Inqaku
Imethylene Blue Nokuphazamiseka Kwe-Bipolar: Ukuhlola Uphando Lwezonyango
Isishwankathelo esifutshane
Imethylene blue iphononongwe ekuphazamisekeni kwe-bipolar ixesha elide kunokuba abantu abaninzi becinga, ukususela kwii-1970s xa abaphandi babekhangela ezinye iindlela nonyango olongezelelweyo kwilithium. Ubungqina obukhoyo bubuncinci: uthotho olunye lweemeko olungafihlwanga, izilingo ezimbini zakudala ezilawulwayo, nophononongo olunye lwangoku apho unyango lwatshintshaniswa, lwabelwa ngokungakhethiyo. Uphawu olufanayo kuzo zonke kukuphucuka kweempawu zodandatheko neempawu ezishiyekileyo xa imethylene blue yongezwa kunyango olwalusele lusetyenziswa. Akukho phononongo lwabonisa isiphumo sokunciphisa imaniya, kwaye akukho phononongo lwavelisa uphawu olucacileyo lokutshintshela kwimaniya, nangona amaqela abathathi-nxaxheba ayemancinci kakhulu ukuba angawuphendula lo mbuzo. Nabani na ovavanya le khompawundi kufuneka azifunde ezi njengezifundo zonyango olongezelelweyo, hayi njengobungqina bonyango olusetyenziswa lodwa, aze athathele ingqalelo izilumkiso zokusebenzisana kwamayeza ngaphambi kokufikelela kwizigqibo ezisebenzisekayo.
Kutheni ukuphazamiseka kwe-bipolar kwatsala ingqalelo kwangethuba
Isizathu asizange sibe kukuba imethylene blue yayifana nesizinzisi sesimo sengqondo esiqhelekileyo. Ngokwakheka kwayo ifana neephenothiazine, kwaye abaphandi bokuqala baqikelela ukuba inokuguqula ivanadate ekwiplasma ibe kuhlobo olungasebenzi kakhulu, ngaloo ndlela itshintshe ukusebenza kwesodium-potassium ATPase, eyayinxulunyaniswa nokujikeleza kwesimo sengqondo. Ukuvavanya le ngcamango, uNaylor noogxa bakhe banyanga izigulana ezibini ezazinezimo zengqondo ezazitshintshatshintsha ngokuqhubekayo, baza babona amaxesha amade esimo sengqondo esizinzileyo; oku kwakhuthaza wonke umsebenzi owalandelayo. Ingxelo kaHowland yembali yemethylene blue kunyango lwengqondo ibeka lo msebenzi kumxholo wawo, ilandelela le khompawundi ukusuka ekubeni yinto eyandulela iiphenothiazine ukuya ekubeni lichiza lovavanyo elichaphazela ingqondo.
Umsebenzi wamva ophathelele kwiindlela zokusebenza wayitshintsha indlela yokucinga ngesizathu sophando, wagxila ekusebenzeni kwemitochondria nakwibhalansi ye-redox. Ukungasebenzi kakuhle kwemitochondria kuye kwanxulunyaniswa nokuphazamiseka kwe-bipolar ngezifundo zeentsapho, iziphumo zovavanyo lokubonakaliswa kwemizila yemfuza emva kokufa, neemodeli zezilwanyana ezifana nempuku enotshintsho kwimfuza ye-POLG1, eneempawu ezifana ne-bipolar eziphendula ngokuyinxenye kwilithium. Uphononongo lukaAlda lwango-2019 lwemethylene blue ekuphazamisekeni kwemithambo-luvo nengqondo lubeka ingcamango yokuba ukukwazi kwale khompawundi ukuthutha ii-electron zidlule kwiindawo ezivaliweyo kwikhonkco lokuthuthwa kwee-electron, kunciphise ukuvuza kweentlobo zeoksijini ezisebenza kakhulu, kuyenza ibe luncedo ekuhloleni iingcamango njengento elungelelanisa ukusebenza kwemitochondria. Olunye uphononongo lwemethylene blue njengomgqatswa wechiza lokunyanga udandatheko longeza ukuthintelwa kwe-MAO-A, ukuvalwa kwe-nitric oxide synthase ne-guanylate cyclase, neziphumo zokunciphisa ukudumba emfanekisweni weendlela zokusebenza. Kodwa ezi ndlela zokusebenza ziseziingcamango. Umbuzo wezonyango ngowokuba izilingo zalinganisa ntoni, kwaye phantsi kwaziphi iimeko.
Izilingo, ngasinye ngokulandelelana
Uthotho lweemeko lukaNarsapur noNaylor: izigulana ezingaphenduliyo kunyango, unyango olungafihlwanga
Ingxelo yokuqala yayiluthotho olungelolawulwayo lwezigulana ezingama-24 ezazigula ixesha elide okanye zigula kakhulu, ezanikwa imethylene blue eyongezelelweyo nge-200 okanye i-300 mg yonke imihla, kangangeentsuku ukuya ngaphezu konyaka. Ezilishumi elinesithoba zazinokugula kwe-bipolar (imaniya nodandatheko), kwaye ezili-14 kwezo zili-19 zagwetywa njengeziphucuke ngokuqinisekileyo, umlinganiselo wokuphendula ongama-74 ekhulwini. Izigulana ezintathu ekwakungaqinisekanga ngoxilongo lwazo lwe-bipolar azizange ziphendule.
Oku makuthathwe njengokuveliswa kwengcamango enokuvavanywa, hayi njengedatha yokusebenza konyango. Kwakungekho kwabiwa ngokungakhethiyo, kwakungekho kufihlwa kolwazi lonyango, kwakungekho sikali silungelelanisiweyo, kwaye amayeza awayesele esetyenziswa awazange achazwe ngokupheleleyo. Inani lama-74 ekhulwini elivela kuthotho olungafihlwanga kwizigulana ezingaphenduliyo kunyango libonisa isigwebo somntu oqwalaselayo nokukhethwa kwezigulana njengoko libonisa ifamakholoji.
UNaylor noogxa bakhe ngo-1986: uthintelo lweminyaka emibini olutshintshanisa unyango kunye nelithium
Esi yayisisifundo esasinjongo inkulu kunazo zonke kwizifundo zokuqala: isilingo seminyaka emibini esatshintshanisa unyango, esasinokwabiwa ngokungakhethiyo nokufihlwa kolwazi kumacala omabini, kwizigulana ezingama-31 ezazinokugula kwe-bipolar. Umthathi-nxaxheba ngamnye kwakufuneka afumane i-300 mg yonke imihla unyaka omnye, aze afumane i-15 mg yonke imihla komnye unyaka, ngokulandelelana okwabelwe ngokungakhethiyo. Idosi ye-15 mg yayisetyenziswa njengento yokuthelekisa, ikhethwe ikakhulu kuba ukutshintsha kombala womchamo kwakusenza kungabi nakwenzeka ukufihla iplacebo engasebenziyo ngokwenene. Okubalulekileyo kukuba wonke umthathi-nxaxheba waqhubeka nelithium ngalo lonke ixesha, ngoko olu yayilunyango olongezelelweyo lokuthintela ukusukela ekuqaleni.
Abali-17 kwabangama-31 bayigqiba yomibini iminyaka. Kwabo bagqibayo, iimpawu zodandatheko zazingaphantsi ngokubalulekileyo ngokwezibalo kunyaka we-300 mg kunakunyaka we-15 mg, ngoxa ubuzaza beempawu zemaniya babungahlukanga phakathi kweedosi. Kwaxelwa ukuba amazinga okulaliswa esibhedlele ayephantsi ngexesha lesilingo kunangaphambi kwaso, nangona uphononongo lukaAlda lwamva luphawula ukuba oku kwakusebenza nakumaxesha e-15 mg, nto leyo eyenza ukutolika kube nzima. Abaphandi ngokwabo babalaselisa ubuthathaka: iqela elincinci labathathi-nxaxheba, ukungagqibi kwabathathi-nxaxheba abangama-45 ekhulwini, izikali ezilula zokulinganisa, ukufihlwa kolwazi okuthandabuzekayo, nokungaqiniseki ukuba i-15 mg yayingasebenzi na ngokwefamakholoji. Le nkxalabo yokugqibela yabonakala ichanile, njengoko kuchazwe ngezantsi.
Uphononongo lukaNaylor lodandatheko ngedosi ephantsi: kutheni “iplacebo” inokuba yayisebenza
Uthelekiso olulandelayo lweeveki ezintathu, olunokufihlwa kolwazi kumacala omabini, lwavavanya i-15 mg yonke imihla xa ithelekiswa neplacebo engasebenziyo kwizigulana ezingama-35 ezazinodandatheko olunzima, lwaza lwafumanisa ukuba imethylene blue yayigqwesa ngokubalulekileyo ngokwezibalo. Eli yayiliqela elalilawulwa ludandatheko lwe-unipolar kunokuba ibe sisilingo se-bipolar, ngoko lifanele libe kubungqina bodandatheko ngokubanzi endaweni yecandelo le-bipolar. Ukubaluleka kwalo kubafundi abanomdla kwi-bipolar kukwindlela yophando: idosi ye-15 mg eyayisetyenziswa njengento yokuthelekisa kuzo zombini izilingo ezazitshintshanisa unyango yayisele igqwese iplacebo engasebenziyo. Ngoko nawuphi na umahluko wonyango olinganiswa ngokuthelekisa ne-15 mg usenokuwubonisa ungaphantsi umahluko opheleleyo xa kuthelekiswa nokungafumani nto, kwaye oku kukwathetha ukuba akukho nasinye kwezi zilingo zakudala esasineqela leplacebo lokwenene.
UAlda noogxa bakhe ngo-2017: isilingo sangoku sonyango olongezelelweyo olutshintshaniswayo
Olona phononongo lungqongqo ukuza kuthi ga ngoku lwabela ngokungakhethiyo abantu abadala abangama-37 abanokuphazamiseka kwe-bipolar I okanye II neempawu ezishiyekileyo kwimethylene blue ye-195 mg yonke imihla xa ithelekiswa ne-15 mg yonke imihla, nganye kangangeeveki ezili-13, unyango lutshintshaniswa. Olu lwaluchazwe ngokucacileyo njengonyango olongezelelweyo: wonke umthathi-nxaxheba wayesele ezinzile ekusebenziseni ilamotrigine kangangeenyanga ezintathu ubuncinane kwaye waqhubeka nayo, kuvunyelwa nelithium, idivalproex, amayeza okunyanga ukuphazamiseka kokubona ubunyani, namayeza okunyanga udandatheko kwiidosi ezizinzileyo. Isilingo sibhalwe ku-PubMed 27284082. Iimpawu ekuqaleni zazithambile ukuya kweziphakathi, nomndilili wamanqaku odandatheko esikalini sikaHamilton omalunga ne-7.6 namanqaku esikali sikaMontgomery-Asberg amalunga ne-12.7.
Iziphumo zazixhasa i-195 mg kwimilinganiselo yodandatheko nexhala. Kwabo bagqibayo, ubungakanani beziphumo babumalunga ne-0.71 kwisikali sikaHamilton sodandatheko, i-0.80 kwisikali sikaMontgomery-Asberg, ne-0.79 kwisikali sikaHamilton sexhala, ngasinye sibalulekile ngokwezibalo. Uhlalutyo olwasebenzisa umlinganiselo wokugqibela okhoyo endaweni yemilinganiselo elandelayo engekhoyo kuzo zonke izigulana ezingama-37 lwavelisa iziphumo ezifanayo ezibalulekileyo ngokwezibalo. Amanqaku emaniya ahlala ephantsi kwaye ezinzile, kungekho siphumo sonyango, kwaye uthotho lweemvavanyo zokuqonda aluzange lubonise nzuzo ibalulekileyo kwimilinganiselo yenkumbulo yamazwi, izakhono zokucwangcisa nokulawula imisebenzi, okanye ingqalelo. Abathathi-nxaxheba abalishumi barhoxa ngezizathu eziquka ukuqatsela kweempawu ze-bipolar, ixhala, ukuqokelelana kolwelo emzimbeni, nokurhoxiswa kwemvume. Iziphumo ezingathandekiyo ubukhulu becala yayikukutsha okwethutyana xa kuchanywa, ukuphazamiseka kwesisu namathumbu, nentloko ebuhlungu.
Itheyibhile yezilingo zonyango: oko kwavavanywa ngokwenene
| Uphononongo | Uyilo no-n | Idosi yemethylene blue | Unyango olusetyenziswa kunye nayo | Imilinganiselo yeziphumo | Isiphumo esiphambili | Imida |
|---|---|---|---|---|---|---|
| UNarsapur noNaylor, uthotho olungafihlwanga | Uthotho lweemeko olungelolawulwayo, 24 xa zizonke (19 zine-bipolar) | 200 ukuya kwi-300 mg yonke imihla, 3 iintsuku ukuya kwi-19 iinyanga | Izigulana ezingaphenduliyo kunyango; unyango olwalusele lusetyenziswa aluchazwanga ngokupheleleyo | Isigwebo sogqirha ngokuphucuka | 14 kwezigulana ezili-19 ze-bipolar zagwetywa njengeziphucukileyo | Akukho qela lokuthelekisa, akukho kufihlwa kolwazi, isiphumo esisekelwe kwisigwebo somntu, ukusetyenziswa konyango okwahlukeneyo |
| UNaylor noogxa bakhe ngo-1986 | Ukutshintshaniswa konyango kweminyaka emi-2 nokufihlwa kolwazi kumacala omabini, 31 baqalisa, 17 bagqiba | 300 mg xa ithelekiswa ne-15 mg, unyaka omnye nganye | Ilithium yaqhubeka kubo bonke abathathi-nxaxheba | Amanqaku eempawu zodandatheko nemaniya, ukulaliswa esibhedlele | Udandatheko olungaphantsi ngobuzaza kwi-300 mg; akukho mahluko kwimaniya | Ukungagqibi kwabathathi-nxaxheba abangama-45 ekhulwini, izikali ezilula, ukufihlwa kolwazi okuphazamisekileyo, i-15 mg isenokuba yayisebenza |
| Uphononongo lukaNaylor lwedosi ephantsi | I-RCT yeeveki ezi-3 enokufihlwa kolwazi kumacala omabini xa ithelekiswa neplacebo engasebenziyo, n=35, udandatheko olunzima | 15 mg yonke imihla | Amayeza awayesele esetyenziswa akachazwanga ngokwaneleyo | Ubuzaza bodandatheko | 15 mg yayigqwesa iplacebo | Asiloqela le-bipolar; akukho bungakanani beziphumo obuchazwe ngamanani kwisishwankathelo esifakwe kwisalathiso |
| UAlda noogxa bakhe ngo-2017 | Ukutshintshaniswa konyango kweeveki ezili-13 nokufihlwa kolwazi kumacala omabini, 37 babelwa ngokungakhethiyo, 27 bagqiba | 195 mg xa ithelekiswa ne-15 mg | Ilamotrigine kubo bonke; ilithium, idivalproex, amayeza okunyanga ukuphazamiseka kokubona ubunyani, namayeza odandatheko avunyelwa ukuba iidosi zizinzile | MADRS, HAM-D, HAM-A, YMRS, CGI-BP, ukuqonda | Ukuphucuka okubalulekileyo ngokwezibalo kodandatheko nexhala kwi-195 mg; akukho siphumo kwimaniya okanye ekuqondeni | Iqela elincinci labathathi-nxaxheba, iimpawu ezishiyekileyo (hayi ezibukhali), ukusetyenziswa kwamayeza amaninzi, iziphumo eziqhubeka zisuka kunyango lwangaphambili, i-15 mg isenokuba yayisebenza |
| Isilingo sikaNaylor semaniya | Uphononongo lwemaniya olunokufihlwa kolwazi kumacala omabini, n=18 | Iinkcukacha azinakuqinisekiswa kwingxelo efakwe kwisalathiso | Alunakufunyanwa kwingxelo efikelelekayo | Iimpawu zemaniya | Akukho nzuzo ibonisiweyo yokunciphisa imaniya | Ingxelo enamaphepha amabini, akukho sishwankathelo sifakwe kwisalathiso, idosi nesikali azinakuqinisekiswa |
Ukufunda ipateni ngokunyanisekileyo
Kukho izinto ezintathu eziqwalaselweyo ezisaseleyo nangona kukho le mida. Okokuqala, icala lesiphumo liyafana: iimpawu zodandatheko neempawu ezishiyekileyo zaphucuka ngedosi ephezulu kuzo zombini izifundo ezilawulwayo ze-bipolar, ngobungakanani beziphumo obuphakathi kwisilingo sangoku. Okwesibini, akukho nto kolu phando ixhasa ibango lokunciphisa imaniya. Isilingo esasinikelwe kwimaniya asizange sibonise nzuzo, kwaye izifundo ezazitshintshanisa unyango azifumananga mahluko kwimaniya; oko kukungabikho kokusebenza kokunyanga imaniya, hayi ubungqina bokuzinziswa kwesimo sengqondo kuzo zombini iziphelo. Okwesithathu, akukho phawu lwemaniya eyavela ngexesha lonyango, kodwa loo ngxelo ayinabunzima bungako. Amanqaku emaniya ekuqaleni ayesondele ku-zero, kwaye amaqela afumana unyango ayenabantu abangamashumi kuphela, ngoko ezi zifundo zazingenakufumanisa umngcipheko wokutshintshela kwimaniya onobukhulu obubalulekileyo kwezonyango. Indlela echanileyo yokuthetha kukuba akukho phawu lokutshintshela kwimaniya labonwayo, hayi ukuba umngcipheko wokutshintshela kuyo wakhutshelwa ngaphandle.
Iingxaki ezimbini zeendlela zophando zifuna ukubalaseliswa kuba zichaphazela bonke ubungqina obukhoyo. Ukufihlwa kolwazi kwakuphazamisekile ngokwendlela ezazakhiwe ngayo zonke izifundo zokutshintshanisa unyango, kuba imethylene blue itshintsha umbala womchamo kwaye idosi ephantsi yokuthelekisa yayikhethwe kanye ukuze ilinganise eso siphumo, nangona kwakucingelwa ukuba ayisebenzi. Kwaye loo ngcinga ayizange ibambe: idosi ephantsi yagqwesa iplacebo engasebenziyo kudandatheko, nto leyo ethetha ukuba uthelekiso oluphambili lwaluphakathi kweedosi ezimbini zonyango olunokusebenza zombini, endaweni yeemvavanyo zechiza xa lithelekiswa neplacebo. Ubungakanani beziphumo obulinganiswe ngale ndlela kunzima ukubutolika kwaye abunakudityaniswa nezilingo eziqhelekileyo zamayeza odandatheko ezilawulwa ngeplacebo.
Kubalulekile apha ukunamathela kumda wesihloko. Ezi zizilingo ze-bipolar ezinemilinganiselo yeziphumo ze-bipolar, kwaye azifanele zixutywe nobungqina obuvela kwamanye amaqela abantu. Abafundi abanomdla kuphando olusondeleyo kwesi sihloko bafanele bajonge iziphumo eziphathelele kwixhala, uphando lokuqonda, kunye neenkcukacha zokhuseleko nokusebenzisana kwamayeza ngokwahlukeneyo, kuba ngasinye siquka uyilo lophando olwahlukileyo nezinto ezahlukeneyo ekufuneka ziqwalaselwe ngomngcipheko.
Umxholo wokhuseleko ekusetyenzisweni kwamayeza amaninzi kwi-bipolar
Izilumkiso ezimbini zichaphazela ngokuthe ngqo izigulana ze-bipolar, ezidla ngokumiselwa amayeza achaphazela iserotonin. Imethylene blue kunye nemveliso yayo yokuguqulwa emzimbeni, i-Azure B, zizithinteli ezinamandla ze-MAO-A ezisebenza ngendlela enokubuyiselwa umva, kwaye ukusetyenziswa kwayo kunye nee-SSRI, ii-SNRI, namanye amayeza achaphazela iserotonin kunokubangela isifo se-serotonin syndrome. Phantse zonke iimeko zetyhefu ezipapashiweyo zaziquka imethylene blue efakwe emthanjeni, kwaye isilingo sangoku se-bipolar savumela amayeza odandatheko kubathathi-nxaxheba abangama-20 kwabangama-37 ngaphandle kwesiganeko esinxulumene neserotonin, kodwa loo mava ambalwa akasigqithi isilumkiso sokusebenzisana kwamayeza, kwaye ulwazi lwangoku lwemveliso efakwa emthanjeni lunesilumkiso esikwibhokisi ngalo mba. Ngokwahlukeneyo, ukuswela i-glucose-6-phosphate dehydrogenase yimeko ethintela ukusetyenziswa kwayo kuba imethylene blue inokubangela ukuqhekeka kweeseli ezibomvu zegazi, kwaye isilingo sangoku asizange sizibandakanye izigulana ezinjalo. Nabani na odibanisa la mayeza ufuna ukubekwa esweni ngugqirha; le yifamakholoji eneendlela zokubangela ingozi yokwenene, hayi ukusebenzisana kwezongezelelo ezingenabungozi.
Oku kuwushiya phi umbuzo
Uphando lwemethylene blue ekuphazamisekeni kwe-bipolar luncinci, ludala, kwaye lubonisa amathuba afuna ukuphandwa, kunye nophononongo olunye lwangoku lokuqala oluhloniphekileyo. Isishwankathelo esinyanisekileyo sesi: imethylene blue njengonyango olongezelelweyo malunga ne-195 ukuya kwi-300 mg yonke imihla yanciphisa ngokuphindaphindiweyo iimpawu zodandatheko neempawu ezishiyekileyo kumaqela amancinci, yabonisa uphawu lokuphucuka kwexhala kanye, ayizange ibonise nzuzo ekuqondeni, ayizange ibonise siphumo sokunciphisa imaniya, kwaye ayizange ibonise phawu lokutshintshela kwimaniya olunokufunyaniswa ngala manani abathathi-nxaxheba. Akukenziwa izilingo ezinkulu ezinolawulo lweplacebo lokwenene, amaqela anexesha elibukhali lodandatheko lwe-bipolar, ukubekwa esweni kokutshintshela kwimaniya okucwangciswe kwangaphambili, neenkqubo ezaneleyo zokufihla ulwazi lonyango. De zenziwe, imethylene blue ihlala ilunyango olongezelelweyo olusaphandwayo kule meko, inomdla owaneleyo ukuba iphandwe ngakumbi kodwa ubungqina buncinci kakhulu ukuba buxhase izigqibo.