Avaliação de novo protótipo “babypump” para circulação extracorpórea (cec): teste de resposta a hemostasia in vitro / Evaluation of a new babypump prototype for extracorporeal circulation (cec): in vitro hemostasis response test

As doenças cardiovasculares são as principais causas de morte no mundo e um dos tratamentos indicados para os casos mais graves é a cirurgia, que nesta condição, necessita de circulação extracorpórea. Estas bombas propulsoras podem ser responsáveis por traumas nas células sanguíneas, levando à hemólise. Este fato motivou este estudo, cujo objetivo é a avaliação do Índice Normalizado de Hemólise, durante um ensaio “in vitro” numa circulação extracorpórea e avaliar o desempenho hidrodinâmico do dispositivo. A metodologia seguiu o procedimento “Teste de Hemólise –HarboeMethod”. Neste ensaio, o dispositivo não suportou chegar até sua rotação máxima, gerando trepidação e ruído. O INH resultou em 2,23 g/100L, esse valor encontra-se acima do valor normal máximo descrito por Nosé(1998) (0,06g/100L.), o qual reprova odispositivo para o uso, sugerindo assim o seu redelineamento, a fim de promover maior resistência ao fluxo imposto.

Reduced graphene oxide: nanotoxicological profile in rats.

BACKGROUND: We have previously demonstrated that reduced graphene oxide (rGO) administered intravenously in rats was detected inside the hippocampus after downregulation of the tight and adherens junction proteins of the blood-brain barrier. While down-regulators of junctional proteins could be useful tools for drug delivery through the paracellular pathway, concerns over toxicity must be investigated before clinical application. Herein, our purpose was to trace whether the rGO inside the hippocampus triggered toxic alterations in this brain region and in target organs (blood, liver and kidney) of rats at various time points (15 min, 1, 3 h and 7 days). RESULTS: The assessed rGO-treated rats (7 mg/kg) were clinically indistinguishable from controls at all the time points. Hematological, histopathological (neurons and astrocytes markers), biochemical (nephrotoxicity and hepatotoxicity assessment) and genotoxicological based tests showed that systemic rGO single injection seemed to produce minimal toxicological effects at the time points assessed. Relative to control, the only change was a decrease in the blood urea nitrogen level 3 h post-treatment and increases in superoxide dismutase activity 1 h and 7 days post-treatment. While no alteration in leukocyte parameters was detected between control and rGO-treated animals, time-dependent leukocytosis (rGO-1 h versus rGO-3 h) and leukopenia (rGO-3 h versus rGO-7 days) was observed intra-treated groups. Nevertheless, no inflammatory response was induced in serum and hippocampus at any time. CONCLUSIONS: The toxic effects seemed to be peripheral and transitory in the short-term analysis after systemic administration of rGO. The effects were self-limited and non-significant even at 7 days post-rGO administration.

Evidences of endocytosis via caveolae following blood-brain barrier breakdown by Phoneutria nigriventer spider venom.

Spider venoms contain neurotoxic peptides aimed at paralyzing prey or for defense against predators; that is why they represent valuable tools for studies in neuroscience field. The present study aimed at identifying the process of internalization that occurs during the increased trafficking of vesicles caused by Phoneutria nigriventer spider venom (PNV)-induced blood-brain barrier (BBB) breakdown. Herein, we found that caveolin-1α is up-regulated in the cerebellar capillaries and Purkinje neurons of PNV-administered P14 (neonate) and 8- to 10-week-old (adult) rats. The white matter and granular layers were regions where caveolin-1α showed major upregulation. The variable age played a role in this effect. Caveolin-1 is the central protein that controls caveolae formation. Caveolar-specialized cholesterol- and sphingolipid-rich membrane sub-domains are involved in endocytosis, transcytosis, mechano-sensing, synapse formation and stabilization, signal transduction, intercellular communication, apoptosis, and various signaling events, including those related to calcium handling. PNV is extremely rich in neurotoxic peptides that affect glutamate handling and interferes with ion channels physiology. We suggest that the PNV-induced BBB opening is associated with a high expression of caveolae frame-forming caveolin-1α, and therefore in the process of internalization and enhanced transcytosis. Caveolin-1α up-regulation in Purkinje neurons could be related to a way of neurons to preserve, restore, and enhance function following PNV-induced excitotoxicity. The findings disclose interesting perspectives for further molecular studies of the interaction between PNV and caveolar specialized membrane domains. It proves PNV to be excellent tool for studies of transcytosis, the most common form of BBB-enhanced permeability.

Absence of mutagenic and recombinagenic activity of multi-walled carbon nanotubes in the Drosophila wing-spot test and Allium cepa test.

In order to assess the safety of the carbon nanotubes to human health and the environment, we investigated the potential toxicity and ability of multi-walled carbon nanotubes (NT), to induce DNA damage by employing the Allium cepa genotoxicity/mutagenicity test and the Somatic Mutation and Recombination Test (SMART) in the fruitfly, Drosophila melanogaster. The results demonstrated that NT did not significantly induce genotoxic or mutagenic effects in the Allium cepa test. All concentrations evaluated in the SMART assay showed survival rates higher than 90percent, indicating the absence of chronic toxicity for NT. Furthermore, the various treatments showed no significant increase in the NT mutation and recombination frequencies in mwh/flr(3) genotype compared to respective negative controls, demonstrating the absence of DNA damage caused by NT.

Osteopontin, a chemotactic protein with cytokine-like properties, is up-regulated in muscle injury caused by Bothrops lanceolatus (fer-de-lance) snake venom.

Osteopontin (OPN) is a chemotactic, adhesive protein whose receptors include some integrins and matrix proteins known to have role in inflammatory and repair processes. We examined the time course of OPN expression at acute and chronic stages after intramuscular injection of Bothrops lanceolatus venom in rats. Additionally, we examined the expression of CD68 (a marker for phagocytic macrophages) and the myogenic factors, myoD and myogenin. There was a biphasic upregulation of OPN (6-48 h and 3-14 days post-venom), i.e., during acute inflammation and myogenic cell proliferation and differentiation phases. OPN was detected in CD68 + macrophages, fibroblasts, normal and damaged myofibers, myoblasts and myotubes. Myogenin was expressed in the cytoplasm (atypical pattern) and nucleus of myoblasts and myotubes from 18 h to 7 days, after which it was expressed only in nuclei. Macrophage numbers, OPN and myogenin expression were still elevated at 7, 14 and 7 days. At 3 days, when OPN achieved the peak, some clusters of myoblasts were within regions of intense collagen deposition. Fibrosis may represent limitation for repairing processes and may explain the small diameter of regenerated fibers at 21 days post-venom. The expression of OPN in the course of venom-induced damage and regeneration suggests stages-specific mediation role along the whole process.