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

Morphologic aspects and structure-properties relations of high impact polystyrene

A tenacificação da matriz vítrea de poliestireno (PS) pela adição de borracha polibutadiênica, que tem como conseqüência um aumento de sua resistência ao impacto, origina um polímero com características singulares, o Poliestireno de Alto Impacto (HIPS). Durante a polimerização in situ de estireno em uma solução de borracha, ocorre a formação de cadeias graftizadas de poliestireno no polibutadieno, as quais aumentam a interação interfacial borracha-PS. O HIPS é um material com ampla aplicação na indústria de embalagens e, principalmente, em gabinetes de refrigeradores, a chamada linha branca. O objetivo deste artigo é destacar e discutir as características estruturais e morfológicas do HIPS e a implicação destas na determinação de suas propriedades. Também foram revisadas as técnicas comumente utilizadas na caracterização morfológica e estrutural do HIPS.Toughening of glassy polystyrene (PS) matrix by polybutadiene rubber addition mainly increases its impact resistance. The rubber modified polymer, known as High Impact Polystyrene (HIPS), has unique features. During the in situ styrene polymerization in a rubber solution grafting of polystyrene chains occurs onto polybutadiene molecules and magnifies the interaction at the rubber-PS interface. The HIPS is a material that has a large application in the packaging industry and refrigerator cabinets. The aim of this paper is to point out and discuss some of the structural and morphological characteristics of HIPS and its correlation with general properties. The standard techniques applied in the characterization of the structure and morphology of HIPS were revised

Blendas de poliestireno e poli ácido lático

PETROBRASUniversidade Federal do Rio Grande do SulQuímicaDepositad

Blendas de poliestireno e poli ácido lático

PETROBRASUniversidade Federal do Rio Grande do SulQuímicaDepositad

Additive antioxidant treatment prevents cognitive impairment after CM.

<p>C57BL/6 (A and B) and SW mice (C and D) (n = 12–20/group) were infected with PbA or PyXL, respectively (10⁶ PRBC). As a control, one group was inoculated with the same number of uninfected RBC (n = 6/group). Starting on day 6 post infection, infected mice were divided into 2 groups and treated orally with chloroquine (25 mg/kg b.w.), chloroquine plus desferoxamine (DFX, 20 mg/kg b.w., i.p.), chloroquine plus N-acetylcysteine (NAC, 20 mg/kg b.w., i.p.) or with the combination of chloroquine/DFX/NAC for 7 days. On day 15 and 16 post-infection all the animals were submitted to open field task training and test sessions, respectively. Data are expressed as mean ± S.E.M. of crossings (<i>A and C</i>) and rearings (<i>B and D</i>) in training (<i>gray bars</i>) and test (<i>black bars</i>) sessions; *significant difference between groups in training and test sessions (<i>p</i><0.05, Student's T test). Panels E–M ilustrate histological examinations (H&E staining) of different brain regions in non-infected (RBC), infected (PRBC, PbA 10⁶) and mice treated with the combination of chloroquine/DFX/NAC (PbA+Cq+AOX). E–G) cerebral cortex; H–J) hippocampus; K–M) and cerebellum. Microvascular congestion and plugging (arrows) were detected in all analyzed regions in PbA-infected mice, but were not seen in controls or treated animals rescued with chloroquine and additive antioxidants. Scale bar, 100 µm.</p

Summary of primary screening results.

<p>Values of individual parameters of Cerebral Malaria (CM) at days 3 and 6 post-infection are shown. Animals infected with malarial parasite (PbA, Pch, PyNXL and PyXL) were compared to animals of the same background inoculated with uninfected RBC. Data are shown as median (upper/lower quartile) or mean ± SD when appropriated. N = 12–15/group.</p><p>*p<0.05 or less by Wilcoxon Signed Rank Test.</p

Time-course of parasitemia and survival rate of C57BL6, BALB/c and Swiss Webster (SW) mice after infection with PbA, Pch, PyNXL or PyXL (n = 12–20/group).

<p>Date on parasitemia (A and B) are shown as mean ± SEM. Comparisons of C57BL6-PbA versus C57BL6-Pch (#), C57BL6-PbA versus BALB/c-PbA (*) and C57BL6-Pch versus BALB/c-PbA (+), were significant by Tukey's Multiple Comparison Test (A). (θ) and (∞) indicate p<0.05 in relation to day 3 post-infection during PyNXL and PyXL infection, respectively (B). Survival curves (C and D) were evaluated by Log-rank (Mantel-Cox) and Gehan-Breslow-Wilcoxon tests.</p