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Investigator-Driven Clinical Research. Imaging biomarkers of progression in Diabetic Retinopathy and Age-Related Macular Degeneration. Contribution for evidence-based clinical eye research.

Nunes, Sandrina
Fonte: Universidade de Coimbra Publicador: Universidade de Coimbra
Tipo: Tese de Doutorado
ENG
Relevância na Pesquisa
36.67%
A Investigação Clínica da Iniciativa do Investigador (ICII) desempenha um papel importante na promoção do conhecimento científico tanto na área do diagnóstico como na área das abordagens terapêuticas, contribuindo como tal para a medicina baseada em evidências bem como para a investigação orientada para o doente. A ICII tem como objectivo a identificação de novos biomarcadores e/ou de novas metodologias que permitam a identificação precoce de doentes com maior risco, a melhoria das atuais abordagens diagnósticas e/ou terapêuticas, a melhoria das estratégias de tratamento e/ou acompanhamento dos doentes, bem como a melhoraria da qualidade, acessibilidade e relação custo-eficácia do sistema de saúde. A investigação clínica em ciências da visão representa menos de 5% da investigação clínica realizada em todo o mundo. A Retinopatia Diabética (RD) e a Degenerescência Macular Relacionada com a Idade (DMI) representam cerca de 20% dessa investigação. Estas duas doenças da retina são a principal causa de perda da visão em todo o mundo tendo, como tal, um elevado impacto socioeconômico na população ativa. A detecção precoce da RD e da DMI, bem como a identificação precoce dos doentes que estão em risco de progredir...

The Alzheimer`s Association external quality control program for cerebrospinal fluid biomarkers

MATTSSON, Niklas; ANDREASSON, Ulf; PERSSON, Staffan; ARAI, Hiroyuki; BATISH, Sat Dev; BERNARDINI, Sergio; BOCCHIO-CHIAVETTO, Luisella; BLANKENSTEIN, Marinus A.; CARRILLO, Maria C.; CHALBOT, Sonia; COART, Els; CHIASSERINI, Davide; CUTLER, Neal; DAHLFORS, G
Fonte: ELSEVIER SCIENCE INC Publicador: ELSEVIER SCIENCE INC
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
36.6%
Background: The cerebrospinal fluid (CSF) biomarkers amyloid beta (A beta)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer`s disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer`s Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. Methods: The program is open for laboratories using commercially available kits for A beta, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Molndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. Results: Forty laboratories participated. Twenty-six used INNOTEST enzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure A beta-(1-42), P-tau(181P), and T-tau), and 5 used Mesa Scale Discovery with the A beta triplex (A beta N-42, A beta N-40, and A beta N-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. Conclusions: Measurements of CSF AD biomarkers show large between-laboratory variability...

Estudo da correlação entre a incidência de metástases em tumores carcinóides típicos broncopulmonares e biomarcadores teciduais, variáveis clínicas e índice de risco; Study of the correlation between metastasis incidence in typical bronchopulmonary carcinoid tumors and clinical features, tissue biomarkers and index risk

Pereira, João Carlos das Neves
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 22/10/2004 PT
Relevância na Pesquisa
36.6%
Carcinóides típicos são proliferações de células neuroendócrinas. Discute-se se são carcinomas ou adenomas, devido ao seu comportamento ambíguo. É imperativo conhecer seu potencial maligno para que se estabeleça o tratamento adequado. Os relatos de metástase exigem uma definição de quais são os critérios que podem ser utilizados para prever o fenômeno. Atualmente é utilizada a classificação proposta por Travis que estratifica os carcinóides em típicos e atípicos. Porém, todos os pacientes acometidos por carcinóide típico, pela classificação, são considerados como sendo de baixo risco para a ocorrência de metástase, o que torna a proposta insuficiente para se definir conduta terapêutica. O gênero, a idade, a localização central ou periférica, o diâmetro tumoral, e o estadiamento TNM, também já foram descritos como tendo correlação com malignidade em carcinóides. Busca-se descobrir outros critérios que possam ser utilizados para auxiliar na determinação do prognóstico, como os biomarcadores celulares e estromais. O estudo do comportamento celular através de marcadores correlacionados com o fenótipo maligno pode ser realizado utilizando-se a técnica de imunohistoquímica, assim como pelo estudo da matriz extracelular. A análise...

Avaliação analítica de potenciais biomarcadores para câncer de bexiga em urina; Analytical evaluation of potential biomarkers for bladder cancer in urine

Alberice, Juliana Vieira
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 11/04/2014 PT
Relevância na Pesquisa
36.6%
O câncer de bexiga é uma neoplasia urogenital que acomete homens e mulheres, sendo que somente no Brasil 8.600 novos casos ao ano são diagnosticados. Cistoscopia transuretral é a conduta padrão no diagnóstico e acompanhamento do câncer de bexiga. Entretanto, tal procedimento é extremamente invasivo e doloroso além de ter elevado custo e não garantir todos os resultados. Assim, busca-se por marcadores moleculares que possam auxiliar no diagnóstico e progressão do câncer de bexiga, bem como diminuir a necessidade de exames invasivos no acompanhamento de pacientes tratados. Nesse sentido, a urina tem papel de destaque como fonte de biomarcadores devido principalmente ao seu caráter não invasivo.
Nesse trabalho foram utilizadas duas abordagens 'ômicas': proteômica e metabolômica, para a busca de biomarcadores em urina para o diagnóstico e prognóstico do câncer de bexiga, respectivamente. Com a abordagem proteômica buscou-se apenas por biomarcadores para o diagnóstico da doença e, utilizando as técnicas de eletroforese 2-DE, OFFGEL e MS, juntamente com análise estatística multivariada, foi possível identificar 32 proteínas que apresentam-se como potenciais marcadores para o câncer de bexiga. A abordagem metabolômica foi empregada para a busca de biomarcadores para reincidência e progressão da doença. As técnicas analíticas utilizadas nessa abordagem...

Identificação e estudo de biomarcadores personalizados para avaliação e seguimento de pacientes com câncer de reto tratados com quimioradioterapia neoadjuvante; Identification and study of personalized biomarkers for assessment and follow-up of patients with rectal cancer treated with neoadjuvant chemoradiotherapy.

Carpinetti-Oliveira, Paola de Avelar
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 20/01/2015 PT
Relevância na Pesquisa
36.6%
O tratamento padrão para pacientes com câncer de reto localmente avançado consiste no uso de quimioradioterapia neoadjuvante (QRTn), seguida por cirurgia. Uma fração significativa dos pacientes responde completamente ao tratamento e no momento da reavaliação não apresenta evidência clínica nem radiológica de doença. Uma abordagem alternativa, Watch and Wait, propõe não operar imediatamente esses pacientes e submetê-los a um protocolo de observação frequente, a fim de evitar as morbidades associadas à cirurgia. No entanto, a avaliação da resposta ao tratamento ainda é um desafio, devido à subjetividade da avaliação clínica e a ausência de exames radiológicos suficientemente sensíveis e específicos para garantir a ausência de células tumorais residuais ou capazes de detectar a recorrência precoce da doença. DNA circulante contendo alterações genéticas específicas do tumor (ctDNA) pode ser encontrado na fração livre de células do sangue e tem sido utilizado para monitorar a dinâmica tumoral em tumores sólidos. Avanços recentes das tecnologias de sequenciamento permitem a identificação eficiente e rápida e a um custo relativamente baixo de alterações genéticas em tumores individuais, superando o problema imposto pela ausência de alterações genéticas recorrentes nesses tumores. Essas alterações podem ser utilizadas como biomarcadores personalizados para monitorar a resposta ao tratamento...

Estudo qualitativo e quantitativo de biomarcadores ácidos e hidrocarbonetos presentes em óleos da Bacia Potiguar; Qualitative and quantitative study of acidic and hydrocarbon biomarkers of oil from the Potiguar Basin

Rosane Alves Fontes
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 07/12/2011 PT
Relevância na Pesquisa
36.72%
rabalho foram sintetizados quatro biomarcadores ácidos, a saber: ácido 5b (H) colânico (2), 5a (H) homopregnânico (4), 8,13-tetraidrocopálico (6) e 15-isocopálico (7). Para tanto, foram utilizadas matérias primas comerciais (ácido litocólico e estigmasterol) e o ácido copálico (extraído e purificado a partir de bálsamo de copaíba). Também foi preparado o biomarcador hidrocarboneto 5b (H) colano (8). Estas moléculas foram sintetizadas com o objetivo de serem utilizadas como padrões de referência na quantificação de biomarcadores ácidos e hidrocarbonetos presentes em dois conjuntos de óleos provenientes da Bacia Potiguar. O conjunto I contém cinco óleos de diferentes origens, sendo dois lacustres (LC-1 e LC-2), um marinho evaporítico (ME) e dois mistos (M-1 e M-2) e o conjunto II contém quatro óleos de mesma evolução térmica e mesma origem (ME-a, ME-b, ME-c e ME-d), todos marinho evaporíticos. O que os distingue são os diferentes níveis de biodegradação. Utilizou-se também o isocopalano (9), previamente preparado e cedido pelo Dr. Imamura (2011), na quantificação de biomarcadores terpanos. Os resultados das análises quantitativas dos biomarcadores terpanos e esteranos, quantificados com os padrões de referência 9 e 8...

Biomarkers for seasonal heat stress: A holistic approach

Pinheiro, Pinheiro, C; Lamy, Lamy, E; Pereira, Pereira, A
Fonte: Knight, C. H. (Ed) Publicador: Knight, C. H. (Ed)
Tipo: Aula
ENG
Relevância na Pesquisa
36.63%
Environmental heat stress, present during the hot and dry summers in Mediterranean climate, severely impairs animal’s performance, particularly in animals of high genetic merit. Although heat stress has been considerable studied in dairy cattle, the mechanisms of seasonal acclimation are less well understood. Besides, in Mediterranean region, there are also great interests in small ruminant dairy species, which are even less well studied. Biomarkers may have great potential in identifying levels of thermal stress. Although often referred, blood cortisol does not allow a full understanding of heat stress, due to its circadian cycle and because the confounding with other types of stress. Consequently, new and better non-invasive methods, than allow to assess stress, are necessary. The hair, faeces or saliva fulfil these requirements. Salivary proteins have been extensively studied in humans, due to their potential as non-invasive biomarkers of pathology and physiology. Nonetheless, in the last years, some research emerged demonstrating the value of saliva for farm animal studies. Based on previous line of research, on ruminant salivary proteome and heat stress, we propose to search for salivary and faeces biomarkers of seasonal acclimation to heat stress and to compare them with other well-known physiological and endocrine indicators. Unlike what occurs at tropical climates where animals must combine a high heat tolerance with high performance; in Mediterranean climate due to high climate seasonality...

Biomarkers for seasonal heat stress

Pinheiro, C.; Lamy, E.; Pereira, A.M.F.
Fonte: The First Dairy Care Conference Publicador: The First Dairy Care Conference
Tipo: Aula
ENG
Relevância na Pesquisa
36.63%
Environmental heat stress, present during the hot and dry summers in Mediterranean climate, severely impairs animal’s performance, particularly in animals of high genetic merit. Although heat stress has been considerable studied in dairy cattle, the mechanisms of seasonal acclimation are less well understood. Biomarkers may have great potential in identifying levels of thermal stress. The blood cortisol does not allow a full understanding of the levels of thermal stress, due to its circadian cycle and because the confounding with other types of stress. Furthermore, it should find non-invasive methods better to assess the stress. The hair, faeces or saliva fulfil these requirements. Saliva has been extensively studied in humans, due to its potential as a non-invasive source of pathology and physiology biomarkers. Nonetheless, in the last years, some research emerged demonstrating the value of this fluid for farm animal studies. Based on previous line of research, on ruminant salivary proteome and heat stress, we propose to search for salivary and faeces biomarkers of seasonal acclimation to heat stress and to compare them with other well-known physiological and endocrine indicators. Contrary to what occurs in tropical climates, where it seeks to match the performance with heat tolerance in Mediterranean climate looking up the physiological versatility. The aim of the study is: i) the identification of reliable biomarkers (saliva...

Accelerating Drug Development Using Biomarkers: A Case Study with Sitagliptin, A Novel DPP4 Inhibitor for Type 2 Diabetes

Krishna, Rajesh; Herman, Gary; Wagner, John A.
Fonte: Springer US Publicador: Springer US
Tipo: Artigo de Revista Científica
Publicado em 07/08/2008 EN
Relevância na Pesquisa
36.63%
The leveraged use of biomarkers presents an opportunity in understanding target engagement and disease impact while accelerating drug development. For effective integration in drug development, it is essential for biomarkers to aid in the elucidation of mechanisms of action and disease progression. The recent years have witnessed significant progress in biomarker selection, validation, and qualification, while enabling surrogate and clinical endpoint qualification and application. Biomarkers play a central role in target validation for novel mechanisms. They also play a central role in the learning/confirming paradigm, particularly when utilized in concert with pharmacokinetic/pharmacodynamic modeling. Clearly, these attributes make biomarker integration attractive for scientific and regulatory applications to new drug development. In this review, applications of proximal, or target engagement, and distal, or disease-related, biomarkers are highlighted using the example of the recent development of sitagliptin for type 2 diabetes, wherein elucidation of target engagement and disease-related biomarkers significantly accelerated sitagliptin drug development. Importantly, use of biomarkers as tools facilitated design of clinical efficacy trials while streamlining dose focus and optimization...

Biomarkers of vitamin B-12 status in NHANES: a roundtable summary123456

Yetley, Elizabeth A; Pfeiffer, Christine M; Phinney, Karen W; Bailey, Regan L; Blackmore, Sheena; Bock, Jay L; Brody, Lawrence C; Carmel, Ralph; Curtin, L Randy; Durazo-Arvizu, Ramón A; Eckfeldt, John H; Green, Ralph; Gregory, Jesse F; Hoofnagle, Andrew
Fonte: American Society for Nutrition Publicador: American Society for Nutrition
Tipo: Artigo de Revista Científica
Publicado em /07/2011 EN
Relevância na Pesquisa
36.6%
A roundtable to discuss the measurement of vitamin B-12 (cobalamin) status biomarkers in NHANES took place in July 2010. NHANES stopped measuring vitamin B-12–related biomarkers after 2006. The roundtable reviewed 3 biomarkers of vitamin B-12 status used in past NHANES—serum vitamin B-12, methylmalonic acid (MMA), and total homocysteine (tHcy)—and discussed the potential utility of measuring holotranscobalamin (holoTC) for future NHANES. The roundtable focused on public health considerations and the quality of the measurement procedures and reference methods and materials that past NHANES used or that are available for future NHANES. Roundtable members supported reinstating vitamin B-12 status measures in NHANES. They noted evolving concerns and uncertainties regarding whether subclinical (mild, asymptomatic) vitamin B-12 deficiency is a public health concern. They identified the need for evidence from clinical trials to address causal relations between subclinical vitamin B-12 deficiency and adverse health outcomes as well as appropriate cutoffs for interpreting vitamin B-12–related biomarkers. They agreed that problems with sensitivity and specificity of individual biomarkers underscore the need for including at least one biomarker of circulating vitamin B-12 (serum vitamin B-12 or holoTC) and one functional biomarker (MMA or tHcy) in NHANES. The inclusion of both serum vitamin B-12 and plasma MMA...

Addition of Inflammatory Biomarkers Did Not Improve Diabetes Prediction in the Community: The Framingham Heart Study

Dallmeier, Dhayana; Larson, Martin G.; Wang, Na; Fontes, João D.; Benjamin, Emelia J.; Fox, Caroline
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
EN_US
Relevância na Pesquisa
36.67%
Background: Prior studies have reported conflicting findings with regard to the association of biomarkers in the prediction of incident type 2 diabetes. We evaluated 12 biomarkers as possible diabetes predictors in the Framingham Heart Study. Methods and results: Biomarkers representing inflammation (C-reactive protein, interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor receptor 2, osteoprotegerin, and fibrinogen), endothelial dysfunction (intercellular adhesion molecule-1), vascular damage (CD40-ligand, P-selectin, and lipoprotein-associated phospholipase A2 mass and activity), and oxidative stress (urinary isoprostanes) were measured in participants without diabetes attending the Offspring seventh (n=2499) or multiethnic Omni second (n=189) examination (1998–2001). Biomarkers were loge transformed and standardized. Multivariable logistic regression tested each biomarker in association with incident diabetes at a follow-up examination (the Offspring eighth and Omni third examination; mean 6.6 years later), with adjustment for age, sex, cohort, body mass index, fasting glucose, systolic blood pressure, high-density lipoprotein cholesterol, triglycerides, and smoking. C statistics were evaluated with and without inflammatory markers. In 2638 participants (56% women...

The association of plasma biomarkers with computed tomography-assessed emphysema phenotypes

Carolan, Brendan J; Hughes, Grant; Morrow, Jarrett; Hersh, Craig P; O’Neal, Wanda K; Rennard, Stephen; Pillai, Sreekumar G; Belloni, Paula; Cockayne, Debra A; Comellas, Alejandro P; Han, Meilan; Zemans, Rachel L; Kechris, Katerina; Bowler, Russell P
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
EN_US
Relevância na Pesquisa
36.63%
Rationale: Chronic obstructive pulmonary disease (COPD) is a phenotypically heterogeneous disease. In COPD, the presence of emphysema is associated with increased mortality and risk of lung cancer. High resolution computed tomography (HRCT) scans are useful in quantifying emphysema but are associated with radiation exposure and high incidence of false positive findings (i.e., nodules). Using a comprehensive biomarker panel, we sought to determine if there was a peripheral blood biomarker signature of emphysema. Methods: 114 plasma biomarkers were measured using a custom assay in 588 individuals enrolled in the COPDGene study. Quantitative emphysema measurements included percent low lung attenuation (%LAA) ≤ −950 HU, ≤ − 910 HU and mean lung attenuation at the 15th percentile on lung attenuation curve (LP15A). Multiple regression analysis was performed to determine plasma biomarkers associated with emphysema independent of covariates age, gender, smoking status, body mass index and FEV1. The findings were subsequently validated using baseline blood samples from a separate cohort of 388 subjects enrolled in the Treatment of Emphysema with a Selective Retinoid Agonist (TESRA) study. Results: Regression analysis identified multiple biomarkers associated with CT-assessed emphysema in COPDGene...

Cardiac and inflammatory biomarkers do not correlate with volume of heart or lung receiving radiation

Kuo, Angera H; Ancukiewicz, Marek; Kozak, Kevin R; Yock, Torunn I; Padera, Timothy P
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
EN_US
Relevância na Pesquisa
36.63%
Background: Thoracic and cardiac irradiation increases the risk of pulmonary and cardiovascular disease. In addition, radiation, often in combination with chemotherapy, can cause treatment-related pneumonitis. Previously, we showed that the common marker for cardiac damage, troponin T, was not elevated by chemoradiation [Lung Cancer 62:351–355, 2008]. In this study, we explore whether dose-volume metrics and biomarkers for cardiac damage, inflammation or angiogenesis could identify patients receiving thoracic radiation who would later have cardiac or pulmonary complications. Findings: To this end, we quantified cardiac biomarkers including c-reactive protein (cRP) as well as a panel of angiogenic and inflammatory molecules in thirty patients who received radiation therapy to the thorax with or without concurrent chemotherapy between May 2006 and May 2007. Serum was collected at baseline, 2 weeks into radiation treatment and at the completion of radiation therapy. Heart and lung dosimetric parameters and clinical risk factors were also examined, along with the monitoring of adverse pulmonary and cardiac events during follow-up. Contrary to our hypothesis, there was no correlation between serum biomarker levels and cardiac radiation dose. Similarly there was little association between lung dose-volume metrics and inflammatory or angiogenic biomarkers. Furthermore...

Recent updates on epigenetic biomarkers for prostate cancer

Chiam, K.; Day, T.K.; Bianco-Miotto, T.
Fonte: Springer Netherlands; Dordrecht Publicador: Springer Netherlands; Dordrecht
Tipo: Parte de Livro
Publicado em //2013 EN
Relevância na Pesquisa
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Epigenetics refers to DNA methylation, histone modifications and microRNAs and these epigenetic modifications are extensively investigated as potential biomarkers for cancer. Characterizing genome wide epigenetic changes involved in prostate cancer development and progression will not only identify potential novel therapeutic targets, since some epigenetic modifications are reversible, but also highlight which epigenetic changes can be used as prostate cancer biomarkers. Epigenetic changes are relatively stable and easy to measure in peripheral samples like blood and urine, further highlighting their importance as powerful tools for assessing patient diagnosis and prognosis. In this review, we outline how epigenetic biomarkers have been used for diagnosis, prognosis and for monitoring therapeutic response in prostate cancer. We also review how epigenetic biomarkers may be more sensitive and specific than current prostate cancer serum markers and the possibility that combining different epigenetic modifications may further enhance the diagnostic and prognostic ability of these epigenetic biomarkers. As epigenome wide studies continue to be performed in larger patient cohorts, we will soon identify the epigenetic modifications involved in prostate tumorigenesis with the resultant identification of new therapeutic targets and robust prostate cancer biomarkers.; Karen Chiam...

Executive summary—Biomarkers of Nutrition for Development: Building a Consensus123

Raiten, Daniel J; Namasté, Sorrel; Brabin, Bernard; Combs, Gerald; L'Abbe, Mary R; Wasantwisut, Emorn; Darnton-Hill, Ian
Fonte: American Society for Nutrition Publicador: American Society for Nutrition
Tipo: Artigo de Revista Científica
EN
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36.66%
The ability to develop evidence-based clinical guidance and effective programs and policies to achieve global health promotion and disease prevention goals depends on the availability of valid and reliable data. With specific regard to the role of food and nutrition in achieving those goals, relevant data are developed with the use of biomarkers that reflect nutrient exposure, status, and functional effect. A need exists to promote the discovery, development, and use of biomarkers across a range of applications. In addition, a process is needed to harmonize the global health community's decision making about what biomarkers are best suited for a given use under specific conditions and settings. To address these needs, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, organized a conference entitled “Biomarkers of Nutrition for Development: Building a Consensus,” which was hosted by the International Atomic Energy Agency. Partners included key multilateral, US agencies and public and private organizations. The assembly endorsed the utility of this initiative and the need for the BOND (Biomarkers of Nutrition for Development) project to continue. A consensus was reached on the requirement to develop a process to inform the community about the relative strengths or weaknesses and specific applications of various biomarkers under defined conditions. The articles in this supplement summarize the deliberations of the 4 working groups: research...

Translational Biomarkers of Neurotoxicity: A Health and Environmental Sciences Institute Perspective on the Way Forward

Roberts, Ruth A.; Aschner, Michael; Calligaro, David; Guilarte, Tomas R.; Hanig, Joseph P.; Herr, David W.; Hudzik, Thomas J.; Jeromin, Andreas; Kallman, Mary J.; Liachenko, Serguei; Lynch, James J.; Miller, Diane B.; Moser, Virginia C.; O’Callaghan, Ja
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN
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36.67%
Neurotoxicity has been linked to a number of common drugs and chemicals, yet efficient and accurate methods to detect it are lacking. There is a need for more sensitive and specific biomarkers of neurotoxicity that can help diagnose and predict neurotoxicity that are relevant across animal models and translational from nonclinical to clinical data. Fluid-based biomarkers such as those found in serum, plasma, urine, and cerebrospinal fluid (CSF) have great potential due to the relative ease of sampling compared with tissues. Increasing evidence supports the potential utility of fluid-based biomarkers of neurotoxicity such as microRNAs, F2-isoprostanes, translocator protein, glial fibrillary acidic protein, ubiquitin C-terminal hydrolase L1, myelin basic protein, microtubule-associated protein-2, and total tau. However, some of these biomarkers such as those in CSF require invasive sampling or are specific to one disease such as Alzheimer’s, while others require further validation. Additionally, neuroimaging methodologies, including magnetic resonance imaging, magnetic resonance spectroscopy, and positron emission tomography, may also serve as potential biomarkers and have several advantages including being minimally invasive. The development of biomarkers of neurotoxicity is a goal shared by scientists across academia...

The association of coffee intake with liver cancer risk is mediated by biomarkers of inflammation and hepatocellular injury: data from the European Prospective Investigation into Cancer and Nutrition

Aleksandrova, Krasimira; Bamia, Christina; Drogan, Dagmar; Lagiou, Pagona; Trichopoulou, Antonia; Jenab, Mazda; Fedirko, Veronika; Romieu, Isabelle; Bueno-de-Mesquita, H. Bas; Pischon, Tobias; Tsilidis, Kostas; Overvad, Kim; Tj?nneland, Anne; Bouton-Ruaul
Fonte: American Society for Nutrition Publicador: American Society for Nutrition
Tipo: Article; published version
EN
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This is the final version of the article. It was first available from American Society for Nutrition via http://dx.doi.org/10.3945/?ajcn.115.116095; BACKGROUND: Higher coffee intake has been purportedly related to a lower risk of liver cancer. However, it remains unclear whether this association may be accounted for by specific biological mechanisms. OBJECTIVE: We aimed to evaluate the potential mediating roles of inflammatory, metabolic, liver injury, and iron metabolism biomarkers on the association between coffee intake and the primary form of liver cancer?hepatocellular carcinoma (HCC). DESIGN: We conducted a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition among125 incident HCC cases matched to 250 controls using an incidence-density sampling procedure. The association of coffee intake with HCC risk was evaluated by using multivariable-adjusted conditional logistic regression that accounted for smoking, alcohol consumption, hepatitis infection, and other established liver cancer risk factors. The mediating effects of 21 biomarkers were evaluated on the basis of percentage changes and associated 95% CIs in the estimated regression coefficients of models with and without adjustment for biomarkers individually and in combination. RESULTS: The multivariable-adjusted RR of having $4 cups (600 mL) coffee/d compared with ...

Mendelian randomization studies of biomarkers and type 2 diabetes; Biomarkers and type 2 diabetes

Abbasi, Ali
Fonte: Bioscientifica Publicador: Bioscientifica
Tipo: Article; accepted version
EN
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This is the author accepted manuscript. The final version is available from Bioscientifica via http://dx.doi.org/10.1530/EC-15-0087; CONTEXT: Many biomarkers are associated with type 2 diabetes (T2D) risk in epidemiological observations. The aim of this study was to identify and summarize current evidence for causal effects of biomarkers on T2D. DESIGN AND METHODS: A systematic literature search in PubMed and EMBASE (until April 2015) was done to identify Mendelian randomization studies that examined potential causal effects of biomarkers on T2D. To replicate the findings of identified studies, data from two large-scale genome-wide association studies (GWAS) were used: 1) DIAbetes Genetics Replication And Meta-analysis (DIAGRAMv3) for T2D, and 2) the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) for glycaemic traits. GWAS summary statistics were extracted for the same genetic variants (or proxy of variants) which were used in the original Mendelian randomization studies. RESULTS: Ten out of 21 biomarkers (from 28 studies) have been reported to be causally associated with T2D in Mendelian randomization. Most biomarkers were investigated in a single cohort study or population. Of the 10 biomarkers that were identified...

Genetics and Biomarkers of Osteoarthritis and Joint Hypermobility

Chen, Hsiang-Cheng
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação Formato: 1892122 bytes; application/pdf
Publicado em //2009 EN_US
Relevância na Pesquisa
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Osteoarthritis (OA) is the most common joint disorder causing chronic disability in the world population. By the year 2030, an estimated one fifth of this population will be affected by OA. Although OA is regarded as a multi-factorial disorder with both environmental and genetic components, the exact pathogenesis remains unknown.

In this study, we hypothesize that biomarkers associated with OA can be used as quantitative traits of OA, and provide enough power to identify new genes or replicate known gene associations for OA. We established an extensive family called the CARRIAGE (CARolinas Region Interaction of Aging, Genes and Environment) family. Then, we measured and analyzed seven OA-related biomarkers (HA, COMP, PIIANP, CPII, C2C, hs-CRP and GSP) in this extensive family to evaluate their association with OA clinical phenotypes. These findings suggest that OA biomarkers can reflect hand OA in this large multigenerational family. Therefore, we performed nonparametric variance components analysis to evaluate heritability for quantitative traits for those biomarkers. Finally, based upon OA biomarkers with high heritability, we performed a genome-wide linkage scan. Our results provide the first evidence of genetic susceptibility loci identified by OA-related biomarkers...

Avaliação de Biomarcadores Geoquímicos e Salinidade em Perfis Sedimentares na Lagoa do Ribeirão em Paulo Lopes, SC; Evaluation of Geochemical Biomarkers and Salinity in Sediment Core in the Lagoa do Ribeirão in Paulo Lopes, SC

Martinho Rau; UFSC; Giovana Anceski Bataglion; UFSC; Luiz Augusto dos Santos Madureira; UFSC
Fonte: Revista Virtual de Química Publicador: Revista Virtual de Química
Tipo: ; Formato: binary/octet-stream
Publicado em 06/05/2013 PT
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Os biomarcadores geoquímicos são compostos presentes na geosfera e estão relacionados com os precursores biológicos específicos, permitindo obter informações sobre as mudanças ambientais que ocorreram ou ainda ocorrem nos ecossistemas aquáticos e suas vizinhanças. A Lagoa do Ribeirão, localizada no município de Paulo Lopes, SC, é o sistema aquático avaliado neste trabalho através de biomarcadores geoquímicos e salinidade, principalmente. Os dados obtidos indicam a predominância de ambiente marinho, quando o nível relativo do mar estava mais elevado que o nível atual, sendo observados os aumentos da salinidade, da fração granulométrica silte+argila, da quantidade de enxofre total, dinosterol e das menores quantidades de biomarcadores geoquímicos de fontes terrestres. Houve um período de transição do ambiente marinho para o ambiente de água doce, caracterizado pela diminuição de carbono orgânico total e aumento da quantidade de areia e de biomarcadores de fontes terrestres. Após este período, a água doce começou a predominar nesta lagoa, caracterizada pelo aumento da quantidade de biomarcadores geoquímicos de origem terrestre como alcanos lineares n-C27, n-C29, n-C31, friedelina, taraxerol, ?-sitosterol e campesterol e pela diminuição da salinidade. Os biomarcadores com maiores concentrações estão situados principalmente nas regiões leste...