RESUMEN
Cinnamaldehyde (CNM) is an essential-oil component with reported anti-infective, anti-inflammatory, and healing effects, making it an interesting compound for the treatment of wound infection. Herein, we evaluated the effects of topical administration of CNM in experimental wounds infected by Staphylococcus aureus. Swiss mice (n = 12/group) were randomly allocated into three groups (CON: animals with uninfected lesions; Sa: animals with untreated infected lesions; Sa + CNM: animals with infected wounds and treated with CNM). Excisional lesions (64 mm2) were induced at the dorsal area followed by the addition of S. aureus (80 µL of a 1.5 × 108 CFU/mL bacterial suspension). The wounds were treated with CNM (200 µg/wound/day) or vehicle (2% DMSO) for 10 days. Skin samples were taken on the 3rd or 10th treatment day for quantification of inflammatory mediators, bacterial load, immunophenotyping, and histological analysis. The treatment with CNM improved the healing process and attenuated the severity of skin lesions infected by S. aureus. These effects were associated with significant decreases in bacterial loads in CNM-treated wounds. The levels of neutrophils, TNF-α, IL-6, NO, and VEGF were decreased in the lesions treated with CNM. Taken together, these data provide further evidence of the effectiveness of CNM for the treatment of skin infections.
Asunto(s)
Infecciones Estafilocócicas , Infección de Heridas , Ratones , Animales , Staphylococcus aureus , Cicatrización de Heridas , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/patología , Infección de Heridas/tratamiento farmacológicoRESUMEN
Eugenia brejoensis Mazine (Myrtaceae) is source of an essential oil (EbEO) with anti-infective activities against Staphylococcus aureus. This study evaluated the antimicrobial and anti-inflammatory potentials of EbEO in S. aureus-infected skin wounds. The excisional lesions (64 mm2) were induced on Swiss mice back (6 to 8-week-old) that were allocated into 3 groups (n = 12): 1) non-infected wounds (CON); 2) wounds infected with S. aureus ATCC 6538 (Sa); 3) S. aureus-infected wounds and treated with EbEO (Sa + EbEO). The infected groups received approximately 104 CFU/wound. The animals were treated with EbEO (10 µg/wound/day) or vehicle from the 1-day post-infection (dpi) until the 10th dpi. The clinical parameters (wound area, presence of exudate, edema intensity, etc.) were daily analyzed. The levels of inflammatory mediators (cytokines, nitric oxide, VEGF) and bacterial load were measured at the cutaneous tissue at 4th dpi and 10th dpi. Topical application of EbEO accelerated wound contraction with an average contraction of 83.48 ± 11.27 % of the lesion area until 6th dpi. In this period, the rates of lesion contraction were 54.28 ± 5.57% and 34.5 ± 2.67% for CON and Sa groups, respectively. The positive effects of EbEO on wound contraction were associated with significantly (p < 0.05) reduction on bacterial load and the release of inflammatory mediators (IL-6, IL-17A, TNF-α, NO and VEGF). Taken together, these data confirm the antimicrobial potential of EbEO and provide insights into its anti-inflammatory effects, making this essential oil an interesting candidate for the development of new therapeutic alternatives for infected cutaneous wounds.
RESUMEN
This work evaluated the immunomodulatory and anti-infective effects of Cratylia mollis lectin (Cramoll) in a model of wound infection induced by S. aureus. Swiss mice were divided into 3 groups (n = 12/group): non-inoculated (Control group); inoculated with S. aureus (Sa group); inoculated with S. aureus and treated with Cramoll (Sa + Cramoll group). In each animal, one lesion (64 mm2) was induced on the back and contaminated with S. aureus (~4.0 × 106 CFU/wound). The treatment with Cramoll (5 µg/animal/day) started 1-day post-infection (dpi) and extended for 10 days. Clinical parameters (wound size, inflammatory aspects, etc.) were daily recorded; while cytokines levels, bacterial load and histological aspects were determined in the cutaneous tissue at 4th dpi or 11th dpi. The mice infected with S. aureus exhibited a delay in wound contraction and the highest inflammatory scores. These effects were impaired by the treatment with Cramoll which reduced the release of key inflammatory mediators (TNF-α, NO, VEGF) and the bacterial load at wound tissue. Histological evaluations showed a restauration of skin structures in the animals treated with Cramoll. Taken together, these results provide more insights about the healing and immunomodulatory properties of Cramoll and suggest this lectin as a lead compound for treatment of wound infection.
Asunto(s)
Antibacterianos/farmacología , Fabaceae , Agentes Inmunomoduladores/farmacología , Lectinas de Plantas/farmacología , Infecciones Estafilocócicas/prevención & control , Staphylococcus aureus/efectos de los fármacos , Infección de Heridas/prevención & control , Animales , Antibacterianos/aislamiento & purificación , Carga Bacteriana , Modelos Animales de Enfermedad , Fabaceae/química , Interacciones Huésped-Patógeno , Agentes Inmunomoduladores/aislamiento & purificación , Ratones , Óxido Nítrico/metabolismo , Lectinas de Plantas/aislamiento & purificación , Infecciones Estafilocócicas/inmunología , Infecciones Estafilocócicas/metabolismo , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/crecimiento & desarrollo , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Infección de Heridas/inmunología , Infección de Heridas/metabolismo , Infección de Heridas/microbiologíaRESUMEN
Plant-derived products have played a fundamental role in the development of new therapeutic agents. This study aimed to analyze antimicrobial, antibiofilm, cytotoxicity and antiproliferative potentials of the extract and fractions from leaves of Himatanthusdrasticus, a plant from the Apocynaceae family. After harvesting, H. drasticus leaves were macerated and a hydroalcoholic extract (HDHE) and fractions were prepared. Antimicrobial tests, such as agar-diffusion, Minimum Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) were carried out against several bacterial species. Staphylococcus aureus, Pseudomonas aeruginosa, Listeria monocytogenes and Klebsiella pneumoniae were inhibited by at least one extract or fraction in the agar-diffusion assay (inhibition halos from 12 mm to 30 mm). However, the lowest MIC value was found for HDHE against K. pneumoniae. In addition, HDHE and its fractions were able to inhibit biofilm formation at sub-inhibitory concentrations (780 µg/mL and 1.56 µg/mL). As the best activities were found for HDHE, we selected it for further assays. HDHE was able to increase ciprofloxacin (CIP) activity against K. pneumoniae, displaying synergistic (initial concentration CIP + HDHE: 2 µg/mL + 600 µg/mL and 2.5 µg/mL + 500 µg/mL) and additive effects (CIP + HDHE: 3 µg/mL + 400 µg/mL). This action seems to be associated with the alteration in bacterial membrane permeability induced by HDHE (as seen by propidium iodide labeling). This extract was non-toxic for red blood cell or human peripheral blood mononuclear cells (PBMCs). Additionally, it inhibited the lipopolysaccharide-induced proliferation of PBMCs. The following compounds were detected in HDHE using HPLC-ESI-MS analysis: plumieride, plumericin or isoplumericin, rutin, quercetin and derivatives, and chlorogenic acid. Based on these results we suggest that compounds from H. drasticus have antimicrobial and antibiofilm activities against K. pneumoniae and display low cytotoxicity and anti-proliferative action in PBMC stimulated with lipopolysaccharide.
Asunto(s)
Antiinfecciosos/química , Apocynaceae/química , Biopelículas/efectos de los fármacos , Flavonoides/química , Furanos/química , Iridoides/química , Hojas de la Planta/química , Antiinfecciosos/aislamiento & purificación , Antiinfecciosos/farmacología , Biopelículas/crecimiento & desarrollo , Permeabilidad de la Membrana Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ciprofloxacina/farmacología , Combinación de Medicamentos , Sinergismo Farmacológico , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Furanos/aislamiento & purificación , Furanos/farmacología , Iridoides/aislamiento & purificación , Iridoides/farmacología , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/fisiología , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/efectos de los fármacos , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Listeria monocytogenes/efectos de los fármacos , Listeria monocytogenes/fisiología , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/química , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/fisiología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiologíaRESUMEN
Infantile hepatic hemangioendothelioma is a severe disease with a high mortality rate. Nevertheless these vascular lesions may experience spontaneous regression within 12 to 18 months. The decision of trying a specific treatment and the choice among the several therapeutic options remains controversial, particularly in those asymptomatic cases of multifocal, bilobular involvement. We describe a case of multifocal, bilobular and asymptomatic infantile hepatic hemangioendothelioma, untreated, and with spontaneous regression before 2 years of age.
Asunto(s)
Hemangioendotelioma/patología , Neoplasias Hepáticas/patología , Diagnóstico Diferencial , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Estadificación de Neoplasias , Remisión EspontáneaRESUMEN
El hemangioendotelioma hepático infantil (HHI) es una enfermedad grave y con elevada mortalidad. A pesar de ello, estas lesiones vasculares pueden evolucionar espontáneamente para su resolución completa entre 12 y 18 meses. La decisión de intentar un tratamiento específico y la elección entre las varias opciones terapéuticas continúa siendo polémica, especialmente en los casos asintomáticos de afectación multifocal o bilobular. Describimos un caso de HHI, multifocal y bilobular, asintomático, no sometido a ningún tipo de terapia y con regresión de las lesiones antes de los 2 años de edad (AU)
Infantile hepatic hemangioendothelioma is a severe disease with a high mortality rate. Nevertheless these vascular lesions may experience spontaneous regression within 12 to 18 months. The decision of trying a specific treatment and the choice among the several therapeutic options remains controversial, particularly in those asymptomatic cases of multifocal, bilobular involvement. We describe a case of multifocal, bilobular and asymptomatic infantile hepatic hemangioendothelioma, untreated, and with spontaneous regression before 2 years of age (AU)
Asunto(s)
Humanos , Masculino , Lactante , Hemangioendotelioma/complicaciones , Hemangioendotelioma/diagnóstico , Regresión Neoplásica Espontánea/genética , Regresión Neoplásica Espontánea/patología , Neoplasias Vasculares/complicaciones , Neoplasias Vasculares/diagnóstico , Insuficiencia Cardíaca/complicaciones , Histiocitoma Fibroso Benigno/complicaciones , Neoplasias Hepáticas/complicaciones , Pared Abdominal , Insuficiencia Cardíaca/patología , Neoplasias Hepáticas/mortalidadRESUMEN
Trefoil factor family domain peptides (TFF) are thought to be involved in mucosal epithelial restitution and wound healing of the gastrointestinal tract and are up-regulated in ulceration and in a variety of solid tumours. It was hypothesized that TFFs are also expressed on mucosal surfaces of the human respiratory tract. Lung tissue, nasal polyps, and sputum samples from seven patients with cystic fibrosis (CF), two with chronic and acute bronchitis, and non-dysplastic material from two cases of bronchial adenocarcinoma were analysed for TFF expression by immunohistochemistry, immunofluorescence, western blot and RT-PCR. Expression of TFF1 and TFF3 was observed in material from all patients. TFFs were localized in goblet and ciliated cells, as well as in some submucosal cells of tracheobronchial tissues and nasal polyps from normal and CF individuals. In sputa of patients with CF and with chronic or acute bronchitis, TFF1 and TFF3 were detected by western blotting. Freshly cultivated nasal epithelial cells transcribed and secreted TFFs and mucins, whereas nasal cells cultivated for 6 weeks still expressed mucins, but not TFFs. Secreted TFFs and mucins also bound to the surface of Staphylococcus aureus in infected CF airways. In conclusion, TFF1 and TFF3 are expressed and secreted in normal and inflamed airways. The association of TFFs with bacteria may contribute to the anti-microbial mucociliary defence system.
Asunto(s)
Mucinas , Proteínas Musculares , Neuropéptidos , Proteínas/metabolismo , Enfermedades Respiratorias/metabolismo , Adenocarcinoma/metabolismo , Anciano , Bronquitis/metabolismo , Enfermedad Crónica , Fibrosis Quística/metabolismo , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Sustancias de Crecimiento/metabolismo , Humanos , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Pólipos Nasales/metabolismo , Péptidos/metabolismo , Sinusitis/metabolismo , Esputo/metabolismo , Staphylococcus aureus/metabolismo , Factor Trefoil-1 , Factor Trefoil-2 , Factor Trefoil-3 , Proteínas Supresoras de TumorRESUMEN
The winged helix transcription factors HNF-3/FKH (forkhead homologs) activate endodermal-derived and acute-phase gene expression and control gut development in Drosophila. Trefoil factor family (TFFs) peptides are vertebrate products secreted by mucin-producing epithelial cells of the gastrointestinal tract involved in restitution and repair of the mucosa. They are positively regulated in ulcerative and neoplastic conditions. We describe a consensus sequence in human and rodent TFF promoters close to the TATAA box showing striking similarity to the binding site of the HNF-3/FKH family. In gel retardation assays, HNF-3 alpha and beta bound predominantly to the site in TFF1 (formerly pS2) and, to a lesser extent, to the sites in TFF2 or TFF3. Mutations generated in this motif severely impaired transcription of TFF1 reporter genes. Cotransfection with expression vectors of HNF-3alpha and beta, but not the related HFH 11A and B, specifically activated the wild-type TFF1 reporter genes. Activation of endogenous expression of TFF1 by HNF-3 alpha and beta gene products was more than 1000 fold in the pancreatic cell line Capan-2 and fivefold in the gastric cell line MKN-45, whereas the intestinal cell lines HUTU 80 and HT-29 displayed no effect. Thus, HNF-3/FKH factors contribute causally to cell-specific regulation of TFF genes and may explain the acute-phase response of TFF peptides.
Asunto(s)
Sustancias de Crecimiento/genética , Mucinas , Proteínas Musculares , Neuropéptidos , Péptidos/genética , Proteínas/genética , Transactivadores/genética , Animales , Secuencia de Bases , Sitios de Unión , Núcleo Celular/química , Núcleo Celular/metabolismo , Sistema Libre de Células/química , Sistema Libre de Células/metabolismo , Proteínas de Unión al ADN/genética , Proteína Forkhead Box M1 , Factores de Transcripción Forkhead , Regulación Neoplásica de la Expresión Génica , Genes Reporteros/genética , Sustancias de Crecimiento/metabolismo , Factor Nuclear 3-alfa del Hepatocito , Factor Nuclear 3-beta del Hepatocito , Humanos , Datos de Secuencia Molecular , Mutagénesis , Proteínas Nucleares/genética , Péptidos/metabolismo , Regiones Promotoras Genéticas , Unión Proteica , Proteínas/metabolismo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Homología de Secuencia de Ácido Nucleico , TATA Box , Transactivadores/metabolismo , Factores de Transcripción/genética , Factor Trefoil-1 , Factor Trefoil-2 , Factor Trefoil-3 , Células Tumorales Cultivadas/química , Células Tumorales Cultivadas/citología , Células Tumorales Cultivadas/metabolismo , Proteínas Supresoras de TumorRESUMEN
Peptides belonging to the trefoil factor family (TFF) protect the gastrointestinal epithelia. Overexpression of TFFs was observed in pathological conditions such as gastritis, ulceration, metaplasia and neoplasia of the gastrointestinal tract. The aims of this work were to investigate the recently described TFF2 gene polymorphism in different European populations. DNA samples from blood of healthy individuals and gastric cancer patients were genotyped using the polymerase chain reaction. They were compared to a gastric cancer population. The results do not show any significant difference in allelic frequencies between gastric cancer patients and healthy individuals from Portugal. However, the frequency of the two alleles found varies considerably among Europeans.
Asunto(s)
Frecuencia de los Genes , Sustancias de Crecimiento/genética , Mucinas , Proteínas Musculares , Neuropéptidos , Péptidos/genética , Polimorfismo Genético , Neoplasias Gástricas/genética , Alelos , Europa (Continente) , Predisposición Genética a la Enfermedad , Humanos , Reacción en Cadena de la Polimerasa , Secuencias Repetidas en Tándem , Factor Trefoil-2 , Factor Trefoil-3RESUMEN
Delayed response to medical treatment sometimes leads to unnecessary liver transplantation in patients with severely decompensated Wilson disease. We report the course of five patients (mean age 13.4 years, range 11 to 15 years) with severely decompensated Wilson disease who were successfully treated medically. Prothrombin time improved after a minimum of 1 month and returned to normal within 3 months to 1 year or more.