RESUMEN
BACKGROUND AND PURPOSE: VBM has been widely used to study GM atrophy in MS. MS lesions lead to segmentation and registration errors that may affect the reliability of VBM results. Improved segmentation and registration have been demonstrated by WM LI before segmentation. DARTEL appears to improve registration versus the USM. Our aim was to compare the performance of VBM-DARTEL versus VBM-USM and the effect of LI in the regional analysis of GM atrophy in MS. MATERIALS AND METHODS: 3T T1 MR imaging scans were acquired from 26 patients with RRMS and 28 age-matched NC. LI replaced WM lesions with normal-appearing WM intensities before image segmentation. VBM analysis was performed in SPM8 by using DARTEL and USM with and without LI, allowing the comparison of 4 VBM methods (DARTEL + LI, DARTEL - LI, USM + LI, and USM - LI). Accuracy of VBM was assessed by using NMI, CC, and a simulation analysis. RESULTS: Overall, DARTEL + LI yielded the most accurate GM maps among the 4 methods (highest NMI and CC, P < .001). DARTEL + LI showed significant GM loss in the bilateral thalami and caudate nuclei in patients with RRMS versus NC. The other 3 methods overestimated the number of regions of GM loss in RRMS versus NC. LI improved the accuracy of both VBM methods. Simulated data suggested the accuracy of the results provided from patient MR imaging analysis. CONCLUSIONS: We introduce a pipeline that shows promise in limiting segmentation and registration errors in VBM analysis in MS.
Asunto(s)
Encéfalo/patología , Aumento de la Imagen , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple Recurrente-Remitente/patología , Adulto , Atrofia , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND AND PURPOSE: Spinal cord atrophy is a common feature of MS. However, it is unknown which cord levels are most susceptible to atrophy. We performed whole cord imaging to identify the levels most susceptible to atrophy in patients with MS versus controls and also tested for differences among MS clinical phenotypes. MATERIALS AND METHODS: Thirty-five patients with MS (2 with CIS, 27 with RRMS, 2 with SPMS, and 4 with PPMS phenotypes) and 27 healthy controls underwent whole cord 3T MR imaging. The spinal cord contour was segmented and assigned to bins representing each C1 to T12 vertebral level. Volumes were normalized, and group comparisons were age-adjusted. RESULTS: There was a trend toward decreased spinal cord volume at the upper cervical levels in PPMS/SPMS versus controls. A trend toward increased spinal cord volume throughout the cervical and thoracic cord in RRMS/CIS versus controls reached statistical significance at the T10 vertebral level. A statistically significant decrease was found in spinal cord volume at the upper cervical levels in PPMS/SPMS versus RRMS/CIS. CONCLUSIONS: Opposing pathologic factors impact spinal cord volume measures in MS. Patients with PPMS demonstrated a trend toward upper cervical cord atrophy. However patients with RRMS showed a trend toward increased volume at the cervical and thoracic levels, which most likely reflects inflammation or edema-related cord expansion. With the disease causing both expansion and contraction of the cord, the specificity of spinal cord volume measures for neuroprotective therapeutic effect may be limited.
Asunto(s)
Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/patología , Médula Espinal/patología , Adolescente , Adulto , Atrofia/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Cognitive deficits affect Asunto(s)
Encéfalo/fisiopatología
, Trastornos del Conocimiento
, Imagen por Resonancia Magnética
, Esclerosis Múltiple Crónica Progresiva
, Índice de Severidad de la Enfermedad
, Adulto
, Anciano
, Cerebelo/fisiopatología
, Trastornos del Conocimiento/diagnóstico
, Trastornos del Conocimiento/etiología
, Trastornos del Conocimiento/fisiopatología
, Femenino
, Lóbulo Frontal/fisiopatología
, Humanos
, Masculino
, Persona de Mediana Edad
, Esclerosis Múltiple Crónica Progresiva/complicaciones
, Esclerosis Múltiple Crónica Progresiva/diagnóstico
, Esclerosis Múltiple Crónica Progresiva/fisiopatología
, Plasticidad Neuronal/fisiología
, Pruebas Neuropsicológicas
, Lóbulo Parietal/fisiopatología
RESUMEN
OBJECTIVES: We investigated motor network function in patients with benign multiple sclerosis (BMS) and contrasted the results with those obtained from patients with secondary progressive multiple sclerosis (SPMS) and healthy controls (HC) to elucidate better the factors associated with a favorable clinical evolution in multiple sclerosis (MS). METHODS: Diffusion tensor (DT) and fMRI scans during the performance of a simple motor task were prospectively acquired from 17 patients with BMS, 15 patients with SPMS, and 17 HC. Patients with BMS and SPMS were matched for age, gender, and disease duration. DT MRI histograms of the normal-appearing white matter (NAWM) and gray matter (GM) were derived. fMRI analysis was performed using SPM5 (Wellcome Department of Cognitive Neurology, London, UK). RESULTS: Compared with HC, patients with BMS and SPMS had increased activations of the left primary sensorimotor cortex. Patients with SPMS also showed increased activations of the left secondary sensorimotor cortex, left inferior frontal gyrus (IFG), right hippocampus, and several visual areas. Compared with HC and patients with BMS, patients with SPMS had reduced activations of the left supplementary motor area, left putamen, and right cerebellum. Compared with patients with BMS, patients with SPMS had increased activations of the left IFG and right middle occipital gyrus. In patients with MS, fMRI changes were correlated with T2 lesion volumes and DT MRI changes in the NAWM and GM. CONCLUSIONS: This study shows that, contrary to what happens in secondary progressive multiple sclerosis, the movement-associated pattern of activations seen in benign multiple sclerosis resembles that of healthy people, and its abnormalities are restricted to the sensorimotor network. The long-term preservation of brain functional adaptive mechanisms in these patients is likely to contribute to their favorable clinical course.
Asunto(s)
Adaptación Fisiológica/fisiología , Encéfalo/fisiopatología , Esclerosis Múltiple/fisiopatología , Red Nerviosa/fisiopatología , Plasticidad Neuronal/fisiología , Adulto , Anciano , Ganglios Basales/patología , Ganglios Basales/fisiopatología , Encéfalo/patología , Mapeo Encefálico , Cerebelo/patología , Cerebelo/fisiopatología , Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , Estudios de Cohortes , Imagen de Difusión por Resonancia Magnética , Femenino , Lateralidad Funcional/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/patología , Red Nerviosa/patología , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Estudios ProspectivosRESUMEN
BACKGROUND: Magnetic Resonance (MR) diffusion tensor imaging (DTI) is able to quantify in vivo tissue microstructure properties and to detect disease related pathology of the central nervous system. Nevertheless, DTI is limited by low spatial resolution associated with its low signal-to-noise-ratio (SNR). AIM: The aim is to select a DTI sequence for brain clinical studies, optimizing SNR and resolution. METHODS AND RESULTS: We applied 6 methods for SNR computation in 26 DTI sequences with different parameters using 4 healthy volunteers (HV). We choosed two DTI sequences for their high SNR, they differed by voxel size and b-value. Subsequently, the two selected sequences were acquired from 30 multiple sclerosis (MS) patients with different disability and lesion load and 18 age matched HV. We observed high concordance between mean diffusivity (MD) and fractional anysotropy (FA), nonetheless the DTI sequence with smaller voxel size displayed a better correlation with disease progression, despite a slightly lower SNR. The reliability of corpus callosum (CC) fiber tracking with the chosen DTI sequences was also tested. CONCLUSIONS: The sensitivity of DTI-derived indices to MS-related tissue abnormalities indicates that the optimized sequence may be a powerful tool in studies aimed at monitoring the disease course and severity.
Asunto(s)
Encéfalo/anatomía & histología , Encéfalo/patología , Imagen de Difusión Tensora/instrumentación , Imagen de Difusión Tensora/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Esclerosis Múltiple/patología , Adulto , Algoritmos , Anisotropía , Cuerpo Calloso/anatomía & histología , Cuerpo Calloso/patología , Evaluación de la Discapacidad , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/patología , Esclerosis Múltiple Recurrente-Remitente/patología , Vías Nerviosas/anatomía & histología , Vías Nerviosas/patología , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Diffusion tensor (DT) magnetic resonance imaging is able to quantify tissue microstructure properties and to detect pathological changes even in the normal appearing tissues. DT sequence parameters which provide optimal SNR and minimum acquisition time, and an individual-based tractography post-processing allowed corpus callosum tractography even in multiple sclerosis (MS) patients also with no need of a-priori atlas. In this preliminary study, we were able to obtain reliable individual-based tractography in 28/30 MS patients. DT-derived indices computed in tracks obtained with individual-based tractography were able to differentiate healthy volunteers from MS patients better than the same indices computed with the atlas method. This indicates that such an optimized sequence may be a reliable tool to be used in future MS studies.
Asunto(s)
Cuerpo Calloso/fisiopatología , Imagen de Difusión por Resonancia Magnética/instrumentación , Esclerosis Múltiple/fisiopatología , Adulto , Anciano , Encéfalo/patología , Mapeo Encefálico/métodos , Estudios de Casos y Controles , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
BACKGROUND: Gray matter (GM) magnetic resonance imaging (MRI) T2 hypointensity, a putative marker of iron deposition, commonly occurs in multiple sclerosis (MS). However, GM T2 hypointensity in benign MS (BMS) has not yet been characterized. OBJECTIVE: To determine the presence of deep GM T2 hypointensity in BMS, compare it to secondary progressive (SP) MS and assess its association with clinical and diffusion tensor (DT) MRI measures. METHODS: Thirty-five cognitively unimpaired BMS, 26 SPMS patients, and 25 healthy controls were analyzed for normalized T2-intensity in the basal ganglia and thalamus, global T2 hyperintense lesion volume, global atrophy, and white matter and GM DT metrics. RESULTS: BMS and SPMS patients showed deep GM T2 hypointensity compared with controls. T2 hypointensity was similar in both MS subgroups and moderately correlated (r = -0.45 to 0.42) with DT MRI metrics. GM T2 hypointensity in BMS showed a weak to moderate correlation (r = -0.44 to -0.35) with disability. CONCLUSIONS: GM in BMS is not spared from structural change including iron deposition. However, while T2 hypointensity is related to global tissue disruption reflected in DT MRI, the expression of benign versus non-benign MS is likely related to other factors.
Asunto(s)
Ganglios Basales/patología , Imagen de Difusión por Resonancia Magnética , Esclerosis Múltiple/patología , Neuronas/patología , Tálamo/patología , Adulto , Atrofia , Ganglios Basales/metabolismo , Cognición , Evaluación de la Discapacidad , Femenino , Humanos , Hierro/metabolismo , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/metabolismo , Índice de Severidad de la Enfermedad , Tálamo/metabolismoRESUMEN
BACKGROUND: Magnetization transfer (MT) magnetic resonance imaging (MRI) can provide quantitative information about the severity of tissue damage in the cervical cord of patients with multiple sclerosis (MS). MT MRI-derived measures of cord damage are correlated with the severity of disease-related locomotor disability. OBJECTIVES: The objective of this study was to investigate whether MT MRI-detectable cervical cord damage is present in early relapsing-remitting (RR) MS. SUBJECTS AND METHODS: We studied 23 patients with 'early' RR MS (i.e., with a disease duration shorter than 5 years) and 10 age-matched healthy control subjects. During a single session, the following sequences were acquired using a 1.5 T scanner: (a) brain dual-echo turbo spin echo; (b) cervical cord fast short-tau inversion recovery; (c) cervical cord gradient echo, without and with MT pulse. Brain T2 lesion volume was measured. Cervical cord lesions were counted and normalized histograms of cord MT ratio (MTR) were produced. RESULTS: One or more cervical cord lesions were found in nine patients (39%). The average cord MTR and the mean histogram peak height values did not differ between patients and controls. There was no significant correlation between brain T2 lesion volume and cervical cord MTR histogram-derived metrics. CONCLUSIONS: Cervical cord tissue damage seems to be limited to macroscopic lesions in patients with early, non-disabling RR MS. Longitudinal studies are warranted to define the dynamics of MS-related cord damage accumulation over time later on in the course of the disease.
Asunto(s)
Imagen por Resonancia Magnética , Esclerosis Múltiple Recurrente-Remitente/patología , Médula Espinal/patología , Adulto , Vértebras Cervicales , Evaluación de la Discapacidad , Diagnóstico Precoz , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
OBJECTIVE: The mirror neuron system (MNS) is an observation-execution matching system activated, in humans, during action observation, motor learning, and imitation of action. We used functional MRI (fMRI) to investigate the properties of the MNS in patients with multiple sclerosis (MS). METHODS: Using a 3 tesla scanner, we acquired fMRI in 16 right-handed patients with relapsing-remitting MS and 14 controls. Two motor tasks were studied. The first consisted of repetitive flexion-extension of the last four fingers of the right hand (simple task) alternated to epochs of rest; the second (MNS task) consisted of observation of a movie showing the hand of another subject while performing the same task. RESULTS: During the simple task, compared to controls, patients with MS had more significant activations of the contralateral primary sensorimotor cortex and supplementary motor area. During the MNS task, both groups showed the activation of several visual areas, the infraparietal sulcus, and the inferior frontal gyrus (IFG), bilaterally. The IFG and the visual areas were significantly more active in patients than controls. The between-group interaction analysis showed that in patients with MS, part of the regions of the MNS were more active also during the simple task. CONCLUSIONS: This study suggests increased activation of the mirror neuron system in patients with multiple sclerosis (MS) with a normal level of function and widespread CNS damage. The potentialities of this system in facilitating clinical recovery in patients with MS and other neurologic conditions should be investigated.
Asunto(s)
Corteza Cerebral/fisiopatología , Imagen por Resonancia Magnética/métodos , Trastornos del Movimiento/diagnóstico , Trastornos del Movimiento/fisiopatología , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/fisiopatología , Adulto , Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/patología , Circulación Cerebrovascular/fisiología , Evaluación de la Discapacidad , Femenino , Dedos/inervación , Dedos/fisiopatología , Humanos , Conducta Imitativa/fisiología , Imagen por Resonancia Magnética/instrumentación , Magnetismo , Masculino , Persona de Mediana Edad , Trastornos del Movimiento/etiología , Red Nerviosa/irrigación sanguínea , Red Nerviosa/patología , Red Nerviosa/fisiopatología , Neuronas/fisiología , Pruebas Neuropsicológicas/normas , Valor Predictivo de las Pruebas , Desempeño Psicomotor/fisiología , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Prader-Willi syndrome (PWS) is a congenital alteration of chromosome pair 15. It is characterized by short stature, muscular hypotonia, hyperphagia, obesity, behavioural and emotional disturbances, hypogonadism and partial Growth Hormone (GH) deficiency. The aim of this study was to assess the long-term effect of GH treatment on the psychological well-being and Quality of Life (QoL) in an adult PWS group. METHODS: A total of 13 PWS patients, their diagnosis confirmed by genetic tests, and their parents were recruited for this study. The participants were administered the 36-Items Short Form Health Survey (SF-36) and the Psychological General Well-Being Index (PGWBI), for the assessment of QoL and psychological well-being, at the beginning of GH treatment, and at following intervals of 6, 12 and 24 months. Modified versions of the same questionnaires were given to the parents. RESULTS: Significant improvement with respect to the baseline was found, on both scales, in the evaluation of both physical and psychological well-being, although the parents' evaluation was less optimistic than that of the patients. CONCLUSION: Our findings suggest that the amelioration of QoL and psychological status is sustained in patients who continue GH treatment.
Asunto(s)
Adaptación Psicológica/efectos de los fármacos , Hormona de Crecimiento Humana/uso terapéutico , Síndrome de Prader-Willi/tratamiento farmacológico , Síndrome de Prader-Willi/psicología , Calidad de Vida/psicología , Adulto , Femenino , Humanos , Estudios Longitudinales , Masculino , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Recent evidence from neuropsychologic and neuroimaging studies suggests that central nervous system involvement in amyotrophic lateral sclerosis (ALS) extends beyond motor neurons. Our purpose was to obtain measures of global and regional atrophy in nondemented patients with ALS to assess subtle structural brain changes. METHODS: MR images, acquired from 16 patients and 9 healthy subjects (HS), were processed by using the Structural Imaging Evaluation of Normalized Atrophy (SIENA) software to estimate whole-brain atrophy measures and the voxel-based morphometry (VBM) method to highlight the selective volumetric decrease of single cerebral areas. In addition, each subject underwent a neuropsychologic examination. RESULTS: In patients with ALS, brain parenchymal fraction was slightly lower compared with HS (P = .012), and seemed to be related to the presence of cognitive impairment. Patients showed a gray matter volume decrease in several frontal and temporal areas bilaterally (P < .001 uncorrected) compared with HS, with a slight prevalence in the right hemisphere. No volume reduction in primary motor cortices of patients was detected. Performances on Symbol Digit Modalities Test were significantly worse in patients compared with HS (P = .025). CONCLUSIONS: The presence of mild whole-brain volume loss and regional frontotemporal atrophy in patients with ALS could explain the presence of cognitive impairment and confirms the idea of ALS as a degenerative brain disease not confined to motor system.
Asunto(s)
Esclerosis Amiotrófica Lateral/patología , Encéfalo/patología , Imagen por Resonancia Magnética , Anciano , Atrofia , Trastornos del Conocimiento/patología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Programas InformáticosRESUMEN
BACKGROUND AND OBJECTIVE: Diffusion tensor (DT) magnetic resonance imaging (MRI) has the potential to disclose subtle abnormalities in the brain of migraine patients. This ability may be increased by the use of high field magnets. A DT MRI on a 3.0 tesla scanner was used to measure the extent of tissue damage of the brain normal appearing white (NAWM) and grey matter in migraine patients with T2 visible abnormalities. METHODS: Dual echo, T1 weighted and DT MRI with diffusion gradients applied in 32 non-collinear directions were acquired from 16 patients with migraine and 15 sex and age matched controls. Lesion load on T2 weighted images was measured using a local thresholding segmentation technique, and brain atrophy assessed on T1 weighted images using SIENAx. Mean diffusivity and fractional anisotropy histograms of the NAWM and mean diffusivity histograms of the grey matter were also derived. RESULTS: Brain atrophy did not differ between controls and patients. Compared with healthy subjects, migraine patients had significantly reduced mean diffusivity histogram peak height of the grey matter (p=0.04). No diffusion changes were detected in patients' NAWM. In migraine patients, no correlation was found between T2 weighted lesion load and brain DT histogram derived metrics, whereas age was significantly correlated with grey matter mean diffusivity histogram peak height (p=0.05, r=-0.52). CONCLUSIONS: DT MRI at high field strength discloses subtle grey matter damage in migraine patients, which might be associated with cognitive changes in these patients.
Asunto(s)
Encéfalo/patología , Imagen de Difusión por Resonancia Magnética , Procesamiento de Imagen Asistido por Computador , Trastornos Migrañosos/patología , Migraña con Aura/patología , Adulto , Factores de Edad , Anisotropía , Atrofia , Daño Encefálico Crónico/patología , Líquido Cefalorraquídeo/fisiología , Trastornos del Conocimiento/patología , Femenino , Humanos , Masculino , Cómputos Matemáticos , Persona de Mediana Edad , Valores de Referencia , Factores de Riesgo , Estadística como AsuntoRESUMEN
OBJECTIVES: To establish the prognostic role of clinical and demographic factors in a hospital-based cohort of MS patients categorized by age at clinical onset and clinical course. METHODS: Eighty-three patients with MS had a clinical onset of the disease in childhood (age <16 years; early-onset MS [EOMS]) and 710 in adult age (between 16 and 65 years; adult-onset MS [AOMS]). Patients were followed for a mean period of observation of 5 years. Univariate and multivariate analyses of clinical and demographic predictors for rapid progression and disability were performed using a stepwise Cox regression model with time-dependent covariates. RESULTS: In EOMS, the Expanded Disability Status Scale (EDSS) evaluated at last clinical examination was lower than in AOMS, despite a longer disease duration. The probability to reach growth disability and progression was significantly lower in EOMS than in AOMS. Median times to reach EDSS score of 4 and secondary progression were longer in EOMS than in AOMS, but the age at both endpoints was significantly lower in EOMS. In EOMS and AOMS, an irreversible disability was related to a secondary progressive course, a sphincteric system involvement at onset, and an older age at onset (in EOMS only for the group >14 years); in AOMS, other unfavorable factors were a pyramidal involvement at onset and a high relapse frequency in the first 2 years. The risk of entering secondary progression was significantly influenced by a high number of relapses in EOMS and by a higher age at onset and a short interattack interval in AOMS. CONCLUSION: A slower rate of progression of disease characterized EOMS patients, suggesting more plasticity to recover in developing CNS, but the early clinical manifestation cannot be considered a positive prognostic factor.
Asunto(s)
Esclerosis Múltiple/fisiopatología , Adolescente , Adulto , Edad de Inicio , Anciano , Niño , Preescolar , Estudios de Cohortes , Evaluación de la Discapacidad , Progresión de la Enfermedad , Femenino , Humanos , Lactante , Italia/epidemiología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/epidemiología , Pronóstico , Tractos Piramidales/fisiopatología , Recurrencia , Análisis de SupervivenciaRESUMEN
It is well established that children with short stature frequently have problems in cognitive development, personality, self-esteem and social relations. This is partly due to the fact that many parents view them as more vulnerable than other children of normal stature and do not allow them to face the normal experiences that correspond to their actual age. The aim of the present study was to assess, through the administration of appropriate psychological tools, a series of psychological and cognitive characteristics [i.e. anxiety, depression, good adjustment, social functioning, feeling of guilt, interpersonal relationship, intelligence quotient (IQ)], as well as variables linked to development of body image, in a group of children suffering from normal growth variants [familial short stature (FSS), no. 10, 4 males/6 females; with constitutional growth delay (CGD), no. 4,4 males; height standard deviation score (HSDS) ranging between -2.4 and -1.9] and in a control group children of normal stature (HSDS between -0.1 and +0.1). Children with short stature significantly differed from normal statured controls as far as Colored Progressive Matrices (CPMs, centiles), IQ (IQ, obtained using the Goodenough test), "Good Adjustment" (Draw-a-Person index, DAP), "Feelings of Guilt" (DAP index), "Height" (as emerges from drawings of the body) are concerned. Significant relationships were found between the height of the subjects (in centiles) and cognitive skills, measured both using CPMs (r=0.408; p=0.017) and Draw-a-Man (DAM) (r=0.359; p=0.037) and between height and feelings of guilt (r=0.325; p=0.027), measured using DAP. CPM scores correlated positively with the "Good Adjustment" index of DAP (r=0.354; p=0.05) and negatively with Children's Depression Inventory (CDI) (r=-0.609; p=0.01), "School Anxiety" index (r=-0.427; p=0.05) and "Total Anxiety" index (r=-0.436; p=0.05) of the Anxiety Scale Questionnaire for the Age of Development, and with 2 indices of DAP, namely, "Feelings of Guilt" (r=-0.461; p=0.01) and "Interpersonal Relationships (Difficulty in Establishing)" (r=-0.455; p=0.01). A significant positive correlation was found between the height of the subject and both the measurement of the "Body of Drawing 3" (r=0.450, p=0.01) and the measurement of the "Body of Drawing 4" (r=0.461, p=0.01), as well as the with the "Total Height of Drawing 4" (r=0.464, p=0.01). Higher indices for anxiety, depression, feelings of guilt and difficulty in establishing interpersonal relationships and lower indices for good adjustment were found in children with CGD as compared to subjects with FSS or normal statured children. Although further additional studies on larger samples are needed to confirm these preliminary observations, the present study underlines the importance of psychological support also during the growth and development in short normal children.
Asunto(s)
Adaptación Psicológica , Estatura , Imagen Corporal , Desarrollo Infantil , Emociones , Inteligencia , Ansiedad , Estatura/genética , Niño , Femenino , Crecimiento , Culpa , Humanos , Relaciones Interpersonales , Masculino , Valores de Referencia , Factores de TiempoRESUMEN
The host defense roles of neutrophil elastase in a porcine skin wound chamber model were explored. Analysis of wound fluid by acid-urea polyacrylamide gel electrophoresis, Western blot, and bacterial overlay confirmed that the neutrophil-derived protegrins constituted the major stable antimicrobial polypeptide in the wound fluid. The application to the wound of 0.10 and 0.25 mM N-methoxysuccinyl-alanine-alanine-proline-valine (AAPV) chloromethyl ketone, a specific neutrophil elastase inhibitor (NEI), blocked the proteolytic activation of protegrins and diminished the associated antimicrobial activity as detected by radial diffusion assay against Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans or by bacterial gel overlay against S epidermidis and E coli. The application of the related cathepsin G inhibitor (CGI), benzyloxycarbonyl-glycine-leucine-phenylalanine (ZGLF) chloromethyl ketone, had no effect. In wound chambers that received 10(6) colony-forming unit (CFU)/mL of S epidermidis, the presence of NEI significantly decreased the 24-hour clearance of bacteria from the wound compared to wounds treated with CGI or solvent only. Neither inhibitor, at 0.10 or 0.25 mM concentration, affected leukocyte accumulation or degranulation in the wound chambers. The in vitro microbicidal decrement due to NEI was restored by an amount of the specific protegrin (PG-1), which was equivalent to the measured difference of protegrin between control and inhibited chambers. Administration of 1 microg/mL exogenous PG-1 4 hours after chamber preparation was sufficient to normalize in vivo antimicrobial activity. Although pharmacologic NEIs are promising candidates as anti-inflammatory drugs, they may impair host defense in part by inhibiting the activation of cathelicidins by neutrophil elastase.
Asunto(s)
Péptidos Catiónicos Antimicrobianos/efectos de los fármacos , Elastasa de Leucocito/farmacología , Heridas y Lesiones/microbiología , Animales , Antibacterianos/metabolismo , Péptidos Catiónicos Antimicrobianos/metabolismo , Bacterias/efectos de los fármacos , Líquidos Corporales/química , Líquidos Corporales/microbiología , Catelicidinas , Catepsina G , Catepsinas/farmacología , Relación Dosis-Respuesta a Droga , Elastasa de Leucocito/antagonistas & inhibidores , Pruebas de Sensibilidad Microbiana , Modelos Animales , Infiltración Neutrófila/efectos de los fármacos , Proteínas/antagonistas & inhibidores , Proteínas/metabolismo , Proteínas/farmacología , Serina Endopeptidasas , Inhibidores de Serina Proteinasa/administración & dosificación , Inhibidores de Serina Proteinasa/farmacología , Serpinas/farmacología , Superóxidos/metabolismo , Porcinos , Heridas y Lesiones/metabolismoRESUMEN
PURPOSE: We investigated the therapeutic potential of the pig-derived antimicrobial peptide protegrin-1 (PG-1) against porcine skin wounds infected with Pseudomonas aeruginosa. MATERIALS AND METHODS: Using a porcine skin wound model, PG-1 was added to the wound fluid either at the time of P. aeruginosa inoculation, four hours after inoculation or 24 hours after inoculation. Wound fluids were analyzed 20-24 hours later by use of colony-forming unit (CFU) assays, semiquantitative immunoblot analysis for PG-1, and radial diffusion assays (RDA) for residual in vitro activity. RESULTS: Results of the CFU assays indicated a 10,000-fold decrease in the number of bacteria when PG-1 was added at the time of inoculation, a 120-fold decrease when added 4 hours after inoculation and a 10-fold decrease when added 24 hours after inoculation. Results of immunoblot analysis and RDA indicated that PG-1 concentrations for each of the three conditions remained increased in wound fluid 20 to 24 hours after treatment, and correlated with increased residual in vitro antimicrobial activity. CONCLUSIONS: These results document that the endogenous antibiotic PG-1 significantly prevented the colonization of P. aeruginosa in wounds and reduced the in vivo bacterial concentration in established wound infections. Therapeutics used in the same animal species from which they were derived are a promising means for preventing and treating localized infections.
Asunto(s)
Antibacterianos/uso terapéutico , Proteínas/uso terapéutico , Infecciones por Pseudomonas/veterinaria , Enfermedades de los Porcinos/tratamiento farmacológico , Infección de Heridas/veterinaria , Animales , Péptidos Catiónicos Antimicrobianos , Femenino , Técnicas In Vitro , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/aislamiento & purificación , Piel/lesiones , Porcinos , Enfermedades de los Porcinos/microbiología , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiologíaRESUMEN
Cell-cell signaling and adhesion regulate transition from the unicellular to the multicellular stage of development in the cellular slime mold Dictyostelium. Essential gene networks involved in these processes have been identified and their interplay dissected. Heterotrimeric G protein-linked signal transduction plays a key role in regulating expression of genes mediating chemotaxis or cell adhesion, as well as coordinating actin-based cell motility during phagocytosis and chemotaxis. Two classes of cell adhesion molecules, one cadherin-like and the second belonging to the IgG superfamily, contribute to the strength of adhesion in Dictyostelium aggregates. The developmental role of genes involved in motility and adhesion, and their degree of redundancy, have been re-assessed by using novel developmental assay conditions which are closer to development in nature.
Asunto(s)
Dictyostelium/metabolismo , Dictyostelium/fisiología , Fagocitosis , Proteínas Protozoarias , Animales , Cadherinas/metabolismo , Adhesión Celular , Moléculas de Adhesión Celular/química , Moléculas de Adhesión Celular/metabolismo , Comunicación Celular , Quimiotaxis , Dictyostelium/genética , Proteínas de Unión al GTP/metabolismo , Inmunoglobulina G/metabolismo , Modelos Biológicos , Fenotipo , Factor de Activación Plaquetaria/metabolismo , Relación Estructura-Actividad , Transducción GenéticaRESUMEN
The ecmB gene of Dictyostelium is expressed at culmination both in the prestalk cells that enter the stalk tube and in ancillary stalk cell structures such as the basal disc. Stalk tube-specific expression is regulated by sequence elements within the cap-site proximal part of the promoter, the stalk tube (ST) promoter region. Dd-STATa, a member of the STAT transcription factor family, binds to elements present in the ST promoter-region and represses transcription prior to entry into the stalk tube. We have characterised an activatory DNA sequence element, that lies distal to the repressor elements and that is both necessary and sufficient for expression within the stalk tube. We have mapped this activator to a 28 nucleotide region (the 28-mer) within which we have identified a GA-containing sequence element that is required for efficient gene transcription. The Dd-STATa protein binds to the 28-mer in an in vitro binding assay, and binding is dependent upon the GA-containing sequence. However, the ecmB gene is expressed in a Dd-STATa null mutant, therefore Dd-STATa cannot be responsible for activating the 28-mer in vivo. Instead, we identified a distinct 28-mer binding activity in nuclear extracts from the Dd-STATa null mutant, the activity of this GA binding activity being largely masked in wild type extracts by the high affinity binding of the Dd-STATa protein. We suggest, that in addition to the long range repression exerted by binding to the two known repressor sites, Dd-STATa inhibits transcription by direct competition with this putative activator for binding to the GA sequence.
Asunto(s)
ADN Protozoario/genética , Dictyostelium/genética , Animales , Secuencia de Bases , Sitios de Unión , Análisis Mutacional de ADN , ADN Protozoario/metabolismo , Proteínas de la Matriz Extracelular/genética , Regulación de la Expresión Génica/genética , Datos de Secuencia Molecular , Regiones Promotoras Genéticas , Proteínas Protozoarias/genética , Transactivadores/metabolismoAsunto(s)
Pérdida de Hueso Alveolar/cirugía , Incisivo/anomalías , Raíz del Diente/anomalías , Implantes Absorbibles , Trasplante Óseo , Colágeno , Legrado , Femenino , Estudios de Seguimiento , Liofilización , Regeneración Tisular Guiada Periodontal/métodos , Humanos , Incisivo/cirugía , Membranas Artificiales , Persona de Mediana Edad , Aplanamiento de la Raíz , Colgajos Quirúrgicos , Conservación de Tejido , Raíz del Diente/cirugía , Trasplante HomólogoRESUMEN
Multiple sclerosis (MS) onset is usually in adult life (age 20-40 years). Discordant data have been reported concerning the frequency of early onset MS (EOMS) that ranges from 2.7% to 5%, whereas there is a general agreement on prevalence of female sex, particularly after puberty. The initial symptoms in EOMS are frequently characterized by visual loss whereas the other functional systems are involved with a variable frequency. Literature data show that EOMS tends to have a relapsing-remitting course, a high rate of recovery from the initial attack, a long time interval between the first and second attacks and a slow progression rate. A poor prognosis is reported in a few cases of EOMS and seems to be related to number of relapses and to the delay between the first and second attacks.