{"id":10277,"date":"2020-04-23T04:01:41","date_gmt":"2020-04-23T01:01:41","guid":{"rendered":"https:\/\/www.synevo.ro\/product\/fosfataza-alcalina-izoenzime\/"},"modified":"2025-01-31T14:24:00","modified_gmt":"2025-01-31T12:24:00","slug":"fosfataza-alcalina-izoenzime","status":"publish","type":"product","link":"https:\/\/old.synevo.md\/ru\/shop\/fosfataza-alcalina-izoenzime\/","title":{"rendered":"\u0418\u0437\u043e\u0444\u0435\u0440\u043c\u0435\u043d\u0442\u044b \u0449\u0435\u043b\u043e\u0447\u043d\u043e\u0439 \u0444\u043e\u0441\u0444\u0430\u0442\u0430\u0437\u044b (\u0429\u0424)"},"content":{"rendered":"<p style=\"text-align: justify;\"><strong><em>\u041e\u0431\u0449\u0430\u044f \u0438\u043d\u0444\u043e\u0440\u043c\u0430\u0446\u0438\u044f<\/em><\/strong><\/p>\n<p style=\"text-align: justify;\">Fosfataza alcalin\u0103 (ALP) este o enzim\u0103 ce face parte din clasa hidrolazelor (ortofosfomonoesterfosfohidrolaza). Serul uman con\u0163ine un amestec variabil de izoenzime ale fosfatazei alcaline (ALP) provenite \u00een principal din ficat, intestin, rinichi \u015fi os, la care se adaug\u0103\u00a0\u00een timpul sarcinii o form\u0103 tranzitorie, form\u0103 placentar\u0103. Anumite tumori maligne pot, de asemenea, produce o izoenzim\u0103 ALP<sup>7<\/sup>.<\/p>\n<p style=\"text-align: justify;\">De\u015fi se poate face o evaluare rezonabil\u0103 \u00een privin\u0163a originii hepatice sau non-hepatice a cre\u015fterii fosfatazei alcaline, utiliz\u00e2nd doar date clinice, exist\u0103 \u015fi metode biochimice ce pot face diferen\u0163ierea \u00eentre izoenzime<sup>1;3<\/sup>.<\/p>\n<p style=\"text-align: justify;\">Cea mai frecvent\u0103 cauz\u0103 de cre\u015ftere a nivelului seric de ALP total este determinat\u0103 de cre\u015fterea valorii plasmatice a <em>izoenzimei hepatice<\/em>. Aceasta cre\u015fte \u00een s\u00e2nge la \u00eenceputul bolilor hepatice \u00eenainte ca celelalte teste func\u0163ionale s\u0103 fie modificate. Hepatita acut\u0103, ciroza, steatoza, afec\u0163iunile hepatice induse de medicamente sau alte toxice, obstruc\u0163ia fluxului biliar determinat\u0103 de carcinomul de cap de pancreas, strictura canalelor biliare, ciroza biliar\u0103 primar\u0103 \u015fi carcinomul metastatic hepatic determin\u0103 cre\u015fterea concentra\u0163iei plasmatice a izoenzimei hepatice a ALP<sup>4<\/sup>. Sunt descrise mai multe izoforme hepatice<sup>5<\/sup>.<\/p>\n<p style=\"text-align: justify;\"><em>Fosfataza alcalin\u0103 de origine osoas\u0103<\/em> \u2013 ostaza \u2013 este o glicoprotein\u0103 tetrameric\u0103 care se g\u0103se\u015fte pe suprafa\u0163a osteoblastului \u015fi intervine \u00een calcificarea matricei osoase, fiind cunoscut\u0103 ca un indicator sensibil \u015fi fidel al metabolismului osos.\u00a0Are un timp de \u00eenjum\u0103t\u0103\u0163ire lung, nu este afectat\u0103 de clearance-ul renal \u015fi nu prezint\u0103 varia\u0163ii diurne<sup>5<\/sup>.<\/p>\n<p style=\"text-align: justify;\">Un nivel ridicat al izoenzimei osoase este \u00eent\u00e2lnit\u00a0\u00een perioada de cre\u015ftere osoas\u0103,\u00a0\u00een cursul procesului de vindecare a fracturilor, c\u00e2t \u015fi\u00a0\u00een afec\u0163iuni ale sistemului osos caracterizate prin hiperactivitate osteoblastic\u0103 \u015fi remodelare osoas\u0103 cum ar fi boala Paget, rahitism, osteomalacie, acromegalie, osteosarcom, sarcom Ewing, metastaze osoase (\u00een special asociate cu carcinom prostatic \u015fi mamar)<sup>4;5;6<\/sup>.<\/p>\n<p style=\"text-align: justify;\">\u00cempreun\u0103 cu ceilal\u0163i markeri de formare sau resorb\u0163ie osoas\u0103, ostaza poate fi utilizat\u0103 \u00een monitorizarea tratamentului antiresorbtiv la femeile cu osteoporoz\u0103 aflate\u00a0\u00een perioada post-menopauz\u0103<sup>6<\/sup>.<\/p>\n<p style=\"text-align: justify;\"><em>Fosfataza alcalin\u0103 intestinal\u0103<\/em> este produs\u0103 la nivelul enterocitelor, este eliberat\u0103 \u00een s\u00e2nge\u00a0\u00een cantit\u0103\u0163i mari,\u00a0\u00een special de persoanele cu grup sanguin B(III) sau O(I), dar este rapid metabolizat\u0103 de ficat. \u00cen condi\u0163ii patologice, cum ar fi: perfora\u0163ia intestinului, afec\u0163iuni ulcerative ale tractului gastrointestinal (stomac, intestin sub\u0163ire \u015fi gros), infarctul acut de intestin \u015fi bolile hepatice (ciroz\u0103, ca urmare a sc\u0103derii metaboliz\u0103rii) concentra\u0163ia seric\u0103 a izoenzimei intestinale cre\u015fte<sup>4<\/sup>.<\/p>\n<p style=\"text-align: justify;\"><em>Forma placentar\u0103<\/em> <em>a ALP<\/em> devine detectabil\u0103 \u00een ser \u00eencep\u00e2nd cu s\u0103pt\u0103m\u00e2na a 16-a de sarcin\u0103. Ocazional tumorile (\u00een special tumorile urologice sau gonadale) pot produce o fosfataz\u0103 alcalin\u0103 identic\u0103 sau similar\u0103 cu forma placentar\u0103 (<em>izoenzimele Regan si Nagao<\/em>) ce determin\u0103 o cre\u015ftere a ALP total \u00een absen\u0163a metastazelor<sup>1;<\/sup><sup>5<\/sup>.<\/p>\n<p style=\"text-align: justify;\"><em>Forma cu mas\u0103 molecular\u0103<\/em> <em>mare<\/em> este fie un complex multienzimatic membranar, fie un complex format din izoenzima hepatic\u0103 \u015fi lipoproteina X (\u201efast liver\u201d ALP). Aceast\u0103 form\u0103 apare \u00een afec\u0163iunile colestatice sau metastatice hepatice, chiar \u015fi atunci c\u00e2nd valorile plasmatice ale ALP sunt normale.<\/p>\n<p style=\"text-align: justify;\"><em>Forma Kasahara a ALP<\/em> este un heterodimer format din forma placentar\u0103 \u015fi intestinal\u0103 a enzimei, care se \u00eent\u00e2lne\u015fte\u00a0\u00een carcinoamele hepatocelulare sau renale<sup>5<\/sup>.<\/p>\n<p style=\"text-align: justify;\"><strong><em>Recomand\u0103ri pentru determinarea izoenzimelor fosfatazei alcaline<\/em><\/strong><\/p>\n<ul style=\"text-align: justify;\">\n<li>Diagnosticul \u015fi monitorizarea tratamentului bolilor hepatice, osoase, intestinale \u015fi paratiroidiene;<\/li>\n<li>Determinarea sursei activit\u0103\u0163ii crescute a fosfatazei alcaline (ALP) \u00een ser;<\/li>\n<li>Diagnosticul diferen\u0163ial al afec\u0163iunilor hepatice \u015fi osoase<sup>1;4;6<\/sup>.<\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><strong><em>Preg\u0103tire pacient<\/em><\/strong> \u2013 \u00e0 jeun (pe nem\u00e2ncate)<sup>3<\/sup>.<\/p>\n<p style=\"text-align: justify;\"><strong><em>Specimen recoltat<\/em><\/strong> \u2013 s\u00e2nge venos<sup>3<\/sup>.<\/p>\n<p style=\"text-align: justify;\"><strong><em>Recipient de recoltare <\/em><\/strong>\u2013 vacutainer f\u0103r\u0103 anticoagulant cu\/f\u0103r\u0103 gel separator<sup>3<\/sup>.<\/p>\n<p style=\"text-align: justify;\"><strong><em>Prelucrare necesar\u0103 dup\u0103 recoltare<\/em><\/strong> \u2013 se separ\u0103 serul prin centrifugare<sup>3<\/sup>.<\/p>\n<p style=\"text-align: justify;\"><strong><em>Volum prob\u0103<\/em><\/strong> \u2013 minim 0.5 mL ser<sup>3<\/sup>.<\/p>\n<p style=\"text-align: justify;\"><strong><em>Cauze\u00a0 de respingere a probei<\/em><\/strong> \u2013 specimen intens hemolizat, lipemic sau contaminat bacterian<sup>3<\/sup>.<\/p>\n<p style=\"text-align: justify;\"><strong><em>Stabilitate prob\u0103 <\/em><\/strong>\u2013 serul separat este stabil <em>7 zile<\/em> la temperatura camerei; <em>7 zile<\/em> la 4-8\u00b0C; <em>2 luni<\/em> la -20\u00b0C<sup>3<\/sup>.<\/p>\n<p style=\"text-align: justify;\"><strong><em>Metod\u0103 <\/em><\/strong>- <span style=\"text-decoration: underline;\">electroforeza urmat\u0103 de analiza activit\u0103\u0163ii enzimatice \u00een frac\u0163iunile separate<\/span>; sunt separate urm\u0103toarele frac\u0163iuni: fosfataza alcalin\u0103 de origine osoas\u0103, fosfataza alcalin\u0103 de origine hepatic\u0103 1, fosfataza alcalin\u0103 de origine hepatic\u0103 2, fosfataza alcalin\u0103 de origine intestinal\u0103 (la 60% din persoanele normale izoenzima intestinal\u0103 este nedecelabil\u0103); fosfataza alcalin\u0103 placentar\u0103 (numai dac\u0103 este cazul, \u00een mod normal nu apare banda corespunz\u0103toare acestei izoenzime)<sup>3<\/sup>.<\/p>\n<p style=\"text-align: justify;\"><strong><em>Valori de referin\u0163\u0103 <\/em><\/strong>\u2013 sunt dependente de v\u00e2rst\u0103 \u015fi sex (vor fi precizate pe fiecare buletin final de rezultate)<sup>3<\/sup>.<\/p>\n<p style=\"text-align: justify;\"><strong><em>Interpretarea rezultatelor<\/em><\/strong><\/p>\n<p style=\"text-align: justify;\"><em>Valori crescute ale izoenzimelor hepatice<\/em>:<\/p>\n<ul style=\"text-align: justify;\">\n<li>\n<div>formele acute, necomplicate de hepatit\u0103 viral\u0103 se asociaz\u0103 cu cre\u015fteri u\u015foare sau moderate (de 2 ori normalul) ale nivelului de ALP, \u00een timp ce formele colestatice determin\u0103 concentra\u0163ii plasmatice de 3-5 ori mai ridicate fa\u0163\u0103 de valorile de referin\u0163\u0103;<\/div>\n<\/li>\n<li>\n<div>cre\u015fteri u\u015foare\/moderate se \u00eenregistreaz\u0103 \u015fi\u00a0\u00een hepatita viral\u0103 cronic\u0103, steatoz\u0103, ciroz\u0103,\u00a0\u00een bolile hepatice de cauz\u0103 infiltrativ\u0103 (sarcoidoz\u0103, tuberculoz\u0103, amiloidoz\u0103, abcese) sau\u00a0\u00een colangita bacterian\u0103<sup>1<\/sup>;<\/div>\n<\/li>\n<li>\n<div>\u00een ingestia cronic\u0103 de alcool fosfataza alcalin\u0103 poate avea valoare normal\u0103 sau crescut\u0103, sunt \u00eens\u0103 constant crescute GGT, AST \u015fi eventual bilirubina<sup>5<\/sup>;<\/div>\n<\/li>\n<li>\n<div>obstruc\u0163ia mecanic\u0103 a c\u0103ilor biliare extrahepatice sau colestaza intrahepatic\u0103 determin\u0103 cre\u015fteri marcate ale izoenzimei hepatice (de 3-10 ori mai mari fa\u0163\u0103 de intervalul de referin\u0163\u0103), care persist\u0103 cateva zile \u015fi se corecteaz\u0103 \u00een aproximativ 10 zile de la interven\u0163ia chirurgical\u0103. Formele complicate cu colangita septic\u0103 se pot prezenta f\u0103r\u0103 cre\u015fteri ale ALP;<\/div>\n<\/li>\n<li>\n<div>valori extreme se \u00eent\u00e2lnesc, de asemenea, \u00een obstruc\u0163ia extrahepatic\u0103 a ductelor biliare determinat\u0103 de tumori (cancerul de cap de pancreas);<\/div>\n<\/li>\n<li>\n<div>ciroza biliar\u0103 primitiv\u0103 este o boal\u0103 inflamatorie, ce apare cu frecven\u0163\u0103 mai mare la femeile cu v\u00e2rste \u00eentre 40 \u015fi 60 ani \u015fi se caracterizeaz\u0103 prin cre\u015fteri (de 5-20 ori) ale nivelului seric de ALP \u00eenaintea apari\u0163iei manifest\u0103rilor clinice;<\/div>\n<\/li>\n<li>afectarea hepatic\u0103 indus\u0103 de medicamente (inclusiv contraceptivele orale) sau alte toxice determin\u0103 cre\u015fteri moderate ale ALP (de 3-5 ori);<\/li>\n<li>\u00een mononucleoza infec\u0163ioas\u0103 \u015fi\u00a0\u00een infec\u0163ia cu citomegalovirus pot ap\u0103rea cre\u015fteri de p\u00e2n\u0103 la 5 ori normalul<sup>4;5<\/sup>.<\/li>\n<\/ul>\n<p style=\"text-align: justify;\">Deoarece electroforetic sunt separate 2 izoforme hepatice, condi\u0163iile asociate cu valori crescute ale acestora sunt urm\u0103toarele:<\/p>\n<div style=\"text-align: justify; padding-left: 30px;\">- <em>izoenzima hepatic\u0103 1 (L1)<\/em> este crescut\u0103 \u00een afec\u0163iuni benigne, cum ar fi: colestaza, ciroza, hepatita viral\u0103, afec\u0163iuni hepatice \u015fi biliare variate. Este de asemenea crescut\u0103 \u00een afec\u0163iuni maligne cu metastaze hepatice, tumori pulmonare, gastrointestinale, limfoame;<\/div>\n<div style=\"text-align: justify; padding-left: 30px;\">- <em>izoenzima hepatic\u0103 <\/em>2 (L2) este crescut\u0103\u00a0 \u00een colestaz\u0103 \u015fi afec\u0163iuni biliare, precum \u015fi\u00a0\u00een cancere\u00a0mamare, hepatice, pulmonare, gastrointestinale, asociate cu metastaze hepatice<sup>6<\/sup>.<\/div>\n<p style=\"text-align: justify;\"><em>Valori crescute ale izoenzimei de origine osoas\u0103<\/em>:<strong><em>\u00a0<\/em><\/strong><\/p>\n<ul style=\"text-align: justify;\">\n<li>\u00cen mod normal nivelul seric al izoenzimei osoase este ridicat la copiii \u00een cre\u015ftere.<\/li>\n<li>Boala Paget se caracterizeaz\u0103 prin cre\u015fteri semnificative ale fosfatazei alcaline serice, astfel c\u0103 pot fi \u00eent\u00e2lnite valori de peste 10-25 ori limita superioar\u0103 a intervalului de referin\u0163\u0103. Exist\u0103 totu\u015fi bolnavi cu forme mai pu\u0163in agresive de boal\u0103 Paget, care au concentra\u0163ii de ALP total la limita superioar\u0103 a intervalului de referin\u0163\u0103 \u015fi la care ostaza reprezint\u0103 un indicator mai sensibil al activit\u0103\u0163ii metabolice osoase<sup>3<\/sup>. De asemenea fosfataza alcalin\u0103 de origine osoas\u0103 scade \u00een cursul tratamentului antiresorbtiv din boala Paget av\u00e2nd astfel utilitate\u00a0\u00een monitorizarea eficien\u0163ei terapiei<sup>5<\/sup>.<\/li>\n<li>Cre\u015fteri moderate pot fi observate \u00een osteomalacie, \u00een timp ce \u00een\u00a0rahitism concentra\u0163ia de ALP osoas\u0103 poate dep\u0103\u015fi de 2-4 ori valoarea normal\u0103.<\/li>\n<li>\u00cen hiperparatiroidismul primar ALP total \u00eenregistreaz\u0103 valori normale sau u\u015for crescute; exist\u0103 \u00eens\u0103 o cre\u015ftere mult mai marcat\u0103 a ostazei care reflect\u0103 mai bine modific\u0103rile sistemului osos.<\/li>\n<li>Acromegalia determin\u0103 modific\u0103ri ale izoenzimei osoase, prin stimularea concentra\u0163iei de IGF-1, care activeaz\u0103 osteoblastele \u015fi implicit formarea de os.<\/li>\n<li>Valori crescute ale ostazei sunt \u00eent\u00e2lnite \u015fi \u00een tumorile osoase osteoblastice.<\/li>\n<li>Tratamentele prelungite cu antiepileptice (fenitoin\u0103, fenobarbital, primidona, carbamazepin\u0103) pot determina \u00een timp osteomalacie \u015fi concentra\u0163ii ridicate de fosfataz\u0103 alcalin\u0103 de origine osoas\u0103, chiar dac\u0103 uneori nivelul total de ALP este normal. Anticonvulsivantele inhib\u0103 secre\u0163ia de calcitonin\u0103, ceea ce duce la o cre\u015ftere a resorb\u0163iei osoase \u015fi modific\u0103ri ale nivelului de ALP.<\/li>\n<li>Timp de 3-4 luni dup\u0103 un transplant renal ALP de origine osoas\u0103 poate \u00eenregistra valori ridicate din cauza administr\u0103rii de substan\u0163e imunosupresoare, cum ar fi corticosteroizii sau ciclosporina A.<\/li>\n<li>La pacien\u0163ii cu neoplasm de prostat\u0103 valorile crescute ale ostazei sunt sugestive pentru dezvoltarea metastazelor osoase.<\/li>\n<li>Concentra\u0163iile de ostaz\u0103 pot fi monitorizate \u00een dinamic\u0103\u00a0\u00een cursul tratamentului antiresorbtiv din osteoporoz\u0103. Mai multe studii au ar\u0103tat faptul c\u0103 un tratament este eficient dac\u0103 se ob\u0163ine o sc\u0103dere a nivelului ostazei cu cel pu\u0163in 25% fa\u0163\u0103 de nivelul bazal,\u00a0\u00een decurs de 3-6 luni de la ini\u0163ierea terapiei. Prin monitorizarea tratamentului se pot identifica pacien\u0163ii non-responderi la tratament; pe de alt\u0103 parte demonstrarea precoce a r\u0103spunsului biochimic al osului poate \u00eembun\u0103t\u0103\u0163i \u015fi stimula complian\u0163a pacientului la terapie<sup>5<\/sup>.<\/li>\n<li>Tratamentul cu hormon de cre\u015ftere al copiilor cu nanism implic\u0103 costuri ridicate, de aceea este nevoie de un marker predictiv, u\u015for de determinat \u015fi care s\u0103 ofere precoce informa\u0163ii asupra r\u0103spunsului la tratament. Studii efectuate \u00een acest domeniu au dus la concluzia c\u0103 ALP de origine osoas\u0103 este un indicator important\u00a0\u00een monitorizarea terapiei cu preparate de hormon de cre\u015ftere. Astfel, se consider\u0103 c\u0103 tratamentul este eficient dac\u0103 se ob\u0163ine o cre\u015ftere semnificativ\u0103 a ostazei fa\u0163\u0103 de nivelul dinaintea tratamentului<sup>5<\/sup><strong><em>.<\/em><\/strong><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><em>Valori crescute ale fosfatazei alcaline placentare sau asem\u0103n\u0103toare celei placentare (\u201eplacental-like\u201d)<\/em>:<\/p>\n<ul style=\"text-align: justify;\">\n<li>exist\u0103 dou\u0103 forme ale izoenzimelor placentare: forma major\u0103 P1 (90%) \u015fi forma minor\u0103 P2 (10%);<\/li>\n<li>apar \u00een s\u0103pt\u0103m\u00e2nile 16-20 ale unei sarcini normale, cresc\u00e2nd p\u00e2n\u0103 la nivelul maxim (de 2 ori normalul) la debutul travaliului<sup>5<\/sup>;<\/li>\n<li>cre\u015fteri ale acestei izoenzime de \u00eent\u00e2lnesc la fum\u0103tori \u015fi\u00a0\u00een unele afec\u0163iuni maligne, cum ar fi seminomul testicular, carcinomul ovarian, de pancreas, gastric, precum \u015fi\u00a0\u00een sarcoame<sup>8<\/sup>.<\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><em>Valori crescute ale izoenzimei intestinale<\/em>: \u00een diverse afec\u0163iuni ulcerative ale tractului gastrointestinal, malabsorb\u0163ie sever\u0103, infarct intestinal<sup>5<\/sup>.<\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">\u00a0<\/span><\/p>\n<p style=\"text-align: justify;\"><strong><span style=\"font-size: small;\">\u0411\u0438\u0431\u043b\u0438\u043e\u0433\u0440\u0430\u0444\u0438\u044f<\/span><\/strong><\/p>\n<div style=\"text-align: justify;\"><span style=\"font-size: small;\">1. Frances Fischbach. Chemistry Studies. In A Manual of Laboratory and Diagnostic Tests. Lippincott Williams &amp; Wilkins, USA, 8 Ed., 2009; 413-415.<\/span><\/div>\n<div style=\"text-align: justify;\"><span style=\"font-size: small;\">2. Frances Fischbach. Effects of the Drugs on Laboratory Tests. In A Manual of Laboratory and Diagnostic Tests. Lippincott Williams &amp; Wilkins, USA, 8 Ed., 2009; 1222-1223.<\/span><\/div>\n<div style=\"text-align: justify;\"><span style=\"font-size: small;\">3. Laborator Synevo. Referin\u0163e specifice tehnologiei de lucru utilizate 2010. Ref Type: Catalog.<\/span><\/div>\n<div style=\"text-align: justify;\"><span style=\"font-size: small;\">4. Laboratory Corporation of America. Directory of Services and Interpretive Guide. Bone-specific Alkaline Phosphatase, Serum. www.labcorp.com 2010. Ref Type: Internet Communication.<\/span><\/div>\n<div style=\"text-align: justify;\"><span style=\"font-size: small;\">5. Lothar Thomas. Enzymes. In Clinical Laboratory Diagnostics-Use and Assessment of Clinical Laboratory Results. TH-Books Verlagsgesellschaft mbH, Frankfurt \/Main, Germany, 1 Ed., 1998, 36-45.<\/span><\/div>\n<div style=\"text-align: justify;\"><span style=\"font-size: small;\">6. Mayo Clinic. Mayo Medical Laboratories. Test Catalog: Alkaline Phosphatase, Total and Isoenzymes, Serum. www.mayomedicallaboratories.com. Ref Type: Internet Communication.<\/span><\/div>\n<div style=\"text-align: justify;\"><span style=\"font-size: small;\">7. Richard A. McPetersen, Matthew R. Pincus. Biochemical Markers of Bone Metabolism. Clinical Enzymology. In Henry\u2019s Clinical Diagnosis and Management by Laboratory Methods \u2013 Sauders Elsevier 21-Ed 2007, 181, 255-257.<\/span><\/div>\n<div style=\"text-align: justify;\"><span style=\"font-size: small;\">8. www.electroforeza.ro\/SeparareaElectroforeticaAIzoenzimelor.aspx. Ref Type: Internet Communication.<\/span><\/div>","protected":false},"excerpt":{"rendered":"<p>\u0429\u0435\u043b\u043e\u0447\u043d\u0430\u044f \u0444\u043e\u0441\u0444\u0430\u0442\u0430\u0437\u0430 \u2013 \u0444\u0435\u0440\u043c\u0435\u043d\u0442, \u043a\u043e\u0442\u043e\u0440\u044b\u0439 \u043d\u0430\u0445\u043e\u0434\u0438\u0442\u0441\u044f \u0432 \u043a\u043b\u0435\u0442\u043a\u0430\u0445 \u043f\u0435\u0447\u0435\u043d\u0438 \u0438 \u0436\u0435\u043b\u0447\u0435\u0432\u044b\u0432\u043e\u0434\u044f\u0449\u0438\u0445 \u043f\u0443\u0442\u0435\u0439 \u0438 \u044f\u0432\u043b\u044f\u0435\u0442\u0441\u044f \u043a\u0430\u0442\u0430\u043b\u0438\u0437\u0430\u0442\u043e\u0440\u043e\u043c \u043e\u043f\u0440\u0435\u0434\u0435\u043b\u0435\u043d\u043d\u044b\u0445 \u0431\u0438\u043e\u0445\u0438\u043c\u0438\u0447\u0435\u0441\u043a\u0438\u0445 \u0440\u0435\u0430\u043a\u0446\u0438\u0439 \u0432 \u044d\u0442\u0438\u0445 \u043a\u043b\u0435\u0442\u043a\u0430\u0445 (\u0432 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\u041e\u043d\u0438 \u0437\u0430\u0442\u0435\u043c \u043e\u0431\u044a\u0435\u0434\u0438\u043d\u044f\u044e\u0442\u0441\u044f \u0432 \u043f\u0435\u0447\u0435\u043d\u043e\u0447\u043d\u044b\u0435 \u043f\u0440\u043e\u0442\u043e\u043a\u0438, \u043a\u043e\u0442\u043e\u0440\u044b\u0435 \u0432\u044b\u0445\u043e\u0434\u044f\u0442 \u0437\u0430 \u043f\u0440\u0435\u0434\u0435\u043b\u044b \u043f\u0435\u0447\u0435\u043d\u0438 \u0438 \u043e\u0431\u0440\u0430\u0437\u0443\u044e\u0442 \u043e\u0431\u0449\u0438\u0439 \u0436\u0435\u043b\u0447\u043d\u044b\u0439 \u043f\u0440\u043e\u0442\u043e\u043a, \u0432\u043f\u0430\u0434\u0430\u044e\u0449\u0438\u0439 \u0432 \u0442\u043e\u043d\u043a\u0438\u0439 \u043a\u0438\u0448\u0435\u0447\u043d\u0438\u043a.<\/p>\n<p>\u0416\u0435\u043b\u0447\u044c \u043d\u0435\u043e\u0431\u0445\u043e\u0434\u0438\u043c\u0430 \u0434\u043b\u044f \u0432\u0441\u0430\u0441\u044b\u0432\u0430\u043d\u0438\u044f \u0436\u0438\u0440\u043e\u0432, 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