RESUMO
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.
Assuntos
Antibacterianos/farmacologia , Fatores Imunológicos/farmacologia , Peptídeos/farmacologia , Animais , Infecções Bacterianas/tratamento farmacológico , Proteínas Sanguíneas/farmacologia , Modelos Animais de Doenças , Feminino , Células HEK293 , Humanos , Imunidade Inata/efeitos dos fármacos , Imunomodulação/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Peptídeos/química , Peptídeos/uso terapêutico , Peptídeos/toxicidade , Células RAW 264.7RESUMO
OBJECTIVE: To determine if 1) Afro-Caribbean women prefer large body sizes, 2) the body size preference of Afro-Caribbean men and women are associated, 3) women's preferences are associated with increased risk of obesity or with weight management behaviors. DESIGN: Population samples of 314 and 487 women, ages 20-55 years, were recruited on Barbados and Dominica with response rates of 74% and 77%, respectively. Body size preferences, stress related variables, and demographic data were ascertained by questionnaire. Height and weight were also measured. On Barbados, body preference data were collected from male partners of participants, and data on intentions to perform weight management behaviors were collected from 175 women. RESULTS: Most women preferred body sizes within normal limits, although women on Dominica had a slightly larger ideal body size (IBS) than did Barbadian women (P<.05). On both islands, the size that women thought men preferred was related to their IBS (P<.0001). Likewise, IBS was associated with increased odds of being overweight (P<.001), however most overweight women (>75%) wanted to be smaller. IBS was not related to the intention to exercise or to eat high fat foods. CONCLUSIONS: It is unlikely that body size preference poses a barrier to intervention efforts to reduce the prevalence of overweight in Afro-Caribbean women.