{"id":9336,"date":"2020-04-23T04:35:06","date_gmt":"2020-04-23T01:35:06","guid":{"rendered":"https:\/\/www.synevo.ro\/product\/vitamina-b12\/"},"modified":"2026-02-19T01:31:25","modified_gmt":"2026-02-18T23:31:25","slug":"vitamina-b12","status":"publish","type":"product","link":"https:\/\/old.synevo.md\/ru\/shop\/vitamina-b12\/","title":{"rendered":"\u0412\u0438\u0442\u0430\u043c\u0438\u043d \u041212"},"content":{"rendered":"<p><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;\">Cobalamina este format\u0103 dintr-un tetrapirol plan cu un atom de cobalt central, o grupare nucleotidic\u0103 (5,6-dimetilbenzimidazol) sub nivelul planului \u015fi o parte prostetic\u0103 deasupra planului. \u00cen func\u0163ie de gruparea prostetic\u0103 se identific\u0103 mai multe forme de cobalamin\u0103: metilcobalamina, care predomin\u0103 \u00een plasm\u0103 \u015fi \u00een citoplasm\u0103, adenozilcobalamina, care predomin\u0103 intramitocondrial, \u015fi ciancobalamina, care este un preparat farmacologic stabil care trebuie convertit \u00een alte forme pentru a fi activ metabolic. Pentru a fi activ\u0103 cobalamina trebuie redus\u0103 din starea natural\u0103 oxidat\u0103 (Co<sup>3+<\/sup> sau Co<sup>2+<\/sup>). Cobalamina redus\u0103 (Co<sup>+<\/sup>) are dou\u0103 roluri cunoscute la om: transformarea metilmalonat CoA \u00een succinil CoA (ca parte a oxid\u0103rii acizilor gra\u015fi), reac\u0163ie catalizat\u0103 de metilmalonil CoA mutaza \u2013 dependent\u0103 de cobalamin\u0103 \u015fi metilarea homocisteinei la metionin\u0103, reac\u0163ie catalizat\u0103 de metionin sintetaza \u015fi care necesit\u0103 prezen\u0163a de metiltetrahidrofolat, metilcobalamina servind drept cofactor. Deficien\u0163a cobalaminei determin\u0103 acumularea de metilmalonil CoA, homocistein\u0103 \u015fi metiltetrahidrofolat, cu sc\u0103derea formei active, tetrahidrofolatul, duc\u00e2nd la alterarea sintezei ADN, rezultatul final fiind oprirea \u00een diferite stadii ale interfazei a precursorilor hematopoietici. Consecin\u0163a este apari\u0163ia anemiei megaloblastice care se poate asocia cu leziuni ireversibile ale SNC (prin deficit de metilare a proteinelor SNC).<\/p>\n<p style=\"text-align: justify;\">Sursa alimentar\u0103 de vitamin\u0103 B12 este reprezentat\u0103 de produsele animale (carne, lactate, ou\u0103). Cobalamina este eliberat\u0103 de proteinele de legare din alimente de c\u0103tre pepsin\u0103 la pH-ul acid din stomac, se leag\u0103 de transcobalamina (TC) I salivar\u0103; \u00een duoden cobalamina este eliberat\u0103 sub ac\u0163iunea proteazelor pancreatice \u015fi se leag\u0103 de factorul intrinsec (FI) (inclusiv cobalamina excretat\u0103 biliar) produs de celulele parietale gastrice. Complexul cobalamin\u0103-FI este endocitat la nivelul celulelor ileale prin intermediul cubilinei \u015fi megalinei, apoi este splitat \u015fi cobalamina se leag\u0103 de TC II (sintetizat\u0103 \u00een ficat), acest complex p\u0103r\u0103sind bazolateral celulele ileale \u015fi intr\u00e2nd \u00een circula\u0163ie la c\u00e2teva ore dup\u0103 ingestie. O parte din cobalamin\u0103 este internalizat\u0103 la nivelul ficatului prin intermediul receptorilor pentru TC II, iar clearance-ul continu\u0103 \u00een circula\u0163ia sistemic\u0103, mai ales la nivelul rinichiului, cu un timp de \u00eenjum\u0103t\u0103\u0163ire de 90 minute. ~70% din cobalamina plasmatic\u0103 este legat\u0103 de TC I (produs\u0103 de leucocite), acest complex nefiind preluat de \u0163esuturi (timp de \u00eenjum\u0103t\u0103\u0163ire 9-10 zile). Con\u0163inutul total de cobalamin\u0103 al organismului este de 2.5 mg la adult, \u00een timp ce pierderile zilnice (biliare \u015fi urinare) sunt de numai 1 \u00b5g. Deficitul alimentar de vitamina B12 este extrem de rar, except\u00e2nd vegetarianismul strict, copiii n\u0103scu\u0163i din mame cu deficien\u0163\u0103 sau \u00een cazul dietei restrictive din fenilcetonurie. Absorb\u0163ia intestinal\u0103 insuficient\u0103 reprezint\u0103 principala cauz\u0103 de deficit de vitamin\u0103 B12<sup>1;2;3<\/sup>.<\/p>\n<p><strong><em>Recomand\u0103ri pentru determinarea vitaminei B12 serice<\/em><\/strong><\/p>\n<ul>\n<li style=\"text-align: justify;\">Anemie megaloblastic\u0103 <strong>\u2022<\/strong> Gastrit\u0103 atrofic\u0103 cronic\u0103<strong> \u2022 <\/strong>Gastrectomie <strong>\u2022<\/strong> Boli ale ileonului terminal (boal\u0103 Crohn, limfom, rezec\u0163ie etc.) <strong>\u2022 <\/strong>Alcoolism cronic<strong> \u2022 <\/strong>Diet\u0103 vegetarian\u0103 prelungit\u0103 (ani)<\/li>\n<li>Ingestia prelungit\u0103 (ani) de inhibitori ai pompei de protoni\/blocan\u0163i de receptori H<sub>2 <\/sub><\/li>\n<li>Pacien\u0163i cu SIDA<sup>2;4<\/sup><\/li>\n<\/ul>\n<p><strong><em>Preg\u0103tire pacient <\/em><\/strong>\u2013 \u00e0 jeun (pe nem\u00e2ncate), \u00eenaintea unei eventuale injec\u0163ii cu vitamina B12, efectu\u0103rii testului Schilling sau administr\u0103rii de radionuclizi<sup>5<\/sup>.<\/p>\n<p><strong><em>Specimen recoltat<\/em><\/strong> <em>- <\/em>\u0432\u0435\u043d\u043e\u0437\u043d\u0430\u044f \u043a\u0440\u043e\u0432\u044c<sup>5<\/sup>.<\/p>\n<p><strong><em>Recipient de recoltare <\/em><\/strong>\u2013 vacutainer f\u0103r\u0103 anticoagulant cu\/f\u0103r\u0103 gel separator<sup>5<\/sup>.<\/p>\n<p><strong><em>Prelucrare necesar\u0103 dup\u0103 recoltare <\/em><\/strong>\u2013 se separ\u0103 serul prin centrifugare<sup>5<\/sup>.<\/p>\n<p><strong><em>Volum prob\u0103<\/em><\/strong> \u2013 minim 0.5 mL ser<sup>5<\/sup>.<\/p>\n<p><strong><em>Stabilitate prob\u0103 <\/em><\/strong>\u2013 serul separat este stabil <em>7 zile<\/em> la 2-8\u00b0C; <em>3 luni<\/em> la -20\u00b0C; se congeleaz\u0103 numai o dat\u0103, se protejeaz\u0103 de lumin\u0103<sup>5<\/sup><sup>;6<\/sup>.<\/p>\n<p><strong><em>Metod\u0103 <\/em><\/strong>- <u>imunochimic\u0103 cu detec\u0163ie prin electrochemiluminiscen\u0163\u0103 (ECLIA)<\/u><sup>5<\/sup>.<\/p>\n<p><strong><em>Interval de referin\u0163\u0103 <\/em><\/strong><em>-<\/em> 197-771 pg\/mL (pentru popula\u0163ia european\u0103)<sup>5<\/sup>.<\/p>\n<p><em>Factori de conversie: pmol\/L x 1.36 = pg\/mL (ng\/L); pg\/mL (ng\/L) x 0.738 = pmol\/L.<\/em><\/p>\n<p><strong><em>Limita de detec\u0163ie <\/em><\/strong><em>-<\/em> 50 pg\/mL (36.9 pmol\/L)<sup>5<\/sup>.<\/p>\n<p><strong><em>Interpretarea rezultatelor<\/em><\/strong><\/p>\n<table class=\"wp-block-table w-100\">\n<tbody>\n<tr>\n<td width=\"612\"><strong><em>Cre\u015fteri<\/em><\/strong><\/td>\n<\/tr>\n<tr>\n<td width=\"612\">\n<p style=\"text-align: justify;\">\u2022 Insuficien\u0163\u0103 renal\u0103, \u2022 Tratament cu vitamina B12, \u2022 Leucemie mieloid\u0103 cronic\u0103, leucemie acut\u0103 promielocitar\u0103, leucemie limfatic\u0103 cronic\u0103, unele cazuri de leucemie monocitar\u0103, \u2022 Policitemie vera,<\/p>\n<p style=\"text-align: justify;\">\u2022 Cancer metastatic adesea cu reac\u0163ie leucemoid\u0103 sau afectare hepatic\u0103, \u2022 Hepatom (cre\u015ftere marcat\u0103 a TC I)<sup>1;4<\/sup><sup>;7<\/sup> \u2022 Hepatit\u0103 acut\u0103\/cronic\u0103, ciroz\u0103<sup>4<\/sup><sup>;7<\/sup>\u2022 Insuficien\u0163\u0103 cardiac\u0103 congestiv\u0103 sever\u0103, diabet, obezitate, BPOC<sup>7<\/sup>; \u2022 Autoanticorpi anti-TC II (rar)<sup>1<\/sup>.<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"612\"><strong><em>Sc\u0103deri <\/em><\/strong><\/td>\n<\/tr>\n<tr>\n<td width=\"612\"><u>Deficit de cobalamin\u0103 subclinic <\/u>(biochimic)<sup>1;2<\/sup>.<\/p>\n<p><u>Deficit de cobalamin\u0103 clinic (simptomatic)<\/u> - <em>anemie megaloblastic\u0103<\/em> \u015fi\/sau manifest\u0103ri neurologice. <em><u>Cauze<\/u>:<\/em><\/p>\n<p>\u2022 Deficit nutri\u0163ional (rar).<\/p>\n<p style=\"text-align: justify;\">\u2022 Anemia pernicioas\u0103 (boal\u0103 autoimun\u0103 caracterizat\u0103 prin atrofia corpului \u015fi fundului gastric, pierderea factorului intrinsec \u015fi prezen\u0163a de autoanticorpi anti-celule parietale gastrice \u015fi anti-factor intrinsec).<\/p>\n<p style=\"text-align: justify;\">\u2022 Deficien\u0163a ereditar\u0103 de factor intrinsec (anemia pernicioas\u0103 ereditar\u0103), \u2022 Malabsorb\u0163ia vitaminei B12 din alimente (chirurgie gastric\u0103, pacien\u0163i v\u00e2rstnici cu gastrit\u0103 atrofic\u0103 cronic\u0103 \u015fi aclorhidrie, infec\u0163ia cu Helicobacter pylori),<\/p>\n<p style=\"text-align: justify;\">\u2022 Insuficien\u0163\u0103 pancreatic\u0103, \u2022 Sindromul Zollinger-Ellison, \u2022 Competi\u0163ia biologic\u0103 pentru vitamina B12: proliferarea bacterian\u0103 a intestinului sub\u0163ire (anomalii structurale: diverticuli, stricturi, fistule, ans\u0103 oarb\u0103, sau ale motilit\u0103\u0163ii: disfunc\u0163ia autonom\u0103 din diabet); infestarea cu Diphyllobothrium latum.<\/p>\n<p style=\"text-align: justify;\">\u2022 Boli ileale: sprue tropical, boli inflamatorii intestinale, boal\u0103 celiac\u0103, rezec\u0163ii ileale, by-pass jejuno-ileal pentru obezitate, radioterapie cu afectarea ileonului, boli ileale infiltrative (limfom, sclerodermie).<\/p>\n<p style=\"text-align: justify;\">\u2022 Malabsorb\u0163ia familial\u0103 selectiv\u0103 a vitaminei B12 (Sindromul Imerslund-Gr\u00e4sbeck).<\/p>\n<p style=\"text-align: justify;\">\u2022 Malabsorb\u0163ia vitaminei B12 indus\u0103 de toxice \u015fi medicamente: alcool, colchicin\u0103, metformin, neomicin\u0103, colestiramin\u0103, acid paraaminosalicilic<sup>1<\/sup>.<\/p>\n<p style=\"text-align: justify;\">\u2022 Deficien\u0163\u0103 u\u015foar\u0103 de tanscobalamin\u0103 I<sup>1<\/sup>.<\/p>\n<p style=\"text-align: justify;\">\u2022 Cauze rare: hipotirodismul primar (50% din pacien\u0163i dezvolt\u0103 aclorhidrie)<sup>4<\/sup><sup>;7<\/sup>, deficit sever de TC I, infec\u0163ie HIV (dezvolt\u0103 aclorhidrie cu sc\u0103derea eliber\u0103rii cobalaminei din alimente), tratament anticonvulsivant, contraceptive orale, mielom multiplu, scleroz\u0103 multipl\u0103, hairy cell leukemia, anemie aplastic\u0103, mielodisplazie, hemoglobinurie paroxistic\u0103 nocturn\u0103, boala Gaucher<sup>1<\/sup>; hemodializ\u0103<sup>1;4<\/sup>.<\/p>\n<p>\u2022 Idiopatic\u0103<sup>1<\/sup><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p style=\"text-align: justify;\">Un nivel seric de vitamina B12 sub limita inferioar\u0103 a intervalului de referin\u021b\u0103 poate determina anemie megaloblastic\u0103 \u0219i neuropatii periferice.<\/p>\n<p style=\"text-align: justify;\">\u00cen prezen\u021ba unor valori sc\u0103zute de vitamina B12 se recomand\u0103 efectuarea de autoanticorpi anti-celule parietale gastrice \u015fi anti-factor intrinsec pentru a stabili cauza deficitului. Pacien\u021bii f\u0103r\u0103 autoanticorpi precum \u0219i cei suspecta\u021bi clinic de deficit dar cu un nivel seric de vitamina B12 situat \u00eentre 150 \u0219i 400 pg\/mL trebuie s\u0103 fie investiga\u021bi cu alte teste, cum ar fi holotranscobalamina (vitamina B12 activ\u0103), homocisteina plasmatic\u0103 sau acidul metilmalonic seric<sup>6<\/sup>.<\/p>\n<p><strong><em>Limite \u015fi interferen\u0163e<\/em><\/strong><\/p>\n<ul>\n<li>Condi\u0163ii fiziologice \u015fi patologice:<\/li>\n<\/ul>\n<p><u>False sc\u0103deri <\/u>(f\u0103r\u0103 semne de deficien\u0163\u0103) :<\/p>\n<ul>\n<li>Sarcin\u0103 (trimestrele II-III): niveluri p\u00e2n\u0103 la &lt;100 ng\/L, se normalizeaz\u0103 la c\u00e2teva zile dup\u0103 na\u015ftere.<\/li>\n<li>Deficit de fola\u0163i: valorile se normalizeaz\u0103 dup\u0103 tratament cu fola\u0163i; trebuie diferen\u0163iat\u0103 de deficitul combinat al ambelor vitamine.<\/li>\n<li>Infec\u0163ie HIV, mielom multiplu, scleroz\u0103 multipl\u0103<sup>1<\/sup>.<\/li>\n<\/ul>\n<p><u>Fals normal\u0103:<\/u><\/p>\n<ul>\n<li>Exist\u0103 un num\u0103r de pacien\u0163i v\u00e2rstnici cu semne \u015fi simptome clare de deficien\u0163\u0103, dar cu niveluri normale de cobalamin\u0103 seric\u0103 (250-350 ng\/L) din motive necunoscute.<\/li>\n<li>Asocierea leucemiei mieloide cronice cu anemie pernicioas\u0103<sup>1<\/sup>.<\/li>\n<li>Medicamente<\/li>\n<\/ul>\n<p><u>Sc\u0103deri<\/u>: anticonvulsivante, acid ascorbic, colestiramin\u0103, clorpromazin\u0103, colchicin\u0103, metformin, neomicin\u0103, octreotid, contraceptive orale, ranitidin\u0103, rifampicin\u0103<sup>8<\/sup>.<\/p>\n<p><u>Cre\u015fter<\/u>i: cloralhidrat, omeprazol<sup>8<\/sup>.<\/p>\n<ul>\n<li>Interferen\u0163e analitice<\/li>\n<\/ul>\n<div>Dac\u0103 pacientul se afl\u0103 \u00een tratament cu biotin\u0103 &gt; 5 mg\/zi, recoltarea de s\u00e2nge pentru determinarea vitaminei B12 se va face la cel pu\u0163in 8 ore de la ultima administrare.<\/div>\n<div>\u00cen cazuri izolate, prezen\u0163a \u00een titruri mari de anticorpi antiantistreptavidin\u0103 sau antiruteniu poate cauza interferen\u0163e, iar rezultatele ob\u0163inute sunt neconcludente<sup>5<\/sup>.<\/div>\n<p><strong><span style=\"font-size: 10pt;\">\u0411\u0438\u0431\u043b\u0438\u043e\u0433\u0440\u0430\u0444\u0438\u044f<\/span><\/strong><\/p>\n<ol>\n<li><span style=\"font-size: 10pt;\">Carmel R.Megalobastic Anemias: Disorders of Impaired DNA Synthesis. In <em>Wintrobe\u2019s Clinical Hematology.<\/em> Lippincott Williams &amp; Wilkins, USA, 2 ed. 2004, 1367-1388.<\/span><\/li>\n<li><span style=\"font-size: 10pt;\">Lothar Thomas.Cobalamin. In <em>Clinical Laboratory Diagnostics-Use and Assessment of Clinical Laboratory Results.<\/em> TH-Books Verlagsgesellschaft mbH, Frankfurt \/Main, Germany,1 ed. 1998, 424-430.<\/span><\/li>\n<li><span style=\"font-size: 10pt;\">Wayne R.DeMott, Lowell L.Tilzer.Haematology. In <em>Laboratory Test Handbook.<\/em> David S. Jacobs, Wayne R. DeMott, Paul R. Finley et al.,LEXI-COMP.Inc., USA, 3 ed. 1994, 612-614.<\/span><\/li>\n<li><span style=\"font-size: 10pt;\">Jacques Wallach. Afec\u0163iuni hematologice. \u00cen <em>Interpretarea testelor de diagnostic.<\/em> Editura \u015etiin\u0163elor Medicale, Rom\u00e2nia, 7 ed. 2001, 502-503.<\/span><\/li>\n<li><span style=\"font-size: 10pt;\">Laborator Synevo. Referin\u0163ele specifice tehnologiei de lucru utilizate 2017. Ref Type: Catalog<\/span><\/li>\n<li><span style=\"font-size: 10pt;\">Mayo Clinic. Mayo Medical Laboratories. Vitamin B12 Assay, Serum. www.mayomedicallaboratories.com. 2017. Ref Type: Internet Communication.<\/span><\/li>\n<li><span style=\"font-size: 10pt;\">\u00a0Frances Fischbach.Blood Studies: Hematology and Coagulation. In <em>A Manual of Laboratory and Diagnostic Tests.<\/em> Lippincott\u00a0Williams &amp; Wilkins, USA, 8 ed. 2009, 139-140.<\/span><\/li>\n<li><span style=\"font-size: 10pt;\">Frances Fischbach.Effects of the Most Commonly Used Drugs on Frequently Ordered Laboratory Tests. In <em>A Manual of Laboratory and Diagnostic Tests.<\/em> Lippincott Williams &amp; Wilkins, USA, 8 ed. 2009, 1257.<\/span><\/li>\n<\/ol>","protected":false},"excerpt":{"rendered":"<p>\u041e\u043f\u0440\u0435\u0434\u0435\u043b\u0435\u043d\u0438\u0435 \u043a\u043e\u043d\u0446\u0435\u043d\u0442\u0440\u0430\u0446\u0438\u0438 \u0432\u0438\u0442\u0430\u043c\u0438\u043d\u0430 \u041212 \u0432 \u0441\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0435 \u043a\u0440\u043e\u0432\u0438 \u2013 \u0441\u0442\u0430\u043d\u0434\u0430\u0440\u0442\u043d\u044b\u0439 \u043c\u0435\u0442\u043e\u0434 \u0434\u0438\u0430\u0433\u043d\u043e\u0441\u0442\u0438\u043a\u0438 \u0435\u0433\u043e \u0434\u0435\u0444\u0438\u0446\u0438\u0442\u0430.<\/p>\n<p>\u0412\u0438\u0442\u0430\u043c\u0438\u043d \u041212 \u0441\u043e\u0434\u0435\u0440\u0436\u0438\u0442\u0441\u044f \u0438\u0441\u043a\u043b\u044e\u0447\u0438\u0442\u0435\u043b\u044c\u043d\u043e \u0432 \u043f\u0440\u043e\u0434\u0443\u043a\u0442\u0430\u0445 \u0436\u0438\u0432\u043e\u0442\u043d\u043e\u0433\u043e \u043f\u0440\u043e\u0438\u0441\u0445\u043e\u0436\u0434\u0435\u043d\u0438\u044f, \u0442\u0430\u043a\u0438\u0445 \u043a\u0430\u043a \u043c\u044f\u0441\u043e (\u043e\u0441\u043e\u0431\u0435\u043d\u043d\u043e \u043f\u0435\u0447\u0435\u043d\u044c \u0438 \u043f\u043e\u0447\u043a\u0438), \u0440\u044b\u0431\u0430, \u044f\u0439\u0446\u0430, \u043c\u043e\u043b\u043e\u0447\u043d\u044b\u0435 \u043f\u0440\u043e\u0434\u0443\u043a\u0442\u044b. \u0412 \u043f\u043e\u0441\u043b\u0435\u0434\u043d\u0438\u0435 \u0433\u043e\u0434\u044b \u0432\u0430\u0436\u043d\u044b\u043c \u0438\u0441\u0442\u043e\u0447\u043d\u0438\u043a\u043e\u043c \u0432\u0438\u0442\u0430\u043c\u0438\u043d\u0430 \u041212, \u043e\u0441\u043e\u0431\u0435\u043d\u043d\u043e \u0434\u043b\u044f \u0432\u0435\u0433\u0435\u0442\u0430\u0440\u0438\u0430\u043d\u0446\u0435\u0432, \u0441\u0442\u0430\u043b\u0438 \u043e\u0431\u043e\u0433\u0430\u0449\u0435\u043d\u043d\u044b\u0435 \u0438\u043c \u043a\u0430\u0448\u0438, \u0445\u043b\u0435\u0431, \u0441\u0443\u0445\u0438\u0435 \u0437\u0430\u0432\u0442\u0440\u0430\u043a\u0438 \u0438 \u0434\u0440\u0443\u0433\u0438\u0435 \u0437\u0435\u0440\u043d\u043e\u0432\u044b\u0435 \u043f\u0440\u043e\u0434\u0443\u043a\u0442\u044b.<\/p>\n<p>\u041212 \u0432\u0430\u0436\u0435\u043d \u0434\u043b\u044f \u0441\u0438\u043d\u0442\u0435\u0437\u0430 \u043d\u0443\u043a\u043b\u0435\u0438\u043d\u043e\u0432\u044b\u0445 \u043a\u0438\u0441\u043b\u043e\u0442, \u043e\u0431\u0440\u0430\u0437\u043e\u0432\u0430\u043d\u0438\u044f \u044d\u0440\u0438\u0442\u0440\u043e\u0446\u0438\u0442\u043e\u0432, \u043a\u043b\u0435\u0442\u043e\u0447\u043d\u043e\u0433\u043e \u0438 \u0442\u043a\u0430\u043d\u0435\u0432\u043e\u0433\u043e \u043e\u0431\u043c\u0435\u043d\u0430, \u043a \u0442\u043e\u043c\u0443 \u0436\u0435 \u043e\u043d \u0443\u0447\u0430\u0441\u0442\u0432\u0443\u0435\u0442 \u0432 \u043f\u043e\u0434\u0434\u0435\u0440\u0436\u0430\u043d\u0438\u0438 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\u0431\u043e\u043b\u044c\u0448\u043e\u0433\u043e \u043a\u043e\u043b\u0438\u0447\u0435\u0441\u0442\u0432\u0430 \u0432\u0438\u0442\u0430\u043c\u0438\u043d\u0430 \u041212, \u043d\u0430\u043f\u0440\u0438\u043c\u0435\u0440 \u0433\u0435\u043c\u043e\u043b\u0438\u0442\u0438\u0447\u0435\u0441\u043a\u043e\u0439 \u0430\u043d\u0435\u043c\u0438\u0438, \u0433\u0438\u043f\u0435\u0440\u0442\u0438\u0440\u0435\u043e\u0437\u0435 \u0438 \u0430\u043b\u044c\u0444\u0430-\u0442\u0430\u043b\u0430\u0441\u0441\u0435\u043c\u0438\u0438.<\/li>\n<\/ul>\n<p><strong id=\"subj7\" class=\"subj-header\">\u0414\u043b\u044f \u0447\u0435\u0433\u043e \u0438\u0441\u043f\u043e\u043b\u044c\u0437\u0443\u0435\u0442\u0441\u044f \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0435?<\/strong><\/p>\n<ul>\n<li>\u0412 \u043f\u0435\u0440\u0432\u0443\u044e \u043e\u0447\u0435\u0440\u0435\u0434\u044c, \u0434\u043b\u044f \u0432\u044b\u044f\u0432\u043b\u0435\u043d\u0438\u044f \u043f\u0440\u0438\u0447\u0438\u043d \u043c\u0430\u043a\u0440\u043e\u0446\u0438\u0442\u0430\u0440\u043d\u043e\u0439 \u0430\u043d\u0435\u043c\u0438\u0438.<\/li>\n<li>\u0427\u0442\u043e\u0431\u044b \u043e\u0446\u0435\u043d\u0438\u0442\u044c \u0441\u043e\u0441\u0442\u043e\u044f\u043d\u0438\u0435 \u0437\u0434\u043e\u0440\u043e\u0432\u044c\u044f \u0438 \u0441\u0431\u0430\u043b\u0430\u043d\u0441\u0438\u0440\u043e\u0432\u0430\u043d\u043d\u043e\u0441\u0442\u044c \u043f\u0438\u0442\u0430\u043d\u0438\u044f \u043f\u0430\u0446\u0438\u0435\u043d\u0442\u043e\u0432 \u0441 \u043f\u0440\u0438\u0437\u043d\u0430\u043a\u0430\u043c\u0438 \u043d\u0435\u0434\u043e\u0435\u0434\u0430\u043d\u0438\u044f \u0438 \u043c\u0430\u043b\u044c\u0430\u0431\u0441\u043e\u0440\u0431\u0446\u0438\u0438, \u043b\u044e\u0434\u0435\u0439, \u0441\u0442\u0440\u0430\u0434\u0430\u044e\u0449\u0438\u0445 \u0430\u043b\u043a\u043e\u0433\u043e\u043b\u0438\u0437\u043c\u043e\u043c \u0438\u043b\u0438 \u0440\u0430\u0437\u043b\u0438\u0447\u043d\u044b\u043c\u0438 \u0444\u043e\u0440\u043c\u0430\u043c\u0438 \u043d\u0430\u0440\u0443\u0448\u0435\u043d\u0438\u044f \u0432\u0441\u0430\u0441\u044b\u0432\u0430\u043d\u0438\u044f (\u0446\u0435\u043b\u0438\u0430\u043a\u0438\u0435\u0439, \u0431\u043e\u043b\u0435\u0437\u043d\u044c\u044e \u041a\u0440\u043e\u043d\u0430).<\/li>\n<li>\u041f\u043e\u0436\u0438\u043b\u044b\u043c \u043b\u044e\u0434\u044f\u043c \u0442\u0435\u0441\u0442 \u043d\u0430 \u041212\u00a0\u043c\u043e\u0436\u0435\u0442 \u043f\u043e\u043c\u043e\u0447\u044c \u043e\u043f\u0440\u0435\u0434\u0435\u043b\u0438\u0442\u044c \u043f\u0440\u0438\u0447\u0438\u043d\u0443 \u0438\u0437\u043c\u0435\u043d\u0435\u043d\u0438\u0439 \u0432 \u043f\u0441\u0438\u0445\u0438\u043a\u0435 \u0438 \u043f\u043e\u0432\u0435\u0434\u0435\u043d\u0438\u0438.<\/li>\n<li>\u041f\u0430\u0446\u0438\u0435\u043d\u0442\u0430\u043c, \u0441\u0442\u0440\u0430\u0434\u0430\u044e\u0449\u0438\u043c \u0434\u0435\u0444\u0438\u0446\u0438\u0442\u043e\u043c \u0432\u0438\u0442\u0430\u043c\u0438\u043d\u0430 \u041212, \u0440\u0435\u0433\u0443\u043b\u044f\u0440\u043d\u043e\u0435 \u043e\u043f\u0440\u0435\u0434\u0435\u043b\u0435\u043d\u0438\u0435 \u0435\u0433\u043e \u043a\u043e\u043d\u0446\u0435\u043d\u0442\u0440\u0430\u0446\u0438\u0438 \u043f\u043e\u0437\u0432\u043e\u043b\u044f\u0435\u0442 \u043a\u043e\u043d\u0442\u0440\u043e\u043b\u0438\u0440\u043e\u0432\u0430\u0442\u044c \u043f\u0440\u043e\u0446\u0435\u0441\u0441 \u043b\u0435\u0447\u0435\u043d\u0438\u044f. \u041e\u0441\u043e\u0431\u0435\u043d\u043d\u043e \u044d\u0442\u043e \u0430\u043a\u0442\u0443\u0430\u043b\u044c\u043d\u043e \u0434\u043b\u044f \u043b\u044e\u0434\u0435\u0439 \u0441 \u0432\u0440\u043e\u0436\u0434\u0451\u043d\u043d\u044b\u043c\u0438 \u0434\u0435\u0444\u0435\u043a\u0442\u0430\u043c\u0438 \u0432\u0441\u0430\u0441\u044b\u0432\u0430\u043d\u0438\u044f \u0432\u0438\u0442\u0430\u043c\u0438\u043d\u0430 \u041212, \u0432\u044b\u043d\u0443\u0436\u0434\u0435\u043d\u043d\u044b\u0445 \u043f\u0440\u0438\u043d\u0438\u043c\u0430\u0442\u044c \u043f\u0440\u0435\u043f\u0430\u0440\u0430\u0442\u044b \u0432\u0441\u044e \u0436\u0438\u0437\u043d\u044c.<\/li>\n<\/ul>\n<p><strong id=\"subj8\" class=\"subj-header\">\u041a\u043e\u0433\u0434\u0430 \u043d\u0430\u0437\u043d\u0430\u0447\u0430\u0435\u0442\u0441\u044f \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0435?<\/strong><\/p>\n<ul>\n<li>\u0415\u0441\u043b\u0438 \u043f\u0440\u0438 \u043e\u0431\u0449\u0435\u043c \u0430\u043d\u0430\u043b\u0438\u0437\u0435 \u043a\u0440\u043e\u0432\u0438, \u043f\u0440\u043e\u0432\u0435\u0434\u0435\u043d\u043d\u043e\u043c \u0440\u0443\u0442\u0438\u043d\u043d\u043e \u0438\u043b\u0438 \u043a\u0430\u043a \u0447\u0430\u0441\u0442\u044c \u0434\u0438\u0430\u0433\u043d\u043e\u0441\u0442\u0438\u043a\u0438 \u0441\u0438\u043c\u043f\u0442\u043e\u043c\u043e\u0432 \u0430\u043d\u0435\u043c\u0438\u0438, \u043e\u0431\u043d\u0430\u0440\u0443\u0436\u0438\u0432\u0430\u044e\u0442 \u044d\u0440\u0438\u0442\u0440\u043e\u0446\u0438\u0442\u044b \u0443\u0432\u0435\u043b\u0438\u0447\u0435\u043d\u043d\u044b\u0445 \u0440\u0430\u0437\u043c\u0435\u0440\u043e\u0432.<\/li>\n<li>\u041f\u0440\u0438 \u0432\u044b\u044f\u0432\u043b\u0435\u043d\u0438\u0438 \u043f\u0440\u0438\u0447\u0438\u043d \u0438\u0437\u043c\u0435\u043d\u0435\u043d\u0438\u0439 \u0432 \u043f\u043e\u0432\u0435\u0434\u0435\u043d\u0438\u0438: \u043f\u043e\u044f\u0432\u043b\u0435\u043d\u0438\u0438 \u0440\u0430\u0437\u0434\u0440\u0430\u0436\u0438\u0442\u0435\u043b\u044c\u043d\u043e\u0441\u0442\u0438, \u0441\u043f\u0443\u0442\u0430\u043d\u043d\u043e\u0441\u0442\u0438 \u0441\u043e\u0437\u043d\u0430\u043d\u0438\u044f, \u0434\u0435\u043f\u0440\u0435\u0441\u0441\u0438\u0438 \u0438\/\u0438\u043b\u0438 \u043f\u0430\u0440\u0430\u043d\u043e\u0439\u0438 (\u043e\u0441\u043e\u0431\u0435\u043d\u043d\u043e \u0443 \u043f\u043e\u0436\u0438\u043b\u044b\u0445 \u043b\u044e\u0434\u0435\u0439).<\/li>\n<li>\u041f\u0440\u0438 \u043d\u0435\u0441\u043f\u0435\u0446\u0438\u0444\u0438\u0447\u0435\u0441\u043a\u0438\u0445 \u0441\u0438\u043c\u043f\u0442\u043e\u043c\u0430\u0445, \u0443\u043a\u0430\u0437\u044b\u0432\u0430\u044e\u0449\u0438\u0445 \u043d\u0430 \u0434\u0435\u0444\u0438\u0446\u0438\u0442 \u0432\u0438\u0442\u0430\u043c\u0438\u043d\u0430 \u041212, \u0442\u0430\u043a\u0438\u0445 \u043a\u0430\u043a \u0433\u043e\u043b\u043e\u0432\u043e\u043a\u0440\u0443\u0436\u0435\u043d\u0438\u0435, \u0441\u043b\u0430\u0431\u043e\u0441\u0442\u044c, \u0443\u0441\u0442\u0430\u043b\u043e\u0441\u0442\u044c, \u0438\u0437\u043c\u0435\u043d\u0435\u043d\u0438\u044f \u0441\u043e \u0441\u0442\u043e\u0440\u043e\u043d\u044b \u0416\u041a\u0422 (\u0433\u043b\u043e\u0441\u0441\u0438\u0442, \u0443\u0432\u0435\u043b\u0438\u0447\u0435\u043d\u0438\u0435 \u043f\u0435\u0447\u0435\u043d\u0438).<\/li>\n<li>\u041f\u0440\u0438 \u043d\u0435\u043e\u0431\u0445\u043e\u0434\u0438\u043c\u043e\u0441\u0442\u0438 \u043f\u0440\u043e\u0432\u0435\u0440\u043a\u0438 \u043d\u0430 \u0434\u0435\u0444\u0438\u0446\u0438\u0442 \u041212\u00a0\u043f\u0430\u0446\u0438\u0435\u043d\u0442\u043e\u0432 \u0441 \u0440\u0430\u0437\u043b\u0438\u0447\u043d\u044b\u043c\u0438 \u043d\u0435\u0432\u0440\u043e\u043b\u043e\u0433\u0438\u0447\u0435\u0441\u043a\u0438\u043c\u0438 \u043d\u0430\u0440\u0443\u0448\u0435\u043d\u0438\u044f\u043c\u0438: \u043f\u0430\u0440\u0435\u0441\u0442\u0435\u0437\u0438\u0435\u0439 \u0438 \u043e\u043d\u0435\u043c\u0435\u043d\u0438\u0435\u043c \u0440\u0443\u043a \u0438\/\u0438\u043b\u0438 \u043d\u043e\u0433, \u043d\u0430\u0440\u0443\u0448\u0435\u043d\u0438\u0435\u043c \u0447\u0443\u0432\u0441\u0442\u0432\u0438\u0442\u0435\u043b\u044c\u043d\u043e\u0441\u0442\u0438, \u043f\u0435\u0440\u0438\u0444\u0435\u0440\u0438\u0447\u0435\u0441\u043a\u043e\u0439 \u043d\u0435\u0432\u0440\u043e\u043f\u0430\u0442\u0438\u0435\u0439.<\/li>\n<li>\u041f\u0440\u0438 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