Photoprotective and antioxidant effects of Rhubarb: Inhibitory action on tyrosinase and tyrosine kinase activities and TNF-α, IL-1α and α-MSH production in human melanocytes

Background: Exposure to ultraviolet (UV) radiation causes various forms of acute and chronic skin damage, including immunosuppression, inflammation, premature aging and photodamage. Furthermore, it induces the generation of reactive oxygen species, produces proinflammatory cytokines and melanocyte-stimulating hormone (MSH) and increases tyrosinase activity. The aim of this study was to evaluate the potential photoprotective effects of Rheum rhaponticum L. rhizome extract on human UV-stimulated melanocytes.Methods: The effects of Rheum rhaponticum rhizome extract on tyrosine kinase activity, and on interleukin-1α (IL-1α), tumour necrosis factor α (TNF-α), and α-MSH production in human epidermal melanocytes were evaluated under UV-stimulated and non-stimulated conditions. Antioxidant activity was evaluated by lipid peroxidation and 1,1-dyphenyl-2-picryl-hydrazyl (DPPH) assays, while anti-tyrosinase activity was evaluated by the mushroom tyrosinase method.Results: Rheum rhaponticum L. rhizome extract showed in vitro antioxidant properties against lipid peroxidation, free radical scavenging and anti-tyrosinase activities, and inhibited the production of IL-1α, TNF-α, α-MSH, and tyrosine kinase activity in melanocytes subjected to UV radiation.Conclusions: These results support the inclusion of Rheum rhaponticum L. rhizome extract into cosmetic, sunscreen and skin care products for the prevention or reduction of photodamage. © 2013 Silveira et al; licensee BioMed Central Ltd.

Effects of (-)-cubebin (Piper cubeba) on cytotoxicity, mutagenicity and expression of p38 MAP kinase and GSTa2 in a hepatoma cell line

(-)-Cubebin is a lignan extracted from the seeds of the pepper Piper cubeba, a commonly eaten spice with beneficial properties, including trypanocidal, anti-inflammatory, analgesic, anti-proliferative and leishmanicidal activities. Because of its therapeutic potential, we investigated the effects of (-)-cubebin on the cytotoxicity, cell proliferation kinetics, mutagenicity and expression of p38 MAP kinase and glutathione S-transferase a2 (GSTa2) using real-time RT-PCR in Rattus norvegicus hepatoma cells. We found that 280 μM (-)-cubebin was cytotoxic after 24, 48 and 72. h of exposure, but not mutagenic at 0.28 μM, 2.8 μM and 28 μM after 26. h. Similarly, exposure to 0.28 μM, 2.8 μM and 28 μM (-)-cubebin for 24, 48, 72 and 96. h did not alter the cell proliferation kinetics. Cells exposed to 28 μM (-)-cubebin for 24. h did not exhibit changes in p38 MAP kinase and GSTa2 expression, indicating that cellular changes were not induced by extracellular stimuli and that (-)-cubebin is likely not metabolized via this pathway. Our results suggest that high levels of (-)-cubebin should be consumed with caution due to the cytotoxic effect observed at the highest concentration. However, at lower concentrations, no cytotoxic, mutagenic or proliferative effects were observed, providing further evidence of the safety of consuming (-)-cubebin. © 2013 Elsevier Inc.

The Mode of Action of Recombinant Mycobacterium tuberculosis Shikimate Kinase: Kinetics and Thermodynamics Analyses

Tuberculosis remains as one of the main cause of mortality worldwide due to a single infectious agent, Mycobacterium tuberculosis. The aroK-encoded M. tuberculosis Shikimate Kinase (MtSK), shown to be essential for survival of bacilli, catalyzes the phosphoryl transfer from ATP to the carbon-3 hydroxyl group of shikimate (SKH), yielding shikimate-3-phosphate and ADP. Here we present purification to homogeneity, and oligomeric state determination of recombinant MtSK. Biochemical and biophysical data suggest that the chemical reaction catalyzed by monomeric MtSK follows a rapid-equilibrium random order of substrate binding, and ordered product release. Isothermal titration calorimetry (ITC) for binding of ligands to MtSK provided thermodynamic signatures of non-covalent interactions to each process. A comparison of steady-state kinetics parameters and equilibrium dissociation constant value determined by ITC showed that ATP binding does not increase the affinity of MtSK for SKH. We suggest that MtSK would more appropriately be described as an aroL-encoded type II shikimate kinase. Our manuscript also gives thermodynamic description of SKH binding to MtSK and data for the number of protons exchanged during this bimolecular interaction. The negative value for the change in constant pressure heat capacity (ΔCp) and molecular homology model building suggest a pronounced contribution of desolvation of non-polar groups upon binary complex formation. Thermodynamic parameters were deconvoluted into hydrophobic and vibrational contributions upon MtSK:SKH binary complex formation. Data for the number of protons exchanged during this bimolecular interaction are interpreted in light of a structural model to try to propose the likely amino acid side chains that are the proton donors to bulk solvent following MtSK:SKH complex formation. © 2013 Rosado et al.

Estádios de maturação de pêssegos 'Aurora-1' para o processamento mínimo

The experiment aimed to verify the effect of maturation stage on the quality of minimally processed peaches. Fruits were used in two stages of maturity, on time corresponding to the background color yellow-green, and mature, which corresponds completely to the background color yellow. The minimum process consisted of washing, sanitizing, enzyme peel, cut lengthwise and removed the stone fruits. Halves obtained were immersed in water chlorinated to 10 mg L-1 of water and left on standing to drain the excess liquid. Afterwards, it was proceeded the packaging of the halves in containers of polyethylene terephthalate (PET) and with transparent lid, and the storage at 3 ± 2 ° C and RH = 65% for 12 days, with assessments every three days. The variables evaluated were appearance, weight loss, firmness, soluble solids, titratable acidity, soluble and reduced sugars, ascorbic acid, total and soluble pectin, coloring and activity of polyphenoloxidase. The storage of minimally processed peaches 'Aurora-1' mature harvested was limited mainly by the loss of freshness and firmness, and because they have darker appearance, and lower levels of reduced sugars and ascorbic acid. Peaches 'Aurora-1', harvested at the maturity stage on time, had better quality and longer duration of their minimally processed products.

In vitro targeting of Polo-like kinase 1 in bladder carcinoma: Comparative effects of four potent inhibitors

Despite the improvements in neoadjuvant chemotherapy, the outcome of patients with advanced bladder cancer has changed very little over the past 30 years. In the present study we tested and compared the in vitro antitumor activities of four different inhibitors of Polo-like kinase 1 (PLK1) (BI 2536, BI 6727, GW843682X, and GSK461364), against 3 bladder carcinoma cell lines RT4, 5637 and T24. The impact on radiosensitivity and drug interactions in simultaneous treatments with cisplatin, methotrexate, and doxorubicin were also investigated. Our results showed that PLK1 inhibition prevented cell proliferation and clonogenicity, causing significant inhibition of invasion of tumor cells, though modest differences were observed between drugs. Moreover, all PLK1 inhibitors induced G2/M arrest, with the subsequent induction of death in all 3 cell lines. Drug interactions studies showed auspicious results for all PLK1 inhibitors when combined with the commonly used cisplatin and methotrexate, though combinations with doxorubicin showed mostly antagonistic effects. Comparably, the four PLK1 inhibitors efficiently sensitized cells to ionizing radiation. Our findings demonstrate that irrespective of the inhibitor used, the pharmacological inhibition of PLK1 constrains bladder cancer growth and dissemination, providing new opportunities for future therapeutic intervention. However, further laboratorial and preclinical tests are still needed to corroborate the usefulness of using them in combination with other commonly used chemotherapeutic drugs. © 2013 Landes Bioscience.

Serum activity of creatine kinase and aminotransferase aspartate enzymes of horses submitted to muscle biopsy and incremental jump test

The objective was to evaluate serum activity of the enzymes creatine kinase (CK) and aspartate aminotransferase (AST), which are leakage enzymes responsive to muscle injury, of athletic horses that underwent muscle biopsy and incremental jump test (IJT) involving incremental jumps. The animals were grouped as follows: the first group, horses with history of superior performance (SP); the second, with a history of inferior performance (IP); and lastly, a control group (CG). All groups underwent biopsy of the gluteus medius muscle, while groups SP and IP were also submitted to the incremental jump test (IJT) 24 hours after biopsy. The IJT consisted of three stages with 40 jumps each, where jump height increased progressively, from 40 to 60 and last, 80cm. Blood samples were drawn before biopsy, and 6 and 24 hours after the exercise as well. The levels of CK serum activity increased 6 hours after exercise and decreased 24 hours later in all groups, including CG. AST activity did not increase after biopsy and exercise. There was no increase of both enzyme activities that could be attributed to the exercise, possibly due to exercise short duration and/or low intensity. We conclude that the muscle biopsy was able to show that there was enough stimulus to cause CK enzyme leakage into the plasma, and consequent detection of increased serum activity, while the incremental jump test did not.

Caracterização do desenvolvimento de pêssegos 'Aurora-1' e sua conservação pós-colheita em dois estádios de maturação

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Sobre a formação do professor de música: o tempo fugidio entre a aurora, o crepúsculo e o silêncio

Pós-graduação em Música - IA

O abaixamento das médias pretônicas no português falado em Aurora do Pará – PA: uma análise variacionista

A presente pesquisa teve como objeto de estudo a investigação do abaixamento das médias pretônicas na variedade do português falado em Aurora do Pará (PA). Pautou-se nos pressupostos da sociolinguística quantitativa de Labov (1972), suporte necessário para investigar e sistematizar a variação de uma comunidade linguística. Além destes, foram utilizados alguns procedimentos metodológicos adotados por Bortoni-Ricardo (1985) para as análises de redes sociais, importantes para o estudo de dialetos em comunidades de migração, como é o caso de Aurora do Pará, localizada na Mesorregião do Nordeste Paraense e que apresenta como particularidade o fato de ter recebido intenso fluxo migratório nas décadas de 60,70 e 80 do século passado. O corpus foi formado a partir de gravações de entrevistas de 28 informantes, divididos em dois grupos: a) um grupo de ancoragem, com 19 informantes migrantes do Ceará (9 (nove) do sexo masculino e 10 (dez) do sexo feminino), distribuídos nas faixas etárias de 30 a 46 anos e de 50 anos acima; b) outro de controle, com 9 (nove) informantes (3 (três) do sexo masculino e 6 (seis) do sexo feminino), paraenses descendentes do grupo de ancoragem. Os dados do corpus submetidos às análises somaram 4.033 ocorrências das vogais-objeto, anterior (2.394) e posterior (1.639). Foram estabelecidas como variáveis extralinguísticas: sexo, grupo de amostra, tempo de residência, e localidade. Para variáveis linguísticas, foram consideradas: natureza da vogal tônica, vogal pre-pretônica quando for oral, vogal pré-pretônica quando for nasal, vogal contígua, distância relativa à sílaba tônica, atonicidade, natureza do sufixo, consoante do onset da sílaba da vogal-alvo, consoante do onset da sílaba da vogal seguinte e peso silábico. Após as análises estatísticas computadas pelo software Goldvarb, os resultados mostraram que no dialeto de Aurora do Pará/PA predominam as variantes de não abaixamento – [.i,e] .71 e [o,u] .74 em detrimento das do abaixamento [E] .28 e [O] .26. Para o abaixamento, as variáveis favorecedoras foram: (i) natureza da vogal tônica, (ii) Vogal pré-pretônica, quando for oral, (iii) Vogal contígua, (iv) Distância relativamente à Sílaba Tônica, (v) Atonicidade, (vi) Natureza do sufixo, (vii) Consoante do onset da sílaba da vogal-alvo, (viii) Consoante do onset da sílaba seguinte, (ix) Peso silábico em relação à sílaba vogal alvo, (x) Sexo, (xi) Faixa etária, (xii) Tempo de residência. Os resultados revelaram perda da marca dialetal dos migrantes cearenses por conta do contato dialetal com outros dialetos e evidenciaram que o abaixamento vocálico no dialeto em questão é motivado, sobretudo pelo processo de harmonia vocálica. Tais resultados são reflexos da rede social dos informantes a qual tem baixa densidade e é uniplex, caracterizando-os como mais propensos a mudanças culturais e inovações linguísticas.

Processamento mínimo de pêssegos ‘Aurora-1’: estádio de maturação, embalagens, temperaturas de conservação e aditivos naturais

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Losses of immunoreactive parvalbumin amacrine and immunoreactive alphaprotein kinase C bipolar cells caused by methylmercury chloride intoxication in the retina of the tropical fish Hoplias malabaricus

To quantify the effects of methylmercury (MeHg) on amacrine and on ON-bipolar cells in the retina, experiments were performed in MeHg-exposed groups of adult trahiras (Hoplias malabaricus) at two dose levels (2 and 6 µg/g, ip). The retinas of test and control groups were processed by mouse anti-parvalbumin and rabbit anti-_aprotein kinase C (_aPKC) immunocytochemistry. Morphology and soma location in the inner nuclear layer were used to identify immunoreactive parvalbumin (PV-IR) and _aPKC (_aPKC-IR) in wholemount preparations. Cell density, topography and isodensity maps were estimated using confocal images. PV-IR was detected in amacrine cells in the inner nuclear layer and in displaced amacrine cells from the ganglion cell layer, and _aPKC-IR was detected in ON-bipolar cells. The MeHg-treated group (6 µg/g) showed significant reduction of the ON-bipolar _aPKC-IR cell density (mean density = 1306 ± 393 cells/mm²) compared to control (1886 ± 892 cells/mm²; P < 0.001). The mean densities found for amacrine PV-IR cells in MeHg-treated retinas were 1040 ± 56 cells/mm² (2 µg/g) and 845 ± 82 cells/mm² (6 µg/g), also lower than control (1312 ± 31 cells/mm²; P < 0.05), differently from the data observed in displaced PV-IR amacrine cells. These results show that MeHg changed the PV-IR amacrine cell density in a dose-dependent way, and reduced the density of _aKC-IR bipolar cells at the dose of 6 µg/g. Further studies are needed to identify the physiological impact of these findings on visual function.

Fertilidade e fauna edáfica em solo sob reflorestamento com paricá (Schizolobium amazonicum Huber ex Ducke) no município de Aurora do Pará

Com este estudo objetivou-se avaliar a variação na fertilidade do solo e na fauna edáfica sob reflorestamento com paricá (Schizolobium amazonicum Heber ex. Ducke) em monocultivo ou em sistema agroflorestal quando comparados com floresta secundária em área experimental considerando a sazonalidade da precipitação no período de 2009 e 2010. A área experimental pertence a Fazenda Tramontina Belém S/A, localizada no nordeste paraense, no município de Aurora do Pará. Foram analisados quatro tratamentos submetidos a reflorestamento com: Curauá (Ananas comosus var. erectifolius L.B.Smith), Paricá (Shizolobium var. amazonicum Huber ex Ducke) sob a forma de monocultivos, Paricá + curauá (Ananas comosus var. erectifolius L.B.Smith; Shizolobium var. amazonicum Huber ex Ducke); Paricá + Mogno + Freijó + Curauá (Shizolobium var. amazonicum Huber ex Ducke; Switenia macrophylla, King; Cordia goeldiana Huber; Ananas comosus var. erectifolius L.B.Smith). As amostragens foram realizadas em dezembro de 2009, abril e julho de 2010, o que caracterizou o período sazonal de transição (estiagem para chuva intensa), chuva intensa e estiagem respectivamente, para avaliar a granulometria, densidade aparente, densidade da partícula, porosidade total e umidade atual, bases trocáveis, soma de bases, CTC, acidez, fósforo, teor de carbono orgânico, pH, em três profundidades diferentes (0 – 10 cm. 10 - 20 cm; 20 – 40 cm) e a ocorrência de macrofauna edáfica. Os resultados mostraram a ação dos períodos sazonais sobre a densidade aparente, densidade da partícula, porosidade total do solo. Fatores químicos como, por exemplo, carbono orgânico, cujos teores variaram entre 5,85 g/kg e 13,00 g/kg, com teores elevados no sistema de cultivo S2, sofreu alterações nos períodos sazonais chuva intensa e estiagem. Quanto a fauna edáfica, foram capturados 9.964 invertebrados pertencentes a 26 táxons diferentes. Os mais abundantes foram Hymenoptera- Formicidae (5.805), Coleoptera (1.454), Acari (862), Collembola (649), Diplopoda (307) e Isopoda (110). Dos 26 táxons identificados, aproximadamente 40% deles apresentaram apenas um representante nas três amostragens efetuadas ou em apenas uma delas. Os maiores valores para frequência relativa ocorreu no sistema de cultivo S2, S4 e S3, respectivamente. O maior valor para frequência absoluta ocorreu durante o período sazonal chuva intensa em S1. As áreas sob reflorestamento com monocultivo e sistema agroflorestal paricà + curauá mostraram melhores desempenhos na recuperação da fertilidade do solo e da fauna edáfica comprovando a eficácia do paricá em monocultivo ou em sistema agroflorestal na recuperação da fertilidade do solo e da fauna edáfica.

Effects of different intensities of physical exercise on insulin sensitivity and protein kinase B/Akt activity in skeletal muscle of obese mice

Objetivo: Investigar os efeitos do exercício físico agudo com diferentes intensidades sobre a sensibilidade à insulina e a atividade da proteína quinase B/Akt no músculo esquelético de camundongos obesos. Método: Foram utilizados camundongos Swiss, divididos aleatoriamente em quatro grupos, que receberam dieta padrão (grupo controle) ou dieta hiperlipídica (grupos obeso sedentário e grupos obesos exercitados 1 e 2), por período de 12 semanas. Dois diferentes protocolos de exercício foram utilizados: natação durante 1 hora com ou sem sobrecarga de 5% da massa corporal. O teste de tolerância à insulina foi realizado para estimar a sensibilidade à insulina. E os níveis protéicos da proteína quinase B/Akt e de sua fosforilação foram determinados no músculo esquelético dos camundongos, através da técnica de Western blot. Resultado: Uma sessão de exercício físico foi capaz de inibir a resistência à insulina em decorrência de uma dieta hiperlipídica. Foi possível demonstrar um aumento na fosforilação da proteína quinase B/Akt, melhora da sinalização da insulina e redução da glicemia de jejum nos camundongos que realizaram 1 hora de natação sem sobrecarga adicional e nos camundongos que realizaram 1 hora de natação com sobrecarga adicional de 5% de sua massa corporal. Entretanto, não houve diferença significativa entre os grupos que realizaram o exercício em diferentes intensidades. Conclusão: Independente da intensidade, o exercício físico aeróbio conseguiu aumentar a sensibilidade à insulina e a fosforilação da proteína quinase B/Akt, revelando ser uma boa forma de tratamento e prevenção do diabetes tipo 2.

Antifungal activity of flavonoids from Heteropterys byrsonimifolia and a commercial source against Aspergillus ochraceus: In silico interactions of these compounds with a protein kinase

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