Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12104/43100
Title: Deflazacort induced stronger immunosuppression than expected
Author: Ringman, J.M.
Diaz-Olavarrieta, C.
Rodriguez, Y.
Chavez, M.
Fairbanks, L.
Paz, F.
Varpetian, A.
Maldonado, H.C.
Macias-Islas, M.A.
Murrell, J.
Ghetti, B.
Kawas, C.
Issue Date: 2005
Abstract: Background: Prospective and case-control studies have demonstrated that memory loss and executive dysfunction occur early in Alzheimer disease (AD). Objective: To investigate these observations by the study of persons at risk for autosomal dominant forms of AD. Methods: Neuropsychological and genetic tests were performed on 51 nondemented at-risk members of 10 Mexican families with two distinct presenilin-1 (PS1) mutations. Test scores were compared between PS1 mutation carriers (MCs; n = 30) and noncarriers (NCs; n = 21) by analyses of variance, co-varying for family and specific mutation. Regression analyses were performed, taking into account age relative to the median age at dementia diagnosis in the family (adjusted age), gender, Beck Depression Inventory (BDI) scores, education, and number of APOE ?4 alleles. Subjects were divided into age tertiles and scores compared within these groups. Composite scores for Verbal Memory, Executive Function/Working Memory, Language, and Visuospatial Function were created, and these scores compared between MCs and NCs. Results: MCs performed worse than NCs on the Mini-Mental State Examination, Trails Making Tests A and B, Delayed Recall of a 10-Word List, and Wechsler Adult Intelligence Scale WAIS Block Design. In multiple linear regression analyses, BDI score, gender, and number of APOE ?4 alleles did not consistently affect test scores. The differences seen between MCs and NCs were due to differences in the oldest tertile. MCs had lower Visuospatial and Executive Function/Working Memory but not Verbal Memory or Language composite scores. Conclusions: This study is consistent with findings in sporadic Alzheimer disease of early problems with memory, Visuospatial function, and particularly with executive function in PSl mutation carriers. Depression, gender, and presence of an APOE ?4 allele did not demonstrate large influences on neuropsychological performance. Copyright " 2005 by AAN Enterprises, Inc.",,,,,,"10.1212/01.wnl.0000172919.50001.d6",,,"http://hdl.handle.net/20.500.12104/43100","http://www.scopus.com/inward/record.url?eid=2-s2.0-23844553466&partnerID=40&md5=8298e983532db3b69c12a64236878d69",,,,,,"4",,"Neurology",,"552
558",,"65",,"Scopus
WOS",,,,,,,,,,,,"Neuropsychological function in nondemented carriers of presenilin-1 mutations",,"Article" "42281","123456789/35008",,"Gonzalez-Castan?da, R.E., Neuroscience Division, Centro de Investigacion Biomedica de Occidente del Instituto Mexicano del Seguro Social, Guadalajara, Mexico; Castellanos-Alvarado, E.A., Neuroscience Division, Centro de Investigacion Biomedica de Occidente del Instituto Mexicano del Seguro Social, Guadalajara, Mexico; Flores-Marquez, M.R., Department of Pathology, Centro Medico Nacional de Occidente del Instituto Mexicano del Seguro Social, Guadalajara, Mexico; Gonzalez-Perez, O., Department of Neurosciences, Centro Universitario en Ciencias de la Salud de la Universidad de Guadalajara, Guadalajara, Mexico; Luquin, S., Department of Neurosciences, Centro Universitario en Ciencias de la Salud de la Universidad de Guadalajara, Guadalajara, Mexico; García-Estrada, J., Neuroscience Division, Centro de Investigacion Biomedica de Occidente del Instituto Mexicano del Seguro Social, Guadalajara, Mexico; Ramos-Remus, C., Department of Rheumatology, Centro Medico Nacional de Occidente del Instituto Mexicano del Seguro Social, Guadalajara, Mexico, Colomos 2292, Providencia, Guadalajara, Jalisco 44620, Mexico",,"Gonzalez-Castaneda, R.E.
Castellanos-Alvarado, E.A.
Flores-Marquez, M.R.
Gonzalez-Perez, O.
Luquin, S.
García-Estrada, J.
Ramos-Remus, C.",,"2007",,"Prednisone (PDN) impairs cognitive functioning and brain structures in humans and animals. Deflazacort (DFZ) is a synthetic glucocorticoid claimed to have lesser side effects than prednisone. The objective of this study was to assess whether chronic administration (90 days) of DFZ produces less neuronal degeneration and glial reactivity than PDN. Male Swiss-Wistar rats were studied. Controls received 0.1 ml distilled water orally. The PDN group received prednisone 5 mg per kg per day orally, and the DFZ group received deflazacort 6 mg per kg per day orally. This model had to be assembled in three different occasions due to excess mortality in the DFZ group. A fourth model was assembled using only the DFZ group and slides of water and PDN-exposed rats from a previous study were used as comparators. The index of degenerated neurons and the number and cytoplasmic transformation of astrocytes and microglia cells were evaluated in the prefrontal cortex, CA1, and CA3 hippocampus. The results show that the overall mortality was 49% in the DFZ group, 4.5% in the PDN group, and none of the controls died. Routine necropsy showed infection in multiple organs. The PDN group had two times higher neuronal degeneration in the prefrontal cortex, almost 11 times in CA1, and four times in CA3 hippocampus when compared with controls and DFZ group. Astrocytes reactivity was increased in the PDN- and DFZ-exposed rats compared with controls. The DFZ group showed an average of four times less microgial cells in the three studied regions when compared with controls and the PDN group. In conclusion, it seems that DFZ at the equivalent licensed dose produced a stronger immunosuppressive effect - systemic and in brain tissue - than PDN, but induced less neuronal damage. The immunesuppressant magnitude of DFZ should be further studied in clinical settings. " Clinical Rheumatology 2006.
URI: http://hdl.handle.net/20.500.12104/40502
http://www.scopus.com/inward/record.url?eid=2-s2.0-34250740520&partnerID=40&md5=56a2ab565bb7682df040a60dcb75d884
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