Ma `lumot

15.4D: Botulizm - biologiya


O'quv maqsadlari

  • Botulinium toksinining uchta asosiy kirish usulini (chaqaloqlar botulizmi yoki kattalardagi ichak toksikozi, oziq-ovqat botulizmi va yara botulizmi) solishtiring va taqqoslang va uning ta'sir mexanizmini tavsiflang.

Botulizmga umumiy nuqtai

Botulizm - botulinum toksinidan kelib chiqadigan kam uchraydigan, lekin ba'zida halokatli paralitik kasallik. Bu sutemizuvchilar, qushlar va baliqlarning keng doirasiga ta'sir qilishi mumkin. Bu toksin anaerob sharoitda Clostridium botulinum bakteriyasi tomonidan ishlab chiqarilgan oqsildir. Toksin inson tanasiga uchta usuldan birida kiradi: bolalarda (chaqaloq botulizmi) yoki kattalarda (kattalar ichak toksemiyasi) bakteriyalar tomonidan oshqozon -ichak traktining kolonizatsiyasi, oziq -ovqatdan toksinni yutish (oziq -ovqat botulizmi) yoki zaharlanish. bakteriya yarasi (yarali botulizm). Botulizmning odamdan odamga yuqishi sodir bo'lmaydi. Barcha shakllar falajga olib keladi, ular odatda yuzning mushaklaridan boshlanadi, so'ngra oyoq -qo'llarga tarqaladi. Og'ir shakllarda nafas olish mushaklarining falajlanishiga olib keladi va nafas etishmovchiligini keltirib chiqaradi. Hayotga xavf tug'diradigan bu murakkablikdan kelib chiqqan holda, botulizmda gumon qilinayotgan barcha holatlar tibbiy favqulodda holat sifatida ko'rib chiqiladi va odatda boshqa manbalardan kelib chiqadigan kasalliklarning oldini olish uchun sog'liqni saqlash xodimlari jalb qilinadi. Botulizmni sporalarni bosim ostida pishirish yoki avtoklavda 121 °C (250 °F) da 30 daqiqa davomida o'ldirish yoki sporalarning o'sishiga to'sqinlik qiladigan sharoitlarni ta'minlash orqali oldini olish mumkin. Chaqaloqlar uchun qo'shimcha ehtiyot choralari ularni asal bilan oziqlantirmaslikni o'z ichiga oladi.

C. botulinum anaerob, gramm musbat, spora hosil qiluvchi tayoqchadir. Botulinium toksini ma'lum bo'lgan eng kuchli toksinlardan biridir: taxminan bir mikrogram odamlar uchun o'limga olib keladi. Somatik asab tizimidagi nerv -mushak birikmalarining presinaptik membranasidan qo'zg'atuvchi neyrotransmitter asetilxolinning chiqarilishini inhibe qilish orqali nerv funktsiyasini blokirovka qilish (nerv -mushak blokadasi) orqali harakat qiladi. Bu falajga olib keladi. Rivojlangan botulizm nafas olish etishmovchiligiga olib kelishi mumkin, bu esa ko'krak qafasining muskullarini falaj qilib qo'yishi mumkin, bu esa nafas qisilishiga olib kelishi mumkin. Barcha holatlarda kasallikni bakterial emas, anaerob sharoitda C. botulinum bakteriyasi ishlab chiqaradigan botulinium toksini keltirib chiqaradi. Zarar ko'rinishi toksin birinchi navbatda yuqori chastotada yonadigan (depolyarizatsiya) nervlarga ta'sir qilganligi sababli yuzaga keladi.

Kirish usullari

Toksinning uchta asosiy kirish usuli ma'lum. G'arb mamlakatlarida eng keng tarqalgan shakl chaqaloq botulizmidir. Bu hayotining dastlabki bosqichida bakteriya bilan koloniya qilingan kichik bolalarda uchraydi. Keyin bakteriya toksinni ichakka chiqaradi, u qonga singib ketadi. Hayotning birinchi yilida asalni iste'mol qilish chaqaloq botulizmi uchun xavf omili sifatida aniqlangan va bu barcha holatlarning beshdan birida omil hisoblanadi. Chaqaloqlar botulizmining kattalar shakli kattalar ichak toksikozi deb ataladi va juda kam uchraydi. Oziq -ovqat botulizmi ifloslangan oziq -ovqat mahsulotlaridan kelib chiqadi, bunda C. botulinum sporalari anaerob sharoitda o'sishiga ruxsat berilgan. Bu odatda uyda konservalangan oziq-ovqat moddalari va fermentlangan pishirilmagan idishlarda sodir bo'ladi. Ko'p odamlar bir xil manbadan oziq -ovqat iste'mol qilishini hisobga olsak, bir vaqtning o'zida bir nechta odamga ta'sir qilish odatiy holdir. Semptomlar odatda ovqatdan 12-36 soat o'tgach paydo bo'ladi, lekin 6 soatdan 10 kungacha ham paydo bo'lishi mumkin. Yara botulizmi yaraning bakteriyalar bilan ifloslanishidan kelib chiqadi, so'ngra toksinni qonga chiqaradi. Bu 1990-yillardan beri vena ichiga giyohvand moddalarni iste'mol qiluvchilarda, ayniqsa qora smolali geroin ishlatadigan va tomirlarga emas, balki teriga geroin yuboradigan odamlarda ko'proq tarqalgan.

Davolash

Hozirgi vaqtda chaqaloq botulizmini davolash uchun mavjud bo'lgan yagona dori-bu botulizm immunoglobulin tomir ichiga-odam (BIG-IV yoki BabyBIG). BabyBIG Kaliforniya sog'liqni saqlash boshqarmasida chaqaloq botulizmini davolash va oldini olish dasturi tomonidan ishlab chiqilgan. Yara va oziq-ovqat botulizmini davolash uchun ikkita asosiy botulinum antitoksin mavjud. Trivalent (A, B, E) botulinum antitoksini butun antikorlardan (Fab va Fc qismlari) foydalangan holda ot manbalaridan olinadi. Ushbu antitoksinni CDC orqali mahalliy sog'liqni saqlash bo'limidan olish mumkin. Ikkinchi antitoksin - bu yetti valentli (A, B, C, D, E, F, G) botulinum antitoksini botulinum antitoksini bo'lib, Fc qismi ajralib chiqqan, F(ab')2 qismlarini tashlab ketgan otlarning "nasoslangan" IgG antikorlaridan olingan. Bu kamroq immunogen antitoksin bo'lib, u kontrendikedir bo'lmagan botulizmning barcha ma'lum shtammlariga qarshi samarali. Bu AQSh armiyasida mavjud.

Asosiy nuqtalar

  • Toksin (lar) inson organizmiga ovqat hazm qilish traktining bakteriya tomonidan kolonizatsiyasi, oziq-ovqatdan toksinni yutish yoki bakteriya bilan yaraning ifloslanishi orqali kiradi.
  • Barcha shakllar falajga olib keladi, ular odatda yuzning mushaklaridan boshlanadi, so'ngra oyoq -qo'llarga tarqaladi.
  • Botulizmni sporalarni bosim ostida pishirish yoki avtoklavda 121 °C (250 °F) da 30 daqiqa davomida o'ldirish yoki sporalarning o'sishiga to'sqinlik qiladigan sharoitlarni ta'minlash orqali oldini olish mumkin.

Asosiy shartlar

  • chaqaloq botulizmi: Clostridium botulinum toksinidan kelib chiqqan zaharlanish, bu erda himoya ichak bakterial florasi paydo bo'lishidan oldin oshqozon-ichak trakti sporalar bilan kolonizatsiyalanadi.
  • spora: Qattiq yoki noqulay sharoitlarda omon qolish uchun bakteriya yoki protist tomonidan ishlab chiqarilgan qalin chidamli zarracha.
  • botulizm: Clostridium botulinum toksinidan kelib chiqqan zaharlanish, noto'g'ri tayyorlangan oziq-ovqatda o'sadigan anaerob bakteriyalar turi.
  • yarali botulizm: sporalar teri ostidagi yaraga kirganda va kislorod bo'lmasa toksin chiqarilganda Clostridium botulinum toksinidan kelib chiqqan zaharlanish.
  • toksin: Biologik organizmlarning biologik jarayonlari natijasida hosil bo'lgan zaharli yoki zaharli modda.

I va II guruh Clostridium botulinum genomlari, neyrotoksinlari va biologiyasi

Butun genomlar ketma-ketligidagi so'nggi o'zgarishlar Clostridium botulinum Group I (proteolitik C. botulinum) va C. botulinum II guruhining (proteolitik bo'lmagan C. botulinum) genomlari, neyrotoksinlari va biologiyasini tushunishga katta hissa qo'shdi. Bu bakteriyalar genomikasini o'rganish uchun ikki xil yondashuvdan foydalaniladi: to'liq genomli mikromarralar va to'liq genom DNK ketma -ketligini to'g'ridan -to'g'ri taqqoslash. C. botulinum I va II guruhlarida hosil bo'lgan har xil turdagi neyrotoksinlar va turli xil neyrotoksin gen klasterlarining xususiyatlari o'rganiladi. Botulinum neyrotoksin genlarining o'ziga xos misollari neyrotoksin geni evolyutsiyasini chuqur muhokama qilish uchun tanlangan. Oziq -ovqatdan kelib chiqqan botulizmning so'nggi holatlari umumlashtiriladi.

Kalit so'zlar: Botulinum neyrotoksin Botulizm Clostridium botulinum Genomics Neurotoxin gen klasteri.

Mualliflik huquqi © 2014 Mualliflar. Elsevier Masson SAS tomonidan nashr etilgan. Barcha huquqlar himoyalangan.


Tashxis va davolash

Chaqaloq botulizm - AQShda botulizmning eng keng tarqalgan turi. Ushbu kasallikning tashxisi va davolash usullari haqida bilib oling.

Tashxis

Agar sizda yoki siz bilgan odamda bo'lsa botulizm belgilari, darhol shifokoringizga murojaat qiling yoki tez yordam xonasiga boring.

Sizning shifokoringiz sizga savollar beradi va alomatlaringizning sababini aniqlash uchun sizni tekshiradi. Ammo, bu maslahatlar, odatda, shifokorning sizga tashxis qo'yishi uchun etarli emas, chunki ba'zi botulizm belgilari Guillain-Barr va eacute sindromi, meningit, miyasteniya gravis, insult va ndash kabi boshqa kasalliklar va ndashlarda ham uchraydi.

Tashxis qo'yish uchun shifokor testlarni buyurishi mumkin. Ushbu testlardan ba'zilari:

  • Miyani skanerlash
  • Orqa miya suyuqligini tekshirish
  • Nerv va mushaklar faoliyatini tekshirish (asab o'tkazuvchanligini o'rganish va elektromiyografiya)
  • Miyasteniya gravis uchun kuchlanish testi

Agar bu testlar sizni nima kasal qilayotganini ko'rsatmasa, sizning shifokoringiz botulizmga olib keladigan toksin yoki bakteriyalarni qidirish uchun laboratoriya testlarini buyurishi mumkin. Bu laboratoriya tekshiruvlari botulizm bor -yo'qligini aniq bilishning yagona yo'li. Tekshiruv natijalarini laboratoriyadan olish uchun bir necha kun kerak bo'ladi. Agar shifokor sizda botulizm borligiga shubha qilsa, darhol davolanishni boshlashingiz mumkin.

Davolash

Botulizm organizmga va asablarga hujum qiladigan toksin tufayli yuzaga keladi, nafas olish qiyinlashadi, mushaklar falaji va hatto o'limga olib keladi.

Shifokorlar botulizmni antitoksin deb nomlangan dori bilan davolashadi, bu esa toksinni boshqa zarar etkazishiga yo'l qo'ymaydi. Antitoksin toksin allaqachon yetkazgan zararni davolamaydi. Sizning alomatlaringiz qanchalik og'irligiga qarab, siz uyga borguningizcha bir necha hafta yoki hatto oylar davomida kasalxonada qolishingiz kerak bo'lishi mumkin.

Agar sizning kasalligingiz og'ir bo'lsa, sizda nafas olish muammolari bo'lishi mumkin. Agar toksin nafas olishda ishtirok etadigan mushaklarni falaj qilsa, sizda hatto nafas olish (nafas olish) etishmovchiligi bo'lishi mumkin. Agar shunday bo'lsa, shifokoringiz sizni o'zingiz nafas olmaguningizcha nafas olish apparati (ventilyator) ga qo'yishi mumkin. Toksin sabab bo'lgan falaj odatda sekin yaxshilanadi. Kasalxonada ko'rsatiladigan tibbiy va hamshiralik yordami sizni tiklanishingizga yordam beradi.

Yara botulizmi bo'lgan odamlar ba'zida bakteriyalar manbasini olib tashlash uchun jarrohlik amaliyotiga muhtoj va antibiotiklarni qabul qilishlari kerak bo'lishi mumkin.

Omon qolish va asoratlar

Antitoksin va zamonaviy tibbiy yordamning rivojlanishi shuni ko'rsatadiki, botulizm bilan og'rigan odamlarning o'lish ehtimoli ancha past, chunki har 100 botulizmdan 50 tasi o'lgan. Bugungi kunda botulizm bilan kasallangan har 100 kishidan 5 dan kamrog'i vafot etadi.

Antitoksin va intensiv tibbiy va hamshiralik yordami bilan ham, botulizm bilan og'rigan ba'zi odamlar nafas etishmovchiligidan vafot etishadi. Boshqalar infektsiyalardan yoki bir necha haftalar yoki oylar davomida falaj bo'lib qolgan boshqa muammolardan o'lishadi.

Botulizmdan omon qolgan bemorlar ko'p yillar davomida charchoq va nafas qisilishiga duch kelishi mumkin va ularga tuzalish uchun uzoq muddatli terapiya kerak bo'lishi mumkin.


Kintzing, J. R. va Kochran, J. R. Knottin peptidlarini diagnostika, terapevtik va dori vositalarini etkazib berish vositalari sifatida ishlab chiqdi. Curr. Fikr. Kimyo Biol. 34, 143–150 (2016)

Gebauer, M. & Skerra, A. Yangi avlod antikor terapevtiklari sifatida ishlab chiqilgan protein iskala. Curr. Fikr. Kimyo Biol. 13, 245–255 (2009)

Zahnd, C. va boshqalar. Samarali o'simtani yuqori aniqlikdagi ankirin bilan takrorlanadigan oqsillar: yaqinlik va molekulyar kattalikning ta'siri. Saraton kasalligi. 70, 1595–1605 (2010)

Vaskes-Lombardi, R. va boshqalar. Antikor bo'lmagan iskala dorilarining qiyinchiliklari va imkoniyatlari. Giyohvand moddalar disklari. Bugun 20, 1271–1283 (2015)

Bhardwaj, G. va boshqalar. Aniq de novo giperstabil cheklangan peptidlarning dizayni. Tabiat 538, 329–335 (2016)

Roklin, G.J. va boshqalar. Ommaviy parallel dizayn, sintez va sinovdan foydalangan holda oqsillarning katlanishini global tahlil qilish. Fan 357, 168–175 (2017)

Berger, S. va boshqalar. Hisoblangan yuqori o'ziga xoslik inhibitörleri BCL2 oilaviy oqsillarining saraton kasalligidagi rolini aniqlaydi. eLife 5, e20352 (2016)

Procko, E. va boshqalar. Epstein-Barr virusli Bcl-2 oqsilining hisoblab chiqilgan inhibitori infektsiyalangan hujayralarda apoptozni keltirib chiqaradi. Hujayra 157, 1644–1656 (2014)

Cleary, M. A. va boshqalar. In situ oligonukleotid sintezi yuqori darajada parallel bo'lgan murakkab nuklein kislota kutubxonalarini ishlab chiqarish. Nat. Usullari 1, 241–248 (2004)

Sun. Ilmiy. Adv. 2, e1600692 (2016)

Fleishman, S. J. va boshqalar. RosettaScripts: Rosetta makromolekulyar modellashtirish to'plamining skript tili interfeysi. PLoS One 6, e20161 (2011)

Hurt, A.C. va boshqalar. 2009 yilgi A H1N1 grippi pandemiyasi davrida antiviral qarshilik: jamoat salomatligi, laboratoriya va klinik istiqbollar. Lanset infektsiyasi. Dis. 12, 240–248 (2012)

Blitzer, A. Spazmodik disfoniya va botulinum toksini: eng katta davolash seriyasidan tajriba. Yevro. J. Neurol. 17, (Qo'shimcha 1), 28-30 (2010)

Koday, M. T. va boshqalar. Hisoblash asosida ishlab chiqilgan gemagglutinin poyasini bog'lovchi protein beradi in vivo grippdan himoya, uy egasining immunitetiga bog'liq emas. PLoS patogini. 12, e1005409 (2016)

Uaythead, T. A. va boshqalar. Chuqur ketma -ketlik yordamida gripp grippi inhibitörlerinin yaqinligini, o'ziga xosligini va funktsiyasini optimallashtirish. Nat. Biotexnologiya. 30, 543–548 (2012)

Fleishman, S. J. va boshqalar. Gemagglutinin grippining saqlanib qolgan ildiz mintaqasiga yo'naltirilgan oqsillarni hisoblash dizayni. Fan 332, 816–821 (2011)

Berntsson, R. P. A., Peng, L., Dong, M. & Stenmark, P. Sinaptotagmin II va GD1a bilan kompleksda botulinum neyrotoksin B bog'lovchi domenining tuzilishi. RCSB Protein ma'lumotlar banki. http://dx.doi.org/10.2210/pdb4kbb/pdb. (2013)

Corti, D. va boshqalar. 1-guruh va 2-guruh grippi A gemagglyutininlari bilan bog'langan plazma hujayralaridan tanlangan neytrallashtiruvchi antikor. Fan 333, 850–856 (2011)

Cass, L. M. R., Efthymiopoulos, C. & amp Bye, A. Sog'lom ko'ngillilarga tomir ichiga, og'iz orqali, nafas olish yoki intranazal yuborishdan keyin zanamivirning farmakokinetikasi. Klinika. Farmakokinet. 36 (1 -ilova), 1–11 (1999)

King, C. va boshqalar. T-hujayrali epitoplarni hisoblash oqsil dizayni bilan olib tashlash. Proc. Natl Akad. Ilmiy. AQSH 111, 8577–8582 (2014)

Huang, P.-S. va boshqalar. RosettaRemodel: moslashuvchan magistral oqsil dizayni uchun umumiy asos. PLoS One 6, e24109 (2011)

Lin, Y.-R. va boshqalar. Yangi shakllangan oqsillarning umumiy shakli va hajmini nazorat qilish. Proc. Natl Akad. Ilmiy. AQSH 112, E5478–E5485 (2015)

Koga, N. va boshqalar. Ideal oqsil tuzilmalarini loyihalash tamoyillari. Tabiat 491, 222–227 (2012)

Silva, D.-A., Correia, B. E. & Procko, E. Motifga asoslangan oqsil-oqsil interfeyslarining dizayni. Mol usullari. Biol. 1414, 285–304 (2016)

Hoover, D. M. & amp; Nuklein kislotalari Res. 30, e43 (2002)

Bawono, P. & Heringa, J. PRALINE: Ko'p tomonlama ketma -ketlikni moslashtirish uchun ko'p qirrali asboblar to'plami. Moldagi usullar. Biol. 1079, 245–262 (2013)

Chjan, J., Kobert, K., Flouri, T. & Stamatakis, A. PEAR: tez va aniq Illumina Paired-End o'qish birlashmasi. Bioinformatika 30, 614–620 (2014)

Chao, G. va boshqalar. Xamirturush yuzasi displey yordamida inson antikorlarini izolyatsiya qilish va muhandislik. Nat. Protokollar 1, 755–768 (2006)

Benatuil, L., Peres, J. M., Belk, J. & amp Hsieh, C.-M. Inson antikorlarining juda katta kutubxonalarini yaratish uchun xamirturushni o'zgartirishning yaxshilangan usuli. Protein Eng. Des. Sel. 23, 155–159 (2010)

Jacobs, T. M., Yumerefendi, H., Kuhlman, B. & amp Leaver-Fay, A. SwiftLib: dinamik dasturlash orqali degenerativ-kodonli kutubxonani tez optimallashtirish. Nuklein kislotalari Res. 43, e34 (2015)

Jin, R., Rummel, A., Binz, T. va Brunger, A. T. Botulinum neyrotoksin B o'zining oqsil retseptorlarini yuqori yaqinlik va o'ziga xoslik bilan taniydi. Tabiat 444, 1092–1095 (2006)

Kabsch, W. XDS. Acta Crystallogr. D Biol. Kristallogr. 66, 125–132 (2010)

Emsley, P. & amp; Cowtan, K. Coot: molekulyar grafikalar uchun model yaratish vositalari. Acta Crystallogr. D Biol. Kristallogr. 60, 2126–2132 (2004)

McCoy, A. J. va boshqalar. Phaser kristallografik dasturi. J. Appl. Kristallogr. 40, 658–674 (2007)

Bryunger, A. T. Erkin R qiymati: kristalli tuzilmalarning aniqligini baholash uchun yangi statistik miqdor. Tabiat 355, 472–475 (1992)

Chen, V. B. va boshqalar. MolProbity: makromolekulyar kristallografiya uchun butun atom tuzilishini tekshirish. Acta Crystallogr. D Biol. Kristallogr. 66, 12–21 (2010)

Otvinovski, Z. & amp Minor, W. Tebranish rejimida to'plangan rentgen nurlarining diffraktsiyasi ma'lumotlarini qayta ishlash. Enzimol usullari. 276, 307–326 (1997)

Adams, P. D. va boshqalar. Makromolekulyar tuzilmalarni avtomatlashtirilgan aniqlash uchun Phenix dasturi. Usullari 55, 94–106 (2011)

Gamblin, S. J. va boshqalar. 1918 yilgi gripp gemagglutininining tuzilishi va retseptorlarini bog'lash xususiyatlari. Fan 303, 1838–1842 (2004)

Van Der Spoel, D. va boshqalar. GROMACS: tez, moslashuvchan va bepul. J. Hisoblash. Kimyo 26, 1701–1718 (2005)

Lindorff-Larsen, K. va boshqalar. Amber ff99SB oqsil kuchlari uchun yon zanjirning burilish potentsiali yaxshilandi. Proteinlar 78, 1950–1958 (2010)

Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W. & Klein, M. L. Suyuq suvni simulyatsiya qilish uchun oddiy potentsial funktsiyalarni solishtirish. J. Chem. Fizika 79, 926–935 (1983)

Hess, B., Bekker, H., Berendsen, H. J. C. & amp; J. Hisoblash. Kimyo 18, 1463–1472 (1997)

Essmann, U. va boshqalar. Yumshoq zarracha to'rli Evald usuli. J. Chem. Fizika 103, 8577–8593 (1995)

Berendsen, H. J. C. Kompyuter simulyatsiyasi materialshunoslik bo'yicha (Eds Meyer. M. & Pontikis, V.) 139–155 (Springer, 1991)

Bussi, G., Donadio, D. & Parrinello, M. Tezlikni o'zgartirish orqali kanonik namuna olish. J. Chem. Fizika 126, 014101 (2007)

Nose, S. & amp Klein, M. L. Molekulyar tizimlar uchun doimiy bosim molekulyar dinamikasi. Mol. Fizika 50, 1055–1076 (1983)


Patogenez

Yuqish:

U tabiatda hamma joyda, saprofit sifatida tuproqda, hayvon go'ngi, sabzavot va dengiz loyida keng tarqalgan. Uyda tayyorlangan konservalar, ziravorlar va baliq mahsulotlari infektsiyaning eng keng tarqalgan manbalari hisoblanadi C. botulinum. Kontaminatsiyalangan asalni yutish chaqaloq botulizmining asosiy sababidir.

Pishirish haroratining etarli emasligi, keyin anaerob sharoitda qadoqlanishi sporalarning o'sishini va neyrotoksin sintezini osonlashtiradi.

Botulinum toksinining ta'sir qilish mexanizmi (BoNT)

Clostridium botulinum hisoblanadi invaziv bo'lmagan. Uning patogenezi kuchli neyrotoksin ishlab chiqarish bilan bog'liq.botulinum toksin (BoNT), ehtimol, insoniyat uchun halokatli bo'lgan eng zaharli modda. Ishlab chiqaradi zaif falaj. Lar bor 7 ta serologik tur A, B, C [C1 C2], D, E, F va G turlari sifatida belgilangan botulinum neyrotoksini. Inson botulizmi asosan A, B, E va F (kamdan-kam) turlaridan kelib chiqadi.

C. botulinum toksini potentsial bioterror agenti sifatida tasniflanadi, lekin botoks yuz ajinlarini yumshatish uchun ishlatiladi.

Kirishdan keyin (yutilganda, nafas olganda yoki yarada hosil bo'ladi) botulinum toksini tashiladi qon orqali periferik xolinergik asab terminallariga. Eng ko'p uchraydigan nerv terminal joylari nerv-mushak birikmalari, postganglionik parasempatik nerv uchlari va periferik gangliyalardir. Bu markaziy asab tizimiga ta'sir qilmaydi.

Oddiy holatda: Periferik va kranial nervlarni qo'zg'atgandan so'ng, atsetilxolin odatda vosita so'nggi plastinkasining nerv tomonidagi pufakchalardan chiqariladi. Keyin atsetilxolin mushaklarning o'ziga xos retseptorlari bilan bog'lanib, induktsiya qiladi qisqarish.

Botulinum toksinining mexanizmi
(Rasm manbai: lumenlearning.com)

Botulinum toksini bog'lanish orqali harakat qiladi uchun xolinergik nervlarning sinaptik pufakchalari, shu bilan chiqarilishining oldini oladi atsetilxolin (Ach) periferik asab tugunlarida, shu jumladan nerv -mushak birikmalarida. Bu mushak tolalari uchun stimulning etishmasligiga, mushaklarning qaytmas bo'shashishiga olib keladi, va zaif falaj.

Botulinum toksinlari falaj falajni keltirib chiqarar ekan, uni strabismus (ko'zning noto'g'riligi), blefarospazm (nazorat qilib bo'lmaydigan miltillash) va miyoklonus kabi spazmli holatlarni davolashda terapevtik usulda qo'llash mumkin.

Klinik ko'rinishlar

  1. Diplopiya (ikki marta ko'rish) yoki ko'rishning xiralashishi
  2. Disfagiya (yutishda qiyinchilik)
  3. Dizartriya (nutqda qiyinchilik) yoki nutqning sustligi
  4. Ixtiyoriy mushaklarning tushayotgan simmetrik bo'sh falaj.
  5. Chuqur tendon reflekslarining pasayishi
  6. Charchoq
  7. Bosh aylanishi
  8. Ko'ngil aynishi
  9. Qabziyat
  10. Nafas olish mushaklarining falaji o'limga olib kelishi mumkin.

Hissiy yoki kognitiv nuqsonlar yo'q

Botulizm turlari

  1. Oziq-ovqat mahsuloti botulizm: Bu uy qurilishi konservalari kabi oldindan hosil bo'lgan botulinum toksini bilan ifloslangan oziq-ovqatlarni iste'mol qilish natijasida yuzaga keladi.
  2. Yarali botulizm: Bu o'sishning natijasi bo'lgan tizimli intoksikatsiya C. botulinum va yaralarda toksin ishlab chiqarish. Bu oshqozon -ichak trakti xususiyatlaridan tashqari, oziq -ovqatdan kelib chiqqan botulizm kabi namoyon bo'ladi.
  3. Bolalar botulizmi: Chaqaloqlar botulizmi kattalarnikiga qaraganda ancha yumshoqroq. Bu spora bilan ifloslangan ovqatni (odatda asal) yutish natijasida yuzaga keladi C. botulinum ≤ 1 yoshgacha bo'lgan bolalar tomonidan. Ichakda sporalar unib chiqadi, vegetativ hujayralar esa botulinum toksinini chiqaradi. Klinik ko'rinishlarga so'rish va yuta olmaslik, zaif ovoz, ptozis, floppy bo'yin va o'ta zaiflik kiradi, shuning uchun floppy bolalar sindromi deb ataladi. O'z-o'zidan o'tadigan kasallikning prognozi, agar qo'llab-quvvatlovchi parvarish va yordam berish orqali boshqarilsa, juda yaxshi.

Sporalar odatda kattalar ichaklarida unib chiqmaydi, lekin chaqaloqlarning ichaklarida unib chiqishi mumkin.


Tarkibi

C. botulinum gram-musbat, tayoqchali, spora hosil qiluvchi bakteriya. Bu majburiy anaerob, ya'ni kislorod hujayralar uchun zaharli. Biroq, C. botulinum kislorod ta'siriga uchragan deyarli barcha hujayralarda muhim antioksidant himoya vositasi bo'lgan superoksid dismutaza fermenti tufayli kislorod izlariga toqat qiladi. [5] C. botulinum u faqat anaerob muhitda bo'lishi mumkin bo'lgan sporulyatsiya paytida neyrotoksin ishlab chiqarishga qodir. C. botulinum To'rtta aniq fenotipik guruhga bo'linadi (I-IV), shuningdek, ishlab chiqarilgan botulinum toksinining antigenligiga qarab ettita serotipga (A-G) bo'linadi. [6] [7]

Guruhlarni tahrirlash

Fiziologik farqlar va 16S rRNK darajasidagi genomlarning ketma -ketligi uning bo'linishini qo'llab -quvvatlaydi C. botulinum turlari I-IV guruhlarga boʻlinadi. [8]

ning guruhlari C. botulinum [8] [9]
Guruh Serotiplar
Men (Proteolitik) A va B va F tipli barcha turdagi A va proteolitik shtammlar
II (proteolitik bo'lmagan) Barcha turdagi E va B va F tipidagi protolitik bo'lmagan shtammlar
III C va D turini kiriting
IV G turi

I va II guruh o'rtasidagi asosiy farqlardan biri shundaki C. botulinum I guruh - mahalliy oqsillarni, masalan, tuxum oqi, pishirilgan go'sht bo'laklarini, ikkinchisi - yo'q. [9] Biroq, II guruh saxaroza, mannoz kabi turli xil uglevodlarni achitishi mumkin. Va ikkalasi ham olingan oqsilni, jelatinni buzishi mumkin. [9] Odam botulizmiga asosan I yoki II guruh sabab bo'ladi C. botulinum. [9] III guruh organizmlari asosan hayvonlarda kasallik keltirib chiqaradi. [9] IV guruh C. botulinum odam yoki hayvon kasalliklariga olib kelishi isbotlanmagan. [9]

Botulinum toksinini tahrirlash

Neyrotoksin ishlab chiqarish turlarni birlashtiruvchi xususiyatdir. Sakkiz turdagi zaharli moddalar aniqlangan, ular bir harf (A-H) bilan ajralib turadi, ularning bir nechtasi odamlarda kasallikka olib kelishi mumkin. Ular oshqozon -ichak traktida topilgan fermentlar ta'sirida degradatsiyaga chidamli. Bu yutilgan toksinni ichakdan qonga singib ketishiga imkon beradi. [3] Biroq, botulinum toksinining barcha turlari 15 daqiqa (900 soniya) davomida 100 ° C ga qizdirilganda tezda yo'q qilinadi. Ma'lum bo'lgan eng zaharli biologik moddalardan biri bo'lgan botulinum toksin - bu bakteriya tomonidan ishlab chiqarilgan neyrotoksin Clostridium botulinum. C. botulinum sakkizta antigenik jihatdan ajralib turadigan ekzotoksinlarni (A, B, C1, C2, D, E, F va G) ishlab chiqadi. [ iqtibos kerak ]

Ko'pgina shtammlar bir turdagi neyrotoksin ishlab chiqaradi, ammo bir nechta toksinlarni ishlab chiqaradigan shtammlar tasvirlangan. C. botulinum B va F toksin turlarini ishlab chiqaradigan Nyu-Meksiko va Kaliforniyada inson botulizmi holatlaridan ajratilgan. [10] Toksin turi Bf deb belgilandi, chunki B tipidagi toksin F turiga qaraganda ko'proq topilgan. Xuddi shunday, Ab va Af toksinlarini ishlab chiqaruvchi shtammlar ham qayd etilgan. [ iqtibos kerak ]

Dalillar shuni ko'rsatadiki, neyrotoksin genlari, ehtimol, virusli (bakteriofag) manbadan gorizontal gen o'tkazish mavzusi bo'lgan. Bu nazariya ba'zi shtammlarda toksin yonida joylashgan integratsion saytlarning mavjudligi bilan tasdiqlanadi C. botulinum. Biroq, bu integratsiya saytlari degradatsiyaga uchragan (C va D turlaridan tashqari), bu shuni ko'rsatadiki C. botulinum evolyutsion o'tmishda toksin genlarini sotib oldi. Shunga qaramay, genlar joylashgan plazmidlar va boshqa harakatlanuvchi elementlar orqali boshqa transferlar sodir bo'ladi. [11]

Botulinum toksinlarining turlari

Faqat A, B, E, F va H turdagi botulinum toksinlari odamlarda kasallik keltirib chiqaradi. A, B va E turlari oziq-ovqat kasalliklari bilan, E turi esa baliq mahsulotlari bilan bog'liq. C turi qushlarda bo'yinbog 'hosil qiladi, D turi boshqa sutemizuvchilarda botulizmni keltirib chiqaradi. G turi bilan hech qanday kasallik bog'liq emas. [12] Toksin turini aniqlashning "oltin standarti" sichqoncha bioassaysi hisoblanadi, lekin hozirda A, B, E va F turlarining genlari miqdoriy PCR yordamida osonlik bilan farqlanishi mumkin. [13] 2013-yilda topilgan va hozirgacha eng halokatli bo'lgan H turiga qarshi antitoksin hali mavjud bo'lmagani uchun tafsilotlar qopqoq ostida saqlanadi. [14]

Organizmlarning bir nechta shtammlari genetik jihatdan boshqasi sifatida aniqlangan Clostridium Odamlarda botulizmni keltirib chiqaradigan turlar: C. butyricum E tipidagi toksin ishlab chiqargan [15] va C. baratii F tipli toksin ishlab chiqargan. [16] [17] qobiliyati C. botulinum Neyrotoksin genlarini tabiiy ravishda boshqa klostridiyalarga o'tkazish, ayniqsa oziq-ovqat sanoatida, konservatsiya tizimlari faqat yo'q qilish yoki inhibe qilish uchun mo'ljallangan. C. botulinum lekin boshqa emas Clostridium turlar. [ iqtibos kerak ]

Ning fenotipik guruhlari Clostridium botulinum
Xususiyatlari I guruh II guruh III guruh IV guruh
Toksin turlari A, B, F B, E, F C, D G
Proteoliz + zaif
Saxaroliz +
Kasallik xosti inson inson hayvon
Toksin geni xromosoma/plazmid xromosoma/plazmid bakteriofag plazmid
Yaqin qarindoshlar C. sporogenlar
C. putrificum
C. butyricum
C. beijerinickii
C. gemolyticum
C. novyy A turi
C. subterminal
C. gemolyticum

Laboratoriya izolyatsiyasi Tahrirlash

Laboratoriyada, C. botulinum odatda kislorod 2% dan kam bo'lgan anaerob muhitda triptoza sulfit sikloserin (TSC) o'sish muhitida ajratiladi. Bunga O ning o'rnini kimyoviy reaktsiyadan foydalanadigan bir nechta tijorat to'plamlari orqali erishish mumkin2 CO bilan2. C. botulinum pH 4,8 dan 7,0 gacha o'sadigan va biokimyoviy identifikatsiya qilish uchun muhim bo'lgan asosiy uglerod manbai sifatida laktozani ishlata olmaydigan lipaz-musbat mikroorganizmdir. [18]

C. botulinum birinchi marta 1895 yilda Emile van Ermengem tomonidan botulizm kasalligiga chalingan uyda davolangan jambondan ajratilgan. [19] Izolyatsiya dastlab shunday nomlangan Bacillus botulinus, kolbasa lotincha so'zidan keyin, botulus. ("Kolbasa bilan zaharlanish" 18- va 19-asrlarda Germaniyada keng tarqalgan muammo bo'lgan va katta ehtimol bilan botulizm sabab bo'lgan.) [20] Biroq, keyingi epidemiyalardan olingan izolatlar har doim anaerob spora hosil qiluvchilar ekanligi aniqlangan, shuning uchun Ida A. Bengtson organizmni jinsga joylashtirishni taklif qildi Clostridium, jins sifatida Bacillus aerobik spora hosil qiluvchi tayoqlar bilan cheklangan edi. [21]

1959 yildan boshlab botulinum neyrotoksinlarini ishlab chiqaradigan barcha turlar (A -G tiplari) belgilandi C. botulinum. Turlarning heterojenligini ko'rsatish uchun muhim fenotipik va genotipik dalillar mavjud. Bu qayta tasniflashga olib keldi C. botulinum G turi shtammlari yangi tur sifatida, C. argentinense. [22]

I guruh C. botulinum botulin toksinini ishlab chiqarmaydigan shtammlar deyiladi C. sporogenlar. [23]

To'liq genom C. botulinum 2007 yilda Wellcome Trust Sanger institutida tartiblangan. [24]

Oziq -ovqat botulizmini tahrirlash

"Oziq-ovqat botulizmining belgilari va alomatlari odatda toksin tanangizga tushganidan keyin 18 dan 36 soatgacha boshlanadi, ammo yutilgan toksin miqdoriga qarab bir necha soatdan bir necha kungacha bo'lishi mumkin." [25]

  • Ikki tomonlama ko'rish
  • Xiralashgan ko'rish
  • Ko'z qovoqlarini tushirish
  • Bulantı, qusish va qorin bo'shlig'i kramplari
  • Noqulay nutq
  • Nafas olishda qiyinchilik
  • Yutish qiyinligi
  • Quruq og'iz
  • Mushaklar kuchsizligi
  • Qabziyat
  • Chuqur tendon reaktsiyalarining kamayishi yoki yo'qligi, masalan, tizzada

Yara botulizmini tahrirlash

Yara botulizmi bilan kasallangan odamlarning ko'pchiligi kuniga bir necha marta giyohvand moddalarni AOK qiladi, shuning uchun toksin tanaga kirgandan keyin alomatlar va alomatlar paydo bo'lishi uchun qancha vaqt kerakligini aniqlash qiyin. Ko'pincha qora smola geroinni in'ektsiya qiladigan odamlarda yara botulizmining belgilari va alomatlari quyidagilardan iborat: [25]

  • Yutish yoki gapirish qiyinligi
  • Yuzning ikkala tomonida yuzning zaifligi
  • Xiralashgan yoki ikki tomonlama ko'rish
  • Ko'z qovoqlarining tushishi
  • Nafas olishda qiyinchilik
  • Shol

Bolalar botulizmini tahrirlash

Agar chaqaloq botulizmi oziq-ovqat, masalan, asal bilan bog'liq bo'lsa, muammolar odatda toksin chaqaloqning tanasiga kirganidan keyin 18-36 soat ichida boshlanadi. Belgilar va alomatlarga quyidagilar kiradi:

  • Kabızlık (ko'pincha birinchi belgi)
  • Mushaklarning kuchsizligi va boshni boshqarishda muammolar tufayli egiluvchan harakatlar
  • Zaif yig'lash
  • Achchiqlanish
  • Drooling
  • Ko'z qovoqlarini tushirish
  • Charchoq
  • Emish yoki ovqatlantirishda qiyinchilik
  • Shol [25]

Botulinum toksinining foydali ta'siri Tahrirlash

Tozalangan botulinum toksini davolash uchun shifokor tomonidan suyultiriladi:

  • Tos suyagining tug'ma egilishi
  • Spazmodik disfaziya (halqum mushaklarining ishlamasligi)
  • Axalaziya (qizilo'ngach torayishi)
  • Strabismus (kesishgan ko'zlar)
  • Yuz mushaklarining falaji
  • Serviksning ishlamay qolishi
  • Tez -tez miltillovchi
  • Saratonga qarshi dori yetkazib berish [26]

Kattalar ichak toksemiyasi Tartibga solish

Botulizmning juda kam uchraydigan shakli, u bolalar botulizmi bilan bir xil yo'l bilan sodir bo'ladi, lekin kattalar orasida. Kamdan kam va kamdan-kam uchraydi. Belgilar va alomatlarga quyidagilar kiradi:

  • Qorin og'riq
  • Xiralashgan ko'rish
  • Diareya
  • Balanssizlik
  • Qo'l va qo'l sohasidagi zaiflik [27]

uchun bir qator miqdoriy so'rovlar C. botulinum Atrof-muhitdagi sporlar ma'lum geografik hududlarda o'ziga xos toksin turlarining tarqalishini taklif qildi, ular hali ham tushuntirilmagan. [ iqtibos kerak ]

Shimoliy Amerika Tahrirlash

A turi C. botulinum g'arbiy hududlardagi tuproq namunalarida ustunlik qiladi, B tipi esa sharqiy hududlarda uchraydi. [28] B tipidagi organizmlar I proteolitik tipga mansub edi. Buyuk ko'llar hududidan cho'kmalar tijorat bilan o'stiriladigan baliqlar orasida botulizm tarqalishidan keyin o'rganildi va faqat E tipidagi sporalar aniqlandi. [29] [30] [31] Tadqiqotda A tipidagi shtammlar ishqoriygacha neytral bo'lgan tuproqlardan ajratilgan (o'rtacha pH 7,5), B tipli shtammlar esa ozgina kislotali tuproqlardan ajratilgan (o'rtacha pH 6,23). [ iqtibos kerak ]

Yevropa tahriri

C. botulinum E turi Norvegiya va Shvetsiya, [32] Daniya, [33] Gollandiya, Polshaning Boltiq bo'yi sohillari va Rossiyada suv cho'kmalarida keng tarqalgan. [28] E turi C. botulinum Haqiqiy suv organizmlari bo'lishi taklif qilindi, bu E tipidagi ifloslanish darajasi va dengizning suv bilan to'lib toshishi o'rtasidagi bog'liqlik bilan ko'rsatildi. Er qurigani sari E tipining darajasi pasayib, B tipi hukmron bo'ldi. [ iqtibos kerak ]

Buyuk Britaniyadan tuproq va cho'kmalarda, C. botulinum B turi ustunlik qiladi. Umuman olganda, tuproqda cho'kindi jinslarga qaraganda kasallik tez -tez uchraydi. Italiyada, Rim yaqinida o'tkazilgan so'rov shuni ko'rsatdiki, ifloslanish darajasi past, barcha shtammlar proteolitik C. botulinum A yoki B turlari [34]

Avstraliya tahriri

C. botulinum Viktoriya tog'li hududlaridan olingan tuproq namunalarida A turi borligi aniqlandi. [35] B tipidagi organizmlar Tasmaniyadan kelgan dengiz loyida aniqlangan. [36] [ tekshirish kerak ] A turi C. botulinum Sidney chekkasida topilgan va A va B tiplari shaharlardan ajratilgan. Kvinslend shtatining Darling-Dauns viloyatining yaxshi aniqlangan hududida o'tkazilgan tadqiqot shuni ko'rsatdiki, C. botulinum otlarda botulizmning ko'p holatlaridan keyin B turi. [ iqtibos kerak ]

C. botulinum mushak funktsiyasini vaqtincha yengillashtirish uchun mushaklarni tanlab falaj qilish uchun ishlatiladigan Botox, Dysport, Xeomin va Neurobloc dorilarini tayyorlash uchun ishlatiladi. U boshqa "yorliqsiz" tibbiy maqsadlarga ega, masalan, trigeminal nevralgiyadan kelib chiqqan kuchli yuz og'rig'ini davolash.

tomonidan ishlab chiqarilgan botulinum toksini C. botulinum ko'pincha potentsial biologik qurol deb ishoniladi, chunki u shunchalik kuchliki, odamni o'ldirish uchun 75 nanogramma kerak bo'ladi.50 1 ng/kg, [37] o'rtacha odamning og'irligini hisobga olsak

75 kg) Uning 1 kilogrammi butun insoniyatni o'ldirish uchun etarli bo'ladi. Taqqoslash uchun, qum og'irligi (350 ng) bo'lgan botulinum toksinining to'rtdan bir qismi odamlar uchun o'lik dozani tashkil qiladi.

"Sichqonchani himoya qilish" yoki "sichqonchani bioassay" testi turini aniqlaydi C. botulinum toksin monoklonal antikorlar yordamida mavjud. Toksinni aniqlash uchun ferment bilan bog'langan immunosorbent tahlilini (ELISA) digoksigenin bilan belgilangan antikorlardan ham foydalanish mumkin [38] va miqdoriy PCR organizmdagi toksin genlarini aniqlay oladi. [13]

C. botulinum tuproq bakteriyasi hisoblanadi. Sporlar ko'p muhitda omon qolishi mumkin va ularni o'ldirish juda qiyin. Ular dengiz sathida qaynoq suv haroratida omon qolishi mumkin, shuning uchun ko'plab oziq-ovqatlar sporalarni o'ldirish uchun etarli bo'lgan yuqori haroratga erishadigan bosimli qaynatish bilan konservalanadi. [ iqtibos kerak ] Bu bakteriyalar tabiatda keng tarqalgan va barcha oziq-ovqat yuzalarida mavjud deb taxmin qilish mumkin. Uning optimal o'sish harorati mezofil diapazonda. Spora shaklida bu issiqlikka chidamli patogen bo'lib, past kislotali ovqatlarda omon qolishi va toksin ishlab chiqarish uchun o'sishi mumkin. Toksin asab tizimiga hujum qiladi va kattalarni 75 ng atrofida o'ldiradi. [37] Bu toksin ovqatni 100 ° C da 10 daqiqa ushlab turish orqali detoksifikatsiya qilinadi. [ iqtibos kerak ]

Botulizmdan zaharlanish konservalangan yoki uy sharoitida konservalangan, kislotasi past bo'lgan ovqatlar tufayli bo'lishi mumkin, ular to'g'ri saqlanish vaqtlari va/yoki bosim yordamida qayta ishlanmagan. [39] Bakteriyaning o'sishini yuqori kislotalilik, erigan shakarning yuqori nisbati, yuqori darajadagi kislorod, juda past namlik darajasi yoki A turi uchun 3 °C (38 °F) dan past haroratlarda saqlash orqali oldini olish mumkin. , kislotasi past bo'lgan, konservalangan sabzavotlarda, masalan, yashil loviya kabi, sporalarni o'ldirish uchun etarlicha isitilmaydi (ya'ni, bosimli muhitda) sporalar o'sishi va toksin ishlab chiqarishi uchun kislorodsiz muhitni ta'minlay oladi. Biroq, tuzlangan bodringlar, agar sporlar mavjud bo'lsa ham, o'sishni oldini olish uchun etarlicha kislotali bo'lib, ular iste'molchi uchun hech qanday xavf tug'dirmaydi. Asal, makkajo'xori siropi va boshqa tatlandırıcılar sporalarni o'z ichiga olishi mumkin, ammo sporalar yuqori konsentrlangan shakar eritmasida rivojlana olmaydi, ammo tatlandırıcı chaqaloqning kam kislorodli, past kislotali ovqat hazm qilish tizimida suyultirilganda sporalar o'sishi va rivojlanishi mumkin. toksin hosil qiladi. Kichkintoylar qattiq ovqat eyishni boshlashlari bilanoq, oshqozon sharbati bakteriya o'sishi uchun juda kislotali bo'ladi. [ iqtibos kerak ]

Oziq-ovqat orqali yuqadigan botulizmni nazorat qilish C. botulinum deyarli butunlay sporalarni termal yo'q qilishga (isitishga) yoki bakteriyalarga spora o'sishini inhibe qilishga va hujayralar o'sishiga va oziq-ovqatda toksinlar ishlab chiqarishga imkon beradi. O'sish uchun qulay shart -sharoitlar turli xil ekologik omillarga bog'liq. ning o'sishi C. botulinum pH darajasi 4,6 [40] dan yuqori bo'lishi bilan tavsiflangan past kislotali ovqatlar uchun xavf hisoblanadi, ammo 4,9 dan past pH uchun o'sish sezilarli darajada sekinlashadi. PH 4,6 dan past bo'lgan o'sishni saqlab qolish uchun ba'zi holatlar va aniq sharoitlar qayd etilgan. [41] [42]

Physicians may consider the diagnosis of botulism based on a patient's clinical presentation, which classically includes an acute onset of bilateral cranial neuropathies and symmetric descending weakness. [43] [44] Other key features of botulism include an absence of fever, symmetric neurologic deficits, normal or slow heart rate and normal blood pressure, and no sensory deficits except for blurred vision. [45] [46] A careful history and physical examination is paramount in order to diagnose the type of botulism, as well as to rule out other conditions with similar findings, such as Guillain-Barre syndrome, stroke, and myasthenia gravis. Depending on the type of botulism considered, different tests for diagnosis may be indicated.

Foodborne botulism: serum analysis for toxins by bioassay in mice should be done, as the demonstration of the toxins is diagnostic. [47]

Wound botulism: isolation of C. botulinum from the wound site should be attempted, as growth of the bacteria is diagnostic. [48]

Adult enteric and infant botulism: isolation and growth of C. botulinum from stool samples is diagnostic. [49] Infant botulism is a diagnosis which is often missed in the emergency room.

Other tests that may be helpful in ruling out other conditions are:

    (EMG) or antibody studies may help with the exclusion of myasthenia gravis and Lambert-Eaton myasthenic syndrome (LEMS). [50]
  • Collection of cerebrospinal fluid (CSF) protein and blood assist with the exclusion of Guillan-Barre syndrome and stroke. [51]
  • Detailed physical examination of the patient for any rash or tick presence helps with the exclusion of any tick transmitted tick paralysis. [52]

In the case of a diagnosis or suspicion of botulism, patients should be hospitalized immediately, even if the diagnosis and/or tests are pending. If botulism is suspected, patients should be treated immediately with antitoxin therapy in order to reduce mortality. Immediate intubation is also highly recommended, as respiratory failure is the primary cause of death from botulism. [53] [54] [55]

In Canada, there are currently only 3 antitoxin therapies available, which are accessible through Health Canada Special Access Program (SAP). [56] The 3 types of antitoxin therapies are: 1) GlaxoSmithKline trivalent Types ABE, 2) NP-018 (heptavalent) Types A to G, and 3) BabyBIG®, Botulism Immune Globulin Intravenous (Human) (BIG-IV) for pediatric patients under the age of one year. [57]

Outcomes vary between one and three months, but with prompt interventions, mortality from botulism ranges from less than 5 percent to 8 percent. [58]

There used to be a formalin-treated toxoid vaccine against botulism (serotypes A-E), but it was discontinued in 2011 due to declining potency in the toxoid stock. It was originally intended for people at risk of exposure. A few new vaccines are under development. [59]


Striming

The transmission of botulism occurs mainly through the consumption of contaminated food and untreated water. In addition, the causative bacteria can reach the body through injuries.

Note that botulism is not a contagious disease, so it is not transmitted between people.

Turlari

There are several types of botulism, namely:

  • Infant botulism: also called lactating botulism or intestinal botulism, this type of disease affects babies less than a year old. The bacteria reaches the gastrointestinal system, causing abdominal pain and constipation.
  • Food botulism : transmitted by contaminated food, especially canned (canned) that are expired, for example, meats, hearts of palm, pickles, honey, etc. This is because this rod-shaped bacteria can survive in environments with little oxygen (anaerobic bacillus).

Can of expired and rusty canning

  • Wound botulism : skin lesions can be favorable for the contamination of the bacteria that causes botulism. Through the released toxins, this type can cause serious skin infections. Injecting drug users are highly prone to contamination.

Canine Botulism

Canine botulism can manifest in domestic animals such as dogs. These animals contract the disease through the consumption of canned food, garbage, contaminated water and carcasses of dead animals.

The symptoms are very similar to those of humans, for example, facial paralysis, weakness and difficulty in swallowing. In most cases, dogs die.

Bovine Botulism

Botulism in ruminants, also called “fallen cow disease”, affects the animal’s central nervous system causing paralysis.

This usually occurs when these animals ingest the spores of the disease-causing bacteria in pastures.

Bovine botulism can also occur with ingestion of contaminated water or due to the conditions of the environment in which they live. In Brazil, it has been a major cause of cattle deaths.


Definition of Botulism

Botulism refers to a clinical condition during which the neyrotoksin ning Clostridium botulinum paralyzes the involuntary muscles by inhibiting the motor nerve endings from synthesizing acetylcholine. Clostridium botulinum commonly releases neurotoxin (Botulinum neurotoxin), which accumulates in the ingichka ichak. A botulinum neurotoxin mainly affects the nervous system and paralyzes the involuntary muscles tananing. Botulism can occur in both humans and animals.

Causes of Botulism

Botulism is caused by a neurotoxin produced by Clostridium botulinum. Neurotoxin is an exotoxin, which affects the nervous system. Botulism is a clinical condition, paralyzes the involuntary muscles and further spreads to the respiratory system and the heart. Asoslangan serological specificity, neurotoxins are categorized into the following seven serological types:

  1. Type A: It is a type of human botulism, which is very common in the western regions of the United States.
  2. Type B: It is also a type of human botulism that occurs frequently, and it is less toxic than type-A.
  3. Type-C: It is not a type of human botulism and causes botulism in cattle, fowls etc.
  4. Type-D: It mostly causes forage poisoning of cattle in South African countries.
  5. Type-E: This type of neurotoxin is obtained chiefly from fish and fish products. Type-E is very toxic to humans.
  6. Type-F: It was first isolated in Denmark and is a type of human botulism.
  7. Type-G: This has been recently isolated from the soil in Argentina, and it is not a type of human botulism.

Food Sources

sporalari Clostridium botulinum sporulate to produce a neurotoxin, which can be present in the following food sources:

  • Canned meat
  • Canned fish
  • Honey syrup
  • Sweet corn
  • Fermented beans
  • Other low acid foods

Spores of Clostridium botulinum generally grows in favourable conditions like:

  1. Low acid
  2. Anaerobic environment
  3. Low sugar
  4. Low salt
  5. And low temperature.

Types of Botulism

There are three forms of botulism caused by Clostridium botulinum:

Foodborne botulism: It spreads by eating food contaminated with the spores produced by the Clostridium botulinum. Foodborne botulism develops after the consumption of unprocessed, undercooked, canned and unrefrigerated food.

  • Symptoms include:
    • Xiralashgan ko'rish
    • Difficulty in swallowing
    • Mushaklar kuchsizligi
    • Quruq og'iz
    • Ko'ngil aynishi
    • Qusish
    • Abdominal cramps
    • Paralysis etc.

    Wound botulism: It spreads when the spores of the bacteria (Clostridium botulinum) enters the body through a kesmoq or any mechanical injuries. sporalari Clostridium botulinum sporulate to produce neurotoxin within the wound. The risk factors include people who are addicted to drugs like heroin.

    • Symptoms include:
      • Slurred speaking
      • Double vision
      • Drooping eyelids
      • Paralysis etc.

      Infant botulism: It spreads by the yutish ning Clostridium botulinum spores that grow in the infant’s intestinal tract of age limit between 2-8 months. Infant botulism develops after the consumption of honey syrup.

      • Symptoms include:
        • Qabziyat
        • Floppy movements
        • Irritation
        • Drooping eyelids
        • Paralysis etc.

        In addition to this, there are some other types also that occur very rarely. Adult botulism is rarely seen, in which the spores of the Clostridium botulinum colonize in the digestive tract of adults. Iatrogenic botulism is very lethal, which occurs by an overdose of botulinum neurotoxin or botox.

        Types of Neurotoxin Effects

        Botulinum neurotoxin can produce the following type of effects:

        1. Local effect: The local effects of Clostridium botulinum includes the following symptoms:
          • Xiralashgan ko'rish
          • Mushaklar kuchsizligi
          • Quruq og'iz
          • Reduced gag reflex etc.
        2. Immunological effect: It occurs by the administration of equine antitoxin.
        3. Metabolic effect: It is characterized by a symptom (respiratory acidosis).

        Symptoms of Botulism disease

        A neurotoxin produced by Clostridium botulinum can affect the cardiovascular, respiratory and central nervous system etc.

        1. Effect on the cardiovascular system: Botulinum neurotoxin blocks the automatic nervous system and leads to cause tachycardia and hypertension.
        2. On respiratory system: A neurotoxin paralyzes the respiratory muscle and results in ventilatory failure, and ultimately leads to death.
        3. Effect on the nervous system:
          • Markaziy asab tizimi: Botulinum neurotoxin paralyzes the cranial nerves and causes symptoms like:
            • Xiralashgan ko'rish
            • Diplopia
            • Dysphonia
            • Dysarthria
            • Dysphagia etc.
          • Peripheral nervous system: After paralyzing cranial nerves, botulinum neurotoxin causes symmetrical descending paralysis, affecting the respiratory muscles.
          • Automatic nervous system: Botulinum neurotoxin blocks the autonomic cholinergic junctions and causes the following symptoms:
            • Xiralashgan ko'rish
            • Orthostatic hypotension
            • Qabziyat
            • Urinary retention etc.
        4. Skeletal and smooth muscles: Botulinum neurotoxin affects the skeletal and smooth muscles by causing gallbladder dysfunction and necrotic fasciitis.
        5. Effect on Gastrointestinal system: A neurotoxin shows the gastrointestinal symptoms after 18-36 hours of incubation, and the symptoms include:
          • Ko'ngil aynishi
          • Qusish
          • Abdominal cramps
          • Diarrhoea
          • It sometimes leads to cause constipation, gastric dilatation and paralytic ileus.
        6. Neurotoxin does not directly affect the hepatic system (liver) and the urinary bladder.

        Pathogenesis

        A neurotoxin produced by the Clostridium botulinum causes botulism by following a given pathogenic cycle:

        1. First, neurotoxin enters the bloodstream through the ingestion of the bacterial spores or from the mucosal surface.
        2. Botulinum neurotoxin blocks the nerve terminal ends.
        3. Then, it binds to the neuronal membrane.
        4. After that, a neurotoxin enters the cytoplasm of the axon terminal.
        5. Then, botulinum neurotoxin blocks the excitatory synaptic transmission and results in interference with the synthesis of neurotransmitter “Asetilkolin”.
        6. Finally, it causes flaccid paralysis, as the nervous system cannot function without the action of acetylcholine. Acetylcholine plays an essential role in producing nerve impulse and the process of muscle contraction.

        Prognoz

        There are many cases of botulism, and if it remains untreated, then the mortality rate reaches about 50-60%. Treated patients may also concur with botulism, with a mortality rate of about 3-5%. The diagnosis or treatment of botulism should be made early otherwise, it can cause major outbreaks.

        Oldini olish

        There are a few first aid measures that can control the transmission of the disease to some extent.

        Foodborne botulism: To prevent its transmission

        • Avoid eating canned food
        • Properly wash and boil the vegetables before eating.
        • Trash the canned food that is bulging or leaking.
        • Avoid eating foods that are added with preservatives.
        • Avoid eating undercooked food.

        Wound botulism: To prevent its transmission

        • Properly sanitize the wounded area.
        • Maintain proper body hygiene.
        • Do not let the wound open to the air, as the spores of Clostridium botulinum can penetrate inside the cells through any cuts or injuries.

        Infant botulism: To prevent infant botulism, keep the body hygienic and don’t give corn or honey syrup to the infants.

        Davolash

        The early symptoms of botulism can be treated by the oral administration of polyvalent antitoxin. Enemas are found effective in the removal of the unabsorbed toxin.

        Tashxis

        Diagnosis of botulism involves the following tests:

        Mouse inoculation test: It is the most reliable and popular method to detect the presence of C.botulinum. Mouse inoculation test involves two series ning testlar. In one experiment, a patient’s stool is injected into the peritoneal cavity of mice. And, in the second test, an equal amount of the patient’s stool plus multivalent antitoxin is injected into the other mice.

        If the mice live, by the injection of antitoxin and stool sample and die by the infusion of an untreated serum sample, then it gives a positive result for botulism. Mouse inoculation test detects the presence of particularly A, B and E serotypes of C. botulinum.

        Physical tests: It includes tests like brain scan, spinal fluid examination, nerve conduction test (electromyography).


        Mode of VAMP substrate recognition and inhibition of Clostridium botulinum neurotoxin F

        Clostridium botulinum neurotoxins (BoNTs) cleave neuronal proteins responsible for neurotransmitter release, causing the neuroparalytic disease botulism. BoNT serotypes B, D, F and G cleave and inactivate vesicle-associated membrane protein (VAMP), each at a unique peptide bond. The specificity of BoNTs depends on the mode of substrate recognition. We have investigated the mechanism of substrate recognition of BoNT F by determining the crystal structures of its complex with two substrate-based inhibitors, VAMP 22-58/Gln58 D -cysteine and 27-58/Gln58 D -cysteine. The inhibitors bind to BoNT F in the canonical direction (as seen for BoNTs A and E substrates) but are positioned specifically via three major exosites away from the active site. The cysteine sulfur of the inhibitors interacts with the zinc and exists as sulfinic acid in the inhibitor VAMP 27-58/Gln58 D -cysteine. Arg133 and Arg171, which form part of two separate exosites, are crucial for substrate binding and catalysis.


        Future directions

        Although some progress has been made in recent years, identification and characterization of the protein receptors for the BoNTs and determination of the mechanism of specificity of CNT binding domains for their receptors is an outstanding problem. Further, understanding the mechanism of LC translocation and activation within the motorneuron, including the effects of pH on the tertiary structures of BoNTs, will be crucial for rational design of engineered BoNT therapeutics. Further structural studies on the endopeptidase domains of BoNTs, including the structural basis behind BoNT substrate specificity, might lead to the development of serotype-specific inhibitors.

        It has been proposed that the extreme neurospecificity of BoNT heavy chains could be applied to deliver engineered molecule in to nerve cells. This can be achieved by the replacement of light chain with desired therapeutic agent that could be reached in the nerve endings without iatrogenic complications which might otherwise occur 182 . Use of fragments of BoNT for the therapeutics of the future is also exciting. For example, harnessing the properties of the BoNT LC endopeptidase fragments for the creation of a range of �signer’ therapeutics is a real possibility following the successful retargeting of the LC/A domain to cells of neuronal and non-neuronal origin 183 . Additionally, the ability of BoNTs to transport large polypeptides across the membranes could be harnessed for the delivery of biopharmaceuticals to cytosolic targets 184 . Derivatives of BoNT/A and BoNT/B can target compounds specifically to human neuroblastoma cells. The therapeutic potential of clostridial toxins is not limited to the neurotoxin for the inhibition of neurotransmitter release, but also has potential as an anticancer drug 62 . The technology termed 𠆌lostridia directed enzyme pro-drug therapy’ (CDEPT) in which intravenously injected clostridial spores are used to target hypoxic regions of solid tumours. Spores get localized to solid tumours exclusively for germination, as they cannot grow in healthy tissues. Genetic modification of the clostridial host to express anti cancer compounds or pro-drug converting enzymes (as in CEDPT), has the potential to lead the localized destruction of solid tumour tissue.

        Botulinum neurotoxins are of great interest to the medical and scientific communities. Despite causing disease, they have become valuable research tools and have wide-ranging applications as pharmaceuticals. As the structure and mechanism of action of the toxins are further dissected, the development of vaccines, serotype-specific inhibitors and novel therapeutics will undoubtedly follow.