ABSTRACT
Antibiotic-resistant infections are predicted to kill 10 million people per year by 2050, costing the global economy $100 trillion. Therefore, there is an urgent need to develop alternative technologies. We have engineered a synthetic peptide called clavanin-MO, derived from a marine tunicate antimicrobial peptide, which exhibits potent antimicrobial and immunomodulatory properties both in vitro and in vivo. The peptide effectively killed a panel of representative bacterial strains, including multidrug-resistant hospital isolates. Antimicrobial activity of the peptide was demonstrated in animal models, reducing bacterial counts by six orders of magnitude, and contributing to infection clearance. In addition, clavanin-MO was capable of modulating innate immunity by stimulating leukocyte recruitment to the site of infection, and production of immune mediators GM-CSF, IFN-γ and MCP-1, while suppressing an excessive and potentially harmful inflammatory response by increasing synthesis of anti-inflammatory cytokines such as IL-10 and repressing the levels of pro-inflammatory cytokines IL-12 and TNF-α. Finally, treatment with the peptide protected mice against otherwise lethal infections caused by both Gram-negative and -positive drug-resistant strains. The peptide presented here directly kills bacteria and further helps resolve infections through its immune modulatory properties. Peptide anti-infective therapeutics with combined antimicrobial and immunomodulatory properties represent a new approach to treat antibiotic-resistant infections.
Subject(s)
Anti-Bacterial Agents/pharmacology , Immunologic Factors/pharmacology , Peptides/pharmacology , Animals , Bacterial Infections/drug therapy , Blood Proteins/pharmacology , Disease Models, Animal , Female , HEK293 Cells , Humans , Immunity, Innate/drug effects , Immunomodulation/drug effects , Mice , Mice, Inbred C57BL , Microbial Sensitivity Tests , Peptides/chemistry , Peptides/therapeutic use , Peptides/toxicity , RAW 264.7 CellsABSTRACT
In order to improve the understanding of the toxicity of pentavalent antimony (Sb(V)), we investigated the acute effects of meglumine antimoniate (MA) on the oxidative stress in heart, liver, kidney, spleen and brain tissue of mice. Levels of lipoperoxidation and protein carbonylation were measured to evaluate the oxidative status, whereas superoxide dismutase/catalase activity and glutathione levels were recorded to examine the antioxidative status. We observed that MA caused significant protein carbonylation in the heart, spleen and brain tissue. Increased lipoperoxidation was found in the liver and brain tissue. An imbalance between superoxide dismutase and catalase activities could be observed in heart, liver, spleen and brain tissue. Our results suggest that MA causes oxidative stress in several vital organs of mice. This indicates that the production of highly reactive oxygen and nitrogen species induced by MA might be involved in some of its toxic adverse effects.
Subject(s)
Antiprotozoal Agents/pharmacology , Meglumine/pharmacology , Organometallic Compounds/pharmacology , Oxidative Stress/drug effects , Animals , Antiprotozoal Agents/adverse effects , Brain/drug effects , Brain Chemistry/drug effects , Catalase/metabolism , Glutathione/analysis , Heart/drug effects , Kidney/chemistry , Kidney/drug effects , Lipid Peroxidation/drug effects , Liver/chemistry , Liver/drug effects , Meglumine/adverse effects , Meglumine Antimoniate , Mice , Myocardium/chemistry , Organometallic Compounds/adverse effects , Protein Carbonylation/drug effects , Spleen/chemistry , Spleen/drug effects , Superoxide Dismutase/metabolismABSTRACT
La identificación del riesgo nutricional en pacientes hospitalizados puede realizarse con técnicas de tamizaje o screening nutricional (SN) de sencilla aplicación. Este estudio tuvo por objetivo valorar la importancia de la inclusión del test de SN en la primera fase del Proceso de Atención de Enfermería (PAE) en pacientes con Accidente Cerebro Vascular (ACV), internados en la Unidad de Terapia Intensiva (UTI) del Hospital San Juan Bautista de Catamarca. Se realizaron mediciones antropométricas directas e indirectas, se aplicó el test de SN para adultos (NRS 2000) de la Sociedad Americana de Nutrición Enteral y Parenteral (ASPEN) y se analizaron sus ítems.
