Fluralaner daws teeb meemYog cov qauv ua kua nrog cov khaub noom ua kua ua cov khoom xyaw tseem ceeb, feem ntau yog siv rau kev tiv thaiv thiab tswj cov tsiaj ectoparasites. Fluralaner cuam tshuam nrog cov hlab hlwb ua haujlwm ntawm cov kab thiab zuam los ntawm kev nyob rau hauv lawv tus txiv tuag taw (GAMA) Cov txheej txheem no yog qhov xaiv siab rau arthropods thiab muaj kev nyab xeeb rau cov tsiaj. Cov kev sim tau qhia tias Floraner tuaj yeem tiv thaiv mub oviposition hauv vitro (conferration ntau dua los yog sib npaug ntawm cov txiaj ntsig tsis tshua muaj (6.25 ng / ml); Hauv ib puag ncig muaj tus mob rau cov dev, tswj kev tswj hwm dev mub mub tau tshaj li 99% hauv 12 asthiv. Nws tuaj yeem siv los kho cov nqaij tawv nqaij mite (liab mite) kis tau tus kab mob hauv cov qaib dib, qe pw qaib, thiab qaib cov qaib. Los ntawm kev tswj hwm nws los ntawm kev haus dej, kev tu dua ntawm mites muaj peev xwm tswj tau zoo, txo qhov kev cuam tshuam rau cov nqaij qaib thiab kev tsim khoom.
Nyob rau tib lub sijhawm, peb lub tuam txhab tsis tsuas yog muab cov hmoov dawb, tab sis kuj cov ntsiav tshuaj thiab cov tshuaj. Yog tias xav tau, thov koj xav tiv tauj peb txhua lub sijhawm.
Peb Cov Khoom
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Counganer COA
Cov khoom lag luam
Fluralaner daws teeb meemyog cov qauv ua kua ntawm imidazole cov tshuaj tua kab, thiab cov tub ntxhais sib xyaw ua ke, ua tiav brohingamod gamma thiab l} glutamate glutamate glutamate glutamate glutamate glutamate glutamate glutamate ged chloride ion raws. Txawm li cas los xij, raws li cov neeg koom nrog cov neeg tseem ceeb hauv cov tub rog Sulphur lub voj voog rau lawv lub zog sib txawv, uas yog qhov sib txawv ntawm cov parasitic hlab.
Cov kab mob leejulizing yog ib hom kab mob uas tau txais lub zog los ntawm cov txiv lws suav (xws li muaj cov roj ntsha thiab txo qis hauv marine, thiab cov chaw ntub dej, thiab kev kho kom muaj kev lag luam pov tseg. Nws cov txheej txheem metabolic tsis tsuas yog tsav thoob ntiaj teb leej faj lub voj voog, tab sis kuj cuam tshuam rau cov kab mob ecosystem los ntawm kev sib txuas ua haujlwm carbon thiab nitrogen mus. Piv txwv li, hauv hypoxic water, leej faj oxidizing sulfate hloov mus rau "Heterrotrophic Sulphic Sulphid Oxidation", nws txo cov tshuaj lom ntawm sulfide rau cov muaj sia. Txawm li cas los xij, cov exacerbation ntawm sulfide paug tshwm sim los ntawm cov kev tshawb fawb los tshawb txog cov kev ua ub no ntawm leej faj oxidizing cov kab mob. Txawm li cas los xij, ib txwm tso cai txwv ib yam li cov hlau hnyav thiab cov cyanides muaj teeb meem tsis muaj txiaj ntsig. Fluralaner, raws li tus tshiab imidazole compound, yog siv dav rau kev tiv thaiv thiab kev nyab xeeb parasement thiab ntev} Lub sijhawm muaj kev tiv thaiv ntev (12 lub limtiam tiv thaiv lub sijhawm (12 asthiv.
Lub tshuab ntawm kev ua thiab hom phiaj tshwj xeeb ntawmFluralaner
Molecular hom kev ua ntawm imidazoline tebchaw
Fluralaner belongs to the imidazole insecticide class, and its chemical structure contains a 5-substituted 4,5-dihydroimidazole ring. It binds to the GABA receptor and L-glutamate gated chloride ion channel (GluCl) in arthropods, inhibiting the opening of chloride ion channels, leading to neuronal hyperpolarization and parasite paralysis and death. Experiments have shown that Fluralaner has a median lethal concentration (LC ₅₀) as low as 6.25 ng/mL for fleas and ticks, and has extremely low affinity for mammalian GABA receptors (>10000 Fold Qhov sib txawv), uas piav qhia txog nws cov kev xaiv siab.
Cov qauv ntawm cov hom phiaj protein
Muaj qhov tseem ceeb amino acids sib txawv ntawm arthropod Gaba receptors thiab cov nqaijmalian homologous protein nyob rau hauv lub ligand los ntawm cov diling sau npe. Piv txwv li, M2-M3 Voj cheeb tsam ntawm Gaba recept nyob rau hauv Drosophila Melianters muaj cov cim ntawm tib neeg Gaba ₐ Receptor yog SER205. Cov txheej txheem no tiv thaiv fluralaner los ntawm kev sib txuas nrog cov khoom siv tsiaj Mammalian, yog li zam qhov nruab nrab ntawm cov hlab ntsha toxicity. Ib yam li ntawd, cov ntawv ua haujlwm zoo nkauj yog muaj cov nqaij, tab sis cov khoom siv homphiaj
Lub zog metabolism yam ntxwv ntawm cov txiv lws suav oxidizing
Cov enzymes thiab txoj kev koom tes nrog rau hauv cov tub rog Sulphur Oxidation
Sulphur oxidizing cov kab mob Mile xyuas cov ulfide oxidation los ntawm ntau enzyme complex, nrog cov kev loj loj nrog:
Sulfide: Quinone oxidoreditase (SQR): catchalyzes oxidation ntawm h ₂ s rau theem pib txiv leej ntoo (s ⁰) thaum hloov hluav taws xob rau ubiquinone (UQ).
Sulphur dioxygenase (sdo): Ntxiv oxidizes s ⁰ rau sulfite (yog li3 α⁻).
Sulfite dehydrogenase (sdh): hloov siab tshiab rau hauv sulfate (yog li ntawd ua tiav cov kev ua tiav oxidation ntawm sulfides.
In marine sulfur oxidizing bacteria such as Beggiatoa and Thioploca, SQR binds to the cell membrane and directly utilizes nitrate (NO ∝⁻) as an electron acceptor to achieve energy synthesis under anaerobic conditions. Piv txwv li, Beggiataa spp. Ob peb sulfide oxidation nrog nitrate txo los ntawm kev thim rov qab electron hloov saw, tsim khoom ATP thiab txhim kho Co. ₂.
Coupling Mechanism ntawm Sulphur Oxidation thiab Zog Zog
Cov tshuab hluav taws xob tso tawm los ntawm cov txiv lws suav oxidation hloov mus rau lub davhlau ya nyob twg los ntawm lub pas dej Quane thiab kev tsim cov protonon thiab ATP synthesis. Noj thomagarita Namibiensis raws li ib qho piv txwv, nws intracellat vacuoles khw nitrate nitrate, thiab periplasmic chaw muaj SQR thiab SDH. Cov hluav taws xob tsim los ntawm sulfide oxidation pauv mus rau nitrate reductase los ntawm Cytochrome C, thiab kwv yees li 1.5 Mol ntawm ATP tuaj yeem tsim rau txhua 1 mol ntawm h ₂ s oxidized. Tsis tas li ntawd, qee cov kab mob sulphizing kab mob (xws li Sulphurimonas Denitrificans) yog tseem siv cov thiosulfate) ua tus pub hluav taws xob los tsim lub zog los ntawm cov "s ₄ Kuv txoj kev taug kev".
Xaiv Inhibition me me ntawm Fluralaner kua ntawm cov kab mob oxidizing
HOM PHIAJ: Tsis muaj kev pab cuam ntawm Gaba / Glucl Raws
Raws li cov prokaryotes, leej faj oxidizing cov kab mob tsis tau pom tias muaj cov homologous rau Gaba receptors lossis glucl raws nyob rau hauv lawv cov roj ntsha. Tag nrho guarome ua kom pom tias cov kev lag luam metabolic ntawm Beggiatooa Spp. Thiab thij spp. Tsuas yog suav nrog leej fajkur oxidase (xws li SQR, SDH), narrate reductase (NAR), thiab ATP Synthease, tab sis tsis muaj neurotransmitter receptor cuam tshuam cov noob. Yog li ntawd, frerrana tsis tuaj yeem cuam tshuam tsis tau nrog cov metabolism ntawm cov leej faj oxidizing cov kab mob los ntawm kev khi rau Gaba / Glucl raws.
Kev ywj pheej ntawm Metabolic Pathways: Tsis muaj tus ntoo khaub lig-}} tshaj ntawm cov txiv lws suav hloov chaw thiab neural teeb liab transduction
Lub zog metabolism ntawm cov leej faj oxidizing cov kab mob relies, thiab lawv cov saw hluav taws xob tsis zoo ib yam li ntawm cov eervous zoo ib yam. Piv txwv li, cov sulphur oxidase system (SQR, DSR, Apr) Yog li ntawd, Frrerrana tsis muaj qhov cuam tshuam ncaj qha rau cov kev ua si tseem ceeb ntawm leej faj oxidizing cov kab mob.
Kev ruaj ntseg ecological kev nyab xeeb: tsis yog phiaj los ntsuas microbial
Laboratory simulation experiments have shown that sulfur oxidizing bacteria (such as Thiobacillus denitrificans) have no significant difference in growth rate compared to the control group in the culture medium containing Fluralaner (10 mg/L) (p>0.05), thiab sulfide oxidation tus nqi (ntsuas los ntawm yog li ₄² ⁻ kev tsim khoom) tsis yog inhibited. Hauv kev sib piv, cov hlau hnyav (xws li Cu ⁺ ⁺, 0.1 mg / l) tuaj yeem tiv thaiv cov txiv lws suav uas tsis muaj kuab lom Ib qho ntxiv, cov kev sim teb pom tias daim ntawv thovFluralaner daws teeb meemrau kev ua yeeb yam dev tsis muaj kev cuam tshuam rau hauv cov qauv hauv zej zog ntawm cov av sulphur oxidizing cov kab mob (Shannon Performance index hloov<5%), further supporting its ecological safety.
Cov ntawv thov muaj peev xwm thiab cov kev txwv
Cov xwm txheej muaj peev xwm rau kev tswj hwm sulphur oxidizing cov kabter
Txawm hais tias Floraner tsis muaj kev cuam tshuam ncaj qha nyhuv ntawm cov kab mob sulpur, nws xaiv cov tshuaj oxidizing muaj cov tswv yim ntawm cov microbial cov kev cai tshiab thev naus laus zis tshiab. Piv txwv li:
Binemediation: Hauv kev kho cov sulfide uas muaj cov dej khib nyiab, ua tiav rau cov kab mob uas tsis muaj kuab lom thiab kev tiv thaiv kab mob ecological.
Cov ntawv thov kev ua liaj ua teb: hauv cov tsiaj txhu thiab nqaij qaib ua liaj ua teb, cov kab mob tsiaj, thiab tsis sib xws txhim kho kev ua haujlwm ntawm cov leeg oxidizing cov kab mob.
Txwv: tsis ncaj ntawm cov tsis muaj metabolic inhibition inhibition
Nws yuav tsum raug sau tseg tias Floraneaner yuav cuam tshuam rau cov txiv lws suav los ntawm kev hloov cov tswv tsev microbe sib txuas lus. Piv txwv li, hauv koalas (pimasterctionsos congereus), fluralaner scabonome (ntawm 12%), uas yuav cuam tshuam nrog kev txhim kho ntawm daim tawv nqaij tom qab kev sib tw ntawm parasite. Hom nyhuv tsis ncaj ncees yuav tsum tau elucidated ntxiv los ntawm ntau omics tsom xam.
Cov kev tawm tsam
Fluralaner yog ib qho compound yog rau chav kawm ntawm isoxzolines, feem ntau yog siv rau cov tsiaj sab nraud xws li dev thiab miv thiab zuam. Nws cov ntawv sau ua kua (xws li cov tshuaj hauv qhov ncauj lossis cov ntxhiab tsw) yog siv dav hauv cov kws kho tsiaj ua haujlwm vim nws cov thawj coj yooj yim. Txawm li cas los xij, zoo li tag nrho cov tshuaj,Fluralaner daws teeb meemTej zaum yuav ua rau muaj kev phiv tsis zoo, tshwj xeeb tshaj yog siv rau lub sijhawm ntev lossis tsis tsim nyog.
Cov Kev Ruaj Ntseg
Kev teb neurological
Tshee thiab ataxia, ua manifested rau mob me me, tshwj xeeb tshaj yog nyob rau hauv thaum ntxov nce qib tom qab kev tswj hwm; Ataxia yog tus cwj pwm los ntawm gait tsis ruaj khov thiab txo kev sib haum xeeb. Isoxhazoline siv yeeb tshuaj yuav cuam tshuam tshwj xeeb cuam tshuam rau Gaba cov khoom siv Mammalian hauv lub pob zeb Mammalian (CNS), txawm hais tias lawv qhov kev xaiv tau qis dua li lawv cov txiaj ntsig ntawm cab. Txawm li cas los xij, ntau dhau ntawm kev tswj hwm, nquag tswj hwm, cov tsiaj me me (cov tub ntxhais hluas lossis cov laus muaj kev nkag siab zoo dua), lossis lub xub ntiag ntawm cov kev puas tsuaj neurological (xws li urilepsy). Eppilsy yog ib qho tsawg kawg nkaus tab sis muaj mob heev uas muaj kev tiv thaiv tonic tonic yias chuazures, uas tej zaum yuav ntev li ob feeb.
Kev tiv thaiv lub plab zom mov
Ntuav thiab raws plab yuav tshwm sim hauv ob peb teev tom qab kev tswj hwm, muaj peev xwm nrog los ntawm kev txo qis. Nws yog vim tias cov tshuaj ncaj qha rau cov roj plab cov plab zom mov thiab ua kom lub hauv paus ntuav ntuav refitx. Tab sis kev tswj hwm, nqos ceev ceev (tsis txaus ntawm cov qaub ncaug), lossis siab siv tshuaj. Tej zaum kuj yuav muaj mob plab tsis xis nyob, tsam plab, lossis cov quav muag. Nws yuav tsum tau muab rau hauv cov koob tshuaj faib lossis noj nrog cov zaub mov kom txo tau tus nqi.
Cov tawv nqaij thiab ua xua
Nrov lossis lub cev khaus, liab liab, tej zaum nrog tus cwj pwm khawb. Kev ua xua lossis cov tshuaj ua xua rau cov hauv paus plaub hau. Kev nyuaj siab ua pa nyuaj, daj ua kom zoo nkauj, thiab kev poob siab kuj tshwm sim, xav tau kev kho mob muaj xwm ceev. Feem ntau vim cov tsiaj muaj kev ua xua rau ISOXAZOLY MEDICS lossis EXPIPIENS (xws li propylene glycol).
Mob siab thiab lub raum toxicity
Lub siab ua kom lub siab ua kom pom tseeb tias yog asymptomatic nce ntawm ntshav almanine aminottransferase (alt) lossis aspartate aminottransferase (ust). Txawm li cas los xij, nws raug nquahu kom kuaj lub siab ua haujlwm ntev rau ntev-} kev siv tshuaj. Kev raug mob raum (tsis tshua muaj) yog tus cwj pwm los ntawm Polyuria, Odiguria, lossis hematuria, nrog rau cov dej hiav txwv creatinine. Tej zaum nws yuav cuam tshuam nrog cov tshuaj lom ntawm cov tshuaj metabolites ntawm lub txim renal. Kev ua xua rau cov tshuaj lossis kev ua kom zoo dua (xws li propylene glycol).
Cim npe nrov: Fluralaner daws, cov neeg muab khoom, chaw tsim khoom, Hoobkas, lag luam wholesale, yuav, nqe, loj, loj, rau muag