{"id":3376,"date":"2021-07-11T22:44:46","date_gmt":"2021-07-11T19:44:46","guid":{"rendered":"https:\/\/geneceutica.ro\/migrena-si-deficienta-dao-1326-2\/"},"modified":"2023-03-22T15:21:29","modified_gmt":"2023-03-22T13:21:29","slug":"migrena-si-deficienta-dao-1326-2","status":"publish","type":"post","link":"https:\/\/geneceutica.ro\/en\/migrena-si-deficienta-dao-1326-2\/","title":{"rendered":"MIGRENA SI DEFICIENTA DAO (diaminoxidaza)"},"content":{"rendered":"<p style=\"text-align: left;\">Migrena este o afec\u021biune al c\u0103rei simptom principal este o durere de cap pulsatil\u0103, care, \u00een mod normal, afecteaz\u0103 doar una dintre emisfere. Este o boal\u0103 extrem de incapacitant\u0103 care produce multiple complica\u021bii celor care sufer\u0103 de aceasta afec\u021biune.<\/p>\n<p style=\"text-align: left;\">O deficien\u021b\u0103 \u00een enzima care descompune histamina, diaminooxidaz\u0103 (DAO), este una dintre cauzele patologiei. Acest articol \u00eencearc\u0103 s\u0103 aduc\u0103 pu\u021bin\u0103 lumin\u0103 asupra acestui subiect.<\/p>\n<p style=\"text-align: left;\">Migrena este a \u0219asea boal\u0103 ca prevalen\u021b\u0103 la nivel mondial; afecteaz\u0103 5-8% dintre b\u0103rba\u021bi \u0219i 15-20% dintre femei, cu un v\u00e2rf la maturitate.<\/p>\n<p style=\"text-align: left;\"><strong>\u201cCe este o migren\u0103?<\/strong><\/p>\n<p style=\"text-align: left;\"><strong>Defini\u021bie \u0219i epidemiologie<\/strong><\/p>\n<p style=\"text-align: left;\">Migrena este o afec\u021biune neurologic\u0103 complex\u0103 \u0219i frecvent\u0103 caracterizat\u0103 prin pusee de dureri de cap\u00a0 moderat-severe, incapacitante, de obicei pulsatile \u0219i unilaterale (de\u0219i pot fi bilaterale), \u00eenso\u021bite de sensibilitate la stimuli senzoriali, grea\u021b\u0103 \u0219i \/ sau v\u0103rs\u0103turi<sup>1.2<\/sup>.<\/p>\n<p style=\"text-align: left;\">Migrena este a \u0219asea cea mai r\u0103sp\u00e2ndit\u0103 boal\u0103 la nivel mondial(2); afecteaz\u0103 5-8% dintre b\u0103rba\u021bi \u0219i 15-20% dintre femei \u0219i atinge maximul la v\u00e2rsta adult. <sup>3<\/sup><\/p>\n<p style=\"text-align: left;\">\u00cen Spania prevalen\u021ba este de 12% in popula\u021bia general\u0103; afecteaz\u0103 peste 4 milioane de pacien\u021bi (80% femei) <sup>4<\/sup>.<\/p>\n<p style=\"text-align: left;\">Raportul &#8220;Global Burden of Disease Study 2017&#8221; (GBD2017) plaseaz\u0103 migrena ca a doua cauz\u0103 principal\u0103 a dizabilit\u0103\u021bii la nivel mondial<sup>5<\/sup>.<\/p>\n<p style=\"text-align: left;\"><strong>Clasificare<\/strong><\/p>\n<p style=\"text-align: left;\">\u00cen func\u021bie de num\u0103rul de atacuri lunare, se distinge migrena episodic\u0103 \u0219i migrena cronic\u0103, acestea put\u00e2nd fi cu sau f\u0103r\u0103 aur\u0103. Aura vizual\u0103 este cea mai frecvent\u0103 (apare la 90% dintre pacien\u021bi), urmat\u0103 de deficite senzoriale \u0219i motorii (furnic\u0103turi \u00eentr-o zon\u0103 mic\u0103 p\u00e2n\u0103 la o parte a corpului, a fe\u021bei \u0219i a limbii) \u0219i p\u00e2n\u0103 la tulbur\u0103ri de limbaj<sup>1<\/sup>.<\/p>\n<p style=\"text-align: left;\"><strong>Migrena episodic\u0103<\/strong> se caracterizeaz\u0103 prin dureri de cap recurente p\u00e2n\u0103 la 15 zile pe lun\u0103, clasificat\u0103 ca migren\u0103 f\u0103r\u0103 aur\u0103 sau migren\u0103 cu aur\u0103, printre alte forme (7).<\/p>\n<p style=\"text-align: left;\">Prevalen\u021ba migrenei episodice \u00een Spania este de 12% \u0219i 20-30% dintre ace\u0219ti pacien\u021bi sufer\u0103 mai mult de 4 crize anual(7).<\/p>\n<p style=\"text-align: left;\"><strong>Migrena cronic\u0103<\/strong> este definit\u0103 ca o durere de cap care apare 15 sau mai multe zile pe lun\u0103, timp de mai mult de 3 luni (cel pu\u021bin 8 zile pe lun\u0103), care prezint\u0103 oricare dintre caracteristicile cefaleei migrenoase1.<\/p>\n<ul>\n<li style=\"text-align: left;\">8% din totalul cazurilor de migren\u0103 corespund migrenei cronice, care \u00een Spania afecteaz\u0103 \u00een mod specific 2% din popula\u021bie(7).<\/li>\n<li style=\"text-align: left;\">Anual, 3% din cazurile de pacien\u021bi cu migren\u0103 episodic\u0103 se transform\u0103 \u00een migren\u0103 cronic\u0103(1).<\/li>\n<\/ul>\n<p style=\"text-align: left;\"><strong>Simptomatologie \u0219i diagnostic<\/strong><\/p>\n<p style=\"text-align: left;\">Simptomele raportate de pacient cu migren\u0103 cuprinde mai multe tipuri de dureri de cap, \u00eenso\u021bite de afec\u021biuni gastro-intestinale, cum ar fi grea\u021b\u0103, v\u0103rs\u0103turi \u0219i crampe abdominale, \u00eempreun\u0103 cu ame\u021beli, ame\u021beli sau vedere incetosata(8).<\/p>\n<p style=\"text-align: left;\">Diagnosticul clinic al migrenei se bazeaz\u0103 pe simptomele raportate de pacien\u021bi care exclud alte cauze.<\/p>\n<p style=\"text-align: left;\">Al\u0103turi de istoricul medical \u0219i revizuirea factorilor de risc, trebuie s\u0103 fie \u00eentotdeauna efectuat\u0103 o examinare general\u0103 fizic\u0103 \u0219i neurologic\u0103 complet\u01031.<\/p>\n<p style=\"text-align: left;\">\u00cen diagnosticul migrenei este dificil s\u0103 se disting\u0103 episoade de migren\u0103 de cefalee.<\/p>\n<p style=\"text-align: left;\"><strong>Managementul \u0219i tratamentul migrenei<\/strong><\/p>\n<p style=\"text-align: left;\">Terapia farmacologic\u0103 a migrenei face distinc\u021bia \u00eentre tratament simptomatic \u0219i preventiv.<\/p>\n<p style=\"text-align: left;\"><strong>Tratamentul simptomatic<\/strong> se concentreaz\u0103 pe ameliorarea durerii, iar prescrip\u021bia sa este necesar\u0103 la majoritatea pacien\u021bilor cu migren\u0103, \u00een timp ce tratamentul <strong>preventiv<\/strong> este indicat pacien\u021bilor cu atacuri de migren\u0103 recurente,\u00eentruc\u00e2t obiectivele sale includ reducerea frecven\u021bei crizelor, a duratei\u00a0 \u0219i intensitatea simptomelor.<\/p>\n<p style=\"text-align: left;\"><strong>Ce se \u00eent\u00e2mpl\u0103 \u00een migren\u0103?<\/strong><\/p>\n<p style=\"text-align: left;\">Fazele migrenei. \u00cen timpul atacului de migren\u0103, apar 4 faze stabilite temporal:<\/p>\n<ol style=\"text-align: left;\">\n<li>Faza prodromal\u0103 sau premonitorie. Precede \u00eenceputul durerii de cap cu zile, ore \u00eenainte de migren\u0103. Simptomele caracteristice \u0219i frecvente sunt: modific\u0103ri ale st\u0103rii de spirit (anxietate, depresie, iritabilitate sau euforie), sonofobie, constipa\u021bie, hiperdipsie (accentuarea senzatiei de sete) \u0219i accentuarea senzatiei de urinare, pofte alimentare, dureri de g\u00e2t, concentrare slab\u0103 \u0219i c\u0103scat frecvent.<\/li>\n<li>Faza aurei. Precede imediat sau \u00eenso\u021be\u0219te migrena. \u00cencepe treptat, dezvolt\u00e2ndu-se \u00een timp de minute p\u00e2n\u0103 la 1 or\u0103.<\/li>\n<li>Faza de cefalee sau faza de migren\u0103. De obicei dureaz\u0103 \u00eentre 4 \u0219i 72 ore, \u00een func\u021bie de fiecare persoan\u0103 \u0219i frecven\u021ba cu care se \u00eent\u00e2mpl\u0103 atacurile.<\/li>\n<li>Faza postdromic\u0103. C\u00e2nd durerea se opre\u0219te, c\u00e2teva ore sau chiar zile mai t\u00e2rziu, pot surveni simptome similare cu faza prodromal\u0103.<\/li>\n<\/ol>\n<p style=\"text-align: left;\"><strong>Mecanisme fiziopatologice<\/strong><\/p>\n<ul>\n<li style=\"text-align: left;\">Mecanismul din spatele durerii de migren\u0103 sugereaz\u0103 un rol fundamental al inflama\u021biei de origine neuronal\u0103 periferic\u0103(13). Anumi\u021bi factori externi \u0219i interni, cum ar fi stresul, modific\u0103rile hormonale sau depresia cortical\u0103 propagat\u0103, pot induce stadiul inflamator.<\/li>\n<li style=\"text-align: left;\">Unele neuropeptide, prin interac\u021biunea cu vasele de s\u00e2nge, provoac\u0103 vasodilata\u021bie, extravazare plasmatic\u0103, activarea celulelor satelite gliale \u0219i degranularea celulelor mastocitare. Mastocitele secret\u0103 mediatori pro-inflamatori \u0219i neurosensibilizatori preformati, incluz\u00e2nd urm\u0103toarele: histamina, bradikinina, serotonina, factorul de necroz\u0103 tumoral\u0103, triptaz\u0103, mediatori lipidici ai inflama\u021biei \u0219i citokinelor. Mediatorii produ\u0219i de mastocite sunt capabili s\u0103 provoace inflama\u021bii locale \u0219i reducerea pH-ului local, reduc\u00e2nd astfel pragul nociceptiv, sensibiliz\u00e2nd neuronii \u0219i, la r\u00e2ndul lor, determin\u00e2nd eliberarea mai multor neuropeptide<sup>15<\/sup>.<\/li>\n<li style=\"text-align: left;\">Migrena este rezultatul inflama\u021biei datorate\u00a0 eliber\u0103rii locale de neuropeptide, cum ar fi peptida legat\u0103 de gena calcitoninei (CGRP). Odat\u0103 eliberate, aceste neuropeptide induc eliberarea de histamin\u0103 din mastocitele adiacente.<\/li>\n<li style=\"text-align: left;\">La r\u00e2ndul s\u0103u, histamina sistemic\u0103 evoc\u0103 eliberarea de CGRP, stabilind astfel o leg\u0103tur\u0103 bidirec\u021bional\u0103 \u00eentre histamin\u0103 \u0219i neuropeptide \u00een inflama\u021bia neurogen\u0103 <sup>16<\/sup>.<\/li>\n<\/ul>\n<p style=\"text-align: left;\"><strong>Ce este histamina?<\/strong><\/p>\n<ul>\n<li style=\"text-align: left;\">Histamina a fost descoperit\u0103 ca o curiozitate chimic\u0103 \u00een 1907, de Windaus \u0219i Vogt1<sup>3<\/sup> este o monoamin\u0103 idazolic\u0103 sintetizat\u0103 din decarboxilarea aminoacidului L-histidin\u0103, catalizat\u0103 de enzima L-histidin carboxilaza<sup>17<\/sup>.<\/li>\n<li style=\"text-align: left;\">Particip\u0103 la o multitudine de mecanisme,at\u00e2t imunologice c\u00e2t \u0219i fiziologice: stimularea secre\u021biei gastrice, contrac\u021bie muscular\u0103, vasodilata\u021bie, proliferarea \/ diferen\u021bierea celulelor, dezvoltarea embrionar\u0103, procese de vindecare, permeabilitate sau imunomodulare <sup>13<\/sup>.<\/li>\n<li style=\"text-align: left;\">\u00cen acela\u0219i timp, ac\u021bioneaz\u0103 ca un neurotransmi\u021b\u0103tor \u00een sistemul nervos \u0219i regleaz\u0103 anumite func\u021bii ale corpului, cum ar fi controlul temperaturii, memoriei, trezire \/ somn \u0219i senza\u021bia de durere <sup>19<\/sup>. Histamina se g\u0103se\u0219te \u00een toate \u021besuturile corpului, \u00een principal \u00een piele, \u021besutul conjunctiv, pl\u0103m\u00e2ni \u0219i tractul gastrointestinal <sup>13<\/sup>.<\/li>\n<li style=\"text-align: left;\">Putem g\u0103si histamina \u00eentr-o mare varietate de tipuri de celule: mastocite, bazofile, celule endoteliale, celule ependimale, neuroni, celule gliale, celule dendritice, celule T, trombocite, celule cromafine suprarenale \u0219i celule asem\u0103n\u0103toare cu enterocromafinele gastrice<sup>13<\/sup>.<\/li>\n<li style=\"text-align: left;\">\u00cen sistemul nervos central (SNC), histamina este produs\u0103 de neuronii histaminergici g\u0103si\u021bi \u00een nucleul tuberomamilar, localizat \u00een partea posterioar\u0103 a hipotalamusului \u0219i care isi extind axonii prin creier<sup>13,17. <\/sup>Dup\u0103 eliberare, este catabolizat\u0103 prin histamin-N-metiltransferaz\u0103 (HNMT) sau DAO (diaminoxidaza).<\/li>\n<li style=\"text-align: left;\">Polimorfismele genetice ale enzimelor care metabolizeaz\u0103 histamina sunt responsabile pentru varia\u021bia interindividual\u0103 a metabolismului histaminic \u0219i sunt asociate cu diverse boli<sup>20<\/sup>.<\/li>\n<li style=\"text-align: left;\">\u00cen SNC, histamina este inactivat\u0103 de HNMT, care se g\u0103se\u0219te \u00een celulele epiteliale, celule hematopoietice, neuroni \u0219i celule gliale.<\/li>\n<li style=\"text-align: left;\">HNMT este exprimat\u0103 \u00een citosolul din celule, oxid\u00e2nd astfel histamina \u00een <strong>spa\u021biul intracelular<\/strong>, spre deosebire de DAO, care \u00ee\u0219i exercit\u0103 rolul prin inactivarea histaminei<strong> extracelulare<\/strong><sup>18<\/sup>.<\/li>\n<li style=\"text-align: left;\">Efectele histaminei sunt produse prin <strong>4 receptori diferi\u021bi cuplati la proteinele G (H1, H2, H3 \u0219i H4)<\/strong>, care difer\u0103 \u00eentre ei prin propriet\u0103\u021bile lor farmacologice \u0219i semnale de transduc\u021bie <sup>17<\/sup>.<\/li>\n<li style=\"text-align: left;\">Histamina, \u00een afar\u0103 de a fi sintetizat\u0103 endogen, intr\u0103 \u00een organism prin ingestia alimentelor care con\u021bin concentra\u021bii mari ale acestei amine<sup>21<\/sup>. De fapt, con\u021binutul aminelor prezente \u00een alimente (inclusiv histamin\u0103 \u0219i tiramina) a fost studiat pe scar\u0103 larg\u0103 datorit\u0103 acestor efecte poten\u021bial toxice<sup>22<\/sup>.<\/li>\n<li style=\"text-align: left;\">Histamina exogen\u0103 poate fi sintetizat\u0103 de diverse bacterii de fermenta\u021bie care efectueaz\u0103 decarboxilarea microbian\u0103 a histidinei prezente \u00een alimente <sup>21<\/sup>. Exist\u0103 multe alimente cu con\u021binut natural ridicat de histamin\u0103 (tabelul 1).<\/li>\n<\/ul>\n<p style=\"text-align: left;\"><strong>Ce este diaminooxidaza (DAO)?<\/strong><\/p>\n<ul>\n<li style=\"text-align: left;\">DAO este responsabil\u0103\u00a0pentru metabolizarea \u00een spa\u021biul extracelular de histamin\u0103 eliberat\u0103 \u0219i ingerat\u0103 prin diet\u0103<sup>18<\/sup>. Aceast\u0103 enzim\u0103 (cunoscut\u0103 \u0219i sub denumirea de histaminaz\u0103) folose\u0219te oxigen pentru degradarea histaminei<sup>24<\/sup>.<\/li>\n<li style=\"text-align: left;\">DAO este o glicoprotein\u0103 cu func\u021bionare optima la un pH de 7,22 <sup>4<\/sup>.<\/li>\n<li style=\"text-align: left;\"><strong>Gena AOC1<\/strong> uman\u0103, care codific\u0103 DAO, este localizat\u0103 pe cromozomul 7q36.1, cu un total de 10 perechi de kilobaze, care constituie 5 exoni \u0219i 4 introni <sup>24<\/sup>.<\/li>\n<li style=\"text-align: left;\">Se p\u0103streaz\u0103 \u00een structuri veziculare asociate cu membrana celulelor epiteliale \u0219i, dup\u0103 un stimul, este secretat\u0103 \u00een circula\u021bie<sup>18<\/sup>.<\/li>\n<li style=\"text-align: left;\">G\u0103sim DAO \u00een diferite \u021besuturi. S-a sugerat c\u0103 DAO poate fi implicat\u0103 \u00een reglarea diviz\u0103rii\u00a0 sau a diferen\u021bierii celulare<sup>20.\u00a0<\/sup> \u00cen acest sens, DAO este exprimatcelulare \u00een \u021besuturi cu o \u00eenalt\u0103 proliferare, cum ar fi m\u0103duva osoas\u0103 \u0219i mucoasa intestinal\u0103, unde nivelurile plasmatice ale acesteia sunt corelate pozitiv cu maturitatea \u0219i integritatea mucoasei intestinale(20). De asemenea, s-g\u0103sit \u00een placent\u0103 \u0219i rinichi \u0219i \u00een cantit\u0103\u021bi reduse \u00een circula\u021bie<sup>18<\/sup>.<\/li>\n<li style=\"text-align: left;\">Activitatea DAO este deosebit de intens\u0103\u00a0\u00een mucoasa intestinal\u0103, unde este principala enzim\u0103 responsabil\u0103 de degradarea alimentelor sau a histaminei exogene.<\/li>\n<li style=\"text-align: left;\">Activitatea DAO redus\u0103 a fost legat\u0103 de afectarea mucoasei intestinale \u00een bolile inflamatorii\u00a0 intestinale \u0219i la pacien\u021bii trata\u021bi cu chimioterapie<sup>18<\/sup>. Evaluarea nivelurilor plasmatice si \u00een mucoasa intestinal\u0103 a enzimei DAO este utilizat\u0103 pentru a determina distrugerea barierei acestei mucoase, deoarece exist\u0103 o cre\u0219tere a nivelurilor circulante \u0219i o sc\u0103dere a concentratiilor din mucoasa intestinal\u0103 consecutiv necrozei \u0219i distrugerii enterocitelor <sup>26.<\/sup><\/li>\n<\/ul>\n<p style=\"text-align: left;\"><strong>Deficien\u021b\u0103 de DAO \u0219i migrena<\/strong><\/p>\n<ul>\n<li style=\"text-align: left;\">Simptomele cauzate de deficien\u021ba de DAO sunt legate direct de activitatea sa enzimatic\u0103. Deficien\u021ba sa declan\u0219eaz\u0103 o imagine care are adesea simptome foarte similare cu cele de patologie alergic\u0103<sup>27<\/sup>.<\/li>\n<li style=\"text-align: left;\">Deficitul acestei enzime se poate datora mai multor factori. Cel mai frecvent factor este varia\u021bia alelic\u0103 \u00een gena care codific\u0103 enzima men\u021bionat\u0103 \u0219i care \u00eei scade activitatea enzimatic\u0103. De asemenea, se poate datora sc\u0103derii sintezei sau transportului \u00een spa\u021biul extracelular printr-un proces fiziopatologic sau chiar prin consumul de droguri sau alcool. Mai multe studii au sugerat c\u0103 o deficien\u021b\u0103 \u00een activitatea enzimatic\u0103, c\u00e2nd vine vorba de degradarea histaminei \u0219i evitarea\u00a0 acumul\u0103rii sale \u00een organism, este legat\u0103 de migren\u0103. \u00centr-o lucrare a lui Izquierdo-Casas et al.<sup>28<\/sup>, \u00een care au fost evaluati 137 de pacien\u021bi cu migren\u0103 \u0219i 61 de control, s-a observat\u00a0 c\u0103 activitatea total\u0103 a DAO a fost redus\u0103 la pacien\u021bii cu migren\u0103 comparativ cu grupul control. \u00cen mod specific, autorii au observat o sc\u0103dere de 87 \u0219i respectiv 44%, lu\u00e2nd valori sub 80 de unit\u0103\u021bi de degradare de histamin\u0103 (HDU) \/ ml ca referin\u021b\u0103 pentru deficien\u021ba de DAO.<\/li>\n<li style=\"text-align: left;\">\u00centr-un alt studiu, au fost analizate variante alelice at\u00e2t DAO, c\u00e2t \u0219i HNMT la femeile mexicane, mame de copii alergici, dintre care jum\u0103tate aveau \u0219i o migren\u0103. \u00cen concordan\u021b\u0103 cu lucr\u0103rile anterioare, a fost observat\u0103 o frecven\u021b\u0103 mai mare a variantelor alelice asociate cu activitatea enzimatic\u0103 mai mic\u0103 la femeile care prezentau simptome de migren\u0103 \u00een compara\u021bie cu cele f\u0103r\u0103 aceast\u0103 simptomatologie<sup>29<\/sup>.<\/li>\n<li style=\"text-align: left;\">\u00cen aceea\u0219i direc\u021bie s-a situat un studiu \u00een regiunea de nord a Indiei, \u00een care 250 de persoane cu migren\u0103 au fost analizate \u00eempreun\u0103 cu\u00a0 250 de persoane de control \u0219i s-a observat c\u0103 popula\u021bia migrenoas\u0103 a avut o frecvent\u0103 mai mare a alelor DAO relationate cu o\u00a0 activitate enzimatic\u0103 redus\u0103.\u00a0 \u00cen plus, \u00een acest studiu s-a observat asocierea acestor alele cu sexul feminin, care, dup\u0103 cum se \u0219tie, are o prevalen\u021b\u0103 mai mare de migren\u0103 <sup>30<\/sup>.<\/li>\n<li style=\"text-align: left;\">Un alt studiu a ar\u0103tat c\u0103 indivizii cu migrene au mai des variante alelice ale genei DAO care codific\u0103 proteine care prezint\u0103 mai pu\u021bin\u0103 activitate enzimatic\u0103<sup>31<\/sup>. Astfel, purt\u0103torii acestor variante alelice ale DAO ar avea niveluri mai ridicate de histamin\u0103 circulant\u0103 \u0219i mai multe probleme asociate cu un exces din aceast\u0103 amin\u0103 biogen\u0103.<\/li>\n<li style=\"text-align: left;\">Activitatea DAO \u00een plasm\u0103 este invers corelat\u0103\u00a0 cu permeabilitatea intestinului, afectat\u0103 \u0219i ea \u00een anumite boli, cum ar fi colita ulceroas\u0103, boala Crohn sau sindromul intestinului iritabil, adesea parte a comorbidit\u0103\u021bii din migren\u0103. \u00cen aceste patologii, jonc\u021biunile dintre celulele epiteliale care marginesc lumenul intestinal nu sunt impermeabile, permi\u021b\u00e2nd trecerea substan\u021belor care ar fi implicate \u00een fiziopatologie.<\/li>\n<li style=\"text-align: left;\">De-a lungul acestei linii, Honzawa \u0219i colab.<sup>32<\/sup> au analizat activitatea plasmatic\u0103 a DAO \u00eentr-un grup de pacien\u021bi cu diferite boli care afecteaz\u0103 permeabilitatea intestinal\u0103.<\/li>\n<li style=\"text-align: left;\">S-a demonstrat\u00a0 c\u0103 pacien\u021bii au prezentat o activitate DAO mai redusa dec\u00e2t cei de control s\u0103n\u0103to\u0219i \u0219i c\u0103 aceast\u0103 activitate era independent\u0103 de gravitatea patologiei pe care o aveau.<\/li>\n<\/ul>\n<p><strong>Sarcina \u0219i migrena<\/strong><\/p>\n<ul>\n<li style=\"text-align: left;\">DAO, care descompune histamina, este produs \u00een cantit\u0103\u021bi mari cantit\u0103\u021bi \u00een placent\u0103 \u0219i se presupune c\u0103 va ac\u021biona ca barier\u0103 metabolic\u0103 pentru a preveni intrarea excesiv\u0103 a histaminei bioactiv\u0103 \u00een circula\u021bia fetal\u0103 sau matern\u0103.<\/li>\n<li style=\"text-align: left;\">Unele studii arat\u0103 c\u0103 activitatea DAO este de 500-1.000 de ori mai mare \u00een stadiul de sarcin\u0103. Femeile care sufer\u0103 de migren\u0103 \u0219i alte simptome asociate cu deficien\u021ba de DAO, observ\u0103 o \u00eembun\u0103t\u0103\u021bire foarte important\u0103 \u00een timpul etapei de gesta\u021bie. Aceast\u0103 cre\u0219tere a\u00a0 DAO \u00eencepe \u00eentre a doua \u0219i a treia lun\u0103 de gesta\u021bie \u0219i multe femei descriu c\u0103 p\u00e2n\u0103 la al\u0103ptare nu mai au simptome(33).<\/li>\n<\/ul>\n<p style=\"text-align: left;\"><strong>Simptome asociate (comorbiditatea migrenei)<\/strong><\/p>\n<ul>\n<li style=\"text-align: left;\">Simptomele cauzate de deficien\u021ba de DAO sunt legate de lipsa sa de activitate enzimatic\u0103, ceea ce duce la acumularea de histamin\u0103. Acestea sunt foarte variate \u0219i\u00a0 depind de organul afectat prin receptorii specifici pentru histamin\u0103 pe care acest organ ii exprim\u0103 (figura 2 \u0219i tabelul 2)<sup> 21<\/sup>.<\/li>\n<\/ul>\n<p style=\"text-align: left;\"><strong>Diagnostic<\/strong><\/p>\n<ul>\n<li style=\"text-align: left;\">Cu c\u00e2\u021biva ani \u00een urm\u0103, singura cale de a diagnostica deficitul DAO a fost printr-o anamnez\u0103 complet\u0103 a pacientului.\u00a0 C\u00e2nd cel pu\u021bin dou\u0103 dintre simptome coincid tipic acumul\u0103rii de histamin\u0103 \u0219i pacientul prezint\u0103 \u00eembun\u0103t\u0103\u021biri dac\u0103 alimentele bogate \u00een histamin\u0103 sunt excluse din diet\u0103 sau cu un supliment DAO, se emitea\u00a0 ipoteza c\u0103 pacientul a suferit de intoleran\u021b\u0103 la histamin\u0103 din cauza deficitului de DAO. Dar \u00een zilele noastre, cu progresele clinice \u0219i \u0219tiin\u021bifice, acest deficit poate fi diagnosticat obiectiv prin variantele genetice care codific\u0103 proteina DAO (gena AOC1) \u0219i care au o capacitate mai mic\u0103 de metabolizare a histaminei.<\/li>\n<li style=\"text-align: left;\">\u00cen orice caz, este recomandabil s\u0103 evalua\u021bi al\u021bi parametri, deoarece pot exista cazuri de deficit de DAO secundar care nu s-ar reflecta \u00eentr-un astfel de test de ADN, chiar dac\u0103 aceste situa\u021bii sunt minoritare. Deficien\u021ba dob\u00e2ndit\u0103 de DAO se poate datora consumului de medicamente care blocheaz\u0103 enzima DAO, inflama\u021biei microvililor intestinali (boala celiac\u0103, boala Crohn,colit\u0103 ulceroas\u0103 \u0219i anorexie nervoas\u0103),\u00a0 interven\u021biilor chirurgicale,\u00a0 consumului de b\u0103uturi alcoolice sau\u00a0 perioada menstrual\u0103, printre al\u021bi factori.<\/li>\n<li style=\"text-align: left;\">\u00cen aceste cazuri, \u00een absen\u021ba biopsiilor DAO intestinale, se includ\u00a0 al\u021bi parametrii analitici, cum ar fi activitatea DAO \u00een plasm\u0103, histamina \u00een plasm\u0103 \u0219i histamina \u00een urin\u0103 de 24 ore.<\/li>\n<li style=\"text-align: left;\">Ar trebui exclus\u0103 posibilitatea unei mastocitoze printr-un test de triptaz\u0103 seric\u0103, precum \u0219i alergiile alimentare \u0219i \/ sau de mediu, folosind metode de diagnostic obi\u0219nuite pentru aceste cazuri.<\/li>\n<li style=\"text-align: left;\">S-a demonstrat c\u0103 utilizarea unui jurnal alimentar este util\u0103 pentru a evita consumul de alimente care provoac\u0103 apari\u021bia de simptome asociate cu deficien\u021ba de DAO.<\/li>\n<\/ul>\n<p style=\"text-align: left;\"><strong>Tratamentul migrenei cu deficit de DAO<\/strong><\/p>\n<ul>\n<li style=\"text-align: left;\">Tratamentul migrenei din cauza deficitului de DAO se bazeaz\u0103 pe reducerea sau eliminarea alimentelor bogate \u00een histamin\u0103 (tabelul 1), fie prin procese de deteriorare, cum ar fi carnea sau pe\u0219tele, prin procese de fermentare, cum ar fi br\u00e2nza sau pentru c\u0103\u00a0 \u00een mod natural con\u021bin histamin\u0103, cum ar fi spanacul,\u00a0 alimentelor bogate \u00een altele amine, cum ar fi citrice, alimentelor care elibereaz\u0103 histamina, cum ar fi albusul de ou sau laptele \u0219i, \u00een final, se limiteaz\u0103\u00a0consumul de alimente care blocheaz\u0103 enzima DAO, cum ar fi b\u0103uturile alcoolice.<\/li>\n<li style=\"text-align: left;\">O diet\u0103 \u00een care aceste tipuri de alimente sunt eliminate s-a dovedit c\u0103 \u00eembun\u0103t\u0103\u021be\u0219te migrena\u00a0 \u0219i alte simptome asociate cauzate de histamin\u0103, precum ro\u0219ea\u021b\u0103, m\u00e2nc\u0103rime, edem al mucoasei gurii, diaree sau constipa\u021bie.<\/li>\n<li style=\"text-align: left;\">\u00centr-un studiu realizat la pacien\u021bi dup\u0103 o diet\u0103 f\u0103r\u0103 histamin\u0103, s-a observat c\u0103 a crescut nivelul de DAO la 50% dintre cei care au urmat-o \u0219i c\u0103 79% au prezentat o \u00eembun\u0103t\u0103\u021bire a simptomelor asociate cu intoleran\u021ba la histamin\u0103 <sup>34<\/sup>.<\/li>\n<li style=\"text-align: left;\">Un studiu clinic a fost realizat recent cu 100 de pacien\u021bi cu migren\u0103 (clasifica\u021bi dup\u0103 criteriile Societatii interna\u021bionale de dureri de cap) \u0219i deficien\u021b\u0103 de DAO (definit ca valori &lt;80 HDU \/ ml), \u00een care placebo sau un supliment DAO au fost administrate aleatoriu \u00een tablete. Durata migrenei a sc\u0103zut semnificativ, iar tratamentul cu DAO a ar\u0103tat rezultate pozitive(35).<\/li>\n<li style=\"text-align: left;\">Aceste date au fost coroborate cu o lucrare ulterioar\u0103 efectuat\u0103 pe 212 de pacien\u021bi care au fost diagnosticati cu migren\u0103 \u0219i deficien\u021b\u0103 de DAO.<\/li>\n<li style=\"text-align: left;\">S-a prescris o diet\u0103 f\u0103r\u0103 histamin\u0103 timp de 3 luni \u0219i un supliment DAO a fost administrat \u00eenainte de micul dejun, pr\u00e2nz \u0219i cin\u0103. Dup\u0103 3 luni de tratament, 34,9% dintre pacien\u021bi au raportat o remisie complet\u0103 a simptomelor, iar 35,8% au avut mai pu\u021bine atacuri \u0219i o durat\u0103 \u0219i intensitate mai scurt\u0103 pe lun\u0103. 29,3% dintre pacien\u021bi nu au prezentat \u00eembun\u0103t\u0103\u021biri semnificative. \u00cen medie, reducerile au fost semnificative, at\u00e2t \u00een ceea ce prive\u0219te num\u0103rul de atacuri(de la 8 la 2 pe lun\u0103) ca si durata (de la 24 la 3 ore) \u0219i intensitatea (de la 8\u00a0 la 4 pe scara durerii) <sup>23<\/sup>.<\/li>\n<li style=\"text-align: left;\">\u00centr-un alt studiu efectuat pe 28 de pacien\u021bi diagnostica\u021bi cu intoleran\u021b\u0103 la histamin\u0103, un supliment DAO a fost prescris \u00eenainte de mese timp de 4 s\u0103pt\u0103m\u00e2ni \u0219i ulterior a fost indicat s\u0103 nu se ia suplimentul \u00een perioada de urm\u0103rire.<\/li>\n<li style=\"text-align: left;\">Pacien\u021bii trebuiau sa completeze un chestionar care a inclus 22 de simptome caracteristice intoleran\u021bei la histamin\u0103. S-a observat c\u0103 simptomele (inclusiv migren\u0103) s-au remis \u00een perioada \u00een care au luat DAO \u0219i au crescut \u00een perioada de urm\u0103rire, c\u00e2nd nu au luat-o (36).<\/li>\n<li style=\"text-align: left;\">\u00centr-un studiu care a analizat retrospectiv 14 pacien\u021bi cu un diagnostic negativ pentru alergia alimentar\u0103 mediat\u0103 de IgE, boala celiac\u0103, hipersecre\u021bia gastric\u0103 \u0219i hipersensibilitatea la nichel, \u0219i care au urmat anterior o diet\u0103 de restric\u021bie alimentar\u0103 cu histamin\u0103, s-a constatat o \u00eembun\u0103t\u0103\u021bire a simptomatologiei. La pacien\u021bii la care suplimentarea cu DAO a fost asociat\u0103 cu restric\u021bia alimentelor care con\u021bin histamin\u0103, s-a observat o \u00eembun\u0103t\u0103\u021bire \u00een cel pu\u021bin unul dintre simptome \u0219i \u00een calitatea vie\u021bii(37).<\/li>\n<\/ul>\n<p style=\"text-align: left;\"><strong>Cum s\u0103 gestiona\u021bi migrena din cauza deficien\u021bei de DAO\u00a0<\/strong><\/p>\n<ul>\n<li style=\"text-align: left;\">Deficitul de DAO determin\u0103 acumularea de histamin\u0103 exogen\u0103 sau dietetic\u0103 \u0219i declan\u0219eaz\u0103 migren\u0103 datorat\u0103 efectului inflamator \u0219i vasodilatator din aceast\u0103 amin\u0103. Cum deja s-a men\u021bionat mai sus, deficien\u021b\u0103 de DAO poate fi rezultatul polimorfismelor genetice din gena AOC1 pentru proteina DAO, sau al reducerii sau bloc\u0103rii enzimei DAO din cauze dob\u00e2ndite ( medicamente, boli inflamatorii ale intestinului, rezec\u021bie a intestinului sub\u021bire, menstrua\u021bie etc.) <sup>21,31<\/sup>.<\/li>\n<li style=\"text-align: left;\">Detectarea deficien\u021bei de DAO \u00een popula\u021bie poate fi de mare ajutor pacien\u021bilor diagnostica\u021bi cu migren\u0103, urticarie cronic\u0103, eczeme atopice, boli\u00a0 inflamatorii intestinale sau fibromialgie<sup>28,35<\/sup>. <strong>Concret, 15% din popula\u021bie sufer\u0103 de deficien\u021b\u0103 de DAO: 20% din cei afectati au 1 sau 2 simptome, 41,3% 3 sau 4 si 33,8% mai mult de 5<\/strong>. Rolul medicului, farmacistului, nutritionistului sau asistentului medical\u00a0 este de mare valoare \u00een detectarea deficien\u021bei de DAO, deoarece poate suspecta c\u0103 pacientul sufer\u0103 de aceasta dac\u0103 se identific\u0103 diferite simptome dup\u0103 punerea unei serii de \u00eentreb\u0103ri (Tabelul 3). Pentru a determina dac\u0103 pacientul are o deficien\u021b\u0103 de DAO, o serie de teste pot fi efectuate pentru a colecta dovezi\u00a0 bazate pe parametrii de baz\u0103 ai diagnosticului (tabelul 3).<\/li>\n<li style=\"text-align: left;\">Medicii pot, de asemenea, recomanda testul genetic molecular al activit\u0103\u021bii acestei enzime, DAO<sup>38<\/sup>.<\/li>\n<li style=\"text-align: left;\">Acest test este u\u0219or de efectuat, deoarece nu este invaziv: se ia proba de saliv\u0103 (din mucoasa bucal\u0103 cu un tampon) \u0219i este trimis\u0103 la laborator, unde se efectueaz\u0103 genotiparea de sensibilitate ridicat\u0103 a celor mai relevante variante ale genei AOC1 (Tabelul 3). Apoi se ob\u021bine raportul , \u00een care sunt precizate variantele \u0219i interpretarea fenotipic\u0103 a activitatii DAO reduse<sup>38<\/sup>.<\/li>\n<li style=\"text-align: left;\">\u00cen cazul \u00een care pacientul prezint\u0103 deficien\u021b\u0103 de enzima DAO, farmacistul\/ medicul poate recomanda tratamente pentru a reduce efectele histaminei, cum ar fi suplimentarea dietetic\u0103 cu DAO (Tabelul 3) sau trimiterea la nutri\u021bionist pentru elaborarea de diete specifice, s\u0103n\u0103toase \u0219i cu histamin\u0103 sc\u0103zut\u0103, deoarece dietele prea restrictive f\u0103r\u0103 \u00eendrumare profesional\u0103 pot duce la alte deficien\u021be nutritive.<\/li>\n<\/ul>\n<p style=\"text-align: left;\"><strong>Suplimentarea DAO la pacient cu migren\u0103: alimente \u00een scopuri medicale speciale<\/strong><\/p>\n<ul>\n<li style=\"text-align: left;\">Alimentele pentru scopuri medicale speciale sunt destinate s\u0103 satisfac\u0103 total sau par\u021bial nevoile nutritionale ale pacien\u021bilor a c\u0103ror capacitate de a ingera, digera, absorbi, metaboliza sau excreta alimentele normale sau anumi\u021bi nutrien\u021bi sau metaboli\u021bi ai acestora este limitata, deficitara sau modificata sau care necesit\u0103 alte substan\u021be nutritive determinate clinic, deoarece tratamentul alimentar nu poate fi efectuat doar prin modificarea dietei normale, ci necesita alte alimente destinate unei diete speciale\u00a0 sau ambele39.<\/li>\n<li style=\"text-align: left;\">Administrarea de DAO oral este o strategie cheie \u00een managementul alimentar al migrenei \u0219i altor patologii asociate cu deficien\u021ba acestei enzime, deoarece histamina este prezenta \u00eentr-o masura variabila \u00een multe alimente din dieta obi\u0219nuit\u0103 \u0219i pentru un pacient cu deficit de DAO este foarte dificil s\u0103 suprime alimentele cu histamin\u0103 deoarece con\u021binutul de histamin\u0103 nu este specificat \u00een mod normal de c\u0103tre produc\u0103tori. Alimentele destinate utiliz\u0103rilor medicale speciale care con\u021bin DAO \u00eempiedic\u0103 absorb\u021bia sistemic\u0103 a histaminei exogene, oferind pacientului cantitatea necesar\u0103 de DAO care completeaz\u0103 propria enzim\u0103 a organismului, \u00eent\u0103rind capacitatea de degradare a histaminei alimentare local \u00een intestinul sub\u021bire \u0219i recuperarea echilibrului natural intre\u00a0 histamina \u0219i DAO, reduc\u00e2nd astfel simptomele patologiilor concomitente(35).<\/li>\n<\/ul>\n<p><strong>\u00a0<\/strong><\/p>\n<p><strong>3. Instrumente pentru diagnosticul, depistarea \u0219i tratamentul deficien\u021bei de DAO la farmacie\/ cabinet medical<\/strong><\/p>\n<p style=\"text-align: left;\"><strong>\u00centreb\u0103ri cheie pentru diagnosticul deficien\u021bei de DAO suspectate<\/strong><\/p>\n<ul style=\"text-align: left;\">\n<li>Suferi\u021bi de atacuri de migren\u0103 sau dureri de cap cel pu\u021bin de dou\u0103 ori pe lun\u0103?<\/li>\n<li>Ave\u021bi uneori constipa\u021bie \u0219i \/ sau diaree f\u0103r\u0103 s\u0103 \u0219ti\u021bi cauza?<\/li>\n<li>Ave\u021bi senza\u021bia de balonare, flatulen\u021b\u0103, dureri sau dureri sau digestie grea dup\u0103 mese?<\/li>\n<li>Te doare spatele, ai dureri musculare \u0219i \/ sau articulare sau contracturi?<\/li>\n<li>E\u0219ti foarte obosit \u0219i nu \u0219tii de ce?<\/li>\n<li>A\u021bi fost vreodat\u0103 suspectat sau diagnosticat cu fibromialgie?<\/li>\n<li>Ave\u021bi pielea uscat\u0103, devine ro\u0219ie \u00een anumite ocazii, ave\u021bi adesea ro\u0219ea\u021b\u0103, cosuri sau erup\u021bii sau vi s-a spus vreodat\u0103 c\u0103 ave\u021bi piele atopic\u0103?<\/li>\n<li>Dac\u0103 pacientul este un copil, a fost suspectat sau diagnosticat cu ADHD?<\/li>\n<\/ul>\n<p>#Parametri de baz\u0103 pentru diagnosticul deficien\u021bei de DAO<\/p>\n<p><strong>Variante alelice ale <a href=\"http:\/\/eneceutica.ro\/deficienta-dao\/diagnosticul-deficientei-de-dao\/\" target=\"_blank\" rel=\"noopener\">genei DAO<\/a> asociate cu un deficit de activitate: <\/strong><\/p>\n<ul>\n<li>rs10156191<\/li>\n<li>rs1049742<\/li>\n<li>rs1049793<\/li>\n<li>rs2052129<\/li>\n<\/ul>\n<p><strong>#Tratamentul deficien\u021bei de DAO<\/strong><\/p>\n<ul>\n<li>Dieta sc\u0103zut\u0103 \u00een <a href=\"https:\/\/geneceutica.ro\/en\/1223-2\/\">alimentele cu histamin\u0103<\/a><\/li>\n<li>Suplimentarea enzimei <a href=\"https:\/\/geneceutica.ro\/en\/product\/daohead\/\">DAO<\/a><\/li>\n<\/ul>\n<p>DAO: diamin oxidaza;<\/p>\n<p>ADHD: tulburare de hiperactivitate cu deficit de aten\u021bie.<\/p>\n<p><strong>#Tabelul 2.<\/strong> Simptomele cauzate de deficitul DAO. Comorbiditatea migrenei<\/p>\n<p>Adaptat de la Maintz \u0219i Novak18.<\/p>\n<table>\n<tbody>\n<tr>\n<td width=\"301\">Sistem<\/td>\n<td width=\"301\">Simptomatologie caracteristica<\/td>\n<\/tr>\n<tr>\n<td width=\"301\">Sistem nervos central<\/td>\n<td width=\"301\">Migren\u0103, dureri de cap, mahmureal\u0103, ame\u021beli,tulburare de deficit de aten\u021bie \u0219i hiperactivitate, vertij, insomnie<\/td>\n<\/tr>\n<tr>\n<td width=\"301\">Sistem digestiv<\/td>\n<td width=\"301\">Sindromul colonului iritabil,constipa\u021bie, sa\u021bietate, durere stomac, v\u0103rs\u0103turi, balonare abdominala<\/p>\n<p>&nbsp;<\/td>\n<\/tr>\n<tr>\n<td width=\"301\">Piele<\/td>\n<td width=\"301\">Urticarie cutanat\u0103, atopie, psoriazis<\/p>\n<p>&nbsp;<\/td>\n<\/tr>\n<tr>\n<td width=\"301\">Sistem muscular<\/td>\n<td width=\"301\">Fibromialgia sistemului muscular, durerile musculare,astenie<\/p>\n<p>&nbsp;<\/td>\n<\/tr>\n<tr>\n<td width=\"301\">Sistem scheletic<\/td>\n<td width=\"301\">Dureri osteopatice<\/td>\n<\/tr>\n<tr>\n<td width=\"301\">Sistem cardiovascular<\/td>\n<td width=\"301\">Hipotensiune, hipertensiune \u0219i aritmii cardiovasculare<\/p>\n<p>&nbsp;<\/td>\n<\/tr>\n<tr>\n<td width=\"301\">Aparat respirator<\/td>\n<td width=\"301\">Rinoreea, astmul<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>&nbsp;<\/p>\n<p><strong>#Tabelul 1.<\/strong> Alimente care determina un con\u021binut ridicat de histamina<\/p>\n<p>Adaptat de la Duelo et al.23.<\/p>\n<table>\n<tbody>\n<tr>\n<td width=\"301\">Bauturi alcoolice fermentate<\/p>\n<p>&nbsp;<\/td>\n<td width=\"301\">Bere, vin spumant, vin<\/p>\n<p>&nbsp;<\/td>\n<\/tr>\n<tr>\n<td width=\"301\">Produse lactate<\/td>\n<td width=\"301\">Lapte, iaurt, br\u00e2nz\u0103 \u00eemb\u0103tr\u00e2nit\u0103, smantana<\/td>\n<\/tr>\n<tr>\n<td width=\"301\">Carne prelucrata<\/td>\n<td width=\"301\">Carnati fermentati sunca, chorizo, salamuri<\/td>\n<\/tr>\n<tr>\n<td width=\"301\">Substante grase<\/td>\n<td width=\"301\">Ciocolata<\/td>\n<\/tr>\n<tr>\n<td width=\"301\">Oua<\/td>\n<td width=\"301\">Albus de ou<\/td>\n<\/tr>\n<tr>\n<td width=\"301\">Pe\u0219te gras (proasp\u0103t<\/p>\n<p>\u0219i conserve) \u0219i fructe de mare<\/td>\n<td width=\"301\">Somon, ton, sardine, midii<\/td>\n<\/tr>\n<tr>\n<td width=\"301\">Legume, leguminoase<\/p>\n<p>\u0219i fructe<\/p>\n<p>&nbsp;<\/td>\n<td width=\"301\">Spanac, tomate, vinete,<\/p>\n<p>dovleac, dovlecel, varz\u0103,<\/p>\n<p>avocado, citrice, banane, kiwi,<\/p>\n<p>c\u0103p\u0219uni, ananas, nuci \u0219i deriva\u021be<\/p>\n<p>soia fermentat\u0103<\/p>\n<p>&nbsp;<\/td>\n<\/tr>\n<tr>\n<td width=\"301\"><\/td>\n<td width=\"301\"><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>&nbsp;<\/p>\n<p>Bibliografie<\/p>\n<ol>\n<li>Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3.\u00aa ed. Cephalalgia. 2018; 38: 1-211.<\/li>\n<li>GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet (Lond). 2017; 390: 1.211-1.259. Tabla<\/li>\n<li>Kahriman A, Zhu S. Migraine and tension-type headache. Semin Neurol. 2018; 38: 608-618.<\/li>\n<li>Matias-Guiu J, Porta-Etessam J, Mateos V, D\u00edaz-Insa S, L\u00f3pez-Gil A, Fern\u00e1ndez C; Scientific Committee of the PALM Program. One-year prevalence of migraine in Spain: a nationwide population-based survey. Cephalalgia. 2011; 31: 463-470.<\/li>\n<li>GBD 2016 Headache Collaborators. Global, regional, and national burden of migraine and tension-type headache, 1990- 2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018; 17: 954-976.<\/li>\n<li>Linde M, Gustavsson A, Stovner LJ, Steiner TJ, Barr\u00e9 J, Katsarava Z, et al. The cost of headache disorders in Europe: the Eurolight project. Eur J Neurol. 2012; 19: 703-711.<\/li>\n<li>Gonz\u00e1lez Oria C, Jurado Cobo CM, Viguera Romero FJ; Grupo de Estudio de Cefaleas de la Sociedad Andaluza de Neurolog\u00eda (SANCE). Gu\u00eda Oficial de Cefaleas 2019.<\/li>\n<li>Charles A. The pathophysiology of migraine: implications for clinical management. Lancet Neurol. 2018; 17: 174-182.<\/li>\n<li>Ezpeleta D, Pozo Rosich, eds. Gu\u00edas diagn\u00f3sticas y terap\u00e9uticas de la Sociedad Espa\u00f1ola de Neurolog\u00eda 2015. 3. Gu\u00eda oficial de pr\u00e1ctica cl\u00ednica en cefaleas. Madrid: Luz\u00e1n; 2015.<\/li>\n<li>Burstein R, Noseda R, Borsook D. Migraine: multiple processes, complex pathophysiology. J Neurosci. 2015; 35: 6.619-6.629.<\/li>\n<li>Charles A. The evolution of a migraine attack: a review of recent evidence. Headache. 2013; 53: 413-419.<\/li>\n<li>Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev. 2017; 97: 553-622.<\/li>\n<li>Yuan H, Silberstein SD. Histamine and migraine. Headache. 2018; 58: 184-193.<\/li>\n<li>Ramachandran R. Neurogenic inflammation and its role in migraine. Semin Immunopathol. 2018; 40: 301-314.<\/li>\n<li>Theoharides TC, Tsilioni I, Bawazeer M. Mast cells, neuroinflammation and pain in fibromyalgia syndrome. Front Cell Neurosci. 2019; 13: 1-8.<\/li>\n<\/ol>\n<ol start=\"16\">\n<li>Richardson JD, Vasko MR. Cellular mechanisms of neurogenic inflammation. J Pharmacol Exp Ther. 2002; 302: 839-845.<\/li>\n<li>.Worm J, Falkenberg K, Olesen J. Histamine and migraine revisited: mechanisms and possible drug targets. J Headache Pain. 2019; 20: 1-12.<\/li>\n<li>Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr. 2007; 85: 1.185-1.196.<\/li>\n<li>Obara I, Telezhkin V, Alrashdi I, Chazot PL. Histamine, histamine receptors, and neuropathic pain relief. Br J Pharmacol. 2019 [DOI: 10.1111\/bph.14696].<\/li>\n<li>Mart\u00ednez C, Ag\u00fandez JAG. Histamine pharmacogenomics. Pharmacogenomics. 2009; 10: 867-883.<\/li>\n<li>Kovacova-Hanuskova E, Buday T, Gavliakova S, Plevkova J. Histamine, histamine intoxication and intolerance. Allergol Immunopathol (Madr). 2015; 43: 498-506.<\/li>\n<li>San Mauro Martin I, Brachero S, Garicano Vilar E. Histamine intolerance and dietary management: a complete review. Allergol Immunopathol (Madr). 2016; 44: 475-483.<\/li>\n<\/ol>\n<ol start=\"21\">\n<li>Duelo A, Berbel M, Mantecon-Laviguerie H, Comas-Bast\u00e9 O, Latorre-Moratalla ML, Veciana-Nogu\u00e8s MT, et al. Low-histamine diet supplemented with exogenous diamine oxidase enzyme is useful for treating migraine in patients with dao deficiency. Ann Nutr Metab. 2018; 73 Supl 2: 1-93.<\/li>\n<li>Schwelberger HG, Feurle J, Houen G. Mapping of the binding sites of human diamine oxidase (DAO) monoclonal antibodies. Inflamm Res. 2018; 67: 245-253.<\/li>\n<\/ol>\n<p>25.Wolvekamp MC, De Bruin RW. Diamine oxidase: an overview of historical, biochemical and functional aspects. Dig Dis. 1994; 12: 2-14.<\/p>\n<ol start=\"26\">\n<li>Cai J, Chen H, Weng M, Jiang S, Gao J. Diagnostic and clinical significance of serum levels of D-lactate and diamine oxidase in patients with Crohn\u2019s disease. Gastroenterol Res Pract. 2019 [DOI: 10.1155\/2019\/8536952].<\/li>\n<li>Mu\u0161ic E, Koro\u0161ec P, \u0160ilar M, Adami K, Ko\u0161nik M, Rijavec M. Serum diamine oxidase activity as a diagnostic test for histamine intolerance. Wien Klin Wochenschr. 2013; 125: 239-243.<\/li>\n<\/ol>\n<ol start=\"28\">\n<li>Izquierdo-Casas J, Comas-Bast\u00e9 O, Latorre-Moratalla ML, Lorente-Gasc\u00f3n M, Duelo A, Vidal-Carou MC, et al. Low serum diamine oxidase (DAO) activity levels in patients with migraine. J Physiol Biochem. 2018; 74: 93-99.<\/li>\n<li>Meza-Vel\u00e1zquez R, L\u00f3pez-M\u00e1rquez F, Espinosa-Padilla S, Rivera-Guillen M, \u00c1vila-Hern\u00e1ndez J, Rosales-Gonz\u00e1lez M, et al. Asociaci\u00f3n de polimorfismos de diaminoxidasa e histamina N-metiltransferasa con la presencia, discapacidad y severidad de migra\u00f1a en un grupo de madres mexicanas de ni\u00f1os al\u00e9rgicos. Neurolog\u00eda. 2017; 32: 500-507.<\/li>\n<\/ol>\n<ol start=\"30\">\n<li>Kaur S, Arif A, Siahbalaei Y, Ahmad U, Nargis F, Pandey AK, et al. Association of diamine oxidase (DAO) variants with the risk for migraine from North Indian population. Meta Gene. 2019 [DOI: 10.1016\/j.mgene.2019.100619].<\/li>\n<li>Garc\u00eda-Mart\u00edn E, Mart\u00ednez C, Serrador M, Alonso-Navarro H, Ayuso P, Navacerrada F, et al. Diamine oxidase rs10156191 and rs2052129 variants are associated with the risk for migraine. Headache. 2015; 55: 276-286.<\/li>\n<li>Honzawa Y, Nakase H, Matsuura M, Chiba T. Clinical significance of serum diamine oxidase activity in inflammatory bowel disease: importance of evaluation of small intestinal permeability. Inflamm Bowel Dis. 2011; 17: 23E-25E.<\/li>\n<li>Maintz L, Schwarzer V, Bieber T, Van der Ven K, Novak N. Effects of histamine and diamine oxidase activities on pregnancy: a critical review. Human Reprod Update. 2008; 14: 485-495. 34.Lackner S, Malcher V, Enko D, Mangge H, Holasek SJ, Schnedl WJ. Histamine-reduced diet and increase of serum diamine oxidase correlating to diet compliance in histamine intolerance. Eur J Clin Nutr. 2019; 73: 102-104.<\/li>\n<\/ol>\n<ol start=\"35\">\n<li>Izquierdo-Casas J, Comas-Bast\u00e9 O, Latorre-Moratalla ML, Lorente-Gasc\u00f3n M, Duelo A, Soler-Singla L, et al. Diamine oxidase (DAO) supplement reduces headache in episodic migraine patients with DAO deficiency: a randomized doubleblind trial. Clin Nutr. 2019; 38: 152-158.<\/li>\n<li>Schnedl WJ, Schenk M, Lackner S, Enko D, Mangge H, Forster F. Diamine oxidase supplementation improves symptoms in patients with histamine intolerance. Food Sci Biotechnol. 2019; 28: 1.779-1.784.<\/li>\n<li>Manzotti G, Breda D, Di Gioacchino M, Burastero SE. Serum diamine oxidase activity in patients with histamine intolerance. Int J Immunopathol Pharmacol. 2016; 29: 105-111.<\/li>\n<\/ol>\n<ol start=\"38\">\n<li>An\u00e1lisis del Estudio gen\u00e9tico molecular de d\u00e9ficit de diaminoxidasa (DAO). Majadahonda (Madrid), 1-2 (2015). 39. Aecosan. Alimentos para usos m\u00e9dicos especiales. Disponible en: http:\/\/www.aecosan.msssi.g<\/li>\n<li>Dr Healthcare https:\/\/dr-healthcare.com\/evidencia-cientifica-y-clinica-en-deficit-de-dao\/<\/li>\n<\/ol>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Migrena este o afec\u021biune al c\u0103rei simptom principal este o durere de cap pulsatil\u0103, care, \u00een mod normal, afecteaz\u0103 doar una dintre emisfere. Este o boal\u0103 extrem de incapacitant\u0103 care produce multiple complica\u021bii celor care sufer\u0103 de aceasta afec\u021biune. O deficien\u021b\u0103 \u00een enzima care descompune histamina, diaminooxidaz\u0103 (DAO), este una dintre cauzele patologiei. Acest articol [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":2825,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[191,128],"tags":[157,131,149,158],"_links":{"self":[{"href":"https:\/\/geneceutica.ro\/en\/wp-json\/wp\/v2\/posts\/3376"}],"collection":[{"href":"https:\/\/geneceutica.ro\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/geneceutica.ro\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/geneceutica.ro\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/geneceutica.ro\/en\/wp-json\/wp\/v2\/comments?post=3376"}],"version-history":[{"count":0,"href":"https:\/\/geneceutica.ro\/en\/wp-json\/wp\/v2\/posts\/3376\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/geneceutica.ro\/en\/wp-json\/wp\/v2\/media\/2825"}],"wp:attachment":[{"href":"https:\/\/geneceutica.ro\/en\/wp-json\/wp\/v2\/media?parent=3376"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/geneceutica.ro\/en\/wp-json\/wp\/v2\/categories?post=3376"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/geneceutica.ro\/en\/wp-json\/wp\/v2\/tags?post=3376"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}