Methylene blue ndi khunyu: mayesero oyambitsa khunyu ndi umboni wa anthu

Munthu wosamalira wodwala amene akufufuza za methylene blue ndi matenda a khunyu amapeza mawu awiri omwe amaoneka ngati akutsutsana. Ena amati methylene blue inachepetsa zochitika za khunyu mwa makoswe. Ena amati chochitika chofanana ndi khunyu chinanenedwa mwa wodwala amene anapatsidwa methylene blue. Zonsezi zingakhale zoona nthawi imodzi, chifukwa zimayankha mafunso osiyanasiyana m'mikhalidwe yosiyanasiyana.

Kusokonezekaku kumabwera chifukwa chotenga mawu akuti "methylene blue ndi khunyu" ngati mfundo imodzi. Koma ndi ziwiri. Yoyamba imafunsa ngati methylene blue, yoperekedwa m'mikhalidwe yoyendetsedwa mosamala, imasintha miyeso ya khunyu m'mayesero a nyama. Yachiwiri imafunsa ngati khunyu yakhala ikuchitika ngati chochitika chosafunika mwa anthu amene akulandira mankhwalawa pa zifukwa zina. Nkhaniyi imasiyanitsa mafunso awiriwa, imayang'ana zimene kafukufuku awiri wa khunyu amene amatchulidwa kwambiri anachita, ndipo imanena momveka bwino zimene sakusonyeza. Kuti mumvetse maziko ake, onani nkhani yofotokoza mwachidule kafukufuku wa methylene blue; ndipo kuti mudziwe njira yowerengera kafukufuku, onani kalozera wowerengera kafukufuku wa methylene blue.

Kafukufuku awiriwa, mwatsatanetsatane

Palibe mayesero mwa anthu amene ayesa methylene blue ngati chithandizo cha matenda a khunyu. Umboni wa mayesero umachokera ku kafukufuku wa nyama. Mapepala awiri amene amatchulidwa kwambiri onse anagwiritsa ntchito makoswe, onse anagwiritsa ntchito mlingo wa 1 mg pa kg woperekedwa m'kati mwa mimba, ndipo onse ananena za zizindikiro zochepetsa khunyu. Koma njira zawo zimayesa malingaliro osiyanasiyana a chithandizo, choncho zotsatira zawo zimatanthauza zinthu zosiyanasiyana.

Kafukufuku 1: chithandizo pambuyo poti khunyu kosaleka kayamba

Mu kafukufuku wa makoswe wa 2018 wokhudza khunyu kosaleka komwe kamapitirira kokha, Cui ndi anzake anayambitsa khunyu kokhalitsa mwa kulimbikitsa mbali ya basolateral ya amygdala ndi magetsi kwa mphindi 25, kenako anatsimikizira ndi EEG kuti khunyu kanali kupitirirabe. Izi n'zofunika chifukwa mayesero oyambitsa khunyu ndi magetsi amasiyanitsa khunyu kenikeniko ndi poizoni wa mankhwala oyambitsa khunyu. Methylene blue inaperekedwa mphindi 5 pambuyo poti khunyu kosaleka katsimikiziridwa kuti kayamba, zomwe zimayimira chithandizo osati kupewa. Kujambula kwa EEG kunapitirira kwa maola 12, ndipo minofu ya ubongo inayesedwa pa maola 24. Nkhani yonse ya mayesero a khunyu kosaleka imafotokoza mwatsatanetsatane kulimbikitsa ndi kujambula kumeneku.

M'maola 12 amenewa, makoswe omwe analandira mankhwala anali ndi avareji ya zochitika zosiyana za khunyu pafupifupi 29 pa EEG, poyerekeza ndi pafupifupi 39 mwa nyama zosalandira mankhwala, kuchepa kwa pafupifupi 26 peresenti. Nthawi yonse ya khunyu inatsikanso kuchoka pa pafupifupi mphindi 62 kufika pa pafupifupi mphindi 44, kuchepa kwa pafupifupi 29 peresenti. Nyama zomwe zinalandira mankhwala zinasonyezanso kuchepa kwa kupsinjika chifukwa cha okosideshoni (malondialdehyde yochepa komanso glutathione yosungika bwino), kuchepa kwa kutayika kwa maselo a mitsempha m'madera a hippocampus a CA1 ndi CA3, ndipo zizindikiro za apoptosis zinasintha m'njira yosonyeza kutetezedwa kwa maselo.

Malire ake ndi omveka. Pafupifupi nyama 12 pa gulu lililonse zinaunikidwa pa zochitika za khunyu, mlingo umodzi wokha unayesedwa kotero palibe tchati chosonyeza mmene zotsatira zimasinthira ndi mlingo, kutsata zotsatira kunatenga maola osati miyezi, ndipo panalibe kuyerekezera ndi mankhwala odziwika oletsa khunyu. Zotsatirazi zimathandiza mfundo yakuti pali zizindikiro zochepetsa khunyu mwachangu ndi kuteteza maselo a mitsempha m'njira imodzi yoyeserera khunyu kosaleka mwa makoswe. Sizikusonyeza kuti methylene blue imateteza ku matenda a khunyu okhalitsa, ndipo sizikunena chilichonse za mlingo kapena chitetezo mwa anthu omwe ali ndi matenda a khunyu.

Kafukufuku 2: kupereka mankhwala khunyu kulikonse koyambitsidwa kusanachitike

Mu kafukufuku wa makoswe wa 2026 wa kindling yoyambitsidwa ndi pentylenetetrazole, Jing ndi anzake anagwiritsa ntchito nthawi yopereka mankhwala yosiyana ndi ya kafukufuku woyamba. Makoswe anapatsidwa mobwerezabwereza mankhwala oyambitsa khunyu (pentylenetetrazole ya 35 mg pa kg, tsiku lina lililonse, maulendo 15), ndipo methylene blue inaperekedwa mphindi 30 asanapatsidwe mankhwala oyambitsa khunyu paulendo uliwonse. Iyi ndi njira yoyesera ya kupewa: imayesa ngati kupereka mankhwala mobwerezabwereza pofuna kupewa kumasokoneza kukula kwa chikhalidwe chogwidwa mosavuta ndi khunyu chifukwa cha kindling, osati ngati mankhwalawo amaletsa khunyu komwe kakuchitika kale kapena kuchiza matenda a khunyu omwe alipo kale.

Khunyu ka kindling kofika pamlingo wathunthu kanayamba mwa 30 peresenti ya makoswe opatsidwa mankhwala pasadakhale, poyerekeza ndi pafupifupi 85 peresenti ya makoswe osapatsidwa mankhwala. Uku kunali kusiyana kwakukulu pakati pa maguluwo, ndipo mtengo wa P womwe unanenedwa unali 0.0078. Kupereka mankhwala pasadakhale kunachedwetsanso kuyamba kwa khunyu ka tonic-clonic kokhudza thupi lonse ndipo kunafupikitsa nthawi yake kakachitika. EEG, kupulumuka kwa maselo a hippocampus, zizindikiro za kupsinjika chifukwa cha okosideshoni, ndi miyeso ya kukumbukira m'mayesero a njira yosochera ya m'madzi zonse zinasonyeza zotsatira zabwino kwambiri m'gulu lopatsidwa mankhwala.

Njirayi ilinso ndi malire ake. Mankhwalawo analipo nthawi iliyonse khunyu lisanayambitsidwe, choncho mayeserowa sangathe kusiyanitsa kuletsa khunyu ndi kusokoneza kukula kwa kindling. Apanso, mlingo umodzi wokha unagwiritsidwa ntchito, magulu ang'onoang'ono omwe anayesedwa minofu ndi khalidwe anali ochepa, kindling imayimira mbali ina koma osati zonse za mmene matenda a khunyu amagwirira ntchito mwa anthu, ndipo mapepala awiriwa ali ndi olemba ena omwewo (Cui ndi Luo akupezeka pa onse awiri), choncho si kubwereza kafukufuku kodziyimira pawokha kwathunthu. Zotsatirazi zimathandiza mfundo yakuti kukula kwa kindling kunachepa pamene makoswe ankapatsidwa mankhwala mobwerezabwereza pofuna kupewa. Sizitsimikizira kuti methylene blue ndi chithandizo kwa aliyense amene ali kale ndi matenda a khunyu.

Tebulo la mayesero ndi mikhalidwe: chida choyambirira

Tebulo ili m'munsimu ndi lofunika kwambiri pofotokozera zomwe zili patsambali. Mzere uliwonse umayamba ndi kufotokoza mkhalidwe wake, kenako umanena ntchito yomwe methylene blue inachita ndi zimene zomwe zinaonedwa zingasonyeze kapena sizingasonyeze. Mayesero opereka mankhwala ndi malipoti a zochitika zosafunika aikidwa m'mizere yosiyanasiyana mwadala.

Mkhalidwe	Ntchito ya methylene blue	Nthawi	Zotsatira zoyezedwa	Zimene ikusonyeza
Khunyu kosaleka koyambitsidwa ndi magetsi mwa makoswe, 2018	Chithandizo choyesera, 1 mg/kg m'kati mwa mimba	5 min pambuyo poti khunyu kosaleka katsimikiziridwa; EEG kwa 12 h	Chiwerengero cha zochitika za khunyu pa EEG ndi nthawi yonse ya khunyu; minofu ya hippocampus pa 24 h	Chizindikiro chochepetsa khunyu mwachangu m'njira imodzi yoyeserera; osati kupewa matenda a khunyu okhalitsa, osati umboni wa kugwira ntchito mwa anthu
Kindling yoyambitsidwa ndi pentylenetetrazole mobwerezabwereza mwa makoswe, 2026	Kupereka mankhwala pasadakhale m'mayesero, 1 mg/kg musanayambitse khunyu paulendo uliwonse	30 min musanapereke mankhwala oyambitsa khunyu paulendo uliwonse mwa maulendo 15	Kuchuluka kwa kindling yofika pamlingo wathunthu, nthawi mpaka khunyu kuyamba ndi nthawi yomwe limatenga, EEG, khalidwe lokhudzana ndi kukumbukira, zizindikiro za minofu	Kuchepa kwa kukula kwa kindling popereka mankhwala pofuna kupewa; osati chithandizo cha matenda a khunyu omwe alipo kale
Methemoglobinemia yopezeka pambuyo pobadwa, kugwiritsa ntchito mankhwala operekedwa ndi chilolezo cha dokotala kudzera mumtsempha	Chithandizo chovomerezeka cha matenda ena	Panthawi ya chithandizo, nthawi zambiri 1 mg/kg	Kuwunika chitetezo	Chochitika chimodzi choopsa chofanana ndi khunyu m'gulu la odwala 24 owunikidwa pa chitetezo malinga ndi zolemba zamakono za methylene blue yoperekedwa kudzera mumtsempha; lipoti la chochitika chotsatira kuperekedwa kwa mankhwala, osati mlingo wa kuchuluka kwa zochitika kapena umboni wa chimene chinachiyambitsa
Vuto la serotonin syndrome lokhudzana ndi mankhwala okhudza serotonin	Choyambitsa kudzera mu kuletsa monoamine oxidase	Pambuyo poperekedwa pamodzi ndi mankhwala a kupsinjika maganizo kapena mankhwala ofanana nawo	Vuto la kuchipatala, lomwe lingaphatikizepo khunyu	Kugwirizana kwa mankhwala kodziwika komwe kuli ndi chenjezo la m'bokosi m'malangizo operekera mankhwala; onani vuto la serotonin syndrome ndi kugwirizana ndi mankhwala a kupsinjika maganizo ndi mankhwala ena okhudza serotonin; kuwunika mwadongosolo kafukufuku kunapeza zochitika 50 zofalitsidwa, zonse zinakhudza kugwiritsa ntchito nthawi imodzi mankhwala a kupsinjika maganizo okhudza serotonin
Kusokonezeka kwa ntchito ya ubongo koyambitsidwa ndi ifosfamide	Chithandizo choperekedwa cha kusokonezeka kwa ubongo pa ntchito yosavomerezedwa mwalamulo ya mankhwalawa	Panthawi kapena pambuyo pa kuvulazidwa kwa mitsempha ndi ifosfamide	Kusokonezeka maganizo, khunyu, chikomokere, kuchira	Khunyu pano limayembekezeredwa kuchokera ku kusokonezeka kwa ubongo komweko, choncho silingonenedwa kuti layambitsidwa ndi methylene blue popanda kufufuza; umboni wa phindu umachokera makamaka ku malipoti a odwala payekha, ndipo odwala 28 mwa 38 omwe analandira chithandizo ananenedwa kuti anali bwino mu ndemanga imodzi ya chithandizo cha kusokonezeka kwa ubongo koyambitsidwa ndi ifosfamide

Chifukwa chake nthawi ndi zotsatira zoyezedwa zimasankha tanthauzo la kafukufuku

Mfundo ziwiri zimakhala ndi tanthauzo lalikulu pa kafukufuku wa khunyu: nthawi yomwe mankhwala anaperekedwa, ndi zimene zinayezedwa.

Choyamba, nthawi. Mankhwala operekedwa nthawi iliyonse khunyu lisanayambitsidwe, monga mu kafukufuku wa kindling, angaoneke kuti akugwira ntchito chifukwa chongochepetsa chochitika chilichonse choyambitsidwa kapena kuchedwetsa kukula kwa kindling. Mankhwala operekedwa khunyu litayamba kale, monga mu kafukufuku wa khunyu kosaleka, amakumana ndi mayesero ovuta kwambiri komanso oyenerera kwambiri pa chithandizo cha kuchipatala. Palibe mwa njira ziwirizi yomwe ikufanana ndi mkhalidwe wa munthu amene ali kale ndi matenda a khunyu ndipo amamwa mankhwala oletsa khunyu tsiku lililonse. N'chifukwa chake nthawi yopereka mankhwala mwa nyama siingasinthidwe kukhala malangizo a chithandizo.

Chachiwiri, zotsatira zoyezedwa. Chiwerengero cha zochitika za khunyu pa EEG m'maola 12, kuchuluka kwa kindling, ndi kusagwidwa ndi khunyu mwa anthu ndi zotsatira zosiyanasiyana. Zizindikiro za minofu monga glutathione kapena chiwerengero cha maselo zimafotokoza njira zomwe zingakhale zikugwira ntchito, ndipo khalidwe m'mayesero a njira yosochera ya m'madzi limasonyeza kugwirizana komwe kungakhalepo ndi mmene makoswe amagwirira ntchito. Koma palibe mwa zimenezi chomwe chili chotsatira choyezedwa cha matenda a khunyu pa chithandizo cha anthu. Kupeza zotsatira zabwino pa minofu pamodzi ndi zotsatira zochepa pa khunyu kumalimbitsa kufotokoza kwa mmene zinthu zikugwirira ntchito m'thupi; sikukweza zotsatira za khunyu kukhala umboni wa chithandizo kwa anthu.

Tanthauzo lake pa zisankho za chithandizo

Zizindikiro zochepetsa khunyu mwa nyama ndi chifukwa chochitira kafukufuku wina, osati chifukwa chosinthira chithandizo. Palibe amene ayenera kuyamba, kusiya, kapena kusintha mankhwala oletsa khunyu operekedwa ndi dokotala potengera kafukufuku wa makoswe, ndipo methylene blue si chithandizo chovomerezeka cha matenda a khunyu m'njira iliyonse yopangira mankhwalawo. Aliyense amene akuganiza zogwiritsa ntchito ayenera choyamba kukambirana ndi dokotala wake za mndandanda wonse wa mankhwala ake, chifukwa kugwirizana ndi mankhwala okhudza serotonin komwe kwatchulidwa pamwambapa ndi ngozi yokhudzana ndi khunyu yotsimikizika kwambiri m'malipoti a anthu, ndipo ingapewedwe.

Chidule chowona chingakwanire m'ndime imodzi. Kafukufuku awiri ang'onoang'ono wa makoswe, pa mlingo wofanana wa 1 mg pa kg, ananena za kuchepa kwa chiwerengero kapena kuopsa kwa zochitika za khunyu: m'modzi pamene mankhwalawo anaperekedwa pambuyo pa khunyu kosaleka koyambitsidwa ndi magetsi, ndipo wina pamene anaperekedwa asanayambitse khunyu mobwerezabwereza ndi mankhwala. Payokha, zolemba za chitetezo mwa anthu zili ndi zochitika zofanana ndi khunyu, makamaka m'mikhalidwe ya kugwirizana kwa mankhwala ndi ya odwala kwambiri, osati pa chithandizo cha matenda a khunyu. Palibe gulu lililonse la umboniwu lomwe limatsimikizira kuti linzake ndi lolakwika, ndipo palibe lomwe limatsimikizira kuti methylene blue ndi chithandizo cha matenda a khunyu. Mafunso ambiri okhudza zotsatirapo zosafunika ndi zinthu zofunika kusamala asonkhanitsidwa m'mafunso ofunsidwa kawirikawiri okhudza chitetezo cha methylene blue.