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. medicine technology fields compounds elucidated β methylβcyclodextrin methyl cyclodextrin Mβ M (M-β , cyclodextrins) 2hydroxypropylβcyclodextrin hydroxypropylβcyclodextrin 2 hydroxypropyl HPβcyclodextrins HP (HP-β-cyclodextrins toxicity measured assessed 60day day 60 treatments βcyclodextrins Mβcyclodextrins pathway Additionally kidneys Here βcyclodextrins, Mβcyclodextrins, 6

Resumo A periodontite e a hipertensão arterial são duas das patologias com maior prevalência global, as evidências relatadas até o momento têm sido favoráveis a uma associação entre elas. Este estudo transversal teve como objetivo avaliar e comparar contagem microbiológicas de pacientes hipertensos e normotensos com periodontite. Dados sociodemográficos, comportamentais, de saúde sistêmica e parâmetros clínicos periodontais foram avaliados. Contagens de A. actinomycetemcomitans, P. intermedia, P. gingivalis e F. nucleatum foram realizadas por reação em cadeia da polimerase em tempo real utilizando amostras de biofilme subgengival. Trinta e oito pacientes foram incluídos nesta análise preliminar, divididos em dois grupos: Grupo Normotenso (GN) (n = 14) e Grupo Hipertenso (GH) (n = 24). Pacientes diagnosticados com periodontite compuseram os dois grupos. A análise dos dados foi realizada com nível de significância de 5%. Não houve diferença significativa entre os grupos para o diagnóstico clínico de periodontite. Além disso, os hipertensos apresentaram maior contagem de P. intermedia, P. gingivalis e F. nucleatum quando comparados aos normotensos. Os parâmetros profundidade de sondagem, sangramento à sondagem e contagem de A. actinomycetemcomitans não apresentaram diferenças estatísticas entre os grupos. Com esses resultados preliminares, pode-se concluir que a presença de hipertensão arterial pode estar associada a uma maior quantidade de bactérias periodontopatogênicas de algumas espécies em indivíduos com periodontite.

Abstract Periodontitis and arterial hypertension are two of the pathologies with the highest global prevalence; evidence reported so far has been favorable to an association between them. This cross-sectional study aimed to evaluate and compare the microbiological counts of hypertensive and normotensive patients with periodontitis. Sociodemographic, behavioral, systemic health data and periodontal clinical parameters were assessed. Counts of A. actinomycetemcomitans, P. intermedia, P. gingivalis and F. nucleatum were performed by real-time polymerase chain reaction using subgingival biofilm samples. Thirty-eight patients were included in this preliminary analysis, divided into two groups: Normotensive Group (NG) (n = 14) and Hypertensive Group (HG) (n = 24). Patients diagnosed with periodontitis composed both groups. Data analysis was performed with significance level of 5%. There was no significant difference between groups for clinical periodontitis diagnosis. In addition, hypertensive individuals had higher P. intermedia, P. gingivalis, and F. nucleatum counts when compared to normotensive individuals. The parameters probing pocket depth, bleeding on probing, and A. actinomycetemcomitans count did not presented statistical differences between groups. With these preliminary results, it can be concluded that the presence of arterial hypertension may be associated with a greater quantity of periodontopathogenic bacterial of some species in individuals with periodontitis.

Abstract: Type 1 diabetes (T1D) is the result of the selective destruction of the pancreatic β-cells by T cells of the immune system. Although spleen is a secondary lymphoid organ, it is also involved in the T1D pathogenesis. However, the alterations in a variety of cellular processes of this disease need to be further understood. We aimed to analyze the benefits of resveratrol, and its complexed form on diabetic complications in the spleen of rats. To this end, we investigated important enzymes of phosphoryl transfer network, and Na+, K+-ATPase activity. Wistar rats were divided into non-diabetic groups: Control, Ethanol, Resveratrol, Hydroxypropyl-β-cyclodextrin, Resveratrol-hydroxypropyl-β-cyclodextrin, and diabetic groups with the same treatments. Diabetes was induced by a single dose of 60 mg/kg of streptozocin intraperitoneally, and treatments by intragastric gavage once daily for 60 days. Hyperglycemia reduced creatine kinase activity, which was reversed by the administration of resveratrol. Na+, K+-ATPase activity was greatly affected, but it was reversed by resveratrol and resveratrol-hydroxypropyl-β-cyclodextrin. This suggest an energetic imbalance in the spleen of diabetic rats, and in case this also occurs in the diabetic patients, it is possible that resveratrol supplementation could be beneficial to the better functioning of the spleen in diabetic patients.

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.

Loque americana é uma grave doença de propagação mundial em abelhas causada pelo Paenibacillus larvae. Extratos de plantas são conhecidos por diminuir ou inibir o crescimento dessa bactéria. O objetivo deste estudo foi avaliar a atividade antimicrobiana dos extratos de Calendula. officinalis, Cariniana domestica, e Nasturtium officinale contra o P. larvae e avaliar a toxicidade dos extratos em abelhas. A atividade in vitro dos extratos contra P. larvae foi avaliada pelo método de microdiluição e as concentrações inibitórias mínimas (MICs) também foram determinadas. As concentrações utilizadas no ensaio de toxicidade foram estabelecidas baseadas nos valores de MIC e pelo método de aplicação por pulverização. O P. larvae foi suscetível aos extratos brutos de C. officinalis e N. officinale avaliados. Para a C. domestica, apenas as frações acetato de etila (EtAc) e butanólica (BuOH) tiveram atividade contra P. larvae. Análises de toxicidade em abelhas não mostraram toxidade para o extrato bruto de N. officinale e fração BuOH de C. domestica durante os 15 dias de tratamento, no entanto, ocorreram algumas mortes de abelhas durante os três primeiros dias de tratamento com C. officinalis e fração EtAc de C. domestica. Os resultados com essas espécies foram pela primeira vez descritos e mostraram que o extrato bruto de N. officinale e a fração BuOH de C. domestica ambos não apresentaram efeitos tóxicos nas concentrações testadas pelo método de aplicação por pulverização e podem ser uma alternativa útil para o tratamento ou prevenção da loque americana.

American foulbrood (AFB) is a serious worldwide spreading disease in bees caused by Paenibacillus larvae. Plants extracts are known to decrease or inhibit the growth of these bacteria. The purpose of this study was to evaluate the antimicrobial activity of Calendula. officinalis, Cariniana domestica, and Nasturtium officinale extracts against the P. larvae and to evaluate the toxicity of the extracts in bees. In vitro activity against P. larvae of the extracts was evaluated by micro dilution method and the minimal inhibitory concentrations (MICs) were also determined. The concentrations used in the toxicity test were established based on the MIC values and by the spraying application method. The P. larvae was susceptible to the evaluated crude extract of C. officinalis and N. officinale. To C. domestica, only the ethyl acetate (EtAc) fraction and n-butanol (BuOH) fractions had activity against P. larvae. Toxicity analysis in bees showed no toxicity for N. officinale crude extract and for C. domestica BuOH fraction during 15 days of treatment, however, some deaths of bees occurred during the first three days of treatment with C. officinalis and C. domestica EtAc fraction. The results with these species were firstly described and showed that N. officinale crude extract and C. domestica BuOH fraction both presented not toxic effects in the concentration tested by the spraying application method, and can be a useful alternative for treatment or prevention of AFB.