Validación externa y reproducibilidad del cuestionario PUMA para el diagnóstico de EPOC en una población latinoamericana: validación externa del cuestionario PUMA / External validation and reproducibility of the PUMA questionnaire for the diagnosis of COPD in a Latin American population: external validation of the PUMA questionnaire

Resumen El uso de escalas de predicción clínica puede incrementar la detección temprana de enfermedad pulmonar obstructiva crónica (EPOC). Su rendimiento en población latinoamericana ha sido pobremente estudiado. Nuestro objetivo fue determinar la validez y reproducibilidad del cuestionario PUMA, como herramienta de tamización en atención primaria en población colombiana, mediante un estudio tipo corte transversal; donde se establecieron las características operativas del cuestionario, área bajo la curva de características operativas del receptor (ACOR) y el mejor punto de corte para esta población. 1.980 sujetos fueron incluidos en el análisis. La prevalencia de EPOC correspondió a 18,9%. La capacidad discriminatoria del cuestionario fue de 0,69 (IC95%: 0,66-0,72), para un punto de corte óptimo mayor de 5, con una sensibilidad del 60%, especificidad 66% y un valor predictivo negativo de 88%. La escala PUMA para tamizaje de pacientes en riesgo de EPOC tiene una capacidad discriminatoria moderada y una excelente reproducibilidad en la población estudiada.

The use of clinical prediction scales may increase the early detection of chronic obstructive pulmonary disease (COPD). The performance characteristics of these scales in the Latin American population is poorly studied. We aimed to evaluate validity and reproducibility of PUMA questionnaire as a screening tool in primary care in a Colombian population. A cross-sectional study was performed. Operational characteristics of the questionnaire, the area under the received operator curve (AUROC), and the best cut-off point of the score were calculated. 1,980 individuals were included in this analysis. Prevalence of COPD was 18.9%. AUROC of the questionary was 0.69 (CI95%: 0.66-0.72), with an optimal cut-off point greater than 5 (sensitivity 60%, specificity 66%); predictive negative value was 88%. PUMA's scale for the screening of patients at risk of COPD has a moderate accuracy and an excellent reproducibility in the studied population.

Amygdala electrical stimulation inducing spatial memory recovery produces an increase of hippocampal bdnf and arc gene expression.

Amygdala seems to promote the consolidation of plastic modification in different brain areas and these long-term brain changes require a rapid de novo RNA and protein synthesis. We have previously shown that basolateral amygdala electrical stimulation produces a partial recovery of spatial memory in fimbria-fornix lesioned animals and it is also able to increase the BDNF protein content in the hippocampus. The emerging question is whether these increased BDNF protein content arises from previously synthesized RNA or from de novo RNA expression. Now we address the question if amygdala electrical stimulation 15min after daily water maze training produces a rapid de novo RNA synthesis in the hippocampus, a critical brain area for spatial memory recovery in fimbria-fornix lesioned animals. In addition, we also study RNA arc expression, a gene which is essential for memory and neural plasticity processes. To this purpose, we study amygdala stimulation effects on the expression of plasticity related-early-genes bdnf and arc in the hippocampus of fimbria-fornix lesioned animals trained in a water-maze for 4days. We also checked on the expression of both genes in non-lesioned, untrained animals (acute condition) at 0.5, 1, 2 and 24h after basolateral amygdala electrical stimulation. Our data from trained animals confirm that daily amygdala electrical stimulation 15min after water maze training produces a partial memory recovery and that is coupled to an increase of bdnf and arc genes expression in the hippocampus. Additionally, the acute study shows that a single session of amygdala stimulation induces a transient increase of both genes (peaking at 30min). These results confirm the memory improving effect of amygdala stimulation in fimbria-fornix-lesioned animals and sustain the assumption that the memory improving effect is mediated by newly synthetized BDNF acting on a memory relevant structure like the hippocampus. The increased amount of BDNF within the hippocampus seems to be locally synthetized by mechanisms activated by the amygdala stimulation.

[Neurofibroma with mucus-producing glands. Report of a case and literature review]. / Neurofibroma con glándulas mucoproductoras. Presentación de un caso y revisión de la literatura.

INTRODUCTION: Most tumors of peripheral nerve sheaths containing glands are malignant tumors associated with Von Recklinghausen's disease. CLINICAL CASE: A 39 year old man consulted with a tumour on a finger of the right hand, which was not painful, and was slow growing. There was no past history of neurofibromatosis. Histological study showed a tumour of the peripheral nerve sheath, a benign type of neurofibroma containing glands. Immunohistochemical techniques confirmed that it had the stroma of a Schwannoma with well-defined glandular epithelial elements. CONCLUSIONS: A neurofibroma with glands is considered to be a rare type of divergent differentiation, and of considerable interest to pathologists, since it must be differentiated from other tumoral lesions. Immunohistochemical study is very useful for this.

[Electroencephalogram findings in lesionectomies: preliminary results]. / Hallazgos del electrocorticograma en lesionectomías: resultados preliminares.

INTRODUCTION: Use of the electrocorticogram (EcoG) in planning lesionectomies is a controversial subject at present. MATERIAL AND METHODS: We describe a series of 5 patients with epileptic crises, 3 with arteriovenous malformations in whom the lesion was completely resected, followed by postoperative angiography, and two with gliomas with low grade malignancy in whom iridium 192 was implanted. RESULTS: 1. The most frequent reason for consultation was convulsions. 2. In our series of patients the commonest site was the frontal zone of the right hemisphere. 3. Potentials with epileptiform characteristics were registered at the edges of the lesions and occasionally over the lesion itself. In two cases electro-clinical crises were seen. 4. The lesions were resected from normal tissue independently of the EcoG results. CONCLUSION: Although they are preliminary findings, the results of the study support the usefulness of this technique to guide the surgical procedures used for the treatment of intractable epilepsy.

[A multidisciplinary approach to the management of cerebral vascular malformations]. / Enfoque multidisciplinario en el manejo de las malformaciones vasculares cerebrales.

INTRODUCTION: Cerebral vascular malformations (CVM) are a heterogeneous group of lesions. One way of classifying them is according to histological criteria, clinical features, imaging findings, electroencephalography and distinctive pathology. OBJECTIVES: To report the results obtained in 16 patients clinically diagnosed as having CVM and operated on in the Centro Internacional de Restauración Neurológica (La Habana, Cuba) between March 1995 and October 1998. We also consider the usefulness of diagnostic tools for neurosurgical management and anatomo-pathological diagnosis. PATIENTS AND METHODS: We review the clinical findings, images, electroencephalograms and diagnostic histology of 16 patients. The gender distribution was 10 men and 6 women who were aged between 9 and 48 years. Stereotaxic resection guided by CAT and angiography was done in all cases. RESULTS: The predominant symptoms were headache and generalized tonic-clonic convulsions. CAT and angiography were helpful in determining the clinical diagnosis and location. The most frequent electroencephalographic finding was focal slowing associated with inactive epileptiform disorders. Histological study showed that there were 3 cases of arteriovenous malformations (AVM), one angioma cavernosa and one mixed vascular malformation (AVM plus angioma cavernosa). The malformation was not resected (it was treated with a clip) in the remaining case. CONCLUSION: Our results show the importance of structural imaging studies and their relationship to functional studies in the presumptive diagnosis of CVM corroborated by post-operative histological diagnosis.

[Clinico-pathological correlation in the main types of dementia]. / Correlación clinicopatológica en los principales tipos de demencias.

INTRODUCTION: Dementia has became a serious health problem in developed countries. The objective of this study was to establish the possible correlation between the initial clinical diagnosis and the anatomopathological criteria. Pathological confirmation of the cases clinically diagnosed as Alzheimer disease/senile dementia Alzheimer type (AD/SDAT) and multi-infarct dementia (MID) was carried out. MATERIAL AND METHODS: Twelve brains from demented patients were studied. Brains were removed at post-mortem intervals of 1-3 hours to guarantee an adequate conservation of the tissue. The brains were weighed, fixed for 4 weeks in 10% buffered neutral formalin and coronally sectioned at intervals of approximately 1 cm. Bilateral sections of neocortex from frontal, temporal, parietal lobes, cingulate gyrus, amygdala, hippocampus, thalamus, cerebellum and unilateral sections of locus ceruleus and substantia nigra were taken. Five micrometer sections of the paraffin embedded material were stained by the following methods: hematoxylin-floxine, Congo red and Bielschowsky silver impregnation. RESULTS: Our neuropathological results showed a high correlation with the initial clinical classification and confirmed the diagnosis of AD/ SDAT in 6 cases, MID in 3 cases and mixed dementia in 1 case. Two cases did not exhibited morphological evidence of dementia. CONCLUSIONS: We concluded that the methodology applied for the morphologic diagnosis of dementia was feasible, useful and reproducible. Further studies will be necessary using a larger number of sample.

[Central neurocytoma]. / Neurocitoma central.

INTRODUCTION: A central neurocytoma (CN) is a rare tumor, of neuronal origin, well-differentiated and found intraventricularly. It mainly affects young adults. Firm diagnosis is made on immunohistochemical (IHQ) and ultrastructural studies, since on optic microscopy it is similar in appearance to an oligodendroglioma or to an ependymoma. PATIENTS AND METHODS: We studied 4 cases, three after surgical resection and one on autopsy. The average age was 29, ranging from 3 to 63. Both sexes were equally affected. In all cases IHQ techniques were used (GFAP, neurofilament, synaptophysin and specific neuronal enolase) and they were studied by electron microscopy. RESULTS: IHQ was negative for GFAP and neurofilament, but intensely positive for synaptophysin and specific neuronal enolase. On ultrastructural study there were few neurofilaments, microtubules and dense central granules typical of neural differentiation. CONCLUSIONS: The findings in our cases lead to diagnosis of NC and confirm that this tumor is a distinct clinicopathological entity.

[Stereotaxic biopsy and 192Ir implant in intracranial tumors. A review of 7 years of experience]. / Biopsia estereotáxica e implante de Ir-192 en tumores intracraneales. Revisión de 7 años de experiencia.

INTRODUCTION: The combination of stereotaxic techniques, advances in neuroimaging and the creation of continually improving software has permitted stereotaxic biopsy of cerebral lesions at the most varied sites. Improvement in the method of permanent interstitial radiation (brachytherapy) improves the precision with which the radioactive sources may be inserted, releasing a maximum dose of radiation to the tumour with minimum radiation to the surrounding tissue. PATIENTS AND METHODS: We treated 237 patients (aged 1 to 78 years) with intracranial lesions, all included in the protocol of our centre. Stereotaxic systems of Leksell, Riechert-Mundinger, Micromar and Estereoflex were used. The procedure was in three stages: acquisition of the image, surgical planning and surgical operation. The imaging guide was the computerized axial tomography (CAT). RESULTS: Stereotaxic biopsy guided by CAT images was done in 153 patients. These were divided into three groups, taking the biopsy findings as the reference: group A (primary tumors, 128), group B (metastatic tumors, 15) and group C (non-malignant lesions, 10). Ninety six permanent implants of 192Ir were inserted, with a low dose of 4-7 cGy/h and a total dose of 80-120 Gy. CONCLUSIONS: Stereotaxic biopsy is a very effective procedure with a significantly low range of complications. The permanent implant with a low dose rate, well situated and using a source of 192Ir is a safe, simple, effective method for the treatment of primary and recurrent glial tumours, and non-glial tumours which fulfil criteria for this type of brachytherapy.

Evaluación in vitro de la capacidad biorremediadora de hongos filamentosos sobre petróleo crudo / Bioremediative Capacity Evaluation in vitro of the filamentous fungi on crude oil

Resumen Objetivo. Evaluar la capacidad biorremediadora de algunas especies de hongos filamentosos en suelos contaminados con petróleo crudo. Métodos. Se aislaron 138 cepas a partir de 90 cultivos primarios en muestras de suelos obtenidas en los municipios de Yondó (Antioquia), Acacías (Meta) y Tumaco (Nariño), se identificaron las especies por medio de claves taxonómicas y la amplificación por PCR de la región ITS ubicándose en siete géneros de hongos filamentosos. Del total de las especies se escogieron tres para el experimento que fueron: Neosartorya sp. Cepa A/N -1, Aspergillus sp. Cepa Y/As-3 y Rhizomucor sp. Cepa 1A/R-1; se realizó la micorremediación con la técnica de Landfarming modificado al diseñarse un microcosmos con 50g de suelo contaminado con petróleo crudo °API de 21.6 a concentraciones de 20.000 ppm y 30.000ppm para cada una de las especies en un inóculo de 300 conidios/ml en agua destilada, ajustado en cámara de Neubauer y las tres especies en consorcio en suelo contaminado con petróleo crudo °API de 21.6 a concentraciones de 40.000ppm, 60.000ppm, 80.000ppm y 100.000ppm con un inóculo de 300 conidios/ml. Se valoró el proceso por espectofotometría. Además se estableció las enzimas empleadas en la micorremediación y la citotoxicidad de las cepas empleadas. Resultado. La micorremediación realizada por las especies individuales fue en promedio entre 2 y 6 días y cuando se aplicaron las tres especies en consorcio se realizó en un promedio entre 6 y 10 días, la enzima empleada es peroxidasa y la citotoxicidad es negativa.

Abstract Objective. Evaluate the bioremediation capacity of some species of filamentous fungi in soils contaminated with crude oil. Methods. 138 strains were isolated from 90 primary culture in soil samples obtained in the municipalities of Yondó (Antioquia), Acacías (Meta) and Tumaco (Nariño), species were identified by means of taxonomic keys and PCR amplification of the ITS region located in seven genera of filamentous fungi. Of the total of the species, three were chosen for the experiment, which were: Neosartorya sp. Cepa A/N- 1, Aspergillus sp. Cepa Y/As -3 and Rhizomucor sp. Cepa 1A/R-1; Micoremediation was performed with the modified Landfarming technique when designing a microcosm with 50g of soil contaminated with crude oil API 21.6 at concentrations of 20,000 ppm and 30,000ppm for each of the species in an inoculum of 300 conidia / ml in water distilled, adjusted in Neubauer chamber and the three species in consortium in soil contaminated with crude oil API 21.6 at concentrations of 40,000ppm, 60,000ppm, 80,000ppm and 100,000ppm with an inoculum of 300 conidia / ml. The process was evaluated by spectrophotometry. In addition, the enzymes used in the micoremediation and cytotoxicity of the strains used were established. Result. The micoremediation performed by the individual species was on average between 2 and 6 days and when the three species were applied in a consortium it was carried out on average between 6 and 10 days, the enzyme used is peroxidase and the cytotoxicity is negative.

Microscopic mild focal cortical dysplasia in temporal lobe dual pathology: an electrocorticography study.

BACKGROUND: Associations between electrophysiological and histological findings might provide an insight into the epileptogenicity of mild focal cortical dysplasia (FCD) in patients with temporal lobe epilepsy (TLE) and a dual pathology. SUBJECTS AND METHODS: A total of 22 patients with pharmacoresistant TLE were included in the study, 16 of them with histologically confirmed hippocampal sclerosis (HS) associated with neocortical temporal mild Palmini Type-I FCD subtypes and 6 with HS. Intraoperative electrocorticography (ECoG) recordings were analysed for epileptiform discharge frequency and morphology. Associations between histological, and electrocorticography pattern findings in these patients were analysed. Electroclinical outcomes in these patients were also evaluated. RESULTS: Neocortical areas with mild Palmini Type-I FCD showed a significantly higher spike frequency (SF) recorded in the inferior temporal gyrus than those neocortical areas in patients with HS. There was a tendency to higher spike frequency and lower amplitude in neocortical areas with histopathologic subtype IB FCD in relation with IA during intraoperative ECoG. Post-SF excision and amplitude were significantly lower during neocortical post-excision intraoperative ECoG than during neocortical pre-excision recording. There was no difference found in the clinical outcome between patients with and without FCD. CONCLUSIONS: Intraoperative electrocorticographic interictal spike frequency recorded in the neocortical inferior temporal gyrus may help to characterize the histopathologic subtypes of mild Palmini Type-I FCD in patients with temporal lobe epilepsy (TLE) and a dual pathology. Our data support the epileptogenicity of neocortical mild FCD in TLE and assessments of ECoG patterns are relevant to determine the extent of the resection in these patients which can influence the electroclinical outcome.

Guanosine-inosine-preferring nucleoside N-glycohydrolase from Crithidia fasciculata.

Protozoan parasites are incapable of de novo purine biosynthesis and obtain purines by salvage pathways. A nucleoside hydrolase which prefers inosine and uridine as substrates (IU-nucleoside hydrolase) has been characterized and implicated in purine salvage in Crithidia fasciculata (Parkin, D. W., Horenstein, B. A., Abdulah, D. R., Estupiñán, B., and Schramm, V. L. (1991) J. Biol. Chem. 31, 20658-20665). Treatment of C. fasciculata with inhibitors of the IU-nucleoside hydrolase did not prevent cell growth, suggesting alternative enzymes. A guanosine-inosine-preferring enzyme (GI-nucleoside hydrolase) has been purified from extracts of C. fasciculata and characterized. The enzyme is an oligomer of M(r) 38,500 subunits. The Vmax/Km for guanosine, inosine, and adenosine are 3.2 x 10(6), 6.2 x 10(6), and 9.8 M-1 S-1, respectively. Deoxynucleosides, nucleotides, and pyrimidine nucleosides are poor substrates. The pH profile for Km is independent of pH, whereas both Vmax and Vmax/Km demonstrate that a single protonated base, pKa 7.7 is required for activity. The transition state inhibitors of IU-nucleoside hydrolase, 1,4-dideoxy-1,4-imino-1-(S)-phenyl-D-ribitol (Horenstein, B. A., and Schramm, V. L. (1993) Biochemistry 32, 9917-9925) and p-nitrophenylriboamidrazone (Boutellier, M., Horenstein, B. A., Semenyaka, A., Schramm, V.L., and Ganem, B. (1994) Biochemistry 33, 3994-4000), are unexceptional inhibitors of the GI-nucleoside hydrolase. The enzyme is inhibited by 3-deazaadenosine and 2-iodoadenosine with Km/Ki values of 145 and 61, respectively. The results demonstrate that this previously uncharacterized enzyme has distinct structure, kinetic, and chemical mechanisms relative to IU-nucleoside hydrolase. Metabolic studies with labeled inosine as the sole purine source indicated that the GI-enzyme is efficient for purine salvage in vivo.

Yeast AMP deaminase. Catalytic activity in Schizosaccharomyces pombe and chromosomal location in Saccharomyces cerevisiae.

The AMP deaminase gene was mapped to chromosome XIII of Saccharomyces cerevisiae strain JM1901. The AMP deaminase gene is located near SUP5, GAL80, SUF7, and SUF22. The presence of AMP deaminase in the fission yeast Schizosaccharomyces pombe was examined by comparing DNA hybridization, protein immunoreactivity, and catalytic activity from S. cerevisiae, known to contain the protein, to S. pombe. DNA hybridization experiments using the cloned S. cerevisiae AMP deaminase gene failed to hybridize to the genomic DNA from S. pombe strain 972h-s. Protein extracts from S. pombe and S. cerevisiae were analyzed in parallel and exhibited comparable AMP deaminase activities. Analysis of reaction intermediates in cell extracts of S. pombe established that IMP is formed directly from AMP without intervening steps. The AMP deaminase of S. pombe was purified 1,100-fold to a specific catalytic activity of 67 mumol/min/mg of protein. Purified protein interacted weakly with polyclonal antibodies prepared against S. cerevisiae AMP deaminase. AMP deaminases from both S. cerevisiae and S. pombe were activated by ATP with micromolar activation constants, are inhibited by coformycin, and are specific for AMP when compared to other purine nucleosides and nucleotides. The results establish that S. pombe contains an AMP deaminase with catalytic properties similar to that from S. cerevisiae, even though the DNA sequences of the genes and the immunoreactivity of the protein from S. pombe differs considerably from the AMP deaminase of S. cerevisiae. Genetic analysis of the pathways of purine metabolism in S. pombe (Pourquié, J., and Heslot, H. (1971) Genet. Res. 18, 33-44) had indicated the absence of AMP deaminase. The presence of a regulated AMP deaminase in S. pombe supports the hypothesis that eukaryotes regulate adenine nucleotide pools by the activity of AMP deaminase.

Transition-state analysis of nucleoside hydrolase from Crithidia fasciculata.

The transition state of nucleoside hydrolase from the trypanosome Crithidia fasciculata has been characterized by multiple Vmax/Km kinetic isotope effects with labeled inosine and adenosine as substrates. Nucleoside hydrolase catalyzes the hydrolysis of the N-glycosidic linkage of the commonly occurring purine and pyrimidine nucleosides, with Vmax/Km ranging over 2 orders of magnitude. The kinetic isotope effects for inosine were [1'-3H] = 1.150 +/- 0.006, [2'-3H] = 1.161 +/- 0.003, [1'-14C] = 1.044 +/- 0.004, [9-15N] = 1.026 +/- 0.004, [4'-3H] = 0.992 +/- 0.003, and [5'-3H] = 1.051 +/- 0.003. The magnitude of the kinetic isotope effects for inosine, an equivalent [1'-3H] kinetic isotope effect for the poor substrate adenosine, and the rapid equilibrium random kinetic mechanism [Parkin D, W., Horenstein, B. A., Abdulah, D. R., Estupiñán, B., & Schramm, V. L. (1991) J. Biol. Chem. (in press)] all indicate that the isotope effects are fully expressed. The kinetic and solvent deuterium isotope effects have been used to analyze the transition-state structure using bond energy bond order vibrational analysis. The transition state involves a protonated hypoxanthine leaving group with a C-N glycosidic bond elongated to approximately 2 A. The ribose group contains substantial carbocationic character, unusually strong hyperconjugation of H2', and a bond length of approximately 3 A to the incoming oxygen nucleophile. The remote isotope effect (4'-3H and 5'-3H) and the results of transition-state calculations provide the most detailed description of the steric and bonding properties of an enzyme-stabilized transition state.

Nucleoside hydrolase from Crithidia fasciculata. Metabolic role, purification, specificity, and kinetic mechanism.

Crithidia fasciculata cells grown on complex medium with added [8-14C, 5'-3H]inosine or [8-14C,5'-3H]adenosine metabolize greater than 50% of the salvaged nucleosides through a pathway involving N-glycoside bond cleavage. Cell extracts contain a substantial nucleoside hydrolase activity but an insignificant purine nucleoside phosphorylase. The nucleoside hydrolase has been purified 1000-fold to greater than 99% homogeneity from kilogram quantities of C. fasciculata. The enzyme is a tetramer of Mr 34,000 subunits to give an apparent holoenzyme Mr of 143,000 by gel filtration. All of the commonly occurring nucleosides are substrates. The Km values vary from 0.38 to 4.7 mM with purine nucleosides binding more tightly than the pyrimidines. Values of Vmax/Km vary from 3.4 x 10(3) M-1 s-1 to 1.7 x 10(5) M-1 s-1 with the pyrimidine nucleosides giving the larger values. The turnover rate for inosine is 32 s-1 at 30 degrees C. The kinetic mechanism with inosine as substrate is rapid equilibrium with random product release. The hydrolytic reaction can be reversed to give an experimental Keq of 106 M with H2O taken as unity. The product dissociation constants for ribose and hypoxanthine are 0.7 and 6.2 mM, respectively. Deoxynucleosides or 5'-substituted nucleosides are poor substrates or do not react, and are poor inhibitors of the enzyme. The enzyme discriminates against methanol attack from solvent during steady-state catalysis, indicating the participation of an enzyme-directed water nucleophile. The pH profile for inosine hydrolysis gives two apparent pKa values of 6.1 with decreasing Vmax/Km values below the pKa and a plateau at higher pH values. These effects are due to the pH sensitivity of the Vmax values, since Km is independent of pH. The pH profile implicates two negatively charged groups which stabilize a transition state with oxycarbonium character.

Giant cell tumor (osteoclastoma) of the petrous bone: case report.

A case of a basal middle fossa giant cell tumor occurring in a 46-year-old man is described. The lesion appeared at the computed tomography (CT) scan examination as an hypodense mass with a peripheral "ring-like" enhancement, and no evident erosion of the skull base. The tumor, which infiltrated the basal temporal parenchyma, was removed via a temporal transzygomatic craniotomy, and extensive drilling of the petrous bone. Despite the occurrence, of significant postoperative complications, the patient ultimately showed a good clinical outcome, with no signs of recurrence at the 1-year follow-up CT scanning. The clinical and diageostic aspects and the management policy, of this rare lesion are discussed.

Trypanosomal nucleoside hydrolase. Resonance Raman spectroscopy of a transition-state inhibitor complex.

The transition state for hydrolysis of the N-ribosidic bond of inosine by nucleoside hydrolase has oxocarbenium character and a protonated leaving group hypoxanthine with an sp2-hybridized C1' of the ribosyl [Horenstein, B. A., Parkin, D. W., Estupinan, B., & Schramm, V. L. (1991) Biochemistry 30, 10788-10795]. These features are incorporated into N-(p-nitrophenyl)-D-riboamidrazone, a transition state analogue which binds with a dissociation constant of 2 nM [Boutellier, M., Horenstein, B. A., Semenyaka, A., Schramm, V. L., & Ganem, B. (1994) Biochemistry 33, 3994-4000]. Resonance Raman and ultraviolet-visible absorbance spectroscopy has established that the inhibitor binds as the neutral, zwitterionic species. The enzyme stabilizes a specific resonance state characterized by the quinonoid form of the p-nitrophenyl group with evidence for ion pairing at the nitro group. Incorporation of 15N into a specific position of the amidrazone reveals that the exo-ribosyl nitrogen bonded to the C1' position carries the proton while that bonded to the p-nitrophenyl carbon is unprotonated. This tautomer carries a distributed positive charge centered at the position analogous to C1' of the ribosyl group at the transition state. The molecular electrostatic potentials for the substrate inosine, the transition state, and the transition state inhibitor are compared at the van der Waals surface of the molecules. The tautomer of the inhibitor bound to the enzyme bears a striking electrostatic resemblance to the transition state determined by kinetic isotope effect analysis. The spectral and resonance Raman properties of free and enzyme-bound inhibitor have permitted tautomeric assignment of these species and establish that the enzyme substantially changes the electronic distribution of the bound inhibitor toward that of the enzyme-stabilized transition state.

Contenido de catecolaminas en tejido suprarrenal humano: diferencias entre el tejido adulto y fetal / Contents of catecholamines in suprarrenal human tissue: differences between adult and fetal tissue

Con el objetivo de realizar una caracterización comparativa entre los niveles de catecolaminas noradrenalina (CA), dopamina (DA) y adrenalina (A) en la glándula adrenal fetal humana (GAF) (n=7) entre 10-12 semanas de edad gestacional y la glándula adrenal adulta (GAA) post-mortem (n=7) de sujetos con edad promedio de 65,4 a 9,4 años, se midieron sus concentraciones utilizando un sistema de cromatografía líquida de alta resolución con detección electroquímica. Las concentraciones (ng/mg peso h£medo) encontradas fueron: NA 24,43 a 7,1; A 3,6 a 2,9 y DA 0,45 a 0,27 para la GAF y NA 58,2 a 37,5, Aa 352,3 a 214,9 y DA 0,19 a 0,07 en la GAA. El valor de la DA fetal fue 2,4 veces superior al detectado en la GAA. Se comprobó por primera vez que la GAF correspondiente a edades gestacionales comprendidas entre las 10 y 12 semanas, es significativamente (p < 0,01) más rica en DA que el tejido adulto

Correlación clinicopatológica en los principales tipos de demencias / Clinic pathological correlation in the main types of dementias

Inrtoducción. La demencia se ha convertido en un serio problema de salud en los países industrializados. Con este trabajo nos proponemos establecer la posible correlación entre el diagnóstico clínico preliminar y el criterio anatomopatológico en los casos ilustrados, y realizar un estudio neuropatológico post mortem para el diagnóstico y clasificación de los pacientes. Material y métodos. Se estudiaron los encéfalos de 12 pacientes dementes con diagnóstico clínico de enfermedad de Alzheimer/demencia senil tipo Alzheimer (EA/DSTA) seis casos y demencia multinfarto (DMI) seis casos. Se practicó la evisceración del encéfalo dentro de las tres primeras horas de fallecido. Los encéfalos se pesaron y fijaron en formol neutro al 10 por ciento posteriormente se realizaron cortes coronales con un intervalo de 1 cm tomando fragmentos bilaterales de corteza frontal, temporal y parietal, girus cingulado, amigdala, hipocampo, tálamo, cerebelo y fragmentos unilaterales de sustancia negra y locus ceréleo, para ser incluidos en parafina, teñidos con hematoxilina/floxina, rojo congo y tinción de Bielchowsky. Resultados. El estudio neuropatológico exhibió una alta correlación en relación a la clasificación clínica inicial, confirmando el diagnóstico de EA/DSTA en 6 casos, DMI en 3 y DMx en 1 caso. En 2 casos no se encontraron evidencias morfológicas que sustentaran los criterios clínicos de demencia. Conclusiones. Podemos concluir que la metodología aplicada para el diagnóstico morfológico resultó factible, útil y reproducible para el diagnóstico, siendo necesario incrementar el número de casos