{"id":219,"date":"2022-07-26T11:35:53","date_gmt":"2022-07-26T09:35:53","guid":{"rendered":"http:\/\/apitoxin.sk\/?p=219"},"modified":"2022-07-27T07:23:11","modified_gmt":"2022-07-27T05:23:11","slug":"aktualne-poznatky-o-vcelom-jede-a-terapii-vcelim-jedom","status":"publish","type":"post","link":"http:\/\/d.r20005.wbsprt.com\/apitoxin.sk\/2022\/07\/26\/aktualne-poznatky-o-vcelom-jede-a-terapii-vcelim-jedom\/","title":{"rendered":"Aktu\u00e1lne poznatky o v\u010de\u013eom jede a terapii v\u010del\u00edm jedom"},"content":{"rendered":"\n<p><\/p>\n\n\n\n<p class=\"has-small-font-size\">1.Medical School, Federal University of Roraima, Boa Vista, Braz\u00edlia<br>2.Katedra biotechnol\u00f3gie a biomedic\u00edny, Technick\u00e1 univerzita v D\u00e1nsku, Lyngby, D\u00e1nsko<br>3.Katedra fyziky a ch\u00e9mie, Fakulta farmaceutick\u00fdch vied v Ribeir\u00e3o Preto, Univerzita v S\u00e3o Paule, Ribeir\u00e3o Preto, Braz\u00edlia<br>4.Katedra biotechnol\u00f3gie a biologickej bezpe\u010dnosti, Univerzita Eski\u015fehir Osmangazi, Eski\u015fehir, Turecko<br>5.Katedra bioch\u00e9mie a imunol\u00f3gie, Lek\u00e1rska fakulta v Ribeir\u00e3o Preto, Univerzita S\u00e3o Paulo, Ribeir\u00e3o Preto, Braz\u00edlia<\/p>\n\n\n\n<p>V\u010dely medonosn\u00e9 mo\u017eno n\u00e1js\u0165 po celom svete a plnia k\u013e\u00fa\u010dov\u00e9 \u00falohy ope\u013eovania v r\u00e1mci svojich prirodzen\u00fdch ekosyst\u00e9mov, ako aj v po\u013enohospod\u00e1rstve. V\u00e4\u010d\u0161ina druhov je zvy\u010dajne u\u010denliv\u00e1 a v\u00e4\u010d\u0161ina interakci\u00ed medzi \u013eu\u010fmi a v\u010delami je bezprobl\u00e9mov\u00e1, napriek ich schopnosti vstrekn\u00fa\u0165 do obet\u00ed komplexn\u00fd jed ako obrann\u00fd mechanizmus. Napriek tomu od n\u00e1hodn\u00e9ho vypustenia afrikanizovan\u00fdch v\u010diel do Braz\u00edlie v roku 1956 a ich n\u00e1sledn\u00e9ho roz\u0161\u00edrenia po celej Amerike po\u010det u\u0161tipnut\u00ed v\u010diel st\u00fapa. Tieto hybridy v\u010diel s\u00fa agres\u00edvnej\u0161ie a n\u00e1chylnej\u0161ie na \u00fatoky, \u010do predstavuje zna\u010dn\u00fa zdravotn\u00fa z\u00e1\u0165a\u017e pre krajiny, ktor\u00e9 kolonizovali. Doteraz sa lie\u010dba tak\u00fdchto u\u0161tipnut\u00ed zvy\u010dajne zameriava na kontrolu potenci\u00e1lnych alergick\u00fdch reakci\u00ed, preto\u017ee v s\u00fa\u010dasnosti neexistuj\u00fa \u017eiadne \u0161pecifick\u00e9 protijedy proti v\u010deliemu jedu. V\u00fdskumn\u00edci sk\u00famali mo\u017enos\u0165 v\u00fdvoja v\u010del\u00edch protijedov, ale to bolo komplikovan\u00e9 ve\u013emi n\u00edzkou imunogenicitou k\u013e\u00fa\u010dov\u00fdch v\u010del\u00edch tox\u00ednov, ktor\u00e9 nedok\u00e1zali vyvola\u0165 siln\u00fa protil\u00e1tkov\u00fa odpove\u010f u imunizovan\u00fdch zvierat. So s\u00fa\u010dasn\u00fdmi \u0161pi\u010dkov\u00fdmi technol\u00f3giami, ako je f\u00e1gov\u00fd displej, je v\u0161ak popri vzostupe monoklon\u00e1lnych protil\u00e1tkov\u00fdch terapeut\u00edk dosiahnute\u013en\u00fd v\u00fdvoj rekombinantn\u00e9ho v\u010delieho protijedu a v posledn\u00fdch rokoch boli hl\u00e1sen\u00e9 s\u013eubn\u00e9 v\u00fdsledky smerom k tomuto cie\u013eu. Tu s\u00fa zhrnut\u00e9 s\u00fa\u010dasn\u00e9 poznatky o biol\u00f3gii jedu afrikanizovan\u00fdch v\u010diel a s\u00fa\u010dasn\u00fdch mo\u017enostiach lie\u010dby proti otrave v\u010diel. Okrem toho je prezentovan\u00fd a diskutovan\u00fd najnov\u0161\u00ed v\u00fdvoj v oblasti protijedov novej gener\u00e1cie v\u010diel.<\/p>\n\n\n\n<p><strong>\u00davod<\/strong><br>V\u010dely s\u00fa ekonomicky prospe\u0161n\u00fd hmyz, ktor\u00e9ho existencia siaha do obdobia kriedy po\u010das druhoh\u00f4r (1). V\u010dely poskytli \u013eu\u010fom nieko\u013eko produktov, ako je med, v\u010del\u00ed vosk, pe\u013e, matersk\u00e1 ka\u0161i\u010dka a propolis (2). Ope\u013euj\u00fa aj \u0161irok\u00fa \u0161k\u00e1lu po\u013enohospod\u00e1rskych plod\u00edn (3). Aj ke\u010f s\u00fa v\u010dely mimoriadne prospe\u0161n\u00e9 pre plodiny a \u013eud\u00ed, predstavuj\u00fa nebezpe\u010denstvo kv\u00f4li svojej schopnosti sp\u00f4sobova\u0165 bolestiv\u00e9 a toxick\u00e9 bodnutia (4). Na\u0161\u0165astie v\u00e4\u010d\u0161ina v\u010diel medonosn\u00fdch nie je vo\u010di \u013eu\u010fom agres\u00edvna a \u00fato\u010dia len vtedy, ke\u010f sa c\u00edtia ohrozen\u00e9. Av\u0161ak kv\u00f4li introdukcii afrikanizovanej v\u010dely, hybrida s vysoko agres\u00edvnym spr\u00e1van\u00edm \u010dlovekom, sa mas\u00edvne \u00fatoky v\u010delieho bodnutia v\u00fdrazne zv\u00fd\u0161ili av s\u00fa\u010dasnosti s\u00fa endemick\u00e9 vo v\u00e4\u010d\u0161ine Ameriky (okrem \u010cile a Kanady) (5). Existuj\u00fa \u0161tandardizovan\u00e9 medic\u00ednske pr\u00edstupy na rie\u0161enie pr\u00edpadov, ke\u010f s\u00fa obete alergick\u00e9 na zlo\u017eky jedu po\u0161t\u00edpan\u00e9 v\u010delami, alebo ke\u010f miernej\u0161ie otravy sp\u00f4sob\u00ed len nieko\u013eko v\u010del\u00edch bodnut\u00ed. Napriek tomu neexistuje \u017eiadny protijed na lie\u010dbu \u0165a\u017ek\u00fdch jedov v\u010diel. Z\u00e1kladn\u00fdm d\u00f4vodom je n\u00edzka imunogenicita prote\u00ednov v\u010delieho jedu (napr\u00edklad melitt\u00edn), ktor\u00e1 br\u00e1ni \u00faspe\u0161nej imuniz\u00e1cii produk\u010dn\u00fdch zvierat, aby sa dosiahli vysok\u00e9 titre protil\u00e1tok v ich plazme, a n\u00e1sledne v\u00fdrazne komplikuje v\u00fdvoj v\u010delieho protijedu (6). . Na v\u00fdvoj lie\u010dby proti siln\u00e9mu jedu v\u010diel je nevyhnutn\u00fd n\u00e1vrh \u00fa\u010dinn\u00e9ho protijedu. Tu s\u00fa presk\u00faman\u00e9 s\u00fa\u010dasn\u00e9 poznatky o biol\u00f3gii v\u010diel, \u0161\u00edren\u00ed afrikanizovan\u00fdch hybridov v\u010diel v Amerike a apar\u00e1te v\u010delieho jedu a tox\u00ednov a poskytuje sa diskusia o s\u00fa\u010dasnej a \u010fal\u0161ej gener\u00e1cii lie\u010dby v\u010delieho jedu.<\/p>\n\n\n\n<p><strong>Druhy v\u010diel, ich spr\u00e1vanie a epidemiol\u00f3gia<\/strong><br>V\u010dely medonosn\u00e9 (druh Apis) s\u00fa spolo\u010densk\u00fd hmyz, ktor\u00fd \u017eije v dobre organizovan\u00fdch spolo\u010denstv\u00e1ch a je ve\u013emi d\u00f4le\u017eit\u00fd pre v\u00fdznamn\u00fa \u010das\u0165 svetov\u00e9ho hospod\u00e1rstva v\u010faka k\u013e\u00fa\u010dovej \u00falohe, ktor\u00fa plnia ako ope\u013eova\u010de v po\u013enohospod\u00e1rstve (7). V poslednom desa\u0165ro\u010d\u00ed sa im v\u0161ak venuje zv\u00fd\u0161en\u00e1 pozornos\u0165 kv\u00f4li inej fyziologickej vlastnosti: ich schopnosti doda\u0165 jedovat\u00e9 bodnutie (8). Druhy v\u010diel, ktor\u00e9 s\u00fa preva\u017ene zodpovedn\u00e9 za \u013eudsk\u00e9 jedy, s\u00fa Apis mellifera mellifera (A. m. mellifera) a A. m. ligustica v Eur\u00f3pe a A. m. scutellata v Afrike (8).<\/p>\n\n\n\n<p>V\u010delie \u017eihadlo nie je nov\u00fdm fenom\u00e9nom. V skuto\u010dnosti sa v\u00fdznamn\u00e9 vystavenie \u013eud\u00ed v\u010del\u00edm bodnutiam datuje pred viac ako 7 000 rokmi, ke\u010f \u013eudia za\u010dali spravova\u0165 popul\u00e1cie v\u010diel t\u00fdm, \u017ee im poskytli umel\u00e9 \u00fale, aby umo\u017enili efekt\u00edvnu \u00farodu ich medu a vosku alebo na \u00fa\u010dely ope\u013eovania (9, 10). Napriek zna\u010dn\u00e9mu \u0161\u013eachtite\u013esk\u00e9mu \u00fasiliu je potrebn\u00e9 v\u010dely \u00faspe\u0161ne domestikova\u0165 a okrem in\u00fdch vlastnost\u00ed nebolo hl\u00e1sen\u00e9 zn\u00ed\u017eenie adit\u00edvnej genetickej vari\u00e1cie, fix\u00e1cia alel spojen\u00fdch so znakmi ekonomick\u00e9ho v\u00fdznamu, zv\u00fd\u0161en\u00e1 krotkos\u0165 a rozvoj \u0161pecifick\u00fdch vlastnost\u00ed plemena ( 11). V skuto\u010dnosti sa zd\u00e1, \u017ee cielen\u00e9 \u0161\u013eachtenie sk\u00f4r zv\u00fd\u0161ilo ne\u017e zn\u00ed\u017eilo genetick\u00fa diverzitu (12).<\/p>\n\n\n\n<p>V\u00e4\u010d\u0161ina komer\u010dn\u00fdch popul\u00e1ci\u00ed v\u010diel medonosn\u00fdch poch\u00e1dza z Eur\u00f3py, hoci z evolu\u010dn\u00e9ho h\u013eadiska poch\u00e1dzaj\u00fa z Afriky a do Eur\u00f3py sa dostali prostredn\u00edctvom dvoch nez\u00e1visl\u00fdch migra\u010dn\u00fdch udalost\u00ed (13). V 20. rokoch 17. storo\u010dia boli eur\u00f3pske v\u010dely medonosn\u00e9 (A. m. mellifera) \u00faspe\u0161ne zavle\u010den\u00e9 do Severnej Ameriky na ope\u013eovanie a produkciu medu. Nesk\u00f4r, v roku 1822, boli zavle\u010den\u00e9 do Austr\u00e1lie (14). Pokusy zopakova\u0165 p\u00f4vodn\u00e9 \u00faspechy zo Severnej Ameriky a Austr\u00e1lie zlyhali v roku 1839 v Braz\u00edlii a v in\u00fdch tropick\u00fdch oblastiach (15, 16). Verilo sa, \u017ee toto zlyhanie pramen\u00ed z ve\u013emi rozdielneho podnebia na oboch kontinentoch. V roku 1955 sa uskuto\u010dnili nov\u00e9 pokusy zah\u0155\u0148aj\u00face africk\u00fa v\u010delu medonosn\u00fa (A. m. scutellata), ktor\u00e1 bola kr\u00ed\u017een\u00e1 s medonosn\u00fdmi v\u010delami eur\u00f3pskeho p\u00f4vodu s cie\u013eom vytvori\u0165 hybridn\u00fd druh, ktor\u00fd by lep\u0161ie prosperoval v tropickom prostred\u00ed a produkoval ve\u013ek\u00e9 mno\u017estvo vysoko kvalitn\u00e9ho medu ( 15 \u2013 18). V nasleduj\u00facom roku v\u0161ak 26 matiek a ich roje afrikanizovan\u00fdch (hybridn\u00fdch) v\u010diel uniklo z laborat\u00f3ria a napadli ve\u013ek\u00e9 \u010dasti Ameriky a roz\u0161\u00edrili sa o 300 \u2013 500 km ro\u010dne (obr\u00e1zok 1) (15 \u2013 17). V\u010dely dosiahli Mexiko v roku 1986, USA v roku 1990 (Texas) a odvtedy sa roz\u0161\u00edrili do mnoh\u00fdch \u0161t\u00e1tov vr\u00e1tane Kalifornie, Arizony, Utahu, Nov\u00e9ho Mexika, Oklahomy, Louisiany, Arkansasu, Alabamy a Floridy (16, 19\u201322). . Hoci klimatick\u00e9 obmedzenia, najm\u00e4 chladn\u00e9 zimy, v\u00fdrazne spomalili \u0161\u00edrenie t\u00fdchto hybridn\u00fdch v\u010diel a v s\u00fa\u010dasnosti obmedzuj\u00fa rozsah ich biotopu, st\u00e1le sa ver\u00ed, \u017ee s\u00fa schopn\u00e9 kolonizova\u0165 Severn\u00fa Ameriku, kde bude ich jedinou prirodzenou bari\u00e9rou tuh\u00e1 zima. Tento rozsah sa pravdepodobne bude roz\u0161irova\u0165 s glob\u00e1lnym n\u00e1rastom tepl\u00f4t (16, 23).<\/p>\n\n\n\n<figure class=\"wp-block-image size-full\"><img decoding=\"async\" loading=\"lazy\" width=\"582\" height=\"815\" src=\"http:\/\/apitoxin.sk\/wp-content\/uploads\/2022\/07\/mapa.jpg\" alt=\"\" class=\"wp-image-220\" srcset=\"http:\/\/d.r20005.wbsprt.com\/apitoxin.sk\/wp-content\/uploads\/2022\/07\/mapa.jpg 582w, http:\/\/d.r20005.wbsprt.com\/apitoxin.sk\/wp-content\/uploads\/2022\/07\/mapa-214x300.jpg 214w\" sizes=\"(max-width: 582px) 100vw, 582px\" \/><figcaption>OBR\u00c1ZOK 1. S\u00fa\u010dasn\u00e9 a predpokladan\u00e9 bud\u00face roz\u0161\u00edrenie afrikanizovan\u00fdch v\u010diel medonosn\u00fdch v Amerike.<\/figcaption><\/figure>\n\n\n\n<p>\u00daspech afrikanizovan\u00fdch v\u010diel v Amerike sa pripisuje kombin\u00e1cii ekologick\u00fdch a genetick\u00fdch faktorov, ktor\u00e9 im poskytli zv\u00fd\u0161en\u00fa kond\u00edciu v porovnan\u00ed s dom\u00e1cimi ope\u013eova\u010dmi (15, 16). Pr\u00edklady zah\u0155\u0148aj\u00fa vy\u0161\u0161iu reproduk\u010dn\u00fa r\u00fdchlos\u0165, krat\u0161\u00ed v\u00fdvojov\u00fd cyklus (t. j. robotniciam trv\u00e1 19 \u2013 20 dn\u00ed namiesto 21 a matk\u00e1m trv\u00e1 14 dn\u00ed namiesto 16, k\u00fdm dospej\u00fa), vy\u0161\u0161ia produkcia\/po\u010detnos\u0165 tr\u00fadov, vy\u0161\u0161ia miera \u00fateku (t. j. n\u00faten\u00e9 premiest\u0148ovanie kol\u00f3ni\u00ed v pr\u00edpade nedostatku potravy) a vy\u0161\u0161ia miera rojenia (prirodzen\u00e1 expanzia a rozmno\u017eovanie kol\u00f3ni\u00ed; 6\u201312-kr\u00e1t ro\u010dne v pr\u00edpade dostatku potravy), ni\u017e\u0161ie potreby skladovania medu, odolnos\u0165 vo\u010di chorob\u00e1m a zn\u00ed\u017een\u00e1 selektivita pri v\u00fdbere hniezdisk (15, 24\u201326). Okrem toho s\u00fa afrikanizovan\u00e9 v\u010dely v\u00fdrazne defenz\u00edvnej\u0161ie ako in\u00e9 v\u010dely. Prejavuje sa to v ich sklone \u00fato\u010di\u0165 s malou stimul\u00e1ciou, zv\u00fd\u0161en\u00fdm po\u010dtom v\u010diel, ktor\u00e9 spolu\u00fato\u010dia vo v\u00e4\u010d\u0161ej vzdialenosti od \u00fa\u013ea ako zvy\u010dajne, ich v\u00fdrazn\u00fdm naliehan\u00edm na prenasledovanie votrelcov po dlh\u0161iu dobu a vyp\u00fa\u0161\u0165an\u00edm \u00fadajne v\u00e4\u010d\u0161\u00edch objemov. z jedu (15, 16). Tieto vlastnosti viedli k tomu, \u017ee s\u00fa be\u017ene zn\u00e1me ako \u201ev\u010dely zabijaky\u201c.<\/p>\n\n\n\n<p>Predpoklad\u00e1 sa, \u017ee zv\u00fd\u0161en\u00e1 agresivita t\u00fdchto v\u010del\u00edch hybridov sp\u00f4sobuje zna\u010dn\u00e9 pokra\u010duj\u00face straty hospod\u00e1rskych zvierat a probl\u00e9my so zdrav\u00edm \u013eud\u00ed, napriek tomu existuje nedostatok spo\u013eahliv\u00fdch inform\u00e1ci\u00ed o frekvencii mas\u00edvnych bodav\u00fdch udalost\u00ed a z\u00e1va\u017en\u00fdch otrav\u00e1ch (8, 27, 28). Tento nedostatok \u00fadajov je pravdepodobn\u00fd preto, \u017ee v\u00e4\u010d\u0161ina v\u010del\u00edch bodnut\u00ed m\u00e1 men\u0161\u00ed medic\u00ednsky v\u00fdznam a u\u0161tipnut\u00ed jedinci nevyh\u013ead\u00e1vaj\u00fa lek\u00e1rsku starostlivos\u0165 (8, 27). Okrem toho nieko\u013eko vl\u00e1dnych agent\u00far zhroma\u017e\u010fuje \u00fadaje o frekvenci\u00e1ch bodnutia (8) a \u010dasto zoskupuje v\u0161etky uhryznutia a bodnutia zvierat v lek\u00e1rskych z\u00e1znamoch z pohotovostn\u00fdch oddelen\u00ed (29). Napr\u00edklad v USA sa vo v\u00fdro\u010dnej spr\u00e1ve Americkej asoci\u00e1cie centier na kontrolu jedov uv\u00e1dza, \u017ee v roku 2017 do\u0161lo k 41 850 uhryznutiam\/u\u0161tipnut\u00edm zvieratami a \u0161tyrom \u00famrtiam, av\u0161ak nedostatok \u0161pecifickosti \u00fadajov znemo\u017e\u0148uje prip\u00edsa\u0165 ur\u010dit\u00fd po\u010det pr\u00edpadov. na otravy v\u010diel (29). Hoci ned\u00e1vna spr\u00e1va Centra pre kontrolu a prevenciu chor\u00f4b (CDC) ukazuje, \u017ee za posledn\u00fdch 5 rokov sa zv\u00fd\u0161il po\u010det neh\u00f4d a \u00famrt\u00ed bodav\u00fdm hmyzom (ro\u010dn\u00fd priemer 62 \u00famrt\u00ed), spr\u00e1va kombinuje nehody sr\u0161\u0148ov, \u00f4s a v\u010diel. spolu (30). Aj ke\u010f existuje jedna pr\u00edkladn\u00e1 spr\u00e1va o otrav\u00e1ch suchozemsk\u00fdmi zvieratami v Braz\u00edlii, kde sa \u00fadaje zbierali v priebehu 12 rokov (8, 27). \u0160t\u00fadia zistila, \u017ee v rokoch 2001 a\u017e 2012 bolo zaznamenan\u00fdch celkovo 1 192 667 otrav, z ktor\u00fdch 66 283 (5,6 %) mo\u017eno prip\u00edsa\u0165 v\u010del\u00e1m. Pozoruhodn\u00e9 je, \u017ee u\u0161tipnutie v\u010delou m\u00e1 druh\u00fa najvy\u0161\u0161iu mieru \u00famrtnosti (0,33 %; 216 \u00famrt\u00ed), pri\u010dom ju prevy\u0161uje iba u\u0161tipnutie hadom (0,43 %; 3 394 \u00famrt\u00ed) (27). \u0160t\u00fadia uk\u00e1zala, \u017ee miera \u00famrtnosti v rokoch 2001 a\u017e 2012 neprejavila \u017eiadne v\u00fdznamn\u00e9 v\u00fdkyvy (27). Vzh\u013eadom na v\u00fdznamn\u00fd v\u00fdskyt v\u010del\u00edch bodnut\u00ed v Braz\u00edlii je pravdepodobn\u00e9, \u017ee podobn\u00e9 probl\u00e9my verejn\u00e9ho zdravia existuj\u00fa aj v in\u00fdch krajin\u00e1ch v Amerike s ve\u013ek\u00fdm po\u010dtom afrikanizovan\u00fdch kol\u00f3ni\u00ed v\u010diel (27, 28). V skuto\u010dnosti sa od ich pr\u00edchodu do USA objavilo nieko\u013eko spr\u00e1v o \u00famrtiach po \u00fatokoch roja afrikanizovan\u00fdch v\u010diel (31). Celkovo vzat\u00e9, zna\u010dn\u00fd po\u010det v\u010del\u00edch bodnut\u00ed a relat\u00edvne vysok\u00e1 miera \u00famrtnosti t\u00fdchto bodnut\u00ed nazna\u010duj\u00fa, \u017ee existuje rast\u00faca medic\u00ednska potreba inovat\u00edvnych mo\u017enost\u00ed lie\u010dby, ako s\u00fa \u0161pecifick\u00e9 v\u010delie protijedy na rie\u0161enie z\u00e1va\u017en\u00fdch jedov. Finan\u010dn\u00e9 vyhliadky v\u00fdvoja produktov proti jedu pre trh s\u00fa v\u0161ak v s\u00fa\u010dasnosti nezn\u00e1me a \u0165a\u017eko predv\u00eddate\u013en\u00e9.<\/p>\n\n\n\n<p><strong>V\u010delie bodnutie a jed<\/strong><br>\u017dihadlo m\u00e1 tri funk\u010dne odli\u0161n\u00e9 \u010dasti; motorick\u00e1 \u010das\u0165, \u017e\u00edhacia \u010das\u0165 a \u010das\u0165 s\u00favisiaca s jedom (obr\u00e1zok 2A) (32\u201334). V \u017e\u00edhacej \u010dasti zohr\u00e1vaj\u00fa d\u00f4le\u017eit\u00fa \u00falohu mandr\u00e9n a lancety. Prekr\u00fdvaj\u00fa ich \u0161tvorstenn\u00e9 ostne, ktor\u00e9 s\u00fa rozmiestnen\u00e9 \u0161pir\u00e1lovito pravoto\u010divo. Tento \u0161pecifick\u00fd typ distrib\u00facie hr\u00e1 z\u00e1sadn\u00fa \u00falohu pri \u0161pir\u00e1lovej rot\u00e1cii \u017eihadla v smere hodinov\u00fdch ru\u010di\u010diek po\u010das prenikania \u017eihadla do rany a zni\u017euje penetra\u010dn\u00fa silu (35). Tieto ostne v\u010dele takmer znemo\u017e\u0148uj\u00fa stiahnu\u0165 \u017eihadlo z elastick\u00e9ho m\u00e4sa cicavcov pri \u00fateku (obr\u00e1zok 2B). T\u00e1to situ\u00e1cia m\u00f4\u017ee \u013eahko vies\u0165 k autot\u00f3mii \u017eihadla, kedy sa \u017eihac\u00ed apar\u00e1t a s n\u00edm spojen\u00e9 svaly oddelia od zvy\u0161ku brucha pri \u00fateku v\u010dely od obete (36).<\/p>\n\n\n\n<figure class=\"wp-block-image size-full\"><img decoding=\"async\" loading=\"lazy\" width=\"955\" height=\"527\" src=\"http:\/\/apitoxin.sk\/wp-content\/uploads\/2022\/07\/ziha.jpg\" alt=\"\" class=\"wp-image-222\" srcset=\"http:\/\/d.r20005.wbsprt.com\/apitoxin.sk\/wp-content\/uploads\/2022\/07\/ziha.jpg 955w, http:\/\/d.r20005.wbsprt.com\/apitoxin.sk\/wp-content\/uploads\/2022\/07\/ziha-300x166.jpg 300w, http:\/\/d.r20005.wbsprt.com\/apitoxin.sk\/wp-content\/uploads\/2022\/07\/ziha-768x424.jpg 768w\" sizes=\"(max-width: 955px) 100vw, 955px\" \/><figcaption>OBR\u00c1ZOK 2.  \u017dihadlo v\u010diel. (A) Jedov\u00fd apar\u00e1t pozost\u00e1va z troch funk\u010dne odli\u0161n\u00fdch \u010dast\u00ed: (1) \u010cas\u0165 s\u00favisiaca s jedom sa sklad\u00e1 z jedov\u00e9ho vaku, dvoch jedov\u00fdch \u017eliaz a bulbu. (2) Motorick\u00e1 \u010das\u0165 sa sklad\u00e1 zo svalov, platni\u010diek a ramena na ka\u017edej strane. (3) Bodav\u00e1 \u010das\u0165 sa sklad\u00e1 z dvoch lancet a mandr\u00e9nu (pozn\u00e1mka: mandr\u00e9n na tomto obr\u00e1zku nie je mo\u017en\u00e9 pozorova\u0165, preto\u017ee pozd\u013a\u017eny rez pre\u0161iel stredom jedov\u00e9ho kan\u00e1la, ktor\u00fd op\u00fa\u0161\u0165a mandr\u00e9n v hornej \u010dasti). (B) Ostne ukotvia \u017eihadlo do ko\u017ee, odkia\u013e sa \u017eihadlo pri \u00faniku v\u010dely ned\u00e1 stiahnu\u0165 (t. j. autot\u00f3mia \u017eihadla).<\/figcaption><\/figure>\n\n\n\n<p>Na rozdiel od v\u0161eobecn\u00e9ho presved\u010denia zost\u00e1vaj\u00fa v\u010dely robotnice na\u017eive 18\u2013114 hod\u00edn po autotomiz\u00e1cii bodnutia a na\u010falej hraj\u00fa svoju \u00falohu obrancov (37). Ke\u010f v\u010dela ute\u010die, jej autotomizovan\u00e9 \u017eihadlo sa na\u010falej zas\u00fava do rany po dobu ~30 s (38) a jed m\u00f4\u017ee by\u0165 st\u00e1le dod\u00e1van\u00fd. Je pozoruhodn\u00e9, \u017ee najmenej 90 % obsahu jedov\u00e9ho vrec\u00fa\u0161ka sa doru\u010d\u00ed v priebehu prv\u00fdch 20 sek\u00fand po bodnut\u00ed (38) a odstr\u00e1nenie bodnutia (pozri \u010das\u0165 Po\u0161kodenie v\u010dely: Klinick\u00e9 prejavy) 1 min\u00fatu po tejto udalosti je nepravdepodobn\u00e9. zn\u00ed\u017ei\u0165 toxicitu vyvolan\u00fa jedom. Pri bodnut\u00ed sa v priemere dostane 140 \u2013 150 \u03bcg jedu a stredn\u00e1 let\u00e1lna d\u00e1vka (LD50) v\u010delieho jedu sa pohybuje medzi 2,8 a 3,5 mg jedu na kg telesnej hmotnosti \u010dloveka (38 \u2013 41). D\u00e1 sa teda \u0161pekulova\u0165, \u017ee nealergick\u00fd \u010dlovek s hmotnos\u0165ou 60 \u2013 70 kg m\u00e1 50 % pravdepodobnos\u0165 \u00famrtia po u\u0161tipnut\u00ed 1 000 \u2013 1 500 v\u010delami, hoci boli hl\u00e1sen\u00e9 aj \u00famrtia sp\u00f4soben\u00e9 iba 200 \u2013 500 bodnutiami (38, 42). . Z\u00e1va\u017enos\u0165 otravy je skuto\u010dne ur\u010den\u00e1 vekom obete, telesnou hmotnos\u0165ou, po\u010dtom bodnut\u00ed a individu\u00e1lnymi charakteristikami obete (imunitn\u00fd stav, komorbidity a predch\u00e1dzaj\u00faca senzibiliz\u00e1cia) (43).<\/p>\n\n\n\n<p>V\u010del\u00ed jed je komplexn\u00e1 zmes zl\u00fa\u010den\u00edn, ktor\u00e9 zah\u0155\u0148aj\u00fa prote\u00edny, peptidy, aminokyseliny, fosfolipidy, cukry, biog\u00e9nne am\u00edny, prchav\u00e9 zl\u00fa\u010deniny, ferom\u00f3ny a ve\u013ek\u00e9 mno\u017estvo vody (>80%) (44\u201346). Zlo\u017eenie v\u010delieho jedu u\u017e bolo objasnen\u00e9 omick\u00fdmi technikami (47\u201349) a frakcion\u00e1ciou jedu (50\u201353). V tomto preh\u013eade bud\u00fa podrobne op\u00edsan\u00e9 iba zlo\u017eky s d\u00f4le\u017eit\u00fdmi klinick\u00fdmi a terapeutick\u00fdmi \u00fa\u010dinkami a s dostato\u010dnou podporou literat\u00fary, zatia\u013e \u010do ostatn\u00e9 zl\u00fa\u010deniny v\u010delieho jedu s\u00fa uveden\u00e9 iba v tabu\u013eke 1. Je d\u00f4le\u017eit\u00e9 zd\u00f4razni\u0165, \u017ee v\u010dely s\u00fa hmyz z radu Hymenoptera, ktor\u00fd zah\u0155\u0148a osy (80). Preto v\u010delie jedy obsahuj\u00fa niektor\u00e9 z rovnak\u00fdch zl\u00fa\u010den\u00edn ako jedy osy, ako je adrenal\u00edn, dopam\u00edn, histam\u00edn, hyaluronid\u00e1za, noradrenal\u00edn, fosfolip\u00e1zy A2 (PLA2s), fosfolip\u00e1zy B (PLB) a seroton\u00edn (81), zatia\u013e \u010do apam\u00edn obsahuj\u00fa iba v\u010delie jedy. (82), melit\u00edn (50) a peptid degranuluj\u00faci \u017e\u00edrne bunky (MCD) (83, 84).<\/p>\n\n\n\n<figure class=\"wp-block-image size-full\"><img decoding=\"async\" loading=\"lazy\" width=\"930\" height=\"820\" src=\"http:\/\/apitoxin.sk\/wp-content\/uploads\/2022\/07\/tab.png\" alt=\"\" class=\"wp-image-225\" srcset=\"http:\/\/d.r20005.wbsprt.com\/apitoxin.sk\/wp-content\/uploads\/2022\/07\/tab.png 930w, http:\/\/d.r20005.wbsprt.com\/apitoxin.sk\/wp-content\/uploads\/2022\/07\/tab-300x265.png 300w, http:\/\/d.r20005.wbsprt.com\/apitoxin.sk\/wp-content\/uploads\/2022\/07\/tab-768x677.png 768w\" sizes=\"(max-width: 930px) 100vw, 930px\" \/><figcaption>TABU\u013dKA 1. Zl\u00fa\u010deniny v\u010delieho jedu.<\/figcaption><\/figure>\n\n\n\n<p>Melitt\u00edn je hlavn\u00e1 a najtoxickej\u0161ia zl\u00fa\u010denina v\u010delieho jedu, ktor\u00e1 tvor\u00ed 50\u201360 % celkov\u00e9ho jedu (85). Melitt\u00edn vyvol\u00e1va iba men\u0161ie alergick\u00e9 reakcie (86), ale sp\u00f4sobuje v\u00e4\u010d\u0161inu bolesti spojenej so v\u010del\u00edm bodnut\u00edm (4), ktor\u00e1 je vyvolan\u00e1 priamym a nepriamym p\u00f4soben\u00edm na prim\u00e1rne nociceptorov\u00e9 bunky. Priame p\u00f4sobenie je sp\u00f4soben\u00e9 melit\u00ednovou aktiv\u00e1ciou term\u00e1lneho nociceptorov\u00e9ho potenci\u00e1lu vaniloidu 1 (TRPV1) prostredn\u00edctvom kask\u00e1dovej dr\u00e1hy PLA2, \u010do vedie k senzibiliz\u00e1cii prim\u00e1rnych nociceptorov (87\u201389). Nepriamy \u00fa\u010dinok je zalo\u017een\u00fd na p\u00f4soben\u00ed melit\u00ednu pri tvorbe p\u00f3rov (obr\u00e1zok 3), ktor\u00fd umo\u017e\u0148uje uvo\u013e\u0148ovanie l\u00e1tok vyvol\u00e1vaj\u00facich boles\u0165, ako s\u00fa H+, adenoz\u00edntrifosf\u00e1t (ATP) a 5-hydroxytryptam\u00edn (5-HT) zo \u017e\u00edrnych buniek. ako aj melit\u00edn sp\u00f4sobuje po\u0161kodenie tkaniva, \u010do vedie k aktiv\u00e1cii receptorov bolesti. Tvorba p\u00f3rov vyvolan\u00e1 melit\u00ednom m\u00f4\u017ee tie\u017e uvo\u013e\u0148ova\u0165 medi\u00e1tory, ako je histam\u00edn, bradykin\u00edn a ATP, ktor\u00e9 aktivuj\u00fa receptory spojen\u00e9 s G-prote\u00ednom (GPCR), \u010do vedie k fosforyl\u00e1cii fosfolip\u00e1zy C (PLC). PLC \u0161tiepi fosfatidylinozitol 4,5-bisfosf\u00e1tintodiacylglycerol (DAG) a inozitol 1,4,5-trifosf\u00e1t (IP3). DAG je endog\u00e9nny aktiv\u00e1tor kanonick\u00fdch kan\u00e1lov s prechodn\u00fdm receptorov\u00fdm potenci\u00e1lom (TRPC), \u010do vedie k nepriamej excit\u00e1cii prim\u00e1rnych nocicept\u00edvnych neur\u00f3nov (t.j. bolesti). Podrobnej\u0161\u00ed preh\u013ead mechanizmu melitt\u00ednu vyvol\u00e1vaj\u00faceho boles\u0165 mo\u017eno n\u00e1js\u0165 inde (4). Melitt\u00edn je klasifikovan\u00fd ako lytick\u00fd peptid, ktor\u00fd je schopn\u00fd ni\u010di\u0165 membr\u00e1nov\u00e9 fosfolipidy, medzi ktor\u00e9 patria erytrocyty, \u010do vedie k hemol\u00fdze (85, 91). Tento \u00fa\u010dinok m\u00f4\u017ee by\u0165 odvoden\u00fd od konforma\u010dnej modifik\u00e1cie, kde sa predpoklad\u00e1, \u017ee molekuly melit\u00ednu sa via\u017eu kolmo na membr\u00e1ny vytv\u00e1raj\u00face p\u00f3ry (90) (obr\u00e1zok 3). Okrem toho m\u00f4\u017ee melit\u00edn zv\u00fd\u0161i\u0165 aktivitu PLA2 (92). Napr\u00edklad aktivita PLA2 bola testovan\u00e1 s melitt\u00ednom a bez neho na lecit\u00ednov\u00fdch lipoz\u00f3moch a bolo pozorovan\u00e9, \u017ee aktivita PLA2 bola 5-kr\u00e1t vy\u0161\u0161ia v pr\u00edtomnosti melit\u00ednu (92). Vo v\u010delom jede mo\u017eno n\u00e1js\u0165 r\u00f4zne izoformy melit\u00ednu, ako je melit\u00edn-S a melitt\u00edn-F. Tieto v\u0161ak existuj\u00fa len v malom mno\u017estve (68, 71). Preuk\u00e1zalo sa, \u017ee melitt\u00edn m\u00e1 antimikrobi\u00e1lnu aktivitu in vitro a in vivo (91), protiz\u00e1palov\u00e9 \u00fa\u010dinky in vitro (93), antiv\u00edrusov\u00fa aktivitu in vitro (94) a protirakovinov\u00e9 \u00fa\u010dinky in vitro a in vivo (95). Nakoniec stoj\u00ed za zmienku, \u017ee melit\u00edn mo\u017eno chemicky syntetizova\u0165, aby sa z\u00edskali vysok\u00e9 mno\u017estv\u00e1 peptidu (69, 96, 97).<\/p>\n\n\n\n<figure class=\"wp-block-image size-full\"><img decoding=\"async\" loading=\"lazy\" width=\"952\" height=\"433\" src=\"http:\/\/apitoxin.sk\/wp-content\/uploads\/2022\/07\/bunka.jpg\" alt=\"\" class=\"wp-image-228\" srcset=\"http:\/\/d.r20005.wbsprt.com\/apitoxin.sk\/wp-content\/uploads\/2022\/07\/bunka.jpg 952w, http:\/\/d.r20005.wbsprt.com\/apitoxin.sk\/wp-content\/uploads\/2022\/07\/bunka-300x136.jpg 300w, http:\/\/d.r20005.wbsprt.com\/apitoxin.sk\/wp-content\/uploads\/2022\/07\/bunka-768x349.jpg 768w\" sizes=\"(max-width: 952px) 100vw, 952px\" \/><figcaption>OBR\u00c1ZOK 3. Model tvorby p\u00f3rov indukovanej melit\u00ednom. Melit\u00edn sa m\u00f4\u017ee viaza\u0165 na membr\u00e1nu bu\u010f v paralelnej orient\u00e1cii (1) alebo v kolmej orient\u00e1cii (2). Kolm\u00e1 orient\u00e1cia vyvol\u00e1va tvorbu p\u00f3rov, zatia\u013e \u010do paraleln\u00e1 orient\u00e1cia je neakt\u00edvna. Predpokladalo sa tie\u017e, \u017ee paraleln\u00e1 orient\u00e1cia chr\u00e1ni membr\u00e1nu, preto\u017ee to br\u00e1ni in\u00fdm molekul\u00e1m melit\u00ednu vo vytv\u00e1ran\u00ed p\u00f3rov. Obr\u00e1zok upraven\u00fd pod\u013ea van den Bogaart et al. (90).<\/figcaption><\/figure>\n\n\n\n<p>Fosfolip\u00e1za A2 (PLA2) je druhou najroz\u0161\u00edrenej\u0161ou zl\u00fa\u010deninou (10\u201312 %) a najalerg\u00e9nnej\u0161\u00edm a najimunog\u00e9nnej\u0161\u00edm prote\u00ednom vo v\u010delom jede (83). Samotn\u00e1 PLA2 je netoxick\u00fd prote\u00edn (44, 83), ale ke\u010f PLA2 vytvor\u00ed komplex s melit\u00ednom, naz\u00fdvan\u00fd v\u010del\u00ed hemolytick\u00fd faktor, \u0161tiepi fosfolipidy bunkovej membr\u00e1ny (98). In vitro m\u00e1 v\u010del\u00ed PLA2 nieko\u013eko aktiv\u00edt, ako s\u00fa trypanoc\u00eddne a antibakteri\u00e1lne \u00fa\u010dinky (99, 100), ochrana neur\u00f3nov sp\u00f4soben\u00e1 pri\u00f3nov\u00fdmi prote\u00ednmi (101) a protin\u00e1dorov\u00e9 vlastnosti (102). Okrem toho bola v\u010delia PLA2 schopn\u00e1 zn\u00ed\u017ei\u0165 hepatotoxicitu sp\u00f4soben\u00fa acetaminof\u00e9nom u my\u0161\u00ed (103). Fosfolip\u00e1za B (PLB) bola tie\u017e hl\u00e1sen\u00e1 ako pr\u00edtomn\u00e1 vo v\u010delom jede (75). PLB vykazuje aktivitu PLA1 aj PLA2, pri\u010dom je zodpovedn\u00e1 za \u0161tiepenie fosfolipidov v polohe sn-1 a sn-2 acylov\u00fdch re\u0165azcov (104), \u010do zvy\u0161uje aktivitu PLA2 (46). PLB s\u00fa tie\u017e d\u00f4le\u017eit\u00fdmi zlo\u017ekami had\u00edch jedov (46, 75, 105, 106).<\/p>\n\n\n\n<p>Apam\u00edn je \u010fal\u0161\u00ed d\u00f4le\u017eit\u00fd peptid vo v\u010delom jede, ktor\u00fd tvor\u00ed 1\u20133 % surov\u00e9ho jedu a je schopn\u00fd alostericky a selekt\u00edvne inhibova\u0165 Ca2+-dependentn\u00e9 K+ kan\u00e1ly (SK kan\u00e1ly), nach\u00e1dzaj\u00face sa v centr\u00e1lnom nervovom syst\u00e9me (CNS) (81, 107, 108). Je zn\u00e1me, \u017ee iba kan\u00e1ly SK2 a SK3 s\u00fa citliv\u00e9 na apam\u00edn, a ke\u010f s\u00fa zablokovan\u00e9, doch\u00e1dza k zn\u00ed\u017eeniu oneskorenej hyperpolariz\u00e1cie buniek, \u010do vedie k zv\u00fd\u0161en\u00e9mu nepretr\u017eit\u00e9mu sp\u00fa\u0161\u0165aniu neur\u00f3nov v mezencefale a mozo\u010dku, \u010d\u00edm sa zvy\u0161uje citlivos\u0165 buniek na excita\u010dn\u00e9 vstupy (107 , 109). Okrem toho je apam\u00edn schopn\u00fd aktivova\u0165 inhibi\u010dn\u00e9 muskar\u00ednov\u00e9 receptory motorick\u00fdch nervov\u00fdch zakon\u010den\u00ed (t. j. zn\u00ed\u017eenie neuromuskul\u00e1rneho prenosu), \u010do bolo experiment\u00e1lne sk\u00faman\u00e9 ako potenci\u00e1lna lie\u010dba proti chorob\u00e1m s vysokou svalovou excitabilitou (110), ako je Parkinsonova choroba (111), u\u010denie deficitn\u00e1 porucha (112) a in\u00e9 postihnutia (81, 113).<\/p>\n\n\n\n<p>Hyaluronid\u00e1za je enz\u00fdm nach\u00e1dzaj\u00faci sa vo v\u010delom jede (1\u20133 %), ako aj v mnoh\u00fdch in\u00fdch \u017eivo\u010d\u00ed\u0161nych jedoch (114\u2013117). Hyaluronid\u00e1za je zodpovedn\u00e1 za r\u00fdchlu distrib\u00faciu tox\u00ednov, ktor\u00e1 je zn\u00e1ma aj ako \u201efaktor \u0161\u00edrenia\u201c, ke\u010f\u017ee tento enz\u00fdm \u0161tiepi kyselinu hyalur\u00f3nov\u00fa z extracelul\u00e1rnej matrice (ECM) (83, 118, 119), \u010do vedie k r\u00fdchlej\u0161iemu a syst\u00e9mov\u00e9mu otr\u00e1veniu rozru\u0161en\u00edm tkan\u00edv ( 120). Okrem toho sa hyaluronid\u00e1za pova\u017euje za siln\u00fd alerg\u00e9n vo v\u010delom jede (121).<\/p>\n\n\n\n<p>Peptid degranuluj\u00faci \u017e\u00edrne bunky (MCD) sa tie\u017e pova\u017euje za d\u00f4le\u017eit\u00fa zlo\u017eku v\u010delieho jedu na z\u00e1klade jeho schopnosti vyvola\u0165 uvo\u013e\u0148ovanie histam\u00ednu zo \u017e\u00edrnych buniek, ktor\u00e9 maj\u00fa \u00fastredn\u00fa \u00falohu pri z\u00e1paloch a alergi\u00e1ch (122). Vo ve\u013ek\u00fdch mno\u017estv\u00e1ch v\u0161ak MCD vykazuje opa\u010dn\u00fd \u00fa\u010dinok, ke\u010f inhibuje degranul\u00e1ciu \u017e\u00edrnych buniek (t. j. inhib\u00edciou uvo\u013e\u0148ovania histam\u00ednu). MCD teda m\u00f4\u017ee p\u00f4sobi\u0165 aj ako antialergick\u00e1 molekula (123). \u0160t\u00fadie skuto\u010dne preuk\u00e1zali, \u017ee MCD peptid vykazuje protiz\u00e1palov\u00fa aktivitu in vitro a in vivo (124, 125).<\/p>\n\n\n\n<p>Okrem vy\u0161\u0161ie uveden\u00fdch zlo\u017eiek v\u010del\u00ed jed obsahuje aj am\u00edny, ako s\u00fa histam\u00edn a katecholam\u00edny (81). Histam\u00edn je schopn\u00fd zv\u00fd\u0161i\u0165 priepustnos\u0165 kapil\u00e1r, \u010d\u00edm prispieva k z\u00e1palovej reakcii, zatia\u013e \u010do katecholam\u00edny (t. j. noradrenal\u00edn a dopam\u00edn) zvy\u0161uj\u00fa distrib\u00faciu v\u010delieho jedu, preto\u017ee okrem in\u00fdch funkci\u00ed zvy\u0161uj\u00fa srdcov\u00fd v\u00fddaj (122).<\/p>\n\n\n\n<p>\u010co sa t\u00fdka in\u00fdch jedov (105, 126, 127), v\u010del\u00ed jed je okrem in\u00fdch faktorov ve\u013emi n\u00e1chyln\u00fd na variabilitu v z\u00e1vislosti od veku v\u010diel, druhu, soci\u00e1lnych podmienok, geografickej lokaliz\u00e1cie (44). Napr\u00edklad mlad\u00e9 robotnice (p\u00e1sa\u010di\/str\u00e1\u017ecovia\/o\u0161etrovatelia) maj\u00fa vy\u0161\u0161ie hladiny apam\u00ednu a ni\u017e\u0161ie hladiny melit\u00ednu v porovnan\u00ed so star\u00fdmi robotnicami (p\u00e1sa\u010di\/str\u00e1\u017ecovia). Naproti tomu v\u010delie kr\u00e1\u013eovn\u00e9 maj\u00fa ni\u017e\u0161ie hladiny melit\u00ednu a apam\u00ednu (128) a vy\u0161\u0161ie hladiny histam\u00ednu (129). Okrem toho mlad\u00e9 v\u010dely maj\u00fa n\u00edzke hladiny histam\u00ednu, zatia\u013e \u010do vo veku 35 dn\u00ed maj\u00fa vysok\u00e9 hladiny tejto molekuly. Melitt\u00edn dosahuje maxim\u00e1lnu koncentr\u00e1ciu, ke\u010f m\u00e1 v\u010dela 4 t\u00fd\u017edne, a potom po\u010das starnutia v\u010diel kles\u00e1; zatia\u013e \u010do promelit\u00edn je najroz\u0161\u00edrenej\u0161\u00ed, ke\u010f s\u00fa v\u010dely star\u00e9 8\u201310 dn\u00ed (130). Hladiny hyaluronid\u00e1zy sa l\u00ed\u0161ia aj u v\u010del\u00edch jedov. Hoci hyaluronid\u00e1za m\u00f4\u017ee by\u0165 detekovan\u00e1 ihne\u010f po tom, ako sa kukly vynoria z vaj\u00ed\u010dok ako dospel\u00fdch v\u010diel (t. j. ekl\u00f3zia), hladiny enz\u00fdmov sa starnut\u00edm v\u010diel zvy\u0161uj\u00fa (131). Zatia\u013e \u010do n\u00edzke koncentr\u00e1cie PLA2 sa nach\u00e1dzaj\u00fa po\u010das vyhynutia v\u010diel, postupne sa zvy\u0161uj\u00fa a najvy\u0161\u0161ie hladiny dosahuj\u00fa, ke\u010f s\u00fa v\u010dely star\u00e9 7\u201310 dn\u00ed (51).<\/p>\n\n\n\n<p>\u010co sa t\u00fdka vari\u00e1ci\u00ed jedu medzi r\u00f4znymi druhmi v\u010diel, africk\u00e9 v\u010dely uvo\u013e\u0148uj\u00fa pri bodnut\u00ed mal\u00e9 mno\u017estvo jedu s ni\u017e\u0161\u00edm mno\u017estvom melit\u00ednu a hyaluronid\u00e1zy a zv\u00fd\u0161en\u00fdm mno\u017estvom PLA2, \u010do mo\u017eno vysvetli\u0165 skuto\u010dnos\u0165ou, \u017ee tieto v\u010dely maj\u00fa men\u0161ie jedov\u00e9 \u017e\u013eazy ako eur\u00f3pske v\u010dely. v\u010dely (132\u2013135). Okrem toho m\u00f4\u017eu ma\u0165 sez\u00f3nne zmeny vplyv na obsah v\u010delieho jedu, preto\u017ee ro\u010dn\u00e9 obdobia ovplyv\u0148uj\u00fa kvety a plody, a teda aj k\u0155menie v\u010diel (104). Produkcia melit\u00ednu sa po\u010das leta men\u00ed (136), zatia\u013e \u010do produkcia melit\u00ednu-S sa zvy\u0161uje po\u010das zimy, \u010do umo\u017e\u0148uje melit\u00ednu-S dosiahnu\u0165 mno\u017estvo 10 % cel\u00e9ho jedu (68).<\/p>\n\n\n\n<p>Sp\u00f4soby dojenia jedu m\u00f4\u017eu tie\u017e ovplyvni\u0165 zlo\u017eenie v\u010delieho jedu. V\u010del\u00ed jed mo\u017eno odobra\u0165 extrakciou jedu \u017eliaz alebo elektrickou stimul\u00e1ciou a jedy zozbieran\u00e9 t\u00fdmito met\u00f3dami predstavuj\u00fa rozdiely v chromatografick\u00fdch profiloch. Prchav\u00e9 zlo\u017eky, ako je histam\u00edn, m\u00f4\u017eu zmizn\u00fa\u0165, ke\u010f sa v\u010del\u00ed jed odoberie elektrickou stimul\u00e1ciou (44, 137). Navy\u0161e, prostredn\u00edctvom proteomickej anal\u00fdzy m\u00f4\u017ee by\u0165 v\u010del\u00ed jed z\u00edskan\u00fd extrakciou \u017e\u013eazy kontaminovan\u00fd prote\u00ednmi z tkaniva \u017e\u013eazy, tak\u017ee iba 40 % z\u00edskan\u00e9ho materi\u00e1lu tvoria skuto\u010dn\u00e9 prote\u00edny v\u010delieho jedu. Vo v\u0161eobecnosti v\u0161ak pri pou\u017eit\u00ed elektrickej stimul\u00e1cie viac ako 80 % z\u00edskan\u00e9ho materi\u00e1lu tvoria prote\u00edny jedu (48).<\/p>\n\n\n\n<p>V\u010delie bodnutia: Klinick\u00e9 prejavy<\/p>\n\n\n\n<p>Bodnutia v\u010diel m\u00f4\u017eu vies\u0165 k miernym a\u017e z\u00e1va\u017en\u00fdm klinick\u00fdm prejavom v z\u00e1vislosti najm\u00e4 od po\u010dtu \u017eihadiel, ktor\u00e9 obe\u0165 dostala. Vek pacienta, hmotnos\u0165, komorbidity a lek\u00e1rska starostlivos\u0165 m\u00f4\u017eu tie\u017e ovplyvni\u0165 z\u00e1va\u017enos\u0165 otravy (28). Navy\u0161e, atopick\u00ed jedinci (napr. jedinci s astmou alebo alergickou rinit\u00eddou) a rodinn\u00e1 anamn\u00e9za alergie na v\u010delie bodnutie s\u00fa spojen\u00e9 s vy\u0161\u0161\u00edm v\u00fdskytom z\u00e1va\u017en\u00fdch reakci\u00ed (138). Typicky mo\u017eno klinick\u00e9 prejavy otravy v\u010diel rozdeli\u0165 na lok\u00e1lne z\u00e1palov\u00e9 reakcie (1), alergick\u00e9 prejavy (2), anafylaktick\u00fd \u0161ok (3) a syst\u00e9mov\u00e9 toxick\u00e9 reakcie (4) (43, 139). (1) Lok\u00e1lne z\u00e1palov\u00e9 reakcie s\u00fa charakterizovan\u00e9 boles\u0165ou, opuchom (ed\u00e9m a eryt\u00e9m), svrben\u00edm a svrben\u00edm v mieste bodnutia. Tieto reakcie poci\u0165uje v\u00e4\u010d\u0161ina nealergick\u00fdch jedincov a zvy\u010dajne ust\u00fapia do 24 hod\u00edn (39). (2) Alergick\u00e9 reakcie na v\u010delie bodnutie s\u00fa z\u00e1visl\u00e9 od IgE a s\u00fa klasifikovan\u00e9 ako reakcie z precitlivenosti I. typu. Tieto reakcie sa vyskytuj\u00fa asi 10 min\u00fat po u\u0161tipnut\u00ed a sympt\u00f3my sa m\u00f4\u017eu l\u00ed\u0161i\u0165 v z\u00e1va\u017enosti. PLA2 sa pova\u017euje za hlavn\u00fa zl\u00fa\u010deninu, ktor\u00e1 vyvol\u00e1va IgE-senzibiliz\u00e1ciu \u017e\u00edrnych buniek, hoci hyaluronid\u00e1zy a melitt\u00edn sa tie\u017e pova\u017euj\u00fa za alerg\u00e9ny (140) (pozri \u010das\u0165 V\u010delie bodnutie a jed). U alergick\u00fdch pacientov sa m\u00f4\u017ee vyvin\u00fa\u0165 syst\u00e9mov\u00e1 \u017eih\u013eavka, pruritus, angioed\u00e9m, vracanie a hna\u010dka (28). (3) V niektor\u00fdch pr\u00edpadoch sa alergick\u00e9 reakcie m\u00f4\u017eu rozvin\u00fa\u0165 do anafylaktickej reakcie, ktor\u00e1 vedie k bronchokonstrikcii a anafylaktick\u00e9mu \u0161oku (39). 25 % a\u017e 70 % pacientov s alergiami na hmyz vykazuje syst\u00e9mov\u00e9 reakcie, ke\u010f s\u00fa vystaven\u00ed alerg\u00e9nu (t. j. v\u010deliemu jedu) (140). Je zauj\u00edmav\u00e9, \u017ee u niektor\u00fdch nealergick\u00fdch jedincov sa m\u00f4\u017ee vyvin\u00fa\u0165 anafylaxia v\u010diel v d\u00f4sledku syst\u00e9movej mastocyt\u00f3zy (141\u2013143). Syst\u00e9mov\u00e1 mastocyt\u00f3za je heterog\u00e9nna porucha charakterizovan\u00e1 prolifer\u00e1ciou mastocytov a rozsahom granul\u00e1cie, ktor\u00e1 je sp\u00f4soben\u00e1 mut\u00e1ciami v g\u00e9ne c-Kit (rastov\u00fd faktor pre mastocyty) (144, 145). (4) Syst\u00e9mov\u00e9 toxick\u00e9 reakcie s\u00fa charakterizovan\u00e9 priamymi toxick\u00fdmi \u00fa\u010dinkami v\u010delieho jedu, nez\u00e1visl\u00fdmi od imunitn\u00fdch mechanizmov, ktor\u00e9 s\u00fa zn\u00e1me aj ako reakcie z\u00e1visl\u00e9 od objemu jedu. Syst\u00e9mov\u00e9 toxick\u00e9 reakcie sa v\u017edy pova\u017euj\u00fa za z\u00e1va\u017en\u00e9 a s\u00fa sp\u00f4soben\u00e9 viacer\u00fdmi bodnutiami (asi 50 s\u00fa\u010dasn\u00fdch bodnut\u00ed). Pacienti trpiaci syst\u00e9mov\u00fdmi toxick\u00fdmi reakciami m\u00f4\u017eu ma\u0165 \u00fanavu, z\u00e1vraty, nevo\u013enos\u0165, vracanie a hna\u010dku, ktor\u00e9 sa m\u00f4\u017eu rozvin\u00fa\u0165 do po\u0161kodenia myokardu, hypertenzie, po\u0161kodenia pe\u010dene, rabdomyol\u00fdzy, hemol\u00fdzy, k\u00f3my a ak\u00fatneho zlyhania obli\u010diek (43, 146, 147). K \u00famrtiam pravdepodobne d\u00f4jde, ke\u010f obe\u0165 dostane asi 500 \u017eihadiel, ktor\u00e9 sa pova\u017euj\u00fa za nevyhnutn\u00e9 na sp\u00f4sobenie smrti priamou toxicitou (42), hoci menej bodnut\u00ed (30 \u2013 50) sa uk\u00e1zalo ako smrte\u013en\u00e9 u det\u00ed (148).<\/p>\n\n\n\n<p>Pri bodnut\u00ed v\u010delou boli hl\u00e1sen\u00e9 aj \u010fal\u0161ie zriedkav\u00e9 klinick\u00e9 prejavy, vr\u00e1tane perif\u00e9rnej neurit\u00eddy (149), Fisherovho syndr\u00f3mu (150), ak\u00fatnej z\u00e1palovej polyradikuloneuropatie (Guillain-Barr\u00e9ho syndr\u00f3m) (151), neuropatie zrakov\u00e9ho nervu (152), septik\u00e9mie (153), bilater\u00e1lnej empy\u00e9m (154) a dokonca \u017eih\u013eavka u die\u0165a\u0165a (12-d\u0148ov\u00e9ho) doj\u010den\u00e9ho matkou, ktor\u00fa u\u0161tipla v\u010dela (155).<\/p>\n\n\n\n<p>S\u00fa\u010dasn\u00e1 lie\u010dba<br>Vo v\u0161eobecnosti existuj\u00fa tri r\u00f4zne scen\u00e1re bodnutia v\u010delou, ktor\u00e9 vy\u017eaduj\u00fa lie\u010dbu. (1) Nieko\u013eko \u017eihadiel na nesenzibilizovan\u00fa osobu; (2) jedno alebo viac \u017eihadiel precitliven\u00e9ho \u010dloveka; a (3) mas\u00edvna otrava v\u010diel viacer\u00fdmi bodnutiami (obr\u00e1zok 4).<\/p>\n\n\n\n<figure class=\"wp-block-image size-full\"><img decoding=\"async\" loading=\"lazy\" width=\"951\" height=\"660\" src=\"http:\/\/apitoxin.sk\/wp-content\/uploads\/2022\/07\/vcell.jpg\" alt=\"\" class=\"wp-image-230\" srcset=\"http:\/\/d.r20005.wbsprt.com\/apitoxin.sk\/wp-content\/uploads\/2022\/07\/vcell.jpg 951w, http:\/\/d.r20005.wbsprt.com\/apitoxin.sk\/wp-content\/uploads\/2022\/07\/vcell-300x208.jpg 300w, http:\/\/d.r20005.wbsprt.com\/apitoxin.sk\/wp-content\/uploads\/2022\/07\/vcell-768x533.jpg 768w\" sizes=\"(max-width: 951px) 100vw, 951px\" \/><figcaption>OBR\u00c1ZOK 4. O\u0161etrenie v\u010delieho bodnutia. Pr\u00edpady v\u010diel m\u00f4\u017eu zah\u0155\u0148a\u0165 nieko\u013eko bodnut\u00ed, ktor\u00e9 m\u00f4\u017eu sp\u00f4sobi\u0165 lok\u00e1lne reakcie alebo anafylaktick\u00fd \u0161ok, ktor\u00e9 si vy\u017eaduj\u00fa lie\u010dbu podobn\u00fa v\u0161etk\u00fdm alergick\u00fdm reakci\u00e1m (zelen\u00e1). Hromadn\u00e9 bodav\u00e9 javy v\u0161ak m\u00f4\u017eu by\u0165 \u017eivot ohrozuj\u00face prostredn\u00edctvom toxick\u00e9ho p\u00f4sobenia jedu, ke\u010f sa vstrekuje vo ve\u013ek\u00fdch mno\u017estv\u00e1ch, \u010do si vy\u017eaduje intenz\u00edvnu lie\u010dbu (vo fialovej farbe). Hoci \u0161pecifick\u00e1 lie\u010dba zatia\u013e nie je k dispoz\u00edcii, len m\u00e1lo v\u00fdskumn\u00edkov zaoberaj\u00facich sa bojom proti jedom pracuje na v\u00fdvoji nov\u00fdch terapi\u00ed proti otrave v\u010diel.<\/figcaption><\/figure>\n\n\n\n<p>Lie\u010dba nieko\u013ek\u00fdch \u017eihadiel na nesenzibilizovanej osobe<br>Nesenzibilizovan\u00ed \u013eudia prezentuj\u00fa iba lokalizovan\u00fa reakciu na v\u010delie bodnutie. Pri norm\u00e1lnej reakcii na v\u010delie bodnutie sa ko\u017ea prejav\u00ed ako oblas\u0165 bolesti, za\u010dervenania a opuchu, ktor\u00e1 m\u00e1 zvy\u010dajne priemer &lt; 10 cm a norm\u00e1lne zmizne do 24 hod\u00edn (156). Experimenty vykonan\u00e9 na mor\u010dat\u00e1ch po\u0161t\u00edpan\u00fdch v\u010delami, ktor\u00fdm boli odstr\u00e1nen\u00e9 tkaniv\u00e1 a podroben\u00e9 histologickej anal\u00fdze, preuk\u00e1zali iba lok\u00e1lny v\u00fdrazn\u00fd z\u00e1pal (t. j. ed\u00e9m, vysok\u00fa bunkov\u00fa infiltr\u00e1ciu a nekr\u00f3zu) po\u010das 24 hod\u00edn po bodnut\u00ed (157). Lek\u00e1rska pomoc je v t\u00fdchto pr\u00edpadoch zbyto\u010dn\u00e1, hoci sa odpor\u00fa\u010da pou\u017eitie lok\u00e1lnych kortikosteroidov, ktor\u00e9 maj\u00fa protiz\u00e1palov\u00e9, imunosupres\u00edvne a antimitog\u00e9nne \u00fa\u010dinky (158). Pri takzvan\u00fdch ve\u013ek\u00fdch lok\u00e1lnych reakci\u00e1ch na bodnutie hmyzom v\u0161ak m\u00f4\u017ee by\u0165 oblas\u0165 opuchu a za\u010dervenania v\u00e4\u010d\u0161ia ako 10 cm v priemere a boles\u0165 m\u00f4\u017ee pretrv\u00e1va\u0165 aj nieko\u013eko dn\u00ed. Hoci je t\u00e1to reakcia pravdepodobne alergick\u00e9ho p\u00f4vodu, nemus\u00ed by\u0165 nevyhnutne sprostredkovan\u00e1 IgE. V tejto situ\u00e1cii mo\u017eno predp\u00edsa\u0165 peror\u00e1lne antihistaminik\u00e1 (156).<\/p>\n\n\n\n<p>Lie\u010dba precitlivenosti<br>Ak osobu precitliven\u00fa na v\u010del\u00ed jed (t. j. alergika) po\u0161t\u00edpe aspo\u0148 jedna v\u010dela, je potrebn\u00e1 okam\u017eit\u00e1 lek\u00e1rska pomoc, preto\u017ee m\u00f4\u017ee d\u00f4js\u0165 k anafylaxii. V\u00e4\u010d\u0161ina \u00famrt\u00ed, ku ktor\u00fdm doch\u00e1dza v tomto pr\u00edpade, je sp\u00f4soben\u00e1 t\u00fdm, \u017ee alergick\u00ed jedinci nedostan\u00fa lek\u00e1rsku starostlivos\u0165 dostato\u010dne r\u00fdchlo (159). Preferovan\u00e1 prv\u00e1 l\u00ednia \u00fa\u010dinku proti anafylaxii sa l\u00ed\u0161i od \u0161t\u00fadie k \u0161t\u00fadii. Niektor\u00e9 \u0161t\u00fadie uv\u00e1dzaj\u00fa ako prv\u00fa l\u00edniu \u00fa\u010dinku opatrn\u00e9 zo\u0161krabovanie v\u010del\u00edch \u017eihadiel (vyh\u00fdban\u00edm sa \u0165ahaniu alebo stl\u00e1\u010daniu \u017eihadiel, \u010do by mohlo vies\u0165 k vstreknutiu v\u00e4\u010d\u0161ieho mno\u017estva jedu) (160), hoci tento \u00fakon je d\u00f4le\u017eit\u00fd najm\u00e4 vtedy, ak sa vykon\u00e1 do 60 s. bodnutie, v ktorom \u017eihadlo vyvrhne v\u0161etok svoj jed (39). In\u00e9 \u0161t\u00fadie uv\u00e1dzaj\u00fa, \u017ee prvou l\u00edniou \u00fa\u010dinku by malo by\u0165 podanie intramuskul\u00e1rneho adrenal\u00ednu (tie\u017e zn\u00e1meho ako epinefr\u00edn) a a\u017e potom odstr\u00e1nenie \u017eihadla (161). Aj ke\u010f sa tieto \u0161t\u00fadie nemusia zhodova\u0165 v tom, \u010di by odstr\u00e1nenie \u017eihadla malo by\u0165 prvou akciou, po ktorej nasleduje adrenal\u00edn, alebo naopak, zhoduj\u00fa sa v tom, \u017ee prv\u00fdm liekom, ktor\u00fd sa m\u00e1 pou\u017ei\u0165, je intramuskul\u00e1rny adrenal\u00edn (39, 160\u2013162). Aj nieko\u013ekomin\u00fatov\u00e9 oneskorenie v podan\u00ed adrenal\u00ednu m\u00f4\u017ee vies\u0165 k hypoxii alebo smrti. Nedostato\u010dn\u00fd pr\u00edstup k vznikaj\u00facemu adrenal\u00ednu skuto\u010dne zohr\u00e1va rozhoduj\u00facu \u00falohu v \u00famrtnosti a morbidite alergick\u00fdch pacientov. Zv\u00fd\u0161ilo sa tak povedomie o potrebe adrenal\u00ednov\u00fdch autoinjektorov na verejn\u00fdch miestach vr\u00e1tane \u0161k\u00f4l, parkov, let\u00edsk a n\u00e1kupn\u00fdch centier (163, 164).<\/p>\n\n\n\n<p>Adrenal\u00edn p\u00f4sob\u00ed ako \u03b1 a \u03b2-agonista. V\u010faka svojmu \u03b1-1 agonistick\u00e9mu \u00fa\u010dinku p\u00f4sob\u00ed ako vazokonstriktor, ktor\u00fd zabra\u0148uje a zmier\u0148uje ed\u00e9m d\u00fdchac\u00edch ciest, hypotenziu a \u0161ok. \u03b2-1 agonistick\u00e9 \u00fa\u010dinky adrenal\u00ednu s\u00fa chronotropn\u00e9 a inotropn\u00e9 a teda zvy\u0161uj\u00fa r\u00fdchlos\u0165 a silu srdcov\u00fdch kontrakci\u00ed, zatia\u013e \u010do \u03b2-2 agonistick\u00e9 \u00fa\u010dinky adrenal\u00ednu ved\u00fa k bronchodilat\u00e1cii (162). Okrem toho \u03b22-adrenergn\u00e9 agonistick\u00e9 \u00fa\u010dinky adrenal\u00ednu tie\u017e zvy\u0161uj\u00fa intracelul\u00e1rne hladiny cyklick\u00e9ho adenoz\u00ednmonofosf\u00e1tu v \u017e\u00edrnych bunk\u00e1ch, \u010do inhibuje \u010fal\u0161ie uvo\u013e\u0148ovanie z\u00e1palov\u00fdch medi\u00e1torov, ako s\u00fa histam\u00edn, leukotri\u00e9ny a prostagland\u00edn D2 (165). Po podan\u00ed adrenal\u00ednu medzi \u010fal\u0161ie lie\u010dby prvej l\u00ednie patr\u00ed kysl\u00edk, intraven\u00f3zna tekutinov\u00e1 resuscit\u00e1cia a inhala\u010dn\u00e9 kr\u00e1tkodobo p\u00f4sobiace \u03b22 agonisty (161, 166, 167). Lie\u010dba druhej l\u00ednie zvy\u010dajne pozost\u00e1va z H1-antihistamin\u00edk, H2-antihistamin\u00edk a glukokortikoidov, ktor\u00e9 sa pod\u00e1vaj\u00fa ako adjuvantn\u00e1 lie\u010dba a pova\u017euj\u00fa sa za volite\u013en\u00e9. Antihistaminik\u00e1 sa odpor\u00fa\u010daj\u00fa len na zmiernenie ko\u017en\u00fdch sympt\u00f3mov, zatia\u013e \u010do glukokortikoidy m\u00f4\u017eu by\u0165 \u00fa\u010dinn\u00e9 pri lie\u010dbe ed\u00e9mu d\u00fdchac\u00edch ciest a m\u00f4\u017eu zabr\u00e1ni\u0165 dlhotrvaj\u00facim sympt\u00f3mom anafylaxie (161, 166).<\/p>\n\n\n\n<p>Prevent\u00edvnou lie\u010dbou pre alergick\u00fdch jedincov je imunoterapia jedom (VIT). VIT pozost\u00e1va z o\u010dkovania mal\u00fdch zvy\u0161uj\u00facich sa mno\u017estiev purifikovan\u00fdch extraktov jedu u alergick\u00e9ho jedinca po\u010das ur\u010dit\u00e9ho \u010dasov\u00e9ho obdobia. V\u00fd\u0165a\u017eky z jedu boli predstaven\u00e9 v 70. rokoch minul\u00e9ho storo\u010dia a odvtedy sa VIT st\u00e1va \u010doraz popul\u00e1rnej\u0161\u00edm. Bolo vyvinut\u00fdch nieko\u013eko r\u00f4znych re\u017eimov pod\u00e1vania na skr\u00e1tenie \u010dasu potrebn\u00e9ho na dosiahnutie udr\u017eiavacieho obdobia a na minimaliz\u00e1ciu ved\u013eaj\u0161\u00edch \u00fa\u010dinkov (168). Pod\u013ea Eur\u00f3pskej akad\u00e9mie pre alergiu a klinick\u00fa imunol\u00f3giu (EAACI) sa VIT m\u00f4\u017ee vykon\u00e1va\u0165 s pou\u017eit\u00edm r\u00f4znych produktov jedu (purifikovan\u00fdch a ne\u010disten\u00fdch, vodn\u00fdch alebo depotn\u00fdch) a r\u00f4znych lie\u010debn\u00fdch protokolov (konven\u010dn\u00e9, klastrov\u00e9, r\u00fdchle a ultrar\u00fdchle), pod\u00e1van\u00e9 subkut\u00e1nnou alebo sublingv\u00e1lnou cestou (169).<\/p>\n\n\n\n<p>Efekt\u00edvna VIT obnovuje imunotoleranciu vo\u010di alerg\u00e9nom r\u00f4znymi mechanizmami: (1) desenzibiliz\u00e1ciou \u017e\u00edrnych buniek a bazofilov; (2) potla\u010denie vroden\u00fdch lymfoidn\u00fdch buniek (ILC2); (3) aktiv\u00e1cia regula\u010dn\u00fdch T buniek (Tregs), ktor\u00e9 zvy\u0161uj\u00fa hladiny interleuk\u00ednu 10 (IL-10) a transformuj\u00faceho rastov\u00e9ho faktora-p (TGF-p); (4) a imunoglobul\u00ednov\u00fd bunkov\u00fd prechod na IgG4 a IgA indukovan\u00fd cytok\u00ednmi Treg (170). Rozhodnutie, \u010di za\u010da\u0165 VIT, z\u00e1vis\u00ed od presnej diagn\u00f3zy, pos\u00fadenia rizika \u010fal\u0161ej alergickej reakcie u osoby, od miery, do akej alergia ovplyv\u0148uje kvalitu \u017eivota osoby, od veku osoby a od sprievodn\u00fdch zdravotn\u00fdch stavov, ako aj od toho, \u010di osoba trp\u00ed s\u00fabe\u017enou poruchou \u017e\u00edrnych buniek. Okrem toho by sa mal vzia\u0165 do \u00favahy alerg\u00e9nov\u00fd pr\u00edpravok (pozri usmernenia EAACI) a podan\u00e1 d\u00e1vka, aby sa predi\u0161lo ne\u017eiaducim \u00fa\u010dinkom a zabezpe\u010dil sa terapeutick\u00fd \u00faspech (169). V ka\u017edom pr\u00edpade je potrebn\u00e9 VIT vykon\u00e1va\u0165 pod lek\u00e1rskym doh\u013eadom kv\u00f4li riziku alergickej reakcie. \u0160t\u00fadia zistila, \u017ee takmer jeden z 10 \u013eud\u00ed lie\u010den\u00fdch VIT mal alergick\u00fa reakciu na lie\u010dbu (171). Ne\u017eiaduce \u00fa\u010dinky s\u00fa v\u0161ak zvy\u010dajne mierne a aj ke\u010f sa v pr\u00edpade syst\u00e9mov\u00fdch ne\u017eiaducich reakci\u00ed odpor\u00fa\u010da zn\u00ed\u017ei\u0165 d\u00e1vku alerg\u00e9nu, pacienti by nemali preru\u0161i\u0165 lie\u010dbu, preto\u017ee VIT je \u00fa\u010dinn\u00e1 pri zni\u017eovan\u00ed rizika n\u00e1slednej syst\u00e9movej reakcie na u\u0161tipnutie v\u010delou. 77\u201384 % lie\u010den\u00fdch pacientov (169).<\/p>\n\n\n\n<p>Terapia proti mas\u00edvnemu otr\u00e1veniu v\u010diel<br>Po\u010diato\u010dn\u00e1 lie\u010dba mas\u00edvnej otravy v\u010diel m\u00e1 rovnak\u00fd priebeh ako v pr\u00edpade precitlivenosti. Alergick\u00e9 a syst\u00e9mov\u00e9 toxick\u00e9 reakcie je \u0165a\u017ek\u00e9 rozl\u00ed\u0161i\u0165, najm\u00e4 v prv\u00fdch min\u00fatach, a anafylaktick\u00fd \u0161ok je najbezprostrednej\u0161\u00edm nebezpe\u010denstvom pre pacienta (172). Akon\u00e1hle sa v\u0161ak zist\u00ed, \u017ee k hypersenzit\u00edvnej udalosti nedoch\u00e1dza (alebo nielen), za\u010dne sa \u0161pecifick\u00e1 lie\u010dba mas\u00edvnej otravy v\u010diel. Ide\u00e1lnou lie\u010dbou proti z\u00e1va\u017en\u00fdm toxick\u00fdm \u00fa\u010dinkom v\u010delieho jedu by bol pravdepodobne protijed. Nie s\u00fa v\u0161ak k dispoz\u00edcii \u017eiadne \u0161pecifick\u00e9 protijedy, hoci sa vynaklad\u00e1 ve\u013ek\u00e9 \u00fasilie (pozri \u010das\u0165 Terapia proti jedom novej gener\u00e1cie) (139). Pacienti, ktor\u00ed maj\u00fa viac ako 50 bodnut\u00ed, by mali by\u0165 monitorovan\u00ed, preto\u017ee cirkuluj\u00face tox\u00edny jedu m\u00f4\u017eu v ich tele pretrv\u00e1va\u0165 hodiny alebo dni a m\u00f4\u017eu ma\u0165 potenci\u00e1l sp\u00f4sobi\u0165 oneskoren\u00e9 reakcie. Spo\u010diatku m\u00f4\u017ee by\u0165 po\u0161t\u00edpan\u00e1 obe\u0165 stabiln\u00e1. O nieko\u013eko hod\u00edn nesk\u00f4r sa v\u0161ak stav obete m\u00f4\u017ee zhor\u0161i\u0165 (28, 172, 173). Klinick\u00e9 monitorovanie by sa malo zamera\u0165 na hladiny kreatin\u00ednu, mo\u010dovinov\u00e9ho dus\u00edka v s\u00e9re, elektrolytov a myoglob\u00ednu, aby sa pos\u00fadila funkcia obli\u010diek a riziko rabdomyol\u00fdzy (172, 174). Okrem toho na kontrolu rozvoja syndr\u00f3mu ak\u00fatnej respira\u010dnej tiesne a acid\u00f3zy je potrebn\u00e9 monitorova\u0165 pH krvi a hladiny kysl\u00edka. Ak pacient vykazuje zn\u00e1mky myoglobin\u00farie, m\u00f4\u017ee sa vykona\u0165 intraven\u00f3zna injekcia hydrog\u00e9nuhli\u010ditanu sodn\u00e9ho na alkaliz\u00e1ciu mo\u010du (t. j. na ur\u00fdchlenie vylu\u010dovania obli\u010dkami). Alkalick\u00e1 diur\u00e9za m\u00f4\u017ee zabr\u00e1ni\u0165 kry\u0161taliz\u00e1cii myoglob\u00ednu v obli\u010dkov\u00fdch tubuloch, \u010do m\u00f4\u017ee nakoniec vies\u0165 k ak\u00fatnemu zlyhaniu obli\u010diek (172). Okrem toho sa \u010dasto pod\u00e1va agres\u00edvna hydrat\u00e1cia a diuretik\u00e1 (139, 174). Pacient m\u00f4\u017ee za\u010da\u0165 s hemo alebo peritone\u00e1lnou dial\u00fdzou, v\u00fdmennou transf\u00faziou alebo plazmafer\u00e9zou, aby sa eliminovali zlo\u017eky jedu s n\u00edzkou molekulovou hmotnos\u0165ou, ako je melit\u00edn alebo PLA2, alebo ak sa rozvinie ak\u00fatne zlyhanie obli\u010diek (5, 172).<\/p>\n\n\n\n<p>Protijedov\u00e1 terapia novej gener\u00e1cie<br>Jednou z prek\u00e1\u017eok produkcie protil\u00e1tok imuniza\u010dn\u00fdmi postupmi pri terapi\u00e1ch zameran\u00fdch na otravu v\u010del\u00edm jedom je nedostato\u010dn\u00e1 imunogenicita nieko\u013ek\u00fdch k\u013e\u00fa\u010dov\u00fdch tox\u00ednov v\u010delieho jedu, ako je melitt\u00edn. Ako u\u017e bolo spomenut\u00e9 (pozri \u010das\u0165 V\u010delie bodnutie a jed), melit\u00edn je lytick\u00fd faktor bunkovej membr\u00e1ny (85, 175) s malou molekulovou ve\u013ekos\u0165ou (5, 176, 177), n\u00e1hodnou konform\u00e1ciou (178) a ve\u013emi hydrof\u00f3bnymi oblas\u0165ami (177). , \u010do vedie k n\u00edzkej imunogenicite (6), \u010do zna\u010dne komplikuje produkciu \u00fa\u010dinn\u00fdch v\u010del\u00edch protijedov, preto\u017ee melit\u00edn nedok\u00e1\u017ee vyvola\u0165 siln\u00fa protil\u00e1tkov\u00fa odpove\u010f u imunizovan\u00fdch zvierat.<\/p>\n\n\n\n<p>Po\u010das posledn\u00fdch desa\u0165ro\u010d\u00ed bolo zaznamenan\u00fdch nieko\u013eko pokusov vyvin\u00fa\u0165 \u00fa\u010dinn\u00fa terapiu otravy v\u010diel. V roku 1996 Schumacher a spol. ohl\u00e1sili prv\u00fd pokus o produkciu v\u010delieho jedu na b\u00e1ze heterol\u00f3gnej protil\u00e1tky. Tu bola produkovan\u00e1 polyklon\u00e1lna zmes protil\u00e1tok imunoglobul\u00ednu G (IgG) postupn\u00fdmi imuniz\u00e1ciami kr\u00e1likov purifikovan\u00fdm PLA2, melit\u00ednom alebo surov\u00fdm v\u010del\u00edm jedom a neutraliza\u010dn\u00e9 kapacity boli \u010falej hodnoten\u00e9 u my\u0161\u00ed. Pozorovalo sa, \u017ee \u0161pecifick\u00e9 anti-PLA2 protil\u00e1tky jasne zn\u00ed\u017eili toxicitu spojen\u00fa s PLA2, ke\u010f sa tox\u00edn my\u0161iam pod\u00e1val samotn\u00fd. Naopak, po pou\u017eit\u00ed surov\u00e9ho jedu to nemalo \u017eiadny v\u00fdznamn\u00fd vplyv na letalitu. Aj ke\u010f sa pou\u017eila kombin\u00e1cia anti-PLA2 a anti-melit\u00ednov\u00fdch protil\u00e1tok, surov\u00e1 letalita jedu sa u my\u0161\u00ed nezn\u00ed\u017eila, hoci autori identifikovali protil\u00e1tky via\u017euce melit\u00edn v kr\u00e1li\u010dom s\u00e9re (176).<\/p>\n\n\n\n<p>V roku 1999 Jones a spol. op\u00edsali odli\u0161n\u00fd pr\u00edstup zalo\u017een\u00fd na Fab (fragment antigen binding) protil\u00e1tkov\u00fdch fragmentoch. V ich \u0161t\u00fadii boli walesk\u00e9 ovce postupne imunizovan\u00e9 v\u010del\u00edm jedom na produkciu IgG, ktor\u00e9 boli \u010falej \u0161tiepen\u00e9 papa\u00ednom, aby sa z\u00edskali Fab fragmenty. Pomocou enz\u00fdmov\u00e9ho imunosorbentn\u00e9ho testu (ELISA) v\u00fdskumn\u00edci preuk\u00e1zali, \u017ee protijed na b\u00e1ze Fab bol schopn\u00fd rozpozna\u0165 melit\u00edn. Okrem toho pomocou \u0161tandardn\u00fdch testov \u00fa\u010dinnosti (ED50) in vivo v\u00fdskumn\u00edci ur\u010dili, \u017ee na neutraliz\u00e1ciu toxick\u00fdch \u00fa\u010dinkov a na zabr\u00e1nenie \u00famrtnosti u my\u0161\u00ed je potrebn\u00fdch 20,5 mg ov\u010dieho antis\u00e9ra na b\u00e1ze Fab, ke\u010f bol protijed predinkubovan\u00fd s 1 mg v\u010del\u00ed jed (179). Nesk\u00f4r antijed na b\u00e1ze fragmentu konskej protil\u00e1tky F(ab&#8216;)2, op\u00edsan\u00fd Santosom a kol. (180), bolo preuk\u00e1zan\u00e9, \u017ee je \u00fa\u010dinn\u00fd pri neutraliz\u00e1cii toxick\u00fdch aktiv\u00edt v\u010delieho jedu in vitro a in vivo. In vitro bola hemolytick\u00e1 aktivita 1 mg v\u010delieho jedu neutralizovan\u00e1 ~50 mg protijedu. In vivo bol konsk\u00fd protijed schopn\u00fd \u00faplne neutralizova\u0165 myotoxick\u00e9 \u00fa\u010dinky v\u010delieho jedu s \u00fa\u010dinnou d\u00e1vkou (ED50) 1,11 mg\/ml (mg v\u010delieho jedu\/ml protijedu) (180). Tie\u017e pomocou imuniz\u00e1cie kon\u00ed Barraviera a spoluautori ned\u00e1vno vyvinuli konsk\u00fd protijed na b\u00e1ze F(ab&#8216;)2 s ED50 1,25 mg\/ml (181). T\u00e1to \u0161t\u00fadia tie\u017e vyvinula protokol pre klinick\u00e9 \u0161t\u00fadie f\u00e1zy I\/II s pou\u017eit\u00edm vytvoren\u00e9ho konsk\u00e9ho protijedu (181).<\/p>\n\n\n\n<p>S\u00fa\u010dasn\u00e9 sp\u00f4soby produkcie protijedov s\u00fa zalo\u017een\u00e9 na postupn\u00fdch imuniz\u00e1ci\u00e1ch r\u00f4znych zvierat, po ktor\u00fdch nasleduje lacn\u00e1 purifik\u00e1cia IgG odvoden\u00fdch od zvieracej plazmy. Napriek historick\u00e9mu klinick\u00e9mu \u00faspechu dosiahnut\u00e9mu s protijedmi poch\u00e1dzaj\u00facimi zo zvieracej plazmy, tieto otravov\u00e9 terapie maj\u00fa tendenciu sp\u00f4sobova\u0165 nepriazniv\u00e9 \u00fa\u010dinky v d\u00f4sledku ich heterol\u00f3gnej povahy (182, 183). Zistilo sa, \u017ee u 6\u201359 % pacientov po u\u0161tipnut\u00ed hadom lie\u010den\u00fdch protijedmi z\u00edskan\u00fdmi z plazmy sa po podan\u00ed protijedu vyskytli ne\u017eiaduce reakcie so skor\u00fdm n\u00e1stupom, zatia\u013e \u010do u 5\u201323 % pacientov sa vyskytli reakcie s oneskoren\u00fdm n\u00e1stupom (s\u00e9rov\u00e1 choroba), s pr\u00edznakmi ako hor\u00fa\u010dka, vyr\u00e1\u017eka a \u017eih\u013eavka (182, 184). Tieto ne\u017eiaduce reakcie s\u00favisiace s jedom s\u00fa hlavne v\u00fdsledkom zlo\u017eenia a kvality protijedu, form\u00e1tu protil\u00e1tky a\/alebo celkov\u00e9ho mno\u017estva prote\u00ednu podan\u00e9ho pacientovi (185). Antijedy poch\u00e1dzaj\u00face z plazmy s\u00fa jedinou komer\u010dne dostupnou mo\u017enos\u0165ou otravovej terapie. S\u00fa\u010dasn\u00fd pokrok dosiahnut\u00fd v oblasti biotechnol\u00f3gie a monoklon\u00e1lnych protil\u00e1tok v\u0161ak pozit\u00edvne prispel k v\u00fdvoju experiment\u00e1lnych antivenomov zalo\u017een\u00fdch na zmesiach \u0161pecifick\u00fdch rekombinantn\u00fdch monoklon\u00e1lnych protil\u00e1tok (186\u2013188). Hoci tieto experiment\u00e1lne protijedy e\u0161te len vst\u00fapia do klinick\u00e9ho prostredia, predpoklad\u00e1 sa, \u017ee envenomingov\u00e9 terapie zalo\u017een\u00e9 na rekombinantn\u00fdch monoklon\u00e1lnych protil\u00e1tkach a fragmentoch protil\u00e1tok bud\u00fa jedn\u00e9ho d\u0148a uveden\u00e9 na trh a \u017ee ich v\u00fdroba bude v bud\u00facnosti ekonomicky realizovate\u013en\u00e1 (189).<\/p>\n\n\n\n<p>V oblasti rekombinantn\u00fdch v\u010del\u00edch protijedov Barbosa a kol. boli prv\u00ed, ktor\u00ed informovali o objave \u00faplne \u013eudsk\u00fdch protil\u00e1tok na b\u00e1ze jednore\u0165azcov\u00fdch variabiln\u00fdch fragmentov (scFv) z\u00edskan\u00fdch prostredn\u00edctvom technol\u00f3gie f\u00e1gov\u00e9ho displeja proti melit\u00ednu a PLA2. Tieto tox\u00edny p\u00f4sobia synergicky a kombin\u00e1cia monoklon\u00e1lnych protil\u00e1tok proti t\u00fdmto tox\u00ednom m\u00f4\u017ee preto n\u00e1js\u0165 uplatnenie pri lie\u010dbe v\u00e1\u017eneho otravy v\u010diel. \u0160pecifick\u00e9 monoklon\u00e1lne protil\u00e1tky proti melit\u00ednu a PLA2 sa vybrali z kni\u017enice f\u00e1gov\u00e9ho displeja a \u010falej sa vybrali na tox\u00ednov\u00fa \u0161pecificitu pomocou ELISA. Boli objaven\u00e9 dva r\u00f4zne scFv klony, pomenovan\u00e9 A7 a C12, proti PLA2 a melitt\u00ednu. Neutraliza\u010dn\u00e9 \u0161t\u00fadie uk\u00e1zali, \u017ee tieto dva klony boli schopn\u00e9 neutralizova\u0165 hemolytick\u00fa aktivitu v\u010delieho jedu in vitro v pomere hmotnosti k hmotnosti 3:1 (scFv:v\u010del\u00ed jed). Okrem toho rovnak\u00e9 monoklon\u00e1lne scFv inhibovali myotoxicitu a oneskorili \u00famrtnos\u0165 u my\u0161\u00ed vystaven\u00fdch 1,5 LD50 v\u010delieho jedu v rovnakom pomere (190). Nesk\u00f4r t\u00ed ist\u00ed v\u00fdskumn\u00edci vybrali dve nov\u00e9 monoklon\u00e1lne protil\u00e1tky proti melit\u00ednu a PLA2 na b\u00e1ze scFv pomocou technol\u00f3gie f\u00e1gov\u00e9ho displeja, pomenovan\u00e9 Afribumab 1 a Afribumab 2. Afribumab 1 a 2 preuk\u00e1zali schopnos\u0165 inhibova\u0165 hemol\u00fdzu v\u010del\u00edm jedom (0,5 \u03bcg) in vitro v pomere hmotnosti k hmotnosti 1:1:1 (v\u010del\u00ed jed:Afribumab 1:Afribumab 2). Pou\u017eit\u00edm my\u0161\u00ed vystaven\u00fdch 2 LD50 v\u010delieho jedu (\u010do zodpoved\u00e1 9,484 \u03bcg\/g v\u010delieho jedu) sa preuk\u00e1zalo, \u017ee kombin\u00e1cia Afribumabu 1 a 2 s rovnak\u00fdm pomerom 1:1:1 zni\u017euje ed\u00e9m a predl\u017euje pre\u017eitie my\u0161\u00ed na viac ako 400 min\u00fat (v porovnan\u00ed s pribli\u017ene 100 min\u00fatami, ke\u010f boli my\u0161i vystaven\u00e9 iba 2 LD50 v\u010delieho jedu) (191). V kombin\u00e1cii tieto \u0161t\u00fadie uk\u00e1zali, \u017ee technol\u00f3gia f\u00e1gov\u00e9ho displeja m\u00f4\u017ee by\u0165 \u00fa\u010dinnou metodol\u00f3giou na selekciu protil\u00e1tok so \u0161pecifickos\u0165ou proti neimunog\u00e9nnym zlo\u017ek\u00e1m v\u010delieho jedu (napr. melitt\u00edn). Tak\u00e9to protil\u00e1tky nebolo mo\u017en\u00e9 \u013eahko generova\u0165 tradi\u010dnej\u0161\u00edmi pr\u00edstupmi na objavovanie protil\u00e1tok zalo\u017een\u00fdch na imuniz\u00e1cii zvierat. Potenci\u00e1lne by tak\u00e9to monoklon\u00e1lne protil\u00e1tky proti k\u013e\u00fa\u010dov\u00fdm tox\u00ednom z v\u010delieho jedu mohli by\u0165 formulovan\u00e9 do rekombinantn\u00e9ho protijedu na lie\u010dbu v\u00e1\u017eneho otravy v\u010diel. Aj ke\u010f presn\u00e9 na\u010dasovanie \u00fa\u010dinn\u00e9ho podania tak\u00e9hoto v\u010delieho jedu nemo\u017eno predpoveda\u0165 z d\u00f4vodu obmedzen\u00fdch znalost\u00ed o toxikokinetike zlo\u017eiek v\u010delieho jedu u \u013eudsk\u00fdch subjektov, je pravdepodobn\u00e9, \u017ee podanie protijedu by sa malo uskuto\u010dni\u0165 do 24 hod\u00edn, preto\u017ee kinetick\u00e9 \u0161t\u00fadie na my\u0161iach preuk\u00e1zali, \u017ee V tomto obdob\u00ed mo\u017eno v\u010del\u00ed jed zisti\u0165 v r\u00f4znych org\u00e1noch, ako s\u00fa obli\u010dky (192).<\/p>\n\n\n\n<p>Ke\u010f\u017ee \u00fa\u010dinn\u00e1 terapeutick\u00e1 intervencia je nevyhnutn\u00e1 pre najz\u00e1va\u017enej\u0161ie pr\u00edpady mas\u00edvnej otravy v\u010diel a ke\u010f\u017ee doteraj\u0161\u00ed stav techniky demon\u0161truje pou\u017eite\u013enos\u0165 r\u00f4znych biotechnologick\u00fdch techn\u00edk a metodol\u00f3gi\u00ed objavovania protil\u00e1tok v tejto oblasti, je pravdepodobn\u00e9, \u017ee vo v\u00fdvoji rekombinantn\u00fdch protijedov proti v\u010del\u00e1m d\u00f4jde k v\u00fdrazn\u00e9mu pokroku. v najbli\u017e\u0161\u00edch desa\u0165ro\u010diach d\u00f4jde k otrav\u00e1m. Zd\u00e1 sa eminentn\u00e9, \u017ee pr\u00edstupy k n\u00e1vrhu a v\u00fdvoju proti jedu zo susednej oblasti otravy had\u00edm uhryznut\u00edm m\u00f4\u017eu by\u0165 prijat\u00e9 pri v\u00fdvoji terapi\u00ed novej gener\u00e1cie na otravu v\u010del\u00edm jedom. Osobitne je opodstatnen\u00e9 sk\u00famanie u\u017eito\u010dnosti r\u00f4znych form\u00e1tov monoklon\u00e1lnych protil\u00e1tok (vr\u00e1tane nanoprotil\u00e1tok) a pr\u00edpadne v\u00e4zbov\u00fdch prote\u00ednov nezalo\u017een\u00fdch na protil\u00e1tkach (ako s\u00fa DARP\u00edny a in\u00e9 vznikaj\u00face skeletov\u00e9 prote\u00edny), preto\u017ee to m\u00f4\u017ee umo\u017eni\u0165 n\u00e1vrh rekombinantn\u00fdch produktov proti jedu s prospe\u0161n\u00fdmi \u00fa\u010dinkami. farmakokinetick\u00e9 vlastnosti, ako je r\u00fdchla distrib\u00facia a schopnos\u0165 prenika\u0165 a zacieli\u0165 tox\u00edny hlboko do tkan\u00edv (182, 193, 194). Tak\u00e9to v\u00fdskumy m\u00f4\u017eu tie\u017e podnieti\u0165 sk\u00famanie strat\u00e9gi\u00ed v\u00fdroby s n\u00edzkymi n\u00e1kladmi pre oligoklon\u00e1lne protil\u00e1tky (189) alebo strat\u00e9gi\u00ed formul\u00e1ci\u00ed na zlep\u0161enie stability a pred\u013a\u017een\u00fa skladovate\u013enos\u0165. Oblas\u0165ou relevantnou pre \u010fal\u0161\u00ed v\u00fdskum m\u00f4\u017ee by\u0165 aj pou\u017eitie lacn\u00fdch inhib\u00edtorov s mal\u00fdmi molekulami. Nakoniec je dokonca mo\u017en\u00e9, \u017ee snahy v r\u00e1mci v\u00fdvoja vylep\u0161en\u00fdch terapeut\u00edk proti v\u010del\u00edm jedom m\u00f4\u017eu podpori\u0165 v\u00fdskum a v\u00fdvoj v oblasti diagnostiky v\u010delieho jedu, \u010do m\u00f4\u017ee pom\u00f4c\u0165 stratifik\u00e1cii pacientov a klinick\u00e9mu rozhodovaniu.<\/p>\n\n\n\n<p>Z\u00e1vere\u010dn\u00e9 pozn\u00e1mky<br>\u00datoky afrikanizovan\u00fdch v\u010diel sa v Braz\u00edlii, odkia\u013e poch\u00e1dzaj\u00fa, pova\u017euj\u00fa za probl\u00e9m verejn\u00e9ho zdravia. Dopady tejto v\u00e1\u017enej hrozby si v\u0161imli aj \u010fal\u0161ie americk\u00e9 krajiny, ke\u010f\u017ee tieto hybridy v\u010diel sa v s\u00fa\u010dasnosti \u0161\u00edria po celej Amerike. V d\u00f4sledku toho sa pravdepodobne zv\u00fd\u0161i po\u010det v\u010del\u00edch bodnut\u00ed a otravy. Rie\u0161enie tohto z\u00e1va\u017en\u00e9ho probl\u00e9mu si vy\u017eaduje dobre pripraven\u00fa lek\u00e1rsku pohotovos\u0165 a \u0161pecifick\u00fa lie\u010dbu proti jedom v\u010diel, ako s\u00fa napr\u00edklad antijedy. K dne\u0161n\u00e9mu d\u0148u existuje vo vedeckej literat\u00fare len nieko\u013eko spr\u00e1v preukazuj\u00facich pozit\u00edvne v\u00fdsledky s pou\u017eit\u00edm imuniz\u00e1cie zvierat a o\u0161etruj\u00faci lek\u00e1ri zatia\u013e nemaj\u00fa k dispoz\u00edcii \u017eiadny protijed na lie\u010dbu v\u00e1\u017eneho otravy v\u010diel. Mo\u017en\u00fdm vysvetlen\u00edm nedostatku komer\u010dn\u00fdch v\u010del\u00edch protijedov je obtia\u017enos\u0165 z\u00edskania \u0161pecifick\u00fdch protil\u00e1tok proti k\u013e\u00fa\u010dov\u00fdm zlo\u017ek\u00e1m v\u010delieho jedu, preto\u017ee tieto maj\u00fa n\u00edzku imunogenicitu. Tradi\u010dn\u00e9 met\u00f3dy zalo\u017een\u00e9 na postupn\u00fdch imuniz\u00e1ci\u00e1ch zvierat preto nedok\u00e1\u017eu generova\u0165 dostato\u010dne vysok\u00e9 titre protil\u00e1tok na terapeutick\u00e9 vyu\u017eitie. Naproti tomu technol\u00f3gia f\u00e1gov\u00e9ho displeja sa uk\u00e1zala ako s\u013eubn\u00e1 metodol\u00f3gia na generovanie protil\u00e1tok proti k\u013e\u00fa\u010dov\u00fdm v\u010del\u00edm tox\u00ednom s n\u00edzkou imunogenitou. T\u00e1to technol\u00f3gia tak m\u00f4\u017ee v bud\u00facnosti umo\u017eni\u0165 v\u00fdvoj \u00fa\u010dinn\u00fdch rekombinantn\u00fdch v\u010del\u00edch protijedov (186\u2013188). T\u00e1to technol\u00f3gia je v\u0161ak st\u00e1le celkom ned\u00e1vnym pr\u00edrastkom na poli v\u00fdvoja protijedov a je potrebn\u00e9 e\u0161te ve\u013ea \u00fasilia, k\u00fdm svetlo sveta uzrie \u00fa\u010dinn\u00fd protijed na lie\u010dbu \u0165a\u017ek\u00fdch jedov v\u010diel.<\/p>\n\n\n\n<p>Autorsk\u00e9 pr\u00edspevky<br>FC, IO, TJ, LA, CS a SA nap\u00edsali \u010das\u0165 recenzie a poskytli kritick\u00fa sp\u00e4tn\u00fa v\u00e4zbu. FK a TJ pripravili fig\u00farky. MP a AL navrhli recenziu, nap\u00edsali \u010das\u0165 rukopisu a poskytli rev\u00edzie. JB dal svoje cenn\u00e9 a profesion\u00e1lne n\u00e1vrhy. V\u0161etci autori pre\u010d\u00edtali a schv\u00e1lili kone\u010dn\u00fd rukopis.<\/p>\n\n\n\n<p>Financovanie<br>\u010eakujeme Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq, N\u00e1rodn\u00e1 rada pre vedeck\u00fd a technologick\u00fd rozvoj, grant \u010d. 307155\/2017-0); Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP, S\u00e3o Paulo Research Foundation, grant \u010d. 2017\/04724-4, \u0161tipendium FC \u010d. 2017\/14035-1 a 2018\/14158-9 a \u0161tipendium ISO 2017\/ ISO 2017 03580-9 a 2018\/21233-7); nad\u00e1cia Villum (\u010d. grantu 00025302).<\/p>\n\n\n\n<p>Vyhl\u00e1senie o konflikte z\u00e1ujmov<br>Autori vyhlasuj\u00fa, \u017ee v\u00fdskum bol vykonan\u00fd bez ak\u00fdchko\u013evek obchodn\u00fdch alebo finan\u010dn\u00fdch vz\u0165ahov, ktor\u00e9 by mohli by\u0165 ch\u00e1pan\u00e9 ako potenci\u00e1lny konflikt z\u00e1ujmov.<\/p>\n\n\n\n<p>Po\u010fakovanie<br>JB (1949\u20132019) zomrel v z\u00e1vere\u010dn\u00fdch f\u00e1zach pr\u00edpravy tohto \u010dl\u00e1nku. T\u00e1to pr\u00e1ca je venovan\u00e1 jeho pamiatke ako v\u010fa\u010dnos\u0165 za v\u0161etky jeho objavy v r\u00e1mci v\u010delieho protijedu a za jeho mentorstvo. \u010eakujeme Cecilie Mullerup Kiel za korekt\u00faru rukopisu.<\/p>\n\n\n\n<h2>Referencie<\/h2>\n\n\n\n<p><a><\/a>1. Engel MS. A new interpretation of the oldest fossil bee (Hymenoptera: Apidae).&nbsp;<em>Novi.<\/em>&nbsp;(2000) 2000:1\u201311. doi: 10.1206\/0003-0082(2000)3296&lt;0001:ANIOTO&gt;2.0.CO;2<\/p>\n\n\n\n<p><a href=\"https:\/\/doi.org\/10.1206\/0003-0082(2000)3296%3C0001:ANIOTO%3E2.0.CO;2\" target=\"_blank\" rel=\"noreferrer noopener\">CrossRef Full Text<\/a>&nbsp;|&nbsp;<a href=\"http:\/\/scholar.google.com\/scholar_lookup?author=MS.+Engel+&amp;publication_year=2000&amp;title=A+new+interpretation+of+the+oldest+fossil+bee+(Hymenoptera%3A+Apidae)&amp;journal=Novi.&amp;volume=2000&amp;pages=1-11\" target=\"_blank\" rel=\"noreferrer noopener\">Google Scholar<\/a><\/p>\n\n\n\n<p><a><\/a>2. 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