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This study aimed to monitor the effects of dipyrone following multiple administrations in northeastern donkeys. Ten castrated male donkeys, aged 6.4 ± 3 years and weighing 130.6 ± 9.8 kg, were administered dipyrone (25 mg/kg IV) every 12 h, resulting in six administrations (D1 to D6) per animal. Blood samples were collected over a 72 h monitoring period. A validated UHPLC-MS/MS method was employed to determine the plasma concentrations of the 4- methylaminoantipyrine (4-MAA) and 4-aminoantipyrine (4-AA). The calculated pharmacokinetic variables of 4-MAA after D1 and D6 were, respectively: Cmax (µg/mL) = 163.60 ± 179.72 and 178.79 ± 196.94; T1/2beta (h) = 2.65 ± 0.65 and 3.37 ± 1.03; and AUC0-t (µg/mL × h) = 240.38 ± 130.87 and 373.52 ± 78.85. The same variables for 4-AA were: Cmax, (µg/mL) = 0.44 ± 0.27 and 0.90 ± 0.31, T1/2beta (h) = 14.77 ± 13.13 and 35.97 and AUC0-t (µg/mL × h) = 3.20 ± 0.43 and 27.73 ± 11.99. Concentrations of 4-MAA exceeded the minimum concentration required for 50% inhibition of cyclooxygenases 1 and 2. However, an accumulation of 4-AA, was observed. Further clinical studies are necessary to ascertain the implications of these findings on the pharmacodynamic response to dipyrone in northeastern donkeys.

Assuntos

RESUMO

In this work, a novel molecularly imprinted polymer (MIP) for use as a solid phase extraction sorbent was developed for the determination of coenzyme Q10 (CoQ10) in liver extract. CoQ10 is an essential cofactor in mitochondrial oxidative phosphorylation and a powerful antioxidant agent found in low concentrations in biological samples. This fact and its high hydrophobicity make the analysis of CoQ10 technically challenging. Accordingly, a MIP was synthesised using coenzyme Q0 as the template, methacrylic acid as the functional monomer, acetonitrile as the porogen, ethylene glycol dimethacrylate as the crosslinker and benzoyl peroxide as the initiator. Various parameters affecting the polymer preparation and extraction efficiency were evaluated. Morphological characterisation of the MIP and its proper comparison with C18 as a sorbent in solid phase extraction were performed. The optimal conditions for the molecularly imprinted solid phase extraction (MISPE) consisted of 400 µL of sample mixed with 30 mg of MIP and 600 µL of water to reach the optimum solution loading. The loading was followed by a washing step consisting of 1 mL of a 1-propanol solution (1-propanol:water, 30:70,v/v) and elution with 1 mL of 1-propanol. After clean-up, the CoQ10 in the samples was analysed by high performance liquid chromatography. The extraction recoveries were higher than 73.7% with good precision (3.6-8.3%). The limits of detection and quantification were 2.4 and 7.5 µg g(-1), respectively, and a linear range between 7.5 and 150 µg g(-1) of tissue was achieved. The new MISPE procedure provided a successful clean-up for the determination of CoQ10 in a complex matrix.

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RESUMO

The patulin, (4hydroxy-4furo[3,2-c]pyran(6H)-1),, is a thermal resistent mycotoxin produced by several species of fungi are common in plants, mainly in derivatives and apples. Studies on the toxicity in animals have shown that mycotoxin has character teratogenic, and carcinogenic in mice immunotoxic. Its biosynthesis is well understood involving a series of reactions of condensation and oxiredução, many catalyzed by enzymes. The danger of contamination of food with patulin, warning about the need for a more rigorous control. Recent research aimed their removal and degradation as well as increase the sensitivity of the tests, making them faster and at less cost. The removal of patulin of food is made with composite adsorbents, with inconvenience to diminish the quality of the product by adsorbs other components desirable. The degradation is made with sulfur compounds, which are not allowed in food in many countries, and the growth of yeasts, such as the production of cider. Many yeasts have resistance against patulin and produce compounds capable degrade it. Here, we reviewed research on patulin with emphasis on its influence in food industry, incidence of patulin in apple juice and other foods, maximum permissible concentrations, health effects, biosynthesis, removal, degradation and most widely used methods for its detection and quantification.

A patulina, 4hidroxi-4furo[3,2-c] pirano(6H)-1, micotoxina termo-resistente, é produzida por várias espécies de fungos, comuns em vegetais, produtos derivados e principalmente em maçãs. Estudos sobre a toxicidade em animais demonstraram esta micotoxina possui caráter teratogênico, cancerígeno e imunotóxico em camundongos. Sua biossíntese é bem compreendida envolvendo uma série de reações de condensação e de oxiredução, muitas catalisadas por enzimas. O perigo da contaminação de alimentos com patulina, alerta sobre a necessidade de um controle mais rigoroso. Pesquisas recentes objetivam sua remoção e degradação, bem como aumentar a sensibilidade das análises, tornando-as mais rápidas e com menores custos. A remoção de patulina de alimentos é feita com compostos adsorventes, com inconveniente de diminuir a qualidade do produto por adsorver outros componentes desejáveis. A degradação é feita com compostos sulfurados, os quais não são permitidos em alimentos em muitos países, e pelo crescimento de leveduras, como no caso da produção de sidras. Muitas leveduras apresentam resistência contra a patulina e produzem compostos capazes de degradá-la. Aqui, foram revisadas pesquisas sobre patulina com ênfase sobre sua influência na indústria de alimentos, incidência de patulina em suco de maçã e outros alimentos, concentrações máximas permit

RESUMO

Patulin is a secondary metabolite produced by different species of fungi, being Penicillium expansum the most important species. Patulin is a mycotoxin that has been found mainly in mature apples used in the production of concentrated apple juice, but it can also be in other fruits, vegetables and nutritious products. Experiments carried out with laboratory animals have demonstrated that this mycotoxin produces several harmful effects, including mutagenicity, teratogenicity, carcinogenicity, immunosuppression and acute intoxications characterized by pulmonary oedema, hemorrhages, damages in the capillaries of liver, spleen and kidneys, as well as cerebral oedema. This revision article approaches physicochemical properties and toxicological aspects of the patulin, as well as its occurrence and strategies to prevent its presence in apple juices.

A patulina é um metabólito secundário produzido por diferentes gêneros e espécies de fungos. Penicillium expansum é certamente a espécie mais importante. É uma micotoxina encontrada principalmente em maçãs maduras utilizadas na produção de suco de maçã concentrado, mas também pode estar presente em outras frutas, vegetais e produtos alimentícios. Experimentos em animais de laboratório demonstraram que esta micotoxina produz diversos efeitos nocivos, incluindo mutagenicidade, teratogenicidade, carcinogenicidade, imunossupressão e intoxicações agudas caracterizadas por edema pulmonar, hemorragias, danos nos capilares hepáticos, do baço e rins, bem como edema cerebral. O presente artigo de revisão aborda aspectos físico-químicos e toxicológicos da patulina, bem como a sua ocorrência e estratégias para prevenir a sua presença em sucos de maçã.