A versatile method for the selective core-crosslinking of hyaluronic acid nanogels via ketone-hydrazide chemistry: from chemical characterization to in vivo biodistribution.

The development of biopolymer-based nanogels has gained particular interest to achieve successful delivery of therapeutics for the treatment of various diseases, such as cancer, infection and diabetes. Herein, we report a new and simple methodology for the covalent stabilization of self-assembled gel nanoparticles based on hyaluronic acid (HA) modified with a thermoresponsive ketone-functional copolymer. This relies on the selective formation of hydrazone crosslinks with bishydrazides within the globular domains of the copolymer chains formed above the cloud point temperature. This approach allows tuning of the crosslinking density by varying the dihydrazide crosslinker to ketone molar ratio. The size distributions and morphology of the nanogels were assessed using dynamic light scattering (DLS), cryo-transmission and scanning electron microscopy. In vitro cellular uptake in several cancer cells and in vivo biodistribution of the nanogels in different mouse tumor models were then explored to assess the effectiveness of this crosslinking strategy. The data from these experiments show prolonged blood circulation, longer than 24 hours, for the crosslinked nanogels and high tumor accumulation.

Synthesis, antileishmanial activity and mechanism of action studies of novel ß-carboline-1,3,5-triazine hybrids.

A series of novel hybrids ß-carboline-1,3,5-triazine were synthesized and evaluated for their in vitro antileishmanial activity against promastigote and amastigote forms of Leishmania amazonensis. Among the compounds tested, the hybrids 9d, 9e, 16a and 16b showed potent activity against the promastigote forms with IC50 values less than 8 µM. Compounds 9e and 16b were also active against amastigote forms, displaying IC50 values of 1.0 ±â€¯0.1 µM and 1.2 ±â€¯0.5 µM, respectively. Besides that, the hybrid 16b bearing the 4-methoxyphenyl group at C-1 of ß-carboline and isopropylamino group at 1,3,5-triazine, showed low toxicity, being 23.5 and 121.4 times more toxic for promastigotes and axenic amastigotes, respectively, than for macrophage J774-A1 cell lines. Investigation of action mechanism in promastigotes showed that compound 16b caused alterations in cell division cycle and an increase of lipid-storage bodies, leading the cells to death through various factors. The accumulation of lipid bodies may be associated with apoptotic cell death.

Oxidative stress parameters as biomarkers of risk factor for diabetic foot among the patients with type 2 diabetes

The aim of this study was to determine whether plasma levels of carbonylated proteins, total antioxidant capacity (TAC) and reduced protein thiols could be suitable biomarkers of risk factors for diabetic foot. Individuals with type 2 diabetes with normal protective sensation (normal foot group) vs. loss of protective sensation and/or signs of peripheral arterial disease and/or foot deformities and/or history of ulcers and/or neuropathic fractures and/or amputation (diabetic foot group) were compared. The diabetic foot group showed higher carbonylated protein levels (P = 0.0457) and lower levels of TAC (P = 0.0148) and reduced protein thiols (P = 0.0088), compared with the normal foot group. In general, several other parameters of risk of diabetes complication (blood levels of glycated hemoglobin, glucose and cholesterol, duration of diabetes, body mass index and waist circumference) showed a tendency of higher values in the diabetic foot group. The results suggest that the plasma levels of carbonylated proteins, TAC and reduced protein thiols could furnish information about the risk of diabetic foot, considering that the changes in these biomarkers were associated with the loss of sensitivity and foot ulcerations.

Comparative performance of lab tests and blood testing device to monitor glucose, total cholesterol and triacylglycerol in type 2 diabetic patients / Desempenho comparativo de testes de laboratório e de dispositivos de teste de sangue para monitorar glicose, colesterol total e triglicérides em pacientes diabéticos tipo 2

The performance of lab tests (LT) and blood testing devices (BTD) to monitor glycemia vs. glycated hemoglobin A1c (A1c) were compared. In addition, the performance of blood glucose, total cholesterol (TC) and triacylglycerol measured by LT and BDT were compared. All parameters were measured based on the same blood samples from overnight fasted type 2 diabetic patients (T2DP). Linear regression analysis was used for all comparisons. The results showed that A1c correlated better with LT-glucose (r = 0.58) than BTD-glucose (r = 0.42). Moreover, LT vs. BTD showed r values of 0.90, 0.82 and 0.92 for glucose, TC and triacylglycerol, respectively. It was concluded that the performance of LT-glucose was better than BDT-glucose. Moreover, since triacylycerol and TC measured by BTD correlated better with LT compared to BDT-glucose vs. LT-glucose, the inclusion of BTD-TC and BTD-triacylglycerol for detecting and monitoring hyperlipidemia in T2DP should be considered.

Comparou-se a performance de avaliação da glicemia através de dosagens laboratoriais (DL) ou dispositivo para teste de sangue capilar (DTSC) vs. hemoglobina glicada A1c (A1c). Comparou-se ainda a performance de avaliação da glicemia, colesterol total (CT) e triacilglicerol (DL vs. DTSC). Avaliou-se estes parametros a partir das mesmas amostras de sangue coletadas em pacientes diabéticos tipo 2 (PDT2) em jejum noturno, sendo as comparações realizadas através de análise de regressão linear. A A1c correlacionou-se melhor com a glicemia-DL (r = 0,58) em relação a glicemia-DTSC (r = 0,42). Comparou-se DL vs. DTSC obtendo se r = 0,90, 0,82 e 0,92 para glicemia, CT e triacilglicerol, respectivamente. Concluiu-se que houve melhor performance da glicose-DL em relação a glicose-DTSC. Além disso, considerando que o triacilglicerol e TC avaliado através de DTSC correlaciona-se melhor com DL em comparação a DTSC-glicose vs. DL-glicose, a inclusão de DTSC-TC e DTSC-triacilglicerol visando detectar e monitorar hyperlipidemia in PDT2 deve ser considerada.