RESUMO
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.
Assuntos
Fosfolipases A2 do Grupo IV/antagonistas & inibidores , Mioblastos/efeitos dos fármacos , Peptídeos/farmacologia , Inibidores de Fosfolipase A2/farmacologia , Animais , Bothrops , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos , Fosfolipases A2 do Grupo IV/isolamento & purificação , Fosfolipases A2 do Grupo IV/metabolismo , Camundongos , Modelos Moleculares , Peptídeos/síntese química , Peptídeos/química , Inibidores de Fosfolipase A2/síntese química , Inibidores de Fosfolipase A2/químicaRESUMO
UNLABELLED: Preoperative localization of the parathyroids using (99m)Tc-sestamibi scanning has not yet been established as a routine diagnostic procedure for primary hyperparathyroidism. Several studies have demonstrated a variable degree of accuracy (70%-98%) in asymptomatic patients. METHODS: We evaluated the accuracy of this technique in 64 patients who underwent scanning between January 2000 and January 2005 according to the clinical manifestations of the disease. RESULTS: The study included 25 asymptomatic patients (group I), 18 nephrolithiasis patients without overt bone disease (group II), and 21 patients with severe bone involvement and osteitis fibrosa cystica (group III). Mean serum calcium in groups I, II, and III was 10.98 +/- 0.02, 11.32 +/- 0.17, and 13.35 +/- 0.35 mg/dL, respectively. Mean serum parathyroid hormone in groups I, II, and III was 135.45 +/- 13.50, 165.85 +/- 15.06, and 579.6 +/- 628.4 pg/mL, respectively. The (99m)Tc-sestamibi scan results were positive in 64% of the patients in group I, in 83% of those in group II, and in 100% of those in group III. Of the patients with severe bone disease, 70% showed increased uptake on the initial images, whereas in the other groups, increased uptake was seen only on the delayed images, as expected. CONCLUSION: Our data show a high degree of accuracy for the use of (99m)Tc-sestamibi scanning as a localizing procedure in severe primary hyperparathyroidism.
Assuntos
Hiperparatireoidismo Primário/diagnóstico por imagem , Glândulas Paratireoides/diagnóstico por imagem , Compostos Radiofarmacêuticos , Tecnécio Tc 99m Sestamibi , Idoso , Feminino , Humanos , Hiperparatireoidismo Primário/complicações , Cálculos Renais/complicações , Masculino , Pessoa de Meia-Idade , Osteíte Fibrosa Cística/complicações , CintilografiaRESUMO
The meat fatty acids (FA) profiles of caprines submitted to different dietary treatments were determined by gas chromatography. The data were treated by Chemometrics to consider all variables together. The contents of saturated FA (SFA), monounsaturated FA (MUFA), polyunsaturated FA (PUFA), omega-3 (n-3) FA, and omega-6 (n-6) FA in 32 samples were analyzed. PUFA:SFA and n-6:n-3 ratios were also considered. The multivariate methods of hierarchical cluster analysis (HCA) and principal component analysis (PCA) were used to analyze the experimental results. HCA can group samples according to their basic composition, and PCA can explain the relationship among the dietary treatments according to the meat fatty acid composition. Treatment 1 presented the highest n-6 FA concentration, PUFA:SFA, and n-6:n-3 ratios, and the lowest MUFA and n-3 concentrations. Opposite results were observed for treatment 4. Treatments 2 and 3 were highly similar with differences mainly in SFA and MUFA concentrations.