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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
        <publisher-loc>S&#227;o Paulo, SP, Brazil</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">XgvcPHsKyCQwg3LSHkxdVYG</article-id>
      <article-id pub-id-type="other">00023</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2006001800023</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(06)08700523</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2006001800023</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Relato de Caso</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Infarto do mioc&#225;rdio em atleta jovem associado ao uso de suplemento diet&#233;tico rico em efedrina</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Forte</surname>
            <given-names>Rafael Yared</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Precoma-Neto</surname>
            <given-names>Daniel</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Chiminacio Neto</surname>
            <given-names>Nelson</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Maia</surname>
            <given-names>Francisco</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Faria-Neto</surname>
            <given-names>Jos&#233; Rocha</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
      </contrib-group>
      <aff id="aff02">
        <addr-line>
          <named-content content-type="city">Curitiba</named-content>
          <named-content content-type="state">Paran&#225;</named-content>
        </addr-line>
        <institution content-type="orgname">Pontif&#237;cia Universidade Cat&#243;lica do Paran&#225;</institution>
        <country country="BR">Brazil</country>
      </aff>
      <aff id="aff01">
        <institution content-type="orgname">Santa Casa de Miseric&#243;rdia de Curitiba</institution>
        <institution content-type="orgdiv1">Hospital da Irmandade </institution>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>11</month>
        <year>2006</year>
      </pub-date>
      <volume>87</volume>
      <issue>5</issue>
      <fpage>e179</fpage>
      <lpage>e181</lpage>
      <history>
        <date date-type="received">
          <day>01</day>
          <month>09</month>
          <year>2005</year>
        </date>
        <date date-type="rev-recd">
          <day>12</day>
          <month>12</month>
          <year>2005</year>
        </date>
        <date date-type="accepted">
          <day>01</day>
          <month>06</month>
          <year>2006</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/" xml:lang="en">
          <license-p>This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.</license-p>
        </license>
      </permissions>
      <abstract>
        <p>Suplementos diet&#233;ticos que cont&#234;m efedrina e outros alcal&#243;ides relacionados &#224; efedrina s&#227;o largamente consumidos em v&#225;rios pa&#237;ses, com prop&#243;sito de est&#237;mulo energ&#233;tico e perda de peso. Mesmo sendo proibida a sua comercializa&#231;&#227;o no Brasil, esses produtos podem ser comprados ilegalmente pela Internet ou em academias. Relatamos a seguir o caso de um jovem atleta, sem fatores de risco para doen&#231;a cardiovascular, que apresentou infarto do mioc&#225;rdio no per&#237;odo em que fez uso de suplemento rico em efedrina.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Infarto agudo do mioc&#225;rdio</kwd>
        <kwd>doen&#231;a coronariana</kwd>
        <kwd>efedrina</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>06</day>
        <month>03</month>
        <year>2007</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>RELATO DE CASO</bold>
    </p>
    <p>
      <bold>Infarto do mioc&#225;rdio em atleta jovem associado ao uso de suplemento diet&#233;tico rico em efedrina</bold>
    </p>
    <p>
      <bold>Rafael Yared Forte; Daniel Precoma-Neto; Nelson Chiminacio Neto; Francisco Maia; Jos&#233; Rocha Faria-Neto</bold>
    </p>
    <p> Hospital da Irmandade da Santa Casa de Miseric&#243;rdia de Curitiba, Pontif&#237;cia Universidade Cat&#243;lica do Paran&#225; - PUCPR, Curitiba, PR</p>
    <p>
      <xref ref-type="corresp" rid="back">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p>Suplementos diet&#233;ticos que cont&#234;m efedrina e outros alcal&#243;ides relacionados &#224; efedrina s&#227;o largamente consumidos em v&#225;rios pa&#237;ses, com prop&#243;sito de est&#237;mulo energ&#233;tico e perda de peso. Mesmo sendo proibida a sua comercializa&#231;&#227;o no Brasil, esses produtos podem ser comprados ilegalmente pela Internet ou em academias. Relatamos a seguir o caso de um jovem atleta, sem fatores de risco para doen&#231;a cardiovascular, que apresentou infarto do mioc&#225;rdio no per&#237;odo em que fez uso de suplemento rico em efedrina.</p>
    <p><bold>Palavras-chave:</bold> Infarto agudo do mioc&#225;rdio, doen&#231;a coronariana, efedrina.</p>
    <p>A efedrina &#233; um alcal&#243;ide simpatomim&#233;tico derivado de plantas do g&#234;nero <italic>Ephedra</italic>, que possui mais de 40 esp&#233;cies distribu&#237;das em regi&#245;es de clima temperado e subtropical. H&#225; s&#233;culos seu uso com fins terap&#234;uticos j&#225; era disseminado entre os chineses, que utilizavam o extrato da planta desidratada (chamada de <italic>Ma huang</italic>) para o tratamento de afec&#231;&#245;es respirat&#243;rias<sup>1</sup>. Na medicina moderna, a efedrina j&#225; foi usada como descongestionante nasal, broncodilatador e vasopressor<sup>2</sup>, por&#233;m, o uso terap&#234;utico desses alcal&#243;ides tornou-se restrito por haver d&#250;vidas quanto ao seu perfil de seguran&#231;a.</p>
    <p>Atualmente, suplementos diet&#233;ticos que cont&#234;m efedrina e outros alcal&#243;ides relacionados &#224; efedrina s&#227;o largamente consumidos em v&#225;rios pa&#237;ses, com prop&#243;sito de est&#237;mulo energ&#233;tico (aumento da performance atl&#233;tica) e perda de peso, apesar de estudos cl&#237;nicos demonstrarem que esta redu&#231;&#227;o &#233; modesta e ocorre apenas em curto prazo<sup>3</sup>. Mesmo sendo proibida a sua comercializa&#231;&#227;o no Brasil, esses produtos podem ser comprados ilegalmente pela Internet ou em academias. Eventos cardiovasculares adversos advindos do uso de efedrina j&#225; s&#227;o bem documentados na literatura, como hipertens&#227;o arterial, taquiarritmias, infarto do mioc&#225;rdio e morte s&#250;bita, al&#233;m de relatos de miocardite associada ao uso de compostos com efedrina. Acredita-se que o vasoespasmo por est&#237;mulo a e b adren&#233;rgico seja o mecanismo tanto da miocardite<sup>4</sup> quanto do infarto agudo do mioc&#225;rdio, e os efeitos adren&#233;rgicos da efedrina, provocando diminui&#231;&#227;o do per&#237;odo refrat&#225;rio, tamb&#233;m permitem o desenvolvimento de arritmias. O efeito cardiovascular da efedrina &#233;, ao menos em parte, semelhante ao da coca&#237;na, droga que tamb&#233;m causa estimula&#231;&#227;o a e b adren&#233;rgica, levando a aumento da press&#227;o arterial, aumento da freq&#252;&#234;ncia card&#237;aca, vasoespasmo coronariano, isquemia, infarto e arritmias<sup>5</sup>.</p>
    <p>Relatamos a seguir o caso de um jovem atleta, sem fatores de risco para doen&#231;a cardiovascular, que apresentou infarto do mioc&#225;rdio no per&#237;odo em que fez uso de suplemento rico em efedrina.</p>
    <p>
      <bold>Relato do caso</bold>
    </p>
    <p>Paciente masculino, 28 anos, lutador de Vale-Tudo e usu&#225;rio de Therma-Pro<sup>&#174;</sup>, um suplemento diet&#233;tico que o paciente utilizava para perda de peso antes das pesagens para lutas. Segundo o pr&#243;prio paciente, al&#233;m da perda de peso (at&#233; 12 kg em 20 dias, quando associado a treino f&#237;sico intenso e dieta), esse produto causava palpita&#231;&#245;es, tremores e ins&#244;nia. J&#225; havia feito o uso pr&#233;vio do produto, sempre apresentando esses sintomas. Durante o per&#237;odo de prepara&#231;&#227;o para uma luta, o paciente iniciou o uso de 4 comprimidos/dia de Therma Pro<sup>&#174;</sup>, evoluindo no terceiro dia com dor tor&#225;cica de forte intensidade, em repouso, tipo aperto, que piorava com esfor&#231;o e melhorava com repouso, com dura&#231;&#227;o prolongada e intermitente. Procurou aux&#237;lio m&#233;dico, tendo recebido prescri&#231;&#227;o de analg&#233;sico, sem melhora do quadro. Ap&#243;s seis dias do sintoma inicial, a dor evoluiu, com s&#237;ncope e hemiparesia direita, tendo sido atendido em outros locais e encaminhado para nosso servi&#231;o apenas 30 dias ap&#243;s o in&#237;cio do quadro. Nesse momento o paciente j&#225; havia recuperado totalmente o d&#233;ficit motor, por&#233;m apresentava insufici&#234;ncia card&#237;aca congestiva classe funcional II (NYHA). N&#227;o relatava hist&#243;ria pregressa de hipertens&#227;o arterial sist&#234;mica, diabetes mellitus, dislipidemia ou hist&#243;ria familiar de doen&#231;as cardiovasculares. Havia fumado meio ma&#231;o de cigarro/dia por cinco anos, por&#233;m j&#225; havia parado de fumar h&#225; 3 anos. Negava uso de drogas il&#237;citas, tendo sido questionado diretamente sobre o uso de coca&#237;na em diversas ocasi&#245;es durante a interna&#231;&#227;o, e negava tamb&#233;m o uso de outros produtos estimulantes, como ester&#243;ides anabolizantes. Ao exame f&#237;sico, apresentava PA de 120/70 mmHg, FC 72 bpm, peso 104 kg e altura 1,77 m. Apesar do &#237;ndice de massa corp&#243;rea na faixa de obesidade (33,2), apresentava grande massa muscular, com pouca adiposidade.</p>
    <p>Os exames complementares mostravam ECG com &#225;rea eletricamente inativa anterior extensa, Rx T&#243;rax normal, colesterol total de 144 mg/dl, HDL 32 mg/dl, LDL 77 mg/dl, triglicer&#237;deos 176 mg/dl, glicemia de jejum 78 mg/dl, hemograma normal e creatinina 1,5 mg/dl. Ecocardiograma evidenciou ventr&#237;culo esquerdo (VE) com dimens&#245;es no limite superior da normalidade e fra&#231;&#227;o de eje&#231;&#227;o de 45%. An&#225;lise da contra&#231;&#227;o segmentar mostrou acinesia &#226;ntero-septal, apical e anterior. Notou-se tamb&#233;m a presen&#231;a de trombo no VE. Foi submetido a cineangiocoronariografia, que mostrou art&#233;ria descendente anterior (DA) oclu&#237;da em sua origem (<xref ref-type="fig" rid="f1el">fig. 1A</xref>), enchendo ter&#231;o m&#233;dio e distal por discreta circula&#231;&#227;o colateral intracoronariana, al&#233;m de trombo em &#225;pice e aumento importante da press&#227;o diast&#243;lica do VE. Pela presen&#231;a de circula&#231;&#227;o colateral, optou-se por angioplastia com <italic>stent</italic> para DA (<xref ref-type="fig" rid="f1el">fig. 1B</xref>). Evoluiu sem intercorr&#234;ncias ap&#243;s o procedimento.</p>
    <p content-type="asset">
      <fig id="f1el">
        <graphic xlink:href="1678-4170-abc-87-05-e179-00023-gf01.jpg"/></fig>
    </p>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>A incid&#234;ncia de doen&#231;a coronariana sintom&#225;tica e Infarto Agudo do Miocardio (IAM) em pacientes jovens, com menos de 40 anos &#233; baixa: apenas 3% dos casos ocorrem em pacientes nessa faixa et&#225;ria<sup>6</sup>. Estudos epidemiol&#243;gicos demonstram que os fatores de risco mais prevalentes nessa popula&#231;&#227;o s&#227;o tabagismo e hist&#243;ria familiar de doen&#231;a cardiovascular. A anamnese sobre o consumo de drogas simpatomim&#233;ticas l&#237;citas ou il&#237;citas (coca&#237;na, "crack") deve sempre ser criteriosa nesses casos, principalmente quando os tradicionais fatores de risco para doen&#231;a ateroscler&#243;tica n&#227;o s&#227;o identificados. No caso aqui descrito, a aus&#234;ncia de fatores de risco e a rela&#231;&#227;o temporal entre o uso do suplemento diet&#233;tico rico em efedrina e a ocorr&#234;ncia do evento agudo sugerem uma forte rela&#231;&#227;o causal.</p>
    <p>A efedrina em sua forma pura e o extrato de <italic>Ma huang</italic>, rico em efedrina e outros alcal&#243;ides semelhantes &#224; efedrina, como a pseudo-efedrina, s&#227;o componentes usuais de suplementos diet&#233;ticos consumidos por atletas de diferentes modalidades esportivas, que procuram r&#225;pida redu&#231;&#227;o de peso e ganho energ&#233;tico. Seu uso &#233; indiscriminado, apesar da advert&#234;ncia de diversos &#243;rg&#227;os de sa&#250;de, como a American Medical Association<sup>7</sup>, e de ser encarado como <italic>doping</italic> pela maioria das entidades desportivas. O uso desses produtos tem sido associado a diversos eventos cardiovasculares e neurol&#243;gicos adversos<sup>8</sup>, e, em abril de 2004, o &#243;rg&#227;o controlador de drogas nos Estados Unidos, FDA, proibiu seu com&#233;rcio, tendo sido esse o primeiro caso em que um suplemento diet&#233;tico teve sua comercializa&#231;&#227;o banida. Apesar de n&#227;o ser um agente causal de grande preval&#234;ncia, o consumo desses suplementos n&#227;o pode ser descartado em casos de morte s&#250;bita de atletas jovens e sem cardiopatia estrutural<sup>9</sup>.</p>
    <p>O produto utilizado pelo paciente descrito, Therma-Pro<sup>&#174;</sup>, apresenta em sua f&#243;rmula, conforme dados dispon&#237;bilizados pelo fabricante, 250 mg de extrato de <italic>Ma huang</italic>, o que equivale a 20 mg de efedrina. A dose utilzada, quatro comprimidos ao dia, &#233; o dobro da preconizada pelo fabricante. Independentemente da dose, a efedrina &#233; uma droga que estimula a libera&#231;&#227;o de catecolaminas end&#243;genas, estimulando receptores a-1 , b-1 e b-2 adren&#233;rgicos<sup>10</sup>. Os efeitos da efedrina s&#227;o de vasoconstri&#231;&#227;o e estimula&#231;&#227;o card&#237;aca, acarretando a eleva&#231;&#227;o aguda da press&#227;o arterial e da freq&#252;&#234;ncia card&#237;aca, al&#233;m de midr&#237;ase, ins&#244;nia, vertigem, cefal&#233;ia e ansiedade. A pseudo-efedrina, que age principalmente por estimula&#231;&#227;o dos receptores b-2 adren&#233;rgicos, causa bronco dilata&#231;&#227;o, enquanto seus efeitos a-agonistas s&#227;o respons&#225;veis por melhora de sintomas de congest&#227;o nasal.</p>
    <p>Na circula&#231;&#227;o coronariana, a efedrina pode causar vasoespasmo<sup>11</sup>, principalmente em indiv&#237;duos com t&#244;nus vagal aumentado, como o jovem paciente aqui descrito, por tratar-se de atleta bem condicionado fisicamente. Este parece ser o mecanismo fisiopatol&#243;gico de muitos dos casos relatados de s&#237;ndrome coronariana aguda associada ao consumo de efedrina, onde os pacientes apresentam cinecoronariografia normal<sup>12</sup>. Entretanto, a trombose <italic>in situ</italic> pode ocorrer associadamente<sup>13</sup> por diferentes raz&#245;es; al&#233;m da lentifica&#231;&#227;o do fluxo coronariano, o espasmo pode ser a causa de rotura da capa fibrosa de placas ateroscler&#243;ticas ainda jovens, que possuem extenso n&#250;cleo lip&#237;dico. No caso dos pacientes que fazem uso de drogas como a efedrina, isso ocorre na presen&#231;a de significativa ativa&#231;&#227;o plaquet&#225;ria pela atividade simpatomim&#233;tica dessa subst&#226;ncia. A associa&#231;&#227;o de espasmo e trombose <italic>in situ</italic> pode ter ocorrido no caso aqui descrito, pois a cinecoronariografia demonstrou oclus&#227;o completa da art&#233;ria descendente anterior, por&#233;m sem evid&#234;ncia de qualquer comprometimento de outros vasos.</p>
    <p>Na aus&#234;ncia de eventos tromb&#243;ticos pr&#233;vios, venosos ou arteriais, e na presen&#231;a de um fator que crescentemente tem sido reconhecido como causa de IAM em pacientes jovens, nenhuma investiga&#231;&#227;o de trombofilia foi realizada neste paciente. A maioria dos polimorfismos de prote&#237;nas do sistema de coagula&#231;&#227;o envolvidos com trombose venosa apresenta muito pouca ou nenhuma associa&#231;&#227;o com IAM<sup>14</sup>. Em nosso meio, Faria-Neto e cols.<sup>15</sup> demonstraram baixa preval&#234;ncia e nenhuma correla&#231;&#227;o do Fator V de Leiden e dos polimorfismos G20210A da protrombina e C677T da metilenotetrahidrofolato redutase (envolvida no metabolismo da homociste&#237;na) com a presen&#231;a de oclus&#227;o coronariana demonstrada pela cinecoronariografia.</p>
    <p>A op&#231;&#227;o por angioplastia tardia da art&#233;ria relacionada ao infarto neste paciente &#233; uma conduta controversa, principalmente na aus&#234;ncia de estudo de viabilidade da &#225;rea afetada. Um grande estudo patrocinado pelo <italic>National Heart, Lung, and Blood Institute</italic> (NHLBI) est&#225; em andamento para testar a hip&#243;tese de que abrir art&#233;rias relacionadas ao infarto tardiamente (3 a 28 dias p&#243;s-IAM) com <italic>stent</italic>, em pacientes assintom&#225;ticos de alto risco (FEVE &lt; 50% e oclus&#227;o proximal de uma grande art&#233;ria), acarreta redu&#231;&#227;o de desfechos compostos de morte, infarto recorrente n&#227;o fatal e ocorr&#234;ncia de insufici&#234;ncia card&#237;aca classe funcional IV<italic>,</italic> com m&#233;dia de 3 anos de seguimento<sup>16</sup>.</p>
    <p>A descri&#231;&#227;o deste caso alerta para a necessidade de orientarmos a comunidade quanto aos riscos envolvidos no consumo de suplementos diet&#233;ticos contendo efedrina, que continuam a ser ilegalmente comercializados sob a promessa de r&#225;pida redu&#231;&#227;o de peso e aumento do rendimento f&#237;sico.</p>
    <p>
      <fn id="back" fn-type="corresp">
        <p>
          <graphic xlink:href="1678-4170-abc-87-05-e179-00023-e01.jpg"/></p>
        <p>
          <bold>Correspond&#234;ncia:</bold>
        </p>
        <p> Jos&#233; Rocha Faria Neto </p>
        <p> Rua Des. Ot&#225;vio do Amaral, 741/802 </p>
        <p> 80730-400 &#150; Curitiba, PR </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="jose.faria@pucpr.br">jose.faria@pucpr.br</email>
        </p>
      </fn>
    </p>
    <p>Recebido em 01/09/05; revisado recebido em 12/12/05; aceito em 01/06/06.</p>
  </body>
  <back>
    <ref-list>
      <ref id="B1">
        <mixed-citation>1. Foster S, Tyler VE. Tyler's honest herbal: A sensible guide to the use of herbs and related remedies. Binghamton, NY: The Haworth Pr, 1999.</mixed-citation>
        <element-citation publication-type="book">
          <source>Tyler's honest herbal: A sensible guide to the use of herbs and related remedies</source>
          <date>
            <year>1999</year>
          </date>
          <person-group person-group-type="author">
            <name>
              <surname>Foster</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Tyler</surname>
              <given-names>VE</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B2">
        <mixed-citation>2. Sympathomimetic agents, in: USPDI: drug information for the health care professional, vol 1, 19th ed. Taunton. MA: World Color Book Services, 1999, 2669-75.</mixed-citation>
        <element-citation publication-type="book">
          <source>USPDI: drug information for the health care professional</source>
          <date>
            <year>1999</year>
          </date>
          <fpage>2669</fpage>
          <lpage>75</lpage>
        </element-citation>
      </ref>
      <ref id="B3">
        <mixed-citation>3. Shekelle PG, Hardy ML, Morton SC, Maglione M, Mojica WA, Suttorp MJ, et al. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. JAMA 2003; 289: 1537-45.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis</article-title>
          <source>JAMA</source>
          <date>
            <year>2003</year>
          </date>
          <fpage>1537</fpage>
          <lpage>45</lpage>
          <volume>289</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Shekelle</surname>
              <given-names>PG</given-names>
            </name>
            <name>
              <surname>Hardy</surname>
              <given-names>ML</given-names>
            </name>
            <name>
              <surname>Morton</surname>
              <given-names>SC</given-names>
            </name>
            <name>
              <surname>Maglione</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Mojica</surname>
              <given-names>WA</given-names>
            </name>
            <name>
              <surname>Suttorp</surname>
              <given-names>MJ</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B4">
        <mixed-citation>4. Zaacks SM, Klein L, Tan CD, Rodriguez ER, Leikin JB. Hypersensitivity myocarditis associated with ephedra use. Clinical toxicology 1999; 37: 485-9.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Hypersensitivity myocarditis associated with ephedra use</article-title>
          <source>Clinical toxicology</source>
          <date>
            <year>1999</year>
          </date>
          <fpage>485</fpage>
          <lpage>9</lpage>
          <volume>37</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Zaacks</surname>
              <given-names>SM</given-names>
            </name>
            <name>
              <surname>Klein</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Tan</surname>
              <given-names>CD</given-names>
            </name>
            <name>
              <surname>Rodriguez</surname>
              <given-names>ER</given-names>
            </name>
            <name>
              <surname>Leikin</surname>
              <given-names>JB</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B5">
        <mixed-citation>5. Lange RA, Hills LD. Cardiovascular complications of cocaine use. N Eng J Med 2003; 345: 351-8.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Cardiovascular complications of cocaine use</article-title>
          <source>N Eng J Med</source>
          <date>
            <year>2003</year>
          </date>
          <fpage>351</fpage>
          <lpage>8</lpage>
          <volume>345</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Lange</surname>
              <given-names>RA</given-names>
            </name>
            <name>
              <surname>Hills</surname>
              <given-names>LD</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B6">
        <mixed-citation>6. Klein LW, Nathan S. Coronary artery disease in young adults. J Am Coll Cardiol 2003; 41: 529-31.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Coronary artery disease in young adults</article-title>
          <source>J Am Coll Cardiol</source>
          <date>
            <year>2003</year>
          </date>
          <fpage>529</fpage>
          <lpage>31</lpage>
          <volume>41</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Klein</surname>
              <given-names>LW</given-names>
            </name>
            <name>
              <surname>Nathan</surname>
              <given-names>S</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B7">
        <mixed-citation>7. Bent S, Tiedt TN, Odden MC, Schlipak MG. The relative safety of ephedra compared with other herbal products. Ann Intern Med 2003; 138: 468-71.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>The relative safety of ephedra compared with other herbal products</article-title>
          <source>Ann Intern Med</source>
          <date>
            <year>2003</year>
          </date>
          <fpage>468</fpage>
          <lpage>71</lpage>
          <volume>138</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Bent</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Tiedt</surname>
              <given-names>TN</given-names>
            </name>
            <name>
              <surname>Odden</surname>
              <given-names>MC</given-names>
            </name>
            <name>
              <surname>Schlipak</surname>
              <given-names>MG</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B8">
        <mixed-citation>8. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000; 343: 1833-8.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids</article-title>
          <source>N Engl J Med</source>
          <date>
            <year>2000</year>
          </date>
          <fpage>1833</fpage>
          <lpage>8</lpage>
          <volume>343</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Haller</surname>
              <given-names>CA</given-names>
            </name>
            <name>
              <surname>Benowitz</surname>
              <given-names>NL</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B9">
        <mixed-citation>9. Maron BJ. Sudden death in young athletes. N Eng J Med 2003; 349: 1064-75.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Sudden death in young athletes</article-title>
          <source>N Eng J Med</source>
          <date>
            <year>2003</year>
          </date>
          <fpage>1064</fpage>
          <lpage>75</lpage>
          <volume>349</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Maron</surname>
              <given-names>BJ</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B10">
        <mixed-citation>10. Andraws R, Chawla P, Brown D. Cardiovascular effects of ephedra alkaloids: A comprehensive review. Progress in cardiovascular diseases 2005; 47: 217-25.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Cardiovascular effects of ephedra alkaloids: A comprehensive review</article-title>
          <source>Progress in cardiovascular diseases</source>
          <date>
            <year>2005</year>
          </date>
          <fpage>217</fpage>
          <lpage>25</lpage>
          <volume>47</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Andraws</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Chawla</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Brown</surname>
              <given-names>D</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B11">
        <mixed-citation>11. Wahl A, Eberli FR, Thomson DA, et al. Coronary artery spasm and non-Q-wave myocardial infarction following intravenous ephedrine in two healthy women under spinal anesthesia. Br J Anaesth 2002; 89: 519-23.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Coronary artery spasm and non-Q-wave myocardial infarction following intravenous ephedrine in two healthy women under spinal anesthesia</article-title>
          <source>Br J Anaesth</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>519</fpage>
          <lpage>23</lpage>
          <volume>89</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Wahl</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Eberli</surname>
              <given-names>FR</given-names>
            </name>
            <name>
              <surname>Thomson</surname>
              <given-names>DA</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B12">
        <mixed-citation>12. Grzesk G, Polak G, Grabczewska Z, Kubica J. Myocardial infarction with normal coronary arteriogram: the role of ephedrine-like alkaloids. Med Sci monit 2004; 10: CS15-21.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Myocardial infarction with normal coronary arteriogram: the role of ephedrine-like alkaloids</article-title>
          <source>Med Sci monit</source>
          <date>
            <year>2004</year>
          </date>
          <fpage>CS15</fpage>
          <lpage>21</lpage>
          <volume>10</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Grzesk</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Polak</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Grabczewska</surname>
              <given-names>Z</given-names>
            </name>
            <name>
              <surname>Kubica</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B13">
        <mixed-citation>13. Sachdeva R, Sivasankaran S, Fishman RF, Zarich SW, McPherson CA. Coronary thrombosis related to use of Xenadrine RFA&#174;. Tex Heart Inst J 2005; 32: 74-7.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Coronary thrombosis related to use of Xenadrine RFA&#174;</article-title>
          <source>Tex Heart Inst J</source>
          <date>
            <year>2005</year>
          </date>
          <fpage>74</fpage>
          <lpage>7</lpage>
          <volume>32</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Sachdeva</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Sivasankaran</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Fishman</surname>
              <given-names>RF</given-names>
            </name>
            <name>
              <surname>Zarich</surname>
              <given-names>SW</given-names>
            </name>
            <name>
              <surname>McPherson</surname>
              <given-names>CA</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B14">
        <mixed-citation>14. Boekholdt SM, Bijsterved NR, Moons AHM, Levi M, Buller HR, Peters RJG. Genetic variation in coagulation and fibrinolytic proteins and their relation with acute myocardial infarction: a systematic review. Circulation 2001; 104: 3063-8.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Genetic variation in coagulation and fibrinolytic proteins and their relation with acute myocardial infarction: a systematic review</article-title>
          <source>Circulation</source>
          <date>
            <year>2001</year>
          </date>
          <fpage>3063</fpage>
          <lpage>8</lpage>
          <volume>104</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Boekholdt</surname>
              <given-names>SM</given-names>
            </name>
            <name>
              <surname>Bijsterved</surname>
              <given-names>NR</given-names>
            </name>
            <name>
              <surname>Moons</surname>
              <given-names>AHM</given-names>
            </name>
            <name>
              <surname>Levi</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Buller</surname>
              <given-names>HR</given-names>
            </name>
            <name>
              <surname>Peters</surname>
              <given-names>RJG</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B15">
        <mixed-citation>15. Faria-Neto JR, Chagas ACP, Bydlowscki SP, Chamone D, Da Luz PL. Aus&#234;ncia de rela&#231;&#227;o entre o fator V de Leiden e dos polimorfismos G20210A da protrombina e C677T da MTHFR com a presen&#231;a de oclus&#227;o coron&#225;ria em uma popula&#231;&#227;o n&#227;o selecionada. Arq Bras Cardiol 2004; 83: S35.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Aus&#234;ncia de rela&#231;&#227;o entre o fator V de Leiden e dos polimorfismos G20210A da protrombina e C677T da MTHFR com a presen&#231;a de oclus&#227;o coron&#225;ria em uma popula&#231;&#227;o n&#227;o selecionada</article-title>
          <source>Arq Bras Cardiol</source>
          <date>
            <year>2004</year>
          </date>
          <fpage>S35</fpage>
          <volume>83</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Faria-Neto</surname>
              <given-names>JR</given-names>
            </name>
            <name>
              <surname>Chagas</surname>
              <given-names>ACP</given-names>
            </name>
            <name>
              <surname>Bydlowscki</surname>
              <given-names>SP</given-names>
            </name>
            <name>
              <surname>Chamone</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Da Luz</surname>
              <given-names>PL</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B16">
        <mixed-citation>16. Hochman JS, Lamas GA, Knatterud GL, Buller CE, Dzavik V, Mark DB, et al.    Design and methodology of occluded artery trial. Am Heart J 2005 Oct; 150(4):    627-42.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Design and methodology of occluded artery trial</article-title>
          <source>Am Heart J</source>
          <date>
            <year>2005</year>
            <month>10</month>
          </date>
          <fpage>627</fpage>
          <lpage>42</lpage>
          <issue>4</issue>
          <volume>150</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Hochman</surname>
              <given-names>JS</given-names>
            </name>
            <name>
              <surname>Lamas</surname>
              <given-names>GA</given-names>
            </name>
            <name>
              <surname>Knatterud</surname>
              <given-names>GL</given-names>
            </name>
            <name>
              <surname>Buller</surname>
              <given-names>CE</given-names>
            </name>
            <name>
              <surname>Dzavik</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Mark</surname>
              <given-names>DB</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Case Report</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Myocardial infarction associated with the use of a dietary supplement rich in ephedrine in a young athlete</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>Dietary supplements containing ephedrine and other alkaloids related to ephedrine are largely consumed in various countries, with the purpose of energetic stimulation and weight loss. Despite the fact that it is not approved for marketing in Brazil, these products may be freely purchased over the Internet or at gyms/fitness centers. We report the case of a young athlete with no risk factors for cardiovascular disease who experienced a myocardial infarction during the period in which he used an ephedrine-rich supplement.</p>
      </abstract>
    </front-stub>
    <body>
      <p>
        <bold>CASE REPORT</bold>
      </p>
      <p>
        <bold>Myocardial infarction associated with the use of a dietary supplement rich in ephedrine in a young athlete</bold>
      </p>
      <p>
        <bold>Rafael Yared Forte; Daniel Precoma-Neto; Nelson Chiminacio Neto; Francisco Maia; Jos&#233; Rocha Faria-Neto</bold>
      </p>
      <p> Hospital da Irmandade da Santa Casa de Miseric&#243;rdia de Curitiba, Pontif&#237;cia Universidade Cat&#243;lica do Paran&#225; - PUCPR, Curitiba, PR, Brazil</p>
      <p>
        <xref ref-type="corresp" rid="back-body2">Mailing Address</xref>
      </p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p>Dietary supplements containing ephedrine and other alkaloids related to ephedrine are largely consumed in various countries, with the purpose of energetic stimulation and weight loss. Despite the fact that it is not approved for marketing in Brazil, these products may be freely purchased over the Internet or at gyms/fitness centers. We report the case of a young athlete with no risk factors for cardiovascular disease who experienced a myocardial infarction during the period in which he used an ephedrine-rich supplement.</p>
      <p><bold>Key words:</bold> Acute myocardial infarction, coronary disease, ephedrine.</p>
      <p>Ephedrine is a sympathomimetic alkaloid derived from plants of the genus <italic>Ephedra</italic>, with more than 40 species distributed in areas of temperate and subtropical climates. For centuries, its use for therapeutic purposes has been disseminated among the Chinese who used the extract of the dehydrated plant (called <italic>Ma huang</italic>) to treat respiratory ailments<sup>1</sup>. In modern medicine, ephedrine has been used as a nasal decongestant, bronchodilator, and vasopressor<sup>2</sup>, but the therapeutic uses of these alkaloids have been restricted because of doubts as to their safety profile.</p>
      <p>Currently, dietary supplements that contain ephedrine and other ephedrine-related alkaloids are widely consumed in several countries for the purpose of energy enhancement (to increase athletic performance) and weight loss, in spite of clinical studies that show that this loss is modest and short-lived<sup>3</sup>. Even though its sale is prohibited in Brazil, these products may be bought illegally over the Internet or at gyms/fitness centers. Cardiovascular adverse events such as arterial hypertension, tachyarrhythmias, myocardial infarction, and sudden death with the use of ephedrine are well documented in literature, besides reports of myocarditis associated with the use of ephedrine-containing compounds. It is believed that the vasospasm by a and b-adrenergic stimulation is the mechanism behind both myocarditis<sup>4</sup> and acute myocardial infarction; the adrenergic effects of ephedrine that cause a reduction in the refractory period allow the development of arrhythmias as well. The cardiovascular effect of ephedrine is, at least in part, similar to that of codeine, a drug that also causes a and b-adrenergic stimulation leading to increased blood pressure, increased heart rate, coronary vasospasm, ischemia, infarction, and arrhythmias<sup>5</sup>.</p>
      <p>We report the case of a young athlete with no risk factors for cardiovascular disease who experienced a myocardial infarction during the period in which he used an ephedrine-rich supplement.</p>
      <p>
        <bold>Case Report</bold>
      </p>
      <p>Our patient is a 28-year-old male, a mixed martial arts fighter, who for some time took Therma-Pro<sup>TM</sup>, a dietary supplement used in order to lose weight before weighing in for the fights. According to the patient, besides the weight loss (up to 12 kg in 20 days, when associated with intense physical training and diet), this product would cause palpitations, tremors, and insomnia. He had used the product before, and always experienced these symptoms. During the period of preparation for a wrestling match, the patient began using four tablets/day of Therma-Pro<sup>TM</sup>, and on the third day developed an intense resting chest pain, described as a tightening sensation, that worsened with effort and improved with rest, with prolonged intermittent duration. He sought medical help, and an analgesic was prescribed to no avail. After six days from the onset of pain, his condition progressed with syncope and hemiparesia on the right, and the patient was seen at other health care centers and referred to our institution merely 30 days after the onset of the clinical picture. On this occasion, that patient had already totally recovered from his motor deficit, but presented with congestive heart failure functional class II (NYHA). He reported no prior history of arterial hypertension, diabetes mellitus, dyslipidemia, or familial history of cardiovascular diseases. He had smoked half a pack of cigarettes a day for five years, but had stopped smoking 3 years prior. He was questioned directly about cocaine use on several occasions during his hospital stay; he denied use of illicit drugs and other stimulants, such as steroids and anabolic products.</p>
      <p>On physical examination his Blood pressure was 120/70 mmHg, Heart rate 72 bpm, weight 104 kg, and height, 1.77m. In spite of a body mass index in the obesity range (33.2), he had a large muscle mass and little adiposity.</p>
      <p>The test results showed an ECG with an extensive electrically inactive anterior area, normal chest X-ray, total cholesterol 144 mg/dl, HDL 32 mg/dl, LDL 77 mg/dl, triglycerides 176 mg/dl, fasting glucose 78 mg/dL, normal complete blood count, and creatinine 1.5 mg/dl. The echocardiogram revealed a left ventricle (LV) with dimensions at the upper limit of normalcy and a 45% ejection fraction. Segment contraction analysis showed anteroseptal, apical, and anterior akinesia. The presence of a thrombus in the LV was also noted. The patient was submitted to a coronary angiography, that identified an anterior descending artery (DA) occluded at its origin (<xref ref-type="fig" rid="en_04f1el-body2">figure 1A</xref>) with mid and distal thirds filling through discreet intracoronary collateral circulation, besides the apical thrombus and a significant increase in LV diastolic pressure. Because of the collateral circulation, angioplasty of the DA with a stent (<xref ref-type="fig" rid="en_04f1el-body2">figure 1B</xref>) was chosen. The patient progressed with no complications after the procedure.</p>
      <p content-type="asset">
        <fig id="en_04f1el-body2">
          <graphic xlink:href="1678-4170-abc-87-05-e179-00023-gf01-en.jpg"/></fig>
      </p>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>The incidence of symptomatic coronary disease and acute myocardial infarction (AMI) in young patients under the age of 40 is low - only 3% of cases occur in patients from this age group<sup>6</sup>. Epidemiological studies have shown that the most prevalent risk factors in this population are smoking and a family history of cardiovascular disease. The history taking as to the use of licit or illicit sympathomimetic drugs (cocaine, "crack") should always be very thorough in these cases, especially when no traditional risk factor for atherosclerotic disease is identified. In the case described above, the absence of risk factors and the temporal association between the use of the ephedrine-rich supplement and the occurrence of the acute event suggest a strong causal relationship.</p>
      <p>Ephedrine in its pure form and the <italic>Ma huang</italic> extract, rich in ephedrine and other alkaloids similar to ephedrine, such as pseudo-ephedrine, are the usual components of dietary supplements consumed by athletes of different sport modalities who seek a quick weight reduction and an energy boost. They are used indiscriminately, despite warnings from health agencies such as the American Medical Association,<sup>7</sup> and the fact of being considered doping by the majority of sports entities. The use of these products has been associated with several adverse cardiovascular and neurologic events.<sup>8</sup> In April 2004, the United States FDA prohibited the sale of these products and it was the first time the sale of a dietary supplement was banned. In spite of not being a greatly prevalent causal agent, the use of these supplements cannot be excluded in cases of sudden death of young athletes with no structural cardiopathy.<sup>9</sup></p>
      <p>According to data available from the manufacturer, the product used by the described patient, Therma-Pro<sup>TM</sup> has in its formula 250 mg of <italic>Ma huang</italic> extract, an equivalent to 20 mg of ephedrine. The dose the patient used, four pills a day, is twice that recommended by the manufacturer. Regardless of the dose, ephedrine is a drug that instigates the release of endogenous catecholamines stimulating a-1, b-1, and b-2 adrenergic receptors<sup>10</sup>. The effects of ephedrine are vasoconstriction and cardiac stimulation, leading to an acute rise in arterial blood pressure and heart rate, besides mydriasis, insomnia, vertigo, headaches, and anxiety. Pseudoephedrine causes bronchodilation, because of its primary action of b-2 adrenergic receptor stimulation, while its a-agonist effects are responsible for improving symptoms of nasal congestion.</p>
      <p>In the coronary circulation, ephedrine can cause vasospasms<sup>11</sup>, especially in individuals with an increased vagal tonus, as was the case of the young man described herein, since he was a physically fit athlete. In many acute coronary syndrome cases associated with the use of ephedrine in patients with normal coronary angiographies, this seems to be the possible physiopathological mechanism<sup>12</sup>. Nevertheless, <italic>in situ</italic> thrombosis may be associated<sup>13</sup> for various reasons: besides slowing the coronary flow, a spasm may cause rupture of the fibrous covering of young atherosclerotic plaques that have an extensive lipid nucleus. In patients who use drugs such as ephedrine, this happens in the presence of significant platelet activation through the sympathomimetic activity of this substance. An association between a spasm and an <italic>in situ</italic> thrombus may have occurred in the case we described, since the coronary angiography showed a complete occlusion of the anterior descending artery, but no evidence that any other vessel had been compromised.</p>
      <p>In the absence of prior thrombotic events, whether venous or arterial, and in the presence of a factor that has increasingly been recognized as a cause of acute myocardial infarction (AMI) in young patients, no thrombophilia investigation was made in this patient. Most polymorphisms of the coagulation system proteins involved with venous thrombosis present little or no association with an AMI<sup>14</sup>. In Brazil, Faria-Neto <italic>et al</italic>.<sup>15</sup> demonstrated a low prevalence and no correlation of Factor V Leiden and prothrombin G20210A and methylenetetrahydrofolate redutase C677T (involved in homocysteine metabolism) polymorphisms with the presence of coronary occlusion shown by coronary angiography.</p>
      <p>The choice of a late angioplasty of the infarction-related artery in this patient is a controversial treatment option, above all in the absence of a study on the viability of the affected area. Currently, a large study sponsored by the National Heart, Lung, and Blood Institute (NHLBI) is underway to test the hypothesis that the late opening of infarction-related arteries (3 to 28 days after the AMI) with a stent, in high-risk asymptomatic patients (LVEF &lt; 50% and proximal occlusion of a large artery), reduces composite death outcomes, non-fatal recurring infarctions, and functional class IV heart failure (average follow-up of three years)<sup>16</sup>.</p>
      <p>The description of this case alerts us as to the need to educate the community regarding the risks involved in the use of dietary supplements containing ephedrine that continue to be sold illegally on the premise of a rapid weight loss and enhanced physical performance.</p>
      <p>
        <bold>References</bold>
      </p>
      <p>
        <fn id="back-body2" fn-type="corresp">
          <p>
            <graphic xlink:href="1678-4170-abc-87-05-e179-00023-e01-en.jpg"/></p>
          <p>
            <bold>Mailing Address:</bold>
          </p>
          <p> Jos&#233; Rocha Faria Neto</p>
          <p> Rua Des. Ot&#225;vio do Amaral, 741/802</p>
          <p> 80730-400 &#150; Curitiba, PR, Brazil</p>
          <p> E-mail: </p>
          <p>
            <email xlink:href="jose.faria@pucpr.br">jose.faria@pucpr.br</email>
          </p>
        </fn>
      </p>
      <p>Manuscript received September 1, 2005; revised manuscript December 12, 2005; accepted June 1, 2006.</p>
    </body>
  </sub-article>
</article>
