Human serum albumin: from bench to bedside.

I. OVERVIEW OF THE ACUTE CORONARYSYNDROME e357A. Definition of Terms e357B. Pathogenesis and Management of ACS e357II. USE OF BIOCHEMICAL MARKERS IN THEINITIAL EVALUATION OF ACS e358A. Diagnosis of Myocardial Infarction e3581. Biochemical Markers of MyocardialNecrosis e3582. Optimal Timing of Sample Acquisition.......e3593. Criteria for Diagnosis of MI e3604. Additional Considerations in the Use ofBiomarkers for Diagnosis of MI e360B. Early Risk Stratification e3611. Biochemical Markers of Cardiac Injury.......e361a. Pathophysiology e361b. Relationship to Clinical Outcomes.........e361c. Decision-Limits e362d. Therapeutic Decision-Making e3622. Natriuretic Peptides e362a. Pathophysiology e362b. Relationship to Clinical Outcomes.........e363c. Decision-Limits e364d. Therapeutic Decision-Making e3653. Biochemical Markers of Inflammation........e365a. Pathophysiology e365b. Relationship to Clinical Outcomes.........e365c. Decision-Limits e365d. Therapeutic Decision-Making e3674. Biochemical Markers of Ischemia e3675. Multimarker Approach e3676. Other Novel Markers e368III. USE OF BIOCHEMICAL MARKERS IN THEMANAGEMENT OF NSTEACS e368A. Clinical Decision-Making e3681. Biochemical Markers of Cardiac Injury.......e3682. Other Biochemical Markers e369

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Characteristics and Utilization of Biochemical Markers in Acute Coronary Syndromes

Oxidative stress is the result of the imbalance between reactive oxygen species (ROS) formation and enzymatic and nonenzymatic antioxidants. Biomarkers of oxidative stress are relevant in the evaluation of the disease status and of the health-enhancing effects of antioxidants. We aim to discuss the major methodological bias of methods used for the evaluation of oxidative stress in humans. There is a lack of consensus concerning the validation, standardization, and reproducibility of methods for the measurement of the following: (1) ROS in leukocytes and platelets by flow cytometry, (2) markers based on ROS-induced modifications of lipids, DNA, and proteins, (3) enzymatic players of redox status, and (4) total antioxidant capacity of human body fluids. It has been suggested that the bias of each method could be overcome by using indexes of oxidative stress that include more than one marker. However, the choice of the markers considered in the global index should be dictated by the aim of the study and its design, as well as by the clinical relevance in the selected subjects. In conclusion, the clinical significance of biomarkers of oxidative stress in humans must come from a critical analysis of the markers that should give an overall index of redox status in particular conditions.

/pdf/measurement-and-clinical-significance-of-biomarkers-of-4b5iqooayx.pdf

Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans

Background: Evaluation of patients who present to the hospital with a complaint of chest pain or other signs or symptoms suggestive of acute coronary syndrome (ACS) is time-consuming, expensive, and problematic. Recent investigations have indicated that increases in biomarkers upstream from biomarkers of necrosis (cardiac troponins I and T), such as inflammatory cytokines, cellular adhesion molecules, acute-phase reactants, plaque destabilization and rupture biomarkers, biomarkers of ischemia, and biomarkers of myocardial stretch may provide earlier assessment of overall patient risk and aid in identifying patients with higher risk of an adverse event.

Approach and Content: The purpose of this review is to provide an overview of the pathophysiology and clinical and analytical characteristics of several biomarkers that may have potential clinical utility to identify ACS patients. These biomarkers (myeloperoxidase, metalloproteinase-9, soluble CD40 ligand, pregnancy-associated plasma protein A, choline, ischemia-modified albumin, unbound free fatty acids, glycogen phosphorylase isoenzyme BB, and placental growth factor) have demonstrated promise and need to be more thoroughly evaluated for commercial development for implementation into routine clinical and laboratory practice.

Summary: Specifications that have been addressed for cardiac troponins and natriuretic peptides will need to be addressed with the same scrutiny for the biomarkers discussed in this review. They include validating analytical imprecision and detection limits, calibrator characterization, assay specificity and standardization, preanalytical issues, and appropriate reference interval studies. Crossing boundaries from research to clinical application will require replication in multiple settings and experimental evidence supporting a pathophysiologic role and, ideally, interventional trials demonstrating that monitoring single or multiple biomarkers improves outcomes.

Future Biomarkers for Detection of Ischemia and Risk Stratification in Acute Coronary Syndrome

### a. definition of terms

Acute coronary syndrome (ACS)1 refers to a constellation of clinical symptoms caused by acute myocardial ischemia (1)(2). Owing to their higher risk for cardiac death or ischemic complications, patients with ACS must be identified among the estimated 8 million patients with nontraumatic chest symptoms presenting for emergency evaluation each year in the US (3). In practice, the terms suspected or possible ACS are often used by medical personnel early in the process of evaluation to describe patients for whom the symptom complex is consistent with ACS but the diagnosis has not yet been conclusively established (1).

Patients with ACS are subdivided into 2 major categories based on the 12-lead electrocardiogram (ECG) at presentation (Fig. 1⇓ ): those with new ST-segment …

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: clinical characteristics and utilization of biochemical markers in acute coronary syndromes.

Patients suffering from myocardial ischemia reportedly exhibit reduced in vitro binding of exogenous Co(2+) to the N-terminal of human serum albumin (HSA). The purpose of our investigation was to simulate changes in the N-terminus of HSA that may account for these ischemia-induced modifications to the cobalt binding site. HPLC, LC-MS and (1)H NMR analyses have shown that the N-terminal region of HSA Asp-Ala-His-Lys binds the transition metals Co(2+) and Ni(2+). Synthetic peptides with the first 2-12 amino acids of the HSA sequence demonstrated that the first three amino acids, Asp-Ala-His, are essential for strong binding of cobalt. Modification of the N-terminus peptide of HSA by way of N-acetylation or the deletion of one or more amino acid resulted in no binding of cobalt. Because the degradation of the susceptible, specific transition metal binding site of HSA may account for the decreased cobalt binding observed during ischemic events, an assay that detects this reduced binding could be useful in the diagnosis of ischemia.

Characterization of the Co2+ and Ni2+ binding amino‐acid residues of the N‐terminus of human albumin

The invention provides a method of inhibiting the effects of platelet activating factor (PAF). For instance, a disease or condition mediated by PAF (particularly inflammation) can be treated or platelet aggregation can be inhibited. The invention also provides a method of inhibiting the production and/or release of interleukin 8 (IL-8) by cells. The effects of PAF and the production and/or release of IL-8 are inhibited according to the invention by a compound of formula (1) wherein R?1 and R2? are defined in the application, or a physiologically-acceptable salt thereof. The invention also provides pharmaceutical compositions comprising these compounds.

Method of using diketopiperazines and composition containing them

Topical compositions comprising a steroid selected from the group consisting of ethisterone and derivatives thereof and trilostane and derivatives thereof and the use of said steroids in the manufacture of a topical medicament for the prevention or treatment of a dermato logical condition that can be so prevented or treated by modifying the growth and interaction of one or more of blood vessels, adipocytes and fibroblasts and/or by modifying fibrosis.

Topical formulations for use in the treatment or prevention of dermatological conditions

Topical compositions for the treatment or prevention of skin cancers comprising a steroid selected from the group consisting of ethisterone and derivatives thereof and trilostane and derivatives thereof, the use of said steroids in the manufacture of a topical medicament for the prevention or treatment of skin cancers that can be so prevented or treated by inhibiting angiogenesis and/or vasculogenesis and a method for the treatment of prevention of a skin cancer that can be so prevented or treated by inhibiting angiogenesis and/or vasculogenesis, said method comprising the topical administration to a patient in need thereof of an effective amount of a steroid selected from said steroids.

Curtis Gerald C

Papers

Characterization of the Co2+ and Ni2+ binding amino‐acid residues of the N‐terminus of human albumin

Method of using diketopiperazines and composition containing them

Topical formulations for use in the treatment or prevention of dermatological conditions

Topical formulations for use in the treatment of prevention of skin cancers

Composés fixant des métaux et leurs utilisations