Cognitive Dysfunction Is Sustained after Rescue Therapy in Experimental Cerebral Malaria, and Is Reduced by Additive Antioxidant Therapy

Neurological impairments are frequently detected in children surviving cerebral malaria (CM), the most severe neurological complication of infection with Plasmodium falciparum. The pathophysiology and therapy of long lasting cognitive deficits in malaria patients after treatment of the parasitic disease is a critical area of investigation. In the present study we used several models of experimental malaria with differential features to investigate persistent cognitive damage after rescue treatment. Infection of C57BL/6 and Swiss (SW) mice with Plasmodium berghei ANKA (PbA) or a lethal strain of Plasmodium yoelii XL (PyXL), respectively, resulted in documented CM and sustained persistent cognitive damage detected by a battery of behavioral tests after cure of the acute parasitic disease with chloroquine therapy. Strikingly, cognitive impairment was still present 30 days after the initial infection. In contrast, BALB/c mice infected with PbA, C57BL6 infected with Plasmodium chabaudi chabaudi and SW infected with non lethal Plasmodium yoelii NXL (PyNXL) did not develop signs of CM, were cured of the acute parasitic infection by chloroquine, and showed no persistent cognitive impairment. Reactive oxygen species have been reported to mediate neurological injury in CM. Increased production of malondialdehyde (MDA) and conjugated dienes was detected in the brains of PbA-infected C57BL/6 mice with CM, indicating high oxidative stress. Treatment of PbA-infected C57BL/6 mice with additive antioxidants together with chloroquine at the first signs of CM prevented the development of persistent cognitive damage. These studies provide new insights into the natural history of cognitive dysfunction after rescue therapy for CM that may have clinical relevance, and may also be relevant to cerebral sequelae of sepsis and other disorders

Mandibular growth and dentoalveolar development in the treatment of Class II, division 1, malocclusion using Balters Bionator according to the skeletal maturation

OBJECTIVE: The purpose of the study was to evaluate the influence of the skeletal maturation in the mandibular and dentoalveolar growth and development during the Class II, division 1, malocclusion correction with Balters bionator. METHODS: Three groups of children with Class II, division 1, malocclusion were evaluated. Two of them were treated for one year with the bionator of Balters appliance in different skeletal ages (Group 1: 6 children, 7 to 8 years old and Group 2: 10 children, 9 to 10 years old) and the other one was followed without treatment (Control Group: 7 children, 8 to 9 years old). Lateral 45 degree cephalometric radiographs were used for the evaluation of the mandibular growth and dentoalveolar development. Tantalum metallic implants were used as fixed and stable references for radiograph superimposition and data acquisition. Student's t test was used in the statistical analysis of the displacement of the points in the condyle, ramus, mandibular base and dental points. Analysis of variance one-fixed criteria was used to evaluate group differences (95% of level of significance). RESULTS: The intragroup evaluation showed that all groups present significant skeletal growth for all points analyzed (1.2 to 3.7 mm), but in an intergroup comparison, the increment of the mandibular growth in the condyle, ramus and mandibular base were not statically different. For the dentoalveolar modifications, the less mature children showed greater labial inclination of the lower incisors (1.86 mm) and the most mature children showed greater first permanent molar extrusion (4.8 mm).OBJETIVO: avaliar a influência da maturação óssea no processo de crescimento e de desenvolvimento mandibular e dentoalveolar durante a correção da Classe II, divisão 1, com o Bionator de Balters. MÉTODOS: foram avaliados três grupos de crianças com Classe II, divisão 1. Dois grupos foram tratados por um ano com o aparelho Bionator de Balters, em diferentes idades esqueléticas (Grupo 1: 6 crianças, com 7 a 8 anos de idade; e Grupo 2: 10 crianças, com 9 a 10 anos); e um grupo sem tratamento (Grupo controle: 7 crianças, com 8 a 9 anos). Telerradiografias laterais em norma de 45º foram utilizadas para a avaliação do crescimento mandibular e para o desenvolvimento dentoalveolar. Implantes metálicos de tântalo foram usados como referência fixa e estável para sobreposições radiográficas e aquisição de dados. Na análise estatística do deslocamento de pontos localizados na região de côndilo, corpo e base mandibular e de pontos dentários, foi empregado o teste t de Student; para avaliar as diferenças entre os grupos, usou-se a análise de variância a um critério de classificação (nível de significância de 95%). RESULTADOS: os grupos, quando avaliados individualmente, apresentaram crescimento de todos os pontos esqueléticos de forma significativa (1,2 a 3,7mm); porém, quando comparados entre si, a quantidade de crescimento na região do côndilo, ramo e base da mandíbula não foi estatisticamente diferente. Quanto às alterações dentárias, ocorreu maior inclinação dos incisivos inferiores para vestibular (1,86mm) nos pacientes menos maduros, e maior extrusão dos primeiros molares permanentes (4,8mm) nos pacientes mais maduros.Barretos UniversityUNESP School of Dentistry of Araraquara Children's Clinic DepartmentUSP FOBRibeirão Preto UniversityUNESP School of Dentistry of Araraquara Children's Clinic Departmen