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Effects of treatment with hydroxyurea in the oral cavity of pediatric patients with sickle cell anemia

Grant number: 14/13469-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): September 01, 2014
Effective date (End): December 31, 2017
Field of knowledge:Health Sciences - Dentistry - Dental Clinics
Principal researcher:Cristiane Yumi Koga Ito
Grantee:Marcia Hiromi Tanaka
Home Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Estadual Paulista (UNESP). Campus de São José dos Campos. São José dos Campos , SP, Brazil


Hydroxyurea (HU) has been considered an effective therapeutic option for the sickle cell anemia (SCA). However, in the literature, no studies on its effects on the oral microflora, saliva and odontogenesis of children with SCA treated with HU were detected. One-hundred twenty five children, aged 6 to 14 years, divided into 5 groups will be included in this study: G1 (25 patients with SCA at the beginning of treatment with HU), G2 (25 patients with SCA and under treatment with HU for 3 months), G3 (25 patients with SCA and under treatment with HU for 6 months), G4 (25 children with SCA and not undergoing treatment with HU) and G5 (25 systemically healthy children with similar profile, paired-control). This study will be divided into 3 subprojects. The first subproject will include the groups G3, G4 and G5 and the aim will be to evaluate the following aspects in pediatric patients with SCA under treatment with HU or not, comparing with controls: 1) presence of oral lesions and potentially superinfectant microorganisms; 2) the incidence of caries and caries risk factors by means of the study of saliva-related microbiological and immunological factors; 3) salivary proteome. For this purpose, the following methodologies will be evaluated: a) presence of species of Candida, staphylococci, enterobacteria and Pseudomonas, as well as the antimicrobial susceptibility of the isolates; b) association between dmf-t/DMF-T, presence of cariogenic bacteria and quantification of anti-Streptococcus mutans IgA and IgM; c) mass spectrometry. The second subproject will include the groups G1, G2 and G3 and has the aim to study longitudinally the bacterial oral microflora and the salivary proteome in children under HU therapy for the period of 3 and 6 months. For this purpose, the samples will be collected at baseline, and after 3 and 6 months of treatment. The samples will be analyzed by Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS) and mass spectrometry. In the subproject 3, the effect of HU on the odontogenesis and the mineralization of dental tissues will be assessed. Fifty-four male Wistar rats will be divided into 3 groups (n = 18). Group 1- animals treated with a single dosis of HU, Group 2- animals treated with sequential dose of HU for one week, and Group 3- control animals treated only with physiologic solution. The specimens will be analyzed by light microscopy (LM), contact microradiography (CMR) and scanning electron microscopy (SEM). The data obtained in the tests will be statistically analyzed using the GraphPad Prism software version 3.02 (GraphPad Software Inc., San Diego, CA, USA). In order to employ the most appropriate test, the adherence to the normal curve will be checked by a test of normality. The results will be analyzed by appropriate statistical tests, with significance level of 5%.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
TEODORO, GUILHERME RODRIGUES; LACERDA GONTIJO, ALINE VIDAL; BORGES, ALINE CHIODI; TANAKA, MARCIA HIROMI; GOUVEA LIMA, GABRIELA DE MORAIS; SALVADOR, MARCOS JOSE; KOGA-ITO, CRISTIANE YUMI. Gallicacid/hydroxypropyl-beta-cyclodextrin complex: Improving solubility for application on in vitro/in vivo Candida albicans biofilms. PLoS One, v. 12, n. 7 JUL 11 2017. Web of Science Citations: 5.

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