Postnatal zinc deficiency due to giardiasis disrupts hippocampal and cerebellar development.

BACKGROUND: Giardiasis and zinc deficiency have been identified as serious health problems worldwide. Although Zn depletion is known to occur in giardiasis, no work has investigated whether changes occur in brain structures. METHODS: Three groups of gerbils were used: control (1), orogastrically inoculated on day 3 after birth with trophozoites of two isolates of Giardia intestinalis (HGINV/WB) group (2 and 3). Estimates were made at five ages covering: establishment of infection, Giardia population growth, natural parasite clearance and a post-infection age. QuantiChrome zinc assay kit, cresyl violet staining and TUNEL technique were used. RESULTS: A significant decrease (p<0.01) in tissue zinc was observed and persisted after infection. Cytoarchitectural changes were observed in 75% of gerbils in the HGINV or WB groups. Ectopic pyramidal neurons were found in the cornus ammonis (CA1-CA3). At 60 and 90 days of age loss of lamination was clearly visible in CA1. In the dentate gyrus (DG), thinning of the dorsal lamina and abnormal thickening of the ventral lamina were observed from 30 days of age. In the cerebellum, we found an increase (p<0.01) in the thickness of the external granular layer (EGL) at 14 days of age that persisted until day 21 (C 3 ± 0.3 µm; HGINV 37 ± 5 µm; WB 28 ± 3 µm); Purkinje cell population estimation showed a significant decrease; a large number of apoptotic somas were observed scattered in the molecular layer; in 60 and 90 days old gerbils we found granular cell heterotopia and Purkinje cell ectopia. The pattern of apoptosis was different in the cerebellum and hippocampus of parasitized gerbils. CONCLUSION: The morphological changes found suggest that neuronal migration is affected by zinc depletion caused by giardiasis in early postnatal life; for the first time, the link between giardiasis-zinc depletion and damaged brain structures is shown. This damage may explain the psychomotor/cognitive delay associated with giardiasis. These findings are alarming. Alterations in zinc metabolism and signalling are known to be involved in many brain disorders, including autism.

Cysticidal activity of extracts and isolated compounds from Teloxys graveolens: In vitro and in vivo studies.

In the search of new alternatives for neurocysticercosis treatment, the cysticidal activity of organic extracts of Teloxys graveolens was evaluated. The in vitro activity of hexane, ethyl acetate and methanol extracts against Taenia crassiceps cysts was tested and the selectivity index relative to human fibroblasts was determined. Subsequently, the in vivo efficacy of the methanolic extract at doses of 200 and 500 mg/kg in the murine cysticercosis model was evaluated. The ultrastructural effects in vitro and in vivo of the methanolic extract were also investigated using scanning electron microscopy. Additionally, a bioassay-guided fractionation for the isolation of the cysticidal components was performed. Our in vitro findings revealed that all extracts exhibited good cysticidal activity with EC50 values from 44.8 to 67.1 µg/mL. Although the ethyl acetate and methanolic extracts displayed low cytotoxicity, the methanolic extract was the most selective. The methanolic extract also showed in vivo efficacy which was similar to that obtained with ABZ. Significant alterations were found on the germinal layer of the cysts, with a high accumulation of granules of glycogen and vacuoles. The bioguided fractionation of methanolic extract led to the isolation of three flavonoids: chrysin, pinocembrin and pinostrobin; among them, pinocembrin was the compound that displayed cysticidal activity. This is the first study which reveals that T. graveolens could be a potential source for cysticidal and non-toxic compounds.

Fibrocollagen-covered prosthesis for a noncircumferential segmental tracheal replacement.

OBJECTIVE: Fibrocollagen-covered polyester meshes can be used as possible substitutions for tracheal segments if they become integrated into the tissue without complications. The aim of this study was to assess a fibrocollagen-covered polyester prosthesis to be used as a substitution for a tracheal segment. METHODS: We performed a blind, randomized experimental assay. Adult Wistar rats were assigned to one of 2 groups. Prostheses were made by implanting polyester tubing in a group of animals to cover them with homologous collagen. They were implanted as substitutions of tracheal segments in the experimental group after creating a defect in the anterior wall of the trachea. Clinical, histomorphologic, and immunohistochemical assessments were made at 4 different time points. RESULTS: The experimental group presented some respiratory distress signs during the first 7 to 10 days, such as stertors, hissing, and low motor activity. After this initial period, the symptoms subsided progressively and disappeared at the end of the first month. These respiratory symptoms caused no mortality. Initially undifferentiated monolayer cells predominated on the implant's surface, but during the last 2 months, the proportion of epithelial and ciliated cells was similar to that seen in control animals. Types I, III, and V collagen fibers were identified around the mesh. The intraluminal area of the tracheas with prostheses and prosthesis thickness were larger during the 4 months of the experiment. The increase in thickness was due to angiogenesis without evidence of fibrosis or chronic inflammation. CONCLUSIONS: Polyester-collagen prostheses used as substitutions of tracheal segments in rats enabled the proliferation of normal respiratory epithelium and maintained tracheal function without collapse, inflammatory reaction, or secondary stenosis.