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Sample records for anti-cyclic citrullinated peptide

  1. Anti-cyclic citrullinated peptide (anti-CCP) antibodies with brucellosis.

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    Kisacik, Bunyamin; Dag, Muhammet Said; Pehlivan, Yavuz; Ugurlu, Kenan; Mercan, Ozge Kaya; Aydinli, Musa; Devay, Seda Duygulu; Sayarlioglu, Mehmet; Onat, Ahmet Mesut

    2014-06-01

    Anti-cyclic citrullinated peptide (anti-CCP) was positive in 11.5 % and rheumatoid factor was positive in 8.8 % of the patients with Brucella. After a comparative evaluation, we have found out that there was not a statistical significance concerning the anti-CCP levels between the patients with brucellosis and healthy control.

  2. The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis

    NARCIS (Netherlands)

    Kroot, EJJA; de Jong, BAW; van Leeuwen, MA; Swinkels, H; van den Hoogen, FHJ; van't Hof, M; van de Putte, LBA; van Rijswijk, MH; van Venrooij, WJ; van Riel, PLCM

    2000-01-01

    Objective. To study the predictive value of anti-cyclic citrullinated peptide antibody (anti-CCP) in patients with recent-onset rheumatoid arthritis (RA). Methods. Outcome in terms of physical disability (Health Assessment Questionnaire) and radiologic damage (modified Sharp method) over 3-year and

  3. Anti-Cyclic Citrullinated Peptide Antibody-Positive Meningoencephalitis in the Preclinical Period of Rheumatoid Arthritis

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    Tomoya Shibahara

    2016-07-01

    Full Text Available Rheumatoid meningoencephalitis (RM is a rare complication of rheumatoid arthritis (RA. This report describes a 63-year-old man with complaints of high-grade fever, headache, and vomiting for several days before admission. Both his serum and cerebrospinal fluid were positive for anti-cyclic citrullinated peptide (CCP antibody and rheumatoid factor, and contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging (MRI showed abnormal gadolinium enhancement of the meninges and high-intensity lesions in the subarachnoid spaces. The patient was diagnosed with RM despite lack of signs suggesting RA. His symptoms drastically improved with intravenous infusion of high-dose methylprednisolone. Two months later, he developed RA. The findings in this patient suggest that RM could develop prior to the onset of RA. Anti-CCP antibody and MRI findings may be useful for the diagnosis of RM, regardless of RA history.

  4. Profiling anti-cyclic citrullinated peptide antibodies in patients with juvenile idiopathic arthritis

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    Tebo Anne E

    2012-08-01

    Full Text Available Abstract Background Anti-citrullinated protein/peptide antibodies (ACPA, have high specificity for rheumatoid arthritis (RA. Some children with juvenile idiopathic arthritis (JIA, phenotypically resemble RA and test positive for rheumatoid factor (RF a characteristic biomarker of RA. We investigated the prevalence of ACPA and its relationship to other serologic markers associated with RA in a well-characterized JIA cohort. Methods Cases were 334 children with JIA, 30 of whom had RF + polyarticular JIA. Sera from all cases and 50 healthy pediatric controls were investigated by ELISA at a single time point for anti-cyclic citrullinated peptide (anti-CCP IgG, RF IgM, IgA and IgG, anti-RA33 IgG, and antinuclear antibodies (ANA. Comparisons between cases and controls were made using Chi-square or Fisher exact tests and T-tests. Results The prevalence of RF was 8% among controls, and 12% among cases (ns. The prevalence of ACPA was 2% in controls and 14.3% in cases (OR 8.2, p Conclusions ACPAs are detectable in 14% of children with JIA. Children with positive ACPA but negative RF are frequent, and may define a distinct subset of children with JIA. ACPA testing should be included in the classification of JIA.

  5. Anti-cyclic citrullinated peptide antibodies in children with Juvenile Idiopathic Arthritis

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    Hamooda, Mohamed; Fouad, Hala; Galal, Nermeen; Sewelam, Nadia; Megahed, Dina

    2016-01-01

    Aim The purpose of present study was to access the prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies in children with Juvenile Idiopathic Arthritis (JIA), and to investigate the clinical significance and diagnostic value of the anti-CCP antibodies in correlation with age, sex & activity. Methods This case-control study was performed on 50 patients with JIA in addition to 40 sex and age-matched children as a control group. The participants were recruited from rheumatology Outpatient Clinic of Cairo University Specialized Pediatric Hospital. Patients were subjected to full history taking, clinical examination, routine laboratory investigations and x-rays on involved joints. Both patients and controls underwent assay of anti-CCP antibodies by AxSYM Anti-CCP IgG Microparticle Enzyme Immunoassay (MEIA) which is a semi-quantitative determination of the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP) in patients’ serum or plasma. Data were analyzed using Mann-Whitney U test, ANOVA, and independent-samples t-test by SPSS version 15. Results Anti-CCP positivity was identified amongst patients with JIA, particularly those JIA patients experiencing RF positive polyarticular disease onset. Above all, it is important that anti-CCP positivity and bone erosions, degree of joint damage, and ESR levels were significantly correlated. Conclusion Anti-CCP could be utilized as a valuable marker in the polyarticular form of JIA to direct early, and could be aggressive therapeutic intervention. PMID:27790341

  6. Anti-Cyclic Citrullinated Peptide (Anti-CCP) and Anti-Mutated Citrullinated Vimentin (Anti-MCV) Relation with Extra-Articular Manifestations in Rheumatoid Arthritis

    OpenAIRE

    2014-01-01

    We evaluated the association between anti-cyclic citrullinated peptide antibodies (anti-CCP) and anti-mutated citrullinated vimentin antibodies (anti-MCV) with the presence of extra-articular (ExRA) manifestations in 225 patients with rheumatoid arthritis (RA). Ninety-five patients had ExRA and 130 had no ExRA. There was no association of anti-CCP and anti-MCV levels with the presence of ExRA as total group (P = 0.40 and P = 0.91, resp.). Making an analysis of individual manifestations, rheum...

  7. RHEUMATOID FACTOR AND ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODIES IN PATIENTS WITH PSORIATIC ARTHRITIS

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    V. V. Badokin

    2011-01-01

    Full Text Available Objective: to define the clinical value of rheumatoid factor (RF and anti-cyclic citrullinated peptide antibodies (anti-CCP in early psori- atic arthritis (PA. Subjects and methods. Fifty-six patients (32 females and 24 males with early PA with a mean duration of 12±6.7 months were studied. The examinees' age ranged from 18 to 76 years (mean age 44±15.5 years. Mean psoriasis duration was 12.5±2.2 years. RF IgM was determined using a high-sensitive nephelometric method on a BN Pro-Spec analyzer (Siemens, Germany and serum anti-CCP concentra- tions were measured by immunochemiluminescence on a COBAS e411 analyzer (Roche, Switzerland. Group 1 included 10 patients with anti-CCP and/or RF (a study group; Group 2 comprised 46 patients without anti-CCP and RF (a control group. Results. There was anti-CCP in 7 (12.5% of the patients with early PA, RF in 8 (14.3%, both of them in 5 (9%. The study group had a severer course of PA accompanied by polyarthritis, inflamed distal interphalangeal joints, axial arthritis, dactylitis, enthesitis, and, in some cases spondylitis and sacroiliitis. In groups 1 and 2, the number of tender joints was 17.6±4 and 10±1.5, respectively (p = 0.04; that of swollen ones, 12.6±1.5 and 7.0±1.1 (p = 0.02; DAS28 index, 5.9±1.7 and 4.5±1.5 (p = 0.02; ESR, 34.5±5.9 and 22±2.3 (p = 0.04, high-sensitive C reactive protein, 70±25.3 and 24.9±5.0 (p = 0.06; and Sharp ratio, 68.7±14.3 and 21.3±3.8 (p < 0.004. Conclusion. In patients with early PA, anti-CCP and RF were encountered with an approximately equal frequency; at the same time, they were associated with polyarthritis, high disease activity, and an erosive process. 

  8. Strong combined gene-environment effects in anti-cyclic citrullinated peptide-positive rheumatoid arthritis

    DEFF Research Database (Denmark)

    Pedersen, Line Merete Blak; Jacobsen, Søren; Garred, Peter;

    2007-01-01

    To study the role of shared epitope (SE) susceptibility genes, alone and in combination with tobacco smoking and other environmental risk factors, for risk of subtypes of rheumatoid arthritis (RA) defined by the presence or absence of serum antibodies against cyclic citrullinated peptides (CCPs)....

  9. Anti-cyclic Citrullinated Peptide Antibody (Anti-CCP and Diagnostic Value for Rheumatoid Arthritis

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    Mehmet Agilli

    2014-02-01

    Full Text Available Rheumatoid arthritis (RA is an inflammatory multisystem disease of unknown etiology characterized by chronic destructive synovitis. It and #8217;s prevalence is about 1% all over the world. Serologic markers are also important beside some clinical situations upon RA diagnosis. Today, the most commonly used laboratory test is rheumatoid factor (RF in patients with suspected RA. RF is sensitive but not a specific biomarker for diagnosing RA. Early diagnosis of RA is essential to prevent of progressive joint damage. In recent years, anticyclic citrullinated peptide/protein antibody (anti-CCP attracts the attention as a remarkable biomarker for early diagnosis. Anti-CCP which is a family of anti-citrullinated protein antibodies (ACPA family, showed quite satisfactory specificity in the diagnosis of RA. Due to the prescence of ACPA was included to 2010 RA diagnostic criteria, in a manner of speaking, importance of anti-CCP was registered. [TAF Prev Med Bull 2014; 13(1.000: 83-88

  10. Association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope and smoking status in Brazilian patients with rheumatoid arthritis

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    Michel Alexandre Yazbek

    2011-01-01

    Full Text Available INTRODUCTION: Epstein-Barr virus exposure appears to be an environmental trigger for rheumatoid arthritis that interacts with other risk factors. Relationships among anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status have been observed in patients with rheumatoid arthritis from different populations. OBJECTIVE: To perform an association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status in Brazilian patients with rheumatoid arthritis. METHODS: In a case-control study, 140 rheumatoid arthritis patients and 143 healthy volunteers who were matched for age, sex, and ethnicity were recruited. Anti-Epstein-Barr nuclear antigen-1 antibodies and anti-cyclic citrullinated peptide antibodies were examined using an enzyme-linked immunosorbent assay, and shared epitope alleles were identified by genotyping. Smoking information was collected from all subjects. A comparative analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status was performed in the patient group. Logistic regression analysis models were used to analyze the risk of rheumatoid arthritis. RESULTS: Anti-Epstein-Barr nuclear antigen-1 antibodies were not associated with anti-cyclic citrullinated peptide antibodies, shared epitope alleles, or smoking status. Anti-cyclic citrullinated peptide antibody positivity was significantly higher in smoking patients with shared epitope alleles (OR = 3.82. In a multivariate logistic regression analysis using stepwise selection, only anti-cyclic citrullinated peptide antibodies were found to be independently associated with rheumatoid arthritis (OR = 247.9. CONCLUSION: Anti-Epstein-Barr nuclear antigen-1 antibodies did not increase the risk of rheumatoid arthritis and were not associated with the rheumatoid arthritis risk factors studied. Smoking

  11. Circulating anti-cyclic citrullinated peptide antibody in patients with rheumatoid arthritis and chronic obstructive pulmonary disease.

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    Yang, Deng-Ho; Tu, Chuan-Chou; Wang, Shou-Cheng; Wei, Cheng-Chung; Cheng, Ya-Wen

    2014-07-01

    Anti-cyclic citrullinated peptide (anti-CCP) antibody is highly specific for diagnosing rheumatoid arthritis (RA). Cigarette smoking is a lifestyle and environmental factor associated with anti-CCP production and is strongly associated with chronic obstructive pulmonary disease (COPD). This study assessed levels of anti-CCP antibodies and rheumatoid factor (RF) among patients with RA and COPD. The study sample comprised 63 patients with RA and 70 patients with COPD, all of whom underwent assessment of anti-CCP antibody and RF levels. Testing revealed that 54.2% of RA patients and 0% of COPD patients were positive for anti-CCP antibodies. Additionally, 82.5% of RA patients and 42% of COPD patients were positive for RF. Among RA patients, levels of anti-CCP antibodies were higher among smokers than among nonsmokers (242.7 ± 128.3 vs. 68.1 ± 112.1, P < 0.001). COPD patients had low titers of RF but were negative for anti-CCP antibodies. The presence of anti-CCP antibodies was a reliable serologic marker in RA diagnosis and was associated with cigarette smoking.

  12. Significance of Anti-cyclic Citrullinated Peptide Autoantibodies in Immune-mediated Inflammatory Skin Disorders with and without Arthritis

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    Grover, Chander; Kashyap, Bineeta; Daulatabad, Deepashree; Dhawan, Amit; Kaur, Iqbal R

    2016-01-01

    Background: Anti-cyclic citrullinated peptides (CCPs) are autoantibodies directed against citrullinated peptides. Rheumatoid factor (RF), an antibody against the Fc portion of IgG, is known to form immune complexes and contribute to the etiopathogenesis of various skin disorders. C-reactive protein (CRP), an acute-phase protein, increases following secretion of interleukin-6 from macrophages and T cells. Anti-CCP, RF, and CRP are well-established immune-markers, their diagnostic potential in immune-mediated skin disorders remains less widely studied. Aims and Objectives: To determine the correlation between anti-CCP, RF, and CRP in immune-mediated inflammatory skin diseases. Materials and Methods: About 61 clinically diagnosed cases of various immune-mediated skin diseases (psoriasis [n = 38], connective tissue diseases such as systemic lupus erythematosus and systemic sclerosis [n = 14], and immunobullous disorders including pemphigus vulgaris and pemphigus foliaceus [n = 9]) were included in the study. These patients were subclassified on the basis of presence or absence of arthritis. Arthritis was present in nine cases of psoriasis and seven connective tissue disorder patients. Detection of serum anti-CCP was done using enzyme-linked immunosorbent assay, whereas CRP and RF levels were detected using latex agglutination technique. Results: Of the 61 specimens, 14.75% had elevated serum anti-CCP levels. RF and CRP levels were elevated in 18.03% and 39.34% specimens, respectively. RF was elevated in 13.16% of inflammatory and 42.88% of connective tissue disorders, whereas anti-CCP was raised in 10.53% of inflammatory and 35.71% of connective tissue disorders. CRP positivity was highest in connective tissue disorders (50%), followed by 39.47% in inflammatory and 22.22% in immunobullous conditions. In none of the immunobullous patients, anti-CCP or RF levels were found to be elevated. Association of the presence of arthritis with elevated anti-CCP was found to be

  13. Usefulness of anti-cyclic citrullinate peptide antibody determination in synovial fluid analysis of patients with rheumatoid arthritis

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    G. Valesini

    2011-09-01

    Full Text Available Objective: To assess the role of anti-cyclic citrullinated peptide (CCP antibody detection in synovial fluid (SF of RA patients compared to OA patients. Methods: We evaluated in 25 RA subjects and 14 OA patients, presenting a knee-joint effusion, the main clinical and laboratory parameters including the number of painful and/or swollen joints, Ritchie index, morning stiffness, ESR, CRP and analysis of SF obtained by therapeutic arthrocentesis. IgG anti-CCP (ELISA, rheumatoid factor (RF and total IgG (nephelometry method were measured in SF and paired serum samples. Results: We found anti-CCP antibodies and RF in 64% (16/25 and 60% (15/25 of RA sera, respectively; 72% (18/25 of RA patients were positive for anti-CCP antibodies or RF. We found a higher SF/serum ratio for anti-CCP (p<0.004 compared to that for total IgG. The calculation of anti-CCP concentration as IgG anti-CCP (units/total IgG (g L-1 revealed higher values in SF than in serum (p<0.046 in RA patients. Among these, correlation analysis showed that anti-CCP/total IgG values in SF correlated with the relative concentration of serum anti-CCP/total IgG (rs=0.842; p<0.00001 and serum anti-CCP antibody levels (rs=0.799; p<0.0001. We did not find any correlation between SF anti-CCP levels and the main characteristics of SF as well as the clinical or laboratory parameters. Conclusion: Our study give evidence for a preferential production of anti-CCP antibodies at RA joint level, confirming the pathogenetic role of these autoantibodies. Moreover, SF determination of anti-CCP, corrected for the total amount of the corresponding immunoglobulin, may be helpful as diagnostic tool in selected cases.

  14. Anti-Cyclic Citrullinated Peptide (Anti-CCP and Anti-Mutated Citrullinated Vimentin (Anti-MCV Relation with Extra-Articular Manifestations in Rheumatoid Arthritis

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    Laura Gonzalez-Lopez

    2014-01-01

    Full Text Available We evaluated the association between anti-cyclic citrullinated peptide antibodies (anti-CCP and anti-mutated citrullinated vimentin antibodies (anti-MCV with the presence of extra-articular (ExRA manifestations in 225 patients with rheumatoid arthritis (RA. Ninety-five patients had ExRA and 130 had no ExRA. There was no association of anti-CCP and anti-MCV levels with the presence of ExRA as total group (P=0.40 and P=0.91, resp.. Making an analysis of individual manifestations, rheumatoid nodules were associated with positivity for rheumatoid factor (RF; (P=0.01, anti-CCP (P=0.048, and anti-MCV (P=0.02. Instead, RF, anti-CCP, or anti-MCV were not associated with SS, chronic anemia, or peripheral neuropathy. Levels of anti-CCP correlated with the score of the Health Assessment Questionnaire-Disability Index (HAQ-Di (r=0.154, P=0.03, erythrocyte sedimentation rate (ESR; (r=0.155, P=0.03, and RF (P=0.254, P<0.001, whereas anti-MCV titres only correlated with RF (r=0.169, P=0.02. On adjusted analysis, ExRA was associated with longer age (P=0.015, longer disease duration (P=0.007, higher DAS-28 score (P=0.002, and higher HAQ-DI score (P=0.007, but serum levels of anti-CCP and anti-MCV were not associated. These findings show the need to strengthen the evaluation of the pathogenic mechanisms implied in each specific ExRA manifestation.

  15. Anti-Cyclic Citrullinated Peptide (Anti-CCP) and Anti-Mutated Citrullinated Vimentin (Anti-MCV) Relation with Extra-Articular Manifestations in Rheumatoid Arthritis

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    Gonzalez-Lopez, Laura; Rocha-Muñoz, Alberto Daniel; Ponce-Guarneros, Manuel; Flores-Chavez, Alejandra; Salazar-Paramo, Mario; Cardona-Muñoz, Ernesto German; Fajardo-Robledo, Nicte Selene; Zavaleta-Muñiz, Soraya Amali; Garcia-Cobian, Teresa; Gamez-Nava, Jorge Ivan

    2014-01-01

    We evaluated the association between anti-cyclic citrullinated peptide antibodies (anti-CCP) and anti-mutated citrullinated vimentin antibodies (anti-MCV) with the presence of extra-articular (ExRA) manifestations in 225 patients with rheumatoid arthritis (RA). Ninety-five patients had ExRA and 130 had no ExRA. There was no association of anti-CCP and anti-MCV levels with the presence of ExRA as total group (P = 0.40 and P = 0.91, resp.). Making an analysis of individual manifestations, rheumatoid nodules were associated with positivity for rheumatoid factor (RF); (P = 0.01), anti-CCP (P = 0.048), and anti-MCV (P = 0.02). Instead, RF, anti-CCP, or anti-MCV were not associated with SS, chronic anemia, or peripheral neuropathy. Levels of anti-CCP correlated with the score of the Health Assessment Questionnaire-Disability Index (HAQ-Di) (r = 0.154, P = 0.03), erythrocyte sedimentation rate (ESR); (r = 0.155, P = 0.03), and RF (P = 0.254, P < 0.001), whereas anti-MCV titres only correlated with RF (r = 0.169, P = 0.02). On adjusted analysis, ExRA was associated with longer age (P = 0.015), longer disease duration (P = 0.007), higher DAS-28 score (P = 0.002), and higher HAQ-DI score (P = 0.007), but serum levels of anti-CCP and anti-MCV were not associated. These findings show the need to strengthen the evaluation of the pathogenic mechanisms implied in each specific ExRA manifestation. PMID:24804270

  16. Onset of polyarticular juvenile idiopathic arthritis with both anti-cyclic citrullinated peptide antibodies and rheumatoid factor in a 3-year-old girl

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    Yasui Kozo

    2012-12-01

    Full Text Available Abstract This report describes 3 year old girl with the unusual presentation of polyarticular juvenile idiopathic arthritis (JIA with anti-cyclic citrullinated peptide (anti-CCP antibodies and a positive rheumatoid factor (RF. She was initially treated with a nonsteroidal anti-inflammatory drug (NSAID; ibuprofen followed by methotrexate (MTX, 10 mg/m2/week and prednisolone (0.25 mg/kg/day, but these treatments were ineffective. Administration of tocilizumab, a humanized antihuman interleukin-6 receptor monoclonal antibody, promptly improved her clinical manifestations, and she has been in complete remission (DAS28

  17. Frequency and diagnostic significance of anti-cyclic citrullinated peptide antibodies (ACCP and anti-modified citrullinated vimentin antibodies (AMCV in children with early juvenile arthritis

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    S O Salugina

    2008-01-01

    Full Text Available Objective. To determine frequency of anti-cyclic citrullinated peptide antibodies (ACCP and anti-modified citrullinated vimentin antibodies (AMCV elevation and their diagnostic significance in children with early juvenile arthritis (JA. Material and methods. ACCP were evaluated in serum of 80 pts with early JA (36 girls, 44 boys, mean age 8,5±5,03 years, AMCV — in 85 pts with early JA (49 girls and 36 boys aged from 1,5 to 16 years (mean age 8,7±4,9 years. Disease duration in all children was less than 6 months. Control group included 54 grown up pts with early rheumatoid arthritis (RA, 27 - with undifferentiated arthritis (UDA and 37 conditionally healthy children. АССР was assessed by immuno-enzyme assay (IEA with commercial kits “Axis Shield Diagnostics" (Great Britain, upper normal limit 5,0 U/ml. AMCV was examined by IEA with commercial kits “Orgentec Diagnostics” (Germany, upper normal limit — 25 U/ml. Results. ACCP was elevated in 7 children with early JA (8,8%. Frequency was higher than in healthy children but lower than in grown up pts with early RA and comparable with UDA. In juvenile rheumatoid arthritis (JRA ACCP were more frequent than in juvenile chronic arthritis (JCA. Concentration was higher in rheumatoid factor (RF positive pts with polyarticular JA. AMCV level was elevated in in 23 (27,1% pts with early JA (more frequent than in healthy donors but less frequent than in grown up pts with early RA and UDA. AMCV was significantly more frequent in JRA than in JCA and in RF positive than in RF negative pts. AMCV concentration in JA was higher than in healthy children but lower than in grown up pts with RA. It was also higher in RF+ than RF- JA. ACCP and AMCV correlated with swollen joint count, tender joint count and RF. AMCV also correlated with ESR and CRP. Conclusion. In pts with early JA ACCP and AMCV are equally or more frequent than RF. In spite of low sensitivity they have high specificity for JRA in contrast

  18. The Diagnostic Utility of Anti-cyclic Citrullinated Peptide Antibodies, Matrix Metalloproteinase-3, Rheumatoid Factor, Erythrocyte Sedimentation Rate, and C-reactive Protein in Patients with Erosive and Non-erosive Rheumatoid Arthritis

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    O. Shovman

    2005-01-01

    Full Text Available Objective: To compare the diagnostic utility of laboratory variables, including matrix metalloproteinase-3 (MMP-3, anti-cyclic citrullinated peptide (CCP antibodies, rheumatoid factor (RF, erythrocyte sedimentation rate (ESR, and C-reactive protein (CRP in patients with erosive and non-erosive rheumatoid arthritis (RA.

  19. Anti-Cyclic Citrullinated Peptide Antibodies and Severity of Interstitial Lung Disease in Women with Rheumatoid Arthritis

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    Ponce-Guarneros, Manuel; Mejía, Mayra; Juárez-Contreras, Pablo; Corona-Sánchez, Esther Guadalupe; Rodríguez-Hernández, Tania Marlen; Salazar-Páramo, Mario; Cardona-Muñoz, Ernesto German; Celis, Alfredo; González-Lopez, Laura

    2015-01-01

    Objective. To evaluate whether serum titers of second-generation anticyclic citrullinated peptide antibodies (anti-CCP2) are associated with the severity and extent of interstitial lung disease in rheumatoid arthritis (RA-ILD). Methods. In across-sectional study, 39 RA-ILD patients confirmed by high-resolution computed tomography (HRCT) were compared with 42 RA without lung involvement (RA only). Characteristics related to RA-ILD were assessed in all of the patients and serum anti-CCP2 titers quantified. Results. Higher anti-CCP2 titers were found in RA-ILD compared with RA only (medians 77.9 versus 30.2 U/mL, P < 0.001). In the logistic regression analysis after adjustment for age, disease duration (DD), smoke exposure, disease activity, functioning, erythrocyte sedimentation rate, and methotrexate (MTX) treatment duration, the characteristics associated with RA-ILD were higher anti-CCP2 titers (P = 0.003) and + RF (P = 0.002). In multivariate linear regression, the variables associated with severity of ground-glass score were anti-CCP2 titers (P = 0.02) and with fibrosis score DD (P = 0.01), anti-CCP2 titers (P < 0.001), and MTX treatment duration (P < 0.001). Conclusions. Anti-CCP2 antibodies are markers of severity and extent of RA-ILD in HRCT. Further longitudinal studies are required to identify if higher anti-CCP2 titers are associated with worst prognosis in RA-ILD. PMID:26090479

  20. Anti-Cyclic Citrullinated Peptide Antibodies and Severity of Interstitial Lung Disease in Women with Rheumatoid Arthritis

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    Alberto Daniel Rocha-Muñoz

    2015-01-01

    Full Text Available Objective. To evaluate whether serum titers of second-generation anticyclic citrullinated peptide antibodies (anti-CCP2 are associated with the severity and extent of interstitial lung disease in rheumatoid arthritis (RA-ILD. Methods. In across-sectional study, 39 RA-ILD patients confirmed by high-resolution computed tomography (HRCT were compared with 42 RA without lung involvement (RA only. Characteristics related to RA-ILD were assessed in all of the patients and serum anti-CCP2 titers quantified. Results. Higher anti-CCP2 titers were found in RA-ILD compared with RA only (medians 77.9 versus 30.2 U/mL, P<0.001. In the logistic regression analysis after adjustment for age, disease duration (DD, smoke exposure, disease activity, functioning, erythrocyte sedimentation rate, and methotrexate (MTX treatment duration, the characteristics associated with RA-ILD were higher anti-CCP2 titers (P=0.003 and + RF (P=0.002. In multivariate linear regression, the variables associated with severity of ground-glass score were anti-CCP2 titers (P=0.02 and with fibrosis score DD (P=0.01, anti-CCP2 titers (P<0.001, and MTX treatment duration (P<0.001. Conclusions. Anti-CCP2 antibodies are markers of severity and extent of RA-ILD in HRCT. Further longitudinal studies are required to identify if higher anti-CCP2 titers are associated with worst prognosis in RA-ILD.

  1. Anti-cyclic citrullinated peptide (CCP) antibody in patients with wood-smoke-induced chronic obstructive pulmonary disease (COPD) without rheumatoid arthritis.

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    Sigari, Naseh; Moghimi, Nasrin; Shahraki, Farhad Saber; Mohammadi, Shilan; Roshani, Daem

    2015-01-01

    Citrullination, a post-translational modification of proteins, is increased in inflammatory processes and is known to occur in smokers. It can induce anti-cyclic citrullinated peptide (CCP) antibodies, the most specific serologic marker for rheumatoid arthritis. Thus far, the incidence of autoimmunity in patients with wood-smoke-induced chronic obstructive pulmonary disease (COPD) resulting in anti-CCP production has not been examined. We hypothesise that anti-CCP antibody level in these patients should be higher than that in healthy subjects. A total of 112 non-rheumatoid arthritis patients, including 56 patients with wood-smoke-induced COPD and 56 patients with tobacco-induced COPD, and 56 healthy non-smoker controls were included. The serum anti-CCP antibody levels were measured and compared between the groups and against smoke exposure and clinical characteristics. The mean anti-CCP antibody levels in wood-smoke-induced COPD group were significantly higher than those in tobacco-induced COPD group (p = 0.03) and controls (p = 0.004). Furthermore, 8 (14.2 %) patients with wood-smoke-induced COPD, 4 (7.14 %) with tobacco-induced COPD and 2 (3.57 %) controls exceeded the conventional cut-off of anti-CCP antibody positivity. No relationship was found between the anti-CCP antibody level and age, gender, duration of disease, Pack-years of smoking, and duration of exposure to wood smoke. Moreover, correlations between anti-CCP antibodies and severity of airflow limitation, CAT scores, mMRC scores of dyspnoea, and GOLD staging of COPD severity were not significant. Wood-smoke-induced COPD could significantly increase the anti-CCP antibody level in non-rheumatoid arthritis patients when compared with that in patients with tobacco-induced COPD and healthy controls.

  2. Relation of rheumatoid factor and anti-cyclic citrullinated peptide antibody with disease activity in rheumatoid arthritis: cross-sectional study.

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    Choe, Jung-Yoon; Bae, Jisuk; Lee, Hwajeong; Bae, Sang-Cheol; Kim, Seong-Kyu

    2013-09-01

    To analyze the association of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP) with non-remission and with disease activity measures in rheumatoid arthritis (RA). Cross-sectional study of consecutive RA patients. Non-remission was defined as a disease activity score (DAS28) ≥ 2.6 at study enrollment. The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) were additionally measured. Serum titers of RF and anti-CCP were transformed into incremental levels (100/units) and log-transformed levels. Analysis of association with non-remission was done with logistic regression models, with and without adjustment for age, sex, disease duration, and corticoid use. Multiple regression models, raw and similarly adjusted, were used to measure the association of RF and anti-CCP with the disease activity measures. A total of 385 patients were included, of whom 286 (74 %) were not in remission. Log-transformed RF level was associated with an increased risk of non-remission after adjustment (OR = 1.32, 95 % CI 1.04-1.67). This association was especially evident in patients with less than 10 years of disease duration (OR = 1.51, 95 % CI 1.15-1.99) and in those using steroids (OR = 2.06, 95 % CI 1.22-3.48). Serum RF titers and log-transformed RF levels showed a small but significant association with DAS28 score (adjusted beta coefficients 0.002 and 0.18, respectively; both p ≤ 0.01), but neither with SDAI or CDAI nor with anti-CCP antibody. : Log-transformed RF levels might be associated with non-remission in RA, especially in patients with short disease duration or on steroids.

  3. Detection of anti-cyclic citrullinated peptide antibodies in patients with rheumatoid arthritis: the clinical significance%抗环瓜氨酸抗体检测在类风湿关节炎中的临床意义

    Institute of Scientific and Technical Information of China (English)

    殷健; 李婷; 包军; 徐沪济

    2011-01-01

    类风湿关节炎( rheumatoid arthritis,RA)是一种主要累及全身多关节的自身免疫性疾病.目前RA仍具有很高的关节致残率和病死率.早期诊断并进行积极治疗可有效减少关节畸形的可能.近年发现的抗瓜氨酸抗体( anti-citrullinated peptide antibodies,ACPA)可在关节破坏发生前即表现出阳性,该抗体与经典的类风湿因子(rheumatoid factor,RF)相比,在RA的诊断中具有相似的敏感性,但具有更高的特异性.研究发现抗环瓜氨酸抗体(anti-cyclic citrullinated peptide antibodies)在RA的早期诊断、预后判断等方面都有重要意义,并有流行病学证据显示其可能在RA的发病中扮演重要角色.%Rheumatoid arthritis (RA) is an autoimmune disease involving multiple joints, and currently it still leads to high disability rate of the joints and high mortality. Early diagnosis and treatment can effectively reduce joint deformities. The recently discovered anti-citrullinated peptide antibodiesC ACPA) can be detected before damage to the joints occurs. Compared with classical rheumatoid factor (RF) ACPA has higher specificity and similar sensitivity in diagnosing RA. Some studies have showned that anti-cyclic citrullinated peptide antibodies play an important role in the early diagnosis of RA and prediction of prognosis; epidemiological evidences also show that ACPA plays an important role on the pathogenesis of RA.

  4. Prevalência de anticorpos contra peptídeos cíclicos citrulinados na artrite idiopática juvenil The prevalence of anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis

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    Sandra H. Machado

    2005-12-01

    Full Text Available OBJETIVOS: Avaliar a presença de anticorpos contra peptídeos cíclicos citrulinados em uma coorte de pacientes com artrite idiopática juvenil. MÉTODOS: A presença de anticorpos contra peptídeos cíclicos citrulinados foi avaliada por ensaio imunoenzimático (ELISA no soro de pacientes com artrite idiopática juvenil com idade inferior a 18 anos, acompanhados no ambulatório de reumatologia pediátrica do Hospital de Clínicas de Porto Alegre, com tempo de diagnóstico de doença de, no mínimo, 6 meses. Também foi estudada a presença do fator reumatóide IgM e do fator antinuclear em células Hep-2 RESULTADOS: Foram analisadas amostras séricas de 45 pacientes com artrite idiopática juvenil. A presença de títulos elevados de anticorpos contra peptídeos cíclicos citrulinados foi encontrada somente no soro de uma criança (2%, a qual apresentava quadro de poliartrite com fator reumatóide reagente. CONCLUSÕES: O anticorpo contra peptídeos cíclicos citrulinados pode ser detectado em crianças com artrite idiopática juvenil, mas em freqüência muito inferior aos adultos com artrite reumatóide. Torna-se importante avaliar se anticorpos contra peptídeos cíclicos citrulinados podem identificar os pacientes com artrite idiopática juvenil com potencial de evolução para artrite reumatóide do adulto.OBJECTIVES: To assess the presence of anti-cyclic citrullinated peptide antibodies in a cohort of patients with juvenile idiopathic arthritis. METHODS: Anti-cyclic citrullinated peptide antibodies was tested for with an enzyme linked immunoabsorbent assay (ELISA in serum samples of patients from the Hospital de Clínicas de Porto Alegre, all less than 18 years old and with previous diagnosis for at least 6 months. IgMRF (rheumatoid factor and antinuclear antibodies in Hep-2 cells were also assayed. RESULTS: Serum samples were analyzed from 45 patients. The presence of high levels of anti-cyclic citrullinated peptide antibodies was found

  5. Macrophage-inducible C-type lectin is associated with anti-cyclic citrullinated peptide antibodies-positive rheumatoid arthritis in men

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    WU Xin-yu; GUO Jian-ping; YIN Fang-rui; LU Xiao-lan; LI Ru; HE Jing; LIU Xu; LI Zhan-guo

    2012-01-01

    Background Macrophage-inducible C-type lectin (MINCLE) is an important member of C-type lectin superfamily,which has been shown evidence for susceptibility to arthritis in animal models.We aimed to investigate the possible association of MINCLE with rheumatoid arthritis (RA) susceptibility in Chinese Hart population.Methods Haplotypes from HapMap database (Chinese Hart Beijing,CHB) were used to select tag-single nucleotide polymorphism (SNP) (r2=0.8) residing in MINCLE gene.A total of 563 patients with RA and 404 healthy controls were TagMan genotyped for SNP rs10841845.Association analyses were performed on the whole data set and on RA subsets based on gender difference and the status of anti-cyclic citrullinated peptide (anti-CCP) antibody in RA patients.Association statistics were calculated by age and sex adjusted logistic regression.Results Overall,MINCLE SNP rs10841845 was not associated with susceptibility to RA.However,following anti-CCP stratification,rs10841845 GG genotypes conferred a significantly protective effects against anti-CCP-positive RA (OR 0.65,95% CI 0.430-0.995,P=0.048).Following gender stratification,SNP rs10841845 G allele appeared to insert its RA protective effect only in male patients,both at allele level (G vs.A OR 0.66,95% CI 0.46-0.93,P=0.018) and at genotype level (GG vs.AA+AG,OR 0.429,95% CI 0.20-0.95,P=0.036).Notably,the male RA protective effect of rs10841845 G allele was only seen in anti-CCP-positive RA (G vs.A:OR 0.64,95% CI 0.43-0.96,P=0.029; GG vs.AA+AG:OR 0.375,95% Cl 0.14-0.94,P=0.038).Furthermore,we observed a significant reduction of Disease Activity Score (DAS) 28 score (3.91±0.70 vs.5.66±0.31,P=0.022) and serum C-reactive protein levels (31.64±24.13 vs.91.80±12.02,P=0.012)in male anti-CCP-positive RA patients carrying rs10841845 GG genotype,compared with patients carrying AA+AG genotypes.Conclusions Our study provides the evidence for a gender specific association between MINCLE rs10841845 and RA

  6. Associação do anticorpo anticitrulina e gravidade da artrite reumatóide Association of anti-cyclic citrullinated peptide antibody and severe rheumatoid arthritis

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    Aldifran Ferreira da Silva

    2006-06-01

    Full Text Available OBJETIVOS: Avaliar a associação do anticorpo antipeptídeo citrulinado cíclico (anti-CCP com distintos parâmetros clínicos, sorológicos e radiológicos. MÉTODOS: Anti-CCP e fator reumatóide (FR foram pesquisados no soro de 100 pacientes com artrite reumatóide (AR. A atividade da doença foi definida por meio de um índice combinado compreendendo cinco parâmetros: número de juntas inflamadas, número de juntas doloridas, rigidez matinal, escala visual analógica (EVA de dor e velocidade de hemossedimentação (VHS. A capacidade funcional foi medida pelo índice HAQ (Health Assessment Questionnaire e a classe funcional foi determinada mediante aplicação dos critérios revisados do American College of Rheumatology (ACR, de 1991. Erosão e pinçamento articular foram graduados pelo índice de Sharp modificado. A análise estatística empregou os testes do Qui-quadrado, Mann Whitney e Kruskal-Wallis. RESULTADOS: Nenhum dos dois anticorpos demonstrou associação significativa com atividade da doença, sexo, idade de início da doença, presença de nódulos subcutâneos e síndrome de Sjögren. A média de idade foi significativamente menor nos pacientes com AR anti-CCP positivos. A positividade para o FR e anti-CCP foi maior nos pacientes com AR com menos de 50 anos em comparação com os pacientes com mais de 50 anos. A AR de início recente (OBJECTIVE: Evaluate the association of Anti-Cyclic Citrullinated Peptide Antibody (anti-CCP with distinct clinic, serological and radiological parameters. METHODS: anti-CCP and rheumatoid factor (RF were determined in the serum of 100 patients with rheumatoid arthritis (RA. Disease activity was defined by means of a combined index with five parameters: number of swollen joints, number of painful joints, morning stiffness, pain visual analogue scale (VAS, and erythrocyte sedimentation rate (ESR. Functional capacity was measured by (Health Assessment Questionnaire HAQ index and the functional class

  7. The status of rheumatoid factor and anti-cyclic citrullinated peptide antibody are not associated with the effect of anti-TNFα agent treatment in patients with rheumatoid arthritis: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Qianwen Lv

    Full Text Available OBJECTIVES: This meta-analysis was conducted to investigate whether the status of rheumatoid factor (RF and anti-cyclic citrullinated peptide (anti-CCP antibody are associated with the clinical response to anti-tumor necrosis factor (TNF alpha treatment in rheumatoid arthritis (RA. METHODS: A systemic literature review was performed using the MEDLINE, SCOPUS, Cochrane Library, ISI Web of Knowledge, and Clinical Trials Register databases, and Hayden's criteria of quality assessment for prognostic studies were used to evaluate all of the studies. The correlation between the RF and anti-CCP antibody status with the treatment effect of anti-TNFα agents was analyzed separately using the Mantel Haenszel method. A fixed-effects model was used when there was no significant heterogeneity; otherwise, a random-effects model was applied. Publication bias was assessed using Egger's linear regression and a funnel plot. RESULTS: A total of 14 studies involving 5561 RA patients meeting the inclusion criteria were included. The overall analysis showed that the pooled relative risk for the predictive effects of the RF and anti-CCP antibody status on patient response to anti-TNFα agents was 0.98 (95% CI: 0.91-1.05, p=0.54 and 0.88 (95% CI: 0.76-1.03, p=0.11, respectively, with I(2 values of 43% (p=0.05 and 67% (p<0.01, respectively. Subgroup analyses of different anti-TNFα treatments (infliximab vs. etanercept vs. adalimumab vs. golimumab, response criteria (DAS28 vs. ACR20 vs. EULAR response, follow-up period (≥ 6 vs. <6 months, and ethnic group did not reveal a significant association for the status of RF and anti-CCP. CONCLUSIONS: Neither the RF nor anti-CCP antibody status in RA patients is associated with a clinical response to anti-TNFα treatment.

  8. The evaluation of rheumatoid factor, anti-cyclic citrullinated peptide antibody and antikeratin antibody in the diagnosis of rheumatoid arthritis%RF、抗CCP抗体和AKA对类风湿性关节炎诊断的评价

    Institute of Scientific and Technical Information of China (English)

    胥国强; 杨佳佳; 蒲泽宴; 康清秀

    2013-01-01

    目的 评价类风湿因子(RF)、抗环瓜氨酸肽(CCP)抗体以及抗角蛋白抗体(AKA)在类风湿性关节炎(RA)诊断中的意义.方法 对177例确诊为RA患者的上述3项指标进行回顾分析.RF、抗CCP抗体和AKA分别用速率散射比浊法、酶联免疫吸附法(ELISA)和间接免疫荧光法(ⅡF)检测.应用x2检验和Pearson相关分析,比较3种抗体在RA诊断中的价值及相关性,并讨论RF、抗CCP抗体与新诊断标准评分的关系.结果 RF、抗CCP抗体和AKA对RA诊断的灵敏度分别是77.40%、64.97%和21.47%;3种抗体中任一抗体阳性的联合检测对RA诊断的灵敏度为85.88%,任2种抗体阳性的灵敏度为58.76%,3种抗体平均阳性的灵敏度为19.21%.抗CCP抗体和AKA在6个不同RF水平组的阳性率均有显著性差异(P<0.05),其中抗CCP抗体阳性率在RF阳性各组与阴性组之间差异显著(P<0.01),并与RF呈正相关(r=0.339,P=0.000);而AKA阳性率在RF阳性各组与阴性组之间无显著性差异(P>0.01),仅在RF值500~1 000 U/mL组的阳性率显著高于RF<20 U/mL组(x2=16.485,P=0.000),AKA与RF呈正相关(r=0.184,P=0.014).抗CCP抗体与AKA呈正相关(r=0.326,P=0.000).2010年ACR/EULAR分类标准评分大于或等于6分在6个不同RF水平组的阳性率无显著性差异(x2 =8.547,P=o.129),且与RF相关(r=0.199,P=0.005);而抗CCP抗体与RA评分不相关(r=0.123,P=0.103).结论 RF、抗CCP抗体和AKA均可作为RA血清学诊断指标,三者两两相关,前两者灵敏度较高,联合检测有助于RA的早期诊断.%Objective To explore the significance of rheumatoid factor(RF),anti-cyclic citrullinated peptide(anti-CCP) antibody and anti keratin antibody(AKA) in the diagnosis of Rheumatoid Arthritis(RA).Methods 177 patients with RA,who had these three tests,were analyzed basing on retrospectively available data.RF,anti-CCP antibody and AKA were respectively detected by nephelometry,Enzyme linked immunosorbent assay(ELISA) and

  9. Rheumatoid factor and anti-cyclic citrullinated peptide antibodies Clinical application of combined detection%类风湿因子与抗环瓜氨酸肽抗体联合检测的临床应用价值

    Institute of Scientific and Technical Information of China (English)

    李韧; 袁斌; 张娟

    2013-01-01

    Objective To investigate the analysis of rheumatoid factor and anti-citrulline antibody combined detection for the clinical application value. Methods Using enzyme-linked immunosorbent assay(ELISA method) to our hospital for the treatment of 150 cases of rheumatoid arthritis(RA) patients(A group), 28 cases of non-RA patients(B group) and 34 cases of healthy people(C group) were detected in serum, compared three groups of serum rheumatoid factor, anti-citrulline antibody for use alone or in combination for the diagnosis of rheumatoid arthritis sensitivity, specificity and so on. Results A group of people for anti-citrulline antibodies and rheumatoid factor positive rate than the B group, C group high(P <0.01); A group of rheumatoid factor alone sensitive than anti-citrulline antibodies for the anti-citrulline antibody specificity for the above rheumatoid factor, combined use of anti-citrulline conversion and rheumatoid factor antibodies, the detection sensitivity and negative predictive values, and Youden index for other than anti-citrulline antibodies or rheumatoid factor when used alone. Conclusion Anti-changer citrulline antibody and rheumatoid factor used in combination for the diagnosis of rheumatoid arthritis with good clinical practice.%目的探讨类风湿因子(RF)与抗环瓜氨酸肽抗体(抗CCP抗体)联合检测的临床应用价值。方法使用酶联免疫吸附法(ELISA 法)检测我院150例类风湿关节炎(RA)患者(A组)、28例非RA患者(B组)以及34例健康人群(C组)的血清,比较三组人群血清中RF、抗CCP抗体单独或联合使用对诊断RA的敏感性、特异性等。结果 A组人群抗CCP抗体和RF阳性率比B组、C组高(P<0.01);A组中单独使用RF的敏感性高于抗CCP抗体,抗CCP抗体的特异性高于RF,联合使用抗CCP抗体和RF,其检测敏感性、阴性预测值及约登指数等高于抗CCP抗体或RF单独使用。结论抗CCP抗体和RF联合使用用于诊断RA具有良好的临床应用价值。

  10. 抗CCP抗体和RF联检在RA诊疗中的临床价值%Clinical Value of Combined Detection of Serum Anti-Cyclic Citrullinated Peptide Antibody(Anti-CCP Ab)and Rheumatoid Factor(RF)in Diagnosis of Rheumatoid Arthritis

    Institute of Scientific and Technical Information of China (English)

    葛文亮

    2010-01-01

    目的:研究抗环瓜氨酸肽(anti-cyclic citrullinated peptide,Anti-CCP)(抗CCP抗体)和RF的检测在类风湿关节炎(RA)诊疗中的临床价值.方法:分别用酶联免疫吸附试验(ELISA)、BeckMan全自动蛋白分析仪同时检测早期RA组(病程<1年)42例,RA组(病程>1年)40例,非RA对照组40例患者血清抗CCP抗体和RF.结果:早期RA组、RA组的抗CCP抗体、RF阳性率显著高于非RA对照组(P<0.05)RA组抗CCP水平显著高于早期RA组(P<0.01),两者RF无显著差别(P>0.05).RA组与早期RA组CCP抗体与RF二者无相关性.结论:联检抗CCP抗体、RF有助于类风湿的早期诊断和预测病情的进展.

  11. The Diagnostic Value of Combinate Determination of Anti-cyclic Citrullinated Peptide Antibody and Rheumatoid Factor for the Rheumatoid Arthritis%抗CCP抗体与RF联合检测对类风湿性关节炎的诊断价值

    Institute of Scientific and Technical Information of China (English)

    游其勇; 易朝阳

    2011-01-01

    目的 探讨联合检测抗环瓜氨酸肽抗体(抗CCP抗体)及类风湿因子(RF)对类风湿关节炎(RA)的临床诊断价值.方法 分别用胶体金免疫层析法(GICA)、速率散射比浊法联合检测52例RA患者、37例非RA的自身免疫性疾病患者和15例正常人血清中抗CCP抗体和RF.结果 抗CCP抗体和RF联合检测的特异性、阳性预测值、阳性似然比、阴性似然比与任何单一项检测比较差异均有统计学意义(P<0.05).结论 联合检测抗CCP抗体和RF可明显提高类风湿关节炎的诊断率.%Objective To evaluate the clinical diagnosic value of anti - cyclic citrullinated peptide(anti- CCP) antibody and rheumatoid factor(RF) in patients with rhetrnatoid arthritis(PA).Methods Anti - CCP antibody was determined by quantitative GICA and rheumatoid factor by BNP nephelometer in 52 cases of PA ,37 cases of non - PA rhetrnatic diseases and 15 healths.Results The diagnosis specificity, positive predictive value, positive/negative likelihood ratios of combinate determination of anti - CCP antibodyand RF were significantly higher than either one.Conclusion The combinate determination of anti - CCP antibody and rheumatoid factor will remarkably improve the accuracy for diagnosis of RA.

  12. Rheumatoid factor and anti-cyclic citrullinated peptides antibody in diagnosing significance in patients with rheumatoid arthritis and their correlation with disease activity%类风湿因子和抗环瓜酸抗体联合检测对类风湿关节炎的诊断价值及与疾病活动的相关性

    Institute of Scientific and Technical Information of China (English)

    李雪飞; 武加标; 任敏

    2011-01-01

    目的:比较类风湿因子(RF)和抗环瓜酸抗体(抗CCP抗体)在类风湿关节炎(RA)诊断及预测疾病活动性中的价值.方法:采用酶联免疫吸附法(ELISA)、速率散射比浊法检测RF和抗CCP抗体,比较它们单独或联合诊断RA的价值,分析RF和抗CCP抗体与疾病活动性的相关性.结果:RF和抗CCP抗体诊断RA的敏感性分别为81.5%和95.4%,特异性分别为58.8%和95.6%,联合诊断RA特异性增高;RF和抗CCP抗体均与C反应蛋白、红细胞沉降率显著相关.结论:RF联合抗CCP抗体应用可进一步提高RA的诊断准确性,RF和抗CCP抗体与RA疾病活动性密切相关.%Objective: To evaluate the diagnostic significance through detecting rheumatoid factor(RF-IgM) and anti-cyclic citrullinated peptide (CCP) antibody and their correlation with disease activity.Methods: We used enzyme-linked immunosorbent assay and rate nephelometry to detect CCP and RF in patients with 65 RA, 68 nonRA.Results: The sensitivity for RF and anti-CCP were 81.5% and 95.4%, respectively, and the specificity were 58.8%, 95.6%, respectively.The specificity was increased by combining the tests.A significant correlation was found between RF, anti-CCP and CRP, ESR, respectively.Conclusion: The higher specificity was achieved by combining the tests.There was an association between RF, anti-CCP and disease activity.

  13. Significance of serum anti-cyclic citrullinated peptide antibodies in diagnosis of juvenile idiopathic arthritis%血清抗环瓜氨酸肽抗体水平对幼年特发性关节炎的诊断价值

    Institute of Scientific and Technical Information of China (English)

    郭桂梅; 何威逊; 朱光华; 王娟

    2013-01-01

    Objective To investigate the clinical significance of serum anti-cyclic citrullinated peptide ( anti-CCP) antibodies in diagnosis of juvenile idiopathic arthritis (JIA). Methods Serum anti-CCP antibodies of 68 children suspected of JIA with fever and arthritis of unknown causes were determined by ELISA, and comprehensive analysis was carried out with clinical data and related laboratory findings. Results Among the 68 children suspected of JIA, there were 10 cases of polyarticular JIA, 13 cases of systemic onset JIA, 8 cases of oligoarticular JIA and 13 cases of enthesitis related JIA. There were 11 cases of other rheumatoid diseases, 8 cases of neoplastic diseases of blood and 5 cases of infectious diseases. The serum anti-CCP level in children suspected of polyarticular JIA was significantly higher than those, in children suspected of systemic onset JIA, oligoarticular JIA and enthesitis related JIA (P <0.05). With serum anti-CCP ≥15.8 RU/mL as the positive threshold value, the area under receiver operating characteristic curve was 0.80, and the sensitivity and specificity in diagnosis of polyarticular JIA were 80% and 67. 6% respectively. The serum anti-CCP level was positively related to serum C-reaction protein level in children suspected of polyarticular JIA (r = 0. 764, P = 0. 017). Conclusion Serum anti-CCP can be used for the diagnosis of polyarticular JIA, and 15.8 RU/mL may be a suitable cut-off level.%目的 探讨血清抗环瓜氨酸肽(anti-CCP)抗体对幼年特发性关节炎(JIA)的诊断价值.方法 采用ELISA法对68例因不明原因发热和关节痛疑诊为JIA患儿进行血清anti-CCP抗体水平检测,并结合临床资料及相关实验室检查指标进行综合分析.结果 68例疑诊JIA患儿中,多关节型JIA 10例,全身型JIA 13例,少关节型JIA 8例,与附着点炎症相关的JIA 13例;其他风湿性疾病11例,血液与肿瘤疾病8例,感染性疾病5例.多关节型JIA患儿的血清anti-CCP水平显著高于全身

  14. Clinical value of anti-cyclic citrullinated peptide antibody combined with rheumatoid factor IgA and IgM for diagnosing rheumatoid arthritis%抗环瓜氨酸肽抗体联合类风湿因子IgA和IgM诊断类风湿关节炎的临床价值

    Institute of Scientific and Technical Information of China (English)

    邢雪梅; 李艳琴; 沈钢; 张军

    2014-01-01

    Objective To evaluate the value of the single or combined detection of anti-keratin antibody (AKA) ,anti-cyclic citrullinated peptide(CCP) antibody and rheumatoid factor (RF) for the diagnosis of rheumatoid arthritis(RA) .Methods Serum AKA ,anti-CCP antibody ,IgA-RF and IgM-RF were detected in 195 cases of RA and 195 controls .AKA was detected by using the indirect immunofluorescence method ,RF and anti-CCP antibody were detected by using ELISA .The specificity and sensitivity of those antibodies in RA were analyzed in the diagnosis of RA .The sensitivity ,specificity ,positive predictive value(PPV) and negative predictive value(NPV) of anti-CCP anti-body combined IgA-RF and/or IgM-RF for diagnosing RA were compared .Results The combination detection of an-ti-CCP antibody ,IgA-RF and IGM-RF had the highest specificity .The positive predictive value of anti-CCP antibody+ IgA-RF was 87 .59% ,which was significantly higher than 78 .49% of anti-CCP antibody + IGM-RF .Conclusion The combined detection of anti-CCP antibody and IgA /IgM-RF can significantly improve the diagnostic efficiency and reduce the misdiagnosis rate .%目的:评估单独或联合检测抗角蛋白抗体(AKA)、抗环瓜氨酸肽(CCP)抗体、类风湿因子(RF)IgA和 IgM 对类风湿关节炎(RA)的诊断价值。方法分别检测195例 RA 患者和195例对照者血清中的 AKA 、抗-CCP 抗体、IgA-RF 和 IgM-RF ,AKA 采用间接免疫荧光的方法检测,抗-CCP 抗体、IgA-RF 和 IgM-RF 采用酶联免疫吸附试验检测,分析上述抗体在 RA 中的敏感性和特异性,比较抗-CCP 抗体联合 IgA-RF 或(和)IgM-RF 诊断RA 的敏感性、特异性、阳性预测值和阴性预测值。结果抗-CCP 抗体、IgA-RF 和 IgM-RF 3项联合检测特异性最高。抗-CCP 抗体+ IgA-RF 的阳性预测值(87.59%)要明显高于抗-CCP 抗体+ IgM-RF(78.49%)。结论抗-CCP抗体与 IgA/IgM-RF 联合检测可以显著提高 RA 的诊断效能,降低误诊率。

  15. Diagnostic value evaluation of serum anti-cyclic citrullinated peptide antibody by contrast detection for rheumatoid arthritis%对比检测血清中抗环瓜氨酸肽抗体对类风湿关节炎的诊断价值评估

    Institute of Scientific and Technical Information of China (English)

    邓毅; 吴雪峰; 雷鸣; 吴建华

    2015-01-01

    Objective To investigate the diagnostic value of serum anti-cyclic citrullinated peptide (anti-CCP) antibody detection for rheumatoid arthritis (RA). Methods There were 86 RA patients (RA group), 44 non-RA patients (non-RA group), and 32 health physical examination people (control group). The level of anti-CCP antibody was detected by enzyme linked immunosorbent assay, and rheumatoid factor (RF) was detected by immunity transmission turbidity. The detection results of every group were compared. Results The Anti-CCP antibody and RF levels of the RA group were significantly higher than those in the non-RA group and the control group (P<0.05). The sensitivity of anti-CCP of the RA group was 69.77%, which was obviously lower than 81.40%of RF (P<0.05). Anti-CCP had higher diagnostic specificity and positive predicted value for RA than RF (P<0.05). The sensitivity, specificity, and negative predicted value of anti-CCP combined with RF were all significantly increased. It had a statistically significant difference from single detection (P<0.05). Conclusion Serum anti-CCP antibody detection has high specificity for the diagnosis of RA, and its combination with RF in detection can improve the accuracy and sensitivity of diagnosis.%目的:探讨检测血清中抗环瓜氨酸肽(抗-CCP)抗体对类风湿关节炎(RA)的诊断价值。方法收集RA患者86例(RA组)、非RA患者44例(非RA组)和健康体检者32例(对照组),分别采用酶联免疫吸附法检测抗-CCP抗体水平,并以免疫透射比浊法检测类风湿因子(RF),比较各组的检测结果。结果 RA组的抗-CCP抗体及RF水平均显著高于非RA组与对照组(P<0.05);RA组的抗-CCP灵敏度为69.77%,显著低于RF的灵敏度81.40%(P<0.05);抗-CCP对RA的诊断特异度与阳性预测值显著高于RF(P<0.05);抗-CCP联合RF的灵敏度、特异度及阴性预测值均获得显著提高,与单项检测相比,差异具有统计学意义(P<0.05)。结论血清抗-CCP抗体

  16. Combined detection rheumatoid factor、anti-cyclic citrullinated peptide antibody and Anti-keratin Antibody in the diagnosis of rheumatoid arthritis%类风湿因子、抗环瓜氨酸肽抗体与抗角蛋白抗体联合测定对类风湿性关节炎诊断价值

    Institute of Scientific and Technical Information of China (English)

    陈建平; 杨曙梅; 杨春兰; 祝文彩

    2014-01-01

    Objective:In the study, we clarity the combined detection of rheumatoid factor(RF)、anti-cyclic citrullinated peptide antibody(Anti-CCP) and anti-keratin antibody(AKA) in the diagnosis of rheumatoid arthritis(RA).Methods:132 patients with RA, 51 patients with other arthritis. RF was measured by immune rate nephelometry. Anti-CCP was measured by chemiluminescence immunoassay. Indirect Immunofluorescence assay was used to detect AKA.Results:The diagnostic sensitivity of RF for RA was 78.0% and the specificity was 64.7%. Whereas the diagnostic sensitivity of Anti-CCP for RA was 75.0% and the specificity was 88.2%. The diagnostic sensitivity of AKA for RA was 75.8% and the specificity was 86.3%. The combined detection of RF、Anti-CCP and AKA had a sensitivity of 63.6%% and the specificity of 96.1%.Conclusions:The results suggest that for diagnosis RA, the sensitivity of RF is better than Anti-CCP and AKA, whereas the specificity of Anti-CCP and AKA is better than RF. Combination of RF、Anti-CCP and AKA may be more helpful in early cliagnosis of RA patients.%目的:本文旨在探讨联合测定类风湿因子(RF)、抗环瓜氨酸肽抗体(Anti-CCP)及抗角蛋白抗体(AKA)在诊断类风湿性关节炎(RA)中的应用价值。方法:分别运用免疫速率散射比浊法、化学发光法及间接免疫荧光法检测132例类RA患者及51例非RA患者血清中的RF、Anti-CCP及AKA。结果:RF对RA敏感性为78.0%,特异性为64.7%,阳性预测值85.1%;Anti-CCP对RA敏感性为75.0%,特异性为88.2%,阳性预测值94.2%;AKA对RA敏感性为75.8%,特异性为86.3%,阳性预测值93.5%;RF、Anti-CCP及AKA联合检测诊断RA的敏感性为63.6%,特异性为96.1%,阳性预测值97.7%。结论: RF在RA诊断中敏感性较Anti-CCP及AKA高,但特异性较Anti-CCP及AKA低;RF、Anti-CCP及AKA联合检测的应用,更有助于类风湿关节炎的早期诊断。

  17. Early diagnostic and predictive value of antikeratin antibody, anti-cyclic citrullinated peptide antibody, and rheumatoid factors in juvenile idiopathic arthritis%4种自身抗体在幼年特发性关节炎早期诊断和预后评估中的意义

    Institute of Scientific and Technical Information of China (English)

    曾萍; 李丰; 唐盈; 刘海英; 关启鸿; 刘云锋; 曾华松

    2011-01-01

    目的 探讨免疫学指标抗角蛋白抗体(AKA)、抗环瓜氨酸肽(抗CCP)、类风湿因子(RF)-IgG、RF-IgM与各分型幼年特发性关节炎(JIA)患儿早期诊断和预后之间的关系.方法 收集76名经系统治疗并坚持随访治疗至少6个月的JIA患儿,在诊断初期进行AKA、抗CCP、RF.IgG、RF-IgM等免疫指标的检测,对不同亚型和预后作阳性检出率的比较,进行敏感性、特异性、相关危险度的统计学分析,并与49例健康儿童作对照比较.结果 多关节炎型组的AKA、抗CCP、RF-IgG、RF-IgM的阳性检出率与正常对照组比较差异有统计学意义,全身型、少关节型、附着点炎相关型的自身抗体阳性检出率与正常对照组差异无统计学意义.4种抗体的检测对多关节炎型组的分型敏感件依次为AKA>抗CCP,RF-IgG>RF-1gM;特异性依次为RF-IgM>AKA>RF-IgG>抗CCP.难治型JIA患儿的AKA阳性检出率与普通JIA患儿差异有统计学意义;相对危险度OR为3.514.结论 AKA、抗CCP、RF-IgG、RF-IgM在JIA不同亚型早期诊断中的作用有区别;AKA、抗CCP抗体的检测对JIA多关节炎型有较好的敏感性和特异性;AKA抗体的出现与难治型JIA相关,是否能作为成为多关节炎型早期诊断和预后评估的血清学指标,有待大样本的研究证实.%Objective To investigate the value of antikeratin antibody ( AKA ), anti-cyclic citrullinated peptide antibody ( anti-CCP ) and rheumatoid factor ( RF-IgG, RF-IgM ) in early diagnosis and prediction of juvenile idiopathic arthritis (JlA). Methods Seventy-six palients with JlA were enrolled and follow-up at least 6 months. The blood samples were collected to measure AKA, anti-CCP, RF-IgG, RF-IgM upon admission. The fiequency of positive AKA, anti-CCP, RF-IgG and RF-IgM in different subtype and refiractoriness were compared. Forty-nine healthy children were enrolled as control group. Results Compared with control group, the positive rates of AKA, anti-CCP,RF-IgG and RF

  18. Detection of anti-cyclic citrullinated peptide antibody in patients with psoriatic arthritis disease and its significance%抗环瓜氨酸肽抗体在银屑病关节炎患者中的检测及意义

    Institute of Scientific and Technical Information of China (English)

    潘虹; 李明

    2013-01-01

    目的 研究抗环瓜氨酸肽(CCP)抗体在银屑病关节炎(PsA)患者中的临床意义,探讨抗CCP抗体与PsA患者伴发关节炎、骨侵蚀破坏的关系及判断预后的意义.方法 采用酶联免疫吸附法,分别检测56例PsA患者血清的抗CCP 抗体水平,分析比较抗CCP 抗体与患者临床特征的关系.结果 抗CCP抗体在PsA患者中的阳性率为12.5%(7/56).抗CCP抗体在PsA五种临床分型中的阳性率分别为7.1%、21.4%、0%、0%、0%,抗CCP抗体阳性率在对称性多关节炎型PsA中明显高于其他四种PsA(P<0.05).抗CCP抗体阳性与阴性PsA患者临床及其他实验室指标比较结果显示:抗CCP抗体阳性组外周关节肿胀数、腕关节受累比例及红细胞沉降率(ESR)均高于抗CCP阴性组(P<0.05);在发病年龄、关节炎病程、阳性家族史、肘关节受累、腊肠指(趾)、腰骶痛和C反应蛋白(CRP)之间比较,差异无统计学意义.结论 12.5%的PsA患者体内存在抗CCP抗体;抗CCP抗体的出现与PsA患者多发性关节炎和骨侵蚀密切相关,对判断PsA关节炎的预后具有重要的临床价值.%Objective To study the clinical significance of anti-cyclic citrullinated peptide antibody( anti-CCP )in patients with psoriatic arthritis( PsA ), and to explore the correlation between anti-CCP and the complicated arthritis and bone erosion and also the significance of anti-CCP in the judgment of prognosis. Methods Enzyme linked immunosorbent assay was used to detect the anti-CCP level in the serum of 56 patients with PsA. The correlation between anti-CCP and the clinical features of those patients was analyzed. Results The positive rate of anti-CCP in patients with PsA was 12. 5 %( 7/56 ). The positive rate of anti-CCP in the five clinical classification of PsA was 7. 1% ,21.4% ,0% ,0% ,0% , respectively. The positive rate of anti-CCP in symmetry polyarthritis PsA was significantly higher that those in the other four kinds of PsA( P <0. 05 ). The

  19. 血清抗环瓜氨酸肽抗体对幼年特发性关节炎和成人类风湿关节炎诊断意义的比较%Diagnostic Value of Anti-Cyclic Citrullinated Peptide Antibodies in Juvenile Idiopahtic Arthritis and Adult Rheumatoid Arthritis

    Institute of Scientific and Technical Information of China (English)

    许峥; 黄小兰; 吴凤岐; 崔小岱; 黄峰; 张江林

    2011-01-01

    目的 比较分析幼年特发性关节炎(JIA)和成人类风湿关节炎(RA)患儿血清抗环瓜氨酸肽(CCP)抗体水平,探讨抗CCP抗体在JIA诊断中的价值和意义.方法 2009年2- 12月首都儿科研究所风湿免疫科确诊的JIA患儿72例.男33例,女39例;年龄(7.58 ±3.93)岁,全身型29例,少关节型27例,多关节型16例.同期在中国人民解放军总医院风湿科确诊的RA患者共65例.男14例,女51例;年龄(47.38±14.28)岁.健康对照组22例,为同期健康查体儿童.男10例,女12例;年龄(14.10±0.38)岁.选用英国Axis- shield Diagnostics Limit公司、德国欧蒙公司和上海富莼科芯公司生产的CCP抗体ELISA检测试剂盒,分别检测JIA患儿、RA患者和健康儿童血清CCP抗体水平.结果 英国Axis- shield Diagnostics Limit公司检测JIA患儿血清抗CCP抗体的阳性率为12.5%(9/72例),RA患者血清阳性率高达73.85%(48/65例),健康对照组无阳性(0/22例).RA患者血清抗CCP抗体阳性率显著高于JIA患儿(P<0.01),其中JIA组中多关节型阳性率31.25%(5/16例),少关节型阳性率14.8% (4/23例),全身型阳性率为0(0/29例),差异有统计学意义(P<0.001).另2家公司试剂盒检测结果.HA患儿血清抗CCP抗体的阳性率为15.3%(11/72例),RA患者血清阳性率为73.85% (48/65例),健康儿童无阳性.RA患者血清和健康儿童血清结果3家公司检测试剂盒完全一致.JIA患儿3种抗CCP抗体试剂盒检测结果之间差异无统计学意义(P>0.05).结论 ELISA方法检测血清抗CCP抗体水平较为稳定可靠,抗CCP抗体在JIA患儿中血清阳性率低于成人RA,抗CCP抗体在JIA各亚型分布差异显著,抗CCP抗体与多关节型相关.%Objective To evaluate the value of anti - cyclic citrullinated peptide antibodies (CCP) in the diagnosis of juvenile idiopathic arthritis (JIA) by analyzing results of detection from both JIA and adult rheumatoid arthritis ( RA) patients. Methods Seventy - two samples with

  20. Application of Rheumatoid Factor and Anti Cyclic Citrullinated Peptide Combined Detection in the Early Diagnosis of Rheumatoid Arthritis%类风湿因子及抗环瓜氨酸肽联合检测在类风湿关节炎早期诊断中应用

    Institute of Scientific and Technical Information of China (English)

    曾频频

    2015-01-01

    目的:探讨类风湿关节炎早期诊断。方法采用整群抽样的方法,选取2013年1月~2015年1月到医院就诊的46例类风湿性关节炎疑似患者和52例确诊类风湿性关节炎1年以上, ELISA法检测血清类风湿因子(RF)、抗环瓜氨酸肽(CCP)水平。结果 RF联和抗CCP抗体诊断疑似类风湿性关节炎,1年以上的类风湿性关节炎的诊断阳性率分别为71.15%和82.61%,明显高于RF和抗CCP抗体单独测试(<0.05)。结论 RF联和抗CCP抗体对早期诊断类风湿性关节炎,效果优于RA和CCP的两中检测单用。%Objective To investigate the ef ect of RF and CCP in the early diagnosis of rheumatoid arthritis. Methods Using cluster sampling, selected in April 2009 to 2012 April to the hospital for treatment of rheumatoid arthritis suspected patients and 46 cases of diagnosed 1 year more than 52 cases that were, by ELISA detection of serum rheumatoid factor (RF) and anti cyclic citrul inated peptide (CCP) levels. Results RF and anti CCP for suspected rheumatoid arthritis and diagnosed for more than 1 year rheumatoid arthritis diagnosis positive rate was 71.15% and 82.61%, was significantly higher than that of RF and anti CCP testing alone ( <0.05). Conclusion In the early diagnosis of RF, the ef ect of RA and CCP was bet er than that of the two.

  1. 抗环瓜氨酸肽抗体和类风湿因子联合检测对类风湿关节炎的临床价值%Clinical value of combined detection of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rhenmatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    阮艳秋; 殷明刚; 刘伟平

    2016-01-01

    目的:探讨抗环瓜氨酸肽(CCP)抗体和类风湿因子(RF)联合检测对类风湿关节炎(RA )诊治的临床价值。方法收集2013年11月至2014年12月该院182例风湿性疾病患者血清,采用 ELISA 方法检测 CCP 抗体,使用免疫透射比浊终点法检测 RF 。结果(1)182例患者中 RA 99例,CCP 中位数是4.20,RF 是392,非类风湿疾病患者83例,CCP 中位数是2.30,RF 是20.1,健康对照者106例,CCP 中位数是1.23,RF 是12.3。健康对照者与非风湿性疾病患者比较,差异无统计学意义(P>0.05);与 RA 患者比较,差异有统计学意义(P <0.01)。(2) CCP 抗体诊断 RA 的特异度是90.5%,RF 是79.2%,CCP 抗体高于 RF ,差异有统计学意义(P <0.05);CCP 抗体和 RF 联合检测诊断 RA 的灵敏度是71.4%,特异度是96.2%,高于单项检测(P<0.01)。 CCP 抗体和 RF 的灵敏度比较,差异无统计学意义(P>0.05)。 CCP 抗体特异度高于 RF 。结论 CCP 抗体和 RF 联合检测有助于 RA 的诊断和疗效监测,具有较高的临床意义。%Objective To estimate the clinical value of combined detection of anti‐cyclic citrullinated peptide (anti‐ccp)antibody and rheumatoid factor(RF) for the rhenmatoid arthritis .Methods Having collected the serum of 182 patients with rheumatic diseases in our hospital from November 2013 to December 2014 .With ELISA method measuring CCP and use immunity transmission turbidity to measurement RF ,the results were compared and ana‐lyzed .Results (1)Among the serum of 182 cases of patients ,99 cases were with rheumatoid arthritis ,with median of CCP 4 .20 and RF 392 .83 cases were with non‐rheumatoid diseases ,that with median of CCP 2 .30 and RF 20 .1 .106 cases of healthy control were ,with median of CCP 1 .23 and RF 12 .3 .Compared with non‐rheumatoid diseases ,P>0 .05 and the difference was of no statistical

  2. 探讨抗环瓜氨酸肽抗体和类风湿因子对类风湿关节炎的诊断价值%Evaluate the value of anti -cyclic citrullinated peptide antibody and rheumatoid factor in the diagnosis of rheumatoid ar-thritis

    Institute of Scientific and Technical Information of China (English)

    莫巧璇; 张间霞; 张劲丰; 苏荣

    2013-01-01

    Objective Evaluate the diagnosis value of anti-cyclic citrullinated antibody (anti CCP antibody ) combined with rheumatoid factor (RF) for rheumatoid arthritis (RA) .Methods From May 2011 to September 2011 ,202 patients with rheumatic disease were selected ,including RA group ,and non-RA group .The quantitative chemiluminescence method to detect anti-CCP antibody ,immune turbidimetric assay to test RF ,and the results were analyzed statistically .Results The diagnostic test sensitivity of anti-CCP antibody ,specificity ,positive and the nega-tive predictive value were ,78% ,80 .6% ,82 .5% ,75 .8% ;RF :89 .9% ,52 .7% ,69% ,81 .7% .To analyze parallel and series test after anti-CCP antibody combined with RF detection ,The above indexes were ,parallel:93 .6% ,51 .6% , 69 .4% ,87 .3% ;series :74 .3% ,81 .7% ,82 .7% ,73 .1% ;The result of comparison in the RA group sensitivity :RF and anti-CCP antibody+RF series testing compared to individual CCP testing was significantly different (P<0 .05) , Beside ,Anti-CCP antibody+RF parallel testing and RF testing was significantly different (P<0 .05) .In the mean of anti-CCP antibody and RF positive results ,RA group and RA group was significantly difference .Conclusion Detec-tion of anti CCP antibody Combined with RF could provide clinical diagnosis for RA than individual testing .It could avoid leakage diagnosis caused by the low anti-CCP antibody sensitivity ,and misdiagnosis caused by RF low specifici-ty ,and provided the basis for clinical early diagnosis .%  目的探讨抗环瓜氨酸肽抗体(抗CCP抗体)、类风湿因子(RF)联合检测对类风湿关节炎(RA)的诊断价值。方法收集2011年5~9月RA和非RA患者202例,分别采用电化学发光法定量检测抗CCP抗体,免疫比浊法检测RF并进行统计学处理。结果抗CCP抗体诊断试验的灵敏度、特异性和阳性、阴性预测值分别为:78.0%、80.6%、82.5%、75.8%;RF为:89.9%、52.7

  3. 抗环瓜氨酸肽抗体在幼年特发性关节炎中的诊断意义%Significance of anti-cyclic citrullinated antibodies in Juvenile Idiopathic arthritis

    Institute of Scientific and Technical Information of China (English)

    刘小惠; 陈月; 刘建国; 蔡素芬; 邓宇虹

    2013-01-01

    Objective To investigate the anti-cyclic citrullinated peptide(anti-cyclic citrullinated petide) antibodies,anti-ker-atin antibodies(anti-keratin antibody,AKA) and anti-perinuclear factor antibody(antiperinuclear factor,APF) joint detection in the diagnosis of juvenile idiopathic arthritis in value. Methods 61 cases of children with JIA and 20 patients with other rheumatic diseases in children,40 cases of healthy children with three detection,and comparative analysis. Results Three testing positive indicators of children with JIA were significantly higher than normal,healthy children;the difference was statistically significant(P<0.01). In the group of children with JIA anti-CCP,AKA,APF a sensitivity of 55.73%,39.34%,26.23%,the sensitivity of anti-CCP was higher than antibodies AKA and APF;the difference was statistically significant (P<0.05). Conclusion Although the sensitivi-ty of anti-CCP antibodies in children with JIA is lower than the sensitivity of adults RA ,but the diagnosis of JIA has a higher sen-sitivity and specificity,especially for polyarticular and oligoarticular JIA diagnosis more valuable.%目的:探讨抗环瓜氨酸肽(anti-cyclic citrullinated petide)抗体、抗角蛋白抗体(anti-keratin antibody,AKA)和抗核周因子抗体(antiperinuclear factor,APF)联合检测在诊断幼年特发性关节炎中的价值。方法对61例JIA患儿与40例健康患儿进行3项检测,并进行比较分析。结果幼年特发性关节炎(juvenile idiopathic arthritis,JIA)患儿的3项检测指标阳性率均明显高于正常健康患儿,差异有统计学意义(P<0.01),在JIA组患儿中抗CCP、AKA、APF的敏感性分别为55.73%、39.34%、26.23%,抗CCP抗体的敏感性高于AKA和APF,差异有统计学意义(P<0.05)。结论抗CCP抗体在JIA患儿中的敏感性虽不及成人类风湿性关节炎(rheumatoid arthritis,RA),但对JIA的诊断仍具有较高的敏感性和特异性,特别是对多关

  4. Meta-Analysis: Diagnostic Accuracy of Anti-Cyclic Citrullinated Peptide Antibody for Juvenile Idiopathic Arthritis

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    Yan Wang

    2015-01-01

    Full Text Available Objective. To estimate the diagnostic accuracy of the anti-CCP test in JIA and to evaluate factors associated with higher accuracy. Methods. Two investigators performed an extensive search of the literature published between January 2000 and January 2014. The included articles were assessed by the Quality Assessment of Diagnostic Accuracy Studies tool. The meta-analysis was performed using a summary ROC (SROC curve and a bivariate random-effect model to estimate sensitivity and specificity across studies. Results. The bivariate meta-analysis yielded a pooled sensitivity and specificity of 10% (95% confidence interval (CI: 6.0%–15.0% and 99.0% (95% CI: 98.0%–100.0%. The area under the SROC curve was 0.96. Sensitivity estimates were highly heterogeneous, which was partially explained by the higher sensitivity in the rheumatoid factor-positive polyarthritis (RF+ PA subtype (48.0%; 95% CI: 31.0%–65.0% than in the other subtypes (17.0%; 95% CI: 14.0%–20.0% and the higher sensitivity of the Inova assay (17.0%; 95% CI: 14.0%–20.%% than the other assays (0.05%; 95% CI: 2.0%–11.0%. Conclusions. Anti-CCP antibody test has a high specificity for the diagnosis of JIA. The sensitivity of this test is low and varies across populations but is higher in RF+ PA than in other JIA subtypes.

  5. THE CLINICAL AND DIAGNOSTIC VALUE OF ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODIES IN EARLY JUVENILEARTHRITIS

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    S O Salugina

    2009-01-01

    Conclusion. In patients with early JA, the detection rate of CCPA is significantly higher than that in healthy children and comparable with that of RF. CCPAs have a high specificity for the diagnosis of JRA (an independent nosological entity within JA are a risk factor of polyarthritis. The early detection of CCPA alone or in combination with RF in JA patients may serve the basis for the early use of active, frequently aggressive therapy.

  6. Citrullinated peptides in the diagnosis of rheumatoid arthritis.

    Science.gov (United States)

    Gómara, María J; Haro, Isabel

    2013-01-01

    Antibodies directed against citrullinated proteins and peptides (ACPAs) are the most specific serological markers available for diagnosing rheumatoid arthritis (RA). ACPAs may be detected several years before symptoms of RA appear, and their presence at disease onset is a good predictor of the development of erosive joint lesions. RA patients can be classified into two major groups: those who have ACPAs and those who do not. The presence of ACPAs at early stages of RA predicts the development of earlier and more widespread joint erosions, and low remission rates.Synthetic peptides can replace cognate proteins in solid-phase assays for specific autoantibody recognition in RA patients. The use of synthetic peptides instead of proteins represents an advantage in terms of the reproducibility of such immunoassays. Proteins also contain non-citrullinated epitopes that are recognized by non-RA sera and this could reduce the specificity of the test. The use of synthetic citrullinated peptides gives absolute control over the exact epitopes presented. Furthermore, it is difficult to prepare sufficient amounts of high-quality antigenic proteins with a well-defined degree of citrullination. Synthetic citrullinated peptides, in contrast, are easily obtained in a pure form with a well-defined chemical structure and the epitopes can be precisely oriented in the plate by covalent binding of the peptides.Chimeric peptides bearing different citrullinated protein domains have recently been used in the design of RA diagnosis systems. The results of the application of those systems indicate that more than one serological test is required to classify RA patients based on the presence or absence of ACPAs. Each of the target molecules reported (fibrin, vimentin and filaggrin) helps to identify a particular subset of RA patients.

  7. Application of synthetic peptides for detection of anti-citrullinated peptide antibodies

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Holm, Bettina Eide; Slot, Ole;

    2016-01-01

    Anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA) and represent an important tool for the serological diagnosis of RA. In this study, we describe ACPA reactivity to overlapping citrullinated Epstein-Barr virus nuclear antigen-1 (EBNA-1)-derived peptides...

  8. Contribution of Peptide Backbone to Anti-Citrullinated Peptide Antibody Reactivity.

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    Nicole Hartwig Trier

    Full Text Available Rheumatoid arthritis (RA is one of the most common autoimmune diseases, affecting approximately 1-2% of the world population. One of the characteristic features of RA is the presence of autoantibodies. Especially the highly specific anti-citrullinated peptide antibodies (ACPAs, which have been found in up to 70% of RA patients' sera, have received much attention. Several citrullinated proteins are associated with RA, suggesting that ACPAs may react with different sequence patterns, separating them from traditional antibodies, whose reactivity usually is specific towards a single target. As ACPAs have been suggested to be involved in the development of RA, knowledge about these antibodies may be crucial. In this study, we examined the influence of peptide backbone for ACPA reactivity in immunoassays. The antibodies were found to be reactive with a central Cit-Gly motif being essential for ACPA reactivity and to be cross-reactive between the selected citrullinated peptides. The remaining amino acids within the citrullinated peptides were found to be of less importance for antibody reactivity. Moreover, these findings indicated that the Cit-Gly motif in combination with peptide backbone is essential for antibody reactivity. Based on these findings it was speculated that any amino acid sequence, which brings the peptide into a properly folded structure for antibody recognition is sufficient for antibody reactivity. These findings are in accordance with the current hypothesis that structural homology rather than sequence homology are favored between citrullinated epitopes. These findings are important in relation to clarifying the etiology of RA and to determine the nature of ACPAs, e.g., why some Cit-Gly-containing sequences are not targeted by ACPAs.

  9. Optimizing the identification of citrullinated peptides by mass spectrometry

    DEFF Research Database (Denmark)

    Bennike, Tue; Lauridsen, Kasper B.; Olesen, Michael Kruse

    2013-01-01

    using digested synovial fluid samples from a rheumatoid arthritis patient. The samples were analyzed using liquid chromatography/tandem MS with electrospray ionization. Our in vivo and in vitro studies clearly demonstrate the inability of trypsin to cleave after citrulline residues. Based on our......Citrullinated proteins have been associated with several diseases and citrullination can most likely function as a target for novel diagnostic agents and unravel disease etiologies. The correct identification of citrullinated proteins is therefore of most importance. Mass spectrometry (MS) driven...

  10. Contribution of peptide backbone to Anti-citrulline-dependent antibody reactivity

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Dam, Catharina; Olsen, Dorthe

    2015-01-01

    Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, affecting approximately 1–2% of the world population. One of the characteristic features of RA is the presence of autoantibodies. Especially the highly specific anti-citrullinated peptide antibodies (ACPAs), which have been...... homology rather than sequence homology are favored between citrullinated epitopes. These findings are important in relation to clarifying the etiology of RA and to determine the nature of ACPAs, e.g. why some Cit-Gly-containing sequences are not targeted by ACPAs....

  11. Mannose-binding lectin gene polymorphisms are associated with disease activity and physical disability in untreated, anti-cyclic citrullinated peptide-positive patients with early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Jacobsen, Søren; Garred, Peter; Madsen, Hans Ole;

    2009-01-01

    high producers (YA/YA). Anti-CCP was present in 93 patients (59%). High scores of disease activity, C-reactive protein-based DAS28 (p=0.02), and physical disability by HAQ (p=0.01) were associated with high MBL2 expression genotypes in a gene-dose dependent way, but only in anti-CCP-positive patients......OBJECTIVE: To study the association between polymorphisms in the mannose-binding lectin gene (MBL2) and disease activity, physical disability, and joint erosions in patients with newly diagnosed rheumatoid arthritis (RA). METHODS: Patients with early RA (n=158) not previously treated with disease...... activity by Disease Activity Score-28 (DAS28 score), physical disability by Health Assessment Questionnaire (HAQ) score, and erosive changes in hands and feet (Sharp-van der Heijde score). RESULTS: Eight patients were homozygous MBL2 defective (O/O), 101 belonged to an intermediate group, and 49 were MBL2...

  12. Environmental risk factors differ between rheumatoid arthritis with and without auto-antibodies against cyclic citrullinated peptides

    DEFF Research Database (Denmark)

    Pedersen, Line Merete Blak; Jacobsen, Søren; Klarlund, Mette;

    2006-01-01

    The aim of this study was to evaluate new and previously hypothesised non-genetic risk factors for serologic subtypes of rheumatoid arthritis (RA) defined by the presence or absence of auto-antibodies to cyclic citrullinated peptides (CCP). In a national case-control study, we included 515 patients...

  13. Accuracy and standardization of diagnostic methods for the detection of antibodies to citrullinated peptides

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    M. Tampoia

    2011-06-01

    Full Text Available Anti-citrullinated peptide antibodies (ACPA have a very high specificity for rheumatoid arthritis, much more than that of the rheumatoid factor. In addition, ACPA can be found in sera in the pre-clinical phase, are associated with more severe joint destruction and with higher disease activity. In recent years, keeping pace with new knowledge and with progress made in the antigenic composition of tests and in the characterization of immunogenic epitopes, many immunoenzymatic (ELISA methods of second and third generation have been produced and marketed commercially, and their use has spread among clinical laboratories. Today, completely automated methods are also available, which are easy to use and with a higher throughput, rendering the diagnostic utility of testing ever faster and more effective. This review takes into consideration the more important characteristics of the new ACPA-ELISA tests now commercially available, and also considers recent progress in standardizing test results.

  14. Anticorpos antipeptídeos citrulinados e fator reumatoide em pacientes sudaneses com infecção por Leishmania donovani Anti-citrullinated peptide antibodies and rheumatoid factor in Sudanese patients with Leishmania donovani infection

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    Erik Ahlin

    2011-12-01

    Full Text Available OBJETIVO: Este estudo avaliou a presença de anticorpos antipeptídeos citrulinados cíclicos (anti-CCP, fator reumatoide (FR e imunocomplexos circulantes (ICC em pacientes sudaneses infectados por Leishmania donovani. PACIENTES E MÉTODOS: Os soros foram coletados de pacientes infectados por Leishmania (n = 116 e de sudaneses saudáveis (n = 93. Dezenove pacientes sudaneses com artrite reumatoide (AR e anti-CCP+ foram incluídos como controles positivos. Os níveis de ICC e anti-CCP foram medidos por ELISA. Para avaliar a reatividade citrulina-específica foi usada a placa-controle com peptídeos-controle cíclicos contendo arginina em vez de citrulina. RESULTADOS: Entre os pacientes infectados por Leishmania e os pacientes com AR e anti-CCP+, a maioria (86% era positiva para FR, enquanto a frequência de positividade para ICC foi maior entre pacientes com leishmaniose visceral (LV (LV 38%; AR e anti-CCP+ 24%. Quando foi analisada a reatividade anti-CCP, 12% dos pacientes com LV foram positivos. Os níveis de anti-CCP entre os pacientes com LV correlacionaram-se bem com os níveis de ICC encontrados (r = 0,65; P OBJECTIVE: The present study evaluated the presence of anti-cyclic citrullinated peptides antibodies (anti-CCP, rheumatoid factor (RF, and circulating immune complexes (CIC in Sudanese patients infected with the Leishmania donovani parasite. PATIENTS AND METHODS: Sera were collected from Leishmania infected patients (n = 116 and healthy Sudanese (n = 93. Nineteen Sudanese anti-CCP+ RA patients were included as positive controls. Levels of CIC and anti-CCP were measured by ELISA. Control plate with cyclic control peptides containing arginine instead of citrulline was used to evaluate citrulline specifi c reactivity. RESULTS: Among Leishmania-infected patients and anti-CCP+ RA patients, most were RF positive (86%, while the frequency of CIC positivity was higher among visceral leishmaniasis (VL patients (VL 38%; anti-CCP+ RA 24%. When

  15. Genetic markers of rheumatoid arthritis susceptibility in anti-citrullinated peptide antibody negative patients

    Science.gov (United States)

    Viatte, Sebastien; Plant, Darren; Bowes, John; Lunt, Mark; Eyre, Stephen; Barton, Anne; Worthington, Jane

    2012-01-01

    Introduction There are now over 30 confirmed loci predisposing to rheumatoid arthritis (RA). Studies have been largely undertaken in patients with anticyclic citrullinated peptide (anti-CCP) positive RA, and some genetic associations appear stronger in this subgroup than in anti-CCP negative disease, although few studies have had adequate power to address the question. The authors therefore investigated confirmed RA susceptibility loci in a large cohort of anti-CCP negative RA subjects. Methods RA patients and controls, with serological and genetic data, were available from UK Caucasian patients (n=4068 anti-CCP positive, 2040 anti-CCP negative RA) and 13,009 healthy controls. HLA-DRB1 genotypes and 36 single nucleotide polymorphisms were tested for association between controls and anti-CCP positive or negative RA. Results The shared epitope (SE) showed a strong association with anti-CCP positive and negative RA, although the effect size was significantly lower in the latter (effect size ratio=3.18, p<1.0E-96). A non-intronic marker at TNFAIP3, GIN1/C5orf30, STAT4, ANKRD55/IL6ST, BLK and PTPN22 showed association with RA susceptibility, irrespective of the serological status, the latter three markers remaining significantly associated with anti-CCP negative RA, after correction for multiple testing. No significant association with anti-CCP negative RA was detected for other markers (eg, AFF3, CD28, intronic marker at TNFAIP3), though the study power for those markers was over 80%. Discussion In the largest sample size studied to date, the authors have shown that the strength of association, the effect size and the number of known RA susceptibility loci associated with disease is different in the two disease serotypes, confirming the hypothesis that they might be two genetically different subsets. PMID:22661644

  16. The clinical significance of antibody determination to cyclic citrullinated peptides in systemic sclerosis

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    Stamenković Bojana

    2012-01-01

    Full Text Available Introduction. Anti-citrullinated peptides antibodies (ACPA are present in 80% of sera of rheumatoid arthritis (RA patients with high specificity for diagnosis and prediction for the development of early erosive arthritis. A few studies have reported a low frequency ACPA in systemic sclerosis (SSc patients with the presence of arthritis. Objective. The aim of our study was to determine the frequency of ACPA in systemic sclerosis (SSc patients, their correlation with clinical manifestations and radiographic features. Methods. The study included 82 patients with SSc, mean age 54.4 years, 59 with the limited (lSSc and 23 with the diffuse (dSSc form of the disease. The control group included 28 healthy age and sex matched subjects. ACPA and rheumatoid factor (RF were determined in all SSc patients and healthy subjects in whom standard radiography of hands and wrists was also done. Results. The presence of ACPA was detected in 11 (13.4% of SSc patients. Their level was not increased in any of the controls. Positive RF was found in 15.9% of SSc patients. Arthritis was present in 17.1%, as well as marginal bone erosions. There was a statistically significant association between positive ACPA and arthritis (p<0.0001 and positive ACPA and marginal bone erosions (p=0.0002. Conclusion. The research confirmed the correlation between ACPA with clinical signs of arthritis and radiographic damage of hand joints. ACPA is a useful diagnostic marker in the identification of SSc patients with arthritis and anatomic bone damage enabling the use of adequate therapy in order to prevent joint damage and poor quality of life.

  17. Anti-citrullinated peptide antibodies in lupus patients with or without deforming arthropathy.

    Science.gov (United States)

    Damián-Abrego, G N; Cabiedes, J; Cabral, A R

    2008-04-01

    The objective was to study the association of antibodies against cyclic citrullinated peptides (anti-CCP) in patients with lupus articular damage. We studied 34 systemic lupus erythematosus patients (30 women) with (n = 14) or without (n = 20) deforming arthropathy. Anti-DNA and arthritis were mandatory inclusion criteria for both groups. As controls, 34 patients with rheumatoid arthritis and nine patients with rheumatoid arthritis and systemic lupus erythematosus (rhupus) were included. Anti-CCP and rheumatoid factor were determined by ELISA and nephelometry respectively. All patients had recent x-ray films of the hands that were evaluated according to Sharp's method. Systemic lupus erythematosus patients had a mean 6.50 +/- 0.86 (SD, range 5-8) American College of Rheumatology (ACR) criteria, rheumatoid arthritis patients met 5.38 +/- 0.60 (range 4-6) ACR criteria for rheumatoid arthritis and rhupus patients had 5.78 +/- 0.44 (range 5-6) criteria for rheumatoid arthritis and 5.11 +/- 0.78 (range 4-6) for systemic lupus erythematosus. Systemic lupus erythematosus patients, with or without deforming arthropathy, had normal serum anti-CCP concentrations. In contrast, rheumatoid arthritis and rhupus patients had 30- and 23-fold higher than normal amounts of anti-CCP (p lupus deforming arthropathy were more frequently positive for rheumatoid factor (65%) than patients with non-deforming arthritis (15%) (p = 0.005). Patients with lupus deforming arthropathy had similar frequency of erosions and mean Sharp's score than rhupus patients. Anti-CCP antibodies do not associate with lupus arthropathy, whether deforming, non-deforming or erosive.

  18. Comparison of Two Assays to Determine Anti-Citrullinated Peptide Antibodies in Rheumatoid Arthritis in relation to Other Chronic Inflammatory Rheumatic Diseases: Assaying Anti-Modified Citrullinated Vimentin Antibodies Adds Value to Second-Generation Anti-Citrullinated Cyclic Peptides Testing

    Science.gov (United States)

    Díaz-Toscano, Miriam Lizette; Olivas-Flores, Eva Maria; Zavaleta-Muñiz, Soraya Amali; Gamez-Nava, Jorge Ivan; Cardona-Muñoz, Ernesto German; Ponce-Guarneros, Manuel; Castro-Contreras, Uriel; Nava, Arnulfo; Salazar-Paramo, Mario; Celis, Alfredo; Fajardo-Robledo, Nicte Selene; Corona-Sanchez, Esther Guadalupe; Gonzalez-Lopez, Laura

    2014-01-01

    Determination of anti-citrullinated peptide antibodies (ACPA) plays a relevant role in the diagnosis of rheumatoid arthritis (RA). To date, it is still unclear if the use of several tests for these autoantibodies in the same patient offers additional value as compared to performing only one test. Therefore, we evaluated the performance of using two assays for ACPA: second-generation anti-citrullinated cyclic peptides antibodies (anti-CCP2) and anti-mutated citrullinated vimentin (anti-MCV) antibodies for the diagnosis of RA. We compared three groups: RA (n = 142), chronic inflammatory disease (CIRD, n = 86), and clinically healthy subjects (CHS, n = 56) to evaluate sensitivity, specificity, predictive values, and likelihood ratios (LR) of these two assays for the presence of RA. A lower frequency of positivity for anti-CCP2 was found in RA (66.2%) as compared with anti-MCV (81.0%). When comparing RA versus other CIRD, sensitivity increased when both assays were performed. This strategy of testing both assays had high specificity and LR+. We conclude that adding the assay of anti-MCV antibodies to the determination of anti-CCP2 increases the sensitivity for detecting seropositive RA. Therefore, we propose the use of both assays in the initial screening of RA in longitudinal studies, including early onset of undifferentiated arthritis. PMID:25025037

  19. Comparison of Two Assays to Determine Anti-Citrullinated Peptide Antibodies in Rheumatoid Arthritis in relation to Other Chronic Inflammatory Rheumatic Diseases: Assaying Anti-Modified Citrullinated Vimentin Antibodies Adds Value to Second-Generation Anti-Citrullinated Cyclic Peptides Testing

    Directory of Open Access Journals (Sweden)

    Miriam Lizette Díaz-Toscano

    2014-01-01

    Full Text Available Determination of anti-citrullinated peptide antibodies (ACPA plays a relevant role in the diagnosis of rheumatoid arthritis (RA. To date, it is still unclear if the use of several tests for these autoantibodies in the same patient offers additional value as compared to performing only one test. Therefore, we evaluated the performance of using two assays for ACPA: second-generation anti-citrullinated cyclic peptides antibodies (anti-CCP2 and anti-mutated citrullinated vimentin (anti-MCV antibodies for the diagnosis of RA. We compared three groups: RA (n=142, chronic inflammatory disease (CIRD, n=86, and clinically healthy subjects (CHS, n=56 to evaluate sensitivity, specificity, predictive values, and likelihood ratios (LR of these two assays for the presence of RA. A lower frequency of positivity for anti-CCP2 was found in RA (66.2% as compared with anti-MCV (81.0%. When comparing RA versus other CIRD, sensitivity increased when both assays were performed. This strategy of testing both assays had high specificity and LR+. We conclude that adding the assay of anti-MCV antibodies to the determination of anti-CCP2 increases the sensitivity for detecting seropositive RA. Therefore, we propose the use of both assays in the initial screening of RA in longitudinal studies, including early onset of undifferentiated arthritis.

  20. A combination of autoantibodies to cyclic citrullinated peptide (CCP) and HLA-DRB1 locus antigens is strongly associated with future onset of rheumatoid arthritis

    NARCIS (Netherlands)

    Berglin, E.; Padyukov, L.; Sundin, U.; Hallmans, G.; Stenlund, H.; Venrooij, W.J.W. van; Klareskog, L.; Dahlqvist, S.R.

    2004-01-01

    Antibodies against cyclic citrullinated peptide (CCP) and rheumatoid factors (RFs) have been demonstrated to predate the onset of rheumatoid arthritis ( RA) by years. A nested case control study was performed within the Northern Sweden Health and Disease study cohort to analyse the presence of share

  1. In ACPA-positive RA patients, antibodies to EBNA35-58Cit, a citrullinated peptide from the Epstein-Barr nuclear antigen-1, strongly cross-react with the peptide β60-74Cit which bears the immunodominant epitope of citrullinated fibrin.

    Science.gov (United States)

    Cornillet, M; Verrouil, E; Cantagrel, A; Serre, G; Nogueira, L

    2015-02-01

    Although several infectious agents and particularly Epstein-Barr virus (EBV) have been suspected to be involved in aetiology of rheumatoid arthritis (RA), their role still remains elusive. Almost 80% of RA sera contain antibodies to citrullinated proteins/peptides. Among them, the autoantibodies to citrullinated human fibrinogen (AhFibA) are composed of two non-cross-reactive subsets directed to immunodominant epitopes borne by the α36-50Cit and β60-74Cit fibrin peptides. RA sera also contain antibodies towards the citrullinated EBNA35-58Cit peptide derived from the EBNA-1 protein of EBV. Here, using a large cohort of RA patients and controls, we showed that for a diagnostic specificity of 98.5%, 47% of the AhFibA-positive patients were anti-EBNA35-58Cit-positive and that almost all (98.5%) the anti-EBNA35-58Cit-positive were AhFibA-positive, whereas 86% were anti-β60-74Cit-positive and only 43% anti-α36-50Cit-positive. AhFibA, anti-EBNA35-58Cit- and anti-β60-74Cit-antibody titres were significantly correlated. Competition assays showed that anti-EBNA35-58Cit antibodies are highly cross-reactive with the β60-74Cit peptide. The demonstration that a citrullinated peptide derived from the EBNA-1 protein of EBV presents a molecular mimicry with human citrullinated fibrin constitutes an additional argument for a possible role of EBV in RA aetiopathogeny.

  2. Positive association between serum thymic stromal lymphopoietin and anti-citrullinated peptide antibodies in patients with rheumatoid arthritis

    Science.gov (United States)

    Koyama, K; Ohba, T; Haro, H; Nakao, A

    2015-01-01

    Thymic stromal lymphopoietin (TSLP) has been suggested recently to play an important role in the pathophysiology of rheumatoid arthritis (RA). However, there is little information on serum TSLP concentrations in RA and its clinical significance. The present study investigated whether serum TSLP concentrations were affected in patients with RA. Using an enzyme-linked immunosorbent assay (ELISA), we measured TSLP concentrations in the serum obtained from 100 patients with RA, 60 patients with osteoarthritis (OA) and 34 healthy volunteers. We also investigated the correlation between serum TSLP concentrations and clinical parameters of disease activity in RA [disease activity score using 28 joint counts (DAS28)-C-reactive protein (CRP), DAS28-erythrocyte sedimentation rate (ESR), Clinical Disease Activity Index (CDAI]), patient’s/-physician’s Visual Analogue Scale (VAS), swollen joints count, tender joints count, CRP, ESR and matrix metalloproteinase-3 (MMP-3) concentrations]. In addition, we investigated the correlation between serum TSLP concentrations and anti-citrullinated peptide antibody (ACPA) and serum tumour necrosis factor (TNF)-α. Serum TSLP levels in patients with RA were significantly higher than those in patients with OA and in healthy volunteers. Interestingly, serum TSLP concentrations were correlated significantly with ACPA titres, but not with other clinical parameters. There was a significant increase in serum TSLP concentrations in patients with RA, which was correlated positively with serum ACPA titres. These findings suggest that in patients with RA, TSLP may play a role in ACPA production by B cells. PMID:25817699

  3. COMBINATION DETECTION OF SERUM ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODY AND RHEUMATOID FACTOR: ITS DIAGNOSTIC VALUE OF RHEUMATOID ARTHRITIS%抗CCP抗体与RF联合检测诊断类风湿关节炎的价值

    Institute of Scientific and Technical Information of China (English)

    陈华丽; 杨文东; 韩景银

    2007-01-01

    目的 探讨联合检测抗环瓜氨酸肽(CCP)抗体和类风湿因子(RF)诊断类风湿关节炎(RA)的价值,并了解抗CCP抗体与RF之间的相关性.方法 采用ELISA法和乳胶增强免疫比浊法,检测79例RA、52例非RA病人血清抗CCP抗体和RF.结果 79例RA病人中单一抗CCP抗体阳性12例,单一RF阳性20例,两项同时阳性40例,同时阴性7例,一致率为59.5%(47/79).52例非RA病人中单一抗CCP抗体阳性2例,单一RF阳性14例,无1例两项同时阳性.RA病人抗CCP抗体与RF阳性率显著高于非RA病人(χ2=49.713、30.666,P<0.01),RF阳性率高于抗CCP抗体,但差异无显著性(P>0.05);非RA病人RF阳性率显著高于抗CCP抗体(χ2=10.636,P<0.01).抗CCP抗体诊断RA的特异度和阳性预测值分别为96.2%、96.3%,灵敏度为65.8%.抗CCP抗体和RF联合检测诊断RA的灵敏度、阴性预测值及准确度分别为91.1%、83.7%、82.4%.抗CCP抗体与RF无相关性(P>0.05).结论 抗CCP抗体诊断RA具有满意的特异度及很高的阳性预测值,对RA有较高诊断价值.抗CCP抗体与RF联合检测更有助于RA的临床诊断.

  4. 抗CCP抗体与RF联合检测在RA诊断中的价值%Value of combined detection of serum anti-cyclic citrullinated peptide antibody and rheumatoid factor in diagnosis of rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    钱明; 袁君君; 郭兆旺; 舒晓春

    2010-01-01

    目的 探讨联合检测抗环瓜氨酸肽(CCP)抗体和类风湿因子(RF)在类风湿关节炎(RA)诊断中的价值.方法 抗-ccp采用化学发光(MEIA)法,RF采用散射速率比浊法检测,取70例RA、130例非RA患者血清检测抗-CCP和RF.结果 70例RA患者中抗-CCP阳性54例,RF阳性52例,两项同时阳性64例,同时阴性6例,故抗-CCP、RF及两者联合检测在RA患者中的阳性率分别为77.1%、74.3%和91.4%;130例非RA患者中抗-CCP阳性5例,RF阳性38例,无1例两项同时阳性,故抗-CCP、RF及抗-CCP和RF联合检测在非RA患者中的阳性率分别为3.85%、29.23%和0.经过统计学分析联合检测与单项检测比较,差异有统计学意义(P<0.01),且RA患者抗-CCP与RF阳性率显著高于非RA患者,差异有统计学意义(P<0.01).结论 抗-CCP和RE联合检测可明显提高RA的诊断率.

  5. Anti-CCP和RF联合检测在诊断RA中的意义%Significance of detecting anti-cyclic citrullinated peptide and rheumatoid factor in the diagnosis of rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    郭玉娟

    2012-01-01

    目的 分析比较抗环瓜氨酸肽抗体(Anti-CCP)和类风湿因子(RF)在类风湿关节炎(RA)中的灵敏度和特异性,探讨将两种指标联合检测在RA诊断中的价值.方法 利用酶联免疫吸附试验和乳胶增强免疫透射比浊法分别测定76例RA 患者,56例非RA 患者血清中的Anti-CCP和RF.结果 Anti-CCP和RF在RA组的阳性率明显高于非RA组.特异度和灵敏度RF分别为76.8%、78.9%,Anti-CCP分别为96.4%、60.5%,将两者联合检测则分别为86.6%、73.1%.结论 Anti-CCP在诊断RA中具有较高的特异性和灵敏度,可作为诊断RA的新的血清学指标.将Anti-CCP和RF联合检测有助于RA的临床诊断.%Objective To analyse the specificily and sensilivily of anli-cyclic cilrullinaled peplide (Anli-CCP) and rheumatoid factor (RF) in the diagnosis of rheumatoid arlhrilis (RA) to invesligale the value when the Iwo anlibodies were used togelher. Methods ELISA and Lalex enhanced immune lurbidimelric were used to deled serum levels of Anli-CCP and RF in 76 palienls wilh RA and 56 non- RA palienls. Results The positive rale of Anli-CCP and RF of palienls wilh RA was significantly higher lhan lhal of non-RA palienls. The diagnostic specificily of RF for RA was 76. 8% and the sensilivily was 78. 9% , whereas the diagnostic specificily of Anti-CCP for RA was 96. 4% and the sensitivity was 60. 5%. The diagnostic specificily of the Anli-CCP and RF was 86. 6% and the sensitivity was 73. 1%. Conclusion The Anti-CCP might have high specificity and sensitivity, which might be used as the new serum sign for the diagnosis of RA. Combined wilh the detection of Anti-CCP and RF , the sensitivity will be higher.

  6. Evidence of fibrinogen as a target of citrullination in IgM rheumatoid factor-positive polyarticular juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    Dehlendorf Amanda B

    2011-03-01

    Full Text Available Abstract Background Several studies have noted the significance of measuring anti-cyclic citrullinated peptide (CCP antibodies in juvenile idiopathic arthritis (JIA as an important indicator for destructive disease, as is the case in rheumatoid arthritis (RA. While the role of anti-CCP antibodies in RA and JIA has become better understood, the identity of the target proteins of this modification has remained elusive. In this study, we evaluated serum from patients with various subtypes of JIA to investigate the presence of anti-deiminated (citrullinated fibrinogen and anti-citrullinated α-enolase antibodies, and their association with RF and anti-CCP antibody isotypes. Methods Sera were obtained from 96 JIA patients, 19 systemic lupus erythematosus (SLE patients, and 10 healthy children. All sera were measured for antibodies against citrullinated and native fibrinogen and α-enolase by an enzyme linked immunosorbent assay (ELISA. In addition, all sera were assayed for anti-CCP antibody isotypes and rheumatoid factor (RF isotypes by ELISA. The relationship between anti-citrullinated fibrinogen and anti-α-enolase antibodies and disease activity and joint damage were also investigated. All results were correlated with clinical and laboratory parameters using Spearman's rho correlation coefficient. Multiple logistic regression analysis was utilized to identify which variables were associated with joint erosions and diagnosis of JIA. Results Thirty-one JIA patients (32% demonstrated reactivity to citrullinated fibrinogen and 9 (9% to citrullinated α-enolase. Reactivity to citrullinated fibrinogen and α-enolase was predominantly found in IgM RF-positive polyarthritis patients. Fourteen JIA patients reacted with native α-enolase and a higher percentage of SLE patients reacted with citrullinated α-enolase when compared to JIA patients. Anti-citrullinated fibrinogen antibodies correlated with the presence of IgG anti-CCP antibodies and IgA and Ig

  7. Uncoupling of collagen II metabolism in newly diagnosed, untreated rheumatoid arthritis is linked to inflammation and antibodies against cyclic citrullinated peptides

    DEFF Research Database (Denmark)

    Christensen, Anne Friesgaard; Hørslev-Petersen, Kim; Christgau, Stephan;

    2010-01-01

    Objective. To investigate the relationship between markers of collagen 11 synthesis and degradation with disease activity measures, autoantibodies, and radiographic outcomes in a 4-year protocol on patients with early rheumatoid arthritis (RA) who are naive to disease-modifying antirheumatic drugs....... Methods. One hundred sixty patients with newly diagnosed, untreated RA entered the Cyclosporine, Methotrexate, Steroid in RA (CIMESTRA) trial. Disease activity and radiograph status were measured at baseline and 4 years. The N-terminal propeptide of collagen IIA (PIIANP) and the crosslinked C......-telopeptide of collagen II (CTX-II) were quantified at baseline by ELISA. PIIANP was also assayed at 2 and 4 years. Anticyclic citrullinated peptide (anti-CCP) was recorded at baseline. An uncoupling index for cartilage collagen metabolism was calculated from PHANP and CTX-II measurements. Results. PIIANP was low...

  8. To evaluate the clinical diagnosic value of anti-cyclic citrul inated peptide(anti-CCP) antibody and rheumatoid factor(RF) in patients with rheumatoid arthritis(RA)%联合检测抗CCP抗体与RF对类风湿关节炎诊断的临床意义

    Institute of Scientific and Technical Information of China (English)

    赵海燕

    2014-01-01

    目的:探讨联合检测抗环瓜氨酸肽抗体(抗CCP抗体)及类风湿因子(RF)对类风湿性关节炎(RA)的临床诊断价值。方法:分别检测130例RA患者,98例非RA的风湿病患者及40例正常人血清的抗CCP抗体和RF。结果:抗CCP抗体和RF联合检测的特异性,阳性预测值,阳性似然比,阴性似然比与任何单一项检测比较均有显著差异(P<0.05)。结论:联合检测抗CCP抗体和RF可明显提高类风湿性关节炎的诊断率。%Objective: To evaluate the clinical diagnosic value of anti-cyclic citrul inated peptide(anti-CCP) antibody and rheumatoid factor(RF) in patients with rheumatoid arthritis(RA). Methods: Anti-CCP antibody was defected by quantitative ELISA and rheumatoid factor by BNP nephelometer in 130 cases of RA, 98 cases of non-RA rheumatic diseases and 40 cases of healthy individuals. Results: The diagnosis specificity, positive predictive value, positive/negative likelihood ratios of combinate determination of anti-CCP antibody and RF were significantly higher than either one. Conclusion: The measurements of anti-CCP antibody and rheumatoid factor wil remarkably improve the accuracy of diagnosis of RA.

  9. Hearing impairment in patients with rheumatoid arthritis: association with anti-citrullinated protein antibodies.

    Science.gov (United States)

    Lobo, Fabrício Silva; Dossi, Mario Orlando; Batista, Lígia; Shinzato, Márcia Midori

    2016-09-01

    It has been suggested that hearing impairment (HI) is one of the extra-articular features of rheumatoid arthritis (RA). Nevertheless, the prevalence and nature of HI in RA is still uncertain. The objectives were to study hearing function in patients with RA using audiometric tests and to examine whether HI correlates with autoantibodies. Hearing functions were investigated in 43 consecutive RA patients and 23 control subjects (less than 60 years old). Their sera were evaluated for the presence of rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), and anti-mutated citrullinated vimentin (anti-MCV) antibodies. HI was observed in 46.5 % of RA patients and in 30.4 % of control subjects, p = 0.32. HI was characterized as sensorineural in 80 and 85.7 % of RA patients and control subjects with HI, respectively, p = 1.00. RA patients had a worse hearing threshold for air conduction at 6 kHz in the right ear (p = 0.019) and had a decreased amplitude of otoacoustic emissions (OAEs) at 2 kHz bilaterally (p = 0.04) compared with control subjects. In the RA group, patients with and without HI were 80 and 34.78 % anti-CCP positive, respectively, p = 0.008. RA patients with and without HI were 85 and 43.48 % anti-MCV positive, respectively, p = 0.013. HI in RA patients was mainly sensorineural and was associated with anti-CCP and anti-MCV antibodies.

  10. Associations of rheumatoid factor and anti-citrullinated peptide antibody with disease progression and treatment outcomes in patients with rheumatoid arthritis.

    Science.gov (United States)

    Katchamart, Wanruchada; Koolvisoot, Ajchara; Aromdee, Emvalee; Chiowchanwesawakit, Praveena; Muengchan, Chayawee

    2015-10-01

    The objective of this study was to investigate the association of rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) status with disease progression and treatment outcomes in patients with rheumatoid arthritis (RA). A total of 276 adult patients who fulfilled the American College of Rheumatology 1987 classification criteria for RA were recruited from the Rheumatology clinic, Siriraj Hospital, from January 2011 to December 2012. Demographic, clinical, and laboratory data were collected at baseline and every 3 months up to 1 year of follow-up. RF and ACPA were measured at baseline. Radiography of the hands and feet was performed at baseline and 1 year. Patients with RF+/ACPA+ had significantly more severe disease activity and impaired functional status than those who had RF-/ACPA-. Although they received more aggressive treatment with methotrexate and combination of non-biologic, disease-modifying antirheumatic drug than other groups, fewer patients in this group achieved remission at 1 year of follow-up, especially when compared to RF-/ACPA- group (12 vs. 18 %). For radiographic erosion, patients with the presence of either RF or ACPA had a higher proportion of hand erosion than seronegative patients at baseline (77, 73, 83, and 32 %, p < 0.001 for RF+/ACPA+, RF+/ACPA-, RF-/ACPA+, and RF-/ACPA-, respectively). After 1 year of follow-up, patients who developed new erosion at the hands were more prevalent in RF+/ACPA+ (32 %) and RF+/ACPA- (33 %) groups. However, "newly developed" feet erosion was most common in RF+/ACPA- group (40 %) than in other groups. Patients with positive either RF or ACPA or both have more severe and aggressive disease that requires intensive treatment to improve outcomes.

  11. Use of anti-citrullinated peptide (Anti –CCP antibodies in distinguishing patients with systemic lupus erythematosus and rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Harry Isbagio

    2004-12-01

    Full Text Available Diagnosis of Rheumatoid arthritis (RA and systemic lupus erythematosus (SLE can be confused in their initial stages. The joints, especially the hands, are commonly affected in both disorders, many patients with SLE are initially misdiagnosed as having RA Given that the outcome for the two diseases is diverse, it would be helpful to have serological marker to distinguish between them at onset. Anti-citrullinated peptide antibodies (anti-CCP have recently been described as highly specific for RA. The objective of this study is to confirm the specificity of anti-CCP antibodies and to determine whether they might distinguish patients with RA from those with SLE. This study is a cross sectional study on a group of patients with RA (n=27, SLE with arthritis (n=20, other autoimmune diseases (non-rheumatic diseases, n = 8, and healthy adults (n=20. Anti-CCP was determined by a commercial Elisa test and Rheumatoid factor (RF was determined by the standard slide latex test. The sensitivity and specificity of anti-CCP for the diagnosis of RA was 63.0% and 97.9% respectively, comparing with RF for RA that was 40.7 % and 85.4 %. Only 1 healthy adult was anti-CCP+, no anti-CCP was detected from SLE and other autoimmune disease. The mean of titer anti CCP in normal healthy adult, other autoimmune diseases, SLE and RA was 1.35 Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 ± 2.04, 0.63 Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 ± 0.59, 0.75 Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 ± 0.59, and 38.17 Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 ± 44.22 RU/ml, respectively. There was a highly significant difference between the mean of titer anti CCP for RA with others diseases (p <0.001. We conclude that detection of anti-CCP is very useful for the diagnosis of RA and distinguishing RA from SLE. (Med J Indones 2004; 13: 227-31Keywords

  12. Cartilage oligomeric matrix protein associates differentially with erosions and synovitis and has a different temporal course in cyclic citrullinated peptide antibody (anti-CCP)-positive versus anti-CCP-negative early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Christensen, Anne F; Lindegaard, Hanne; Hørslev-Petersen, Kim;

    2011-01-01

    -suppressive effect. We aimed to compare circulating cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in untreated anti-CCP-positive and anti-CCP-negative RA, and to study the temporal pattern of COMP through 4 years of treatment, including the relationship to imaging and clinical findings......OBJECTIVE: Cyclic citrullinated peptide antibody (anti-CCP)-positive and anti-CCP-negative rheumatoid arthritis (RA) have been suggested as 2 distinctive disease subsets with respect to disease activity and prognosis. Previously, we proposed that anti-CCP antibodies might have a chondrocyte......-CCP, Health Assessment Questionnaire, visual analog scale scores for pain and global and physician assessment, and magnetic resonance imaging (MRI) of the nondominant hand were recorded at baseline. COMP in serum was measured by ELISA at inclusion and serially through 4 years. RESULTS: Median baseline COMP...

  13. The Comparision of Anti-cyclic Citrullinated Peptide Antibody and Rheumatoid Factor in Rheumatoid Arthritis Diagnosis%抗环瓜氨酸多肽抗体和类风湿因子在类风湿性关节炎诊断中的比较

    Institute of Scientific and Technical Information of China (English)

    周厚清; 许赤多; 张辉; 董敏

    2009-01-01

    目的:检测抗环瓜氨酸肽(CCP)抗体在类风湿性关节炎(RA)中的阳性率,探讨抗CCP抗体检测在RA中的意义.方法:用ELISA方法检测30例RA,35例其他风湿性疾病,20例非风湿性疾病中的抗CCP抗体的分布.用免疫比浊法测定类风湿因子(RF),比较抗CCP抗体与RF的相关性.结果:30例RA病人中,抗CCP抗体的阳性率为73.33%.抗CCP抗体对RA的敏感性和特异性分别为73.33%和94.54%.RF的阳性率为76.67%.RF抗体对RA的敏感性和特异性分别为76.67%和80.0%.抗CCP抗体与RF之间呈正相关性.结论:抗CCP抗体对RA具有良好的敏感性和特异性,可视为RA新的血清学诊断指标,能用于RA的诊断.同时联合检测抗CCP抗体和RF有助于提高RA检测的敏感性和特异性.

  14. Evaluation of Clinical Usefulness of Antikeratin Antibody, Antiperinuclear Factor and Anti-Cyclic Citrullinated Peptide Antibody in Juvenile Rheumatoid Arthritis%血清抗角蛋白抗体、抗核周因子和抗环瓜氨酸肽抗体在幼年类风湿关节炎应用中的评价

    Institute of Scientific and Technical Information of China (English)

    韩彤昕; 李彩凤; 何晓琥; 王江; 邝伟英; 周怡芳

    2007-01-01

    目的 评价抗角蛋白抗体(AKA)、抗核周因子(APF)和抗环瓜氨酸肽抗体(anti-CCP)在幼年类风湿关节炎(JRA)应用中的意义.方法 收集76例JRA及54例非JRA患儿,健康对照30例血清,测定其AKA、APF和抗CCP水平,对JRA诊断敏感性、特异性进行评价,并对JRA患儿中3种抗体阳性和阴性组的临床症状、体征及实验室检查指标进行比较,并作统计学分析.结果 AKA、APF和抗CCP及联合检测ROC曲线下面积略高于0.5, 但Pa>0.05.单一抗体检测灵敏度为30%~50%,联合检测灵敏度无增加.单一抗体检测的特异度为50%~80%,联合检测特异度增加至80%~85%.JRA组AKA(+)病例较多出现关节强直,心包积液,骨质稀疏,肺炎支原体抗体阳性率相对高,且ASO、ESR、CRP水平较高,Pa<0.05;APF(+)病例较多出现关节强直,骨质稀疏,肺炎支原体抗体阳性率相对高,而且ASO、ESR、CRP水平较高,有显著差异(P<0.05),抗CCP(+)病例与抗CCP(-)病例比较,在临床表现、实验室检查方面无显著差异.结论 AKA、APF、抗CCP抗体对JRA缺乏早期诊断意义及特异性,AKA、APF对判断疾病的活动性、病理损害程度和预后有临床意义.

  15. 类风湿因子、抗环瓜氨酸肽抗体和葡萄糖-6-磷酸酶联合检测在类风湿关节炎中的临床意义%Clinical value of rheumatoid factor combined with anti-cyclic citrullinated peptide antibodies and glucose-6-phosphatase in diagnosis of rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    胡玲

    2012-01-01

    目的 探讨及评价类风湿因子(RF)联合抗环瓜氨酸肽(CCP)抗体和G-6-磷酸酶(GPI)检测在自身类风湿性关节炎(RA)诊断中的意义.方法 选择我院2009~2010年收治的RA患者80例(A组),非RA自身免疫病患者60例(B组),健康体检者52例(C组),取空腹血制备血清,采用速率散射免疫比浊法检测RF,以酶联免疫固相吸附试验法(ELISA)检测抗CCP抗体,采用双抗体夹心酶联免疫固相吸附试验法检测血清GPI水平,并分析RF、抗CCP抗体和GPI在诊断RA中的价值.结果 RA患者中RF、抗CCP抗体、GPI的敏感性分别为63.75%,70.00%和83.75%,以GPI最高;三者特异性分别为66.25%、90.00%和91.25%;三项指标联合检测敏感性为96.25%,显著高于任意单项指标(P < 0.05),且阳性符合率为91.25%.结论 抗CCP抗体和GPI可作为RA诊断的实验室有效指标,临床中与RF联合应用可以起到增加敏感性,提高阳性符合率的互补作用.%Objective To explore and evaluate the clinical value of RF combined with CCP and GPI in diagnosis of rheumatoid arthritis. Methods 80 patients with rheumatoid arthritis, 60 patients with other autoimmune diseases and 52 normal people were selected and divided into A, B and C group, blood serums were prepared and RF, anti-CCP and GPI were detected by immunization rate nephelometry, enzyme-linked immunosorbent assay and double antibody sandwich enzyme-linked immunosorbent. Results The sensitivity of RF, anti-CCP and GPI in RA patients were 63.75%, 70.00% and 83.75% respectively, the GPI was higher than the other index, and the specificity of the three index were 66.25%, 90.00% and 91.25% respectively. The sensitivity in combination was 96.25%, which was higher than any single index (P < 0.05), and the positive coincidence rate was 91.25%. Conclusion Anti-CCP and GPI are effective indicators in diagnosis of RA, the two index combination with RF have the effects on improvement of the sensitivity and the positive coincidence rate.

  16. 抗环瓜氨酸肽抗体与类风湿因子IgM联合检测在类风湿关节炎早期诊断中的应用%Application of combined detection of anti-cyclic citrullinated peptide antibody and rheumatoid factor IgM-RF in rheumatoid arthritis early diagnosis

    Institute of Scientific and Technical Information of China (English)

    李光迪; 刘芳; 张长菊

    2007-01-01

    目的 探讨抗环瓜氨酸肽抗体(anti-CCP)、类风湿因子IgM(IgM-RF)联合检测在类风湿关节炎(RA)早期诊断中的价值.方法 用ELISA法对84例RA、96例非 RA和26例健康献血者中anti-CCP抗体及IgM-RF进行检测;分析anti-CCP抗体、IgM-RF及两者联合检测的敏感度、特异度、阳性似然比、阴性似然比.结果 RA患者anti-CCP抗体的含量约为15.73±3.35 RU/ml;IgM-RF约为79.93±33.83 RU/mL,均显著高于非RA组和健康对照组(P<0.01).anti-CCP抗体及IgM-RF对诊断RA的敏感度、特异度、阳性似然比、阴性似然比分别为: anti-CCP抗体(67.9%、94.8%、13.02、0.34),IgM-RF(71.4%、79.2%、3.43、0.36).anti-CCP抗体与IgM-RF联合检测敏感度和特异度分别为65.5%、96.9%,阳性似然比、阴性似然比分别为21.13、0.36.提示anti-CCP抗体的特异度、阳性似然比明显高于IgM-RF,IgM-RF较anti-CCP抗体有较高的敏感度,两者联合检测可提高诊断的特异度和阳性似然比,但不能提高敏感度.结论 anti-CCP抗体和IgM-RF联合检测可提高诊断的特异度和阳性似然比,对RA的早期诊断有较好的临床价值.

  17. Diagnostic value of anti-cyclic citrullinated peptide antibody, antikeratin antibody and rheumatoid factor in patients with rheumatoid arthritis%类风湿关节炎患者血清自身抗体对其诊断价值分析

    Institute of Scientific and Technical Information of China (English)

    尹海琴; 李宝全; 巩路

    2011-01-01

    目的:分析抗环瓜氨酸肽抗体(抗CCP抗体)、抗角质蛋白抗体(AKA)及各型类风湿因子(RF)联合检测对类风湿关节炎(RA)诊断与病情活动等方面的作用.方法:选取80例RA患者和75例非RA患者,进行相关实验室指标测定,并对结果进行统计学分析.结果:RF-IgG、RF-IgA、RF-lgM、AKA及抗CCP抗体对RA的敏感性为:RF-IgM>抗CCP抗体>RF-IgG>RF-IgA>AKA;特异性为:AKA>抗CCP抗体>RF-IgG>RF-IgA>RF-IgM;联合检测2种、3种、5种抗体对RA的敏感性和特异性分别是:RF-IgA+RF-lgM为51.3%/81.3%,RF-IgG+RF-IgA+RF-lgM为43.8%/89.3%,RF-IgA+RF-lgM+抗CCP抗体为45%/98.7%,RF-lgA+RF-lgM+AKA为22.5%/98.7%,RF-IgG+RF-IgA+RF-lgM+抗CCP抗体+AKA为18.8%/100%;抗CCP抗体阳性和阴性患者在RF滴度值、ESR和晨僵方面差异存在统计学意义(P<0.05).结论:抗CCP抗体在诊断RA中的价值优于AKA和RF;抗CCP抗体在一定程度上可能有助于早期诊断和活动性的监测;RF与抗CCP抗体、AKA联合检测可进一步提高对RA诊断的特异性.%Objective: To analyze the value of anti-CCP,anti-AKA and rheumatoid factor antibodies(RF-IgA, RF-IgG, RF-IgM) in diagnosis and prognosis in patients with rheumatoid arthritis (RA). Methods: 80 RA patients and 75 patients with other rheumatic diseases were investigated,the relationship between them was analysed with SPSS17.0 software. Results:The sensitivity of RF-IgG, RF-IgA, RFIgM, anti-AKA and anti-CCP was RF-IgM>anti-CCP>RF-IgG> RF-IgA>AKA;and the specificity was AKA>anti-CCP>RF-IgG>RF-IgA>RF-IgM ;The sensitivity and specificity of combined detection of RF-IgA and RF-IgM were 51.3% and 81.3%, that of combined detection of RF-IgG, RF-IgA and RF-IgM were 43.8% and 89.3%, that of combined detection of RF-IgA, RF-IgM and anti-CCP were 45% and 98.7%,that of combined detection of RF-IgA, RF-lgM and AKA were 22.5% and 98.7%,that of combined detection of RF-IgG,RF-IgA,RF-IgM,anti-CCP and AKA were 18.8% and 100%; There were statistically significant (P<0.05) in RF titer values, ESR and morning stiffness in anti-CCP antibody-positive and-negative patients. Conclusion:Anti-CCP antibodies in the diagnosis of RA is more valuable than the AKA and RF;Anti-CCP antibodies, in a certain extent, may contribute to judgments and disease activity monitoring;the specificity of diagnosis of RA can be enhanced by joint detection of RF,AKA and anti-CCP.

  18. Value of anti-cyclic peptide containing citrulline antibody for the early diagnosis of rheumatoid arthritis%类风湿关节炎早期诊断中抗环瓜氨酸肽抗体检测的意义

    Institute of Scientific and Technical Information of China (English)

    葛艳玲; 宋慧; 刘武征; 杨凯楠

    2015-01-01

    目的 探讨单独或联合检测抗环瓜氨酸肽抗体(anti-CCP)、类风湿因子(RF)对类风湿关节炎(RA)早期诊断的价值. 方法 选取2012-2014年门诊及住院患者1 961例,已确诊为RA患者共509例(RA组),非RA患者共1 028例(非RA组),初步诊断非RA,随诊确诊为RA患者424例(初诊非RA随诊为RA组),分别采用速率散射比浊法检测RF;电化学发光法检测anti-CCP.结果 RA组与非RA组比较,单独检测anti-CCP与联合检测anti-CCP/RF的敏感度比较差异无统计学意义(P>0.05),而特异度(88.6%比60.4%)比较差异有统计学意义(P0.05), but the specificity between two groups (88.6%vs. 60.4%) was significant difference ( P<0.05). There were significant differences in the sensitivity (81.7% vs. 74.3%) and specificity (88.6% vs. 66.0%) between by using anti-CCP antibody alone and RF alone.In firstly was not diagnosed RA but later was diagnosed RA group, there were significantly difference in sensitivity (98.3%vs. 82.1%) and specificity (91.6%vs. 81.5%) by using anti-CCP antibody alone and RF alone. Conclusion There is important clinical value by using anti-CCP antibody alone for the early diagnosis of RA.

  19. 抗环瓜氨酸肽抗体与类风湿因子联合检测在类风湿关节炎诊断中的意义%Diagnostic significance of combined detection of serum anti cyclic citrullinated-peptide antibody and rheumatoid factor in rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    范云燕; 余静

    2009-01-01

    目的 探讨联合检测抗环瓜氨酸肽(CCP)抗体和类风湿因子(RF)在类风湿关节炎(RA)诊断中的意义.方法 抗-CCP采用ELISA法,RF采用散射速率比浊法检测,检测59例RA、48例非RA患者血清抗抗-CCP和RF.结果 59例RA患者中单一抗-CCP阳性8例,单一RF阳性16例,两项同时阳性30例,同时阴性5例,故抗-CCP、RF及两者联合检测在RA患者中的阳性率分别为64.40% 、77.97%和91.53%;48例非RA患者中单一抗-CCP阳性2例,单一RF阳性14例,无1例两项同时阳性,故抗-CCP、RF及抗-CCP和RF联合检测在非RA患者中的阳性率分别为4.16% 、29.16%和0.经过统计学分析联合检测与单项检测比较差异有统计学意义(P<0.01),且RA患者抗-CCP与RF阳性率显著高于非RA患者,差异有统计学意义(χ2= 41.15、25.60,P<0.01 ).结论 抗-CCP和RF联合检测可明显提高RA的诊断率.

  20. Diagnostic Values of Combined Detection of Rheumatoid Factor, Anticyclic Citrullinated Peptide Antibody and Antikeratin Antibody in Rheumatoid Arthritis%类风湿因子、抗环瓜氨酸多肽抗体和抗角蛋白抗体联合检测在类风湿关节炎诊断中的价值

    Institute of Scientific and Technical Information of China (English)

    张新刚; 张晓莉; 蒋莉; 郭韵; 王晓非

    2012-01-01

    Objective To evaluate the diagnostic values of combined detection of rheumatoid factor (RF), antieyclic citrullinated peptide antibody and antikeratin antibody (AKA) in rheumatoid arthritis (RA). Methods Sera from 278 RA patients and 510 controls were ana-lyzed. RF,antieyclic citrullinated peptide antibody and AKA were detected using immune turbidimetry,ELISA and indirect immunofluores-cence,respectively. The distributions of these antibodies were compared to determine the diagnostic values of combined detection of RF,anti-eyelie citrullinated peptide antibody and AKA in RA patients. Results In the single antibody detection,RF had the highest sensitivity (79.86% ), antieyclic citrullinated peptide antibody had the highest specificity (94.51 %) and the highest positive predictive value (88.03% ), RF( 87.16%) or antieyclic citrullinated peptide antil>ody (87%) had the highest negative predictive value, antieyclic citrullinated peptide an-tibody had the highest PLR( 13.5) ,RF(0.27) or antieyelie citrullinated peptide antibody(0.27) had the lowest NLR. In the combined de-tection, RF and antieyclic citrullinated peptide antibody showed the highest sensitivity (67.63%),and highest specificity (96.27%) was ob-served with antieyclic citrullinated peptide antibody and AKA;RF and AKA had the highest positive predictive value( 89.55%) ,RF and an-tieyclic citrullinated peptide antibody had the highest negative predictive value (84.32% ),RF and AKA had the highest PLR( 15.72),RF and antieyclic citrullinated peptide antibody had the lowest NLR (0.34). Conclusion The combined detection between the three antibodies obviously improved the earlier diagnosis of RA. The diagnostic value of antieyclic citrullinated peptide antibody was superior to AKA and RF. The combined detection of RF and antieyclic citrullinated peptide antibody had the most significant diagnostic value.%目的 评估类风湿因子(RF)、抗环瓜氨酸多肽(CCP)抗体和抗角蛋白抗体(AKA)联合检测在类

  1. IgG reactivity against citrullinated myelin basic protein in multiple sclerosis.

    Science.gov (United States)

    de Seze, J; Dubucquoi, S; Lefranc, D; Virecoulon, F; Nuez, I; Dutoit, V; Vermersch, P; Prin, L

    2001-07-02

    An increased level of citrullinated myelin basic protein (MBP-C8) has been reported in the brains of multiple sclerosis (MS) patients. However, the involvement of the immune response to post-translational modified MBP in the pathophysiology of MS remains speculative. The aim of this study was to compare the levels of immunoglobulin G antibodies to several MBP epitopes, before and after citrullination, in the cerebrospinal fluid (CSF) and sera of MS patients using enzyme-linked immunosorbent assay (ELISA). We analyzed antibody reactivity against various MBP-peptides in the CSF and sera of 60 MS patients, and 30 patients with other neurological diseases (OND) as controls. The peptides tested were: MBP(75-98) (peptide 1), native (peptide 2) and citrullinated (peptide 3) MBP(108-126) (ARG(122)-->Cit(122)), and native (peptide 4) and citrullinated (peptide 5) MBP(151-170) (ARG(159, 170)-->Cit(159, 170)). All selected peptides could support an immune reactivity in CSF and sera of MS and OND patients. A higher reactivity against peptide 4 was found in the CSF of MS patients compared with OND patients (P<0.0001), but not against citrullinated peptides (peptides 3 and 5). However, we observed that the citrullination state of peptide 2 modified the patterns of immune reactivity more markedly in MS patients (P<0.0001) than in OND patients (P<0.02). Although some MBP epitopes could be a potential target in MS, our data did not demonstrate any difference of antibody response to MBP peptides in their citrullinated forms.

  2. How citrullination invaded rheumatoid arthritis research

    OpenAIRE

    van Venrooij, W J; Pruijn, G.J.M.

    2014-01-01

    Citrullination and the immune response to citrullinated proteins have been fundamental for the early recognition of rheumatoid arthritis by serological tests and a better understanding of its pathophysiology. In the first years after the initial publications, the focus was on the antibodies directed to citrullinated proteins. It is now realized that citrullinating enzymes and citrullinated proteins may have important roles in the maintenance of the inflammatory processes in the joints. There ...

  3. Interrelationships between glutamine and citrulline metabolism

    Science.gov (United States)

    This article analyzes the contribution of glutamine to the synthesis of citrulline and reviews the evidence that glutamine supplementation increases citrulline production. Glutamine supplementation has been proposed in the treatment of critically ill patients; however, a recent large multicenter ran...

  4. Physical Characteristics of a Citrullinated Pro-Filaggrin Epitope Recognized by Anti-Citrullinated Protein Antibodies in Rheumatoid Arthritis Sera

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Holm, Bettina Eide; Slot, Ole;

    2016-01-01

    whether biotin labelling influence antibody recognition. The full-length cyclic pro-filaggrin peptide and a linear form with a N-terminal biotin, was recognized to the same level, whereas, a notable difference in ACPA reactivity to the linear peptides with a C-terminal biotin was found, probably due...... amino acid in position 4 C-terminal to citrulline. Collectively, peptide structure, length, the presence of charged amino acids and biotin labelling markedly influence antibody reactivity. In relation to the clinical diagnostics of ACPA, these findings may reflect the differences in diagnostic assays...

  5. Citrullinated Chemokines in Rheumatoid Arthritis

    Science.gov (United States)

    2014-10-01

    Clavel C, Arnaud J, Nogueira L, et al. Epitopes of human fibrin recognized by the rheumatoid arthritis-specific autoantibodies to citrullinated... Clavel C, Chapuy-Regaud S, Al Badine R, Mechin MC, et al. Peptidyl arginine deiminase type 2 (PAD-2) and PAD-4 but not PAD-1, PAD-3, and PAD-6 are

  6. Diagnostic significance of combined testing of anti-cyclic citrullinated peptide antibody and hidden rheumatoid factor immunoglobulin M in patients with juvenile rheumatoid arthritis%抗环瓜氨酸肽抗体和隐匿性类风湿因子免疫球蛋白M型在诊断早期幼年类风湿关节炎中的意义

    Institute of Scientific and Technical Information of China (English)

    滕庆; 刘永革; 何晓琥

    2004-01-01

    目的检测抗环瓜氨酸肽(CCP)抗体及隐匿性类风湿因子IgM型(HRF-IgM),并探讨其在幼年类风湿关节炎(JRA)早期诊断中的临床意义.方法用人工合成CCP链为抗原检测抗CCP抗体;对27例早期诊断的JRA做动态检测,通过阳性预测值(PPV)和阴性预测值(NPV)确定抗CCP抗体和HRF-IgM对早期诊断的JRA的特异性和敏感性.结果抗CCP抗体和HRF-IgM总阳性率分别为58.5%、65.0%.后者敏感性要高于前者,病情越重或受累的关节越多,抗体检出率越高.对早期JRA的PPV、抗CCP抗体特异性要高于HRF-IgM.当两种实验联合应用时,对具有早期关节炎表现发展成JRA的PPV为93.7%.结论抗C℃P抗体和HRF-IgM在JRA患儿均有较高的检出率,并与疾病严重程度有关.抗CCP抗体与HRF-IgM联合应用时,可使JRA的PPV进一步提高.

  7. Post-translational modifications in rheumatoid arthritis and atherosclerosis: Focus on citrullination and carbamylation.

    Science.gov (United States)

    Spinelli, Francesca Romana; Pecani, Arbi; Conti, Fabrizio; Mancini, Riccardo; Alessandri, Cristiano; Valesini, Guido

    2016-09-01

    Coronary heart disease is the main cause of mortality in patients with rheumatoid arthritis (RA), a disease known to be associated with accelerated atherosclerosis. The role of inflammation and immunity in atherosclerotic process offers possible explanations for the increased cardiovascular risk in patients with RA. The immune response to citrullinated peptides has been extensively studied in RA; antibodies directed to citrullinated peptides are now a cornerstone for RA diagnosis. However, few studies have investigated the response to citrullinated peptides and the development of atherosclerotic plaque. Antibodies to carbamylated proteins can be detected before the clinical onset of RA, suggesting a potential predictive role for these antibodies; on the other hand, carbamylation of lipoproteins has been described in patients with cardiovascular disease. This review examines the role of citrullination and carbamylation, two post-translational protein modifications that appear to be involved in the pathogenesis of both RA and atherosclerosis, expanding the similarities between these two diseases. Further investigation on the role of the immune response to modified proteins may contribute to a better comprehension of cardiovascular disease in patients with RA.

  8. Presence of antibodies to cyclic citrullinated peptides in juvenile-onset systemic lupus erythematosus%儿童系统性红斑狼疮抗环瓜氨酸肽抗体检测及其临床意义

    Institute of Scientific and Technical Information of China (English)

    刘海英; 刘云锋; 关启鸿; 钟艳玲; 皮蕾; 张白杜; 郭彩娇; 曾华松

    2010-01-01

    Objective To determine the prevalence of antibodies to cyclic citrullinated peptides (antiCCP) in patients with juvenile-onset systemic lupus erythematosus (JSLE) and its potential clinical significance. Methods Anti-CCP was measured in sera from patients with JSLE (n=47), juvenile idiopathic arthritis (JIA, n=54) and the sera from age-matched healthy children (n=40) using the third generation of anti-CCP ELISA commercial kit. The association of anti-CCP with other laboratory parameters and clinical features, especially arthritic symptoms in JSLE was also analyzed. T-test, Mann-Whitney U test, Chi-square and Fisher's exact test were used for statistical analysis. Results Out of the 47 JSLE patients, 6 (13%) were anti-CCP positive, which was significantly higher than that of the healthy controls( 13% vs 0, P<0.05 ), but not different from that of the JIA group (26%, P=0.098). RF was more prevalent in JSLE patients with anti-CCP than patients without (83% vs 15%, P<0.01 ), but there was no difference in other laboratory parameters and the clinical features ineluding the occurrence of arthritis (67% vs 51%, P>0.05). As one of the initial symptoms, arthritis was observed in 25 of 47 JSLE patients and no one had developed deforming arthropathy.There was no statistical difference in anti-CCP positivity between JSLE patients with and without articular involvement ( 16% vs 9%, P>0.05 ). Anti-CCP was not detected in any of the 3 patients with JSLE who had experienced joint pain and limited activity during 3 years follow-up. Conclusion Anti-CCP could be detected in patients with JSLE. It is noteworthy when differentiate from juvenile idiopathic arthritis, but the presence of anti-CCP does not relate with the occurrence of arthritis at presentation and persistence of arthritis in JSLE.%目的 检测儿童系统性红斑狼疮(JSLE)患者血清抗环瓜氨酸肽(CCP)抗体水平,了解抗CCP抗体在该病中的阳性检出率以及探讨其与

  9. Phenylglyoxal-Based Visualization of Citrullinated Proteins on Western Blots

    Directory of Open Access Journals (Sweden)

    Sanne M. M. Hensen

    2015-04-01

    Full Text Available Citrullination is the conversion of peptidylarginine to peptidylcitrulline, which is catalyzed by peptidylarginine deiminases. This conversion is involved in different physiological processes and is associated with several diseases, including cancer and rheumatoid arthritis. A common method to detect citrullinated proteins relies on anti-modified citrulline antibodies directed to a specific chemical modification of the citrulline side chain. Here, we describe a versatile, antibody-independent method for the detection of citrullinated proteins on a membrane, based on the selective reaction of phenylglyoxal with the ureido group of citrulline under highly acidic conditions. The method makes use of 4-azidophenylglyoxal, which, after reaction with citrullinated proteins, can be visualized with alkyne-conjugated probes. The sensitivity of this procedure, using an alkyne-biotin probe, appeared to be comparable to the antibody-based detection method and independent of the sequence surrounding the citrulline.

  10. Intestinal and hepatic metabolism of glutamine and citrulline in humans.

    Science.gov (United States)

    van de Poll, Marcel C G; Ligthart-Melis, Gerdien C; Boelens, Petra G; Deutz, Nicolaas E P; van Leeuwen, Paul A M; Dejong, Cornelis H C

    2007-06-01

    Glutamine plays an important role in nitrogen homeostasis and intestinal substrate supply. It has been suggested that glutamine is a precursor for arginine through an intestinal-renal pathway involving inter-organ transport of citrulline. The importance of intestinal glutamine metabolism for endogenous arginine synthesis in humans, however, has remained unaddressed. The aim of this study was to investigate the intestinal conversion of glutamine to citrulline and the effect of the liver on splanchnic citrulline metabolism in humans. Eight patients undergoing upper gastrointestinal surgery received a primed continuous intravenous infusion of [2-(15)N]glutamine and [ureido-(13)C-(2)H(2)]citrulline. Arterial, portal venous and hepatic venous blood were sampled and portal and hepatic blood flows were measured. Organ specific amino acid uptake (disposal), production and net balance, as well as whole body rates of plasma appearance were calculated according to established methods. The intestines consumed glutamine at a rate that was dependent on glutamine supply. Approximately 13% of glutamine taken up by the intestines was converted to citrulline. Quantitatively glutamine was the only important precursor for intestinal citrulline release. Both glutamine and citrulline were consumed and produced by the liver, but net hepatic flux of both amino acids was not significantly different from zero. Plasma glutamine was the precursor of 80% of plasma citrulline and plasma citrulline in turn was the precursor of 10% of plasma arginine. In conclusion, glutamine is an important precursor for the synthesis of arginine after intestinal conversion to citrulline in humans.

  11. Serum Levels of Anticyclic Citrullinated Peptide Antibodies, Interleukin-6, Tumor Necrosis Factor-α, and C-Reactive Protein Are Associated with Increased Carotid Intima-Media Thickness: A Cross-Sectional Analysis of a Cohort of Rheumatoid Arthritis Patients without Cardiovascular Risk Factors

    Directory of Open Access Journals (Sweden)

    Mónica Vázquez-Del Mercado

    2015-01-01

    Full Text Available The main cause of death in rheumatoid arthritis (RA is cardiovascular events. We evaluated the relationship of anticyclic citrullinated peptide (anti-CCP antibody levels with increased carotid intima-media thickness (cIMT in RA patients. Methods. Forty-five anti-CCP positive and 37 anti-CCP negative RA patients, and 62 healthy controls (HC were studied. All groups were assessed for atherogenic index of plasma (AIP and cIMT. Anti-CCP, C-reactive protein (CRP, and levels of tumor necrosis factor alpha (TNFα and interleukin-6 (IL-6 were measured by enzyme-linked immunosorbent assay (ELISA. Results. The anti-CCP positive RA patients showed increased cIMT compared to HC and anti-CCP negative (P<0.001. Anti-CCP positive versus anti-CCP negative RA patients, had increased AIP, TNFα and IL-6 (P<0.01, and lower levels of high density lipoprotein cholesterol (HDL-c (P=0.02. The cIMT correlated with levels of anti-CCP (r=0.513, P=0.001, CRP (r=0.799, P<0.001, TNFα (r=0.642, P=0.001, and IL-6 (r=0.751, P<0.001. In multiple regression analysis, cIMT was associated with CRP (P<0.001 and anti-CCP levels (P=0.03. Conclusions. Levels of anti-CCP and CRP are associated with increased cIMT and cardiovascular risk supporting a clinical role of the measurement of cIMT in RA in predicting and preventing cardiovascular events.

  12. Serum Levels of Anticyclic Citrullinated Peptide Antibodies, Interleukin-6, Tumor Necrosis Factor-α, and C-Reactive Protein Are Associated with Increased Carotid Intima-Media Thickness: A Cross-Sectional Analysis of a Cohort of Rheumatoid Arthritis Patients without Cardiovascular Risk Factors

    Science.gov (United States)

    Vázquez-Del Mercado, Mónica; Nuñez-Atahualpa, Lourdes; Figueroa-Sánchez, Mauricio; Gómez-Bañuelos, Eduardo; Rocha-Muñoz, Alberto Daniel; Martín-Márquez, Beatriz Teresita; Martínez-García, Erika Aurora; Macias-Reyes, Héctor; Gamez-Nava, Jorge Ivan; Navarro-Hernandez, Rosa Elena; Nuñez-Atahualpa, María Alejandra; Andrade-Garduño, Javier

    2015-01-01

    The main cause of death in rheumatoid arthritis (RA) is cardiovascular events. We evaluated the relationship of anticyclic citrullinated peptide (anti-CCP) antibody levels with increased carotid intima-media thickness (cIMT) in RA patients. Methods. Forty-five anti-CCP positive and 37 anti-CCP negative RA patients, and 62 healthy controls (HC) were studied. All groups were assessed for atherogenic index of plasma (AIP) and cIMT. Anti-CCP, C-reactive protein (CRP), and levels of tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Results. The anti-CCP positive RA patients showed increased cIMT compared to HC and anti-CCP negative (P < 0.001). Anti-CCP positive versus anti-CCP negative RA patients, had increased AIP, TNFα and IL-6 (P < 0.01), and lower levels of high density lipoprotein cholesterol (HDL-c) (P = 0.02). The cIMT correlated with levels of anti-CCP (r = 0.513, P = 0.001), CRP (r = 0.799, P < 0.001), TNFα (r = 0.642, P = 0.001), and IL-6 (r = 0.751, P < 0.001). In multiple regression analysis, cIMT was associated with CRP (P < 0.001) and anti-CCP levels (P = 0.03). Conclusions. Levels of anti-CCP and CRP are associated with increased cIMT and cardiovascular risk supporting a clinical role of the measurement of cIMT in RA in predicting and preventing cardiovascular events. PMID:25821796

  13. Citrullination and Carbamylation in the Pathophysiology of Rheumatoid Arthritis

    OpenAIRE

    Pruijn, Ger J. M.

    2015-01-01

    The discovery that citrullination was crucial for the recognition of antigens by the most disease-specific class of autoantibodies in rheumatoid arthritis had a huge impact on studies aimed at understanding autoimmunity in this disease. In addition to the detailed characterization of anti-citrullinated protein antibodies, various studies have addressed the identity of citrullinated antigens. These investigations were facilitated by new methods to characterize these proteins, the analysis of p...

  14. Glutamine: precursor or nitrogen donor for citrulline synthesis?

    Science.gov (United States)

    Marini, Juan C; Didelija, Inka Cajo; Castillo, Leticia; Lee, Brendan

    2010-07-01

    Although glutamine is considered the main precursor for citrulline synthesis, the current literature does not differentiate between the contribution of glutamine carbon skeleton vs. nonspecific nitrogen (i.e., ammonia) and carbon derived from glutamine oxidation. To elucidate the role of glutamine and nonspecific nitrogen in the synthesis of citrulline, l-[2-(15)N]- and l-[5-(15)N]glutamine and (15)N-ammonium acetate were infused intragastrically in mice. The amino group of glutamine labeled the three nitrogen groups of citrulline almost equally. The amido group and ammonium acetate labeled the ureido and amino groups of citrulline, but not the delta-nitrogen. D(5)-glutamine also infused in this arm of the study, which traces the carbon skeleton of glutamine, was utilized poorly, accounting for only 0.2-0.4% of the circulating citrulline. Dietary glutamine nitrogen (both N groups) incorporation was 25-fold higher than the incorporation of its carbon skeleton into citrulline. To investigate the relative contributions of the carbon skeleton and nonspecific carbon of glutamine, arginine, and proline to citrulline synthesis, U-(13)C(n) tracers of these amino acids were infused intragastrically. Dietary arginine was the main precursor for citrulline synthesis, accounting for approximately 40% of the circulating citrulline. Proline contribution was minor (3.4%), and glutamine was negligible (0.4%). However, the glutamine tracer resulted in a higher enrichment in the ureido group, indicating incorporation of nonspecific carbon from glutamine oxidation into carbamylphosphate used for citrulline synthesis. In conclusion, dietary glutamine is a poor carbon skeleton precursor for the synthesis of citrulline, although it contributes both nonspecific nitrogen and carbon to citrulline synthesis.

  15. N-Carbamoylputrescine, a citrulline-derived polyamine, is not a significant citrulline metabolite in rats.

    Science.gov (United States)

    Ramani, D; Nakib, S; Chen, H; Garbay, C; Loukaci, A; Cynober, L; De Bandt, J P

    2012-04-01

    Citrulline, a key amino acid of the urea cycle, has been shown to play a regulatory role in protein and energy metabolism in mammals. We questioned whether N-carbamoyl-putrescine (NCP), the decarboxylated derivative of citrulline, could play a role in the biological properties of this amino acid. To evidence the presence of NCP in mammalian tissues, we developed a sensitive reverse-phase high-performance liquid chromatography (HPLC) with fluorimetric detection method with precolumn dansyl derivatization and solid-phase extraction for the determination of NCP together with polyamines in biological samples. Dansyl NCP was identified with a 5.85-min retention time. Linearity was obtained in a concentration range of 0.125 to 12.5 μM. Intraday and day-to-day relative coefficients of variation ranged from 8.9% to 12.3% and from 14% to 14.3%, respectively. Recovery rates in serum ranged from 75% to 83%. Thereafter, we used this method to search for the presence of NCP in serum, muscle, liver, jejunum, and ileum in rats after both short-term intraperitoneal injection and long-term oral citrulline supplementation. We failed to detect NCP in these animals. These data suggest that NCP is not a significant citrulline metabolite in rats.

  16. Citrullination regulates pluripotency and histone H1 binding to chromatin

    DEFF Research Database (Denmark)

    Christophorou, Maria A; Castelo-Branco, Gonçalo; Halley-Stott, Richard P

    2014-01-01

    Citrullination is the post-translational conversion of an arginine residue within a protein to the non-coded amino acid citrulline. This modification leads to the loss of a positive charge and reduction in hydrogen-bonding ability. It is carried out by a small family of tissue-specific vertebrate...

  17. Extrarenal citrulline disposal in mice with impaired renal function

    Science.gov (United States)

    The endogenous synthesis of arginine, a semiessential amino acid, relies on the production of citrulline by the gut and its conversion into arginine by the kidney in what has been called the "intestinal-renal axis" for arginine synthesis. Although the kidney is the main site for citrulline disposal,...

  18. Reduced TCR‐dependent activation through citrullination of a T‐cell epitope enhances Th17 development by disruption of the STAT3/5 balance

    Science.gov (United States)

    Tibbitt, Christopher; Falconer, Jane; Stoop, Jeroen; van Eden, Willem; Robinson, John H.

    2016-01-01

    Citrullination is a post‐translational modification of arginine that commonly occurs in inflammatory tissues. Because T‐cell receptor (TCR) signal quantity and quality can regulate T‐cell differentiation, citrullination within a T‐cell epitope has potential implications for T‐cell effector function. Here, we investigated how citrullination of an immunedominant T‐cell epitope affected Th17 development. Murine naïve CD4+ T cells with a transgenic TCR recognising p89‐103 of the G1 domain of aggrecan (agg) were co‐cultured with syngeneic bone marrow‐derived dendritic cells (BMDC) presenting the native or citrullinated peptides. In the presence of pro‐Th17 cytokines, the peptide citrullinated on residue 93 (R93Cit) significantly enhanced Th17 development whilst impairing the Th2 response, compared to the native peptide. T cells responding to R93Cit produced less IL‐2, expressed lower levels of the IL‐2 receptor subunit CD25, and showed reduced STAT5 phosphorylation, whilst STAT3 activation was unaltered. IL‐2 blockade in native p89‐103‐primed T cells enhanced the phosphorylated STAT3/STAT5 ratio, and concomitantly enhanced Th17 development. Our data illustrate how a post‐translational modification of a TCR contact point may promote Th17 development by altering the balance between STAT5 and STAT3 activation in responding T cells, and provide new insight into how protein citrullination may influence effector Th‐cell development in inflammatory disorders. PMID:27173727

  19. Citrullination and carbamylation in the pathophysiology of rheumatoid arthritits

    Directory of Open Access Journals (Sweden)

    Ger J.M. Pruijn

    2015-04-01

    Full Text Available The discovery that citrullination was crucial for the recognition of antigens by the most disease-specific class of autoantibodies in rheumatoid arthritis had a huge impact on studies aimed at understanding autoimmunity in this disease. In addition to the detailed characterization of anti-citrullinated protein antibodies, various studies have addressed the identity of citrullinated antigens. These investigations were facilitated by new methods to characterize these proteins, the analysis of protein citrullination by peptidylarginine deiminases, the generation of a catalogue of citrullinated proteins present in the inflamed joints of patients and the finding that the formation of extracellular traps is dependent on the activity of peptidylarginine deiminase activity. Recently, it was found that in addition to citrullination also carbamylation, which results in chemically highly related modified proteins, yields antigens that are targeted by rheumatoid arthritis patient sera. Here, all of these aspects will be discussed, culminating in current ideas about the involvement of citrullination and carbamylation in pathophysiological processes in autoimmunity, especially rheumatoid arthritis.

  20. Citrullination and carbamylation in the pathophysiology of rheumatoid arthritis.

    Science.gov (United States)

    Pruijn, Ger J M

    2015-01-01

    The discovery that citrullination was crucial for the recognition of antigens by the most disease-specific class of autoantibodies in rheumatoid arthritis (RA) had a huge impact on studies aimed at understanding autoimmunity in this disease. In addition to the detailed characterization of anti-citrullinated protein antibodies, various studies have addressed the identity of citrullinated antigens. These investigations were facilitated by new methods to characterize these proteins, the analysis of protein citrullination by peptidylarginine deiminases, the generation of a catalog of citrullinated proteins present in the inflamed joints of patients and the finding that the formation of extracellular traps is dependent on the activity of peptidylarginine deiminase activity. Recently, it was found that in addition to citrullination also carbamylation, which results in chemically highly related modified proteins, yields antigens that are targeted by rheumatoid arthritis patient sera. Here, all of these aspects will be discussed, culminating in current ideas about the involvement of citrullination and carbamylation in pathophysiological processes in autoimmunity, especially RA.

  1. Arginine and citrulline supplementation in sports and exercise: ergogenic nutrients?

    Science.gov (United States)

    Sureda, Antoni; Pons, Antoni

    2012-01-01

    Dietary L-citrulline malate supplements may increase levels of nitric oxide (NO) metabolites, although this response has not been related to an improvement in athletic performance. NO plays an important role in many functions in the body regulating vasodilatation, blood flow, mitochondrial respiration and platelet function. L-Arginine is the main precursor of NO via nitric oxide synthase (NOS) activity. Additionally, L-citrulline has been indicated to be a second NO donor in the NOS-dependent pathway, since it can be converted to L-arginine. The importance of L-citrulline as an ergogenic support derives from the fact that L-citrulline is not subject to pre-systemic elimination and, consequently, could be a more efficient way to elevate extracellular levels of L-arginine by itself. L-Citrulline malate can develop beneficial effects on the elimination of NH(3) in the course of recovery from exhaustive muscular exercise and also as an effective precursor of L-arginine and creatine. Dietary supplementation with L-citrulline alone does not improve exercise performance. The ergogenic response of L-citrulline or L-arginine supplements depends on the training status of the subjects. Studies involving untrained or moderately healthy subjects showed that NO donors could improve tolerance to aerobic and anaerobic exercise. However, when highly-trained subjects were supplemented, no positive effect on performance was indicated.

  2. Mitochondria: role of citrulline and arginine supplementation in MELAS syndrome.

    Science.gov (United States)

    El-Hattab, Ayman W; Emrick, Lisa T; Chanprasert, Sirisak; Craigen, William J; Scaglia, Fernando

    2014-03-01

    Mitochondria are found in all nucleated human cells and generate most of the cellular energy. Mitochondrial disorders result from dysfunctional mitochondria that are unable to generate sufficient ATP to meet the energy needs of various organs. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a frequent maternally inherited mitochondrial disorder. There is growing evidence that nitric oxide (NO) deficiency occurs in MELAS syndrome and results in impaired blood perfusion that contributes significantly to several complications including stroke-like episodes, myopathy, and lactic acidosis. Both arginine and citrulline act as NO precursors and their administration results in increased NO production and hence can potentially have therapeutic utility in MELAS syndrome. Citrulline raises NO production to a greater extent than arginine, therefore, citrulline may have a better therapeutic effect. Controlled studies assessing the effects of arginine or citrulline supplementation on different clinical aspects of MELAS syndrome are needed.

  3. Local administration of glucocorticoids decreases synovial citrullination in rheumatoid arthritis

    OpenAIRE

    2012-01-01

    Introduction Protein citrullination is present in the rheumatoid synovium, presumably contributing to the perpetuation of chronic inflammation, in the presence of specific autoimmunity. As a result, the present study examined the possibility that effective antirheumatic treatment will decrease the level of synovial citrullination. Methods Synovial biopsies were obtained from 11 rheumatoid arthritis (RA) patients before and after 8 weeks of treatment with 20 mg methotrexate weekly, 15 RA patie...

  4. 联合检测类风湿因子、抗环瓜氨酸多肽抗体和抗角蛋白抗体在类风湿关节炎诊断中的价值%Diagnostic Values of Combined Detection of Rheumatoid Factor,Anticyclic Citrullinated Peptide Antibody and Antikeratin Antibody in Rheumatoid Arthritis

    Institute of Scientific and Technical Information of China (English)

    陈朴; 张立营; 李熙建; 龙琴

    2013-01-01

    Objective:To evaluate the significance of the combination of serum rheumatoid factor(RF),anticyclic citrullinated peptide antibody(anti CCP)and antikeratin antibody in the diagnostic value of rheumatoid arthritis(RA).Method:Serum from 150 RA patients and 75 non-RA patients were analyzed.RF,anti CCP and AKA were detected using immune turbidimetry、ELISA and indirect immunofluorescence respectively.The distributions of these antibodies were compared to determine the diagnostic values of combined detection of RF,anti CCP and AKA in RA patients.Result:The sensitivity of single antibody detection in RF was the highest(82.0%),specificity of AKA was the highest(93.33%),the positive predictive value of AKA was the highest(94.05%),and negative predictive value of RF was the highest(67.47%);the sensitivity of combined detection of anti CCP antibody to RF+in the highest(43.33%),specificity to RF+anti CCP+AKA was the highest(100%),the positive predictive value for RF+anti CCP+AKA was the highest (100%),and negative predictive value of RF+anti CCP antibody was highest(44.81%).Conclusion:RF diagnosis of RA sensitivity is highest,but specific to RF+anti CCP+AKA is the highest,the three combined detection can improve the diagnostic value of the RA.%目的:研究类风湿因子(RF)、抗环瓜氨酸多肽(CCP)抗体和抗角蛋白抗体(AKA)联合检测在类风湿关节炎(RA)诊断中的价值。方法:分别应用免疫比浊法、ELISA法和间接免疫荧光染色法检测150例RA患者和75例非RA患者血清中的RF、抗CCP抗体和AKA水平,并分析三种抗体在RA诊断中的价值。结果:单一抗体检测中敏感性以RF最高(82.0%),特异性以AKA最高(93.33%),阳性预测值以AKA最高(94.05%),阴性预测值以RF最高(67.47%);联合检测中敏感性以RF+抗CCP抗体最高(43.33%),特异性以RF+抗CCP+AKA最高(100%),阳性预测值以RF+抗CCP+AKA最高(100%),阴性预

  5. Citrullination regulates pluripotency and histone H1 binding to chromatin

    Science.gov (United States)

    Christophorou, Maria A.; Castelo-Branco, Gonçalo; Halley-Stott, Richard P.; Oliveira, Clara Slade; Loos, Remco; Radzisheuskaya, Aliaksandra; Mowen, Kerri A.; Bertone, Paul; Silva, José C. R.; Zernicka-Goetz, Magdalena; Nielsen, Michael L.; Gurdon, John B.; Kouzarides, Tony

    2014-03-01

    Citrullination is the post-translational conversion of an arginine residue within a protein to the non-coded amino acid citrulline. This modification leads to the loss of a positive charge and reduction in hydrogen-bonding ability. It is carried out by a small family of tissue-specific vertebrate enzymes called peptidylarginine deiminases (PADIs) and is associated with the development of diverse pathological states such as autoimmunity, cancer, neurodegenerative disorders, prion diseases and thrombosis. Nevertheless, the physiological functions of citrullination remain ill-defined, although citrullination of core histones has been linked to transcriptional regulation and the DNA damage response. PADI4 (also called PAD4 or PADV), the only PADI with a nuclear localization signal, was previously shown to act in myeloid cells where it mediates profound chromatin decondensation during the innate immune response to infection. Here we show that the expression and enzymatic activity of Padi4 are also induced under conditions of ground-state pluripotency and during reprogramming in mouse. Padi4 is part of the pluripotency transcriptional network, binding to regulatory elements of key stem-cell genes and activating their expression. Its inhibition lowers the percentage of pluripotent cells in the early mouse embryo and significantly reduces reprogramming efficiency. Using an unbiased proteomic approach we identify linker histone H1 variants, which are involved in the generation of compact chromatin, as novel PADI4 substrates. Citrullination of a single arginine residue within the DNA-binding site of H1 results in its displacement from chromatin and global chromatin decondensation. Together, these results uncover a role for citrullination in the regulation of pluripotency and provide new mechanistic insights into how citrullination regulates chromatin compaction.

  6. Maternal citrulline supplementation prevents prenatal dexamethasone-induced programmed hypertension.

    Science.gov (United States)

    Tain, Y L; Sheen, J M; Chen, C C; Yu, H R; Tiao, M M; Kuo, H C; Huang, L T

    2014-05-01

    Glucocorticoids are administered to premature infants to accelerate pulmonary maturation. In experimental model, prenatal dexamethasone (DEX) results in reduced nephron number and adulthood hypertension. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), can cause oxidative stress and is involved in the development of hypertension. L-citrulline can be converted to l-arginine (the substrate for NOS) in the body. Thus we intended to determine if maternal L-citrulline therapy can prevent prenatal DEX-induced programmed hypertension by restoration ADMA/nitric oxide (NO) balance, alterations of renin-angiotensin system (RAS) and sodium transporters, and epigenetic regulation by histone deacetylases (HDACs). Male offspring were assigned to four groups: control, pregnancy rats received intraperitoneal DEX (0.2 mg/kg body weight) daily on gestational days 15 and 16 (DEX), pregnancy rats received 0.25% L-citrulline in drinking water during the entire pregnancy and lactation period (CIT), and DEX + CIT. We found DEX group developed hypertension at 16 weeks of age, which was prevented by maternal L-citrulline therapy. Prenatal DEX exposure increased plasma ADMA concentrations and reduced renal NO production. However, L-citrulline reduced plasma ADMA level and increased renal level of NO in DEX + CIT group. Next, prenatal DEX-induced programmed hypertension is related to increased mRNA expression of angiotensin and angiotensin II type 1 receptor, and class I HDACs in the kidney. Prenatal DEX exposure increased renal protein abundance of Na(+)/Cl(-) cotransporter (NCC), which was prevented by L-citrulline therapy. The beneficial effects of L-citrulline therapy include restoration of ADMA/NO balance and alteration of NCC, to prevent the prenatal DEX-induced programmed hypertension.

  7. Relation Analysis of Synovial Anti-Citrullinated Epitope Peptide Expression and Peptidyl Arginine Deiminase 4 Gene in the Rheumatoid Arthritis Patient%类风湿关节炎患者滑膜抗环瓜氨酸肽表位表达与肽酰基精氨酸脱亚氨酶4基因的相关性分析

    Institute of Scientific and Technical Information of China (English)

    沈小辉; 喻伟; 杨菲

    2016-01-01

    Objective To investigate the relation of synovial anti-citrullinated epitope peptide(CCP)expression and peptidyl arginine deiminase 4 (PADI4)gene in the rheumatoid arthritis patient.Methods From February 2013 to 2015 in Dongfeng General Hospital Affiliated to Hubei University,selected 110 patients with rheumatoid arthritis as the observation group, and selected 110 healthy people at the same period in this hospital for medical examination as the control group,both groups were given the synovial CCP expression positive rate and PADI4 gene expression detecting and correlation analysis.Results The synovial anti-CCP expression positive rates in the observation group and the control group were 70.9% and 9.1% re-spectively,and the observation group were significantly higher than the control group (P<0.05).The PADI4-104 genotype expression frequency compared between the observation group and control group,the difference were statistically significant (P<0.05).The G/G expression was more in the observation group,while the control group was more wit the C/G expres-sion.Pearson correlation analysis showed that in the observation group,synovial CCP positive expression were significant correlated to the expression of genotype PADI4-104 (r=0.344,P<0.05).Logistic regression analysis showed PADI4-104 genotype frequency were the main factors for the synovial CCP epitope expression (P<0.05).Conclusion The rheumatoid arthritis was more with synovial anti-CCP positive expression.There were also PADI4 polymorphism disorder expression, and clear correlation between the two.Thus impact the incidence of rheumatoid arthritis.%目的探讨类风湿关节炎患者滑膜抗环瓜氨酸肽(CCP)表位表达与肽酰基精氨酸脱亚氨酶4(PADI4)基因的相关性。方法2013年2月~2015年选择在湖北医药学院附属东风医院风湿免疫科住院的类风湿关节炎患者110例作为观察组,同期选择在该院进行体检的健康者110例作为对照

  8. Physical characteristics of a citrullinated pro-filaggrin epitope recognized by anti-citrullinated protein antibodies in rheumatoid arthritis sera

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Holm, Bettina Eide; Slot, Ole

    2016-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease of complex etiology. A characteristic feature of a subset of RA is the presence of anti-citrullinated protein antibodies (ACPA), which correlate with a progressive disease course. In this study, we employed streptavidin capture enzyme...

  9. Citrulline as a Biomarker in the Murine Total-Body Irradiation Model: Correlation of Circulating and Tissue Citrulline to Small Intestine Epithelial Histopathology.

    Science.gov (United States)

    Jones, Jace W; Tudor, Gregory; Li, Fei; Tong, Yan; Katz, Barry; Farese, Ann M; MacVittie, Thomas J; Booth, Catherine; Kane, Maureen A

    2015-11-01

    The use of plasma citrulline as a biomarker for gastrointestinal acute radiation syndrome via exposure to total-body irradiation in a murine model was investigated. The radiation exposure covered lethal, mid-lethal, and sub-lethal gastrointestinal acute radiation syndrome. Plasma citrulline profiles were generated over the first 6 d following total-body irradiation exposure of 6-15 Gy. In addition, plasma citrulline was comprehensively evaluated in the context of matching small intestine citrulline and histopathology. Higher plasma citrulline was significantly associated with lower irradiation doses over the first 6 d following the irradiation insult. Furthermore, higher plasma citrulline was significantly associated with higher crypt survival. The correlation of the plasma citrulline to crypt survival was more robust for higher irradiation doses and for later time points. The data suggested plasma citrulline was most informative for reflecting gastrointestinal injury resulting from exposure to 9-15 Gy total-body irradiation covering time-points 2-5 d post the irradiation insult.

  10. Restoration of impaired nitric oxide production in MELAS syndrome with citrulline and arginine supplementation.

    Science.gov (United States)

    El-Hattab, Ayman W; Hsu, Jean W; Emrick, Lisa T; Wong, Lee-Jun C; Craigen, William J; Jahoor, Farook; Scaglia, Fernando

    2012-04-01

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most common mitochondrial disorders. Although the pathogenesis of stroke-like episodes remains unclear, it has been suggested that mitochondrial proliferation may result in endothelial dysfunction and decreased nitric oxide (NO) availability leading to cerebral ischemic events. This study aimed to assess NO production in subjects with MELAS syndrome and the effect of the NO precursors arginine and citrulline. Using stable isotope infusion techniques, we assessed arginine, citrulline, and NO metabolism in control subjects and subjects with MELAS syndrome before and after arginine or citrulline supplementation. The results showed that subjects with MELAS had lower NO synthesis rate associated with reduced citrulline flux, de novo arginine synthesis rate, and plasma arginine and citrulline concentrations, and higher plasma asymmetric dimethylarginine (ADMA) concentration and arginine clearance. We conclude that the observed impaired NO production is due to multiple factors including elevated ADMA, higher arginine clearance, and, most importantly, decreased de novo arginine synthesis secondary to decreased citrulline availability. Arginine and, to a greater extent, citrulline supplementation increased the de novo arginine synthesis rate, the plasma concentrations and flux of arginine and citrulline, and NO production. De novo arginine synthesis increased markedly with citrulline supplementation, explaining the superior efficacy of citrulline in increasing NO production. The improvement in NO production with arginine or citrulline supplementation supports their use in MELAS and suggests that citrulline may have a better therapeutic effect than arginine. These findings can have a broader relevance for other disorders marked by perturbations in NO metabolism.

  11. Plasma citrulline levels predict intestinal toxicity in patients treated with pelvic radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Onal, Cem; Kotek, Ayse; Arslan, Gungor; Topkan, Erkan (Dept. of Radiation Oncology, Baskent Univ. Faculty of Medicine, Adana (Turkey)), E-mail: hcemonal@hotmail.com; Unal, Birsel (Dept. of Biochemistry, Baskent Univ. Faculty of Medicine, Ankara (Turkey)); Yavuz, Aydin; Yavuz, Melek (Dept. of Radiation Oncology, Akdeniz Univ. Faculty of Medicine, Antalya (Turkey))

    2011-11-15

    Background. Radiotherapy (RT) for abdominal and pelvic malignancies often causes severe small bowel toxicity. Citrulline concentrations are known to decrease with intestinal failure. We thus evaluated the feasibility of plasma citrulline levels in predicting radiation-induced intestinal toxicity. Material and methods. Fifty-three patients (36 prostate cancer, 17 endometrial cancer) who received 45 Gy pelvic RT using conventional fractionation were prospectively evaluated. Patients with prostate cancer received an additional 25-30.6 Gy conformal boost. Plasma citrulline levels were assessed on day 0, mid- (week 3) and post-RT (week 8), and four months post-RT. Dose-volume histogram, citrulline concentration changes, and weekly intestinal toxicity scores were analyzed. Results. Mean age was 63 years (range: 43-81 years) and mean baseline citrulline concentration was 38.0 +- 10.1 mumol/l. Citrulline concentrations were significantly reduced at week 3 (27.4 +- 5.9 mumol/l; p < 0.0001), treatment end (29.9 +- 8.8 mumol/l; p < 0.0001), and four months post-treatment (34.3 +- 12.1; p 0.01). The following factor pairs were significantly positively correlated: Citrulline concentration/mean bowel dose during, end of treatment, and four months post-RT; dose-volume parameters/citrulline change groups; cumulative mean radiation dose/intestinal toxicity at end and four months post-RT; citrulline changes/intestinal toxicity during and end of RT. Citrulline concentration changes significantly differed during treatment according to RTOG intestinal toxicity grades (p < 0.0001). Although the citrulline changes differed significantly within RTOG intestinal toxicity grades (p = 0.003), the difference between Grade 0 and Grade 1 did not differ significantly at the end of the treatment. At four months after RT, no significant differences were apparent. Conclusion. Citrulline-based assessment scores are objective and should be considered in measuring radiation-induced intestinal toxicity

  12. Left ventricular function in treatment-naive early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Løgstrup, Brian B; Deibjerg, Lone K; Nielsen, Agnete Desirèe;

    2014-01-01

    BACKGROUND: The role of inflammation and anti-cyclic citrullinated peptide antibodies (anti-CCP) in the pathogenesis of cardiovascular disease in early rheumatoid arthritis (RA) remains unclear. Previous studies have suggested that both disease activity and disease duration are associated...

  13. The effect of citrulline and arginine supplementation on lactic acidemia in MELAS syndrome.

    Science.gov (United States)

    El-Hattab, Ayman W; Emrick, Lisa T; Williamson, Kaitlin C; Craigen, William J; Scaglia, Fernando

    2013-12-01

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disorder in which nitric oxide (NO) deficiency may play a role in the pathogenesis of several complications including stroke-like episodes and lactic acidosis. Supplementing the NO precursors arginine and citrulline restores NO production in MELAS syndrome. In this study we evaluated the effect of arginine or citrulline on lactic acidemia in adults with MELAS syndrome. Plasma lactate decreased significantly after citrulline supplementation, whereas the effect of arginine supplementation did not reach statistical significance. These results support the potential therapeutic utility of arginine and citrulline in MELAS syndrome and suggest that citrulline supplementation may be more efficacious. However, therapeutic efficacy of these compounds should be further evaluated in clinical trials.

  14. Structure and pathogenicity of antibodies specific for citrullinated collagen type II in experimental arthritis

    DEFF Research Database (Denmark)

    Uysal, Hüseyin; Bockermann, Robert; Nandakumar, Kutty S

    2009-01-01

    Antibodies to citrulline-modified proteins have a high diagnostic value in rheumatoid arthritis (RA). However, their biological role in disease development is still unclear. To obtain insight into this question, a panel of mouse monoclonal antibodies was generated against a major triple helical...... collagen type II (CII) epitope (position 359-369; ARGLTGRPGDA) with or without arginines modified by citrullination. These antibodies bind cartilage and synovial tissue, and mediate arthritis in mice. Detection of citrullinated CII from RA patients' synovial fluid demonstrates that cartilage-derived CII...

  15. Single cell cloning and recombinant monoclonal antibodies generation from RA synovial B cells reveal frequent targeting of citrullinated histones of NETs

    Science.gov (United States)

    Corsiero, Elisa; Bombardieri, Michele; Carlotti, Emanuela; Pratesi, Federico; Robinson, William; Migliorini, Paola; Pitzalis, Costantino

    2016-01-01

    Objectives Rheumatoid arthritis (RA) is characterised by breach of self-tolerance towards citrullinated antigens with generation of anti-citrullinated peptide/proteins antibodies (ACPA). Currently, the nature and source of citrullinated antigens driving the humoral autoimmune response within synovial ectopic lymphoid structures (ELS) is a crucial unknown aspect of RA pathogenesis. Here we characterised the autoreactive B-cell response of lesional B cells isolated from ELS+RA synovium. Methods Single synovial tissue CD19+cells were Fluorescence Activated Cell Sorting (FACS)-sorted and VH/VL Ig genes cloned to generate recombinant monoclonal antibodies (rmAbs) from patients with ELS+/ACPA+RA. Results RA-rmAbs immunoreactivity analysis provided the following key findings: (1) in a chIP-based array containing 300 autoantigens and in a ‘citrullinome’ multiplex assay, a strong reactivity against citrullinated histones H2A/H2B (citH2A/H2B) was observed in ∼40% of RA-rmAbs, followed by cit-fibrinogen and cit-vimentin; (2) anti-citH2A/H2B-reactive RA-rmAbs (but not anti-citH2A/H2B negative) selectively recognised neutrophil extracellular traps (NETs) from peripheral blood and/or RA joint neutrophils; (3) anti-citH2A/citH2B and anti-NET immunobinding was dependent on affinity maturation and was completely abrogated following reversion of hypermutated IgVH/VL genes to germline sequences; (4) ELS+ (not ELS−) RA synovial tissues engrafted into Severe Combined ImmunoDeficiency (SCID) mice released human anti-citH2A/citH2B and anti-NET antibodies in association with the intra-graft expression of CXCL13 and lymphotoxin (LT)-β, two master regulators of ELS. Conclusion We provided novel evidence that B cells differentiated within synovial ELS in the RA joints frequent target deiminated proteins which could be generated during NETosis of RA synovial neutrophils including histones. Thus, NETs could represent a source of citrullinated antigens fuelling the ACPA autoimmune

  16. Anticorpos antiproteínas citrulinadas e a artrite reumatóide Auto-antibodies to citrullinated proteins and rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Renata Trigueirinho Alarcon

    2007-06-01

    the illness. Examples of citrullinated antigens recognized by autoantibodies in rheumatoid arthritis are profillagrin, fillagrin and vimentin. Cells and tissues rich in those proteins have been used as substrate for the first laboratory assays for the detection of this class of autoantibodies. The discovery that the epitopes recognized by these autoantibodies are citrullin-bearing peptides permited the development of ELISA assays. The ELISA format allows better standardization and higher reproducibility for the tests, resulting in worldwide acceptance of these autoantibodies as the most specific and early serologic markers for the diagnosis of rheumatoid arthritis. There is controversy regarding the ability of these autoantibodies in predicting disease evolution. The role of antibodies to citrullinated peptides in the pathophysiology of rheumatoid arthritis is supported by their extreme specificity for the disease, by the finding of citrullinated proteins in inflamed synovia, by the intraarticular production of these autoantibodies and by the extreme affinity of citrullinated peptides for HLA-DRB1 molecules bearing the shared epitope. These findings forecast the possibility of novel and exciting discoveries towards a better understanding of the pathophysiology of rheumatoid arthritis.

  17. Potential role for PADI-mediated histone citrullination in preimplantation development

    Directory of Open Access Journals (Sweden)

    Kan Rui

    2012-06-01

    Full Text Available Abstract Background The peptidylarginine deiminases (PADIs convert positively charged arginine residues to neutrally charged citrulline on protein substrates in a process that is known as citrullination or deimination. Previous reports have documented roles for histone citrullination in chromatin remodeling and gene regulation in several tissue types, however, a potential role for histone citrullination in chromatin-based activities during early embryogenesis has not been investigated. Results In the present study, we tested by laser scanning confocal indirect immunofluorescence microscopy whether specific arginine residues on the histone H3 and H4 N-terminal tails (H4R3, H3R2 + 8 + 17, and H3R26 were citrullinated in mouse oocytes and preimplantation embryos. Results showed that all of the tested residues were deiminated with each site showing a unique localization pattern during early development. Given these findings, we next tested whether inhibition of PADI activity using the PADI-specific inhibitor, Cl-amidine, may affect embryonic development. We found that treatment of pronuclear stage zygotes with Cl-amidine reduces both histone H3 and H4 tail citrullination and also potently blocks early cleavage divisions in vitro. Additionally, we found that the Cl-amidine treatment reduces acetylation at histone H3K9, H3K18, and H4K5 while having no apparent effect on the repressive histone H3K9 dimethylation modification. Lastly, we found that treatment of zygotes with trichostatin A (TSA to induce hyperacetylation also resulted in an increase in histone citrullination at H3R2 + 8 + 17. Conclusions Given the observed effects of Cl-amidine on embryonic development and the well documented correlation between histone acetylation and transcriptional activation, our findings suggest that histone citrullination may play an important role in facilitating gene expression in early embryos by creating a chromatin environment that is

  18. Citrulline as a Biomarker in the Non-human Primate Total- and Partial-body Irradiation Models: Correlation of Circulating Citrulline to Acute and Prolonged Gastrointestinal Injury.

    Science.gov (United States)

    Jones, Jace W; Bennett, Alexander; Carter, Claire L; Tudor, Gregory; Hankey, Kim G; Farese, Ann M; Booth, Catherine; MacVittie, Thomas J; Kane, Maureen A

    2015-11-01

    The use of plasma citrulline as a biomarker for acute and prolonged gastrointestinal injury via exposure to total- and partial-body irradiation (6 MV LINAC-derived photons; 0.80 Gy min) in nonhuman primate models was investigated. The irradiation exposure covered gastrointestinal injuries spanning lethal, mid-lethal, and sub-lethal doses. The acute gastrointestinal injury was assessed via measurement of plasma citrulline and small intestinal histopathology over the first 15 d following radiation exposure and included total-body irradiation at 13.0 Gy, 10.5 Gy, and 7.5 Gy and partial-body irradiation at 11.0 Gy with 5% bone marrow sparing. The dosing schemes of 7.5 Gy total-body irradiation and 11.0 Gy partial-body irradiation included time points out to day 60 and day 180, respectively, which allowed for correlation of plasma citrulline to prolonged gastrointestinal injury and survival. Plasma citrulline values were radiation-dependent for all radiation doses under consideration, with nadir values ranging from 63-80% lower than radiation-naïve NHP plasma. The nadir values were observed at day 5 to 7 post irradiation. Longitudinal plasma citrulline profiles demonstrated prolonged gastrointestinal injury resulting from acute high-dose irradiation had long lasting effects on enterocyte function. Moreover, plasma citrulline did not discriminate between total-body or partial-body irradiation over the first 15 d following irradiation and was not predictive of survival based on the radiation models considered herein.

  19. Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced Arginase Activity

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    Karolina A.P. Wijnands

    2015-06-01

    Full Text Available Enhanced arginase-induced arginine consumption is believed to play a key role in the pathogenesis of sickle cell disease-induced end organ failure. Enhancement of arginine availability with l-arginine supplementation exhibited less consistent results; however, l-citrulline, the precursor of l-arginine, may be a promising alternative. In this study, we determined the effects of l-citrulline compared to l-arginine supplementation on arginine-nitric oxide (NO metabolism, arginine availability and microcirculation in a murine model with acutely-enhanced arginase activity. The effects were measured in six groups of mice (n = 8 each injected intraperitoneally with sterile saline or arginase (1000 IE/mouse with or without being separately injected with l-citrulline or l-arginine 1 h prior to assessment of the microcirculation with side stream dark-field (SDF-imaging or in vivo NO-production with electron spin resonance (ESR spectroscopy. Arginase injection caused a decrease in plasma and tissue arginine concentrations. l-arginine and l-citrulline supplementation both enhanced plasma and tissue arginine concentrations in arginase-injected mice. However, only the citrulline supplementation increased NO production and improved microcirculatory flow in arginase-injected mice. In conclusion, the present study provides for the first time in vivo experimental evidence that l-citrulline, and not l-arginine supplementation, improves the end organ microcirculation during conditions with acute arginase-induced arginine deficiency by increasing the NO concentration in tissues.

  20. Is there a link between carbamylation and citrullination in periodontal disease and rheumatoid arthritis?

    Science.gov (United States)

    Bright, R; Proudman, S M; Rosenstein, E D; Bartold, P M

    2015-06-01

    The remarkable similarity in inflammatory response and pathology of periodontal disease and rheumatoid arthritis has been recognized for several decades. However, how these two disease may be interrelated has been less clear. During the pathogenesis of rheumatoid arthritis there is a preclinical immunological phase which precedes the clinical manifestation of rheumatoid arthritis. During this phase serum autoantibodies appear many years before the clinical signs and symptoms of rheumatoid arthritis become apparent. To date, the two best studied autoantibodies have been rheumatoid factor and anti-citrullinated protein antibodies (ACPA). Of these the production of ACPA has been considered very important due to their high predictive value in future manifestation of rheumatoid arthritis. Citrullination is a common post-translational modification of proteins based on the enzymatic conversion of arginine into citrulline. Extra-articular citrullination and production of ACPA, as a priming immunological experience, is well documented in many tissues including the inflamed gingival tissues associated with periodontal disease. More recently, carbamylation of proteins has also been implicated in the pathogenesis of rheumatoid arthritis in a manner similar to citrullination. Carbamylation is a post translational modification of proteins by an enzyme-independent modification of lysine residues against which autoantibodies are subsequently induced. In this article we hypothesise that, like citrullination, carbamylation of proteins and associated antibody production during the gingival inflammation associated with gingivitis and periodontitis may play a role in the pathogenesis of rheumatoid arthritis.

  1. Plasma arginine and ornithine are the main citrulline precursors in mice infused with arginine-free diets.

    Science.gov (United States)

    Marini, Juan C; Didelija, Inka Cajo; Castillo, Leticia; Lee, Brendan

    2010-08-01

    Dietary arginine is the main dietary precursor for citrulline synthesis, but it is not known if other precursors can compensate when arginine is absent in the diet. To address this question, the contributions of plasma and dietary precursors were determined by using multitracer protocols in conscious mice infused i.g. either an arginine-sufficient diet [Arg(+)] or an arginine-free diet [Arg(-)]. The plasma entry rate of citrulline and arginine did not differ between the 2 diet groups (156 +/- 6 and 564 +/- 30 micromol kg(-1) h(-1), respectively); however, the entry rate of ornithine was greater in the mice fed the Arg(+) than the Arg(-) diet (332 +/- 33 vs. 180 +/- 16 micromol kg(-1) h(-1)). There was a greater utilization of plasma ornithine for the synthesis of citrulline (49 +/- 4 vs. 36 +/- 3 micromol kg(-1) h(-1), 30 +/- 3% vs. 24 +/- 2% of citrulline entry rate) in the mice fed the Arg(-) diet than the Arg(+) diet. The utilization of plasma arginine did not differ between the 2 diet groups for citrulline synthesis, either through plasma ornithine (approximately 29 +/- 3 micromol kg(-1) h(-1)) or at the site of citrulline synthesis (approximately 12 +/- 3 micromol kg(-1) h(-1)). The contribution of dietary proline to the synthesis of citrulline was mainly at the site of citrulline production (17 +/- 1 micromol kg(-1) h(-1)), rather than through plasma ornithine (5 +/- 0.4 micromol kg(-1) h(-1)). Dietary glutamine was utilized only at the site of citrulline synthesis (4 +/- 0.2 micromol kg(-1) h(-1)). Dietary glutamine and proline made a greater contribution to the synthesis of citrulline in mice fed the Arg(-) diet but remained minor sources for citrulline production. Plasma arginine and ornithine are able to support citrulline synthesis during arginine-free feeding.

  2. The periodontium of periodontitis patients contains citrullinated proteins which may play a role in ACPA (anti-citrullinated protein antibody) formation

    NARCIS (Netherlands)

    Nesse, Willem; Westra, Johanna; van der Wal, Jacqueline E.; Abbas, Frank; Nicholas, Anthony P.; Vissink, Arjan; Brouwer, Elisabeth; Westra J., [No Value

    2012-01-01

    Aim To determine the presence and location (stroma versus epithelium) of citrullinated proteins in periodontitis tissue as compared to non-periodontitis tissue and synovial tissue of RA patients. Materials & Methods Periodontitis, healthy periodontal and RA-affected synovial tissue samples were coll

  3. L-citrulline-malate influence over branched chain amino acid utilization during exercise.

    Science.gov (United States)

    Sureda, Antoni; Córdova, Alfredo; Ferrer, Miguel D; Pérez, Gerardo; Tur, Josep A; Pons, Antoni

    2010-09-01

    Exhaustive exercise induces disturbances in metabolic homeostasis which can result in amino acid catabolism and limited L-arginine availability. Oral L-citrulline supplementation raises plasma L-arginine concentration and augments NO-dependent signalling. Our aim was to evaluate the effects of diet supplementation with L-citrulline-malate prior to intense exercise on the metabolic handle of plasma amino acids and on the products of metabolism of arginine as creatinine, urea and nitrite and the possible effects on the hormonal levels. Seventeen voluntary male pre-professional cyclists were randomly assigned to one of two groups: control or supplemented (6 g L-citrulline-malate 2 h prior exercise) and participated in a 137-km cycling stage. Blood samples were taken in basal conditions, 15 min after the race and 3 h post race (recovery). Most essential amino acids significantly decreased their plasma concentration as a result of exercise; however, most non-essential amino acids tended to significantly increase their concentration. Citrulline-malate ingestion significantly increased the plasma concentration of citrulline, arginine, ornithine, urea, creatinine and nitrite (p urea.

  4. Potential Role of Peptidylarginine Deiminase Enzymes and Protein Citrullination in Cancer Pathogenesis

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    Sunish Mohanan

    2012-01-01

    Full Text Available The peptidylarginine deiminases (PADs are a family of posttranslational modification enzymes that catalyze the conversion of positively charged protein-bound arginine and methylarginine residues to the uncharged, nonstandard amino acid citrulline. This enzymatic activity is referred to as citrullination or, alternatively, deimination. Citrullination can significantly affect biochemical pathways by altering the structure and function of target proteins. Five mammalian PAD family members (PADs 1–4 and 6 have been described and show tissue-specific distribution. Recent reviews on PADs have focused on their role in autoimmune diseases. Here, we will discuss the potential role of PADs in tumor progression and tumor-associated inflammation. In the context of cancer, increasing clinical evidence suggests that PAD4 (and possibly PAD2 has important roles in tumor progression. The link between PADs and cancer is strengthened by recent findings showing that treatment of cell lines and mice with PAD inhibitors significantly suppresses tumor growth and, interestingly, inflammatory symptoms. At the molecular level, transcription factors, coregulators, and histones are functional targets for citrullination by PADs, and citrullination of these targets can affect gene expression in multiple tumor cell lines. Next generation isozyme-specific PAD inhibitors may have therapeutic potential to regulate both the inflammatory tumor microenvironment and tumor cell growth.

  5. Myelin Basic Protein Citrullination in Multiple Sclerosis: A Potential Therapeutic Target for the Pathology.

    Science.gov (United States)

    Yang, Lei; Tan, Dewei; Piao, Hua

    2016-08-01

    Multiple sclerosis (MS) is a multifactorial demyelinating disease characterized by neurodegenerative events and autoimmune response against myelin component. Citrullination or deimination, a post-translational modification of protein-bound arginine into citrulline, catalyzed by Ca(2+) dependent peptidylarginine deiminase enzyme (PAD), plays an essential role in physiological processes include gene expression regulation, apoptosis and the plasticity of the central nervous system, while aberrant citrullination can generate new epitopes, thus involving in the initiation and/or progression of autoimmune disorder like MS. Myelin basic protein (MBP) is the major myelin protein and is generally considered to maintain the stability of the myelin sheath. This review describes the MBP citrullination and its consequence, as well as offering further support for the "inside-out" hypothesis that MS is primarily a neurodegenerative disease with secondary inflammatory demyelination. In addition, it discusses the role of MBP citrullination in the immune inflammation and explores the potential of inhibition of PAD enzymes as a therapeutic strategy for the disease.

  6. L-citrulline supplementation reverses the impaired airway relaxation in neonatal rats exposed to hyperoxia

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    Sopi Ramadan B

    2012-08-01

    Full Text Available Abstract Background Hyperoxia is shown to impair airway relaxation via limiting L-arginine bioavailability to nitric oxide synthase (NOS and reducing NO production as a consequence. L-arginine can also be synthesized by L-citrulline recycling. The role of L-citrulline supplementation was investigated in the reversing of hyperoxia-induced impaired relaxation of rat tracheal smooth muscle (TSM. Methods Electrical field stimulation (EFS, 2–20 V-induced relaxation was measured under in vitro conditions in preconstricted tracheal preparations obtained from 12 day old rat pups exposed to room air or hyperoxia (>95% oxygen for 7 days supplemented with L-citrulline or saline (in vitro or in vivo. The role of the L-citrulline/L-arginine cycle under basal conditions was studied by incubation of preparations in the presence of argininosuccinate synthase (ASS inhibitor [α-methyl-D, L-aspartate, 1 mM] or argininosuccinate lyase inhibitor (ASL succinate (1 mM and/or NOS inhibitor [Nω-nitro-L-arginine methyl ester; 100 μM] with respect to the presence or absence of L-citrulline (2 mM. Results Hyperoxia impaired the EFS-induced relaxation of TSM as compared to room air control (p ; 0.5 ± 0.1% at 2 V to 50.6 ± 5.7% at 20 V in hyperoxic group: 0.7 ± 0.2 at 2 V to 80.0 ± 5.6% at 20 V in room air group. Inhibition of ASS or ASL, and L-citrulline supplementation did not affect relaxation responses under basal conditions. However, inhibition of NOS significantly reduced relaxation responses (p in vivo and in vitro also reversed the hyperoxia-impaired relaxation. The differences were significant (p ; 0.8 ± 0.3% at 2 V to 47.1 ± 4.1% at 20 V without L-citrulline; 0.9 ± 0.3% at 2 V to 68.2 ± 4.8% at 20 V with L-citrulline. Inhibition of ASS or ASL prevented this effect of L-citrulline. Conclusion The results indicate the presence of an L-citrulline/L-arginine cycle in the airways of rat pups

  7. Effects of L-citrulline diet on stress-induced cold hypersensitivity in mice

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    Yoshinori Kobayashi

    2014-01-01

    Full Text Available Background: L-citrulline is an amino acid discovered in watermelon (Citrullus lanatus, Cucurbitaceae and is a known component of the nitric oxide (NO cycle that plays an important role in adjusting blood circulation and supplying NO and a key component of the endothelium-derived relaxing factor. Objective: The objective of this study is to evaluate the effect of L-citrulline on a newly established stress-induced cold hypersensitivity mouse model. Materials and Methods: When normal mice were forced to swim in water at 25°C for 15 min, their core body temperature dropped to 28.9°C, and then quickly recovered to normal temperature after the mice were transferred to a dry cage at room temperature (25°C. A 1-h immobilization before swimming caused the core body temperature to drop to ca. 24.1°C (4.8°C lower than normal mice, and the speed of core body temperature recovery dropped to 57% of the normal control. We considered this delay in recovery from hypothermia to be a sign of stress-induced cold hypersensitivity. Similar cold hypersensitivity was induced by administration of 50 mM L-NG-nitroarginine methyl ester, a NO synthesis inhibitor. Results: In this study, we showed that recovery speed from the stress-induced hypothermia remarkably improved in mice fed a 1% L-citrulline-containing diet for 20 days. Furthermore, the nonfasting blood level of L-arginine and L-citrulline increased significantly in the L-citrulline diet group, and higher serum nitrogen oxide levels were observed during recovery from the cold. Conclusions: These results suggested that oral L-citrulline supplementation strengthens vascular endothelium function and attenuates stress-induced cold hypersensitivity by improving blood circulation.

  8. Potential role for peptidylarginine deiminase 2 (PAD2 in citrullination of canine mammary epithelial cell histones.

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    Brian D Cherrington

    Full Text Available Peptidylarginine Deiminases (PADs convert arginine residues on substrate proteins to citrulline. Previous reports have documented that PAD2 expression and activity varies across the estrous cycle in the rodent uterus and pituitary gland, however, the expression and function of PAD2 in mammary tissue has not been previously reported. To gain more insight into potential reproductive roles for PAD2, in this study we evaluated PAD2 expression and localization throughout the estrous cycle in canine mammary tissue and then identified possible PAD2 enzymatic targets. Immunohistochemical and immunofluorescence analysis found PAD2 expression is low in anestrus, limited to a distinct, yet sparse, subset of epithelial cells within ductal alveoli during estrus/early diestrus, and encompasses the entire epithelium of the mammary duct in late diestrus. At the subcellular level, PAD2 is expressed in the cytoplasm, and to a lesser extent, the nucleus of these epithelial cells. Surprisingly, stimulation of canine mammary tumor cells (CMT25 shows that EGF, but not estrogen or progesterone, upregulates PAD2 transcription and translation suggesting EGF regulation of PAD2 and possibly citrullination in vivo. To identify potential PAD2 targets, anti-pan citrulline western blots were performed and results showed that citrullination activity is limited to diestrus with histones appearing to represent major enzymatic targets. Use of site-specific anti-citrullinated histone antibodies found that the N-terminus of histone H3, but not H4, appears to be the primary target of PAD activity in mammary epithelium. This observation supports the hypothesis that PAD2 may play a regulatory role in the expression of lactation related genes via histone citrullination during diestrus.

  9. Rheumatoid Factors: Clinical Applications

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    Francesca Ingegnoli

    2013-01-01

    Full Text Available Rheumatoid factors are antibodies directed against the Fc region of immunoglobulin G. First detected in patients with rheumatoid arthritis 70 years ago, they can also be found in patients with other autoimmune and nonautoimmune conditions, as well as in healthy subjects. Rheumatoid factors form part of the workup for the differential diagnosis of arthropathies. In clinical practice, it is recommended to measure anti-cyclic citrullinated peptide antibodies and rheumatoid factors together because anti-cyclic citrullinated peptide antibodies alone are only moderately sensitive, and the combination of the two markers improves diagnostic accuracy, especially in the case of early rheumatoid arthritis. Furthermore, different rheumatoid factor isotypes alone or in combination can be helpful when managing rheumatoid arthritis patients, from the time of diagnosis until deciding on the choice of therapeutic strategy.

  10. Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology

    DEFF Research Database (Denmark)

    Vassiliadis, E.; Oliveira, C. P.; Alvares-da-Silva, M. R.;

    2012-01-01

    -citrulline (VICM) was developed and evaluated in a carbon tetrachloride (CCl4) (n=52 + 28 controls) rat model of liver fibrosis and two clinical cohorts of adult patients with hepatitis C (HCV) (n=92) and non-alcoholic fatty liver disease (NAFLD) (n=62), and compared to healthy controls. Results: In CCl4-treated...

  11. Current Challenges and Limitations in Antibody-Based Detection of Citrullinated Histones

    Science.gov (United States)

    Neeli, Indira; Radic, Marko

    2016-01-01

    Studies on NETosis demand reliable and convenient markers to monitor the progress of this form of cell death. Because a determining step in the release of nuclear chromatin NETs requires the conversion of arginine residues to citrulline residues in histones by peptidylarginine deiminase, citrullinated histones can provide such a marker. Here, we evaluate antibody reagents for the detection of citrulline residues in histones and observe alarming differences between commercial antisera and mouse and rabbit monoclonal antibodies in their ability to detect their nominal target residues. Differences between antibodies that are currently used to detect citrulline residues in histones could jeopardize efforts to reach a scientific consensus and instead lead to inconsistent and even conflicting conclusions regarding the regulation of histone deimination. Our results will assist others in planning their initial or ongoing studies on peptidylarginine deiminase activity with the use of currently available antibodies. Furthermore, we argue that, along with the careful attention to experimental conditions and calcium concentrations, validated antibody reagents are urgently needed to avoid possible setbacks in the research on NETosis. PMID:27933065

  12. Current Challenges and Limitations in Antibody-Based Detection of Citrullinated Histones

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    Indira Neeli

    2016-11-01

    Full Text Available Studies on NETosis demand reliable and convenient markers to monitor the progress of this form of cell death. Because a determining step in the release of nuclear chromatin NETs requires the conversion of arginine residues to citrulline residues in histones by peptidylarginine deiminase, citrullinated histones can provide such a marker. Here, we evaluate antibody reagents for the detection of citrulline residues in histones and observe alarming differences between commercial antisera and mouse and rabbit monoclonal antibodies in their ability to detect their nominal target residues. Differences between antibodies that are currently used to detect citrulline residues in histones could jeopardize efforts to reach a scientific consensus and instead lead to inconsistent and even conflicting conclusions regarding the regulation of histone deimination. Our results will assist others in planning their initial or ongoing studies on peptidylarginine deiminase activity with the use of currently available antibodies. Further, we argue that, along with the careful attention to experimental conditions and calcium concentrations, validated antibody reagents are urgently needed to avoid possible setbacks in the research on NETosis.

  13. Impaired nitric oxide production in children with MELAS syndrome and the effect of arginine and citrulline supplementation.

    Science.gov (United States)

    El-Hattab, Ayman W; Emrick, Lisa T; Hsu, Jean W; Chanprasert, Sirisak; Almannai, Mohammed; Craigen, William J; Jahoor, Farook; Scaglia, Fernando

    2016-04-01

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most frequent maternally inherited mitochondrial disorders. The pathogenesis of this syndrome is not fully understood and believed to result from several interacting mechanisms including impaired mitochondrial energy production, microvasculature angiopathy, and nitric oxide (NO) deficiency. NO deficiency in MELAS syndrome is likely to be multifactorial in origin with the decreased availability of the NO precursors, arginine and citrulline, playing a major role. In this study we used stable isotope infusion techniques to assess NO production in children with MELAS syndrome and healthy pediatric controls. We also assessed the effect of oral arginine and citrulline supplementations on NO production in children with MELAS syndrome. When compared to control subjects, children with MELAS syndrome were found to have lower NO production, arginine flux, plasma arginine, and citrulline flux. In children with MELAS syndrome, arginine supplementation resulted in increased NO production, arginine flux, and arginine concentration. Citrulline supplementation resulted in a greater increase of these parameters. Additionally, citrulline supplementation was associated with a robust increase in citrulline concentration and flux and de novo arginine synthesis rate. The greater effect of citrulline in increasing NO production is due to its greater ability to increase arginine availability particularly in the intracellular compartment in which NO synthesis takes place. This study, which is the first one to assess NO metabolism in children with mitochondrial diseases, adds more evidence to the notion that NO deficiency occurs in MELAS syndrome, suggests a better effect for citrulline because of its greater role as NO precursor, and indicates that impaired NO production occurs in children as well as adults with MELAS syndrome. Thus, the initiation of treatment with NO precursors may be

  14. Increased plasma citrulline in mice marks diet-induced obesity and may predict the development of the metabolic syndrome.

    Science.gov (United States)

    Sailer, Manuela; Dahlhoff, Christoph; Giesbertz, Pieter; Eidens, Mena K; de Wit, Nicole; Rubio-Aliaga, Isabel; Boekschoten, Mark V; Müller, Michael; Daniel, Hannelore

    2013-01-01

    In humans, plasma amino acid concentrations of branched-chain amino acids (BCAA) and aromatic amino acids (AAA) increase in states of obesity, insulin resistance and diabetes. We here assessed whether these putative biomarkers can also be identified in two different obesity and diabetic mouse models. C57BL/6 mice with diet-induced obesity (DIO) mimic the metabolic impairments of obesity in humans characterized by hyperglycemia, hyperinsulinemia and hepatic triglyceride accumulation. Mice treated with streptozotocin (STZ) to induce insulin deficiency were used as a type 1 diabetes model. Plasma amino acid profiling of two high fat (HF) feeding trials revealed that citrulline and ornithine concentrations are elevated in obese mice, while systemic arginine bioavailability (ratio of plasma arginine to ornithine + citrulline) is reduced. In skeletal muscle, HF feeding induced a reduction of arginine levels while citrulline levels were elevated. However, arginine or citrulline remained unchanged in their key metabolic organs, intestine and kidney. Moreover, the intestinal conversion of labeled arginine to ornithine and citrulline in vitro remained unaffected by HF feeding excluding the intestine as prime site of these alterations. In liver, citrulline is mainly derived from ornithine in the urea cycle and DIO mice displayed reduced hepatic ornithine levels. Since both amino acids share an antiport mechanism for mitochondrial import and export, elevated plasma citrulline may indicate impaired hepatic amino acid handling in DIO mice. In the insulin deficient mice, plasma citrulline and ornithine levels also increased and additionally these animals displayed elevated BCAA and AAA levels like insulin resistant and diabetic patients. Therefore, type 1 diabetic mice but not DIO mice show the "diabetic fingerprint" of plasma amino acid changes observed in humans. Additionally, citrulline may serve as an early indicator of the obesity-dependent metabolic impairments.

  15. Increased plasma citrulline in mice marks diet-induced obesity and may predict the development of the metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Manuela Sailer

    Full Text Available In humans, plasma amino acid concentrations of branched-chain amino acids (BCAA and aromatic amino acids (AAA increase in states of obesity, insulin resistance and diabetes. We here assessed whether these putative biomarkers can also be identified in two different obesity and diabetic mouse models. C57BL/6 mice with diet-induced obesity (DIO mimic the metabolic impairments of obesity in humans characterized by hyperglycemia, hyperinsulinemia and hepatic triglyceride accumulation. Mice treated with streptozotocin (STZ to induce insulin deficiency were used as a type 1 diabetes model. Plasma amino acid profiling of two high fat (HF feeding trials revealed that citrulline and ornithine concentrations are elevated in obese mice, while systemic arginine bioavailability (ratio of plasma arginine to ornithine + citrulline is reduced. In skeletal muscle, HF feeding induced a reduction of arginine levels while citrulline levels were elevated. However, arginine or citrulline remained unchanged in their key metabolic organs, intestine and kidney. Moreover, the intestinal conversion of labeled arginine to ornithine and citrulline in vitro remained unaffected by HF feeding excluding the intestine as prime site of these alterations. In liver, citrulline is mainly derived from ornithine in the urea cycle and DIO mice displayed reduced hepatic ornithine levels. Since both amino acids share an antiport mechanism for mitochondrial import and export, elevated plasma citrulline may indicate impaired hepatic amino acid handling in DIO mice. In the insulin deficient mice, plasma citrulline and ornithine levels also increased and additionally these animals displayed elevated BCAA and AAA levels like insulin resistant and diabetic patients. Therefore, type 1 diabetic mice but not DIO mice show the "diabetic fingerprint" of plasma amino acid changes observed in humans. Additionally, citrulline may serve as an early indicator of the obesity-dependent metabolic

  16. Chronic tophaceous gout with anti-CCP positivity: A rare presentation

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    Vikram Haridas

    2016-07-01

    Full Text Available Persistent gout may progress into a condition termed as chronic tophaceous gout, which involves the deposition of nodular mass of uric acid crystals called tophi in various soft tissue areas of the body. Generally, the anti-cyclic citrullinated peptide (anti-CCP antibody testing is considered as a highly specific confirmatory test for RA. We present here a rare case report of chronic tophaceous gouty arthritis with anti-CCP positivity.

  17. Citrullination in Rheumatoid Arthritis—A Process Promoted by Neutrophil Lysis?

    Science.gov (United States)

    Gazitt, Tal; Lood, Christian; Elkon, Keith B.

    2016-01-01

    Anti-citrullinated protein antibodies (ACPAs) are highly specific serologic markers for rheumatoid arthritis (RA) and can pre-date clinical disease onset by up to 10 years, also predicting erosive disease. The process of citrullination, the post-translational conversion of arginine to citrulline residues, is mediated by peptidylarginine deiminase (PAD) enzymes present in polymorphonuclear cells (PMNs). Calcium ions (Ca2+) are required for PAD activation, but the intracellular Ca2+ concentration in normal cells is much lower than the optimal Ca2+ concentration needed for PAD activation. For this reason, it has been proposed that PAD activation, and thus citrullination, occurs only during PMN cell death when PAD enzymes leak out of the cells into the extracellular matrix, or extracellular Ca2+ enters the cells, with the high Ca2+ concentration activating PAD. Recently, using artificial in vitro systems to corroborate their hypothesis, Romero et al. demonstrated that “hypercitrullination,” citrullination of multiple intracellular proteins, occurs within synovial fluid (SF) cells of RA patients, and that only modes of death leading to membranolysis such as perforin-granzyme pathway or complement membrane attack complex activation cause hypercitrullination. In order for Romero’s hypothesis to hold, it is reasonable to surmise that PMN-directed lysis should occur in the rheumatoid joint or the circulation of RA patients. Research conducted thus far has shown that immunoglobulin G (IgG) targeting PMNs are present in RA SF and mediate PMN activation. However, the role of anti-PMN IgG in mediating complement activation and subsequent PMN lysis and hypercitrullination has not been fully evaluated. PMID:27824546

  18. Citrullination in Rheumatoid Arthritis—A Process Promoted by Neutrophil Lysis?

    Directory of Open Access Journals (Sweden)

    Tal Gazitt

    2016-10-01

    Full Text Available Anti-citrullinated protein antibodies (ACPAs are highly specific serologic markers for rheumatoid arthritis (RA and can pre-date clinical disease onset by up to 10 years, also predicting erosive disease. The process of citrullination, the post-translational conversion of arginine to citrulline residues, is mediated by peptidylarginine deiminase (PAD enzymes present in polymorphonuclear cells (PMNs. Calcium ions (Ca2+ are required for PAD activation, but the intracellular Ca2+ concentration in normal cells is much lower than the optimal Ca2+ concentration needed for PAD activation. For this reason, it has been proposed that PAD activation, and thus citrullination, occurs only during PMN cell death when PAD enzymes leak out of the cells into the extracellular matrix, or extracellular Ca2+ enters the cells, with the high Ca2+ concentration activating PAD. Recently, using artificial in vitro systems to corroborate their hypothesis, Romero et al. demonstrated that “hypercitrullination,” citrullination of multiple intracellular proteins, occurs within synovial fluid (SF cells of RA patients, and that only modes of death leading to membranolysis such as perforin-granzyme pathway or complement membrane attack complex activation cause hypercitrullination. In order for Romero’s hypothesis to hold, it is reasonable to surmise that PMN-directed lysis should occur in the rheumatoid joint or the circulation of RA patients. Research conducted thus far has shown that immunoglobulin G (IgG targeting PMNs are present in RA SF and mediate PMN activation. However, the role of anti-PMN IgG in mediating complement activation and subsequent PMN lysis and hypercitrullination has not been fully evaluated.

  19. Mitochondrial citrulline synthesis from ammonia and glutamine in the liver of ureogenic air-breathing catfish, Clarias batrachus (Linnaeus).

    Science.gov (United States)

    Kharbuli, Zaiba Y; Biswas, Kuheli; Saha, Nirmalendu

    2007-12-01

    The possible synthesis of citrulline, a rate limiting step for urea synthesis via the ornithine-urea cycle (OUC) in teleosts was tested both in the presence of ammonia and glutamine as nitrogen-donating substrates by the isolated liver mitochondria of ureogenic air-breathing walking catfish, C. batrachus. Both ammonia and glutamine could be used as nitrogen-donating substrates for the synthesis of citrulline by the isolated liver mitochondria, since the rate of citrulline synthesis was almost equal in presence of both the substrates. The citrulline synthesis by the isolated liver mitochondria requires succinate at a concentration of 0.1 mM as an energy source, and also requires the involvement of intramitochondrial carbonic anhydrase activity for supplying HCO3 as another substrate for citrulline synthesis. The rate of citrulline synthesis was further stimulated significantly by the isolated liver mitochondria of the fish after pre-exposure to 25 mM NH4Cl for 7 days. Due to possessing this biochemical adaptational strategy leading to the amelioration of ammonia toxicity mainly by channeling ammonia directly and/or via the formation of glutamine to the OUC, this air-breathing catfish could succeed in surviving in high external ammonia, which it faces in its natural habitat in certain seasons of the year.

  20. The 2007 ESPEN Sir David Cuthbertson Lecture: amino acids between and within organs. The glutamate-glutamine-citrulline-arginine pathway.

    Science.gov (United States)

    Deutz, Nicolaas E P

    2008-06-01

    In daily practice, the plasma concentration of amino acids is usually viewed as a parameter of production. However, both a high production and/or a reduced disposal capacity can result in an increased plasma concentration. In this presentation, I will discuss my research on interorgan relationships of the amino acids glutamate, glutamine, citrulline and arginine to explain the regulation of the plasma arginine level. The reduced glutamine disposal during liver failure is related to enhanced plasma glutamine level without any change in muscle and gut production or consumption rate. In contrast during sepsis, a small reduction in plasma glutamine is related to a substantially enhanced organ glutamate and glutamine production or consumption rate. These observations are a good example that plasma levels are directly related to production or consumption rates. Because glutamine breakdown in the gut produces citrulline, there is a good relation between the amount of metabolically active gut tissue and gut and whole body citrulline production. Arginine is produces from citrulline in the kidney and a reduced gut glutamine to citrulline conversion during sepsis explains the reduced de novo arginine production that is related to the reduced plasma arginine level. The interorgan route between muscle, gut, liver and kidney of the amino acids glutamate, glutamine, citrulline and arginine is a very good example of how complicated the regulation of plasma amino acid levels can be. However, in-depth research is necessary and will give us important clues to new nutritional strategies.

  1. Peptidylarginine deiminase 2-catalyzed histone H3 arginine 26 citrullination facilitates estrogen receptor α target gene activation.

    Science.gov (United States)

    Zhang, Xuesen; Bolt, Michael; Guertin, Michael J; Chen, Wei; Zhang, Sheng; Cherrington, Brian D; Slade, Daniel J; Dreyton, Christina J; Subramanian, Venkataraman; Bicker, Kevin L; Thompson, Paul R; Mancini, Michael A; Lis, John T; Coonrod, Scott A

    2012-08-14

    Cofactors for estrogen receptor α (ERα) can modulate gene activity by posttranslationally modifying histone tails at target promoters. Here, we found that stimulation of ERα-positive cells with 17β-estradiol (E2) promotes global citrullination of histone H3 arginine 26 (H3R26) on chromatin. Additionally, we found that the H3 citrulline 26 (H3Cit26) modification colocalizes with ERα at decondensed chromatin loci surrounding the estrogen-response elements of target promoters. Surprisingly, we also found that citrullination of H3R26 is catalyzed by peptidylarginine deiminase (PAD) 2 and not by PAD4 (which citrullinates H4R3). Further, we showed that PAD2 interacts with ERα after E2 stimulation and that inhibition of either PAD2 or ERα strongly suppresses E2-induced H3R26 citrullination and ERα recruitment at target gene promoters. Collectively, our data suggest that E2 stimulation induces the recruitment of PAD2 to target promoters by ERα, whereby PAD2 then citrullinates H3R26, which leads to local chromatin decondensation and transcriptional activation.

  2. Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology

    DEFF Research Database (Denmark)

    Vassiliadis, Efstathios; Oliveira, Claudia P; Alvares-da-Silva, Mario R;

    2012-01-01

    -citrulline (VICM) was developed and evaluated in a carbon tetrachloride (CCl(4)) (n=52 + 28 controls) rat model of liver fibrosis and two clinical cohorts of adult patients with hepatitis C (HCV) (n=92) and non-alcoholic fatty liver disease (NAFLD) (n=62), and compared to healthy controls. RESULTS: In CCl(4.......75, PNAFLD cohort, VICM levels were 20.6% higher in F0 (339...... ±12 ng/mL, PNAFLD patients. These data...

  3. Streptococcus pyogenes arginine and citrulline catabolism promotes infection and modulates innate immunity.

    Science.gov (United States)

    Cusumano, Zachary T; Watson, Michael E; Caparon, Michael G

    2014-01-01

    A bacterium's ability to acquire nutrients from its host during infection is an essential component of pathogenesis. For the Gram-positive pathogen Streptococcus pyogenes, catabolism of the amino acid arginine via the arginine deiminase (ADI) pathway supplements energy production and provides protection against acid stress in vitro. Its expression is enhanced in murine models of infection, suggesting an important role in vivo. To gain insight into the function of the ADI pathway in pathogenesis, the virulence of mutants defective in each of its enzymes was examined. Mutants unable to use arginine (ΔArcA) or citrulline (ΔArcB) were attenuated for carriage in a murine model of asymptomatic mucosal colonization. However, in a murine model of inflammatory infection of cutaneous tissue, the ΔArcA mutant was attenuated but the ΔArcB mutant was hyperattenuated, revealing an unexpected tissue-specific role for citrulline metabolism in pathogenesis. When mice defective for the arginine-dependent production of nitric oxide (iNOS(-/-)) were infected with the ΔArcA mutant, cutaneous virulence was rescued, demonstrating that the ability of S. pyogenes to utilize arginine was dispensable in the absence of nitric oxide-mediated innate immunity. This work demonstrates the importance of arginine and citrulline catabolism and suggests a novel mechanism of virulence by which S. pyogenes uses its metabolism to modulate innate immunity through depletion of an essential host nutrient.

  4. Does Citrulline Have Protective Effects on Liver Injury in Septic Rats?

    Directory of Open Access Journals (Sweden)

    Bin Cai

    2016-01-01

    Full Text Available Citrulline (Cit supplementation was proposed to serve as a therapeutic intervention to restore arginine (Arg concentrations and improve related functions in sepsis. This study explored whether citrulline had positive effects on liver injury and cytokine release in the early stages of sepsis. The cecal ligation and puncture (CLP model was utilized in our study. Rats were divided into four groups: normal, Cit, CLP, and CLP+Cit. The CLP group and CLP+Cit group were separated into 6-, 12-, and 24-hour groups, according to the time points of sacrifice after surgery. Intragastric administration of L-citrulline was applied to rats in Cit and CLP+Cit groups before surgery. Serum AST and ALT levels and levels of MDA, SOD, NO, and iNOS in the liver tissues were evaluated. Plasma concentrations of Cit and Arg were assessed using HPLC-MS/MS. Serum concentrations of cytokines and chemokines were calculated by Luminex. Results showed SOD activities of CLP+Cit groups were significantly higher than that of CLP groups, contrasting with the MDA and NO levels which were significantly lower in CLP+Cit groups than in CLP groups. In addition, plasma concentrations of TNF-α, IL-6, and IL-1β were significantly lower in the CLP+Cit 6-hour group than in the CLP 6-hour group.

  5. The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males.

    Science.gov (United States)

    Suzuki, Takashi; Morita, Masahiko; Hayashi, Toshio; Kamimura, Ayako

    2017-02-01

    We investigated the effects of combining 1 g of l-citrulline and 1 g of l-arginine as oral supplementation on plasma l-arginine levels in healthy males. Oral l-citrulline plus l-arginine supplementation more efficiently increased plasma l-arginine levels than 2 g of l-citrulline or l-arginine, suggesting that oral l-citrulline and l-arginine increase plasma l-arginine levels more effectively in humans when combined.

  6. Antibodies to mutated citrullinated vimentin in patients with chronic hepatitis C virus genotype IV infection-related arthropathy.

    Science.gov (United States)

    Zehairy, M; Soliman, E; Daghaidy, A

    2012-11-01

    One of the extra-hepatic manifestations of hepatitis C virus (HCV) infection is polyarthritis that mimics rheumatoid arthritis (RA). Anti-mutated citrullinated vimentin (MCV) was recently introduced in the diagnostic workup of RA, but its exact role in HCV infection and its related arthropathy is still unclear. The aim of the study is to determine the prevalence of anti-MCV antibodies in HCV-infected patients with or without articular involvement, and to investigate whether anti-MCV antibodies have an additional role to anticyclic citrullinated peptide (CCP) antibodies and rheumatoid factor (RF) in differentiating patients with RA from patients with HCV-related arthropathy. Fifty-five HCV-infected patients (HCV RNA positive) and 30 RA patients (fulfilling the American College of Rheumatology classification criteria for RA and negative for HCV) were included. Anti-MCV antibodies, anti-CCP antibodies, RF and cryoglobulins were measured. Articular involvement in hepatitis C patients was evaluated. Articular involvement was detected in 30/55 (54.5%) of HCV-infected patients. The most frequent pattern was symmetric polyarthralgias and the most frequent joints to be involved were the wrists, metacarpophalangeal joints, shoulders and knees. In HCV arthropathy, anti-MCV was positive in 9/30 (30%), anti-CCP in 0% and RF in 22/30 (73.3%). Whereas, in chronic HCV without arthropathy, anti-MCV was positive in 8 patients (32%), anti-CCP in one patient (4%) and RF in 23/25 (92.0%). There was no significant difference between the two HCV groups as regards the frequencies of anti-MCV (P = 0.89), anti-CCP (P = 0.93) and RF (P = 0.15). In RA, anti-MCV was positive in 93.3% anti-CCP in 96.7% and RF in 86.7%. There was no significant difference in RF between RA and HCV arthropathy (P = 0.33). Meanwhile, there was a highly significant difference between both groups regarding anti-MCV and anti-CCP (P < 0.0001 for each). The sensitivity of anti-MCV, anti-CCP and RF for RA was 93.3, 96

  7. Reduced TCR-dependent activation through citrullination of a T-cell epitope enhances Th17 development by disruption of the STAT3/5 balance

    NARCIS (Netherlands)

    Tibbitt, Christopher; Falconer, Jane; Stoop, Jeroen; van Eden, Willem; Robinson, John H.; Hilkens, Catharien M U

    2016-01-01

    Citrullination is a post-translational modification of arginine that commonly occurs in inflammatory tissues. Because T-cell receptor (TCR) signal quantity and quality can regulate T-cell differentiation, citrullination within a T-cell epitope has potential implications for T-cell effector function.

  8. Quantitative analysis of 15N labeled positional isomers of glutamine and citrulline via electrospray ionization tandem mass spectrometry of their dansyl derivatives

    Science.gov (United States)

    The enteral metabolism of glutamine and citrulline are intertwined because, while glutamine is one of the main fuel sources for the enterocyte, citrulline is one of its products. It has been shown that the administration of 15N labeled glutamine results in the incorporation of the 15N label into cit...

  9. Extracellular citrulline levels in the nucleus accumbens during the acquisition and extinction of a classical conditioned reflex with pain reinforcement.

    Science.gov (United States)

    Savel'ev, S A; Saul'skaya, N B

    2007-03-01

    Studies on Sprague-Dawley rats using in vivo microdialysis and HPLC showed that the acquisition and performance of a classical conditioned reflex with pain reinforcement was accompanied by increases in the concentrations of citrulline (a side product of nitric oxide formation) and arginine (the substrate of NO synthase) in the intercellular space of the nucleus accumbens. During extinction of the reflex, there was a decrease in the elevation of extracellular citrulline in this brain structure, which correlated with the extent of extinction of the reflex. Recovery of the reflex led to increases in arginine and citrulline levels in the nucleus accumbens. These data suggest that there is an increase in nitric oxide production in the nucleus accumbens during the acquisition and performance of a classical conditioned reflex with pain reinforcement, which decreases as the reflex is extinguished and recovers with recovery of the reflex.

  10. Enzymatic syntheses of carbamyl phosphate, L-citrulline, and N-carbamyl L-aspartate labeled with either 13N or 11C.

    Science.gov (United States)

    Gelbard, A S; Kaseman, D S; Rosenspire, K C; Meister, A

    1985-01-01

    [13N]- and [11C]carbamyl phosphate, L-[omega-13N]citrulline, L-[ureido-11C]citrulline, [carbamyl-13N]- and [carbamyl-11C]carbamyl-L-aspartate were synthesized using carbamyl phosphate synthetase co-immobilized with either aspartate transcarbamylase or ornithine transcarbamylase. Carbamyl L-[13N]aspartate was enzymatically prepared from carbamyl phosphate and L-[13N]aspartate. The tissue distribution of radioactivity in mice after injection of radiolabeled ammonia, carbamyl phosphate or citrulline was studied. The tissue distribution of isotope derived from [13N]carbamyl phosphate and [13N]ammonia were similar, with the exception of liver, brain and pancreas, in which 13NH3 uptake was higher after retroorbital injection. The distribution of label derived from L-[omega-13N]- and L-[ureido-11C]citrulline was similar. Substantial tumor (Sarcoma-180) uptake of label from L-citrulline was observed.

  11. 瓜氨酸化修饰对纤维蛋白原多肽抗原性的影响%Impact of citrullination upon antigenicity of fibrinogen

    Institute of Scientific and Technical Information of China (English)

    赵义; 田昕; 栗占国

    2010-01-01

    目的 研究瓜氨酸化修饰对人纤维蛋白原(Fg)多肽抗原性的影响,探讨针对瓜氨酸化Fg的自身免疫应答在类风湿关节炎(RA)发病中的分子机制.方法 体外对人Fg进行瓜氨酸化修饰,用修饰后Fg刺激RA患者及对照组外周血单个核细胞,通过~3H掺人法观察细胞增殖情况;通过计算机软件对人Fg α链进行瓜氨酸化修饰前后的抗原性分析,从中筛选出1条多肽,并体外合成原型肽和瓜氨酸替换肽,通过在表达HLA-DRB1细胞系中的直接肽结合试验和抗体竞争肽结合试验,评价瓜氨酸化修饰对Fg多肽与HLA-DRB1亲合力的影响;另外,在体外采用抗原提呈及活化系统,通过检测细胞增殖情况观察瓜氨酸化修饰对Fg多肽激活T细胞作用的影响.结果 瓜氨酸化修饰的Fg和野生型Fg对RA患者外周血单个核细胞的激活作用略高于对照组,但差异无统计学意义(P>0.05).多肽结合试验和细胞活化试验证实,瓜氨酸替换肽与HLA-DRB1的结合力明显高于原型肽,而且瓜氨酸替换肽对T细胞的活化作用强于原型肽,二者差异有统计学意义(SI为2.26±0.14比1.65±0.53,P 0. 05 ). As predicted, the citrullinated substitute peptide from fibrinogen alpha chain was more prone to bind to HLA-DR4 molecule than wild-type peptide and could induce a stronger proliferation of T cells than wild-type peptide (SI, 2. 26±0. 14 vs 1.65±0. 53, P<0. 01 ) in the experiments of cell lines.Conclusions Citrullination can enhance the antigenicity of fibrinogen peptides by increasing the binding of fibrinogen peptides to HLA-DR4 molecules and inducing the specific T cell activation.

  12. Citrullination of histone H3 interferes with HP1-mediated transcriptional repression.

    Directory of Open Access Journals (Sweden)

    Priyanka Sharma

    2012-09-01

    Full Text Available Multiple Sclerosis (MS is an autoimmune disease associated with abnormal expression of a subset of cytokines, resulting in inappropriate T-lymphocyte activation and uncontrolled immune response. A key issue in the field is the need to understand why these cytokines are transcriptionally activated in the patients. Here, we have examined several transcription units subject to pathological reactivation in MS, including the TNFα and IL8 cytokine genes and also several Human Endogenous RetroViruses (HERVs. We find that both the immune genes and the HERVs require the heterochromatin protein HP1α for their transcriptional repression. We further show that the Peptidylarginine Deiminase 4 (PADI4, an enzyme with a suspected role in MS, weakens the binding of HP1α to tri-methylated histone H3 lysine 9 by citrullinating histone H3 arginine 8. The resulting de-repression of both cytokines and HERVs can be reversed with the PADI-inhibitor Cl-amidine. Finally, we show that in peripheral blood mononuclear cells (PBMCs from MS patients, the promoters of TNFα, and several HERVs share a deficit in HP1α recruitment and an augmented accumulation of histone H3 with a double citrulline 8 tri-methyl lysine 9 modifications. Thus, our study provides compelling evidence that HP1α and PADI4 are regulators of both immune genes and HERVs, and that multiple events of transcriptional reactivation in MS patients can be explained by the deficiency of a single mechanism of gene silencing.

  13. Newborn screening for dihydrolipoamide dehydrogenase deficiency: Citrulline as a useful analyte

    Directory of Open Access Journals (Sweden)

    Shane C. Quinonez

    2014-01-01

    Full Text Available Dihydrolipoamide dehydrogenase deficiency, also known as maple syrup urine disease (MSUD type III, is caused by the deficiency of the E3 subunit of branched chain alpha-ketoacid dehydrogenase (BCKDH, α-ketoglutarate dehydrogenase (αKGDH, and pyruvate dehydrogenase (PDH. DLD deficiency variably presents with either a severe neonatal encephalopathic phenotype or a primarily hepatic phenotype. As a variant form of MSUD, it is considered a core condition recommended for newborn screening. The detection of variant MSUD forms has proven difficult in the past with no asymptomatic DLD deficiency patients identified by current newborn screening strategies. Citrulline has recently been identified as an elevated dried blood spot (DBS metabolite in symptomatic patients affected with DLD deficiency. Here we report the retrospective DBS analysis and second-tier allo-isoleucine testing of 2 DLD deficiency patients. We show that an elevated citrulline and an elevated allo-isoleucine on second-tier testing can be used to successfully detect DLD deficiency. We additionally recommend that DLD deficiency be included in the “citrullinemia/elevated citrulline” ACMG Act Sheet and Algorithm.

  14. l-Citrulline ameliorates cerebral blood flow during cortical spreading depression in rats: Involvement of nitric oxide- and prostanoids-mediated pathway.

    Science.gov (United States)

    Kurauchi, Yuki; Mokudai, Koichi; Mori, Asami; Sakamoto, Kenji; Nakahara, Tsutomu; Morita, Masahiko; Kamimura, Ayako; Ishii, Kunio

    2017-02-17

    l-Citrulline is a potent precursor of l-arginine, and exerts beneficial effect on cardiovascular system via nitric oxide (NO) production. Migraine is one of the most popular neurovascular disorder, and imbalance of cerebral blood flow (CBF) observed in cortical spreading depression (CSD) contributes to the mechanism of migraine aura. Here, we investigated the effect of l-citrulline on cardiovascular changes to KCl-induced CSD. in rats. Intravenous injection of l-citrulline prevented the decrease in CBF, monitored by laser Doppler flowmetry, without affecting mean arterial pressure and heart rate during CSD. Moreover, l-citrulline attenuated propagation velocity of CSD induced by KCl. The effect of l-citrulline on CBF change was prevented by l-NAME, an inhibitor of NO synthase, but not by indomethacin, an inhibitor of cyclooxygenase. On the other hand, attenuation effect of l-citrulline on CSD propagation velocity was prevented not only by l-NAME but also by indomethacin. In addition, propagation velocity of CSD was attenuated by intravenous injection of NOR3, a NO donor, which was diminished by ODQ, an inhibitor of soluble guanylyl cyclase. These results suggest that NO/cyclic GMP- and prostanoids-mediated pathway differently contribute to the effect of l-citrulline on the maintenance of CBF.

  15. Enzymatic production of l-citrulline by hydrolysis of the guanidinium group of l-arginine with recombinant arginine deiminase.

    Science.gov (United States)

    Song, Wei; Sun, Xia; Chen, Xiulai; Liu, Dongxu; Liu, Liming

    2015-08-20

    In this study, a simple, efficient enzymatic production process for the environmentally friendly synthesis of l-citrulline from l-arginine was developed using arginine deiminase (ADI) from Lactococcus lactis. Following overexpression of L. lactis ADI in Escherichia. coli BL21 (DE3) and experimental evolution using error-prone PCR, mutant FMME106 was obtained with a Km for l-arginine of 3.5mM and a specific activity of 195.7U/mg. This mutant exhibited a maximal conversion of 92.6% and achieved a final l-citrulline concentration of 176.9g/L under optimal conditions (190g/L l-arginine, 15g/L whole-cell biocatalyst treated with 2% isopropanol for 30min, 50°C, pH 7.2, 8h). The average l-citrulline synthesis rate of 22.1g/L/h is considerably higher than that reported for other similar biocatalytic approaches, therefore the process developed in the present work has great potential for large-scale production of l-citrulline.

  16. Apo AIV and Citrulline Plasma Concentrations in Short Bowel Syndrome Patients: The Influence of Short Bowel Anatomy

    Science.gov (United States)

    Targarona, Jordi; Ruiz, Jorge; García, Natalia; Oró, Denise; García-Villoria, Judit; Creus, Gloria; Pita, Ana M.

    2016-01-01

    Introduction Parenteral nutrition (PN) dependence in short bowel syndrome (SBS) patients is linked to the functionality of the remnant small bowel (RSB). Patients may wean off PN following a period of intestinal adaptation that restores this functionality. Currently, plasma citrulline is the standard biomarker for monitoring intestinal functionality and adaptation. However, available studies reveal that the relationship the biomarker with the length and function of the RSB is arguable. Thus, having additional biomarkers would improve pointing out PN weaning. Aim By measuring concomitant changes in citrulline and the novel biomarker apolipoprotein AIV (Apo AIV), as well as taking into account the anatomy of the RSB, this exploratory study aims to a better understanding of the intestinal adaptation process and characterization of the SBS patients under PN. Methods Thirty four adult SBS patients were selected and assigned to adapted (aSBS) and non-adapted (nSBS) groups after reconstructive surgeries. Remaining jejunum and ileum lengths were recorded. The aSBS patients were either on an oral diet (ORAL group), those with intestinal insufficiency, or on oral and home parenteral nutrition (HPN group), those with chronic intestinal failure. Apo AIV and citrulline were analyzed in plasma samples after overnight fasting. An exploratory ROC analysis using citrulline as gold standard was performed. Results Biomarkers, Apo AIV and citrulline showed a significant correlation with RSBL in aSBS patients. In jejuno-ileocolic patients, only Apo AIV correlated with RSBL (rb = 0.54) and with ileum length (rb = 0.84). In patients without ileum neither biomarker showed any correlation with RSBL. ROC analysis indicated the Apo AIV cut-off value to be 4.6 mg /100 mL for differentiating between the aSBS HPN and ORAL groups. Conclusions Therefore, in addition to citrulline, Apo AIV can be set as a biomarker to monitor intestinal adaptation in SBS patients. As short bowel anatomy is shown

  17. A putative transport protein is involved in citrulline excretion and re-uptake during arginine deiminase pathway activity by Lactobacillus sakei.

    Science.gov (United States)

    Rimaux, Tom; Rivière, Audrey; Hebert, Elvira María; Mozzi, Fernanda; Weckx, Stefan; De Vuyst, Luc; Leroy, Frédéric

    2013-04-01

    Arginine conversion through the arginine deiminase (ADI) pathway is a common metabolic trait of Lactobacillus sakei which is ascribed to an arc operon and which inquisitively involves citrulline excretion and re-uptake. The aim of this study was to verify whether a putative transport protein (encoded by the PTP gene) plays a role in citrulline-into-ornithine conversion by L. sakei strains. This was achieved through a combination of fermentation experiments, gene expression analysis via quantitative real-time reverse transcription PCR (RT-qPCR) and construction of a PTP knock-out mutant. Expression of the PTP gene was modulated by environmental pH and was highest in the end-exponential or mid-exponential growth phase for L. sakei strains CTC 494 and 23K, respectively. In contrast to known genes of the arc operon, the PTP gene showed low expression at pH 7.0, in agreement with the finding that citrulline-into-ornithine conversion is inhibited at this pH. The presence of additional energy sources also influenced ADI pathway activity, in particular by decreasing citrulline-into-ornithine conversion. Further insight into the functionality of the PTP gene was obtained with a knock-out mutant of L. sakei CTC 494 impaired in the PTP gene, which displayed inhibition in its ability to convert extracellular citrulline into ornithine. In conclusion, results indicated that the PTP gene may putatively encode a citrulline/ornithine antiporter.

  18. Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis - A prospective cohort study

    NARCIS (Netherlands)

    Gaalen, F.A. van; Linn-Rasker, S.P.; Venrooij, W.J.W. van; Jong, B.A. de; Breedveld, F.C.; Verweij, C.L.; Toes, R.E.M.; Huizinga, T.W.J.

    2004-01-01

    Objective. Rheumatoid arthritis (RA) is a common, severe, chronic inflammatory joint disease. Since the disease may initially be indistinguishable from other forms of arthritis, early diagnosis can be difficult. Autoantibodies seen in RA can be detected years before clinical symptoms develop. In an

  19. Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study.

    NARCIS (Netherlands)

    Gaalen, van FA; Linn-Rasker, SP; Venrooij, W.J.; Jong, B.A.; Breedveld, F.C.; Verweij, C.L.; Toes, RE; Huizinga, T.W.

    2004-01-01

    OBJECTIVE: Rheumatoid arthritis (RA) is a common, severe, chronic inflammatory joint disease. Since the disease may initially be indistinguishable from other forms of arthritis, early diagnosis can be difficult. Autoantibodies seen in RA can be detected years before clinical symptoms develop. In an

  20. Environmental pH determines citrulline and ornithine release through the arginine deiminase pathway in Lactobacillus fermentum IMDO 130101.

    Science.gov (United States)

    Vrancken, G; Rimaux, T; Weckx, S; De Vuyst, L; Leroy, F

    2009-11-15

    Sourdough lactic acid bacteria (LAB) need to be adapted to a highly acidic and, therefore, challenging environment. Different mechanisms are employed to enhance competitiveness, among which conversion of arginine into ornithine through the arginine deiminase (ADI) pathway is an important one. A combined molecular and kinetic approach of the ADI pathway in Lactobacillus fermentum IMDO 130101, a highly competitive sourdough LAB strain, identified mechanisms with advantageous technological effects and quantified the impact of these effects. First, molecular analysis of the arcBCAD operon of 4.8 kb revealed the genes encoding the enzymes ornithine transcarbamoylase, carbamate kinase, arginine deiminase, and an arginine/ornithine (A/O) antiporter, respectively, with an additional A/O antiporter 702.5 kb downstream of the ADI operon. The latter could play a role in citrulline transport. Second, pH-controlled batch fermentations were carried out, generating data for the development of a mathematical model to describe the temporal evolution of the three amino acids involved in the ADI pathway (arginine, citrulline, and ornithine) as a result of the activity of these enzymes and transporter(s). Free arginine in the medium was converted completely into a mixture of citrulline and ornithine under all conditions tested. However, the ratio between these end-products and the pattern of their formation showed variation as a function of environmental pH. Under optimal pH conditions for growth, citrulline release and some further conversion into ornithine was observed. When growing under sub-optimal pH conditions, ornithine was the main product of the ADI pathway. These kinetic data suggest a role in adaptation of L. fermentum IMDO 130101 to growth under sub-optimal conditions.

  1. Modular pathway engineering of Corynebacterium glutamicum for production of the glutamate-derived compounds ornithine, proline, putrescine, citrulline, and arginine.

    Science.gov (United States)

    Jensen, Jaide V K; Eberhardt, Dorit; Wendisch, Volker F

    2015-11-20

    The glutamate-derived bioproducts ornithine, citrulline, proline, putrescine, and arginine have applications in the food and feed, cosmetic, pharmaceutical, and chemical industries. Corynebacterium glutamicum is not only an excellent producer of glutamate but also of glutamate-derived products. Here, engineering targets beneficial for ornithine production were identified and the advantage of rationally constructing a platform strain for the production of the amino acids citrulline, proline, and arginine, and the diamine putrescine was demonstrated. Feedback alleviation of N-acetylglutamate kinase, tuning of the promoter of glutamate dehydrogenase gene gdh, lowering expression of phosphoglucoisomerase gene pgi, along with the introduction of a second copy of the arginine biosynthesis operon argCJB(A49V,M54V)D into the chromosome resulted in a C. glutamicum strain producing ornithine with a yield of 0.52 g ornithine per g glucose, an increase of 71% as compared to the parental ΔargFRG strain. Strains capable of producing 0.41 g citrulline per g glucose, 0.29 g proline per g glucose, 0.30 g arginine per g glucose, and 0.17 g putrescine per g glucose were derived from the ornithine-producing platform strain by plasmid-based overexpression of appropriate pathway modules with one to three genes.

  2. The Supplementation of Branched-Chain Amino Acids, Arginine, and Citrulline Improves Endurance Exercise Performance in Two Consecutive Days

    Directory of Open Access Journals (Sweden)

    I-Shiung Cheng, Yi-Wen Wang, I-Fan Chen, Gi-Sheng Hsu, Chun-Fang Hsueh, Chen-Kang Chang

    2016-09-01

    Full Text Available The central nervous system plays a crucial role in fatigue during endurance exercise. Branched-chain amino acids (BCAA could reduce cerebral serotonin synthesis by competing with its precursor tryptophan for crossing the blood brain barrier. Arginine and citrulline could prevent excess hyperammonemia accompanied by BCAA supplementation. This study investigated the combination of BCAA, arginine, and citrulline on endurance performance in two consecutive days. Seven male and three female endurance runners ingested 0.17 g·kg-1 BCAA, 0.05 g·kg-1 arginine and 0.05 g·kg-1 citrulline (AA trial or placebo (PL trial in a randomized cross-over design. Each trial contained a 5000 m time trial on the first day, and a 10000 m time trial on the second day. The AA trial had significantly better performance in 5000 m (AA: 1065.7 ± 33.9 s; PL: 1100.5 ± 40.4 s and 10000 m (AA: 2292.0 ± 211.3 s; PL: 2375.6 ± 244.2 s. The two trials reported similar ratings of perceived exertion. After exercise, the AA trial had significantly lower tryptophan/BCAA ratio, similar NH3, and significantly higher urea concentrations. In conclusion, the supplementation could enhance time-trial performance in two consecutive days in endurance runners, possibly through the inhibition of cerebral serotonin synthesis by BCAA and the prevention of excess hyperammonemia by increased urea genesis.

  3. Asymmetric Dimethylarginine Is a Well Established Mediating Risk Factor for Cardiovascular Morbidity and Mortality-Should Patients with Elevated Levels Be Supplemented with Citrulline?

    Science.gov (United States)

    McCarty, Mark F

    2016-07-08

    The arginine metabolite asymmetric dimethylarginine (ADMA) is a competitive inhibitor and uncoupler of endothelial nitric oxide synthase (eNOS), an enzyme that acts in multifarious ways to promote cardiovascular health. This phenomenon likely explains, at least in part, why elevated ADMA has been established as an independent risk factor for cardiovascular events, ventricular hypertrophy, and cardiovascular mortality. Fortunately, the suppressive impact of ADMA on eNOS activity can be offset by increasing intracellular arginine levels with supplemental citrulline. Although the long-term impact of supplemental citrulline on cardiovascular health in patients with elevated ADMA has not yet been studied, shorter-term clinical studies of citrulline administration demonstrate effects suggestive of increased NO synthesis, such as reductions in blood pressure and arterial stiffness, improved endothelium-dependent vasodilation, increased erection hardness, and increased ejection fractions in patients with heart failure. Supplemental citrulline could be a practical option for primary or secondary prevention of cardiovascular events and mortality, as it is inexpensive, has a mild flavor, and is well tolerated in doses (3-6 g daily) that can influence eNOS activity. Large and long-term clinical trials, targeting patients at high risk for cardiovascular events in whom ADMA is elevated, are needed to evaluate citrulline's potential for aiding cardiovascular health.

  4. The presence of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor on patients with rheumatoid arthritis (RA) does not interfere with the chance of clinical remission in a follow-up of 3 years.

    Science.gov (United States)

    da Mota, Licia Maria Henrique; Dos Santos Neto, Leopoldo Luiz; de Carvalho, Jozélio Freire; Pereira, Ivânio Alves; Burlingame, Rufus; Ménard, Henri A; Laurindo, Ieda Maria Magalhães

    2012-12-01

    Autoantibodies in early rheumatoid arthritis (RA) have important diagnostic value. The association between the presence of autoantibodies against cyclic citrullinated peptide and the response to treatment is controversial. To prospectively evaluate a cohort of patients with early rheumatoid arthritis (peptide antibodies (anti-CCP) and citrullinated anti-vimentin (anti-Sa) with the occurrence of clinical remission, forty patients diagnosed with early RA at the time of diagnosis were evaluated and followed for 3 years, in use of standardized therapeutic treatment. Demographic and clinical data were recorded, disease activity score 28 (DAS 28), as well as serology tests (ELISA) for RF (IgM, IgG, and IgA), anti-CCP (CCP2, CCP3, and CCP3.1) and anti-Sa in the initial evaluation and at 3, 6, 12, 18, 24, and 36 months of follow-up. The outcome evaluated was the percentage of patients with clinical remission, which was defined by DAS 28 lower than 2.6. Comparisons were made through the Student t test, mixed-effects regression analysis, and analysis of variance (significance level of 5%). The mean age was 45 years, and a female predominance was observed (90%). At the time of diagnosis, RF was observed in 50% of cases (RF IgA-42%, RF IgG-30%, and RF IgM-50%), anti-CCP in 50% (no difference between CCP2, CCP3, and CCP3.1) and anti-Sa in 10%. After 3 years, no change in the RF prevalence and anti-CCP was observed, but the anti-Sa increased to 17.5% (P = 0.001). The percentage of patients in remission, low, moderate, and intense disease activity, according to the DAS 28, was of 0, 0, 7.5, and 92.5% (initial evaluation) and 22.5, 7.5, 32.5, and 37.5% (after 3 years). There were no associations of the presence of autoantibodies in baseline evaluation and in serial analysis with the percentage of clinical remission during follow-up of 3 years The presence of autoantibodies in early RA has no predictive value for clinical remission in early RA.

  5. A novel role for protein arginine deiminase 4 in pluripotency: the emerging role of citrullinated histone H1 in cellular programming.

    Science.gov (United States)

    Slade, Daniel J; Horibata, Sachi; Coonrod, Scott A; Thompson, Paul R

    2014-08-01

    Histone post-translational modifications (PTMs) alter the chromatin architecture, generating "open" and "closed" states, and these structural changes can modulate gene expression under specific cellular conditions. While methylation and acetylation are the best-characterized histone PTMs, citrullination by the protein arginine deiminases (PADs) represents another important player in this process. In addition to "fine tuning" chromatin structure at specific loci, histone citrullination can also promote rapid global chromatin decondensation during the formation of extracellular traps (ETs) in immune cells. Recent studies now show that PAD4-mediated citrullination of histone H1 at promoter elements can also promote localized chromatin decondensation in stem cells, thus regulating the pluripotent state. These observations suggest that PAD-mediated histone deimination profoundly affects chromatin structure, possibly above and beyond that of other PTMs. Additionally, these recent findings further enhance our understanding of PAD biology and the important contributions that these enzymes play in development, health, and disease.

  6. Demonstration of extracellular peptidylarginine deiminase (PAD) activity in synovial fluid of patients with rheumatoid arthritis using a novel assay for citrullination of fibrinogen

    DEFF Research Database (Denmark)

    Damgaard, Dres; Senolt, Ladislav; Nielsen, Michael Friberg

    2014-01-01

    INTRODUCTION: Members of the peptidylarginine deiminase (PAD) family catalyse the posttranslational conversion of peptidylarginine to peptidylcitrulline. Citrullination of proteins is well described in rheumatoid arthritis (RA), and hypercitrullination of proteins may be related to inflammation...... in general. PAD activity has been demonstrated in various cell lysates, but so far not in synovial fluid. We aimed to develop an assay for detection of PAD activity, if any, in synovial fluid from RA patients. METHODS: An enzyme-linked immunosorbent assay using human fibrinogen as the immobilized substrate...... for citrullination and anti-citrullinated fibrinogen antibody as the detecting agent were used for measurement of PAD activity in synovial fluid samples from five RA patients. The concentrations of PAD2 and calcium were also determined. RESULTS: Approximately 150 times lower levels of recombinant human PAD2 (rhPAD2...

  7. Peptide identification

    Science.gov (United States)

    Jarman, Kristin H [Richland, WA; Cannon, William R [Richland, WA; Jarman, Kenneth D [Richland, WA; Heredia-Langner, Alejandro [Richland, WA

    2011-07-12

    Peptides are identified from a list of candidates using collision-induced dissociation tandem mass spectrometry data. A probabilistic model for the occurrence of spectral peaks corresponding to frequently observed partial peptide fragment ions is applied. As part of the identification procedure, a probability score is produced that indicates the likelihood of any given candidate being the correct match. The statistical significance of the score is known without necessarily having reference to the actual identity of the peptide. In one form of the invention, a genetic algorithm is applied to candidate peptides using an objective function that takes into account the number of shifted peaks appearing in the candidate spectrum relative to the test spectrum.

  8. L-citrulline protects from kidney damage in type 1 diabetic mice.

    Directory of Open Access Journals (Sweden)

    Maritza J Romero

    2013-12-01

    Full Text Available Rationale. Diabetic nephropathy is a major cause of end-stage renal disease, associated with endothelial dysfunction. Chronic supplementation of L-arginine (L-arg, the substrate for endothelial nitric oxide synthase (eNOS, failed to improve vascular function. L-citrulline (L-cit supplementation not only increases L-arg synthesis, but also inhibits cytosolic arginase I (Arg I, a competitor of eNOS for the use of L-arg, in the vasculature. Aims. To investigate whether L-cit treatment reduces diabetic nephropathy in streptozotocin (STZ-induced type 1 diabetes in mice and rats and to study its effects on arginase II (ArgII function, the main renal isoform. Methods. STZ-C57BL6 mice received L-cit or vehicle supplemented in the drinking water. For comparative analysis, diabetic ArgII knock out mice and L-cit-treated STZ-rats were evaluated. Results. L-cit exerted protective effects in kidneys of STZ-rats, and markedly reduced urinary albumin excretion, tubulo-interstitial fibrosis and kidney hypertrophy, observed in untreated diabetic mice. Intriguingly, L-cit treatment was accompanied by a sustained elevation of tubular ArgII at 16 wks and significantly enhanced plasma levels of the anti-inflammatory cytokine IL-10. Diabetic ArgII knock out mice showed greater BUN levels, hypertrophy, and dilated tubules than diabetic wild type mice. Despite a marked reduction in collagen deposition in ArgII knock out mice, their albuminuria was not significantly different from diabetic wild type animals. L-cit also restored NO/ROS balance and barrier function in high glucose-treated monolayers of human glomerular endothelial cells. Moreover, L-cit also has the ability to establish an anti-inflammatory profile, characterized by increased IL-10 and reduced IL-1beta and IL-12(p70 generation in the human proximal tubular cells. Conclusions. L-cit supplementation established an anti-inflammatory profile and significantly preserved the nephron function during type 1

  9. Are plasma citrulline and glutamine biomarkers of intestinal absorptive function in patients with short bowel syndrome?

    Science.gov (United States)

    Luo, Menghua; Fernández-Estívariz, Concepción; Manatunga, Amita K; Bazargan, Niloofar; Gu, Li H; Jones, Dean P; Klapproth, Jan-Michael; Sitaraman, Shanthi V; Leader, Lorraine M; Galloway, John R; Ziegler, Thomas R

    2007-01-01

    Sensitive biomarkers for intestinal absorptive function would be clinically useful in short bowel syndrome (SBS). Citrulline (Cit) is a product of the metabolism of glutamine (Gln) and derived amino acids by enterocytes. Cit is produced almost exclusively by the gut, which is also a major site of Gln metabolism. The goals of this study were to examine whether plasma Cit and Gln concentrations are biomarkers of residual small intestinal length and nutrient absorptive functions in adult SBS patients followed prospectively. We studied 24 stable adults with severe SBS receiving chronic parenteral nutrition (PN) in a double-blind, randomized trial of individualized dietary modification +/- recombinant human growth hormone (GH). During a baseline week, intestinal absorption studies (% absorption of fluid, kcal, nitrogen, fat, carbohydrate, sodium, phosphorus, and magnesium) were performed and concomitant plasma Cit and Gln concentrations determined. Individualized dietary modification and treatment with subcutaneous injection of placebo (n = 9) or GH (0.1 mg/kg daily x 21 days, then 3 times/week; n = 15) were then begun. PN weaning was initiated after week 4 and continued as tolerated for 24 weeks. Repeat plasma amino acid determination and nutrient absorption studies were performed at weeks 4 and 12. Residual small bowel length at baseline was positively correlated with baseline plasma Cit (r = 0.467; p = .028). However, no significant correlations between absolute Cit or Gln concentrations and the percent absorption of nutrient substrates at any time point were observed. Similarly, no correlation between the change in Cit or GLN concentration and the change in % nutrient absorption was observed (baseline vs weeks 4 and 12, respectively). By weeks 12 and 24, 7 and 13 subjects were weaned completely from PN, respectively. However, baseline plasma Cit or Gln did not predict PN weaning at these time points. We concluded that plasma Cit (but not Gln) concentrations appeared

  10. Asymmetric Dimethylarginine Is a Well Established Mediating Risk Factor for Cardiovascular Morbidity and Mortality—Should Patients with Elevated Levels Be Supplemented with Citrulline?

    Science.gov (United States)

    McCarty, Mark F.

    2016-01-01

    The arginine metabolite asymmetric dimethylarginine (ADMA) is a competitive inhibitor and uncoupler of endothelial nitric oxide synthase (eNOS), an enzyme that acts in multifarious ways to promote cardiovascular health. This phenomenon likely explains, at least in part, why elevated ADMA has been established as an independent risk factor for cardiovascular events, ventricular hypertrophy, and cardiovascular mortality. Fortunately, the suppressive impact of ADMA on eNOS activity can be offset by increasing intracellular arginine levels with supplemental citrulline. Although the long-term impact of supplemental citrulline on cardiovascular health in patients with elevated ADMA has not yet been studied, shorter-term clinical studies of citrulline administration demonstrate effects suggestive of increased NO synthesis, such as reductions in blood pressure and arterial stiffness, improved endothelium-dependent vasodilation, increased erection hardness, and increased ejection fractions in patients with heart failure. Supplemental citrulline could be a practical option for primary or secondary prevention of cardiovascular events and mortality, as it is inexpensive, has a mild flavor, and is well tolerated in doses (3–6 g daily) that can influence eNOS activity. Large and long-term clinical trials, targeting patients at high risk for cardiovascular events in whom ADMA is elevated, are needed to evaluate citrulline’s potential for aiding cardiovascular health. PMID:27417628

  11. Asymmetric Dimethylarginine Is a Well Established Mediating Risk Factor for Cardiovascular Morbidity and Mortality—Should Patients with Elevated Levels Be Supplemented with Citrulline?

    Directory of Open Access Journals (Sweden)

    Mark F. McCarty

    2016-07-01

    Full Text Available The arginine metabolite asymmetric dimethylarginine (ADMA is a competitive inhibitor and uncoupler of endothelial nitric oxide synthase (eNOS, an enzyme that acts in multifarious ways to promote cardiovascular health. This phenomenon likely explains, at least in part, why elevated ADMA has been established as an independent risk factor for cardiovascular events, ventricular hypertrophy, and cardiovascular mortality. Fortunately, the suppressive impact of ADMA on eNOS activity can be offset by increasing intracellular arginine levels with supplemental citrulline. Although the long-term impact of supplemental citrulline on cardiovascular health in patients with elevated ADMA has not yet been studied, shorter-term clinical studies of citrulline administration demonstrate effects suggestive of increased NO synthesis, such as reductions in blood pressure and arterial stiffness, improved endothelium-dependent vasodilation, increased erection hardness, and increased ejection fractions in patients with heart failure. Supplemental citrulline could be a practical option for primary or secondary prevention of cardiovascular events and mortality, as it is inexpensive, has a mild flavor, and is well tolerated in doses (3–6 g daily that can influence eNOS activity. Large and long-term clinical trials, targeting patients at high risk for cardiovascular events in whom ADMA is elevated, are needed to evaluate citrulline’s potential for aiding cardiovascular health.

  12. Citrullination of central nervous system proteins during the development of experimental autoimmune encephalomyelitis.

    NARCIS (Netherlands)

    Raijmakers, R.; Vogelzangs, J.H.P.; Croxford, J.L.; Wesseling, P.; Venrooij, W.J.W. van; Pruijn, G.J.M.

    2005-01-01

    Immunization of mammals with central nervous system (CNS)-derived proteins or peptides induces experimental autoimmune encephalomyelitis (EAE), a disease resembling the human autoimmune disease multiple sclerosis (MS). Both diseases are accompanied by destruction of a part of the of the myelin sheat

  13. Identification of urinary peptide biomarkers associated with rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Angelique Stalmach

    Full Text Available Early diagnosis and treatment of rheumatoid arthritis are associated with improved outcomes but current diagnostic tools such as rheumatoid factor or anti-citrullinated protein antibodies have shown limited sensitivity. In this pilot study we set out to establish a panel of urinary biomarkers associated with rheumatoid arthritis using capillary electrophoresis coupled to mass spectrometry. We compared the urinary proteome of 33 participants of the Scottish Early Rheumatoid Arthritis inception cohort study with 30 healthy controls and identified 292 potential rheumatoid arthritis-specific peptides. Amongst them, 39 were used to create a classifier model using support vector machine algorithms. Specific peptidic fragments were differentially excreted between groups; fragments of protein S100-A9 and gelsolin were less abundant in rheumatoid arthritis while fragments of uromodulin, complement C3 and fibrinogen were all increasingly excreted. The model generated was subsequently tested in an independent test-set of 31 samples. The classifier demonstrated a sensitivity of 88% and a specificity of 93% in diagnosing the condition, with an area under the receiver operating characteristic curve of 0.93 (p<0.0001. These preliminary results suggest that urinary biomarkers could be useful in the early diagnosis of rheumatoid arthritis. Further studies are currently being undertaken in larger cohorts of patients with rheumatoid arthritis and other athridities to assess the potential of the urinary peptide based classifier in the early detection of rheumatoid arthritis.

  14. A tale of two citrullines--structural and functional aspects of myelin basic protein deimination in health and disease.

    Science.gov (United States)

    Harauz, George; Musse, Abdiwahab A

    2007-02-01

    Myelin basic protein (MBP) binds to negatively charged lipids on the cytosolic surface of oligodendrocyte membranes and is responsible for adhesion of these surfaces in the multilayered myelin sheath. The pattern of extensive post-translational modifications of MBP is dynamic during normal central nervous system (CNS) development and during myelin degeneration in multiple sclerosis (MS), affecting its interactions with the myelin membranes and with other molecules. In particular, the degree of deimination (or citrullination) of MBP is correlated with the severity of MS, and may represent a primary defect that precedes neurodegeneration due to autoimmune attack. That the degree of MBP deimination is also high in early CNS development indicates that this modification plays major physiological roles in myelin assembly. In this review, we describe the structural and functional consequences of MBP deimination in healthy and diseased myelin.

  15. Antimicrobial Peptides

    Directory of Open Access Journals (Sweden)

    Ali Adem Bahar

    2013-11-01

    Full Text Available The rapid increase in drug-resistant infections has presented a serious challenge to antimicrobial therapies. The failure of the most potent antibiotics to kill “superbugs” emphasizes the urgent need to develop other control agents. Here we review the history and new development of antimicrobial peptides (AMPs, a growing class of natural and synthetic peptides with a wide spectrum of targets including viruses, bacteria, fungi, and parasites. We summarize the major types of AMPs, their modes of action, and the common mechanisms of AMP resistance. In addition, we discuss the principles for designing effective AMPs and the potential of using AMPs to control biofilms (multicellular structures of bacteria embedded in extracellular matrixes and persister cells (dormant phenotypic variants of bacterial cells that are highly tolerant to antibiotics.

  16. Effects of Supplemental Citrulline-Malate Ingestion on Blood Lactate, Cardiovascular Dynamics, and Resistance Exercise Performance in Trained Males.

    Science.gov (United States)

    Wax, Benjamin; Kavazis, Andreas N; Luckett, William

    2016-01-01

    Citrulline-malate (CM) has been proposed to provide an ergogenic effect during resistance exercise; however, there is a paucity of research investigating these claims. Therefore, we investigated the impact that CM supplementation would have on repeated bouts of resistance exercise. Fourteen resistance-trained males participated in a randomized, counterbalanced, double-blind study. Subjects were randomly assigned to placebo (PL) or CM (8 g) and performed three sets each of chin-ups, reverse chin-ups, and push-ups to failure. One week later, subjects ingested the other supplement and performed the same protocol. Blood lactate (BLa), heart rate (HR), and blood pressure (BP) were measured preexercise, with BLa measured a second time immediately following the last set, while HR and BP were measured 5 and 10 min postexercise. Citrulline-malate ingestion significantly increased the amount of repetitions performed for each exercise (chin-ups: PL = 28.4 ± 7.1, CM = 32.2 ± 5.6, p = .003; reverse chin-ups: PL = 26.6 ± 5.6, CM = 32.1 ± 7.1, p = .017; push-ups: PL = 89.1 ± 37.4, CM = 97.7 ± 36.1, p < .001). Blood lactate data indicated a time effect (p < .001), but no treatment differences (p = .935). Systolic BP data did not show differences for time (p = .078) or treatment (p = .119). Diastolic BP data did not show differences for time (p = .069), but indicated treatment differences (p = .014) for subjects ingesting CM. Collectively, these findings suggests that CM increased upper-body resistance performance in trained college-age males.

  17. Periodontitis increases rheumatic factor serum levels and citrullinated proteins in gingival tissues and alter cytokine balance in arthritic rats

    Science.gov (United States)

    Corrêa, Mônica G.; Sacchetti, Silvana B.; Ribeiro, Fernanda Vieira; Pimentel, Suzana Peres; Casarin, Renato Corrêa Viana; Cirano, Fabiano Ribeiro; Casati, Marcio Z.

    2017-01-01

    This study investigated some immunological features by experimental periodontitis (EP) and rheumatoid arthritis (RA) disease interact in destructive processes in arthritic rats. Rats were assigned to the following groups: EP +RA; RA; EP; and Negative Control. RA was induced by immunizations with type-II collagen and a local immunization with Complete Freund’s adjuvant in the paw. Periodontitis was induced by ligating the right first molars. The serum level of rheumatoid factor (RF) and anti-citrullinated protein antibody (ACCPA) were measured before the induction of EP (T1) and at 28 days after (T2) by ELISA assay. ACCPA levels were also measured in the gingival tissue at T2. The specimens were processed for morphometric analysis of bone loss, and the gingival tissue surrounding the first molar was collected for the quantification of interleukin IL-1β, IL-4, IL-6, IL-17 and TNF-α using a Luminex/MAGpix assay. Paw edema was analyzed using a plethysmometer. Periodontitis increased the RF and ACCPA levels in the serum and in the gingival tissue, respectively. Besides, the level of paw swelling was increased by EP and remained in progress until the end of the experiment, when EP was associated with RA. Greater values of IL-17 were observed only when RA was present, in spite of PE. It can be concluded that periodontitis increases rheumatic factor serum levels and citrullinated proteins level in gingival tissues and alter cytokine balance in arthritic rats; at the same time, arthritis increases periodontal destruction, confirming the bidirectional interaction between diseases. PMID:28358812

  18. Peptide arrays for screening cancer specific peptides.

    Science.gov (United States)

    Ahmed, Sahar; Mathews, Anu Stella; Byeon, Nara; Lavasanifar, Afsaneh; Kaur, Kamaljit

    2010-09-15

    In this paper, we describe a novel method to screen peptides for specific recognition by cancer cells. Seventy peptides were synthesized on a cellulose membrane in an array format, and a direct method to study the peptide-whole cell interaction was developed. The relative binding affinity of the cells for different peptides with respect to a lead 12-mer p160 peptide, identified by phage display, was evaluated using the CyQUANT fluorescence of the bound cells. Screening allowed identification of at least five new peptides that displayed higher affinity (up to 3-fold) for MDA-MB-435 and MCF-7 human cancer cells compared to the p160 peptide. These peptides showed very little binding to the control (noncancerous) human umbilical vein endothelial cells (HUVECs). Three of these peptides were synthesized separately and labeled with fluorescein isothiocyanate (FITC) to study their uptake and interaction with the cancer and control cells using confocal laser scanning microscopy and flow cytometry. The results confirmed the high and specific affinity of an 11-mer peptide 11 (RGDPAYQGRFL) and a 10-mer peptide 18 (WXEAAYQRFL) for the cancer cells versus HUVECs. Peptide 11 binds different receptors on target cancer cells as its sequence contains multiple recognition motifs, whereas peptide 18 binds mainly to the putative p160 receptor. The peptide array-whole cell binding assay reported here is a complementary method to phage display for further screening and optimization of cancer targeting peptides for cancer therapy and diagnosis.

  19. Effect of an hyperbaric nitrogen narcotic ambience on arginine and citrulline levels, the precursor and co-product of nitric oxide, in rat striatum.

    Science.gov (United States)

    Vallée, Nicolas; Rissoe, Jean-Jacques; Blatteau, Jean-Eric

    2011-07-05

    Previous studies performed in the laboratory have shown that nitrogen narcosis induces a decrease in striatal glutamate and dopamine levels. Although we stimulated the N-methyl-D-aspartate (NMDA) receptor, an important glutamate receptor required for motor and locomotor activity managed by the striatum, and demonstrated that the receptor was effective when exposed to nitrogen at 3MPa, it was not possible to return the striatal glutamate level to its base values. We conclude that it was the striatopetal neurons of the glutamatergic pathways that were mainly affected in this hyperbaric syndrome, without understanding the principal reasons. Hence we sought to establish what happens in the vicinity of the plasma membrane, downstream the NMDA-Receptor, and we used the hypothesis that there could be neuronal nitric oxide synthase (nNOS) disturbances. A microdialysis study was performed in rat striatum in order to analyse levels of citrulline, the NO co-product, and arginine, the NO precursor. Those both NO metabolites were detectable with an HPLC coupled to a fluorimetric detector. Exposure to pressurized nitrogen induced a reduction in citrulline (-18.9%) and arginine (-10.4%) levels. Under the control normobaric conditions, the striatal NMDA infusion enhanced the citrulline level (+85.6%), whereas under 3 MPa of nitrogen, the same NMDA infusion did not change the citrulline level which remains equivalent to that of the baseline. The level of arginine increased (+45.7%) under normobaric conditions but a decrease occurred in pressurized nitrogen (-51.6%). Retrodialysis with Saclofen and KCl in the prefrontal cortex under normobaric conditions led to an increase in striatal levels of citrulline (+30.5%) and a decrease in arginine levels (-67.4%). There was no significant difference when nitrogen at 3MPa was added. To conclude, the synthesis of citrulline/NO is reduced in nitrogen narcosis while it seems possible to activate it artificially by infusion. We have suggested

  20. Effect of an hyperbaric nitrogen narcotic ambience on arginine and citrulline levels, the precursor and co-product of nitric oxide, in rat striatum

    Directory of Open Access Journals (Sweden)

    Vallée Nicolas

    2011-07-01

    Full Text Available Abstract Previous studies performed in the laboratory have shown that nitrogen narcosis induces a decrease in striatal glutamate and dopamine levels. Although we stimulated the N-methyl-D-aspartate (NMDA receptor, an important glutamate receptor required for motor and locomotor activity managed by the striatum, and demonstrated that the receptor was effective when exposed to nitrogen at 3MPa, it was not possible to return the striatal glutamate level to its base values. We conclude that it was the striatopetal neurons of the glutamatergic pathways that were mainly affected in this hyperbaric syndrome, without understanding the principal reasons. Hence we sought to establish what happens in the vicinity of the plasma membrane, downstream the NMDA-Receptor, and we used the hypothesis that there could be neuronal nitric oxide synthase (nNOS disturbances. A microdialysis study was performed in rat striatum in order to analyse levels of citrulline, the NO co-product, and arginine, the NO precursor. Those both NO metabolites were detectable with an HPLC coupled to a fluorimetric detector. Exposure to pressurized nitrogen induced a reduction in citrulline (-18.9% and arginine (-10.4% levels. Under the control normobaric conditions, the striatal NMDA infusion enhanced the citrulline level (+85.6%, whereas under 3 MPa of nitrogen, the same NMDA infusion did not change the citrulline level which remains equivalent to that of the baseline. The level of arginine increased (+45.7% under normobaric conditions but a decrease occurred in pressurized nitrogen (-51.6%. Retrodialysis with Saclofen and KCl in the prefrontal cortex under normobaric conditions led to an increase in striatal levels of citrulline (+30.5% and a decrease in arginine levels (-67.4%. There was no significant difference when nitrogen at 3MPa was added. To conclude, the synthesis of citrulline/NO is reduced in nitrogen narcosis while it seems possible to activate it artificially by infusion

  1. Effects of type II collagen epitope carbamylation and citrullination in human leucocyte antigen (HLA)-DR4(+) monozygotic twins discordant for rheumatoid arthritis.

    Science.gov (United States)

    De Santis, M; Ceribelli, A; Cavaciocchi, F; Generali, E; Massarotti, M; Isailovic, N; Crotti, C; Scherer, H U; Montecucco, C; Selmi, C

    2016-09-01

    The aim of this study is to investigate the effect of the native, citrullinated or carbamylated type II human collagen T cell- and B cell-epitopes on the adaptive immune response in rheumatoid arthritis (RA). Peripheral blood T and B cells obtained from a human leucocyte D4-related (antigen DR4(-) HLA-DR4)(+) woman with early RA, her healthy monozygotic twin and an unrelated HLA-DR3(+) woman with early RA were analysed for activation (CD154/CD69), apoptosis (annexin/7-aminoactinomycin), cytokine production [interferon (IFN)γ/interleukin (IL)-17/IL-4/IL-10/IL-6] and functional phenotype (CD45Ra/CCR7) after stimulation with the collagen native T cell epitope (T261-273), the K264 carbamylated T cell epitope (carT261-273), the native B cell epitope (B359-369) or the R360 citrullinated B cell epitope (citB359-369), and the combinations of these. The T cell memory compartment was activated by T cell epitopes in both discordant DR4(+) twins, but not in the DR3(+) RA. The collagen-specific activation of CD4(+) T cells was induced with both the native and carbamylated T cell epitopes only in the RA twin. Both T cell epitopes also induced IL-17 production in the RA twin, but a greater IL-4 and IL-10 response in the healthy twin. The citrullinated B cell epitope, particularly when combined with the carbamylated T cell epitope, induced B cell activation and an increased IL-6/IL-10 ratio in the RA twin compared to a greater IL-10 production in the healthy twin. Our data suggest that circulating collagen-specific T and B cells are found in HLA-DR4(+) subjects, but only RA activated cells express co-stimulatory molecules and produce proinflammatory cytokines. Carbamylation and citrullination further modulate the activation and cytokine polarization of T and B cells.

  2. Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case–control study

    OpenAIRE

    Fisher, Benjamin A; Cartwright, Alison J; Quirke, Anne-Marie; de Pablo, Paola; Romaguera, Dora; Panico, Salvatore; Mattiello, Amalia; Gavrila, Diana; Navarro, Carmen; Sacerdote, Carlotta; Vineis, Paolo; Tumino, Rosario; Lappin, David F; Apazidou, Danae; Culshaw, Shauna

    2015-01-01

    Background: \\ud Antibodies to citrullinated proteins (ACPA) occur years before RA diagnosis. Porphyromonas gingivalis expresses its own peptidylarginine deiminase (PPAD), and is a proposed aetiological factor for the ACPA response. Smoking is a risk factor for both ACPA-positive RA and periodontitis. We aimed to study the relation of these factors to the risk of RA in a prospective cohort.\\ud \\ud Methods: \\ud We performed a nested case–control study by identifying pre-RA cases in four populat...

  3. Roles of export genes cgmA and lysE for the production of L-arginine and L-citrulline by Corynebacterium glutamicum.

    Science.gov (United States)

    Lubitz, Dorit; Jorge, João M P; Pérez-García, Fernando; Taniguchi, Hironori; Wendisch, Volker F

    2016-10-01

    L-arginine is a semi-essential amino acid with application in cosmetic, pharmaceutical, and food industries. Metabolic engineering strategies have been applied for overproduction of L-arginine by Corynebacterium glutamicum. LysE was the only known L-arginine exporter of this bacterium. However, an L-arginine-producing strain carrying a deletion of lysE still accumulated about 10 mM L-arginine in the growth medium. Overexpression of the putative putrescine and cadaverine export permease gene cgmA was shown to compensate for the lack of lysE with regard to L-arginine export. Moreover, plasmid-borne overexpression of cgmA rescued the toxic effect caused by feeding of the dipeptide Arg-Ala to lysE-deficient C. glutamicum and argO-deficient Escherichia coli strains. Deletion of the repressor gene cgmR improved L-arginine titers by 5 %. Production of L-lysine and L-citrulline was not affected by cgmA overexpression. Taken together, CgmA may function as an export system not only for the diamine putrescine and cadaverine but also for L-arginine. The major export system for L-lysine and L-arginine LysE may also play a role in L-citrulline export since production of L-citrulline was reduced when lysE was deleted and improved by 45 % when lysE was overproduced.

  4. Human peptide transporters

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Brodin, Birger; Jørgensen, Flemming Steen;

    2002-01-01

    Peptide transporters are epithelial solute carriers. Their functional role has been characterised in the small intestine and proximal tubules, where they are involved in absorption of dietary peptides and peptide reabsorption, respectively. Currently, two peptide transporters, PepT1 and PepT2...

  5. Isotypes of Epstein-Barr Virus Antibodies in Rheumatoid Arthritis: Association with Rheumatoid Factors and Citrulline-Dependent Antibodies

    Directory of Open Access Journals (Sweden)

    Marie Wulff Westergaard

    2015-01-01

    Full Text Available In order to study the humoral immune response against Epstein-Barr virus (EBV in patients with rheumatoid arthritis (RA and to compare it with the two major autoantibody types in RA, plasma samples from 77 RA patients, 28 patients with systemic lupus erythematosus (SLE, and 28 healthy controls (HCs were investigated by enzyme-linked immunosorbent assays (ELISA. Increased percentages of positives and concentrations of IgG/IgA/IgM antibodies against the latent EBV nuclear antigen-1 (EBNA-1 were observed in RA patients compared to SLE patients and HCs. Increased concentrations and percentages of positives of IgG/IgA/IgM against the early lytic EBV antigen diffuse (EAD were also found in RA patients compared to HCs but were highest in SLE patients. Furthermore, associations between the elevated EBNA-1 IgA and EBNA-1 IgM levels and the presence of IgM and IgA rheumatoid factors (RFs and anti-citrullinated protein antibodies (ACPAs, IgG and between elevated IgA concentrations against EAD and the presence of RFs and ACPAs in RA patients were found. Thus, RA patients had elevated antibodies of all isotypes characteristic of latent EBV infection (whereas SLE patients had elevated antibodies characteristic of lytic EBV infection. Notably, for IgM and IgA (but not IgG, these were associated with the presence of characteristic RA autoantibodies.

  6. Extracellular expression of natural cytosolic arginine deiminase from Pseudomonas putida and its application in the production of L-citrulline.

    Science.gov (United States)

    Su, Lingqia; Ma, Yue; Wu, Jing

    2015-11-01

    The Pseudomonas putida arginine deiminase (ADI), a natural cytosolic enzyme, and Thermobifida fusca cutinase were co-expressed in Escherichia coli, and the optimized cutinase gene was used for increasing its expression level. 90.9% of the total ADI protein was released into culture medium probably through a nonspecific leaking mechanism caused by the co-expressed cutinase. The enzymatic properties of the extracellular ADI were found to be similar to those of ADI prepared by conventional cytosolic expression. Extracellular production of ADI was further scaled up in a 3-L fermentor. When the protein expression was induced by IPTG (25.0μM) and lactose (0.1gL(-1)h(-1)) at 30°C, the extracellular ADI activity reached 101.2UmL(-1), which represented the highest ADI production ever reported. In addition, the enzymatic synthesis of l-citrulline was performed using the extracellularly expressed ADI, and the conversion rate reached 100% with high substrate concentration at 650gL(-1).

  7. The feeding route (enteral or parenteral) affects the plasma response of the dipetide Ala-Gln and the amino acids glutamine, citrulline and arginine, with the administration of Ala-Gln in preoperative patients.

    Science.gov (United States)

    Melis, Gerdien C; Boelens, Petra G; van der Sijp, Joost R M; Popovici, Theodora; De Bandt, Jean-Pascal; Cynober, Luc; van Leeuwen, Paul A M

    2005-07-01

    Enhancement of depressed plasma concentrations of glutamine and arginine is associated with better clinical outcome. Supplementation of glutamine might be a way to provide the patient with glutamine, and also arginine, because glutamine provides the kidney with citrulline, from which the kidney produces arginine when plasma levels of arginine are low. The aim of the present study was to investigate the parenteral and enteral response of the administered dipeptide Ala-Gln, glutamine, citrulline and arginine. Therefore, seven patients received 20 g Ala-Gln, administered over 4 h, parenterally or enterally, on two separate occasions. Arterial blood samples were taken before and during the administration of Ala-Gln. ANOVA and a paired t test were used to test differences (Pglutamine was observed with parenteral infusion of the dipeptide, although enteral infusion also significantly increased plasma levels of glutamine. The highest plasma response of citrulline was observed with the enteral administration of the dipeptide, although parenteral administration also increased plasma levels of citrulline. Plasma arginine increased significantly with parenteral infusion, but not with enteral administration of Ala-Gln. In conclusion, administrations of Ala-Gln, parenteral or enteral, resulted in an increased plasma glutamine response, as compared with baseline. Interestingly, in spite of the high availability of citrulline with enteral administration of the dipeptide, only parenteral infusion of Ala-Gln increased plasma arginine concentration.

  8. Quantitative Metabolomic Analysis of Urinary Citrulline and Calcitroic Acid in Mice after Exposure to Various Types of Ionizing Radiation

    Directory of Open Access Journals (Sweden)

    Maryam Goudarzi

    2016-05-01

    Full Text Available With the safety of existing nuclear power plants being brought into question after the Fukushima disaster and the increased level of concern over terrorism-sponsored use of improvised nuclear devices, it is more crucial to develop well-defined radiation injury markers in easily accessible biofluids to help emergency-responders with injury assessment during patient triage. Here, we focused on utilizing ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS to identify and quantitate the unique changes in the urinary excretion of two metabolite markers, calcitroic acid and citrulline, in mice induced by different forms of irradiation; X-ray irradiation at a low dose rate (LDR of 3.0 mGy/min and a high dose rate (HDR of 1.1 Gy/min, and internal exposure to Cesium-137 (137Cs and Strontium-90 (90Sr. The multiple reaction monitoring analysis showed that, while exposure to 137Cs and 90Sr induced a statistically significant and persistent decrease, similar doses of X-ray beam at the HDR had the opposite effect, and the LDR had no effect on the urinary levels of these two metabolites. This suggests that the source of exposure and the dose rate strongly modulate the in vivo metabolomic injury responses, which may have utility in clinical biodosimetry assays for the assessment of exposure in an affected population. This study complements our previous investigations into the metabolomic profile of urine from mice internally exposed to 90Sr and 137Cs and to X-ray beam radiation.

  9. Serum anticyclic citrullinated protein antibody titers are correlated with the response to biological agents in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Takahashi R

    2014-05-01

    Full Text Available Ryo Takahashi, Sakiko Isojima, Masayu Umemura, Yoko Miura, Nao Oguro, Syo Ishii, Shinya Seki, Takahiro Tokunaga, Hiroyuki Tsukamoto, Hidekazu Furuya, Ryo Yanai, Tsuyoshi KasamaDivision of Rheumatology, Department of Medicine, Showa University School of Medicine,Tokyo, Japan Abstract: Anticyclic citrullinated protein antibody (ACPA is known as an important indicator for diagnosis of rheumatoid arthritis (RA. Our aim was to examine the relationship between the serum ACPA titer at baseline and responsiveness to biological agents (antagonists of either tumor necrosis factor or interleukin 6 in patients with RA. ACPA was measured using second-generation chemiluminescent enzyme immunoassay. Disease activity was assessed using disease activity scores 28. Fifty-seven RA patients with biological agents were enrolled, and the median ACPA titer at baseline was 110.0 U/mL. The median ACPA titer was 23.3 U/mL and 183.0 U/mL in the good and moderate response groups, respectively, which were significantly lower than in the no response group (404.0 U/mL. In addition, 69.2% and 26.9% of patients with low (<100 U/mL and moderate (100–499 U/mL basal ACPA titers showed a moderate to good response. Of the patients with higher (≥500 U/mL basal ACPA titers, only 14.0% and 42.5% showed a good or moderate response, respectively. The remission rate was 77.8% in the ACPA-negative, which was significantly higher than the rate of 25% in the ACPA-positive patients. The results suggest that the ACPA titers are correlated with the efficacy of the biological agents used in patients with RA.Keywords: biological agents, remission

  10. Acute ingestion of citrulline stimulates nitric oxide synthesis but does not increase blood flow in healthy young and older adults with heart failure.

    Science.gov (United States)

    Kim, Il-Young; Schutzler, Scott E; Schrader, Amy; Spencer, Horace J; Azhar, Gohar; Deutz, Nicolaas E P; Wolfe, Robert R

    2015-12-01

    To determine if age-associated vascular dysfunction in older adults with heart failure (HF) is due to insufficient synthesis of nitric oxide (NO), we performed two separate studies: 1) a kinetic study with a stable isotope tracer method to determine in vivo kinetics of NO metabolism, and 2) a vascular function study using a plethysmography method to determine reactive hyperemic forearm blood flow (RH-FBF) in older and young adults in the fasted state and in response to citrulline ingestion. In the fasted state, NO synthesis (per kg body wt) was ∼ 50% lower in older vs. young adults and was related to a decreased rate of appearance of the NO precursor arginine. Citrulline ingestion (3 g) stimulated de novo arginine synthesis in both older [6.88 ± 0.83 to 35.40 ± 4.90 μmol · kg body wt(-1) · h(-1)] and to a greater extent in young adults (12.02 ± 1.01 to 66.26 ± 4.79 μmol · kg body wt(-1) · h(-1)). NO synthesis rate increased correspondingly in older (0.17 ± 0.01 to 2.12 ± 0.36 μmol · kg body wt(-1) · h(-1)) and to a greater extent in young adults (0.36 ± 0.04 to 3.57 ± 0.47 μmol · kg body wt(-1) · h(-1)). Consistent with the kinetic data, RH-FBF in the fasted state was ∼ 40% reduced in older vs. young adults. However, citrulline ingestion (10 g) failed to increase RH-FBF in either older or young adults. In conclusion, citrulline ingestion improved impaired NO synthesis in older HF adults but not RH-FBF, suggesting that factors other than NO synthesis play a role in the impaired RH-FBF in older HF adults, and/or it may require a longer duration of supplementation to be effective in improving RH-FBF.

  11. PeptideAtlas

    Data.gov (United States)

    U.S. Department of Health & Human Services — PeptideAtlas is a multi-organism, publicly accessible compendium of peptides identified in a large set of tandem mass spectrometry proteomics experiments. Mass...

  12. Antimicrobial Peptides in 2014

    Directory of Open Access Journals (Sweden)

    Guangshun Wang

    2015-03-01

    Full Text Available This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms.

  13. Peptide Nucleic Acids (PNA)

    DEFF Research Database (Denmark)

    2002-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  14. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  15. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2003-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  16. Peptide Nucleic Acid Synthons

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  17. Peptide-Carrier Conjugation

    DEFF Research Database (Denmark)

    Hansen, Paul Robert

    2015-01-01

    To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....

  18. PH dependent adhesive peptides

    Science.gov (United States)

    Tomich, John; Iwamoto, Takeo; Shen, Xinchun; Sun, Xiuzhi Susan

    2010-06-29

    A novel peptide adhesive motif is described that requires no receptor or cross-links to achieve maximal adhesive strength. Several peptides with different degrees of adhesive strength have been designed and synthesized using solid phase chemistries. All peptides contain a common hydrophobic core sequence flanked by positively or negatively charged amino acids sequences.

  19. The role of citrullinated proteins in the pathogenesis of rheumatoid arthritis%蛋白质瓜氨酸化及其在类风湿关节炎中的意义

    Institute of Scientific and Technical Information of China (English)

    钟兵; 方勇飞

    2015-01-01

    类风湿关节炎(rheumatoid arthritis,RA)的发病机制至今尚未阐明。 RA 患者体内发现越来越多的抗瓜氨酸化蛋白抗体(ACPA)提示瓜氨酸化可能参与其发病过程。本文从蛋白质的瓜氨酸化过程、生理功能,ACPA 在 RA 的诊断、预后及发病机制中的作用进行综述,试图更全面地了解蛋白质的瓜氨酸化在 RA 发病各环节中的作用。%The mechanism of rheumatoid arthritis(RA)has not been clarified.More and more anti-citrullinated protein antibod-ies(ACPA)have been found in RA patients ,suggesting that citrullinated proteins may be involved in the pathogenesis of RA .This paper reviews the process of protein citrullination ,physiological function and the role of ACPA in the diagnosis ,prognosis and pathogenesis of RA in order to get a more comprehensive understanding of the role of citrullinated proteins in the pathogenesis of RA .

  20. 抗瓜氨酸化蛋白抗体特异性免疫复合物在类风湿关节炎中的作用%Pathogenic role of anti-citrullinated protein antibody specific immune complexes and its pathogenesis in rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    高德玉

    2013-01-01

    Rheumatoid arthritis(RA) is a common chronic immuine disease characterized by autoimmune inflammatory reaction in joints. Citmllination of peptide in synovial tissue is the post-translational conversion of arginine to citmlline,and involved in the generation of anti-citmllinated protein antibodies(ACPA)and pathogenesis of RA. High amounts of Immune complex are usually found in RA synovial fluids (SF) and on the surface of chondrocytes. IC in the sera and SF are involved in activation of complement cascade in RA synovial tissue and induction of cytokines secretion, which can cause the irreversible damage of joints. Because of the pathogenic nature of IC in RA, it is important to identify the antigens in these complexes. The interaction of citrullinated protein deposits with locally produced ACPA results in the formation of immune complexes were able to chronically maintain inflammation. Since anti-citmllinated protein antibodies and citrullinated immune complexes are noticeable higher than that in health)' control, it may contribute to the diagnosis and pathogenic evaluation of RA.%类风湿关节炎(rheumatoid arthritis,RA)是一种以关节组织内炎症损害为主要病理变化的自身免疫性疾病.蛋白质抗原或多肽的瓜氨酸化是一种蛋白质翻译后修饰过程,并且与RA的发病过程及抗瓜氨酸蛋白抗体(anti-citrullinated protein antibodies,ACPA)产生有关.在RA患者血液及关节滑膜液、血清和软骨细胞表层可发现大量免疫复合物(immune complex,IC)存在.IC可激活RA患者体内补体系统并促进细胞因子等炎性介质的释放,引起关节骨和软骨组织发生损伤,进而引起不可逆的关节畸变等功能损害.IC中抗原成分的鉴定对于深入了解RA的发病机制非常重要.含有抗瓜氨酸化蛋白的IC的沉积及作用可以诱发细胞因子的产生,进而引起持续性慢性炎症.RA患者滑膜液及血清中ACPA及其特异性IC显著高于正常人,提示ACPA特异

  1. Topical peptides as cosmeceuticals

    Directory of Open Access Journals (Sweden)

    Varadraj Vasant Pai

    2017-01-01

    Full Text Available Peptides are known to have diverse biological roles, most prominently as signaling/regulatory molecules in a broad variety of physiological processes including defense, immunity, stress, growth, homeostasis and reproduction. These aspects have been used in the field of dermatology and cosmetology to produce short, stable and synthetic peptides for extracellular matrix synthesis, pigmentation, innate immunity and inflammation. The evolution of peptides over the century, which started with the discovery of penicillin, has now extended to their usage as cosmeceuticals in recent years. Cosmeceutical peptides may act as signal modulators of the extracellular matrix component, as structural peptides, carrier peptides and neurotransmitter function modulators. Transdermal delivery of peptides can be made more effective by penetration enhancers, chemical modification or encapsulation of peptides. The advantages of using peptides as cosmeceuticals include their involvement in many physiological functions of the skin, their selectivity, their lack of immunogenicity and absence of premarket regulatory requirements for their use. However, there are disadvantages: clinical evidence for efficacy is often weak, absorption may be poor due to low lipophilicity, high molecular weight and binding to other ingredients, and prices can be quite high.

  2. Levels of l-arginine and l-citrulline in patients with erectile dysfunction of different etiology.

    Science.gov (United States)

    Barassi, A; Corsi Romanelli, M M; Pezzilli, R; Damele, C A L; Vaccalluzzo, L; Goi, G; Papini, N; Colpi, G M; Massaccesi, L; Melzi d'Eril, G V

    2017-03-01

    Nitric oxide is a physiologic signal essential to penile erection. l-citrulline (l-Cit) is converted into l-arginine (l-Arg), the precursor from which nitric oxide is generated. The level of l-Arg and l-Cit in the field of male sexual function remains relatively underexplored. The aim of the study was to evaluate the level of serum l-Arg and of l-Cit in a group of patients with erectile dysfunction. Diagnosis and severity of erectile dysfunction was based on the IIEF-5 and its etiology was classified as arteriogenic (A-ED), borderline (BL-ED), and non-arteriogenic (NA-ED) with penile echo-color-Doppler in basal condition and after intracaversous injection of prostaglandin E1. Serum l-Arg and l-Cit concentrations were measured by a cation-exchange chromatography system. l-Arg and l-Cit levels of men with A-ED were compared with those of male with BL-ED and NA-ED. Median level of l-Arg and l-Cit in 122 erectile dysfunction patients (41 A-ED, 23 ED-BL, 58 NA-ED) was 82.7 and 35.4 μmol/L, respectively. l-Arg and l-Cit levels in control patients were not significantly different (p = 0.233 and p = 0.561, respectively) than in total erectile dysfunction patients. l-Arg and l-Cit levels in control patients were significantly higher (p  0.50) was observed in controls and in both BL-ED and NA-ED patients. Patients with severe/complete-erectile dysfunction (IIEF-5 l-Arg or l-Cit level significantly lower (-17%, p L) than those with mild-erectile dysfunction (IIEF-5 = 16-20). l-Arg and l-Cit levels in A-ED were significantly lower (p l-Arg under 82.7 μmol/L or l-Cit under 35.4 μmol/L and in the same population, the median peak systolic velocity values were lower in l-Arg deficient (29 vs. 35; p l-Cit deficient (31 vs. 33, p > 0.3) but without reaching the statistical significance. Our study shows that a significant proportion of erectile dysfunction patients have low l-Arg or l-Cit level and that this condition is more frequent in patients with arteriogenic

  3. EPR investigation of gamma-irradiated L-citrulline, α-methyl-DL-serine, 3-fluoro-DL-valine and N-acetyl-L-cysteine

    Science.gov (United States)

    Osmanoğlu, Y. Emre; Sütçü, Kerem; Başkan, M. Halim

    2017-02-01

    The spectroscopic parameters of the paramagnetic species produced in gamma-irradiated L-citrulline, α-methyl-DL-serine, 3-fluoro-DL-valine and N-acetyl-L-cysteine were investigated at room temperature at a dose of 20 kGy by using EPR technique. The paramagnetic species were attributed to NH2CONH(CH2)3ĊNH2COOH, HOCH2ĊCH3COOH and HOĊHCCH3NH2COOH, CH3CH3ĊCHNH2COOH and SHCH2ĊNHCOCH3COOH radicals, respectively. EPR data of the unpaired electron with the environmental protons and 14N nucleus were used to characterize the contributing radicals produced in gamma irradiated compounds. In this paper, the stability of these compounds at room temperature after irradiation was also studied.

  4. Insulin C-peptide test

    Science.gov (United States)

    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

  5. Arginine methylation and citrullination of splicing factor proline- and glutamine-rich (SFPQ/PSF) regulates its association with mRNA.

    Science.gov (United States)

    Snijders, Ambrosius P; Hautbergue, Guillaume M; Bloom, Alex; Williamson, James C; Minshull, Thomas C; Phillips, Helen L; Mihaylov, Simeon R; Gjerde, Douglas T; Hornby, David P; Wilson, Stuart A; Hurd, Paul J; Dickman, Mark J

    2015-03-01

    Splicing factor proline- and glutamine-rich (SFPQ) also commonly known as polypyrimidine tract-binding protein-associated-splicing factor (PSF) and its binding partner non-POU domain-containing octamer-binding protein (NONO/p54nrb), are highly abundant, multifunctional nuclear proteins. However, the exact role of this complex is yet to be determined. Following purification of the endogeneous SFPQ/NONO complex, mass spectrometry analysis identified a wide range of interacting proteins, including those involved in RNA processing, RNA splicing, and transcriptional regulation, consistent with a multifunctional role for SFPQ/NONO. In addition, we have identified several sites of arginine methylation in SFPQ/PSF using mass spectrometry and found that several arginines in the N-terminal domain of SFPQ/PSF are asymmetrically dimethylated. Furthermore, we find that the protein arginine N-methyltransferase, PRMT1, catalyzes this methylation in vitro and that this is antagonized by citrullination of SFPQ. Arginine methylation and citrullination of SFPQ/PSF does not affect complex formation with NONO. However, arginine methylation was shown to increase the association with mRNA in mRNP complexes in mammalian cells. Finally we show that the biochemical properties of the endogenous complex from cell lysates are significantly influenced by the ionic strength during purification. At low ionic strength, the SFPQ/NONO complex forms large heterogeneous protein assemblies or aggregates, preventing the purification of the SFPQ/NONO complex. The ability of the SFPQ/NONO complex to form varying protein assemblies, in conjunction with the effect of post-translational modifications of SFPQ modulating mRNA binding, suggests key roles affecting mRNP dynamics within the cell.

  6. Long-term effects of maternal citrulline supplementation on renal transcriptome prevention of nitric oxide depletion-related programmed hypertension: the impact of gene-nutrient interactions.

    Science.gov (United States)

    Tain, You-Lin; Lee, Chien-Te; Huang, Li-Tung

    2014-12-15

    Maternal malnutrition can elicit gene expression leading to fetal programming. L-citrulline (CIT) can be converted to L-arginine to generate nitric oxide (NO). We examined whether maternal CIT supplementation can prevent N(G)-nitro-L-arginine-methyl ester (L-NAME, NO synthase inhibitor)-induced programmed hypertension and examined their effects on the renal transcriptome in male offspring using next generation RNA sequencing (RNA-Seq) technology. Pregnant Sprague-Dawley rats received L-NAME administration at 60mg/kg/day subcutaneously via osmotic minipump during pregnancy alone or with additional 0.25% L-citrulline solution in drinking water during the whole period of pregnancy and lactation. Male offspring were assigned to three groups: control, L-NAME, and L-NAME + CIT. L-NAME exposure induced hypertension in the 12-week-old offspring, which CIT therapy prevented. Identified differentially expressed genes in L-NAME and CIT-treated offspring kidneys, including Guca2b, Hmox1, Hba2, Hba-a2, Dusp1, and Serpine1 are related to regulation of blood pressure (BP) and oxidative stress. In conclusion, our data suggests that the beneficial effects of CIT supplementation are attributed to alterations in expression levels of genes related to BP control and oxidative stress. Our results suggest that early nutritional intervention by CIT has long-term impact on the renal transcriptome to prevent NO depletion-related programmed hypertension. However, our RNA-Seq results might be a secondary phenomenon. The implications of epigenetic regulation at an early stage of programming deserve further clarification.

  7. Descriptors for antimicrobial peptides

    DEFF Research Database (Denmark)

    Jenssen, Håvard

    2011-01-01

    of antimicrobial drugs, and computational methods utilizing molecular descriptors can significantly accelerate the development of new peptide drug candidates. Areas covered: This paper gives a broad overview of peptide and amino-acid scale descriptors available for AMP modeling and highlights which...

  8. PNA Peptide chimerae

    DEFF Research Database (Denmark)

    Koch, T.; Næsby, M.; Wittung, P.;

    1995-01-01

    Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields.......Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields....

  9. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds known as peptide nucleic acids, bind complementary DNA and RNA strands, and generally do so more strongly than the corresponding DNA or RNA strands while exhibiting increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from...

  10. Bacteriocin Inducer Peptides

    Science.gov (United States)

    Novel peptides produced by bacteriocin-producing bacteria stimulate the production of bacteriocins in vitro. The producer bacteria are cultured in the presence of a novel inducer bacteria and a peptide having a carboxy terminal sequence of VKGLT in order to achieve an increase in bacteriocin produc...

  11. Avian host defense peptides

    NARCIS (Netherlands)

    Cuperus, Tryntsje; Coorens, M.; van Dijk, A.; Haagsman, H.P.

    2013-01-01

    Host defense peptides (HDPs) are important effector molecules of the innate immune system of vertebrates. These antimicrobial peptides are also present in invertebrates, plants and fungi. HDPs display broad-spectrum antimicrobial activities and fulfill an important role in the first line of defense

  12. APD: the Antimicrobial Peptide Database

    OpenAIRE

    Wang, Zhe; Wang, Guangshun

    2004-01-01

    An antimicrobial peptide database (APD) has been established based on an extensive literature search. It contains detailed information for 525 peptides (498 antibacterial, 155 antifungal, 28 antiviral and 18 antitumor). APD provides interactive interfaces for peptide query, prediction and design. It also provides statistical data for a select group of or all the peptides in the database. Peptide information can be searched using keywords such as peptide name, ID, length, net charge, hydrophob...

  13. Case of interstitial lung disease with anti-EJ and anti-CCP antibodies preceding rheumatoid arthritis.

    Science.gov (United States)

    Tomioka, Hiromi; Kaneko, Masahiro; Kogata, Yoshinori; Katsuyama, Eiji; Ishikawa, Seiko; Fujii, Takao

    2012-06-01

    Autoantibodies against aminoacyl-tRNA synthetases (ARSs) are highly specific for myositis and/or interstitial lung disease. We report a rare case of double positive antibodies (anti-EJ antibody, the least common among anti-aminoacyl-tRNA synthetase antibodies, and anti-cyclic citrullinated peptide antibody, reported to be specific for rheumatoid arthritis) in a patient who presented with interstitial lung disease and later developed rheumatoid arthritis. The patient did not have clinically apparent myositis over a period of careful follow-up of several years. The initial pulmonary pathologic findings showed a nonspecific interstitial pneumonia pattern, with the formation of lymphoid follicles, which should be recognized as the first manifestation of rheumatoid arthritis.

  14. Interactions between smoking, increased serum levels of anti-CCP antibodies, rheumatoid factors, and erosive joint disease in patients with early, untreated rheumatoid arthritis

    DEFF Research Database (Denmark)

    Krol, A.; Garred, P; Heegaard, N H H;

    2015-01-01

    OBJECTIVES: To determine to what extent shared epitopes, smoking, and anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with disease activity and erosive disease in patients with rheumatoid arthritis (RA) at disease onset. METHOD: RA patients not previously treated with disease...... or antibodies. All antibody levels measured were associated with smoking and shared epitopes. CONCLUSIONS: Shared epitopes and smoking were associated with the production of anti-CCP antibodies and rheumatoid factors of IgM and IgA isotypes, which again were associated with erosive disease at presentation only...... in smokers. As shared epitopes and smoking were not directly associated with erosive disease, smoking may enhance the development of erosive disease in RA at different levels or through separate pathways....

  15. Left ventricular function in treatment-naive early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Løgstrup, Brian B; Deibjerg, Lone K; Hedemann-Andersen, Agnete;

    2014-01-01

    BACKGROUND: The role of inflammation and anti-cyclic citrullinated peptide antibodies (anti-CCP) in the pathogenesis of cardiovascular disease in early rheumatoid arthritis (RA) remains unclear. Previous studies have suggested that both disease activity and disease duration are associated...... with atherosclerosis and a higher mortality rate caused primarily by coronary artery disease. OBJECTIVE: We investigated how disease activity, anti-CCP status and coronary calcium score in treatment-naive early RA impacts left ventricular (LV) systolic function. METHODS: Fifty-tree patients (30 women) with mean age 58...... by computed tomography by calculating the Agaston score. One experienced senior rheumatologist and one experienced cardiologist performed all the clinical assessments as well as all the transthoracic echocardiography (TTE) and coronary CT analysis. RESULTS: Disease activity scores before treatment at baseline...

  16. Identification of ESM-1 as a new endothelial biomarker in the pathogenesis of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Gönül Gürol Ciftci

    2016-05-01

    Full Text Available The aim of this study was to investigate the use of ESM-1 (endothelial cell-specific molecule-1 as a new biomarker for the pathogenesis of rheumatoid arthritis (RA. The study cohort was divided into four groups according to the DAS28 disease activity score: 16 patients were classified as being in remission (DAS28 5.1; 20 healthy subjects were included as a control group. Serum samples were gathered from the patients with documented seropositivity for rheumatoid factor (RF and anti-cyclic citrullinated peptide antibodies in order to assess RF IgM and ESM-1. ESM-1 levels were significantly higher in patients with RA than in healthy subjects (p = 0.035. The data presented here strongly indicate ESM-1 as an attractive target for the treatment of inflammation-related diseases, such as RA.

  17. Increased soluble programmed death-1 (sPD-1) is associated with disease activity and radiographic progression in early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Greisen, S. R.; Rasmussen, T. K.; Stengaard-Pedersen, K.

    2014-01-01

    OBJECTIVES: Programmed death-1 (PD-1) is an immunoregulatory molecule functioning by down-regulating immune responses. PD-1 is present on follicular helper T cells (TFH) and is important in the formation of plasma cells. PD-1 exists in a bioactive soluble form (sPD-1) and is thought to be implica......OBJECTIVES: Programmed death-1 (PD-1) is an immunoregulatory molecule functioning by down-regulating immune responses. PD-1 is present on follicular helper T cells (TFH) and is important in the formation of plasma cells. PD-1 exists in a bioactive soluble form (sPD-1) and is thought...... Questionnaire (HAQ) score, immunoglobulin M rheumatoid factor (IgM-RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, C-reactive protein (CRP), interleukin-21 (IL-21), and total Sharp score (TSS). We also measured sPD-1 in plasma from healthy volunteers (HV) (n = 20) and in plasma and synovial fluid...

  18. Argininosuccinate Synthetase Is a Functional Target for a Snake Venom Anti-hypertensive Peptide

    Science.gov (United States)

    Guerreiro, Juliano R.; Lameu, Claudiana; Oliveira, Eduardo F.; Klitzke, Clécio F.; Melo, Robson L.; Linares, Edlaine; Augusto, Ohara; Fox, Jay W.; Lebrun, Ivo; Serrano, Solange M. T.; Camargo, Antonio C. M.

    2009-01-01

    Bj-BPP-10c is a bioactive proline-rich decapeptide, part of the C-type natriuretic peptide precursor, expressed in the brain and in the venom gland of Bothrops jararaca. We recently showed that Bj-BPP-10c displays a strong, sustained anti-hypertensive effect in spontaneous hypertensive rats (SHR), without causing any effect in normotensive rats, by a pharmacological effect independent of angiotensin-converting enzyme inhibition. Therefore, we hypothesized that another mechanism should be involved in the peptide activity. Here we used affinity chromatography to search for kidney cytosolic proteins with affinity for Bj-BPP-10c and demonstrate that argininosuccinate synthetase (AsS) is the major protein binding to the peptide. More importantly, this interaction activates the catalytic activity of AsS in a dose-de pend ent manner. AsS is recognized as an important player of the citrulline-NO cycle that represents a potential limiting step in NO synthesis. Accordingly, the functional interaction of Bj-BPP-10c and AsS was evidenced by the following effects promoted by the peptide: (i) increase of NO metabolite production in human umbilical vein endothelial cell culture and of arginine in human embryonic kidney cells and (ii) increase of arginine plasma concentration in SHR. Moreover, α-methyl-dl-aspartic acid, a specific AsS inhibitor, significantly reduced the anti-hypertensive activity of Bj-BPP-10c in SHR. Taken together, these results suggest that AsS plays a role in the anti-hypertensive action of Bj-BPP-10c. Therefore, we propose the activation of AsS as a new mechanism for the anti-hypertensive effect of Bj-BPP-10c in SHR and AsS as a novel target for the therapy of hypertension-related diseases. PMID:19491403

  19. Anti-antimicrobial Peptides

    Science.gov (United States)

    Ryan, Lloyd; Lamarre, Baptiste; Diu, Ting; Ravi, Jascindra; Judge, Peter J.; Temple, Adam; Carr, Matthew; Cerasoli, Eleonora; Su, Bo; Jenkinson, Howard F.; Martyna, Glenn; Crain, Jason; Watts, Anthony; Ryadnov, Maxim G.

    2013-01-01

    Antimicrobial or host defense peptides are innate immune regulators found in all multicellular organisms. Many of them fold into membrane-bound α-helices and function by causing cell wall disruption in microorganisms. Herein we probe the possibility and functional implications of antimicrobial antagonism mediated by complementary coiled-coil interactions between antimicrobial peptides and de novo designed antagonists: anti-antimicrobial peptides. Using sequences from native helical families such as cathelicidins, cecropins, and magainins we demonstrate that designed antagonists can co-fold with antimicrobial peptides into functionally inert helical oligomers. The properties and function of the resulting assemblies were studied in solution, membrane environments, and in bacterial culture by a combination of chiroptical and solid-state NMR spectroscopies, microscopy, bioassays, and molecular dynamics simulations. The findings offer a molecular rationale for anti-antimicrobial responses with potential implications for antimicrobial resistance. PMID:23737519

  20. Tumor penetrating peptides

    Directory of Open Access Journals (Sweden)

    Tambet eTeesalu

    2013-08-01

    Full Text Available Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC, contains the integrin-binding RGD motif. RGD mediates tumor homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular zip code of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is

  1. Immunotherapy with Allergen Peptides

    OpenAIRE

    Larché Mark

    2007-01-01

    Specific allergen immunotherapy (SIT) is disease-modifying and efficacious. However, the use of whole allergen preparations is associated with frequent allergic adverse events during treatment. Many novel approaches are being designed to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity. One approach is the use of short synthetic peptides which representing dominant T cell epitopes of the allergen. Short peptides exhibit markedly reduced capacity to cro...

  2. Antimicrobial Peptides in Echinoderms

    OpenAIRE

    Li, C; Haug, T; K Stensvåg

    2010-01-01

    Antimicrobial peptides (AMPs) are important immune effector molecules for invertebrates, including echinoderms, which lack a vertebrate-type adaptive immune system. Here we summarize the knowledge of such peptides in echinoderms. Strongylocins are a novel family of cysteine-rich AMPs, recently identified in the sea urchins, Strongylocentrotus droebachiensis and S. purpuratus. Although these molecules present diverse amino acid sequences, they share an identical cysteine arrangement pattern, d...

  3. Natriuretic Peptides, Diagnostic and Prognostic Biomarkers

    NARCIS (Netherlands)

    J.H.W. Rutten (Joost)

    2010-01-01

    textabstractIn humans, the natriuretic peptide family consists of three different types of peptides: atrial natriuretic peptide (synonym: atrial natriuretic factor), B-type natriuretic peptide (synonym: brain natriuretic peptide) and C-natriuretic peptide.1 Atrial natriuretic peptide (ANP) was the f

  4. Natriuretic Peptides, Diagnostic and Prognostic Biomarkers

    OpenAIRE

    Rutten, Joost

    2010-01-01

    textabstractIn humans, the natriuretic peptide family consists of three different types of peptides: atrial natriuretic peptide (synonym: atrial natriuretic factor), B-type natriuretic peptide (synonym: brain natriuretic peptide) and C-natriuretic peptide.1 Atrial natriuretic peptide (ANP) was the fi rst natriuretic peptide to be discovered and in humans ANP is predominantly formed in the cardiomyocytes of the atria.2 B-type natriuretic peptide (BNP) was fi rst discovered in porcine brain hen...

  5. Diversity-Oriented Peptide Stapling

    DEFF Research Database (Denmark)

    Tran, Thu Phuong; Larsen, Christian Ørnbøl; Røndbjerg, Tobias

    2017-01-01

    The introduction of macrocyclic constraints in peptides (peptide stapling) is an important tool within peptide medicinal chemistry for stabilising and pre-organising peptides in a desired conformation. In recent years, the copper-catalysed azide-alkyne cycloaddition (CuAAC) has emerged...... as a powerful method for peptide stapling. However, to date CuAAC stapling has not provided a simple method for obtaining peptides that are easily diversified further. In the present study, we report a new diversity-oriented peptide stapling (DOPS) methodology based on CuAAC chemistry. Stapling of peptides...... incorporating two azide-modified amino acids with 1,3,5-triethynylbenzene efficiently provides (i, i+7)- and (i, i+9)-stapled peptides with a single free alkyne positioned on the staple, that can be further conjugated or dimerised. A unique feature of the present method is that it provides easy access...

  6. Electron transfer in peptides.

    Science.gov (United States)

    Shah, Afzal; Adhikari, Bimalendu; Martic, Sanela; Munir, Azeema; Shahzad, Suniya; Ahmad, Khurshid; Kraatz, Heinz-Bernhard

    2015-02-21

    In this review, we discuss the factors that influence electron transfer in peptides. We summarize experimental results from solution and surface studies and highlight the ongoing debate on the mechanistic aspects of this fundamental reaction. Here, we provide a balanced approach that remains unbiased and does not favor one mechanistic view over another. Support for a putative hopping mechanism in which an electron transfers in a stepwise manner is contrasted with experimental results that support electron tunneling or even some form of ballistic transfer or a pathway transfer for an electron between donor and acceptor sites. In some cases, experimental evidence suggests that a change in the electron transfer mechanism occurs as a result of donor-acceptor separation. However, this common understanding of the switch between tunneling and hopping as a function of chain length is not sufficient for explaining electron transfer in peptides. Apart from chain length, several other factors such as the extent of the secondary structure, backbone conformation, dipole orientation, the presence of special amino acids, hydrogen bonding, and the dynamic properties of a peptide also influence the rate and mode of electron transfer in peptides. Electron transfer plays a key role in physical, chemical and biological systems, so its control is a fundamental task in bioelectrochemical systems, the design of peptide based sensors and molecular junctions. Therefore, this topic is at the heart of a number of biological and technological processes and thus remains of vital interest.

  7. Valor crítico da citrulina para as complicações do enxerto no transplante de intestino Critical value of citrulline for complications of intestinal transplant graft

    Directory of Open Access Journals (Sweden)

    André Ibrahim David

    2008-10-01

    Full Text Available OBJETIVO: Analisar, numa ampla amostra, o valor crítico da citrulina que confirma a presença das principais complicações do enxerto: rejeição e infecção. MÉTODOS: Foram coletadas 2135 amostras de citrulina sérica, na forma de gota de sangue seca, de 57 doentes submetidos a transplante de intestino/multivisceral no Jackson Memorial Hospital na Universidade de Miami, de março de 2004 a abril de 2006. Todas as amostras são do pós-operatório três meses em diante, passada a conhecida curva de elevação da citrulina após a recuperação das lesões causadas pela isquemia e reperfusão do pós-transplante. RESULTADOS: Utilizando um valor limite menor que 13 µmoles/L, a sensibilidade da citrulina foi de 96,4% para detectar rejeicão celular aguda (RCA moderada ou grave. A especificidade para as complicações mais freqüentes, rejeição e infecção foi de 54%-74% nas crianças e 83%-88% nos adultos, e o valor preditivo negativo (VPN foi > 99%. CONCLUSÃO: A citrulina pode ser utilizada como método não-invasivo para avaliar a evolução do enxerto intestinal após três meses do TI. Os episódios de RCA moderado e grave podem ser afastados quando o valor da citrulina for maior que 13 µmoles/L devido ao alto valor preditivo negativo.OBJECITIVE: A biochemical marker for detection of acute cellular rejection following small intestine transplantation has been sought. Citrulline, a non- protein amino acid synthesized mainly by functioning enterocytes, has been proposed. Trial sensitivity has been reportedly high but with low specificity. Thus, the goal was to determine, in a sufficiently large analysis, the significant value of citrulline level in the post-transplant setting, which would correlate with complications such as rejection and infection. METHODS: Since March, 2004 2,135 dried blood spot (DBS citrulline samples were obtained from 57 small intestine transplant recipients three months or more after post-transplant, i.e., once

  8. Citrulina plasmática como marcador de pérdida de masa enterocitaria en la enfermedad celíaca en la infancia Plasma citrulline as a marker of loss of enterocitary mass in coeliac disease in childhood

    Directory of Open Access Journals (Sweden)

    J. Blasco Alonso

    2011-08-01

    Full Text Available Introducción: La citrulina plasmática no está incorporada a las proteínas endógenas ni exógenas y constituye un teórico marcador de la atrofia vellositaria. El objetivo del estudio es relacionar los niveles plasmáticos de citrulina y arginina con la severidad de la afectación de la mucosa intestinal en pacientes celiacos. Material y métodos: Estudio transversal de cohortes en niños entre 16 meses y 14 años: 46 con enfermedad celíaca al diagnóstico; 9 celíacos siguiendo dieta sin gluten y 42 controles. Se determina concentración plasmática de aminoácidos, en mmol/L, y variables clínicas y analíticas asociadas. Resultados: No diferencias estadísticamente significativas en IMC, edad o función renal, con ligero incremento de esteatorrea en celíacos. Citrulina, arginina y glutamina plasmáticas significativamente más bajas en los casos (17,7 μmol/l, 38,7 μmol/l, 479,6 μmol/l respectivamente que en controles (28,9 μmol/l, 56,2 μmol/l, 563,7 μmol/l. Citrulina plasmática significativamente más baja en grados avanzados de atrofia (13,8 μmol/l vs 19,7 μmol/l, p Introduction: Plasma citrulline is not incorporated in endogenous or exogenous proteins so it is a theoretical marker of villous atrophy. Our aim was to correlate plasma citrulline levels with severity of villous atrophy in celiac patients. Methods: Observational case-control study longitudinal in children 16 month-old to 14 year-old: 48 with untreated celiac disease, 9 celiac children under gluten free diet and 35 non-celiac healthy children. Plasma amino acids concentration is determined, expressed in μmol/L, and so are other clinical and analytical data. Results: No statistically significative difference found in the referring to BMI, age or renal function. Small increase in fecal fat in celiac children. Citrulline, arginine and glutamine are significantly lower in cases (17.7 μmol/l, 38.7 μmol/l, 479.6 μmol/l respectively than in controls (28.9 μmol/l, 56

  9. NITRIC OXIDE (NO, CITRULLINE - NO CYCLE ENZYMES, GLUTAMINE SYNTHETASE AND OXIDATIVE STRESS IN ANOXIA (HYPOBARIC HYPOXIA AND REPERFUSION IN RAT BRAIN

    Directory of Open Access Journals (Sweden)

    M. Swamy, Mohd Jamsani Mat Salleh, K. N .S. Sirajudeen, Wan Roslina Wan Yusof, G. Chandran

    2010-01-01

    Full Text Available Nitric oxide is postulated to be involved in the pathophysiology of neurological disorders due to hypoxia/ anoxia in brain due to increased release of glutamate and activation of N-methyl-D-aspartate receptors. Reactive oxygen species have been implicated in pathophysiology of many neurological disorders and in brain function. To understand their role in anoxia (hypobaric hypoxia and reperfusion (reoxygenation, the nitric oxide synthase, argininosuccinate synthetase, argininosuccinate lyase, glutamine synthetase and arginase activities along with the concentration of nitrate /nitrite, thiobarbituric acid reactive substances and total antioxidant status were estimated in cerebral cortex, cerebellum and brain stem of rats subjected to anoxia and reperfusion. The results of this study clearly demonstrated the increased production of nitric oxide by increased activity of nitric oxide synthase. The increased activities of argininosuccinate synthetase and argininosuccinate lyase suggest the increased and effective recycling of citrulline to arginine in anoxia, making nitric oxide production more effective and contributing to its toxic effects. The decreased activity of glutamine synthetase may favor the prolonged availability of glutamic acid causing excitotoxicity leading to neuronal damage in anoxia. The increased formation of thiobarbituric acid reactive substances and decreased total antioxidant status indicate the presence of oxidative stress in anoxia and reperfusion. The increased arginase and sustained decrease of GS activity in reperfusion group likely to be protective.

  10. Immunotherapy with Allergen Peptides

    Directory of Open Access Journals (Sweden)

    Larché Mark

    2007-06-01

    Full Text Available Specific allergen immunotherapy (SIT is disease-modifying and efficacious. However, the use of whole allergen preparations is associated with frequent allergic adverse events during treatment. Many novel approaches are being designed to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity. One approach is the use of short synthetic peptides which representing dominant T cell epitopes of the allergen. Short peptides exhibit markedly reduced capacity to cross link IgE and activate mast cells and basophils, due to lack of tertiary structure. Murine pre-clinical studies have established the feasibility of this approach and clinical studies are currently in progress in both allergic and autoimmune diseases.

  11. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  12. β-PEPTIDES CYCLOBUTANIQUES

    OpenAIRE

    Fernandez, Carlos

    2008-01-01

    The synthesis of β-amino acids, structural analogues of?-Amino acids, is an issue essential in the development of oligopeptides. A lot of work has been conducted on the behavior of β-peptide (sequence of β-amino acids) as well as peptides mixed (mixed β-and β- amino acids). As a result, the conformational preference of β-amino acids will induce the appearance of a three-dimensional structure of the oligopeptide ordered. Thus, several types of helices, sheets and elbows were observed in β-olig...

  13. Invertebrate FMRFamide related peptides.

    Science.gov (United States)

    Krajniak, Kevin G

    2013-06-01

    In 1977 the neuropeptide FMRFamide was isolated from the clam, Macrocallista nimbosa. Since then several hundred FMRFamide-related peptides (FaRPs) have been isolated from invertebrate animals. Precursors to the FaRPs likely arose in the cnidarians. With the transition to a bilateral body plan FaRPs became a fixture in the invertebrate phyla. They have come to play a critical role as neurotransmitters, neuromodulators, and neurohormones. FaRPs regulate a variety of body functions including, feeding, digestion, circulation, reproduction, movement. The evolution of the molecular form and function of these omnipresent peptides will be considered.

  14. Dicyclopropylmethyl peptide backbone protectant.

    Science.gov (United States)

    Carpino, Louis A; Nasr, Khaled; Abdel-Maksoud, Adel Ali; El-Faham, Ayman; Ionescu, Dumitru; Henklein, Peter; Wenschuh, Holger; Beyermann, Michael; Krause, Eberhard; Bienert, Michael

    2009-08-20

    The N-dicyclopropylmethyl (Dcpm) residue, introduced into amino acids via reaction of dicyclopropylmethanimine hydrochloride with an amino acid ester followed by sodium cyanoborohydride or triacetoxyborohydride reduction, can be used as an amide bond protectant for peptide synthesis. Examples which demonstrate the amelioration of aggregation effects include syntheses of the alanine decapeptide and the prion peptide (106-126). Avoidance of cyclization to the aminosuccinimide followed substitution of Fmoc-(Dcpm)Gly-OH for Fmoc-Gly-OH in the assembly of sequences containing the sensitive Asp-Gly unit.

  15. Biosynthesis of cardiac natriuretic peptides

    DEFF Research Database (Denmark)

    Goetze, Jens Peter

    2010-01-01

    . An inefficient post-translational prohormone maturation will also affect the biology of the cardiac natriuretic peptide system. This review aims at summarizing the myocardial synthesis of natriuretic peptides focusing on B-type natriuretic peptide, where new data has disclosed cardiac myocytes as highly...

  16. Peptide vectors for gene delivery: from single peptides to multifunctional peptide nanocarriers.

    Science.gov (United States)

    Raad, Markus de; Teunissen, Erik A; Mastrobattista, Enrico

    2014-07-01

    The therapeutic use of nucleic acids relies on the availability of sophisticated delivery systems for targeted and intracellular delivery of these molecules. Such a gene delivery should possess essential characteristics to overcome several extracellular and intracellular barriers. Peptides offer an attractive platform for nonviral gene delivery, as several functional peptide classes exist capable of overcoming these barriers. However, none of these functional peptide classes contain all the essential characteristics required to overcome all of the barriers associated with successful gene delivery. Combining functional peptides into multifunctional peptide vectors will be pivotal for improving peptide-based gene delivery systems. By using combinatorial strategies and high-throughput screening, the identification of multifunctional peptide vectors will accelerate the optimization of peptide-based gene delivery systems.

  17. Biochemical functionalization of peptide nanotubes with phage displayed peptides

    Science.gov (United States)

    Swaminathan, Swathi; Cui, Yue

    2016-09-01

    The development of a general approach for the biochemical functionalization of peptide nanotubes (PNTs) could open up existing opportunities in both fundamental studies as well as a variety of applications. PNTs are spontaneously assembled organic nanostructures made from peptides. Phage display has emerged as a powerful approach for identifying selective peptide binding motifs. Here, we demonstrate for the first time the biochemical functionalization of PNTs via peptides identified from a phage display peptide library. The phage-displayed peptides are shown to recognize PNTs. These advances further allow for the development of bifunctional peptides for the capture of bacteria and the self-assembly of silver particles onto PNTs. We anticipate that these results could provide significant opportunities for using PNTs in both fundamental studies and practical applications, including sensors and biosensors nanoelectronics, energy storage devices, drug delivery, and tissue engineering.

  18. 抗突变型瓜氨酸波形蛋白检测在类风湿关节炎诊断中的意义%Detection of the Antibodies of Anti-mutated Citrullinated Vimentin in Diagnosis of Rheumatoid Arthritis

    Institute of Scientific and Technical Information of China (English)

    陈霞

    2011-01-01

    Objective To analyze diagnostic value of anti-mutated citrullinated vimentin(anti-MCV),antibody for rheumatoid arthritis (RA). Methods Enzyme-linked immunosorbent assay(ELISA)was used to detect the level of serum anti-MCV antibody and anti-cyclin citrullinated peptides(CCP) antibody in 41 patients with RA,39 patients with other autoimmune diseases and 30 healthy controls.Mann-Whitney U test and Spearman correlation were used for statistical analysis, the diagnostic value of these two antibodies for RA were compared by receiver operating characteristic curve (ROC). Results The median level of anti-MCV was significantly higher in RA group (410. 00 U/ml) than that of other autoimmune diseases group (10. 60 U/ml) and healthy control group (8. 30 U/ml) (U=242. 0,P<0. 01,and (7 = 318. 0,P<0. 01,re-spectively). According to receiver operating characteristic curve analysis,area under the curve of anti-MCV was 0.901, standard error was 0. 032,95%CI (0. 838~0. 963) ;area under the curve of anti-CCP was 0. 918,standard error was 0. 027, 95%CI (0. 865~0. 970). The diagnostic value of them are similar. In RA the sensitivity of Anti-MCV super to that of Anti-CCP,but show lower specific than Anti-CCP. Anti-MCV has correlated to Anti-CCP(r=0. 615,P<0. 01). Conclusion Anti-MCV is a valuable index for the diagnosis of RA. And it could be a good new serum marker.%目的 探讨血清抗突变型瓜氨酸波形蛋白(MCV)抗体水平在诊断类风湿性关节炎(RA)中的意义.方法 用酶联免疫吸附试验(ELISA)测定41例RA患者、39例非RA患者和30例健康体检者血清抗MCV抗体、抗CCP抗体水平,采用Mann-Whitney U检验、Spearman相关分析,并用ROC曲线比较对RA的诊断价值.结果 RA组抗MCV抗体水平(中位数410.00 U/ml)明显高于非RA组(中位数10.60 U/ml)和健康对照组(中位数8.30 U/ml)(U值分别为242.0和318.0,P值均<0.01).抗MCV抗体ROC曲线下面积为0.901,标准误0.032,其95%的近似可信区间为0.838~0.963.

  19. Radiolabelled peptides for oncological diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Laverman, Peter; Boerman, Otto C.; Oyen, Wim J.G. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Sosabowski, Jane K. [Queen Mary University of London, Centre for Molecular Oncology, Barts Cancer Institute, London (United Kingdom)

    2012-02-15

    Radiolabelled receptor-binding peptides targeting receptors (over)expressed on tumour cells are widely under investigation for tumour diagnosis and therapy. The concept of using radiolabelled receptor-binding peptides to target receptor-expressing tissues in vivo has stimulated a large body of research in nuclear medicine. The {sup 111}In-labelled somatostatin analogue octreotide (OctreoScan trademark) is the most successful radiopeptide for tumour imaging, and was the first to be approved for diagnostic use. Based on the success of these studies, other receptor-targeting peptides such as cholecystokinin/gastrin analogues, glucagon-like peptide-1, bombesin (BN), chemokine receptor CXCR4 targeting peptides, and RGD peptides are currently under development or undergoing clinical trials. In this review, we discuss some of these peptides and their analogues, with regard to their potential for radionuclide imaging of tumours. (orig.)

  20. APD: the Antimicrobial Peptide Database.

    Science.gov (United States)

    Wang, Zhe; Wang, Guangshun

    2004-01-01

    An antimicrobial peptide database (APD) has been established based on an extensive literature search. It contains detailed information for 525 peptides (498 antibacterial, 155 antifungal, 28 antiviral and 18 antitumor). APD provides interactive interfaces for peptide query, prediction and design. It also provides statistical data for a select group of or all the peptides in the database. Peptide information can be searched using keywords such as peptide name, ID, length, net charge, hydrophobic percentage, key residue, unique sequence motif, structure and activity. APD is a useful tool for studying the structure-function relationship of antimicrobial peptides. The database can be accessed via a web-based browser at the URL: http://aps.unmc.edu/AP/main.html.

  1. Supplementation with Phycocyanobilin, Citrulline, Taurine, and Supranutritional Doses of Folic Acid and Biotin—Potential for Preventing or Slowing the Progression of Diabetic Complications

    Directory of Open Access Journals (Sweden)

    Mark F. McCarty

    2017-03-01

    Full Text Available Oxidative stress, the resulting uncoupling of endothelial nitric oxide synthase (eNOS, and loss of nitric oxide (NO bioactivity, are key mediators of the vascular and microvascular complications of diabetes. Much of this oxidative stress arises from up-regulated nicotinamide adenine dinucleotide phosphate (NADPH oxidase activity. Phycocyanobilin (PhyCB, the light-harvesting chromophore in edible cyanobacteria such as spirulina, is a biliverdin derivative that shares the ability of free bilirubin to inhibit certain isoforms of NADPH oxidase. Epidemiological studies reveal that diabetics with relatively elevated serum bilirubin are less likely to develop coronary disease or microvascular complications; this may reflect the ability of bilirubin to ward off these complications via inhibition of NADPH oxidase. Oral PhyCB may likewise have potential in this regard, and has been shown to protect diabetic mice from glomerulosclerosis. With respect to oxidant-mediated uncoupling of eNOS, high-dose folate can help to reverse this by modulating the oxidation status of the eNOS cofactor tetrahydrobiopterin (BH4. Oxidation of BH4 yields dihydrobiopterin (BH2, which competes with BH4 for binding to eNOS and promotes its uncoupling. The reduced intracellular metabolites of folate have versatile oxidant-scavenging activity that can prevent oxidation of BH4; concurrently, these metabolites promote induction of dihydrofolate reductase, which functions to reconvert BH2 to BH4, and hence alleviate the uncoupling of eNOS. The arginine metabolite asymmetric dimethylarginine (ADMA, typically elevated in diabetics, also uncouples eNOS by competitively inhibiting binding of arginine to eNOS; this effect is exacerbated by the increased expression of arginase that accompanies diabetes. These effects can be countered via supplementation with citrulline, which efficiently enhances tissue levels of arginine. With respect to the loss of NO bioactivity that contributes to

  2. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to citrulline-malate and faster recovery from muscle fatigue after exercise pursuant to Article 13(5) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    to citrulline-malate and faster recovery from muscle fatigue after exercise. Citrulline-malate is sufficiently characterised. The claimed effect is “maintenance of ATP levels through reduction of lactates in excess for an improved recovery from muscle fatigue”. The target population proposed by the applicant...... is healthy children above six years of age and adults. The Panel considers that faster recovery from muscle fatigue after exercise contributing to the restoration of muscle function is a beneficial physiological effect. A total of 33 references were considered as pertinent to the claim by the applicant...... to the methodological limitations of the study. A number of mechanistic, animal and in vitro studies were submitted. In the absence of evidence for an effect of consumption of citrulline-malate on a faster recovery from muscle fatigue after exercise in humans, these studies cannot be used as a source of data...

  3. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2014. Scientific Opinion on the substantiation of a health claim related to citrulline-malate and faster recovery from muscle fatigue after exercise pursuant to Article 13(5) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    the human study for the scientific substantiation of the claim. A health claim on citrulline-malate and faster recovery from muscle fatigue after exercise has already been assessed by the Panel with an unfavourable outcome. The additional information submitted by the applicant did not provide evidence...... on the scientific substantiation of a health claim related to citrulline-malate and faster recovery from muscle fatigue after exercise. The Panel considers that citrulline-malate is sufficiently characterised. The claimed effect proposed by the applicant is “improved recovery from muscle fatigue”. Faster recovery...... function. The evidence provided by the applicant did not establish that a faster reduction of blood lactate concentrations through a dietary intervention leads to faster recovery from muscle fatigue by contributing to the restoration of muscle function after exercise. No conclusions could be drawn from...

  4. Anti-citrullinated protein antibodies suppress let-7a expression in monocytes from patients with rheumatoid arthritis and facilitate the inflammatory responses in rheumatoid arthritis.

    Science.gov (United States)

    Lai, Ning-Sheng; Yu, Hui-Chun; Yu, Chia-Li; Koo, Malcolm; Huang, Hsien-Bin; Lu, Ming-Chi

    2015-12-01

    We hypothesized that anti-citrullinated protein antibodies (ACPAs) could affect the expression of miRNAs in monocytes and contribute to the inflammatory responses in rheumatoid arthritis (RA). The expression profiles of 270 human miRNAs, co-cultured with ACPAs or human immunoglobulin G (IgG), were analyzed using real-time polymerase chain reaction. Ten miRNAs exhibited differential expression in U937 cells after co-cultured with ACPAs compared with human IgG. The expression levels of these miRNAs were investigated in monocytes from 21 ACPA-positive RA patients and 13 controls. Among these miRNAs, the expression levels of let-7a was decreased in monocytes from ACPA-positive RA patients. The expression levels of let-7a showed a negative correlation with positivity of rheumatoid factor in patients sampled. We found that transfection of U937 cells with let-7a mimic suppressed K-Ras protein expression. In the ACPA-mediated signaling pathway, transfection of U937 cells with let-7a mimic suppressed the ACPA-enhanced phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), and the expression and secretion of interleukin (IL)-1β. In conclusion, ACPA-mediated decreased let-7a expression in monocytes from ACPA-positive RA patients. Decreased let-7a expression was associated with the positivity of RF in ACPA-positive RA patients. The decreased expression of let-7a could facilitate the inflammatory pathway via enhanced ACPA-mediated phosphorylation of ERK1/2 and JNK and increased expression of IL-1β through an increase in the expression of Ras proteins.

  5. Antimicrobial Peptides (AMPs

    Directory of Open Access Journals (Sweden)

    Mehrzad Sadredinamin

    2016-04-01

    Full Text Available Antimicrobial peptides (AMPs are extensive group of molecules that produced by variety tissues of invertebrate, plants, and animal species which play an important role in their immunity response. AMPs have different classifications such as; biosynthetic machines, biological sources, biological functions, molecular properties, covalent bonding patterns, three dimensional structures, and molecular targets.These molecules have multidimensional properties including antimicrobial activity, antiviral activity, antifungal activity, anti-parasite activity, biofilm control, antitumor activity, mitogens activity and linking innate to adaptive immunity that making them promising agents for therapeutic drugs. In spite of this advantage of AMPs, their clinical developments have some limitation for commercial development. But some of AMPs are under clinical trials for the therapeutic purpose such as diabetic foot ulcers, different bacterial infections and tissue damage. In this review, we emphasized on the source, structure, multidimensional properties, limitation and therapeutic applications of various antimicrobial peptides.

  6. Antimicrobial peptides in Echinoderms

    Directory of Open Access Journals (Sweden)

    C Li

    2010-05-01

    Full Text Available Antimicrobial peptides (AMPs are important immune effector molecules for invertebrates, including echinoderms, which lack a vertebrate-type adaptive immune system. Here we summarize the knowledge of such peptides in echinoderms. Strongylocins are a novel family of cysteine-rich AMPs, recently identified in the sea urchins, Strongylocentrotus droebachiensis and S. purpuratus. Although these molecules present diverse amino acid sequences, they share an identical cysteine arrangement pattern, dissimilar to other known AMPs. A family of heterodimeric AMPs, named centrocins, are also present in S. droebachiensis. Lysozymes and fragments of larger proteins, such as beta-thymocins, actin, histone 2A and filamin A have also been shown to display antimicrobial activities in echinoderms. Future studies on AMPs should be aimed in revealing how echinoderms use these AMPs in the immune response against microbial pathogens.

  7. Avian host defense peptides.

    Science.gov (United States)

    Cuperus, Tryntsje; Coorens, Maarten; van Dijk, Albert; Haagsman, Henk P

    2013-11-01

    Host defense peptides (HDPs) are important effector molecules of the innate immune system of vertebrates. These antimicrobial peptides are also present in invertebrates, plants and fungi. HDPs display broad-spectrum antimicrobial activities and fulfill an important role in the first line of defense of many organisms. It is becoming increasingly clear that in the animal kingdom the functions of HDPs are not confined to direct antimicrobial actions. Research in mammals has indicated that HDPs have many immunomodulatory functions and are also involved in other physiological processes ranging from development to wound healing. During the past five years our knowledge about avian HDPs has increased considerably. This review addresses our current knowledge on the evolution, regulation and biological functions of HDPs of birds.

  8. Peptides and Food Intake

    OpenAIRE

    Carmen Sobrino Crespo; Aranzazu Perianes Cachero; Lilian Puebla Jiménez; Vicente eBarrios; Eduardo eArilla

    2014-01-01

    The mechanisms for controlling food intake involve mainly an interplay between gut, brain, and adipose tissue (AT), among the major organs. Parasympathetic, sympathetic, and other systems are required for communication between the brain satiety center, gut, and AT. These neuronal circuits include a variety of peptides and hormones, being ghrelin the only orexigenic molecule known, whereas the plethora of other factors are inhibitors of appetite, suggesting its physiological relevance in the r...

  9. [C-peptide physiological effects].

    Science.gov (United States)

    Shpakov, A O; Granstrem, O K

    2013-02-01

    In the recent years there were numerous evidences that C-peptide, which was previously considered as a product of insulin biosynthesis, is one of the key regulators of physiological processes. C-peptide via heterotrimeric G(i/o) protein-coupled receptors activates a wide range of intracellular effector proteins and transcription factors and, thus, controls the inflammatory and neurotrophic processes, pain sensitivity, cognitive function, macro- and microcirculation, glomerular filtration. These effects of C-peptide are mainly expressed in its absolute or relative deficiency occurred in type 1 diabetes mellitus and they are less pronounced when the level of C-peptide is close to normal. Replacement therapy with C-peptide prevents many complications of type 1 diabetes, such as atherosclerosis, diabetic peripheral neuropathy, and nephropathy. C-peptide interacts with the insulin hexamer complexes and induces their dissociation and, as a result, regulates the functional activity of the insulin signaling system. At the same time, C-peptide at the concentrations above physiological may demonstrate pro-inflammatory effects on the endothelial cells and cause atherosclerotic changes in the vessels, which should be considered in the study of pathogenic mechanisms of complications of type 2 diabetes mellitus, where the level of C peptide is increased, as well as in the development of approaches for C-peptide application in clinic. This review is devoted contemporary achievements and unsolved problems in the study of C-peptide, as an important regulator of physiological and biochemical processes.

  10. The Clinical Application of Anti-CCP in Rheumatoid Arthritis and Other Rheumatic Diseases

    Directory of Open Access Journals (Sweden)

    CT Chou

    2007-01-01

    Full Text Available Rheumatoid arthritis (RA is a common rheumatic disease in Caucasians and in other ethnic groups. Diagnosis is mainly based on clinical features. Before 1998, the only serological laboratory test that could contribute to the diagnosis was that for rheumatoid factor (RF. The disease activity markers for the evaluation of clinical symptoms or treatment outcome were the erythrocyte sedimentation rate (ESR and C-reactive protein (CRP. As a matter of fact, the diagnosis of early RA is quite impossible, as the clinical criteria are insuffi cient at the beginning stage of the disease. In 1998, Schelleken reported that a high percentage of RA patients had a specifi c antibody that could interact with a synthetic peptide which contained the amino acid citrulline. The high specifi city (98% for RA of this new serological marker, anti-cyclic citrullinated antibody (anti-CCP antibody, can be detected early in RA, before the typical clinical features appear. The presence or absence of this antibody can easily distinguish other rheumatic diseases from RA. Additionally, the titer of anti-CCP can be used to predict the prognosis and treatment outcome after DMARDs or biological therapy. Therefore, with improvement of sensitivity, the anti-CCP antibody will be widely used as a routine laboratory test in the clinical practice for RA.

  11. PADI4 Haplotypes in Association with RA Mexican Patients, a New Prospect for Antigen Modulation

    Directory of Open Access Journals (Sweden)

    Maria Guadalupe Zavala-Cerna

    2013-01-01

    Full Text Available Peptidyl arginine deiminase IV (PAD 4 is the responsible enzyme for a posttranslational modification called citrullination, originating the antigenic determinant recognized by anti-cyclic citrullinated peptide antibodies (ACPA. Four SNPs (single nucleotide polymorphisms have been described in PADI4 gene to form a susceptibility haplotype for rheumatoid arthritis (RA; nevertheless, results in association studies appear contradictory in different populations. The aim of the study was to analyze if the presence of three SNPs in PADI4 gene susceptibility haplotype (GTG is associated with ACPA positivity in patients with RA. This was a cross-sectional study that included 86 RA patients and 98 healthy controls. Polymorphisms PADI4_89, PADI4_90, and PADI4_92 in the PADI4 gene were genotyped. The susceptibility haplotype (GTG was more frequent in RA patients; interestingly, we found a new haplotype associated with RA with a higher frequency (GTC. There were no associations between polymorphisms and high scores in Spanish HAQ-DI and DAS-28, but we did find an association between RARBIS index and PADI4_89, PADI4_90 polymorphisms. We could not confirm an association between susceptibility haplotype presence and ACPA positivity. Further evidence about proteomic expression of this gene will determine its participation in antigenic generation and autoimmunity.

  12. Bothrops jararaca peptide with anti-hypertensive action normalizes endothelium dysfunction involved in physiopathology of preeclampsia.

    Directory of Open Access Journals (Sweden)

    Gabriel Benedetti

    Full Text Available Preeclampsia, a pregnancy-specific syndrome characterized by hypertension, proteinuria and edema, is a major cause of fetal and maternal morbidity and mortality especially in developing countries. Bj-PRO-10c, a proline-rich peptide isolated from Bothrops jararaca venom, has been attributed with potent anti-hypertensive effects. Recently, we have shown that Bj-PRO-10c-induced anti-hypertensive actions involved NO production in spontaneous hypertensive rats. Using in vitro studies we now show that Bj-PRO-10c was able to increase NO production in human umbilical vein endothelial cells from hypertensive pregnant women (HUVEC-PE to levels observed in HUVEC of normotensive women. Moreover, in the presence of the peptide, eNOS expression as well as argininosuccinate synthase activity, the key rate-limiting enzyme of the citrulline-NO cycle, were enhanced. In addition, excessive superoxide production due to NO deficiency, one of the major deleterious effects of the disease, was inhibited by Bj-PRO-10c. Bj-PRO-10c induced intracellular calcium fluxes in both, HUVEC-PE and HUVEC, which, however, led to activation of eNOS expression only in HUVEC-PE. Since Bj-PRO-10c promoted biological effects in HUVEC from patients suffering from the disorder and not in normotensive pregnant women, we hypothesize that Bj-PRO-10c induces its anti-hypertensive effect in mothers with preeclampsia. Such properties may initiate the development of novel therapeutics for treating preeclampsia.

  13. Structural Characterization of Peptide Antibodies

    DEFF Research Database (Denmark)

    Chailyan, Anna; Marcatili, Paolo

    2015-01-01

    The role of proteins as very effective immunogens for the generation of antibodies is indisputable. Nevertheless, cases in which protein usage for antibody production is not feasible or convenient compelled the creation of a powerful alternative consisting of synthetic peptides. Synthetic peptides...... can be modified to obtain desired properties or conformation, tagged for purification, isotopically labeled for protein quantitation or conjugated to immunogens for antibody production. The antibodies that bind to these peptides represent an invaluable tool for biological research and discovery...

  14. Improving Peptide Applications Using Nanotechnology.

    Science.gov (United States)

    Narayanaswamy, Radhika; Wang, Tao; Torchilin, Vladimir P

    2016-01-01

    Peptides are being successfully used in various fields including therapy and drug delivery. With advancement in nanotechnology and targeted delivery carrier systems, suitable modification of peptides has enabled achievement of many desirable goals over-riding some of the major disadvantages associated with the delivery of peptides in vivo. Conjugation or physical encapsulation of peptides to various nanocarriers, such as liposomes, micelles and solid-lipid nanoparticles, has improved their in vivo performance multi-fold. The amenability of peptides to modification in chemistry and functionalization with suitable nanocarriers are very relevant aspects in their use and have led to the use of 'smart' nanoparticles with suitable linker chemistries that favor peptide targeting or release at the desired sites, minimizing off-target effects. This review focuses on how nanotechnology has been used to improve the number of peptide applications. The paper also focuses on the chemistry behind peptide conjugation to nanocarriers, the commonly employed linker chemistries and the several improvements that have already been achieved in the areas of peptide use with the help of nanotechnology.

  15. Antitumor Peptides from Marine Organisms

    Directory of Open Access Journals (Sweden)

    Mi Sun

    2011-10-01

    Full Text Available The biodiversity of the marine environment and the associated chemical diversity constitute a practically unlimited resource of new antitumor agents in the field of the development of marine bioactive substances. In this review, the progress on studies of antitumor peptides from marine sources is provided. The biological properties and mechanisms of action of different marine peptides are described; information about their molecular diversity is also presented. Novel peptides that induce apoptosis signal pathway, affect the tubulin-microtubule equilibrium and inhibit angiogenesis are presented in association with their pharmacological properties. It is intended to provide useful information for further research in the fields of marine antitumor peptides.

  16. The Pig PeptideAtlas

    DEFF Research Database (Denmark)

    Hesselager, Marianne Overgaard; Codrea, Marius; Sun, Zhi;

    2016-01-01

    underrepresented in existing repositories. We here present a significantly improved build of the Pig PeptideAtlas, which includes pig proteome data from 25 tissues and three body fluid types mapped to 7139 canonical proteins. The content of the Pig PeptideAtlas reflects actively ongoing research within...... the veterinary proteomics domain, and this article demonstrates how the expression of isoform-unique peptides can be observed across distinct tissues and body fluids. The Pig PeptideAtlas is a unique resource for use in animal proteome research, particularly biomarker discovery and for preliminary design of SRM...

  17. Solid-phase peptide synthesis

    DEFF Research Database (Denmark)

    Jensen, Knud Jørgen

    2013-01-01

    This chapter provides an introduction to and overview of peptide chemistry with a focus on solid-phase peptide synthesis. The background, the most common reagents, and some mechanisms are presented. This chapter also points to the different chapters and puts them into perspective.......This chapter provides an introduction to and overview of peptide chemistry with a focus on solid-phase peptide synthesis. The background, the most common reagents, and some mechanisms are presented. This chapter also points to the different chapters and puts them into perspective....

  18. Anticancer peptides from bacteria

    Directory of Open Access Journals (Sweden)

    Tomasz M. Karpiński

    2013-08-01

    Full Text Available Cancer is a leading cause of death in the world. The rapid development of medicine and pharmacology allows to create new and effective anticancer drugs. Among modern anticancer drugs are bacterial proteins. Until now has been shown anticancer activity among others azurin and exotoxin A from Pseudomonas aeruginosa, Pep27anal2 from Streptococcus pneumoniae, diphtheria toxin from Corynebacterium diphtheriae, and recently discovered Entap from Enterococcus sp. The study presents the current data regarding the properties, action and anticancer activity of listed peptides.

  19. Peptides and Food Intake

    Science.gov (United States)

    Sobrino Crespo, Carmen; Perianes Cachero, Aránzazu; Puebla Jiménez, Lilian; Barrios, Vicente; Arilla Ferreiro, Eduardo

    2014-01-01

    The mechanisms for controlling food intake involve mainly an interplay between gut, brain, and adipose tissue (AT), among the major organs. Parasympathetic, sympathetic, and other systems are required for communication between the brain satiety center, gut, and AT. These neuronal circuits include a variety of peptides and hormones, being ghrelin the only orexigenic molecule known, whereas the plethora of other factors are inhibitors of appetite, suggesting its physiological relevance in the regulation of food intake and energy homeostasis. Nutrients generated by food digestion have been proposed to activate G-protein-coupled receptors on the luminal side of enteroendocrine cells, e.g., the L-cells. This stimulates the release of gut hormones into the circulation such as glucagon-like peptide-1 (GLP-1), oxyntomodulin, pancreatic polypeptides, peptide tyrosine tyrosine, and cholecystokinin, which inhibit appetite. Ghrelin is a peptide secreted from the stomach and, in contrast to other gut hormones, plasma levels decrease after a meal and potently stimulate food intake. Other circulating factors such as insulin and leptin relay information regarding long-term energy stores. Both hormones circulate at proportional levels to body fat content, enter the CNS proportionally to their plasma levels, and reduce food intake. Circulating hormones can influence the activity of the arcuate nucleus (ARC) neurons of the hypothalamus, after passing across the median eminence. Circulating factors such as gut hormones may also influence the nucleus of the tractus solitarius (NTS) through the adjacent circumventricular organ. On the other hand, gastrointestinal vagal afferents converge in the NTS of the brainstem. Neural projections from the NTS, in turn, carry signals to the hypothalamus. The ARC acts as an integrative center, with two major subpopulations of neurons influencing appetite, one of them coexpressing neuropeptide Y and agouti-related protein (AgRP) that increases food

  20. Exploring Protein-Peptide Binding Specificity through Computational Peptide Screening.

    Directory of Open Access Journals (Sweden)

    Arnab Bhattacherjee

    2013-10-01

    Full Text Available The binding of short disordered peptide stretches to globular protein domains is important for a wide range of cellular processes, including signal transduction, protein transport, and immune response. The often promiscuous nature of these interactions and the conformational flexibility of the peptide chain, sometimes even when bound, make the binding specificity of this type of protein interaction a challenge to understand. Here we develop and test a Monte Carlo-based procedure for calculating protein-peptide binding thermodynamics for many sequences in a single run. The method explores both peptide sequence and conformational space simultaneously by simulating a joint probability distribution which, in particular, makes searching through peptide sequence space computationally efficient. To test our method, we apply it to 3 different peptide-binding protein domains and test its ability to capture the experimentally determined specificity profiles. Insight into the molecular underpinnings of the observed specificities is obtained by analyzing the peptide conformational ensembles of a large number of binding-competent sequences. We also explore the possibility of using our method to discover new peptide-binding pockets on protein structures.

  1. Prevalence of anti-citrullinated protein antibodies (ACPA in patients with diffuse large B-cell lymphoma (DLBCL: a case-control study.

    Directory of Open Access Journals (Sweden)

    Gunter Assmann

    Full Text Available BACKGROUND: Antibodies against citrullinated proteins (ACPA have been recognised as the most specific serum marker for rheumatoid arthritis. However, serum autoantibodies such as anti-nuclear antibodies have also been detected in the sera of different lymphatic malignancies without accompanying rheumatologic disease. Therefore, we conducted a study to evaluate the prevalence of ACPA in diffuse large B-cell non-Hodgkin lymphoma (DLBCL. METHODS: Sera of 395 DLBCL patients and 258 age-matched healthy controls were investigated to evaluate the prevalence of ACPA and RF. ACPA-positive data were stratified into subgroups of RF positivity and established prognostic parameters for DLBCL, including overall survival. In addition, the ACPA serum concentrations levels were compared to an ACPA-positive RA cohort (n = 175. The statistics were performed with χ2 test and Mann- Whitney-U test; Kaplan-Meyer curves (log rank test were used to analyse the overall survival. P-value <0.05 was statistically significant. RESULTS: ACPA, but not RF, occurred significantly more frequently in the sera of DLBCL patients than in healthy controls (3.5% versus 0.8%, p = 0.030. However, the ACPA serum concentration levels were significantly lower than in RA patients (median 10.4 versus 124.1 U/ml, p = 0.0001. After subgroup stratification, ACPA positivity in DLBCL was significantly associated with male gender (4.4% versus 0%, p = 0.022; odds ratio 1.046, CI 1.014-1.079 and with RF-IgM seropositivity (1.77% versus 0%, p = 0.043, but not with prognostic parameters for DLBCL. CONCLUSIONS: DLBCL is associated with a significantly higher prevalence of ACPA, with an increased prevalence in male patients, and simultaneous RF-IgM positivity. However, ACPA is not prognostic for DLBCL. The prevalence of RF-IgM, -IgA, or -IgG did not differ from healthy controls.

  2. Endocrine cells producing regulatory peptides.

    Science.gov (United States)

    Solcia, E; Usellini, L; Buffa, R; Rindi, G; Villani, L; Zampatti, C; Silini, E

    1987-07-15

    Recent data on the immunolocalization of regulatory peptides and related propeptide sequences in endocrine cells and tumors of the gastrointestinal tract, pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptides are the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, alpha-MSH and CLIP (corticotropin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenaline-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.

  3. Endogenous opioid peptides and epilepsy

    NARCIS (Netherlands)

    J. Haffmans (Judith)

    1985-01-01

    textabstractIn recent years a large number of pept:ides, many of which were originall.y characterized in non-neural tissues, have been reported to be present in the central nervous system ( CNS) . The detection of these peptides within the CNS has raised many questions regarding their source and mec

  4. Urinary Peptides in Rett Syndrome.

    Science.gov (United States)

    Solaas, K. M.; Skjeldal, O.; Gardner, M. L. G.; Kase, B. F.; Reichelt, K. L.

    2002-01-01

    A study found a significantly higher level of peptides in the urine of 53 girls with Rett syndrome compared with controls. The elevation was similar to that in 35 girls with infantile autism. Levels of peptides were lower in girls with classic Rett syndrome than those with congenital Rett syndrome. (Contains references.) (Author/CR)

  5. Peptide Antibiotics for ESKAPE Pathogens

    DEFF Research Database (Denmark)

    Thomsen, Thomas Thyge

    and toxicity by utilizing of the fruit fly Drosophila melanogaster as a whole animal model. This was carried out by testing of antimicrobial peptides targeting Gram-positive bacteria exemplified by the important human pathogen methicillin resistant S. aureus (MRSA). The peptide BP214 was developed from...

  6. Biosynthesis of cardiac natriuretic peptides

    DEFF Research Database (Denmark)

    Goetze, Jens Peter

    2010-01-01

    Cardiac-derived peptide hormones were identified more than 25 years ago. An astonishing amount of clinical studies have established cardiac natriuretic peptides and their molecular precursors as useful markers of heart disease. In contrast to the clinical applications, the biogenesis of cardiac...

  7. Synthetic peptides for antibody production

    NARCIS (Netherlands)

    Zegers, N.D.

    1995-01-01

    Synthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps that lead to the uni

  8. Peptide-LNA oligonucleotide conjugates

    DEFF Research Database (Denmark)

    Astakhova, I Kira; Hansen, Lykke Haastrup; Vester, Birte

    2013-01-01

    properties, peptides were introduced into oligonucleotides via a 2'-alkyne-2'-amino-LNA scaffold. Derivatives of methionine- and leucine-enkephalins were chosen as model peptides of mixed amino acid content, which were singly and doubly incorporated into LNA/DNA strands using highly efficient copper......Although peptide-oligonucleotide conjugates (POCs) are well-known for nucleic acids delivery and therapy, reports on internal attachment of peptides to oligonucleotides are limited in number. To develop a convenient route for preparation of internally labeled POCs with improved biomedical......(i)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry. DNA/RNA target binding affinity and selectivity of the resulting POCs were improved in comparison to LNA/DNA mixmers and unmodified DNA controls. This clearly demonstrates that internal attachment of peptides to oligonucleotides can significantly...

  9. Purification and use of E. coli peptide deformylase for peptide deprotection in chemoenzymatic peptide synthesis

    NARCIS (Netherlands)

    Di Toma, Claudia; Sonke, Theo; Quaedflieg, Peter J.; Janssen, Dick B.

    2013-01-01

    Peptide deformylases (PDFs) catalyze the removal of the formyl group from the N-terminal methionine residue in nascent polypeptide chains in prokaryotes. Its deformylation activity makes PDF an attractive candidate for the biocatalytic deprotection of formylated peptides that are used in chemoenzyma

  10. Potential of phage-displayed peptide library technology to identify functional targeting peptides

    Science.gov (United States)

    Krumpe, Lauren RH; Mori, Toshiyuki

    2010-01-01

    Combinatorial peptide library technology is a valuable resource for drug discovery and development. Several peptide drugs developed through phage-displayed peptide library technology are presently in clinical trials and the authors envision that phage-displayed peptide library technology will assist in the discovery and development of many more. This review attempts to compile and summarize recent literature on targeting peptides developed through peptide library technology, with special emphasis on novel peptides with targeting capacity evaluated in vivo. PMID:20150977

  11. 重组精氨酸脱亚胺酶制备L-瓜氨酸的工艺条件优化%Optimization of Preparing L-citrulline by Recombinant Arginine Deiminase

    Institute of Scientific and Technical Information of China (English)

    马越; 宿玲恰; 吴丹; 吴敬

    2015-01-01

    将来源于Pseudomonas putida ACCC 10185的ADI编码基因克隆到表达载体pET-24a(+)中,转化Escherichia coli BL21(DE3),通过超声波破碎得到粗酶液,酶活检测ADI酶活为26 U/mL发酵液。对酶转化L-精氨酸盐酸盐生成L-瓜氨酸的反应条件进行了优化,结果表明,当底物L-精氨酸盐酸盐浓度650 g/L,反应初始pH6.0,温度37℃,加酶量24 U/g底物,转速100-200 r/min,转化时间7 h,L-瓜氨酸转化率达到100%,是目前国内外报道的酶法制备L-瓜氨酸的最高水平。%ThearcAgene encoding ADI from Pseudomonas putida ACCC 10185 was cloned into the expression vector pET-24a (+). The vector was then transformed intoEscherichia coli BL21(DE3)for intracellular production of ADI. The crude enzyme was obtained by ultrasonic treatment, and activity in the fermentation broth of recombinantE. coli BL21(DE3)was 26 U/mL. Furthermore, the condition for enzymatic conversion of L-arginine monohydrochloride to L-citrulline by the recombinant ADI was optimized. At 650 g/L of L-arginine monohydrochloride, pH6.0, 37℃, 100-200 r/min, and 24 U ADI per gram substrate incubated for 7 hours, 100% of the L-arginine monohydrochloride was transformed into L-citrulline, which was the highest level of preparing L-citrulline by enzyme method in home and abroad presently.

  12. Study on the Production of L-citrulline by Engineering Bacteria and Applied to the Tobacco%L-瓜氨酸的工程菌制备及在卷烟中的应用

    Institute of Scientific and Technical Information of China (English)

    胡延奇

    2012-01-01

    L-citrulline was produced by arginine deiminase from engineering bacteria.Factors which affected the yield of L-citrulline were studied,including culture medium,inducing conditions and cell conversion.The optimum culture were found to be 5 g/L glucose,20 g/L tryptone,1 g/L K2HPO4·3H2O and 1 g/L MgSO4·7H2O.The optimum inducing conditions were found to be the cell OD600 1.0,the temperature 25 ℃,the time 7 h and lactose 5 g/L.Under the optimum cell conditions: the pH 6.0,the temperature 40 ℃,and substrate concentration 60 g/L,55.1 g/L of L-citrulline could be obtained.The cells could be used for 3 times and the yields were stable.The findings in cigarette show that it was the best effect when the amount was 0.02%.%利用工程菌中的精氨酸托亚氨基酶转化制备L-瓜氨酸,进行了培养基、诱导条件和细胞转化条件的研究。培养基最佳组成为:葡萄糖质量浓度5 g/L,胰蛋白胨20 g/L,K2HPO4.3H2O 1 g/L,MgSO4.7H2O 1 g/L;最佳诱导条件为:OD600值1.0,诱导温度25℃,诱导时间7 h,诱导剂(乳糖)5 g/L;最佳的细胞转化条件为:pH 6.0,温度40℃,精氨酸质量浓度60 g/L。在最佳条件下瓜氨酸的产量达55.1 g/L,细胞可连续使用三次,且产量稳定。在卷烟中的初步应用研究结果显示:当其用量为0.02%时综合效果最好。

  13. Radiopharmaceutical development of radiolabelled peptides

    Energy Technology Data Exchange (ETDEWEB)

    Fani, Melpomeni; Maecke, Helmut R. [University Hospital Freiburg, Department of Nuclear Medicine, Freiburg (Germany)

    2012-02-15

    Receptor targeting with radiolabelled peptides has become very important in nuclear medicine and oncology in the past few years. The overexpression of many peptide receptors in numerous cancers, compared to their relatively low density in physiological organs, represents the molecular basis for in vivo imaging and targeted radionuclide therapy with radiolabelled peptide-based probes. The prototypes are analogs of somatostatin which are routinely used in the clinic. More recent developments include somatostatin analogs with a broader receptor subtype profile or with antagonistic properties. Many other peptide families such as bombesin, cholecystokinin/gastrin, glucagon-like peptide-1 (GLP-1)/exendin, arginine-glycine-aspartic acid (RGD) etc. have been explored during the last few years and quite a number of potential radiolabelled probes have been derived from them. On the other hand, a variety of strategies and optimized protocols for efficient labelling of peptides with clinically relevant radionuclides such as {sup 99m}Tc, M{sup 3+} radiometals ({sup 111}In, {sup 86/90}Y, {sup 177}Lu, {sup 67/68}Ga), {sup 64/67}Cu, {sup 18}F or radioisotopes of iodine have been developed. The labelling approaches include direct labelling, the use of bifunctional chelators or prosthetic groups. The choice of the labelling approach is driven by the nature and the chemical properties of the radionuclide. Additionally, chemical strategies, including modification of the amino acid sequence and introduction of linkers/spacers with different characteristics, have been explored for the improvement of the overall performance of the radiopeptides, e.g. metabolic stability and pharmacokinetics. Herein, we discuss the development of peptides as radiopharmaceuticals starting from the choice of the labelling method and the conditions to the design and optimization of the peptide probe, as well as some recent developments, focusing on a selected list of peptide families, including somatostatin

  14. Peptide primary messengers in plants

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The peptide primary messengers regulate embryonic development,cell growth and many other activities in animal cells. But recent evidence verified that peptide primary messengers are also involved in plant defense responses, the recognition between pollen and stigma and keep the balance between cell proliferation and differentiations in shoot apical meristems. Those results suggest that plants may actually make wide use of peptide primary messengers, both in embryonic development and late life when they rally their cells to defend against pathogens and insect pests. The recent advance in those aspects is reviewed.

  15. Next generation natriuretic peptide measurement

    DEFF Research Database (Denmark)

    Hunter, Ingrid; Goetze, Jens P

    2012-01-01

    Plasma measurement of natriuretic peptides is a "must" for clinical laboratories. For the next generation measurement, the unraveling of the molecular complexity of the peptides points toward a more qualitative assessment, as the posttranslational processing also changes with disease. Changes...... in the molecular heterogeneity could in itself contain valuable information of clinical status, and the time seems right for industry and dedicated researchers in the field to get together and discuss the next generation natriuretic peptide measurement. In such an environment, new strategies can be developed...

  16. New vasoactive peptides in cirrhosis

    DEFF Research Database (Denmark)

    Kimer, Nina; Goetze, Jens Peter; Bendtsen, Flemming;

    2014-01-01

    BACKGROUND: Patients with cirrhosis have substantial circulatory imbalance between vasoconstrictive and vasodilating forces. The study of circulatory vasoactive peptides may provide important pathophysiological information. This study aimed to assess concentrations, organ extraction and relations...... to haemodynamic changes in the pro-peptides copeptin, proadrenomedullin and pro-atrial natriuretic peptide (proANP) in patients with cirrhosis. MATERIALS AND METHODS: Fifty-four cirrhotic patients and 15 controls were characterized haemodynamically during a liver vein catheterization. Copeptin, proadrenomedullin...... found no extraction of copeptin, proadrenomedullin or proANP over the liver. Copeptin correlated with portal pressure (R=0·50, P

  17. Diagnostic significance of detection of anti-citrullinated peptide antibodies in juvenile rheumatoid arthritis%抗瓜氨酸肽抗体谱在幼年类风湿关节炎诊断中的意义

    Institute of Scientific and Technical Information of China (English)

    茹晋丽; 李小峰; 张莉芸; 魏华; 胡学芳; 牛红青

    2007-01-01

    目的 探讨抗环瓜氨酸肽抗体(抗CCP抗体)、类风湿因子(RF)、抗核周因子(APF)、抗角蛋白抗体(AKA)对幼年类风湿关节炎(JRA)诊断的意义,并与类风湿关节炎(RA)进行比较.方法 分别采用酶联免疫吸附试验(ELISA)、胶乳凝集法、间接免疫荧光法检测54例JRA患者、31例非RA对照组、116例成人RA患者血清中的抗CCP抗体、RF、APF、AKA.结果 54例JRA患者抗CCP抗体、RF、APF、AKA的敏感性分别为61.1%、57.4%、37.0%、18.5%,特异性分别为96.8%、93.6%、96.8%、100%.抗CCP抗体与RF在JRA的敏感性差异无统计学意义,但明显高于APF、AKA;4种抗体在JRA的特异性比较差异无统计学意义.RA患者中4种抗体敏感性分别为82.3%、78.3%、48.7%、25.4%,特异性分别为95.7%、73.7%、91.6%、94.0%.4种抗体在JRA诊断中的敏感性均明显低于RA组,RF在JRA患者中特异性明显高于RA患者,而其他3种抗体的特异性在两组患者比较差异无统计学意义.结论 虽然抗CCP抗体谱在JRA诊断中的敏感性不及RA组,但对JRA的诊断仍具有较好的敏感性和特异性,可用于JRA的诊断.

  18. Targeting the Eph System with Peptides and Peptide Conjugates.

    Science.gov (United States)

    Riedl, Stefan J; Pasquale, Elena B

    2015-01-01

    Eph receptor tyrosine kinases and ephrin ligands constitute an important cell communication system that controls development, tissue homeostasis and many pathological processes. Various Eph receptors/ephrins are present in essentially all cell types and their expression is often dysregulated by injury and disease. Thus, the 14 Eph receptors are attracting increasing attention as a major class of potential drug targets. In particular, agents that bind to the extracellular ephrin-binding pocket of these receptors show promise for medical applications. This pocket comprises a broad and shallow groove surrounded by several flexible loops, which makes peptides particularly suitable to target it with high affinity and selectivity. Accordingly, a number of peptides that bind to Eph receptors with micromolar affinity have been identified using phage display and other approaches. These peptides are generally antagonists that inhibit ephrin binding and Eph receptor/ ephrin signaling, but some are agonists mimicking ephrin-induced Eph receptor activation. Importantly, some of the peptides are exquisitely selective for single Eph receptors. Most identified peptides are linear, but recently the considerable advantages of cyclic scaffolds have been recognized, particularly in light of potential optimization towards drug leads. To date, peptide improvements have yielded derivatives with low nanomolar Eph receptor binding affinity, high resistance to plasma proteases and/or long in vivo half-life, exemplifying the merits of peptides for Eph receptor targeting. Besides their modulation of Eph receptor/ephrin function, peptides can also serve to deliver conjugated imaging and therapeutic agents or various types of nanoparticles to tumors and other diseased tissues presenting target Eph receptors.

  19. Screening of TACE Peptide Inhibitors from Phage Display Peptide Library

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To obtain the recombinant tumor necrosis factor-α converting enzyme (TACE) ectodomain and use it as a selective molecule for the screening of TACE peptide inhibitors, the cDNA coding catalytic domain (T800) and full-length ectodomain (T1300) of TACE were amplified by RTPCR, and the expression plasmids were constructed by inserting T800 and T1300 into plasmid pET28a and pET-28c respectively. The recombinant T800 and T1300 were induced by IPTG, and SDSPAGE and Western blotting analysis results revealed that T800 and T1300 were highly expressed in the form of inclusion body. After Ni2+-NTA resin affinity chromatography, the recombinant proteins were used in the screening of TACE-binding peptides from phage display peptide library respectively. After 4 rounds of biopanning, the positive phage clones were analyzed by ELISA, competitive inhibition assay and DNA sequencing. A common amino acid sequence (TRWLVYFSRPYLVAT) was found and synthesized. The synthetic peptide could inhibit the TNF-α release from LPS-stimulated human peripheral blood mononuclear cells (PBMC) up to 60.3 %. FACS analysis revealed that the peptide mediated the accumulation of TNF-α on the cell surface. These results demonstrate that the TACE-binding peptide is an effective antagonist of TACE.

  20. Viral O-GalNAc peptide epitopes

    DEFF Research Database (Denmark)

    Olofsson, Sigvard; Blixt, Klas Ola; Bergström, Tomas

    2016-01-01

    on a novel three-step procedure that identifies any reactive viral O-glycosyl peptide epitope with respect to (i) relevant peptide sequence, (ii) the reactive glycoform out of several possible glycopeptide isomers of that peptide sequence, and (iii) possibly tolerated carbohydrate or peptide structural...

  1. Neoglycolipidation for modulating peptide properties

    DEFF Research Database (Denmark)

    van Witteloostuijn, Søren Blok

    The alarming increase in the prevalence of obesity and associated comorbidities such as type 2 diabetes emphasizes the urgent need for new drugs with both anorectic and antidiabetic eects. Several peptide hormones secreted from the gastrointestinal tract play an important role in the physiological...... regulation of appetite, food intake, and glucose homeostasis, and many of these peptides display a signicant potential for treatment of obesity and/or type 2 diabetes. This Ph.D. thesis describes three novel approaches for utilizing gut peptides as the starting point for developing obesity and diabetes drugs...... of food intake, which was enhanced compared to native NMU. Project II explored the design, synthesis, and characterization of neoglycolipidated analogs of glucagon-like peptide 1 (GLP-1). Neoglycolipidation reduced lipophilicity and maintained or even improved in vitro potency towards the GLP-1 receptor...

  2. Activity and Stability of Arginine Deiminase for Producing L-citrulline%L-瓜氨酸酶法制备中精氨酸脱亚氨酸酶的活性与稳定性研究

    Institute of Scientific and Technical Information of China (English)

    李加友; 曹瑜; 刘毅; 钱绍松; 焦庆才

    2005-01-01

    A novel Enterococcus faecalis strain designated NJ402 was found with high activity of arginine deiminase (ADI). The optimum condition for catalytic activity was determined in terms of temperature (about 40℃),thermostability (available 37℃) and pH (6-7). The effects of substrate and product concentration were studied.The effects of various metal ions added in reaction mixtures on the biocatalyst were investigated and ADI of NJ402was found to exhibit Co2+ dependence, different from previous reports. Surfactant, cetyl trimethyl ammonium bromide, was one of the most important keys for producing L-citrulline. The enzyme in resting cells possessed the quality of high stability for reuse.

  3. Peptides and proteins

    Energy Technology Data Exchange (ETDEWEB)

    Bachovchin, W.W.; Unkefer, C.J.

    1994-12-01

    Advances in magnetic resonance and vibrational spectroscopy make it possible to derive detailed structural information about biomolecular structures in solution. These techniques are critically dependent on the availability of labeled compounds. For example, NMR techniques used today to derive peptide and protein structures require uniformity {sup 13}C-and {sup 15}N-labeled samples that are derived biosynthetically from (U-6-{sup 13}C) glucose. These experiments are possible now because, during the 1970s, the National Stable Isotope Resource developed algal methods for producing (U-6-{sup 13}C) glucose. If NMR techniques are to be used to study larger proteins, we will need sophisticated labelling patterns in amino acids that employ a combination of {sup 2}H, {sup 13}C, and {sup 15}N labeling. The availability of these specifically labeled amino acids requires a renewed investment in new methods for chemical synthesis of labeled amino acids. The development of new magnetic resonance or vibrational techniques to elucidate biomolecular structure will be seriously impeded if we do not see rapid progress in labeling technology. Investment in labeling chemistry is as important as investment in the development of advanced spectroscopic tools.

  4. Antimicrobial peptides in crustaceans

    Directory of Open Access Journals (Sweden)

    RD Rosa

    2010-11-01

    Full Text Available Crustaceans are a large and diverse invertebrate animal group that mounts a complex and efficient innate immune response against a variety of microorganisms. The crustacean immune system is primarily related to cellular responses and the production and release of important immune effectors into the hemolymph. Antimicrobial proteins and/or peptides (AMPs are key components of innate immunity and are widespread in nature, from bacteria to vertebrate animals. In crustaceans, 15 distinct AMP families are currently recognized, although the great majority (14 families comes from members of the order Decapoda. Crustacean AMPs are generally cationic, gene-encoded molecules that are mainly produced by circulating immune-competent cells (hemocytes or are derived from unrelated proteins primarily involved in other biological functions. In this review, we tentatively classified the crustacean AMPs into four main groups based on their amino acid composition, structural features and multi-functionality. We also attempted to summarize the current knowledge on their implication both in an efficient response to microbial infections and in crustacean survival.

  5. Antimicrobial peptides in annelids

    Directory of Open Access Journals (Sweden)

    A Tasiemski

    2008-06-01

    Full Text Available Gene encoded antimicrobial peptides (AMPs are widely distributed among living organisms including plants, invertebrates and vertebrates. They constitute important effectors of the innate immune response by exerting multiple roles as mediators of inflammation with impact on epithelial and inflammatory cells influencing diverse processes such as cytokine release, cell proliferation, angiogenesis, wound healing, chemotaxis and immune induction. In invertebrates, most of the data describe the characterization and/or the function of AMPs in the numerically and economically most representative group which are arthropods. Annelids are among the first coelomates and are therefore of special phylogenetic interest. Compared to other invertebrate groups, data on annelid’s immunity reveal heavier emphasis on the cellular than on the humoral response suggesting that immune defense of annelids seems to be principally developed as cellular immunity.This paper gives an overview of the variety of AMPs identified in the three classes of annelids, i.e. polychaetes, oligochaetes and achaetes. Their functions, when they have been studied, in the humoral or cellular response of annelids are also mentioned.

  6. Natriuretic peptides in cardiometabolic regulation and disease

    DEFF Research Database (Denmark)

    Zois, Nora E; Bartels, Emil D; Hunter, Ingrid

    2014-01-01

    decade. Dysregulation of the natriuretic peptide system has been associated with obesity, glucose intolerance, type 2 diabetes mellitus, and essential hypertension. Moreover, the natriuretic peptides have been implicated in the protection against atherosclerosis, thrombosis, and myocardial ischaemia. All...... these conditions can coexist and potentially lead to heart failure, a syndrome associated with a functional natriuretic peptide deficiency despite high circulating concentrations of immunoreactive peptides. Therefore, dysregulation of the natriuretic peptide system, a 'natriuretic handicap', might be an important...

  7. Peptides and Anti-peptide Antibodies for Small and Medium Scale Peptide and Anti-peptide Affinity Microarrays: Antigenic Peptide Selection, Immobilization, and Processing.

    Science.gov (United States)

    Zhang, Fan; Briones, Andrea; Soloviev, Mikhail

    2016-01-01

    This chapter describes the principles of selection of antigenic peptides for the development of anti-peptide antibodies for use in microarray-based multiplex affinity assays and also with mass-spectrometry detection. The methods described here are mostly applicable to small to medium scale arrays. Although the same principles of peptide selection would be suitable for larger scale arrays (with 100+ features) the actual informatics software and printing methods may well be different. Because of the sheer number of proteins/peptides to be processed and analyzed dedicated software capable of processing all the proteins and an enterprise level array robotics may be necessary for larger scale efforts. This report aims to provide practical advice to those who develop or use arrays with up to ~100 different peptide or protein features.

  8. Versatile Peptide C-Terminal Functionalization via a Computationally Engineered Peptide Amidase

    NARCIS (Netherlands)

    Wu, Bian; Wijma, Hein J.; Song, Lu; Rozeboom, Henriette J.; Poloni, Claudia; Tian, Yue; Arif, Muhammad I.; Nuijens, Timo; Quaedflieg, Peter J. L. M.; Szymanski, Wiktor; Feringa, Ben L.; Janssen, Dick B.

    2016-01-01

    The properties of synthetic peptides, including potency, stability, and bioavailability, are strongly influenced by modification of the peptide chain termini. Unfortunately, generally applicable methods for selective and mild C-terminal peptide functionalization are lacking. In this work, we explore

  9. Peptides and Food Intake

    Directory of Open Access Journals (Sweden)

    Carmen Sobrino Crespo

    2014-04-01

    Full Text Available Nutrients created by the digestion of food are proposed to active G protein coupled receptors on the luminal side of enteroendocrine cells e.g. the L-cell. This stimulates the release of gut hormones. Hormones released from the gut and adipose tissue play an important rol in the regulation of food intake and energy expenditure (1.Many circulating signals, including gut hormones, can influence the activity of the arcuate nucleus (ARC neurons directly, after passing across the median eminence. The ARC is adjacent to the median eminence, a circumventricular organ with fenestrated capillaries and hence an incomplete blood-brain barrier (2. The ARC of the hypothalamus is believed to play a crucial role in the regulation of food intake and energy homeostasis. The ARC contains two populations of neurons with opposing effect on food intake (3. Medially located orexigenic neurons (i.e those stimulating appetite express neuropeptide Y (NPY and agouti-related protein (AgRP (4-5. Anorexigenic neurons (i.e. those inhibiting appetite in the lateral ARC express alpha-melanocyte stimulating hormone (α-MSH derived from pro-opiomelanocortin (POMC and cocaine and amphetamine-regulated transcript (CART (6. The balance between activities of these neuronal circuits is critical to body weight regulation.In contrast, other peripheral signals influence the hypothalamus indirectly via afferent neuronal pathway and brainstem circuits. In this context gastrointestinal’s vagal afferents are activated by mechanoreceptors and chemoreceptors, and converge in the nucleus of the tractus solitaries (NTS of the brainstem. Neuronal projections from the NTS, in turn, carry signals to the hypotalamus (1, 7. Gut hormones also alter the activity of the ascending vagal pathway from the gut to the brainstem. In the cases of ghrelin and Peptide tyrosine tyrosine (PYY, there are evidences for both to have a direct action on the arcuate nucleus and an action via the vagus nerve a

  10. Automated solid-phase peptide synthesis to obtain therapeutic peptides

    Directory of Open Access Journals (Sweden)

    Veronika Mäde

    2014-05-01

    Full Text Available The great versatility and the inherent high affinities of peptides for their respective targets have led to tremendous progress for therapeutic applications in the last years. In order to increase the drugability of these frequently unstable and rapidly cleared molecules, chemical modifications are of great interest. Automated solid-phase peptide synthesis (SPPS offers a suitable technology to produce chemically engineered peptides. This review concentrates on the application of SPPS by Fmoc/t-Bu protecting-group strategy, which is most commonly used. Critical issues and suggestions for the synthesis are covered. The development of automated methods from conventional to essentially improved microwave-assisted instruments is discussed. In order to improve pharmacokinetic properties of peptides, lipidation and PEGylation are described as covalent conjugation methods, which can be applied by a combination of automated and manual synthesis approaches. The synthesis and application of SPPS is described for neuropeptide Y receptor analogs as an example for bioactive hormones. The applied strategies represent innovative and potent methods for the development of novel peptide drug candidates that can be manufactured with optimized automated synthesis technologies.

  11. Selective Intracellular Delivery of Recombinant Arginine Deiminase (ADI) Using pH-Sensitive Cell Penetrating Peptides To Overcome ADI Resistance in Hypoxic Breast Cancer Cells.

    Science.gov (United States)

    Yeh, Tzyy-Harn; Chen, Yun-Ru; Chen, Szu-Ying; Shen, Wei-Chiang; Ann, David K; Zaro, Jennica L; Shen, Li-Jiuan

    2016-01-04

    Arginine depletion strategies, such as pegylated recombinant arginine deiminase (ADI-PEG20), offer a promising anticancer treatment. Many tumor cells have suppressed expression of a key enzyme, argininosuccinate synthetase 1 (ASS1), which converts citrulline to arginine. These tumor cells become arginine auxotrophic, as they can no longer synthesize endogenous arginine intracellularly from citrulline, and are therefore sensitive to arginine depletion therapy. However, since ADI-PEG20 only depletes extracellular arginine due to low internalization, ASS1-expressing cells are not susceptible to treatment since they can synthesize arginine intracellularly. Recent studies have found that several factors influence ASS1 expression. In this study, we evaluated the effect of hypoxia, frequently encountered in many solid tumors, on ASS1 expression and its relationship to ADI-resistance in human MDA-MB-231 breast cancer cells. It was found that MDA-MB-231 cells developed ADI resistance in hypoxic conditions with increased ASS1 expression. To restore ADI sensitivity as well as achieve tumor-selective delivery under hypoxia, we constructed a pH-sensitive cell penetrating peptide (CPP)-based delivery system to carry ADI inside cells to deplete both intra- and extracellular arginine. The delivery system was designed to activate the CPP-mediated internalization only at the mildly acidic pH (6.5-7) associated with the microenvironment of hypoxic tumors, thus achieving better selectivity toward tumor cells. The pH sensitivity of the CPP HBHAc was controlled by recombinant fusion to a histidine-glutamine (HE) oligopeptide, generating HBHAc-HE-ADI. The tumor distribution of HBHAc-HE-ADI was comparable to ADI-PEG20 in a mouse xenograft model of human breast cancer cells in vivo. In addition, HBHAc-HE-ADI showed increased in vitro cellular uptake in cells incubated in a mildly acidic pH (hypoxic conditions) compared to normal pH (normoxic conditions), which correlated with p

  12. Peptides: A new class of anticancer drugs

    Directory of Open Access Journals (Sweden)

    Ryszard Smolarczyk

    2009-07-01

    Full Text Available Peptides are a novel class of anticancer agents embracing two distinct categories: natural antibacterial peptides, which are preferentially bound by cancer cells, and chemically synthesized peptides, which bind specifically to precise molecular targets located on the surface of tumor cells. Antibacterial peptides bind to both cell and mitochondrial membranes. Some of these peptides attach to the cell membrane, resulting in its disorganization. Other antibacterial peptides penetrate cancer cells without causing cell membrane damage, but they disrupt mitochondrial membranes. Thanks to phage and aptamer libraries, it has become possible to obtain synthetic peptides blocking or activating some target proteins found in cancer cells as well as in cells forming the tumor environment. These synthetic peptides can feature anti-angiogenic properties, block enzymes indispensable for sustained tumor growth, and reduce tumor ability to metastasize. In this review the properties of peptides belonging to both categories are discussed and attempts of their application for therapeutic purposes are outlined.

  13. Exploration of the Medicinal Peptide Space.

    Science.gov (United States)

    Gevaert, Bert; Stalmans, Sofie; Wynendaele, Evelien; Taevernier, Lien; Bracke, Nathalie; D'Hondt, Matthias; De Spiegeleer, Bart

    2016-01-01

    The chemical properties of peptide medicines, known as the 'medicinal peptide space' is considered a multi-dimensional subset of the global peptide space, where each dimension represents a chemical descriptor. These descriptors can be linked to biofunctional, medicinal properties to varying degrees. Knowledge of this space can increase the efficiency of the peptide-drug discovery and development process, as well as advance our understanding and classification of peptide medicines. For 245 peptide drugs, already available on the market or in clinical development, multivariate dataexploration was performed using peptide relevant physicochemical descriptors, their specific peptidedrug target and their clinical use. Our retrospective analysis indicates that clusters in the medicinal peptide space are located in a relatively narrow range of the physicochemical space: dense and empty regions were found, which can be explored for the discovery of novel peptide drugs.

  14. Perspectives and Peptides of the Next Generation

    Science.gov (United States)

    Brogden, Kim A.

    Shortly after their discovery, antimicrobial peptides from prokaryotes and eukaryotes were recognized as the next potential generation of pharmaceuticals to treat antibiotic-resistant bacterial infections and septic shock, to preserve food, or to sanitize surfaces. Initial research focused on identifying the spectrum of antimicrobial agents, determining the range of antimicrobial activities against bacterial, fungal, and viral pathogens, and assessing the antimicrobial activity of synthetic peptides versus their natural counterparts. Subsequent research then focused on the mechanisms of antimicrobial peptide activity in model membrane systems not only to identify the mechanisms of antimicrobial peptide activity in microorganisms but also to discern differences in cytotoxicity for prokaryotic and eukaryotic cells. Recent, contemporary work now focuses on current and future efforts to construct hybrid peptides, peptide congeners, stabilized peptides, peptide conjugates, and immobilized peptides for unique and specific applications to control the growth of microorganisms in vitro and in vivo.

  15. Peptide synthesis using unprotected peptides through orthogonal coupling methods.

    Science.gov (United States)

    Tam, J P; Lu, Y A; Liu, C F; Shao, J

    1995-01-01

    We describe an approach to the synthesis of peptides from segments bearing no protecting groups through an orthogonal coupling method to capture the acyl segment as a thioester that then undergoes an intramolecular acyl transfer to the amine component with formation of a peptide bond. Two orthogonal coupling methods to give the covalent ester intermediate were achieved by either a thiol-thioester exchange mediated by a trialkylphosphine and an alkylthiol or a thioesterification by C alpha-thiocarboxylic acid reacting with a beta-bromo amino acid. With this approach, unprotected segments ranging from 4 to 37 residues were coupled to aqueous solution to give free peptides up to 54 residues long with high efficiency. Images Fig. 1 PMID:8618926

  16. Peptide Vaccine: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Weidang Li

    2014-07-01

    Full Text Available Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.

  17. Twilight reloaded: the peptide experience

    Science.gov (United States)

    Weichenberger, Christian X.; Pozharski, Edwin; Rupp, Bernhard

    2017-01-01

    The de facto commoditization of biomolecular crystallography as a result of almost disruptive instrumentation automation and continuing improvement of software allows any sensibly trained structural biologist to conduct crystallo­graphic studies of biomolecules with reasonably valid outcomes: that is, models based on properly interpreted electron density. Robust validation has led to major mistakes in the protein part of structure models becoming rare, but some depositions of protein–peptide complex structure models, which generally carry significant interest to the scientific community, still contain erroneous models of the bound peptide ligand. Here, the protein small-molecule ligand validation tool Twilight is updated to include peptide ligands. (i) The primary technical reasons and potential human factors leading to problems in ligand structure models are presented; (ii) a new method used to score peptide-ligand models is presented; (iii) a few instructive and specific examples, including an electron-density-based analysis of peptide-ligand structures that do not contain any ligands, are discussed in detail; (iv) means to avoid such mistakes and the implications for database integrity are discussed and (v) some suggestions as to how journal editors could help to expunge errors from the Protein Data Bank are provided. PMID:28291756

  18. Peptide-enhanced oral delivery of therapeutic peptides and proteins

    DEFF Research Database (Denmark)

    Kristensen, Mie; Foged, Camilla; Berthelsen, Jens;

    2013-01-01

    throughout the gastrointestinal (GI) tract, chemical stability is an inherent challenge when employing amino acid-based excipients for oral delivery, and multiple approaches have been investigated to improve this. The exact mechanisms of transepithelial translocation are discussed, and it is believed......Systemic therapy upon oral delivery of biologics, such as peptide and protein drugs is limited due to their large molecular size, their low enzymatic stability and their inability to cross the intestinal epithelium. Ways to overcome the epithelial barrier include the use of peptide-based excipients...

  19. Recent development of peptide self-assembly

    Institute of Scientific and Technical Information of China (English)

    Xiubo Zhao; Fang Pan; Jian R. Lu

    2008-01-01

    Amino acids are the building blocks to build peptides and proteins. Recent development in peptide synthesis has however enabled us to mimic this natural process by preparing various long and short peptides possessing different conformations and biological functions. The self-assembly of short designed peptides into molecular nanostructures is becoming a growing interest in nanobiotechnology. Self-assembled peptides exhibit several attractive features for applications in tissue regeneration, drug delivery, biological surface engineering as well as in food science, cosmetic industry and antibiotics. The aim of this review is to introduce the readers to a number of representative studies on peptide self-assembly.

  20. Characterization of Synthetic Peptides by Mass Spectrometry

    DEFF Research Database (Denmark)

    Prabhala, Bala K; Mirza, Osman; Højrup, Peter;

    2015-01-01

    Mass spectrometry (MS) is well suited for analysis of the identity and purity of synthetic peptides. The sequence of a synthetic peptide is most often known, so the analysis is mainly used to confirm the identity and purity of the peptide. Here, simple procedures are described for MALDI-TOF-MS an......Mass spectrometry (MS) is well suited for analysis of the identity and purity of synthetic peptides. The sequence of a synthetic peptide is most often known, so the analysis is mainly used to confirm the identity and purity of the peptide. Here, simple procedures are described for MALDI...

  1. NCAM Mimetic Peptides: An Update

    DEFF Research Database (Denmark)

    Berezin, Vladimir; Bock, Elisabeth

    2008-01-01

    pharmacological tools interfering with NCAM functions. Recent progress in our understanding of the structural basis of NCAM-mediated cell adhesion and signaling has allowed a structure-based design of NCAM mimetic peptides. Using this approach a number of peptides termed P2, P1-B, P-3-DE and P-3-G, whose...... sequences contain one or several NCAM homophilic binding sites involved in NCAM binding to itself, have been identified. By means of NMR titration analysis and molecular modeling a number of peptides derived from NCAM and targeting NCAM heterophilic ligands such as the fibroblast growth factor receptor...... in vitro and in vivo, making them attractive pharmacological tools suitable for drug development for the treatment of neurodegenerative disorders and impaired memory....

  2. Antiviral active peptide from oyster

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    An active peptide against herpes virus was isolated from the enzymic hydrolysate of oyster (Crassostrea gigas) and purified with the definite direction hydrolysis technique in the order of alcalase and bromelin. The hydrolysate was fractioned into four ranges of molecular weight (>10 kDa, 10-5 kDa, 5-1 kDa and <1 kDa) using ultrafiltration membranes and dialysis. The fraction of 10?5 kDa was purified using consecutive chromatographic methods including DEAE Sephadex A-25 column, Sephadex G-25 column, and high performance liquid chromatogram (HPLC) by activity-guided isolation. The antiviral effect of the obtained peptide on herpetic virus was investigated in Vero cells by observing cytopathic effect (CPE). The result shows that the peptide has high inhibitory activity on herpetic virus.

  3. 抗突变型瓜氨酸波形蛋白抗体及相关自身抗体在幼年特发性关节炎中的检测意义%Antibodies to mutated citrullinated vimentin and some associated autoantibodies in juvenile idiopathic arthritis

    Institute of Scientific and Technical Information of China (English)

    张露月; 茹晋丽; 颉晓香; 车国柱; 靳雪琴; 李小峰

    2015-01-01

    Objective To compare the diagnostic value of antibodies to mutated citrullinated vimentin (MCV) and some associated autoantibodies in juvenile idiopathic arthritis and to further analyze the relation between antibodies and inflammatory markers.Method Antibodies to cyclic citrullinated peptides (CCP) and anti-MCV antibodies were detected by enzyme-linked immunosorbent assay (ELISA), antiperinuclear factor (APF) and antikeratin antibody (AKA) by indirect immunofluorescent assay, as well as rheumatoid factor (RF) by latex agglutination test in serum samples from 113 patients with JIA and 56 children without rheumatoid arthritis.Result (1) The positive rate of anti-MCV antibodies, anti-CCP antibodies, and RF was 16.8%, 14.2%, and 21.2% in the JIA.In the other group, the positive rate was 2.2% , 2.2% , and 6.5%.There was a significant difference between the two groups (x2 =8.105,6.337, 7.036, P < 0.05).The positive rate of AKA and APF were not significantly different.The area under the ROC curve of anti-MCV antibodies, anti-CCP antibodies, RF, AKA, APF was 0.579, 0.561, 0.578, 0.539, 0.505.(2) The positive rate of anti-MCV antibodies and anti-CCP antibodies were higher than other antibodies.In the RF-positive polyarticular disease patients, they were higher than those in the other subtypes (P < 0.05).Antibody levels were not significantly different (P > 0.05) from other subtypes.(3) The swollen joint counts and tender joint counts had a low correlation to anti-MCV antibodies, anti-CCP antibodies, RF, AKA and APF.No correlation was found between ESR, CRP and anti-MCV antibodies, anti-CCP antibodies, RF, AKA and APF.Conclusion The diagnostic value of anti-MCV antibodies is low for JIA.The positive rate of anti-MCV antibodies was higher than the other antibodies in the classification of JIA.There was a low correlation between anti-MCV antibodies, anti-CCP antibodies, RF, AKA, APF and swollen joint counts, tender joint counts.%目的 比较抗突变型瓜

  4. Peptides and the new endocrinology

    Science.gov (United States)

    Schwyzer, Robert

    1982-01-01

    The discovery of regulatory peptides common to the nervous and the endocrine systems (brain, gut, and skin) has brought about a revolution in our concepts of endocrinology and neurology. We are beginning to understand some of the complex interrelationships between soma and psyche that might, someday, be important for an integrated treatment of diseases. Examples of the actions of certain peptides in the periphery and in the central nervous system are given, and their biosynthesis and molecular anatomy as carriers for information are discussed.

  5. Novel Formulations for Antimicrobial Peptides

    Directory of Open Access Journals (Sweden)

    Ana Maria Carmona-Ribeiro

    2014-10-01

    Full Text Available Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy.

  6. An enhancer peptide for membrane-disrupting antimicrobial peptides

    Directory of Open Access Journals (Sweden)

    Zhang Hong

    2010-02-01

    Full Text Available Abstract Background NP4P is a synthetic peptide derived from a natural, non-antimicrobial peptide fragment (pro-region of nematode cecropin P4 by substitution of all acidic amino acid residues with amides (i.e., Glu → Gln, and Asp → Asn. Results In the presence of NP4P, some membrane-disrupting antimicrobial peptides (ASABF-α, polymyxin B, and nisin killed microbes at lower concentration (e.g., 10 times lower minimum bactericidal concentration for ASABF-α against Staphylococcus aureus, whereas NP4P itself was not bactericidal and did not interfere with bacterial growth at ≤ 300 μg/mL. In contrast, the activities of antimicrobial agents with a distinct mode of action (indolicidin, ampicillin, kanamycin, and enrofloxacin were unaffected. Although the membrane-disrupting activity of NP4P was slight or undetectable, ASABF-α permeabilized S. aureus membranes with enhanced efficacy in the presence of NP4P. Conclusions NP4P selectively enhanced the bactericidal activities of membrane-disrupting antimicrobial peptides by increasing the efficacy of membrane disruption against the cytoplasmic membrane.

  7. Production and characterization of peptide antibodies

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Hansen, Paul Robert; Houen, Gunnar

    2012-01-01

    Proteins are effective immunogens for generation of antibodies. However, occasionally the native protein is known but not available for antibody production. In such cases synthetic peptides derived from the native protein are good alternatives for antibody production. These peptide antibodies...... are powerful tools in experimental biology and are easily produced to any peptide of choice. A widely used approach for production of peptide antibodies is to immunize animals with a synthetic peptide coupled to a carrier protein. Very important is the selection of the synthetic peptide, where factors...... such as structure, accessibility and amino acid composition are crucial. Since small peptides tend not to be immunogenic, it may be necessary to conjugate them to carrier proteins in order to enhance immune presentation. Several strategies for conjugation of peptide-carriers applied for immunization exist...

  8. Histidine-Containing Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2000-01-01

    Peptide nucleic acids containing histidine moieties are provided. These compounds have applications including diagnostics, research and potential therapeutics.......Peptide nucleic acids containing histidine moieties are provided. These compounds have applications including diagnostics, research and potential therapeutics....

  9. Recent advances in solid phase peptide synthesis

    OpenAIRE

    White, P.D.

    2016-01-01

    Since its introduction by Merrifield half a century ago, solid phase peptide synthesis has evolved to become the enabling technology for the development of peptide therapeutics. Using modern methods, 100 - 1000s of peptides can be routinely synthesised in parallel for screening as leads for drug development and peptide APIs are produced in ton scale. In this talk I consider the state of art and report on recent advances to overcome remaining issues such as aspartimide formation, racemisation ...

  10. Development and use of engineered peptide deformylase in chemoenzymatic peptide synthesis

    NARCIS (Netherlands)

    Di Toma, Claudia

    2012-01-01

    Deze thesis beschrijft het onderzoek naar potentieel van het gebruik van het peptide deformylase (PDF) in chemo enzymatische peptide synthese. PDF is geschikt voor selective N terminale deformylatie van bepaalde N-formyl-peptides zonder gelijktijdige hydrolyse van de peptide binding. Door de uitdagi

  11. The evolution of peptide hormones.

    Science.gov (United States)

    Niall, H D

    1982-01-01

    Despite limitations in our present knowledge it is already possible to discern the main features of peptide hormone evolution, since the same mechanisms (and indeed the same hormone molecules) function in many different ways. This underlying unity of organization has its basis in the tendency of biochemical networks, once established, to survive and diversify. The most surprising recent findings in endocrinology have been the discovery of vertebrate peptide hormones in multiple sites within the same organism, and the reports, persuasive but requiring confirmation, of vertebrate hormones in primitive unicellular organisms (20, 20a). Perhaps the major challenge for the future is to define the roles and interactions of the many peptide hormones identified in brain (18). The most primitive bacteria and the human brain, though an enormous evolutionary distance apart, may have more in common than we have recognized until now. As Axelrod & Hamilton have pointed out in a recent provocative article, "The Evolution of Cooperation" (1), bacteria, though lacking a brain, are capable of adaptive behavior that can be analysed in terms of game theory. It is clear that we can learn a great deal about the whole evolutionary process from a study of the versatile and durable peptide hormones molecules.

  12. Glucagon-like peptide-1

    DEFF Research Database (Denmark)

    Holst, Jens Juul

    2006-01-01

    The incretin hormones are intestinal polypeptides that enhance postprandial insulin secretion. Gastric inhibitory polypeptide (GIP) was initially thought to regulate gastric acid secretion, whereas glucagon-like peptide-1 (GLP-1) was discovered as a result of a systematic search for intestinal...

  13. Water drives peptide conformational transitions

    CERN Document Server

    Nerukh, Dmitry

    2011-01-01

    Transitions between metastable conformations of a dipeptide are investigated using classical molecular dynamics simulation with explicit water molecules. The distribution of the surrounding water at different moments before the transitions and the dynamical correlations of water with the peptide's configurational motions indicate that water is the main driving force of the conformational changes.

  14. Glucagon-like peptide-1

    DEFF Research Database (Denmark)

    Deacon, C F; Holst, Jens Juul; Carr, R D

    1999-01-01

    Type 2 diabetes mellitus is a metabolic disease resulting in raised blood sugar which, if not satisfactorily controlled, can cause severe and often debilitating complications. Unfortunately, for many patients, the existing therapies do not give adequate control. Glucagon-like peptide-1 (GLP-1) is...

  15. Peptides and metallic nanoparticles for biomedical applications.

    NARCIS (Netherlands)

    Kogan, M.J.; Olmedo, I.; Hosta, L.; Guerrero, A.R.; Cruz Ricondo, L.J.; Albericio, F.

    2007-01-01

    In this review, we describe the contribution of peptides to the biomedical applications of metallic nanoparticles. We also discuss strategies for the preparation of peptide-nanoparticle conjugates and the synthesis of the peptides and metallic nanoparticles. An overview of the techniques used for th

  16. Double-Stranded Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2001-01-01

    A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  17. Toxins and antimicrobial peptides: interactions with membranes

    Science.gov (United States)

    Schlamadinger, Diana E.; Gable, Jonathan E.; Kim, Judy E.

    2009-08-01

    The innate immunity to pathogenic invasion of organisms in the plant and animal kingdoms relies upon cationic antimicrobial peptides (AMPs) as the first line of defense. In addition to these natural peptide antibiotics, similar cationic peptides, such as the bee venom toxin melittin, act as nonspecific toxins. Molecular details of AMP and peptide toxin action are not known, but the universal function of these peptides to disrupt cell membranes of pathogenic bacteria (AMPs) or a diverse set of eukaryotes and prokaryotes (melittin) is widely accepted. Here, we have utilized spectroscopic techniques to elucidate peptide-membrane interactions of alpha-helical human and mouse AMPs of the cathelicidin family as well as the peptide toxin melittin. The activity of these natural peptides and their engineered analogs was studied on eukaryotic and prokaryotic membrane mimics consisting of <200-nm bilayer vesicles composed of anionic and neutral lipids as well as cholesterol. Vesicle disruption, or peptide potency, was monitored with a sensitive fluorescence leakage assay. Detailed molecular information on peptidemembrane interactions and peptide structure was further gained through vibrational spectroscopy combined with circular dichroism. Finally, steady-state fluorescence experiments yielded insight into the local environment of native or engineered tryptophan residues in melittin and human cathelicidin embedded in bilayer vesicles. Collectively, our results provide clues to the functional structures of the engineered and toxic peptides and may impact the design of synthetic antibiotic peptides that can be used against the growing number of antibiotic-resistant pathogens.

  18. Activity of Cathelicidin Peptides against Chlamydia spp.

    Science.gov (United States)

    Donati, Manuela; Di Leo, Korinne; Benincasa, Monica; Cavrini, Francesca; Accardo, Silvia; Moroni, Alessandra; Gennaro, Renato; Cevenini, Roberto

    2005-01-01

    The in vitro activity of six cathelicidin peptides against 25 strains of Chlamydia was investigated. SMAP-29 proved to be the most active peptide, reducing the inclusion numbers of all 10 strains of Chlamydia trachomatis tested by ≥50% at 10 μg/ml. This peptide was also active against C. pneumoniae and C. felis. PMID:15728927

  19. Single-molecule studies on individual peptides and peptide assemblies on surfaces.

    Science.gov (United States)

    Yang, Yanlian; Wang, Chen

    2013-10-13

    This review is intended to reflect the recent progress in single-molecule studies of individual peptides and peptide assemblies on surfaces. The structures and the mechanism of peptide assembly are discussed in detail. The contents include the following topics: structural analysis of single peptide molecules, adsorption and assembly of peptides on surfaces, folding structures of the amyloid peptides, interaction between amyloid peptides and dye or drug molecules, and modulation of peptide assemblies by small molecules. The explorations of peptide adsorption and assembly will benefit the understanding of the mechanisms for protein-protein interactions, protein-drug interactions and the pathogenesis of amyloidoses. The investigations on peptide assembly and its modulations could also provide a potential approach towards the treatment of the amyloidoses.

  20. Peptide array-based characterization and design of ZnO-high affinity peptides.

    Science.gov (United States)

    Okochi, Mina; Sugita, Tomoya; Furusawa, Seiji; Umetsu, Mitsuo; Adschiri, Tadafumi; Honda, Hiroyuki

    2010-08-15

    Peptides with both an affinity for ZnO and the ability to generate ZnO nanoparticles have attracted attention for the self-assembly and templating of nanoscale building blocks under ambient conditions with compositional uniformity. In this study, we have analyzed the specific binding sites of the ZnO-binding peptide, EAHVMHKVAPRP, which was identified using a phage display peptide library. The peptide binding assay against ZnO nanoparticles was performed using peptides synthesized on a cellulose membrane using the spot method. Using randomized rotation of amino acids in the ZnO-binding peptide, 125 spot-synthesized peptides were assayed. The peptide binding activity against ZnO nanoparticles varied greatly. This indicates that ZnO binding does not depend on total hydrophobicity or other physical parameters of these peptides, but rather that ZnO recognizes the specific amino acid alignment of these peptides. In addition, several peptides were found to show higher binding ability compared with that of the original peptides. Identification of important binding sites in the EAHVMHKVAPRP peptide was investigated by shortened, stepwise sequence from both termini. Interestingly, two ZnO-binding sites were found as 6-mer peptides: HVMHKV and HKVAPR. The peptides identified by amino acid substitution of HKVAPR were found to show high affinity and specificity for ZnO nanoparticles.

  1. Brain natriuretic peptide measurement in pulmonary medicine.

    Science.gov (United States)

    Salerno, Daniel; Marik, Paul E

    2011-12-01

    Serum levels of natriuretic peptides are well established as important biomarkers in patients with cardiac disease. Less attention has been placed on the role of natriuretic peptides in patients with pulmonary conditions. In several well-defined groups of patients with pulmonary disease natriuretic peptides provide the clinician with clinically valuable information. A limitation of the interpretation of natriuretic peptides in pulmonary disease is the confounding effect of concurrent conditions such as heart failure, hypoxia, sepsis and renal failure. The present paper reviews the role of natriuretic peptides for diagnosis, risk stratification and prognosis of several pulmonary disorders.

  2. Fabrication of Odor Sensor Using Peptide

    Science.gov (United States)

    Hotokebuchi, Yuta; Hayashi, Kenshi; Toko, Kiyoshi; Chen, Ronggang; Ikezaki, Hidekazu

    We report fabrication of an odor sensor using peptides. Peptides were designed to acquire the specific reception for a target odor molecule. Au surface of the sensor electrode was coated by the designed peptide using the method of self assembled monolayers (SAMs). Functionalized Au surfaces by the peptides were confirmed by ellipsometry and cyclic voltammetry. The odorants of vanillin, phenethyl alcohol and hexanol were discriminated by QCM sensor with the peptide surface. Moreover, we verified specific interaction between amino acid (Trp) and vanillin by fluorescence assay.

  3. Towards the MHC-peptide combinatorics.

    Science.gov (United States)

    Kangueane, P; Sakharkar, M K; Kolatkar, P R; Ren, E C

    2001-05-01

    The exponentially increased sequence information on major histocompatibility complex (MHC) alleles points to the existence of a high degree of polymorphism within them. To understand the functional consequences of MHC alleles, 36 nonredundant MHC-peptide complexes in the protein data bank (PDB) were examined. Induced fit molecular recognition patterns such as those in MHC-peptide complexes are governed by numerous rules. The 36 complexes were clustered into 19 subgroups based on allele specificity and peptide length. The subgroups were further analyzed for identifying common features in MHC-peptide binding pattern. The four major observations made during the investigation were: (1) the positional preference of peptide residues defined by percentage burial upon complex formation is shown for all the 19 subgroups and the burial profiles within entries in a given subgroup are found to be similar; (2) in class I specific 8- and 9-mer peptides, the fourth residue is consistently solvent exposed, however this observation is not consistent in class I specific 10-mer peptides; (3) an anchor-shift in positional preference is observed towards the C terminal as the peptide length increases in class II specific peptides; and (4) peptide backbone atoms are proportionately dominant at the MHC-peptide interface.

  4. Computer-Aided Design of Antimicrobial Peptides

    DEFF Research Database (Denmark)

    Fjell, Christopher D.; Hancock, Robert E.W.; Jenssen, Håvard

    2010-01-01

    chemical parameters with biological activities of the peptide, using statistical methods. In this review we will discuss two different in silico strategies of computer-aided antibacterial peptide design, a linear correlation model build as an extension of traditional principal component analysis (PCA......) and a non-linear artificial neural network model. Studies on structurally diverse peptides, have concluded that the PCA derived model are able to guide the antibacterial peptide design in a meaningful way, however requiring rather a high homology between the peptides in the test-set and the in silico...... library, to ensure a successful prediction. In contrast, the neural network model, though significantly less explored in relation to antimicrobial peptide design, has proven extremely promising, demonstrating impressive prediction success and ranking of random peptide libraries correlating well...

  5. Biology of the CAPA peptides in insects.

    Science.gov (United States)

    Predel, R; Wegener, C

    2006-11-01

    CAPA peptides have been isolated from a broad range of insect species as well as an arachnid, and can be grouped into the periviscerokinin and pyrokinin peptide families. In insects, CAPA peptides are the characteristic and most abundant neuropeptides in the abdominal neurohemal system. In many species, CAPA peptides exert potent myotropic effects on different muscles such as the heart. In others, including blood-sucking insects able to transmit serious diseases, CAPA peptides have strong diuretic or anti-diuretic effects and thus are potentially of medical importance. CAPA peptides undergo cell-type-specific sorting and packaging, and are the first insect neuropeptides shown to be differentially processed. In this review, we discuss the current knowledge on the structure, distribution, receptors and physiological actions of the CAPA peptides.

  6. The first salamander defensin antimicrobial peptide.

    Directory of Open Access Journals (Sweden)

    Ping Meng

    Full Text Available Antimicrobial peptides have been widely identified from amphibian skins except salamanders. A novel antimicrobial peptide (CFBD was isolated and characterized from skin secretions of the salamander, Cynops fudingensis. The cDNA encoding CFBD precursor was cloned from the skin cDNA library of C. fudingensis. The precursor was composed of three domains: signal peptide of 17 residues, mature peptide of 41 residues and intervening propeptide of 3 residues. There are six cysteines in the sequence of mature CFBD peptide, which possibly form three disulfide-bridges. CFBD showed antimicrobial activities against Staphylococcus aureus, Bacillus subtilis, Candida albicans and Escherichia coli. This peptide could be classified into family of β-defensin based on its sequence similarity with β-defensins from other vertebrates. Evolution analysis indicated that CFBD was close to fish β-defensin. As far as we know, CFBD is the first β-defensin antimicrobial peptide from salamanders.

  7. Therapeutic uses of gastrointestinal peptides.

    Science.gov (United States)

    Redfern, J S; O'Dorisio, T M

    1993-12-01

    The GI tract is one of nature's great pharmacies. Most, if not all, biologically active peptides can be found there, and it is quite likely that others remain to be discovered. Our ability to exploit this resource has expanded considerably over the past two decades. Advances in analytical techniques have allowed investigators to rapidly isolate and purify new compounds from tissue extracts. Sequencing and de novo synthesis of newly discovered peptides are now routine, and the structural modifications required to alter activity and tailor a compound to a particular use are easily made. A number of gastrointestinal peptides or their analogues for use in clinical studies are available from commercial sources (see Table 7). Somatostatin is the first gut peptide to successfully complete development and yield a pharmaceutical compound with a broad range of action. Several of the peptides discussed in this article have similar potential. TRH stands out as a candidate because of its effectiveness in the treatment of experimental spinal cord injury and a variety of shock states. Such a broad range of action in critical fields may justify the intensive development required to yield potent, long-acting, and highly specific analogues. Similarly, the antimetastatic and immunostimulant properties of the enkephalins offer promise for new therapies in the treatment of AIDS, ARC, and cancer. Studies with amylin may lead to new and more precise regimens of blood sugar control in insulin-dependent diabetics and could in turn, prevent some of the worst long-term effects of the disease. The development of effective intranasal forms of GHRH could spare children with GH-GHRH deficiency the distress of repeated injections and help to prevent excessive GH blood levels. Secretin, glucagon, or CGRP might be used one day in cardiovascular emergencies, and VIP or its analogues could prove effective in the treatment of asthma. Although preliminary results with many of these peptides are

  8. Anionic phospholipids modulate peptide insertion into membranes.

    Science.gov (United States)

    Liu, L P; Deber, C M

    1997-05-06

    While the insertion of a hydrophobic peptide or membrane protein segment into the bilayer can be spontaneous and driven mainly by the hydrophobic effect, anionic lipids, which comprise ca. 20% of biological membranes, provide a source of electrostatic attractions for binding of proteins/peptides into membranes. To unravel the interplay of hydrophobicity and electrostatics in the binding of peptides into membranes, we designed peptides de novo which possess the typical sequence Lys-Lys-Ala-Ala-Ala-X-Ala-Ala-Ala-Ala-Ala-X-Ala-Ala-Trp-Ala-Ala-X-Ala-Al a-Ala-Lys-Lys-Lys-Lys-amide, where X residues correspond to "guest" residues which encompass a range of hydrophobicity (Leu, Ile, Gly, and Ser). Circular dichroism spectra demonstrated that peptides were partially (40-90%) random in aqueous buffer but were promoted to form 100% alpha-helical structures by anionic lipid micelles. In neutral lipid micelles, only the relatively hydrophobic peptides (X = L and I) spontaneously adopted the alpha-helical conformation, but when 25% of negatively charged lipids were mixed in to mimic the content of anionic lipids in biomembranes, the less hydrophobic (X = S and G) peptides then formed alpha-helical conformations. Consistent with these findings, fluorescence quenching by the aqueous-phase quencher iodide indicated that in anionic (dimyristoylphosphatidylglycerol) vesicles, the peptide Trp residue was buried in the lipid vesicle hydrophobic core, while in neutral (dimyristoylphosphatidylcholine) vesicles, only hydrophobic (X = L and I) peptides were shielded from the aqueous solution. Trp emission spectra of peptides in the presence of phospholipids doxyl-labeled at the 5-, 7-, 10-, 12-, and 16-fatty acid positions implied not only a transbilayer orientation for inserted peptides but also that mixed peptide populations (transbilayer + surface-associated) may arise. Overall results suggest that for hydrophobic peptides with segmental threshold hydrophobicity below that which

  9. Encapsulation of bioactive whey peptides in soy lecithin-derived nanoliposomes: Influence of peptide molecular weight.

    Science.gov (United States)

    Mohan, Aishwarya; McClements, David Julian; Udenigwe, Chibuike C

    2016-12-15

    Encapsulation of peptides can be used to enhance their stability, delivery and bioavailability. This study focused on the effect of the molecular weight range of whey peptides on their encapsulation within soy lecithin-derived nanoliposomes. Peptide molecular weight did not have a major impact on encapsulation efficiency or liposome size. However, it influenced peptide distribution amongst the surface, core, and bilayer regions of the liposomes, as determined by electrical charge (ζ-potential) and FTIR analysis. The liposome ζ-potential depended on peptide molecular weight, suggesting that the peptide charged groups were in different locations relative to the liposome surfaces. FTIR analysis indicated that the least hydrophobic peptide fractions interacted more strongly with choline on the liposome surfaces. The results suggested that the peptides were unequally distributed within the liposomes, even at the same encapsulation efficiency. These findings are important for designing delivery systems for commercial production of encapsulated peptides with improved functional attributes.

  10. Taylor Dispersion Analysis as a promising tool for assessment of peptide-peptide interactions

    DEFF Research Database (Denmark)

    Høgstedt, Ulrich B; Schwach, Grégoire; van de Weert, Marco

    2016-01-01

    . In this work, we show that protein-protein and peptide-peptide interactions can advantageously be investigated by measurement of the diffusion coefficient using Taylor Dispersion Analysis. Through comparison to Dynamic Light Scattering it was shown that Taylor Dispersion Analysis is well suited...... for the characterization of protein-protein interactions of solutions of α-lactalbumin and human serum albumin. The peptide-peptide interactions of three selected peptides were then investigated in a concentration range spanning from 0.5mg/ml up to 80mg/ml using Taylor Dispersion Analysis. The peptide-peptide interactions...... determination indicated that multibody interactions significantly affect the PPIs at concentration levels above 25mg/ml for the two charged peptides. Relative viscosity measurements, performed using the capillary based setup applied for Taylor Dispersion Analysis, showed that the viscosity of the peptide...

  11. Taylor Dispersion Analysis as a promising tool for assessment of peptide-peptide interactions.

    Science.gov (United States)

    Høgstedt, Ulrich B; Schwach, Grégoire; van de Weert, Marco; Østergaard, Jesper

    2016-10-10

    Protein-protein and peptide-peptide (self-)interactions are of key importance in understanding the physiochemical behavior of proteins and peptides in solution. However, due to the small size of peptide molecules, characterization of these interactions is more challenging than for proteins. In this work, we show that protein-protein and peptide-peptide interactions can advantageously be investigated by measurement of the diffusion coefficient using Taylor Dispersion Analysis. Through comparison to Dynamic Light Scattering it was shown that Taylor Dispersion Analysis is well suited for the characterization of protein-protein interactions of solutions of α-lactalbumin and human serum albumin. The peptide-peptide interactions of three selected peptides were then investigated in a concentration range spanning from 0.5mg/ml up to 80mg/ml using Taylor Dispersion Analysis. The peptide-peptide interactions determination indicated that multibody interactions significantly affect the PPIs at concentration levels above 25mg/ml for the two charged peptides. Relative viscosity measurements, performed using the capillary based setup applied for Taylor Dispersion Analysis, showed that the viscosity of the peptide solutions increased with concentration. Our results indicate that a viscosity difference between run buffer and sample in Taylor Dispersion Analysis may result in overestimation of the measured diffusion coefficient. Thus, Taylor Dispersion Analysis provides a practical, but as yet primarily qualitative, approach to assessment of the colloidal stability of both peptide and protein formulations.

  12. Characterization of Peptide Antibodies by Epitope Mapping Using Resin-Bound and Soluble Peptides.

    Science.gov (United States)

    Trier, Nicole Hartwig

    2015-01-01

    Characterization of peptide antibodies through identification of their target epitopes is of utmost importance. Understanding antibody specificity at the amino acid level provides the key to understand the specific interaction between antibodies and their epitopes and their use as research and diagnostic tools as well as therapeutic agents. This chapter describes a straightforward strategy for mapping of continuous peptide antibody epitopes using resin-bound and soluble peptides. The approach combines three different types of peptide sets for full characterization of peptide antibodies: (1) overlapping peptides, used to locate antigenic regions; (2) truncated peptides, used to identify the minimal peptide length required for antibody binding; and (3) substituted peptides, used to identify the key residues important for antibody binding and to determine the specific contribution of key residues. For initial screening resin-bound peptides are used for epitope estimation, while soluble peptides subsequently are used for fine mapping. The combination of resin-bound peptides and soluble peptides for epitope mapping provides a time-sparing and straightforward approach for characterization of peptide antibodies.

  13. The Equine PeptideAtlas

    DEFF Research Database (Denmark)

    Bundgaard, Louise; Jacobsen, Stine; Sorensen, Mette A.

    2014-01-01

    data mining resource. The advantages of the Equine PeptideAtlas are demonstrated by examples of mining the contents for information on potential and well-known equine acute phase proteins, which have extensive general interest in the veterinary clinic. The extracted information will support further......Progress in MS-based methods for veterinary research and diagnostics is lagging behind compared to the human research, and proteome data of domestic animals is still not well represented in open source data repositories. This is particularly true for the equine species. Here we present a first...... analyses, and emphasizes the value of the Equine PeptideAtlas as a resource for the design of targeted quantitative proteomic studies....

  14. [Heterogenous expression of antimicrobial peptides].

    Science.gov (United States)

    Song, Shanshan; Hu, Guobin; Dong, Xianzhi

    2009-12-01

    Antimicrobial peptides (AMPs), a class of short proteins with a broad spectrum of antibacterial activities, are isolated from a wide variety of animals, both vertebrates and invertebrates, and plants as well as from bacteria and fungi. They are a key component of the innate immune response in most multicellular organisms. Owing to their potent, broad-spectrum antibacterial activities and uneasy developing of drug resistance, these peptides are of great clinical significance. However, preparation of AMPs at a large scale is a severe challenge to the development of the commercial products. Undoubtedly, construction of high-level biological expression systems for the production of AMPs is the key in its clinical application process. Herein, we summarize the progress in researches on heterogenous expression of AMPs in prokaryotic expression systems and eukaryotic expression systems.

  15. Peptide Membranes in Chemical Evolution*

    OpenAIRE

    2009-01-01

    Simple surfactants achieve remarkable long-range order in aqueous environments. This organizing potential is seen most dramatically in biological membranes where phospholipid assemblies both define cell boundaries and provide a ubiquitous structural scaffold for controlling cellular chemistry. Here we consider simple peptides that also spontaneously assemble into exceptionally ordered scaffolds, and review early data suggesting that these structures maintain the functional diversity of protei...

  16. Antimicrobial peptides in human sepsis

    Directory of Open Access Journals (Sweden)

    Lukas eMartin

    2015-08-01

    Full Text Available Nearly 100 years ago, antimicrobial peptides (AMPs were identified as an important part of innate immunity. They exist in species from bacteria to mammals and can be isolated in body fluids and on surfaces constitutively or induced by inflammation. Defensins have anti-bacterial effects against Gram-positive and Gram-negative bacteria as well as anti-viral and anti-yeast effects. Human neutrophil peptides (HNP 1-3 and human beta-defensins (HBDs 1-3 are some of the most important defensins in humans. Recent studies have demonstrated higher levels of HNP -1-3 and HBD-2 in sepsis. The bactericidal/permeability increasing protein (BPI attenuates local inflammatory response and decreases systemic toxicity of endotoxins. Moreover, BPI might reflect the severity of organ dysfunction in sepsis. Elevated plasma lactoferrin is detected in patients with organ failure. HNP-1-3, lactoferrin, BPI and heparin-binding protein (HBP are increased in sepsis. Human lactoferrin peptide 1-11 (hLF 1-11 possesses antimicrobial activity and modulates inflammation. The recombinant form of lactoferrin (talactoferrin alpha, TLF has been shown to decrease mortality in critically ill patients. A phase II/III study with TLF in sepsis did not confirm this result. The growing number of multiresistant bacteria is an ongoing problem in sepsis therapy. Furthermore, antibiotics are known to promote the liberation of pro-inflammatory cell components and thus augment the severity of sepsis. Compared to antibiotics, AMPs kill bacteria but also neutralize pathogenic factors such as lipopolysaccharide (LPS. The obstacle to applying naturally occurring AMPs is their high nephro- and neurotoxicity. Therefore, the challenge is to develop peptides to treat septic patients effectively without causing harm. This overview focuses on natural and synthetic AMPs in human and experimental sepsis and their potential to provide significant improvements in the treatment of critically ill with severe

  17. Recent Advances in Peptide Immunomodulators.

    Science.gov (United States)

    Zerfas, Breanna L; Gao, Jianmin

    2015-01-01

    With the continued rise in antibiotic-resistant bacteria, there is an immense need for the development of new therapeutic agents. Host-defense peptides (HDPs) offer a unique alternative to many of the current approved antibiotics. By targeting the host rather than the pathogen, HDPs offer several benefits over traditional small molecule drug treatments, such as a slower propensity towards resistance, broad-spectrum activity and lower risk of patients developing sepsis. However, natural peptide structures have many disadvantages as well, including susceptibility to proteolytic degradation, significant costs of synthesis and host toxicity. For this reason, much work has been done to examine peptidomimetic structures, in the hopes of finding a structure with all of the desired qualities of an antibiotic drug. Recently, this research has included synthetic constructs that mimic the behavior of HDPs but have no structural similarity to peptides. This review article focuses on the progression of this field of research, beginning with an analysis of a few prominent examples of natural HDPs and moving on to describe how the information learned by studying them have led to the current design platforms.

  18. Identification of novel human immunodeficiency virus type 1-inhibitory peptides based on the antimicrobial peptide database.

    Science.gov (United States)

    Wang, Guangshun; Watson, Karen M; Peterkofsky, Alan; Buckheit, Robert W

    2010-03-01

    To identify novel anti-HIV-1 peptides based on the antimicrobial peptide database (APD; http://aps.unmc.edu/AP/main.php), we have screened 30 candidates and found 11 peptides with 50% effective concentrations (EC(50)) of 1, increases in the Arg contents of amphibian maximin H5 and dermaseptin S9 peptides and the database-derived GLK-19 peptide improved the TIs. These examples demonstrate that the APD is a rich resource and a useful tool for developing novel HIV-1-inhibitory peptides.

  19. Bioprospecting open reading frames for peptide effectors.

    Science.gov (United States)

    Xiong, Ling; Scott, Charles

    2014-01-01

    Recent successes in the development of small-molecule antagonists of protein-protein interactions designed based on co-crystal structures of peptides bound to their biological targets confirm that short peptides derived from interacting proteins can be high-value ligands for pharmacologic validation of targets and for identification of druggable sites. Evolved sequence space is likely to be enriched for interacting peptides, but identifying minimal peptide effectors within genomic sequence can be labor intensive. Here we describe the use of incremental truncation to diversify genetic material on the scale of open reading frames into comprehensive libraries of constituent peptides. The approach is capable of generating peptides derived from both continuous and discontinuous sequence elements, and is compatible with the expression of free linear or backbone cyclic peptides, with peptides tethered to amino- or carboxyl-terminal fusion partners or with the expression of peptides displayed within protein scaffolds (peptide aptamers). Incremental truncation affords a valuable source of molecular diversity to interrogate the druggable genome or evaluate the therapeutic potential of candidate genes.

  20. Chemical Methods for Peptide and Protein Production

    Directory of Open Access Journals (Sweden)

    Istvan Toth

    2013-04-01

    Full Text Available Since the invention of solid phase synthetic methods by Merrifield in 1963, the number of research groups focusing on peptide synthesis has grown exponentially. However, the original step-by-step synthesis had limitations: the purity of the final product decreased with the number of coupling steps. After the development of Boc and Fmoc protecting groups, novel amino acid protecting groups and new techniques were introduced to provide high quality and quantity peptide products. Fragment condensation was a popular method for peptide production in the 1980s, but unfortunately the rate of racemization and reaction difficulties proved less than ideal. Kent and co-workers revolutionized peptide coupling by introducing the chemoselective reaction of unprotected peptides, called native chemical ligation. Subsequently, research has focused on the development of novel ligating techniques including the famous click reaction, ligation of peptide hydrazides, and the recently reported a-ketoacid-hydroxylamine ligations with 5-oxaproline. Several companies have been formed all over the world to prepare high quality Good Manufacturing Practice peptide products on a multi-kilogram scale. This review describes the advances in peptide chemistry including the variety of synthetic peptide methods currently available and the broad application of peptides in medicinal chemistry.

  1. Human Antimicrobial Peptides and Proteins

    Directory of Open Access Journals (Sweden)

    Guangshun Wang

    2014-05-01

    Full Text Available As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids with a net charge between −3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32 can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized

  2. Unifying protein inference and peptide identification with feedback to update consistency between peptides.

    Science.gov (United States)

    Shi, Jinhong; Chen, Bolin; Wu, Fang-Xiang

    2013-01-01

    We first propose a new method to process peptide identification reports from databases search engines. Then via it we develop a method for unifying protein inference and peptide identification by adding a feedback from protein inference to peptide identification. The feedback information is a list of high-confidence proteins, which is used to update an adjacency matrix between peptides. The adjacency matrix is used in the regularization of peptide scores. Logistic regression (LR) is used to compute the probability of peptide identification with the regularized scores. Protein scores are then calculated with the LR probability of peptides. Instead of selecting the best peptide match for each MS/MS, we select multiple peptides. By testing on two datasets, the results have shown that the proposed method can robustly assign accurate probabilities to peptides, and have a higher discrimination power than PeptideProphet to distinguish correct and incorrect identified peptides. Additionally, not only can our method infer more true positive proteins but also infer less false positive proteins than ProteinProphet at the same false positive rate. The coverage of inferred proteins is also significantly increased due to the selection of multiple peptides for each MS/MS and the improvement of their scores by the feedback from the inferred proteins.

  3. Interpreting peptide mass spectra by VEMS

    DEFF Research Database (Denmark)

    Mathiesen, Rune; Lundsgaard, M.; Welinder, Karen G.;

    2003-01-01

    of peptide MS/MS spectra imported in text file format. Peaks are annotated, the monoisotopic peaks retained, and the b-and y-ion series identified in an interactive manner. The called peptide sequence is searched against a local protein database for sequence identity and peptide mass. The report compares...... the calculated and the experimental mass spectrum of the called peptide. The program package includes four accessory programs. VEMStrans creates protein databases in FASTA format from EST or cDNA sequence files. VEMSdata creates a virtual peptide database from FASTA files. VEMSdist displays the distribution...... of masses up to 5000 Da. VEMSmaldi searches singly charged peptide masses against the local database....

  4. Synthesis of peptide .alpha.-thioesters

    Science.gov (United States)

    Camarero, Julio A.; Mitchell, Alexander R.; De Yoreo, James J.

    2008-08-19

    Disclosed herein is a new method for the solid phase peptide synthesis (SPPS) of C-terminal peptide .alpha. thioesters using Fmoc/t-Bu chemistry. This method is based on the use of an aryl hydrazine linker, which is totally stable to conditions required for Fmoc-SPPS. When the peptide synthesis has been completed, activation of the linker is achieved by mild oxidation. The oxidation step converts the acyl-hydrazine group into a highly reactive acyl-diazene intermediate which reacts with an .alpha.-amino acid alkylthioester (H-AA-SR) to yield the corresponding peptide .alpha.-thioester in good yield. A variety of peptide thioesters, cyclic peptides and a fully functional Src homology 3 (SH3) protein domain have been successfully prepared.

  5. Use of Galerina marginata genes and proteins for peptide production

    Energy Technology Data Exchange (ETDEWEB)

    Hallen-Adams, Heather E.; Scott-Craig, John S.; Walton, Jonathan D.; Luo, Hong

    2017-03-21

    The present invention relates to compositions and methods comprising genes and peptides associated with cyclic peptides and cyclic peptide production in mushrooms. In particular, the present invention relates to using genes and proteins from Galerina species encoding peptides specifically relating to amatoxins in addition to proteins involved with processing cyclic peptide toxins. In a preferred embodiment, the present invention also relates to methods for making small peptides and small cyclic peptides including peptides similar to amanitin. Further, the present inventions relate to providing kits for making small peptides.

  6. Use of Galerina marginata genes and proteins for peptide production

    Science.gov (United States)

    Hallen-Adams, Heather E.; Scott-Craig, John S.; Walton, Jonathan D.; Luo, Hong

    2016-03-01

    The present invention relates to compositions and methods comprising genes and peptides associated with cyclic peptides and cyclic peptide production in mushrooms. In particular, the present invention relates to using genes and proteins from Galerina species encoding peptides specifically relating to amatoxins in addition to proteins involved with processing cyclic peptide toxins. In a preferred embodiment, the present invention also relates to methods for making small peptides and small cyclic peptides including peptides similar to amanitin. Further, the present inventions relate to providing kits for making small peptides.

  7. Current scenario of peptide-based drugs: the key roles of cationic antitumor and antiviral peptides

    Directory of Open Access Journals (Sweden)

    Kelly eMulder

    2013-10-01

    Full Text Available Cationic antimicrobial peptides (AMPs and host defense peptides (HDPs show vast potential as peptide-based drugs. Great effort has been made in order to exploit their mechanisms of action, aiming to identify their targets as well as to enhance their activity and bioavailability. In this review, we will focus on both naturally occurring and designed antiviral and antitumor cationic peptides, including those here called promiscuous, in which multiple targets are associated with a single peptide structure. Emphasis will be given to their bio-chemical features, selectivity against extra targets and molecular mechanisms. Peptides which possess antitumor activity against different cancer cell lines will be discussed, as well as peptides which inhibit virus replication, focusing on their applications for human health, animal health and agriculture, and their potential as new therapeutic drugs. Moreover, the development of production and nano-delivery systems for both classes of cationic peptides and perspectives on improving them will be considered.

  8. The Function and Development of Soybean Peptides

    Institute of Scientific and Technical Information of China (English)

    Yang Caiyan; Song Junmei

    2009-01-01

    Soybean peptides are small molecules hydrolyzed soy protein,from three to six amino acid composition of the peptide mixture,in 1000Da molecular weight below.Because it has a lot of good physical and chemical properties and physiological functions,in many areas has been widely used.This paper reviews the soybean peptide physical and chemical characteristics,physiological functions,technology and applications in the food industry.

  9. A Novel Peptide from Buthus Martensii Karch

    Institute of Scientific and Technical Information of China (English)

    Zheng Yu CAO; Xuan XIAO; Xue Mei LIU; Xiao Tian LIANG; De Quan YU

    2004-01-01

    A novel peptide was purified and characterized from Buthus martensii Karch.The peptide,named BmK M6,is a single-chain polypeptide cross-linked by four intramolecular disulfide bridges.The molecular weight of the peptide was determined by MOLDI-TOF-MS as 7034 Da.The partial amino acid sequence of BmK M6 from N-terminal is VRDAYIAKPEN CVYECGITQDCNKLCTENG.

  10. Tulane/Xavier Vaccine Peptide Program

    Science.gov (United States)

    2014-09-01

    resin bound peptide -PEG conjugate to remove copper and uncoupled PEG. After removal from the resin, MALDI-TOF MS analysis of the product...synthesized) was used to further modify the peptide with a singly modified PEG chain bearing a terminal alkyne functionality through a copper -catalyzed azide...COVERED (From - To) 1 July 2010 – 30 June 201 4. TITLE AND SUBTITLE Tulane/Xavier Vaccine Peptide Program 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c

  11. Opioid Peptides: Potential for Drug Development

    OpenAIRE

    Aldrich, Jane V.; McLaughlin, Jay P.

    2012-01-01

    Opioid receptors are important targets for the treatment of pain and potentially for other disease states (e.g. mood disorders and drug abuse) as well. Significant recent advances have been made in identifying opioid peptide analogs that exhibit promising in vivo activity for treatment of these maladies. This review focuses on the development and evaluation of opioid peptide analogs demonstrating activity after systemic administration, and recent clinical evaluations of opioid peptides for po...

  12. Acylation of Glucagon-like peptide-2

    DEFF Research Database (Denmark)

    Trier, Sofie; Linderoth, Lars; Bjerregaard, Simon;

    2014-01-01

    These results show that membrane interactions play a prominent role during intestinal translocation of an acylated peptide. Acylation benefits permeation for shorter and medium chains due to increased membrane interactions, however, for longer chains insertion in the membrane becomes dominant and...... and hinders translocation, i.e. the peptides get 'stuck' in the cell membrane. Applying a transcellular absorption enhancer increases the dynamics of membrane insertion and detachment by fluidizing the membrane, thus facilitating its effects primarily on membrane associated peptides....

  13. GAMPMS: Genetic algorithm managed peptide mutant screening.

    Science.gov (United States)

    Long, Thomas; McDougal, Owen M; Andersen, Tim

    2015-06-30

    The prominence of endogenous peptide ligands targeted to receptors makes peptides with the desired binding activity good molecular scaffolds for drug development. Minor modifications to a peptide's primary sequence can significantly alter its binding properties with a receptor, and screening collections of peptide mutants is a useful technique for probing the receptor-ligand binding domain. Unfortunately, the combinatorial growth of such collections can limit the number of mutations which can be explored using structure-based molecular docking techniques. Genetic algorithm managed peptide mutant screening (GAMPMS) uses a genetic algorithm to conduct a heuristic search of the peptide's mutation space for peptides with optimal binding activity, significantly reducing the computational requirements of the virtual screening. The GAMPMS procedure was implemented and used to explore the binding domain of the nicotinic acetylcholine receptor (nAChR) α3β2-isoform with a library of 64,000 α-conotoxin (α-CTx) MII peptide mutants. To assess GAMPMS's performance, it was compared with a virtual screening procedure that used AutoDock to predict the binding affinity of each of the α-CTx MII peptide mutants with the α3β2-nAChR. The GAMPMS implementation performed AutoDock simulations for as few as 1140 of the 64,000 α-CTx MII peptide mutants and could consistently identify a set of 10 peptides with an aggregated binding energy that was at least 98% of the aggregated binding energy of the 10 top peptides from the exhaustive AutoDock screening.

  14. Insect inducible antimicrobial peptides and their applications.

    Science.gov (United States)

    Ezzati-Tabrizi, Reyhaneh; Farrokhi, Naser; Talaei-Hassanloui, Reza; Alavi, Seyed Mehdi; Hosseininaveh, Vahid

    2013-12-01

    Antimicrobial peptides (AMPs) are found as important components of the innate immune system (host defense) of all invertebrates. These peptides can be constitutively expressed or induced in response to microbial infections. Indeed, they vary in their amino acid sequences, potency and antimicrobial activity spectra. The smaller AMPs act greatly by disrupting the structure or function of microbial cell membranes. Here, the insect innate immune system with emphasis on inducible antimicrobial peptide properties against microbial invaders has been discussed.

  15. A cyclic peptidic serine protease inhibitor

    DEFF Research Database (Denmark)

    Zhao, Baoyu; Xu, Peng; Jiang, Longguang;

    2014-01-01

    Peptides are attracting increasing interest as protease inhibitors. Here, we demonstrate a new inhibitory mechanism and a new type of exosite interactions for a phage-displayed peptide library-derived competitive inhibitor, mupain-1 (CPAYSRYLDC), of the serine protease murine urokinase...... pocket, its carbonyl group aligning improperly relative to Ser195 and the oxyanion hole, explaining why the peptide is an inhibitor rather than a substrate. Substitution of the P1 Arg with novel unnatural Arg analogues with aliphatic or aromatic ring structures led to an increased affinity, depending...... of this peptidic inhibitor, a concept different from conventional attempts at improving inhibitor affinity by reducing the entropic burden....

  16. Peptide-stabilized, fluorescent silver nanoclusters

    DEFF Research Database (Denmark)

    Gregersen, Simon; Vosch, Tom André Jos; Jensen, Knud Jørgen

    2016-01-01

    . Herein, we demonstrate how solid-phase methods can increase throughput dramatically in peptide ligand screening and in initial evaluation of fluorescence intensity and chemical stability of peptide-stabilized AgNCs (P-AgNCs). 9-Fluorenylmethyloxycarbonyl (Fmoc) solid-phase peptide synthesis......Few-atom silver nanoclusters (AgNCs) can exhibit strong fluorescence; however, they require ligands to prevent aggregation into larger nanoparticles. Fluorescent AgNCs in biopolymer scaffolds have so far mainly been synthesized in solution, and peptides have only found limited use compared to DNA...

  17. Modulation of autoimmunity with artificial peptides

    Science.gov (United States)

    La Cava, Antonio

    2010-01-01

    The loss of immune tolerance to self antigens leads to the development of autoimmune responses. Since self antigens are often multiple and/or their sequences may not be known, one approach to restore immune tolerance uses synthetic artificial peptides that interfere or compete with self peptides in the networks of cellular interactions that drive the autoimmune process. This review describes the rationale behind the use of artificial peptides in autoimmunity and their mechanisms of action. Examples of use of artificial peptides in preclinical studies and in the management of human autoimmune diseases are provided. PMID:20807590

  18. Synthesis of stabilized alpha-helical peptides.

    Science.gov (United States)

    Bernal, Federico; Katz, Samuel G

    2014-01-01

    Stabilized alpha-helical (SAH) peptides are valuable laboratory tools to explore important protein-protein interactions. Whereas most peptides lose their secondary structure when isolated from the host protein, stapled peptides incorporate an all-hydrocarbon "staple" that reinforces their natural alpha-helical structure. Thus, stapled peptides retain their functional ability to bind their native protein targets and serve multiple experimental uses. First, they are useful for structural studies such as NMR or crystal structures that map and better define binding sites. Second, they can be used to identify small molecules that specifically target that interaction site. Third, stapled peptides can be used to test the importance of specific amino acid residues or posttranslational modifications to the binding. Fourth, they can serve as structurally competent bait to identify novel binding partners to specific alpha-helical motifs. In addition to markedly improved alpha-helicity, stapled peptides also display resistance to protease cleavage and enhanced cell permeability. Most importantly, they are useful for intracellular experiments that explore the functional consequences of blocking particular protein interactions. Because of their remarkable stability, stapled peptides can be applied to whole-animal, in vivo studies. Here we describe a protocol for the synthesis of a peptide that incorporates an all-hydrocarbon "staple" employing a ring-closing olefin metathesis reaction. With proper optimization, stapled peptides can be a fundamental, accurate laboratory tool in the modern chemical biologist's armory.

  19. Polycyclic Peptides: A New Type of Cavitand,

    Science.gov (United States)

    PEPTIDES, MOLECULAR STRUCTURE, MOLECULES, SYNTHESIS, ETHERS, DEXTRINS , PROTEINS, AMINO ACIDS, RESIDUES, CROSSLINKING(CHEMISTRY), DIMERS, CESIUM, CARBON, OXYGEN, NITROGEN, CAVITIES, NUCLEAR MAGNETIC RESONANCE.

  20. Endomorphins and related opioid peptides.

    Science.gov (United States)

    Okada, Yoshio; Tsuda, Yuko; Bryant, Sharon D; Lazarus, Lawrence H

    2002-01-01

    Opioid peptides and their G-protein-coupled receptors (delta, kappa, mu) are located in the central nervous system and peripheral tissues. The opioid system has been studied to determine the intrinsic mechanism of modulation of pain and to develop uniquely effective pain-control substances with minimal abuse potential and side effects. Two types of endogenous opioid peptides exist, one containing Try-Gly-Gly-Phe as the message domain (enkephalins, endorphins, dynorphins) and the other containing the Tyr-Pro-Phe/Trp sequence (endomorphins-1 and -2). Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2), which has high mu receptor affinity (Ki = 0.36 nM) and remarkable selectivity (4000- and 15,000-fold preference over the delta and kappa receptors, respectively), was isolated from bovine and human brain. In addition, endomorphin-2 (Tyr-Pro-Phe-Phe-NH2), isolated from the same sources, exhibited high mu receptor affinity (Ki = 0.69 nM) and very high selectivity (13,000- and 7500-fold preference relative to delta and kappa receptors, respectively). Both opioids bind to mu-opioid receptors, thereby activating G-proteins, resulting in regulation of gastrointestinal motility, manifestation of antinociception, and effects on the vascular systems and memory. To develop novel analgesics with less addictive properties, evaluation of the structure-activity relationships of the endomorphins led to the design of more potent and stable analgesics. Opioidmimetics and opioid peptides containing the amino acid sequence of the message domain of endomorphins, Tyr-Pro-Phe/Trp, could exhibit unique binding activity and lead to the development of new therapeutic drugs for controlling pain.

  1. Atrial natriuretic peptides in plasma

    DEFF Research Database (Denmark)

    Goetze, Jens P; Holst Hansen, Lasse; Terzic, Dijana

    2015-01-01

    Measurement of cardiac natriuretic peptides in plasma has gained a diagnostic role in the assessment of heart failure. Plasma measurement is though hampered by the marked instability of the hormones, which has led to the development of analyses that target N-terminal fragments from the prohormone....... These fragments are stable in plasma and represent surrogate markers of the actual natriuretic hormone. Post-translational processing of the precursors, however, is revealing itself to be a complex event with new information still being reported on proteolysis, covalent modifications, and amino acid...

  2. Production of bioactive soy peptides

    OpenAIRE

    Bissegger, Sonja; Crelier, Simon

    2008-01-01

    Objectif Les antioxidants synthétiques sont souvent utilisés dans l’industrie alimentaire pour empêcher le déterioration des produits. Mais ces ingrédients sont potentiellement nocifs pour la santé, des travaux de recherche sont effectués pour identifier des antioxidants d’origine naturelle. Le but de ce travail de diplôme est de produire des peptides de protéine de soja avec des propriétés antioxidantes, au moyen d’une digestion enzymatique hydrolytique. Résultats Après une digestion enzymat...

  3. Biodiscovery of Aluminum Binding Peptides

    Science.gov (United States)

    2013-08-01

    34Sequestration of zinc oxide by fimbrial designer chelators," Appl. Environ. Microbiol. 66(1), 10-14 (2000). [26] Hnilova, M., et al., "Peptide-directed co...et al., "Biomimetic synthesis and patterning of silver nanoparticles," Nat. Mater. 1(3), 169-172 (2002). [5] Van Dorst, B., et al., "Phage display...Biotechnol. 68(4), 505-509 (2005). [10] Lee, Y. J., et al., "Fabricating genetically engineered high-power lithium-ion batteries using multiple virus genes

  4. Peptide-Based Polymer Therapeutics

    Directory of Open Access Journals (Sweden)

    Aroa Duro-Castano

    2014-02-01

    Full Text Available Polypeptides are envisaged to achieve a major impact on a number of different relevant areas such as biomedicine and biotechnology. Acquired knowledge and the increasing interest on amino acids, peptides and proteins is establishing a large panel of these biopolymers whose physical, chemical and biological properties are ruled by their controlled sequences and composition. Polymer therapeutics has helped to establish these polypeptide-based constructs as polymeric nanomedicines for different applications, such as disease treatment and diagnostics. Herein, we provide an overview of the advantages of these systems and the main methodologies for their synthesis, highlighting the different polypeptide architectures and the current research towards clinical applications.

  5. Synthetic peptide vaccines: palmitoylation of peptide antigens by a thioester bond increases immunogenicity

    DEFF Research Database (Denmark)

    Beekman, N.J.C.M.; Schaaper, W.M.M.; Tesser, G.I.;

    1997-01-01

    Synthetic peptides have frequently been used to immunize animals. However, peptides less than about 20 to 30 amino acids long are poor immunogens. In general, to increase its immunogenicity, the presentation of the peptide should be improved, and molecular weight needs to be increased. Many attem...

  6. Driving engineering of novel antimicrobial peptides from simulations of peptide-micelle interactions

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Langham, Allison A; Kaznessis, Yiannis N

    2006-01-01

    peptides and their interaction with membrane mimics. In this article, we discuss the promise and the challenges of widely used models and detail our recent work on peptide-micelle simulations as an attractive alternative to peptide-bilayer simulations. We detail our results with two large structural...

  7. APD2: the updated antimicrobial peptide database and its application in peptide design.

    Science.gov (United States)

    Wang, Guangshun; Li, Xia; Wang, Zhe

    2009-01-01

    The antimicrobial peptide database (APD, http://aps.unmc.edu/AP/main.php) has been updated and expanded. It now hosts 1228 entries with 65 anticancer, 76 antiviral (53 anti-HIV), 327 antifungal and 944 antibacterial peptides. The second version of our database (APD2) allows users to search peptide families (e.g. bacteriocins, cyclotides, or defensins), peptide sources (e.g. fish, frogs or chicken), post-translationally modified peptides (e.g. amidation, oxidation, lipidation, glycosylation or d-amino acids), and peptide binding targets (e.g. membranes, proteins, DNA/RNA, LPS or sugars). Statistical analyses reveal that the frequently used amino acid residues (>10%) are Ala and Gly in bacterial peptides, Cys and Gly in plant peptides, Ala, Gly and Lys in insect peptides, and Leu, Ala, Gly and Lys in amphibian peptides. Using frequently occurring residues, we demonstrate database-aided peptide design in different ways. Among the three peptides designed, GLK-19 showed a higher activity against Escherichia coli than human LL-37.

  8. Production of peptide antisera specific for mouse and rat proinsulin C-peptide 2

    DEFF Research Database (Denmark)

    Blume, N; Madsen, O D; Kofod, Hans;

    1990-01-01

    Mice and rats have two functional non-allelic insulin genes. By using a synthetic peptide representing a common sequence in mouse and rat C-peptide 2 as antigen, we have produced rabbit antisera specific for an epitope which is not present in mouse or rat C-peptide 1. Long-term immunization did n...

  9. Synthetic peptide vaccines: palmitoylation of peptide antigens by an thioester bond increases immunogenicity

    NARCIS (Netherlands)

    Beekman, N.J.C.M.; Schaaper, W.M.M.; Tesser, G.I.; Dalsgaard, K.; Langeveld, J.P.M.; Boshuizen, R.S.; Meloen, R.H.

    1997-01-01

    Synthetic peptides have frequently been used to immunize animals. However, peptides less than about 20 to 30 amino acids long are poor immunogens. In general, to increase its immunogenicity, the presentation of the peptide should be improved, and molecular weight needs to be increased. Many attempts

  10. 谷氨酸棒状杆菌发酵生产L 瓜氨酸及发酵条件优化%Optimization of L-citrulline production by Corynebacterium glutamicum

    Institute of Scientific and Technical Information of China (English)

    丁叶; 郝宁; 胡洁; 谭玉岩; 郭格格

    2016-01-01

    以代谢控制发酵理论为指导,重点对C. glutamicum 366菌株进行摇瓶发酵条件的优化。应用响应面法优化发酵培养基的配比,优化后的发酵培养基:葡萄糖63.33 g/L、精氨酸196.96 mg/L、( NH4)2 SO445.79 g/L、生物素35.72μg/L、K2 HPO4·3H2 O 1.0 g/L、KH2 PO41.0 g/L、MgSO4·7H2 O、0.25 g/L、MnSO4·H2 O 0.02 g/L、FeSO4·7H2 O 0.02 g/L、ZnCl21 mg/L、CuSO40.2 mg/L、VB1200μg/L、CaCO330 g/L。摇瓶发酵培养条件:温度30℃、摇床转速200 r/min、初始pH 7.0。在此发酵条件下,菌株进行摇瓶发酵72 h,产L 瓜氨酸14.96 g/L,相比优化之前提高了75.8%。%We optimized the fermentation for L-citrulline production by C. glutamicum 366 strain. Mediam was optimized by response surface analysis Design-Expert software. The fermentation conditions were also studied. The optimum medium was:glucose 63. 33 g/L,arginine 196. 96 mg/L,ammonium sulfate 45. 79 g/L,biotin 35. 72 μg/L,K2HPO4·3H2O 1. 0 g/L,KH2PO4 1. 0 g/L,MgSO4·7H2O 0. 25 g/L,MnSO4· H2 O 0. 02 g/L, FeSO4·7H2 O 0. 02 g/L, ZnCl2 1 mg/L, CuSO4 0. 2 mg/L, vitamin B1 200 μg/L and CaCO3 30 g/L.The optimum fermentation conditions were:temperature at 30 ℃,the rotate speed of 200 r/min,initial pH 7. 0.Under this condition,the production of L-citrulline was 14. 96 g/L after 72 h shake flask fermentation,increased by 75. 8% compared to the control.

  11. Intestinal renal metabolism of L-citrulline and L-arginine following enteral or parenteral infusion of L-alanyl-L-[2,15N]glutamine or L-[2,15N]glutamine in mice.

    Science.gov (United States)

    Boelens, Petra G; van Leeuwen, Paul A M; Dejong, Cornelis H C; Deutz, Nicolaas E P

    2005-10-01

    Previously, we observed increased plasma arginine (ARG) concentrations after glutamine (GLN)-enriched diets, in combination with clinical benefits. GLN delivers nitrogen for ARG synthesis, and the present study was designed to quantify the interorgan relationship of exogenous L-GLN or GLN dipeptide, by enteral or parenteral route, contributing to intestinal citrulline (CIT) and renal de novo ARG synthesis in mice. To study this, we used a multicatheterized mouse model with Swiss mice (n = 43) in the postabsorptive state. Stable isotopes were infused into the jugular vein or into the duodenum {per group either free L-[2,(15)N]GLN or dipeptide L-ALA-L-[2,(15)N]GLN, all with L-[ureido-(13)C-(2)H(2)]CIT and L-[guanidino-(15)N(2)-(2)H(2)]ARG} to establish renal and intestinal ARG and CIT metabolism. Blood flow was measured using (14)C-para-aminohippuric acid. Net intestinal CIT release, renal uptake of CIT, and net renal ARG efflux was found, as assessed by arteriovenous flux measurements. Quantitatively, more de novo L-[2,(15)N]CIT was produced when free L-[2,(15)N]GLN was given than when L-ALA-L-[2,(15)N]GLN was given, whereas renal de novo L-[2,(15)N]ARG was similar in all groups. In conclusion, the intestinal-renal axis is hereby proven in mice in that L-[2,(15)N]GLN or dipeptide were both converted into de novo renal L-[2,(15)N]ARG; however, not all was derived from intestinal L-[2,(15)N]CIT production. In this model, the feeding route and form of GLN did not influence de novo renal ARG production derived from GLN.

  12. Antimicrobial peptides in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    A Bogaerts

    2010-01-01

    Full Text Available The nematode Caenorhabditis elegans is one of the most successful model species for experimental research because of its sequenced genome, the versatile genetic toolkit and the straightforward breeding among others. In natural conditions however, this tiny worm is constantly surrounded by micro-organisms, simultaneously a source of indispensable nutrition and inevitable pathogens. Lacking an adaptive immune system, the worm solely relies on its innate immune defence to cope with its challenging life style. Hence C. elegans is an excellent model to gain more insight in innate immunity, which is remarkably preserved between invertebrate and vertebrate animals. The innate defence consists of receptors to detect potential pathogens, a complex network of signalling pathways and last but not least, effector molecules to abolish harmful microbes. In this review, we focus on the antimicrobial peptides, a vital subgroup of effector molecules. We summarise the current knowledge of the different families of C. elegans antimicrobial peptides, comprising NLPs, caenacins, ABFs, caenopores, and a recently discovered group with antifungal activity among which thaumatin-like proteins.

  13. C-peptide and diabetic kidney disease.

    Science.gov (United States)

    Brunskill, N J

    2017-01-01

    Kidney disease is a serious development in diabetes mellitus and poses an increasing clinical problem. Despite increasing incidence and prevalence of diabetic kidney disease, there have been no new therapies for this condition in the last 20 years. Mounting evidence supports a biological role for C-peptide, and findings from multiple studies now suggest that C-peptide may beneficially affect the disturbed metabolic and pathophysiological pathways leading to the development of diabetic nephropathy. Studies of C-peptide in animal models and in humans with type 1 diabetes all suggest a renoprotective effect for this peptide. In diabetic rodents, C-peptide reduces glomerular hyperfiltration and albuminuria. Cohort studies of diabetic patients with combined islet and kidney transplants suggest that maintained C-peptide secretion is protective of renal graft function. Further, in short-term studies of patients with type 1 diabetes, administration of C-peptide is also associated with a lowered hyperfiltration rate and reduced microalbuminuria. Thus, the available information suggests that type 1 diabetes should be regarded as a dual hormone deficiency disease and that clinical trials of C-peptide in diabetic nephropathy are both justified and urgently required.

  14. Protein identification by peptide mass fingerprinting

    DEFF Research Database (Denmark)

    Hjernø, Karin

    2007-01-01

      Peptide mass fingerprinting is an effective way of identifying, e.g., gel-separated proteins, by matching experimentally obtained peptide mass data against large databases. However, several factors are known to influence the quality of the resulting matches, such as proteins contaminating...

  15. Peptidomic Identification of Serum Peptides Diagnosing Preeclampsia.

    Directory of Open Access Journals (Sweden)

    Qiaojun Wen

    Full Text Available We sought to identify serological markers capable of diagnosing preeclampsia (PE. We performed serum peptide analysis (liquid chromatography mass spectrometry of 62 unique samples from 31 PE patients and 31 healthy pregnant controls, with two-thirds used as a training set and the other third as a testing set. Differential serum peptide profiling identified 52 significant serum peptides, and a 19-peptide panel collectively discriminating PE in training sets (n = 21 PE, n = 21 control; specificity = 85.7% and sensitivity = 100% and testing sets (n = 10 PE, n = 10 control; specificity = 80% and sensitivity = 100%. The panel peptides were derived from 6 different protein precursors: 13 from fibrinogen alpha (FGA, 1 from alpha-1-antitrypsin (A1AT, 1 from apolipoprotein L1 (APO-L1, 1 from inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4, 2 from kininogen-1 (KNG1, and 1 from thymosin beta-4 (TMSB4. We concluded that serum peptides can accurately discriminate active PE. Measurement of a 19-peptide panel could be performed quickly and in a quantitative mass spectrometric platform available in clinical laboratories. This serum peptide panel quantification could provide clinical utility in predicting PE or differential diagnosis of PE from confounding chronic hypertension.

  16. New Biodegradable Peptide-based Polymer Constructs

    NARCIS (Netherlands)

    van Dijk, M.

    2009-01-01

    Peptide-based polymers are of increasing interest, since they can be applied for a variety of purposes such as drug delivery devices, scaffolds for tissue engineering and -repair, and as novel biomaterials. Peptide-based polymers are common in nature and often exhibit special characteristics. Howeve

  17. Structure and Design of Multipotent Peptide Microbicides

    Science.gov (United States)

    1988-08-01

    Project goal. ~$e goal of this project is to design novel peptide antibiotics using a naturally occurring family of peptides, known as defensins, as...coupling of taurine , glycinamide, and arginine amide. " 3. Solution Structures. in collaborative studies performed with Arthur Pardi, we have

  18. Engineered Adhesion Peptides for Improved Silicon Adsorption.

    Science.gov (United States)

    Ramakrishnan, Sathish Kumar; Jebors, Said; Martin, Marta; Cloitre, Thierry; Agarwal, Vivechana; Mehdi, Ahmad; Martinez, Jean; Subra, Gilles; Gergely, Csilla

    2015-11-01

    Engineering peptides that present selective recognition and high affinity for a material is a major challenge for assembly-driven elaboration of complex systems with wide applications in the field of biomaterials, hard-tissue regeneration, and functional materials for therapeutics. Peptide-material interactions are of vital importance in natural processes but less exploited for the design of novel systems for practical applications because of our poor understanding of mechanisms underlying these interactions. Here, we present an approach based on the synthesis of several truncated peptides issued from a silicon-specific peptide recovered via phage display technology. We use the photonic response provided by porous silicon microcavities to evaluate the binding efficiency of 14 different peptide derivatives. We identify and engineer a short peptide sequence (SLVSHMQT), revealing the highest affinity for p(+)-Si. The molecular recognition behavior of the obtained peptide fragment can be revealed through mutations allowing identification of the preferential affinity of certain amino acids toward silicon. These results constitute an advance in both the engineering of peptides that reveal recognition properties for silicon and the understanding of biomolecule-material interactions.

  19. Protein identification by peptide mass fingerprinting

    DEFF Research Database (Denmark)

    Hjernø, Karin

    2007-01-01

      Peptide mass fingerprinting is an effective way of identifying, e.g., gel-separated proteins, by matching experimentally obtained peptide mass data against large databases. However, several factors are known to influence the quality of the resulting matches, such as proteins contaminating the s...

  20. A cyclic peptidic serine protease inhibitor

    DEFF Research Database (Denmark)

    Zhao, Baoyu; Xu, Peng; Jiang, Longguang;

    2014-01-01

    Peptides are attracting increasing interest as protease inhibitors. Here, we demonstrate a new inhibitory mechanism and a new type of exosite interactions for a phage-displayed peptide library-derived competitive inhibitor, mupain-1 (CPAYSRYLDC), of the serine protease murine urokinase...

  1. Milk proteins as precursors of bioactive peptides

    Directory of Open Access Journals (Sweden)

    Marta Dziuba

    2009-03-01

    Full Text Available Milk proteins, a source of bioactive peptides, are the subject of numerous research studies aiming to, among others, evaluate their properties as precursors of biologically active peptides. Physiologically active peptides released from their precursors may interact with selected receptors and affect the overall condition and health of humans. By relying on the BIOPEP database of proteins and bioactive peptides, developed by the Department of Food Biochemistry at the University of Warmia and Mazury in Olsztyn (www.uwm.edu.pl/biochemia, the profiles of potential activity of milk proteins were determined and the function of those proteins as bioactive peptide precursors was evaluated based on a quantitative criterion, i.e. the occurrence frequency of bioactive fragments (A. The study revealed that milk proteins are mainly a source of peptides with the following types of activity: antihypertensive (Amax = 0.225, immunomodulating (0.024, smooth muscle contracting (0.011, antioxidative (0.029, dipeptidyl peptidase IV inhibitors (0.148, opioid (0.073, opioid antagonistic (0.053, bonding and transporting metals and metal ions (0.024, antibacterial and antiviral (0.024, and antithrombotic (0.029. The enzymes capable of releasing bioactive peptides from precursor proteins were determined for every type of activity. The results of the experiment indicate that milk proteins such as lactoferrin, α-lactalbumin, β-casein and κ-casein hydrolysed by trypsin can be a relatively abundant source of biologically active peptides.

  2. [Application on food preservative of antimicrobial peptides].

    Science.gov (United States)

    Zhao, Hongyan; Mu, Yu; Zhao, Baohua

    2009-07-01

    Antimicrobial peptides are an integral component of the innate immune system, it can counteract outer membrane pathogen such as bacteria, fungi, viruses, protozoan and so on. Owing to the sterilization and innocuity, it has the potential to be crude food preservative. In this paper the uses of antibacterial peptides in the food preservative were analyzed.

  3. Prediction of twin-arginine signal peptides

    DEFF Research Database (Denmark)

    Bendtsen, Jannick Dyrløv; Nielsen, Henrik; Widdick, D.;

    2005-01-01

    peptides and 84% of the annotated cleavage sites of these Tat signal peptides were correctly predicted. This method generates far less false positive predictions on various datasets than using simple pattern matching. Moreover, on the same datasets TatP generates less false positive predictions than...

  4. Peptide Mass Fingerprinting of Egg White Proteins

    Science.gov (United States)

    Alty, Lisa T.; LaRiviere, Frederick J.

    2016-01-01

    Use of advanced mass spectrometry techniques in the undergraduate setting has burgeoned in the past decade. However, relatively few undergraduate experiments examine the proteomics tools of protein digestion, peptide accurate mass determination, and database searching, also known as peptide mass fingerprinting. In this experiment, biochemistry…

  5. Antimicrobial peptides in innate immune responses

    DEFF Research Database (Denmark)

    Sorensen, O.E.; Borregaard, N.; Cole, A.M.

    2008-01-01

    Antimicrobial peptides (AMPs) are ancient effector molecules in the innate immune response of eukaryotes. These peptides are important for the antimicrobial efficacy of phagocytes and for the innate immune response mounted by epithelia of humans and other mammals. AMPs are generated either by de ...

  6. Trandermal Peptides for Large Molecule Delivery

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ A research team, led by Prof. WEN Longping from the University of Science and Technology of China under CAS,has successfully screened out a trandermal peptide, using biotechnology. The new peptide is able to deliver insulin into human body through skin, rendering an immediate therapeutic effect. The finding was published in the March 27 issue of the journal Natural Biotechnology.

  7. Antimicrobial Peptides, Infections and the Skin Barrier

    DEFF Research Database (Denmark)

    Clausen, Maja-Lisa; Agner, Tove

    2016-01-01

    The skin serves as a strong barrier protecting us from invading pathogens and harmful organisms. An important part of this barrier comes from antimicrobial peptides (AMPs), which are small peptides expressed abundantly in the skin. AMPs are produced in the deeper layers of the epidermis...

  8. High Prevalence of Antinuclear Antibodies in Children with Thyroid Autoimmunity

    Directory of Open Access Journals (Sweden)

    Maria Segni

    2014-01-01

    Full Text Available Background. Antinuclear antibodies (ANA are a hallmark of many autoimmune diseases and can be detected many years before disease onset. Autoimmune thyroid diseases (AITD are frequently associated with other organ- and non-organ-specific autoimmune disorders. Objectives. To assess the prevalence of ANA in pediatric patients with AITD and their clinical correlations. Methods. Ninety-three consecutive pediatric patients with AITD were enrolled (86 children with chronic lymphocytic thyroiditis and 7 with Graves’ disease. ANA, anti-double DNA (anti-dsDNA antibodies, anti-extractable nuclear antigen (anti-ENA, anti-cyclic citrullinated peptide antibodies (anti-CCP, and rheumatoid factor (RF was obtained. Signs and symptoms potentially related to rheumatic diseases in children were investigated by a questionnaire. Results. ANA positivity was found in 66/93 children (71%, anti-ENA in 4/93 (4.3%, anti-dsDNA in 1/93 (1.1%, RF in 3/93 (3.2%, and anti-CCP in none. No significant differences were found between the ANA-positive and ANA-negative groups with respect to age, sex, L-thyroxine treatment, or prevalence of other autoimmune diseases. Overall, parental autoimmunity was found in 23%. Conclusions. ANA positivity was demonstrated in 71% of children with AITD. ANA positivity was not related to overt immune-rheumatic diseases. However, because the positivity of ANA can occur even many years before the onset of systemic autoimmune diseases, prospective studies are warranted.

  9. Analysis of foot structural damage in rheumatoid arthritis: clinical evaluation by validated measures and serological correlations

    Directory of Open Access Journals (Sweden)

    E. Bartoloni Bocci

    2011-06-01

    Full Text Available Objective: To examine foot involvement in rheumatoid arthritis (RA and to characterize structural alterations in patients with anti-cyclic citrullinated peptide (CCP antibody-positive and -negative disease. Methods: Seventy-eight patients with RA with foot pain were consecutively enrolled. The Manchester Hallux Valgus (MHV rating scale was used to evaluate the hallux valgus deformity degree. The Foot Posture Index (FPI6, a novel, foot-specific outcome measure, was adopted in order to quantify variation in the position of the foot. The findings were correlated with disease duration and presence or absence of anti-CCP antibodies. Results: About 84.6% patients had different degrees of hallux valgus and 65.4% subjects had a pronated foot. These two foot alterations were prevalently found in patients with long-standing disease and circulating anti-CCP antibodies. On the contrary, RA patients without anti-CCP and early disease essentially displayed a supinated foot without relevant hallux valgus deformity. Conclusion: Our findings allowed to identify different anatomic foot alterations in RA patients according to disease duration and negative prognostic factors such as anti-CCP antibodies. Our findings support the role of an accurate analysis of foot structural damage and may suggest the usefulness of a correct plantar orthosis prescription also in early phases of the disease.

  10. Joint Involvement in Primary Sjögren’s Syndrome: An Ultrasound “Target Area Approach to Arthritis”

    Directory of Open Access Journals (Sweden)

    Luis M. Amezcua-Guerra

    2013-01-01

    Full Text Available Objective. To characterize the ultrasound (US pattern of joint involvement in primary Sjögren’s syndrome (pSS. Methods. Seventeen patients with pSS, 18 with secondary Sjögren’s syndrome (sSS, and 17 healthy controls underwent US examinations of various articular regions. Synovitis (synovial hypertrophy/joint effusion, power Doppler (PD signals, and erosions were assessed. Results. In patients with pSS, synovitis was found in the metacarpophalangeal joints (MCP, 76%, wrists (76%, and knees (76%, while the proximal interphalangeal joints, elbows, and ankles were mostly unscathed. Intra-articular PD signals were occasionally detected in wrists (12%, elbows (6%, and knees (6%. Erosions were evident in the wrists of three (18% patients with pSS, one of these also having anti-cyclic citrullinated peptide (anti-CCP antibodies. While US synovitis does not discriminate between sSS and pSS, demonstration of bone erosions in the 2nd MCP joints showed 28.8% sensitivity and 100% specificity for diagnosing sSS; in comparison, these figures were 72.2 and 94.1% for circulating anti-CCP antibodies. Conclusions. In pSS, the pattern of joint involvement by US is polyarticular, bilateral, and symmetrical. Synovitis is the US sign most commonly found in patients with pSS, especially in MCP joints, wrists, and knees, and bone erosions also may occur.

  11. Joint Involvement in Primary Sjögren's Syndrome: An Ultrasound “Target Area Approach to Arthritis”

    Science.gov (United States)

    Amezcua-Guerra, Luis M.; Vargas, Angelica; Rodriguez-Henriquez, Pedro; Solano, Carla; Hernández-Díaz, Cristina; Castillo-Martinez, Diana; Ventura-Ríos, Lucio; Gutiérrez, Marwin; Pineda, Carlos

    2013-01-01

    Objective. To characterize the ultrasound (US) pattern of joint involvement in primary Sjögren's syndrome (pSS). Methods. Seventeen patients with pSS, 18 with secondary Sjögren's syndrome (sSS), and 17 healthy controls underwent US examinations of various articular regions. Synovitis (synovial hypertrophy/joint effusion), power Doppler (PD) signals, and erosions were assessed. Results. In patients with pSS, synovitis was found in the metacarpophalangeal joints (MCP, 76%), wrists (76%), and knees (76%), while the proximal interphalangeal joints, elbows, and ankles were mostly unscathed. Intra-articular PD signals were occasionally detected in wrists (12%), elbows (6%), and knees (6%). Erosions were evident in the wrists of three (18%) patients with pSS, one of these also having anti-cyclic citrullinated peptide (anti-CCP) antibodies. While US synovitis does not discriminate between sSS and pSS, demonstration of bone erosions in the 2nd MCP joints showed 28.8% sensitivity and 100% specificity for diagnosing sSS; in comparison, these figures were 72.2 and 94.1% for circulating anti-CCP antibodies. Conclusions. In pSS, the pattern of joint involvement by US is polyarticular, bilateral, and symmetrical. Synovitis is the US sign most commonly found in patients with pSS, especially in MCP joints, wrists, and knees, and bone erosions also may occur. PMID:23936829

  12. Differentially methylated DNA regions in monozygotic twin pairs discordant for rheumatoid arthritis.An epigenome - wide study.

    Directory of Open Access Journals (Sweden)

    Anders Jørgen Svendsen

    2016-11-01

    Full Text Available Objectives: In an explorative epigenome-wide association study (EWAS to search for gene independent, differentially methylated DNA positions (DMPs and regions (DMRs associated with rheumatoid arthritis (RA by studying monozygotic (MZ twin pairs discordant for rheumatoid arthritis.Methods: Genomic DNA was isolated from whole blood samples from 28 monozygotic (MZ twin pairs discordant for RA. DNA methylation was measured using the HumanMethylation450 BeadChips. Smoking, anti-cyclic citrullinated peptide antibodies and immunosuppressive treatment were included as covariates. Pathway analysis was performed using GREAT.Results: Smoking was significantly associated with hypomethylation of a DMR overlapping the promoter region of the RNF5 and the AGPAT1, which are implicated in inflammation and autoimmunity, whereas DMARD treatment induced hypermethylation of the same region. Additionally, the promotor region of both S100A6 and EFCAB4B were hypomethylated and both genes have previously been associated with RA. We replicated several candidate genes identified in a previous EWAS in treatment naïve RA singletons. Gene set analysis indicated the involvement of immunologic signatures and cancer-related pathways in RA.Conclusion: We identified several differentially methylated regions associated with RA which may represent environmental effects or consequences of the disease and plausible biological pathways pertinent to the pathogenesis of rheumatoid arthritis

  13. A Rare Case of Cardiac Tamponade Induced by Chronic Rheumatoid Arthritis.

    Science.gov (United States)

    Yousuf, Tariq; Kramer, Jason; Kopiec, Adam; Bulwa, Zachary; Sanyal, Shuvani; Ziffra, Jeffrey

    2015-09-01

    Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease primarily involving the joint synovium. RA is a systemic disease which has many known extra-articular manifestations. We present a unique case of a patient with long standing RA who presented with a primary complaint of chest and back pain. Echocardiography revealed borderline normal left ventricular function and a large pericardial effusion with the finding of elevated intrapericardial pressure suspicious for cardiac tamponade. Infectious workup was all found to be negative. The presence and elevation of anti-cyclic citrullinated peptide antibody, rheumatoid factor and C-reactive protein (CRP) confirmed the patient was having an active flare-up of RA. It was determined that this flare-up was the cause of the cardiac tamponade. A pericardiocentesis was performed and 850 mL of bloody fluid was drained. The patient remained stable following the pericardiocentesis. At his follow-up visit, repeat echocardiogram showed no signs for pericardial effusion. Although there has been extensive study of RA, there are only a few documented cases noting the occurrence of cardiac tamponade in these patients. Therefore, it is important for the clinician to be aware of and recognize this potentially serious cardiac outcome associated with a common rheumatologic condition.

  14. The Multifaceted Aspects of Interstitial Lung Disease in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Lorenzo Cavagna

    2013-01-01

    Full Text Available Interstitial lung disease (ILD is a relevant extra-articular manifestation of rheumatoid arthritis (RA that may occur either in early stages or as a complication of long-standing disease. RA related ILD (RA-ILD significantly influences the quoad vitam prognosis of these patients. Several histopathological patterns of RA-ILD have been described: usual interstitial pneumonia (UIP is the most frequent one, followed by nonspecific interstitial pneumonia (NSIP; other patterns are less commonly observed. Several factors have been associated with an increased risk of developing RA-ILD. The genetic background plays a fundamental but not sufficient role; smoking is an independent predictor of ILD, and a correlation with the presence of rheumatoid factor and anti-cyclic citrullinated peptide antibodies has also been reported. Moreover, both exnovo occurrence and progression of ILD have been related to drug therapies that are commonly prescribed in RA, such as methotrexate, leflunomide, anti-TNF alpha agents, and rituximab. A greater understanding of the disease process is necessary in order to improve the therapeutic approach to ILD and RA itself and to reduce the burden of this severe extra-articular manifestation.

  15. Vitamin D receptor gene polymorphism in rheumatoid arthritis and its association with atherosclerosis

    Directory of Open Access Journals (Sweden)

    Amal M El-Barbary

    2015-01-01

    Patients and methods This study included forty early rheumatoid arthritis patients and forty healthy controls. Disease activity score 28 (DAS-28, Modified Health Assessment Questionnaire (MHAQ, Carotid intima-media thickness (cIMT were assessed using B-mode ultrasound, Erythrocyte sedimentation rate (ESR, C reactive protein (CRP, Lipid profile, anti cyclic citrullinated PolyPeptid (anti-CCP, serum interleukin-6, Total serum vitamin D and genotype determination of BsmI, FokI polymorphism and allel frequency were measured. Results Vitamin D deficiency was observed in 25% of patients. There was no significant difference between RA patients and controls regarding the distribution of BsmI genotype frequencies and allele. However, a significant difference between rheumatoid arthritis patients and controls regarding the distribution of FokI genotype and allele frequencies was found. In addition, FokI polymorphism and the F allele was significantly associated with RA. anti-CCP, interleukin-6 levels, (cIMT and vitamin D deficiency were significantly higher in the presence of bb homozygote of BsmI genotypes and FF homozygote of FokI genotypes. A significant negative correlation between 25 hydroxy vitamin D levels with (DAS-28, ESR, (CRP, and IL-6 (P < 0.001. However, there was positive correlation between 25 hydroxyvitamin D levels and HDL-C (P < 0.001.

  16. Clinical value of combined detection of RF and anti-CCP antibody in diagnosis of rheumatoid arthritis%联合检测抗CCP抗体和RF在类风湿关节炎中的诊断价值

    Institute of Scientific and Technical Information of China (English)

    刘其爱; 马小燕; 张弘

    2013-01-01

    Objective To evaluate the clinical value of anti-cyclic citrullinated peptide(CCP) antibody in the diagnosis of rheumatoid arthritis( RA).Methods 87 cases of patients with RA and 69 cases of patients with other autoimmune diseases (control group) were detected for serum anti-CCP antibody by KLISA and for RF by turbidimetry method.36 healthy subjects were enrolled as healthy control group.Diagnostic sensitivity and specificity of anti - CCP antibodies and RF in RA were compared.Results The sensitivity of anti - CCP antibody was 60.9% ,of RF was 67.2% and there was no significant difference between them(P> 0.05).The specificity of anti -CCP antibody was 94.2% ,of RF was 72.5% ,and the difference was significant(P0.05).抗 CCP 抗体的特异度为94.2%,RF 为72.5 %,差异有统计学意义(P<0.05).两者联合检测特异性为97.1 %.结论 抗CCP 抗体在RA诊断中具有较高的特异性,可作为诊断RA的理想血清学指标.两者联合检测可提高检测的特异度.

  17. Recent paradigm shifts in the diagnosis and treatment of rheumatoid arthritis.

    Science.gov (United States)

    Jung, Young Ok; Kim, Hyun Ah

    2012-12-01

    Rheumatoid arthritis (RA) is a progressive inflammatory disease with severe symptoms of pain and stiffness. Chronic persistent inflammation of RA often leads to joint destruction, deformity and limitation of function, which ultimately results in significant deterioration of quality of life (QoL). RA is characterized pathogenetically by immunologically driven, chronic synovitis, and production of autoantibodies, such as rheumatoid factor and anti-cyclic citrullinated peptide antibodies. Although the cause of RA is yet unknown, advances in the molecular biology led to in-depth understanding of its pathogenesis, and have fostered the recent development of novel treatments. The last decade has seen the dramatic change in the landscape of RA treatment with more aggressive therapy early in the disease course and with treatment guided by a structured assessment of disease activity, with the ultimate goal of reaching remission. In addition, prevention and control of joint damage and improvement in QoL are important goals. To achieve these goals, a multidisciplinary approach to reduce disease activity with disease modifying antirheumatic drugs and biological therapy is needed. We also need to find ways to identify those patients who are at risk for more rapid disease progression who would benefit from intensive therapy early in the course of disease.

  18. GITRL modulates the activities of p38 MAPK and STAT3 to promote Th17 cell differentiation in autoimmune arthritis.

    Science.gov (United States)

    Tang, Xinyi; Tian, Jie; Ma, Jie; Wang, Jiemin; Qi, Chen; Rui, Ke; Wang, Yungang; Xu, Huaxi; Lu, Liwei; Wang, Shengjun

    2016-02-23

    The glucocorticoid-induced TNFR family-related protein (GITR) and its ligand play a critical role in the pathogenesis of autoimmune arthritis by enhancing the Th17 cell response, but their molecular mechanisms remain largely unclear. This study aims to define the role of p38 mitogen-activated protein kinases (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling in GITRL-induced Th17 cells in autoimmune arthritis. We found that the p38 phosphorylation was enhanced by GITRL in activated CD4+T cells, and the p38 inhibitor restrained the GITRL-induced Th17 cell expansion in a dose-dependent manner. Moreover, there was decreased STAT3 activity on Tyr705 and Ser727 with the p38 inhibitor in vitro. Notably, the p38 inhibitor could prevent GITRL-treated arthritis progression and markedly decrease the Th17 cell percentages. The phosphorylation of the Tyr705 site was significantly lower in the GITRL-treated CIA mice administrated with the p38 inhibitor. A significantly higher phosphorylation of p38 was detected in RA patients and had a positive relationship with the serum level of anti-cyclic citrullinated peptide (anti-CCP) antibody. Our findings have indicated that GITRL could promote Th17 cell differentiation by p38 MAPK and STAT3 signaling in autoimmune arthritis.

  19. The Effect of SHH-Gli Signaling Pathway on the Synovial Fibroblast Proliferation in Rheumatoid Arthritis.

    Science.gov (United States)

    Qin, Suping; Sun, Dexu; Li, Hui; Li, Xiangyang; Pan, Wei; Yan, Chao; Tang, Renxian; Liu, Xiaomei

    2016-04-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by chronic synovitis. This study aims to investigate the role of sonic hedgehog (SHH)-Gli signaling pathway in synovial fibroblast proliferation in rheumatoid arthritis. The expression of serum SHH in RA patients group was significantly increased compared with the systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and healthy subject (healthy control, HC) groups, respectively; serum SHH expression of RA patients was positively correlated with rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP Ab), while there was no significant correlation between SHH expression and erythrocyte sedimentation rate (ESR). SHH, Ptch, Smo, and Gli molecules were highly expressed in rat RA-synovial fibroblast (RA-SF); after blocking the SHH-Gli signaling pathway with a Gli specific inhibitor, Gli-antagonist 61 (GANT61), RA-SF proliferation was inhibited in a dose-dependent manner and the apoptosis rate of RA-SF was increased as well; the expression levels of fibroblast growth factor receptor 1 (FGFR1) and FGFR3 declined in SF cells after GANT61 treatment. Our results suggest that SHH-Gli pathway is involved in the pathogenesis of RA, and blocking SHH-Gli pathway inhibits RA-SF cell proliferation and increases cell apoptosis, which may shed light on developing new ideas for RA treatment.

  20. Remission of rheumatoid arthritis and potential determinants: a national multi-center cross-sectional survey.

    Science.gov (United States)

    Wang, Guan-Ying; Zhang, Sa-Li; Wang, Xiu-Ru; Feng, Min; Li, Chun; An, Yuan; Li, Xiao-Feng; Wang, Li-Zhi; Wang, Cai-Hong; Wang, Yong-Fu; Yang, Rong; Yan, Hui-Ming; Wang, Guo-Chun; Lu, Xin; Liu, Xia; Zhu, Ping; Chen, Li-Na; Jin, Hong-Tao; Liu, Jin-Ting; Guo, Hui-Fang; Chen, Hai-Ying; Xie, Jian-Li; Wei, Ping; Wang, Jun-Xiang; Liu, Xiang-Yuan; Sun, Lin; Cui, Liu-Fu; Shu, Rong; Liu, Bai-Lu; Yu, Ping; Zhang, Zhuo-Li; Li, Guang-Tao; Li, Zhen-Bin; Yang, Jing; Li, Jun-Fang; Jia, Bin; Zhang, Feng-Xiao; Tao, Jie-Mei; Lin, Jin-Ying; Wei, Mei-Qiu; Liu, Xiao-Min; Ke, Dan; Hu, Shao-Xian; Ye, Cong; Han, Shu-Ling; Yang, Xiu-Yan; Li, Hao; Huang, Ci-Bo; Gao, Ming; Lai, Bei; Cheng, Yong-Jing; Li, Xing-Fu; Song, Li-Jun; Yu, Xiao-Xia; Wang, Ai-Xue; Wu, Li-Jun; Wang, Yan-Hua; He, Lan; Sun, Wen-Wen; Gong, Lu; Wang, Xiao-Yuan; Wang, Yi; Zhao, Yi; Li, Xiao-Xia; Wang, Yan; Zhang, Yan; Su, Yin; Zhang, Chun-Fang; Mu, Rong; Li, Zhan-Guo

    2015-02-01

    The aim of this study is to investigate the remission rate of rheumatoid arthritis (RA) in China and identify its potential determinants. A multi-center cross-sectional study was conducted from July 2009 to January 2012. Data were collected by face-to-face interviews of the rheumatology outpatients in 28 tertiary hospitals in China. The remission rates were calculated in 486 RA patients according to different definitions of remission: the Disease Activity Score in 28 joints (DAS28), the Simplified Disease Activity Index (SDAI), the Clinical Disease Activity Index (CDAI), and the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definition. Potential determinants of RA remission were assessed by univariate and multivariate analyses. The remission rates of RA from this multi-center cohort were 8.6% (DAS28), 8.4% (SDAI), 8.2% (CDAI), and 6.8% (Boolean), respectively. Favorable factors associated with remission were: low Health Assessment Questionnaire (HAQ) score, absence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP), and treatment of methotrexate (MTX) and hydroxychloroquine (HCQ). Younger age was also predictive for the DAS28 and the Boolean remission. Multivariate analyses revealed a low HAQ score, the absence of anti-CCP, and the treatment with HCQ as independent determinants of remission. The clinical remission rate of RA patients was low in China. A low HAQ score, the absence of anti-CCP, and HCQ were significant independent determinants for RA remission.

  1. MRI bone oedema is the strongest predictor of subsequent radiographic progression in early rheumatoid arthritis. Results from a 2 year randomized controlled trial (CIMESTRA)

    DEFF Research Database (Denmark)

    Hetland, M L; Ejbjerg, B; Hørslev-Petersen, K

    2008-01-01

    /placebo-cyclosporine. Baseline magnetic resonance imaging (MRI) of the wrist (wrist-only-group:N=130) or MRI of wrist and MCP-joints (wrist+MCP-group:N=89) (OMERACT RAMRIS), x-rays of hands, wrists and forefeet (Sharp/vdHeijde Score (TSS)), disease activity score (DAS28), anti-cyclic-citrullinated-peptide-antibodies (anti...... variables. RESULTS: Baseline values: median DAS28: 5.6 (range: 2.4-8.0); anti-CCP positive: 61%; radiographic erosions: 56%. At 2 years: DAS28: 2.0 (0.5-5.7), in DAS-remission: 56%, radiographic progression: 26% (wrist+MCP-group, similar for wrist-only-group). MRI bone oedema score was the only independent.......50, respectively). The results were confirmed by sensitivity analyses. CONCLUSION: In a RCT aiming at remission in early RA patients, baseline RAMRIS MRI bone oedema score of MCP and wrist joints (and of wrist only) was the strongest independent predictor of radiographic progression in hands, wrists and forefeet...

  2. In rheumatoid arthritis patients treated with tocilizumab, the rate of clinical disease activity index (CDAI) remission at 24 weeks is superior in those with higher titers of IgM-rheumatoid factor at baseline.

    Science.gov (United States)

    Kawashiri, Shin-Ya; Kawakami, Atsushi; Iwamoto, Naoki; Fujikawa, Keita; Aramaki, Toshiyuki; Tamai, Mami; Yamasaki, Satoshi; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Migita, Kiyoshi; Mizokami, Akinari; Aoyagi, Kiyoshi; Eguchi, Katsumi

    2011-08-01

    We aimed to evaluate the efficacy of tocilizumab in patients with rheumatoid arthritis (RA), using the clinical disease activity index (CDAI), and to determine the baseline variables associated with CDAI remission. Fifty-eight patients with active RA were enrolled. We tried to evaluate whether baseline variables were associated with CDAI remission at 24 weeks. Twenty-two of the 58 patients (37.9%) had received tumor necrosis factor (TNF) inhibitors. The continuation rate of tocilizumab at 24 weeks was 87.9%. The seropositivity rates of IgM-rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies at baseline were both 91.4%. The rate of CDAI remission at 24 weeks was 20.7%. We selected baseline variables including age, gender, duration of disease, concomitant use of glucocorticoids, concomitant use of methotrexate (MTX), previous anti-TNF therapy, titer of anti-CCP antibodies (high or low toward median), titer of IgM-RF (high or low toward median), and CDAI, and found that a high titer of IgM-RF was the only variable to be associated with CDAI remission, according to univariate and logistic regression analyses. This is a new finding, and may be specific to tocilizumab as compared with previous observations in anti-TNF therapy.

  3. Peptide based diagnostics: are random-sequence peptides more useful than tiling proteome sequences?

    Science.gov (United States)

    Navalkar, Krupa Arun; Johnston, Stephan Albert; Stafford, Phillip

    2015-02-01

    Diagnostics using peptide ligands have been available for decades. However, their adoption in diagnostics has been limited, not because of poor sensitivity but in many cases due to diminished specificity. Numerous reports suggest that protein-based rather than peptide-based disease detection is more specific. We examined two different approaches to peptide-based diagnostics using Coccidioides (aka Valley Fever) as the disease model. Although the pathogen was discovered more than a century ago, a highly sensitive diagnostic remains unavailable. We present a case study where two different approaches to diagnosing Valley Fever were used: first, overlapping Valley Fever epitopes representing immunodominant Coccidioides antigens were tiled using a microarray format of presynthesized peptides. Second, a set of random sequence peptides identified using a 10,000 peptide immunosignaturing microarray was compared for sensitivity and specificity. The scientific hypothesis tested was that actual epitope peptides from Coccidioides would provide sufficient sensitivity and specificity as a diagnostic. Results demonstrated that random sequence peptides exhibited higher accuracy when classifying different stages of Valley Fever infection vs. epitope peptides. The epitope peptide array did provide better performance than the existing immunodiffusion array, but when directly compared to the random sequence peptides, reported lower overall accuracy. This study suggests that there are competing aspects of antibody recognition that involve conservation of pathogen sequence and aspects of mimotope recognition and amino acid substitutions. These factors may prove critical when developing the next generation of high-performance immunodiagnostics.

  4. Use of Peptide Libraries for Identification and Optimization of Novel Antimicrobial Peptides.

    Science.gov (United States)

    Ashby, Martin; Petkova, Asya; Gani, Jurnorain; Mikut, Ralf; Hilpert, Kai

    2017-01-01

    The increasing rates of resistance among bacteria and to a lesser extent fungi have resulted in an urgent need to find new molecules that hold therapeutic promise against multidrug-resistant strains. Antimicrobial peptides have proven very effective against a variety of multidrug-resistant bacteria. Additionally, the low levels of resistance reported towards these molecules are an attractive feature for antimicrobial drug development. Here we summarise information on diverse peptide libraries used to discover or to optimize antimicrobial peptides. Chemical synthesized peptide libraries, for example split and mix method, tea bag method, multi-pin method and cellulose spot method are discussed. In addition biological peptide library screening methods are summarized, like phage display, bacterial display, mRNA-display and ribosomal display. A few examples are given for small peptide libraries, which almost exclusively follow a rational design of peptides of interest rather than a combinatorial approach.

  5. Antioxidant activity of yoghurt peptides: Part 2 – Characterisationof peptide fractions

    DEFF Research Database (Denmark)

    Farvin, Sabeena; Baron, Caroline; Nielsen, Nina Skall;

    2010-01-01

    The aim of the present study was to elucidate previous findings showing that peptide fractions isolated from yoghurt had antioxidant effects. Therefore, peptides and free amino acids released during fermentation of milk were characterised. Yoghurt samples were stripped from sugars and lactic acid...... antioxidant activity in these fractions.......The aim of the present study was to elucidate previous findings showing that peptide fractions isolated from yoghurt had antioxidant effects. Therefore, peptides and free amino acids released during fermentation of milk were characterised. Yoghurt samples were stripped from sugars and lactic acid...... the peptides identified contained at least one proline residue. Some of the identified peptides included the hydrophobic amino acid residues Val or Leu at the N-terminus and Pro, His or Tyr in the amino acid sequence, which is characteristic of antioxidant peptides. In addition, the yoghurt contained...

  6. Role of peptide bond in the realization of biological activity of short peptides.

    Science.gov (United States)

    Khavinson, V Kh; Tarnovskaya, S I; Lin'kova, N S; Chervyakova, N A; Nichik, T E; Elashkina, E V; Chalisova, N I

    2015-02-01

    We performed a comparative analysis of biological activity of Lys-Glu peptide and its amino acid constituents. It was established that Lys-Glu stimulated proliferation of splenic cells in organotypic culture, while the mixture of glutamic acid and lysine inhibited culture growth. Using the method of molecular docking, we showed that glutamic acid, lysine, and Lys-Glu peptide can interact with different DNA sequences. The energy of interaction and the most beneficial localization of glutamic acid, lysine, and Lys-Glu peptide in DNA molecule was calculated. We demonstrated the interaction of the peptide and amino acids with DNA along the minor groove. The energy of DNA interaction with the peptide is higher than with individual amino acids. The peptide bonds increase the interaction of Lys-Glu peptide with DNA, which potentiates the biological effect on cell proliferation in organotypic culture of splenic cells.

  7. Review stapling peptides using cysteine crosslinking.

    Science.gov (United States)

    Fairlie, David P; Dantas de Araujo, Aline

    2016-11-01

    Stapled peptides are an emerging class of cyclic peptide molecules with enhanced biophysical properties such as conformational and proteolytic stability, cellular uptake and elevated binding affinity and specificity for their biological targets. Among the limited number of chemistries available for their synthesis, the cysteine-based stapling strategy has received considerable development in the last few years driven by facile access from cysteine-functionalized peptide precursors. Here we present some recent advances in peptide and protein stapling where the side-chains of cysteine residues are covalently connected with a range of different crosslinkers affording bisthioether macrocyclic peptides of varying topology and biophysical properties. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 843-852, 2016.

  8. Novel peptide-based protease inhibitors

    DEFF Research Database (Denmark)

    Roodbeen, Renée

    This thesis describes the design and synthesis of peptide-based serine protease inhibitors. The targeted protease, urokinase-type plasminogen activator (uPA) activates plasminogen, which plays a major role in cancer metastasis. The peptide upain-2 (S 1 ,S 12-cyclo-AcCSWRGLENHAAC-NH2) is a highly......, the disulfide bridge was replaced with amide bonds of various lengths. The novel peptides did not retain their inhibitory activity, but formed the basis for another strategy. Second, bicyclic peptides were obtained by creating head-to-tail cyclized peptides that were made bicyclic by the addition of a covalent...... increased. Finally, the effect of multivalent display of upain-2 was investigated. Several dimers of upain-2 were made and the attachment of upain-2 via the Copper-catalyzed Azide-Alkyne Cycloaddition (CuAAC) onto an alkyne functionalized carbohydrate scaffold was investigated. Besides the synthesis...

  9. Design of Asymmetric Peptide Bilayer Membranes.

    Science.gov (United States)

    Li, Sha; Mehta, Anil K; Sidorov, Anton N; Orlando, Thomas M; Jiang, Zhigang; Anthony, Neil R; Lynn, David G

    2016-03-16

    Energetic insights emerging from the structural characterization of peptide cross-β assemblies have enabled the design and construction of robust asymmetric bilayer peptide membranes. Two peptides differing only in their N-terminal residue, phosphotyrosine vs lysine, coassemble as stacks of antiparallel β-sheets with precisely patterned charged lattices stabilizing the bilayer leaflet interface. Either homogeneous or mixed leaflet composition is possible, and both create nanotubes with dense negative external and positive internal solvent exposed surfaces. Cross-seeding peptide solutions with a preassembled peptide nanotube seed leads to domains of different leaflet architecture within single nanotubes. Architectural control over these cross-β assemblies, both across the bilayer membrane and along the nanotube length, provides access to highly ordered asymmetric membranes for the further construction of functional mesoscale assemblies.

  10. Harnessing supramolecular peptide nanotechnology in biomedical applications

    Science.gov (United States)

    Chan, Kiat Hwa; Lee, Wei Hao; Zhuo, Shuangmu; Ni, Ming

    2017-01-01

    The harnessing of peptides in biomedical applications is a recent hot topic. This arises mainly from the general biocompatibility of peptides, as well as from the ease of tunability of peptide structure to engineer desired properties. The ease of progression from laboratory testing to clinical trials is evident from the plethora of examples available. In this review, we compare and contrast how three distinct self-assembled peptide nanostructures possess different functions. We have 1) nanofibrils in biomaterials that can interact with cells, 2) nanoparticles that can traverse the bloodstream to deliver its payload and also be bioimaged, and 3) nanotubes that can serve as cross-membrane conduits and as a template for nanowire formation. Through this review, we aim to illustrate how various peptides, in their various self-assembled nanostructures, possess great promise in a wide range of biomedical applications and what more can be expected. PMID:28223805

  11. Peptide binding specificity of the chaperone calreticulin

    DEFF Research Database (Denmark)

    Sandhu, N.; Duus, K.; Jorgensen, C.S.;

    2007-01-01

    Calreticulin is a molecular chaperone with specificity for polypeptides and N-linked monoglucosylated glycans. In order to determine the specificity of polypeptide binding, the interaction of calreticulin with polypeptides was investigated using synthetic peptides of different length and composit......Calreticulin is a molecular chaperone with specificity for polypeptides and N-linked monoglucosylated glycans. In order to determine the specificity of polypeptide binding, the interaction of calreticulin with polypeptides was investigated using synthetic peptides of different length...... and composition. A large set of available synthetic peptides (n=127) was tested for binding to calreticulin and the results analysed by multivariate data analysis. The parameter that correlated best with binding was hydrophobicity while beta-turn potential disfavoured binding. Only hydrophobic peptides longer...... a peptide-binding specificity for hydrophobic sequences and delineate the fine specificity of calreticulin for hydrophobic amino acid residues....

  12. Chemical reactions directed Peptide self-assembly.

    Science.gov (United States)

    Rasale, Dnyaneshwar B; Das, Apurba K

    2015-05-13

    Fabrication of self-assembled nanostructures is one of the important aspects in nanoscience and nanotechnology. The study of self-assembled soft materials remains an area of interest due to their potential applications in biomedicine. The versatile properties of soft materials can be tuned using a bottom up approach of small molecules. Peptide based self-assembly has significant impact in biology because of its unique features such as biocompatibility, straight peptide chain and the presence of different side chain functionality. These unique features explore peptides in various self-assembly process. In this review, we briefly introduce chemical reaction-mediated peptide self-assembly. Herein, we have emphasised enzymes, native chemical ligation and photochemical reactions in the exploration of peptide self-assembly.

  13. Antimicrobial peptides important in innate immunity.

    Science.gov (United States)

    Cederlund, Andreas; Gudmundsson, Gudmundur H; Agerberth, Birgitta

    2011-10-01

    Antimicrobial peptides are present in all walks of life, from plants to animals, and they are considered to be endogenous antibiotics. In general, antimicrobial peptides are determinants of the composition of the microbiota and they function to fend off microbes and prevent infections. Antimicrobial peptides eliminate micro-organisms through disruption of their cell membranes. Their importance in human immunity, and in health as well as disease, has only recently been appreciated. The present review provides an introduction to the field of antimicrobial peptides in general and discusses two of the major classes of mammalian antimicrobial peptides: the defensins and the cathelicidins. The review focuses on their structures, their main modes of action and their regulation.

  14. Concentration effects on peptide elution from pendant PEO layers.

    Science.gov (United States)

    Wu, Xiangming; Ryder, Matthew P; McGuire, Joseph; Schilke, Karl F

    2014-06-01

    In earlier work, we have provided direction for development of responsive drug delivery systems based on modulation of structure and amphiphilicity of bioactive peptides entrapped within pendant polyethylene oxide (PEO) brush layers. Amphiphilicity promotes retention of the peptides within the hydrophobic inner region of the PEO brush layer. In this work, we describe the effects of peptide surface density on the conformational changes caused by peptide-peptide interactions, and show that this phenomenon substantially affects the rate and extent of peptide elution from PEO brush layers. Three cationic peptides were used in this study: the arginine-rich amphiphilic peptide WLBU2, the chemically identical but scrambled peptide S-WLBU2, and the non-amphiphilic homopolymer poly-l-arginine (PLR). Circular dichroism (CD) was used to evaluate surface density effects on the structure of these peptides at uncoated (hydrophobic) and PEO-coated silica nanoparticles. UV spectroscopy and a quartz crystal microbalance with dissipation monitoring (QCM-D) were used to quantify changes in the extent of peptide elution caused by those conformational changes. For amphiphilic peptides at sufficiently high surface density, peptide-peptide interactions result in conformational changes which compromise their resistance to elution. In contrast, elution of a non-amphiphilic peptide is substantially independent of its surface density, presumably due to the absence of peptide-peptide interactions. The results presented here provide a strategy to control the rate and extent of release of bioactive peptides from PEO layers, based on modulation of their amphiphilicity and surface density.

  15. Encapsulation of Enzymes and Peptides

    Science.gov (United States)

    Meesters, Gabrie M. H.

    A large part of formulated peptides and proteins, e.g., enzymes used as food ingredients, are formulated in a liquid form. Often, they are dissolved in water to which glycerol or sorbitol is added to reduce the water activity of the liquid, thus reducing the change of microbial growth. Still, there are reasons to formulate them in a solid form. Often, these reasons are stability, since a dry formulation is often much better than liquid formulations, and less transportation cost, since less mass is transported if one gets rid of the liquid; however, most of the times, the reason is that the product is mixed with a solid powder. Here, a liquid addition would lead to lump formation.

  16. Antimicrobial peptides of multicellular organisms

    Science.gov (United States)

    Zasloff, Michael

    2002-01-01

    Multicellular organisms live, by and large, harmoniously with microbes. The cornea of the eye of an animal is almost always free of signs of infection. The insect flourishes without lymphocytes or antibodies. A plant seed germinates successfully in the midst of soil microbes. How is this accomplished? Both animals and plants possess potent, broad-spectrum antimicrobial peptides, which they use to fend off a wide range of microbes, including bacteria, fungi, viruses and protozoa. What sorts of molecules are they? How are they employed by animals in their defence? As our need for new antibiotics becomes more pressing, could we design anti-infective drugs based on the design principles these molecules teach us?

  17. Antimicrobial peptides in the brain.

    Science.gov (United States)

    Su, Yanhua; Zhang, Kai; Schluesener, Hermann J

    2010-10-01

    Antimicrobial peptides (AMPs) are an evolutionarily conserved component of the innate immune system of many species. The brain is an immunologically privileged organ but can produce a robust immune response against pathogens and cell debris, promoting rapid and efficient clearance. AMPs may be critically involved in the innate immune system of the brain. Though the mechanisms of AMPs' action in the brain still need further elucidation, many studies have shown that AMPs are multifunctional molecules in the brain. In addition to antimicrobial action, they take part in congenital and adaptive immune reactions (immunoregulation), function as signaling molecules in tissue repair, inflammation and other important processes through different mechanisms, and they might, in addition, become diagnostic markers of brain disease.

  18. A Peptide/MHCII conformer generated in the presence of exchange peptide is substrate for HLA-DM editing

    OpenAIRE

    Andrea Ferrante; Jack Gorski

    2012-01-01

    The mechanism of HLA-DM (DM) activity is still unclear. We have shown that DM-mediated peptide release from HLA-DR (DR) is dependent on the presence of exchange peptide. However, DM also promotes a small amount of peptide release in the absence of exchange peptide. Here we show that SDS-PAGE separates purified peptide/DR1 complexes (pDR1) into two conformers whose ratio is peptide K d-dependent. In the absence of exchange peptide, DM only releases peptide from the slower migrating conformer. ...

  19. Identification of a novel skin penetration enhancement peptide by phage display peptide library screening.

    Science.gov (United States)

    Kumar, Sunny; Sahdev, Preety; Perumal, Omathanu; Tummala, Hemachand

    2012-05-07

    Skin is an important site for local or systemic application of drugs. However, a majority of drugs have poor permeability through the skin's topmost layer, stratum corneum (SC). The aim of this study was to identify safe and smaller peptides that could enhance the skin penetration of drug molecules. By screening phage display peptide library, we have identified a T2 peptide (LVGVFH), which enhanced the penetration of bacteriophages (~800 nm long bacterial viruses) across porcine and mouse skin. Pretreating the skin with synthetic T2 peptide at pH 4.5 resulted in significant penetration enhancement of hydrophilic drug 5-fluorouracil (5-FU) across skin. FTIR spectroscopy showed that the T2 peptide interacted with skin lipids to enhance the skin penetration. Pretreating the skin with T2 peptide enhanced the partitioning of small molecules with different lipophilicities (5-FU, fluorescein isothiocyanate, and rhodamine 123 hydrochloride) into skin. Fluorescence studies showed that T2 peptide enhanced the diffusion of these molecules into intercellular lipids of SC and thus enhanced the penetration into the skin. Histidine at the c-terminus of T2 peptide was identified to be critical for the skin penetration enhancement. T2 peptide interacted with skin lipids to cause skin penetration enhancement. The study identified a novel, safe, and noninvasive peptide to improve the skin penetration of drugs without chemical conjugation.

  20. Interactions of Bio-Inspired Membranes with Peptides and Peptide-Mimetic Nanoparticles

    Directory of Open Access Journals (Sweden)

    Michael Sebastiano

    2015-08-01

    Full Text Available Via Dissipative Particle Dynamics (DPD and implicit solvent coarse-grained (CG Molecular Dynamics (MD we examine the interaction of an amphiphilic cell-penetrating peptide PMLKE and its synthetic counterpart with a bio-inspired membrane. We use the DPD technique to investigate the interaction of peptide-mimetic nanoparticles, or nanopins, with a three-component membrane. The CG MD approach is used to investigate the interaction of a cell-penetrating peptide PMLKE with single-component membrane. We observe the spontaneous binding and subsequent insertion of peptide and nanopin in the membrane by using CG MD and DPD approaches, respectively. In addition, we find that the insertion of peptide and nanopins is mainly driven by the favorable enthalpic interactions between the hydrophobic components of the peptide, or nanopin, and the membrane. Our study provides insights into the mechanism underlying the interactions of amphiphilic peptide and peptide-mimetic nanoparticles with a membrane. The result of this study can be used to guide the functional integration of peptide and peptide-mimetic nanoparticles with a cell membrane.

  1. Analysis of the endogenous peptide profile of milk: identification of 248 mainly casein-derived peptides.

    Science.gov (United States)

    Baum, Florian; Fedorova, Maria; Ebner, Jennifer; Hoffmann, Ralf; Pischetsrieder, Monika

    2013-12-06

    Milk is an excellent source of bioactive peptides. However, the composition of the native milk peptidome has only been partially elucidated. The present study applied matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) directly or after prefractionation of the milk peptides by reverse-phase high-performance liquid chromatography (RP-HPLC) or OFFGEL fractionation for the comprehensive analysis of the peptide profile of raw milk. The peptide sequences were determined by MALDI-TOF/TOF or nano-ultra-performance liquid chromatography-nanoelectrospray ionization-LTQ-Orbitrap-MS. Direct MALDI-TOF-MS analysis led to the assignment of 57 peptides. Prefractionation by both complementary methods led to the assignment of another 191 peptides. Most peptides originate from α(S1)-casein, followed by β-casein, and α(S2)-casein. κ-Casein and whey proteins seem to play only a minor role as peptide precursors. The formation of many, but not all, peptides could be explained by the activity of the endogenous peptidases, plasmin or cathepsin D, B, and G. Database searches revealed the presence of 22 peptides with established physiological function, including those with angiotensin-converting-enzyme (ACE) inhibitory, immunomodulating, or antimicrobial activity.

  2. Identification of peptides that selectively bind to myoglobin by biopanning of phage displayed-peptide library.

    Science.gov (United States)

    Padmanaban, Guruprasath; Park, Hyekyung; Choi, Ji Suk; Cho, Yong-Woo; Kang, Woong Chol; Moon, Chan-Il; Kim, In-San; Lee, Byung-Heon

    2014-10-10

    Biopanning of phage displayed-peptide library was performed against myoglobin, a marker for the early assessment of acute myocardial infarction (AMI), to identify peptides that selectively bind to myoglobin. Using myoglobin-conjugated magnetic beads, phages that bound to myoglobin were collected and amplified for the next round of screening. A 148-fold enrichment of phage titer was observed after five rounds of screening relative to the first round. After phage binding ELISA, three phage clones were selected (3R1, 3R7 and 3R10) and the inserted peptides were chemically synthesized. The analysis of binding affinity showed that the 3R7 (CPSTLGASC) peptide had higher binding affinity (Kd=57 nM) than did the 3R1 (CNLSSSWIC) and 3R10 (CVPRLSAPC) peptide (Kd=125 nM and 293 nM, respectively). Cross binding activity to other proteins, such as bovine serum albumin, troponin I, and creatine kinase-MB, was minimal. In a peptide-antibody sandwich ELISA, the selected peptides efficiently captured myoglobin. Moreover, the concentrations of myoglobin in serum samples measured by a peptide-peptide sandwich assay were comparable to those measured by a commercial antibody-based kit. These results indicate that the identified peptides can be used for the detection of myoglobin and may be a cost effective alternative to antibodies.

  3. The novel amyloid-beta peptide aptamer inhibits intracellular amyloid-beta peptide toxicity

    Institute of Scientific and Technical Information of China (English)

    Xu Wang; Yi Yang; Mingyue Jia; Chi Ma; Mingyu Wang; Lihe Che; Yu Yang; Jiang Wu

    2013-01-01

    Amyloid β peptide binding alcohol dehydrogenase (ABAD) decoy peptide (DP) can competitively antagonize binding of amyloid β peptide to ABAD and inhibit the cytotoxic effects of amyloid β peptide. Based on peptide aptamers, the present study inserted ABAD-DP into the disulfide bond of human thioredoxin (TRX) using molecular cloning technique to construct a fusion gene that can express the TRX1-ABAD-DP-TRX2 aptamer. Moreover, adeno-associated virus was used to allow its stable expression. Immunofluorescent staining revealed the co-expression of the transduced fusion gene TRX1-ABAD-DP-TRX2 and amyloid β peptide in NIH-3T3 cells, indicating that the TRX1-ABAD-DP-TRX2 aptamer can bind amyloid β peptide within cells. In addition, cell morphology and MTT results suggested that TRX1-ABAD-DP-TRX2 attenuated amyloid β peptide-induced SH-SY5Y cell injury and improved cell viability. These findings confirmed the possibility of constructing TRX-based peptide aptamer using ABAD-DP. Moreover, TRX1-ABAD-DP-TRX2 inhibited the cytotoxic effect of amyloid β peptide.

  4. Conus Peptides A Rich Pharmaceutical Treasure

    Institute of Scientific and Technical Information of China (English)

    Cheng-Zhong WANG; Cheng-Wu CHI

    2004-01-01

    Marine predatory cone snails (genus Conus) with over 500 species represent what is arguably the largest single genus of marine animals alive today. All Conus are venomous and utilize a complex mixture of Conus peptides to capture their preys and for other biological purposes. Each component of Conus peptides selectively targets a specific subtype of ion channels, neurotransmitter receptors or transporters.Owing to their diversity, more than 50,000 distinct active peptides are theoretically estimated in Conus venoms. These diversified toxins are generally categorized into several superfamilies and/or families based on their characteristic arrangements of cysteine residues and pharmacological actions. Some mechanisms underlying the remarkable diversity of Conus peptides have been postulated: the distinctive gene structure, gene duplication and/or allelic selection, genus speciation, and sophisticated expression pattern and posttranslational modification of these peptides. Due to their highly pharmacological potency and target selectivity, Conus peptides have attracted extensive attention with their potentials to be developed as new research tools in neuroscience field and as novel medications in clinic for pain, epilepsy and other neuropathic disorders. Several instructive lessons for our drug development could be also learnt from these neuropharmacological "expertises". Conus peptides comprise a rich resource for neuropharmacologists, and most of them await to be explored.

  5. Creating functional peptide architectures at interfaces

    Science.gov (United States)

    Tirrell, Matthew

    2001-03-01

    Short peptide sequences, derived from whole proteins, can be useful synthetic agents for conferring a specific biological function to a material surface. Their ability to do this depends on delivering them to the surface in a biologically recognizable form, that is in a spatial configuration that is not too different from that adopted by the peptide in the whole protein. Most functional proteins have secondary and tertiary levels of structure that are essential to their activities; peptides have simpler but no less important structures. In our work, we have focussed on peptides derived from extracellular matrix proteins. We have found that attaching synthetic lipid tails to peptides fragments gives them two very useful properties for surface modification. The hydrophobic tails give rise to a self-assembly capacity enabling these molecules to organize into membrane, monolayer and bilayer structures. Less expected is that this level of self-assembly induces a second level in the peptide headgroup. Peptides from alpha-helical and triple-helical regions of protein are induced by the lipid tails to form protein-like secondary structures and therefore to have more effective biological activity.

  6. Multifunctional Prenylated Peptides for Live Cell Analysis

    Science.gov (United States)

    Wollack, James W.; Zeliadt, Nicholette A.; Mullen, Daniel G.; Amundson, Gregg; Geier, Suzanne; Falkum, Stacy; Wattenberg, Elizabeth V.; Barany, George; Distefano, Mark D.

    2009-01-01

    Protein prenylation is a common post-translational modification present in eukaryotic cells. Many key proteins involved in signal transduction pathways are prenylated and inhibition of prenylation can be useful as a therapeutic intervention. While significant progress has been made in understanding protein prenylation in vitro, we have been interested in studying this process in living cells, including the question of where prenylated molecules localize. Here, we describe the synthesis and live cell analysis of a series of fluorescently labeled multifunctional peptides, based on the C-terminus of the naturally prenylated protein CDC42. A synthetic route was developed that features a key Acm to Scm protecting group conversion. This strategy was compatible with acid-sensitive isoprenoid moieties, and allowed incorporation of an appropriate fluorophore as well as a cell-penetrating sequence (penetratin). These peptides are able to enter cells through different mechanisms, depending on the presence or absence of the penetratin vehicle and the nature of the prenyl group attached. Interestingly, prenylated peptides lacking penetratin are able to enter cells freely through an energy-independent process, and localize in a perinuclear fashion. This effect extends to a prenylated peptide that includes a full “CAAX box” sequence (specifically, CVLL). Hence, these peptides open the door for studies of protein prenylation in living cells, including enzymatic processing and intracellular peptide trafficking. Moreover, the synthetic strategy developed here should be useful for the assembly of other types of peptides that contain acid sensitive functionalities. PMID:19425596

  7. Peptide design for antimicrobial and immunomodulatory applications.

    Science.gov (United States)

    Haney, Evan F; Hancock, Robert E W

    2013-11-01

    The increasing threat of antibiotic resistance in pathogenic bacteria and the dwindling supply of antibiotics available to combat these infections poses a significant threat to human health throughout the world. Antimicrobial peptides (AMPs) have long been touted as the next generation of antibiotics capable of filling the anti-infective void. Unfortunately, peptide-based antibiotics have yet to realize their potential as novel pharmaceuticals, in spite of the immense number of known AMP sequences and our improved understanding of their antibacterial mechanism of action. Recently, the immunomodulatory properties of certain AMPs have become appreciated. The ability of small synthetic peptides to protect against infection in vivo has demonstrated that modulation of the innate immune response is an effective strategy to further develop peptides as novel anti-infectives. This review focuses on the screening methods that have been used to assess novel peptide sequences for their antibacterial and immunomodulatory properties. It will also examine how we have progressed in our ability to identify and optimize peptides with desired biological characteristics and enhanced therapeutic potential. In addition, the current challenges to the development of peptides as anti-infectives are examined and the strategies being used to overcome these issues are discussed.

  8. Cysteine-containing peptides having antioxidant properties

    Science.gov (United States)

    Bielicki, John K.

    2008-10-21

    Cysteine containing amphipathic alpha helices of the exchangeable apolipoproteins, as exemplified by apolipoprotein (apo) A-I.sub.Milano (R173C) and apoA-I.sub.Paris, (R151C) were found to exhibit potent antioxidant activity on phospholipid surfaces. The addition of a free thiol, at the hydrophobic/hydrophilic interface of an amphipathic alpha helix of synthetic peptides that mimic HDL-related proteins, imparts a unique antioxidant activity to these peptides which inhibits lipid peroxidation and protects phospholipids from water-soluble free radical initiators. These peptides can be used as therapeutic agents to combat cardiovascular disease, ischemia, bone disease and other inflammatory related diseases.

  9. Clickable Polymeric Coating for Oriented Peptide Immobilization.

    Science.gov (United States)

    Sola, Laura; Gori, Alessandro; Cretich, Marina; Finetti, Chiara; Zilio, Caterina; Chiari, Marcella

    2016-01-01

    A new methodology for the fabrication of an high-performance peptide microarray is reported, combining the higher sensitivity of a layered Si-SiO2 substrate with the oriented immobilization of peptides using a N,N-dimethylacrylamide-based polymeric coating that contains alkyne monomers as functional groups. This clickable polymer allows the oriented attachment of azido-modified peptides via a copper-mediated azide/alkyne cycloaddition. A similar coating that does not contain the alkyne functionality has been used as comparison, to demonstrate the importance of a proper orientation for facilitating the probe recognition and interaction with the target antibody.

  10. Brain natriuretic peptide: Diagnostic potential in dogs

    Directory of Open Access Journals (Sweden)

    Spasojević-Kosić Ljubica

    2009-01-01

    Full Text Available The endocrine role of the heart is evident in the secretion of noradrenaline and natriuretic peptides. The secretion of natriuretic peptides presents a useful mechanism for different conditions of cardiac dysfunction. Brain natriuretic peptide (BNP has been accepted in human cardiology as a biomarker for cardiac insufficiency and coronary arterial disease. The specificity of the BNP structure is specie-specific, so that the testing of diagnostic and prognostic potential in dogs requires the existence of a test that is a homologue for that animal specie. The existence of an adequate method for measuring BNP concentration makes possible its implementation as a screening test in everyday clinical practice. .

  11. Imaging tumors with peptide-based radioligands

    Energy Technology Data Exchange (ETDEWEB)

    Behr, T. M.; Gotthardt, M.; Barth, A.; Behe, M. [Philipps-University of Marburg, Dept. of Nuclear Medicine, Marburg (Germany)

    2001-06-01

    Regulatory peptides are small, readily diffusable and potent natural substances with a wide spectrum of receptor-mediated actions in humans. High affinity receptors for these peptides are (over)-expressed in many neoplasms, and these receptors may represent, therefore, new molecular targets for cancer diagnosis and therapy. This review aims to give an overview of the peptide-based radiopharmaceuticals which are presently already commercially available or which are in advanced stages of their clinical testing so that their broader availability is anticipated soon. Physiologically, these peptides bind to and act through G protein-coupled receptors in the cell membrane. Historically, somatostatin analogs are the first class of receptor binding peptides having gained clinical application. In {sup 111}In-DTPA-(D-Phe{sup 1})-octreotide is the first and only radio peptide which has obtained regulatory approval in Europe and the United States to date. Extensive clinical studies involving several thousands of patients have shown that the major clinical application of somatostatin receptor scintigraphy is the detection and the staging of gastroenteropancreatic neuroendocrine tumors (carcinoids). In these tumors, octreotide scintigraphy is superior to any other staging method. However, its sensitivity and accuracy in other, more frequent neoplasms is limited. Radiolabeled vasoactive intestinal peptide (VIP) has been shown to visualize the majority of gastrointestinal adenocarcinomas, as well as some neuroendocrine tumors, including insulinomas (the latter being often missed by somatostatin receptor scintigraphy). Due to the outstanding diagnostic accuracy of the pentagastrin test in detecting the presence, persistence, or recurrence of medullary thyroid cancer (MTC), it was postulated the expression of the corresponding (i.e. cholecystokinin (CCK-)-B) receptor type in human MTC. This receptor is also widely expressed on human small-cell lung. Indeed, {sup 111}In-labeled DTPA

  12. Immunocytochemical and Immunohistochemical Staining with Peptide Antibodies.

    Science.gov (United States)

    Friis, Tina; Pedersen, Klaus Boberg; Hougaard, David; Houen, Gunnar

    2015-01-01

    Peptide antibodies are particularly useful for immunocytochemistry (ICC) and immunohistochemistry (IHC), where antigens may denature due to fixation of tissues and cells. Peptide antibodies can be made to any defined sequence, including unknown putative proteins and posttranslationally modified sequences. Moreover, the availability of large amounts of the antigen (peptide) allows inhibition/adsorption controls, which are important in ICC/IHC, due to the many possibilities for false-positive reactions caused by immunoglobulin Fc receptors, nonspecific reactions, and cross-reactivity of primary and secondary antibodies with other antigens and endogenous immunoglobulins, respectively. Here, simple protocols for ICC and IHC are described together with recommendations for appropriate controls.

  13. Asymmetric catalysis with short-chain peptides.

    Science.gov (United States)

    Lewandowski, Bartosz; Wennemers, Helma

    2014-10-01

    Within this review article we describe recent developments in asymmetric catalysis with peptides. Numerous peptides have been established in the past two decades that catalyze a wide variety of transformations with high stereoselectivities and yields, as well as broad substrate scope. We highlight here catalytically active peptides, which have addressed challenges that had thus far remained elusive in asymmetric catalysis: enantioselective synthesis of atropoisomers and quaternary stereogenic centers, regioselective transformations of polyfunctional substrates, chemoselective transformations, catalysis in-flow and reactions in aqueous environments.

  14. Activity of Cathelicidin Peptides against Simkania negevensis.

    Science.gov (United States)

    Donati, Manuela; Di Francesco, Antonietta; Di Paolo, Maria; Fiani, Natascia; Benincasa, Monica; Gennaro, Renato; Nardini, Paola; Foschi, Claudio; Cevenini, Roberto

    2011-01-01

    The in vitro activity of six cathelicidin peptides against the reference strain Z of Simkania negevensis was investigated. Five peptides-PG-1, Bac7, SMAP-29, BMAP-27, and BMAP-28-proved to be active at very low concentrations (1 to 0.1 μg/mL), while LL-37 cathelicidin was ineffective even at a concentration of 100 μg/mL. In comparison to chlamydiae, S. negevensis proved to be more susceptible to the antimicrobial peptides tested.

  15. Exploiting Protected Maleimides to Modify Oligonucleotides, Peptides and Peptide Nucleic Acids

    Directory of Open Access Journals (Sweden)

    Clément Paris

    2015-04-01

    Full Text Available This manuscript reviews the possibilities offered by 2,5-dimethylfuran-protected maleimides. Suitably derivatized building blocks incorporating the exo Diels-Alder cycloadduct can be introduced at any position of oligonucleotides, peptide nucleic acids, peptides and peptoids, making use of standard solid-phase procedures. Maleimide deprotection takes place upon heating, which can be followed by either Michael-type or Diels-Alder click conjugation reactions. However, the one-pot procedure in which maleimide deprotection and conjugation are simultaneously carried out provides the target conjugate more quickly and, more importantly, in better yield. This procedure is compatible with conjugates involving oligonucleotides, peptides and peptide nucleic acids. A variety of cyclic peptides and oligonucleotides can be obtained from peptide and oligonucleotide precursors incorporating protected maleimides and thiols.

  16. Copper-Aβ Peptides and Oxidation of Catecholic Substrates: Reactivity and Endogenous Peptide Damage.

    Science.gov (United States)

    Pirota, Valentina; Dell'Acqua, Simone; Monzani, Enrico; Nicolis, Stefania; Casella, Luigi

    2016-11-14

    The oxidative reactivity of copper complexes with Aβ peptides 1-16 and 1-28 (Aβ16 and Aβ28) against dopamine and related catechols under physiological conditions has been investigated in parallel with the competitive oxidative modification undergone by the peptides. It was found that both Aβ16 and Aβ28 markedly increase the oxidative reactivity of copper(II) towards the catechol compounds, up to a molar ratio of about 4:1 of peptide/copper(II). Copper redox cycling during the catalytic activity induces the competitive modification of the peptide at selected amino acid residues. The main modifications consist of oxidation of His13/14 to 2-oxohistidine and Phe19/20 to ortho-tyrosine, and the formation of a covalent His6-catechol adduct. Competition by the endogenous peptide is rather efficient, as approximately one peptide molecule is oxidized every 10 molecules of 4-methylcatechol.

  17. Collagen-like peptides and peptide-polymer conjugates in the design of assembled materials

    OpenAIRE

    Luo, Tianzhi; Kiick, Kristi L.

    2013-01-01

    Collagen is the most abundant protein in mammals, and there has been long-standing interest in understanding and controlling collagen assembly in the design of new materials. Collagen-like peptides (CLP), also known as collagen-mimetic peptides (CMP) or collagen-related peptides (CRP), have thus been widely used to elucidate collagen triple helix structure as well as to produce higher-order structures that mimic natural collagen fibers. This mini-review provides an overview of recent progress...

  18. A statistical approach to determining responses to individual peptides from pooled-peptide ELISpot data.

    Science.gov (United States)

    Ström, Peter; Støer, Nathalie; Borthwick, Nicola; Dong, Tao; Hanke, Tomáš; Reilly, Marie

    2016-08-01

    To investigate in detail the effect of infection or vaccination on the human immune system, ELISpot assays are used to simultaneously test the immune response to a large number of peptides of interest. Scientists commonly use "peptide pools", where, instead of an individual peptide, a test well contains a group of peptides. Since the response from a well may be due to any or many of the peptides in the pool, pooled assays usually need to be followed by confirmatory assays of a number of individual peptides. We present a statistical method that enables estimation of individual peptide responses from pool responses using the Expectation Maximization (EM) algorithm for "incomplete data". We demonstrate the accuracy and precision of these estimates in simulation studies of ELISpot plates with 90 pools of 6 or 7 peptides arranged in three dimensions and three Mock wells for the estimation of background. In analysis of real pooled data from 6 subjects in a HIV-1 vaccine trial, where 199 peptides were arranged in 80 pools if size 9 or 10, our estimates were in very good agreement with the results from individual-peptide confirmatory assays. Compared to the classical approach, we could identify almost all the same peptides with high or moderate response, with less than half the number of confirmatory tests. Our method facilitates efficient use of the information available in pooled ELISpot data to avoid or reduce the need for confirmatory testing. We provide an easy-to-use free online application for implementing the method, where on uploading two spreadsheets with the pool design and pool responses, the user obtains the estimates of the individual peptide responses.

  19. Sexual communication via peptide and protein pheromones.

    Science.gov (United States)

    Touhara, Kazushige

    2008-12-01

    Pheromones are specific substances utilized by various organisms for intraspecific communication about sex, strain, or species. Although pheromones in terrestrial animals tend to be volatile airborne chemicals, large non-volatile molecules such as peptides and proteins are also utilized for sociosexual communication. Peptide pheromones are recognized by specific receptors expressed in the vertebrate vomeronasal organ that comprises a unique chemosensory system. The information is sent to the hypothalamic area wherein the signal is further integrated, leading to various pheromonal outputs. In this review, current knowledge on the structure and function of peptide and protein pheromones in vertebrates as well as the mechanisms underlying receptor-mediated signal processing will be summarized. The present review will also discuss why, from chemical and ecological points of view, peptide pheromones evolved.

  20. Charge Transport Phenomena in Peptide Molecular Junctions

    Directory of Open Access Journals (Sweden)

    Alessandra Luchini

    2008-01-01

    Full Text Available Inelastic electron tunneling spectroscopy (IETS is a valuable in situ spectroscopic analysis technique that provides a direct portrait of the electron transport properties of a molecular species. In the past, IETS has been applied to small molecules. Using self-assembled nanoelectronic junctions, IETS was performed for the first time on a large polypeptide protein peptide in the phosphorylated and native form, yielding interpretable spectra. A reproducible 10-fold shift of the I/V characteristics of the peptide was observed upon phosphorylation. Phosphorylation can be utilized as a site-specific modification to alter peptide structure and thereby influence electron transport in peptide molecular junctions. It is envisioned that kinases and phosphatases may be used to create tunable systems for molecular electronics applications, such as biosensors and memory devices.

  1. Biologically Active and Antimicrobial Peptides from Plants

    Directory of Open Access Journals (Sweden)

    Carlos E. Salas

    2015-01-01

    Full Text Available Bioactive peptides are part of an innate response elicited by most living forms. In plants, they are produced ubiquitously in roots, seeds, flowers, stems, and leaves, highlighting their physiological importance. While most of the bioactive peptides produced in plants possess microbicide properties, there is evidence that they are also involved in cellular signaling. Structurally, there is an overall similarity when comparing them with those derived from animal or insect sources. The biological action of bioactive peptides initiates with the binding to the target membrane followed in most cases by membrane permeabilization and rupture. Here we present an overview of what is currently known about bioactive peptides from plants, focusing on their antimicrobial activity and their role in the plant signaling network and offering perspectives on their potential application.

  2. An antifungal peptide from baby lima bean.

    Science.gov (United States)

    Wang, H X; Ng, T B

    2006-12-01

    A 6-kDa antifungal peptide with inhibitory activity on mycelial growth in Fusarium oxysporum, Mycosphaerella arachidicola, and Physalospora piricola was isolated from baby lima beans. The peptide suppressed growth in M. arachidicola with an IC(50) of 0.87 muM and inhibited activity of HIV-1 reverse transcriptase with an IC(50) of 4 muM. The peptide exhibited an N-terminal amino acid sequence similar to those of leguminous defensins. The isolation procedure comprised ion exchange chromatography on diethylaminoethyl (DEAE)-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on carboxymethyl (CM)-cellulose, and gel filtration by fast protein liquid chromatography on Superdex 75. The peptide was unadsorbed on DEAE-cellulose and Affi-gel blue gel but was adsorbed on CM-cellulose.

  3. Polymer-Peptide Nanoparticles: Synthesis and Characterization

    Science.gov (United States)

    Dong, He; Shu, Jessica Y.; Xu, Ting

    2010-03-01

    Conjugation of synthetic polymers to peptides offers an efficient way to produce novel supramolecular structures. Herein, we report an attempt to prepare synthetic micellar nanoparticles using amphiphilic peptide-polymer conjugates as molecular building blocks. Spherical nanoparticles were formed upon dissolution of peptides in PBS buffer through the segregation of hydrophobic and hydrophilic segments. Both molecular and nano- structures were thoroughly investigated by a variety of biophysical techniques, including circular dichroism (CD), dynamic light scattering (DLS), size exclusion chromatography (SEC), transmission electron microscopy (TEM) and small angle X-ray scattering (SAXS). The results demonstrate that structural properties of these biohybrid materials depend on both the geometry of the hydrophobic domain and the size of synthetic polymers. Given the diversity of functional peptide sequences, hydrophilic polymers and hydrophobic moieties, these materials would be expected to self-assemble into various types of nanostructures to cover a wide range of biological applications.

  4. Ribosomally synthesized peptides from natural sources.

    Science.gov (United States)

    Singh, Nidhi; Abraham, Jayanthi

    2014-04-01

    There are many antibiotic-resistant microbial pathogens that have emerged in recent years causing normal infections to become harder and sometimes impossible to treat. The major mechanisms of acquired resistance are the ability of the microorganisms to destroy or modify the drug, alter the drug target, reduce uptake or increase efflux of the drug and replace the metabolic step targeted by the drug. However, in recent years, resistant strains have been reported from almost every environment. New antimicrobial compounds are of major importance because of the growing problem of bacterial resistance, and antimicrobial peptides have been gaining a lot of interest. Their mechanism of action, however, is often obscure. Antimicrobial peptides are widespread and have a major role in innate immunity. An increasing number of peptides capable of inhibiting microbial growth are being reviewed here. In this article, we consider the possible use of antimicrobial peptides against pathogens.

  5. Bachem - insights into peptide chemistry achievements by the world's leading independent manufacturer of peptides.

    Science.gov (United States)

    Mergler, Monika; Loidl, Günther; Diekmann, Martina; Dick, Fritz

    2013-01-01

    The Swiss fine chemicals company Bachem, pioneer and specialist in the chemical synthesis of peptides, has also become an internationally leading manufacturer of peptide active pharmaceutical ingredients (APIs). In response to increasing demands in scale and purity, Bachem's research efforts centered on the chemistry involved in solid-phase peptide synthesis and the production of the required amino acid derivatives with the aim of a continuous improvement of the technology. The resulting optimized protocols together with high-throughput equipment enabled us to manufacture long peptide APIs and, more recently, even pharma-grade glycoproteins in industrial scale.

  6. Investigating peptide sequence variations for 'double-click' stapled p53 peptides.

    Science.gov (United States)

    Lau, Yu Heng; de Andrade, Peterson; Sköld, Niklas; McKenzie, Grahame J; Venkitaraman, Ashok R; Verma, Chandra; Lane, David P; Spring, David R

    2014-06-28

    Stapling peptides for inhibiting the p53/MDM2 interaction is a promising strategy for developing anti-cancer therapeutic leads. We evaluate double-click stapled peptides formed from p53-based diazidopeptides with different staple positions and azido amino acid side-chain lengths, determining the impact of these variations on MDM2 binding and cellular activity. We also demonstrate a K24R mutation, necessary for cellular activity in hydrocarbon-stapled p53 peptides, is not required for analogous 'double-click' peptides.

  7. Post-translational Modifications of Natural Antimicrobial Peptides and Strategies for Peptide Engineering.

    Science.gov (United States)

    Wang, Guangshun

    2012-02-01

    Natural antimicrobial peptides (AMPs) are gene-coded defense molecules discovered in all the three life domains: Eubacteria, Archaea, and Eukarya. The latter covers protists, fungi, plants, and animals. It is now recognized that amino acid composition, peptide sequence, and post-translational modifications determine to a large extent the structure and function of AMPs. This article systematically describes post-translational modifications of natural AMPs annotated in the antimicrobial peptide database (http://aps.unmc.edu/AP). Currently, 1147 out of 1755 AMPs in the database are modified and classified into more than 17 types. Through chemical modifications, the peptides fold into a variety of structural scaffolds that target bacterial surfaces or molecules within cells. Chemical modifications also confer desired functions to a particular peptide. Meanwhile, these modifications modulate other peptide properties such as stability. Elucidation of the relationship between AMP property and chemical modification inspires peptide engineering. Depending on the objective of our design, peptides may be modified in various ways so that the desired features can be enhanced whereas unwanted properties can be minimized. Therefore, peptide design plays an essential role in developing natural AMPs into a new generation of therapeutic molecules.

  8. CART peptide in the nucleus accumbens regulates psychostimulants: Correlations between psychostimulant and CART peptide effects.

    Science.gov (United States)

    Job, Martin O; Kuhar, Michael J

    2017-02-16

    In this study, we reexamined the effect of Cocaine-and-Amphetamine-Regulated-Transcript (CART) peptide on psychostimulant (PS)-induced locomotor activity (LMA) in individual rats. The Methods utilized were as previously published. The PS-induced LMA was defined as the distance traveled after PS administration (intraperitoneal), and the CART peptide effect was defined as the change in the PS-induced activity after bilateral intra-NAc administration of CART peptide. The experiments included both male and female Sprague-Dawley rats, and varying the CART peptide dose and the PS dose. While the average effect of CART peptide was to inhibit PS-induced LMA, the effect of CART peptide on individual PS-treated animals was not always inhibitory and sometimes even produced an increase or no change in PS-induced LMA. Upon further analysis, we observed a linear correlation, reported for the first time, between the magnitude of PS-induced LMA and the CART peptide effect. Because CART peptide inhibits PS-induced LMA when it is large, and increases PS-induced LMA when it is small, the peptide can be considered a homeostatic regulator of dopamine (DA)-induced LMA, which supports our earlier homeostatic hypothesis.

  9. Evolution of Antimicrobial Peptides to Self-Assembled Peptides for Biomaterial Applications

    Directory of Open Access Journals (Sweden)

    Alice P. McCloskey

    2014-10-01

    Full Text Available Biomaterial-related infections are a persistent burden on patient health, recovery, mortality and healthcare budgets. Self-assembled antimicrobial peptides have evolved from the area of antimicrobial peptides. Peptides serve as important weapons in nature, and increasingly medicine, for combating microbial infection and biofilms. Self-assembled peptides harness a “bottom-up” approach, whereby the primary peptide sequence may be modified with natural and unnatural amino acids to produce an inherently antimicrobial hydrogel. Gelation may be tailored to occur in the presence of physiological and infective indicators (e.g. pH, enzymes and therefore allow local, targeted antimicrobial therapy at the site of infection. Peptides demonstrate inherent biocompatibility, antimicrobial activity, biodegradability and numerous functional groups. They are therefore prime candidates for the production of polymeric molecules that have the potential to be conjugated to biomaterials with precision. Non-native chemistries and functional groups are easily incorporated into the peptide backbone allowing peptide hydrogels to be tailored to specific functional requirements. This article reviews an area of increasing interest, namely self-assembled peptides and their potential therapeutic applications as innovative hydrogels and biomaterials in the prevention of biofilm-related infection.

  10. cis-Peptide Bonds: A Key for Intestinal Permeability of Peptides? .

    Science.gov (United States)

    Marelli, Udaya Kiran; Ovadia, Oded; Frank, Andreas Oliver; Chatterjee, Jayanta; Gilon, Chaim; Hoffman, Amnon; Kessler, Horst

    2015-10-19

    Recent structural studies on libraries of cyclic hexapeptides led to the identification of common backbone conformations that may be instrumental to the oral availability of peptides. Furthermore, the observation of differential Caco-2 permeabilities of enantiomeric pairs of some of these peptides strongly supports the concept of conformational specificity driven uptake and also suggests a pivotal role of carrier-mediated pathways for peptide transport, especially for scaffolds of polar nature. This work presents investigations on the Caco-2 and PAMPA permeability profiles of 13 selected N-methylated cyclic pentaalanine peptides derived from the basic cyclo(-D-Ala-Ala4 -) template. These molecules generally showed moderate to low transport in intestinal epithelia with a few of them exhibiting a Caco-2 permeability equal to or slightly higher than that of mannitol, a marker for paracellular permeability. We identified that the majority of the permeable cyclic penta- and hexapeptides possess an N-methylated cis-peptide bond, a structural feature that is also present in the orally available peptides cyclosporine A and the tri-N-methylated analogue of the Veber-Hirschmann peptide. Based on these observations it appears that the presence of N-methylated cis-peptide bonds at certain locations may promote the intestinal permeability of peptides through a suitable conformational preorganization.

  11. Synthesizing and modifying peptides for chemoselective ligation and assembly into quantum dot-peptide bioconjugates.

    Science.gov (United States)

    Algar, W Russ; Blanco-Canosa, Juan B; Manthe, Rachel L; Susumu, Kimihiro; Stewart, Michael H; Dawson, Philip E; Medintz, Igor L

    2013-01-01

    Quantum dots (QDs) are well-established as photoluminescent nanoparticle probes for in vitro or in vivo imaging, sensing, and even drug delivery. A critical component of this research is the need to reliably conjugate peptides, proteins, oligonucleotides, and other biomolecules to QDs in a controlled manner. In this chapter, we describe the conjugation of peptides to CdSe/ZnS QDs using a combination of polyhistidine self-assembly and hydrazone ligation. The former is a high-affinity interaction with the inorganic surface of the QD; the latter is a highly efficient and chemoselective reaction that occurs between 4-formylbenzoyl (4FB) and 2-hydrazinonicotinoyl (HYNIC) moieties. Two methods are presented for modifying peptides with these functional groups: (1) solid phase peptide synthesis; and (2) solution phase modification of pre-synthesized, commercial peptides. We further describe the aniline-catalyzed ligation of 4FB- and HYNIC-modified peptides, in the presence of a fluorescent label on the latter peptide, as well as subsequent assembly of the ligated peptide to water-soluble QDs. Many technical elements of these protocols can be extended to labeling peptides with other small molecule reagents. Overall, the bioconjugate chemistry is robust, selective, and modular, thereby potentiating the controlled conjugation of QDs with a diverse array of biomolecules for various applications.

  12. In Silico Models for Designing and Discovering Novel Anticancer Peptides

    Science.gov (United States)

    Tyagi, Atul; Kapoor, Pallavi; Kumar, Rahul; Chaudhary, Kumardeep; Gautam, Ankur; Raghava, G. P. S.

    2013-10-01

    Use of therapeutic peptides in cancer therapy has been receiving considerable attention in the recent years. Present study describes the development of computational models for predicting and discovering novel anticancer peptides. Preliminary analysis revealed that Cys, Gly, Ile, Lys, and Trp are dominated at various positions in anticancer peptides. Support vector machine models were developed using amino acid composition and binary profiles as input features on main dataset that contains experimentally validated anticancer peptides and random peptides derived from SwissProt database. In addition, models were developed on alternate dataset that contains antimicrobial peptides instead of random peptides. Binary profiles-based model achieved maximum accuracy 91.44% with MCC 0.83. We have developed a webserver, which would be helpful in: (i) predicting minimum mutations required for improving anticancer potency; (ii) virtual screening of peptides for discovering novel anticancer peptides, and (iii) scanning natural proteins for identification of anticancer peptides (http://crdd.osdd.net/raghava/anticp/).

  13. Natriuretic peptides, obesity and cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Yaniel Castro-Torres

    2015-02-01

    Full Text Available Obesity, hypertension and heart failure are conditions commonly associated with each other. Recent investigations have demonstrated that low plasmatic levels of natriuretic peptides are linked with obesity. Thus, knowing the actions of these hormones in water and salt homeostasis, it is possible to establish that low levels of natriuretic peptides may be the common denominator among obesity, hypertension and heart failure. Knowledge on this topic is crucial to develop further investigation for definitive conclusions.

  14. Antimicrobial peptide action on parasites.

    Science.gov (United States)

    Torrent, Marc; Pulido, David; Rivas, Luis; Andreu, David

    2012-08-01

    Diseases caused by protozoan parasites can pose a severe thread to human health and are behind some serious neglected tropical diseases like malaria and leishmaniasis. Though several different drugs have been developed in order to eradicate these diseases, a successful candidate has not yet been discovered. Among the most active compounds tested, antimicrobial peptides (AMPs) are particularly appealing because of their wide spectrum of action. AMPs have been described to perturb protozoan homeostasis by disrupting the cellular membranes but also by interfering with key processes in the parasite metabolism. In this review we describe the diverse mechanisms of action of AMPs on protozoan targets and how they can be exploited to treat diseases. Moreover, we describe with detail the antimicrobial action of AMPs on two major parasitical infections: leishmaniasis and malaria. All the features reviewed here show that AMPs are promising drugs to target protozoan parasites and that further understanding of the mechanism of action of these compounds will lead to improved drugs that could be worth to test in a clinical phase.

  15. Membrane manufacture for peptide separations

    KAUST Repository

    Kim, Dooli

    2016-06-07

    Nanostructured polymeric membranes are key tools in biomedical applications such as hemodialysis, protein separations, in the food industry, and drinking water supply from seawater. Despite of the success in different separation processes, membrane manufacture itself is at risk, since the most used solvents are about to be banned in many countries due to environmental and health issues. We propose for the first time the preparation of polyethersulfone membranes based on dissolution in the ionic liquid 1-ethyl-3-methylimidazolium dimethylphosphate ([EMIM]DEP). We obtained a series of membranes tailored for separation of solutes with molecular weight of 30, 5, 1.3, and 1.25 kg mol-1 with respective water permeances of 140, 65, 30 and 20 Lm-2h-1bar-1. We demonstrate their superior efficiency in the separation of complex mixtures of peptides with molecular weights in the range of 800 to 3500 gmol-1. Furthermore, the thermodynamics and kinetics of phase separation leading to the pore formation in the membranes were investigated. The rheology of the solutions and the morphology of the prepared membranes were examed and compared to those of polyethersulfone in organic solvents currently used for membrane manufacture.

  16. Liquid-phase synthesis of bridged peptides using olefin metathesis of a protected peptide with a long aliphatic chain anchor.

    Science.gov (United States)

    Aihara, Keisuke; Komiya, Chiaki; Shigenaga, Akira; Inokuma, Tsubasa; Takahashi, Daisuke; Otaka, Akira

    2015-02-01

    Bridged peptides including stapled peptides are attractive tools for regulating protein-protein interactions (PPIs). An effective synthetic methodology in a heterogeneous system for the preparation of these peptides using olefin metathesis and hydrogenation of protected peptides with a long aliphatic chain anchor is reported.

  17. Peptide imprinted receptors for the determination of the small cell lung cancer associated biomarker progastrin releasing peptide

    DEFF Research Database (Denmark)

    Qader, A. A.; Urraca, J.; Torsetnes, S. B.

    2014-01-01

    Peptide imprinted polymers were developed for detection of progastrin releasing peptide (ProGRP); a low abundant blood based biomarker for small cell lung cancer. The polymers targeted the proteotypic nona-peptide sequence NLLGLIEAK and were used for selective enrichment of the proteotypic peptide...

  18. Affinity-based release of polymer-binding peptides from hydrogels with the target segments of peptides.

    Science.gov (United States)

    Serizawa, Takeshi; Fukuta, Hiroki; Date, Takaaki; Sawada, Toshiki

    2016-02-01

    Peptides with affinities for the target segments of polymer hydrogels were identified by biological screening using phage-displayed peptide libraries, and these peptides exhibited an affinity-based release capability from hydrogels. The results from cell culture assays demonstrated the sustained anticancer effects of the drug-conjugated peptides that were released from the hydrogels.

  19. Evolution of cyclic peptide protease inhibitors.

    Science.gov (United States)

    Young, Travis S; Young, Douglas D; Ahmad, Insha; Louis, John M; Benkovic, Stephen J; Schultz, Peter G

    2011-07-05

    We report a bacterial system for the evolution of cyclic peptides that makes use of an expanded set of amino acid building blocks. Orthogonal aminoacyl-tRNA synthetase/tRNA(CUA) pairs, together with a split intein system were used to biosynthesize a library of ribosomal peptides containing amino acids with unique structures and reactivities. This peptide library was subsequently used to evolve an inhibitor of HIV protease using a selection based on cellular viability. Two of three cyclic peptides isolated after two rounds of selection contained the keto amino acid p-benzoylphenylalanine (pBzF). The most potent peptide (G12: GIXVSL; X=pBzF) inhibited HIV protease through the formation of a covalent Schiff base adduct of the pBzF residue with the ε-amino group of Lys 14 on the protease. This result suggests that an expanded genetic code can confer an evolutionary advantage in response to selective pressure. Moreover, the combination of natural evolutionary processes with chemically biased building blocks provides another strategy for the generation of biologically active peptides using microbial systems.

  20. [Peptide phage display in biotechnology and biomedicine].

    Science.gov (United States)

    Kuzmicheva, G A; Belyavskaya, V A

    2016-07-01

    To date peptide phage display is one of the most common combinatorial methods used for identifying specific peptide ligands. Phage display peptide libraries containing billions different clones successfully used for selection of ligands with high affinity and selectivity toward wide range of targets including individual proteins, bacteria, viruses, spores, different kind of cancer cells and variety of nonorganic targets (metals, alloys, semiconductors etc.) Success of using filamentous phage in phage display technologies relays on the robustness of phage particles and a possibility to genetically modify its DNA to construct new phage variants with novel properties. In this review we are discussing characteristics of the most known non-commercial peptide phage display libraries of different formats (landscape libraries in particular) and their successful applications in several fields of biotechnology and biomedicine: discovery of peptides with diagnostic values against different pathogens, discovery and using of peptides recognizing cancer cells, trends in using of phage display technologies in human interactome studies, application of phage display technologies in construction of novel nano materials.

  1. Peptide-modified surfaces for enzyme immobilization.

    Directory of Open Access Journals (Sweden)

    Jinglin Fu

    Full Text Available BACKGROUND: Chemistry and particularly enzymology at surfaces is a topic of rapidly growing interest, both in terms of its role in biological systems and its application in biocatalysis. Existing protein immobilization approaches, including noncovalent or covalent attachments to solid supports, have difficulties in controlling protein orientation, reducing nonspecific absorption and preventing protein denaturation. New strategies for enzyme immobilization are needed that allow the precise control over orientation and position and thereby provide optimized activity. METHODOLOGY/PRINCIPAL FINDINGS: A method is presented for utilizing peptide ligands to immobilize enzymes on surfaces with improved enzyme activity and stability. The appropriate peptide ligands have been rapidly selected from high-density arrays and when desirable, the peptide sequences were further optimized by single-point variant screening to enhance both the affinity and activity of the bound enzyme. For proof of concept, the peptides that bound to β-galactosidase and optimized its activity were covalently attached to surfaces for the purpose of capturing target enzymes. Compared to conventional methods, enzymes immobilized on peptide-modified surfaces exhibited higher specific activity and stability, as well as controlled protein orientation. CONCLUSIONS/SIGNIFICANCE: A simple method for immobilizing enzymes through specific interactions with peptides anchored on surfaces has been developed. This approach will be applicable to the immobilization of a wide variety of enzymes on surfaces with optimized orientation, location and performance, and provides a potential mechanism for the patterned self-assembly of multiple enzymes on surfaces.

  2. Biomathematical description of synthetic peptide libraries.

    Directory of Open Access Journals (Sweden)

    Timo Sieber

    Full Text Available Libraries of randomised peptides displayed on phages or viral particles are essential tools in a wide spectrum of applications. However, there is only limited understanding of a library's fundamental dynamics and the influences of encoding schemes and sizes on their quality. Numeric properties of libraries, such as the expected number of different peptides and the library's coverage, have long been in use as measures of a library's quality. Here, we present a graphical framework of these measures together with a library's relative efficiency to help to describe libraries in enough detail for researchers to plan new experiments in a more informed manner. In particular, these values allow us to answer-in a probabilistic fashion-the question of whether a specific library does indeed contain one of the "best" possible peptides. The framework is implemented in a web-interface based on two packages, discreteRV and peptider, to the statistical software environment R. We further provide a user-friendly web-interface called PeLiCa (Peptide Library Calculator, http://www.pelica.org, allowing scientists to plan and analyse their peptide libraries.

  3. Peptide pheromone signaling in Streptococcus and Enterococcus.

    Science.gov (United States)

    Cook, Laura C; Federle, Michael J

    2014-05-01

    Intercellular chemical signaling in bacteria, commonly referred to as quorum sensing (QS), relies on the production and detection of compounds known as pheromones to elicit coordinated responses among members of a community. Pheromones produced by Gram-positive bacteria are comprised of small peptides. Based on both peptide structure and sensory system architectures, Gram-positive bacterial signaling pathways may be classified into one of four groups with a defining hallmark: cyclical peptides of the Agr type, peptides that contain Gly-Gly processing motifs, sensory systems of the RNPP family, or the recently characterized Rgg-like regulatory family. The recent discovery that Rgg family members respond to peptide pheromones increases substantially the number of species in which QS is likely a key regulatory component. These pathways control a variety of fundamental behaviors including conjugation, natural competence for transformation, biofilm development, and virulence factor regulation. Overlapping QS pathways found in multiple species and pathways that utilize conserved peptide pheromones provide opportunities for interspecies communication. Here we review pheromone signaling identified in the genera Enterococcus and Streptococcus, providing examples of all four types of pathways.

  4. SPdb – a signal peptide database

    Directory of Open Access Journals (Sweden)

    Tan Tin

    2005-10-01

    Full Text Available Abstract Background The signal peptide plays an important role in protein targeting and protein translocation in both prokaryotic and eukaryotic cells. This transient, short peptide sequence functions like a postal address on an envelope by targeting proteins for secretion or for transfer to specific organelles for further processing. Understanding how signal peptides function is crucial in predicting where proteins are translocated. To support this understanding, we present SPdb signal peptide database http://proline.bic.nus.edu.sg/spdb, a repository of experimentally determined and computationally predicted signal peptides. Results SPdb integrates information from two sources (a Swiss-Prot protein sequence database which is now part of UniProt and (b EMBL nucleotide sequence database. The database update is semi-automated with human checking and verification of the data to ensure the correctness of the data stored. The latest release SPdb release 3.2 contains 18,146 entries of which 2,584 entries are experimentally verified signal sequences; the remaining 15,562 entries are either signal sequences that fail to meet our filtering criteria or entries that contain unverified signal sequences. Conclusion SPdb is a manually curated database constructed to support the understanding and analysis of signal peptides. SPdb tracks the major updates of the two underlying primary databases thereby ensuring that its information remains up-to-date.

  5. Peptide Toxins in Solitary Wasp Venoms

    Science.gov (United States)

    Konno, Katsuhiro; Kazuma, Kohei; Nihei, Ken-ichi

    2016-01-01

    Solitary wasps paralyze insects or spiders with stinging venom and feed the paralyzed preys to their larva. Accordingly, the venoms should contain a variety of constituents acting on nervous systems. However, only a few solitary wasp venoms have been chemically studied despite thousands of species inhabiting the planet. We have surveyed bioactive substances in solitary wasp venoms found in Japan and discovered a variety of novel bioactive peptides. Pompilidotoxins (PMTXs), in the venoms of the pompilid wasps Anoplius samariensis and Batozonellus maculifrons, are small peptides consisting of 13 amino acids without a disulfide bond. PMTXs slowed Na+ channel inactivation, in particular against neuronal type Na+ channels, and were rather selective to the Nav1.6 channel. Mastoparan-like cytolytic and antimicrobial peptides are the major components of eumenine wasp venoms. They are rich in hydrophobic and basic amino acids, adopting a α-helical secondary structure, and showing mast cell degranulating, antimicrobial and hemolytic activities. The venom of the spider wasp Cyphononyx fulvognathus contained four bradykinin-related peptides. They are hyperalgesic and, dependent on the structure, differently associated with B1 or B2 receptors. Further survey led to the isolation of leucomyosuppressin-like FMRFamide peptides from the venoms of the digger wasps Sphex argentatus and Isodontia harmandi. These results of peptide toxins in solitary wasp venoms from our studies are summarized. PMID:27096870

  6. Peptide Toxins in Solitary Wasp Venoms

    Directory of Open Access Journals (Sweden)

    Katsuhiro Konno

    2016-04-01

    Full Text Available Solitary wasps paralyze insects or spiders with stinging venom and feed the paralyzed preys to their larva. Accordingly, the venoms should contain a variety of constituents acting on nervous systems. However, only a few solitary wasp venoms have been chemically studied despite thousands of species inhabiting the planet. We have surveyed bioactive substances in solitary wasp venoms found in Japan and discovered a variety of novel bioactive peptides. Pompilidotoxins (PMTXs, in the venoms of the pompilid wasps Anoplius samariensis and Batozonellus maculifrons, are small peptides consisting of 13 amino acids without a disulfide bond. PMTXs slowed Na+ channel inactivation, in particular against neuronal type Na+ channels, and were rather selective to the Nav1.6 channel. Mastoparan-like cytolytic and antimicrobial peptides are the major components of eumenine wasp venoms. They are rich in hydrophobic and basic amino acids, adopting a α-helical secondary structure, and showing mast cell degranulating, antimicrobial and hemolytic activities. The venom of the spider wasp Cyphononyx fulvognathus contained four bradykinin-related peptides. They are hyperalgesic and, dependent on the structure, differently associated with B1 or B2 receptors. Further survey led to the isolation of leucomyosuppressin-like FMRFamide peptides from the venoms of the digger wasps Sphex argentatus and Isodontia harmandi. These results of peptide toxins in solitary wasp venoms from our studies are summarized.

  7. Antimicrobial cyclic peptides for plant disease control.

    Science.gov (United States)

    Lee, Dong Wan; Kim, Beom Seok

    2015-03-01

    Antimicrobial cyclic peptides derived from microbes bind stably with target sites, have a tolerance to hydrolysis by proteases, and a favorable degradability under field conditions, which make them an attractive proposition for use as agricultural fungicides. Antimicrobial cyclic peptides are classified according to the types of bonds within the ring structure; homodetic, heterodetic, and complex cyclic peptides, which in turn reflect diverse physicochemical features. Most antimicrobial cyclic peptides affect the integrity of the cell envelope. This is achieved through direct interaction with the cell membrane or disturbance of the cell wall and membrane component biosynthesis such as chitin, glucan, and sphingolipid. These are specific and selective targets providing reliable activity and safety for non-target organisms. Synthetic cyclic peptides produced through combinatorial chemistry offer an alternative approach to develop antimicrobials for agricultural uses. Those synthesized so far have been studied for antibacterial activity, however, the recent advancements in powerful technologies now promise to provide novel antimicrobial cyclic peptides that are yet to be discovered from natural resources.

  8. Antimicrobial Cyclic Peptides for Plant Disease Control

    Directory of Open Access Journals (Sweden)

    Dong Wan Lee

    2015-03-01

    Full Text Available Antimicrobial cyclic peptides derived from microbes bind stably with target sites, have a tolerance to hydrolysis by proteases, and a favorable degradability under field conditions, which make them an attractive proposition for use as agricultural fungicides. Antimicrobial cyclic peptides are classified according to the types of bonds within the ring structure; homodetic, heterodetic, and complex cyclic peptides, which in turn reflect diverse physicochemical features. Most antimicrobial cyclic peptides affect the integrity of the cell envelope. This is achieved through direct interaction with the cell membrane or disturbance of the cell wall and membrane component biosynthesis such as chitin, glucan, and sphingolipid. These are specific and selective targets providing reliable activity and safety for non-target organisms. Synthetic cyclic peptides produced through combinatorial chemistry offer an alternative approach to develop antimicrobials for agricultural uses. Those synthesized so far have been studied for antibacterial activity, however, the recent advancements in powerful technologies now promise to provide novel antimicrobial cyclic peptides that are yet to be discovered from natural resources.

  9. Factors Affecting Peptide Interactions with Surface-Bound Microgels

    OpenAIRE

    2016-01-01

    Effects of electrostatics and peptide size on peptide interactions with surface-bound microgels were investigated with ellipsometry, confocal microscopy, and atomic force microscopy (AFM). Results show that binding of cationic poly-L-lysine (pLys) to anionic, covalently immobilized, poly(ethyl acrylate-co-methacrylic acid) microgels increased with increasing peptide net charge and microgel charge density. Furthermore, peptide release was facilitated by decreasing either microgel or peptide ch...

  10. Immunocytochemical detection of vasoactive intestinal peptide-like and peptide histidine isoleucine-like peptides in the nervous system and the excretory system of adult Nippostrongylus brasiliensis.

    Science.gov (United States)

    Foster, N

    1998-05-01

    Vasoactive intestinal peptide-like and peptide histidine isoleucine-like immunoreactivities were detected in the excretory duct of adult male and female Nippostrongylus brasiliensis, thus indicating the source of these two physiologically active peptides previously isolated from the excretory/secretory products of adult N. brasiliensis. In the nervous system immunoreactivity to both these peptides was confined to females and was found in the neurons of the ovijector associated ganglion. This is consistent with co-synthesis of vasoactive intestinal peptide-like and peptide histidine isoleucine-like peptides which has also been shown to occur in all mammalian vasoactive intestinal peptid-ergic neurons studied to date. However, in addition to this, and in common to some previous studies on helminth vasoactive intestinal peptide and peptide histidine isoleucine immunoreactivities, co-synthesis of the peptides was not indicated in a pair of branched neurons which projected posteriorly and peripherally from the ganglion associated with the ovijector of females and which terminated in two pairs of ganglia also exhibiting vasoactive intestinal peptide-like immunoreactivity only. The position of these ganglia indicated that they innervate muscles close to the body wall and may be responsible for the muscular contractions required for expulsion of eggs from female Nippostrongylus brasiliensis. This is also the first study to successfully detect these peptides in the excretory system of gastrointestinal nematodes.

  11. Sequential and competitive adsorption of peptides at pendant PEO layers.

    Science.gov (United States)

    Wu, Xiangming; Ryder, Matthew P; McGuire, Joseph; Snider, Joshua L; Schilke, Karl F

    2015-06-01

    Earlier work provided direction for development of responsive drug delivery systems based on modulation of the structure, amphiphilicity, and surface density of bioactive peptides entrapped within pendant polyethylene oxide (PEO) brush layers. In this work, we describe the sequential and competitive adsorption behavior of such peptides at pendant PEO layers. Three cationic peptides were used for this purpose: the arginine-rich, amphiphilic peptide WLBU2, a peptide chemically identical to WLBU2 but of scrambled sequence (S-WLBU2), and the non-amphiphilic peptide poly-L-arginine (PLR). Optical waveguide lightmode spectroscopy (OWLS) was used to quantify the rate and extent of peptide adsorption and elution at surfaces coated with PEO. UV spectroscopy and time-of-flight secondary ion mass spectrometry (TOF-SIMS) were used to quantify the extent of peptide exchange during the course of sequential and competitive adsorption. Circular dichroism (CD) was used to evaluate conformational changes after adsorption of peptide mixtures at PEO-coated silica nanoparticles. Results indicated that amphiphilic peptides are able to displace adsorbed, non-amphiphilic peptides in PEO layers, while non-amphiphilic peptides were not able to displace more amphiphilic peptides. In addition, peptides of greater amphiphilicity dominated the adsorption at the PEO layer from mixtures with less amphiphilic or non-amphiphilic peptides.

  12. Interaction of antimicrobial peptides with lipid membranes

    Energy Technology Data Exchange (ETDEWEB)

    Hanulova, Maria

    2008-12-15

    This study aims to investigate the difference in the interaction of antimicrobial peptides with two classes of zwitterionic peptides, phosphatidylethanolamines (PE) and phosphatidylcholines (PC). Further experiments were performed on model membranes prepared from specific bacterial lipids, lipopolysaccharides (LPS) isolated from Salmonella minnesota. The structure of the lipid-peptide aqueous dispersions was studied by small-and wide-angle X-ray diffraction during heating and cooling from 5 to 85 C. The lipids and peptides were mixed at lipid-to-peptide ratios 10-10000 (POPE and POPC) or 2-50 (LPS). All experiments were performed at synchrotron soft condensed matter beamline A2 in Hasylab at Desy in Hamburg, Germany. The phases were identified and the lattice parameters were calculated. Alamethicin and melittin interact in similar ways with the lipids. Pure POPC forms only lamellar phases. POPE forms lamellar phases at low temperatures that upon heating transform into a highly curved inverse hexagonal phase. Insertion of the peptide induced inverse bicontinuous cubic phases which are an ideal compromise between the curvature stress and the packing frustration. Melittin usually induced a mixture of two cubic phases, Im3m and Pn3m, with a ratio of lattice parameters close to 1.279, related to the underlying minimal surfaces. They formed during the lamellar to hexagonal phase transition and persisted during cooling till the onset of the gel phase. The phases formed at different lipid-to-peptide ratios had very similar lattice parameters. Epitaxial relationships existed between coexisting cubic phases and hexagonal or lamellar phases due to confinement of all phases to an onion vesicle, a vesicle with several layers consisting of different lipid phases. Alamethicin induced the same cubic phases, although their formation and lattice parameters were dependent on the peptide concentration. The cubic phases formed during heating from the lamellar phase and their onset

  13. Peptide-membrane interactions of arginine-tryptophan peptides probed using quartz crystal microbalance with dissipation monitoring.

    KAUST Repository

    Rydberg, Hanna A

    2014-04-18

    Membrane-active peptides include peptides that can cross cellular membranes and deliver macromolecular cargo as well as peptides that inhibit bacterial growth. Some of these peptides can act as both transporters and antibacterial agents. It is desirable to combine the knowledge from these two different fields of membrane-active peptides into design of new peptides with tailored actions, as transporters of cargo or as antibacterial substances, targeting specific membranes. We have previously shown that the position of the amino acid tryptophan in the peptide sequence of three arginine-tryptophan peptides affects their uptake and intracellular localization in live mammalian cells, as well as their ability to inhibit bacterial growth. Here, we use quartz crystal microbalance with dissipation monitoring to assess the induced changes caused by binding of the three peptides to supported model membranes composed of POPC, POPC/POPG, POPC/POPG/cholesterol or POPC/lactosyl PE. Our results indicate that the tryptophan position in the peptide sequence affects the way these peptides interact with the different model membranes and that the presence of cholesterol in particular seems to affect the membrane interaction of the peptide with an even distribution of tryptophans in the peptide sequence. These results give mechanistic insight into the function of these peptides and may aid in the design of membrane-active peptides with specified cellular targets and actions.

  14. Peptide-membrane interactions of arginine-tryptophan peptides probed using quartz crystal microbalance with dissipation monitoring.

    Science.gov (United States)

    Rydberg, Hanna A; Kunze, Angelika; Carlsson, Nils; Altgärde, Noomi; Svedhem, Sofia; Nordén, Bengt

    2014-07-01

    Membrane-active peptides include peptides that can cross cellular membranes and deliver macromolecular cargo as well as peptides that inhibit bacterial growth. Some of these peptides can act as both transporters and antibacterial agents. It is desirable to combine the knowledge from these two different fields of membrane-active peptides into design of new peptides with tailored actions, as transporters of cargo or as antibacterial substances, targeting specific membranes. We have previously shown that the position of the amino acid tryptophan in the peptide sequence of three arginine-tryptophan peptides affects their uptake and intracellular localization in live mammalian cells, as well as their ability to inhibit bacterial growth. Here, we use quartz crystal microbalance with dissipation monitoring to assess the induced changes caused by binding of the three peptides to supported model membranes composed of POPC, POPC/POPG, POPC/POPG/cholesterol or POPC/lactosyl PE. Our results indicate that the tryptophan position in the peptide sequence affects the way these peptides interact with the different model membranes and that the presence of cholesterol in particular seems to affect the membrane interaction of the peptide with an even distribution of tryptophans in the peptide sequence. These results give mechanistic insight into the function of these peptides and may aid in the design of membrane-active peptides with specified cellular targets and actions.

  15. Peptide dot immunoassay and immunoblotting: electroblotting from aluminum thin-layer chromatography plates and isoelectric focusing gels to activated nitrocellulose

    DEFF Research Database (Denmark)

    Bjerrum, O.J.; Holm, A.; Lauritzen, Edgar;

    1993-01-01

    Peptide dot immunoassay, electroblotting, activated nitrocellulose, dot blot, membranes, peptides and proteins......Peptide dot immunoassay, electroblotting, activated nitrocellulose, dot blot, membranes, peptides and proteins...

  16. Escherichia coli Peptide Binding Protein OppA Has a Preference for Positively Charged Peptides

    NARCIS (Netherlands)

    Klepsch, M. M.; Kovermann, M.; Löw, C.; Balbach, J.; Permentier, H. P.; Fusetti, F.; de Gier, J. W.; Gier, Jan-Willem de; Slotboom, D. J.; Berntsson, R. P. -A.

    2011-01-01

    The Escherichia coli peptide binding protein OppA is an essential component of the oligopeptide transporter Opp. Based on studies on its orthologue from Salmonella typhimurium, it has been proposed that OppA binds peptides between two and five amino acids long, with no apparent sequence selectivity.

  17. Peptide segment ligation:A new method for synthesis of peptide and protein

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    @@ The protein structure-function relationships are always highlighted in the field of life science. Protein synthesis from genomic sequence data is gaining significance in the "post-genomic era" of biomedical research by providing direct access to functional proteins. The manually or automatically stepwise solid phase peptide synthesis (SPPS) allows peptide of up to 60 residues to be routinely constructed in good yield and high purity[1,2]. The assembly of longer proteins via the gene engineering technology (e.g. recombinant DNA-based molecular biology or site- directed mutagenesis) and convergent peptide synthesis are necessary. Although the current biosynthetic method allows unnatural amino acids to be incorporated into proteins or peptides[3], only ?-peptide in the protein backbone can be obtained. A lot of problems associated with the classic convergent peptide synthesis approach, such as the poor solubility, inadequate purification techniques, and limited characterization methods with the fully protected segment[6]. However, totally chemical synthetic method can easily obtain ?- or ?-peptide[4] and even branch peptide[5].

  18. The non-peptidic part determines the internalization mechanism and intracellular trafficking of peptide amphiphiles.

    Directory of Open Access Journals (Sweden)

    Dimitris Missirlis

    Full Text Available BACKGROUND: Peptide amphiphiles (PAs are a class of amphiphilic molecules able to self-assemble into nanomaterials that have shown efficient in vivo targeted delivery. Understanding the interactions of PAs with cells and the mechanisms of their internalization and intracellular trafficking is critical in their further development for therapeutic delivery applications. METHODOLOGY/PRINCIPAL FINDINGS: PAs of a novel, cell- and tissue-penetrating peptide were synthesized possessing two different lipophilic tail architectures and their interactions with prostate cancer cells were studied in vitro. Cell uptake of peptides was greatly enhanced post-modification. Internalization occurred via lipid-raft mediated endocytosis and was common for the two analogs studied. On the contrary, we identified the non-peptidic part as the determining factor of differences between intracellular trafficking and retention of PAs. PAs composed of di-stearyl lipid tails linked through poly(ethylene glycol to the peptide exhibited higher exocytosis rates and employed different recycling pathways compared to ones consisting of di-palmitic-coupled peptides. As a result, cell association of the former PAs decreased with time. CONCLUSIONS/SIGNIFICANCE: Control over peptide intracellular localization and retention is possible by appropriate modification with synthetic hydrophobic tails. We propose this as a strategy to design improved peptide-based delivery systems.

  19. New dendrimer - Peptide host - Guest complexes: Towards dendrimers as peptide carriers

    DEFF Research Database (Denmark)

    Boas, Ulrik; Sontjens, S.H.M.; Jensen, Knud Jørgen;

    2002-01-01

    Adamantyl urea and adamantyl thiourea modified poly(propylene imine) dendrimers act as hosts for N-terminal tert-butoxycarbonyl (Boc)-protected peptides and form chloroform-soluble complexes. investigations with NMR spectroscopy show that the peptide is bound to the dendrimer by ionic interactions...

  20. Clinical relevance of intestinal peptide uptake

    Institute of Scientific and Technical Information of China (English)

    Hugh; James; Freeman

    2015-01-01

    AIM: To determine available information on an independent peptide transporter 1(Pep T1) and its potential relevance to treatment, this evaluation was completed.METHODS: Fully published English language literature articles sourced through Pub Med related to protein digestion and absorption, specifically human peptide and amino acid transport, were accessed and reviewed.Papers from 1970 to the present, with particular emphasis on the past decade, were examined. In addition,abstracted information translated to English in Pub Med was also included. Finally, studies and reviews relevant to nutrient or drug uptake, particularly in human intestine were included for evaluation. This work represents a summary of all of these studies with particular reference to peptide transporter mediated assimilation of nutrients and pharmacologically active medications.RESULTS: Assimilation of dietary protein in humans involves gastric and pancreatic enzyme hydrolysis to luminal oligopeptides and free amino acids. During the ensuing intestinal phase, these hydrolytic products are transported into the epithelial cell and, eventually, the portal vein. A critical component of this process is the uptake of intact di-peptides and tri-peptides by an independent Pep T1. A number of "peptide-mimetic" pharmaceutical agents may also be transported through this carrier, important for uptake of different antibiotics, antiviral agents and angiotensin-converting enzyme inhibitors. In addition, specific peptide products of intestinal bacteria may also be transported by Pep T1, with initiation and persistence of an immune response including increased cytokine production and associated intestinal inflammatory changes. Interestingly, these inflammatory changes may also be attenuated with orallyadministered anti-inflammatory tripeptides administered as site-specific nanoparticles and taken up by this Pep T1 transport protein. CONCLUSION: Further evaluation of the role of this transporter in treatment of

  1. Multifunctional host defense peptides: antimicrobial peptides, the small yet big players in innate and adaptive immunity.

    Science.gov (United States)

    Auvynet, Constance; Rosenstein, Yvonne

    2009-11-01

    The term 'antimicrobial peptides' refers to a large number of peptides first characterized on the basis of their antibiotic and antifungal activities. In addition to their role as endogenous antibiotics, antimicrobial peptides, also called host defense peptides, participate in multiple aspects of immunity (inflammation, wound repair, and regulation of the adaptive immune system) as well as in maintaining homeostasis. The possibility of utilizing these multifunctional molecules to effectively combat the ever-growing group of antibiotic-resistant pathogens has intensified research aimed at improving their antibiotic activity and therapeutic potential, without the burden of an exacerbated inflammatory response, but conserving their immunomodulatory potential. In this minireview, we focus on the contribution of small cationic antimicrobial peptides - particularly human cathelicidins and defensins - to the immune response and disease, highlighting recent advances in our understanding of the roles of these multifunctional molecules.

  2. Urinary Peptide Levels in Patients with Chronic Renal Failure

    Directory of Open Access Journals (Sweden)

    Mungli Prakash

    2010-10-01

    Full Text Available Introduction: Peptide levels in urine are found to be decreased in renal failure. In the current study urinary peptide levels were determined in chronic renal failure (CRF patients. Method: 86 CRF patients and 80 healthy controls were selected for the study. Urinary proteins and peptide levels were determined by spectrophotometer based Lowry and Bradford methods. Urinary creatinine levels were determined by clinical chemistry analyzer. Results: There was significant decrease in urinary peptide levels in CRF patients and Urinary % peptides were significantly decreased in CRF patients as compared to healthy controls. Urinary % peptides correlated negatively with proteinuria. Conclusion: we have found decrease in urinary peptides and % urinary peptides in CRF patients and possibly measurement of % urinary peptides may possibly serve as better indicator in early detection of impairment in renal function.

  3. Mycobacteria attenuate nociceptive responses by formyl peptide receptor triggered opioid peptide release from neutrophils.

    Directory of Open Access Journals (Sweden)

    Heike L Rittner

    2009-04-01

    Full Text Available In inflammation, pain is regulated by a balance of pro- and analgesic mediators. Analgesic mediators include opioid peptides which are secreted by neutrophils at the site of inflammation, leading to activation of opioid receptors on peripheral sensory neurons. In humans, local opioids and opioid peptides significantly downregulate postoperative as well as arthritic pain. In rats, inflammatory pain is induced by intraplantar injection of heat inactivated Mycobacterium butyricum, a component of complete Freund's adjuvant. We hypothesized that mycobacterially derived formyl peptide receptor (FPR and/or toll like receptor (TLR agonists could activate neutrophils, leading to opioid peptide release and inhibition of inflammatory pain. In complete Freund's adjuvant-induced inflammation, thermal and mechanical nociceptive thresholds of the paw were quantified (Hargreaves and Randall-Selitto methods, respectively. Withdrawal time to heat was decreased following systemic neutrophil depletion as well as local injection of opioid receptor antagonists or anti-opioid peptide (i.e. Met-enkephalin, beta-endorphin antibodies indicating an increase in pain. In vitro, opioid peptide release from human and rat neutrophils was measured by radioimmunoassay. Met-enkephalin release was triggered by Mycobacterium butyricum and formyl peptides but not by TLR-2 or TLR-4 agonists. Mycobacterium butyricum induced a rise in intracellular calcium as determined by FURA loading and calcium imaging. Opioid peptide release was blocked by intracellular calcium chelation as well as phosphoinositol-3-kinase inhibition. The FPR antagonists Boc-FLFLF and cyclosporine H reduced opioid peptide release in vitro and increased inflammatory pain in vivo while TLR 2/4 did not appear to be involved. In summary, mycobacteria activate FPR on neutrophils, resulting in tonic secretion of opioid peptides from neutrophils and in a decrease in inflammatory pain. Future therapeutic strategies may aim

  4. Peptide consensus sequence determination for the enhancement of the antimicrobial activity and selectivity of antimicrobial peptides

    Science.gov (United States)

    Almaaytah, Ammar; Ajingi, Ya’u; Abualhaijaa, Ahmad; Tarazi, Shadi; Alshar’i, Nizar; Al-Balas, Qosay

    2017-01-01

    The rise of multidrug-resistant bacteria is causing a serious threat to the world’s human population. Recent reports have identified bacterial strains displaying pan drug resistance against antibiotics and generating fears among medical health specialists that humanity is on the dawn of entering a post-antibiotics era. Global research is currently focused on expanding the lifetime of current antibiotics and the development of new antimicrobial agents to tackle the problem of antimicrobial resistance. In the present study, we designed a novel consensus peptide named “Pepcon” through peptide consensus sequence determination among members of a highly homologous group of scorpion antimicrobial peptides. Members of this group were found to possess moderate antimicrobial activity with significant toxicity against mammalian cells. The aim of our design method was to generate a novel peptide with an enhanced antimicrobial potency and selectivity against microbial rather than mammalian cells. The results of our study revealed that the consensus peptide displayed potent antibacterial activities against a broad range of Gram-positive and Gram-negative bacteria. Our membrane permeation studies displayed that the peptide efficiently induced membrane damage and consequently led to cell death through the process of cell lysis. The microbial DNA binding assay of the peptide was found to be very weak suggesting that the peptide is not targeting the microbial DNA. Pepcon induced minimal cytotoxicity at the antimicrobial concentrations as the hemolytic activity was found to be zero at the minimal inhibitory concentrations (MICs). The results of our study demonstrate that the consensus peptide design strategy is efficient in generating peptides. PMID:28096686

  5. Peptide inhibition of human cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Morris Cindy A

    2011-02-01

    Full Text Available Abstract Background Human cytomegalovirus (HCMV is the most prevalent congenital viral infection in the United States and Europe causing significant morbidity and mortality to both mother and child. HCMV is also an opportunistic pathogen in immunocompromised individuals, including human immunodeficiency virus (HIV- infected patients with AIDS, and solid organ and allogeneic stem cell transplantation recipients. Current treatments for HCMV-associated diseases are insufficient due to the emergence of drug-induced resistance and cytotoxicity, necessitating novel approaches to limit HCMV infection. The aim of this study was to develop therapeutic peptides targeting glycoprotein B (gB, a major glycoprotein of HCMV that is highly conserved across the Herpesviridae family, that specifically inhibit fusion of the viral envelope with the host cell membrane preventing HCMV entry and infection. Results Using the Wimley-White Interfacial Hydrophobicity Scale (WWIHS, several regions within gB were identified that display a high potential to interact with lipid bilayers of cell membranes and hydrophobic surfaces within proteins. The ability of synthetic peptides analogous to WWIHS-positive sequences of HCMV gB to inhibit viral infectivity was evaluated. Human foreskin fibroblasts (HFF were infected with the Towne-GFP strain of HCMV (0.5 MOI, preincubated with peptides at a range of concentrations (78 nm to 100 μM, and GFP-positive cells were visualized 48 hours post-infection by fluorescence microscopy and analyzed quantitatively by flow cytometry. Peptides that inhibited HCMV infection demonstrated different inhibitory concentration curves indicating that each peptide possesses distinct biophysical properties. Peptide 174-200 showed 80% inhibition of viral infection at a concentration of 100 μM, and 51% and 62% inhibition at concentrations of 5 μM and 2.5 μM, respectively. Peptide 233-263 inhibited infection by 97% and 92% at concentrations of 100

  6. Encoded libraries of chemically modified peptides.

    Science.gov (United States)

    Heinis, Christian; Winter, Greg

    2015-06-01

    The use of powerful technologies for generating and screening DNA-encoded protein libraries has helped drive the development of proteins as pharmaceutical ligands. However the development of peptides as pharmaceutical ligands has been more limited. Although encoded peptide libraries are typically several orders of magnitude larger than classical chemical libraries, can be more readily screened, and can give rise to higher affinity ligands, their use as pharmaceutical ligands is limited by their intrinsic properties. Two of the intrinsic limitations include the rotational flexibility of the peptide backbone and the limited number (20) of natural amino acids. However these limitations can be overcome by use of chemical modification. For example, the libraries can be modified to introduce topological constraints such as cyclization linkers, or to introduce new chemical entities such as small molecule ligands, fluorophores and photo-switchable compounds. This article reviews the chemistry involved, the properties of the peptide ligands, and the new opportunities offered by chemical modification of DNA-encoded peptide libraries.

  7. Dinosaur Peptides Suggest Mechanisms of Protein Survival

    Energy Technology Data Exchange (ETDEWEB)

    San Antonio, James D.; Schweitzer, Mary H.; Jensen, Shane T.; Kalluri, Raghu; Buckley, Michael; Orgel, Joseph P.R.O. (Harvard-Med); (IIT); (NCSU); (UPENN); (Manchester); (Orthovita)

    2011-09-16

    Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a 'preservation motif', and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival.

  8. Glucagon-Like Peptide-1 Gene Therapy

    Directory of Open Access Journals (Sweden)

    Anne M. Rowzee

    2011-01-01

    Full Text Available Glucagon-like peptide 1 (GLP-1 is a small peptide component of the prohormone, proglucagon, that is produced in the gut. Exendin-4, a GLP-1 receptor agonist originally isolated from the saliva of H. suspectum or Gila monster, is a peptide that shares sequence and functional homology with GLP-1. Both peptides have been demonstrated to stimulate insulin secretion, inhibit glucagon secretion, promote satiety and slow gastric emptying. As such, GLP-1 and Exendin-4 have become attractive pharmaceutical targets as an adjunctive therapy for individuals with type II diabetes mellitus, with several products currently available clinically. Herein we summarize the cell biology leading to GLP-1 production and secretion from intestinal L-cells and the endocrine functions of this peptide and Exendin-4 in humans. Additionally, gene therapeutic applications of GLP-1 and Exendin-4 are discussed with a focus on recent work using the salivary gland as a gene therapy target organ for the treatment of diabetes mellitus.

  9. Peptide synthesis in early earth hydrothermal systems

    Science.gov (United States)

    Lemke, K.H.; Rosenbauer, R.J.; Bird, D.K.

    2009-01-01

    We report here results from experiments and thermodynamic calculations that demonstrate a rapid, temperature-enhanced synthesis of oligopeptides from the condensation of aqueous glycine. Experiments were conducted in custom-made hydrothermal reactors, and organic compounds were characterized with ultraviolet-visible procedures. A comparison of peptide yields at 260??C with those obtained at more moderate temperatures (160??C) gives evidence of a significant (13 kJ ?? mol-1) exergonic shift. In contrast to previous hydrothermal studies, we demonstrate that peptide synthesis is favored in hydrothermal fluids and that rates of peptide hydrolysis are controlled by the stability of the parent amino acid, with a critical dependence on reactor surface composition. From our study, we predict that rapid recycling of product peptides from cool into near-supercritical fluids in mid-ocean ridge hydrothermal systems will enhance peptide chain elongation. It is anticipated that the abundant hydrothermal systems on early Earth could have provided a substantial source of biomolecules required for the origin of life. Astrobiology 9, 141-146. ?? 2009 Mary Ann Liebert, Inc. 2009.

  10. Preparation of Soy Peptides by Liquid Fermentation

    Institute of Scientific and Technical Information of China (English)

    LiLi; YangXiaoqun; ZhaoMouming; LiangShizhong

    2002-01-01

    Many kinds of microorganism can produce a mount of protease which subsequently hydrolysis the protein of the medium into peptides when they grow in protein containing liquid medium.In the present investigation,the conditions of preparing soybean peptides by liquid fermentation were studied,following results were obtained:(1)SPI is a nice nitrogen source and meanwhile an inducible factor of protease production;its concentration can be as high as 3%-4%.(2)Sucrose is the best carbon source;its concentration is 1%-4%.(3)Under the conditions of 28℃,initial pH6.0,inoculum size 4%,cell age 36hr and fermentation time 24hr-30hr,we can obtain soybean peptides or fermentation liquor with good flavor,its DH reaches 25%-30% and the yield rate can be as high as 75%.(4)Mass spectrograph indicate the MW of the fermentation liquid or the soybean peptides mainly distribute at about 4000Dal,these imply a promising prospect of industrial application of submerged fermentation in producing soybean peptides.

  11. Antimicrobial Peptides in Innate Immunity against Mycobacteria.

    Science.gov (United States)

    Shin, Dong-Min; Jo, Eun-Kyeong

    2011-10-01

    Antimicrobial peptides/proteins are ancient and naturallyoccurring antibiotics in innate immune responses in a variety of organisms. Additionally, these peptides have been recognized as important signaling molecules in regulation of both innate and adaptive immunity. During mycobacterial infection, antimicrobial peptides including cathelicidin, defensin, and hepcidin have antimicrobial activities against mycobacteria, making them promising candidates for future drug development. Additionally, antimicrobial peptides act as immunomodulators in infectious and inflammatory conditions. Multiple crucial functions of cathelicidins in antimycobacterial immune defense have been characterized not only in terms of direct killing of mycobacteria but also as innate immune regulators, i.e., in secretion of cytokines and chemokines, and mediating autophagy activation. Defensin families are also important during mycobacterial infection and contribute to antimycobacterial defense and inhibition of mycobacterial growth both in vitro and in vivo. Hepcidin, although its role in mycobacterial infection has not yet been characterized, exerts antimycobacterial effects in activated macrophages. The present review focuses on recent efforts to elucidate the roles of host defense peptides in innate immunity to mycobacteria.

  12. Does Citrulline Malate Enhance Physical Performance

    Science.gov (United States)

    2010-10-01

    then returned for their second VO2 max test. After the second test, subjects ingested 6 g/d of the other condition’s capsules for 14 days, and then...returned for their third and final VO2 max test. VO2max, lactate threshold, maximum watts reached, ratings of perceived exertion and pre- and post...ingested 6 g/d of either CM or a placebo for 14 days. Subjects then returned for their second VO2 max test. After the second test, subjects

  13. Spider-Venom Peptides as Therapeutics

    Directory of Open Access Journals (Sweden)

    Glenn F. King

    2010-12-01

    Full Text Available Spiders are the most successful venomous animals and the most abundant terrestrial predators. Their remarkable success is due in large part to their ingenious exploitation of silk and the evolution of pharmacologically complex venoms that ensure rapid subjugation of prey. Most spider venoms are dominated by disulfide-rich peptides that typically have high affinity and specificity for particular subtypes of ion channels and receptors. Spider venoms are conservatively predicted to contain more than 10 million bioactive peptides, making them a valuable resource for drug discovery. Here we review the structure and pharmacology of spider-venom peptides that are being used as leads for the development of therapeutics against a wide range of pathophysiological conditions including cardiovascular disorders, chronic pain, inflammation, and erectile dysfunction.

  14. Peptide Vaccine Therapy in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Shi-Yu Yang

    2012-08-01

    Full Text Available Colorectal cancer is the third most common cause of cancer-related deaths and the second most prevalent (after breast cancer in the western world. High metastatic relapse rates and severe side effects associated with the adjuvant treatment have urged oncologists and clinicians to find a novel, less toxic therapeutic strategy. Considering the limited success of the past clinical trials involving peptide vaccine therapy to treat colorectal cancer, it is necessary to revise our knowledge of the immune system and its potential use in tackling cancer. This review presents the efforts of the scientific community in the development of peptide vaccine therapy for colorectal cancer. We review recent clinical trials and the strategies for immunologic monitoring of responses to peptide vaccine therapy. We also discuss the mechanisms underlying the therapy and potential molecular targets in colon cancer.

  15. Amyloid fibrils compared to peptide nanotubes.

    Science.gov (United States)

    Zganec, Matjaž; Zerovnik, Eva

    2014-09-01

    Prefibrillar oligomeric states and amyloid fibrils of amyloid-forming proteins qualify as nanoparticles. We aim to predict what biophysical and biochemical properties they could share in common with better researched peptide nanotubes. We first describe what is known of amyloid fibrils and prefibrillar aggregates (oligomers and protofibrils): their structure, mechanisms of formation and putative mechanism of cytotoxicity. In distinction from other neuronal fibrillar constituents, amyloid fibrils are believed to cause pathology, however, some can also be functional. Second, we give a review of known biophysical properties of peptide nanotubes. Finally, we compare properties of these two macromolecular states side by side and discuss which measurements that have already been done with peptide nanotubes could be done with amyloid fibrils as well.

  16. Peptide Based Radiopharmaceuticals: Specific Construct Approach

    Energy Technology Data Exchange (ETDEWEB)

    Som, P; Rhodes, B A; Sharma, S S

    1997-10-21

    The objective of this project was to develop receptor based peptides for diagnostic imaging and therapy. A series of peptides related to cell adhesion molecules (CAM) and immune regulation were designed for radiolabeling with 99mTc and evaluated in animal models as potential diagnostic imaging agents for various disease conditions such as thrombus (clot), acute kidney failure, and inflection/inflammation imaging. The peptides for this project were designed by the industrial partner, Palatin Technologies, (formerly Rhomed, Inc.) using various peptide design approaches including a newly developed rational computer assisted drug design (CADD) approach termed MIDAS (Metal ion Induced Distinctive Array of Structures). In this approach, the biological function domain and the 99mTc complexing domain are fused together so that structurally these domains are indistinguishable. This approach allows construction of conformationally rigid metallo-peptide molecules (similar to cyclic peptides) that are metabolically stable in-vivo. All the newly designed peptides were screened in various in vitro receptor binding and functional assays to identify a lead compound. The lead compounds were formulated in a one-step 99mTc labeling kit form which were studied by BNL for detailed in-vivo imaging using various animals models of human disease. Two main peptides usingMIDAS approach evolved and were investigated: RGD peptide for acute renal failure and an immunomodulatory peptide derived from tuftsin (RMT-1) for infection/inflammation imaging. Various RGD based metallopeptides were designed, synthesized and assayed for their efficacy in inhibiting ADP-induced human platelet aggregation. Most of these peptides displayed biological activity in the 1-100 µM range. Based on previous work by others, RGD-I and RGD-II were evaluated in animal models of acute renal failure. These earlier studies showed that after acute ischemic injury the renal cortex displays

  17. Anisotropic membrane curvature sensing by antibacterial peptides

    CERN Document Server

    Gómez-Llobregat, Jordi; Lindén, Martin

    2014-01-01

    Many proteins and peptides have an intrinsic capacity to sense and induce membrane curvature, and play crucial roles for organizing and remodeling cell membranes. However, the molecular driving forces behind these processes are not well understood. Here, we describe a new approach to study curvature sensing, by simulating the direction-dependent interactions of single molecules with a buckled lipid bilayer. We analyze three antimicrobial peptides, a class of membrane-associated molecules that specifically target and destabilize bacterial membranes, and find qualitatively different sensing characteristics that would be difficult to resolve with other methods. These findings provide new insights into the microscopic mechanisms of antimicrobial peptides, which might aid the development of new antibiotics. Our approach is generally applicable to a wide range of curvature sensing molecules, and our results provide strong motivation to develop new experimental methods to track position and orientation of membrane p...

  18. Sensitising capacity of peptides from food allergens

    DEFF Research Database (Denmark)

    Bøgh, Katrine Lindholm

    , MALDI-TOF mass spectrometry, amino acid analysis and GPC. To study the sensitising capacity groups of BN rats were immunised with the intact allergen or digestion products hereof by i.p. immunisation and specific antibody responses were examined by ELISAs, RBL-assay or avidity measurements. Comparison...... of peptide fragments of up to Mr 2,000, yet both the peptide fragments in the gastric as well as in the gastro-duodenal digests were aggregated to complexes of larger sizes. After separation of the digested Ara h 1 into fractions the sensitising capacity was lost, though the IgE-binding capacity was retained...... found for both the intact as well as the digested Ara h 1. Digested BLG with peptide sizes of up to Mr 4,500 could on the other hand not induce any sensitisation response in the BN rats. They were instead suggested to possess tolerogenic capacity when co-administered together with intact BLG...

  19. Design and Application of Antimicrobial Peptide Conjugates

    Directory of Open Access Journals (Sweden)

    Andre Reinhardt

    2016-05-01

    Full Text Available Antimicrobial peptides (AMPs are an interesting class of antibiotics characterized by their unique antibiotic activity and lower propensity for developing resistance compared to common antibiotics. They belong to the class of membrane-active peptides and usually act selectively against bacteria, fungi and protozoans. AMPs, but also peptide conjugates containing AMPs, have come more and more into the focus of research during the last few years. Within this article, recent work on AMP conjugates is reviewed. Different aspects will be highlighted as a combination of AMPs with antibiotics or organometallic compounds aiming to increase antibacterial activity or target selectivity, conjugation with photosensitizers for improving photodynamic therapy (PDT or the attachment to particles, to name only a few. Owing to the enormous resonance of antimicrobial conjugates in the literature so far, this research topic seems to be very attractive to different scientific fields, like medicine, biology, biochemistry or chemistry.

  20. Identification of antimicrobial peptides by using eigenvectors.

    Science.gov (United States)

    Polanco, Carlos

    2016-01-01

    Antibacterial peptides are subject to broad research due to their potential application and the benefit they can provide for a wide range of diseases. In this work, a mathematical-computational method, called the Polarity Vector Method, is introduced that has a high discriminative level (>70%) to identify peptides associated with Gram (-) bacteria, Gram (+) bacteria, cancer cells, fungi, insects, mammalian cells, parasites, and viruses, taken from the Antimicrobial Peptides Database. This supervised method uses only eigenvectors from the incident polar matrix of the group studied. It was verified with a comparative study with another extensively verified method developed previously by our team, the Polarity Index Method. The number of positive hits of both methods was up to 98% in all the tests conducted.