الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 152 |  |  |
| | | from | 152 | | |
Abstract
Biomarkers complement other clinical information by providing quantitative data regarding a pathophysiological mechanism that can be used for the early diagnosis of a specific disease, to monitor and guide treatment.(19) PCT and CRP are both proteins produced in response to infection and/or inflammation. CRP is a well-established biomarker of infection and inflammation (27). While PCT is an approved in surviving sepsis campaign guidelines. (13) lactate level greater than 2 mmol/L is part of septic shock identification(21).
Pro-inflammatory cytokines (TNF, IL-1β and IL-6 )are markers of the hyper-inflammatory phase of sepsis.(26)
Complement proteins used as biomarkers in sepsis however they are not widely used and they does not appear to be a major role for monitoring(26). activated neutrophils and monocytes are part of sepsis which can be dected by analyzing the levels of certain cell differentiation molecules on the PMN cell surface, using quantitative flow cytometry ex: CD64(52) CD11b(55) and TREM-1(56)
HBP and sRAGE are prognostic biomarkers that predict shock and (worsening and DIC) correspondly. (58)(59)
Biomarkers that detect the immunosuppressive phase of sepsis include low levels of HLA-DR expression (69) elevated levels of IL-10 (72) and for less extent TGF-β level (75).
Other biomarkers include angiopoietins, soluble adhesion molecules, endocan(76), suPAR(77) Mid-regional pro-adrenomedullin (MR-proADM)(82) and D-dimer(85).
New biomarkers also hold the promise of allowing clinicians to detect kidney injury earlier, to guide future therapy, and to better prognosticate of AKI, differential diagnosis of AKI. (90)
Biomarkers for ischemic kidney injury could be monitored in the blood or urine. Although there have been over 20 unique biomarkers of AKI identified or under investigation, NGAL, cystatin C (CyC), interleukin (IL-18) and Kidney Injury Molecule-1 (KIM-1) are the most important biomarkers of AKI. (91)
Serum NGAL (sNGAL) is quite sensitive for diagnosing AKI, but its utility may be limited by its lack of specificity. (103)
Urinary NGAL is probably more reflective of local renal injury, because systemic NGAL in serum or plasma may be derived from stressed immune cells and injured epithelial cells of the lungs and the gastrointestinal tract (106).
Urinary NGAL levels rise rapidly < 2 hours from initial insult and time to peak level is 6 hours. (100)
Elevated levels of urinary cystatin C may reflect tubular dysfunction and tubuleinterstitial disease. Data suggest that appearance of increased concentrations of cystatin C in urine may be a sensitive marker of renal tubular injury and may correlate with severity of AKI.(92)
IL-18 is more specific to ischemic AKI and other forms of acute tubular necrosis and does not seem to be affected by prerenal azotemia, chronic kidney disease, or urinary tract infections or nephrotoxic AKI.(111)
However IL-8 may be influenced by various systemic inflammatory states, endotoxaemia, immunological injury, cisplatin toxicity and septic shock. (110)
IL-18 also offers prognostic information regarding severity and mortality at the time of AKI diagnosis. (91)
Biomarkers in ALI are classified according to pathophysiology to 1-Cell-specific markers , 2-Mediators of lung injury and 3-Coagulation markers. (119)
(1)- Cell-specific biologic markers measured in both plasma and bronchoalveolar lavage fluid include:
a- Endothelial injury markers as: angiopoietin-2 levels which were strongly and independently predictive of poor outcomes (122), Von Willebrand factor which plasma level was a good predictive tool for the severity, mortality, and prolonged mechanical ventilation(125), P-selectin(127), Intercellular adhesion molecule-1 (ICAM-1) that independently associated with mortality and fewer ventilator- and organ failure-free day(130), Vascular endothelial growth factor(VEGF). (132)
b- Epithelial injury markers as: surfactant proteins SP-D that indicate damage to the respiratory membrane(139), Receptor for advanced glycation end-products (RAGE) that correlate with physiologic measures of more severe lung injury and predict worse outcome(136).
(2)- Mediators of lung injury include: pro-inflammatory cytokines interleukins (IL) such as IL-1β, TNFα, IL-6, and IL-8 which possess potent pro-inflammatory actions, as well as the anti-inflammatory interleukins including IL-1ra, IL-10 and IL-13 (148)(147)(119)
(3)- Coagulation markers of ALI include activated protein C, plasminogen activator inhibitor (PAI-1) and thrombomodulin.(147)
Classical biomarkers of ACS are CK-MB and troponin.however recent biomarkers include : (1)- Plaque destabilization biomarkers: 1-Matrix metalloproteinases (MMPs), MMP-1, MMP-9 and IL-6 levels alone or in combination may prove useful to exclude CAD (188) MMP3 is also elevated after acute MI, and associated with left ventricular dysfunction(189). 2- Myeloperoxidase (MPO)which emerged as an early marker of myocyte necrosis(201) 3- Pregnancy-associated plasma protein A (PAPP-A)(204) 4- VCAM-1, ICAM-1 and E-selectin increase within the first 72 hours in UAP and Non-Q MI(206). (2)- Biomarkers of myocardial ischemia: Ischemia-modified albumin (IMA) (217), Heart fatty acid-binding protein (H-FABP) (231).
Biochemical biomarkers of ischemic stroke:
Protein biomarkers can be classified by their pathophysiological role in stroke. Markers of ischemic brain injury include S100 calcium binding protein B (S-100B), neuron-specific enolase (NSE), myelin basic protein (MBP), and glial fibrillary acidic protein (GFAP). (239)
Several proteins involved in inflammation and immune response have also been identified as biomarkers of ischemic stroke, including C-reactive protein (CRP), interleukin-6 (IL-6), tissue necross factor-alpha (TNF-α), vascular cell adhesion protein 1 (VCAM 1), inter-cellular adhesion molecule 1 (ICAM 1), N-methyl-d-aspartate (NMDA) receptor antibodies and matrix metalloproteinases (MMPs) . Similarly, molecules involved in acute thrombosis have also been associated with ischemic stroke, including fibrinogen, D-Dimer and von-Willebrand factor (vWF).(239)