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Cholesteatoma is a mass formed by the keratinizing squamous epithelium in the tympanic cavity and/or mastoid that can lead to the destruction of surrounding structures in the ear. It can arise at any age. Symptoms are non-specific and diagnosis may be difficult on otoscopic examination. The management of cholesteatoma is surgical; mastoid obliteration has reduced the incidence of recurrent cholesteatoma in recent years. The use of diffusion-weighted MRI has proven to be a reliable technique for the detection and follow-up of cholesteatoma.
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Colesteatoma del Oído Medio/diagnóstico por imagen , Oído Medio/diagnóstico por imagen , Apófisis Mastoides/diagnóstico por imagen , Colesteatoma del Oído Medio/cirugía , Imagen de Difusión por Resonancia Magnética , Oído Medio/cirugía , Humanos , Apófisis Mastoides/cirugíaRESUMEN
Barrett's esophagus is the only known mucosal precursor for the highly malignant esophageal adenocarcinoma. Malignant degeneration of non-dysplastic Barrett's esophagus occurs in < 0.6% per year in Dutch surveillance cohorts. Therefore, it has been proposed to increase the surveillance intervals from 3 to 5 years, potentially increasing development of advanced stage interval cancers. To prevent such cases robust biomarkers for more optimal stratification over longer follow up periods for non-dysplastic Barrett's patients are required. In this multi-center study, aberrations for chromosomes 7, 17, and structural abnormalities for c-MYC, CDKN2A, TP53, Her-2/neu and 20q assessed by DNA fluorescence in situ hybridization on brush cytology specimens, were used to determine marker scores and to perform clonal diversity measurements, as described previously. In this study, these genetic biomarkers were combined with clinical variables and analyzed to obtain the most efficient cancer prediction model after an extended period of follow-up (median time of 7 years) by applying Cox regression modeling, bootstrapping and leave-one-out analyses. A total of 334 patients with Barrett's esophagus without dysplasia from 6 community hospitals (n = 220) and one academic center (n = 114) were included. The annual progression rate to high grade dysplasia and/or esophageal adenocarcinoma was 1.3%, and to adenocarcinoma alone 0.85%. A prediction model including age, Barrett circumferential length, and a clonicity score over the genomic set including chromosomes 7, 17, 20q and c-MYC, resulted in an area under the curve of 0.88. The sensitivity and specificity of this model were 0.91 and 0.38. The positive and negative predictive values were 0.13 (95% CI 0.09 to 0.19) and 0.97 (95% CI 0.93 to 0.99). We propose the implementation of the model to identify non-dysplastic Barrett's patients, who are required to remain in surveillance programs with 3-yearly surveillance intervals from those that can benefit from less frequent or no surveillance.
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Esófago de Barrett/diagnóstico , Biomarcadores/metabolismo , Adulto , Anciano , Área Bajo la Curva , Esófago de Barrett/genética , Esófago de Barrett/patología , Cromosomas Humanos Par 17/genética , Cromosomas Humanos Par 7/genética , Progresión de la Enfermedad , Neoplasias Esofágicas/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Hiperplasia , Masculino , Persona de Mediana Edad , Países Bajos , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas c-myc/genética , Curva ROC , Factores de RiesgoRESUMEN
BACKGROUND: Limited research has been published regarding movement behaviour of adult persons with haemophilia (PWH). It is hypothesized that avoidance of activities and more sedentary behaviour cause poorer physical functioning. AIM: To determine differences in movement behaviour between PWH and healthy adults. METHODS: Movement behaviour was measured with an accelerometer distinguishing between; lying/non-wear, sitting, standing, walking, running and cycling. Time spent on activities was compared between PWH and healthy adults, using absolute time spent on activities and activities as percentage of wear time. RESULTS: One hundred and five PWH (32 mild/moderate with a mean age of 42.8 ± 15.1, severe 42.1 ± 13.6) and 98 healthy adults (mean age 41.9 ± 15.5) showed that adults with severe haemophilia sit and stand more than healthy adults (4.5 [CI 0.6-8.4] and 4.2 [CI 1.8-6.6] h/wk, respectively) and walk and run less (3.4 [CI 1.4-5.3] hours and 33.6 [CI 19.0-41.7] min/wk, respectively). Patients with mild/moderate haemophilia stand more than healthy adults (3.3 [CI 0.1-6.4] h/wk). Differences in sitting between severe haemophilia and healthy adults and differences in standing between mild/moderate haemophilia and healthy adults disappeared when using activities as percentage of wear time. CONCLUSION: Movement behaviour of adults with severe haemophilia differs from healthy adults, mainly due to less walking and less running. No differences were found in other activities and postures or the distribution of movement behaviour over the day. No significant differences were found between adults with mild/moderate haemophilia and healthy adults.
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Hemofilia A/fisiopatología , Movimiento , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Postura , Carrera , CaminataRESUMEN
INTRODUCTION: Monitoring clinical outcome in persons with haemophilia (PWH) is essential in order to provide optimal treatment for individual patients and compare effectiveness of treatment strategies. Experience with measurement of activities and participation in haemophilia is limited and consensus on preferred tools is lacking. AIM: The aim of this study was to give a comprehensive overview of the measurement properties of a selection of commonly used tools developed to assess activities and participation in PWH. METHODS: Electronic databases were searched for articles that reported on reliability, validity or responsiveness of predetermined measurement tools (5 self-reported and 4 performance based measurement tools). Methodological quality of the studies was assessed according to the COSMIN checklist. Best evidence synthesis was used to summarize evidence on the measurement properties. RESULTS: The search resulted in 3453 unique hits. Forty-two articles were included. The self-reported Haemophilia Acitivity List (HAL), Pediatric HAL (PedHAL) and the performance based Functional Independence Score in Haemophilia (FISH) were studied most extensively. Methodological quality of the studies was limited. Measurement error, cross-cultural validity and responsiveness have been insufficiently evaluated. CONCLUSION: Albeit based on limited evidence, the measurement properties of the PedHAL, HAL and FISH are currently considered most satisfactory. Further research needs to focus on measurement error, responsiveness, interpretability and cross-cultural validity of the self-reported tools and validity of performance based tools which are able to assess limitations in sports and leisure activities.
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Hemofilia A/epidemiología , Hemofilia A/patología , HumanosRESUMEN
INTRODUCTION: Joint bleeds in patients with haemophilia may result in haemophilic arthropathy. Monitoring joint health is essential for identifying early signs of deterioration and allows timely adjustment of treatment. AIM: The aim was to describe changes in joint health over 5-10 years follow-up and identify factors associated with joint health deterioration in patients with haemophilia. METHODS: A post hoc analysis was performed from previous cohort studies in patients with moderate/severe haemophilia, ≥16 years. Joint health of ankles, knees and elbows was measured with the Haemophilia Joint Health Score (HJHS) from 2006-2008 (T0) to 2011-2016 (T1). Analyses were performed on patient level (ΔHJHS-total) and joint level (ΔHJHS-joint). Deterioration was defined as ΔHJHS-total ≥4 and ΔHJHS-joint ≥2. RESULTS: Sixty-two patients (median age 25, 73% severe haemophilia, median [interquartile range] 0.0 [0.0;2.0] joint bleeds between T0 to T1) were included. After median 8 years, HJHS-total deteriorated in 37% and HJHS-joint in 17%. Ankle joints (31%) showed deterioration more often than elbows (19%) and knees (3%). Deterioration of HJHS-total was only associated with severe haemophilia. Deterioration of HJHS-joint was weakly associated with a lower HJHS at baseline and more self-reported limitations in activities, and strongly with more joint bleeds between T0 and T1 and presence of synovitis. CONCLUSION: In 37% of patients with moderate/severe haemophilia and low joint bleeding rates, joint health deteriorated over 5-10 years. Ankle and elbow joints showed deterioration most frequently. Factors found in this study help to identify which joints need frequent monitoring in patients with haemophilia with access to early prophylaxis.
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Articulación del Tobillo/fisiopatología , Articulación del Codo/fisiopatología , Hemofilia A/fisiopatología , Hemofilia B/fisiopatología , Adolescente , Adulto , Estudios de Seguimiento , Hemartrosis/diagnóstico , Hemartrosis/fisiopatología , Hemofilia A/tratamiento farmacológico , Hemofilia A/patología , Hemofilia B/tratamiento farmacológico , Hemofilia B/patología , Humanos , Artropatías/diagnóstico , Artropatías/fisiopatología , Persona de Mediana Edad , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND: Depression is one of the most common and debilitating non-motor symptoms of Parkinson's disease (PD). The neurocognitive mechanisms underlying depression in PD are unclear and treatment is often suboptimal. METHODS: We investigated the role of striatal dopamine in reversal learning from reward and punishment by combining a controlled medication withdrawal procedure with functional magnetic resonance imaging in 22 non-depressed PD patients and 19 PD patients with past or present depression. RESULTS: PD patients with a depression (history) exhibited impaired reward v. punishment reversal learning as well as reduced reward v. punishment-related BOLD signal in the striatum (putamen) compared with non-depressed PD patients. No effects of dopaminergic medication were observed. CONCLUSIONS: The present findings demonstrate that impairments in reversal learning from reward v. punishment and associated striatal signalling depend on the presence of (a history of) depression in PD.
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Trastorno Depresivo/fisiopatología , Imagen por Resonancia Magnética/métodos , Enfermedad de Parkinson/fisiopatología , Castigo , Putamen/fisiopatología , Aprendizaje Inverso/fisiología , Recompensa , Anciano , Trastorno Depresivo/diagnóstico por imagen , Trastorno Depresivo/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Putamen/diagnóstico por imagenRESUMEN
Barrett's esophagus (BE) with high-grade dysplasia (HGD) defines a group of individuals at high risk of progression to esophageal adenocarcinoma (EA). Fluorescence in situ hybridization (FISH) has been shown to be useful for the detection of dysplasia and EA in endoscopic brushing specimens from BE patients. The aim of this study was to determine whether FISH in combination with histological findings would further identify more rapid progressors to EA. This is a retrospective cohort study of high-risk patients, having a history of biopsy-confirmed HGD without EA, with an endoscopic brushing specimen analyzed by FISH while undergoing endoscopic surveillance and treatment between April 2003 and October 2010. Brushing specimens were assessed by FISH probes targeting 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2), and 20q13 (ZNF217) and evaluated for the presence of polysomy, defined as multiple chromosomal gains (displaying ≥ 3 signals for ≥ 2 probes). Specimens containing ≥ 4 cells exhibiting polysomy were considered polysomic. HGD was confirmed by at least two experienced gastrointestinal pathologists. Of 245 patients in this study, 93 (38.0%) had a polysomic FISH result and 152 (62.0%) had a non-polysomic FISH result. Median follow-up was 3.6 years (interquartile range [IQR] 2-5 years). Patients with a polysomic FISH result had a significantly higher risk of developing EA within 2 years (14.2%) compared with patients with a non-polysomic FISH result (1.4%, P < 0.001). These findings suggest that a polysomic FISH result in BE patients with simultaneous HGD identifies patients at a higher risk for developing EA compared with those with non-polysomy.
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Adenocarcinoma/genética , Esófago de Barrett/genética , Inhibidor p18 de las Quinasas Dependientes de la Ciclina/genética , Neoplasias Esofágicas/genética , Hibridación Fluorescente in Situ/métodos , Proteínas Proto-Oncogénicas c-myc/genética , Receptor ErbB-2/genética , Transactivadores/genética , Adenocarcinoma/patología , Anciano , Esófago de Barrett/patología , Estudios de Cohortes , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Sondas de ADN , Progresión de la Enfermedad , Neoplasias Esofágicas/patología , Esofagoscopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de RiesgoRESUMEN
INTRODUCTION: The overlap in symptoms between joint bleeds and flare-ups of haemophilia arthropathy (HA) creates difficulties in differentiating between the two conditions. Diagnosis of haemarthrosis is currently empirically made based upon clinical presentations. However, no standard diagnostic criteria are available. To offer appropriate treatment, rapid and accurate diagnosis is essential. Additionally, adequate differentiation can decrease health costs significantly. AIM: The aim of this study was to identify signs and symptoms to differentiate between an intra-articular joint bleed and an acute flare-up of HA in patients with haemophilia and make an initial proposal of items to include in a diagnostic criteria set. METHODS: Six focus group interviews with a total of 13 patients and 15 professionals were carried out. The focus groups were structured following the Nominal Group Technique (NGT). RESULTS: The most important signs and symptoms used to differentiate between joint bleeds and HA were (i) course of the symptoms, (ii) cause of the complaints, (iii) joint history, (iv) type of pain and (v) degree of impairments in range of motion. CONCLUSION: This qualitative study provides insight into signs and symptoms that are currently used to differentiate between joint bleeds and flare-ups of HA. Results of this study can be used to develop a valid and standardized clinical diagnostic criteria set to differentiate between these two conditions. Further research is necessary to validate the signs and symptoms found in this study.
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Hemartrosis/diagnóstico , Hemofilia A/patología , Artropatías/diagnóstico , Pacientes/psicología , Médicos/psicología , Adulto , Grupos Focales , Humanos , Entrevistas como Asunto , Articulaciones/fisiopatología , Persona de Mediana Edad , Enfermeras y Enfermeros/psicología , Rango del Movimiento ArticularRESUMEN
INTRODUCTION: Elderly patients with haemophilia (PWH) suffer from both haemarthrosis and haemophilic arthropathy (HA). Diagnosis of haemarthrosis in PWH is currently based on clinical presentation. No diagnostic protocols or validated criteria are available to identify haemarthrosis or to differentiate haemarthrosis from HA. AIM: The aim of this study is to identify symptoms and signs that can be used to differentiate haemarthrosis from HA. METHODS: A narrative literature review was performed on symptoms associated with haemarthrosis and symptoms associated with HA. Additionally, literature on the diagnosis of haemarthrosis in patients without haemophilia, imaging techniques and biomarkers was searched. RESULTS: This review shows that there is no consensus about the symptoms associated with haemarthrosis and that there is limited literature about the symptoms associated with HA. Additionally, symptoms associated with haemarthrosis partly overlap with symptoms of HA, particularly those symptoms associated with flare-ups of HA. Due to the overlap in symptoms differentiating between these conditions is complex. Furthermore, differentiating based on imaging techniques or biomarkers causes practical difficulties. CONCLUSION: Despite the overlap in symptoms, differentiating between joint bleeds and flare-ups of HA based on clinical presentation still seems the most convenient and practical solution. Further research is necessary to identify specific symptoms that can be used to differentiate between the two conditions.
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Hemartrosis/diagnóstico , Hemartrosis/etiología , Hemofilia A/complicaciones , Hemofilia B/complicaciones , Artropatías/diagnóstico , Artropatías/etiología , Biomarcadores , Biopsia con Aguja , Enfermedad Crónica , Diagnóstico Diferencial , Diagnóstico por Imagen/métodos , HumanosRESUMEN
Barrett's esophagus (BE) is the strongest risk factor for the development of esophageal adenocarcinoma. However, the risk of cancer progression is difficult to ascertain in individuals, as a significant number of patients with BE do not necessarily progress to esophageal adenocarcinoma. There are several issues with the current strategy of using dysplasia as a marker of disease progression. It is subject to sampling error during biopsy acquisition and interobserver variability among gastrointestinal pathologists. Ideal biomarkers with high sensitivity and specificity are needed to accurately detect high-risk BE patients for early intervention and appropriate cost-effective surveillance. To date, there are no available molecular tests in routine clinical practice despite known genetic and epigenetic aberrations in the Barrett's epithelium. In this review, we present potential biomarkers for the prediction of malignant progression in BE. These include markers of genomic instability, tumor suppressor loci abnormalities, epigenetic changes, proliferation markers, cell cycle predictors, and immunohistochemical markers. Further work in translating biomarkers for routine clinical use may eventually lead to accurate risk stratification.
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Esófago de Barrett/diagnóstico , Biomarcadores de Tumor/análisis , Biomarcadores/análisis , Neoplasias Esofágicas/diagnóstico , Adenocarcinoma/diagnóstico , Transformación Celular Neoplásica/patología , Progresión de la Enfermedad , Detección Precoz del Cáncer , Predicción , Humanos , Factores de RiesgoRESUMEN
Developments in membrane based blood purification therapies often come with longer treatment times and therefore longer blood-material contact, which requires long-term membrane biocompatibility. In this study, we develop for the first time membranes for blood purification using the material SlipSkin™, which is a copolymer, made from N-vinylpyrrolidone (NVP) and butylmethacrylate (BMA). Specific attention is focused on understanding the mechanism of pore formation and the tailoring of the membrane mechanical and transport properties to obtain the optimal membrane for blood purification therapies. Polymer composition, solvent type and solvent evaporation time influence membrane morphology and membranes with sieving properties of cascade filters in plasma fractionation applications are developed. The new membranes have very good blood compatibility properties; in fact compared to benchmark flat membranes currently used in the clinic, they have lower platelet adhesion while all other properties (contact activation, thrombogenicity, leukocyte adhesion, hemolysis and complement activation) are also very good and comparable to the benchmarks.
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In the field of biofabrication, tissue engineering and regenerative medicine, there are many methodologies to fabricate a building block (scaffold) which is unique to the target tissue or organ that facilitates cell growth, attachment, proliferation and/or differentiation. Currently, there are many techniques that fabricate three-dimensional scaffolds; however, there are advantages, limitations and specific tissue focuses of each fabrication technique. The focus of this initiative is to utilize an existing technique and expand the library of biomaterials which can be utilized to fabricate three-dimensional scaffolds rather than focusing on a new fabrication technique. An expanded library of biomaterials will enable the precision extrusion deposition (PED) device to construct three-dimensional scaffolds with enhanced biological, chemical and mechanical cues that will benefit tissue generation. Computer-aided motion and extrusion drive the PED to precisely fabricate micro-scaled scaffolds with biologically inspired, porosity, interconnectivity and internal and external architectures. The high printing resolution, precision and controllability of the PED allow for closer mimicry of tissues and organs. The PED expands its library of biopolymers by introducing an assisting cooling (AC) device which increases the working extrusion temperature from 120 to 250 °C. This paper investigates the PED with the integrated AC's capabilities to fabricate three-dimensional scaffolds that support cell growth, attachment and proliferation. Studies carried out in this paper utilized a biopolymer whose melting point is established to be 200 °C. This polymer was selected to illustrate the newly developed device's ability to fabricate three-dimensional scaffolds from a new library of biopolymers. Three-dimensional scaffolds fabricated with the integrated AC device should illustrate structural integrity and ability to support cell attachment and proliferation.
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Ingeniería de Tejidos/instrumentación , Andamios del Tejido , Fosfatasa Alcalina/metabolismo , Animales , Biopolímeros/química , Biopolímeros/toxicidad , Calcio/metabolismo , Línea Celular , Supervivencia Celular , Diseño Asistido por Computadora , Ratones , Microscopía Electrónica de Rastreo , Microscopía Fluorescente , Porosidad , Ingeniería de Tejidos/métodosRESUMEN
The enormous need of orthopaedic (surgical) implants such as osteosynthesis plates is difficult to be fulfilled in developing countries commonly rely on imported ones. One of the alternatives is utilization of local resources, but only after they have been proven safe to use, to overcome this problem. Surface properties are some of the determining factors of safety for those implants. We have succeeded in developing prototype of osteosynthesis plate and the results indicate that Indonesian-made plates need improvement with regards to the surface quality of physical characterization.
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Placas Óseas , Sustitutos de Huesos , Ensayo de Materiales , Cerámica , Materiales Biocompatibles Revestidos , Fuerza Compresiva , Humanos , Indonesia , Dispositivos de Fijación Ortopédica , TermogravimetríaRESUMEN
Isotopically substituted rhodamine dyes provide ideal probes for the study of single-molecule surface enhanced Raman scattering (SM-SERS) events through multiple-analyte techniques. Isotopic editing should, in principle, provide probes that have identical chemical properties (and surface chemistries); while exhibiting at the same time distinct Raman features which enable us to identify single-molecule SERS events. We present here a specific example of two-analyte SM-SERS based on the isotopic substitution of a methyl ester rhodamine dye. The dyes are carefully characterized (in both standard and SERS conditions) to confirm experimentally their similar chemical properties. We then demonstrate their utility for bi-analyte SERS (BiASERS) experiments and, as an example, highlight the transition from a single, to a few, to many molecules in the statistics of SM-SERS signals.
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Although peripheral nerves exhibit regeneration capacities after transection injuries, the success of nerve repair depends crucially on the length of the gap. In addition to autologous nerve grafting as the conventional neurosurgical treatment to overcome long gaps, alternative strategies are needed. Numerous experimental studies have been undertaken to find the optimal material for production of artificial prostheses, which can be introduced as conduits between the nerve stumps. The current study follows the aim to establish polysialic acid (polySia), a homopolymer of alpha2,8-linked sialic acid residues, as a novel, biocompatible, and bioresorbable material for nerve tissue engineering. As a first step towards this goal, protocols for efficient coating of cell culture dishes with soluble polySia were established. In addition, primary nerve cells which are candidates for reconstructive therapies, including neonatal and adult Schwann cells, neural progenitor cells, spinal ganglionic neurons and motoneurons were cultured on polySia substrates. Cultures were evaluated with regard to cell survival and cell proliferation capacities. polySia turned out to be stable under cell culture conditions, and induced degradable and degradation products had no negative effects on cell cultures. Furthermore, polySia revealed its compatibility for several cell types derived from rat embryonic, postnatal and adult nervous tissue when used as a substrate.
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Técnicas de Cultivo de Célula/métodos , Neuronas/citología , Neuronas/fisiología , Células de Schwann/citología , Células de Schwann/fisiología , Ácidos Siálicos/química , Ingeniería de Tejidos/métodos , Animales , Animales Recién Nacidos , Proliferación Celular , Supervivencia Celular , Células Cultivadas , Materiales Biocompatibles Revestidos/química , Ensayo de Materiales , Ratas , Ratas Sprague-DawleyRESUMEN
Stem cells are currently considered as alternative cell resources for restorative transplantation strategies in Parkinson's disease. However, the mechanisms that induce differentiation of a stem cell toward the dopaminergic phenotype are still partly unknown thus hampering the production of dopaminergic neurons from stem cells. In the past, FGF-20 has been found to promote the survival of ventral mesencephalic (VM) dopaminergic (DA) neurons in culture. We hereby provide evidence that FGF-20, a growth factor of the FGF family, is expressed in the adult and 6-OHDA-lesioned striatum and substantia nigra, but is not expressed by VM glia or DA neurons, suggesting that FGF-20 may work on DA neurons in a paracrine- or target-derived manner. We also found that co-culture of Nurr1-NSCs with Schwann cells overexpressing FGF-20 induced the acquisition of a neuronal morphology by the NSCs and the expression of tyrosine hydroxylase (TH) as assessed by immunocytochemistry, cell ELISA, and Western blot analysis. RT-PCR showed, that both, Schwann cells and Nurr1-NSCs (differentiated or not), expressed the FGF-1 receptor suggesting that both direct and indirect actions of FGF-20 are possible. We show that differentiated Nurr1 cells retained both neuronal morphology and TH expression after transplantation into the striatum of 6-OHDA-lesioned postnatal or adult rats, but that neuritogenesis was only observed after postnatal grafts. Thus, our results suggest that FGF-20 promotes the differentiation of Nurr1-NSCs into TH-positive neurons and that additional factors are required for the efficient differentiation of DA neurons in the adult brain.
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Proteínas de Unión al ADN/metabolismo , Factores de Crecimiento de Fibroblastos/farmacología , Neuronas/citología , Neuronas/metabolismo , Células Madre/citología , Células Madre/metabolismo , Factores de Transcripción/metabolismo , Tirosina 3-Monooxigenasa/metabolismo , Animales , Encefalopatías/inducido químicamente , Encefalopatías/metabolismo , Encefalopatías/cirugía , Diferenciación Celular/efectos de los fármacos , Línea Celular , Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Haz Prosencefálico Medial/efectos de los fármacos , Mesencéfalo/metabolismo , Ratones , Neuronas/enzimología , Neuronas/trasplante , Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares , Oxidopamina/farmacología , Fenotipo , Ratas , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Trasplante de Células Madre , Células Madre/enzimología , Células Madre/fisiologíaRESUMEN
Basic fibroblast growth factor (FGF-2) has been shown to enhance the survival and neurite extension of various types of neurons including spinal ganglion neurons. In addition, endogenous FGF-2 and FGF receptors are upregulated following peripheral nerve lesion in ganglia and at the lesion site. FGF-2 protein is expressed in different isoforms (18 kDa, 21 kDa, 23 kDa) and differentially regulated after nerve injury. In the rat we analyzed the regenerative capacity of the high molecular weight (HMW) FGF-2 isoforms (21/23 kDa) to support the regeneration of the axotomized adult sciatic nerve across long gaps. The nerve stumps were inserted into the opposite ends of a silicone chamber resulting in an interstump gap of 15 mm. Silicone tubes were filled with Matrigel or a mixture of Schwann cells (SC) and Matrigel. SC were prepared from newborn rats and transfected to overexpress HMW FGF-2. Four weeks after the operation procedure, channels were analyzed with regard to tissue cables bridging both nerve stumps and myelinated axons distal to the original proximal nerve stump. Peripheral nerves interposed with HMW Schwann cells displayed significantly enhanced nerve regeneration, with the greatest number of tissue cables containing myelinated axons and the highest number of myelinated axons. These results suggest that a cellular substrate together with a source of a trophic factor could be a promising tool to promote nerve regeneration and, therefore, become useful also for a clinical approach to repair long gaps.
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Factor 2 de Crecimiento de Fibroblastos/metabolismo , Regeneración Nerviosa , Neuronas/fisiología , Isoformas de Proteínas/metabolismo , Células de Schwann/fisiología , Siliconas/metabolismo , Animales , Animales Recién Nacidos , Técnicas de Cultivo de Célula/métodos , Colágeno/metabolismo , Combinación de Medicamentos , Factor 2 de Crecimiento de Fibroblastos/química , Factor 2 de Crecimiento de Fibroblastos/genética , Procesamiento de Imagen Asistido por Computador , Laminina/metabolismo , Fibras Nerviosas Mielínicas/metabolismo , Fibras Nerviosas Mielínicas/ultraestructura , Neuronas/ultraestructura , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Proteoglicanos/metabolismo , Ratas , Ratas Sprague-Dawley , Células de Schwann/ultraestructura , Nervio Ciático/citología , Nervio Ciático/metabolismo , Nervio Ciático/cirugíaRESUMEN
Helicobacter pylori infection results in chronic gastritis, which is initiated by the release of cytokines like interleukin (IL)-12 and IL-8 from mononuclear cells, and IL-8 from gastric epithelial cells. The severity of gastritis is influenced both by host factors and by bacterial factors such as the Cag proteins and the vacuolating cytotoxin VacA. Amounts of IL-12 and IL-8 produced by monocytic THP-1 cells differed considerably between the eight H. pylori isolates tested, but in contrast to H. pylori-induced IL-8 production by gastric epithelial cells, did not correlate to the Cag and VacA types of the strains. Apparently, in addition to Cag and VacA, other bacterial factors determine the extent in which H. pylori induced IL production in monocytes.