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 <front>
  <journal-meta>
   <journal-id journal-id-type="publisher-id">Russian Journal of Biological Physics and Chemisrty</journal-id>
   <journal-title-group>
    <journal-title xml:lang="en">Russian Journal of Biological Physics and Chemisrty</journal-title>
    <trans-title-group xml:lang="ru">
     <trans-title>АКТУАЛЬНЫЕ ВОПРОСЫ БИОЛОГИЧЕСКОЙ ФИЗИКИ И ХИМИИ</trans-title>
    </trans-title-group>
   </journal-title-group>
   <issn publication-format="print">2499-9962</issn>
  </journal-meta>
  <article-meta>
   <article-id pub-id-type="publisher-id">54583</article-id>
   <article-categories>
    <subj-group subj-group-type="toc-heading" xml:lang="ru">
     <subject>МЕДИЦИНСКАЯ БИОФИЗИКА И БИОФИЗИЧЕСКАЯ ХИМИЯ</subject>
    </subj-group>
    <subj-group subj-group-type="toc-heading" xml:lang="en">
     <subject>MEDICAL BIOPHYSICS AND BIOPHYSICAL CHEMISTRY</subject>
    </subj-group>
    <subj-group>
     <subject>МЕДИЦИНСКАЯ БИОФИЗИКА И БИОФИЗИЧЕСКАЯ ХИМИЯ</subject>
    </subj-group>
   </article-categories>
   <title-group>
    <article-title xml:lang="en">Role of the nitrogen oxide system and pro-inflammatory cytokines in the pathogenetic mechanisms of degenerative joint diseases</article-title>
    <trans-title-group xml:lang="ru">
     <trans-title>Роль системы оксида азота и провоспалительных цитокинов в механизмах патогенеза дегенеративных заболеваний суставов</trans-title>
    </trans-title-group>
   </title-group>
   <contrib-group content-type="authors">
    <contrib contrib-type="author">
     <name-alternatives>
      <name xml:lang="ru">
       <surname>Внуков</surname>
       <given-names>В В</given-names>
      </name>
      <name xml:lang="en">
       <surname>Vnukov</surname>
       <given-names>V V</given-names>
      </name>
     </name-alternatives>
     <xref ref-type="aff" rid="aff-1"/>
    </contrib>
    <contrib contrib-type="author">
     <name-alternatives>
      <name xml:lang="ru">
       <surname>Кролевец</surname>
       <given-names>И В</given-names>
      </name>
      <name xml:lang="en">
       <surname>Krolevets</surname>
       <given-names>I V</given-names>
      </name>
     </name-alternatives>
     <xref ref-type="aff" rid="aff-2"/>
    </contrib>
    <contrib contrib-type="author">
     <name-alternatives>
      <name xml:lang="ru">
       <surname>Плотников</surname>
       <given-names>А А</given-names>
      </name>
      <name xml:lang="en">
       <surname>Plotnikov</surname>
       <given-names>A A</given-names>
      </name>
     </name-alternatives>
     <xref ref-type="aff" rid="aff-3"/>
    </contrib>
    <contrib contrib-type="author">
     <name-alternatives>
      <name xml:lang="ru">
       <surname>Ананян</surname>
       <given-names>А А</given-names>
      </name>
      <name xml:lang="en">
       <surname>Ananyan</surname>
       <given-names>A A</given-names>
      </name>
     </name-alternatives>
     <xref ref-type="aff" rid="aff-4"/>
    </contrib>
    <contrib contrib-type="author">
     <name-alternatives>
      <name xml:lang="ru">
       <surname>Колесников</surname>
       <given-names>М А</given-names>
      </name>
      <name xml:lang="en">
       <surname>Kolesnikov</surname>
       <given-names>M A</given-names>
      </name>
     </name-alternatives>
     <xref ref-type="aff" rid="aff-5"/>
    </contrib>
    <contrib contrib-type="author">
     <name-alternatives>
      <name xml:lang="ru">
       <surname>Милютина</surname>
       <given-names>Н П</given-names>
      </name>
      <name xml:lang="en">
       <surname>Milyutina</surname>
       <given-names>N P</given-names>
      </name>
     </name-alternatives>
     <email>natmilut@rambler.ru</email>
     <xref ref-type="aff" rid="aff-6"/>
    </contrib>
   </contrib-group>
   <aff-alternatives id="aff-1">
    <aff>
     <institution xml:lang="ru">Южный федеральный университет</institution>
     <country>ru</country>
    </aff>
    <aff>
     <institution xml:lang="en">Southern Federal University, Academy of Biology and Biotechnology</institution>
     <country>ru</country>
    </aff>
   </aff-alternatives>
   <aff-alternatives id="aff-2">
    <aff>
     <institution xml:lang="ru">Ростовский государственный медицинский университет Минздрава РФ</institution>
     <country>ru</country>
    </aff>
    <aff>
     <institution xml:lang="en">Rostov State Medical University</institution>
     <country>ru</country>
    </aff>
   </aff-alternatives>
   <aff-alternatives id="aff-3">
    <aff>
     <institution xml:lang="ru">Южный федеральный университет</institution>
     <country>ru</country>
    </aff>
    <aff>
     <institution xml:lang="en">Southern Federal University, Academy of Biology and Biotechnology</institution>
     <country>ru</country>
    </aff>
   </aff-alternatives>
   <aff-alternatives id="aff-4">
    <aff>
     <institution xml:lang="ru">Южный федеральный университет</institution>
     <country>ru</country>
    </aff>
    <aff>
     <institution xml:lang="en">Southern Federal University, Academy of Biology and Biotechnology</institution>
     <country>ru</country>
    </aff>
   </aff-alternatives>
   <aff-alternatives id="aff-5">
    <aff>
     <institution xml:lang="ru">Городская клиническая больница № 2</institution>
     <country>ru</country>
    </aff>
    <aff>
     <institution xml:lang="en">City Clinical Hospital No.2</institution>
     <country>ru</country>
    </aff>
   </aff-alternatives>
   <aff-alternatives id="aff-6">
    <aff>
     <institution xml:lang="ru">Южный федеральный университет</institution>
     <country>ru</country>
    </aff>
    <aff>
     <institution xml:lang="en">Southern Federal University, Academy of Biology and Biotechnology</institution>
     <country>ru</country>
    </aff>
   </aff-alternatives>
   <pub-date publication-format="print" date-type="pub" iso-8601-date="2020-12-25T20:22:29+03:00">
    <day>25</day>
    <month>12</month>
    <year>2020</year>
   </pub-date>
   <pub-date publication-format="electronic" date-type="pub" iso-8601-date="2020-12-25T20:22:29+03:00">
    <day>25</day>
    <month>12</month>
    <year>2020</year>
   </pub-date>
   <volume>5</volume>
   <issue>4</issue>
   <fpage>665</fpage>
   <lpage>671</lpage>
   <history>
    <date date-type="received" iso-8601-date="2020-12-20T20:22:29+03:00">
     <day>20</day>
     <month>12</month>
     <year>2020</year>
    </date>
    <date date-type="accepted" iso-8601-date="2020-12-20T20:22:29+03:00">
     <day>20</day>
     <month>12</month>
     <year>2020</year>
    </date>
   </history>
   <self-uri xlink:href="https://rusjbpc.ru/en/nauka/article/54583/view">https://rusjbpc.ru/en/nauka/article/54583/view</self-uri>
   <abstract xml:lang="ru">
    <p>В работе исследовали уровни оксида азота, провоспалительных цитокинов (IL-1β, IL-6, IL-18, TNFα), лептина и мочевой кислоты в плазме крови и синовиальной жидкости (СЖ) как биомаркеров посттравматического гонартроза (ПТГА), а также их ассоциацию с рентгенологической стадией ПТГА. Установлено, что у пациентов с ранними и поздними стадиями посттравматического артроза коленного сустава повышен уровень циркулирующих провоспалительных медиаторов: нитритов/нитратов (NOx-), IL-6 и мочевой кислоты по сравнению со здоровыми лицами. Циркулирующие уровни NOx-, IL-1β, IL-6, мочевой кислоты, лептина и комбинации IL-6 и лептина могут быть потенциальными диагностическими тестами в соответствии с результатами ROC-анализа. Уровни NOx-, IL-6, IL-18 и лептина в плазме достоверно коррелировали с их содержанием в СЖ. Тяжесть ПTГA коррелировала с уровнем лептина в плазме и СЖ, а также с уровнем синовиального IL-18. Исследована ассоциация полиморфных вариантов генов nNOS и eNOS с риском развития посттравматического гонартроза (ПТГА) у жителей Ростовской области. Установлено, что аллель -84A полиморфного гена nNOS ассоциирован с риском развития ПТГА.</p>
   </abstract>
   <trans-abstract xml:lang="en">
    <p>It was investigated the levels of nitric oxide, pro-inflammatory cytokines (IL-1β, IL-6, IL-18, TNFα), leptin and uric acid in blood plasma and synovial fluid (SF) as biomarkers of post-traumatic gonarthrosis (PTGA), as well as their association with radiological stage of PTGA. It was found that in patients with early and late stages of post-traumatic arthrosis of the knee joint, the level of circulating pro-inflammatory mediators: nitrites / nitrates (NOx), IL-6, and uric acid was increased compared with healthy individuals. Circulating levels of NOx, IL-1, IL-6, uric acid, leptin, and a combination of IL-6 and leptin can be potential diagnostic tests according to the ROC curve analysis. Plasma levels of NOx, IL-6, IL-18, and leptin significantly correlated with their levels in the SF. The severity of PTGA correlated with the level of leptin in plasma and SF, as well as with the level of synovial IL-18. The association of polymorphic variants of the nNOS and eNOS genes with the risk of developing post-traumatic gonarthrosis (PTGA) in residents of the Rostov region was studied. It has been established that the -84A allele of the nNOS polymorphic gene is associated with the risk of developing PTGA.</p>
   </trans-abstract>
   <kwd-group xml:lang="ru">
    <kwd>посттравматический гонартроз</kwd>
    <kwd>плазма крови</kwd>
    <kwd>синовиальная жидкость</kwd>
    <kwd>оксид азота</kwd>
    <kwd>провоспалительные цитокины</kwd>
    <kwd>лептин</kwd>
    <kwd>гены NO-синтаз</kwd>
   </kwd-group>
   <kwd-group xml:lang="en">
    <kwd>post-traumatic gonarthrosis</kwd>
    <kwd>blood plasma</kwd>
    <kwd>synovial fluid</kwd>
    <kwd>nitric oxide</kwd>
    <kwd>pro-inflammatory cytokines</kwd>
    <kwd>leptin</kwd>
    <kwd>NO synthase genes</kwd>
   </kwd-group>
  </article-meta>
 </front>
 <body>
  <p></p>
 </body>
 <back>
  <ref-list>
   <ref id="B1">
    <label>1.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Loeser R.F., Steven R.G., Carla R.S., Goldring M.B. Osteoarthritis: A Disease of the Joint as an Organ. Arthritis Rheum., 2012, vol. 64, no. 6. DOI: 10.1002/art.34453.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Loeser R.F., Steven R.G., Carla R.S., Goldring M.B. Osteoarthritis: A Disease of the Joint as an Organ. Arthritis Rheum., 2012, vol. 64, no. 6. DOI: 10.1002/art.34453.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B2">
    <label>2.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Saito T., Tanaka S. Molecular mechanisms underlying osteoarthritis development: Notch and NF-κB. Arthritis Res. Ther, 2017, vol. 19, no. 94. DOI: 10.1186/s13075-017-1296-y.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Saito T., Tanaka S. Molecular mechanisms underlying osteoarthritis development: Notch and NF-κB. Arthritis Res. Ther, 2017, vol. 19, no. 94. DOI: 10.1186/s13075-017-1296-y.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B3">
    <label>3.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Каратеев А.Е., Лила А.М. Остеоартрит: современная клиническая концепция и некоторые перспективные терапевтические подходы. Научно-практич. ревматол, 2018, т. 56, № 1. DOI: org/10.14412/1995-4484-2018-70-81.  @@Karateev A.E., Lila A.M. Osteoartrit: sovremennaya klinicheskaya koncepciya i nekotorye perspektivnye terapevticheskie podhody. Nauchno-praktich. revmatol, 2018, vol. 56, no. 1. DOI: org/10.14412/1995-4484-2018-70-81. (In Russ.)
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Karateev A.E., Lila A.M. Osteoartrit: sovremennaya klinicheskaya koncepciya i nekotorye perspektivnye terapevticheskie podhody. Nauchno-praktich. revmatol, 2018, t. 56, № 1. DOI: org/10.14412/1995-4484-2018-70-81.  @@Karateev A.E., Lila A.M. Osteoartrit: sovremennaya klinicheskaya koncepciya i nekotorye perspektivnye terapevticheskie podhody. Nauchno-praktich. revmatol, 2018, vol. 56, no. 1. DOI: org/10.14412/1995-4484-2018-70-81. (In Russ.)
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B4">
    <label>4.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Vnukov V.V., Panina S.B., Krolevets I.V., Milutina N.P., Ananyan A.A., Zabrodin M.A., Plotnikov A.A. Specificities of Oxidative Stress in the Blood and Synovial Fluid in Knee Osteoarthritis. Advances in Gerontology, 2015, vol. 5, no. 4. DOI: 10.1134/S2079057015040220.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Vnukov V.V., Panina S.B., Krolevets I.V., Milutina N.P., Ananyan A.A., Zabrodin M.A., Plotnikov A.A. Specificities of Oxidative Stress in the Blood and Synovial Fluid in Knee Osteoarthritis. Advances in Gerontology, 2015, vol. 5, no. 4. DOI: 10.1134/S2079057015040220.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B5">
    <label>5.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Abramson S.B. Nitric oxide in inflammation and pain associated with osteoarthritis. Arthritis Res. Ther., 2008, vol. 10, no. S2. DOI: 10.1186/ar2463.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Abramson S.B. Nitric oxide in inflammation and pain associated with osteoarthritis. Arthritis Res. Ther., 2008, vol. 10, no. S2. DOI: 10.1186/ar2463.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B6">
    <label>6.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Mabey T., Honsawek S. Cytokines as biochemical markers for knee osteoarthritis. J. Am. Acad. Orthop. Surg., 2015, vol. 6, no. 1. DOI: 10.5312/wjo.v6.i1.95.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Mabey T., Honsawek S. Cytokines as biochemical markers for knee osteoarthritis. J. Am. Acad. Orthop. Surg., 2015, vol. 6, no. 1. DOI: 10.5312/wjo.v6.i1.95.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B7">
    <label>7.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Olson S.A., Horne P., Furman B., Huebner J., Al-Rashid M., Kraus V.B., Guilak F. The role of cytokines in posttraumatic arthritis. Am. Acad. Orthop. Surg., 2014, vol. 22, no. 1. DOI: 10.5435/JAAOS-22-01-29.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Olson S.A., Horne P., Furman B., Huebner J., Al-Rashid M., Kraus V.B., Guilak F. The role of cytokines in posttraumatic arthritis. Am. Acad. Orthop. Surg., 2014, vol. 22, no. 1. DOI: 10.5435/JAAOS-22-01-29.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B8">
    <label>8.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Vnukov V.V., Krolevets I.V., Panina S.B., Milyutina N.P., Ananyan A.A., Plotnikov A.A., Zabrodin M.A. The Association Between NO-Synthase Gene Polymorphisms and the Development of Post-Traumatic Knee Osteoarthritis Among Residents of Rostov Region.Russian J. Genetics: Applied Research, 2017, vol. 7, no. 2. DOI: 10.1134/S2079059717020150.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Vnukov V.V., Krolevets I.V., Panina S.B., Milyutina N.P., Ananyan A.A., Plotnikov A.A., Zabrodin M.A. The Association Between NO-Synthase Gene Polymorphisms and the Development of Post-Traumatic Knee Osteoarthritis Among Residents of Rostov Region.Russian J. Genetics: Applied Research, 2017, vol. 7, no. 2. DOI: 10.1134/S2079059717020150.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B9">
    <label>9.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Anderson D.D., Chubinskaya S., Guilak F., Martin J.A., Oegema T.R., Olson S.A., Buckwalter J.A. Post-Traumatic Osteoarthritis: Improved Understanding and Opportunities for Early Intervention. J. Orthop. Res., 2011, vol. 29, no 6. DOI: 10.1002/jor.21359.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Anderson D.D., Chubinskaya S., Guilak F., Martin J.A., Oegema T.R., Olson S.A., Buckwalter J.A. Post-Traumatic Osteoarthritis: Improved Understanding and Opportunities for Early Intervention. J. Orthop. Res., 2011, vol. 29, no 6. DOI: 10.1002/jor.21359.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B10">
    <label>10.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Valdes A.M., Spector T.D. The contribution of genes to osteoarthritis. Rheum. Dis. Clin. North. Am., 2008, vol. 34, no. 3, doi.org/10.1016/j.rdc.2008.04.008.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Valdes A.M., Spector T.D. The contribution of genes to osteoarthritis. Rheum. Dis. Clin. North. Am., 2008, vol. 34, no. 3, doi.org/10.1016/j.rdc.2008.04.008.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B11">
    <label>11.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Valdes A.M., Doherty S.A., Muir K.R., Wheeler M., Maciewicz R.A., Zhang W., Dohert М. The genetic contribution to severe post-traumatic osteoarthritis. Ann. Rheum. Dis., 2013, vol. 72, no. 10. DOI: 10.1136/annrheumdis-2012-202562.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Valdes A.M., Doherty S.A., Muir K.R., Wheeler M., Maciewicz R.A., Zhang W., Dohert M. The genetic contribution to severe post-traumatic osteoarthritis. Ann. Rheum. Dis., 2013, vol. 72, no. 10. DOI: 10.1136/annrheumdis-2012-202562.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B12">
    <label>12.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Голиков П.П., Николаева Н.Ю. Метод определения нитрита/нитрата (NOx-) в сыворотке крови. Биомед. химия, 2004, т. 50, № 1.  @@Golikov P.P., Nikolaeva N.Yu. Metod opredeleniya nitrita/nitrata (NOx-) v syvorotke krovi. Biomed. himiya, 2004, vol. 50, no. 1. (In Russ.)
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Golikov P.P., Nikolaeva N.Yu. Metod opredeleniya nitrita/nitrata (NOx-) v syvorotke krovi. Biomed. himiya, 2004, t. 50, № 1.  @@Golikov P.P., Nikolaeva N.Yu. Metod opredeleniya nitrita/nitrata (NOx-) v syvorotke krovi. Biomed. himiya, 2004, vol. 50, no. 1. (In Russ.)
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B13">
    <label>13.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Simundic A.-M. Diagnostic Accuracy. Part 1: Basic Concepts: Sensitivity and Specificity, ROC Analysis, STARD Statement. Point of Care, 2012, vol. 11, no 1.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Simundic A.-M. Diagnostic Accuracy. Part 1: Basic Concepts: Sensitivity and Specificity, ROC Analysis, STARD Statement. Point of Care, 2012, vol. 11, no 1.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B14">
    <label>14.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Furman B.D., Mangiapani D.S., Zeitler E., Bailey K.N., Horne P.H., Huebner J.L., Kraus V.B., Guilak F., Olson S.A. Targeting pro-inflammatory cytokines following joint injury: acute intra-articular inhibition of interleukin-1 following knee injury prevents post-traumatic arthritis. Arthritis Research &amp; Therapy, 2014, vol. 16, no. 3. DOI: 10.1186/ar4591.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Furman B.D., Mangiapani D.S., Zeitler E., Bailey K.N., Horne P.H., Huebner J.L., Kraus V.B., Guilak F., Olson S.A. Targeting pro-inflammatory cytokines following joint injury: acute intra-articular inhibition of interleukin-1 following knee injury prevents post-traumatic arthritis. Arthritis Research &amp; Therapy, 2014, vol. 16, no. 3. DOI: 10.1186/ar4591.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B15">
    <label>15.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Bigoni M., Sacerdote P., Turati M., Franchi S., Gandolla M., Gaddi D., Moretti S., Munegato D., Augusti C.A., Bresciani E., Omeljaniuk R.J., Locatelli V., Torsello A. Acute and late changes in intraarticular cytokine levels following anterior cruciate ligament injury. J. Orthop. Res., 2013, vol. 31, no. 2. DOI: 10.1002/jor.22208.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Bigoni M., Sacerdote P., Turati M., Franchi S., Gandolla M., Gaddi D., Moretti S., Munegato D., Augusti C.A., Bresciani E., Omeljaniuk R.J., Locatelli V., Torsello A. Acute and late changes in intraarticular cytokine levels following anterior cruciate ligament injury. J. Orthop. Res., 2013, vol. 31, no. 2. DOI: 10.1002/jor.22208.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B16">
    <label>16.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Teunis T., Beekhuizen M., van Osch G.V.M., Schuurman A.H., Creemers L.B., van Minnen L.P. Soluble mediators in posttraumatic wrist and primary knee osteoarthritis. Arch. Bone. Jt. Surg., 2014, vol. 2, no. 3. DOI: abjs.mums.ac.ir.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Teunis T., Beekhuizen M., van Osch G.V.M., Schuurman A.H., Creemers L.B., van Minnen L.P. Soluble mediators in posttraumatic wrist and primary knee osteoarthritis. Arch. Bone. Jt. Surg., 2014, vol. 2, no. 3. DOI: abjs.mums.ac.ir.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B17">
    <label>17.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Ning L., Ishijima M., Kaneko H., Kurihara H., Arikawa-Hirasawa E., Kubota M., Liu L., Xu Z., Futami I., Yusup A., Miyahara K., Xu S., Kaneko K., Kurosawa H. Correlations between both the expression levels of inflammatory mediators and growth factor in medial perimeniscal synovial tissue and the severity of medial knee osteoarthritis.Int. Orthop., 2011, vol. 35, no. 6. DOI: 10.1007/s00264-010-1045-1.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Ning L., Ishijima M., Kaneko H., Kurihara H., Arikawa-Hirasawa E., Kubota M., Liu L., Xu Z., Futami I., Yusup A., Miyahara K., Xu S., Kaneko K., Kurosawa H. Correlations between both the expression levels of inflammatory mediators and growth factor in medial perimeniscal synovial tissue and the severity of medial knee osteoarthritis.Int. Orthop., 2011, vol. 35, no. 6. DOI: 10.1007/s00264-010-1045-1.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B18">
    <label>18.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              de Albornoz P.M., Forriol F. Changes in synovial fluid in different knee-joint diseases. Rev. Esp. Cir. Ortop. Traumatol., 2012, vol. 56, no. 2. DOI: 10.1016/j.recote.2012.03.003.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              de Albornoz P.M., Forriol F. Changes in synovial fluid in different knee-joint diseases. Rev. Esp. Cir. Ortop. Traumatol., 2012, vol. 56, no. 2. DOI: 10.1016/j.recote.2012.03.003.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B19">
    <label>19.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Ku J.H., Lee C.K., Joo B.S., An B.M., Choi S.H., Wang T.H., Cho H.L. Correlation of synovial fluid leptin concentrations with the severity of osteoarthritis. Clin. Rheumatol., 2009, vol. 28, no. 8. DOI: org/10.1007/s10067-009-1242-8.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Ku J.H., Lee C.K., Joo B.S., An B.M., Choi S.H., Wang T.H., Cho H.L. Correlation of synovial fluid leptin concentrations with the severity of osteoarthritis. Clin. Rheumatol., 2009, vol. 28, no. 8. DOI: org/10.1007/s10067-009-1242-8.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B20">
    <label>20.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Cao R., Brakenhielm E., Wahlestedt C., Thyberg J., Cao Y. (2001) Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF. Proc. Natl. Acad. Sci. USA, 2001, vol. 98, no. 11. DOI: 10.1073/pnas.101564798.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Cao R., Brakenhielm E., Wahlestedt C., Thyberg J., Cao Y. (2001) Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF. Proc. Natl. Acad. Sci. USA, 2001, vol. 98, no. 11. DOI: 10.1073/pnas.101564798.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B21">
    <label>21.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Denoble A.E., Huffman K.M., Stabler T.V., Kelly S.J., Hershfield M.S., McDaniel G.E., Coleman R.E., Kraus V.B. Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation. Proc. Natl. Acad. Sci. USA, 2011, vol. 108, no. 5. DOI: 10.1073/pnas.1012743108.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Denoble A.E., Huffman K.M., Stabler T.V., Kelly S.J., Hershfield M.S., McDaniel G.E., Coleman R.E., Kraus V.B. Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation. Proc. Natl. Acad. Sci. USA, 2011, vol. 108, no. 5. DOI: 10.1073/pnas.1012743108.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B22">
    <label>22.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Jitprasertwong P., Jaedicke K.M., Nile C.J., Preshaw P.M., Taylor J.J. Leptin enhances the secretion of interleukin (IL)-18, but not IL-1β, from human monocytes via activation of caspase-1. Cytokine, 2014, vol. 65, no. 2. DOI: 10.1016/j.cyto.2013.10.008.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Jitprasertwong P., Jaedicke K.M., Nile C.J., Preshaw P.M., Taylor J.J. Leptin enhances the secretion of interleukin (IL)-18, but not IL-1β, from human monocytes via activation of caspase-1. Cytokine, 2014, vol. 65, no. 2. DOI: 10.1016/j.cyto.2013.10.008.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B23">
    <label>23.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Vecchione C., Maffei A., Colella S., Aretini A., Poulet R., Frati G., Gentile M.T., Fratta L., Trimarco V., Trimarco B., Lembo G. Leptin effect on endothelial nitric oxide is mediated through Akt-endothelial nitric oxide synthase phosphorylation pathway. Diabetes, 2002, vol. 51, no. 1. DOI: 10.2337/diabetes.51.1.168.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Vecchione C., Maffei A., Colella S., Aretini A., Poulet R., Frati G., Gentile M.T., Fratta L., Trimarco V., Trimarco B., Lembo G. Leptin effect on endothelial nitric oxide is mediated through Akt-endothelial nitric oxide synthase phosphorylation pathway. Diabetes, 2002, vol. 51, no. 1. DOI: 10.2337/diabetes.51.1.168.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B24">
    <label>24.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Joffin N., Niang F., Forest C., Jaubert A.-M. Is there NO help for leptin? Biochimie, 2012, vol. 94, no. 10. DOI: 10.1016/j.biochi.2012.06.017.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Joffin N., Niang F., Forest C., Jaubert A.-M. Is there NO help for leptin? Biochimie, 2012, vol. 94, no. 10. DOI: 10.1016/j.biochi.2012.06.017.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B25">
    <label>25.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Abramson S.B. Osteoarthritis and nitric oxide. Osteoarthritis Cartilage, 2008, vol. 16, no. S2. DOI: 10.1016/S1063-4584(08)60008-4.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Abramson S.B. Osteoarthritis and nitric oxide. Osteoarthritis Cartilage, 2008, vol. 16, no. S2. DOI: 10.1016/S1063-4584(08)60008-4.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B26">
    <label>26.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Feelisch M. The chemical biology of nitric oxide - an outsider’s reflections about its role in osteoarthritis. Osteoarthritis Cartilage, 2008, vol. 16, no. 2. DOI: 10.1016/S1063-4584(08)60007-2.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Feelisch M. The chemical biology of nitric oxide - an outsider’s reflections about its role in osteoarthritis. Osteoarthritis Cartilage, 2008, vol. 16, no. 2. DOI: 10.1016/S1063-4584(08)60007-2.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B27">
    <label>27.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Castro R.R., Cunha F.Q., Silva F.S.Jr., Rocha F.A. A quantitative approach to measure joint pain in experimental osteoarthritis-evidence of a role for nitric oxide. Osteoarthritis Cartilage, 2006, vol. 14, no. 8. DOI: 10.1016/j.joca.2006.01.013.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Castro R.R., Cunha F.Q., Silva F.S.Jr., Rocha F.A. A quantitative approach to measure joint pain in experimental osteoarthritis-evidence of a role for nitric oxide. Osteoarthritis Cartilage, 2006, vol. 14, no. 8. DOI: 10.1016/j.joca.2006.01.013.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B28">
    <label>28.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Pautz A., Art J., Hahn S., Nowag S., Voss C., Kleinert H. Regulation of the expression of inducible nitric oxide synthase. Nitric Oxide, 2010, vol. 23, no. 2. DOI: 10.1016/j.niox.2010.04.007.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Pautz A., Art J., Hahn S., Nowag S., Voss C., Kleinert H. Regulation of the expression of inducible nitric oxide synthase. Nitric Oxide, 2010, vol. 23, no. 2. DOI: 10.1016/j.niox.2010.04.007.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B29">
    <label>29.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Loeser R.F., Carlson C.S., Del Carlo M., Cole A. Detection of nitrotyrosine in aging and osteoarthritic cartilage: Correlation of oxidative damage with the presence of interleukin-1beta and with chondrocyte resistance to insulin-like growth factor 1. Arthritis Rheum., 2002, vol. 46, no. 9. DOI: 10.1002/art.10496.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Loeser R.F., Carlson C.S., Del Carlo M., Cole A. Detection of nitrotyrosine in aging and osteoarthritic cartilage: Correlation of oxidative damage with the presence of interleukin-1beta and with chondrocyte resistance to insulin-like growth factor 1. Arthritis Rheum., 2002, vol. 46, no. 9. DOI: 10.1002/art.10496.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B30">
    <label>30.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Yan Q., Feng Q., Beier F. Endothelial nitric oxide synthase deficiency in mice results in reduced chondrocyte proliferation and endochondral bone growth. Arthritis Rheum., 2010, vol. 62, no. 7. DOI: 10.1002/art.27486.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Yan Q., Feng Q., Beier F. Endothelial nitric oxide synthase deficiency in mice results in reduced chondrocyte proliferation and endochondral bone growth. Arthritis Rheum., 2010, vol. 62, no. 7. DOI: 10.1002/art.27486.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B31">
    <label>31.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Yan Q., Feng Q., Beier F. Reduced chondrocyte proliferation, earlier cell cycle exit and increased apoptosis in neuronal nitric oxide synthase-deficient mice. Osteoarthritis Cartilage, 2012, vol. 20, no. 2. DOI: 10.1016/j.joca. 2011.11.014.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Yan Q., Feng Q., Beier F. Reduced chondrocyte proliferation, earlier cell cycle exit and increased apoptosis in neuronal nitric oxide synthase-deficient mice. Osteoarthritis Cartilage, 2012, vol. 20, no. 2. DOI: 10.1016/j.joca. 2011.11.014.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B32">
    <label>32.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Miao X., Garcia-Barcelo M.M., So M., Tang W., Dong X., Wang B., Mao J., Ngan E.S., Chen Y., Lui V.C., Wong K.K., Liu L., Tam P.K. Lack of association between nNOS -84G &gt; A polymorphism and risk of infantile hypertrophic pyloric stenosis in a Chinese population. J. Pediatr. Surg., 2010, vol. 45, no. 4. DOI: 10.1016/j.jpedsurg. 2009.07.067.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Miao X., Garcia-Barcelo M.M., So M., Tang W., Dong X., Wang B., Mao J., Ngan E.S., Chen Y., Lui V.C., Wong K.K., Liu L., Tam P.K. Lack of association between nNOS -84G &gt; A polymorphism and risk of infantile hypertrophic pyloric stenosis in a Chinese population. J. Pediatr. Surg., 2010, vol. 45, no. 4. DOI: 10.1016/j.jpedsurg. 2009.07.067.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B33">
    <label>33.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Olson S.Y., Garban H.J. Regulation of apoptosis-related genes by nitric oxide in cancer. Nitric Oxide, 2008, vol. 19, no. 2. DOI: 10.1016/j.niox.2008.04.005.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Olson S.Y., Garban H.J. Regulation of apoptosis-related genes by nitric oxide in cancer. Nitric Oxide, 2008, vol. 19, no. 2. DOI: 10.1016/j.niox.2008.04.005.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B34">
    <label>34.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Nakayama M., Yasue H., Yoshimura M., Shimasaki Y., Kugiyama K., Ogawa H., Motoyama T., Saito Y., Ogawa Y., Miyamoto Y., Nakao K. T-786 C mutation in the 5’-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation, 1999, vol. 99, no. 22. DOI: 10.1161/01.cir.99.22.2864.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Nakayama M., Yasue H., Yoshimura M., Shimasaki Y., Kugiyama K., Ogawa H., Motoyama T., Saito Y., Ogawa Y., Miyamoto Y., Nakao K. T-786 C mutation in the 5’-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation, 1999, vol. 99, no. 22. DOI: 10.1161/01.cir.99.22.2864.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B35">
    <label>35.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">
            
              Asif A.R., Oellerich M., Armstrong V.W., Hecker M., Cattaruzza M. T-786C polymorphism of the nos-3 gene and the endothelial cell response to fluid shear stress - a proteome analyses. J. Proteome. Res., 2009, vol. 8, no. 6. DOI: 10.1021/pr800998k.
            
          </mixed-citation>
     <mixed-citation xml:lang="en">
            
              Asif A.R., Oellerich M., Armstrong V.W., Hecker M., Cattaruzza M. T-786C polymorphism of the nos-3 gene and the endothelial cell response to fluid shear stress - a proteome analyses. J. Proteome. Res., 2009, vol. 8, no. 6. DOI: 10.1021/pr800998k.
            
          </mixed-citation>
    </citation-alternatives>
   </ref>
  </ref-list>
 </back>
</article>
