Investigating the antiproliferative activities of new CuII complexes with pyridine hydrazone derivatives of nalidixic acid.

To further explore the structural features and potential antibacterial and antitumor activities of polynuclear CuII coordination compounds with nalidixic acid (nx) derivatives, new complexes bearing nx hydrazones with N-pyridinyl moieties substituted at positions 2 and 3 (h2py and h3py) were synthesized. Complexes [Cu3(C18H16N5O2)2(C18H17N5O2)2(H2O)]4BF4∙H2O (1), and [Cu3(C18H16N5O2)2(C18H17N5O2)2(H2O)3]4BF4∙3H2O (%) (2) were synthesized using h2py and h3py with Cu(BF4)2∙nH2O as precursor, whereas the [Cu(C18H17N5O2)Cl2]∙0.5H2O complex (3) was synthesized with h2py and CuCl2∙2H2O. Crystallographic studies of complex 1, showed that coordination of hydrazones to CuII occurs by tridentate modes of type κ3(O,N,N') as well as bidentate modes of type κ2(O',N″). Complexes 1, 2 and 3 had their antiproliferative activities evaluated in vitro against a panel of tumor cells by the determination of GI50 values. Complexes 1 and 2 were more active than complex 3, suggesting an effect of the complex charge on their activities. The interactions of such complexes towards bovine serum albumin (BSA) and DNA plasmid (pGEX-4 T1) were investigated using fluorescence spectroscopy and gel electrophoresis. All complexes were shown to interact with the DNA model as metallonucleases, but no interaction with BSA was observed. DNA molecular docking of complex 1 encompassing both its trinuclear (TN) form and a possible mononuclear (MN) derivative suggests that naphthyridyl ring performs π-stacking interactions with DNA. The TN species were also shown to be possible minor groove binders.

Silver Nimesulide Complex in Bacterial Cellulose Membranes as an Innovative Therapeutic Method for Topical Treatment of Skin Squamous Cell Carcinoma.

Oxidative stress and inflammation act on skin squamous cell carcinoma (SSCC) development and progression. Curative therapy for SSCC patients is mainly based on surgical resection, which can cause various sequelae. Silver ions have in vitro activities over tumor cells, while nimesulide has antioxidant and anti-inflammatory activities. This study aimed to evaluate the effects of a silver(I) complex with nimesulide (AgNMS) incorporated in a sustained release device based on bacterial cellulose membrane, named AgNMS@BCM, on topic SSCC treatment. The antiproliferative effect of AgNMS complex was evaluated in the SCC4, SCC15 and FaDu SCC lines. AgNMS complex activity on exposure of phosphatidylserine (PS) residues and multicaspase activation were evaluated on FaDu cells by flow cytometry. The AgNMS@BCM effects were evaluated in a SSCC model induced by 7,12-dimethylbenzanthracene/12-o-tetradecanoyl-phorbol-13-acetate (DMBA/TPA) in mice. Toxicity and tumor size were evaluated throughout the study. AgNMS complex showed antiproliferative activity in SCC15 and FaDu lines in low to moderate concentrations (67.3 µM and 107.3 µM, respectively), and induced multicaspase activation on FaDu cells. The AgNMS@BCM did not induce toxicity and reduced tumor size up to 100%. Thus, the application of AgNMS@BCM was effective and safe in SSCC treatment in mice, and can be seen as a potential and safe agent for topic treatment of SSCC in humans.

Hydroalcoholic Extract of Myrcia bella Loaded into a Microemulsion System: A Study of Antifungal and Mutagenic Potential.

Myrcia bella is a medicinal plant used for the treatment of diabetes, hemorrhages, and hypertension in Brazilian folk medicine. Considering that plant extracts are attractive sources of new drugs, the aim of the present study was to verify the influence of incorporating 70% hydroalcoholic of M. bella leaves in nanostructured lipid systems on the mutagenic and antifungal activities of the extract. In this work, we evaluated the antifungal potential of M. bella loaded on the microemulsion against Candida sp for minimum inhibitory concentration, using the microdilution technique. The system was composed of polyoxyethylene 20 cetyl ether and soybean phosphatidylcholine (10%), grape seed oil, cholesterol (10%: proportion 5/1), and purified water (80%). To investigate the mutagenic activity, the Ames test was used with the Salmonella Typhimurium tester strains. M. bella, either incorporated or free, showed an important antifungal effect against all tested strains. Moreover, the incorporation surprisingly inhibited the mutagenicity presented by the extract. The present study attests the antimicrobial properties of M. bella extract, contributing to the search for new natural products with biological activities and suggesting caution in its use for medicinal purposes. In addition, the results emphasize the importance of the use of nanotechnology associated with natural products as a strategy for the control of infections caused mainly by the genus Candida sp.

A multipurpose natural and renewable polymer in medical applications: Bacterial cellulose.

Bacterial cellulose (BC) produced by some bacteria, among them Gluconacetobacter xylinum, which secrets an abundant 3D networks fibrils, represents an interesting emerging biocompatible nanomaterial. Since its discovery BC has shown tremendous potential in a wide range of biomedical applications, such as artificial skin, artificial blood vessels and microvessels, wound dressing, among others. BC can be easily manipulated to improve its properties and/or functionalities resulting in several BC based nanocomposites. As example BC/collagen, BC/gelatin, BC/Fibroin, BC/Chitosan, etc. Thus, the aim of this review is to discuss about the applicability in biomedicine by demonstrating a variety of forms of this biopolymer highlighting in detail some qualities of bacterial cellulose. Therefore, various biomedical applications ranging from implants and scaffolds, carriers for drug delivery, wound-dressing materials, etc. that were reported until date will be presented.

Aspectos biológiocos do envelhecimento / Biological aspects of aging

As alterações que caracterizam a senescência são facilmente observáveis ou mesmo sentidas por todos nós, mas os mecanismos biológicos que concorrem para o seu desenvolvimento permanecem, em grande parte, desconhecidos. Várias são as teorias que tentam explicar o mecanismo da gênese do envelhecimento celular, mas nenhuma delas conseguiu sucesso total, o que reflete a dificuldade de entender na íntegra este processo

Rotavirus and adenovirus in diarrheic and non-diarrheic feces of children, in Araraquara, SP, Brazil

Procurando verificar a participaçäo de rotavirus e adenovirus na etiologia da gastrenterite infantil, 280 amostras de fezes de crianças da faixa etária de 0 a 5 anos foram coletadas em Araraquara-SP, sendo 140 de crianças com diarréia e 140 do grupo de controle. A pesquisa desses vírus foi realizada através de um ensaio imunoenzimático (EIARA) e adicionalmente, rotavirus foi pesquisado através da eletroforese em gel de poliacrilamida (PAGE). No grupo diarréico, rotavirus foi detectado em 8,6% das amostras usando EIARA e em 7,9% usando PAGE. Nenhuma das amostras do grupo controle se mostrou positiva para esse vírus. Adenovirus foi detectado em 2,9% das amostras do grupo diarréico e em 1,4 % das fezes do grupo controle. Os resultados mostram que o rotavirus participam ativamente da etiologia da diarreia infantil em nossa cidade