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1.
Appl Microbiol Biotechnol ; 107(2-3): 623-638, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36562803

RESUMO

COVID-19 patients have often required prolonged endotracheal intubation, increasing the risk of developing ventilator-associated pneumonia (VAP). A preventive strategy is proposed based on an endotracheal tube (ETT) modified by the in situ deposition of eucalyptus-mediated synthesized silver nanoparticles (AgNPs). The surfaces of the modified ETT were embedded with AgNPs of approximately 28 nm and presented a nanoscale roughness. Energy dispersive X-ray spectroscopy confirmed the presence of silver on and inside the coated ETT, which exhibited excellent antimicrobial activity against Gram-positive and Gram-negative bacteria, and fungi, including multidrug-resistant clinical isolates. Inhibition of planktonic growth and microbial adhesion ranged from 99 to 99.999% without cytotoxic effects on mammalian cells. Kinetic studies showed that microbial adhesion to the coated surface was inhibited within 2 h. Cell viability in biofilms supplemented with human tracheal mucus was reduced by up to 95%. In a porcine VAP model, the AgNPs-coated ETT prevented adhesion of Pseudomonas aeruginosa and completely inhibited bacterial invasion of lung tissue. The potential antimicrobial efficacy and safety of the coated ETT were established in a randomized control trial involving 47 veterinary patients. The microbial burden was significantly lower on the surface of the AgNPs-coated ETT than on the uncoated ETT (p < 0.05). KEY POINTS: • Endotracheal tube surfaces were modified by coating with green-synthesized AgNPs • P. aeruginosa burden of endotracheal tube and lung was reduced in a porcine model • Effective antimicrobial activity and safety was demonstrated in a clinical trial.


Assuntos
Anti-Infecciosos , COVID-19 , Doenças Transmissíveis , Nanopartículas Metálicas , Pneumonia Associada à Ventilação Mecânica , Humanos , Animais , Suínos , Antibacterianos/farmacologia , Prata/farmacologia , Hospitais Veterinários , Nanopartículas Metálicas/química , Cinética , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Anti-Infecciosos/farmacologia , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Pneumonia Associada à Ventilação Mecânica/microbiologia , Biofilmes , Intubação Intratraqueal/métodos , Mamíferos
2.
Front Immunol ; 13: 1000491, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36275765

RESUMO

Peritoneal adhesions commonly occur after abdominal or pelvic surgery. These scars join internal organs to each other or to the cavity wall and can present with abdominal or pelvic pain, and bowel obstruction or female infertility. The mechanisms underlying adhesion formation remain unclear and thus, effective treatments are not forthcoming. Peritoneal macrophages accumulate after surgery and previous studies have attributed either pro- or anti-scarring properties to these cells. We propose that there are complex and nuanced responses after surgery with respect to both resident and also monocyte-derived peritoneal macrophage subpopulations. Moreover, we contend that differences in responses of specific macrophage subpopulations in part explain the risk of developing peritoneal scars. We characterized alterations in peritoneal macrophage subpopulations after surgery-induced injury using two strains of mice, BALB/c and C57BL/6, with known differences in macrophage response post-infection. At 14 days post-surgery, BALB/c mice displayed more adhesions compared with C57BL/6 mice. This increase in scarring correlated with a lower influx of monocyte-derived macrophages at day 3 post-surgery. Moreover, BALB/c mice showed distinct macrophage repopulation dynamics after surgery. To confirm a role for monocyte-derived macrophages, we used Ccr2-deficient mice as well as antibody-mediated depletion of CCR2 expressing cells during initial stages of adhesion formation. Both Ccr2-deficient and CCR2-depleted mice showed a significant increase in adhesion formation associated with the loss of peritoneal monocyte influx. These findings revealed an important protective role for monocyte-derived cells in reducing adhesion formation after surgery.


Assuntos
Macrófagos Peritoneais , Monócitos , Camundongos , Feminino , Animais , Camundongos Endogâmicos C57BL , Monócitos/patologia , Cicatriz/patologia , Macrófagos/patologia , Aderências Teciduais , Receptores de Quimiocinas , Camundongos Endogâmicos BALB C
3.
Int J Biol Macromol ; 216: 235-250, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35780920

RESUMO

Effective treatment of infected wounds requires a comprehensive wound dressing with a combination of antibacterial, antioxidative, and anti-inflammatory effects. Biodegradable wound dressings incorporating nanostructured material were developed using polyvinyl alcohol with xanthan gum, hypromellose, or sodium carboxymethyl cellulose and extensively evaluated for antibacterial and wound healing efficacy. Synthesized silver nanoparticles and wound dressings displayed λmax at 420 nm with zeta potential ≈ - 35 mV. Significant growth inhibition with >99 % reduction in CFU/ml (p < 0.05) against important wound pathogens including Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, and Candida albicans were observed. Within 1 h of treatment, hypromellose nanocomposite demonstrated excellent bactericidal effects with a 99.9 % of reduction in growth. In addition, wound dressings demonstrated inhibitory activities against free radical scavengers. Wound dressings demonstrated a significant reduction in the inflammatory response in RAW 264.7 macrophages (p < 0.001). Ex-vivo diffusion demonstrated zero-order release and steady-state flux between 0.1571-0.2295 µg/ml/cm2h with 0.124-0.144 permeability coefficient after 10 h. Usage in animals further confirmed that the hypromellose nanocomposite accelerated the wound healing process with biocompatibility. The results suggested that hybrid biodegradable dressings can be effectively applied to treat infected wounds and attenuate inflammatory responses.


Assuntos
Nanopartículas Metálicas , Infecção dos Ferimentos , Animais , Antibacterianos/farmacologia , Bandagens , Carboximetilcelulose Sódica/farmacologia , Escherichia coli , Derivados da Hipromelose/farmacologia , Polissacarídeos Bacterianos , Álcool de Polivinil/farmacologia , Prata/farmacologia , Sódio/farmacologia , Cicatrização , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia
4.
J Biomater Appl ; 31(8): 1215-1224, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28181448

RESUMO

Fibrin glue, which is formed from the action of thrombin (a serine protease) on fibrinogen, has been developed for use as an adhesive to increase the success of skin graft surgery. The objective of this study was to evaluate if bubaline fibrin glue would promote skin graft survival in pigs. The grafting was divided into two steps. First, granulation wound preparation was performed in a healthy swine by creating four full-skin depth wounds (3 × 12 cm2) at the dorsal part of the loin area on each side. Second, pinch and punch skin grafting, where eight skin discs (0.6 cm diameter) were regularly placed (0.6 cm distance apart) in the granulation tissue bed of each wound, was performed 5 days later. The bubaline fibrin glue was added prior to application of the 16 skin graft discs in two of the wounds, while no glue was added to the other 16 skin graft discs in the other two wounds. The number of surviving graft pieces and histological examination was evaluated after 3, 7, and 14 days post-operation and compared by pairing between the control and the bubaline fibrin glue groups. The number of grafts that remained at 3 and 7 days post-operation and the number of new microvessels at 3 days post-operation were significantly higher ( p < 0.05) in the bubaline fibrin glue group than in the control group. However, there was no significant difference in the number of fibroblasts, the intensity of scarring and the intensity of inflammation between the two groups, except for the significantly lower intensity of inflammation at 7 days post-operation in the bubaline fibrin glue group. In conclusion, bubaline fibrin glue has the advantage of decreasing the skin graft loss by approximately 31.3-37.5% compared with the control group and also promotes angiogenesis.


Assuntos
Adesivo Tecidual de Fibrina/uso terapêutico , Lacerações/patologia , Lacerações/terapia , Transplante de Pele/métodos , Animais , Terapia Combinada/métodos , Feminino , Suínos , Adesivos Teciduais/uso terapêutico , Resultado do Tratamento
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