RESUMO
Abscess formation is a common complication of severe life-threatening infections caused by obligate anaerobes. Fusobacterium necrophorum is among the frequently detected anaerobic pathogens from clinical specimens associated with liver abscesses, skin and soft tissue infections, or oral abscesses. The antimicrobial therapy for this kind of infection needs to be optimized. Here, we examined the possibility of treating F. necrophorum-induced abscess wound infections with candidate therapeutics based on three endolysins with activity against a broad spectrum of aerobe Gram-negative pathogens. Antibacterial gel containing three Gram-negative bacteria-targeting endolysins, LysAm24, LysAp22, and LysECD7, was formulated for topical use. Abscess formation was induced in rabbits with F. necrophorum and caused systemic infection. The survival and lifespan of the animals, general parameters, and biochemical and hematological blood tests were analyzed to assess the effectiveness of the gel treatment for the wound infection. The administration of the investigated gel twice per day for 5 days resulted in less acute inflammation, with decreased leukocytes and segmented neutrophils in the blood, retardation of infection progression, and an almost two-fold increase in the lifespan of the animals compared to the placebo group. The results indicate that endolysin-based therapy is an effective approach to treat anaerobic bacterial infections. The use of endolysins as independent pharmaceuticals, or their combination with antibiotics, could significantly reduce the development of complications in infectious diseases caused by sensitive bacterial species.
RESUMO
Using a wide range of different physical and chemical methods, it was found that the oxidative stress caused by addition of hydrogen peroxide to the incubation medium has a significant effect on the conformation of haematoporphyrin, influencing the oxygen-binding properties of haemoglobin in red blood cells. Morphofunctional characteristics of red blood cells change; in particular, we have observed the transformation of erythrocytes, their transition into echinocytes. In erythrocytes, in response to increased lipid peroxidation (LPO) antioxidant enzymes become active. The use of natural antioxidants (ß-carotene and resveratrol) works towards reducting the level of oxidative processes. Resveratrol has the greatest antioxidant effect.
Assuntos
Antioxidantes/farmacologia , Eritrócitos/efeitos dos fármacos , Hemoglobinas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Catalase/química , Catalase/metabolismo , Eritrócitos/metabolismo , Hemoglobinas/química , Humanos , Peróxido de Hidrogênio/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Oxigênio/metabolismo , Ligação Proteica/efeitos dos fármacos , Resveratrol/farmacologia , beta Caroteno/farmacologiaRESUMO
This study shows that membrane-associated cytoskeletal protein structures and the erythrocyte morphology undergo profound changes during hypoxia. Hypoxia also intensified oxidative processes in the lipid phase of the bilayer of red blood cell membranes. Sodium nitroprusside impaired the morphology of red blood cells and altered quantitative and qualitative composition of membrane-skeletal proteins. The findings suggest that hypoxia causes changes at all levels of red blood cell organization, which can cause the functional disorders of hemoglobin oxygen-transporting properties and, eventually, the complete degradation of red blood cells. The use of flavonoids has a protective effect against hypoxia.