Rapid and prolonged response of oligodendrocyte lineage cells in standard acute cuprizone demyelination model revealed by in situ hybridization.

Dietary administration of a copper chelator, cuprizone (CPZ), has long been reported to induce intense and reproducible demyelination of several brain structures such as the corpus callosum. Despite the widespread use of CPZ as an animal model for demyelinating diseases such as multiple sclerosis (MS), the mechanism by which it induces demyelination and then allows robust remyelination is still unclear. An intensive mapping of the cell dynamics of oligodendrocyte (OL) lineage during the de- and remyelination course would be particularly important for a deeper understanding of this model. Here, using a panel of OL lineage cell markers as in situ hybridization (ISH) probes, including Pdgfra, Plp, Mbp, Mog, Enpp6, combined with immunofluorescence staining of CC1, SOX10, we provide a detailed dynamic profile of OL lineage cells during the entire course of the model from 1, 2, 3.5 days, 1, 2, 3, 4,5 weeks of CPZ treatment, as well as after 1, 2, 3, 4 weeks of recovery from CPZ treatment. The result showed an unexpected early death of mature OLs and response of OL progenitor cells (OPCs) in vivo upon CPZ challenge, and a prolonged upregulation of myelin-forming OLs compared to the intact control even 4 weeks after CPZ withdrawal. These data may serve as a basic reference system for future studies of the effects of any intervention on de- and remyelination using the CPZ model, and imply the need to optimize the timing windows for the introduction of pro-remyelination therapies in demyelinating diseases such as MS.

Safety Assessment of Zinc Salts as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 27 inorganic and organometallic zinc salts as used in cosmetic formulations; these salts are specifically of the 2+ (II) oxidation state cation of zinc. These ingredients included in this report have various reported functions in cosmetics, including hair conditioning agents, skin conditioning agents, cosmetic astringents, cosmetic biocides, preservatives, oral care agents, buffering agents, bulking agents, chelating agents, and viscosity increasing agents. The Panel reviewed the relevant data for these ingredients, and concluded that these 27 ingredients are safe in cosmetics in the present practices of use and concentration described in this safety assessment when formulated to be non-irritating.

Biocompatibility of EDTA, EGTA and citric acid

Este estudo in vivo avaliou o potencial irritativo do EDTA, EGTA, ácido cítrico e soro fisiológico (controle) durante a fase exsudativa do processo inflamatório. Aplicou-se, intravenosamente na veia caudal lateral de 32 ratos machos da linhagem "Wistar", variação albina, 20 mg/kg de azul de Evans 2%. Em seguida, no tecido subcutâneo da região dorsal dos animais injetou-se 0,01 mL das soluções testes. Após os intervalos de ½, 1, 3 e 6 horas, os animais foram sacrificados, suas peles dorsais foram excisadas e submetidas à análise do corante extravasado pela espectrofotometria de absorção de luz. Os dados obtidos foram avaliados pela análise de variância a 2 critérios e teste de Tukey. Em todos os períodos de tempo estudados, os maiores valores de corante extravasado foram observados no grupo do EDTA seguido pelos grupos do EGTA e ácido cítrico, em comparação ao grupo controle. Houve diferença estatisticamente significante entre todas as soluções testadas (p<0.01). Quando considerado o fator tempo, notou-se diferença significante entre os grupos de 3 e 6 horas (p<0.05). Entretanto, não houve diferença entre os grupos de tempo de ½ e 1 hora. Dentre os ácidos orgânicos avaliados, os resultados demonstraram que o ácido cítrico apresentou o menor potencial irritativo.