a critical overview on both in vivo as well as in vitro markers for endothelial integrity. Additionally, an in-depth description of the mechanisms that disrupt the delicate balance between endothelial damage and repair will be given. Finally, the effects of lifestyle interventions and pharmacotherapy on endothelial dysfunction will be reviewed. PMID:23691262

  17. Endocrine dysfunction in sepsis: a beneficial or deleterious host response?

    PubMed

    Gheorghiţă, Valeriu; Barbu, Alina Elena; Gheorghiu, Monica Livia; Căruntu, Florin Alexandru

    2015-03-01

    Sepsis is a systemic, deleterious inflammatory host response triggered by an infective agent leading to severe sepsis, septic shock and multi-organ failure. The host response to infection involves a complex, organized and coherent interaction between immune, autonomic, neuroendocrine and behavioral systems. Recent data have confirmed that disturbances of the autonomic nervous and neuroendocrine systems could contribute to sepsis-induced organ dysfunction. Through this review, we aimed to summarize the current knowledge about the endocrine dysfunction as response to sepsis, specifically addressed to vasopressin, copeptin, cortisol, insulin and leptin. We searched the following readily accessible, clinically relevant databases: PubMed, UpToDate, BioMed Central. The immune system could be regarded as a "diffuse sensory organ" that signals the presence of pathogens to the brain through different pathways, such as the vagus nerve, endothelial activation/dysfunction, cytokines and neurotoxic mediators and the circumventricular organs, especially the neurohypophysis. The hormonal profile changes substantially as a consequence of inflammatory mediators and microorganism products leading to inappropriately low levels of vasopressin, sick euthyroid syndrome, reduced adrenal responsiveness to ACTH, insulin resistance, hyperglycemia as well as hyperleptinemia. In conclusion, clinical diagnosis of this "pan-endocrine illness" is frequently challenging due to the many limiting factors. The most important benefits of endocrine markers in the management of sepsis may be reflected by their potential to be used as biomarkers in different scoring systems to estimate the severity of the disease and the risk of death.

  18. Gonadal dysfunction in systemic diseases.

    PubMed

    Karagiannis, Asterios; Harsoulis, Faidon

    2005-04-01

    Gonadal function is significantly affected in many acute and chronic systemic diseases. As the function of the testes and the ovaries is determined by the integrity of the hypothalamic-pituitary-gonadal axis, it is obvious that a systemic disease may affect one or more levels of the axis in such a manner that the gonadal dysfunction may have various clinical and laboratory manifestations. In this brief review, the most common disturbances seen in the main systemic diseases will be discussed.

  19. Temporomandibular joint pain and dysfunction.

    PubMed

    Herb, Kathleen; Cho, Sung; Stiles, Marlind Alan

    2006-12-01

    Pain caused by temporomandibular disorders originates from either muscular or articular conditions, or both. Distinguishing the precise source of the pain is a significant diagnostic challenge to clinicians, and effective management hinges on establishing a correct diagnosis. This paper examines terminology and regional anatomy as it pertains to functional and dysfunctional states of the temporomandibular joint and muscles of mastication. A review of the pathophysiology of the most common disorders is provided. Trends in evaluation, diagnosis, treatment, and research are presented.

  20. Hypnotic metaphor and sexual dysfunction.

    PubMed

    Gilmore, L G

    1987-01-01

    Although hypnosis can be very effective in alleviating sexual problems, few sex therapists use hypnotic methods. This paper seeks to encourage a greater use of hypnosis among clinicians by presenting: a description of the new hypnosis exemplified in the work of Milton H. Erickson; an explanation of one of Erickson's most important and innovative methods, the use of multiple embedded metaphors; and case histories illustrating the application of hypnotic approaches to sexual dysfunction.

  1. Mitochondrial dysfunction and organophosphorus compounds

    SciTech Connect

    Karami-Mohajeri, Somayyeh; Abdollahi, Mohammad

    2013-07-01

    Organophosphorous (OPs) pesticides are the most widely used pesticides in the agriculture and home. However, many acute or chronic poisoning reports about OPs have been published in the recent years. Mitochondria as a site of cellular oxygen consumption and energy production can be a target for OPs poisoning as a non-cholinergic mechanism of toxicity of OPs. In the present review, we have reviewed and criticized all the evidences about the mitochondrial dysfunctions as a mechanism of toxicity of OPs. For this purpose, all biochemical, molecular, and morphological data were retrieved from various studies. Some toxicities of OPs are arisen from dysfunction of mitochondrial oxidative phosphorylation through alteration of complexes I, II, III, IV and V activities and disruption of mitochondrial membrane. Reductions of adenosine triphosphate (ATP) synthesis or induction of its hydrolysis can impair the cellular energy. The OPs disrupt cellular and mitochondrial antioxidant defense, reactive oxygen species generation, and calcium uptake and promote oxidative and genotoxic damage triggering cell death via cytochrome C released from mitochondria and consequent activation of caspases. The mitochondrial dysfunction induced by OPs can be restored by use of antioxidants such as vitamin E and C, alpha-tocopherol, electron donors, and through increasing the cytosolic ATP level. However, to elucidate many aspect of mitochondrial toxicity of Ops, further studies should be performed. - Highlights: • As a non-cholinergic mechanism of toxicity, mitochondria is a target for OPs. • OPs affect action of complexes I, II, III, IV and V in the mitochondria. • OPs reduce mitochondrial ATP. • OPs promote oxidative and genotoxic damage via release of cytochrome C from mitochondria. • OP-induced mitochondrial dysfunction can be restored by increasing the cytosolic ATP.

  2. Circulating tumour markers in breast cancer.

    PubMed

    Seregni, Ettore; Coli, Antonio; Mazzucca, Nicola

    2004-06-01

    A large number of markers have been proposed for breast cancer, but among them only CA 15.3, CEA and cytokeratins (i.e. TPA, TPS and Cyfra 21.1) are currently used in clinical practice. Serum marker levels reflect tumour burden and for this reason they are not sensitive enough to be used for screening and early diagnosis of primary breast cancer. By contrast, the role of tumour markers is established in the diagnosis of recurrent disease and in the evaluation of response to treatment. In the former case, however, prospective randomised studies are required to demonstrate any survival benefit when earlier therapeutic interventions are instituted upon elevation of serum markers. In the second case, tumour marker evaluation represents a simple, objective method for monitoring of therapeutic response that seems to offer significant advantages over conventional imaging methods (e.g. objectivity, modifications in tumour biology). Furthermore, research studies are ongoing to identify and validate new biochemical parameters which can be of use not only in advanced disease but also in other stages of the diagnostic work-up of breast cancer.

  3. Gut dysfunction in Parkinson's disease

    PubMed Central

    Mukherjee, Adreesh; Biswas, Atanu; Das, Shyamal Kumar

    2016-01-01

    Early involvement of gut is observed in Parkinson’s disease (PD) and symptoms such as constipation may precede motor symptoms. α-Synuclein pathology is extensively evident in the gut and appears to follow a rostrocaudal gradient. The gut may act as the starting point of PD pathology with spread toward the central nervous system. This spread of the synuclein pathology raises the possibility of prion-like propagation in PD pathogenesis. Recently, the role of gut microbiota in PD pathogenesis has received attention and some phenotypic correlation has also been shown. The extensive involvement of the gut in PD even in its early stages has led to the evaluation of enteric α-synuclein as a possible biomarker of early PD. The clinical manifestations of gastrointestinal dysfunction in PD include malnutrition, oral and dental disorders, sialorrhea, dysphagia, gastroparesis, constipation, and defecatory dysfunction. These conditions are quite distressing for the patients and require relevant investigations and adequate management. Treatment usually involves both pharmacological and non-pharmacological measures. One important aspect of gut dysfunction is its contribution to the clinical fluctuations in PD. Dysphagia and gastroparesis lead to inadequate absorption of oral anti-PD medications. These lead to response fluctuations, particularly delayed-on and no-on, and there is significant relationship between levodopa pharmacokinetics and gastric emptying in patients with PD. Therefore, in such cases, alternative routes of administration or drug delivery systems may be required. PMID:27433087

  4. Tumour markers in diagnosis and management.

    PubMed

    Warnes, T W; Smith, A

    1987-01-01

    The 20-year period since the discovery of AFP by Abelev has seen the introduction of a wide range of new tumour markers and it is now clear that PLC is biologically heterogeneous. Hepatoblastomas, fibrolamellar carcinomas, hepatocellular carcinomas and cholangiocarcinomas may secrete a variety of distinctive markers which are predominantly glycoproteins, and may resemble those found in placenta or fetal liver. Diagnostically, AFP remains the best marker for HCC, both in sensitivity and specificity; it is known to consist of isoforms. In patients with elevated serum AFP and filling defects on liver scan, Con A reactive AFP may differentiate PLC from hepatic metastases, whilst fucosylated AFP may distinguish PLC from benign disorders when AFP is non-diagnostically elevated. With this recognition of tumour heterogeneity the value of a multiple-marker approach has become apparent. The measurement of vitamin B12 binding protein and neurotensin should lead to the detection of most patients with the fibrolamellar variant of HCC and many of these should be resectable. In patients with normal serum AFP levels, HCC-associated GGTP is of major value whilst in low-incidence areas for HCC, patients should also be screened for H-ALP; using a multiple marker approach in high-risk groups, 90% of clinically diagnosed hepatocellular carcinomas are serologically positive. The Chinese and Alaskan studies, in which small, potentially resectable tumours were detected, suggest that it is now possible to achieve 5-year survival figures of up to 60% in HCC patients detected by screening. The value of such a strategy in low-incidence countries is currently under study. In patient monitoring, as in diagnosis, AFP remains the outstanding marker. In AFP-negative patients, other markers including vitamin B12-binding protein, neurotensin, HCC-specific isoenzymes, des-gamma-carboxy-prothrombin and alpha-fucosidase, are of undoubted diagnostic value, but their value as indicants of disease

  5. Erectile dysfunction in patients with cardiovascular disease

    PubMed Central

    Ophuis, A.J.M. Oude; Nijeholt, A.A.B. Lycklama à

    2006-01-01

    Erectile dysfunction is a highly prevalent disease, especially in cardiovascular-compromised men. Many of the well-established risk factors for cardiovascular disease are also risk factors for erectile dysfunction. A correlation between erectile dysfunction and endothelial dysfunction is well established. It is postulated that erectile dysfunction with an arteriovascular aetiology can predate and be an indicator of potential coronary artery disease. In this paper we will attempt to increase awareness among cardiologists for the predictive value of erectile dysfunction for future cardiovascular disease in order to optimise cardiovascular risk management. The treatment of erectile dysfunction and cardiovascular interactions is also discussed in detail. ImagesFigure 1AFigure 1B PMID:25696612

  6. Psychological and interpersonal dimensions of sexual function and dysfunction

    PubMed Central

    Assalian, Pierre

    2013-01-01

    Introduction Sex therapy techniques comprise behavioural and cognitive as well as psychodynamic and educational interventions, like reading (‘bibliotherapy’), videotapes and illustrations of anatomical models. Contemporary approaches focus on desire, pleasure and satisfaction. Discussion It is important to assess medical and biological factors involved in the genesis of sexual dysfunctions. Sex therapy techniques were developed by Masters and Johnson, and their premise was to eliminate ‘performance anxiety’ by emphasising the undemanding nature of the sexual relation. New methods were introduced, like Internet-administered techniques, and ‘mindfulness therapy’, and they proved to be effective. Conclusions Psychological treatments have some relieving effects on sexual dysfunction, but for studies of the outcomes it is difficult to meet the requirements of evidence-based medicine. PMID:26558085

  7. Telomere dysfunction drives aberrant hematopoietic differentiation and myelodysplastic syndrome.

    PubMed

    Colla, Simona; Ong, Derrick Sek Tong; Ogoti, Yamini; Marchesini, Matteo; Mistry, Nipun A; Clise-Dwyer, Karen; Ang, Sonny A; Storti, Paola; Viale, Andrea; Giuliani, Nicola; Ruisaard, Kathryn; Ganan Gomez, Irene; Bristow, Christopher A; Estecio, Marcos; Weksberg, David C; Ho, Yan Wing; Hu, Baoli; Genovese, Giannicola; Pettazzoni, Piergiorgio; Multani, Asha S; Jiang, Shan; Hua, Sujun; Ryan, Michael C; Carugo, Alessandro; Nezi, Luigi; Wei, Yue; Yang, Hui; D'Anca, Marianna; Zhang, Li; Gaddis, Sarah; Gong, Ting; Horner, James W; Heffernan, Timothy P; Jones, Philip; Cooper, Laurence J N; Liang, Han; Kantarjian, Hagop; Wang, Y Alan; Chin, Lynda; Bueso-Ramos, Carlos; Garcia-Manero, Guillermo; DePinho, Ronald A

    2015-05-11

    Myelodysplastic syndrome (MDS) risk correlates with advancing age, therapy-induced DNA damage, and/or shorter telomeres, but whether telomere erosion directly induces MDS is unknown. Here, we provide the genetic evidence that telomere dysfunction-induced DNA damage drives classical MDS phenotypes and alters common myeloid progenitor (CMP) differentiation by repressing the expression of mRNA splicing/processing genes, including SRSF2. RNA-seq analyses of telomere dysfunctional CMP identified aberrantly spliced transcripts linked to pathways relevant to MDS pathogenesis such as genome stability, DNA repair, chromatin remodeling, and histone modification, which are also enriched in mouse CMP haploinsufficient for SRSF2 and in CD34(+) CMML patient cells harboring SRSF2 mutation. Together, our studies establish an intimate link across telomere biology, aberrant RNA splicing, and myeloid progenitor differentiation.

  8. Asthma: vocal cord dysfunction (VCD) and other dysfunctional breathing disorders.

    PubMed

    Balkissoon, Ron; Kenn, Klaus

    2012-12-01

    Vocal cord dysfunction (VCD) and dysfunctional breathing (DB) disorders may mimic or coexist with asthma, leading to overtreatment with corticosteroids with consequent morbidity. Iatrogenic complications can be averted by early and correct diagnosis. VCD, also termed paradoxical vocal fold motion disorder (PVFMD), is characterized by intermittent paradoxical adduction of the vocal cords, mainly during inspiration, leading to airflow obstruction and dyspnea. Patients with VCD may have repetitive emergency room visits due to acute dyspnea (mimicking exacerbations of asthma). In the seminal descriptions of VCD, young women (often with psychiatric issues) predominated; however, other groups at increased risk for developing VCD include elite athletes, military recruits, and individuals exposed to irritants (inhaled or aspirated). Chronic postnasal drip, laryngopharyngeal reflux (LPR), and gastroesophageal reflux (GER) may lead to laryngeal hyperresponsiveness. The diagnosis of VCD may be difficult because physical exam and spirometry may be normal between episodes. During symptomatic episodes, spirometry typically reveals variable extrathoracic airway obstruction (truncated inspiratory flow volume loop). The gold standard for identifying VCD is flexible fiberoptic rhinolaryngoscopy. Management of VCD includes identification and treatment of underlying disorders (eg, chronic postnasal drip, LPR, GER, anxiety, depression) and a multidisciplinary approach (including highly trained speech therapists). Speech therapy and biofeedback play a critical role in teaching techniques to override various dysfunctional breathing habits. When postnasal drip, LPR, or GER coexist, these disorders should be aggressively treated. With successful therapy, corticosteroids can often be discontinued. During severe, acute episodes of VCD, therapeutic strategies include heliox (80% helium/20% oxygen), topical lidocaine, anxiolytics, and superior laryngeal blocks with Clostridium botulinum toxin

  9. Lead toxicity promotes autonomic dysfunction with increased chemoreceptor sensitivity.

    PubMed

    Geraldes, Vera; Carvalho, Mafalda; Goncalves-Rosa, Nataniel; Tavares, Cristiano; Laranjo, Sérgio; Rocha, Isabel

    2016-05-01

    Mortality and morbidity by toxic metals is an important issue of occupational health. Lead is an ubiquitous heavy metal in our environment despite having no physiological role in biological systems. Being an homeostatic controller is expected that the autonomic nervous system would show a degree of impairment in lead toxicity. In fact, sympathoexcitation associated to high blood pressure and tachypnea has been described together with baroreflex dysfunction. However, the mechanisms underlying the autonomic dysfunction and the interplay between baro- and chemoreflex are not yet fully clarified. The angiotensinogenic PVN-NTS axis (paraventricular nucleus of the hypothalamus - nucleus tractus solitarius axis) is a particularly important neuronal pathway that could be responsible for the autonomic dysfunction and the cardiorespiratory impairment in lead toxicity. Within the current work, we addressed in vivo, baro- and chemoreceptor reflex behaviour, before and after central angiotensin inhibition, in order to better understand the cardiorespiratory autonomic mechanisms underlying the toxic effects of long-term lead exposure. For that, arterial pressure, heart rate, respiratory rate, sympathetic and parasympathetic activity and baro- and chemoreceptor reflex profiles of anaesthetized young adult rats exposed to lead, from foetal period to adulthood, were evaluated. Results showed increased chemosensitivity together with baroreceptor reflex impairment, sympathetic over-excitation, hypertension and tachypnea. Chemosensitivity and sympathetic overexcitation were reversed towards normality values by NTS treatment with A-779, an angiotensin (1-7) antagonist. No parasympathetic changes were observed before and after A-799 treatment. In conclusion, angiotensin (1-7) at NTS level is involved in the autonomic dysfunction observed in lead toxicity. The increased sensitivity of chemoreceptor reflex expresses the clear impairment of autonomic outflow to the cardiovascular and

  10. The Swift Turbidity Marker

    ERIC Educational Resources Information Center

    Omar, Ahmad Fairuz; MatJafri, Mohd Zubir

    2011-01-01

    The Swift Turbidity Marker is an optical instrument developed to measure the level of water turbidity. The components and configuration selected for the system are based on common turbidity meter design concepts but use a simplified methodology to produce rapid turbidity measurements. This work is aimed at high school physics students and is the…

  11. Endothelial dysfunction as a predictor of cardiovascular disease in type 1 diabetes

    PubMed Central

    Bertoluci, Marcello C; Cé, Gislaine V; da Silva, Antônio MV; Wainstein, Marco V; Boff, Winston; Puñales, Marcia

    2015-01-01

    Macro and microvascular disease are the main cause of morbi-mortality in type 1 diabetes (T1DM). Although there is a clear association between endothelial dysfunction and atherosclerosis in type 2 diabetes, a cause-effect relationship is less clear in T1DM. Although endothelial dysfunction (ED) precedes atherosclerosis, it is not clear weather, in recent onset T1DM, it may progress to clinical macrovascular disease. Moreover, endothelial dysfunction may either be reversed spontaneously or in response to intensive glycemic control, long-term exercise training and use of statins. Acute, long-term and post-prandial hyperglycemia as well as duration of diabetes and microalbuminuria are all conditions associated with ED in T1DM. The pathogenesis of endothelial dysfunction is closely related to oxidative-stress. NAD(P)H oxidase over activity induces excessive superoxide production inside the mitochondrial oxidative chain of endothelial cells, thus reducing nitric oxide bioavailability and resulting in peroxynitrite formation, a potent oxidant agent. Moreover, oxidative stress also uncouples endothelial nitric oxide synthase, which becomes dysfunctional, inducing formation of superoxide. Other important mechanisms are the activation of both the polyol and protein kinase C pathways as well as the presence of advanced glycation end-products. Future studies are needed to evaluate the potential clinical applicability of endothelial dysfunction as a marker for early vascular complications in T1DM. PMID:26069717

  12. Cardiovascular Disease Prevention in Men with Vascular Erectile Dysfunction: The View of the Preventive Cardiologist.

    PubMed

    Shah, Nishant P; Cainzos-Achirica, Miguel; Feldman, David I; Blumenthal, Roger S; Nasir, Khurram; Miner, Martin M; Billups, Kevin L; Blaha, Michael J

    2016-03-01

    Vascular erectile dysfunction is a powerful marker of increased cardiovascular risk. However, current guidelines lack specific recommendations on the role that the evaluation of vascular erectile dysfunction should play in cardiovascular risk assessment, as well on the risk stratification strategy that men with vascular erectile dysfunction should undergo. In the last 3 years, erectile dysfunction experts have made a call for more specific guidance and have proposed the selective use of several prognostic tests for further cardiovascular risk assessment in these patients. Among them, stress testing has been prioritized, whereas other tests are considered second-line tools. In this review, we provide additional perspective from the viewpoint of the preventive cardiologist. We discuss the limitations of current risk scores and the potential interplay between erectile dysfunction assessment and the use of personalized prognostic tools, such as the coronary artery calcium score, in the cardiovascular risk stratification and management of men with vascular erectile dysfunction. Finally, we present an algorithm for primary care physicians, urologists, and cardiologists to aid clinical decision-making.

  13. Sexual dysfunction and neuroendocrine correlates of posttraumatic stress disorder in combat veterans: Preliminary findings.

    PubMed

    Lehrner, Amy; Flory, Janine D; Bierer, Linda M; Makotkine, Iouri; Marmar, Charles R; Yehuda, Rachel

    2016-01-01

    Sexual dysfunction is not a symptom of PTSD but is a common clinical complaint in trauma survivors with this disorder. In that there are biological parallels in the neuroendocrine processes underlying both PTSD and sexual behavior, we conducted an exploratory investigation of the relationship of PTSD and related neuroendocrine indicators with sexual dysfunction in armed service veterans. Major Depressive Disorder, highly comorbid with PTSD and sexual dysfunction, was also assessed. In veterans with PTSD, sexual problems were associated with plasma DHEA and cortisol, urinary catecholamines, and glucocorticoid sensitivity, even when controlling for the effects of comorbid depression. In a subsample analysis, testosterone levels did not distinguish PTSD or sexual dysfunction, suggesting that sexual problems reported by veterans in this sample were not the result of organic disorder. PTSD did predict higher dihydrotestosterone (DHT) levels, which were associated with sexual problems. More detailed assessment of sexual dysfunction in biologically informed studies of PTSD is warranted to clarify the relationships of PTSD symptomatology and related neurobiology with sexual dysfunction.

  14. Pharmacotherapy of Sexual Dysfunctions : Current Status

    PubMed Central

    Avasthi, Ajith; Biswas, Parthasarathy

    2004-01-01

    The sexual dysfunctions are one of the most prevalent conditions. Sexual dysfunctions can have profound effect on the psychological well-being of an individual and the psychosexual relationship of a couple. Management of the sexual dysfunction should be preceded by an accurate diagnosis reached after a complete medical and sexual history and physical examination. Current focus of researchers has been on understanding the pathophysiology of erectile dysfunction, premature ejaculation and other sexual dysfunctions that can help in developing newer pharmacological cures for these conditions. Recently, a number of clinical trials have studied the potential effectiveness of the phosphodiesterase (PDE)-5 inhibitor sildenafil in the treatment of Erectile Dysfunction (ED) and Premature Ejaculation (PME). The introduction of PDE-5 inhibitors like sildenafil, vardenafil and tadalafil has revolutionized the treatment of sexual dysfunctions. This review focuses on the recent pharmacological advances in the treatment of common sexual dysfunctions like ED and PME with special focus on the role of PDE-5 inhibitors. Also discussed is the pharmacological treatment of other less prevalent and recognized disorders like female sexual dysfunction, drug induced sexual dysfunction etc. PMID:21224902

  15. Swallowing dysfunction following endotracheal intubation

    PubMed Central

    Tsai, Min-Hsuan; Ku, Shih-Chi; Wang, Tyng-Guey; Hsiao, Tzu-Yu; Lee, Jang-Jaer; Chan, Ding-Cheng; Huang, Guan-Hua; Chen, Cheryl Chia-Hui

    2016-01-01

    Abstract To evaluate postextubation swallowing dysfunction (PSD) 21 days after endotracheal extubation and to examine whether PSD is time-limited and whether age matters. For this prospective cohort study, we evaluated 151 adult critical care patients (≥20 years) who were intubated for at least 48 hours and had no pre-existing neuromuscular disease or swallowing dysfunction. Participants were assessed for time (days) to pass bedside swallow evaluations (swallow 50 mL of water without difficulty) and to resume total oral intake. Outcomes were compared between younger (20–64 years) and older participants (≥65 years). PSD, defined as inability to swallow 50 mL of water within 48 hours after extubation, affected 92 participants (61.7% of our sample). At 21 days postextubation, 17 participants (15.5%) still failed to resume total oral intake and were feeding-tube dependent. We found that older participants had higher PSD rates at 7, 14, and 21 days postextubation, and took significantly longer to pass the bedside swallow evaluations (5.0 vs 3.0 days; P = 0.006) and to resume total oral intake (5.0 vs 3.0 days; P = 0.003) than their younger counterparts. Older participants also had significantly higher rates of subsequent feeding-tube dependence than younger patients (24.1 vs 5.8%; P = 0.008). Excluding patients with pre-existing neuromuscular dysfunction, PSD is common and prolonged. Age matters in the time needed to recover. Swallowing and oral intake should be monitored and interventions made, if needed, in the first 7 to 14 days postextubation, particularly for older patients. PMID:27310972

  16. Why mental disorders are just mental dysfunctions (and nothing more): some Darwinian arguments.

    PubMed

    De Block, Andreas

    2008-09-01

    Mental disorders are often thought to be harmful dysfunctions. Jerome Wakefield has argued that such dysfunctions should be understood as failures of naturally selected functions. This suggests, implicitly, that evolutionary biology and other Darwinian disciplines hold important information for anyone working on answering the philosophical question, 'what is a mental disorder?'. In this article, the author argues that Darwinian theory is not only relevant to the understanding of the disrupted functions, but it also sheds light on the disruption itself, as well as on the harm that attends the disruption. The arguments advanced here are partially based on the view that a core feature of Darwinism is that it stresses the environmental relativity of functions and dysfunctions. These arguments show a very close empirical connection between social judgments (values) and dysfunctions (psychopathology), which is of interest for psychiatric theory. Philosophically, they lead to the conclusion that the concept of mental disorder is identical to the concept of mental dysfunction. Consequently, it is both misleading and redundant to conceptualize mental disorders as 'harmful dysfunctions', and not simply as 'mental dysfunctions'.

  17. Endothelial dysfunction: a comprehensive appraisal

    PubMed Central

    Esper, Ricardo J; Nordaby, Roberto A; Vilariño, Jorge O; Paragano, Antonio; Cacharrón, José L; Machado, Rogelio A

    2006-01-01

    The endothelium is a thin monocelular layer that covers all the inner surface of the blood vessels, separating the circulating blood from the tissues. It is not an inactive organ, quite the opposite. It works as a receptor-efector organ and responds to each physical or chemical stimulus with the release of the correct substance with which it may maintain vasomotor balance and vascular-tissue homeostasis. It has the property of producing, independently, both agonistic and antagonistic substances that help to keep homeostasis and its function is not only autocrine, but also paracrine and endocrine. In this way it modulates the vascular smooth muscle cells producing relaxation or contraction, and therefore vasodilatation or vasoconstriction. The endothelium regulating homeostasis by controlling the production of prothrombotic and antithrombotic components, and fibrynolitics and antifibrynolitics. Also intervenes in cell proliferation and migration, in leukocyte adhesion and activation and in immunological and inflammatory processes. Cardiovascular risk factors cause oxidative stress that alters the endothelial cells capacity and leads to the so called endothelial "dysfunction" reducing its capacity to maintain homeostasis and leads to the development of pathological inflammatory processes and vascular disease. There are different techniques to evaluate the endothelium functional capacity, that depend on the amount of NO produced and the vasodilatation effect. The percentage of vasodilatation with respect to the basal value represents the endothelial functional capacity. Taking into account that shear stress is one of the most important stimulants for the synthesis and release of NO, the non-invasive technique most often used is the transient flow-modulate "endothelium-dependent" post-ischemic vasodilatation, performed on conductance arteries such as the brachial, radial or femoral arteries. This vasodilatation is compared with the vasodilatation produced by drugs that

  18. Drug addiction and sexual dysfunction.

    PubMed

    Zaazaa, Adham; Bella, Anthony J; Shamloul, Rany

    2013-09-01

    This article attempts to review the most current and the well-established facts concerning drug addiction and sexual dysfunction. Surprisingly, even though alcohol is prevalent in many societies with many myths surrounding its sexual-enhancing effects, current scientific research cannot provide a solid conclusion on its effect on sexual function. Unfortunately, the same concept applies to tobacco smoking; however, most of the current knowledge tends to support the notion that it, indeed, can negatively affect sexual function. Similar ambiguities also prevail with substances of abuse.

  19. Male sexual dysfunction in Asia

    PubMed Central

    Ho, Christopher CK; Singam, Praveen; Hong, Goh Eng; Zainuddin, Zulkifli Md

    2011-01-01

    Sex has always been a taboo subject in Asian society. However, over the past few years, awareness in the field of men's sexual health has improved, and interest in sexual health research has recently increased. The epidemiology and prevalence of erectile dysfunction, hypogonadism and premature ejaculation in Asia are similar in the West. However, several issues are specific to Asian males, including culture and beliefs, awareness, compliance and the availability of traditional/complementary medicine. In Asia, sexual medicine is still in its infancy, and a concerted effort from the government, relevant societies, physicians and the media is required to propel sexual medicine to the forefront of health care. PMID:21643001

  20. Angelman syndrome and thyroid dysfunction.

    PubMed

    Monterrubio-Ledezma, C E; Bobadilla-Morales, L; Pimentel-Gutiérrez, H J; Corona-Rivera, J R; Corona-Rivera, A

    2012-01-01

    Angelman syndrome (AS) is a neurogenetic syndrome, has a prevalence of 1:10,000 to 1:40,000. Patients with AS have genetic alterations in maternal imprinting gene UB3A (15q11-q13) and molecular evaluations confirm the diagnosis. Our aim is to report a new case with AS and subclinical hypothyroidism (SCH) without goiter. Thyroid dysfunction has not been described as part of alterations in AS; the exact pathogenic mechanisms of SCH in patients with AS remains incompletely unknown.

  1. Vocal cord dysfunction during wartime.

    PubMed

    Craig, T; Sitz, K; Squire, E; Smith, L; Carpenter, G

    1992-11-01

    Vocal cord dysfunction (VCD) often masquerades as asthma. The diagnosis is rarely suspected, but should be considered in cases of asthma that present atypically or that fail to respond to standard therapy. The frequency of VCD would be expected to increase during times of stress, including periods of war, since it is thought to be a conversion reaction. A high level of suspicion for VCD is essential to make the diagnosis so as to avoid unnecessary, potentially toxic medications and to direct the patient to prompt psychiatric care, which along with speech therapy, is the cornerstone of care.

  2. Vaccination-related shoulder dysfunction.

    PubMed

    Bodor, Marko; Montalvo, Enoch

    2007-01-08

    We present two cases of shoulder pain and weakness following influenza and pneumococcal vaccine injections provided high into the deltoid muscle. Based on ultrasound measurements, we hypothesize that vaccine injected into the subdeltoid bursa caused a periarticular inflammatory response, subacromial bursitis, bicipital tendonitis and adhesive capsulitis. Resolution of symptoms followed corticosteroid injections to the subacromial space, bicipital tendon sheath and glenohumeral joint, followed by physical therapy. We conclude that the upper third of the deltoid muscle should not be used for vaccine injections, and the diagnosis of vaccination-related shoulder dysfunction should be considered in patients presenting with shoulder pain following a vaccination.

  3. All biology is computational biology

    PubMed Central

    2017-01-01

    Here, I argue that computational thinking and techniques are so central to the quest of understanding life that today all biology is computational biology. Computational biology brings order into our understanding of life, it makes biological concepts rigorous and testable, and it provides a reference map that holds together individual insights. The next modern synthesis in biology will be driven by mathematical, statistical, and computational methods being absorbed into mainstream biological training, turning biology into a quantitative science. PMID:28278152

  4. All biology is computational biology.

    PubMed

    Markowetz, Florian

    2017-03-01

    Here, I argue that computational thinking and techniques are so central to the quest of understanding life that today all biology is computational biology. Computational biology brings order into our understanding of life, it makes biological concepts rigorous and testable, and it provides a reference map that holds together individual insights. The next modern synthesis in biology will be driven by mathematical, statistical, and computational methods being absorbed into mainstream biological training, turning biology into a quantitative science.

  5. Aortic Stiffness, Cerebrovascular Dysfunction, and Memory

    PubMed Central

    Cooper, Leroy L.; Mitchell, Gary F.

    2016-01-01

    Background Aortic stiffness is associated with cardiovascular and cerebrovascular events and cognitive decline. This mini-review focuses on relations of aortic stiffness with microvascular dysfunction and discusses the contribution of abnormal pulsatile hemodynamics to cerebrovascular damage and cognitive decline. We also provide a rationale for considering aortic stiffness as a putative and important contributor to memory impairment in older individuals. Summary Aging is associated with stiffening of the aorta but not the muscular arteries, which reduces wave reflection and increases the transmission of pulsatility into the periphery. Aortic stiffening thereby impairs a protective mechanism that shields the peripheral microcirculation from excessive pulsatility within downstream target organs. Beyond midlife, aortic stiffness increases rapidly and exposes the cerebral microcirculation to abnormal pulsatile mechanical forces that are associated with microvascular damage and remodeling in the brain. Aortic stiffening and high-flow pulsatility are associated with alterations in the microvasculature of the brain; however, a mechanistic link between aortic stiffness and memory has not been established. We showed that in a community-based sample of older individuals, cerebrovascular resistance and white matter hyperintensities - markers of cerebrovascular remodeling and damage - mediated the relation between higher aortic stiffness and lower performance on memory function tests. These data suggest that microvascular and white matter damage associated with excessive aortic stiffness contribute to impaired memory function with advancing age. Key Messages Increasing evidence suggests that vascular etiologies - including aortic stiffness and microvascular damage - contribute to memory impairment and the pathogenesis of dementia, including Alzheimer's disease. Interventions that reduce aortic stiffness may delay memory decline among older individuals. PMID:27752478

  6. [Oxidative stress and endothelial dysfunction].

    PubMed

    Jarasūniene, Dalia; Simaitis, Audrius

    2003-01-01

    Growing numbers of morbidity and mortality due to the Coronary Heart Disease (CHD) is recognized as the more increasing challenge in the world. The initial stage of atherosclerosis, early diagnosis and treatment of CHD are the main objectives of current research. Endothelium dysfunction, the earliest expression of the atherosclerotic process is associated with subtle biochemical changes that gradually are transformed into the structural changes of the arterial wall. The theory of free radicals is the most common among the atherosclerosis explanations. Overproduction or impaired neutralization of the free radicals accounts for oxidative stress that is causing substantial damage to the low density lipoproteins, nitric oxyde (NO), endothelium cells, tissue cells and finally leads to the endothelium dysfuction. Pathophysiology of oxidative stress and its role in the endothelium dysfunction are discussed in this paper. Positive role of various medications (statins, angiotensin converting enzym inhibitors, aldosteron antagonists, estrogens, antioxidants, b-blockers with vasodilatative properties) to the oxidative stress and consequently to the endothelium dysfuction are discussed as well.

  7. [Diaphragm dysfunction : Facts for clinicians].

    PubMed

    Bruells, C S; Marx, G

    2016-10-20

    Diaphragm function is crucial for patient outcome in the ICU setting and during the treatment period. The occurrence of an insufficiency of the respiratory pump, which is predominantly formed by the diaphragm, may result in intubation after failure of noninvasive ventilation. Especially patients suffering from chronic obstructive pulmonary disease are in danger of hypercapnic respiratory failure. Changes in biomechanical properties and fiber texture of the diaphragm are further cofactors directly leading to a need for intubation and mechanical ventilation. After intubation and the following inactivity the diaphragm is subject to profound pathophysiologic changes resulting in atrophy and dysfunction. Besides this inactivity-triggered mechanism (termed as ventilator-induced diaphragmatic dysfunction) multiple factors, comorbidities, pharmaceutical agents and additional hits during the ICU treatment, especially the occurrence of sepsis, influence diaphragm homeostasis and can lead to weaning failure. During the weaning process monitoring of diaphragm function can be done with invasive methods - ultrasound is increasingly established to monitor diaphragm contraction, but further and better powered studies are in need to prove its value as a diagnostic tool.

  8. Referential Markers and Agreement Markers in Functional Discourse Grammar

    ERIC Educational Resources Information Center

    Hengeveld, Kees

    2012-01-01

    It follows from the ordering principles that are applied in Functional Discourse Grammar that the positional possibilities of markers of agreement and those of cross-reference are different. Markers of cross reference are predicted to occur closer to the verb stem, while markers of agreement would occupy peripheral positions. This paper tests…

  9. [The impact of detecting endothelial dysfunction in atherosclerosis: Role of positron emission tomography (PET)].

    PubMed

    Alexánderson-Rosas, Erick; Calleja-Torres, Rodrigo; Martínez-García, Alfonso; Lamothe-Molina, Pedro Alberto; Ochoa-López, Juan Manuel; Meléndez, Gabriela; Kimura-Hayama, Eric; Meave-González, Aloha

    2010-01-01

    The endothelium plays an important role in the regulation of the intracellular fluid, vascular permeability, and modulation of vascular focal tone and angiogenesis. Endothelial dysfunction is manifested by the loss of the endothelium ability to modulate physiology changes in its vascular bed, and actually it is considered a prognostic marker of coronary artery disease. The relevance of assessing endothelial dysfunction relies in that it has been observed in different pathologies like DM, dyslipidemia, hypertension, tabaquism and in immunologic diseases like antiphospholipid syndrome and systemic lupus. PET is a non invasive method that allows the absolute quantification of myocardial blood flow during rest, stress and adrenergic stimulation, which allows to asses endothelial function. Therefore PET is a useful diagnostic technique to identify patients with endothelial dysfunction, and in the assessment of its response to administered therapy, allowing an optimal control and prevention of secondary adverse events of these diseases.

  10. Recent Advances on Pathophysiology, Diagnostic and Therapeutic Insights in Cardiac Dysfunction Induced by Antineoplastic Drugs

    PubMed Central

    Molinaro, Marilisa; Ameri, Pietro; Marone, Giancarlo; Petretta, Mario; Abete, Pasquale; Di Lisa, Fabio; De Placido, Sabino; Bonaduce, Domenico; Tocchetti, Carlo G.

    2015-01-01

    Along with the improvement of survival after cancer, cardiotoxicity due to antineoplastic treatments has emerged as a clinically relevant problem. Potential cardiovascular toxicities due to anticancer agents include QT prolongation and arrhythmias, myocardial ischemia and infarction, hypertension and/or thromboembolism, left ventricular (LV) dysfunction, and heart failure (HF). The latter is variable in severity, may be reversible or irreversible, and can occur soon after or as a delayed consequence of anticancer treatments. In the last decade recent advances have emerged in clinical and pathophysiological aspects of LV dysfunction induced by the most widely used anticancer drugs. In particular, early, sensitive markers of cardiac dysfunction that can predict this form of cardiomyopathy before ejection fraction (EF) is reduced are becoming increasingly important, along with novel therapeutic and cardioprotective strategies, in the attempt of protecting cardiooncologic patients from the development of congestive heart failure. PMID:26583088

  11. Lipoprotein marker for hypertriglyceridemia

    DOEpatents

    Cubicciotti, Roger S.; Karu, Alexander E.; Krauss, Ronald M.

    1986-01-01

    Methods and compositions are provided for the detection of a particular low density lipoprotein which has been found to be a marker for patients suffering from type IV hypertriglyceridemia. A monoclonal antibody capable of specifically binding to a characteristic epitopic site on this LDL subspecies can be utilized in a wide variety of immunoassays. Hybridoma cell line SPL.IVA5A1 was deposited at the American Type Culture Collection on Mar. 29, 1984, and granted accession no. HB 8535.

  12. Serum tumor markers.

    PubMed

    Perkins, Greg L; Slater, Evan D; Sanders, Georganne K; Prichard, John G

    2003-09-15

    Monoclonal antibodies are used to detect serum antigens associated with specific malignancies. These tumor markers are most useful for monitoring response to therapy and detecting early relapse. With the exception of prostate-specific antigen (PSA), tumor markers do not have sufficient sensitivity or specificity for use in screening. Cancer antigen (CA) 27.29 most frequently is used to follow response to therapy in patients with metastatic breast cancer. Carcinoembryonic antigen is used to detect relapse of colorectal cancer, and CA 19-9 may be helpful in establishing the nature of pancreatic masses. CA 125 is useful for evaluating pelvic masses in postmenopausal women, monitoring response to therapy in women with ovarian cancer, and detecting recurrence of this malignancy. Alpha-fetoprotein (AFP), a marker for hepatocellular carcinoma, sometimes is used to screen highly selected populations and to assess hepatic masses in patients at particular risk for developing hepatic malignancy. Testing for the beta subunit of human chorionic gonadotropin (beta-hCG) is an integral part of the diagnosis and management of gestational trophoblastic disease. Combined AFP and beta-hCG testing is an essential adjunct in the evaluation and treatment of nonseminomatous germ cell tumors, and in monitoring the response to therapy. AFP and beta-hCG also may be useful in evaluating potential origins of poorly differentiated metastatic cancer. PSA is used to screen for prostate cancer, detect recurrence of the malignancy, and evaluate specific syndromes of adenocarcinoma of unknown primary.

  13. Diabetes and sexual dysfunction: current perspectives

    PubMed Central

    Maiorino, Maria Ida; Bellastella, Giuseppe; Esposito, Katherine

    2014-01-01

    Diabetes mellitus is one of the most common chronic diseases in nearly all countries. It has been associated with sexual dysfunction, both in males and in females. Diabetes is an established risk factor for sexual dysfunction in men, as a threefold increased risk of erectile dysfunction was documented in diabetic men, as compared with nondiabetic men. Among women, evidence regarding the association between diabetes and sexual dysfunction are less conclusive, although most studies have reported a higher prevalence of female sexual dysfunction in diabetic women as compared with nondiabetic women. Female sexual function appears to be more related to social and psychological components than to the physiological consequence of diabetes. Hyperglycemia, which is a main determinant of vascular and microvascular diabetic complications, may participate in the pathogenetic mechanisms of sexual dysfunction in diabetes. Moreover, diabetic people may present several clinical conditions, including hypertension, overweight and obesity, metabolic syndrome, cigarette smoking, and atherogenic dyslipidemia, which are themselves risk factors for sexual dysfunction, both in men and in women. The adoption of healthy lifestyles may reduce insulin resistance, endothelial dysfunction, and oxidative stress – all of which are desirable achievements in diabetic patients. Improved well-being may further contribute to reduce and prevent sexual dysfunction in both sexes. PMID:24623985

  14. The relationship between depression and erectile dysfunction.

    PubMed

    Seidman, S N; Roose, S P

    2000-06-01

    Normal sexual function is a biopsychosocial process; sexual dysfunction almost always has organic and psychologic components, and it requires multidisciplinary, goal-directed evaluation and treatment. Factors such as aging, declining testosterone levels, medical illness, certain medications, and comorbid depressive illness can contribute to sexual dysfunction. Erectile dysfunction (ED) is the most common male sexual dysfunction encountered in the clinical setting. Comorbidity between ED and depressive illness is high, but the causal relationship is unclear, and likely bidirectional. In this article, we review the existing literature on the relationship between depression and ED.

  15. Mitochondrial Dysfunction and Immune Cell Metabolism in Sepsis

    PubMed Central

    2017-01-01

    Sepsis is a life threatening condition mediated by systemic infection, but also triggered by hemorrhage and trauma. These are significant causes of organ injury implicated in morbidity and mortality, as well as post-sepsis complications associated with dysfunction of innate and adaptive immunity. The role of cellular bioenergetics and loss of metabolic plasticity of immune cells is increasingly emerging in the pathogenesis of sepsis. This review describes mitochondrial biology and metabolic alterations of immune cells due to sepsis, as well as indicates plausible therapeutic opportunities. PMID:28378540

  16. A SOMATIC-MARKER THEORY OF ADDICTION

    PubMed Central

    Verdejo-García, Antonio; Bechara, Antoine

    2009-01-01

    Similar to patients with ventromedial prefrontal cortex (VMPC) lesions, substance abusers show altered decision-making, characterized by a tendency to choose the immediate reward, at the expense of negative future consequences. The somatic-marker model proposes that decision-making depends on neural substrates that regulate homeostasis, emotion and feeling. According to this model, there should be a link between alterations in processing emotions in substance abusers, and their impairments in decision-making. A growing evidence from neuroscientific studies indicate that core aspects of addiction may be explained in terms of abnormal emotional/homeostatic guidance of decision-making. Behavioural studies have revealed emotional processing and decision-making deficits in substance abusers. Neuroimaging studies have shown that altered decision-making in addiction is associated with abnormal functioning of a distributed neural network critical for the processing of emotional information, and the experience of “craving”, including the VMPC, the amygdala, the striatum, the anterior cingulate cortex, and the insular/somato-sensory cortices, as well as non-specific neurotransmitter systems that modulate activities of neural processes involved in decision-making. The aim of this paper is to review this growing evidence, and to examine the extent of which these studies support a somatic-marker theory of addiction. We conclude that there are at least two underlying types of dysfunctions where emotional signals (somatic-markers) turns in favor of immediate outcomes in addiction: (1) a hyperactivity in the amygdala or impulsive system, which exaggerates the rewarding impact of available incentives, and (2) hypoactivity in the prefrontal cortex or reflective system, which forecasts the long-term consequences of a given action. PMID:18722390

  17. Inside the Spiral of Dysfunction: The Personal Consequences of Working for a Dysfunctional Leader

    ERIC Educational Resources Information Center

    Shuck, Brad; Rose, Kevin; Bergman, Matt

    2015-01-01

    Dysfunctional leaders suffocate others with coercive power and ego, are unpredictable, and often lack self-awareness about their dysfunction. Dysfunctional leaders are incredibly difficult to work with and can cause a series of cascading personal consequences for employees who work with them. This Perspectives in Human Resource Development essay…

  18. Serum from Varicose Patients Induces Senescence-Related Dysfunction of Vascular Endothelium Generating Local and Systemic Proinflammatory Conditions

    PubMed Central

    Mikuła-Pietrasik, Justyna; Uruski, Paweł; Aniukiewicz, Krzysztof; Sosińska, Patrycja; Krasiński, Zbigniew; Tykarski, Andrzej

    2016-01-01

    Although the role of endothelium in varicose vein development is indisputable, the effect of the pathology on biological properties of endothelial cells remains unclear. Here we examined if the presence of varicose veins affects senescence of endothelial cells (HUVECs) and, if so, what will be the local and systemic outcome of this effect. Experiments showed that HUVECs subjected to serum from varicose patients display improved proliferation, increased expression of senescence marker, SA-β-Gal, and increased generation of reactive oxygen species (ROS), as compared with serum from healthy donors. Both increased SA-β-Gal activity and ROS release were mediated by TGF-β1, the concentration of which in varicose serum was elevated and the activity of which in vitro was prevented using specific neutralizing antibody. Senescent HUVECs exposed to varicose serum generated increased amounts of ICAM-1, VCAM-1, P-selectin, uPA, PAI-1, and ET-1. Direct comparison of sera from varicose and healthy donors showed that pathological serum contained increased level of ICAM-1, VCAM-1, P-selectin, uPA, and ET-1. Calendar age of healthy subjects correlated positively with serum uPA and negatively with P-selectin. Age of varicose patients correlated positively with ICAM-1, VCAM-1, and ET-1. Collectively, our findings indicate that the presence of varicose veins causes a senescence-related dysfunction of vascular endothelium, which leads to the development of local and systemic proinflammatory environment. PMID:27994710

  19. Biological Technicians

    MedlinePlus

    ... Biological technicians typically need a bachelor’s degree in biology or a closely related field. It is important ... Biological technicians typically need a bachelor’s degree in biology or a closely related field. It is important ...

  20. Hypoparathyroidism presenting as cognitive dysfunction

    PubMed Central

    Kumar, Gunjan; Kaur, Darshpreet; Aggarwal, Puneet; Khurana, Tilak

    2013-01-01

    Metabolic dysfunction in hypoparathyroidism is an important cause of intracranial calcifications, which cause cognitive impairment depending on the calcified areas leading to difficulties in executing activities of daily living. We report a case of a 25-year-old man who presented with gradually decreasing organisational skills, memory problems and difficulty in carrying out daily activities. CT imaging of the brain showed extensive calcification in the basal ganglia and cerebral white matter. Comprehensive health-related quality of life and cognitive assessment revealed significant affliction in his activities of daily living along with impairment in recall memory, executive functions and verbal fluency. Owing to late diagnosis, chronicity of cognitive problems could not prevent him from discontinuing his college education. PMID:23709145

  1. Psychopathy: cognitive and neural dysfunction.

    PubMed

    R Blair, R James

    2013-06-01

    Psychopathy is a developmental disorder marked by emotional deficits and an increased risk for antisocial behavior. It is not equivalent to the diagnosis Antisocial Personality Disorder, which concentrates only on the increased risk for antisocial behavior and not a specific cause-ie, the reduced empathy and guilt that constitutes the emotional deficit. The current review considers data from adults with psychopathy with respect to the main cognitive accounts of the disorder that stress either a primary attention deficit or a primary emotion deficit. In addition, the current review considers data regarding the neurobiology of this disorder. Dysfunction within the amygdala's role in reinforcement learning and the role of ventromedial frontal cortex in the representation of reinforcement value is stressed. Data is also presented indicating potential difficulties within parts of temporal and posterior cingulate cortex. Suggestions are made with respect to why these deficits lead to the development of the disorder.

  2. Hypoparathyroidism presenting as cognitive dysfunction.

    PubMed

    Kumar, Gunjan; Kaur, Darshpreet; Aggarwal, Puneet; Khurana, Tilak

    2013-05-23

    Metabolic dysfunction in hypoparathyroidism is an important cause of intracranial calcifications, which cause cognitive impairment depending on the calcified areas leading to difficulties in executing activities of daily living. We report a case of a 25-year-old man who presented with gradually decreasing organisational skills, memory problems and difficulty in carrying out daily activities. CT imaging of the brain showed extensive calcification in the basal ganglia and cerebral white matter. Comprehensive health-related quality of life and cognitive assessment revealed significant affliction in his activities of daily living along with impairment in recall memory, executive functions and verbal fluency. Owing to late diagnosis, chronicity of cognitive problems could not prevent him from discontinuing his college education.

  3. Flibanserin for female sexual dysfunction.

    PubMed

    Reviriego, C

    2014-08-01

    Hypoactive sexual desire disorder (HSDD) is the most commonly described form of female sexual dysfunction. There is currently no pharmacological therapy approved to treat HSDD, and therefore, there is an unmet medical need for the development of efficacious treatment alternatives. Flibanserin is a novel, non-hormonal drug for the treatment of HSDD in pre- and postmenopausal women, although the application submitted to the U.S. Food and Drug Administration by Sprout Pharmaceuticals is only for premenopausal women. Flibanserin works by correcting an imbalance of the levels of the neurotransmitters that affect sexual desire. More specifically, flibanserin increases dopamine and norepinephrine, both responsible for sexual excitement, and decreases serotonin, responsible for sexual inhibition. Clinically, flibanserin has exhibited some encouraging results in terms of its ability to increase the frequency of satisfying sexual events, and the intensity of sexual desire. However, adverse events such as dizziness, nausea, fatigue and somnolence, typical of a centrally acting drug, are also frequently related to flibanserin treatment.

  4. Pharmacotherapeutic management of erectile dysfunction.

    PubMed

    Hawksworth, D J; Burnett, A L

    2015-12-01

    Erectile dysfunction is a common condition in aging men and significantly affects their quality of life and interpersonal relationships. Its prevalence and incidence are associated with aging, lifestyle factors and cardiovascular comorbidities. Preoccupation with male virility has been present for centuries, and a wide variety of herbs and potions have been used to treat any sexual deficiencies. Recent major advances in understanding of erectile physiology and pathophysiology led to development of currently available systemic and local pharmacotherapies. They are designed to work either centrally or peripherally and to either suppress anti-erectile mechanisms, enhance the pro-erectile ones or influence both. Since all the current formulations have variable safety and efficacy profiles, the search for highly specific, simple, convenient and clinically effective impotence treatments or prophylactics continues.

  5. Ulnar intrinsic anatomy and dysfunction.

    PubMed

    Dell, Paul C; Sforzo, Christopher R

    2005-01-01

    Normal hand function is a balance between the extrinsic and intrinsic musculature. Although individually the intrinsics are small muscles in diameter, collectively they represent a large muscle that contributes approximately 50% of grip strength. Dysfunction of the intrinsics consequently leads to impaired grip and pinch strength as well recognized deformities. Low ulnar nerve palsy preserves ulnar innervated extrinsics resulting in sensory loss, digital clawing, thumb deformity, abduction of the small finger, and asynchronous finger motion. High ulnar nerve palsy is characterized by the above plus paralysis of the ulnar profundi and the flexor carpi ulnaris. Understanding the normal anatomy allows the clinician to identify the site of the lesion and plan appropriate surgical intervention. This article revisits the classic work of Richard J. Smith on ulnar nerve palsy with contemporary perspective.

  6. Heterosis, marker mutational processes and population inbreeding history.

    PubMed Central

    Tsitrone, A; Rousset, F; David, P

    2001-01-01

    Genotype-fitness correlations (GFC) have previously been studied using allozyme markers and have often focused on short-term processes such as recent inbreeding. Thus, models of GFC usually neglect marker mutation and only use heterozygosity as a genotypic index. Recently, GFC have also been reported (i) with DNA markers such as microsatellites, characterized by high mutation rates and specific mutational processes and (ii) using new individual genotypic indices assumed to be more precise than heterozygosity. The aim of this article is to evaluate the theoretical impact of marker mutation on GFC. We model GFC due to short-term processes generated by the current breeding system (partial selfing) and to long-term processes generated by past population history (hybridization). Various mutation rates and mutation models corresponding to different kinds of molecular markers are considered. Heterozygosity is compared to other genotypic indices designed for specific marker types. Highly mutable markers (such as microsatellites) are particularly suitable for the detection of GFC that evolve in relation to short-term processes, whereas GFC due to long-term processes are best observed with intermediate mutation rates. Irrespective of the marker type and population scenario, heterozygosity usually provides higher correlations than other genotypic indices under most biologically plausible conditions. PMID:11779819

  7. Near infrared radiation rescues mitochondrial dysfunction in cortical neurons after oxygen-glucose deprivation.

    PubMed

    Yu, Zhanyang; Liu, Ning; Zhao, Jianhua; Li, Yadan; McCarthy, Thomas J; Tedford, Clark E; Lo, Eng H; Wang, Xiaoying

    2015-04-01

    Near infrared radiation (NIR) is known to penetrate and affect biological systems in multiple ways. Recently, a series of experimental studies suggested that low intensity NIR may protect neuronal cells against a wide range of insults that mimic diseases such as stroke, brain trauma and neurodegeneration. However, the potential molecular mechanisms of neuroprotection with NIR remain poorly defined. In this study, we tested the hypothesis that low intensity NIR may attenuate hypoxia/ischemia-induced mitochondrial dysfunction in neurons. Primary cortical mouse neuronal cultures were subjected to 4 h oxygen-glucose deprivation followed by reoxygenation for 2 h, neurons were then treated with a 2 min exposure to 810-nm NIR. Mitochondrial function markers including MTT reduction and mitochondria membrane potential were measured at 2 h after treatment. Neurotoxicity was quantified 20 h later. Our results showed that 4 h oxygen-glucose deprivation plus 20 h reoxygenation caused 33.8 ± 3.4 % of neuron death, while NIR exposure significantly reduced neuronal death to 23.6 ± 2.9 %. MTT reduction rate was reduced to 75.9 ± 2.7 % by oxygen-glucose deprivation compared to normoxic controls, but NIR exposure significantly rescued MTT reduction to 87.6 ± 4.5 %. Furthermore, after oxygen-glucose deprivation, mitochondria membrane potential was reduced to 48.9 ± 4.39 % of normoxic control, while NIR exposure significantly ameliorated this reduction to 89.6 ± 13.9 % of normoxic control. Finally, NIR significantly rescued OGD-induced ATP production decline at 20 min after NIR. These findings suggest that low intensity NIR can protect neurons against oxygen-glucose deprivation by rescuing mitochondrial function and restoring neuronal energetics.

  8. On the Etiology of Sexual Dysfunction

    ERIC Educational Resources Information Center

    Apfelbaum, Bernard

    1977-01-01

    Lack of consideration of the sexually functional population has led to misconceptions about causes of sexual dysfunction functioning. Automatic functioning can mask effects of pathogenic influences on sexuality, making these effects appear random, confounding etiological issues and creating the belief that causes of sexual dysfunction and disorder…

  9. Male Pseudoheterosexuality and Minimal Sexual Dysfunction

    ERIC Educational Resources Information Center

    Gutstadt, Joseph P.

    1976-01-01

    There is often a correlation between "pseudoheterosexuality" and minor sexual dysfunction. Insight alone is not sufficient to provide relief, but when the patient can be helped to a comfortable acceptance of his homosexual feelings as a normal and healthy facet of his personality, very often the dysfunction is relieved. (Author)

  10. Heart Rate Variability: A Risk Factor for Female Sexual Dysfunction.

    PubMed

    Stanton, Amelia M; Lorenz, Tierney A; Pulverman, Carey S; Meston, Cindy M

    2015-09-01

    Heart rate variability (HRV) is a measure of autonomic nervous system activity, which reflects an individual's ability to adapt to physiological and environmental changes. Low resting HRV has been linked to several mental health conditions, including depression, anxiety, and alcohol dependence (Kemp et al. in Biological Psychiatry 67(11):1067-1074, 2010. doi:10.1016/j.biopsych.2009.12.012; Kemp et al. in PloS One, 7(2):e30777, 2012; Quintana et al. in Drug and Alcohol Dependence, 132(1-2):395-398, 2013. doi:10.1016/j.drugalcdep.2013.02.025). HRV has also been used as a method for indexing the relative balance of sympathetic nervous system (SNS) activity to parasympathetic nervous system activity. This balance--in particular, moderately dominant SNS activity--has been shown to play a significant role in women's genital sexual arousal in the laboratory; however, the role of SNS activity in clinically relevant sexual arousal function is unknown. The present study assessed the feasibility of using HRV as an index of women's self-reported sexual arousal function outside the laboratory. Sexual arousal function, overall sexual function, and resting HRV were assessed in 72 women, aged 18-39. Women with below average HRV were significantly more likely to report sexual arousal dysfunction (p < .001) and overall sexual dysfunction (p < .001) than both women with average HRV and women with above average HRV. In conclusion, low HRV may be a risk factor for female sexual arousal dysfunction and overall sexual dysfunction.

  11. Neural correlates of obsessive-compulsive related dysfunctional beliefs.

    PubMed

    Alonso, Pino; Orbegozo, Arantxa; Pujol, Jesús; López-Solà, Clara; Fullana, Miquel Àngel; Segalàs, Cinto; Real, Eva; Subirà, Marta; Martínez-Zalacaín, Ignacio; Menchón, José M; Harrison, Ben J; Cardoner, Narcís; Soriano-Mas, Carles

    2013-12-02

    There have been few attempts to integrate neurobiological and cognitive models of obsessive-compulsive disorder (OCD), although this might constitute a key approach to clarify the complex etiology of the disorder. Our study aimed to explore the neural correlates underlying dysfunctional beliefs hypothesized by cognitive models to be involved in the development and maintenance of OCD. We obtained a high-resolution magnetic resonance image from fifty OCD patients and 30 healthy controls, and correlated them, voxel-wise, with the severity of OC-related dysfunctional beliefs assessed by the Obsessive Beliefs Questionnaire-44. In healthy controls, significant negative correlations were observed between anterior temporal lobe (ATL) volume and scores on perfectionism/intolerance of uncertainty and overimportance/need to control thoughts. No significant correlations between OBQ-44 domains and regional gray matter volumes were observed in OCD patients. A post-hoc region-of-interest analysis detected that the ATLs was bilaterally smaller in OCD patients. On splitting subjects into high- and low-belief subgroups, we observed that such brain structural differences between OCD patients and healthy controls were explained by significantly larger ATL volumes among healthy subjects from the low-belief subgroup. Our results suggest a significant correlation between OC-related dysfunctional beliefs and morphometric variability in the anterior temporal lobe, a brain structure related to socio-emotional processing. Future studies should address the interaction of these correlations with environmental factors to fully characterize the bases of OC-related dysfunctional beliefs and to advance in the integration of biological and cognitive models of OCD.

  12. Mutations of ESPN cause autosomal recessive deafness and vestibular dysfunction

    PubMed Central

    Naz, S; Griffith, A; Riazuddin, S; Hampton, L; Battey, J; Khan, S; Riazuddin, S; Wilcox, E; Friedman, T

    2004-01-01

    We mapped a human deafness locus DFNB36 to chromosome 1p36.3 in two consanguineous families segregating recessively inherited deafness and vestibular areflexia. This phenotype co-segregates with either of two frameshift mutations, 1988delAGAG and 2469delGTCA, in ESPN, which encodes a calcium-insensitive actin-bundling protein called espin. A recessive mutation of ESPN is known to cause hearing loss and vestibular dysfunction in the jerker mouse. Our results establish espin as an essential protein for hearing and vestibular function in humans. The abnormal vestibular phenotype associated with ESPN mutations will be a useful clinical marker for refining the differential diagnosis of non-syndromic deafness. PMID:15286153

  13. Dicer1 dysfunction promotes stemness and aggression in endometrial carcinoma.

    PubMed

    Wang, Xiao-Jun; Jiang, Fei-Zhou; Tong, Huan; Ke, Jie-Qi; Li, Yi-Ran; Zhang, Hui-Lin; Yan, Xiao-Fang; Wang, Fang-Yuan; Wan, Xiao-Ping

    2017-04-01

    Endometrial carcinoma is one of the most common gynecological malignancies, but the molecular events involved in the development and progression of endometrial carcinoma remain unclear. Dicer1 and cancer stem cells play important roles in cell motility and survival. This study investigated the role of the let-7 family and Dicer1 in the stemness of endometrial carcinoma cells. We profiled Dicer1 expression in clinical samples and explored its relationship with stem cell-associated markers and clinical parameters. We showed that Dicer1 dysfunction leads to the enrichment of tumor stemness features and tumor aggression both in vitro and in vivo. We also identified the mechanism related to this potential tumor-predisposing phenotype: loss of Dicer1 induced abnormal expression of the let-7 family, which comprises well-known tumor suppressors, thus regulating stemness in endometrial carcinoma cells.

  14. Attachment, borderline personality, and romantic relationship dysfunction.

    PubMed

    Hill, Jonathan; Stepp, Stephanie D; Wan, Ming Wai; Hope, Holly; Morse, Jennifer Q; Steele, Miriam; Steele, Howard; Pilkonis, Paul A

    2011-12-01

    Previous studies have implicated attachment and disturbances in romantic relationships as important indicators for Borderline Personality Disorder (BPD). The current research extends our current knowledge by examining the specific associations among attachment, romantic relationship dysfunction, and BPD, above and beyond the contribution of emotional distress and nonromantic interpersonal functioning in two distinct samples. Study 1 comprised a community sample of women (N = 58) aged 25-36. Study 2 consisted of a psychiatric sample (N = 138) aged 21-60. Results from both Study 1 and Study 2 demonstrated that (1) attachment was specifically related to BPD symptoms and romantic dysfunction, (2) BPD symptoms were specifically associated with romantic dysfunction, and (3) the association between attachment and romantic dysfunction was statistically mediated by BPD symptoms. The findings support specific associations among attachment, BPD symptoms, and romantic dysfunction.

  15. Pathophysiology of bladder dysfunction in Parkinson's disease.

    PubMed

    Sakakibara, Ryuji; Tateno, Fuyuki; Kishi, Masahiko; Tsuyuzaki, Yohei; Uchiyama, Tomoyuki; Yamamoto, Tatsuya

    2012-06-01

    Bladder dysfunction (urinary urgency/frequency) is a common non-motor disorder in Parkinson's disease (PD). In contrast to motor disorders, bladder dysfunction is sometimes non-responsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine basal ganglia-frontal circuit, which normally suppresses the micturition reflex. The pathophysiology of the bladder dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. These treatments might be beneficial in maximizing the patients' quality of life.

  16. Endothelial Dysfunction in Renal Failure: Current Update.

    PubMed

    Radenkovic, Miroslav; Stojanovic, Marko; Prostran, Milica

    2016-01-01

    Endothelial dysfunction is principally characterized by impaired endothelium- dependent transduction mechanisms related to vascular relaxation, as an outcome of decreased release of endothelium-derived relaxing factors, mainly nitric oxide, as well as augmented oxidative stress, increased inflammation and predominance of vascular action produced by endothelium-derived contracting factors. Current data strongly suggest that pathological development of different types of kidney impairment with further progression to renal failure includes notable vascular changes associated with endothelial dysfunction. In accordance, this scientific field represents an advancing area of investigation, involving different biomarkers of endothelial dysfunction linked to renal impairment, as well as clinical findings with new information that can provide a more comprehensive understanding of the role of endothelial dysfunction in kidney disease. With regards to quoted facts, the aim of this article was to review the latest data related to endothelial dysfunction and renal failure by selection of relevant articles released from 2010 to 2015.

  17. Understanding taste dysfunction in patients with cancer.

    PubMed

    McLaughlin, Laura; Mahon, Suzanne M

    2012-04-01

    Taste dysfunction is a significant but underestimated issue for patients with cancer. Impaired taste results in changes in diet and appetite, early satiety, and impaired social interactions. Nurses can play a key role in educating patients and families on the pathophysiology of taste dysfunction by suggesting interventions to treat the consequences of taste dysfunction, when available, and offering psychosocial support as patients cope with this often devastating consequence of treatment. Taste recognition helps humans identify the nutritional quality of food and signals the digestive tract to begin secreting enzymes. Spoiled or tainted foods typically are recognized by their bad taste. Along with the other sensory systems, taste is crucial for helping patients treated for cancer feel normal. This article will review the anatomy and physiology of taste; define the different types of taste dysfunction, including the underlying pathophysiologic basis related to cancer treatment; and discuss potential nursing interventions to manage the consequences of taste dysfunction.

  18. Diastolic dysfunction in the critically ill patient.

    PubMed

    Suárez, J C; López, P; Mancebo, J; Zapata, L

    2016-11-01

    Left ventricular diastolic dysfunction is a common finding in critically ill patients. It is characterized by a progressive deterioration of the relaxation and the compliance of the left ventricle. Two-dimensional and Doppler echocardiography is a cornerstone in its diagnosis. Acute pulmonary edema associated with hypertensive crisis is the most frequent presentation of diastolic dysfunction critically ill patients. Myocardial ischemia, sepsis and weaning failure from mechanical ventilation also may be associated with diastolic dysfunction. The treatment is based on the reduction of pulmonary congestion and left ventricular filling pressures. Some studies have found a prognostic role of diastolic dysfunction in some diseases such as sepsis. The present review aims to analyze thoroughly the echocardiographic diagnosis and the most frequent scenarios in critically ill patients in whom diastolic dysfunction plays a key role.

  19. Prehypertension and Left Ventricular Diastolic Dysfunction in Middle-Aged Koreans

    PubMed Central

    Jang, Shin Yi; Kim, Sujin; Lee, Chang Kwan; Cho, Eun Jeong; Cho, Soo Jin

    2016-01-01

    Background and Objectives Left ventricular diastolic dysfunction is known to be a marker of myocardial damage, in particular myocardial fibrosis resulting from hypertension (HT). However, few studies have shown an association between the grade of diastolic dysfunction and blood pressure classification. We investigated the association between diastolic dysfunction and prehypertension (preHT) in apparently healthy adults who underwent routine health examinations. Subjects and Methods The study sample included 4261 Koreans, 45 to 64 years of age with no previous history of HT, diabetes mellitus, malignancy, proven coronary artery disease, or valvular heart disease based on echocardiography, who underwent routine health examinations including echocardiography. The subjects were classified into three groups based on resting blood pressure: prehypertensive, hypertensive, and normotensive. Results The prevalence of preHT in our study was 42.1%. After adjusting for age, gender, smoking status, alcohol consumption, fasting blood sugar, serum lipid profile, and body mass index, left ventricular diastolic dysfunction grades 1 and 2 were significantly more frequent in subjects with preHT (odds ratio [OR] 1.66 [95% confidence interval {CI} 1.40-1.96] and 1.37 [95% CI 0.95-1.97], respectively). When analyzed according to gender, the increased OR was especially notable in males. Conclusion Left ventricular diastolic dysfunction appears to be significantly associated with preHT in Korean middle-aged males. PMID:27482263

  20. Iterative marker excision system.

    PubMed

    Myronovskyi, Maksym; Rosenkränzer, Birgit; Luzhetskyy, Andriy

    2014-05-01

    The deletions of large genomic DNA fragments and consecutive gene knockouts are prerequisites for the generation of organisms with improved properties. One of the key issues in this context is the removal of antibiotic resistance markers from engineered organisms without leaving an active recombinase recognition site. Here, we report the establishment of an iterative marker excision system (IMES) that solves this problem. Based on the phiC31 integrase and its mutant att sites, IMES can be used for highly effective deletion of DNA fragments between inversely oriented B-CC and P-GG sites. The B-CC and P-GG sites are derived from attB and attP by substitution of the central core TT dinucleotide with CC and GG, respectively. An unnatural RR site that resides in the chromosome following deletion is the joining product of the right shoulders of B-CC and P-GG. We show that the RR sites do not recombine with each other as well as the RR site recombines with B-CC. The recombination efficiencies between RR and P-GG or RR and LL are only 0.1 % and 1 %, respectively. Thus, IMES can be used for multistep genomic engineering without risking unwanted DNA recombination. The fabrication of multi-purpose antibiotic cassettes and examples of the utilisation of IMES are described.

  1. Abdominal contributions to cardiorenal dysfunction in congestive heart failure.

    PubMed

    Verbrugge, Frederik H; Dupont, Matthias; Steels, Paul; Grieten, Lars; Malbrain, Manu; Tang, W H Wilson; Mullens, Wilfried

    2013-08-06

    Current pathophysiological models of congestive heart failure unsatisfactorily explain the detrimental link between congestion and cardiorenal function. Abdominal congestion (i.e., splanchnic venous and interstitial congestion) manifests in a substantial number of patients with advanced congestive heart failure, yet is poorly defined. Compromised capacitance function of the splanchnic vasculature and deficient abdominal lymph flow resulting in interstitial edema might both be implied in the occurrence of increased cardiac filling pressures and renal dysfunction. Indeed, increased intra-abdominal pressure, as an extreme marker of abdominal congestion, is correlated with renal dysfunction in advanced congestive heart failure. Intriguing findings provide preliminary evidence that alterations in the liver and spleen contribute to systemic congestion in heart failure. Finally, gut-derived hormones might influence sodium homeostasis, whereas entrance of bowel toxins into the circulatory system, as a result of impaired intestinal barrier function secondary to congestion, might further depress cardiac as well as renal function. Those toxins are mainly produced by micro-organisms in the gut lumen, with presumably important alterations in advanced heart failure, especially when renal function is depressed. Therefore, in this state-of-the-art review, we explore the crosstalk between the abdomen, heart, and kidneys in congestive heart failure. This might offer new diagnostic opportunities as well as treatment strategies to achieve decongestion in heart failure, especially when abdominal congestion is present. Among those currently under investigation are paracentesis, ultrafiltration, peritoneal dialysis, oral sodium binders, vasodilator therapy, renal sympathetic denervation and agents targeting the gut microbiota.

  2. Therapeutically targeting mitochondrial redox signalling alleviates endothelial dysfunction in preeclampsia

    PubMed Central

    McCarthy, Cathal; Kenny, Louise C.

    2016-01-01

    Aberrant placentation generating placental oxidative stress is proposed to play a critical role in the pathophysiology of preeclampsia. Unfortunately, therapeutic trials of antioxidants have been uniformly disappointing. There is provisional evidence implicating mitochondrial dysfunction as a source of oxidative stress in preeclampsia. Here we provide evidence that mitochondrial reactive oxygen species mediates endothelial dysfunction and establish that directly targeting mitochondrial scavenging may provide a protective role. Human umbilical vein endothelial cells exposed to 3% plasma from women with pregnancies complicated by preeclampsia resulted in a significant decrease in mitochondrial function with a subsequent significant increase in mitochondrial superoxide generation compared to cells exposed to plasma from women with uncomplicated pregnancies. Real-time PCR analysis showed increased expression of inflammatory markers TNF-α, TLR-9 and ICAM-1 respectively in endothelial cells treated with preeclampsia plasma. MitoTempo is a mitochondrial-targeted antioxidant, pre-treatment of cells with MitoTempo protected against hydrogen peroxide-induced cell death. Furthermore MitoTempo significantly reduced mitochondrial superoxide production in cells exposed to preeclampsia plasma by normalising mitochondrial metabolism. MitoTempo significantly altered the inflammatory profile of plasma treated cells. These novel data support a functional role for mitochondrial redox signaling in modulating the pathogenesis of preeclampsia and identifies mitochondrial-targeted antioxidants as potential therapeutic candidates. PMID:27604418

  3. Catalase Deficiency Accelerates Diabetic Renal Injury Through Peroxisomal Dysfunction

    PubMed Central

    Hwang, Inah; Lee, Jiyoun; Huh, Joo Young; Park, Jehyun; Lee, Hi Bahl; Ho, Ye-Shih; Ha, Hunjoo

    2012-01-01

    Mitochondrial reactive oxygen species (ROS) play an important role in diabetes complications, including diabetic nephropathy (DN). Plasma free fatty acids (FFAs) as well as glucose are increased in diabetes, and peroxisomes and mitochondria participate in FFA oxidation in an interconnected fashion. Therefore, we investigated whether deficiency of catalase, a major peroxisomal antioxidant, accelerates DN through peroxisomal dysfunction and abnormal renal FFA metabolism. Diabetes was induced by multiple injections of low-dose streptozotocin into catalase knock-out (CKO) and wild-type (WT) C57BL/6 mice. Murine mesangial cells (MMCs) transfected with catalase small interfering RNA followed by catalase overexpression were used to further elucidate the role of endogenous catalase. Despite equivalent hyperglycemia, parameters of DN, along with markers of oxidative stress, were more accelerated in diabetic CKO mice than in diabetic WT mice up to 10 weeks of diabetes. CKO mice and MMCs showed impaired peroxisomal/mitochondrial biogenesis and FFA oxidation. Catalase deficiency increased mitochondrial ROS and fibronectin expression in response to FFAs, which were effectively restored by catalase overexpression or N-acetylcysteine. These data provide unprecedented evidence that FFA-induced peroxisomal dysfunction exacerbates DN and that endogenous catalase plays an important role in protecting the kidney from diabetic stress through maintaining peroxisomal and mitochondrial fitness. PMID:22315314

  4. MiRSEA: Discovering the pathways regulated by dysfunctional MicroRNAs

    PubMed Central

    Xu, Yanjun; Jiang, Ying; Zhang, Chunlong; Li, Chunquan; Li, Xia

    2016-01-01

    Recent studies have shown that dysfunctional microRNAs (miRNAs) are involved in the progression of various cancers. Dysfunctional miRNAs may jointly regulate their target genes and further alter the activities of canonical biological pathways. Identification of the pathways regulated by a group of dysfunctional miRNAs could help uncover the pathogenic mechanisms of cancer and facilitate development of new drug targets. Current miRNA-pathway analyses mainly use differentially-expressed miRNAs to predict the shared pathways on which they act. However, these methods fail to consider the level of differential expression level, which could improve our understanding of miRNA function. We propose a novel computational method, MicroRNA Set Enrichment Analysis (MiRSEA), to identify the pathways regulated by dysfunctional miRNAs. MiRSEA integrates the differential expression levels of miRNAs with the strength of miRNA pathway associations to perform direct enrichment analysis using miRNA expression data. We describe the MiRSEA methodology and illustrate its effectiveness through analysis of data from hepatocellular cancer, gastric cancer and lung cancer. With these analyses, we show that MiRSEA can successfully detect latent biological pathways regulated by dysfunctional miRNAs. We have implemented MiRSEA as a freely available R-based package on CRAN (https://cran.r-project.org/web/packages/MiRSEA/). PMID:27474169

  5. Role of mitochondrial dysfunction in hyperglycaemia-induced coronary microvascular dysfunction: Protective role of resveratrol.

    PubMed

    Joshi, Mandar S; Williams, David; Horlock, Duncan; Samarasinghe, Thilini; Andrews, Karen L; Jefferis, Ann-Maree; Berger, Philip J; Chin-Dusting, Jaye P; Kaye, David M

    2015-05-01

    Microvascular complications are now recognized to play a major role in diabetic complications, and understanding the mechanisms is critical. Endothelial dysfunction occurs early in the course of the development of complications; the precise mechanisms remain poorly understood. Mitochondrial dysfunction may occur in a diabetic rat heart and may act as a source of the oxidative stress. However, the role of endothelial cell-specific mitochondrial dysfunction in diabetic vascular complications is poorly studied. Here, we studied the role of diabetes-induced abnormal endothelial mitochondrial function and the resultant endothelial dysfunction. Understanding the role of endothelial mitochondrial dysfunction in diabetic vasculature is critical in order to develop new therapies. We demonstrate that hyperglycaemia leads to mitochondrial dysfunction in microvascular endothelial cells, and that mitochondrial inhibition induces endothelial dysfunction. Additionally, we show that resveratrol acts as a protective agent; resveratrol-mediated mitochondrial protection may be used to prevent long-term diabetic cardiovascular complications.

  6. Erectile dysfunction in COPD patients.

    PubMed

    Turan, Onur; Ure, Iyimser; Turan, Pakize Ayse

    2016-02-01

    Sexual dysfunction is a common problem in chronic obstructive pulmonary disease (COPD). We aimed to assess the presence of erectile dysfunction (ED) in COPD patients. Ninety-three outpatients who had been diagnosed as COPD and followed in Bolvadin State Hospital, Afyon, Turkey, were included in the study. All patients underwent pulmonary function tests and arterial blood gas analysis. They completed International Physical Activity Questionnaire (IPAQ), Medical Research Council (MRC) Dyspnea Scale, Short Form 36-item Scale (SF-36), and International Index of Erectile Function (IIEF) Questionnaire. The mean age of 10 (10.8%) mild, 46 (49.5%) moderate, 28 (30.1%) severe, and 9 (9.7%) very severe COPD patients was 61.4 ± 9.8 years. Varying degrees of ED were detected in 67.7% of COPD patients. All patients with hypoxemia had ED. IPAQ score and all SF-36 parameters were low in patients with ED, while MRC score was high. Forced expiratory volume in one second, forced vital capacity, partial pressure of oxygen in blood, oxygen (O2) saturation, IPAQ score, and role-physical parameters were statistically low in ED patients (p = 0.04, 0.02, <0.01, <0.01, 0.02, and 0.04, respectively); MRC score was statistically higher in patients with ED (p = 0.02). Patients with moderate and severe ED had statistically lower score of mental health (p < 0.01 and p = 0.02, respectively). There was a positive correlation between IIEF score and IPAQ scores (p < 0.01), MRC scores (p = 0.01), general health (p < 0.01), role-physical (p < 0.01), role-emotional (p < 0.01), physical functioning (p < 0.01), and mental health (p < 0.01) parameters in SF-36. ED is frequently seen in COPD patients. Hypoxemia, smoking, and limitation of physical activity are thought to be associated with ED in COPD as mechanisms. Quality of life and the functional capacity are negatively affected with the presence of ED. It is important for a physician to question the sexual functions in patients with COPD. The

  7. A Lack of Bioactive Predictability for Marker Compounds Commonly Used for Herbal Medicine Standardization

    PubMed Central

    Ruiz, Guillermo G.; Nelson, Erik O.; Kozin, Adam F.; Turner, Tiffany C.; Waters, Robert F.; Langland, Jeffrey O.

    2016-01-01

    The use of botanical medicine by practitioners and the general public has dramatically increased in recent years. Most of these botanical therapeutics are obtained through commercial manufacturers or nutraceutical companies. The current standard of practice that manufacturers typically use to standardize botanicals is done based on the level of a well-known, abundant marker compound present in the botanical. This study evaluated the putative correlation between the level of a marker compound and the biological activity of eight common botanicals. Overall, the standardization of a botanical based on a marker compound was found not to be a reliable method when compared to in vitro bioactivity. A marker compound is often not the biologically active component of a plant and therefore the level of such a marker compound does not necessarily correlate with biological activity or therapeutic efficacy. PMID:27458926

  8. Auditory Dysfunction in Patients with Cerebrovascular Disease

    PubMed Central

    2014-01-01

    Auditory dysfunction is a common clinical symptom that can induce profound effects on the quality of life of those affected. Cerebrovascular disease (CVD) is the most prevalent neurological disorder today, but it has generally been considered a rare cause of auditory dysfunction. However, a substantial proportion of patients with stroke might have auditory dysfunction that has been underestimated due to difficulties with evaluation. The present study reviews relationships between auditory dysfunction and types of CVD including cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage, cerebrovascular malformation, moyamoya disease, and superficial siderosis. Recent advances in the etiology, anatomy, and strategies to diagnose and treat these conditions are described. The numbers of patients with CVD accompanied by auditory dysfunction will increase as the population ages. Cerebrovascular diseases often include the auditory system, resulting in various types of auditory dysfunctions, such as unilateral or bilateral deafness, cortical deafness, pure word deafness, auditory agnosia, and auditory hallucinations, some of which are subtle and can only be detected by precise psychoacoustic and electrophysiological testing. The contribution of CVD to auditory dysfunction needs to be understood because CVD can be fatal if overlooked. PMID:25401133

  9. Microalbuminuria - A better marker in hypertensive disorders of pregnancy.

    PubMed

    Babu, Ruby P; Christy, Alap; Hegde, Anupama; Manjrekar, Poornima; Joseph, Maria

    2015-09-01

    To assess the role of microalbuminuria in pre-eclampsia (PE) as a diagnostic marker, we studied 40 PE cases and 40 normotensive controls at 24 ± 4 weeks of gestation in women 20-35 years of age. The patients with PE had significant microalbuminuria in comparison with the controls, in addition to deranged renal function tests. The receiver operating characteristic curve showed that microalbuminuria had the highest sensitivity (100%) and good specificity (77.6%). Microalbuminuria had the highest area under the curve (0.869) for both diagnosis of PE and renal function assessment. Microalbuminuria also had a good correlation with systolic blood pressure in the cases with mild grades of renal dysfunction. Microalbuminuria is a specific marker in PE and it also helps to assess the renal function status. Therefore, microalbuminuria may be used in the early diagnosis and management of PE patients in order to reduce the immediate and long-term complications.

  10. Biological Filters.

    ERIC Educational Resources Information Center

    Klemetson, S. L.

    1978-01-01

    Presents the 1978 literature review of wastewater treatment. The review is concerned with biological filters, and it covers: (1) trickling filters; (2) rotating biological contractors; and (3) miscellaneous reactors. A list of 14 references is also presented. (HM)

  11. Randomized reverse marker strategy design for prospective biomarker validation.

    PubMed

    Eng, Kevin H

    2014-08-15

    We describe a novel study design for validating marker-based treatment strategies meant to select among possible therapeutic options using a biologic marker. Studying existing designs in realistic scenarios, we demonstrate that this design is more than four times more efficient for testing the interaction between a marker and its intended treatment. Our analysis employs a simple parametric framework that uncovers systematic biases in currently proposed designs and suggests how they may be accommodated or enumerated. In the context of markers for choosing a treatment for recurrent ovarian cancer, our proposal requires sample sizes on the order of recently completed phases II and III studies making validation studies for this clinical decision scenario viable.

  12. Polyphenols in preventing endothelial dysfunction.

    PubMed

    Biegańska-Hensoldt, Sylwia; Rosołowska-Huszcz, Danuta

    2017-03-27

    One of the main causes of mortality in developed countries is atherosclerosis. The pathogenesis of atherosclerosis is associated with endothelial dysfunction. Consumption of food rich in natural antioxidants including polyphenols significantly improves endothelial cells functions. Polyphenols have a beneficial effect on the human body and play an important part in protecting the cardiovascular system. Polyphenols present in food have antioxidant, anti-inflammatory, antihypertensive, antithrombotic and antiproliferative properties. Catechins cause an increase in the activity of endothelial nitric oxide synthase (eNOS) and increased production of nitric oxide (NO) and decrease in blood pressure. Catechins also reduce platelet adhesion, lower the concentration of C-reactive protein and tumor necrosis factor alpha and interleukin-6. Resveratrol inhibits NADPH oxidase expression, increases the expression of eNOS and NO production as well as decreases the expression of proinflammatory cytokines, and also lowers the concentration of the soluble forms of adhesion molecules - sICAM-1 and sVCAM-1 in blood. Quercetin reduces the blood level of low density lipoprotein cholesterol, lowers blood pressure, reduces the concentration of C-reactive protein and F2-isoprostane level. Curcumin has antagonistic activity to homocysteine. Curcumin increases the expression of eNOS and reduces oxidative DNA damage in rat cardiomyocytes. Numerous attempts are taken for improving the bioavailability of polyphenols in order to increase their use in the body.

  13. The anatomy of group dysfunction.

    PubMed

    Hayes, David F

    2014-04-01

    The dysfunction of the radiology group has 2 components: (1) the thinking component-the governance structure of the radiology group; how we manage the group; and (2) the structural component-the group's business model and its conflict with the partner's personal business model. Of the 2 components, governance is more important. Governance must be structured on classic, immutable business management principles. The structural component, the business model, is not immutable. In fact, it must continually change in response to the marketplace. Changes in the business model should occur only if demanded or permitted by the marketplace; instituting changes for other reasons, including personal interests or deficient knowledge of the deciders, is fundamentally contrary to the long-term interests of the group and its owners. First, we must learn basic business management concepts to appreciate the function and necessity of standard business models and standard business governance. Peter Drucker's The Effective Executive is an excellent primer on the subjects of standard business practices and the importance of a functional, authorized, and fully accountable chief executive officer.

  14. Tumor-induced immune dysfunction.

    PubMed

    Kiessling, R; Wasserman, K; Horiguchi, S; Kono, K; Sjöberg, J; Pisa, P; Petersson, M

    1999-10-01

    Immune system-based approaches for the treatment of malignant disease over the past decades have often focused on cytolytic effector cells such as cytotoxic T lymphocytes (CTL), and natural killer (NK) cells. It has also been demonstrated that tumor-bearing mice can be cured using a wide variety of approaches, some of which involve cytokine-mediated enhancement of CTL and NK cell activity. However, the apparent success in mice stands in contrast to the current situation in the clinic, wherein only a minority of patients have thus far benefited from CTL- or NK cell-based antitumor approaches. The underlying causes of tumor-associated immune suppression of CTL and NK cell activity are discussed, and features of interest shared with HIV infection, leprosy, and rheumatoid arthritis are also be mentioned. Remarkable and very recent observations have shed more light upon the causes of dysfunctional alterations in CTL and NK cells often associated with these diseases, that in turn have suggested new immunotherapeutic approaches for cancer and infectious disease.

  15. Mitochondrial dysfunction in neuromuscular disorders.

    PubMed

    Katsetos, Christos D; Koutzaki, Sirma; Melvin, Joseph J

    2013-09-01

    This review deciphers aspects of mitochondrial (mt) dysfunction among nosologically, pathologically, and genetically diverse diseases of the skeletal muscle, lower motor neuron, and peripheral nerve, which fall outside the traditional realm of mt cytopathies. Special emphasis is given to well-characterized mt abnormalities in collagen VI myopathies (Ullrich congenital muscular dystrophy and Bethlem myopathy), megaconial congenital muscular dystrophy, limb-girdle muscular dystrophy type 2 (calpainopathy), centronuclear myopathies, core myopathies, inflammatory myopathies, spinal muscular atrophy, Charcot-Marie-Tooth neuropathy type 2, and drug-induced peripheral neuropathies. Among inflammatory myopathies, mt abnormalities are more prominent in inclusion body myositis and a subset of polymyositis with mt pathology, both of which are refractory to corticosteroid treatment. Awareness is raised about instances of phenotypic mimicry between cases harboring primary mtDNA depletion, in the context of mtDNA depletion syndrome, and established neuromuscular disorders such as spinal muscular atrophy. A substantial body of experimental work, derived from animal models, attests to a major role of mitochondria (mt) in the early process of muscle degeneration. Common mechanisms of mt-related cell injury include dysregulation of the mt permeability transition pore opening and defective autophagy. The therapeutic use of mt permeability transition pore modifiers holds promise in various neuromuscular disorders, including muscular dystrophies.

  16. Biological Variation and Diagnostic Accuracy of Dehydration Assessment Markers

    DTIC Science & Technology

    2010-07-01

    reference intakes for water, potassium , sodium, chloride, and sulfate. Washington, DC: National Academies Press, 2005:73–185. 3. Manz F. Hydration and...requirements (eg, climate, activity, and dietary solute load) (2, 20), acute changes in body mass (Bm) may be used to accurately measure de- hydration across...both clinical and sports medicine disciplines (8, 21–25). When the balance between fluid intake and output is carefully controlled experimentally, a

  17. Biological Markers of Environmental Carcinogens in Breast Cancer

    DTIC Science & Technology

    1996-10-01

    to correlate well with SSCP techniques for mutant detection (35). p5 3 analysis by immunohistochemistry is ongoing as tissue blocks are released to us...2291 7. Felton JS, Knize MG. Occurrence, identification, and bacterial mutagenicity of heterocyclic amines in cooked food . Mutat Res 1991;259:205...as well as the workplace environment, drinking water and food (5). Incomplete combustion of organic material, including fossil fuels, is the major

  18. Biological Markers of Cognition in Prodromal Huntington's Disease: A Review

    ERIC Educational Resources Information Center

    Papp, Kathryn V.; Kaplan, Richard F.; Snyder, Peter J.

    2011-01-01

    Huntington's disease (HD), an autosomal-dominant genetic disorder, has historically been viewed as a degenerative movement disorder but it also includes psychiatric symptoms and progressive cognitive decline. There has been a lack of consensus in the literature about whether or not cognitive signs can be detected in carriers before clinical…

  19. Biological (molecular and cellular) markers of toxicity. [Oryzias latipes

    SciTech Connect

    Shugart, L.R.

    1991-04-01

    The objective of this study is to evaluate the use of the Japanese Medaka (Oryzias latipes) as a predictor of genotoxicity following exposure to carcinogens. The early molecular events associated with genotoxicity in Medaka tissues following exposure to known carcinogens will be investigated. The primary endpoint for most small fish carcinogenesis studies is histopathogenic identification of a neoplastic lesion. Such lesions usually occur in the liver, and histogenesis of liver neoplasms in fish is similar to that in rodents. Because of the latent period between initial contact with chemical agents in the environmental and subsequent expression of deleterious effects, development of sensitive assays for detection and estimating early exposure is needed. Carcinogen-induced DNA damage will be assessed as a possible measure of severity of exposure, correlated with activation of liver enzymes. 6 refs., 2 figs., 1 tab.

  20. Monitoring dredging effectiveness using biological and chemical markers of exposure

    EPA Science Inventory

    Sediments in portions of the Ashtabula and Ottawa rivers are contaminated with polychlorinated biphenyls (PCBs) and polyaromatic hydrocarbons (PAHs) and both rivers have been designated by the International Joint Commission as a Great Lakes Area of Concern. Approximately 550,000...

  1. Developmental Dyslexia: Early Precursors, Neurobehavioral Markers, and Biological Substrates

    ERIC Educational Resources Information Center

    Benasich, April A., Ed.; Fitch, R. Holly, Ed.

    2012-01-01

    Understanding the precursors and early indicators of dyslexia is key to early identification and effective intervention. Now there's a single research volume that brings together the very latest knowledge on the earliest stages of dyslexia and the diverse genetic, neurobiological, and cognitive factors that may contribute to it. Based on findings…

  2. CD14(+)CD16(++) "nonclassical" monocytes are associated with endothelial dysfunction in patients with coronary artery disease.

    PubMed

    Urbanski, Karol; Ludew, Dominik; Filip, Grzegorz; Filip, Magdalena; Sagan, Agnieszka; Szczepaniak, Piotr; Grudzien, Grzegorz; Sadowski, Jerzy; Jasiewicz-Honkisz, Barbara; Sliwa, Tomasz; Kapelak, Boguslaw; McGinnigle, Eilidh; Mikolajczyk, Tomasz; Guzik, Tomasz J

    2017-02-23

    Endothelial dysfunction and inflammation are key mechanisms of vascular disease. We hypothesised that heterogeneity of monocyte subpopulations may be related to the development of vascular dysfunction in coronary artery disease (CAD). Therefore, we examined the relationships between monocyte subsets (CD14(++)CD16(-) "classical - Mon1", CD14(++)CD16(+) "intermediate - Mon2" and CD14(+)CD16(++) "nonclassical - Mon3"), endothelial function and risk factor profiles in 130 patients with CAD undergoing coronary artery bypass grafting. This allowed for direct nitric oxide (NO) bioavailability assessment using isometric tension studies ex vivo (acetylcholine; ACh- and sodium-nitropruside; SNP-dependent) in segments of internal mammary arteries. The expression of CD14 and CD16 antigens and activation markers were determined in peripheral blood mononuclear cells using flow cytometry. Patients with high CD14(+)CD16(++) "nonclassical" and low CD14(++)CD16(-) "classical" monocytes presented impaired endothelial function. High frequency of CD14(+)CD16(++) "nonclassical" monocytes was associated with increased vascular superoxide production. Furthermore, endothelial dysfunction was associated with higher expression of activation marker CD11c selectively on CD14(+)CD16(++) monocytes. Nonclassical and classical monocyte frequencies remained independent predictors of endothelial dysfunction when major risk factors for atherosclerosis were taken into account (β=0.18 p=0.04 and β=-0.19 p=0.03, respectively). In summary, our data indicate that CD14(+)CD16(++) "nonclassical" monocytes are associated with more advanced vascular dysfunction measured as NO- bioavailability and vascular reactive oxygen species production.

  3. Velo-pharyngeal dysfunction: Evaluation and management

    PubMed Central

    Marsh, Jeffrey L.

    2009-01-01

    Separation of the nasal and oral cavities by dynamic closure of the velo-pharyngeal port is necessary for normal speech and swallowing. Velo-pharyngeal dysfunction (VPD) may either follow repair of a cleft palate or be independent of clefting. While the diagnosis of VPD is made by audiologic perceptual evaluation of speech, identification of the mechanism of the dysfunction requires instrumental visualization of the velo-pharyngeal port during specific speech tasks. Matching the specific intervention for management of VPD with the type of dysfunction, i.e. differential management for differential diagnosis, maximizes the result while minimizing the morbidity of the intervention. PMID:19884668

  4. Sexual dysfunction within an adult developmental perspective.

    PubMed

    Fagan, P J; Meyer, J K; Schmidt, C W

    1986-01-01

    The focus of this paper is on the adult who has adequately mastered the oedipal stage of psychosexual development and who presents with a sexual dysfunction. Drawing on the developmental sequence of Erik Erikson, the authors suggest that failure to address adequately an adult psychosocial crisis may result in sexual dysfunction. There may be both adult developmental deficits and regression to adolescent and adult stages previously negotiated. Both may be symptomatically represented by sexual dysfunction. The authors urge that the sexual and marital problems be evaluated within an adult developmental framework and that the therapy address the psychosocial issues which are appropriate to the developmental stage of the patient.

  5. Management of Chronic Spinal Cord Dysfunction

    PubMed Central

    Abrams, Gary M.; Ganguly, Karunesh

    2015-01-01

    Purpose of Review: Both acute and chronic spinal cord disorders present multisystem management problems to the clinician. This article highlights key issues associated with chronic spinal cord dysfunction. Recent Findings: Advances in symptomatic management for chronic spinal cord dysfunction include use of botulinum toxin to manage detrusor hyperreflexia, pregabalin for management of neuropathic pain, and intensive locomotor training for improved walking ability in incomplete spinal cord injuries. Summary: The care of spinal cord dysfunction has advanced significantly over the past 2 decades. Management and treatment of neurologic and non-neurologic complications of chronic myelopathies ensure that each patient will be able to maximize their functional independence and quality of life. PMID:25651225

  6. Male Sexual Dysfunction and Chronic Kidney Disease

    PubMed Central

    Edey, Matthew M.

    2017-01-01

    Male sexual dysfunction is common in chronic kidney disease (CKD), particularly in end-stage renal disease. Historically, this cause of considerable morbidity has been under-reported and under-recognized. The ideal approach to diagnosis and management remains unclear due to a paucity of good quality data, but an understanding of the pathophysiology is necessary in order to address the burden of this important complication of CKD. This paper will review the endocrine dysfunction that occurs in renal disease, particularly the hypothalamic–pituitary–gonadal axis, discuss the causes of erectile dysfunction, infertility, and altered body image and libido in these patients and suggest appropriate treatment interventions. PMID:28382300

  7. [Management of autonomic dysfunction in Parkinson's disease].

    PubMed

    Crespo-Burillo, José A; Alarcia-Alejos, Raquel

    2015-04-16

    Autonomic dysfunction is a common manifestation in patients with in Parkinson's disease, which can sometimes precede motor impairment. It can be expressed as orthostatic and postprandial hypotension, supine hypertension, hypersalivation, constipation, delayed gastric emptying, dyshidrosis, bladder and sexual dysfunction. It impairs the quality of life of patients and complicates the management of motor symptoms. Evidence available to treat complications is low. Our aim is to review the pathophysiology and clinical features of autonomic dysfunction in Parkinson's disease and provide a practical approach to handling the available evidence.

  8. Potential markers of oxidative stress in stroke.

    PubMed

    Cherubini, Antonio; Ruggiero, Carmelinda; Polidori, M Cristina; Mecocci, Patrizia

    2005-10-01

    Free radical production is increased in ischemic and hemorrhagic stroke, leading to oxidative stress that contributes to brain damage. The measurement of oxidative stress in stroke would be extremely important for a better understanding of its pathophysiology and for identifying subgroups of patients that might receive targeted therapeutic intervention. Since direct measurement of free radicals and oxidized molecules in the brain is difficult in humans, several biological substances have been investigated as potential peripheral markers. Among lipid peroxidation products, malondialdehyde, despite its relevant methodological limitations, is correlated with the size of ischemic stroke and clinical outcome, while F2-isoprostanes appear to be promising, but they have not been adequately evaluated. 8-Hydroxy-2-deoxyguanosine has been extensively investigated as markers of oxidative DNA damage but no study has been done in stroke patients. Also enzymatic and nonenzymatic antioxidants have been proposed as indirect markers. Among them ascorbic acid, alpha-tocopherol, uric acid, and superoxide dismutase are related to brain damage and clinical outcome. After a critical evaluation of the literature, we conclude that, while an ideal biomarker is not yet available, the balance between antioxidants and by-products of oxidative stress in the organism might be the best approach for the evaluation of oxidative stress in stroke patients.

  9. Smart markers for watershed-based cell segmentation.

    PubMed

    Koyuncu, Can Fahrettin; Arslan, Salim; Durmaz, Irem; Cetin-Atalay, Rengul; Gunduz-Demir, Cigdem

    2012-01-01

    Automated cell imaging systems facilitate fast and reliable analysis of biological events at the cellular level. In these systems, the first step is usually cell segmentation that greatly affects the success of the subsequent system steps. On the other hand, similar to other image segmentation problems, cell segmentation is an ill-posed problem that typically necessitates the use of domain-specific knowledge to obtain successful segmentations even by human subjects. The approaches that can incorporate this knowledge into their segmentation algorithms have potential to greatly improve segmentation results. In this work, we propose a new approach for the effective segmentation of live cells from phase contrast microscopy. This approach introduces a new set of "smart markers" for a marker-controlled watershed algorithm, for which the identification of its markers is critical. The proposed approach relies on using domain-specific knowledge, in the form of visual characteristics of the cells, to define the markers. We evaluate our approach on a total of 1,954 cells. The experimental results demonstrate that this approach, which uses the proposed definition of smart markers, is quite effective in identifying better markers compared to its counterparts. This will, in turn, be effective in improving the segmentation performance of a marker-controlled watershed algorithm.

  10. Ensete superbum ameliorates renal dysfunction in experimental diabetes mellitus

    PubMed Central

    Sreekutty, MS; Mini, S

    2016-01-01

    Objective(s): Hyperglycemia mediated oxidative stress plays a key role in the pathogenesis of diabetic complications like nephropathy. In the present study, we evaluated the effect of ethanolic extract of Ensete superbum seeds (ESSE) on renal dysfunction and oxidative stress in streptozotocin-induced diabetic rats. Materials and Methods: Glucose, HbA1c, total protein, albumin, renal function markers (urea, uric acid and creatinine), and lipid peroxidation levels were evaluated. Renal enzymatic and non-enzymatic antioxidants were examined along with renal histopathological study. Results: ESSE (400 mg/kg BW t) administration reduced glucose and HbA1c, and improved serum total protein and albumin in diabetic rats. ESSE in diabetic rats recorded decrement in renal function markers and renal lipid peroxidation products along with significant increment in enzymatic and non-enzymatic antioxidants. Renal morphological abnormalities of diabetic rats were markedly ameliorated by E. superbum. Conclusion: These results suggest that the antioxidant effect of E. superbum could ameliorate oxidative stress and delay/prevent the progress of diabetic nephropathy in diabetes mellitus. PMID:27096072

  11. Urinary markers for bladder cancer

    PubMed Central

    Smith, Zachary L.

    2013-01-01

    Bladder cancer has the fifth highest incidence of all malignancies in the United States, with a propensity to recur, requiring lifelong surveillance after diagnosis. Urinary markers of disease have been of extreme interest in this field in an effort to simplify surveillance schedules and improve early detection of tumors. Many markers have been described, but most remain investigational. However, some markers have undergone clinical trials and are approved for clinical use. In this review, urinary markers and their application for screening and surveillance of bladder cancer are discussed. PMID:23864929

  12. Global end-diastolic volume an emerging preload marker vis-a-vis other markers - Have we reached our goal?

    PubMed Central

    Kapoor, P. M; Bhardwaj, Vandana; Sharma, Amita; Kiran, Usha

    2016-01-01

    A reliable estimation of cardiac preload is helpful in the management of severe circulatory dysfunction. The estimation of cardiac preload has evolved from nuclear angiography, pulmonary artery catheterization to echocardiography, and transpulmonary thermodilution (TPTD). Global end-diastolic volume (GEDV) is the combined end-diastolic volumes of all the four cardiac chambers. GEDV has been demonstrated to be a reliable preload marker in comparison with traditionally used pulmonary artery catheter-derived pressure preload parameters. Recently, a new TPTD system called EV1000™ has been developed and introduced into the expanding field of advanced hemodynamic monitoring. GEDV has emerged as a better preload marker than its previous conventional counterparts. The advantage of it being measured by minimum invasive methods such as PiCCO™ and newly developed EV1000™ system makes it a promising bedside advanced hemodynamic parameter. PMID:27716702

  13. [Behavioral approach to sexual dysfunctions].

    PubMed

    Gellman, C

    1983-01-01

    The basic principles of those behaviourist approaches are: - Treatment of the couple, no matter which partner is apparently "responsible" for the sexual problem, and mutual involvement of both partners. - Sexual information and education regarding the cycle of sexual response, anatomy, biology, and sexual techniques. - Changing negative attitudes vis-à-vis sexuality. - Elimination of sexual anxieties. - Improvement of verbal and corporal communication within the couple. - Learning to know oneself and others better--Initiation to psychological attention and observation.

  14. [Vascular dysfunction in metabolic disorders: evaluation of some therapeutic interventions].

    PubMed

    Bouskela, Eliete; Kraemer de Aguiar, Luiz Guillherme; Nivoit, Pierre; Bahia, Luciana R; Villela, Nivaldo R; Bottino, Daniel A

    2007-03-01

    Cardiovascular diseases continue to be the main cause of death in most industrialized countries. Endothelial dysfunction, a systemic process, is the earliest known marker of atherosclerosis and has become a major focus in acute ischemic disorders. We are investigating the hypothesis that, in these diseases, microvascular and endothelial dysfunctions occur simultaneously and precede the onset of macrovascular disease. We studied, to our knowledge for the first time in the same subjects, microvascular and endothelial functions in 11 patients with type 2 diabetes. 36 metabolic syndrome patients (NCEP-ATPIII criteria) and 25 young obese women matched with healthy controls. Micro vascular morphology and hemodynamics were evaluated non-invasively by means of nailfold videocapillaroscopy. Red blood cell velocity (RBCV, mm/s) was measured at rest and after release from 60 s of arterial occlusion (RBCVmax, mm/s) at the finger base, along with the time to reach RBCVmax (TRBCVmax, s), by video analysis with Cap Image software. Venous occlusion plethysmography was performed after intra-arterial infusions of acetylcholine and sodium nitroprusside to assess endo thelial-dependent and -independent vasodilation, respectively. We found similar results in the three groups of subjects, namely a significant decrease in RBCVmax, an increase in TRBCVmax, and a decrease in endothelial-dependent vasodilation. These findings clearly demonstrate that the two dysfunctions occur simultaneously in these groups of patients. Several mechanisms which could impair micro vascular and endothelial functions are associated with insulin resistance, and drugs that act on insulin resistance might thus be beneficial. Metformin, given to 16 first-degree relatives of patients with type 2 diabetes mellitus, who had the metabolic syndrome and normal glucose tolerance (ADA criteria), improved endothelial-dependent vasodilation and microcirculatory function. Rosiglitazone, given to 18 patients with the

  15. Neither Proteinuria Nor Albuminuria Is Associated With Endothelial Dysfunction in HIV-Infected Patients Without Diabetes or Hypertension

    PubMed Central

    Shen, Changyu; Mather, Kieren J.; Agarwal, Rajiv; Dubé, Michael P.

    2011-01-01

    It is unknown whether systemic endothelial dysfunction underlies the association between nephropathy and cardiovascular disease (CVD) in persons infected with human immunodeficiency virus (HIV). Spot urine protein to creatinine ratio, spot urine albumin to creatinine ratio, creatinine clearance, estimated glomerular filtration rate, and flow-mediated dilation (FMD) of the brachial artery were evaluated in 123 study participants infected with HIV (58 receiving antiretroviral therapy [ART] and 65 not receiving ART) with no history of diabetes or hypertension. None of the renal markers, modeled as either continuous or categorical variables, correlated with FMD. Contrary to expectations, endothelial dysfunction may not be the link between nephropathy and CVD in HIV. PMID:22013226

  16. Erectile Dysfunction: MedlinePlus Health Topic

    MedlinePlus

    ... Erection problems - aftercare (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Erectile Dysfunction updates ... Erection problems - aftercare Prolactin blood test Related Health Topics Penis Disorders National Institutes of Health The primary ...

  17. Academic Achievement and Minimal Brain Dysfunction

    ERIC Educational Resources Information Center

    Edwards, R. Philip; And Others

    1971-01-01

    The investigation provided no evidence that a diagnosis of minimal brain dysfunction based on a pediatric neurological evaluation and/or visual-motor impairment as measured by the Bender-Gestalt, is a useful predictor of academic achievement. (Author)

  18. Erectile Dysfunction: A Sign of Heart Disease?

    MedlinePlus

    ... of plaques in the arteries of your body (atherosclerosis) was believed to be the reason why erectile ... the penis, and aids in the development of atherosclerosis. Erectile dysfunction does not always indicate an underlying ...

  19. Marital sexual dysfunction:introductory concepts.

    PubMed

    Levine, S B

    1976-04-01

    The concepts presented in this overview of marital sexual dysfunction are derived from increasing clinical experience with couples who seek help for their sexual problems. These couples, in marked contrast to couples with good sexual functioning, usually report a steady state of emotional dissatisfaction and minimal physical pleasure from sex. The affectual and behavioral consequences of persistent dysfunction are reviewed. Sexual therapy is discussed in terms of its two elements, sensate focus and psychotherapy. The various tastks which the sexual therapist may have to accomplish with individual couples are described. Consideration is given to the specific hypothese usually offered as explanation for sexual dysfunction-i.e., organic factors, varying degrees of relationship failure, poor communication, sexual ignorance, performance anxiety, and intrapsychic residua of past experience. A protocol for the screening physician to use in the formulation of a reasonable clinical plan for dysfunctional couples is included.

  20. Erectile dysfunction in the cardiovascular patient.

    PubMed

    Vlachopoulos, Charalambos; Jackson, Graham; Stefanadis, Christodoulos; Montorsi, Piero

    2013-07-01

    Erectile dysfunction is common in the patient with cardiovascular disease. It is an important component of the quality of life and it also confers an independent risk for future cardiovascular events. The usual 3-year time period between the onset of erectile dysfunction symptoms and a cardiovascular event offers an opportunity for risk mitigation. Thus, sexual function should be incorporated into cardiovascular disease risk assessment for all men. A comprehensive approach to cardiovascular risk reduction (comprising of both lifestyle changes and pharmacological treatment) improves overall vascular health, including sexual function. Proper sexual counselling improves the quality of life and increases adherence to medication. This review explores the critical connection between erectile dysfunction and cardiovascular disease and evaluates how this relationship may influence clinical practice. Algorithms for the management of patient with erectile dysfunction according to the risk for sexual activity and future cardiovascular events are proposed.

  1. Temporomandibular dysfunction and headache disorder.

    PubMed

    Speciali, José G; Dach, Fabíola

    2015-02-01

    It has been well established that primary headaches (especially migraine, chronic migraine, and tension-type headache) and temporomandibular dysfunction (TMD) are comorbid diseases, with the presence of one of them in a patient increasing the prevalence of the others. The relationship between the 2 diseases may involve the sharing of common physiopathological aspects. Studies about the treatment of this disease association have shown that a simultaneous therapeutic approach to the 2 diseases is more effective than the separate treatment of each. As a consequence, specialists in orofacial pain are now required to know the criteria for the diagnosis of headaches, and headache physicians are required to know the semiologic aspects of orofacial pain. Nevertheless, a headache may be attributed to TMD, instead be an association of 2 problems - TMD and primary headaches - in these cases a secondary headache, described in item 11.7 of the International Classification of Headache Disorders, is still a controversial topic. Attempts to determine the existence of this secondary headache with a specific or suggestive phenotype have been frustrated. The conclusion that can be reached based on the few studies published thus far is that this headache has a preferential unilateral or bilateral temporal location and migraine-like or tension-type headache-like clinical characteristics. In the present review, we will consider the main aspects of the TMD-headache relationship, that is, comorbidity of primary headaches and TMD and clinical aspects of the headaches attributed to TMD from the viewpoint of the International Headache Society and of a group of specialists in orofacial pain. This paper aims to explore our understanding of the association between TMD and headaches in general and migraine in particular.

  2. Environmental enteric dysfunction: An overview

    PubMed Central

    Crane, Rosie J.; Jones, Kelsey D. J.; Berkley, James A.

    2015-01-01

    Background Environmental enteric dysfunction (EED) refers to an incompletely defined syndrome of inflammation, reduced absorptive capacity, and reduced barrier function in the small intestine. It is widespread among children and adults in low- and middle-income countries. Understanding of EED and its possible consequences for health is currently limited. Objective A narrative review of the current understanding of EED: epidemiology, pathogenesis, therapies, and relevance to child health. Methods Searches for key papers and ongoing trials were conducted using PUBMED 1966–June 2014; ClinicalTrials.gov; the WHO Clinical Trials Registry; the Cochrane Library; hand searches of the references of retrieved literature; discussions with experts; and personal experience from the field. Results EED is established during infancy and is associated with poor sanitation, certain gut infections, and micronutrient deficiencies. Helicobacter pylori infection, small intestinal bacterial overgrowth (SIBO), abnormal gut microbiota, undernutrition, and toxins may all play a role. EED is usually asymptomatic, but it is important due to its association with stunting. Diagnosis is frequently by the dual sugar absorption test, although other biomarkers are emerging. EED may partly explain the reduced efficacy of oral vaccines in low- and middle-income countries and the increased risk of serious infection seen in children with undernutrition. Conclusions Despite its potentially significant impacts, it is currently unclear exactly what causes EED and how it can be treated or prevented. Ongoing trials involve nutritional supplements, water and sanitation interventions, and immunomodulators. Further research is needed to better understand this condition, which is of likely crucial importance for child health and development in low- and middle-income settings. PMID:25902619

  3. Postprostatectomy Erectile Dysfunction: A Review

    PubMed Central

    Salonia, Andrea; Briganti, Alberto; Montorsi, Francesco

    2016-01-01

    In the current era of the early diagnosis of prostate cancer (PCa) and the development of minimally invasive surgical techniques, erectile dysfunction (ED) represents an important issue, with up to 68% of patients who undergo radical prostatectomy (RP) complaining of postoperative erectile function (EF) impairment. In this context, it is crucial to comprehensively consider all factors possibly associated with the prevention of post-RP ED throughout the entire clinical management of PCa patients. A careful assessment of both oncological and functional baseline characteristics should be carried out for each patient preoperatively. Baseline EF, together with age and the overall burden of comorbidities, has been strongly associated with the chance of post-RP EF recovery. With this goal in mind, internationally validated psychometric instruments are preferable for ensuring proper baseline EF evaluations, and questionnaires should be administered at the proper time before surgery. Careful preoperative counselling is also required, both to respect the patient's wishes and to avoid false expectations regarding eventual recovery of baseline EF. The advent of robotic surgery has led to improvements in the knowledge of prostate surgical anatomy, as reflected by the formal redefinition of nerve-sparing techniques. Overall, comparative studies have shown significantly better EF outcomes for robotic RP than for open techniques, although data from prospective trials have not always been consistent. Preclinical data and several prospective randomized trials have demonstrated the value of treating patients with oral phosphodiesterase 5 inhibitors (PDE5is) after surgery, with the concomitant potential benefit of early re-oxygenation of the erectile tissue, which appears to be crucial for avoiding the eventual penile structural changes that are associated with postoperative neuropraxia and ultimately result in severe ED. For patients who do not properly respond to PDE5is, proper

  4. Mitochondrial dysfunction in myofibrillar myopathy.

    PubMed

    Vincent, Amy E; Grady, John P; Rocha, Mariana C; Alston, Charlotte L; Rygiel, Karolina A; Barresi, Rita; Taylor, Robert W; Turnbull, Doug M

    2016-10-01

    Myofibrillar myopathies (MFM) are characterised by focal myofibrillar destruction and accumulation of myofibrillar elements as protein aggregates. They are caused by mutations in the DES, MYOT, CRYAB, FLNC, BAG3, DNAJB6 and ZASP genes as well as other as yet unidentified genes. Previous studies have reported changes in mitochondrial morphology and cellular positioning, as well as clonally-expanded, large-scale mitochondrial DNA (mtDNA) deletions and focal respiratory chain deficiency in muscle of MFM patients. Here we examine skeletal muscle from patients with desmin (n = 6), ZASP (n = 1) and myotilin (n = 2) mutations and MFM protein aggregates, to understand how mitochondrial dysfunction may contribute to the underlying mechanisms causing disease pathology. We have used a validated quantitative immunofluorescent assay to study respiratory chain protein levels, together with oxidative enzyme histochemistry and single cell mitochondrial DNA analysis, to examine mitochondrial changes. Results demonstrate a small number of clonally-expanded mitochondrial DNA deletions, which we conclude are due to both ageing and disease pathology. Further to this we report higher levels of respiratory chain complex I and IV deficiency compared to age matched controls, although overall levels of respiratory deficient muscle fibres in patient biopsies are low. More strikingly, a significantly higher percentage of myofibrillar myopathy patient muscle fibres have a low mitochondrial mass compared to controls. We concluded this is mechanistically unrelated to desmin and myotilin protein aggregates; however, correlation between mitochondrial mass and muscle fibre area is found. We suggest this may be due to reduced mitochondrial biogenesis in combination with muscle fibre hypertrophy.

  5. The role of dysfunctional HDL in atherosclerosis

    PubMed Central

    Navab, Mohamad; Reddy, Srinivasa T.; Van Lenten, Brian J.; Anantharamaiah, G. M.; Fogelman, Alan M.

    2009-01-01

    This review focuses on HDL function in modulating LDL oxidation and LDL-induced inflammation. Dysfunctional HDL has been identified in animal models and humans with chronic inflammatory diseases including atherosclerosis. The loss of antiinflammatory function correlated with a loss of function in reverse cholesterol transport. In animal models and perhaps in humans, dysfunctional HDL can be improved by apoA-I mimetic peptides that bind oxidized lipids with high affinity. PMID:18955731

  6. Erectile dysfunction: physiology, causes and patient management.

    PubMed

    Steggall, Martin J

    This article examines the prevalence, causes, identification, assessment and treatment options for men with erectile dysfunction. Erectile dysfunction is thought to affect one in ten men across the UK and is often a consequence of pathology and/or pharmacology. Treatment can be offered to all patients, but the keys to management are identification, accurate assessment and focused therapy. Nurses are well placed to identify and support men who have this distressing problem.

  7. Towards an analysis of dysfunctional grammar.

    PubMed

    Rigaudeau-McKenna, B

    2005-01-01

    This article applies Systemic Functional Linguistics (SFL) to the study of language dysfunction. It demonstrates the potential that Systemic Functional analysis can offer to one aspect of the analysis of language dysfunction--the failure to realise complexes of clauses. For the purpose of analysis, new concepts and new measures have been created. The newly defined concepts and measures are illustrated in the discourse data of normally developing children and adolescents with brain injury.

  8. Salivary gland dysfunction following radioactive iodine therapy

    SciTech Connect

    Wiesenfeld, D.; Webster, G.; Cameron, F.; Ferguson, M.M.; MacFadyen, E.E.; MacFarlane, T.W.

    1983-02-01

    Radioactive iodine is used extensively for the treatment of thyrotoxicosis and thyroid carcinoma. Iodine is actively taken up by the salivary glands and, following its use, salivary dysfunction may result as a consequence of radiation damage. The literature is reviewed and a case is reported in which a patient presented with a significant increase in caries rate attributed to salivary dysfunction following radioactive iodine therapy for a thyroid carcinoma.

  9. BIOMARKERS IN DIABETES: HEMOGLOBIN A1c, VASCULAR AND TISSUE MARKERS

    PubMed Central

    Lyons, Timothy J; Basu, Arpita

    2012-01-01

    Biomarkers are conventionally defined as ‘biological molecules that represent health and disease states.’ They typically are measured in readily available body fluids (blood or urine), lie outside the causal pathway, are able to detect sub-clinical disease, and are used to monitor clinical and sub-clinical disease burden and response to treatments. Biomarkers can be “direct” endpoints of the disease itself, or “indirect” or surrogate endpoints. New technologies (such as metabolomics, proteomics, genomics) bring a wealth of opportunity to develop new biomarkers. Other new technologies enable the development of non-molecular, functional or bio-physical tissue-based biomarkers. Diabetes mellitus is a complex disease affecting almost every tissue and organ system, with metabolic ramifications extending far beyond impaired glucose metabolism. Biomarkers may reflect the presence and severity of hyperglycemia (i.e. diabetes itself), or the presence and severity of the vascular complications of diabetes. Illustrative examples are considered in this brief review. In blood, hemoglobin A1c (HbA1c) may be considered as a biomarker for the presence and severity of hyperglycemia, implying diabetes or pre-diabetes, or, over time, as a “biomarker for a risk factor”, i.e. hyperglycemia as a risk factor for diabetic retinopathy, nephropathy, and other vascular complications of diabetes. In tissues, glycation and oxidative stress resulting from hyperglycemia and dyslipidemia lead to widespread modification of biomolecules by advanced glycation end products (AGEs). Some of these altered species may serve as biomarkers, whereas others may lie in the causal pathway for vascular damage. New non-invasive technologies can detect tissue damage mediated by AGE formation: these include indirect measures such as pulse wave analysis (a marker of vascular dysfunction) and more direct markers such as skin autofluorescence (a marker of long-term accumulation of AGEs). In the future

  10. Salivary Acetylcholinesterase Activity Is Increased in Parkinson's Disease: A Potential Marker of Parasympathetic Dysfunction

    PubMed Central

    Fedorova, Tatyana; Knudsen, Cindy Soendersoe; Mouridsen, Kim; Nexo, Ebba; Borghammer, Per

    2015-01-01

    Introduction. Decreased salivary flow and xerostomia are frequent findings in Parkinson's disease (PD), possibly caused by alterations in the parasympathetic tonus. Here we explore salivary acetylcholinesterase (AChE) activity as a potential biomarker in PD. Methods. We measured salivary flow, AChE activity, and total protein concentration in 30 PD patients and 49 healthy controls. We also performed exploratory correlation analyses with disease duration, motor symptom severity, autonomic complaints, and other nonmotor symptoms. Results. PD patients displayed significantly decreased salivary flow rate, significantly increased salivary AChE activity, and total protein concentration. Importantly, the AChE activity/total protein ratio was significantly increased in PD patients, suggesting that increased AChE activity cannot be explained solely by upconcentration of saliva. The Unified PD Rating Scale (UPDRS) score displayed significant correlation with total salivary protein (P = 0.002) and near-significant correlation with salivary flow (P = 0.07). Color vision test scores were also significantly correlated with AChE activity (P = 0.04) and total protein levels (P = 0.002). Conclusion. Salivary AChE activity is increased in PD patients compared to healthy controls. Future studies are needed to elucidate whether this parameter reflects the extent of neuronal damage and parasympathetic denervation in the salivary glands of PD patients. PMID:25767737

  11. Index markers of chronic fatigue syndrome with dysfunction of TCA and urea cycles

    PubMed Central

    Yamano, Emi; Sugimoto, Masahiro; Hirayama, Akiyoshi; Kume, Satoshi; Yamato, Masanori; Jin, Guanghua; Tajima, Seiki; Goda, Nobuhito; Iwai, Kazuhiro; Fukuda, Sanae; Yamaguti, Kouzi; Kuratsune, Hirohiko; Soga, Tomoyoshi; Watanabe, Yasuyoshi; Kataoka, Yosky

    2016-01-01

    Chronic fatigue syndrome (CFS) is a persistent and unexplained pathological state characterized by exertional and severely debilitating fatigue, with/without infectious or neuropsychiatric symptoms, lasting at least 6 consecutive months. Its pathogenesis remains incompletely understood. Here, we performed comprehensive metabolomic analyses of 133 plasma samples obtained from CFS patients and healthy controls to establish an objective diagnosis of CFS. CFS patients exhibited significant differences in intermediate metabolite concentrations in the tricarboxylic acid (TCA) and urea cycles. The combination of ornithine/citrulline and pyruvate/isocitrate ratios discriminated CFS patients from healthy controls, yielding area under the receiver operating characteristic curve values of 0.801 (95% confidential interval [CI]: 0.711–0.890, P < 0.0001) and 0.750 (95% CI: 0.584–0.916, P = 0.0069) for training (n = 93) and validation (n = 40) datasets, respectively. These findings provide compelling evidence that a clinical diagnostic tool could be developed for CFS based on the ratios of metabolites in plasma. PMID:27725700

  12. Novel markers of inflammatory response and hepatic dysfunction in canine leishmaniasis.

    PubMed

    Tonin, Alexandre A; Calado, Andréa M C; Bottari, Nathieli B; Dalenogare, Diéssica; Thomé, Gustavo R; Duarte, Thiago; Duarte, Marta M M F; Morsch, Vera M; Schetinger, Maria R C; Alves, Leucio C; Tinucci-Costa, Mirela; Da Silva, Aleksandro S

    2016-02-01

    Dogs are the main host of Leishmania infantum, and the clinical presentation may range from asymptomatic to systemic manifestations. The immune mechanisms in infected, but clinically healthy dogs, prevails Th1 response mediated by cytokines. In this sense, adenosine deaminase (ADA) and butyrylcholinesterase (BChE) are considered as key enzymes in several physiological processes, including the modulation of inflammatory process. Considering the variable immune response against Leishmania and the known participation of ADA and BChE, the aim of this study was to assess the relation between these two enzymes with the inflammatory response as well as hepatic function in dogs naturally infected with L. infantum. For this purpose, the activity of ADA and BChE was assessed in sera of 24 dogs naturally infected with L. infantum, plus 17 healthy dogs. The naturally infected dogs had clinical signs compatible with leishmaniasis and sera activities of ADA (P<0.01) and BChE (P<0.05) decreased, when compared to the healthy group. The reduction of ADA activity probably represented an effect on inflammatory response, especially due to the decreased hydrolysis of extracellular adenosine, might in order to protect against tissue damage and, also, setting a down-regulation on pro-inflammatory cytokines. BChE enzyme had no effect on modulating the immune response in leishmaniasis, but it decreased, a fact may related to deficiency of synthesis in the liver. Therefore, ADA and BChE activities reduced probably in order to protect against extra tissue damage and due failure in synthesis, respectively.

  13. "Doughnut" technetium pyrophosphate myocardial scintigrams. A marker of severe left ventricular dysfunction.

    PubMed

    Nicod, P; Corbett, J R; Rude, R E; Dehmer, G J; Smucker, M; Buja, L M; Parkey, R W; Lewis, S E; Willerson, J T

    1982-10-01

    The "doughnut" pattern on Tc-99m pyrophosphate (PPi) myocardial scintigraphy is characterized by a border of tracer uptake surrounding a central zone of relatively decreased activity. This pattern is generally associated with large transmural anterior myocardial infarcts (MI) caused by occlusion or critical stenosis of the left anterior descending coronary artery. Such infarcts typically involve a significant portion of the anterior wall and are associated with a complicated clinical course and poor prognosis. In order to evaluate the relationship between the presence of the doughnut pattern and left ventricular (LV) function, radionuclide ventriculography was performed within 15 days after infarction in 58 patients with transmural anterior MI. In patients without previous MI, 15/38 (39.5%) had doughnut scintigrams. These patients demonstrated significant reductions in LV ejection fraction (EF) (28 +/- 10% versus 45 +/- 12%, P less than 0.001) and normalized LV wall motion scores (29 +/- 11% versus 61 +/- 10%, P less than 0.001) when compared with patients with "nondoughnut" scintigrams. Patients with doughnut scintigrams had a significantly greater incidence of severe septal hypokinesis (P less than 0.001) and apical dyskinesis (P less than 0.03). LV end-systolic volumes were also larger in the patients with doughnut scintigrams (73 +/- 32 ml versus 40 +/- 17 mI/M2, P less than 0.005). In contrast, there was no significant difference in LVEF, normalized LV wall motion score, or LV volumes between doughnut and nondoughnut groups in patients with previous MI.

  14. Thyroid hormone dysfunction during pregnancy: A review

    PubMed Central

    Alemu, Aynadis; Terefe, Betelihem; Abebe, Molla; Biadgo, Belete

    2016-01-01

    Thyroid dysfunctions such as hypothyroidism, thyrotoxicosis and thyroid nodules may develop during pregnancy leading to abortion, placental abruptions, preeclampsia, preterm delivery and reduced intellectual function in the offspring. Epidemiological data have shown the significant role of maternal thyroid hormone in fetal neurologic development and maternal health. It has been suggested that the deleterious effects of thyroid dysfunction can also extend beyond pregnancy and delivery to affect neuro-intellectual development in the early life of the child. Pregnancy poses an important challenge to the maternal thyroid gland as hormone requirements are increased during gestation as a result of an increase in thyroid- binding globulin, the stimulatory effect of HCG on TSH receptors, and increased peripheral thyroid hormone requirements. Maternal thyroid dysfunction is associated with increased risk for early abortion, preterm delivery, neonatal morbidity and other obstetrical complications. Early diagnosis for thyroid dysfunction of pregnant women and treatment of thyroid dysfunction during pregnancy is important and cost effective to avoid both fetal and maternal complications secondary to thyroid dysfunction. Therefore the aim of this review was to assess the thyroid function changes occurring during pregnancy, the different disorders with their maternal and fetal implications, the laboratory diagnosis and the best ways of management of these conditions. PMID:27981252

  15. Vascular endothelial dysfunction and pharmacological treatment

    PubMed Central

    Su, Jin Bo

    2015-01-01

    The endothelium exerts multiple actions involving regulation of vascular permeability and tone, coagulation and fibrinolysis, inflammatory and immunological reactions and cell growth. Alterations of one or more such actions may cause vascular endothelial dysfunction. Different risk factors such as hypercholesterolemia, homocystinemia, hyperglycemia, hypertension, smoking, inflammation, and aging contribute to the development of endothelial dysfunction. Mechanisms underlying endothelial dysfunction are multiple, including impaired endothelium-derived vasodilators, enhanced endothelium-derived vasoconstrictors, over production of reactive oxygen species and reactive nitrogen species, activation of inflammatory and immune reactions, and imbalance of coagulation and fibrinolysis. Endothelial dysfunction occurs in many cardiovascular diseases, which involves different mechanisms, depending on specific risk factors affecting the disease. Among these mechanisms, a reduction in nitric oxide (NO) bioavailability plays a central role in the development of endothelial dysfunction because NO exerts diverse physiological actions, including vasodilation, anti-inflammation, antiplatelet, antiproliferation and antimigration. Experimental and clinical studies have demonstrated that a variety of currently used or investigational drugs, such as angiotensin-converting enzyme inhibitors, angiotensin AT1 receptors blockers, angiotensin-(1-7), antioxidants, beta-blockers, calcium channel blockers, endothelial NO synthase enhancers, phosphodiesterase 5 inhibitors, sphingosine-1-phosphate and statins, exert endothelial protective effects. Due to the difference in mechanisms of action, these drugs need to be used according to specific mechanisms underlying endothelial dysfunction of the disease. PMID:26635921

  16. Blueberry Microsatellite Markers Identify Cranberries

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Forty-six blueberry simple sequence repeat (SSR) markers or microsatellites were tested for the ability to amplify a polymorphic marker in eight American cranberry accessions. Sixteen SSRs resulted in informative and polymorphic SSR primer pairs and were used to fingerprint 16 economically important...

  17. Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis

    PubMed Central

    Rossignol, D A; Frye, R E

    2012-01-01

    A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (∼0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although

  18. Carotid artery intima-media thickness and erectile dysfunction in patients with metabolic syndrome

    PubMed Central

    Unal, Mustafa; Aksoy, Duygu Yazgan; Aydın, Yusuf; Tanriover, Mine Durusu; Berker, Dilek; Karakaya, Jale; Guler, Serdar

    2014-01-01

    Background Metabolic syndrome (MS) has become a pandemic in Turkey, as is the case globally. Increase in carotid artery intima-media thickness (CIMT) and erectile dysfunction (ED) may be evident before the clinical signs of cardiovascular disease appear. We aimed to investigate the prevalence of increased CIMT and ED as markers of atherosclerotic disease in patients with MS. Material/Methods Thirty-two patients with MS and 29 healthy controls were included. Anthropometric and biochemical parameters, along with total testosterone (TT), high sensitive C-reactive protein (hs-CRP), were recorded. Carotid artery intima-media thickness was measured. Erectile dysfunction was assessed with International Index of Erectile Function. Results Patients with MS had higher BMI, fasting plasma glucose, post-prandial plasma glucose, insulin, HOMA-IR, total cholesterol, triglycerides, hs-CRP, and CIMT, whereas TT levels were lower (p<0.0001). The prevalence and severity of erectile dysfunction were higher in patients with MS (p<0.0001). Erectile dysfunction scores correlated inversely with CIMT. MS patients with ED were older and had higher CIMT compared to those without ED. Increase in age and HOMA and decrease in TT increased the risk of ED. When KIMT exceeding the 95th percentile of healthy controls was accepted as a risk factor for CVD, presence of ED was the only determinant for this increase. Conclusions Erectile dysfunction was more prevalent and severe in patients with MS and correlated with subclinical endothelial dysfunction. Total testosterone deficiency was prominent among MS patients. Presence of ED points to an increased risk of cardiovascular disease when MS is present. PMID:24869934

  19. Evaluation of snake envenomation-induced renal dysfunction in dogs using early urinary biomarkers of nephrotoxicity.

    PubMed

    Hrovat, A; Schoeman, J P; de Laat, B; Meyer, E; Smets, P; Goddard, A; Nagel, S; Daminet, S

    2013-10-01

    Renal dysfunction in dogs envenomed by poisonous snakes is currently detected using traditional serum and urinary biomarkers such as creatinine and proteinuria. However, these markers lack sensitivity at the early stages of renal dysfunction and their diagnostic accuracy is affected by pre-analytical factors commonly occurring in these dogs, such as haemolysis and haemoglobinuria. Early detection of renal dysfunction would allow for the identification of dogs requiring intensive treatment and monitoring and may help inform prognosis. The aim of this study was to evaluate the performance of several novel urinary biomarkers of glomerular dysfunction, namely, urinary albumin (uAlb), immunoglobulin G (uIgG) and C-reactive protein (uCRP) and of proximal tubular dysfunction (urinary retinol binding protein (uRBP)) compared to traditional end points in dogs with renal damage caused by snake envenomation. Biomarker results were compared between 19 dogs bitten by snakes producing either neurotoxins or cytotoxins and 10 clinically healthy controls. uAlb, uIgG, and uRBP were significantly increased in snake-envenomed dogs at presentation compared to controls, whereas only uIgG and uCRP were significantly elevated 24h post-envenomation. The urinary protein:creatinine ratio was also increased in envenomed dogs compared to controls, but because of the presence of haematuria and haemoglobinuria, differentiation between pre-renal and renal proteinuria was not possible. The results showed that these novel urinary biomarkers may assist in better detecting renal dysfunction in dogs envenomed by poisonous snakes at the acute disease stage compared to traditional laboratory endpoints.

  20. Unraveling pancreatic islet biology by quantitative proteomics

    SciTech Connect

    Zhou, Jianying; Dann, Geoffrey P.; Liew, Chong W.; Smith, Richard D.; Kulkarni, Rohit N.; Qian, Weijun

    2011-08-01

    The pancreatic islets of Langerhans play a critical role in maintaining blood glucose homeostasis by secreting insulin and several other important peptide hormones. Impaired insulin secretion due to islet dysfunction is linked to the pathogenesis underlying both Type 1 and Type 2 diabetes. Over the past 5 years, emerging proteomic technologies have been applied to dissect the signaling pathways that regulate islet functions and gain an understanding of the mechanisms of islet dysfunction relevant to diabetes. Herein, we briefly review some of the recent quantitative proteomic studies involving pancreatic islets geared towards gaining a better understanding of islet biology relevant to metabolic diseases.

  1. Erectile dysfunction: oral pharmacotherapy options.

    PubMed

    Vitezic, D; Pelcic, J Mrsic

    2002-09-01

    Erectile dysfunction (ED) (impotence) is a widespread, age-related problem, which affects 52% of men between 40 and 70 years of age. It is classified as psychogenic, organic, or mixed psychogenic and organic. ED is not a problem only of men, because the relationship between partners can also be disturbed. Therefore, adequate treatment of ED is needed and the most convenient and simplest way is oral drug therapy. Sildenafil, phosphodiesterase-(PDE)-5-selective inhibitor has been the drug of choice for patients with ED since it has been launched in March 1998. The results of various studies have confirmed the efficacy of the drug in men with ED of various etiologies, as well as the positive effect of sildenafil on the quality of a partnership. The most frequent adverse effects documented with sildenafil usage are headache, flushes, dyspepsia, visual disturbances and nasal congestion/rhinitis. These adverse effects are dose-related, usually transient and mild, with low withdrawal rate. Several studies performed recently have shown that sildenafil is a safe and effective treatment of ED in patients with cardiovascular disease, who do not take nitrates or nitrate donors concomitantly. Other oral medications for ED include apomorphine, phentolamine, yohimbine, trazodone, testosterone and new PDE-5 inhibitors in Phase III clinical trials, such as vardenafil and tadalafil. It is obvious, according to recent data, that the concept of PDE-5 inhibition has a central position in oral pharmacotherapy of ED. However, larger clinical studies of efficacy and safety should be carried out using most of the other above-mentioned oral agents and these may also gain a place in the therapy of ED. There are no studies directly comparing sildenafil and other treatments of ED or assessing its role in combination with other therapies. According to the present knowledge, the quality of life, not only of patients but also of their sexual partners, will be improved significantly with

  2. Vorticity is a marker of diastolic ventricular interdependency in pulmonary hypertension

    PubMed Central

    Browning, James; Schroeder, Joyce D.; Shandas, Robin; Kheyfets, Vitaly O.; Buckner, J. Kern; Hunter, Kendall S.; Hertzberg, Jean R.; Fenster, Brett E.

    2016-01-01

    Abstract Our objective was to determine whether left ventricular (LV) vorticity (ω), the local spinning motion of a fluid element, correlated with markers of ventricular interdependency in pulmonary hypertension (PH). Maladaptive ventricular interdependency is associated with interventricular septal shift, impaired LV performance, and poor outcomes in PH patients, yet the pathophysiologic mechanisms underlying fluid-structure interactions in ventricular interdependency are incompletely understood. Because conformational changes in chamber geometry affect blood flow formations and dynamics, LV ω may be a marker of LV-RV (right ventricular) interactions in PH. Echocardiography was performed for 13 PH patients and 10 controls for assessment of interdependency markers, including eccentricity index (EI), and biventricular diastolic dysfunction, including mitral valve (MV) and tricuspid valve (TV) early and late velocities (E and A, respectively) as well as MV septal and lateral early tissue Doppler velocities (e′). Same-day 4-dimensional cardiac magnetic resonance was performed for LV E (early)-wave ω measurement. LV E-wave ω was significantly decreased in PH patients (P = 0.008) and correlated with diastolic EI (Rho = −0.53, P = 0.009) as well as with markers of LV diastolic dysfunction, including MV E(Rho = 0.53, P = 0.011), E/A (Rho = 0.56, P = 0.007), septal e′ (Rho = 0.63, P = 0.001), and lateral e′ (Rho = 0.57, P = 0.007). Furthermore, LV E-wave ω was associated with indices of RV diastolic dysfunction, including TV e′ (Rho = 0.52, P = 0.012) and TV E/A (Rho = 0.53, P = 0.009). LV E-wave ω is decreased in PH and correlated with multiple echocardiographic markers of ventricular interdependency. LV ω may be a novel marker for fluid-tissue biomechanical interactions in LV-RV interdependency. PMID:27162613

  3. Vorticity is a marker of diastolic ventricular interdependency in pulmonary hypertension.

    PubMed

    Schäfer, Michal; Browning, James; Schroeder, Joyce D; Shandas, Robin; Kheyfets, Vitaly O; Buckner, J Kern; Hunter, Kendall S; Hertzberg, Jean R; Fenster, Brett E

    2016-03-01

    Our objective was to determine whether left ventricular (LV) vorticity (ω), the local spinning motion of a fluid element, correlated with markers of ventricular interdependency in pulmonary hypertension (PH). Maladaptive ventricular interdependency is associated with interventricular septal shift, impaired LV performance, and poor outcomes in PH patients, yet the pathophysiologic mechanisms underlying fluid-structure interactions in ventricular interdependency are incompletely understood. Because conformational changes in chamber geometry affect blood flow formations and dynamics, LV ω may be a marker of LV-RV (right ventricular) interactions in PH. Echocardiography was performed for 13 PH patients and 10 controls for assessment of interdependency markers, including eccentricity index (EI), and biventricular diastolic dysfunction, including mitral valve (MV) and tricuspid valve (TV) early and late velocities (E and A, respectively) as well as MV septal and lateral early tissue Doppler velocities (e'). Same-day 4-dimensional cardiac magnetic resonance was performed for LV E (early)-wave ω measurement. LV E-wave ω was significantly decreased in PH patients (P = 0.008) and correlated with diastolic EI (Rho = -0.53, P = 0.009) as well as with markers of LV diastolic dysfunction, including MV E(Rho = 0.53, P = 0.011), E/A (Rho = 0.56, P = 0.007), septal e' (Rho = 0.63, P = 0.001), and lateral e' (Rho = 0.57, P = 0.007). Furthermore, LV E-wave ω was associated with indices of RV diastolic dysfunction, including TV e' (Rho = 0.52, P = 0.012) and TV E/A (Rho = 0.53, P = 0.009). LV E-wave ω is decreased in PH and correlated with multiple echocardiographic markers of ventricular interdependency. LV ω may be a novel marker for fluid-tissue biomechanical interactions in LV-RV interdependency.

  4. Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction.

    PubMed

    Raeder, Helge; Johansson, Stefan; Holm, Pål I; Haldorsen, Ingfrid S; Mas, Eric; Sbarra, Véronique; Nermoen, Ingrid; Eide, Stig A; Grevle, Louise; Bjørkhaug, Lise; Sagen, Jørn V; Aksnes, Lage; Søvik, Oddmund; Lombardo, Dominique; Molven, Anders; Njølstad, Pål Rasmus

    2006-01-01

    Dysfunction of the exocrine pancreas is observed in diabetes, but links between concurrent exocrine and endocrine pancreatic disease and contributing genetic factors are poorly characterized. We studied two families with diabetes and exocrine pancreatic dysfunction by genetic, physiological and in vitro functional studies. A genome-wide screen in Family 1 linked diabetes to chromosome 9q34 (maximal lod score 5.07). Using fecal elastase deficiency as a marker of exocrine pancreatic dysfunction refined the critical chromosomal region to 1.16 Mb (maximal lod score 11.6). Here, we identified a single-base deletion in the variable number of tandem repeats (VNTR)-containing exon 11 of the carboxyl ester lipase (CEL) gene, a major component of pancreatic juice and responsible for the duodenal hydrolysis of cholesterol esters. Screening subjects with maturity-onset diabetes of the young identified Family 2, with another single-base deletion in CEL and a similar phenotype with beta-cell failure and pancreatic exocrine disease. The in vitro catalytic activities of wild-type and mutant CEL protein were comparable. The mutant enzyme was, however, less stable and secreted at a lower rate. Furthermore, we found some evidence for an association between common insertions in the CEL VNTR and exocrine dysfunction in a group of 182 unrelated subjects with diabetes (odds ratio 4.2 (1.6, 11.5)). Our findings link diabetes to the disrupted function of a lipase in the pancreatic acinar cells.

  5. The Loss Of Macrophage Fatty Acid Oxidation Does Not Potentiate Systemic Metabolic Dysfunction.

    PubMed

    Gonzalez-Hurtado, Elsie; Lee, Jieun; Choi, Joseph; Selen Alpergin, Ebru S; Collins, Samuel L; Horton, Maureen R; Wolfgang, Michael J

    2017-02-21

    Fatty acid oxidation in macrophages has been suggested to play a causative role in high-fat diet-induced metabolic dysfunction, particularly in the etiology of adipose driven insulin resistance. To understand the contribution of macrophage fatty acid oxidation directly to metabolic dysfunction in high-fat diet-induced obesity, we generated mice with a myeloid-specific knockout of carnitine palmitoyltransferase 2 (CPT2 Mϕ-KO), an obligate step in mitochondrial long-chain fatty acid oxidation. While fatty acid oxidation was clearly induced upon IL-4 stimulation, fatty acid oxidation deficient CPT2 Mϕ-KO bone marrow derived macrophages (BMDM) displayed canonical markers of M2 polarization following IL-4 stimulation in vitro. In addition, loss of macrophage fatty acid oxidation in vivo did not alter the progression of high-fat diet induced obesity, inflammation, macrophage polarization, oxidative stress, or glucose intolerance. These data suggest that although alternatively activated macrophages up-regulate fatty acid oxidation, fatty acid oxidation is dispensable for macrophage polarization and high-fat diet-induced metabolic dysfunction. Macrophage fatty acid oxidation likely plays a correlative rather than causative role in systemic metabolic dysfunction.

  6. Damage to Olfactory Progenitor Cells Is Involved in Cigarette Smoke-Induced Olfactory Dysfunction in Mice.

    PubMed

    Ueha, Rumi; Ueha, Satoshi; Kondo, Kenji; Sakamoto, Takashi; Kikuta, Shu; Kanaya, Kaori; Nishijima, Hironobu; Matsushima, Kouji; Yamasoba, Tatsuya

    2016-03-01

    Exposure to cigarette smoke is a major cause of olfactory dysfunction. However, the underlying mechanisms by which cigarette smoke interferes with the highly regenerative olfactory nerve system remain unclear. To investigate whether cigarette smoke induces olfactory dysfunction by disrupting cell proliferation and cell survival in the olfactory epithelium (OE), we developed a mouse model of smoking that involved intranasal administration of a cigarette smoke solution (CSS). Immunohistological analyses and behavioral testing showed that CSS administration during a period of 24 days reduced the number of olfactory marker protein-positive mature olfactory receptor neurons (ORNs) in the OE and induced olfactory dysfunction. These changes coincided with a reduction in the number of SOX2(+) ORN progenitors and Ki-67(+) proliferating cells in the basal layer of the OE, an increase in the number of caspase-3(+) apoptotic cells, and an increase in the expression of mRNA for the inflammatory cytokines IL-1β and IL-6. Notably, the proliferating ORN progenitor population recovered after cessation of treatment with CSS, resulting in the subsequent restoration of mature ORN numbers and olfaction. These results suggest that SOX2(+) ORN progenitors are targets of CSS-induced impairment of the OE, and that by damaging the ORN progenitor population and increasing ORN death, CSS exposure eventually overwhelms the regenerative capacity of the epithelium, resulting in reduced numbers of mature ORNs and olfactory dysfunction.

  7. Etiology and Early Marker Studies (EEMS) | Division of Cancer Prevention

    Cancer.gov

    The Etiology and Early Marker Studies (EEMS) is a component of the PLCO Trial. By collecting biologic materials and risk factor information from trial participants before the diagnosis of disease, PLCO EEMS adds substantial value to the trial, providing a resource for cancer research, focused, in particular, on cancer etiology and early markers. Etiologic studies investigate the environmental, biochemical and genetic risk factors for cancer. Early detection studies aim to develop reproducible, diagnostics-ready biomarkers of early disease. | Risk factor data and biospecimens collected before the diagnosis of disease from participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

  8. Antibiotics May Trigger Mitochondrial Dysfunction Inducing Psychiatric Disorders

    PubMed Central

    Stefano, George B.; Samuel, Joshua; Kream, Richard M.

    2017-01-01

    Clinical usage of several classes of antibiotics is associated with moderate to severe side effects due to the promotion of mitochondrial dysfunction. We contend that this may be due to perturbation of unique evolutionary relationships that link selective biochemical and molecular aspects of mitochondrial biology to conserved enzymatic processes derived from bacterial progenitors. Operationally, stereo-selective conformational matching between mitochondrial respiratory complexes, cytosolic and nuclear signaling complexes appears to support the conservation of a critically important set of chemical messengers required for existential regulation of homeostatic cellular processes. Accordingly, perturbation of normative mitochondrial function by select classes of antibiotics is certainly reflective of the high degree of evolutionary pressure designed to maintain ongoing bidirectional signaling processes between cellular compartments. These issues are of critical importance in evaluating potentially severe side effects of antibiotics on complex behavioral functions mediated by CNS neuronal groups. The CNS is extremely dependent on delivery of molecular oxygen for m