000112528 001__ 112528
000112528 005__ 20230519145617.0
000112528 0247_ $$2doi$$a10.1016/j.ijpddr.2021.10.001
000112528 0248_ $$2sideral$$a127530
000112528 037__ $$aART-2021-127530
000112528 041__ $$aeng
000112528 100__ $$aSánchez-Sánchez, R.
000112528 245__ $$aA short-term treatment with BKI-1294 does not protect foetuses from sheep experimentally infected with Neospora caninum tachyzoites during pregnancy
000112528 260__ $$c2021
000112528 5060_ $$aAccess copy available to the general public$$fUnrestricted
000112528 5203_ $$aThe Neospora caninum Calcium-dependent protein kinase 1 (NcCDPK1) inhibitor BKI-1294 had demonstrated excellent efficacy in a pregnant mouse model of neosporosis, and was also highly efficacious in a pregnant sheep model of toxoplasmosis. In this work, we present the efficacy of BKI-1294 treatment (dosed 5 times orally every 48 h) starting 48 h after intravenous infection of sheep with 105 Nc-Spain7 tachyzoites at mid-pregnancy. In the dams, BKI-1294 plasma concentrations were above the IC50 for N. caninum for 12–15 days. In treated sheep, when they were compared to untreated ones, we observed a minor increase in rectal temperature, higher IFN¿ levels after blood stimulation in vitro, and a minor increase of IgG levels against N. caninum soluble antigens through day 28 post-infection. Additionally, the anti-NcSAG1 and anti-NcSAG4 IgGs were lower in treated dams on days 21 and 42 post-infection. However, BKI-1294 did not protect against abortion (87% foetal mortality in both infected groups, treated and untreated) and did not reduce transplacental transmission, parasite load or lesions in placentomes and foetal brain. The lack of foetal protection was likely caused by short systemic exposure in the dams and suboptimal foetal exposure to this parasitostatic drug, which was unable to reduce replication of the likely established N. caninum tachyzoites in the foetus at the moment of treatment. New BKIs with a very low plasma clearance and good ability to cross the blood-brain and placental barriers need to be developed. © 2021 The Authors
000112528 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000112528 590__ $$a4.284$$b2021
000112528 592__ $$a0.923$$b2021
000112528 594__ $$a6.9$$b2021
000112528 591__ $$aPARASITOLOGY$$b7 / 39 = 0.179$$c2021$$dQ1$$eT1
000112528 593__ $$aInfectious Diseases$$c2021$$dQ1
000112528 591__ $$aPHARMACOLOGY & PHARMACY$$b104 / 279 = 0.373$$c2021$$dQ2$$eT2
000112528 593__ $$aPharmacology (medical)$$c2021$$dQ1
000112528 593__ $$aPharmacology$$c2021$$dQ1
000112528 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000112528 700__ $$aFerre, I.
000112528 700__ $$aRe, M.
000112528 700__ $$aPérez-Arroyo, B.
000112528 700__ $$aCleofé-Resta, D.
000112528 700__ $$aHerrero García, V.
000112528 700__ $$aPizarro Díaz, M.
000112528 700__ $$0(orcid)0000-0003-0042-8800$$aFerrer, L.M.$$uUniversidad de Zaragoza
000112528 700__ $$0(orcid)0000-0002-8474-2831$$aRuiz, H.$$uUniversidad de Zaragoza
000112528 700__ $$aVallejo-García, R.
000112528 700__ $$aBenavides, J.
000112528 700__ $$aHulverson, M.A.
000112528 700__ $$aChoi, R.
000112528 700__ $$aWhitman, G.R.
000112528 700__ $$aHemphill, A.
000112528 700__ $$aVan Voorhis, W.C.
000112528 700__ $$aOrtega-Mora, L.M.
000112528 7102_ $$11009$$2617$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Medicina y Cirugía Animal
000112528 773__ $$g17 (2021), 176-185$$tInternational journal for parasitology, drugs and drug resistance$$x2211-3207
000112528 8564_ $$s5549114$$uhttps://zaguan.unizar.es/record/112528/files/texto_completo.pdf$$yVersión publicada
000112528 8564_ $$s2392894$$uhttps://zaguan.unizar.es/record/112528/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000112528 909CO $$ooai:zaguan.unizar.es:112528$$particulos$$pdriver
000112528 951__ $$a2023-05-18-16:11:52
000112528 980__ $$aARTICLE