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Journal of Chromatography. B,... Jul 2011The aim of this study is to develop a standardized LC-MS/MS method for accurate measurement of desmosine (DES) and isodesmosine (IDS) in all body fluids as biomarkers...
The aim of this study is to develop a standardized LC-MS/MS method for accurate measurement of desmosine (DES) and isodesmosine (IDS) in all body fluids as biomarkers for in vivo degradation of matrix tissue elastin in man and animals. A reproducible three-step analytical procedure: (1) sample hydrolysis in 6N HCl, (2) SPE by a CF1 cartridge with addition of acetylated pyridinoline as internal standard (IS), and (3) LC/MSMS analysis by SRM monitoring of transition ions; DES or IDS (m/z 526-481+397) and IS (m/z 471-128) was developed. The method achieves accurate measurements of DES/IDS in accessible body fluids (i.e. urine, plasma, and sputum). LOQ of DES/IDS in body fluids is 0.1 ng/ml. The % recoveries and reproducibility from urine, plasma, and sputum samples are above 99 ± 8% (n = 3), 94 ± 9% (n = 3) and 87 ± 11% (n = 3), with imprecision 8%, 9% and 10%, respectively. The proposed method was applied to measure DES/IDS in body fluids of patients with chronic obstructive pulmonary disease (COPD) and healthy controls. Total DES/IDS in sputum and plasma is increased over normal controls along with the free DES/IDS in urine in patients. DES/IDS can be used to study the course of COPD and the response to therapy. This practical and reliable LC-MS/MS method is proposed as a standardized method to measure DES and IDS in body fluids. This method can have wide application for investigating diseases which involve elastic tissue degradation.
Topics: Amino Acids; Biomarkers; Case-Control Studies; Chromatography, Liquid; Desmosine; Elastin; Humans; Hydrochloric Acid; Hydrolysis; Isodesmosine; Pulmonary Disease, Chronic Obstructive; Reproducibility of Results; Sensitivity and Specificity; Sputum; Tandem Mass Spectrometry
PubMed: 21621489
DOI: 10.1016/j.jchromb.2011.05.011 -
Early Human Development Jan 1988Desmosine has been quantitated in the normally grown fetal and early infant lung by radioimmunoassay. Desmosine could first be detected at 22 weeks gestation: the...
Desmosine has been quantitated in the normally grown fetal and early infant lung by radioimmunoassay. Desmosine could first be detected at 22 weeks gestation: the concentration of desmosine expressed per milligram lung DNA increased in approximately linear form up to about 55 weeks postconceptional age. The concentration in peripheral lung was approximately half that in whole lung homogenates. Lungs of infants dying with acute HMD and lungs of growth retarded infants showed no significant differences from the normals, although there was a tendency for higher desmosine concentrations in prematurely born growth retarded infants.
Topics: Amino Acids; Desmosine; Elastin; Fetus; Humans; Hyaline Membrane Disease; Infant, Newborn; Lung; Radioimmunoassay
PubMed: 3345708
DOI: 10.1016/0378-3782(88)90087-4 -
European Journal of Biochemistry Aug 19761. Desmosine and isodesmosine were separated by ion-exchange and paper chromatography, after acid hydrolysis of purified elastin from beef ligamentum nuchae. The...
1. Desmosine and isodesmosine were separated by ion-exchange and paper chromatography, after acid hydrolysis of purified elastin from beef ligamentum nuchae. The fractions obtained by ion-exchange chromatography were clearly mixtures of related compounds. The desmosine fraction could be resolved into seven compounds and the isodesmosine into four by paper chromatography. 2. Desmosine was maximally degraded by irradiation at 274 nm and isodesmosine at 285 nm. These wavelengths did not correspond to the absorption maxima of the cross links, but to shoulders of the main absorption peaks. 3. When irradiated at their optimum wavelengths, but at various pH, both desmosine and isodesmosine seemed quite stable at pH greater than 8.5. Between pH 8 and 5, the photolytic rate was maximum and decreased slightly at more acidic pH. Below pH 4.0, one of the products of photolysis was free lysine. 4. In analogy to the mechanism of the photolytic degradation of N-methyl pyridinium chloride, it appears that the (iso)desmosines were degraded via the formation of an open amino aldehyde, which was hydrolysed at acid pH to give free lysine and a substituted glutaconic aldehyde.
Topics: Amino Acids; Animals; Cattle; Desmosine; Elastin; Hydrogen-Ion Concentration; Isodesmosine; Ligaments; Magnetic Resonance Spectroscopy; Photolysis; Spectrophotometry, Ultraviolet; Ultraviolet Rays
PubMed: 9274
DOI: 10.1111/j.1432-1033.1976.tb10644.x -
Annals of the American Thoracic Society Aug 2016Biomarkers of pathogenesis in chronic obstructive pulmonary disease (COPD) can significantly accelerate drug development. In COPD related to alpha-1 antitrypsin... (Review)
Review
Biomarkers of pathogenesis in chronic obstructive pulmonary disease (COPD) can significantly accelerate drug development. In COPD related to alpha-1 antitrypsin deficiency, the role of neutrophil elastase and its inhibition by alpha-1 antitrypsin protein focused interest on elastin degradation and the development of pulmonary emphysema. Amino acids desmosine and isodesmosine are unique cross-links in mature elastin fibers and can serve as biomarkers of elastin degradation when measured in body fluids. This review gives a perspective on what has been learned by the earliest measurements of desmosine and isodesmosine followed by later studies using methods of increased sensitivity and specificity and the meaning for developing new therapies. Also included are brief statements on the biomarkers fibrinogen, CC-16, and Aa-Val-360 in COPD.
Topics: Biomarkers; Desmosine; Elastin; Fibrinogen; Humans; Isodesmosine; Leukocyte Elastase; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Uteroglobin; alpha 1-Antitrypsin Deficiency
PubMed: 27564670
DOI: 10.1513/AnnalsATS.201509-574KV -
COPD Aug 2012
Review
Topics: Biomarkers; Bronchodilator Agents; Chromatography, High Pressure Liquid; Desmosine; Disease Progression; Drug Monitoring; Elastin; Humans; Isodesmosine; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Tandem Mass Spectrometry
PubMed: 22734624
DOI: 10.3109/15412555.2012.697753 -
Organic Letters Mar 2014The tetrasubstituted pyridinium amino acids isodesmosine and desmosine are cross-linkers of elastin and are attractive biomarkers for the diagnosis of chronic...
The tetrasubstituted pyridinium amino acids isodesmosine and desmosine are cross-linkers of elastin and are attractive biomarkers for the diagnosis of chronic obstructive pulmonary disease (COPD). In this study, the biomimetic total synthesis of isodesmosine and desmosine via a lanthanide-promoted Chichibabin pyridine synthesis using the corresponding aldehyde and amine hydrochloride is reported.
Topics: Biomarkers; Biomimetics; Cross-Linking Reagents; Desmosine; Elastin; Humans; Isodesmosine; Lanthanoid Series Elements; Molecular Structure; Pulmonary Disease, Chronic Obstructive; Pyridines; Pyridinium Compounds
PubMed: 24597689
DOI: 10.1021/ol500333t -
Biochemical and Biophysical Research... Jul 2011The development of atherosclerotic lesions and abdominal aortic aneurysms involves degradation and loss of extracellular matrix components, such as collagen and elastin....
The development of atherosclerotic lesions and abdominal aortic aneurysms involves degradation and loss of extracellular matrix components, such as collagen and elastin. Releases of the elastin cross-links desmosine (DES) and isodesmosine (IDE) may reflect elastin degradation in cardiovascular diseases. This study investigated the production of soluble elastin cross-linking structures by proteinases implicated in arterial diseases. Recombinant MMP-12 and neutrophil elastase liberated DES and IDE as amino acids from insoluble elastin. DES and IDE were also released from insoluble elastin exposed to monocyte/macrophage cell lines or human primary macrophages derived from peripheral blood monocytes. Elastin oxidized by reactive oxygen species (ROS) liberated more unconjugated DES and IDE than did non-oxidized elastin when incubated with MMP-12 or neutrophil elastase. These results support the exploration of free DES and IDE as biomarkers of elastin degradation.
Topics: Animals; Biomarkers; Cardiovascular Diseases; Cell Line; Desmosine; Elastin; Humans; Isodesmosine; Leukocyte Elastase; Matrix Metalloproteinase 12; Mice; Reactive Oxygen Species; Recombinant Proteins
PubMed: 21726534
DOI: 10.1016/j.bbrc.2011.06.124 -
Increase in urinary desmosine and pyridinoline during postpartum involution of the uterus in humans.Proceedings of the Society For... Oct 1995One of the most rapid changes in collagen and elastin content of a tissue occurs in the uterus following postpartum involution. We measured the urinary excretion of...
One of the most rapid changes in collagen and elastin content of a tissue occurs in the uterus following postpartum involution. We measured the urinary excretion of specific amino acid markers for mature elastin (desmosine [DES] and isodesmosine [IDES]) and fibrillar collagen (hydroxylysyl pyridinoline [HP] and lysyl pyridinoline [LP]) before and after parturition in three gravid subjects. For that purpose, we used an isotope dilution method coupled with gel filtration and HPLC. The highest DES values were found 2-5 weeks postpartum and were 18-45 micrograms/g creatinine or two to six times those found for healthy neversmoking nongravid females (7.7 +/- 0.3 micrograms/g creatinine, mean +/- SE). The highest levels of urinary HP for each subject were found 2-3 weeks after parturition and were 115-607 nmol/mmol creatinine or 4-21 times those found for healthy neversmoking nongravid females (28.1 +/- 1.3 nmol/mmol creatinine). For the gravid subjects as a group and also for each subject, the mean values for urinary DES, IDES, HP, and HP/LP during the first 6 weeks postpartum were significantly greater than the mean baseline values beginning 27 weeks postpartum. For the gravid subjects as a group, the mean value for urinary HP/LP during the first 6 weeks postpartum was significantly greater than the value during the 20 weeks preceding parturition. This suggested that the tissue(s) of origin of the excess HP, during the 6 weeks following parturition, was not bony and was consistent with a uterine origin.
Topics: Amino Acids; Collagen; Creatinine; Desmosine; Elastin; Female; Humans; Kinetics; Postpartum Period; Pregnancy; Reference Values; Smoking; Uterus
PubMed: 7675796
DOI: 10.3181/00379727-210-43922 -
Analytical Biochemistry May 1977
Topics: Amino Acids; Animals; Cattle; Cricetinae; Desmosine; Elastin; Female; Humans; Isodesmosine; Lung; Rats; Skin; Swine; Uterus
PubMed: 869169
DOI: 10.1016/0003-2697(77)90372-4 -
American Journal of Obstetrics and... Nov 1987Incompetence of the uterine cervix is a syndrome of painless, progressive dilatation and effacement occurring between the sixteenth and twenty-fourth weeks of gestation...
Incompetence of the uterine cervix is a syndrome of painless, progressive dilatation and effacement occurring between the sixteenth and twenty-fourth weeks of gestation that represents abnormal functioning. It may serve as a model to elucidate normal function. Because the incompetent cervix results in painless opening of this organ without uterine contraction before term gestation, it is considered one of the causes of midtrimester spontaneous abortion, habitual spontaneous abortion, and early preterm labor. Untreated, it leads to rapid expulsion and often death of the fetus. We used light microscopy to compare decreased elastic fibers in incompetent cervices with those of normal nonpregnant and pregnant cervices. Morphologic analysis of this difference was extended to biochemical quantification of elastin content in one patient with cervical incompetence. The decrease in elastin suggests that one function of cervical elastin may be to maintain a closed and undilated cervix throughout gestation. There may be a relationship between changes in cross-linked elastin and the incompetent cervix; further studies are therefore indicated.
Topics: Amino Acids; Cervix Uteri; Desmosine; Elastic Tissue; Elastin; Female; Humans; Pregnancy; Uterine Cervical Incompetence
PubMed: 3688067
DOI: 10.1016/s0002-9378(87)80277-6