Evaluation of the anti-inflammatory effects of synthesised tanshinone I and isotanshinone I analogues in zebrafish

During inflammation, dysregulated neutrophil behaviour can play a major role in a range of chronic inflammatory diseases, for many of which current treatments are generally ineffective. Recently, specific naturally occurring tanshinones have shown promising anti-inflammatory effects by targeting neutrophils in vivo, yet such tanshinones, and moreover, their isomeric isotanshinone counterparts, are still a largely underexplored class of compounds, both in terms of synthesis and biological effects. To explore the anti-inflammatory effects of isotanshinones, and the tanshinones more generally, a series of substituted tanshinone and isotanshinone analogues was synthesised, alongside other structurally similar molecules. Evaluation of these using a transgenic zebrafish model of neutrophilic inflammation revealed differential anti-inflammatory profiles in vivo, with a number of compounds exhibiting promising effects. Several compounds reduce initial neutrophil recruitment and/or promote resolution of neutrophilic inflammation, of which two also result in increased apoptosis of human neutrophils. In particular, the methoxy-substituted tanshinone 39 specifically accelerates resolution of inflammation without affecting the recruitment of neutrophils to inflammatory sites, making this a particularly attractive candidate for potential pro-resolution therapeutics, as well as a possible lead for future development of functionalised tanshinones as molecular tools and/or chemical probes. The structurally related β-lapachones promote neutrophil recruitment but do not affect resolution. We also observed notable differences in toxicity profiles between compound classes. Overall, we provide new insights into the in vivo anti-inflammatory activities of several novel tanshinones, isotanshinones, and structurally related compounds

Performance of Holstein heifers fed sugarcane silages treated with urea, sodium benzoate or Lactobacillus buchneri Desempenho de novilhas Holandesas alimentadas com silagens de cana-de-açúcar tratadas com uréia, benzoato de sódio ou Lactobacillus buchneri

The objective of this work was to evaluate the performance of heifers fed sugarcane silages produced with and without additives. Thirty-two Holstein heifers were randomly assigned, in a block design, to evaluate rations (46% silage; 54% concentrate; 12% crude protein) containing silages treated with (fresh basis) urea (0.5%), sodium benzoate (0.1%) or Lactobacillus buchneri (3.64x10(5) cfu g-1 ). Inoculation with L. buchneri improved daily gain (1.24 vs. 0.94 kg day-1 ), and the addition of benzoate resulted in better feed conversion (7.6 vs. 9.4 kg of dry matter per kg of live weight), in relation to the untreated silage (control). Treatments did not affect dry matter intake (mean of 2.19% of live weight). Rations containing silages treated with benzoate or L. buchneri showed lower cost per kg of weight gain. Treatment with urea did not improve animal performance, but the cost per kg of weight gain was lower than that of the control ration.<br>O objetivo deste trabalho foi avaliar a performance de novilhas alimentadas com silagens de cana-de-açúcar tratadas com aditivos. Trinta e duas novilhas Holandesas foram aleatoriamente distribuídas em um delineamento em blocos, para avaliar rações (46% silagem; 54% concentrado; 12% proteína bruta) contendo silagem tratada com (base matéria verde) uréia (0,5%), benzoato de sódio (0,1%) ou Lactobacillus buchneri (3,64x10(5) ufc g-1 ). A inoculação de L. buchneri melhorou o ganho diário (1,24 vs. 0,94 kg dia-1) e a adição de benzoato melhorou a conversão alimentar (7,6 vs. 9,4 kg de matéria seca por kg de peso vivo), relativamente ao controle (silagem não tratada). Os tratamentos não afetaram o consumo de matéria seca (2,19% do peso vivo). As rações com silagens tratadas com benzoato ou L. buchneri mostraram menor custo por kg de ganho de peso. O tratamento com uréia não melhorou o desempenho animal, mas o custo por kg de ganho de peso foi menor do que na dieta controle

Silagens de grãos de milho puro e com adição de grãos de soja, de girassol ou uréia Quality of corn grain silage added with soybean, sunflower or urea

O objetivo deste trabalho foi avaliar a composição química e a estabilidade em aerobiose de silagens de grãos de milho, ensilados com adição de soja crua, girassol ou uréia. Em delineamento inteiramente casualizado, com quatro repetições, foram avaliados os tratamentos: grãos de milho; grãos de milho mais grãos de soja; grãos de milho mais grãos de girassol; e grãos de milho mais uréia. Foram utilizados, como silos experimentais, tonéis de plástico com capacidade para 200 kg, que permaneceram vedados por nove meses. Avaliaram-se: a composição química, a degradabilidade ruminal da matéria seca e da proteína bruta, o desaparecimento do amido no rúmen e a estabilidade aeróbia das silagens. Todos os tratamentos tiveram efeito sobre a degradabilidade efetiva da matéria seca e da proteína bruta, e também sobre a composição química das silagens, especialmente nos teores de proteína bruta e extrato etéreo. A adição de 20% de grãos de soja, de girassol ou uréia (1%), na silagem de grãos de milho, melhora sua composição químico-bromatológica, porém reduz a degradabilidade efetiva da matéria seca e da proteína bruta. A adição de uréia à silagem de grãos úmidos de milho diminui as perdas de matéria seca e melhora a estabilidade em aerobiose.<br>The objective of this work was to evaluate the chemical composition and aerobic stability of corn grain silage, added with crude soybean, sunflower or urea. The following treatments, arranged in a completely randomized design, with four replications, were evaluated: corn grain; corn grain plus soybean grain; corn grain plus sunflower grain; and corn grain plus urea. Plastic barrels with 200 kg of capacity were used as experimental silos and kept closed for nine months. Chemical composition, dry matter and crude protein ruminal degradability, starch ruminal disappearance, and the aerobic stability of silages were evaluated. The addition of soybean, sunflower or urea on silages influenced the effective degradability of dry matter and crude protein, and the chemical composition, especially in relation to crude protein and ether extract contents. The addition of 20% soybean, sunflower or urea (1%) in corn grain silage improves chemical composition, but decreases the effective degradability of dry matter and crude protein. Urea addition to moist corn grain silage reduces losses on dry matter and improves the aerobic stability

Avaliação das metaloproteinases de matriz -2 e -9 em gatos com desmineralização óssea secundária à tirotoxicose induzida Evaluation of matrix metalloproteinases -2 and -9 in cats under bone demineralization secondary to induced thyrotoxicosis

Observou-se significativo aumento de atividade das formas ativas das metaloproteinases -2 e -9 em gatos com tirotoxicose induzida e desmineralização óssea. As formas pró e intermediária da metaloproteinase -2 elevaram-se com 14 dias de administração hormonal, porém, posteriormente, houve uma tendência de queda. Observou-se correlação negativa entre a forma ativa das metaloproteinases de matriz -2 e -9 e a densidade mineral óssea da extremidade distal do rádio. Os resultados sugerem aumento da degradação da matriz colágena secundária com a elevação dos hormônios tiroidianos.<br>Significant increase of activity of active forms of matrix metalloproteinases -2 and -9 in cats under induced thyrotoxicosis and bone demineralization was observed. Pro and intermediated forms of matrix metalloproteinases -2 and -9 increased at 14 days of hormonal treatment, followed by decrease tendency. A negative correlation between active forms of matrix metalloproteinases -2 and -9 and bone mineral density of radius distal extremity was also observed. The results suggest an increase of collagen matrix degradation secondary to high levels of thyroid hormones