Chinyorwa
Kushandiswa kwezuva nezuva uye kwenguva refu kwe-methylene blue: chii chakadzidzwa?
Tsvakurudzo haisati yasimbisa chirongwa chakajairika chekushandisa methylene blue zuva nezuva kuvanhu vakuru vane utano. Kushandiswa kunodzokororwa muvanhu kwakadzidzwa, kusanganisira muyedzo mudiki wepfungwa wemwedzi mitanhatu. Miedzo yakareba iripowo yeformulation ine hukama asi yakasiyana pamakemikari. Hapana rimwe remapoka aya rinosimbisa kuti solution yekutengesa isina kutsanangurwa yakachengeteka kana kuti inobatsira kana ikashandiswa pasina mugumo wakatarwa.
Mubvunzo unobatsira wakanyatsojeka kupfuura kuti “Pane akamboidzidza kwenguva refu here?” Mubvunzo wacho ndewekuti: chinhu chipi, chakapihwa nenzira ipi, kuna ani, kwenguva yakareba sei, uye ndezvipi zvakabuda zvakayerwa?
Verenga nguva yekushandiswa nenguva yekutevera zvakasiyana
Nguva yekushandiswa inotsanangura nguva iyo kurapwa kwakapiwa. Nguva yekutevera inotsanangura nguva iyo vatsvakurudzi vakazotarisa vatori vechikamu mushure mezvo. Kutevera kwemwedzi mitatu mushure memazuva mashanu ekurapwa hakurevi kupiwa mushonga kwemwedzi mitatu. Saizvozvowo, kudzidza kunopera mbeva dzava nemwedzi 30 hakurevi kuti dzakarapwa kwemwedzi 30.
Mufananidzo wepamusoro unoratidza musiyano uyu nenzira yekutsanangura. Madotsi awo ndeekutsanangura chete, haasi data rakayerwa muchidzidzo. Chati iri pasi apa inopa nguva chaidzo kubva kuzvidzidzo zvakasarudzwa. “Hapana nguva yakasiyana yekutevera yakataurwa” zvinoreva kuti gwaro rakadomwa harisimbisi imwe nguva yekucherechedza isina kurapwa; hazvirevi kuti zvese zvaigona kuitika gare gare zvakaongororwa zvikawanikwa zvakajairika.
Chati yenguva dzezvidzidzo
| Chidzidzo nemuenzaniso | Formulation nenzira yekupa | Nguva yekushandiswa | Kucherechedzwa kana kutevera | Mubvunzo mukuru wakayerwa |
|---|---|---|---|---|
| Rodriguez nevamwe: brain imaging yevakuru vane utano | USP methylene blue, methylthioninium chloride; nemuromo | Kupihwa kamwe chete | Baseline neMRI yakadzokororwa kutanga 60 minutes mushure mezvo | Shanduko dzenguva pfupi mukuyerera kweropa muuropi nemanetwork, kwete kuchengeteka kwekushandiswa kwenguva refu |
| Ibarra-Estrada nevamwe: varwere 91 vane septic shock | Methylene blue musaline; intravenous infusion | Infusion nhatu dzemazuva akatevedzana, imwe neimwe ichitora six hours | Zvakabuda mukurapwa zvakaongororwa kusvika day 28 | Kushandiswa kwevasopressor, zvakabuda muchipatara, kufa nemigumisiro isingadiwi |
| Zoellner nevamwe: vatori vechikamu 42 vane PTSD | Methylene blue; nemuromo, pamwe chete nepsychotherapy | Kupihwa mushure mezvikamu five zvemazuva akatevedzana zveimaginal exposure | Ongororo kusvika pakutevera kwemwedzi mitatu | Zviratidzo nekushanda mushure mekupindira kupfupi kwakabatanidzwa |
| Gureev nevamwe: C57BL/6 mice | MB pamatanho two akataurwa ekushandiswa kwezuva nezuva; nzira yekupa haina kutsanangurwa zvakajeka mumethods | Four weeks | Fecal sampling vhiki rega rega; maze testing mumazuva five ekupedzisira; hapana nguva yakasiyana yekudzoreredza yakataurwa | Kuumbwa kwemicrobiome nekuita muma maze |
| Jena naChainy: female Wistar rats | Methylene blue mumvura yekunwa; nemuromo | 30 days | Kutora ropa, chiropa neitsvo pakupera kwechidzidzo | Zviyero zvakasarudzwa zveoxidative stress neserum; mhuka five paboka |
| Alda nevamwe: vatori vechikamu 37 vane bipolar disorder | Methylene blue capsules; nemuromo; higher versus lower active dose | 26-week crossover: nguva two dze12-week dzekurapwa pamwe nemavhiki etitration necrossover | Kushanya nguva nenguva panguva yekurapwa; cognition yakaongororwa pabaseline, weeks 13 and 26 | Zviratidzo zvemood zvakasara, cognition nekutolerability pamwe nekurapwa kwagara kuripo |
| Poudel nevamwe: skeletal aging mumice | MB mumvura yekunwa kune aged female C57BL/6J mice; MB muchikafu kune male and female UM-HET3 mice | Six or 12 months kune aged females; 15 months muUM-HET3 mice, kubva pazera seven kusvika 22 months | Zviyero zvemapfupa pamagumo akatarwa; hapana kutevera kwakasiyana kusina kurapwa | Chimiro chemapfupa chine chekuita nezera, kwete ongororo yakazara yekuchengeteka muvanhu |
| Gauthier nevamwe: varwere 891 vane Alzheimer’s disease | Leuco-methylthioninium bis(hydromethanesulfonate), LMTM; nemuromo | 15-month randomized treatment period | Ongororo dzekiriniki nedzekuchengeteka panguva yemuyedzo | Cognition, kushanda kwezuva nezuva nezviitiko zvisingadiwi; low-dose LMTM control |
| Auerbach nevamwe: F344/N rats and B6C3F1 mice | Methylene blue trihydrate mumethylcellulose; oral gavage | Two years, five days per week | Kuongororwa kwekurarama netissue pathology kusvika chidzidzo chapera | Chronic toxicity necarcinogenicity |
Mitsetse iyi haigoni kuchinjaniswa semazano emadosi. Oral gavage inoendesa chinhu chacho zvakananga mudumbu; mvura yekunwa nechikafu zvinobvumira maitiro akasiyana ekutora. Intravenous infusion inodarika intestinal absorption. Kureba kwenguva yekushandiswa hakugoni kugadzirisa misiyano iyoyo.
Zvatinodzidza kubva pakushandiswa kunodzokororwa muvanhu
Muyedzo webipolar unopa ruzivo rwakakosha zvikuru pamusoro pekushandiswa kunodzokororwa kwemethylene blue nemuromo kupfuura brain scan imwe chete. Zvisinei, vatori vechikamu 27 chete kubva pa37 vakapedza muyedzo. Vatori vechikamu vaiva nebipolar disorder, vakanga vatogamuchira lamotrigine, uye vaiongororwa panguva yekurapwa. Kuenzanisa kwakashandisa dose yakaderera yemethylene blue panzvimbo peinert placebo. Dhizaini iyi haigoni kusimbisa kuchengeteka kwekushandiswa kunoenderera muvanhu vane utano kana kubvisa zvine chokwadi njodzi dzisingawanzoitiki.
Muyedzo weAlzheimer unoda mumwe musiyano wakakosha. LMTM iformulation yakadzikiswa uye yakagadzikana yemethylthioninium ine counterions dzakasiyana, kwete ordinary methylene blue chloride solution. Nguva yayo ye15-month haifaniri kuratidzwa sekunge yaiva 15 months yekuedzwa kweconsumer methylene blue product. Prespecified primary analysis haina kuratidza kubatsira kwemadosi epamusoro zvichienzaniswa nelow-dose control. Gastrointestinal ne urinary adverse events pamwe nekuderera kwehemoglobin zvakataurwa. Kucherechedza kwenguva refu kwakapa ruzivo rwekuchengeteka; hakuna kusimbisa kusavapo kwenjodzi.
Zvinowedzerwa nezvidzidzo zvemhuka
Zvidzidzo zvemhuka zvinogona kuongorora tissues nekushandiswa kunodzokororwa izvo zvingava zvakaoma kuongorora muvanhu. Zvinoratidzawo kuti mhedzisiro yakanaka pachiyero chimwe chete haina kukwana.
Mukuedza kwemakonzo kwe30-day, liver lipid peroxidation yakawedzera asi chiyero cheitsvo chakaderera. Zviyero zvakati wandei zveantioxidant hazvina kuchinja. Kudaidza chidzidzo chose kuti “antioxidant protection” kwaizovanza musiyano uyu unoenderana nenhengo. Mukuedza kwembeva kwefour-week, kushandiswa kwepamusoro kwakakonzera shanduko huru mumicrobiome. Chidzidzo hachina kusimbisa kana shanduko idzodzo dzakaramba dziripo mushure mekumisa.
Kushandiswa kwenguva refu hakuna kungoerekana kwapa mhedzisiro yaidiwa. Miedzo yeskeletal aging haina kudzivirira kurasika kwemapfupa kunoenderana nezera. Kukosha kwayo kune zvirevo zvelongevity kunoenderana neendpoint: bone morphology, survival, nehupenyu hurefu hwevanhu mibvunzo yakasiyana.
Chidzidzo chenguva refu cheNational Toxicology Program chakawana carcinogenic activity ine mazinga ehumbowo akasiyana pakati pebonde nemarudzi emhuka. Gwaro rine chekuita nazvo re two-year rakataurawo anemia mune mamwe mapoka akashandiswa chinhu ichi. Zvakawanikwa izvi hazvipi nhamba yenjodzi yekenza yechirongwa chekutengesa kuvanhu. Asi zvinoramba pfungwa yekutora two years yekupa mhuka sechiratidzo chisina kuoma chekuchengeteka. Tsananguro yehumbowo hwecarcinogenicity inoongorora zvakawanikwa izvi zvakasiyana.
Addiction, withdrawal, tolerance uye cycling
Mazwi aya anotsanangura mibvunzo yakasiyana.
- Addiction inosanganisira kutadza kudzora kushandiswa nekuenderera mberi uchishandisa pasinei nekukuvadza. Zvidzidzo zviri pamusoro hazvisimbisi methylene blue addiction syndrome. Hazvinawo kugadzirwa kuti zviratidze kusavapo kwedependence liability kune vanoshandisa kwenguva refu vasina kutarisirwa.
- Withdrawal inoreva syndrome inodzokororwa mushure mekuderedza kana kumisa chinhu. Handina kuwana controlled evidence inotsanangura characteristic methylene blue withdrawal syndrome. Kuneta, anxiety kana kusanyatsokwanisa kuisa pfungwa mushure mekumisa chinhu chinhu chinofanira kuferefetwa, asi hazvina kukwana pachazvo kuti zvionekwe sewithdrawal. Kudzoka kwedambudziko raivapo kare, zvimwe zvinhu, uye shanduko dzekurara zvinogona kuomesa kududzirwa.
- Tolerance inoreva kuderera kwemhinduro pakushandiswa kwakafanana nekufamba kwenguva. Kuderera kwekunzwa kwe“boost” hakuratidzi chikonzero chacho kana kuti dose yakakura ndiyo yakakodzera. Miedzo yaizoda zviyero zvakajairwa zvinodzokororwa nezviyero zvekushandiswa kuti iongorore chirevo ichocho.
- Cycling inoreva kuronga nguva dzekushandisa nekusashandisa chinhu. Humbowo hwakataurwa hahusimbisi schedule inodzivirira tolerance, dependence kana cumulative harm. Protocol yemhuka yetoxicology yefive-days-per-week ischedule yekuedza, kwete zano recycling kuvanhu.
Mhedzisiro yekutsvaga inogona zvakare kuvhiringidza chinhu chiri kuongororwa nechinhu chiri kukonzera dependence. Semuenzaniso, kuyedza pamusoro peopioid tolerance newithdrawal kwakashandisa methylene blue mucell model yakaiswa maopioid. Chakanga chisiri chidzidzo chewithdrawal kubva kumethylene blue.
Mibvunzo isati yagadziriswa
Kuvanhu vakuru vane utano vanoshandisa methylene blue kakawanda, tsvakurudzo yakadomwa haisimbisi nguva iyo kubatsira kunoramba kuripo, nguva yakanakisisa yekumisa, cycling schedule yakasimbiswa, kana reliable rates yemigumisiro isingadiwi inononoka kuoneka. Haisimbisewo kana normal short-term laboratory result ichifembera kuchengeteka makore gare gare.
Cumulative risk nedrug accumulation zvine hukama asi zvakasiyana. Kushandiswa kunodzokororwa kunogona kuva kwakakosha kunyange mushonga usingaunganidziki zvachose, uye mushonga mutsva unopindirana nawo unogona kushandura njodzi mushure menguva isina dambudziko. Current intravenous PROVAYBLUE label inonyora serious serotonergic interactions, njodzi yehemolytic anemia uye higher exposure kana kidney function yakaderera. Haisi mvumo yekushandiswa nemuromo pasina mugumo wakatarwa.
Pakuita sarudzo yemunhu, ruzivo runobatsira ndirwo formulation chaiyo, nzira yekupa, huwandu, frequency, zuva rekutanga, mimwe mishonga uye chero zviratidzo. Ongorora kuti methylene blue inogara kwenguva yakareba sei mumuviri pamwe nemigumisiro yayo isingadiwi uye contraindications. Nhoroondo yekuti wakamboishandisa usingava nedambudziko humbowo pamusoro pekushandiswa kwakapfuura, kwete vimbiso pamusoro pekushandiswa kunotevera.