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Selenium nanoparticles (SeNPs) have been used as a potential alternative to other forms of selenium in nutritional supplements for the treatment and prevention of inflammatory and oxidative stress-related diseases. Zearalenone (ZEA) is a foodborne mycotoxin present in grains that poses a health threat. Here, we investigated the adverse impacts of ZEA on intestinal homeostasis and explored the protective effects of probiotic-synthesized SeNPs against its damage. Results showed that ZEA reduced mucin and tight junction proteins expression in jejunum, induced inflammatory process and oxidative stress which in turn increased intestinal permeability in mice. ZEA-induced intestinal toxicity was further verified in vitro. Intracellular redox imbalance triggered endoplasmic reticulum (ER) stress in intestinal epithelial cells, which caused structural damage to the ER. Remarkably, SeNPs exhibited a counteractive effect by inducing a decrease in intracellular levels of Inositol 1,4,5-trisphosphate (IP3) and Ca2+, along with a reduction in the expression level of IP3 receptor. SeNPs effectively mitigated ZEA-induced ER stress was related to the increased activity of selenium-dependent antioxidant enzymes and the expression of ER-resident selenoproteins. Furthermore, SeNPs significantly inhibited the activation of PERK/eIF2α/ATF4/CHOP pathway in vitro and in vivo. In addition, SeNPs effectively reversed ZEA-induced gut microbiota dysbiosis and increased the abundance of short-chain fatty acid-producing beneficial bacteria (Alloprevotella and Muribaculaceae). The Spearman correlation analysis suggested that the structure of gut microbiota was closely related to the SeNPs attenuation of ZEA-induced intestinal toxicity. This study provides new insights into ZEA-induced intestinal toxicity and identifies a novel potential nutrient SeNPs to overcome adverse effects.
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Estrés del Retículo Endoplásmico , Nanopartículas , Selenio , Zearalenona , Zearalenona/toxicidad , Animales , Selenio/farmacología , Ratones , Nanopartículas/toxicidad , Estrés del Retículo Endoplásmico/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Masculino , Suplementos Dietéticos , Mucosa Intestinal/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Sustancias Protectoras/farmacología , Intestinos/efectos de los fármacos , HumanosRESUMEN
High-fat diet (HFD) consumption can induce intestinal barrier dysfunction and disrupt glucose metabolism. Our previous studies have demonstrated that polysaccharides obtained from the fruits of Lycium barbarum L. (LBPs) could suppress acute experimental diabetes as well as colitis in mice. In the present study, the modulating effects of a purified fraction of LBPs, named LBPs-4, on glucose homeostasis and intestinal barrier function in mice fed with a HFD were investigated. Our results indicated that the oral administration of LBP-4 (200 mg per kg per day) improved hyperglycemia, glucose intolerance, insulin resistance and islet ß-cell hyperplasia in HFD-fed mice. Moreover, LBPs-4 intervention enhanced the intestinal barrier integrity by increasing the expression levels of zonula occludens 1 and claudin-1 and the number of goblet cells in the colon. LBPs-4 also modulated the composition of gut microbiota by increasing the relative abundances of butyrate producer Allobaculum and acetate producer Romboutsia. The results of fecal transplantation experiments, transferring of microbiota from LBPs-4-fed donor mice to HFD-fed recipient mice, validated the cause-effect relationship between LBPs-4-evoked changes in the gut microbiota and improvement of glucose homeostasis and intestinal barrier function. Collectively, these findings suggested that LBPs-4 might be developed as promising prebiotics to improve glucose metabolism and gut health.
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Lycium , Ratones , Animales , Dieta Alta en Grasa/efectos adversos , Frutas , Polisacáridos/farmacología , Homeostasis , Glucosa , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: The optimal vascular access strategy in elderly patients receiving haemodialysis (HD) remains controversial. We aim to report the outcomes of arteriovenous fistula (AVF) in elderly patients initiated on maintenance HD in our centre. METHODS: Medical records of 688 incident patients initiated on HD from 2010 to 2012 in a tertiary centre were retrospectively reviewed. Patients' characteristics and AVF outcomes were compared among those < 65 years (non-elderly), ≥ 65-75 years (early elderly) and ≥ 75 years (late elderly). RESULTS: There were 418 non-elderly, 184 early elderly and 86 late elderly patients. There is a higher proportion of brachiocephalic and brachiobasilic fistula created in the late elderly (24.9% vs. 37.0% vs. 41.8%, p = 0.001). The outcomes of accesses created were comparable in the 3 age groups with similar proportions of functional AVFs (80.4% vs. 79.3% vs. 75.6%, p = 0.832) and comparable 1-, 3- and 5-year primary and secondary patency rates (p = 0.351 and 0.282, respectively). However, a longer maturation time (2.78 vs. 2.86 vs. 3.72 months, p = 0.010) and a higher mean number of interventions to assist maturation of the first AVF were required in late elderly patients (0.19 vs. 0.22 vs. 0.35, p = 0.014). Following AVF creation, median patient survival in the non-elderly, early and late elderly was 65.2 vs. 55.1 vs. 49.8 months respectively. CONCLUSION: AVFs created in elderly patients have comparable outcomes compared to non-elderly patients although more interventions are required to assist maturation with a longer maturation time necessitating early access creation to allow for time needed due to maturation delay.
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Derivación Arteriovenosa Quirúrgica , Diálisis Renal , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Anthocyanins have been shown to exert certain antiobesity properties, but the specific relationship between anthocyanin-induced beneficial effects and the gut microbiota remains unclear. Petunidin-3-O-[rhamnopyranosyl-(trans-p-coumaroyl)]-5-O-(ß-D-glucopyranoside) (P3G) is the main anthocyanin monomer from the fruit of Lycium ruthenicum Murray. Therefore, in this study, we investigated the antiobesity and remodeling effects of P3G on gut microbiota through a high-fat diet (HFD)-induced obesity mouse model and a fecal microbiota transplantation experiment. P3G was found to reduce body weight gain, fat accumulation, and liver steatosis in HFD-induced obese mice. Moreover, supplementation with P3G alleviated the HFD-induced imbalance in gut microbiota composition, and transferring the P3G-regulated gut microbiota to recipient mice provided comparable protection against obesity. This is the first time evidence is provided that P3G has an antiobesity effect by changing the intestinal microbiota. Our present data highlight a link between P3G intervention and enhancement in gut barrier integrity. This may be a promising option for obesity prevention.
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BACKGROUND: Alveolar echinococcosis (AE) is a zoonotic parasitic disease caused by Echinococcus multilocularis larval tapeworm infections in humans that severely impairs the health of affected patients in the northern hemisphere. METHODS: The expression levels of 20 cytokines associated with AE infection were measured by enzyme-linked immunosorbent assay, and the correlations between these cytokines were analysed in the R programming language. RESULTS: Serum cytokine levels differed among individuals in both the AE patient and healthy control groups. The results of the correlations among the cytokines showed obvious differences between the two groups. In the AE patients group, Th1 and Th2 cytokines formed a more complicated network than that in the healthy control group. CONCLUSIONS: The altered correlations between Th1 and Th2 cytokines may be closely associated with AE infection, which may provide a new explanation for the essential differences between AE patients and healthy individuals.
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Equinococosis/inmunología , Balance Th1 - Th2 , Adulto , Animales , Citocinas/sangre , Equinococosis/sangre , Echinococcus multilocularis , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
INTRODUCTION: The ability to successfully cannulate the arteriovenous fistula reliably is a critical step in the delivery of hemodialysis therapy. The av-Guardian vascular access system (Advent Access, Singapore) is designed to overcome the technical barrier to establishing reliable blunt needle access in patients with mature arteriovenous fistula. METHODS: This was a first-in-man, prospective, non-randomized trial (registered on the Australian New Zealand Clinical Trial Registry (ACTRN12617000501347)) performed to assess the safety and feasibility of achieving repeatable successful cannulation via av-Guardian vascular access system to facilitate blunt needling in patients with mature arteriovenous fistula. The primary endpoints of the study included rate of successful hemodialysis sessions via av-Guardian vascular access system cannulation over 3 months and safety of the implants. RESULTS: A total of six patients (four patients with brachiocephalic and two with radiocephalic arteriovenous fistula) were enrolled in the study. A pair of av-Guardian vascular access system were implanted, one each at the arterial and venous cannulation sites, under local anesthesia. Overall, the rate of successful cannulation through the av-Guardian vascular access system over 3 months in 216 hemodialysis sessions was 98.1% (212/216) at the arterial site and 94.4% (204/216) at the venous site. Significantly, 90% and 85.5% of the cannulations at the arterial and venous site, respectively, were successful at first attempt. Blood flow rates within the arteriovenous fistula were unaffected by the devices. CONCLUSION: The results demonstrated the safety and feasibility of a subcutaneously implanted, extravascular device in achieving repeatable successful cannulation via a constant site, to facilitate blunt needling in matured arteriovenous fistula in limited number of patients.
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Derivación Arteriovenosa Quirúrgica , Cateterismo/instrumentación , Fallo Renal Crónico/terapia , Diálisis Renal , Dispositivos de Acceso Vascular , Adulto , Derivación Arteriovenosa Quirúrgica/efectos adversos , Cateterismo/efectos adversos , Diseño de Equipo , Estudios de Factibilidad , Femenino , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/fisiopatología , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados no Aleatorios como Asunto , Estudios Prospectivos , Singapur , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIM: Traditional apprenticeship model (AM) of teaching in invasive procedures such as temporary haemodialysis catheter (THDC) insertion can result in propagation of errors and complications. Simulation-based learning (SBL) offers standardization of skills and allows trainees to repeatedly practice invasive procedures prior to performing them on actual patient. METHODS: Retrospective cohort study of first-, second- and third-year Nephrology Fellows from a tertiary teaching hospital from September 2008 to September 2015. The intervention group (n = 9) received simulation training in ultrasound-guided THDC placement. The historical control group (n = 12) received training through traditional AM. The primary and secondary outcomes were the immediate complications and success rates of THDC insertion. RESULTS: A total of 2481 THDCs were placed in 1787 patients. Success rate of internal jugular THDC placement for AM vs. SBL Fellow was 99.8% versus 100% (P = 0.90), while the success rate for femoral THDC placement was 99.6% versus 99.2% (P = 0.53). SBL Fellows reported fewer overall peri-procedure complications (8.3% vs. 11.2%, P = 0.02) and mechanical complications (1% vs. 2.4%, P = 0.02) compared to AM Fellows. The rate of reported technical difficulty was similar (7.5% vs. 9.2%, P = 0.17). After adjusting for side and site of THDC placement, body mass index and laboratory indices, THDC inserted by AM Fellows were independently associated with increased overall peri-procedure complications (OR = 1.396, 95% CI: 1.052-1.854, P = 0.02) and mechanical complications (OR = 2.481, 95% CI: 1.178-4.810, P = 0.02). CONCLUSIONS: Simulation-based learning was associated with lower procedure related complications and should be an integral component in the teaching of procedural skills in Nephrology.
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Cateterismo Venoso Central/instrumentación , Catéteres Venosos Centrales , Educación de Postgrado en Medicina/métodos , Nefrólogos/economía , Nefrología/educación , Diálisis Renal/instrumentación , Entrenamiento Simulado , Adulto , Anciano , Cateterismo Venoso Central/efectos adversos , Competencia Clínica , Curriculum , Femenino , Humanos , Curva de Aprendizaje , Masculino , Persona de Mediana Edad , Diálisis Renal/efectos adversos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVES: To better understand the molecular mechanisms of regeneration and explore the potential signalling pathways as therapeutic targets for heart attacks. RESULTS: After treatment with the MEK inhibitor AZD6244 upon cardiac injury, the core members in MAPK/ERK signalling-mek and erk-demonstrate elevated expression, and these proteins are deposited at the injury site in zebrafish. pERK is also induced in non-cardiomyocytes near the injury site. Furthermore, the induced expression of a dominant-negative form of MEK1 inhibits zebrafish cardiac regeneration, characterized by increased cardiac fibrosis (a hallmark of regenerative failure), reduced or delayed production of regenerative myocardium, and migration of FLI1+ endothelial cells, without direct inhibition of cardiomyocyte proliferation. CONCLUSION: Appropriate activation of MAPK/ERK signalling is essential for zebrafish cardiac regeneration.
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Corazón/fisiología , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Regeneración , Transducción de Señal , Pez Cebra/fisiología , Animales , Bencimidazoles/administración & dosificación , Inhibidores de Proteínas Quinasas/administración & dosificaciónRESUMEN
Objective: To investigate the prevalence of echinococcosis in Yushu Prefecture of Qinghai Province in 2012. Methods: Two to three towns were selected in each of Chengduo, Nangqian, Qu malai, Yushu, Zaduo and Zhiduo Counties from June to August in 2012. Ultrasound examination was conducted for residents aged over 1 year, and ELISA was performed to detect serum antibody against Echinococcus. Visceral dissection was performed to detect hydatid infection in rodents and livestock. ELISA was used to detect Echinococcus antigen in collected dog feces. Results: A total of 7 025 residents received ultrasound examination, of whom 319 showed hydatid cysts with a morbidity rate of 4.54%. ELISA showed a serum antibody positive rate of 16.38% ï¼457/2 790ï¼. The mobidity of hydatid disease was highest in Chengduo County ï¼7.41%, 181/2 444ï¼, and the rate of serum antibody was highest in Yushu County ï¼23.18%, 127/548ï¼. The morbidity and serum antibody in males were 3.91% ï¼118/3 018ï¼ and 13.93% ï¼172/1 235ï¼ respectively, and those in females were 5.02% ï¼201/4 007ï¼ and 18.33% ï¼285/1 555ï¼. In terms of age distribution, the morbidity was relatively higher in residents of 60- ï¼8.39%, 38/453ï¼ and 40- years ï¼6.61%, 67/1 014ï¼; and the rate of serum antibody was highest in residents over 70 years ï¼33.93%, 19/56ï¼. In terms of occupation, the morbidity was relatively higher in herdsmen ï¼5.28%, 252/4 777ï¼, Herdsmen-peasants ï¼6.52%, 24/368ï¼, and religious workersï¼3.37%, 11/326ï¼, while the rate of serum antibody was relatively higher in childrenï¼24%, 6/25ï¼, religious workers ï¼18.79%, 31/165ï¼ and herdsmenï¼18.34%, 328/1 788ï¼. In terms of education level, the morbidity and the rate of serum antibody were both highest in the uneducatedï¼5.04%, 41/4 779; 18.34%, 359/1 958, respectivelyï¼. In terms of residential pattern, the morbidity and the rate of serum antibody were both highest in those who were settled in winter and nomadic in summer ï¼8.25%, 227/2 753; 19.48%, 158/811, respectivelyï¼. There were significant differences in the morbidity and the rate of serum antibody in aspects of residential region, sex, age, occupation, education level and residential pattern (P<0.05 or P<0.01). In 872 rodents detected, the Echinococcus hydatid rate was 0.46% ï¼4/872ï¼, while in 809 cattle and sheep detected, the Echinococcus hydatid rate was 10.14% ï¼82/809ï¼. The fecal antigen positive rate in 838 samples of dog feces was 10.74%ï¼90/838ï¼. Conclusion: It shows a high morbidity of hydatid diesease and serum antibody positive rate in residents, a high Echinococcus hydatid rate in cattle and sheep, and a high fecal antigen positive rate in dogs in Yushu Prefecture.
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Equinococosis , Echinococcus , Adulto , Distribución por Edad , Anciano , Animales , Antígenos Helmínticos , Bovinos , Ambiente , Ensayo de Inmunoadsorción Enzimática , Heces , Femenino , Humanos , Lactante , Ganado , Prevalencia , Estaciones del Año , Ovinos , Encuestas y Cuestionarios , UltrasonografíaAsunto(s)
Cilios/metabolismo , Prostaglandinas/metabolismo , Animales , AMP Cíclico/metabolismo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Transducción de Señal , Pez Cebra/crecimiento & desarrollo , Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismoRESUMEN
Echinococcosis is highly endemic over large parts of the Qinghai-Tibet Plateau (QTP), China. Based on a large number of samples, we present data on the current presence, host distribution, and genetic diversity of Echinococcus in the Qinghai Province, located in the northeastern corner of the QTP and constituting >25% of the area of the plateau. We used 521 samples (including 451 newly collected samples and 70 samples from our previous study) from humans, yaks, sheep, goats, dogs, fox, plateau pikas, and voles in 36 counties, and genotyped them using the mitochondrial DNA marker cytochrome oxidase subunit I (cox1) gene and the maximum parsimony and Bayesian reconstruction methods. Based on the 792 bp sequence matrix, we recorded 177 variable sites; 157 were parsimony-informative. A total of 105 haplotypes (H1-H105) were detected, of which H1-H15 and H90-H104, H16-H17, H18-H89, and H105 belonged to Echinococcus shiquicus, Echinococcus multilocularis, Echinococcus granulosus, and Echinococcus canadensis, respectively. Our results showed that, (i) the Qinghai Province was under a high burden of Echinococcus epidemiology; (ii) E. granulosus was the main echinococcosis threat to the local people, and the followed is E. multilocularis; (iii) there are a considerable number of haplotypes shared by domestic animals (sheep, yaks, and dogs) and humans, demonstrating the close relationship between human and domestic animals epidemiology; (iv) the threat of E. shiquicus on humans and livestock can be mostly ignored, while the infection risk of E. canadensis echinococcosis should not be neglected.
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Equinococosis/epidemiología , Echinococcus/genética , Mamíferos/parasitología , Animales , Arvicolinae , Secuencia de Bases , Teorema de Bayes , Bovinos , Ciclooxigenasa 1/genética , ADN de Helmintos/química , ADN de Helmintos/genética , ADN Mitocondrial/química , ADN Mitocondrial/genética , Perros , Equinococosis/parasitología , Echinococcus/aislamiento & purificación , Monitoreo Epidemiológico , Zorros , Variación Genética , Genotipo , Cabras , Haplotipos , Humanos , Lagomorpha , Análisis de Secuencia de ADN/veterinaria , Ovinos , Tibet/epidemiologíaRESUMEN
INTRODUCTION: Parenteral nutrition (PN) is an important supportive therapy. However, it is expensive and associated with significant complications. Our aim is to describe the patients given PN in 2006, to compare with the 2001 cohort and determine if PN had been prescribed for the appropriate indications. MATERIALS AND METHODS: A retrospective cohort study of adult patients receiving PN between January and December 2006 was undertaken in a single institution. Appropriateness of indications for PN was based on the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) guidelines 2002. RESULTS: One hundred and eighty-two patients received 194 courses (102 males, 92 females) of PN. Median age was 62 years (range, 16 to 100). Eighty-two percent were surgical patients and 18% were medical patients. Median PN duration was 9 days (range, 2 to 115). Common indications were surgeons' anticipation of non-functioning gut postoperatively [47 (24.2%) courses], postoperative complications [33 (17.0%) courses] and postoperative ileus [31 (16.1%) courses]. Indications for PN met A.S.P.E.N. guidelines in 93.3% of cases compared to 78.3% in 2001. In 1.5% of cases, we were unable to determine if the indications met the guidelines. Ten courses did not meet the guidelines; 3 had PN for <7 days preoperatively, 6 had PN because the managing team thought the patients were critically ill and 1 was given PN for refusal to eat because of depression. CONCLUSION: Since 2001, there has been an increase in the proportion of PN given for appropriate indications. However, physician education with respect to the benefit of PN for preoperative and critically ill patients with functioning guts needs reinforcing.
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Cuidados Críticos/métodos , Hospitalización , Nutrición Parenteral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Prescripción Inadecuada/prevención & control , Prescripción Inadecuada/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Nutrición Parenteral/estadística & datos numéricos , Estudios Retrospectivos , Adulto JovenRESUMEN
Abnormal dopamine (DA) signaling is often suggested as causative in schizophrenia. The other prominent hypothesis for this disorder, largely driven by epidemiological data, is that certain adverse events during the early stages of brain development increase an individual's risk of developing schizophrenia later in life. However, the clinical and preclinical literature consistently implicates behavioural, cognitive, and pharmacological abnormalities, implying that DA signaling is abnormal in the adult brain. How can we reconcile these two major hypotheses underlying much of the clinical and basic research into schizophrenia? In this study we have transiently knocked down tyrosine hydroxylase (TH, the rate limiting enzyme in DA synthesis) gene expression in the early stages of brain development in zebrafish using morpholinos. We show that by adulthood, TH and DA levels have returned to normal and basic DA-mediated behaviours, such as locomotion, are also normal. However, when they were exposed to a novel environment the levels of freezing and immediate positioning in deeper zones were significantly reduced in these adult fish. The neurochemistry underlying these behaviours is complex, and the exact mechanisms for these abnormal behaviours remains unknown. This study demonstrates that early transient alterations in DA ontogeny can produce persistent alterations in adult brain function and suggests that the zebrafish may be a promising model animal for future studies directed at clarifying the basic neurodevelopmental mechanisms behind complex psychiatric disease.
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Envejecimiento/fisiología , Conducta Animal/fisiología , Técnicas de Silenciamiento del Gen , Tirosina 3-Monooxigenasa/genética , Pez Cebra/crecimiento & desarrollo , Pez Cebra/fisiología , Envejecimiento/efectos de los fármacos , Animales , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/enzimología , Encéfalo/patología , Buceo , Dopamina/metabolismo , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/metabolismo , Reacción Cataléptica de Congelación/efectos de los fármacos , Habituación Psicofisiológica/efectos de los fármacos , Larva/efectos de los fármacos , Locomoción/efectos de los fármacos , Morfolinos/farmacologíaRESUMEN
Biomaterial scaffolds are categorized into artificial or natural polymers, or combinations of the two. Artificial polymers often undergo serum protein adsorption, elicit foreign body and encapsulation immune responses post-implantation. Large pore bovine electrospun collagen I was therefore screened as a candidate for human keratinocyte and fibroblast cell scaffolds. Human HaCaT keratinocyte and dermal fibroblasts were seeded on electrospun denatured collagen I microfiber (DCM) scaffolds and after 72 h Livedead(®) assays performed to determine adhesive cell, survival and scaffold penetration. Both keratinocytes and fibroblasts attached to and survived on DCM scaffolds, however only fibroblasts migrated over and into this biomaterial. HaCaT keratinocytes remained largely stationary on the scaffold surface in discrete islands of monolayered cells. For this reason, normal human epidermal keratinocyte (NHEK) scaffold interactions were assessed using scanning and transmission electron microscopy (EM) that demonstrated DCM scaffolds comprised networks of interlocking and protruding collagen fibers with a mean diameter of 2-5 µm, with a mean inter-fiber pore size of 6.7 µm (range 3-10 µm) and scaffold thickness 50-70 µm. After 72 h the keratinocytes and fibroblasts on DCM scaffolds had attached, flattened and spread over the entire scaffold with assembly of lamellapodia and focal adhesion (FA)-like junctions. Using transmission EM, NHEKs and HaCaT keratinocytes assembled desmosomes, lamellapodia and FA junctions, however, neither hemidesmosomes nor basal lamina were present. In long term (21 day) co-culture fibroblasts migrated throughout the scaffold and primary keratinocytes (and to a lesser extend HaCaTs) stratified on the scaffold surface forming a human skin equivalent (HSE). In vivo testing of these HSEs on immunocompetent (BalbC) and immunodeficient (SCID) excisionally wounded model mice demonstrated scaffold wound biocompatibility and ability to deliver human cells after scaffold biodegradation.
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Materiales Biocompatibles/química , Colágeno/química , Fibroblastos/citología , Queratinocitos/citología , Microfibrillas/ultraestructura , Trasplante de Piel/métodos , Andamios del Tejido/química , Animales , Bovinos , Células Cultivadas , Técnicas de Cocultivo , Fibroblastos/fisiología , Fibroblastos/trasplante , Humanos , Queratinocitos/fisiología , Queratinocitos/trasplante , Ensayo de Materiales , Ratones , Ratones SCID , Desnaturalización Proteica , Piel/ultraestructura , Ingeniería de Tejidos/métodosRESUMEN
Previously, we reported that fetuin-A is a major component of ovine foetal skin and significantly enhances 'wound closure' in primary keratinocyte cultures. In this study, we found that in human newborn foreskin, a high level of fetuin-A protein is detected throughout the dermis. However, in adult skin a low level of fetuin-A is observed throughout the epidermal and dermal layers, except at regions surrounding hair follicles and at the epidermal-dermal junction where the level of fetuin-A is relatively high. Fetuin-A significantly induces actin-rich protrusions in human primary keratinocytes. Interestingly, blockade of epidermal growth factor (EGF) receptor signalling has a limited effect on fetuin-A promoted 'wound closure' on primary human keratinocytes, but significantly inhibits fetuin-A's effect on HaCaT cells. These results indicate that high levels of fetuin-A may partially contribute to less scar formation in newborn foreskin and that the effect of fetuin-A on primary keratinocyte migration is independent of EGF receptor signalling.
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Proteínas Sanguíneas/farmacología , Movimiento Celular/efectos de los fármacos , Receptores ErbB/metabolismo , Queratinocitos/citología , Queratinocitos/metabolismo , Transducción de Señal/fisiología , Línea Celular , Relación Dosis-Respuesta a Droga , Factor de Crecimiento Epidérmico , Humanos , Queratinocitos/efectos de los fármacos , Factor de Crecimiento Transformador alfa , alfa-2-Glicoproteína-HSRESUMEN
Using our porcine model of deep dermal partial thickness burn injury, various durations (10min, 20min, 30min or 1h) and delays (immediate, 10min, 1h, 3h) of 15 degrees C running water first aid were applied to burns and compared to untreated controls. The subdermal temperatures were monitored during the treatment and wounds observed weekly for 6 weeks, for re-epithelialisation, wound surface area and cosmetic appearance. At 6 weeks after the burn, tissue biopsies were taken of the scar for histological analysis. Results showed that immediate application of cold running water for 20min duration is associated with an improvement in re-epithelialisation over the first 2 weeks post-burn and decreased scar tissue at 6 weeks. First aid application of cold water for as little as 10min duration or up to 1h delay still provides benefit.
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Quemaduras/patología , Quemaduras/terapia , Crioterapia/métodos , Primeros Auxilios , Agua/administración & dosificación , Animales , Biopsia , Temperatura Corporal , Cicatriz/patología , Epitelio/patología , Tejido de Granulación/patología , Porcinos , Factores de Tiempo , Cicatrización de Heridas/fisiologíaRESUMEN
Commercially available generic Superglue (cyanoacrylate glue) can be used as an alternative mounting medium for stained resin-embedded semithin sections. It is colourless and contains a volatile, quick-setting solvent that produces permanent mounts of semithin sections for immediate inspection under the light microscope. Here, we compare the use of cyanoacrylate glue for mounting semithin sections with classical dibutyl phthalate xylene (DPX) in terms of practical usefulness, effectiveness and the quality of the final microscopic image.
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Adhesivos , Cianoacrilatos , Técnicas de Preparación Histocitológica/métodos , Dibutil Ftalato , Resinas Epoxi , Humanos , Microscopía Electrónica de Transmisión , Adhesión en Plástico , XilenosRESUMEN
BACKGROUND: Silver dressings have been widely and successfully used to prevent cutaneous wounds, including burns, chronic ulcers, dermatitis and other cutaneous conditions, from infection. However, in a few cases, skin discolouration or argyria-like appearances have been reported. This study investigated the level of silver in scar tissue post-burn injury following application of Acticoat, a silver dressing. METHODS: A porcine deep dermal partial thickness burn model was used. Burn wounds were treated with this silver dressing until completion of re-epithelialization, and silver levels were measured in a total of 160 scars and normal tissues. RESULTS: The mean level of silver in scar tissue covered with silver dressings was 136 microg/g, while the silver level in normal skin was less than 0.747 microg/g. A number of wounds had a slate-grey appearance, and dissection of the scars revealed brown-black pigment mostly in the middle and deep dermis within the scar. The level of silver and the severity of the slate-grey discolouration were correlated with the length of time of the silver dressing application. CONCLUSIONS: These results show that silver deposition in cutaneous scar tissue is a common phenomenon, and higher levels of silver deposits and severe skin discolouration are correlated with an increase in the duration of this silver dressing application.
Asunto(s)
Quemaduras/terapia , Cicatriz/terapia , Pigmentación/efectos de los fármacos , Poliésteres/efectos adversos , Polietilenos/efectos adversos , Plata/efectos adversos , Plata/metabolismo , Animales , Quemaduras/metabolismo , Quemaduras/patología , Cicatriz/metabolismo , Cicatriz/patología , Dermis/metabolismo , Dermis/patología , Femenino , Humanos , Poliésteres/farmacología , Polietilenos/farmacología , Plata/farmacología , PorcinosRESUMEN
This study describes the evaluation of a clinical scar scale for our porcine burn scars, which includes scar cosmetic outcome, colour, height and hair, supplemented with reference porcine scar photographs representing each scar outcome and scar colour scores. A total of 72 porcine burn scars at week 6 after burn were rated in vivo and/or on photographs. Good agreements were achieved for both intra-rater reliability (correlation is 0.86-0.98) and inter-rater reliability (ICC=80-85%). The results showed statistically significant correlations for each pair in this clinical scar scale (p<0.01), with the best correlation found between scar cosmetic outcome and scar colour. A multivariate principle components analysis revealed that this clinical scar assessment was highly correlated with scar histology, wound size, and re-epithelialisation data (p<0.001). More severe scars are clinically characterised by darker purple colouration, more elevation, no presence of hair, histologically by thicker scar tissue, thinner remaining normal dermis, are more likely to have worse contraction, and slower re-epithelialisation. This study demonstrates that our clinical scar scale is a reliable, independent and valuable tool for assessing porcine burn outcome and truthfully reflects scar appearance and function. To our knowledge, this is the first study demonstrating a high correlation between clinical scar assessment and scar histology, wound contraction and re-epithelialisation data on porcine burn scars. We believe that the successful use of porcine scar scales is invaluable for assessing potential human burn treatments.