Testing the efficacy of antimicrobial peptides in the topical treatment of induced osteomyelitis in rats

Joint replacement infections and osteomyelitis are among the most serious complications in orthopaedics and traumatology. The risk factors for these infections are often bacterial resistance to antimicrobials. One of the few solutions available to control bacterial resistance involves antimicrobials, which have a different mechanism of action from traditional antibiotics. Antimicrobial peptides (AMP) appear to be highly promising candidates in the treatment of resistant infections. We have identified several AMP in the venom of various wild bees and designed analogues that show potent antimicrobial activity and low toxicity against eukaryotic cells. The aim of the present study was to test the efficacy of one of those synthetic peptide analogues for the treatment of acute osteomyelitis invoked in laboratory rats. Femoral cavities of 20 laboratory Wistar rats were infected with Staphylococcus aureus. After 1 week, eight rats received an injectable calcium phosphate carrier alone, another eight rats were treated with a calcium phosphate mixed with AMP, and four rats were left without any further treatment. After another week, all rats were euthanized and radiographs were made of both the operated and healthy limbs. The animals with the carrier alone exhibited more severe acute osteomyelitis on radiographs in comparison to the recipients of the calcium phosphate carrier loaded AMP and untreated infected individuals. Based on the results of the above mentioned experiment, it was concluded that when injected directly into the site of femoral acute osteomyelitis, the calcium phosphate carrier mixed with AMP reduced osteomyelitis signs visible on radiographs.     

Bone grafts as vancomycin carriers in local therapy of resistant infections

The level of an antibiotic capable of inhibiting the etiological agent at the site of infection is an essential prerequisite for successful antibiotic therapy. In some cases, locally applied antibiotics may compensate for limitations of systemic administration and shorten systemic therapy. We aimed at verifying to what extent vancomycin (Van) bound to ground bone grafts is usable in the treatment of serious infections. The levels of released Van significantly exceeded the Van minimum inhibitory concentration, which can suppress Van-sensitive staphylococci and Van intermediate Staphylococcus aureus, for the whole period of a 16-day measurement. Our results indicate that bone grafts can be used as Van carriers in therapy of osteomyelitis caused by Van-sensitive Staphylococcus strains.     

A computational study of the interaction between dopamine and DNA/RNA nucleosides

The interaction between protonated dopamine and neutral RNA and DNA nucleosides was studied by means of density functional theory calculations in vacuum and in implicit water. On the most stable complexes formed with each of the nucleosides, the vertical absorption excitation energies were evaluated and compared with the values of separated dopamine and corresponding nucleoside. The most stable complex was formed with guanosine and the spectral changes in this complex resulted in a significant reduction of the oscillator strength of the first dopamine’s transition. In the first guanosine’s transition, a redshift of 0.2 eV was found combined with a reduction of the oscillator strength.     

Inhibition of Na235SO4 incorporation of granulomatous tissue by a glycosamine derivative

The effect of N-acetyl-4-6-(p-oxy-benzylidene)-D-glycosamine on Na235SO4 incorporation has been studied in vitro. The 0.25-2.0 mmoles of the compound significantly inhibited the Na235SO4 incorporation of granulomatous tissue. The inhibitory effect proved to be dose dependent.     

Effect of the aminoacid composition of model α-helical peptides on the physical properties of lipid bilayers and peptide conformation: a molecular dynamics simulation

The interaction of a model Lys flanked α-helical peptides K₂-X₂₄-K₂, (X = A,I,L,L+A,V) with lipid bilayers composed of dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC) both, in a gel and in a liquid-crystalline state, has been studied by molecular dynamics simulations. It has been shown that these peptides cause disordering of the lipid bilayer in the gel state but only small changes have been monitored in a liquid-crystalline state. The peptides affect ordering of the surrounding lipids depending on the helix stability which is determined by amino acid side chains – their volume, shape, etc. We have shown that the helix does not keep the linear shape in all simulations but often bends or breaks. During some simulations with a very small difference between hydrophobic length of peptide and membrane thickness the peptide exhibits negligible tilt. At the same time changes in peptide conformations during simulations resulted in appearance of superhelix.