List of Contributors
Page: iiii-v (3)
Author: Juan Antonio Vílchez
DOI: 10.2174/9781681084954117010003
Biomarkers in Pre-eclampsia: Is it Possible to Predict it?
Page: 1-22 (22)
Author: Ana Martínez-Ruiz, Irene De-Miguel-Elízaga and Natalia Sancho- Rodríguez
DOI: 10.2174/9781681084954117010004
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Abstract
pre-eclampsia is a syndrome with high maternal and fetal mortality. The pathophysiology remains unknown. Prediction, diagnosis and management of the disease has allowed the identification of multiple biomarkers, some of which help to predict those at risk. Some of these biomarkers have demonstrated, even in isolation, an effi-ciency of the test that allows to incorporate them into clinical practice. The combination of these biomarkers and clinical factors may help predict pre-eclampsia risk by developing integrated clinical risk models. This chapter aims to delve into the literature related to biomarkers in pre-eclampsia and its possible clinical applications.
Metabolic Syndrome and Inflammation: Interrelated Aspects and Biomarkers Involved
Page: 23-56 (34)
Author: Jose Pedregosa-Díaz, María Henar García-Lagunar and María Dolores Albaladejo-Otón
DOI: 10.2174/9781681084954117010005
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Abstract
Metabolic syndrome is considered a cluster of cardiovascular risk factors that are presented both in a single individual. They include insulin resistance, type 2 diabetes mellitus, dyslipidemia, hypertension and central obesity. Metabolic syndrome is related to systemic alterations that involve several tissues, such as liver, muscle, adipose tissue, stomach and immune system, varying the production of many biomolecules. Due to the main outcome of this clinical state being cardiovascular disease, metabolic syndrome has become a significant clinical priority.This global disturbance can be first detected and monitored later by several plasmatic biomarkers. This chapter intends to review a battery of avant-garde biomarkers related to metabolic syndrome.
Liver Fibrosis Biomarkers
Page: 57-79 (23)
Author: Iria Cebreiros-López
DOI: 10.2174/9781681084954117010006
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Abstract
Chronic liver diseases of differing etiologies are among the leading causes of mortality and morbidity worldwide. Establishing accurate staging of liver disease is very important for enabling both therapeutic decisions and prognostic evaluations. A liver biopsy is considered the gold standard for assessing the stage of hepatic fibrosis, but it has many limitations. During the last decade, several noninvasive markers for assessing the stage of hepatic fibrosis have been developed. Some have been well validated and are comparable to liver biopsy. This chapter will focus on the various noninvasive biochemical markers used to stage liver fibrosis.
Iron Metabolism: New Biomarkers Implicated
Page: 80-120 (41)
Author: Ana Hernando- Holgado and M. Pilar Gallego-Hernanz
DOI: 10.2174/9781681084954117010007
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Abstract
Human organisms require sufficient amounts of iron to satisfy metabolic needs and to accomplish specialized functions such as erythropoiesis, cellular immune response and oxidative metabolism. Despite its abundance, iron physico-chemical properties (practically insoluble at neutral pH under aerobic conditions) hinder its availability and thus specific ligands have evolved for absorption, transport and storage. Iron plays a corner-stone role both in erythropoiesis and inflammation. Iron deficit leads to anemia, but this deficit can be functional (with normal storage) or a true lack of iron: the accuracy of diagnosis results in a completely different treatment. Correct assessment of iron metabolism allows to diagnose and treat (not only in treatment decision-making, but. also predicting and assessing response to treatment) anemia. In this chapter, we review principal biomarkers related to iron metabolism as hemoglobin (whose levels are used as a measure of anemia), ferritin (related to iron storage and inflammation), hepcidin (related mainly to inflammation), transferrin and its receptors and other proteins involved in absorption and transport. Finally we review the phases of iron deficiency and its main clinical manifestation: anemia, both ferropenic and inflammation anemia, as well as clinical implication of iron overload.
Equations of Glomerular Filtration Rate and Biomarkers to Evaluate Renal Function: A Perspective
Page: 121-152 (32)
Author: Irene Gutiérrez-García and Juan Antonio Vílchez
DOI: 10.2174/9781681084954117010008
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Abstract
Early kidney disease is asymptomatic and strongly associated with morbidity and mortality, hence an accurate estimation of kidney function is crucial for its diagnosis. In turn, an appropriate diagnosis and treatment of chronic and acute kidney disease depends on early detection. Currently markers like blood concentrations of creatinine and Cystatin-C are used to estimate glomerular filtration rate, and others as proteinuria help to assess renal damage, but all of these have different limitations indicating the need for new biomarkers that can discriminate and detect damage, especially in the most critical situation during the development of kidney disease. Given that kidneys are the most important excretory organ, changes in blood concentration levels of a wide variety of metabolites can be a reflection of reduction of kidney function and renal damage. An ideal biomarker for renal disease has to be able to predict early diagnosis of kidney disease, allowing for identification of the type and etiology of the lesion, as well as initiation and monitoring of treatments. In this chapter, we describe the most relevant eGFR equation and biomarkers for kidney diseases.
Biomarkers of Bone Turnover: Molecular Approaches and Clinical Relevance
Page: 153-188 (36)
Author: Irene de Miguel-Elízaga, Ana Martínez-Ruíz, Natalia Sancho-Rodríguez and Miriam Martínez-Villanueva
DOI: 10.2174/9781681084954117010009
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Abstract
Osteoporosis, a disease characterized by low bone mass and deterioration of bone microarchitecture, leads to increased fragility and susceptibility to fracture. It is an important public health problem of the elderly and it is expected to rise with an increased life expectancy in the next years. Bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) is considered as the gold standard of bone status assessment despite the associated limitations. In recent years great progress has been made in the identification and characterization of biomarkers to aid the knowledge of metabolic bone disease and within the last years, a large number of new bone turnover markers (BTM) with increased specificity and sensitivity have been developed. BTM of formation and desorption are released during the process of bone remodeling. Bone biomarkers can be a great tool for the diagnosis of osteoporosis, but their use in clinical practice is limited because there are subjected to various preanalytical and analytical variations. Also, BTM are frequently used to provide valid information about the effectiveness of osteoporosis treatment (antiresorptive or bone formation therapies) although they are not useful alone to estimate bone loss. In this review, conventional and novel BTMs, their use and limitations into clinical practice, available diagnostic methods and current recommendations are discussed.
Vitamin D: from Bone Metabolism to New Applications
Page: 189-222 (34)
Author: Marta M. Castañeda San Cirilo
DOI: 10.2174/9781681084954117010010
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Abstract
Vitamin D is a fat-soluble vitamin, which has been classically associated with rickets and osteomalacia. The main function of Vitamin D is the regulation of calcium and phosphorus homeostasis. Plasma levels of 25-hydroxyvitamin D or calcidiol are considered the status indicator of Vitamin D in the human body, although it is biologically inert. 25-hydroxyvitamin D is transformed by 1α-hydroxylase to produce 1,25-dihydroxyvitamin D or calcitriol, the active metabolite of the vitamin. Vitamin D performs its actions through the Vitamin D receptor (VDR) that is present in more than 40 different tissues, as well as the enzyme 1α-hydroxylase, so it is now thought that Vitamin D may play a role in other physiological mechanisms. In the recent years, great interest has been a roused in Vitamin D and its involvement in different pathologies. However, the results of the studies are unclear, due to the involvement of mixed patients of different races, diagnostic criteria, latitude and season blood draw and the confounding variables such as age, BMI or sex not taken into account. The purpose of this chapter is to review the most recent publications of Vitamin D, in relation to new applications such as: diabetes, cancer, pregnancy and cardiovascular disease.
New Research About Biomarkers and Atrial Fibrillation
Page: 223-250 (28)
Author: Diana Hernández-Romero, Vanessa Roldán, Mariano Valdés and Francisco Marín
DOI: 10.2174/9781681084954117010011
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Abstract
Atrial fibrillation (AF) is the most common sustained chronic cardiac arrhythmia in clinical practice, increasing the risk of stroke, thromboembolism and mortality. The pathophysiology of AF is complex, including inflammation, oxidative stress, structural remodeling with apoptosis or fibrosis, leading to remodeling in the atria. However, the underlying mechanisms involved in the development of AF are not fully understood. Biomarkers, mainly determined in peripheral blood may increase our knowledge of the pathophysiology of AF with important implications in the assessment of AF diagnosis, prognosis, or therapy decision-making. The aim of this chapter is to provide an exhaustive overview of the knowledge about classical and novel biomarkers in AF and their implications, diagnostic and therapeutic potential.
Current Trends in Biomarkers of Acute Coronary Syndrome
Page: 251-284 (34)
Author: Carmen María Puche-Morenilla, Luis García de Guadiana Romualdo and Juan Antonio Vílchez
DOI: 10.2174/9781681084954117010012
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Abstract
Evaluation of patients presented to the emergency department with a complaint of chest pain or other signs and/or symptoms suggestive of acute coronary syndrome (ACS) is expensive and time-consuming. Nowadays, cardiac troponins (cardiac troponins I and T) are established as the standard biomarkers for prognostic evaluation and the detection of myocardial lesion of patients with ACS. Several studies have demonstrated that increases in biomarkers upstream from biomarkers of myocardial injury such as acute phase reactants, markers of inflammation, plaque destabilization and rupture biomarkers, cellular adhesion molecules and biomarkers of ischemia may identify patients with higher risk of having a cardiac event. The focus of this review is to provide information on biomarkers, specifically cardiac troponin, interleukin-6 and copeptin, which has become very important to improve the diagnosis of acute coronary syndrome and to predict prognosis following an actual event.
Physiopathology of Thrombotic Diseases and Platelet Derived Biomarkers
Page: 285-308 (24)
Author: Silvia Montoro- García and Sara María Martínez-Sánchez
DOI: 10.2174/9781681084954117010013
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Abstract
Thromboembolic disease includes a wide concept enclosing arterial and venous thrombosis. However, their physiopathologies show different effectors. The haemostatic system is a very complex mechanism with several roles such as maintenance of vascular permeability, production of an occlusive thrombus if vascular injury and its lysis. Biomarkers in cardiovascular medicine are useful non-invasive and sensitive tools adding information of the disease state and the possible management of these patients. The current chapter will attempt to provide the reader an insight into the mechanisms that accompany the pathological development of thrombus, particularly platelet-related. The endothelium, platelets and coagulation factors continue to attract widespread attention because of two independent mechanisms involved in atherothrombosis, aspects of both of which will be addressed in the following sections together with novel biomarkers such as microparticles, miRNAs or monocyte-platelet aggregates.
Importance of Biomarkers in Heart Failure: Classic and New Aspects
Page: 309-340 (32)
Author: Juan Antonio Vílchez, Pablo Perez-Cañadas, Francisco Marín and Jordi Ordóñez-Llanos
DOI: 10.2174/9781681084954117010014
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Abstract
Despite wide range of biomarkers studied in heart failure (HF), only natriuretic peptides have become standard-of-care biomarkers in HF and are currently the elected biomarkers that have crossed the field of research commonly used in daily practice. To achieve this knowledge, many biomarkers related to different pathophysiological effects in HF have been studied, being these pathways: myocardial stretch, myocyte injury, extracellular matrix and fibrotic state, inflammation, renal dysfunction, neurohormonal activation, and oxidative stress. The aim of this review was to summarize the published data about biomarkers studied in HF, focusing on data from randomized prospective clinical trials and large community-based cohorts. We also reviewed the new trends in those biomarkers and their application on this pathology.
Emerging Biomarkers in Peripheral Artery Disease
Page: 341-370 (30)
Author: Isabel Fort-Gallifa, Anna Hernandez-Aguilera, Vicente Martín-Paredero, Jorge Joven and Jordi Camps
DOI: 10.2174/9781681084954117010015
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Abstract
Peripheral artery disease is probably the most common cardiovascular disease. It affects extensive areas of arteries in the lower extremities. Almost invariably, it is the result of a sustained and asymptomatic progression of the disease, and effective preventive measures are applied too late. In peripheral artery disease, the degree of atherosclerosis is greater than in patients with adverse events in other arterial territories. Different aspects of atherosclerosis may also be represented, and designing strategies for prompt identification could facilitate therapeutic goals. The main objective of this chapter is to describe biomarkers that can be measured in serum or plasma, which help diagnose, monitor and/or predict the course of the disease. This chapter defines and describes established biomarkers, emerging biomarkers and candidate biomarkers. This chapter includes short descriptions of their main characteristics and their usefulness in the clinical evaluation of peripheral artery disease. Our aim is to give reader a perspective on the advances made in the research laboratory over the recent years in the analysis of these patients.
Early Neonatal Sepsis Biomarkers
Page: 371-396 (26)
Author: Natalia Sancho-Rodríguez, Marta Sancho-Rodríguez, Irene De-Migue-Elízaga and Ana Martínez-Ruiz
DOI: 10.2174/9781681084954117010016
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Abstract
Early-onset neonatal sepsis is currently a major cause of morbidity and mortality in neonatal period and its rapid diagnosis can help to establish an effective antibiotic treatment. The suspicion diagnosis of neonatal sepsis is based on a number of risk factors and non-specific clinical and laboratory parameters, therefore in many cases it is difficult to assess when it is the proper period to initiate antibiotic treatment. Confirmatory diagnosis depends on the results of blood cultures in the neonatal period, hence the importance of a biochemical marker that allows predicting the likelihood infection, as well as supporting the diagnosis of sepsis. Therefore identifying tools for rapid detection of neonatal sepsis is an objective of great importance in perinatal medicine, as an early and accurate diagnosis leads to an appropriate treatment thus potentially improving the final prognosis of these patients. The objective of this work is to study different markers of early neonatal sepsis, biochemical and haematological, particularly in cord blood; and establish its potential clinical usefulness. New techniques of molecular biology in cord blood are being studied in different types of samples, both blood and neonatal cord blood.
Sepsis: Traditional and Emergent Biomarkers for Diagnosis and Prognosis
Page: 397-435 (39)
Author: Luis García de Guadiana-Romualdo, Patricia Esteban-Torrella and María Dolores Albaladejo-Otón
DOI: 10.2174/9781681084954117010017
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Abstract
Sepsis and its related complications are associated with significant morbidity and mortality among populations worldwide. Early diagnosis and prompt initial management are keys to improve sepsis outcome. Therefore, biological markers (biomarkers) can be useful for identifying or ruling out sepsis, identifying patients who may benefit from specific therapies or assessing the response to therapy. Although numerous biomarkers have been investigated, only two biomarkers are currently used in the clinical practice, C-reactive protein (CRP) and procalcitonin (PCT). Both were included in 2001 in the revised definition of sepsisas variables to diagnose sepsis, but even these have limited ability to distinguish sepsis from other inflammatory conditions or to predict outcome, and there is a continuous search for better biomarkers of sepsis. Moreover, the recent Third Consensus Definitions for Sepsis and Septic Shock does not include the use of biomarkers as tools for management of sepsis and, probably, to redefine the role of these biomarkers is necessary. The purpose of this review is to describe the most relevant sepsis biomarkers used currently in the clinical practice and discuss the future role of some emergent biomarkers for the management of sepsis.
Biomarkers in Saliva as a Tool for Health Diagnosis
Page: 436-468 (33)
Author: Ana M. Moreno-Fuentes and Carmen Nieto-Sánchez
DOI: 10.2174/9781681084954117010018
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Abstract
Over the last years, there has been an increasing attention over the use of saliva as a proper diagnostic fluid. One of the most interesting aspects in saliva based diagnosis is the non-invasive method of obtaining oral samples. This is a safe method for both, the health worker and the patient, related to the management of saliva samples. The utility of the whole saliva sample as an instrument of salivary diagnosis has been proven in almost all the research fields. The relation between saliva based components and blood based components has been proven and hence, salivary diagnosis could be a proper and accurate tool for disease diagnosis. The research of salivary biomarkers in viral and bacterial infections, autoimmune diseases, endocrine diseases, oncology, systemic diseases, stress assessment, medication detection and forensic science among others, is becoming a reality. It is expected that, with the help of current technological advances, salivary analysis which owns the analytical sensitivity and specificity required for this technology, could be used as a valuable tool and a diagnostic medium to achieve successful findings. However, there is a lot of work to do due to the fact that, some results from certain investigations still remain contradictory. Definitions of Words and Terms According to the National Institutes of Health (NIH), a Biomarker is an objectively measured and evaluated indicator of normal biological processes, pathogenic processes or pharmacological responses to a therapeutic intervention [1]. Saliva is a complex fluid composed of different secretions from the major and minor salivary glands.
Endocrine Disruptors: What Do We Know about the Effects and Risk Factors in Humans?
Page: 469-504 (36)
Author: Africa de Béjar-Almira, Alice Charlotte Viney and Marta M. Castañeda San Cirilo
DOI: 10.2174/9781681084954117010019
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Abstract
In the last few decades, the theme of endocrine disruption and endocrine disrupting chemicals has become more and more relevant, raising alarm in the scientific community and amongst public health officials, as well as questioning the traditional concepts of toxicology. This chapter is a revision and summary of the latest information and articles concerning this subject. It discusses the terms and definitions of endocrine disruption, the sources and mechanisms of action of these chemicals both naturally and artificially made, reviewing the potential adverse development, reproductive, neurological, and immune effects that they can have on the different systems in the body, and how they can relate to the different epidemics of cancer, diabetes and obesity. It also provides the latest up-to-date information on the tests and methods used to detect and assess these entities, offering ideas and lines of future investigation to attempt to better understand the knowledge in this field and reduce the potential threat of these environmental hazards to mankind.
Monitoring of Monoclonal Antibodies, A New Window in the Use of Biomarkers in Pharmacology
Page: 505-527 (23)
Author: Enrique Jiménez-Santos, Iris Muñoz-García, Maria S García-Simón, Jose Pedregosa-Díaz and Juan Antonio Vílchez
DOI: 10.2174/9781681084954117010020
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Abstract
Pharmacology has been a major field of clinical laboratory. Firstly in the emergency measures for the diagnosis of possible poisoning, and secondly in the monitoring of various treatments, mainly antibiotics and anticonvulsants, but also others in such as antidepressants, digitalis, anxiolytics, etc. The discovery of biological treatments, based on the use of monoclonal antibodies, and their use for the treatment of various chronic diseases, whether the digestive tract or the rheumatic diseases, is considered a big step in favor of patients and their quality of life. However, these treatments have had a worse response than they were supposed to, sometimes due to their own immunogenicity of these monoclonal antibodies in the organism, triggering responses to the drug itself, which reduces their effectiveness and also involves high costs and secondary effects to patients. That is why the biological monitoring of drugs has been proven to be a way to improve treatment adherence, and cost-effectiveness. In turn, it is also important to determine the presence of antibodies generated by the patient in response to the drug, because these cases determine inefficient and highly expensive treatments and the injury to the patient.
Introduction
Biomarkers are any measurable biochemical characteristics of an organism that reflect a particular physiological state. Biomarkers can take many different forms including particular proteins or peptides, antibodies, cell types, metabolites, hormones, enzyme levels, compounds related to genomics, etc. A biomarker can also be a substance introduced into a patient to assess the internal organ systems role. In medicine, biomarkers considered as compounds isolated from serum, urine, or other fluids, can be used as an indicator of the presence or severity of a particular disease state. The use of biomarkers is becoming a fundamental practice in medicine, Biomarker research involves a significantly greater scope of laboratory medicine. This monograph presents information on several types of biomarkers for general pathologies (preeclampsia, metabolic syndrome, iron metabolism, bone disease, liver function, renal function), cardiovascular pathology (including atrial fibrillation, peripheral artery disease, thrombotic disorders) and sepsis. Additional information on endocrine and salivary biomarkers is also presented. New Trends in Biomarkers and Diseases: An Overview is an ideal reference for medical students, pathology trainees and clinical researchers seeking information on biomarkers in medicine.