RESUMEN
Multiple sclerosis (MS) is associated with inflammatory lesions in the brain and spinal cord. The detection of such inflammatory lesions using magnetic resonance imaging (MRI) is important in the consideration of the diagnosis and differential diagnoses of MS, as well as in the monitoring of disease activity and predicting treatment efficacy. Although there is strong evidence supporting the use of MRI for both the diagnosis and monitoring of disease activity, there is a lack of evidence regarding which MRI protocols to use, the frequency of examinations, and in what clinical situations to consider MRI examination. A national workshop to discuss these issues was held in Stockholm, Sweden, in August 2015, which resulted in a Swedish consensus statement regarding the use of MRI in the care of individuals with MS. The aim of this consensus statement is to provide practical advice for the use of MRI in this setting. The recommendations are based on a review of relevant literature and the clinical experience of workshop attendees. It is our hope that these recommendations will benefit individuals with MS and guide healthcare professionals responsible for their care.
Asunto(s)
Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/diagnóstico por imagen , Guías de Práctica Clínica como Asunto , Humanos , Imagen por Resonancia Magnética/normas , Neurología/organización & administración , Sociedades Médicas , SueciaRESUMEN
The interaction of N-(4-ethoxyphenyl)p-benzoquinone imine (NEPBQI), a metabolite formed during peroxidase catalyzed metabolism of p-phenetidine, with GSH and its effects in isolated rat hepatocytes were investigated. When reacted with GSH NEPBQI formed both a mono- and a diglutathione conjugate as well as GSSG. Formation of glutathione conjugates and GSSG also occurred when NEPBQI was added to isolated hepatocytes. The formation of GSSG was, however, only detectable if the hepatocytes had been pretreated with the GSSG reductase inhibitor BCNU (1,3-bis-(2-chloroethyl-1-nitrosourea). Similarly, NEPBQI caused a rapid decrease in cellular free protein thiols when added to hepatocytes, however this was expressed at higher concentrations than for effects on GSH. The protein thiol decrease was correlated with protein binding of NEPBQI. NEPBQI was also shown to be toxic to isolated hepatocytes. At a concentration of 400 microM extensive bleb formation was followed by loss of cell membrane integrity and cell death. To assess further the subcellular metabolism of NEPBQI microsomes and cytosol was used. NEPBQI was found to be preferentially reduced by cytochrome P-450 reductase in the microsomes whereas DT-diaphorase catalyzed its reduction in cytosol. NEPBQI did not undergo significant redox cycling since no formation of O2 was observed. Thus, the cytotoxic effect of NEPBQI appears to be due to protein arylation rather than redox cycling.
Asunto(s)
Benzoquinonas , Hígado/efectos de los fármacos , Quinonas/toxicidad , Animales , Carmustina/farmacología , Glutatión/análogos & derivados , Glutatión/metabolismo , Disulfuro de Glutatión , Masculino , Peroxidasas/metabolismo , Fenetidina/metabolismo , Proteínas/metabolismo , Ratas , Ratas EndogámicasRESUMEN
Twenty rats were exposed for 60 min to 14C-labeled toluene (1,950 mg/m3) in the inspired air. The largest amounts of toluene and its metabolites were found in the white adipose tissue. In a second series of experiments seven healthy male subjects were exposed to 375 mg/m3 of toluene in the air rest and during light, moderate and heavy physical exercise on a bicycle ergometer. The duration of each exposure period was 30 min. Of the seven male subjects three were thin, one was slightly overweight, and three were excessively overweight. The concentration of toluene in the alveolar air and the total uptake of toluene were determined during exposure. The thin subjects had a higher concentration of toluene in alveolar air than the other subjects both at rest and during exercise. The total uptake of toluene in the body during exposure showed that the subjects with the least amount of adipose tissue had the smallest uptake and the subjects with the largest amount of adipose tissue had the largest uptake.
Asunto(s)
Tejido Adiposo/metabolismo , Contaminantes Atmosféricos/metabolismo , Tolueno/metabolismo , Adulto , Animales , Peso Corporal , Exposición a Riesgos Ambientales , Humanos , Masculino , Esfuerzo Físico , Ratas , Pruebas de Función Respiratoria , Factores de Tiempo , Distribución TisularRESUMEN
Twelve subjects were exposed to 300 or 600 mg/m3 of butyl alcohol in inspired air during rest and during exercise on a bicycle ergometer. Exposure lasted 2 h. The results were puzzling in view of the high blood/air partition coefficient for butyl alcohol. The arterial blood concentration was low. The concentration in the last part of the expired air, i.e., the ""alveolar'' concentration, was low. The quotient of ""alveolar'' concentration X 100/inspired concentration was low in relation to the low percentage uptake. However the high solubility of butyl alcohol in water may explain the results. Butyl alcohol was probably partially taken up in the water of the dead space mucous membranes during inspiration. It was then partially released from the membranes. Therefore the concentration of butyl alcohol in the last part of expiration was probably not the same as the concentration in the alveolar air.
Asunto(s)
Butanoles/metabolismo , Adulto , Butanoles/sangre , Exposición a Riesgos Ambientales , Humanos , Masculino , Alveolos Pulmonares/metabolismo , Relación Ventilacion-PerfusiónRESUMEN
BACKGROUND AND PURPOSE: Brain atrophy is a manifestation of tissue damage in MS. Reduction in brain parenchymal fraction is an accepted marker of brain atrophy. In this study, the approach of synthetic tissue mapping was applied, in which brain parenchymal fraction was automatically calculated based on absolute quantification of the tissue relaxation rates R1 and R2 and the proton attenuation. MATERIALS AND METHODS: The BPF values of 99 patients with MS and 35 control subjects were determined by using SyMap and tested in relationship to clinical variables. A subset of 5 patients with MS and 5 control subjects were also analyzed with a manual segmentation technique as a reference. Reproducibility of SyMap was assessed in a separate group of 6 healthy subjects, each scanned 6 consecutive times. RESULTS: Patients with MS had significantly lower BPF (0.852 ± 0.0041, mean ± SE) compared with control subjects (0.890 ± 0.0040). Significant linear relationships between BPF and age, disease duration, and Expanded Disability Status Scale scores were observed (P < .001). A strong correlation existed between SyMap and the reference method (r = 0.96; P < .001) with no significant difference in mean BPF. Coefficient of variation of repeated SyMap BPF measurements was 0.45%. Scan time was <6 minutes, and postprocessing time was <2 minutes. CONCLUSIONS: SyMap is a valid and reproducible method for determining BPF in MS within a clinically acceptable scan time and postprocessing time. Results are highly congruent with those described using other methods and show high agreement with the manual reference method.
Asunto(s)
Algoritmos , Encéfalo/patología , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/patología , Reconocimiento de Normas Patrones Automatizadas/métodos , Adolescente , Adulto , Anciano , Atrofia/patología , Femenino , Humanos , Aumento de la Imagen/métodos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Brain size is commonly described in relation to ICV, whereby accurate assessment of this quantity is fundamental. Recently, an optimized MR sequence (QRAPMASTER) was developed for simultaneous quantification of T1, T2, and proton density. ICV can be measured automatically within minutes from QRAPMASTER outputs and a dedicated software, SyMRI. Automatic estimations of ICV were evaluated against the manual segmentation. MATERIALS AND METHODS: In 19 healthy subjects, manual segmentation of ICV was performed by 2 neuroradiologists (Obs1, Obs2) by using QBrain software and conventional T2-weighted images. The automatic segmentation from the QRAPMASTER output was performed by using SyMRI. Manual corrections of the automatic segmentation were performed (corrected-automatic) by Obs1 and Obs2, who were blinded from each other. Finally, the repeatability of the automatic method was evaluated in 6 additional healthy subjects, each having 6 repeated QRAPMASTER scans. The time required to measure ICV was recorded. RESULTS: No significant difference was found between reference and automatic (and corrected-automatic) ICV (P > .25). The mean difference between the reference and automatic measurement was -4.84 ± 19.57 mL (or 0.31 ± 1.35%). Mean differences between the reference and the corrected-automatic measurements were -0.47 ± 17.95 mL (-0.01 ± 1.24%) and -1.26 ± 17.68 mL (-0.06 ± 1.22%) for Obs1 and Obs2, respectively. The repeatability errors of the automatic and the corrected-automatic method were <1%. The automatic method required 1 minute 11 seconds (SD = 12 seconds) of processing. Adding manual corrections required another 1 minute 32 seconds (SD = 38 seconds). CONCLUSIONS: Automatic and corrected-automatic quantification of ICV showed good agreement with the reference method. SyMRI software provided a fast and reproducible measure of ICV.
Asunto(s)
Algoritmos , Encéfalo/anatomía & histología , Encéfalo/fisiología , Interpretación de Imagen Asistida por Computador/métodos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Reconocimiento de Normas Patrones Automatizadas/métodos , Adulto , Femenino , Humanos , Aumento de la Imagen/métodos , Masculino , Tamaño de los Órganos/fisiología , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadAsunto(s)
Contaminantes Ocupacionales del Aire , Contaminantes Atmosféricos , Tolueno , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/metabolismo , Contaminantes Ocupacionales del Aire/análisis , Contaminantes Ocupacionales del Aire/metabolismo , Exposición a Riesgos Ambientales , Humanos , Esfuerzo Físico , Impresión , Respiración , Tolueno/análisis , Tolueno/metabolismo , Tolueno/envenenamientoRESUMEN
4-Ethoxyaniline (p-phenetidine) is oxidized by peroxidases to form several products, one of which is 4-[(4-ethoxyphenyl)imino]-2,5-cyclohexadien-1-one (1). This compound reacts with N-acetylcysteine (NAC) in methanol-phosphate buffers, generating at least four different products. Four major products, 4-[(4-ethoxyphenyl)amino]phenol (2), 3-(N-acetylcystein-S-yl)-4-[(4-ethoxyphenyl)amino]phenol (3), 2,5-bis(N-acetylcystein-S-yl)-4-[(4-ethoxyphenyl)-amino]phenol (4), and 2,5-bis(N-acetylcystein-S-yl)-4-[(4-ethoxyphenyl)imino]-2,5- cyclohexadien-1-one (5), were isolated and identified by NMR spectroscopy and mass spectrometry. The relative ratio between the formed products depends on the pH, the concentration of NAC, and the reaction time. Compound 2, which is the reduced form of 1, was the dominating product when the reaction took place at pH 3, whereas formation of the mono conjugate (3) was more extensive at a neutral pH. Under alkaline conditions 2 and 3 were oxidized by 1 or O2. The oxidized form of 3 was subsequently attacked by a second molecule of NAC, generating the bis conjugate (4). Unless an excess of NAC was present, compound 4 underwent rapid oxidation to 5. Quinone imines, like 1, generating mono conjugates, which are more reactive than the quinone imines per se, are likely to inflict an increased toxic potential and an increased stress on the endogenous thiol pool, resulting in an overall greater toxicity.
Asunto(s)
Acetilcisteína/metabolismo , Benzoquinonas/metabolismo , Peroxidasas/farmacología , Fenetidina/metabolismo , Glutatión/metabolismo , Concentración de Iones de Hidrógeno , Oxidación-ReducciónRESUMEN
The toxicity of some metabolic products pertinent to 4-ethoxyaniline in isolated hepatocytes were investigated. The compounds investigated were 4-ethoxynitrosobenzene (1), 4-ethoxy-4'-nitrosodiphenylamine (2), 3,6-bis(4-ethoxy-phenylimino)-4-ethoxy-1,4-cyclohexadienylamine (3), 4-(4-ethoxyphenylimino)-2,3-dimethyl-2,5-cyclohexadiene-1-one (4) and 4-(4-ethoxyphenylimino)-2,6-dimethyl-2,5-cyclohexadiene-1-one (5). Of these, 1, 2 and 3 are oxidation products of 4-ethoxyaniline. Compounds 4 and 5 are dimethyl analogues of previously investigated oxidation product 4-(4-ethoxyphenylimino(-2,5-cyclohexadiene-1-one (NEPBQI). Among the investigated compounds, 1 and 2 were the most toxic towards isolated hepatocytes. In hepatocytes treated with compounds 1, 2 and 4, loss of cell viability was also accompanied by surface bleb formation. All compounds except 3 reacted with GSH resulting in depletion of cellular GSH. No formation of GSSG was observed, however. Thus, the GSH depletion was apparently due to conjugate formation rather than oxidation. No superoxide dismutase inhibitable reduction of acetylated cytochrome c was observed, thus none of the compounds undergoes measurable redox cycling.