[Efficacy and safety of transcranial magnetic stimulation in patients with non-fluent aphasia, following an ischaemic stroke. A controlled, randomised and double-blind clinical trial]. / Eficacia y seguridad de la estimulacion magnetica transcraneal en pacientes con afasia no fluente, posterior a ictus isquemico. Ensayo clinico controlado, aleatorizado y doble ciego.

INTRODUCTION: Non-fluent aphasia is a frequent complication in post-ischemic stroke patients, with repetitive transcranial magnetic stimulation (rTMS) being one of the possible treatment alternatives. AIM: To assess the efficacy and safety of rTMS in patients with non-fluent after-ischemic stroke aphasia. PATIENTS AND METHODS: Double blind, randomized controlled clinical trial in post-stroke patients who were assigned to receive 10 sessions (one daily) of active treatment or placebo of rTMS, without the addition of language therapy. The baseline characteristics were compared initially and the efficacy between the active group versus the placebo group at day 30 was evaluated through a Mann-Whitney U test. RESULTS: 82 patients were included: active group (n = 41) and placebo group (n = 41). At baseline, statistically significant differences were found between the groups in favor of the placebo in the domains of the Boston test of auditory compression (p = 0.024), denomination (p = 0.014) and praxis (p = 0.026), and also occurred on the 30th day in the naming domains (p = 0.037) and reading (p = 0.001). There were 39 adverse reactions: 23 (26.83%) in the active group vs 16 (21.96%) in the placebo group (p = 0.290); the majority corresponded to episodes of mild headache. CONCLUSION: rTMS is a safe therapy, however, given the conditions of this study, we could not demonstrate the efficacy of rTMS versus placebo in patients with non-fluent aphasia with involvement of Broca's area after an ischemic stroke.

TITLE: Eficacia y seguridad de la estimulacion magnetica transcraneal en pacientes con afasia no fluente, posterior a ictus isquemico. Ensayo clinico controlado, aleatorizado y doble ciego.Introduccion. La afasia no fluente es una complicacion frecuente en pacientes postictus isquemico y la estimulacion magnetica transcraneal repetitiva (EMTr) representa una de las posibles alternativas de tratamiento. Objetivo. Evaluar la eficacia y la seguridad de la EMTr en pacientes con afasia no fluente postictus isquemico. Pacientes y metodos. Ensayo clinico controlado doble ciego, aleatorizado, en pacientes postictus isquemico que fueron asignados a recibir 10 sesiones (una diaria) de tratamiento activo o placebo de EMTr, sin adicion de terapia del lenguaje. Las caracteristicas basales fueron comparadas inicialmente, y la eficacia entre el grupo activo frente al grupo placebo el dia 30 se evaluo a traves de una prueba U de Mann-Whitney. Resultados. Se incluyo a 82 pacientes: grupo activo (n = 41) y grupo placebo (n = 41). Se encontraron diferencias basales estadisticamente significativas entre los grupos a favor del placebo en los dominios del test de Boston de compresion auditiva (p = 0,024), denominacion (p = 0,014) y praxis (p = 0,026), e igualmente ocurrio el dia 30 en los dominios de denominacion (p = 0,037) y lectura (p = 0,001). Se presentaron 39 reacciones adversas, 23 en el grupo activo (26,83%) frente a 16 (21,96%) en el grupo placebo (p = 0,290), y la mayoria correspondia a episodios de cefalea leve. Conclusion. La EMTr es una terapia segura, pero dadas las condiciones de este estudio, no pudo demostrarse la eficacia de la EMTr frente al placebo en pacientes con afasia no fluente con afectacion del area de Broca posterior a un ictus isquemico.

Clinical features predict responsiveness to imatinib in platelet-derived growth factor receptor-alpha-negative hypereosinophilic syndrome.

BACKGROUND: With the exception of the presence of the FIP1L1-PDGFRA fusion gene, little is known about predictors of imatinib response in clinically-defined hypereosinophilic syndrome (HES). METHODS: Subjects with FIP1L1-PDGFRA-myeloid neoplasm (FP; n =12), PDGFRA-negative HES with ≥4 criteria suggestive of a myeloid neoplasm (MHES; n =10), or steroid-refractory PDGFRA-negative HES with <4 myeloid criteria (SR; n = 5) were enrolled in a prospective study of imatinib therapy (NCT00044304: registered at clinicaltrials.gov). The primary outcome was an eosinophil count <1.5 × 109/L at one month and improvement of clinical symptoms. Clinical, molecular, and bone marrow responses to imatinib were assessed. A retrospective cohort of 18 subjects with clinically-defined HES who received imatinib (300-400 mg daily ≥ 1 month) were classified according to the criteria used in the prospective study. RESULTS: Overall, imatinib response rates were 100% in the FP group (n = 16), 54% in the MHES group (n = 13) and 0% in the SR group (n = 16). The presence of ≥ 4 myeloid features was the sole predictor of response. After ≥ 18 months in complete remission, imatinib was tapered and discontinued in 8 FP and 1 MHES subjects. Seven subjects (6 FP, 1 MHES) remain in remission off therapy for a median of 29 months (range 14-36). CONCLUSIONS: Clinical features of MHES predict imatinib response in PDGFRA-negative HES.

Gastritis / Gastritis

La gastritis es una lesión inflamatoria de la mucosa gástrica, producida en respuesta a la agresión de diferentes agentes exógenos y endógenos. Se presenta en forma aguda y crónica. El diagnóstico se establece ya sea por la clínica, la endoscopía o el estudio histopatológico de la mucosa del estómago.

Hemorragia digestiva alta no varicosa / Digestive hemorrhage high non-varicose

La hemorragia digestiva alta, se define como la pérdida de sangre que se produce en el segmento del tubo digestivo comprendido entre el esfinter esofágico superior y el ángulo de Treitz. Puede tener curso agudo o crónico y obedece a múltiples causas. Es la emeergencia mas frecuente manejada por los gastroenterólogos.

Hemorragia digestiva alta varicosa / Digestive hemorrhage high varicose

La hemorragia digestiva alta varicosa se define como la visualización de sangrado de una várice esofágica o gástrica el momento de la endoscopia, o la presencia de sangre en el estomago en presencia de várices esofágicas o gastricas importantes sin sangrado activo, en ausencia de otras lesiones de esófago, estómago o duodeno que justifiquen sangrado.

Hemorragia digestiva baja / Digestive hemorrhage lowers

La hemorragia digestiva baja, es la eliminación de sangre por el ano proveniente de una lesión ubicada en el segmento del tubo digestivo comprendido entre el ángulo de Treitz y el ano. El sangrado crónico, leve, no visible , que corresponde a la denominación de sangre oculta en heces.

Involvement of surface cysteines in activity and multimer formation of thimet oligopeptidase.

Thimet oligopeptidase is a metalloenzyme involved in regulating neuropeptide processing. Three cysteine residues (246, 248, 253) are known to be involved in thiol activation of the enzyme. In contrast to the wild-type enzyme, the triple mutant (C246S/C248S/C253S) displays increased activity in the absence of dithiothreitol. Dimers, purportedly formed through cysteines 246, 248 and 253, have been thought to be inactive. However, analysis of the triple mutant by native gel electrophoresis reveals the existence of dimers and multimers, implying that oligomer formation is mediated by other cysteines, probably on the surface, and that some of these forms are enzymatically active. Isolation and characterization of iodoacetate-modified monomers and dimers of the triple mutant revealed that, indeed, certain dimeric forms of the enzyme are still fully active, whereas others show reduced activity. Cysteine residues potentially involved in dimerization were identified by modeling of thimet oliogopeptidase to its homolog, neurolysin. Five mutants were constructed; all contained the triple mutation C246S/C248S/C253S and additional substitutions. Substitutions at C46 or C682 and C687 prevented multimer formation and inhibited dimer formation. The C46S mutant had enzymatic activity comparable to the parent triple mutant, whereas that of C682S/C687S was reduced. Thus, the location of intermolecular disulfide bonds, rather than their existence per se, is relevant to activity. Dimerization close to the N-terminus is detrimental to activity, whereas dimerization near the C-terminus has little effect. Altering disulfide bond formation is a potential regulatory factor in the cell owing to the varying oxidation states in subcellular compartments and the different compartmental locations and functions of the enzyme.

Evaluation of the mutagenicity of antimalarial products isolated from Solanum nudum (Solanaceae).

Diosgenone is a major component of the hexane extract from the plant Solanum nudum (Solanaceae). The products from degraded and acetylated diosgenone that showed in vitro antimalarial activity against the FCB-2 strain of Plasmodium falciparum and methanol, dichloromethane and ethereal extracts of Solanum nudum were tested for their mutagenic activity using the Ames test with the TA-97a, TA-98, TA-100 and TA-102 strains of Salmonella typhimurium. These compounds were not mutagenic at the tested concentrations.

Evaluation of mutagenic activity of several antimalarial extracts from Eupatorium inulaefolium.

Eupatorium inulaefolium is used as an antimalarial agent by traditional healers of the Tumaco region (Nariño-Colombia). Several extracts of this plant have been tested by our laboratory and in vitro antimalarial activity against the FCB-2 strain of Plasmodium falciparum has been confirmed. For this reason, the mutagenic effect of the methanol, dichloromethane, and hexane extracts of Eupatorium inulaefolium (number 83377 university of Antioquia herbarium) were evaluated using the Ames test. None of the extracts evaluated had mutagenic effects on TA-98 or TA-100 strains of Salmonella typhimurium.

The neuropeptide processing enzyme EC 3.4.24.15 is modulated by protein kinase A phosphorylation.

The metalloendopeptidase EC (EP24.15) is a neuropeptide-metabolizing enzyme expressed predominantly in brain, pituitary, and testis, and is implicated in several physiological processes and diseases. Multiple putative phosphorylation sites in the primary sequence led us to investigate whether phosphorylation effects the specificity and/or the kinetics of substrate cleavage. Only protein kinase A (PKA) treatment resulted in serine phosphorylation with a stoichiometry of 1.11 +/- 0.12 mol of phosphate/mol of recombinant rat EP24.15. Mutation analysis of each putative PKA site, in vitro phosphorylation, and phosphopeptide mapping indicated serine 644 as the phosphorylation site. Phosphorylation effects on catalytic activity were assessed using physiological (GnRH, GnRH(1-9), bradykinin, and neurotensin) and fluorimetric (MCA-PLGPDL-Dnp and orthoaminobenzoyl-GGFLRRV-Dnp-edn) substrates. The most dramatic change upon PKA phosphorylation was a substrate-specific, 7-fold increase in both K(m) and k(cat) for GnRH. In both rat PC12 and mouse AtT-20 cells, EP24.15 was serine-phosphorylated, and EP24.15 phosphate incorporation was enhanced by forskolin treatment, and attenuated by H89, consistent with PKA-mediated phosphorylation. Cloning of the full-length mouse EP24.15 cDNA revealed 96.7% amino acid identity to the rat sequence, and conservation at serine 644, consistent with its putative functional role. Therefore, PKA phosphorylation is suggested to play a regulatory role in EP24.15 enzyme activity.

Glycosylation of GIRK1 at Asn119 and ROMK1 at Asn117 has different consequences in potassium channel function.

GIRK (G protein-gated inward rectifier K(+) channel) proteins play critical functional roles in heart and brain physiology. Using antibodies directed to either GIRK1 or GIRK4, site-directed mutagenesis, and specific glycosidases, we have investigated the effects of glycosylation in the biosynthesis and heteromerization of these proteins expressed in oocytes. Both GIRK1 and GIRK4 have one extracellular consensus N-glycosylation site. Using chimeras between GIRK1 and GIRK4 as well as a GIRK1 N-glycosylation mutant, we report that GIRK1 was glycosylated at Asn(119), whereas GIRK4 was not glycosylated at Asn(132). GIRK1 membrane-spanning domain 1 was required for optimal glycosylation at Asn(119) because a chimera that contained GIRK4 membrane-spanning domain 1 significantly reduced the addition of a carbohydrate structure at this site. This finding may partly account for the reason that GIRK4 is not glycosylated at Asn(132), either as a homomer or when coexpressed with GIRK1. When the GIRK1(N119Q) mutant was coexpressed with GIRK4, the biophysical properties of the heteromeric channel and the magnitude of the agonist-induced currents were similar to those of controls. Thus, N-glycosylation of GIRK1 at Asn(119) does not appear to affect its physical association with GIRK4, the routing of the heteromer to the cell surface, or heteromeric channel function, unlike the dramatic functional effects of N-glycosylation of ROMK1 at Asn(117) (Schwalbe, R. A., Wang, Z., Wible, B. A., and Brown, A. M. (1995) J. Biol. Chem. 270, 15336-15340).

Zinc coordination and substrate catalysis within the neuropeptide processing enzyme endopeptidase EC 3.4.24.15. Identification of active site histidine and glutamate residues.

Endopeptidase EC 3.4.24.15 (EP24.15) is a zinc metalloendopeptidase that is broadly distributed within the brain, pituitary, and gonads. Its substrate specificity includes a number of physiologically important neuropeptides such as neurotensin, bradykinin, and gonadotropin-releasing hormone, the principal regulatory peptide for reproduction. In studying the structure and function of EP24.15, we have employed in vitro mutagenesis and subsequent protein expression to genetically dissect the enzyme and allow us to glean insight into the mechanism of substrate binding and catalysis. Comparison of the sequence of EP24.15 with bacterial homologues previously solved by x-ray crystallography and used as models for mammalian metalloendopeptidases, indicates conserved residues. The active site of EP24.15 exhibits an HEXXH motif, a common feature of zinc metalloenzymes. Mutations have confirmed the importance, for binding and catalysis, of the residues (His473, Glu474, and His477) within this motif. A third putative metal ligand, presumed to coordinate directly to the active site zinc ion in concert with His473 and His477, has been identified as Glu502. Conservative alterations to these residues drastically reduces enzymatic activity against both a putative physiological substrate and a synthetic quenched fluorescent substrate as well as binding of the specific active site-directed inhibitor, N-[1-(RS)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate, the binding of which we have shown to be dependent upon the presence, and possibly coordination, of the active site zinc ion. These studies contribute to a more complete understanding of the catalytic mechanism of EP24.15 and will aid in rational design of inhibitors and pharmacological agents for this class of enzymes.

A recombinant inwardly rectifying potassium channel coupled to GTP-binding proteins.

GTP-binding (G) proteins have been shown to mediate activation of inwardly rectifying potassium (K+) channels in cardiac, neuronal and neuroendocrine cells. Here, we report functional expression of a recombinant inwardly rectifying channel which we call KGP (or hpKir3.4), to signify that it is K+ selective, G-protein-gated and isolated from human pancreas. KGP expression in Xenopus oocytes resulted in sizeable basal (or agonist-independent) currents while coexpression with a G-protein-linked receptor, yielded additional agonist-induced currents. Coexpression of KGP and hGIRK1 (a human brain homolog of GIRK1/Kir3.1) produced much larger basal currents than those observed with KGP or hGIRK1 alone, and upon coexpression with receptor, similarly large agonist-induced currents could be obtained. Pertussis toxin treatment significantly diminished agonist-dependent currents due to either KGP or KGP/hGIRK1 expression. Interestingly, PTX also significantly reduced basal KGP or KGP/hGIRK1 currents, suggesting that basal activity is largely the result of G-protein gating as well. When the two channels were coexpressed with receptor, the relative increase in current elicited by agonist was similar whether KGP and hGIRK1 were expressed alone or together. When in vitro translated or when expressed in Xenopus oocytes or CHO mammalian cells, KGP gave rise to a nonglycosylated 45-kD protein. Antibodies directed against either KGP or hGIRK1 coprecipitated both proteins coexpressed in oocytes, providing evidence for the heteromeric assembly of the two channels and suggesting that the current potentiation seen with coexpression of the two channel subunits is due to specific interactions between them. An endogenous oocyte protein similar in size to KGP was also coprecipitated with hGIRK1.

Aging lengthens circadian period for wheel-running activity in C57BL mice.

Previous reports of age effects on circadian period in rodents show a slight shortening of period with age, with the exception of house mice (Mus domesticus) where a number of studies report mixed results. The present study consists of three comparisons of circadian period for wheel-running activity in young vs. older C57BL inbred mice following entrainment to 16:8 LD, 12:12 LD and 8:16 LD photoperiods. The free-running circadian period (tau(DD)) for wheel-running activity was significantly longer in older mice following entrainment to all three photoperiods. These results support a model of heterogeneous effects of aging on circadian period among different rodent species, and suggest that the lengthening of circadian period with age in house mice is not a function of age-dependent differences in after-effects imposed by prior entrainment.

[Student perception of processes, services and activities of school life the the medical sciences campus]. / Percepción estudiantil sobre procesos, servicios y actividades de la vida estudiantil en el recinto de ciencias médicas.

During academic year 1989-90 a study was developed at the Medical Sciences Campus to gather the opinion of students, concerning diverse aspects of student life. For this purpose the questionnaire "Student Perception about the Medical Sciences Campus" was administered to enrolled students. The findings from this study helped identify diverse aspects of student life that should be revaluated or strengthened. Various recommendations were presented concerning: scheduling of services; physical facilities; social, cultural and sports activities and student participation, among others. It's principle objective was to provide information that would help administrations in the decision making process for institutional planning.