RESUMO
Biofilms of multidrug-resistant bacteria in chronic wounds pose a great challenge in wound care. Herein, we report the topical delivery of molecularly engineered antimicrobial peptides using electrospun nanofiber dressings as a carrier for the treatment of biofilms of multidrug-resistant bacteria in diabetic wounds. Molecularly engineered human cathelicidin peptide 17BIPHE2 was successfully encapsulated in the core of pluronic F127/17BIPHE2-PCL core-shell nanofibers. The in vitro release profiles of 17BIPHE2 showed an in initial burst followed by a sustained release over 4 weeks. The peptide nanofiber formulations effectively killed methicillin-resistant Staphylococcus aureus (MRSA) USA300. Similarly, the 17BIPHE2 peptide containing nanofibers could also effectively kill other bacteria including Klebsiella pneumoniae (104 to 106 CFU) and Acinetobacter baumannii (104 to 107 CFU) clinical strains in vitro without showing evident cytotoxicity to skin cells and monocytes. Importantly, 17BIPHE2-containing nanofiber dressings without debridement caused five-magnitude decreases of the MRSA USA300 CFU in a biofilm-containing chronic wound model based on type II diabetic mice. In combination with debridement, 17BIPHE2-containing nanofiber dressings could completely eliminate the biofilms, providing one possible solution to chronic wound treatment. Taken together, the biodegradable nanofiber-based wound dressings developed in this study can be utilized to effectively deliver molecularly engineered peptides to treat biofilm-containing chronic wounds.
Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bandagens , Biofilmes/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Nanofibras/administração & dosagem , Engenharia de Proteínas , Infecção dos Ferimentos/tratamento farmacológico , Administração Cutânea , Animais , Antibacterianos/química , Peptídeos Catiônicos Antimicrobianos/química , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Nanofibras/química , Poloxâmero/química , Poliésteres/química , Pele/efeitos dos fármacos , Pele/microbiologia , Infecção dos Ferimentos/patologia , CatelicidinasRESUMO
BACKGROUND: Oftentimes, obese dialysis patients develop a viable dialysis access but the access is too deep for cannulation and needs a superficialization procedure. METHODS: We present our 14-patient cohort in whom we performed liposuction to superficialize viable but deep vascular accesses. Out of 14 patients, 12 had arteriovenous fistulas and 2 arteriovenous grafts. The primary end points were the ability to superficialize a completely unusable access and to remove the hemodialysis catheter (3patients), or to significantly extend the useful length of a deep access in which only a very short segment was used and to continue to use the access post-surgery without the need to place a dialysis catheter (11 patients). RESULTS: The study goal was met in 13 out of 14 patients. In two of three patients, the catheters were removed and their access usable length was 14 and 13 cm, respectively. The accesses could be used immediately after liposuction in all patients in which this applied-11 patients. The usable access length increased from a mean of 5 to 12.7 cm. The access mean depth decreased from 10.8 mm pre-surgery to 7 mm post-surgery and 5.3 mm 4 weeks after surgery. The mean volume of fat removed was 43.8 cc. We had only one surgical complication: bleeding that was readily controlled with manual pressure. All patients were discharged to home the same day. Postoperative pain was mild. CONCLUSION: Liposuction is effective, safe, and seems to be the least invasive technique of superficialization.
Assuntos
Adiposidade , Derivação Arteriovenosa Cirúrgica , Implante de Prótese Vascular , Lipectomia , Obesidade/fisiopatologia , Diálise Renal , Adulto , Idoso , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Implante de Prótese Vascular/efeitos adversos , Feminino , Humanos , Lipectomia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular , Adulto JovemRESUMO
Solar ultraviolet radiation (UVR) is a major environmental hazard for the skin, and UVB (280-320 nm) has been proposed to be a main factor for melanoma development. In response to sunlight exposure, the skin has adapted a number of innate resistance mechanisms. Among them is the small heat shock protein of 27 kDa (HSP27) known to play a role in the protection of cells from variety of environmental insults including UV irradiation. In this study, we demonstrated that UVB irradiation of cultured normal epidermal melanocytes initiates changes in HSP27 phosphorylation and localization. In unstressed melanocytes, HSP27 was present as the non-phosphorylated isoform. UVB irradiation with a physiological dose (7-25 mJ/cm(2)) resulted in the formation of a mono-phosphorylated isoform and sometimes a bi-phosphorylated isoform. The UVB-induced HSP27 phosphorylation was inhibited when melanocytes were treated with the antioxidant N-acetyl cysteine or inhibitor of p38 MAP kinase prior to UVB exposure, suggesting that UVB induced HSP27 phosphorylation through reactive oxygen species/p38 MAP kinase pathway. In response to UBV irradiation, HSP27 in melanocytes translocated from the cytoplasm to the nucleus. The HSP27 responses may provide some protective role against UVB-induced cell damage in the skin.
Assuntos
Proteínas de Choque Térmico/metabolismo , Melanócitos/metabolismo , Melanócitos/efeitos da radiação , Proteínas de Neoplasias/metabolismo , Raios Ultravioleta , Células Cultivadas , Células Epidérmicas , Epiderme/metabolismo , Epiderme/efeitos da radiação , Regulação da Expressão Gênica/efeitos da radiação , Proteínas de Choque Térmico HSP27 , Proteínas de Choque Térmico/genética , Humanos , Melanócitos/citologia , Chaperonas Moleculares , Proteínas de Neoplasias/genética , Fosforilação/efeitos da radiação , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Transporte Proteico/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Natural and synthetic fillers have revolutionized aesthetic facial rejuvenation and soft-tissue augmentation. We present a case highlighting the dangers of filler self-injection. A 37-year-old woman self-injected a dermal filler around both temples. She immediately experienced left--side hearing loss, blanching over the left face, and pain. Prompt treatment with hyaluronidase, topical nitro paste, and warm compresses ensued. An emergency computed tomography angiogram showed occlusion of a superficial temporal artery branch. We treated her with enoxaparin, aspirin, dexamethasone, piperacillin-tazobactam, and intradermal lidocaine. After 6 hyperbaric oxygen therapy (HBO2) treatments in 3 days, the patient showed improvement in appearance with markedly decreased ischemic discoloration and her hearing returned to baseline. Algorithms for treating such injuries generally neglect HBO2. HBO2 is thought to be efficacious in these situations by a variety of mechanisms: oxygenation of ischemic tissues, reduction of edema, amelioration of ischemic/reperfusion injury, promotion of angiogenesis and collagen maturation. Her resolved hearing highlights the utility of HBO2 in sudden hearing loss as well. Injectors should have guidelines for using product, not only on patients but staff as well. Filler courses should include handling complications and include HBO2 in their guidelines. Clinicians should remind patients to seek treatment from qualified clinicians. The goal of a bargain price using self-injection may quickly become expensive and disfiguring.
RESUMO
AIM: The aim of this study was to develop a nanofiber-based dressing capable of local sustained delivery of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) and augmenting human CAMP induction. MATERIALS & METHODS: Nanofibrous wound dressings containing 1,25(OH)2D3 were successfully prepared by electrospinning, which were examined in vitro, in vivo and ex vivo. RESULTS: 1,25(OH)2D3 was successfully loaded into nanofibers with encapsulation efficiency larger than 90%. 1,25(OH)2D3 showed a sustained release from nanofibers over 4 weeks. Treatment of U937 and HaCaT cells with 1,25(OH)2D3-loaded poly(ϵ-caprolactone) nanofibers significantly induced hCAP18/LL37 expression in monocytes and keratinocytes, skin wounds of humanized transgenic mice and artificial wounds of human skin explants. CONCLUSION: 1,25(OH)2D3 containing nanofibrous dressings could enhance innate immunity by inducing antimicrobial peptide production.
Assuntos
Anti-Infecciosos/administração & dosagem , Peptídeos Catiônicos Antimicrobianos/metabolismo , Nanofibras/administração & dosagem , Vitamina D/análogos & derivados , Animais , Anti-Infecciosos/química , Peptídeos Catiônicos Antimicrobianos/química , Bandagens/microbiologia , Linhagem Celular , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/microbiologia , Camundongos , Camundongos Transgênicos , Monócitos/efeitos dos fármacos , Nanofibras/química , Vitamina D/administração & dosagem , Vitamina D/química , Técnicas de Fechamento de FerimentosRESUMO
AIM: The aim of this study was to develop nanofiber-based sutures capable of inducing endogenous antimicrobial peptide production. METHODS: We used co-axial electrospinning deposition and rolling to fabricate sutures containing pam3CSK4 peptide and 25-hydroxyvitamin D3 (25D3). RESULTS: The diameters and mechanical properties of the sutures were adjustable to meet the criteria of United States Pharmacopeia designation. 25D3 exhibited a sustained release from nanofiber sutures over 4 weeks. Pam3CSK4 peptide also showed an initial burst followed by a sustained release over 4 weeks. The co-delivery of 25D3 and pam3CSK4 peptide enhanced cathelicidin antimicrobial peptide production from U937 cells and keratinocytes compared with 25D3 delivery alone. In addition, the 25D3/pam3CSK4 peptide co-loaded nanofiber sutures did not significantly influence proliferation of keratinocytes, fibroblasts, or the monocytic cell lines U937 and HL-60. CONCLUSION: The use of 25D3/pam3CSK4 peptide co-loaded nanofiber sutures could potentially induce endogenous antimicrobial peptide production and reduce surgical site infections.
Assuntos
Peptídeos Catiônicos Antimicrobianos/biossíntese , Calcifediol/farmacologia , Lipopeptídeos/farmacologia , Nanofibras/química , Suturas , Fenômenos Biomecânicos , Calcifediol/química , Linhagem Celular , Proliferação de Células , Portadores de Fármacos , Liberação Controlada de Fármacos , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , Lipopeptídeos/química , Tamanho da Partícula , Pele/metabolismo , Propriedades de Superfície , CatelicidinasRESUMO
Electrospun nanofibers represent a novel class of materials that show great potential in many biomedical applications including biosensing, regenerative medicine, tissue engineering, drug delivery and wound healing. In this work, we review recent advances in electrospun nanofibers for wound healing. This article begins with a brief introduction on the wound, and then discusses the unique features of electrospun nanofibers critical for wound healing. It further highlights recent studies that have used electrospun nanofibers for wound healing applications and devices, including sutures, multifunctional dressings, dermal substitutes, engineered epidermis and full-thickness skin regeneration. Finally, we finish with conclusions and future perspective in this field.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanofibras/química , Nanofibras/uso terapêutico , Regeneração/efeitos dos fármacos , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Bandagens , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Desenho de Equipamento , Humanos , Nanotecnologia/instrumentação , Nanotecnologia/métodos , Medicina Regenerativa/instrumentação , Medicina Regenerativa/métodos , Pele/efeitos dos fármacos , Pele Artificial , Suturas , Alicerces Teciduais/químicaRESUMO
Glass fronted gas fireplaces (GFGFs) have exterior surfaces that can reach extremely high temperatures. Burn injuries from contact with the glass front can be severe with long-term sequelae. The Consumer Product Safety Commission reported that these injuries are uncommon, whereas single-center studies indicate a much higher frequency. The purpose of this multi-institutional study was to determine the magnitude and severity of GFGF injuries in North America. Seventeen burn centers elected to participate in this retrospective chart review. Chart review identified 402 children ≤10 years of age who sustained contact burns from contact with GFGF, who were seen or admitted to the study hospitals from January 2006 to December 2010. Demographic, burn, treatment, and financial data were collected. The mean age of the study group was 16.8 ± 13.3 months. The majority suffered burns to their hands (396, 98.5%), with burns to the face being the second, much less common site (14, 3.5%). Two hundred and sixty-nine required rehabilitation therapy (66.9%). The number of GFGF injuries reported was 20 times greater than the approximately 30 injuries estimated by the Consumer Product Safety Commission's 10-year review. For the affected children, these injuries are painful, often costly and occasionally can lead to long-term sequelae. Given that less than a quarter of burn centers contributed data, the injury numbers reported herein support a need for broader safety guidelines for gas fireplaces in order to have a significant impact on future injuries.
Assuntos
Acidentes Domésticos/estatística & dados numéricos , Queimaduras/epidemiologia , Incêndios , Vidro , Utensílios Domésticos , Tato , Unidades de Queimados , Queimaduras/diagnóstico , Queimaduras/terapia , Canadá , Criança , Pré-Escolar , Combustíveis Fósseis , Humanos , Lactente , Estudos Retrospectivos , Estados UnidosRESUMO
Wounding skin generates an endogenous electric field of 100-200 mV/mm in the immediate vicinity of the wound. When keratinocytes are exposed to direct current electric fields of this magnitude, they exhibit galvanotaxis, or directional migration toward the cathode, suggesting that wound-generated electric fields provide migrational cues that contribute to wound healing. Because melanocytes must also migrate into the healing wound to repigment it, their motility in response to electric fields of physiologic magnitude was examined. Human skin-derived melanocytes, either exposed to 100 mV/mm direct current electric fields or nonexposed controls, both exhibited motility rates of 9 micro m/hour, significantly (three- to five-fold) lower than the motility rates of keratinocytes under identical conditions. However, in sharp contrast to keratinocytes, melanocytes exhibited no directional migration in the electric field. Additionally, neither the number of primary dendrites per cell, nor the orientation of the dendrites with respect to the field vector, nor the average length of the dendrites was significantly different in melanocytes exposed to the electric field as compared to nonexposed controls. Thus, in marked contrast to keratinocytes, human skin-derived melanocytes do not respond to direct current electric fields of physiologic magnitude with either directional migration or reorientation of dendrites. This may account for the delay in repigmentation that often accompanies wound reepithelialization.