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In this paper, we study the number of limit cycles that can bifurcate from a periodic annulus of discontinuous planar piecewise linear Hamiltonian differential system with three zones separated by two parallel straight lines, such that the linear differential system, given by the piecewise one, in the region between the two straight lines (called of central subsystem) has a saddle at a point equidistant from these lines (obviously, the others subsystems have saddles and centers). We prove that the maximum number of limit cycles that bifurcate from the periodic annulus of this kind of piecewise Hamiltonian differential systems, by linear perturbations, is at least six. For this, we obtain normal forms for the systems and study the number of zeros of its Melnikov functions defined in two and three zones., Comment: arXiv admin note: text overlap with arXiv:2207.05177, arXiv:2109.10311

In this paper, we study the existence of limit cycles in continuous and discontinuous planar piecewise linear Hamiltonian differential systems with two or three zones separated by straight lines and such that the linear systems that define the piecewise one have isolated singular points, i.e. centers or saddles. In this case, we show that if the planar piecewise linear Hamiltonian differential system is either continuous or discontinuous with two zones, then it has no limit cycles. Now, if the planar piecewise linear Hamiltonian differential system is discontinuous with three zones, then it has at most one limit cycle, and there are examples with one limit cycle. More precisely, without taking into account the position of the singular points in the zones, we present examples with the unique limit cycle for all possible combinations of saddles and centers., 22 pages, 6 figures

This work was supported by the Araucária Foundation, a Research Founding Agency from Paraná State – Brazil, CAPES and CNPq.

This work was supported by the Paraná State Research Funding Agency (Araucária Foundation – project # FA-SESA 073/2016 - CP 04/2016) and by the Federal Agencies CAPES and CNPq (project # CNPq PVE 401271/2014-5).

Morita-Baylis-Hillman acetates and alpha-bromonitroalkenes have been employed in cascade reactions with lawsone and 2-aminonaphthoquinone for the one-pot synthesis of heterocycle fused quinonoid compounds. The reactions reported here utilized the 1,3-binucleophilic potential of hydroxy- and aminonaphthoquinones and the 1,2/1,3-bielectrophilic potential of bromonitroalkenes and Morita-Baylis Hillman acetates for the synthesis of pyrrole and furan fused naphthoquinones. The synthesized compounds were evaluated against HCT-116 (human colon carcinoma cells), PC3 (human prostate cancer cells), HL-60 (human promyelocytic leukemia cells), SF295 (human glioblastoma cells) and NCI-H460 (human lung cancer cells) and exhibited antitumor activity with IC50 values as low as < 2 mu M. Selected compounds were also evaluated against OVCAR-8 (ovary), MX-1 (breast) and JURKAT (leukemia) cell lines. The cytotoxic potential of the quinones evaluated was also assayed using non-tumor cells, exemplified by peripheral blood mononuclear (PBMC) and L929 cells. (C) 2018 Elsevier Masson SAS. All rights reserved.

In this work, we characterize nor-β-lapachone-loaded (NβL-loaded) microcapsules prepared using an emulsification/solvent extraction technique. Features such as surface morphology, particle size distribution, zeta potential, optical absorption, Raman and Fourier transform infrared spectra, thermal analysis data, drug encapsulation efficiency, drug release kinetics and in vitro cytotoxicity were studied. Spherical microcapsules with a size of 1.03 ± 0.46 μm were produced with an encapsulation efficiency of approximately 19%. Quantum DFT calculations were also performed to estimate typical interaction energies between a single nor-β-lapachone molecule and the surface of the microparticles. The NβL-loaded PLGA microcapsules exhibited a pronounced initial burst release. After the in vitro treatment with NβL-loaded microcapsules, a clear phagocytosis of the spheres was observed in a few minutes. The cytotoxic activity against a set of cancer cell lines was investigated .

Prostate cancer is one of the most common malignant tumors in males and it has become a major worldwide public health problem. This study characterizes the encapsulation of Nor-v-lapachone (NvL) in poly(d,l-lactide-co-glycolide) (PLGA) microcapsules and evaluates the cytotoxicity of the resulting drug-loaded system against metastatic prostate cancer cells. The microcapsules presented appropriate morphological features and the presence of drug molecules in the microcapsules was confirmed by different methods. Spherical microcapsules with a size range of 1.03 ± 0.46 mm were produced with an encapsulation efficiency of approximately 19%. Classical molecular dynamics calculations provided an estimate of the typical adsorption energies of NvL on PLGA. Finally, the cytotoxic activity of NvL against PC3M human prostate cancer cells was demonstrated to be significantly enhanced when delivered by PLGA microcapsules in comparison with the free drug.

We report the preparation of a series of indolylquinone and pyridine derivatives in order to evaluate structure-activity relationships in human gastric (AGS), lung (SK-MES-1), bladder (J82) cancer cell lines and human normal lung fibroblasts (MCR-5). Two correlations tendency between half-wave redox potentials against their antineoplasic activity were found making it possible to establish that for epithelial human gastric cancer (AGS) cell lines and human normal lung fibroblasts (MCR-5). The quinone bioreduction should correspond to a one electron process under normomix conditions, whilst for all other lines this process should correspond to a two electron attachment via a hypoxic process.

Avaliou-se o efeito da adição de diferentes tipos e concentrações de soro sobre o desenvolvimento e a sobrevivência de folículos ovarianos pré-antrais (FOPA) caprinos in vitro. Além disso, verificou-se a relação entre as concentrações de nitrito presentes no meio de cultivo e a viabilidade folicular. Cada par ovariano foi dividido em 29 fragmentos, sendo um destinado ao controle. Os fragmentos foram cultivados por um ou sete dias em meio essencial mínimo suplementado (MEM+) ou MEM+ com diferentes concentrações (10 ou 20%) de soro fetal bovino (SFB), soro de cabra em estro (SCE) ou soro de cabra em diestro (SCD). Na análise morfológica após sete dias, apenas o tratamento com 10% de SFB apresentou percentual de FOPA normais similar ao MEM+ (P>0,05). A análise ultra-estrutural dos folículos cultivados por sete dias com MEM+ ou MEM+ com 10% de SFB mostrou danos oocitários, porém células da granulosa normais. A análise do meio de cultivo revelou correlação positiva entre a viabilidade folicular e a produção de nitrito. A suplementação com soro não melhorou a viabilidade de FOPA e a concentração de nitrito no meio de cultivo funcionou como um indicador da viabilidade das células da granulosa de FOPA caprinos cultivados in vitro. ______________________________________________________________________________________________________________ ABSTRACT The effect of the addition of different types and concentrations of sera on the viability and development of caprine preantal follicles (PAF) in vitro cultured was analyzed. In addition, it was evaluated the correlation between nitrite concentrations in culture medium and folicular viability. Each ovarian pair was divided in 29 fragments and one was used as control. The fragments were cultured for one or seven days in minimal essential medium (MEM+) or MEM+ with different concentrations of (10 or 20%) bovine fetal serum (BFS), estrous goat serum (EGS), or diestrous goat serum (DGS). After seven days, the morphological analysis showed that only the treatment with 10% BFS maintained the percentage of normal PAF similar to MEM+ (P>0.05). The ultrastructural analysis of follicles cultured for seven days in MEM+ or MEM+ with 10% BFS showed some oocyte damage, although the granulosa cells were normal. Analysis of culture medium revealed a positive correlation between follicular viability and nitrite production. Supplementation with serum did not improve the viability of PAF and nitrite levels in culture medium served as an indicator of viability of granulose cells from caprine PAF in vitro cultured.

Avaliou-se o efeito da adição de diferentes tipos e concentrações de soro sobre o desenvolvimento e a sobrevivência de folículos ovarianos pré-antrais (FOPA) caprinos in vitro. Além disso, verificou-se a relação entre as concentrações de nitrito presentes no meio de cultivo e a viabilidade folicular. Cada par ovariano foi dividido em 29 fragmentos, sendo um destinado ao controle. Os fragmentos foram cultivados por um ou sete dias em meio essencial mínimo suplementado (MEM+) ou MEM+ com diferentes concentrações (10 ou 20%) de soro fetal bovino (SFB), soro de cabra em estro (SCE) ou soro de cabra em diestro (SCD). Na análise morfológica após sete dias, apenas o tratamento com 10% de SFB apresentou percentual de FOPA normais similar ao MEM+ (P>0,05). A análise ultra-estrutural dos folículos cultivados por sete dias com MEM+ ou MEM+ com 10% de SFB mostrou danos oocitários, porém células da granulosa normais. A análise do meio de cultivo revelou correlação positiva entre a viabilidade folicular e a produção de nitrito. A suplementação com soro não melhorou a viabilidade de FOPA e a concentração de nitrito no meio de cultivo funcionou como um indicador da viabilidade das células da granulosa de FOPA caprinos cultivados in vitro. The effect of the addition of different types and concentrations of sera on the viability and development of caprine preantal follicles (PAF) in vitro cultured was analyzed. In addition, it was evaluated the correlation between nitrite concentrations in culture medium and folicular viability. Each ovarian pair was divided in 29 fragments and one was used as control. The fragments were cultured for one or seven days in minimal essential medium (MEM+) or MEM+ with different concentrations of (10 or 20%) bovine fetal serum (BFS), estrous goat serum (EGS), or diestrous goat serum (DGS). After seven days, the morphological analysis showed that only the treatment with 10% BFS maintained the percentage of normal PAF similar to MEM+ (P>0.05). The ultrastructural analysis of follicles cultured for seven days in MEM+ or MEM+ with 10% BFS showed some oocyte damage, although the granulosa cells were normal. Analysis of culture medium revealed a positive correlation between follicular viability and nitrite production. Supplementation with serum did not improve the viability of PAF and nitrite levels in culture medium served as an indicator of viability of granulose cells from caprine PAF in vitro cultured.

Caatinga flora which are found in a poor Brazilian region contain a substantial number of endemic taxa with biomedical and social importance for regional communities. This study examined the antioxidant and cytotoxic potential of 35 samples (extracts/fractions) from 12 Caatinga species and determined the antiproliferative and genotoxic action of dichloromethane fraction from Mimosa caesalpiniifolia stem bark (DC-Mca) on human and vegetal cells. Samples were assessed for chemopreventive ability, toxic effects on Artemia salina shrimp as well as cytotoxicity on tumor cell lines and erythrocytes. DC-Mca was also tested with respect to antiproliferative and genotoxic effects upon normal leukocytes and meristematic cells from A. cepa roots. Some extracts reduced free radical levels >95% and 7 samples exhibited a lethal concentration (LC) 50

Made available in DSpace on 2019-03-19T02:10:12Z (GMT). No. of bitstreams: 1 tese_13064_Tese - Ludmilla Carvalho Rangel Resgala.pdf: 62257785 bytes, checksum: 0ef7d0d02747dcb6a07d245c61609e65 (MD5) Previous issue date: 2019-02-28 Os danos celulares podem ser causados por fatores relacionados ao envelhecimento ou provocados por agentes causadores de estresse. Nesse estudo, nosso objetivo geral foi estudar a ultraestrutura de doenças metabólicas. Dentre as doenças metabólicas relacionadas ao envelhecimento destacam-se a osteoporose e a doença de Alzheimer (DA) e, para esse estudo, utilizamos camundongos C57 Black 6, de 12 meses de idade, SHAM, ovariectomizadas (OVX), APOEKO e APOEKO/OVX como modelos de osteoporose e DA. Através da análise ultraestrutural, revelamos que os danos causados no cérebro de animais APOEKO, como arterosclerose, quebra da barreira hematoencefálica, ativação de micróglia, formação de NFT`s e perda de neurópilo foram potencializados pela depleção de estrogênio. Nossos dados acerca da ultraestrutura óssea revelaram que os danos à microarquitetura óssea dos animais APOEKO/OVX foram mais graves, tal como ocorreu no cérebro, quando comparados aos outros grupos. Além disso, descrevemos, pela primeira vez, que a amiloidose em animais APOEKO é potencializada pela deficiência de estrogênio (OVX). No que diz respeito ao estudo ultraestrutural da doença metabólica provocada por estresse, utilizamos como modelo ratas Wistar tratadas com 100 ng/kg/dia de tributilestanho (TBT), um organoestanho poluente considerado altamente tóxico, por um período de 15 dias. Nossos resultados revelaram que o estresse por TBT foi capaz de desencadear danos na microarquitetura óssea das vértebras das ratas, em um processo semelhante à osteoporose. Além disso, vimos que a densidade mineral (DMO) óssea foi menor nas ratas tratadas. Nossos estudos demonstram também, pela primeira vez, que o TBT é um poluente capaz de promover graves danos no metabolismo ósseo, como desenvolvimento de osteoporose. Possivelmente, o TBT atua afetando o metabolismo do estrogênio na manutenção da microarquitetura óssea ou ainda substituindo erroneamente outros íons divalentes como Ca2+ ou Mg2+ na formação da matriz mineral óssea.