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      Objective and Measurable Biomarkers in Chronic Subjective Tinnitus

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          Abstract

          Tinnitus is associated with increased social costs and reduced quality of life through sleep disorders or psychological distress. The pathophysiology of chronic subjective tinnitus, which accounts for most tinnitus, has not been clearly elucidated. This is because chronic subjective tinnitus is difficult to evaluate objectively, and there are no objective markers that represent the diagnosis or therapeutic effect of tinnitus. Based on the results of studies on patients with chronic subjective tinnitus, objective and measurable biomarkers that help to identify the pathophysiology of tinnitus have been summarized. A total of 271 studies in PubMed, 303 in EMBASE, and 45 in Cochrane Library were found on biomarkers related to chronic subjective tinnitus published until April 2021. Duplicate articles, articles not written in English, review articles, case reports, and articles that did not match our topic were excluded. A total of 49 studies were included. Three specimens, including blood, saliva, and urine, and a total of 58 biomarkers were used as indicators for diagnosis, evaluation, prognosis, and therapeutic effectiveness of tinnitus. Biomarkers were classified into eight categories comprising metabolic, hemostatic, inflammatory, endocrine, immunological, neurologic, and oxidative parameters. Biomarkers can help in the diagnosis, measure the severity, predict prognosis, and treatment outcome of tinnitus.

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          Most cited references119

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          Brain-derived neurotrophic factor.

          Since the purification of BDNF in 1982, a great deal of evidence has mounted for its central roles in brain development, physiology, and pathology. Aside from its importance in neural development and cell survival, BDNF appears essential to molecular mechanisms of synaptic plasticity. Basic activity-related changes in the central nervous system are thought to depend on BDNF modification of synaptic transmission, especially in the hippocampus and neocortex. Pathologic levels of BDNF-dependent synaptic plasticity may contribute to conditions such as epilepsy and chronic pain sensitization, whereas application of the trophic properties of BDNF may lead to novel therapeutic options in neurodegenerative diseases and perhaps even in neuropsychiatric disorders.
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            Decreased serum brain-derived neurotrophic factor levels in major depressed patients.

            Recent findings with animal models have suggested a possible role for brain-derived neurotrophic factor (BDNF) in depression. We have therefore hypothesized that depression could be characterized by low levels of serum BDNF. Major depressed patients (15F + 15M) diagnosed according to DSM-IV criteria and healthy controls (15F + 15M) participated in the study. Serum BDNF was assayed with the ELISA method and the severity of depression was evaluated with Montgomery-Asberg-Depression Rating Scale (MADRS). BDNF levels were significantly lower in patients than in controls: 22.6 +/- 3 and 26.5 +/- 7 ng/ml (t-test = 2.7; d.f. = 58; P < 0.01). They were negatively correlated to the MADRS scores (r = -0.55; P < 0.02). Female patients were more depressed and released less BDNF than men. Analysis of covariance (MADRS and gender as independent variable vs. BDNF as dependent variable) indicated that depression severity mainly accounted for the negative correlation. These results suggest that major depression is characterized by low serum BDNF levels and support the hypothesis of neurotrophic factor involvement in affective disorders.
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              Salivary cortisol in psychoneuroendocrine research: recent developments and applications.

              The assessment of cortisol in saliva has proven a valid and reliable reflection of the respective unbound hormone in blood. To date, assessment of cortisol in saliva is a widely accepted and frequently employed method in psychoneuroendocrinology. Due to several advantages over blood cortisol analyses (e.g., stress-free sampling, laboratory independence, lower costs) saliva cortisol assessment can be the method of choice in basic research and clinical environments. The determination of cortisol in saliva can facilitate stress studies including newborns and infants and replace blood sampling for diagnostic endocrine tests like the dexamethasone suppression test. The present paper provides an up-to-date overview of recent methodological developments, novel applications as well as a discussion of possible future applications of salivary cortisol determination.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                21 June 2021
                June 2021
                : 22
                : 12
                : 6619
                Affiliations
                [1 ]Department of Otolaryngology, Head & Neck Surgery, School of Medicine, Kyung Hee University, Seoul 02447, Korea; kkang814@ 123456naver.com (D.-W.K.); hoon0700@ 123456naver.com (S.-H.K.)
                [2 ]Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Korea; sgskim@ 123456khu.ac.kr
                [3 ]St. Vincent’s Hospital, The Catholic University of Korea, Suwon 16247, Korea; dcpark@ 123456catholic.ac.kr
                Author notes
                [* ]Correspondence: yeo2park@ 123456gmail.com ; Tel.: +82-2-958-8980; Fax: +82-2-958-8470
                Author information
                https://orcid.org/0000-0003-0057-9131
                https://orcid.org/0000-0001-5045-5060
                https://orcid.org/0000-0001-8021-1024
                Article
                ijms-22-06619
                10.3390/ijms22126619
                8235100
                34205595
                2206b3b9-faf5-43d3-91fc-319cccee684c
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 12 May 2021
                : 17 June 2021
                Categories
                Review

                Molecular biology
                biomarker,tinnitus,pathophysiology
                Molecular biology
                biomarker, tinnitus, pathophysiology

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