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Biochemical characterization of the GM2 gangliosidosis B1 variant
Tutor, J.C.;
Brazilian Journal of Medical and Biological Research , 2004, DOI: 10.1590/S0100-879X2004000600001
Abstract: the deficiency of the a isoenzyme of ?-hexosaminidase (hex) produced by different mutations of the gene that codes for the a subunit (tay-sachs disease) has two variants with enzymological differences: the b variant consists of the absence of hex a isoenzyme and the b1 variant produces an inactive hex a isoenzyme for the hydrolysis of the gm2 ganglioside and synthetic substrates with negative charge. in contrast to the early childhood form of the b variant, the b1 variant appears at a later clinical stage (3 to 7 years of age) with neurodegenerative symptoms leading to the death of the patient in the second decade of life. the most frequent mutation responsible for the gm2 gangliosidosis b1 variant is r178h, which has a widespread geographic and ethnic distribution. the highest incidence has been described in portugal, which has been suggested as the point of origin of this mutation. biochemical characterization of this lysosomal disease is carried out using negatively charged synthetic a subunit-specific sulfated substrates, since hex a isoenzyme heat-inactivation assays are not applicable. however, the determination of the apparent activation energy of hex using the neutral substrate 3,3'-dichlorophenolsulfonphthaleinyl n-acetyl-?-d-glucosaminide, may offer a valid alternative. the presence of an a subunit in the a? heterodimer hex a means that its activation energy (41.8 kj/mol) is significantly lower than that of the ?? homodimer hex b (75.1 kj/mol); however, as mutation inactivates the a subunit, the hex a of the b1 variant presents an activation energy that is similar to that of the hex b isoenzyme.
Biochemical characterization of the GM2 gangliosidosis B1 variant
Tutor J.C.
Brazilian Journal of Medical and Biological Research , 2004,
Abstract: The deficiency of the A isoenzyme of -hexosaminidase (Hex) produced by different mutations of the gene that codes for the alpha subunit (Tay-Sachs disease) has two variants with enzymological differences: the B variant consists of the absence of Hex A isoenzyme and the B1 variant produces an inactive Hex A isoenzyme for the hydrolysis of the GM2 ganglioside and synthetic substrates with negative charge. In contrast to the early childhood form of the B variant, the B1 variant appears at a later clinical stage (3 to 7 years of age) with neurodegenerative symptoms leading to the death of the patient in the second decade of life. The most frequent mutation responsible for the GM2 gangliosidosis B1 variant is R178H, which has a widespread geographic and ethnic distribution. The highest incidence has been described in Portugal, which has been suggested as the point of origin of this mutation. Biochemical characterization of this lysosomal disease is carried out using negatively charged synthetic alpha subunit-specific sulfated substrates, since Hex A isoenzyme heat-inactivation assays are not applicable. However, the determination of the apparent activation energy of Hex using the neutral substrate 3,3'-dichlorophenolsulfonphthaleinyl N-acetyl- -D-glucosaminide, may offer a valid alternative. The presence of an alpha subunit in the alpha heterodimer Hex A means that its activation energy (41.8 kJ/mol) is significantly lower than that of the homodimer Hex B (75.1 kJ/mol); however, as mutation inactivates the alpha subunit, the Hex A of the B1 variant presents an activation energy that is similar to that of the Hex B isoenzyme.
Colgajo de perforantes de arteria epigrástica superior para cobertura de defecto cutáneo preesternal
García Tutor,E.; Marré Medina,D.;
Cirugía Plástica Ibero-Latinoamericana , 2008, DOI: 10.4321/S0376-78922008000200007
Abstract: perforator flaps nowadays represent a very good therapeutic alternative for reconstruction and coverage of skin defects. their advantages such as the minimal morbidity of the donor site, their good and easy postsurgical recovery, great versatility and rather simple surgical approach and technique are some of the reasons why these flaps have been rapidly developed over the last decade, being the flap based on perforator from de deep inferior epigastric artery, diep flap, probably their main model. a flap of similar characteristics based on perforators coming from the superior epigastric artery has been recently described for the coverage of the lower sternum region. in this article we present a clinical case in which a wound in this area that had been previously exposed to radiotherapy is treated with a superiorepigastric perforator flap, achieving complete coverage of the defect and an acceptable aesthetic result.
Colgajo de perforantes de arteria epigrástica superior para cobertura de defecto cutáneo preesternal Covergae of a presternal skin defect with a superior epigastric perforator Flap
E. García Tutor,D. Marré Medina
Cirugía Plástica Ibero-Latinoamericana , 2008,
Abstract: Los colgajos basados en arterias perforantes representan hoy en día una muy buena alternativa para la reconstrucción y cobertura de defectos cutáneos. Sus numerosas ventajas tales como la mínima morbilidad de la zona donante, su fácil recuperación postquirúrgica, su gran versatilidad y la simplicidad que presentan tanto en su planteamiento prequirúrgico como en la técnica misma, han sido algunos de los motivos por los que durante la última década su uso ha tenido un desarrollo notable, siendo quizás el colgajo DIEP el mayor representante de este grupo. Recientemente se ha descrito un tipo de colgajo de similares características basado en arterias perforantes de la arteria epigástrica superior para la cobertura de defectos de la región preesternal baja. En el trabajo actual presentamos un caso clínico en el que una lesión en dicha zona previamente sometida a radioterapia es tratada con este colgajo, obteniendo una cobertura completa de la herida y un resultado estético aceptable. Perforator flaps nowadays represent a very good therapeutic alternative for reconstruction and coverage of skin defects. Their advantages such as the minimal morbidity of the donor site, their good and easy postsurgical recovery, great versatility and rather simple surgical approach and technique are some of the reasons why these flaps have been rapidly developed over the last decade, being the flap based on perforator from de deep inferior epigastric artery, DIEP flap, probably their main model. A flap of similar characteristics based on perforators coming from the superior epigastric artery has been recently described for the coverage of the lower sternum region. In this article we present a clinical case in which a wound in this area that had been previously exposed to radiotherapy is treated with a superiorepigastric perforator flap, achieving complete coverage of the defect and an acceptable aesthetic result.
Important Determinants for Fucoidan Bioactivity: A Critical Review of Structure-Function Relations and Extraction Methods for Fucose-Containing Sulfated Polysaccharides from Brown Seaweeds
Marcel Tutor Ale,J?rn D. Mikkelsen,Anne S. Meyer
Marine Drugs , 2011, DOI: 10.3390/md9102106
Abstract: Seaweeds—or marine macroalgae—notably brown seaweeds in the class Phaeophyceae, contain fucoidan. Fucoidan designates a group of certain fucose-containing sulfated polysaccharides (FCSPs) that have a backbone built of (1→3)-linked α-l-fucopyranosyl or of alternating (1→3)- and (1→4)-linked α-l-fucopyranosyl residues, but also include sulfated galactofucans with backbones built of (1→6)-β-d-galacto- and/or (1→2)-β-d-mannopyranosyl units with fucose or fuco-oligosaccharide branching, and/or glucuronic acid, xylose or glucose substitutions. These FCSPs offer several potentially beneficial bioactive functions for humans. The bioactive properties may vary depending on the source of seaweed, the compositional and structural traits, the content (charge density), distribution, and bonding of the sulfate substitutions, and the purity of the FCSP product. The preservation of the structural integrity of the FCSP molecules essentially depends on the extraction methodology which has a crucial, but partly overlooked, significance for obtaining the relevant structural features required for specific biological activities and for elucidating structure-function relations. The aim of this review is to provide information on the most recent developments in the chemistry of fucoidan/FCSPs emphasizing the significance of different extraction techniques for the structural composition and biological activity with particular focus on sulfate groups.
Eficiencia diagnóstica de la predicción de concentraciones de digoxina en función de la tasa de filtración glomerular mediante un modelo hiperbólico
González-López,J.; Tutor,J.C.;
Nefrología (Madrid) , 2011,
Abstract: background: inappropriate doses and high serum concentrations of digoxin are highly prevalent in patients with renal impairment, and the drug dosage adjustment according to the glomerular filtration rate (gfr) is recommended. the aim of our study was to evaluate the dependence degree of digoxin total clearance (cl) on gfr, and the diagnostic efficiency of a predictive model for serum digoxin steady-state concentrations (css) from estimated gfr by cockcroft-gault formula. methods: in 400 outpatients treated orally with digoxin, serum css were determined (fluorescence polarization immunoassay from abbott laboratories), and total cl was calculated. the prediction of css was carried out using a hyperbolic model developed by konishi et al in japan (j clin pharm ther 2002;27:257), and the constants of the equation were modified for a caucasian population. results: only 26% of the digoxin cl interindividual variability may be explained by differences in gfr, and this fact is a serious limitation for the derived predictive models. a 65% diagnostic efficiency was obtained for original and modified hyperbolic models in the correct classification of predicted css as subtherapeutic, therapeutic or supratherapeutic with respect to obtained css concentrations. conclusions: the diagnostic efficiency obtained in the prediction of serum digoxin concentrations from estimated gfr values is unacceptable for the drug dosage adjustment in clinical practice.
Fucose-Containing Sulfated Polysaccharides from Brown Seaweeds Inhibit Proliferation of Melanoma Cells and Induce Apoptosis by Activation of Caspase-3 in Vitro
Marcel Tutor Ale,Hiroko Maruyama,Hidekazu Tamauchi,J?rn D. Mikkelsen,Anne S. Meyer
Marine Drugs , 2011, DOI: 10.3390/md9122605
Abstract: Fucose-containing sulfated polysaccharides (FCSPs) extracted from seaweeds, especially brown macro-algae, are known to possess essential bioactive properties, notably growth inhibitory effects on tumor cells. In this work, we conducted a series of in vitro studies to examine the influence of FCSPs products from Sargassum henslowianum C. Agardh (FSAR) and Fucus vesiculosus (FVES), respectively, on proliferation of melanoma B16 cells and to investigate the underlying apoptosis promoting mechanisms. Cell viability analysis showed that both FCSPs products, i.e., FSAR and FVES, decreased the proliferation of the melanoma cells in a dose-response fashion, with FSAR being more potent at lower dosages, and FVES being relatively more anti-proliferative than FSAR at higher dosages. Flow cytometric analysis by Annexin V staining of the melanoma cells exposed to the FCSPs products confirmed that both FSAR and FVES induced apoptosis. The FCSPs-induced apoptosis was evidenced by loss of plasma membrane asymmetry and translocation of the cell membrane phospholipids and was accompanied by the activation of caspase-3. The FCSPs bioactivity is proposed to be attributable to distinct structural features of the FCSPs, particularly the presence of sulfated galactofucans (notably in S. henslowianum) and sulfated fucans (notably in F. vesiculosus). This study thus indicates that unfractionated FCSPs may exert bioactive effects on skin cancer cells via induction of apoptosis through cascades of reactions that involve activation of caspase-3.
Análisis de perforantes de la epigástrica inferior profunda con Angio TC 3D, Eco Doppler color y Doppler simple de ultrasonidos en colgajo DIEP: resultados preliminares
Castro García,J.; García-Tutor,E.; Alonso,A.; Pina,L.; De Luis,E.;
Cirugía Plástica Ibero-Latinoamericana , 2008, DOI: 10.4321/S0376-78922008000300007
Abstract: the aim of this report, is to validate the angio-ct technique with three-dimentional reconstruction as a preoperative planning tool, after comparison with doppler ultrasound and color- duplex. between january 2006 and march 2007, we studied 11 consecutive patients (13 diep) in whom a prospective comparative followed up was performed comparing, the findings observed using doppler ultrasound, colour-duplex and angio-ct with three-dimentional reconstruction. surgical procedure findings were considered as the reference value. the evaluation procedure included the election of the most suitable perforator vessels, taking account of the location, caliber and anatomical relationships with the muscle. the angio-ct with three-dimentional reconstruction showed 100% specificity (ci 95% 75.3-100), and very high positive predictive value. in this way, this technique could be considered as an excellent tool for preoperative evaluation of perforators flaps. color-duplex showed that in 46,1% of the patients (ci 95% 19,2-74%) the selected perforator matched with the intraoperatively selected. using doppler ultrasound only in 30,8% of the cases (ic 95% 9,1-61,4%) this result was observed. in this report, angio-ct with three-dimentional reconstruction has revealed as a very high specificity technique, that allows a great account of important information, only comparable with anatomical dissection and ahead from doppler ultrasound and color-dupplex.
Análisis de perforantes de la epigástrica inferior profunda con Angio TC 3D, Eco Doppler color y Doppler simple de ultrasonidos en colgajo DIEP: resultados preliminares Analysis of deep inferior epigastric perforating vessels with 3D CT angiography, color Doppler ultrasonography and Doppler in diep flaps: preliminary results
J. Castro García,E. García-Tutor,A. Alonso,L. Pina
Cirugía Plástica Ibero-Latinoamericana , 2008,
Abstract: Nuestro objetivo es la validación de la Angio TC tridimensional como herramienta de planificación de los colgajos DIEP, comparándolo con el Doppler de ultrasonidos (US) y eco Doppler color. Entre enero de 2006 y marzo de 2007 se realiza en 11 pacientes (13 DIEP) un estudio comparativo prospectivo entre el Doppler de US, eco Doppler color y Angio TC con reconstrucción tridimensional, utilizando como dato de referencia los hallazgos intraoperatorios. En dicho proceso se localiza la mejor perforante que pueda servir como pedículo al colgajo DIEP en función de su localización, calibre, trayecto y relaciones anatómicas con respecto al músculo. La Angio TC con reconstrucción tridimensional, demuestra una especificidad del 100% (IC 95% 75.3-100) lo que le convierte en una prueba con un alto valor predictivo positivo y una excelente herramienta en la planificación de los colgajos de perforantes. El eco Doppler color determinó, que tan sólo en un 46,1% (IC 95% 19,2-74,9) de los pacientes, la perforante seleccionada por la prueba de forma preoperatoria, coincidía con la perforante elegida en quirófano. Con el Doppler de US, en un 30,8 % (IC 95% 9,1-61,4) de los colgajos estudiados, coincidía la mejor perforante escogida de forma preoperatoria, con los hallazgos obtenidos tras la disección del colgajo. En el presente estudio, la Angio TC tridimensional se ha mostrado como una técnica con una gran especificidad que proporciona valiosa información, sólo comparable con la disección anatómica y por delante de pruebas como el Doppler de ultrasonidos y el eco Doppler color. The aim of this report, is to validate the Angio-CT technique with three-dimentional reconstruction as a preoperative planning tool, after comparison with Doppler ultrasound and color- Duplex. Between january 2006 and march 2007, we studied 11 consecutive patients (13 DIEP) in whom a prospective comparative followed up was performed comparing, the findings observed using Doppler ultrasound, Colour-Duplex and Angio-CT with three-dimentional reconstruction. Surgical procedure findings were considered as the reference value. The evaluation procedure included the election of the most suitable perforator vessels, taking account of the location, caliber and anatomical relationships with the muscle. The Angio-CT with three-dimentional reconstruction showed 100% specificity (CI 95% 75.3-100), and very high positive predictive value. In this way, this technique could be considered as an excellent tool for preoperative evaluation of perforators flaps. Color-Duplex showed that in 46,1% of the patients (CI 95% 1
Non-O1 Vibrio cholerae inguinal skin and soft tissue infection with bullous skin lesions in a patient with a penis squamous cell carcinoma
Aitziber Aguinaga, María E Portillo, Jose R Yuste, Jose L del Pozo, Emilio García-Tutor, Jose L Pérez-Gracia, José Leiva
Annals of Clinical Microbiology and Antimicrobials , 2009, DOI: 10.1186/1476-0711-8-17
Abstract: Vibrio cholerae is mainly related to water sources [1]. Contaminated seawater exposure or contaminated seafood ingestion are frequently associated with diarrhoea and/or extraintestinal infections such as otitis media, skin and soft tissue infections (SSTI) and bacteremia [1,2]. Vibrio spp. is a pathogen rarely isolated in cancer patients, and in most cases it is associated with haematological diseases. Although the clinical picture may have a wide range in Vibrio spp. SSTI, bullous lesions are almost exclusively associated with V. vulnificus infection [3,4] and have rarely been reported with non-O1 V. cholerae infections [4,5].We report here the case of a non-O1 V. cholerae SSTI presenting bullous skin lesions in a diabetic patient with a solid tumour.A 36-year-old patient from the Canary Islands (Spain) with controlled type II diabetes mellitus was diagnosed with a moderately differentiated squamous cell carcinoma of the penis in December 2006 in his local hospital. The patient underwent a partial penectomy. In the initial follow-up after surgery, the abdominal CT and granulation tissue were normal. The patient had been exposed to seawater and seafood from December 2006 to October 2007 when bullous skin lesions were observed in both inguinal regions during a examination. Lesions were fitted with inguinal metastases, and the patient underwent inguinal surgery followed by radiotherapy.In November 2007 he was admitted to our hospital for a second consultation. Physical examination showed stinking lesions in both inguinal regions with cellulitis and bullae. Patient underwent an abdominal computed tomography (CT) scan with contrast that revealed the existence of several large necrotic adenopathies in the inguinal, scrotal and pubic areas (Figure 1). A right abdominal wall nodule and a left groin abscess extending from psoas muscle to skin were also observed. A CT scan of the chest showed pulmonary lesions compatible with metastases. Initial laboratory findings showed in
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