Cognitive Dysfunction in Multiple Sclerosis: Educational Level as a Protective Factor.

Most people with MS experience cognitive deficits especially in attention, memory, information processing, and executive functions, negatively impacting on their quality of life. Cognitive variables of short-term memory, logical memory, and verbal fluency in 65 patients with multiple sclerosis (MS) were analysed in conjunction with sociodemographic variables such as sex, age, and educational level that might influence disease progression. We found that psychoeducational variables exerted a significant effect on the cognitive status of patients with MS. Thus, when considering sex, age, educational level, and type of MS (SPMS or RRMS), tests for between-subject effects revealed statistically significant differences in all three cognitive variables. In addition, we found that the type of MS and time since onset also generated significant cognitive differences. Our study shows that educational achievement or level is a protective factor against the disease, acting as a source of intellectual enrichment that promotes cognitive reserve in patients with MS. Further longitudinal studies assessing disease progression and prognosis in patients with MS would be useful in order to determine the specific importance of these variables in such patients and in strategies that could enhance their performance in neuropsychological assessment tasks.

Successful thrombolytic therapy for recurrent right ventricular thrombosis in Behçet's disease.

Behçet's disease (BD) is a chronic inflammatory multisystem disorder characterised by recurrent oral and genital aphtosis and ocular involvement. Thrombophlebitis and major vessel thrombosis are common manifestations of vascular involvement in BD patients, whereas intracardiac thrombosis is extremely rare. We describe a 22-year-old woman who presented with deep vein thrombosis and recurrent right ventricular thrombosis complicated by pulmonary embolism. At the time, she complained of fever, recurrent painful oral and genital aphtae and papulo-pustular skin rash so she was diagnosed with BD. She received intravenous streptokinase 50,000 units/hour for three days plus corticosteroids with complete recovery. A review of intracardiac thrombosis in BD is presented and the use of thrombolytic therapy in this rare condition is briefly discussed.

Clastosome: a subtype of nuclear body enriched in 19S and 20S proteasomes, ubiquitin, and protein substrates of proteasome.

Nuclear bodies represent a heterogeneous class of nuclear structures. Herein, we describe that a subset of nuclear bodies is highly enriched in components of the ubiquitin-proteasome pathway of proteolysis. We coined the term clastosome (from the Greek klastos, broken and soma, body) to refer to this type of nuclear body. Clastosomes contain a high concentration of 1) ubiquitin conjugates, 2) the proteolytically active 20S core and the 19S regulatory complexes of the 26S proteasome, and 3) protein substrates of the proteasome. Although detected in a variety of cell types, clastosomes are scarce under normal conditions; however, they become more abundant when proteasomal activity is stimulated. In contrast, clastosomes disappear when cells are treated with proteasome inhibitors. Protein substrates of the proteasome that are found concentrated in clastosomes include the short-lived transcription factors c-Fos and c-Jun, adenovirus E1A proteins, and the PML protein. We propose that clastosomes are sites where proteolysis of a variety of protein substrates is taking place.

La satisfacción laboral y profesional de los profesores

La especial relevancia e incidencia de la profesión docente en las generaciones jóvenes hace especialmente pertinente estudiar su satisfacción, ya que ello incide de forma directa en el desempeño y eficacia de su profesión. El objetivo de este trabajo es proceder a una revisión de los principales estudios sobre satisfacción laboral y profesional de los profesores, partiendo de una conceptualización por autores y usando una visión determinada de la forma en que obtienen los datos y las categorías de medida. La metodología ha consistido en seleccionar tres bases de datos temáticas y los resultados del ISBN para extraer las aportaciones de los últimos 10 años sobre el tema. Los resultados muestran una pluralidad de enfoques y perspectivas dependiendo del origen científico de cada investigador. Además, señalan la mayoría de mujeres en los niveles no universitarios y una satisfacción media-alta con la profesión, destacando en forma positiva el aspecto relacional, y en forma negativa, la valoración y el sueldo. Como mejora pudieran incluirse más referencias en inglés pero ello haría el artículo interminable.

The high relevance and influence of teachers in the younger generations makes the study of those teachers´ satisfaction really important, as it directly affects their professional performance and efficiency. This research work aims to revise the main studies about labor and professional satisfaction among teachers, starting with a conceptualization classified by authors and using a determined vision of the way data are obtained and of the measuring categories. The methodology followed has been the selection of three thematic databases and the ISBN´s results to extract the contributions on the subject published over the last ten years. The results show a plurality in the focuses and viewpoints depending on the scientific origin of every researcher. Besides, women are remarked as a majority in the educational levels below higher education and a satisfaction in levels between medium and high with the profession, highlighting, in a positive way, the relational aspect and, in a negative one, the valuation and the salaries. As an improvement, more references in English could have been included, but in that case the paper would have turned out being an endless work.

A especial relevância e incidência da profissão docente nas gerações jovens faz especialmente pertinente estudar sua satisfação, já que isto incide de forma direta no desempenho e eficácia de sua profissão. O objetivo deste trabalho é proceder a uma revisão dos principais estudos sobre satisfação laboral e profissional dos professores, partindo de uma conceptualização por autores e usando uma visão determinada da forma em que obtém os dados e as categorias de medida. A metodologia há consistido em selecionar três bases de dados temáticas e os resultados do ISBN para extrair as contribuições dos últimos 10 anos sobre o assunto. Os resultados mostram uma pluralidade de enfoques e perspectivas dependendo da origem científico de cada investigador. Ademais, assinalam a maioria de mulheres nos níveis não universitários e uma satisfação media-alta com a profissão, destacando em forma positiva o aspecto relacional, e em forma negativa, a valoração e o salário. Como melhora pudessem incluir-se mais referências em inglês mas isto faria o artigo interminável.

Serum biotinidase activity in children treated with valproic acid and carbamazepine.

There is evidence that valproic acid causes a reduction of serum biotinidase enzyme activity. We determined the serum concentration of antiepileptic drugs, transaminases, gamma-glutamyl transferase, ammonia, and biotinidase enzyme activity in 57 children treated with valproic acid, in 17 children treated with carbamazepine, and in 75 age- and sex-matched healthy controls. There were no significant differences in the serum biotinidase enzyme activity between the patients treated with valproic acid, the patients treated with carbamazepine, and the control group. Hyperammonemia was detected in 8 patients treated with valproic acid. Hair loss was observed in 3 female patients treated with valproic acid, and the alopecia disappeared with the oral administration of biotin (10 mg/ d) in 3 months. These results suggest that the treatment with valproic acid does not alter the serum biotinidase enzyme activity.

Topical fusidic acid for treatment of Clostridium perfringens Keratitis.

PURPOSE: To report the therapeutic outcome of primary corneal infection by Clostridium perfringens. METHODS: A 65-year-old cleaning lady had pain, decreased visual acuity, redness, and photophobia in her left eye for 4 days. A paracentral corneal ulcer with subepithelial bullae and several frothy bubbles in the ulcer bed was found. Two different cultures were positive for C. perfringens. RESULTS: Treatment with topical fusidic acid 1% was given, and the corneal infiltrate regressed within 6 weeks to a faint corneal opacity. CONCLUSIONS: Clostridium perfringens keratitis can be treated successfully with topical fusidic acid.

Proteasome dynamics during cell cycle in rat Schwann cells.

The proteasome is responsible for most of the protein degradation that takes place in the cytoplasm and nucleus. Immunofluorescence and electron microscopy are used to study proteasome dynamics during the cell cycle in rat Schwann cells. During interphase, the proteasome is present in the nucleus and cytoplasm and shows no colocalization with cytoskeletal components. Some cytoplasmic proteasomes always localize in the centrosome both in interphase and in mitotic cells and only associate with microtubules during mitosis. The proteasome exits the nucleus during prophase. In anaphase, the proteasome becomes prominent in the region between the two sets of migrating chromosomes and in association with interzonal microtubules and stem bodies. In telophase, the proteasome begins to reenter the nucleus and is prominent in the midbody region until the end of cytokinesis. The proteasome does not colocalize with actin or vimentin during mitosis, except for colocalization with actin in the sheet-like lamellipodia, which serve as substrate attachments for the cell during mitosis. During S phase, nuclear proteasomes colocalize with foci of BrdU incorporation, but this association changes with time: maximal at early S phase and declining as S phase progresses to the end. These results are discussed in relation to the biochemical pathways involved in cell cycle progression.

The proteasome is a major autoantigen in multiple sclerosis.

Multiple sclerosis seems to be an autoimmune disease of unknown aetiology affecting the white matter of the CNS. It is generally accepted that the autoimmune response is directed against specific components of myelin. We show here that proteasome, a ubiquitous protease complex composed of 14 different subunits, is a target for autoantibodies (IgG and IgM classes) present in the serum (66%, 73 out of 110) and in the CSF (61%, 16 out of 26) of patients with multiple sclerosis. Using recombinant proteasomal subunits we demonstrate the presence of specific autoantibodies against subunits C2, C8, C9 and C5 in multiple sclerosis patients. Recombinant C2 constructs allow us to localize an immunodominant autoepitope recognized by the sera of multiple sclerosis patients within the C-terminal of C2 proteasomal subunit (251-DEPAEKADEPMEH-263). In addition, two constructs of the recombinant proteasomal subunits C2 and C8 were also used to study the proliferation of peripheral blood mononuclear cells from multiple sclerosis patients; 12 out of 30 (40%) multiple sclerosis patients show positive proliferation with one or both of these recombinant subunits. The high prevalence of anti-proteasome autoantibodies in multiple sclerosis sera compared with sera from patients with other chronic inflammatory conditions: systemic lupus erythematosus (35%, 35 out of 100), primary Sjogren's syndrome (16%, 5 out of 31), vasculitis (0 out of 20), sarcoidosis (7%, 1 out of 13) and Behcet's disease (19%, 4 out of 21) suggest that humoral autoreactivity to proteasome could be a useful test in multiple sclerosis patients that may be of help in the diagnosis and/or progression of this chronic inflammatory disease. Finally, these results suggest that some global abnormality in B and/or T cell function is also involved in the chronic inflammatory response observed in multiple sclerosis patients, as it is frequently observed in other human organ-specific autoimmune diseases.

alpha-Synuclein expression levels do not significantly affect proteasome function and expression in mice and stably transfected PC12 cell lines.

alpha-Synuclein (alpha-syn) is a small protein of unknown function that is found aggregated in Lewy bodies, the histopathological hallmark of sporadic Parkinson disease and other synucleinopathies. Mutations in the alpha-syn gene and a triplication of its gene locus have been identified in early onset familial Parkinson disease. alpha-Syn turnover can be mediated by the proteasome pathway. A survey of published data may lead to the suggestion that overexpression of alpha-syn wild type, and/or their variants (A53T and A30P), may produce a decrease in proteasome activity and function, contributing to alpha-syn aggregation. To investigate the relationship between synuclein expression and proteasome function we have studied proteasome peptidase activities and proteasome subunit expression (alpha, beta-constitutive, and inducible) in mice either lacking alpha-syn (knock-out mice) or transgenic for human alpha-syn A30P (under control of PrP promoter, at a time when no clear gliosis can be observed). Similar studies are presented in PC12 cells overexpressing enhanced yellow fluorescent protein fusion constructs of human wild type, A30P, and A53T alpha-syn. In these cell lines we have also analyzed the assembly of 20 S proteasome complex and the degradation rate of a well known substrate of the proteasome pathway, Ikappabalpha. Overall the data obtained led us to the conclusion that alpha-synuclein expression levels by themselves have no significant effect on proteasome peptidase activity, subunit expression, and proteasome complex assembly and function. These results strengthen the suggestion that other mechanisms resulting in synuclein aggregation (not simply expression levels) may be the key to understand the possible effect of aggregated synuclein on proteasome function.