A "green" strategy to construct non-covalent, stable and bioactive coatings on porous MOF nanoparticles.

Nanoparticles made of metal-organic frameworks (nanoMOFs) attract a growing interest in gas storage, separation, catalysis, sensing and more recently, biomedicine. Achieving stable, versatile coatings on highly porous nanoMOFs without altering their ability to adsorb molecules of interest represents today a major challenge. Here we bring the proof of concept that the outer surface of porous nanoMOFs can be specifically functionalized in a rapid, biofriendly and non-covalent manner, leading to stable and versatile coatings. Cyclodextrin molecules bearing strong iron complexing groups (phosphates) were firmly anchored to the nanoMOFs' surface, within only a few minutes, simply by incubation with aqueous nanoMOF suspensions. The coating procedure did not affect the nanoMOF porosity, crystallinity, adsorption and release abilities. The stable cyclodextrin-based coating was further functionalized with: i) targeting moieties to increase the nanoMOF interaction with specific receptors and ii) poly(ethylene glycol) chains to escape the immune system. These results pave the way towards the design of surface-engineered nanoMOFs of interest for applications in the field of targeted drug delivery, catalysis, separation and sensing.

Human galectin-3 selective and high affinity inhibitors. Present state and future perspectives.

Over the last decade an increasing number of studies have been published reporting on the inhibitory potency or selectivity that several types of ligands show against human galectin-3 (hGal-3). The reason for this interest lies in the many important roles galectins play both in intra and extra-cellular functions. Among galectins, galectin-3 stands out because it is the only known member of its subfamily in mammals, is small and monomeric but capable of aggregating, and is known to be involved in a large number of disease processes, from cancer to heart failure. These characteristics and roles make hGal-3 an ideal target for drugs. Since it binds ß-galactosides, like the rest of the galectin family of proteins, the search and design of potent and at the same time selective inhibitors for it is not an easy task. Herein we discuss the chemical features of the most potent inhibitors described so far, as well as the structural basis of their exhibited selectivity, in order to shed light on the rational design of drugs against this target.

Abordaje del tromboembolismo pulmonar en la sala de autopsias / Approach of pulmonary embolism at the autopsy room

No disponible

Urachal adenocarcinoma with late brain metastases.

OBJECTIVE: To describe a case of urachal adenocarcinoma with late brain metastases in a sixty one year old man who presented abdominal discomfort and hematuria during six months. METHODS: The clinical suspicion was bladder tumor and diagnostic studies were performed (urinary cytology, cystoscopy, abdominal ultrasound and abdominopelvic CT scan). Surgical treatment was performed. RESULTS: Negative urinary cytology. Cystoscopy showed a lesion with infiltration of the bladder dome. Ultrasound and CT scan showed a five centimeter rounded lesion, with intermediate density, internal echoes and calcifications on the anterior supravesical middle line, that infiltrated the bladder. The extension study had not findings. Partial cystectomy and lymphadenectomy were performed. The histopathologic diagnosis was mucin-secreting urachal adenocarcinoma. After five years without disease the patient suffered lung and brain metastases. CONCLUSIONS: Urachal adenocarcinoma is a tumor which must be distinguished of primary bladder adeno-carcinoma. The mucing-secreting adenocarcinoma can be associated with calcifications that can be demostrated on imaging studies. Late metastases without signs of local recurrence (after five years without disease) are an infrequent clinical-pathologic finding.

Application of gas chromatography-hybrid chemical ionization mass spectrometry to the analysis of diclofenac in wastewater samples.

Hybrid chemical ionization (HCI), a new and useful alternative to conventional chemical ionization mass spectrometry, has been applied to the analysis of the pharmaceutical diclofenac in wastewater samples. This technique takes advantage of the high versatility of ion trap (IT) spectrometers combined with external ionization sources. In hybrid configuration, reagent ions are generated in the external source through electron ionisation (EI) of a reagent gas. These reagent ions are then drawn into the ion trap and only those selected are allowed to react with analytes eluting from the GC column. These ion-molecule reactions create analyte ions which are held in the ion trap. In this study ion-molecule reactions between C(3)F(5)(+) cations, generated from perfluorotributylamine (FC43), and diclofenac molecules have been investigated. The observed reaction products were [M+C(3)F(5)-H(2)O](+) adduct ions, which result from the initial electrophilic addition of C(3)F(5)(+) cations to the diclofenac molecule followed by the rapid loss of H(2)O. Further fragmentation of these ions by MS/MS yielded enough daughter ions for a reliable identification of diclofenac in complex matrices. The GC-HCI-MS/MS method applied to wastewater samples provided highly enhanced selectivity and sensibility, with a detection limit in real samples of 3.0 ng/L, for a solid-phase extraction (SPE) pre-concentration factor of 400. Other performance characteristics of the method, such as linearity and precision were also satisfactory. Finally, the method was successfully applied to the analysis of wastewater samples taken from the effluent of an urban sewage treatment plant (STP).

Structure of concanavalin A at pH 8: bound solvent and crystal contacts.

Concanavalin A has been crystallized in the presence of the ligand (6-S-beta-D-galactopyranosyl-6-thio)-cyclomaltoheptaose. The crystals are isomorphous to those reported for ConA complexed with peptides at low resolution (3.00-2.75 angstroms). The structure was solved at 1.9 angstroms, with free R and R values of 0.201 and 0.184, respectively. As expected, no molecules of the ligand were bound to the protein. Soaking in the cryobuffer left its fingerprint as 25 molecules of glycerol in the bound solvent, most of them at specific positions. The fact that a glycerol molecule is located in the sugar-binding pocket of each of the four subunits in the asymmetric unit and another is located in two of the peptide-binding sites suggests a recognition phenomenon rather than a displacement of water molecules by glycerol. Crystal contact analysis shows that a relation exists between the residues that form hydrogen bonds to other asymmetric units and the space group: contact Asp58-Ser62 is a universal feature of ConA crystals, while Ser66-His121, Asn69-Asn118 and Tyr100-His205 contacts are general features of the C222(1) crystal form.

Influencia del grado de la severidad de la estenosis, del diámetro del vaso y del modelo de stent en el fenómeno del retroceso elástico en angioplastia coronaria. Evaluación angiográfica / No disponible

Objetivos: El fenómeno de retroceso elástico, tras la implantación del stent, sigue siendo de gran importancia en el éxito del procedimiento angiográfico. El objetivo de este estudio es valorar la influencia que el tamaño del vaso, el modelo de stent y el modelo angiográfico de lesión, puedan tener en el retroceso elástico. Material y métodos: Se incluyeron en el estudio 61 pacientes, en los que se implantaron con éxito 81 stents de diferentes modelos. Se valoró mediante angiografía coronaria cuantitativa los diámetros durante la implantación y tras la retirada del balón. Los resultados fueron analizados en función del modelo de stent, de las características del vaso y de las características angiográficas de la lesión. Resultados: No se hallaron diferencias significativas en el fenómeno del retroceso elástico en relación a la longitud, simetría y severidad de la lesión. Tampoco en relación al modelo de stent empleado. Sí hubo diferencias si se tenía en cuenta el tamaño del vaso, siendo significativamente menor en los vasos pequeños (<2,75 mm). Discusión: El hallazgo de que el retroceso elástico sea menor en los vasos pequeños supone una paradoja. Tradicionalmente se ha considerado el pequeño tamaño del vaso como un factor de riesgo independiente para el desarrollo de reestenosis tras la implantación del stent. Este hallazgo mantiene la polémica sobre el empleo del stent en vasos pequeños (AU)

Purpose: Stent recoil following stent deployment is still a very important outcome predictor after angiographic intervention. The aim of this study is to assess the influence of device model, angiographic characteristics of the lesion and vessel size on stent recoil. Methods: 61 consecutive patients were included in the study. 81 stents were successfully deployed. Maximal balloon diameter at peak pressure and maximal lumen diameter after stenting were measured by QCA (quantitative coronary angiography) Results: There were no significant differences regarding either the model of device or length, symmetry or severity of the lesion. There were significant differences regarding the vessel size. Stent recoil was greater in small vessels (<2,75 mm). Discussion: This finding is a paradox. The small size of the vessel has been always identified as an independent risk factor for the development of stenosis. The use of stents in small vessels remains controversial (AU)

Utilidad de la infusión de adenosin trifosfato (ATP) en el diagnóstico de los pacientes con síncope de origen desconocido / No disponible

El síncope es una patología frecuente en los servicios de Urgencias que se acompaña de un alto índice de recurrencias. A pesar de las pruebas utilizadas en su estudio, en un alto porcentaje de pacientes no se puede filiar la etiología. Esta revisión analiza el fundamento, la utilidad y las implicaciones terapéuticas del test de infusión de ATP, recientemente incorporado en el estudio del síncope de origen desconocido (AU)

Syncope is a common clinical problem in the emergency room. Many patients have recurrences of syncope at follow up. Although many tests have been used for the evaluation of syncope, in some cases it is not possible to find the aetiology. In this paper we analyse the basis, utility and therapeutic implications of ATP test in the diagnosis of syncope of unknown origin (AU)

Binding affinity properties of dendritic glycosides based on a beta-cyclodextrin core toward guest molecules and concanavalin A.

The inclusion behavior and concanavalin A binding properties of hepta-antennated and newly synthesized tetradeca-antennated C-6-branched mannopyranosyl and glucopyrannosyl cyclomaltoheptaose (beta-cyclodextrin) derivatives have been evaluated by isothermal titration microcalorimetry and enzyme-linked lectin assay (ELLA), respectively. The synthesis of three first-order dendrimers based on a beta-cyclodextrin core containing 14 1-thio-beta-D-glucose, 1-thio-beta-mannose, and 1-thio-beta-rhamnose residues was performed following a convergent approach and involving (1) preparation of a thiolated bis-branched glycoside building block and (2) attachment of the building block onto heptakis(6-deoxy-6-iodo)-beta-cyclodextrin. Calorimetric titrations performed at 25 degrees C in buffered aqueous solution (pH 7.4) gave the affinity constants and the thermodynamic parameters for the inclusion complex formation of these beta-cyclodextrin derivatives with guests sodium 8-anilino-1-naphthalensulfonate (ANS) and 2-naphthalenesulfonate. The host capability of the persubstituted beta-cyclodextrins decreased with respect to the native beta-CD when sodium 2-naphthalenesulfonate was used as a guest and improved when ANS was used as a guest molecule. Heptavalent mannoclusters based on beta-CD cores enhance the lectin binding affinity due to the cluster effect; however, the increase of the valency from 7 to 14 ligands did not contribute to the improvement of the concanavalin A binding affinity. In addition, the synthesized hyperbranched mannoCDs lost completely the capability as a host molecules.

[Multiple bladder inverted papillomas]. / Papilomas invertidos vesicales múltiples.

OBJECTIVE: To describe the clinical and histological findings of the unusual involvement of the urinary bladder by multiple inverted papillomas of transitional cells. METHODS/RESULTS: A 53-year-old male presented with obstructive symptoms and gross hematuria lasting for one year. Ultrasound examination of the urinary bladder demonstrated two polypoid masses. Transurethral resection was performed and histopathological examination of specimens showed a subepithelial, non-atypical cell proliferation arranged in a trabecular pattern. DNA-ploidy showed diploid population and ki-67 determination revealed a low proliferation index. CONCLUSIONS: Multiple inverted papillomas of the urinary bladder are very rare. Histological examination is essential for the definitive diagnosis. Determination of DNA-ploidy and proliferative index may be useful for appropriate management of this disease.

Utilidad de la braquiterapia intravascular en la prevención de la reestenosis secundaria a angioplastia transluminal coronaria / Efficacy of the intravascular brachytherapy for the prevention of the secondary restenosis to the transluminal coronary angioplasty

La radioterapia intravascular coronaria ha demostrado de manera convincente en estudios clínicos y experimentales que produce una disminución favorable del proceso de reestenosis. Hay evidencia suficiente para definir a dicha técnica como la principal terapia actual en el manejo de la reestenosis intra stent. Existe experiencia acumulada de hasta 3 años en pacientes tratados con radiación gamma y múltiples estudios en varios centros demuestran beneficios similares con emisores beta. Como efectos adversos de la braquiterapia se han descrito el desarrollo de nuevas estenosis en los márgenes de la lesión tratada (el ‘efecto borde’) y la oclusión trombótica tardía. A pesar de esto, la mayoría de investigadores cree que estos problemas pueden ser evitados y que la radiación intravascular es la terapia de elección en pacientes con alto riesgo de reestenosis tras intervención percutánea de revascularización coronaria. Ahora que se ha pasado de la experimentación animal a la fase clínica, y mientras la investigación continua, la tecnología está siendo optimizada para encontrar nuevas fuentes y vías de administración de la radiación que puedan ser lanzadas al mercado. El presente artículo revisa una serie de sistemas de radioterapia y hace una puesta al día sobre el empleo de la braquiterapia intravascular en pacientes cardiológicos (AU)

Intravascular radiotherapy has convincingly shown in several experimental and clinical studies to result in a marked and favorable control of the restenotic process. The evidence that radiation therapy constitutes a major breakthrough therapy for patients with in-stent restenosis is convincing, and the safety and long-lasting benefit with gamma-radiation at 3 years has been demonstrated. It is known that this benefit comes at the price of an excess of new stenoses at the lesion edge (the edge effect) and late (>1 month) thrombotic occlusion compared with control groups. However, investigators believe these problems can be avoided and that radiation therapy is the first-line treatment in this group of patients. Intravascular radiotherapy has moved from animal experiments via the safety and feasibility testing into the phase of clinical trials of efficacy in large numbers of patients. While ongoing research continues to search for new sources and delivery techniques, currently available technology is being optimized in pursuit advanced intravascular radiotherapy systems and resumes the principal issues of intravascular brachytherapy in the cardiology field (AU)

Colon cancer: p53 expression and DNA ploidy. Their relation to proximal or distal tumor site.

Overexpression of nuclear p53 and DNA ploidy were analyzed in a series of 65 colorectal adenocarcinomas and correlated with standard clinical and pathological variables (Dukes stage, tumor site, histological grade and type, and nature of the tumor margins). Immunohistochemical tests were done with the DO-7 monoclonal antibody, using formalin-fixed tissue samples and an antigen retrieval solution. Levels of p53 expression were evaluated using a semiquantitative grading system (CAS 200, BD). Nuclear staining of more than 15% of neoplastic cells was observed in 35 samples (53.8%), which were classified as p53-positive. DNA content was measured by flow cytometry in samples of fresh tissue. Tumor site had a significant direct relationship with DNA ploidy (p < 0.01) and p53 expression (p < 0.001). Proximal tumors were more frequently diploid than were distal tumors (78.6% vs 32%). Moreover, distal neoplasms showed more p53 expression than proximal tumors (64.6% vs 14.3%). However, there was no correlation between the other clinical or pathological variables and the pathological parameter p53 expression and DNA ploidy. Our data support the hypothesis that mechanisms of colorectal carcinogenesis may differ in proximal and distal neoplasms.

[Bladder transitional cell carcinoma rating, systematization of grading and value of DNA ploidy]. / Contribución a la categorización de los CCT de vejiga, sistemátización de la gradación y utilidad de la ploidía de ADN.

UNLABELLED: TCCs are an heterogenous group of tumors with an uncertain biologic behaviour, especially intermediate grade (G2). Histologic grade and pathologic stage have revealed only partially useful on predicting the outcome. OBJECTIVE: Search and statement of objective and cuantitative parameters able to define prognostic subgroups to TCCs. MATERIAL AND METHOD: We studied consecutive 106 patients with TCC in order to: 1) Identify every variable with independent predictive value in classifying cases of TCC in a three (1,2,3) or two (high/low) grades systems. 2) Make a correlation between DNA ploidy obtained by image analysis and DNA ploidy and S-phase obtained by flow cytometry. RESULTS: Every variable used to define the histologic grade showed significative correlation with both gradation systems. In multivariate analysis, the presence of superficial cells and the mitotic counts revealed us the most valuable variables in predicting the histologic grade. DNA-ploidy (both obtained by static an flow cytometry) correlated well with grade, stage, growth pattern and necrosis, whereas S-phase did so with grade, mitotic index and DNA ploidy. Image cytometry showed similars results to those of flow cytometry and also was able to detect aneuploidy when an situ carcinoma or dysplasia were present in the adyacent mucosa.

[Value of Markovian nuclear texture to predict progression in surface transitional cell carcinoma of the bladder]. / Utilidad de las texturas nucleares Markovianas en la predicción de la progresión en los CCT superficiales de vejiga.

The aim of this work has been to determine if the DNA and nuclear Markovian textures of tissue sections evaluated by image cytometry correlate with the histologic grade and the progression probability of superficial transitional carcinoma of the bladder. In our study, DNA ploidy is related to histologic grade in that aneuploidy frequency increases with a higher grade of malignancy. Image analyses of superficial TCC tissue sections of the bladder, has allowed us to identify "sub-visual parameters" as well as nuclear textures that according to our results can be useful in clarifying the evolutive behaviour of these tumours. Two Markovian textures that identify entropy (TXI) and mean internal contrast (TXB) allow to discriminate between histologic grades as well as progression or non-progression. In conclusion, image analysis cytometry of paraffin embedded tissue sections of TCC of the bladder supplies densitometric parameters related to grade and provides valuable information for the prediction of progression. Quantification of chromatin pattern description in Feulgen-stained nuclei using the Markovian method can be useful in this context.

Selective pivaloylation and diphenylacetylation of cyclomalto-oligosaccharides.

Regioselective acylation of cyclomalto-oligosaccharides was achieved using pivaloyl and diphenylacetyl chlorides. The reaction of cyclomaltohexaose (1) with pivaloyl chloride gave the hexakis(2,6-di-O-pivaloyl) derivative 19 in 66% yield. Similar reaction with cyclomalto-heptaose (2) led to the octakis(2I,6I,6II,6III,6IV,6V,6VI ,6VII-O-pivaloyl) 26 and the 17 heptakis(6-O-pivaloyl) derivatives in 34 and 26% yields, respectively. The octakis(6-O-pivaloyl) derivative 18 was the only compound isolated (72%) in the reaction of pivaloyl chloride with cyclomalto-octaose (3). Diphenylacetylation of 1-3 gave the symmetrical (20-22) and the non-symmetrical (27-29) per(6-O-diphenylacetyl) esters as major and minor products, respectively.

Acute ascending polyradiculoneuritis in a case of Creutzfeldt-Jakob disease.

A patient is described who showed subacute dementia and ataxia and, finally, acute asending polyradiculoneuritis. At necropsy, together with the cerebral and cerebellar lesions that are typical of Creutzfeldt-Jakob disease, the lesions of the spinal motor neurons, the spinal ganglia, and of the roots and peripheral nerves were analogous with those of the Guillain-Barré-Landry syndrome. The aetiological possibility is discussed either that this is a simple and unique association, or that the disorder is related to the virus nature of Creutzfeldt-Jakob disease.