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1.
Biochem J ; 450(3): 559-71, 2013 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-23282185

RESUMEN

PVL (Panton-Valentine leukocidin) and other Staphylococcus aureus ß-stranded pore-forming toxins are important virulence factors involved in various pathologies that are often necrotizing. The present study characterized leukotoxin inhibition by selected SCns (p-sulfonato-calix[n]arenes): SC4, SC6 and SC8. These chemicals have no toxic effects on human erythrocytes or neutrophils, and some are able to inhibit both the activity of and the cell lysis by leukotoxins in a dose-dependent manner. Depending on the type of leukotoxins and SCns, flow cytometry revealed IC50 values of 6-22 µM for Ca2+ activation and of 2-50 µM for cell lysis. SCns were observed to affect membrane binding of class S proteins responsible for cell specificity. Electrospray MS and surface plasmon resonance established supramolecular interactions (1:1 stoichiometry) between SCns and class S proteins in solution, but not class F proteins. The membrane-binding affinity of S proteins was Kd=0.07-6.2 nM. The binding ability was completely abolished by SCns at different concentrations according to the number of benzenes (30-300 µM; SC8>SC6≫SC4). The inhibitory properties of SCns were also observed in vivo in a rabbit model of PVL-induced endophthalmitis. These calixarenes may represent new therapeutic avenues aimed at minimizing inflammatory reactions and necrosis due to certain virulence factors.


Asunto(s)
Calixarenos/farmacología , Exotoxinas/antagonistas & inhibidores , Exotoxinas/metabolismo , Staphylococcus aureus/metabolismo , Animales , Toxinas Bacterianas/antagonistas & inhibidores , Toxinas Bacterianas/metabolismo , Calixarenos/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Proteínas Hemolisinas/antagonistas & inhibidores , Proteínas Hemolisinas/metabolismo , Humanos , Sustancias Macromoleculares/metabolismo , Modelos Biológicos , Fenoles/metabolismo , Fenoles/farmacología , Unión Proteica/efectos de los fármacos , Unión Proteica/fisiología , Conejos , Esfingomielina Fosfodiesterasa/antagonistas & inhibidores , Esfingomielina Fosfodiesterasa/metabolismo , Staphylococcus aureus/patogenicidad , Factores de Virulencia/antagonistas & inhibidores , Factores de Virulencia/metabolismo
2.
Arq. ciênc. vet. zool. UNIPAR ; 15(1): 13-37, jan-jun. 2012. ilus
Artículo en Portugués | LILACS | ID: lil-681422

RESUMEN

A criação de caprinos e ovinos para corte em Palotina está crescendo devido à instalação de frigoríficos na região e, a fim de conhecer estes animais, foram visitados 15 criatórios e preencheu-se um questionário. Ademais, coletou-se sangue e fezes de 183 animais previamente submetidos a exame clínico. Os ovinos correspondiam a 74% dos animais e as raças tinham aptidão ao corte. Os animais eram mantidos em sistema semi-intensivo, criados a pasto e suplementados com concentrado e sal mineral apropriado para pequenos ruminantes. A maioria dos animais tinham entre seis e 18 meses e a castração de machos era rotineira. Havia preocupação com a verminose, mas o controle baseava-se exclusivamente em métodos farmacológicos. Verificou-se que os animais apresentavam mucosas levemente hipocoradas, associadas ao hematócrito (%) de 26,89±0,63 e 32,35±0,84 e presença de 1053,33±279,55 e 1578,47±352,69 ovos por grama de fezes em caprinos e ovinos, respectivamente, sendo a Cooperia o parasita frequente. O estado clínico geral dos animais era bom, porém já que os produtores investiam em genética e nutrição, seria aconselhável abater os animais precocemente e melhorar a prevenção das helmintoses para reduzir os gastos de produção.


Production of meat goat and sheep in Palotina has been growing due to installation of regional slaughterhouses. To know more about these animals, 15 properties were visited and a questionnaire was filled out. Moreover, blood and excrements were collected from 183 animals previously submitted to clinical examination. Sheep corresponded to 74% of animals, and their breeds had weight increase. Animals were kept in a semi-intensive system, where they grazed and were supplemented with concentrate and appropriate mineral salt for small ruminants. Most of the animals were between 6 and 18 months old and males were routinely castrated. Helminthiasis was a problem, but control was based only on pharmacological methods. Mucous was a little pale, packed cell (%) volume was from 26.89±0.63 to 32.3±0.84 and there were from 1053.33±2795 to 1578.47±352.69 eggs per gram of excrements in goats and sheep, respectively. Cooperia was the most frequent parasite. The general clinical state of the animals was good; however, since producers invest in genetics and nutrition, it would be advisable to slaughter animals precociously and improve the prevention of helminthiasis to reduce expenses.


La creación de caprinos y ovinos para engorde y matanza en Palotina está creciendo debido a la instalación de frigoríficos en la región y, a fin de conocer estos animales, se visitó 15 granjas y se rellenó un cuestionario. Además, se recolectó sangre y excrementos de 183 animales, previamente sometidos a examen clínico. Los ovinos correspondían a 74% de los animales y las razas tenían tendencia para producción de carne. Los animales eran mantenidos en sistema semi-intensivo, creados a pasto y suplementados con concentrado y sal mineral apropiado para pequeños rumiantes. La mayoría de los animales tenía entre seis y dieciocho meses y la castración de los machos era rutinera. Había preocupación con gusanos, pero el control se basaba exclusivamente en métodos farmacológicos. Se comprobó que los animales presentaban mucosas levemente pálidas, asociadas al hematocrito (%) de 26,89±0,63 y 32,35±0,84 y 32,35±0,84 y presencia de 1053,33±279,55 y 1578,47±352,69 huevos por gramo de excrementos en caprinos y ovinos, respectivamente, siendo la Cooperia el parasito frecuente. El estado clínico general de los animales era bueno, pero como los productores invierten en genética y nutrición, sería aconsejable sacrificar los animales prematuramente y mejorar la prevención de helmintos para reducir los costos de producción.


Asunto(s)
Animales , Cabras/genética , Farmacología/métodos , Hematócrito/veterinaria , Rumiantes
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