Diagnostic Potential of Saliva: Current State and Future Applications
01 May 2011-Clinical Chemistry (American Association for Clinical Chemistry)-Vol. 57, Iss: 5, pp 675-687
TL;DR: Saliva has the potential to become a first-line diagnostic sample of choice owing to the advancements in detection technologies coupled with combinations of biomolecules with clinical relevance as mentioned in this paper, however, these technologies have not yet been integrated into current clinical practice and work flow.
Abstract: BACKGROUND: Over the past 10 years, the use of saliva as a diagnostic fluid has gained attention and has become a translational research success story. Some of the current nanotechnologies have been demonstrated to have the analytical sensitivity required for the use of saliva as a diagnostic medium to detect and predict disease progression. However, these technologies have not yet been integrated into current clinical practice and work flow. CONTENT: As a diagnostic fluid, saliva offers advantages over serum because it can be collected noninvasively by individuals with modest training, and it offers a cost-effective approach for the screening of large populations. Gland-specific saliva can also be used for diagnosis of pathology specific to one of the major salivary glands. There is minimal risk of contracting infections during saliva collection, and saliva can be used in clinically challenging situations, such as obtaining samples from children or handicapped or anxious patients, in whom blood sampling could be a difficult act to perform. In this review we highlight the production of and secretion of saliva, the salivary proteome, transportation of biomolecules from blood capillaries to salivary glands, and the diagnostic potential of saliva for use in detection of cardiovascular disease and oral and breast cancers. We also highlight the barriers to application of saliva testing and its advancement in clinical settings. SUMMARY: Saliva has the potential to become a first-line diagnostic sample of choice owing to the advancements in detection technologies coupled with combinations of biomolecules with clinical relevance.
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TL;DR: Although wearable biosensors hold promise, a better understanding of the correlations between analyte concentrations in the blood and noninvasive biofluids is needed to improve reliability.
Abstract: Wearable biosensors are garnering substantial interest due to their potential to provide continuous, real-time physiological information via dynamic, noninvasive measurements of biochemical markers in biofluids, such as sweat, tears, saliva and interstitial fluid. Recent developments have focused on electrochemical and optical biosensors, together with advances in the noninvasive monitoring of biomarkers including metabolites, bacteria and hormones. A combination of multiplexed biosensing, microfluidic sampling and transport systems have been integrated, miniaturized and combined with flexible materials for improved wearability and ease of operation. Although wearable biosensors hold promise, a better understanding of the correlations between analyte concentrations in the blood and noninvasive biofluids is needed to improve reliability. An expanded set of on-body bioaffinity assays and more sensing strategies are needed to make more biomarkers accessible to monitoring. Large-cohort validation studies of wearable biosensor performance will be needed to underpin clinical acceptance. Accurate and reliable real-time sensing of physiological information using wearable biosensor technologies would have a broad impact on our daily lives.
1,579 citations
TL;DR: In future studies, combined investigations of a particular compound with regard to human matrices such as breath, urine, saliva and cell culture investigations will lead to novel scientific progress in the field.
Abstract: Breath analysis is a young field of research with its roots in antiquity. Antoine Lavoisier discovered carbon dioxide in exhaled breath during the period 1777-1783, Wilhelm (Vilem) Petters discovered acetone in breath in 1857 and Johannes Muller reported the first quantitative measurements of acetone in 1898. A recent review reported 1765 volatile compounds appearing in exhaled breath, skin emanations, urine, saliva, human breast milk, blood and feces. For a large number of compounds, real-time analysis of exhaled breath or skin emanations has been performed, e.g., during exertion of effort on a stationary bicycle or during sleep. Volatile compounds in exhaled breath, which record historical exposure, are called the 'exposome'. Changes in biogenic volatile organic compound concentrations can be used to mirror metabolic or (patho)physiological processes in the whole body or blood concentrations of drugs (e.g. propofol) in clinical settings-even during artificial ventilation or during surgery. Also compounds released by bacterial strains like Pseudomonas aeruginosa or Streptococcus pneumonia could be very interesting. Methyl methacrylate (CAS 80-62-6), for example, was observed in the headspace of Streptococcus pneumonia in concentrations up to 1420 ppb. Fecal volatiles have been implicated in differentiating certain infectious bowel diseases such as Clostridium difficile, Campylobacter, Salmonella and Cholera. They have also been used to differentiate other non-infectious conditions such as irritable bowel syndrome and inflammatory bowel disease. In addition, alterations in urine volatiles have been used to detect urinary tract infections, bladder, prostate and other cancers. Peroxidation of lipids and other biomolecules by reactive oxygen species produce volatile compounds like ethane and 1-pentane. Noninvasive detection and therapeutic monitoring of oxidative stress would be highly desirable in autoimmunological, neurological, inflammatory diseases and cancer, but also during surgery and in intensive care units. The investigation of cell cultures opens up new possibilities for elucidation of the biochemical background of volatile compounds. In future studies, combined investigations of a particular compound with regard to human matrices such as breath, urine, saliva and cell culture investigations will lead to novel scientific progress in the field.
549 citations
TL;DR: The data suggest that there is a strong direct effect of the endogenous circadian clock on multiple human metabolic pathways that is independent of sleep or feeding, and they identify multiple potential small-molecule biomarkers of human circadian phase and sleep pressure.
Abstract: The circadian clock orchestrates many aspects of human physiology, and disruption of this clock has been implicated in various pathologies, ranging from cancer to metabolic syndrome and diabetes. Although there is evidence that metabolism and the circadian clockwork are intimately linked on a transcriptional level, whether these effects are directly under clock control or are mediated by the rest-activity cycle and the timing of food intake is unclear. To answer this question, we conducted an unbiased screen in human subjects of the metabolome of blood plasma and saliva at different times of day. To minimize indirect effects, subjects were kept in a 40-h constant routine of enforced posture, constant dim light, hourly isocaloric meals, and sleep deprivation. Under these conditions, we found that ~15% of all identified metabolites in plasma and saliva were under circadian control, most notably fatty acids in plasma and amino acids in saliva. Our data suggest that there is a strong direct effect of the endogenous circadian clock on multiple human metabolic pathways that is independent of sleep or feeding. In addition, they identify multiple potential small-molecule biomarkers of human circadian phase and sleep pressure.
488 citations
TL;DR: Reports here are microfluidic models for eccrine sweat generation and flow which are coupled with review of blood-to-sweat biomarker partition pathways, therefore providing insights such as how biomarker concentration changes with sweat flow rate.
Abstract: Non-invasive and accurate access of biomarkers remains a holy grail of the biomedical community. Human eccrine sweat is a surprisingly biomarker-rich fluid which is gaining increasing attention. This is especially true in applications of continuous bio-monitoring where other biofluids prove more challenging, if not impossible. However, much confusion on the topic exists as the microfluidics of the eccrine sweat gland has never been comprehensively presented and models of biomarker partitioning into sweat are either underdeveloped and/or highly scattered across literature. Reported here are microfluidic models for eccrine sweat generation and flow which are coupled with review of blood-to-sweat biomarker partition pathways, therefore providing insights such as how biomarker concentration changes with sweat flow rate. Additionally, it is shown that both flow rate and biomarker diffusion determine the effective sampling rate of biomarkers at the skin surface (chronological resolution). The discussion covers a broad class of biomarkers including ions (Na(+), Cl(-), K(+), NH4 (+)), small molecules (ethanol, cortisol, urea, and lactate), and even peptides or small proteins (neuropeptides and cytokines). The models are not meant to be exhaustive for all biomarkers, yet collectively serve as a foundational guide for further development of sweat-based diagnostics and for those beginning exploration of new biomarker opportunities in sweat.
459 citations
TL;DR: A review of available and in-development diagnostic tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) including nanomaterial-based tools is presented in this paper.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every corner of the globe, causing societal instability. The resultant coronavirus disease 2019 (COVID-19) leads to fever, sore throat, cough, chest and muscle pain, dyspnoea, confusion, anosmia, ageusia and headache. These can progress to life-threatening respiratory insufficiency, also affecting the heart, kidney, liver and nervous systems. The diagnosis of SARS-CoV-2 infection is often confused with that of influenza and seasonal upper respiratory tract viral infections. Due to available treatment strategies and required containments, rapid diagnosis is mandated. This Review brings clarity to the rapidly growing body of available and in-development diagnostic tests, including nanomaterial-based tools. It serves as a resource guide for scientists, physicians, students and the public at large.
409 citations
References
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TL;DR: The evidence is recounted that atherosclerosis, the main cause of CAD, is an inflammatory disease in which immune mechanisms interact with metabolic risk factors to initiate, propagate, and activate lesions in the arterial tree.
Abstract: ecent research has shown that inflammation plays a key role in coronary artery disease (CAD) and other manifestations of atherosclerosis. Immune cells dominate early atherosclerotic lesions, their effector molecules accelerate progression of the lesions, and activation of inflammation can elicit acute coronary syndromes. This review highlights the role of inflammation in the pathogenesis of atherosclerotic CAD. It will recount the evidence that atherosclerosis, the main cause of CAD, is an inflammatory disease in which immune mechanisms interact with metabolic risk factors to initiate, propagate, and activate lesions in the arterial tree. A decade ago, the treatment of hypercholesterolemia and hypertension was expected to eliminate CAD by the end of the 20th century. Lately, however, that optimistic prediction has needed revision. Cardiovascular diseases are expected to be the main cause of death globally within the next 15 years owing to a rapidly increasing prevalence in developing countries and eastern Europe and the rising incidence of obesity and diabetes in the Western world. 1 Cardiovascular diseases cause 38 percent of all deaths in North America and are the most common cause of death in European men under 65 years of age and the second most common cause in women. These facts force us to revisit cardiovascular disease and consider new strategies for prediction, prevention, and treatment.
7,551 citations
TL;DR: New insights into inflammation in atherosclerosis not only increase the understanding of this disease, but also have practical clinical applications in risk stratification and targeting of therapy for this scourge of growing worldwide importance.
Abstract: Atherosclerosis, formerly considered a bland lipid storage disease, actually involves an ongoing inflammatory response. Recent advances in basic science have established a fundamental role for inflammation in mediating all stages of this disease from initiation through progression and, ultimately, the thrombotic complications of atherosclerosis. These new findings provide important links between risk factors and the mechanisms of atherogenesis. Clinical studies have shown that this emerging biology of inflammation in atherosclerosis applies directly to human patients. Elevation in markers of inflammation predicts outcomes of patients with acute coronary syndromes, independently of myocardial damage. In addition, low-grade chronic inflammation, as indicated by levels of the inflammatory marker C-reactive protein, prospectively defines risk of atherosclerotic complications, thus adding to prognostic information provided by traditional risk factors. Moreover, certain treatments that reduce coronary risk also limit inflammation. In the case of lipid lowering with statins, this anti-inflammatory effect does not appear to correlate with reduction in low-density lipoprotein levels. These new insights into inflammation in atherosclerosis not only increase our understanding of this disease, but also have practical clinical applications in risk stratification and targeting of therapy for this scourge of growing worldwide importance.
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TL;DR: New insights are provided on inflammatory processes involved in atherosclerosis development provide important links between risk factors and the mechanisms of atherogenesis and a major challenge for future research is to implement these new insights in order to improve strategies for prediction, prevention and treatment of cardiovascular events.
Abstract: It is now generally recognized that atherosclerosis is a chronic inflammatory disease, characterized by overrecruitment of leukocytes (monocytes and T-cells) to the site of inflammation. Vascular injury in response to cardiovascular risk factors promotes endothelial dysfunction, resulting in enhanced adhesion molecule expression and secretion of pro-inflammatory cytokines and chemokines. This, in turn, leads to adherence, migration and accumulation of leukocytes within atherosclerotic lesions. The recent findings on inflammatory processes involved in atherosclerosis development provide important links between risk factors and the mechanisms of atherogenesis. Thus, research interest has increasingly focused on inflammatory biomarkers as means of predicting the risk of future clinical events. Indeed, elevated plasma levels of molecules such as soluble intercellular adhesion molecule-1, interleukin-6 or C-reactive protein (CRP) have been shown to represent inflammatory markers of future cardiovascular risk. Among these, CRP has emerged as the most powerful and accessible for clinical use. A major challenge for future research is to implement these new insights in order to improve strategies for prediction, prevention and treatment of cardiovascular events.
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Book•
01 Jan 1999
TL;DR: This book discusses Laboratory Principles, Laboratory Management, and Biochemical Aspects of Hematology, as well as selecting and Interpretation of Laboratory Procedures for Selection and Evaluation of Methods.
Abstract: Part I: Laboratory Principles. General Laboratory Techniques and Procedures. Specimen Collection and Processing, Sources of Biological Variation. Part II: Analytical Techniques and Instrumentation. Spectrophotometric Techniques. Fluorometry, Nephelometry, And Turbidimetry. Basic Principles of Radioactivity and Its Measurement. Electrochemistry. Electrophoresis. Chromatography/Mass Spectrometry. Principlesof Immunochemical Techniques. Automation in the Clinical Laboratory. Part III: Chemometrics. Statistical Procedures. Selection and Interpretation of Laboratory Procedures. Selection and Evaluation of Methods. Establishment and Use of Reference Values. Part IV: Laboratory Management. Clinical Laboratory Informatics. Laboratory Management. Quality Management. Part V: Analytes. Nucleic Acid Biochemistry and Diagnostic Applications. Amino Acids. Proteins. Cytokines. Clinical Enzymology. Tumour Markers. Carbohydrates. Lipids, Lipoproteins, And Apolipoproteins. Therapeutic Drug Monitoring. Clinical Toxicology. Toxic Metals. Vitamins. Trace Elements. Electrolytes and Blood Gases. Part VI: Pathophysiology. Physiology and Disorders of Wates, Electrolyte, And Acid-Base Metabolism. Liver Function. Cardiac Function. Renal Function and Nitrogen Metabolics. Gastric, Pancreatic, And Intestinal Function. Organ Transplantation. Nutritional Assessment, Therapy, And Monitoring. Mineral and Bone Metabolism. General Endocrine Function. Pituitary Function. Thyroid Function. Function of the Adrenal Cortex. Cathecol Amines and Serotonin. Reproductive Endocrine Function. Biochemical Aspects of Hematology. Porphyrins and Disorders of Porphyrin Metabolism. Clinical Chemistry of Pregnancy. Lysosomal Storage Disease. Appendix.
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