RESUMEN
OBJECTIVES: The aim of this study was to evaluate a short-term non-specific home-based 6-week cognitive training for its effect on neuropsychological deficits and depression. SUBJECTS AND METHODS: Cognitive and affective abilities of patients with MS were compared with healthy controls using an identical neuropsychological test battery. Re-testing was performed after 6 weeks of cognitive home-based training. RESULTS: Patients already showed cognitive deficits at baseline. Cognitive training resulted in a significant improvement in several skills, in particular with respect to visuoconstructive and figural long-term memory. In addition, prior depressed mood and quality of life improved in MS patients during the training period and remained up to 6 months. CONCLUSIONS: Our study corroborated the early appearance of neuropsychological deficits in MS. Mental training, although unspecific, lead to improvements with respect to attention and memory functions in patients, and to some degree in control subjects, which may last for more than 6 months.
Asunto(s)
Afecto , Trastornos del Conocimiento/rehabilitación , Esclerosis Múltiple/rehabilitación , Adulto , Trastornos del Conocimiento/etiología , Terapia Cognitivo-Conductual/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/psicología , Pruebas Neuropsicológicas , Evaluación de Programas y Proyectos de Salud , Calidad de Vida , TiempoRESUMEN
The isolation and structures of a new patellamide (patellamide D) and two new lissoclinamides (lissoclinamides 4 and 5) from the aplousobranch ascidian Lissoclinum patella are described. Structures were determined largely by using two-dimensional NMR techniques and mass spectrometry. These peptides and other members of the patellamide and lissoclinamide families that have been reported previously are found within the obligate algal symbiont of the genus Prochloron. The cytotoxicities of the compounds toward fibroblast and tumor cell lines are reported. One of these compounds, lissoclinamide 4, is markedly more toxic than other members of the family. Structure-activity relationships are discussed.
Asunto(s)
Péptidos Cíclicos/aislamiento & purificación , Urocordados/análisis , Animales , Línea Celular Transformada , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , ADN/biosíntesis , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Conformación Molecular , Estructura Molecular , Péptidos Cíclicos/farmacología , Relación Estructura-Actividad , Células Tumorales Cultivadas , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Two new lissoclinamides (lissoclinamides 7 and 8) have been isolated from the aplousobranch ascidian Lissoclinum patella. These lissoclinamides are cyclic heptapeptides with the same structural features as lissoclinamides 4 and 5 reported earlier, containing an oxazoline ring, one proline, one valine, two phenylalanine residues, and thiazole and/or thiazoline rings. All four peptides have the same sequence of amino acids around the ring and differ from one another only in their stereochemistry or the number of thiazole and thiazoline rings. The cytotoxicities of the compounds were tested with human fibroblast and bladder carcinoma cell lines and normal lymphocytes. Slight changes in structure resulted in marked differences in the cytotoxicities of these compounds. The most potent is lissoclinamide 7, containing two thiazoline rings, which rivals didemnin B in cytotoxicity in vitro.
Asunto(s)
Supervivencia Celular/efectos de los fármacos , Péptidos Cíclicos/aislamiento & purificación , Urocordados , Animales , Espectroscopía de Resonancia Magnética , Péptidos Cíclicos/farmacología , Conformación Proteica , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
A wide range of toxins with interesting pharmacological properties have been isolated from ascidians. These include cyclic peptides, one of which, didemnin B, is undergoing clinical trials for cancer chemotherapy and is also a powerful immunosuppressive agent. Other classes of toxins from these organisms are alkaloids, macrolides, polyethers, prenylated hydroquinones and others of diverse chemical structure. The majority of these compounds are cytotoxic and in some cases the mechanisms of action have been investigated. The toxins are most likely used for chemical defense but the question of how the ascidians themselves escape the toxic actions is also not resolved.
Asunto(s)
Acetamidas , Toxinas Marinas/química , Piranos , Alcaloides/química , Secuencia de Aminoácidos , Animales , Carotenoides/química , Éteres Cíclicos/química , Datos de Secuencia Molecular , Péptidos Cíclicos/química , Compuestos de Espiro , UrocordadosRESUMEN
In 25 patients under treatment or during follow-up for acute lymphoblastic leukemia magnetic resonance imaging (MRI) of both knees was compared to history and physical examination to detect osteonecrosis. Results of MRI were classified as: O, normal bone marrow (BM); 1, diffuse decrease in signal intensity; 2, circumscript lesions. Patients clinically suspected of osteonecrosis had a statistically significant increased incidence of Type 2 lesions. Three patients with a BM relapse also showed Type 2 lesions. Circumscript lesions of the epiphyses were seen exclusively in the four patients with clinical suspicion of osteonecrosis during BM remission and this may be a MR finding strongly indicative of osteonecrosis. Patients with Type 2 lesions during BM remission had received systemic chemotherapy for a statistically significant longer period than the other patients. Using MRI findings we suspect that at least four patients suffered osteonecrosis due to chemotherapy. MRI is a promising means of detecting this disorder.