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1.
Heliyon ; 5(8): e02308, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31485519

RESUMO

The development and use of nanomaterials are increasing significantly. Among nanomaterials, carbon nanotubes are of particular interest due to its distinctive physicochemical properties. This material composed of sheets of graphite has very high thermal conductivity, metallic-type electrical conductivity, stiffness, toughness and unique ability to bond to itself in an extended network with extraordinary strength. Its application in the industry is continuously growing, which could lead to the accumulation in the environment and a consequent impact on both humans and ecosystems. Considering that environmental systems are dynamic, it is difficult to predict the risks associated with the release of nanomaterials to the environment. Bioindicators are useful tools as primary signals of environmental risk, and their responses reveal the organism and ecosystem health. In the present study, we evaluated the impact of multi-walled carbon nanotubes with different dimensions and agglomeration pattern on zebrafish embryo and larvae; mainly, studies were focused on physiological and behavioral responses. In embryos, measurements were hatching rate, morphology changes, and viability. In larvae, locomotor activity, heart rate, innate inflammatory response, general and tissue-specific morphology were measured. MWCNT-S (short, wide and mostly dispersed) caused depression of the locomotor activity of larvae, indicating an alteration of the central nervous system, and depression of neutrophil migration activity. MWCNT-L (long, thin and agglomerated) caused malformations during larval development, a decrease of neutrophil migration and alteration of cardiac rhythm. Results obtained for both carbon nanotubes were different, highlighting the importance of dimensions of the same nanomaterial, and also the kind of agglomeration and shape adopted, for the toxic effects on organisms.

2.
Neurotoxicol Teratol ; 66: 17-24, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29366689

RESUMO

Epilepsy is a neurological disorder treated with antiepileptic drugs (AEDs). Since AEDs are administered in women in childbearing age, it is critical to study if drugs are capable of inducing developmental toxicity. Along the bibliography available, there is no research comparing teratogenicity and anticonvulsant effect within the same study. In the present study, we evaluated the teratogenic and anticonvulsant effects of six different AEDs: carbamazepine, levetiracetam, lamotrigine, phenobarbital, phenytoin and valproic acid. Zebrafish was the selected animal model because of its small size, rapid external development and similar neurophysiology to mammals. Zebrafish embryo and larvae were exposed to AEDs. Embryo development was monitored by their hatching and morphology. In larvae, locomotor activity was measured as a parameter of neurotoxicity. Finally, anticonvulsant effect was determined after exposure to AEDs in zebrafish larvae treated with the proconvulsant drug pentylenetetrazole. Our results suggest that lamotrigine and phenytoin could be suitable non-teratogenic and efficient anticonvulsant options for epilepsy treatment.


Assuntos
Anticonvulsivantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Larva/efeitos dos fármacos , Teratogênese/efeitos dos fármacos , Peixe-Zebra/embriologia , Animais , Anticonvulsivantes/toxicidade , Avaliação Pré-Clínica de Medicamentos
3.
Biophys Rev ; 9(5): 775-791, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28884420

RESUMO

In recent years, the use of commercial nanoparticles in different industry and health fields has increased exponentially. However, the uncontrolled application of nanoparticles might present a potential risk to the environment and health. Toxicity of these nanoparticles is usually evaluated by a fast screening assay in zebrafish (Danio rerio). The use of this vertebrate animal model has grown due to its small size, great adaptability, high fertilization rate and fast external development of transparent embryos. In this review, we describe the toxicity of different micro- and nanoparticles (carbon nanotubes, dendrimers, emulsions, liposomes, metal nanoparticles, and solid lipid nanoparticles) associated to their biophysical properties using this model. The main biophysical properties studied are size, charge and surface potential due to their impact on the environment and health effects. The review also discusses the correlation of the effects of the different nanoparticles on zebrafish. Special focus is made on morphological abnormalities, altered development and abnormal behavior. The last part of the review debates changes that should be made in future directions in order to improve the use of the zebrafish model to assess nanotoxicity.

4.
J Mol Endocrinol ; 47(2): 167-77, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21727153

RESUMO

Acromegaly is associated with cardiac hypertrophy, which is believed to be a direct consequence of chronically elevated GH and IGF1. Given that insulin is important for cardiac growth and function, and considering that GH excess induces hyperinsulinemia, insulin resistance, and cardiac alterations, it is of interest to study insulin sensitivity in this tissue under chronic conditions of elevated GH. Transgenic mice overexpressing GH present cardiomegaly and perivascular and interstitial fibrosis in the heart. Mice received an insulin injection, the heart was removed after 2  min, and immunoblotting assays of tissue extracts were performed to evaluate the activation and abundance of insulin-signaling mediators. Insulin-induced tyrosine phosphorylation of the insulin receptor (IR) was conserved in transgenic mice, but the phosphorylation of IR substrate 1 (IRS1), its association with the regulatory subunit of the phosphatidylinositol 3-kinase (PI3K), and the phosphorylation of AKT were decreased. In addition, total content of the glucose transporter GLUT4 was reduced in transgenic mice. Insulin failed to induce the phosphorylation of the mammalian target of rapamycin (mTOR). However, transgenic mice displayed increased basal activation of the IR/IRS1/PI3K/AKT/mTOR and p38 signaling pathways along with higher serine phosphorylation of IRS1, which is recognized as an inhibitory modification. We conclude that GH-overexpressing mice exhibit basal activation of insulin signaling but decreased sensitivity to acute insulin stimulation at several signaling steps downstream of the IR in the heart. These alterations may be associated with the cardiac pathology observed in these animals.


Assuntos
Hormônio do Crescimento/metabolismo , Coração/efeitos dos fármacos , Insulina/farmacologia , Miocárdio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Bovinos , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Feminino , Hormônio do Crescimento/genética , Immunoblotting , Imunoprecipitação , Camundongos , Camundongos Transgênicos , Ratos , Transdução de Sinais/genética
7.
Carbohydr Res ; 183(2): 175-82, 1988 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-3063382

RESUMO

The trisaccharide allyl O-(3,4-di-O-methyl-beta-D-glucopyranosyl)-(1----4)-O-(2,3-di-O-methyl-al pha-L- rhamnopyranosyl)-(1----2)-3-O-methyl-alpha-L-rhamnopyranoside was synthesized from partially methylated monosaccharide derivatives. Condensation of 1,4-di-O-acetyl-2,3-di-O-methyl-alpha-L-rhamnopyranose promoted by boron trifluoride etherate with the appropriate alcohol proceeded stereoselectively and with very high yields. Selective deacetylation and glycosylation with 2,4-di-O-acetyl-3,6-di-O-methyl-alpha-D-glucopyranosyl bromide led to a trisaccharide. The acrylamide copolymers of mono-, di-, and tri-saccharide were compared in their ability to specifically bind antibodies from leprosy patients.


Assuntos
Antígenos de Bactérias , Haptenos , Mycobacterium leprae/imunologia , Trissacarídeos/síntese química , Acetilação , Anticorpos Antibacterianos/imunologia , Configuração de Carboidratos , Sequência de Carboidratos , Fenômenos Químicos , Química , Glicosilação , Humanos , Hanseníase/imunologia , Metilação , Dados de Sequência Molecular , Estrutura Molecular , Polímeros
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