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.

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.

Environmental Nanoparticles Reach Human Fetal Brains.

Anthropogenic ultrafine particulate matter (UFPM) and industrial and natural nanoparticles (NPs) are ubiquitous. Normal term, preeclamptic, and postconceptional weeks(PCW) 8-15 human placentas and brains from polluted Mexican cities were analyzed by TEM and energy-dispersive X-ray spectroscopy. We documented NPs in maternal erythrocytes, early syncytiotrophoblast, Hofbauer cells, and fetal endothelium (ECs). Fetal ECs exhibited caveolar NP activity and widespread erythroblast contact. Brain ECs displayed micropodial extensions reaching luminal NP-loaded erythroblasts. Neurons and primitive glia displayed nuclear, organelle, and cytoplasmic NPs in both singles and conglomerates. Nanoscale Fe, Ti, and Al alloys, Hg, Cu, Ca, Sn, and Si were detected in placentas and fetal brains. Preeclamptic fetal blood NP vesicles are prospective neonate UFPM exposure biomarkers. NPs are reaching brain tissues at the early developmental PCW 8-15 stage, and NPs in maternal and fetal placental tissue compartments strongly suggests the placental barrier is not limiting the access of environmental NPs. Erythroblasts are the main early NP carriers to fetal tissues. The passage of UFPM/NPs from mothers to fetuses is documented and fingerprinting placental single particle composition could be useful for postnatal risk assessments. Fetal brain combustion and industrial NPs raise medical concerns about prenatal and postnatal health, including neurological and neurodegenerative lifelong consequences.

In vitro and in vivo cysticidal activity of extracts and isolated flavanone from the bark of Prunus serotina: A bio-guided study.

Currently, neurocysticercosis treatment involves two drugs: albendazole and praziquantel; however, their efficacy is suboptimal and new cysticidal drugs are needed. The present paper reports the cysticidal activity of extracts of the bark from Prunus serotina against Taenia crassiceps cysts and the isolation and identification of the main components of the most active extract. Results showed that all extracts displayed in vitro cysticidal activity (EC50=17.9-88.5µg/mL), being the methanolic the most active and selective. Also, methanolic extract exhibited in vivo efficacy at 300mg/kg which was similar to that obtained with albendazole. Bio-guided fractionation of methanolic extract led the isolation of 2,3-dihydro-5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one (naringenin, NGN), 3,4,5-trimethoxybenzoic acid and 1,3,5-trimethoxybenzene. NGN exhibited in vitro activity, in a time-concentration-dependent manner (EC50=89.3µM]. Furthermore, NGN at a dose of 376.1µmol/kg displayed similar in vivo efficacy than those obtained with albendazole at 188.4µmol/kg. NGN also caused a high level of damage in all parasite tissue in a similar manner than that observed with the methanolic extract. This study represents the first report of the cysticidal properties of the bark of P. serotina. NGN was identified as the main active compound of this specie and other studies are required to explore the potential of this flavanone as cysticidal agent.

Bioabsorbable implant as a tracheal wall substitute in young developing canines.

This study evaluated a polylactic and polyglycolic acid (PLA/PGA) implant as a partial tracheal substitute in young developing canines. This experimental and longitudinal study included local stray pups that received substitution of a short cervical tracheal segment with a PLA 85%/PGA 15% plaque. We measured clinical, endoscopic, and tomographic variables for 1 year, at which time we performed histomorphological evaluations of the implant using light and electron microscopy. There were no adverse events throughout the clinical progression. On endoscopic evaluation, the implant was covered with mucosal tissue beginning in the first month, without granulation or stenosis, and the circular shape of the trachea was altered. Tomographic images of the tracheal area at the implant site were similar to adjacent healthy areas (p = 0.423). At the end of the follow-up period, the plaque had biodegraded, and the space was covered by pseudostratified epithelium and ciliated cells similar to the neighboring tissue. Implantation of a PLA/PGA plaque constituted an effective (functional) replacement of a short semicircular cervical tracheal segment without limiting the growth of the recipient. Additional studies are required to prove the efficacy of these implants for larger tracheal segment replacements and in subjects at different stages of development.

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.