RESUMO
INTRODUCTION AND OBJECTIVES: Instability is a frequent symptom after whiplash (WL) with alterations in postural control in chronic phases. The main objective of our study was to evaluate if there were objective alterations in postural control in the acute phases after a WL, as well as to determine the presence or absence of oculomotor alterations in early phases. MATERIAL AND METHODS: A posturographic study was carried out using the NedSVE/IBV system, as well as an oculomotor assessment, in a sample of 44 patients with WL in the first 24h after the accident. RESULTS: More than half of the patients had a global assessment below normal. The predominant sensory pattern was vestibular. The main parameters of the Romberg test (total displacement, swept area, average speed, anteroposterior and mediolateral displacement and anteroposterior force) increased following the sequence Romberg open eyes, Romberg foam rubber open eyes, Romberg closed eyes, and Romberg foam rubber closed eyes. Concerning the comparison with normality and using the reference values of the Institute of Biomechanics of Valencia, the data from the WL patients showed significant differences in all the parameters analysed, except for gait assessment and the mediolateral directional rhythmic control. CONCLUSIONS: Our data confirm that patients in the acute phase of WL have worse postural control than non-injured persons. The results suggest that patients with WL have greater visual dependence. Only a minority of patients had oculomotor abnormalities during early examination.
Assuntos
Equilíbrio Postural , Traumatismos em Chicotada , Fenômenos Biomecânicos , Humanos , Valores de Referência , Traumatismos em Chicotada/complicaçõesRESUMO
Desmosine (DES) and isodesmosine (IDES) are two unusual, tetrafunctional, pyridinium ring-containing amino acids involved in elastin cross-linking. Being amino acids unique to mature, cross-linked elastin, they are useful for discriminating peptides derived from elastin breakdown from precursor elastin peptides. According to these features, DES and IDES have been extensively discussed as potentially attractive indicators of elevated lung elastic fibre turnover and markers of the effectiveness of agents with the potential to reduce elastin breakdown. In the present manuscript, immunology-based and separation methods for the evaluation of DES and IDES are discussed, along with studies reporting increased levels of urine excretion in chronic obstructive pulmonary disease (COPD) patients with and without alpha(1)-antitrypsin deficiency. The results of the application of DES and IDES as surrogate end-points in early clinical trials in COPD are also reported. Finally, recent advances in detection techniques, including liquid chromatography tandem mass spectrometry and high-performance capillary electrophoresis with laser-induced fluorescence, are discussed. These techniques allow detection of DES and IDES at very low concentration in body fluids other than urine, such as plasma or sputum, and will help the understanding of whether DES and IDES are potentially useful in monitoring therapeutic intervention in COPD.
Assuntos
Desmosina/sangue , Elastina/metabolismo , Doença Pulmonar Obstrutiva Crônica/sangue , Adulto , Criança , Cromatografia Líquida/métodos , Feminino , Humanos , Isodesmosina/sangue , Masculino , Modelos Biológicos , Peptídeos/química , Fumar , Espectrometria de Massas em Tandem/métodos , Deficiência de alfa 1-Antitripsina/sangueRESUMO
Prolidase is a naturally occurring enzyme involved in the final stage of protein catabolism. Deficient enzyme activity causes prolidase deficiency (PD), a rare autosomal recessive inherited disorder whose main manifestations are chronic, intractable ulcerations of the skin, particularly of lower limbs. Although several attempts have been made towards the treatment of this pathology, a cure for this disease has yet to be found. The purpose of this work is to evaluate the possibility of enzyme replacement therapy through prolidase microencapsulation in biodegradable microspheres. The poly(D,L-lactide-co-glycolide) (PLGA) prolidase loaded microparticulate systems have been prepared utilizing the w-o-w double emulsion solvent evaporation method. They have been characterized "in vitro" by morphological analysis, total protein content and an in vitro dissolution test of active protein. "Ex vivo" evaluation of prolidase activity from the microspheres has been performed on cellular extracts of cultured skin fibroblasts from healthy subjects (controls) and from patients affected by PD. The results reported in this work on prolidase from pig kidney (available on the market) demonstrate the positive role of microencapsulation as a process of enzymatic activity stabilization inside PLGA microspheres achieving both in vitro and ex vivo active enzyme release. This formulation can be proposed as a parenteral depot drug delivery system.
Assuntos
Avaliação de Medicamentos/métodos , Enzimas Imobilizadas/farmacocinética , Adulto , Animais , Biodegradação Ambiental , Células Cultivadas , Dipeptidases/administração & dosagem , Dipeptidases/farmacocinética , Ativação Enzimática/fisiologia , Enzimas Imobilizadas/administração & dosagem , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/enzimologia , Humanos , Masculino , Microesferas , Pessoa de Meia-Idade , Pele/efeitos dos fármacos , Pele/enzimologia , SuínosRESUMO
Prolidase deficiency (PD) is a rare autosomal recessive disorder caused by inadequate levels of the cytosolic exopeptidase prolidase (E.C. 3.4.13.9), for which there is not, as yet, a resolutive cure. We have investigated whether biodegradable microspheres loaded with prolidase could release active enzyme inside cells, to consider this system as a possible therapeutic approach for prolidase deficiency. Poly(lactide-co-glycolide) microspheres were prepared, modifying the classical double emulsion solvent evaporation method to mitigate the burst effect of the enzyme from the microspheres. Ex-vivo experiments were performed, by incubating microencapsulated prolidase with cultured fibroblasts from PD patients and from controls, to determine the amount of active enzyme delivered to the cells. The microparticulate drug delivery system described carried small amounts of active prolidase inside fibroblasts, ensuring a response to the intracellular accumulation of X-Pro dipeptides, the mechanism that is supposed to be responsible for the development of clinical manifestations of this disorder in man. A positive result of the presence of active enzyme inside cells was an improvement in fibroblast shape.
Assuntos
Dipeptidases/administração & dosagem , Dipeptidases/metabolismo , Fibroblastos/efeitos dos fármacos , Poliglactina 910/química , Biodegradação Ambiental , Células Cultivadas , Dipeptidases/deficiência , Portadores de Fármacos/química , Ativação Enzimática/efeitos dos fármacos , Fibroblastos/enzimologia , Humanos , Microesferas , Pele/citologia , Fatores de TempoRESUMO
Soil samples, and samples of leaves of Plantago major (great plantain) and grass (mixed species) were collected from the vicinity of an oil refinery in Zelzate, Belgium, and analysed for seven polycyclic aromatic hydrocarbons (PAHs). The samples from the site adjacent to the refinery (site 1) contained very high total PAH-concentrations: namely 300, 8 and 2 microg/g dry wt. for soil, P. major and grass, respectively. Concentrations in samples from more remote sites (up to 4 km from the refinery) were a factor of 10-30 lower than those from site 1, but between them the differences were small. The PAH-profiles of the plant samples, in contrast with those of the soil samples, appeared to shift to higher contributions of gaseous PAHs with increasing distance from the refinery. This can be explained by particle-bound PAHs being deposited closer to the source than gaseous PAHs. It is suggested that particle-bound deposition is relatively more important for deposition to soil than to plants, due to blow-off and wash-off of the compounds from the leaves. The total PAH-concentrations in the leaves of P. major were higher than those measured in the grass samples, probably due to differences in aerodynamic surface roughness, leaf orientation and/or leaf age. However, the concentration ratios of P. major/grass were not constant for the different sites, varying from 1.2 to 8.8. Therefore, it appears that a precise prediction of PAH-concentrations for one plant species from known concentrations of another species is not possible. When errors in predicted concentrations need to be smaller than a factor of approximately 10, the sampling strategy has to be focussed on all species of interest.
Assuntos
Poluentes Ambientais/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Indústrias , Petróleo , Plantas/química , Poluentes do Solo/análise , Distribuição TecidualRESUMO
Introducción y objetivos La sensación de inestabilidad es un síntoma frecuente tras un latigazo cervical (LC), existiendo alteraciones objetivas del control postural en fases crónicas. El objetivo fundamental de nuestro estudio fue evaluar las alteraciones objetivas del control postural, así como la presencia o ausencia de alteraciones oculomotoras en las fases agudas tras un LC. Material y métodos Se realizó un estudio posturográfico mediante sistema NedSVE/IBV y una valoración oculomotora en una muestra de 44 sujetos afectos de LC en las primeras 24h tras el accidente. Resultados Más de la mitad de los pacientes estudiados presentaron una valoración global por debajo de la normalidad. El patrón sensorial predominante fue el denominado patrón vestibular. Los parámetros fundamentales del test de Romberg (desplazamiento total, área de barrido, velocidad media, desplazamientos anteroposterior y mediolateral y fuerza anteroposterior) aumentaron siguiendo la secuencia Romberg ojos abiertos, Romberg gomaespuma ojos abiertos, Romberg ojos cerrados y Romberg gomaespuma ojos cerrados. En cuanto a la comparación con la normalidad y utilizando los valores de referencia del Instituto de Biomecánica de Valencia, los datos de los pacientes de LC muestran diferencias significativas en todos los parámetros analizados, salvo en la valoración de la marcha y el control rítmico direccional mediolateral. Conclusiones Nuestros datos confirman que los pacientes en fase aguda del LC presentan un peor control postural desde las primeras horas tras el accidente. Los resultados evidencian que los pacientes con LC tienen una mayor dependencia visual. Solo una minoría de los pacientes presentan alteraciones oculomotoras durante la exploración temprana (AU)
Introduction and objectives Instability is a frequent symptom after whiplash (WL) with alterations in postural control in chronic phases. The main objective of our study was to evaluate if there were objective alterations in postural control in the acute phases after a WL, as well as to determine the presence or absence of oculomotor alterations in early phases. Material and methods A posturographic study was carried out using the NedSVE/IBV system, as well as an oculomotor assessment, in a sample of 44 patients with WL in the first 24h after the accident. Results More than half of the patients had a global assessment below normal. The predominant sensory pattern was vestibular. The main parameters of the Romberg test (total displacement, swept area, average speed, anteroposterior and mediolateral displacement and anteroposterior force) increased following the sequence Romberg open eyes, Romberg foam rubber open eyes, Romberg closed eyes, and Romberg foam rubber closed eyes. Concerning the comparison with normality and using the reference values of the Institute of Biomechanics of Valencia, the data from the WL patients showed significant differences in all the parameters analysed, except for gait assessment and the mediolateral directional rhythmic control. Conclusions Our data confirm that patients in the acute phase of WL have worse postural control than non-injured persons. The results suggest that patients with WL have greater visual dependence. Only a minority of patients had oculomotor abnormalities during early examination (AU)
Assuntos
Humanos , Equilíbrio Postural , Traumatismos em Chicotada/complicações , Fenômenos Biomecânicos , Valores de ReferênciaRESUMO
Batten disease, or human late-infantile neuronal ceroid lipofuscinosis (LINCL) is a familiar progressive degenerative disease affecting children, caused by a deficiency of a lysosomal proteinase (tripeptidyl peptidase I, TPP-I) and characterized by the accumulation of autofluorescent storage bodies in the brain and other tissues of the body. Current methodology used to diagnose this disease needs to be improved in order to have less invasive techniques with higher resolution and shorter assay time. In this report, we discuss the potential merits of micellar electrokinetic chromatography as an excellent tool that requires minute samples but offers high resolution and a short running time for monitoring TPP-I activity in human and animal specimens.
Assuntos
Eletroforese Capilar/métodos , Endopeptidases/análise , Lipofuscinoses Ceroides Neuronais/diagnóstico , Lipofuscinoses Ceroides Neuronais/enzimologia , Aminopeptidases , Animais , Plaquetas/enzimologia , Bovinos , Cromatografia/métodos , Dipeptidil Peptidases e Tripeptidil Peptidases , Endopeptidases/sangue , Endopeptidases/deficiência , Fibroblastos/enzimologia , Humanos , Lactente , Leucócitos/enzimologia , Lisossomos/enzimologia , Camundongos , Micelas , Ratos , Serina Proteases , Tripeptidil-Peptidase 1RESUMO
BACKGROUND: Prolidase deficiency is a rare genetic disorder for which a cure has not yet been found. OBJECTIVES: To assess the effectiveness of apheresis exchange as a new therapeutic approach. METHODS: Apheresis exchanges were repeated monthly for four consecutive months, in parallel, on two patients, replacing prolidase-deficient red blood cells with normal filtered cells. Prolidase activity and urinary dipeptides were determined at regular intervals. RESULTS: The constant presence of active prolidase inside cells allowed a continuous, although partial, degradation of imidodipeptides, with a concomitant improvement of skin ulceration. CONCLUSIONS: Apheresis exchange could be a reasonable way of obtaining a clinical improvement in these patients.
Assuntos
Remoção de Componentes Sanguíneos/métodos , Dipeptidases/deficiência , Úlcera da Perna/terapia , Adulto , Eletroforese Capilar , Eritrócitos/enzimologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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