Revisiting aminocoumarins for the treatment of melioidosis.

Burkholderia pseudomallei causes melioidosis, a potentially lethal disease that can establish both chronic and acute infections in humans. It is inherently recalcitrant to many antibiotics, there is a paucity of effective treatment options and there is no vaccine. In the present study, the efficacies of selected aminocoumarin compounds, DNA gyrase inhibitors that were discovered in the 1950s but are not in clinical use for the treatment of melioidosis were investigated. Clorobiocin and coumermycin were shown to be particularly effective in treating B. pseudomallei infection in vivo. A novel formulation with dl-tryptophan or l-tyrosine was shown to further enhance aminocoumarin potency in vivo. It was demonstrated that coumermycin has superior pharmacokinetic properties compared with novobiocin, and the coumermycin in l-tyrosine formulation can be used as an effective treatment for acute respiratory melioidosis in a murine model. Repurposing of existing approved antibiotics offers new resources in a challenging era of drug development and antimicrobial resistance.

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.

Consumer Acceptability of Dry Cured Meat from Cull Ewes Reared with Different Linseed Supplementation Levels and Feeding Durations.

Dry cured meat—‘cecina’—is a traditional, although not well-known, dry product that could add value to cull ewes. Because of this, the aim of the study was to assess consumer acceptability of ‘cecina’ from cull ewes finished with different levels of linseed (5, 10 or 15%) for different periods before slaughtering (30, 50 or 70 days). One hundred and fifty consumers evaluated colour acceptability, fatness and odour, flavour and overall acceptability of ‘cecina’ from those 9 treatments. Additionally, habits of consumption of cured products and preferences for different species and willingness to pay for ‘cecina’ were investigated. Linseed supplementation was identified as the most important factor for sensorial attributes (p < 0.01), with the preferred ‘cecina’ being that with 5% and 10% supplementation. Feeding duration only modified the fatness acceptability (p < 0.01). ‘Cecina’ from small ruminants is a product consumed occasionally by the majority of participants; however, it presented an adequate overall acceptability. Consequently, elaborating ‘cecina’ would be a feasible strategy to improve the income of farmers.

Dumbbell-shaped spinal solitary fibrous tumor: Combined approach and a review of the literature.

INTRODUCTION: Spinal solitary fibrous tumors are rare entities, particularly when considered in a dumbbell-shaped form. CASE DESCRIPTION: The authors report on a 23-year-old female patient with dorsalgia and a D11-D12 dumbbell-shaped lesion on MRI, and highly vascularized on angiography. After a biopsy-based diagnosis, an integrated approach was performed with a preoperative embolization of the feeding intercostal arteries and an en bloc resection. At 3 months postoperatively, the patient had no pain or other neurologic symptoms and a complete resection was performed and documented on MRI. CONCLUSION: To our knowledge, only 3 previous reports of dumbbell-shaped spinal solitary fibrous tumors were carried-out and this is the first case, to our knowledge, treated by pre-operatory embolization. Nevertheless, this tumor should be considered among other spinal dumbbell-shaped lesions with a differential diagnosis, i.e. meningioma and schwannoma.

Differences in accuracy of 99mTc-sestamibi scanning between severe and mild forms of primary hyperparathyroidism.

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.

Correlation of animal diet and fatty acid content in young goat meat by gas chromatography and chemometrics.

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.