Antimyotoxic Activity of Synthetic Peptides Derived from Bothrops atrox Snake Gamma Phospholipase A2 Inhibitor Selected by Virtual Screening.

BACKGROUND: Several studies have aimed to identify molecules that inhibit the toxic actions of snake venom phospholipases A2 (PLA2s). Studies carried out with PLA2 inhibitors (PLIs) have been shown to be efficient in this assignment. OBJECTIVE: This work aimed to analyze the interaction of peptides derived from Bothrops atrox PLIγ (atPLIγ) with a PLA2 and to evaluate the ability of these peptides to reduce phospholipase and myotoxic activities. METHODS: Peptides were subjected to molecular docking with a homologous Lys49 PLA2 from B. atrox venom modeled by homology. Phospholipase activity neutralization assay was performed with BthTX-II and different ratios of the peptides. A catalytically active and an inactive PLA2 were purified from the B. atrox venom and used together in the in vitro myotoxic activity neutralization experiments with the peptides. RESULTS: The peptides interacted with amino acids near the PLA2 hydrophobic channel and the loop that would be bound to calcium in Asp49 PLA2. They were able to reduce phospholipase activity and peptides DFCHNV and ATHEE reached the highest reduction levels, being these two peptides the best that also interacted in the in silico experiments. The peptides reduced the myotubes cell damage with a highlight for the DFCHNV peptide, which reduced by about 65%. It has been suggested that myotoxic activity reduction is related to the sites occupied in the PLA2 structure, which could corroborate the results observed in molecular docking. CONCLUSION: This study should contribute to the investigation of the potential of PLIs to inhibit the toxic effects of PLA2s.

Risk of urolithiasis in patients with Cystic Fibrosis

Introduction: It has been generally admitted that kidneys are not affected in Cystic fibrosis (CF) patients. Anyway, there are several studies demonstrating a higher prevalence of calcium oxalate nephrolithiasis prevalence in CF patients compared to normal population. The aim of our study was to evaluate renal disease regional prevalence in CF patients Methods: Cross-sectional regional controlled study. Index group = 20 CF subjects4- 30 years old controlled in a CF outpatient clinic in atertiary hospital. Control group = 73 healthy subjects randomly selected among the 100 subjects who completed the follow-up visits of the RICARDIN study. Physical examination and renal function analysis were conducted in both groups. CF patients had their functional measurements repeated in a 20 month interval. Renal ultrasonography was performed only in CF patients. Results: Height estimated creatinine clearance in CF patients were not statistically different from controls. Oxaluria (0.77mg/kg/24 h, p = 0.001) and phosphate excretion (18.98 mg/kg/24 h, p = 0.04) were significantly higher while citrate (7.76mg/kg/24 h, p = 0.04) and magnesium (1.60mg/kg/24 h, p = 0.04) excretion were significantly lower in CF patients than normal population reference values. No signs of nephrolithiasis ornephrocalcinosis were found. Conclusions: CF patients showed a conserved renal function , without ecographic abnormalities. CF patients showed increased urinary elimination of phosphate and oxalate and lower citrate and magnesium elimination, findings that predispose these patients to suffer from urolithiasis in the future (AU)

Introducción: generalmente, se ha aceptado que el riñón no sea un órgano afectado en la Fibrosis Quística (FQ). Diferentes estudios han demostrado que los pacientes con FQ tienen una mayor predisposición a padecer nefrolitiasis por cálculos de oxalato cálcico que la población general. Objetivo: estudiar la prevalencia autonómica de enfermedad renal en pacientes con FQ. Pacientes y métodos: estudio transversal analítico de ámbito autonómico, con grupo control. Grupo índice: 20 pacientes con FQ de 4-30 años de edad. Grupo control: 73 sujetos sanos, seleccionados al azar entre los 100 individuos de 13-21años de edad que completaron el seguimiento longitudinal del estudio RICARDIN. Realización en ambos grupos de estudio de examen físico y pruebas analíticas de función renal, repitiendo en el grupo FQ la recogida de datos 20 meses después. Ecografía renal sólo en el grupo índice. Resultados: el filtrado glomerular estimado por la talla no alcanzó diferencias significativas en el grupo FQ respecto al control. Los pacientes del grupo FQ presentaron valores significativamente más altos de oxaluria (0,77mg/kg/24 h, p = 0,001) y fosfaturia (18,98 mg/kg/24 h, p =0,04), y valores más bajos de citraturia (7,76 mg/kg/24 h,p = 0,04) y magnesuria (1,60 mg/kg/24 h, p = 0,04) que los valores normales de referencia. La ecografía renal no demostró en ningún caso hallazgos sugerentes de nefrocalcinosis ni nefrolitiasis. Conclusiones: los pacientes con FQ presentan una función renal conservada, sin diferencias significativas con los controles. Estos pacientes presentan alteraciones en la excreción urinaria de solutos que pueden favorecer la formación futura de cálculos renales (AU)