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Salivary biomarkers : diagnostic potential in oral and systemic diseases in epidemiological surveys

机译:唾液生物标志物:流行病学调查在口腔和全身疾病中的诊断潜力

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摘要

Human saliva is a fluid with many biological functions, and essential for the maintenance of oral health. Several studies report local and systemic biomarkers appearing in saliva, including electrolytes, blood products, enzymes and tissue destruction molecules, inflammatory markers as well as proteins putatively associated with different diseases. However, the clinical utility of salivary diagnostics for the assessment of oral and systemic disease remains elusive. The general aim of this project was to investigate the utility of salivary biomarkers for diagnostic potential of oral- and systemic diseases in large populations.This thesis consists of two different projects:(i). Skåne cohort - A cross-sectional study (Studies I and II): 451 individuals were randomly selected and enrolled for these investigations, including 51% women. All participants were asked to complete a questionnaire, a medical history was taken, a clinical examination was made and stimulated saliva samples were collected.(ii). PAROKRANK sub-cohort (Periodontal disease and the relation to myocardial infarction) (Studies III and IV): A case-control study comprising 400 subjects. In total 200 consecutive patients with a first acute myocardial infarction (AMI) admitted to coronary care units in Sweden from May 2010 to December 2011, and 200 controls without previous AMI, matched for age, gender, residential area were included during the same time period. Dental examinations were performed, blood and stimulated saliva samples were collected eight to ten weeks after the myocardial infarction (MI). Matched controls were examined within one to two weeks after the MI patients.Study I: The aim of this study was to investigate if selected salivary biomarkers could be used for epidemiological studies for detection of periodontitis. Our findings showed that patients with severe periodontitis had elevated salivary concentrations of interleukin (IL) -1β (IL-1β) and matrix metalloproteinase (MMP) -8 (MMP-8), as well as and increased ratio of MMP-8/ tissue inhibitor of metalloproteinase-1 (TIMP-1).Study II: The aim of this study was to investigate if certain salivary biomarkers could be used for detection of common systemic inflammatory diseases. The results of our study showed that salivary IL-8 concentrations were higher in patients with bowel disease and subjects who had experience of tumor diseases. MMP-8 levels were elevated in saliva from patients with diabetes, muscle and joint diseases or previously had undergone cardiac surgery.Study III: The aim of this study was to investigate whether salivary concentrations of selected cardiovascular biomarkers could be used to identify patients with a previous MI and whether such markers, in plasma and saliva, were related to periodontal status. There was no difference between participants with or without MI in regards of N-terminal prohormone of brain natriuretic peptide (NT- pro BNP) and growth differentiation factor-15 (GDF-15) levels in saliva. However, cystatin C, NT- pro BNP and GDC-15 levels were higher in MI patients with other co-morbidities. The levels of cystatin C were lower in saliva from patients with MI. GDF-15 levels correlated with periodontal status in both groups. Further, there was no correlation between plasma and saliva levels.Study IV: The aim of this study was to explore the levels of the inflammatory markers, MMP-8, MMP-9, TIMP-1 and myeloperoxidase (MPO) in saliva with regards to previous MI and periodontal disease. The analyzed biomarkers correlated significantly with each other and most of the periodontal parameters in both study groups. Salivary MMP-8 and MPO levels were significantly higher in non- MI subjects.In conclusion, the findings in this project indicates that certain salivary biomarkers have the potential to be used for screening purposes in epidemiological studies related to both oral and systemic diseases. In addition, the selected salivary biomarkers in our studies could be seen as markers for increased local and systemic inflammation.
机译:人唾液是一种具有多种生物学功能的液体,对于维持口腔健康至关重要。几项研究报告了唾液中出现的局部和全身生物标志物,包括电解质,血液制品,酶和组织破坏分子,炎症标志物以及可能与不同疾病相关的蛋白质。但是,唾液诊断在评估口腔和全身性疾病方面的临床应用仍然难以捉摸。该项目的总体目标是研究唾液生物标志物在大范围人群口腔和全身疾病诊断潜力中的应用。本论文包括两个不同的项目:(i)。斯科讷队列研究-一项横断面研究(研究I和II):随机选择了451个人并进行了这些研究,其中包括51%的女性。要求所有参与者填写问卷,记录病史,进行临床检查并收集刺激的唾液样本。(ii)。 PAROKRANK子队列(牙周疾病及其与心肌梗塞的关系)(研究III和IV):一项病例对照研究,包括400名受试者。从2010年5月至2011年12月,瑞典总共有200例首次患有急性心肌梗塞(AMI)的患者被纳入冠心病监护病房,并在同一时间段内纳入了200例无先前AMI的对照,这些患者的年龄,性别和居住地区均匹配。在心肌梗塞(MI)后八到十周进行牙科检查,收集血液和刺激唾液样本。在MI患者之后的一到两周内检查了匹配的对照。研究I:本研究的目的是研究是否可以将选定的唾液生物标志物用于流行病学研究以检测牙周炎。我们的研究结果表明,患有严重牙周炎的患者唾液中白细胞介素(IL)-1β(IL-1β)和基质金属蛋白酶(MMP)-8(MMP-8)的浓度升高,并且MMP-8 /组织比例增加金属蛋白酶1(TIMP-1)的抑制剂。研究II:本研究的目的是研究某些唾液生物标记物是否可用于检测常见的全身性炎症性疾病。我们的研究结果表明,肠病患者和有肿瘤疾病经验的受试者唾液中的IL-8浓度较高。患有糖尿病,肌肉和关节疾病或曾经接受过心脏手术的患者的唾液中MMP-8水平升高。研究III:这项研究的目的是研究唾液中所选择的心血管生物标志物的浓度是否可用于鉴定患有心血管疾病的患者。先前的心梗以及血浆和唾液中的此类标志物是否与牙周状态有关。在有或没有MI的参与者之间,唾液中脑钠肽的N末端激素(NT-pro BNP)和生长分化因子-15(GDF-15)水平没有差异。但是,在患有其他合并症的MI患者中,胱抑素C,NT-pro BNP和GDC-15的水平较高。 MI患者唾液中胱抑素C含量较低。两组中GDF-15水平与牙周状态相关。此外,血浆和唾液水平之间没有相关性。研究IV:本研究的目的是就唾液中炎症标志物,MMP-8,MMP-9,TIMP-1和髓过氧化物酶(MPO)的水平进行研究。以前的心梗和牙周疾病。在两个研究组中,分析的生物标志物彼此之间以及大多数牙周参数之间具有显着相关性。非MI受试者的唾液MMP-8和MPO水平显着较高。总而言之,本项目的发现表明某些唾液生物标志物有可能用于与口腔和全身疾病相关的流行病学研究中进行筛查。此外,在我们的研究中选择的唾液生物标志物可以被视为局部和全身炎症增加的标志物。

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    Rathnayake Nilminie;

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  • 年度 2014
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