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Toyonobu Usuki - One of the best experts on this subject based on the ideXlab platform.

  • synthesis of Desmosine d4 improvement of isotopic purity by d h exchange of amino groups
    Tetrahedron Letters, 2017
    Co-Authors: Daisuke Watanabe, Rina Suzuki, Toyonobu Usuki
    Abstract:

    Abstract Desmosine is a crosslinking pyridinium amino acid of elastin, which is a useful biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD) by LC–MS/MS analysis. We previously reported a synthesis of Desmosine-d 4 , which is useful as an internal standard for quantitative LC–MS/MS analysis of Desmosines, by deuterogenation of an alkyne group; however, the isotopic purity of the Desmosine-d 4 was only ca . 50%. The present report describes a new synthesis of Desmosine-d 4 that improves the isotopic purity to ca . 90% by exchanging the protons of the amino groups to deuterium using deuterogenation.

  • [13C3,15N1]-labeled isoDesmosine: A potential internal standard for LC–MS/MS analysis of Desmosines in elastin degradation
    Bioorganic & medicinal chemistry letters, 2015
    Co-Authors: Takahiro Tanigawa, Akira Komatsu, Toyonobu Usuki
    Abstract:

    Abstract IsoDesmosine and Desmosine are crosslinking amino acids that are present only in elastin. They are useful biomarkers for the degradation of elastin, which occurs during the progression of chronic obstructive pulmonary disease (COPD) and related diseases. This Letter describes the synthesis of [ 13 C 3 , 15 N 1 ]-labeled isoDesmosine, using Chichibabin pyridine synthesis as a key reaction. The labeled isoDesmosine is a potential internal standard for the quantitative LC–MS/MS analysis of Desmosines in elastin degradation.

  • total synthesis of the copd biomarker Desmosine via stepwise sonogashira cross coupling reactions
    Bulletin of the Chemical Society of Japan, 2015
    Co-Authors: Haruka Yamada, Takahiro Hayashi, Toyonobu Usuki
    Abstract:

    Desmosine, a COPD biomarker and elastin crosslinker, is a tetrasubstituted pyridinium amino acid. In this paper, the total synthesi so f Desmosine is described utilizing stepwise and regioselective palladium-catalyzed Sonogashira crosscoupling reactions of trihalopyridines and terminal alkynes as key steps. The 13-step synthesis starting from 4hydroxypyridine was achieved i n1 1% overall yield.

  • Syntheses of natural and deuterated Desmosines via palladium-catalyzed cross-coupling reactions
    Tetrahedron, 2015
    Co-Authors: Rina Suzuki, Hiroto Yanuma, Takahiro Hayashi, Haruka Yamada, Toyonobu Usuki
    Abstract:

    Abstract Desmosine is a crosslinking pyridinium amino acid of elastin and is an attractive biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD). Herein, we describe the total synthesis of natural Desmosine and its deuterated derivatives. The synthesized deuterated derivatives could be used as internal standards for the development of an isotope-dilution liquid chromatography–mass spectrometry (LC–MS/MS) analytical method for the accurate determination of Desmosine in clinical samples. The key features of our synthesis are stepwise chemo- and regioselective palladium-catalyzed Sonogashira and Negishi cross-coupling reactions for the efficient introduction of the amino acid side chains onto the pyridine core.

  • Synthesis and LC-MS/MS analysis of Desmosine-CH2, a potential internal standard for the degraded elastin biomarker Desmosine
    Organic & biomolecular chemistry, 2014
    Co-Authors: Yuko Murakami, Gerard M Turino, Yong Y Lin, Hiroto Yanuma, Rina Suzuki, Toyonobu Usuki
    Abstract:

    Desmosine-CH2, an analog of the elastic tissue degradation biomarker Desmosine, can be regarded as a potential internal standard for precise quantification of Desmosines by LC-MS/MS. In this study, the chemical synthesis of Desmosine-CH2 was completed in 22% overall yield in five steps. The LC-MS/MS analysis of Desmosine-CH2 was also achieved.

Barry Starcher - One of the best experts on this subject based on the ideXlab platform.

  • urinary Desmosine a biomarker of structural lung injury during cf pulmonary exacerbation
    Pediatric Pulmonology, 2012
    Co-Authors: Theresa A. Laguna, Barry Starcher, Brandie D. Wagner, Shelley A. Mann, Scott D. Sagel, Heidi K. Luckey Tarro, Frank J. Accurso
    Abstract:

    Rationale Cystic fibrosis (CF) lung disease is characterized by structural changes and remodeling in airway architecture and lung parenchyma. Neutrophilic inflammation and infection lead to injury and breakdown of airway matrix constituents, including elastin. The non-invasive measurement of urinary Desmosine (UDes), a breakdown product of elastin, may be reflective of ongoing lung injury and may serve as a biomarker of active short-term damage during pulmonary exacerbation. Our objectives were to measure Desmosine in the urine of CF patients hospitalized for treatment of a pulmonary exacerbation and to explore the correlation between Desmosine concentration and other markers of clinical improvement, including lung function and inflammatory mediators. Methods Urine and blood samples plus lung function measurements were collected at up to three points during hospitalization for treatment of a CF pulmonary exacerbation. We used a repeated measures model, adjusted for age and time between measurements, to compare log transformed urine Desmosine concentrations across multiple time points and to correlate those concentrations with related clinical variables. Change in UDes concentration was investigated using a statistical model that incorporated normalization factors to account for variations in urinary concentration. Results Desmosine was measured by radioimmunoassay (RIA) in 155 spot urine samples from 53 CF patients hospitalized for 63 pulmonary exacerbations (range of results: 0–235 pmol Des/ml). Specific gravity (SG) adjusted UDes concentration decreased significantly during admission for CF pulmonary exacerbation, P < 0.01 (average length of stay = 11 days). No correlation was observed between UDes concentration and lung function or inflammatory markers. Conclusions UDes decreased significantly following treatment for an acute pulmonary exacerbation and may be a useful biomarker of short-term injury to the CF lung. Further investigation is needed to evaluate the utility of UDes concentration in the long-term progression of CF lung disease. Pediatr Pulmonol. 2012. 47:856–863. © 2012 Wiley Periodicals, Inc.

  • Urinary Desmosine: a biomarker of structural lung injury during CF pulmonary exacerbation.
    Pediatric pulmonology, 2012
    Co-Authors: Theresa A. Laguna, Barry Starcher, Brandie D. Wagner, Shelley A. Mann, Scott D. Sagel, Heidi K. Luckey Tarro, Frank J. Accurso
    Abstract:

    Rationale Cystic fibrosis (CF) lung disease is characterized by structural changes and remodeling in airway architecture and lung parenchyma. Neutrophilic inflammation and infection lead to injury and breakdown of airway matrix constituents, including elastin. The non-invasive measurement of urinary Desmosine (UDes), a breakdown product of elastin, may be reflective of ongoing lung injury and may serve as a biomarker of active short-term damage during pulmonary exacerbation. Our objectives were to measure Desmosine in the urine of CF patients hospitalized for treatment of a pulmonary exacerbation and to explore the correlation between Desmosine concentration and other markers of clinical improvement, including lung function and inflammatory mediators. Methods Urine and blood samples plus lung function measurements were collected at up to three points during hospitalization for treatment of a CF pulmonary exacerbation. We used a repeated measures model, adjusted for age and time between measurements, to compare log transformed urine Desmosine concentrations across multiple time points and to correlate those concentrations with related clinical variables. Change in UDes concentration was investigated using a statistical model that incorporated normalization factors to account for variations in urinary concentration. Results Desmosine was measured by radioimmunoassay (RIA) in 155 spot urine samples from 53 CF patients hospitalized for 63 pulmonary exacerbations (range of results: 0–235 pmol Des/ml). Specific gravity (SG) adjusted UDes concentration decreased significantly during admission for CF pulmonary exacerbation, P 

  • The Utility of Urine Desmosine as a Marker of Lung Injury in Spine Surgery
    HSS Journal, 2010
    Co-Authors: Stavros G. Memtsoudis, Barry Starcher, Valeria Buschiazzo, Michael K. Urban, Federico P. Girardi
    Abstract:

    The objective of this prospective observational study was to determine if urine Desmosine levels, a marker of lung injury, increase in response to the periopreative insults of anterior and posterior spine surgery. Desmosine, a stable breakdown product of elastin, has been proposed as a surrogate marker of lung injury in patients with COPD, tobacco use, and ARDS. We recently evaluated this marker in patients undergoing knee surgery, but the utility of Desmosine as a marker of lung injury in patients undergoing spine surgery remains unstudied. In this study, we enrolled ten consecutive patients, who underwent anterior/posterior spine surgery. Patient demographics and perioperative data were recorded. Urine samples were collected at baseline, 1 day, and 3 days postoperatively and analyzed for levels of Desmosine using a previously validated radioimmunoassay. Desmosine levels were 35.9 ± 18.2 pmol/mg creatinine at baseline, 38.7 ± 11 pmol/mg creatinine on postoperative day 1, and 70.5 ± 49.1 pmol/mg creatinine on postoperative day 3, respectively. Desmosine/creatinine ratios measured on day 3 postoperatively were significantly elevated compared to levels at baseline, and represented a 96.3% increase. No difference was seen between levels at baseline and day 1 postoperatively. In conclusion, we were able to show a significant increase in urine Desmosine levels associated with anterior/posterior spine surgery. In the context of previous studies, our findings suggest that Desmosine may be a marker of lung injury in this setting. However, further research is warranted for validation and correlation of Desmosine levels to clinical markers and various degrees of lung injury.

  • Urine Desmosine as a Marker of Lung Injury Following Total Knee Arthroplasty. A Pilot Study
    HSS Journal, 2009
    Co-Authors: Stavros G. Memtsoudis, Barry Starcher, Alejandro González Della Valle, Kethy Jules-elysee, Thomas P. Sculco
    Abstract:

    Lung injury following total knee arthroplasty (TKA) may occur secondary to embolization of bone debris, fat, and cement. Clinically relevant respiratory failure is rare and is therefore difficult to study. To facilitate future investigations on this subject, we evaluated the utility of the elastin breakdown product Desmosine as a potential marker of lung injury during TKA surgery. The goals of this study were to answer (1) if Desmosine levels would increase in response to the perioperative insults in patients undergoing TKA and (2) if this increase would differ among unilateral and bilateral TKA procedures. Twenty consecutive patients (ten unilateral and ten bilateral TKAs) were enrolled. Urine samples were collected before surgery and at 1 and 3 days postoperatively and analyzed for levels of Desmosine using a validated radioimmunoassay. Baseline Desmosine/creatinine ratios were higher in the unilateral as compared to the bilateral TKA group ( p  = 0.003). Tourniquet times, intraoperative estimated blood loss, and transfusion requirements among bilateral TKA patients were significantly higher than those of unilateral TKA recipients. Desmosine levels increased in both groups, but the rise was significant only in the bilateral group. We detected a significant increase in urine Desmosine levels associated with bilateral but not unilateral TKA surgery. In the context of previous studies, our findings suggest that Desmosine may be a marker of postoperative lung injury. Further research is warranted for validation and correlation of Desmosine levels to clinical markers and various degrees of lung injury.

  • Higher urine Desmosine levels are associated with mortality in patients with acute lung injury
    American journal of physiology. Lung cellular and molecular physiology, 2006
    Co-Authors: Dana E. Mcclintock, Barry Starcher, Mark D. Eisner, B. Taylor Thompson, Doug Hayden, Gwynne D. Church, Michael A. Matthay
    Abstract:

    Desmosine is a stable breakdown product of elastin that can be reliably measured in urine samples. We tested the hypothesis that higher baseline urine Desmosine would be associated with higher mort...

Frank J. Accurso - One of the best experts on this subject based on the ideXlab platform.

  • urinary Desmosine a biomarker of structural lung injury during cf pulmonary exacerbation
    Pediatric Pulmonology, 2012
    Co-Authors: Theresa A. Laguna, Barry Starcher, Brandie D. Wagner, Shelley A. Mann, Scott D. Sagel, Heidi K. Luckey Tarro, Frank J. Accurso
    Abstract:

    Rationale Cystic fibrosis (CF) lung disease is characterized by structural changes and remodeling in airway architecture and lung parenchyma. Neutrophilic inflammation and infection lead to injury and breakdown of airway matrix constituents, including elastin. The non-invasive measurement of urinary Desmosine (UDes), a breakdown product of elastin, may be reflective of ongoing lung injury and may serve as a biomarker of active short-term damage during pulmonary exacerbation. Our objectives were to measure Desmosine in the urine of CF patients hospitalized for treatment of a pulmonary exacerbation and to explore the correlation between Desmosine concentration and other markers of clinical improvement, including lung function and inflammatory mediators. Methods Urine and blood samples plus lung function measurements were collected at up to three points during hospitalization for treatment of a CF pulmonary exacerbation. We used a repeated measures model, adjusted for age and time between measurements, to compare log transformed urine Desmosine concentrations across multiple time points and to correlate those concentrations with related clinical variables. Change in UDes concentration was investigated using a statistical model that incorporated normalization factors to account for variations in urinary concentration. Results Desmosine was measured by radioimmunoassay (RIA) in 155 spot urine samples from 53 CF patients hospitalized for 63 pulmonary exacerbations (range of results: 0–235 pmol Des/ml). Specific gravity (SG) adjusted UDes concentration decreased significantly during admission for CF pulmonary exacerbation, P < 0.01 (average length of stay = 11 days). No correlation was observed between UDes concentration and lung function or inflammatory markers. Conclusions UDes decreased significantly following treatment for an acute pulmonary exacerbation and may be a useful biomarker of short-term injury to the CF lung. Further investigation is needed to evaluate the utility of UDes concentration in the long-term progression of CF lung disease. Pediatr Pulmonol. 2012. 47:856–863. © 2012 Wiley Periodicals, Inc.

  • Urinary Desmosine: a biomarker of structural lung injury during CF pulmonary exacerbation.
    Pediatric pulmonology, 2012
    Co-Authors: Theresa A. Laguna, Barry Starcher, Brandie D. Wagner, Shelley A. Mann, Scott D. Sagel, Heidi K. Luckey Tarro, Frank J. Accurso
    Abstract:

    Rationale Cystic fibrosis (CF) lung disease is characterized by structural changes and remodeling in airway architecture and lung parenchyma. Neutrophilic inflammation and infection lead to injury and breakdown of airway matrix constituents, including elastin. The non-invasive measurement of urinary Desmosine (UDes), a breakdown product of elastin, may be reflective of ongoing lung injury and may serve as a biomarker of active short-term damage during pulmonary exacerbation. Our objectives were to measure Desmosine in the urine of CF patients hospitalized for treatment of a pulmonary exacerbation and to explore the correlation between Desmosine concentration and other markers of clinical improvement, including lung function and inflammatory mediators. Methods Urine and blood samples plus lung function measurements were collected at up to three points during hospitalization for treatment of a CF pulmonary exacerbation. We used a repeated measures model, adjusted for age and time between measurements, to compare log transformed urine Desmosine concentrations across multiple time points and to correlate those concentrations with related clinical variables. Change in UDes concentration was investigated using a statistical model that incorporated normalization factors to account for variations in urinary concentration. Results Desmosine was measured by radioimmunoassay (RIA) in 155 spot urine samples from 53 CF patients hospitalized for 63 pulmonary exacerbations (range of results: 0–235 pmol Des/ml). Specific gravity (SG) adjusted UDes concentration decreased significantly during admission for CF pulmonary exacerbation, P 

  • Sputum Desmosine During Hospital Admission for Pulmonary Exacerbation in Cystic Fibrosis
    Chest, 2009
    Co-Authors: Theresa A. Laguna, Brandie D. Wagner, Heidi K. Luckey, Shelley A. Mann, Scott D. Sagel, Warren E. Regelmann, Frank J. Accurso
    Abstract:

    Background Cystic fibrosis (CF) lung disease is characterized by structural changes in the airways and parenchyma. No sputum biomarker exists to measure the degree of active structural destruction during pulmonary exacerbation in patients with CF. The noninvasive measurement of Desmosine, a breakdown product of elastin, may reflect ongoing lung injury and serve as a biomarker of short-term damage. Our objectives were to measure Desmosine in the sputum of patients with CF hospitalized for treatment of a pulmonary exacerbation and to explore the correlation between Desmosine levels and other markers of clinical improvement, including lung function and inflammatory mediators, following hospitalization. Methods Sputum and blood samples collected and lung function measurements were made at multiple time points during hospitalization. We used a repeated measures model, adjusted for age and time between measurements, to compare log-transformed sputum Desmosine levels across multiple time points and to correlate those levels with related variables. Results Desmosine levels were measured by radioimmunoassay in 71 expectorated sputum samples from 19 patients with CF hospitalized for 26 pulmonary exacerbations (range of results, 0 to 200 pmol/L Desmosine/mL). Sputum Desmosine levels decreased significantly during the first week of hospitalization (p = 0.04). Desmosine levels were positively associated with plasma C-reactive protein (ρ = 0.59; p = 0.03), sputum interleukin-8 (ρ = 0.86; p Conclusions Sputum Desmosine, a novel measure of acute structural lung injury, may serve as a marker of structural lung damage occurring during exacerbations of lung disease in CF.

Paolo Iadarola - One of the best experts on this subject based on the ideXlab platform.

  • Micellar electrokinetic chromatography with laser induced detection and liquid chromatography tandem mass-spectrometry-based Desmosine assays in urine of patients with Chronic Obstructive Pulmonary Disease: a comparative analysis.
    Journal of chromatography. A, 2012
    Co-Authors: Fabio Ferrari, Simona Viglio, Carmine Tinelli, Marco Fumagalli, Maurizio Luisetti, Jan Stolk, Paolo Piccinini, Paolo Iadarola
    Abstract:

    Abstract Evidences accumulated over the past years that Desmosines could be attractive indicators of elastic fibre degradation in Chronic Obstructive Pulmonary Disease have raised substantial interest with the development of reliable assays to measure their concentration in body fluids. It is a firm belief of researchers working in this field that accurate assessment of Desmosine concentration would improve the understanding of elastin metabolism disorders and allow these cross-links to become a useful tool in the diagnosis and clinical management of these diseases. From among the variety of techniques available on the market, HPLC; CE and LC–MS have proved to be successful tools for measuring Desmosines in biological fluids. However, differences in the analytical performance of methods may hinder the comparability of data, thus limiting the analytical strength and clinical utility of methods themselves. To address the relative contribution of different factors to the exact quantification of Desmosines, the full potential of MEKC-LIF and LC–MS, the two systems that better than others offer more selective and sensitive detection for Desmosine analysis, was studied on 56 urine samples. The results of this systematic comparative study underline the significant benefits of LC–MS over MEKC-LIF in terms of precision and sensitivity. Nevertheless, MEKC-LIF could be an attractive alternative in routine laboratories lacking the LC–MS instrumentation and skills to run these methods.

  • long term variability of Desmosine isoDesmosine as biomarker in alpha 1 antritrypsin deficiency related copd
    COPD: Journal of Chronic Obstructive Pulmonary Disease, 2011
    Co-Authors: Laura Fregonese, Fabio Ferrari, Marco Fumagalli, Maurizio Luisetti, Jan Stolk, Paolo Iadarola
    Abstract:

    Desmosine and isoDesmosine are products of elastin breakdown which are candidate biomarkers to measure lung destruction in COPD. Data exist on the burden of Desmosines in urine and plasma in COPD but long-term changes have never been investigated. We determined the changes of Desmosine levels over 14 months in urine and plasma of patients with type ZZ alpha-1-antitryspsin deficiency-related COPD. Urines and plasma for determination of Desmosines were collected from 11 ex-smokers with moderate/severe emphysema at monthly intervals for 14 months. Spirometry and gas transfer were assessed at baseline and 6-month intervals. At baseline and month 14, eleven healthy partners of patients volunteered to give a blood sample for detection of Desmosines. Desmosines were determined by capillary electrophoresis combined with laser-induced fluorescence. Urine and plasma Desmosines were significantly increased after 14 months in patients (p = 0.027 and p = 0.0005, respectively). Plasma Desmosines of healthy partners at baseline were 4-fold lower than from patients and not significantly different from values at month 14. Only a significant decline in lung gas transfer occurred in patients (p = 0.015). The variability of Desmosines was higher in urine than in plasma (coefficient of variation 0.17 and 0.087, respectively). As longitudinal Desmosine changes likely reflect the elevated elastic fiber turnover associated with the progression of lung damage and destruction in COPD, they appear to be a suitable marker for application in long-term studies. Plasma Desmosines were more stable long-term biomarkers than Desmosines in urine.

  • Long-term variability of Desmosine/isoDesmosine as biomarker in alpha-1-antritrypsin deficiency-related COPD.
    COPD, 2011
    Co-Authors: Laura Fregonese, Fabio Ferrari, Marco Fumagalli, Maurizio Luisetti, Jan Stolk, Paolo Iadarola
    Abstract:

    Desmosine and isoDesmosine are products of elastin breakdown which are candidate biomarkers to measure lung destruction in COPD. Data exist on the burden of Desmosines in urine and plasma in COPD but long-term changes have never been investigated. We determined the changes of Desmosine levels over 14 months in urine and plasma of patients with type ZZ alpha-1-antitryspsin deficiency-related COPD. Urines and plasma for determination of Desmosines were collected from 11 ex-smokers with moderate/severe emphysema at monthly intervals for 14 months. Spirometry and gas transfer were assessed at baseline and 6-month intervals. At baseline and month 14, eleven healthy partners of patients volunteered to give a blood sample for detection of Desmosines. Desmosines were determined by capillary electrophoresis combined with laser-induced fluorescence. Urine and plasma Desmosines were significantly increased after 14 months in patients (p = 0.027 and p = 0.0005, respectively). Plasma Desmosines of healthy partners at baseline were 4-fold lower than from patients and not significantly different from values at month 14. Only a significant decline in lung gas transfer occurred in patients (p = 0.015). The variability of Desmosines was higher in urine than in plasma (coefficient of variation 0.17 and 0.087, respectively). As longitudinal Desmosine changes likely reflect the elevated elastic fiber turnover associated with the progression of lung damage and destruction in COPD, they appear to be a suitable marker for application in long-term studies. Plasma Desmosines were more stable long-term biomarkers than Desmosines in urine.

  • Short-term variability of biomarkers of proteinase activity in patients with emphysema associated with type Z alpha-1-antitrypsin deficiency
    Respiratory Research, 2005
    Co-Authors: Jan Stolk, Paolo Iadarola, Laura Annovazzi, Chiara Zanone, Barbara Veldhuisen, Elly M Versteeg, Toine H Van Kuppevelt, Willem Nieuwenhuizen, Maurizio Luisetti
    Abstract:

    Background The burden of proteinases from inflammatory cells in the lung of subjects with type Pi ZZ of alpha-1-antitrypsin deficiency is higher than in those without the deficiency. Cross-sectional studies have shown increased levels of biomarkers of extracellular matrix degradation in vivo . Longitudinal variability of these biomarkers is unknown but desirable for clinical studies with proteinase inhibitors. Methods We measured three different types of biomarkers, including Desmosines, elastase-formed fibrinogen fragments and heparan sulfate epitope JM403, in plasma and urine for a period of 7 weeks in a group of 12 patients who participated in a placebo-controlled study to assess the safety of a single inhalation of hyaluronic acid. Results Effect of study medication on any of the biomarkers was not seen. Baseline Desmosines in plasma and urine correlated with baseline CO diffusion capacity (R = 0.81, p = 0.01 and R = 0.65, p = 0.05). Mean coefficient of variation within patients (CVi) for plasma and urine Desmosines was 18.7 to 13.5%, respectively. Change in urinary Desmosine levels correlated significantly with change in plasma Desmosine levels (R = 0.84, p < 0.01). Mean CVi for fibrinogen fragments in plasma was 20.5% and for JM403 in urine was 27.8%. No correlations were found between fibrinogen fragments or JM403 epitope and Desmosines. Conclusion We found acceptable variability in our study parameters, indicating the feasibility of their use in an evaluation of biochemical efficacy of alpha-1-antitrypsin augmentation therapy in Pi Z subjects.

  • High levels of Desmosines in urine and plasma of patients with pseudoxanthoma elasticum
    European journal of clinical investigation, 2004
    Co-Authors: Laura Annovazzi, Simona Viglio, D. Gheduzzi, I. Pasquali-ronchetti, Chiara Zanone, Giuseppe Cetta, Paolo Iadarola
    Abstract:

    Background Pseudoxanthoma elasticum ( PXE ), a rare heritable disorder caused by mutations of the ABCC6 gene, is characterized by fragmentation and mineralization of elastic fibres. We determined the extent of degradation of elastin by measuring and comparing the amount of Desmosines in plasma and urine of PXE patients, healthy carriers and normal subjects. Methods Using capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) we measured the amount of Desmosines in the urine of 46 individuals (14 PXE patients, 17 healthy carriers and 15 controls) and in the plasma of 56 subjects (18 PXE patients, 23 healthy carriers and 15 controls). Pseudoxanthoma elasticum patients and carriers were identified by clinical, structural and molecular biology analyses. Results The urinary excretion of Desmosines was two-fold higher in PXE patients than in controls (P < 0.01); the values for healthy carriers were intermediate between those of PXE patients and controls. A very similar trend between patients and their relatives was observed for plasma Desmosines. There was a significant correlation between the amount of the Desmosines in plasma and urine. Moreover, a positive correlation was observed between urinary Desmosine content and age of the patients as well as between urinary Desmosine content and severity of clinical manifestations. Conclusions Both the urinary and plasma Desmosine concentrations indicate that elastin degradation is higher in PXE patients and, to a lesser extent, in healthy carriers than in normal subjects. Data seem to indicate that the amount of elastin breakdown products correlates with the age of patients as well as with the severity of the disease. Abbreviations CE-LIF, capillary electrophoresis laser-induced fluorescence; PXE, Pseudoxanthoma elasticum; FITC, fluoresceine isothiocyanate; DES, Desmosine; IDES, isoDesmosine; MS, mass spectrometry.

Chim C. Lang - One of the best experts on this subject based on the ideXlab platform.

  • P6505Urinary Desmosine, an elastin-specific degradation product is associated with maximum aortic root size and aortic z-scores in patients with bicuspid aortic valve
    European Heart Journal, 2019
    Co-Authors: Zaid Iskandar, Jeffrey T.-j. Huang, Ify R. Mordi, L D Miller, Calvin W.l. Chin, David Goudie, C Mcwilliam, Jonathan Berg, A Neagoie, Chim C. Lang
    Abstract:

    Abstract Background Bicuspid aortic valve (BAV) is the commonest congenital cardiac abnormality affecting up to 2% of the general population. BAV is highly diverse in phenotype however a common feature is its inherent risk of morbidity and mortality from aortic root dilatation and dissection. Aortic dilatation involves elastin degradation and Desmosine is an amino acid cross-link that is released into the bloodstream and urine following elastin degradation. It is known from an earlier pilot study (DESMA) of Desmosine in Marfan Syndrome (MFS) patients that plasma Desmosine among patients with MFS is significantly elevated and correlates with aortic size however whether this same observation is seen in other forms of inherited aortopathies such as BAV is unclear. Objectives 1. To investigate whether patients with BAV have higher elastin degradation as indicated by plasma Desmosine and urinary Desmosine levels. 2. To explore the relationship between plasma and urinary Desmosine levels with aortic root size in patients with BAV. Methods We measured urinary (ng/mg creatinine) and plasma Desmosine (ng/mL) in 20 patients with BAV and healthy control subjects using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Aortic root size and corresponding Z-scores were measured on echocardiogram. Correlation was analysed with Spearman's rank test. Results The patients with BAV were predominantly male (n=15, 75%) with a mean age of 50.5 years ± 17.6 [SD]. All the BAV patients had normal LV systolic function and none had prior aortic root surgery or were current smokers. Nine BAV patients had treated hypertension. Compared to controls, both plasma Desmosine (0.30±0.10 vs 0.26±0.075 ng/mL, p=0.01) and urinary Desmosine (15.9±4.6 vs 7.2±2.8 ng/mg creatinine, p<0.001) were significantly elevated in patients with BAV. Urinary and plasma Desmosine (Figure 1) were also significantly correlated (r=0.55, p=0.01). There was a significant association between urinary Desmosine and maximal aortic root size and Z-scores in the BAV cohort (Figure 2) compared to controls (p=0.02), however this was not seen with plasma Desmosine. Conclusions Urinary and plasma Desmosine levels are significantly higher in patients with BAV compared to controls. Urinary Desmosine is also significantly associated with maximal aortic root size, reflecting higher elastin degradation. This suggests a potential use of Desmosine as a biomarker to monitor disease progression in patients with BAV. Acknowledgement/Funding Anonymous Trust

  • 126 Urinary Desmosine, a biomarker of elastin degradation is significantly elevated and associated with maximum aortic root size and aortic Z-scores in patients with bicuspid aortic valve
    Valve Disease Pericardial Disease Cardiomyopathy, 2019
    Co-Authors: Zaid Iskandar, Jeffrey T.-j. Huang, Ify R. Mordi, Calvin W.l. Chin, David Goudie, C Mcwilliam, Jonathan Berg, A Neagoie, Lynn Miller, Chim C. Lang
    Abstract:

    Introduction Bicuspid aortic valve (BAV) affects up to 2% of the general population and is associated with a significant risk of aortic dilatation and aortic dissection. Therefore, patients are normally routinely followed up with serial echocardiography. Aortic dilatation involves elastin breakdown as part of extracellular matrix degradation. Desmosine is a specific amino acid cross-link between mature elastin molecules and is released into plasma and urine following elastin degradation. Following on from previous pilot data in the DESMA study on patients with Marfan Syndrome which demonstrated a significant correlation between plasma Desmosine and aortic root size, we explored whether this same relationship is seen in patients with other forms of aortopathies, specifically the BAV cohort. Methods Urinary and plasma Desmosine were measured in 20 patients with BAV and compared to age-matched healthy controls. Urinary Desmosine (uDES) and plasma Desmosine (pDES) levels were measured in the same laboratory using liquid chromatography-tandem mass spectrometry (LC-MS). Results The cohort was predominantly male (75%) and mean age was 49.3±17.3 years old. All the patients had normal LV systolic function and 9 (45%) patients had treated hypertension. Mean aortic root size was 35±5.8mm. Compared to controls, both uDES (15.9 ± 4.6 vs 7.2 ± 2.8 ng/mg creatinine, p Conclusion Urinary and plasma Desmosine levels are significantly higher in patients with BAV compared to controls. Urinary Desmosine is also significantly associated with aortic root size and z-score, reflecting higher elastin degradation in patients with larger aortic roots. This suggests a potential utility of Desmosine as a biomarker in patients with BAV. Larger studies are needed to test this hypothesis. Conflict of Interest None

  • PLASMA Desmosine, AN ELASTIN DEGRADATION PRODUCT, PREDICTS OUTCOMES IN AT RISK POPULATIONS
    Journal of the American College of Cardiology, 2019
    Co-Authors: Zaid Iskandar, Jeffrey T.-j. Huang, Ify R. Mordi, Chim C. Lang, James D. Chalmers, David Newby, Matt Bown, Anna Maria Choy
    Abstract:

    Recent evidence suggest that elastin fragmentation plays a key role in plaque destabilization and rupture. Plasma Desmosine is an elastin specific degradation product. We have reviewed the predictive value of plasma Desmosine for outcome in a cohort of patient with cardiovascular disease and in 2