|
1kits (Ebipipa 10) .
| Omuwendo: | |
|---|---|
▎ Enzimba ya Sel
Ensibuko: PubChem |
Omutendera: TKPRPGP Ensengekera ya molekyu: C 33H 57N 11O9 Obuzito bwa molekyu: 751.9 g/mol Ennamba ya CAS: 129954-34-3 PubChem CID: 11765600. Enkola y’okukuuma eddagala lino Ebigambo ebifaanagana: Sel |
▎ Sel Okunoonyereza ku
Sel y’akola mu kunoonyereza kuliwa?
Okukyusa obusimu n’enkola ya Endogenous Opioid System:
Enkola ya opioid ez’omunda yeenyigira mu nkola y’okukyusakyusa obusimu ereetebwa opioid ez’ebweru. Sel, eddagala eriweweeza ku kweraliikirira eryakolebwa nga lyesigamiziddwa ku regulatory peptide tuftsin, liyinza okuziyiza emirimu gya enkephalin-degrading enzymes, bwe kityo ne kyongera ku mutindo gwa leucine enkephalin mu plasma (Nadorova AV, 2022). Kino kiraga nti Sel eyinza okukozesa ebikolwa byayo nga etereeza enkola ya opioid ey’omunda.
Okweraliikirira n‟okutabuka mu mbeera y‟omuntu bye bimu ku bizibu ebisinga okutawaanya obulamu bw‟omutwe mu nsi yonna. Eddagala eritera okukozesebwa mu bujjanjabi eriweweeza ku kweraliikirira okusinga lissa ku kulungamya eddagala ly’emirimu gy’enkola y’obwongo ekwata GABA. Wabula eddagala ng’eryo litera okuba n’ebizibu ebiwerako mu bujjanjabi ng’okwesigamira n’okulemererwa okujjukira (Vyunova TV, 2018). Waliwo okweyongera okutegeera omulimu gwa neuropeptides ne bioactive lipids mu pathophysiology y’obuzibu bw’embeera n’okweraliikirira. Heptapeptide Sel eraga ebikolwa eby’ekiseera ekiwanvu eby’okukendeeza okweraliikirira n’okunywa (nootropic effects) (Vyunova TV, 2018).
Enkola y’okukola kwa Sel eri etya?
Enkola ki ey’okukola kwa Sel ku kweraliikirira n’obuzibu bw’embeera y’omuntu?
Okulungamya Enkola ya GABA Receptor System:
Okweraliikirira n‟obuzibu mu mbeera y‟omuntu bye bizibu ebisinga okutawaanya obulamu bw‟omutwe mu nsi yonna. Eddagala eritera okukozesebwa mu bujjanjabi eriweweeza ku kweraliikirira okusinga likola ebikolwa byalyo nga litereeza emirimu gy’enkola y’okukwata GABA mu bwongo, naye litera okuba n’ebizibu ng’okwesigamira n’okulemererwa okujjukira. Okunoonyereza kuzudde nti eddagala lya heptapeptide Sel (Thr-Lys-Pro-Arg-Pro-Gly-Pro) lirina kye likola ku kweraliikirira n’obuzibu bw’embeera y’omuntu. Enkola z’okwekenneenya radioligand-receptor ziraga nti Sel ekosa [3H] GABA okusiba nga positive allosteric modulator. Ekikolwa kya Sel ekigatta ne benzodiazepines ezimu nakyo kitereeza omulimu gw’okusiba [3H] GABA mu ngeri eyeetongodde. Ekikolwa kino si kya kwongerako era kya njawulo ku kukozesa ekintu kyonna kyokka. Sel asobola okuziyiza emirimu gy’okulungamya eddagala lya diazepam ne olanzapine. Ekifo kyayo eky’okusiba kirabika kya njawulo ku ky’eddagala lino, naye kiyinza okukwatagana ekitundu [1] . Bwe kityo kiteeberezebwa nti emu ku nkola za molekyu ez’ekikolwa kya Sel eky’okukendeeza okweraliikirira eyinza okuba nga yeekuusa ku subtype-selective concentration-dependent allosteric regulation of GABA receptors.
Enkola ya Sel eri etya mu kuwummuza eddagala eriweweeza ku bulumi erireetebwa morphine?
Okuziyiza Okuggyamu Morphine Reaction:
Okunoonyereza okumu kulaga nti ekirungo kya peptide Sel kisobola okunafuya enkola y’okuggyayo envunza ku morphine ku ddoozi ezimu. Okugeza, mu nkola y’okuggyayo morphine ereetebwa naloxone, empiso emu ey’omu lubuto eya Sel (0.3mg/kg) esobola okukendeeza ku muwendo gwonna ogw’obulwadde bw’okuggyayo morphine ne 39.6%, okukendeeza ennyo ku bubonero nga convulsive reactions, ptosis, n’obuzibu mu kuyimirira, n’okwongera ku tactile sensitivity threshold y’envunza ezisinziira ku morphine nga emirundi 9 [2] . Kino kiraga nti Sel ayinza okukosa mu ngeri etali butereevu enkola y’okukendeeza obulumi eya morphine ng’etereeza enkola y’obusimu okwesigamira ku morphine.
Enkolagana y’eddagala eriweweeza ku bulumi n’eddagala lya Morphine:
Mu kugezesa ebisolo, abanoonyereza baakizudde nti Sel alaga eddagala eriweweeza ku bulumi erya synergistic analgesic effect bwe likozesebwa nga ligatta wamu ne morphine. Morphine asobola okuleeta okukendeeza ku bulumi ku ddaala eritali limu ku ddoozi ezimu, era wadde nga Sel yennyini talina kikolwa kya kukendeeza bulumi kyeyoleka, bw’ekozesebwa wamu ne morphine ku ddoozi eyeetongodde (0.9mg/kg), esobola okwongera ku latency y’okuddamu kw’ebibe eri ebbugumu erisikirizibwa, okutumbula eddagala erikendeeza obulumi okutuuka ku 29.9% ku kikolwa ekisinga obunene ekisoboka (MBE) [3] . Kino kiraga nti Sel ayinza okutumbula eddagala eriweweeza ku bulumi erya morphine ng’ayita mu kkubo erimu.
Okukola ku nkola ya Enkephalin:
Okusinziira ku kunoonyereza ku bikolwa by’omubiri ebya Sel n’ebitundutundu byayo, kiteeberezebwa nti Sel akola ku mutimbagano gw’enkola ya cascade eya peptides n’abatabaganya okuyita mu enkephalin. Enkephalin kika kya endogenous opioid peptide era ekola kinene mu kulungamya obulumi. Sel eyinza okukosa eddagala eriweweeza ku bulumi erya morphine nga etereeza emirimu gy’enziyiza ezisaanya enkephalin n’okwongera ku mutindo gwa leucine enkephalin mu plasma [4]..
Ebikolwa bya Sel (0.3 mg/kg) ku kutegeera ekintu ekipya mu nvunza ezaakakasibwa okunywa omwenge.
Ensibuko:PubMed [7] .
Musingi ki oguyinza okukolebwa Sel mu kujjanjaba obuzibu bw’obunafu mu bulwadde bwa COVID oluvannyuma?
Okusinziira ku bikolwa by’obusimu obuziyiza endwadde:
Okusinziira ku kifo ekikulu eky’obuzibu bw’abaserikale b’omubiri mu ntandikwa y’obulwadde bwa COVID-19, eddagala eririna ebikolwa eby’okukyusa obusimu obuziyiza endwadde lirabika nga lisuubiza mu kujjanjaba obulwadde bw’oluvannyuma lwa COVID. Sel ddagala lya peptide eryatondebwa nga lyesigamiziddwa ku immunomodulator tafcin. Mu kujjanjaba obulwadde bw’obulwadde bwa COVID oluvannyuma, Sel ayinza okumalawo obubonero bw’obunafu ng’atereeza abaserikale b’omubiri n’okutereeza abaserikale b’omubiri obutakola bulungi. Okugeza, Sel ayinza okuba n’omulimu obutereevu ku nkolagana y’abaserikale b’omubiri oba okukola mu ngeri etali butereevu nga akendeeza ku kuddamu oluvannyuma lw’okunyigirizibwa, bwe kityo n’akuuma embeera eya bulijjo ey’enkola y’abaserikale b’omubiri [5]..
Obuzibu bw‟okukendeeza okweraliikirira n‟okulongoosa embeera y‟omuntu:
Mu bulwadde bwa COVID oluvannyuma, abalwadde batera okufuna obuzibu mu mbeera ng’okweraliikirira n’okwennyamira, nga buwerekerwako obunafu n’okukendeera kw’emirimu. Okunoonyereza kulaga nti Sel asobola okumalawo obubonero bw’okweraliikirira n’okwennyamira mu nkola y’obujjanjabi. Enkola yaayo ey’okukola eyinza okuba nga yeekuusa ku Sel okulungamya enkola y’obusimu obutambuza obusimu mu bwongo. Okugeza, Sel ayinza okukola nga positive allosteric modulator okukosa [3H] GABA okusiba, bwe kityo okulungamya emirimu gy’enkola ya GABA receptor n’okukola anxiolytic effect [1]..
Enkola y’okukuuma obusimu:
Mu kunoonyereza kuno, abalwadde baawuddwamu ebibinja bibiri. Ekibinja ekimu kyakozesa ekizibu ekikuuma obusimu (cholitilin, mexidol, milgamma) ne Sel, ate ekirala kyakozesa ekizibu ky’okukuuma obusimu kyokka. Ebivuddemu biraga nti abalwadde abakozesa Sel baalina ebikosa ebirungi mu nsonga z’obunafu n’okukendeera kw’emirimu gy’obwongo. Kino kiraga nti Sel ayinza okukola mu ngeri ey’okukwatagana n’ekizibu ky’okukuuma obusimu okukola ekikolwa eky’okukuuma obusimu, bwe kityo n’alongoosa obubonero bw’obunafu bw’abalwadde [5]..
Ebikolwa by’okulwanyisa akawuka:
Okunoonyereza kuzudde nti Sel alina eddagala eritta akawuka mu kugezesa obulwadde bwa ssennyiga. Wadde mu kiseera kino tewali bukakafu bulaga butereevu nti Sel erina eddagala eriziyiza akawuka ka COVID-19, okusinziira ku ngeri gy’akola mu kukwatibwa akawuka ka ssennyiga, Sel ayinza okuba n’akakwate akamu ku kawuka ka COVID-19 ng’ayita mu nkola emu, bw’atyo n’ayamba okujjanjaba obuzibu bw’obunafu mu bulwadde bw’oluvannyuma lwa COVID. Okugeza, mu kunoonyereza mu vivo, Sel yaleeta okulaga obuzaale bwa interferon-α (IFN-α), ekiyinza okuyamba okutumbula obusobozi bw’omubiri okulwanyisa akawuka [6]..
Biki ebiva mu Sel?
Obuzibu bw‟okukendeeza okweraliikirira n‟okulongoosa embeera y‟omuntu:
Mu bulwadde bwa COVID oluvannyuma, abalwadde batera okufuna obuzibu mu mbeera ng’okweraliikirira n’okwennyamira, nga buwerekerwako obunafu n’okukendeera kw’emirimu. Okunoonyereza kulaga nti Sel asobola okumalawo obubonero bw’okweraliikirira n’okwennyamira mu nkola y’obujjanjabi. Enkola yaayo ey’okukola eyinza okuba nga yeekuusa ku Sel okulungamya enkola y’obusimu obutambuza obusimu mu bwongo. Okugeza, Sel ayinza okukola nga positive allosteric modulator okukosa [3H] GABA okusiba, bwe kityo okulungamya emirimu gy’enkola ya GABA receptor n’okukola anxiolytic effect [1]..
Enkola y’okukuuma obusimu:
Mu kunoonyereza kuno, abalwadde baawuddwamu ebibinja bibiri. Ekibinja ekimu kyakozesa ekizibu ekikuuma obusimu (cholitilin, mexidol, milgamma) ne Sel, ate ekirala kyakozesa ekizibu ky’okukuuma obusimu kyokka. Ebivuddemu biraga nti abalwadde abakozesa Sel baalina ebikosa ebirungi mu nsonga z’obunafu n’okukendeera kw’emirimu gy’obwongo. Kino kiraga nti Sel ayinza okukola mu ngeri ey’okukwatagana n’ekizibu ky’okukuuma obusimu okukola ekikolwa eky’okukuuma obusimu, bwe kityo n’alongoosa obubonero bw’obunafu bw’abalwadde [5]..
Okumalawo Obulumi Obuleetebwa Morphine:
Okunoonyereza okumu kulaga nti Sel, eddagala eriweweeza ku kweraliikirira eryakolebwa nga lyesigamiziddwa ku regulatory peptide tuftsin, lirina kye likola ku ddagala eriweweeza ku bulumi erireetebwa morphine mu bikolwa by’ebisolo. Okugeza, ddoozi ya morphine bw’eba 3.0mg/kg (empiso mu lubuto), esobola okuleeta antinociception, nga esinga okukolebwa (MBE) ya 9%. Wadde nga sel dose ya 0.9mg/kg terina antinociceptive effect ku bwayo, bweba nga tennaba kujjanjabwa na morphine, esobola okwongera ku latent reaction time ne kireeta antinociceptive effect ya 29.9% MBE [3]..
Okukendeeza ku Bubonero Obukyayi obw’Okuggyamu Morphine:
Enkola ya peptide tuftsin analog Sel yasomesebwa mu nkola y’okuggyayo morphine eyaleetebwa naloxone. Empiso emu eya Sel mu lubuto ku ddoozi y’okweraliikirira eya 0.3mg/kg esobola okukendeeza ku muwendo gwonna ogw’obulwadde bw’okuggyayo morphine ne 39.6%, nnyo (p30.0001) okukendeeza ku kukonziba, ptosis, n’obuzibu bw’okuyimirira, n’okwongera ku tactile sensitivity threshold y’envunza ezisinziira ku morphine emirundi 9 bwe zigeraageranyizibwa n’ekibinja ekifuga ekirungi. Mu kiseera kye kimu, Sel eri wansi katono ku diazepam ku ddoozi ya 2mg/kg mu nkola y’eddagala (okukendeeza ku muwendo gwonna ogw’obulwadde bwa morphine withdrawal syndrome ne 49.3% n’okwongera ku sensitivity threshold emirundi 13). Nolwekyo, okufaananako diazepam, Sel asobola okukendeeza ku bubonero obukyayi obw’okuggyawo morphine mu kwesigama ku opioid mu nvunza [2]..
Okuziyiza obuzibu bw’okujjukira obuva ku ethanol:
Mu nvunza ezaafuna 10% ethanol ng’ensibuko yazo yokka ey’amazzi okumala wiiki 30, ebikolwa bya Sel, eddagala eriweweeza ku kweraliikirira erikolebwa mu peptide eryakolebwa okuva mu peptide tuftsin ey’omunda, ku buzibu bw’okujjukira n’emiwendo gya brain-derived neurotrophic factor (BDNF) byanoonyezebwa. Mu kukebera okutegeera ebintu, Sel yalaga ebikolwa eby’okutumbula okutegeera mu nvunza ez’emyezi 9 ezitakwatibwa ethanol era n’eziyiza okukula kw’obuzibu bw’okujjukira n’okussaayo omwoyo obuva ku ethanol mu kiseera ky’okuggya omwenge. Okugezesa mu vitro kwalaga nti Sel esobola okuziyiza okweyongera kw’emiwendo gya BDNF okuva mu ethanol mu hippocampus ne prefrontal cortex. Okusinziira ku ebyo waggulu, kiyinza okumalirizibwa nti kino ekirungo kya synaptogenic kirina akakwate akalungi ku buzibu bw’okujjukira obuva ku myaka obukwatagana n’okwesigamira ku mwenge obutawona, era kikakasa nti enkola z’obusimu ezikwata ku BDNF zeenyigira mu nkola y’okukola kwa Sel [7]..
Obujjanjabi bw'obulwadde bw'obulwadde bwa COVID-19:
Obulwadde bwa post-COVID-19 bubaawo oluvannyuma lw’okukwatibwa COVID-19 era buyinza n’okulabibwa mu mbeera z’obulwadde obutono oba obutaliiko bubonero. Obubonero obusinga okulabika mu bulwadde bwa bridge syndrome bwe bukoowu n’okukendeera kw’emirimu, n’eddirirwa obuzibu mu kutegeera. Okusinziira ku kifo ekikulu eky’okutaataaganyizibwa kw’abaserikale b’omubiri mu ntandikwa y’obulwadde bwa COVID-19, eddagala eriweweeza ku busimu obuziyiza endwadde eririna ebikolwa obutereevu okukyusa abaserikale b’omubiri oba eryo erikuuma enkola y’abaserikale b’omubiri mu ngeri etali butereevu nga likendeeza ku kuddamu oluvannyuma lw’okunyigirizibwa lirina ekisuubizo ekiyinza okujjanjaba.
Sel ddagala lya peptide eryakolebwa nga lyesigamiziddwa ku immunomodulator tafcin, ekola bulungi mu kujjanjaba obusimu obw’enjawulo n’obuzibu obulinga obw’obusimu. Sel bw’ekozesebwa ku ddoozi y’amatondo 2-3 emirundi ena olunaku okumala ennaku 30 ez’omuddiring’anwa, Sel akola bulungi mu kujjanjaba abalwadde abakooye n’okulemererwa okutegeera. Okumalawo okweraliikirira n‟obubonero bw‟okwennyamira nakyo kisobola okulabibwa [5]..
Okutereeza obuzibu mu kutegeera n’enneewulira mu balwadde abalina obulwadde bw’olususu obuyitibwa atopic dermatitis: Okunoonyereza kwekenneenya obuzibu mu kutegeera n’enneewulira mu balwadde 65 abalina obulwadde bw’olususu obuyitibwa atopic dermatitis (AD) era ne kwawulamu abalwadde mu bibinja bibiri ebigeraageranyizibwa mu bibalo.
Ekibinja ekisooka eky’abalwadde baafuna obujjanjabi obw’eddagala obwa bulijjo ku bulwadde bw’olususu obuyitibwa atopic dermatitis (BT), ate ekibinja ekyokubiri ne bafuna eddagala erigatta serank ne BT nga bayita mu kuweebwa mu nnyindo (S + BT), nga baweebwa emirundi esatu buli lunaku, nga buli ddoozi essiddwamu amatondo abiri mu buli nnyindo, okumala ennaku 14 zonna awamu. Ekibinja ekifuga kyalimu abantu 30 abalamu. Okweraliikirira kw’omuntu (LT), okweraliikirira okukola (RT), emiwendo gya yohimbine, emiwendo gya β-endorphin mu musaayi, n’omutindo gw’obulamu (QOL) byakeberebwa nga tebannaba kujjanjabwa n’ennaku 30 oluvannyuma lw’okutandika obujjanjabi.
Ebyavudde mu kunoonyereza biraga nti emiwendo gya RT mu balwadde ba AD gyali waggulu emirundi 4.2 okusinga egyo mu kibinja ekifuga, emiwendo gya LT gyali waggulu emirundi 3.2, ate emiwendo gya yekhtumia gyali waggulu emirundi 18. Mu kibinja kya BT, RT yakendeera emirundi 1.4 ate LT yakendeera emirundi 1.3 oluvannyuma lw’ennaku 30 oluvannyuma lw’okutandika obujjanjabi. Mu kibinja kya C+BT, okukendeera mu LT ne RT kwali kwa maanyi mu ngeri y’emu, byombi emirundi 2.4.
Tewaaliwo nkyukakyuka nnene mu bubonero bwa yekutumia oba β-endorphin levels mu musaayi gw’abalwadde mu kibinja kya BT. Mu kibinja kya S+BT, obuzibu bw’enneewulira bwa Alexis bwakendeera emirundi 1.2, ate emiwendo gya β-endorphin mu musaayi gyeyongera emirundi 1.9. Omuwendo gw’obulamu bw’abalwadde mu kibinja kya BT gwakendeera emirundi 1.2 oluvannyuma lw’ennaku 30 oluvannyuma lw’okutandika obujjanjabi, ate ogw’abalwadde mu kibinja kya S+BT gwakendeera emirundi 1.7. Ekimalirizibwa kiri nti emitendera egy’okweraliikirira okw’obuntu, okweraliikirira okw’okuddamu, ne yekhtumia mu balwadde ba AD bikendeeza ku mutindo gw’obulamu bwabwe. Okukozesa regulatory peptide Sel mu bujjanjabi obw’enjawulo obw’abalwadde ba AD kulina ekikolwa ekitereeza ku buzibu bw’enneewulira n’okutegeera, okukendeeza ku miwendo gy’okweraliikirira kw’omuntu, okweraliikirira okuddamu, ne yekhtumia, okwongera ku miwendo gya β-endorphin mu musaayi, n’okutumbula omutindo gw’obulamu bw’abalwadde [8]..
Mu kumaliriza, ng’eddagala lya peptide ery’obutonde eryakolebwa nga lyesigamiziddwa ku kibinja kya peptide eky’obutonde, Sel alaze obusobozi bw’okukozesa mu ngeri ez’enjawulo mu nkola y’obujjanjabi n’okunoonyereza. Omugaso gwayo omukulu guli mu kuwa eby’okugonjoola ebipya ku ndwadde ng’obuzibu bw’okweraliikirira, obuzibu obuva ku situleesi, okulemererwa okujjukira, n’obuzibu bw’abaserikale b’omubiri nga tulung’amya enkola y’obusimu obutambuza obusimu, okutumbula enkola y’abaserikale b’omubiri, n’okulongoosa enkola y’okutegeera. Okunoonyereza mu bujjanjabi kukakasizza nti Sel asobola bulungi okumalawo obubonero bw’okweraliikirira n’okwennyamira, okulongoosa obunafu n’obuzibu bw’okutegeera mu bulwadde bwa COVID oluvannyuma lw’obulwadde bwa COVID, n’okukwatagana n’okutumbula eddagala eriziyiza okuzimba mu kujjanjaba obulwadde bw’olususu obuyitibwa atopic dermatitis. Bw’ogeraageranya n’eddagala ery’ekinnansi, lirina ebizibu ebitono, liwangaala nnyo, era liraga ebirungi eby’enjawulo mu by’okukendeeza obulumi, okulwanyisa emize, n’okukuuma obusimu.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Vyunova TV mukugu mu by’obusimu, eddagala, ebiramu, era munoonyereza mu Russia. Akoze kinene mu by’obulamu (biochemistry & molecular biology), kemiko, biophysics, pharmacology & pharmacy, ne physiology. Vyunova abadde akwatagana n'amatendekero ag'ettutumu nga National Research Center 'Kurchatov Institute' ne Russian Academy of Sciences. Okunoonyereza kwa Vyunova era kuvuddeko okufuna patent eziwerako, nga kulaga enkola ye ey’obuyiiya ku bizibu bya ssaayansi. Okwewaayo kwe okutumbula okumanya mu mirimu gye kimufudde omuntu ow’ekitiibwa mu bannassaayansi. Vyunova TV ewandiikiddwa mu kiwandiiko ekijuliziddwa [1].
