Abstract Although widely used in medicine, separation technology, and other fields, the effects of cyclodextrins on the activities of phosphoryl transfer enzymes have not been previously evaluated. In vivo studies evaluated the function of cyclodextrins as active compounds. Despite the use of cyclodextrins as active compounds, the effects of cyclodextrins on hepatic and renal tissues remain to be fully elucidated. The primary objective of this study was to evaluate the effects of β- cyclodextrins, methyl-β-cyclodextrin (M-β- cyclodextrins), and (2-hydroxypropyl)-β-cyclodextrin (HP-β-cyclodextrins) on enzyme activities regulating the maintenance of energy homeostasis in the kidney and liver tissues in relation to toxicity. Serum levels of liver and kidney markers were measured, and oxidative stress parameters were assessed. After 60-day treatments, we observed that the administration of β-cyclodextrins and M-β-cyclodextrins inhibited the hepatic activity of pyruvate kinase, an irreversible enzyme within the glycolytic pathway. Additionally, administration of HP-β-cyclodextrins inhibited creatine kinase activity and increased the total sulfhydryl content in kidneys. Here, we demonstrated for the first time that β-cyclodextrins, M-β-cyclodextrins, and HP-β-cyclodextrins cause bioenergetic dysfunction in renal and hepatic tissues. These findings suggest that understanding the balance between cyclodextrins’ efficacy and adverse effects is essential for better accepting their use in medicine.

Abstract The characteristics of milk are controlled by several genes, with emphasis on the four genes from casein, CSN1S1; CSN1S2; CSN2 and CSN3, which are responsible encoding of fractions the milk protein. The study of genetic variants in these genes, seek to investigate alleles, insertions or deletions, that can directly reflect on productive characteristics, indicating differences in milk quality, composition and yield. The CSN1S1 and CSN3 genes were analyzed in lactating Murrah buffaloes using nucleotide sequencing. An SNP was found in the amplified fragment of the CSN1S1 gene, located in nucleotide number 2,123 of the promoter region in position nt-258 (A/G). As for the CSN3 gene, two SNPs of exon number 4 were identified in codons 33 (ACC/ATC) and 34 (ACC/ACT) of the analyzed fragment. This study contributes to important associations between genetic variants and the desired characteristics of milk and its derivatives in future studies, because the variants found may be associated with the quality of milk, enabling genetic selection to be assisted by molecular markers, indicating a major advance that makes it possible to select animals early.

Resumo Os princípios e as técnicas aplicadas na extração de DNA desempenham um papel crucial na obtenção de material genético purificado. O presente estudo investiga a eficiência de oito protocolos na extração de DNA de Hypostomus commersoni, um importante componente ictiofaunístico de riachos da América do Sul. A qualidade das amostras foi avaliada por espectrofotometria, eletroforese em gel e amplificação por marcadores de PCR-RAPD. A eficiência da extração de DNA foi influenciada tanto pelo método aplicado quanto pelo tecido-alvo de escolha. Maiores concentrações e rendimento de DNA foram obtidos a partir do tecido ocular, com um espectro positivo de incubação em tampão de lise por até 36 horas após a coleta da amostra, utilizando tecidos frescos e na presença de alta concentração de proteinase K (20 mg.ml-1). Nestas condições, as amostras foram amplificadas com sucesso. Até o momento, não há registro de descrição para os parâmetros analisados neste trabalho, nem a descrição de marcadores RAPD para a espécie H. commersoni.

Abstract The principle and the techniques applied in DNA extraction play a pivotal role in the obtention of a purified genetic material. The present study investigates the efficiency of eight protocols in the DNA extraction of Hypostomus commersoni, an essential component of South American freshwater ichthyofauna. The quality of samples was assessed through spectrophotometry, gel electrophoresis, and PCR-RAPD markers amplification. The efficiency of DNA extraction was influenced both by the method applied and the target-tissue of choice. Higher concentrations and yield of DNA were obtained from ocular tissue, with a positive spectrum of incubation in lysis buffer for up to 36 hours after sample collection, using fresh tissues and in the presence of a high concentration of Proteinase K (20 mg.ml-1). In these conditions, samples were successfully amplified. To date, there is no record of description for the parameters analyzed in this work, neither the description of RAPD markers for the species H. commersoni.

ABSTRACT Creatine acts intracellularly as energy buffer and storage, demonstrating protective effects in animal models of neurodegenerative diseases. However, its permeability throught blood-brain barrier (BBB) is reduced. The aim of the present study was developing a carrier to facilitate the delivery of creatine to the central nervous system. Creatine nanoliposomes were produced, characterized and assayed in models of toxicity in vitro and in vivo. Particles showed negative zeta potential (-12,5 mV), polydispersity index 0.237 and medium-size of 105 nm, which was confirmed by transmission electron microscopy (TEM) images. Toxicity assay in vitro was evaluated with blank liposomes (no drug) or creatine nanoliposomes at concentrations of 0.02 and 0.2 mg/mL, that did not influence the viability of Vero cells. The result. of the comet assay that the nanoliposomes are not genotoxic, togeher with cell viability demonstrated that the nanoliposomes are not toxic. Besides, in vivo assays not demonstrate toxicity in hematological and biochemical markers of young rats. Nevertheless, increase content of creatine in the cerebral cortex tissue after subchronic treatment was observed. Altogether, results indicate increase permeability of creatine to the BBB that could be used as assay for in vivo studies to confirm improved effect than free creatine.

Abstract This paper introduces a hybrid approach for obtaining S-N curves with reduced number of tests associated to statistically simulated data. In order to validate the proposal, two validation process were developed. One using a methodology to generate S-N curves based on Monte Carlo simulations and other using actual data according Zhao et al. (1998), allowing to compare the hybrid approach with the experimental curve S-N obtained with high replication. In both validation process, a good accuracy was verified. Subsequently, the fatigue analysis of a fillet welded joint was carried out using finite element analysis to evaluate the cumulative damage and fatigue life, enabling comparison between the proposed method and standard NBR 8800 (2008). The results obtained with the proposed methodology allowed more accuracy results and less conservative than standard for the same weld detail class, both for fatigue life and for cumulative fatigue damage evaluations.