RESUMO
Piscirickettsia salmonis is one of the main pathogens causing considerable economic losses in salmonid farming. The DNA gyrase of several pathogenic bacteria has been the target of choice for antibiotic design and discovery for years, due to its key function during DNA replication. In this study, we carried out a combined in silico and in vitro approach to antibiotic discovery targeting the GyrA subunit of Piscirickettsia salmonis. The in silico results of this work showed that flumequine (-6.6 kcal/mol), finafloxacin (-7.2 kcal/mol), rosoxacin (-6.6 kcal/mol), elvitegravir (-6.4 kcal/mol), sarafloxacin (-8.3 kcal/mol), orbifloxacin (-7.9 kcal/mol), and sparfloxacin (-7.2 kcal/mol) are docked with good affinities in the DNA binding domain of the Piscirickettsia salmonis GyrA subunit. In the in vitro inhibition assay, it was observed that most of these molecules inhibit the growth of Piscirickettsia salmonis, except for elvitegravir. We believe that this methodology could help to significantly reduce the time and cost of antibiotic discovery trials to combat Piscirickettsia salmonis within the salmonid farming industry.
Assuntos
Doenças dos Peixes , Piscirickettsia , Animais , Antibacterianos/farmacologia , Piscirickettsia/genética , DNA Girase/genética , Doenças dos Peixes/tratamento farmacológico , Doenças dos Peixes/microbiologiaRESUMO
Renibacterium salmoninarum is one of the oldest known fish bacterial pathogens. This Gram-positive bacterium is the causative agent of Bacterial Kidney Disease (BKD), a chronic infection that primarily infects salmonids at low temperatures. Externally, infected fish may show exophthalmos, skin blisters, ulcerations, and hemorrhages at the base of the fins and along the lateral line. Internally, the kidney, heart, spleen, and liver may show signs of inflammation. The best characterized virulence factor of R. salmoninarum is p57, a 57 kDa protein located on the bacterial cell surface and secreted into surrounding fish tissue. The p57 protein in fish is the main mediator in suppressing the immune system, reducing antibody production, and intervening in cytokine activity. In this review, we will discuss aspects such as single nucleotide polymorphisms (SNPs) that modify the DNA sequence, variants in the number of copies of MSA genes, physical-chemical properties of the signal peptides, and the limited iron conditions that can modify p57 expression and increase the virulence of R. salmoninarum.
Assuntos
Doenças dos Peixes , Infecções por Bactérias Gram-Positivas , Animais , Proteômica , Virulência/genética , Proteínas da Membrana Bacteriana Externa/genética , Genômica , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Positivas/veterinária , Infecções por Bactérias Gram-Positivas/microbiologiaRESUMO
The aim was to study whether ozone affects vascular endothelium by causing inducible nitric oxide synthase (iNOS) expression and tyrosine nitration. We also studied biomarkers of endothelial function. Male Wistar rats were exposed to ozone (0.25ppm, 4h/day) or filtered air (control, ozone <0.05ppm). After ozone exposure, blood samples were taken to measure 6-keto prostaglandin F1α (6-keto PGF1α), dehydro-thromboxane B(2) (DH-TxB(2)), endothelin-1 and NO(2)(-)/NO(3)(-) (NO(x)(-)). iNOS and nitrotyrosine were detected in aorta by immunohistochemistry. Nitrotyrosine was also detected by immunoelectromicroscopy. Control aortae failed to show either iNOS or nitrotyrosine. Time-dependent positive iNOS and nitrotyrosine cells were observed in exposed animals. Except for NO(x)(-), endothelial markers decreased after 14 days of ozone exposure (P<0.05). After 28 days of ozone, 6-keto PGF1α remained low (P<0.05) while DH-TxB(2) increased (P<0.05). It is concluded that ozone causes endothelial dysfunction manifested early with peroxynitrite formation and lately with changes in endothelial markers.
RESUMO
Se estudió una muestra de 242 pacientes comprobadamente diabéticos en los que se consideró su relación con la dolencia mental que motivó su hospitalización, así como la distribución por sexo y edad; se investigó la clínica de la enfermedad diabética tanto en su aspecto sintomático como en los signos de afectación neurológica, cardiovascular y renal; también se estudió la expresión humoral así como las respuestas a las pruebas diagnósticas de uso común y se hizo hincapié en el estudio de las grasas (colesterol y lípidos totales), a las alteraciones electrocardiográficas y a los datos aportados por el examen radiológico y los cambios retinianos. Se estudió la modalidad de diabetes en consideración a su forma de tratamiento y en su relación con la influencia psicofarmacológica en la evolución de los casos
Assuntos
Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Diabetes Mellitus/epidemiologia , Transtornos Mentais , Tempo de InternaçãoRESUMO
El estudio mediante preguntas abiertas y de selección a dos grupos de alumnos de cuarto año de medicina que participaron en una actividad docente experimental donde se impartió el tema de los trastornos de personalidad obsesiva y paranoide, utilizando comparativamente las técnicas de escenificación y conferencia, evidenció iguales resultados inmediatos en lo relativo a posibilidad de reproducir y reconocer los conocimientos transmitidos, pero mejores redimientos a favor de la escenificación, luego de transcurridos quince días, especialmente en los relativo a reproducción de la materia que resultó de más difícil asimilación. Los autores recomiendan profundizar en el estudio de la escenificación in vivo como recurso docente y sugieren se incremente la utilización de otras técnicas basadas en imágenas en movimiento cuando no sea factible la valoración de enfermos modelos, en la enseñanza de la psicopatología