Natural life cycle of Versteria cuja (Taeniidae) in Argentina and histopathology of metacestodiasis in intermediate hosts.

Using morphological and molecular studies, the life cycle of Versteria cuja (Cestoda: Taeniidae) was elucidated, involving subterranean rodents (Ctenomyidae) as intermediate hosts, and the lesser grison, Galictis cuja (Mustelidae), as definitive host. Metacestodes (cysticerci and polycephalic larvae) were found mainly in the liver but also in spleen, pancreas, lungs and small intestine of 2 species of tuco-tucos (Ctenomys spp.) from Chubut, Argentina. Identity of the metacestodes with the adult was based primarily on the number, size and shape of rostellar hooks: 40­48 hooks in 2 rows, particularly small (10­16 µm total length by 6­10 µm wide), composed of handle, blade and guard with characteristic shapes. Genetic analysis (cox1 gen mtDNA) performed on metacestodes from both intermediate hosts corroborated their conspecificity with adults of V. cuja from lesser grisons in the same locality. Histopathological study showed the hepatic parenchyma altered by the presence of cysts containing larvae, each surrounded by a capsule of connective tissue with inflammatory infiltrate, atrophied hepatocytes and an increase of bile ducts. In the lung, in addition to the cysts, dilated alveoli, oedema and hyperaemic blood vessels were observed. This is the first report of a natural life cycle of a Versteria species from South America. It shows strong similarities with that described for a North American zoonotic lineage of Versteria, confirming a close relationship between V. cuja and this North American lineage, as previously demonstrated by molecular studies. Consequently, the zoonotic potential of V. cuja should not be disregarded.

A new species of Versteria (Cestoda: Taeniidae) parasitizing Galictis cuja (Carnivora: Mustelidae) from Patagonia, Argentina: Morphological and molecular characterization.

Via morphological and molecular analysis, we describe a new species of taeniid from Patagonia (Argentina): Versteria cuja n. sp., parasitizing the Lesser grison Galictis cuja (Molina) (Carnivora: Mustelidae). This is the first report of a species of Versteria in Argentina and for a native mustelid. The new species (the third in the genus Versteria) is proposed using an integrative taxonomic approach, based on traditional morphology (distinctive morphological and morphometric diagnostic characters), genetic distances and phylogeny based on molecular data, the distinct geographical distribution, and the different definitive host species. Versteria cuja n. sp. mainly differs from Versteria mustelae (Gmelin, 1790) (from Europe) in the number of testes (54-85 vs. 83-127 in V. mustelae), the rostellum size (39-75 vs. 85-180 µm in V. mustelae), the genital atrium size (170-420 vs. 68-91 µm in V. mustelae) and in the hooks' shape. It also differs from the African species Versteria brachyacantha (Baer and Fain, 1951) by having smaller measurements regarding the main diagnostic characters, i.e. size of scolex, rostellum and suckers, number, size and shape of rostellar hooks, number of testes, and by having smooth cirrus (vs. cirrus covered with hair-like bristles in V. brachyacantha). Phylogenetical analysis using cox1 showed our specimens clustering with North American isolates of Versteria sp. in a well-supported American clade (mean genetic divergence 0.024), separated from another clade composed of different isolates of V. mustelae (0.093). The close relationship between the new species and the North American species, known as "zoonotic" Versteria sp., and responsible for fatal infections by metacestodes in free-ranging wildlife (rodents), captive primates and immunosuppressed people, lead us to think that the zoonotic potential of Versteria cuja n. sp. should not be discarded.

Correlation coefficients for predicting canine diameters from premolar and molar sizes.

BACKGROUND/PURPOSE: The permanent canine is the most widely used tooth for sex estimation because it is the tooth with the highest degree of sexual dimorphism; however, there are several factors that can limit the analysis (e.g., pathologies, postmortem loss). The aim of this work was to analyse the correlation between the dimensions of the canines and those of the premolars and molars, and evaluate the correspondence of real and predicted canine dimensions by applying the equations developed. MATERIALS AND METHODS: The sample was composed of digital models of 80 adult individuals from Temuco, Chile. The buccolingual and mesiodistal diameters of the canine, premolar and molar dental crowns were measured and Pearson's linear regression analysis was performed in order to determine the correlation between the diameters. The equations obtained from the reference subsample were applied to a validation subsample to predict canine dimensions from the dimensions of the postcanine teeth. RESULTS: Four regression equations were obtained, all for prediction of the size of the lower canines, whose correlation coefficient ranged from 0.701 to 0.738. The regression equations developed with the reference sample were tested on the validation sample using a Student's t-test for paired samples and the intraclass correlation coefficient. The differences between actual dental size and that predicted by the equations were not significantly different, and concordance analysis showed a moderate degree (0.485-0.585). CONCLUSION: There is a limited correlation of canine dimensions with respect to premolars and molars. The correspondence between the actual and predicted canines dimensions is moderate.

Evaluation of the TRPM2 channel as a biomarker in breast cancer using public databases analysis / Evaluación del canal TRPM2 como biomarcador en cáncer de mama mediante el análisis de bases de datos públicos

Abstract: Background: Breast cancer is one of the most common malignancies affecting women. Recent investigations have revealed a major role of ion channels in cancer. The transient receptor potential melastatin-2 (TRPM2) is a plasma membrane and lysosomal channel with important roles in cell migration and cell death in immune cells and tumor cells. Methods: In this study, we investigated the prognostic value of TRPM2 channel in breast cancer, analyzing public databases compiled in Oncomine™ (Thermo Fisher, Ann Arbor, MI) and online Kaplan-Meier Plotter platforms. Results: The results revealed that TRPM2 mRNA overexpression is significant in situ and invasive breast carcinoma compared to normal breast tissue. Furthermore, multi-gene validation using Oncomine™ showed that this channel is coexpressed with proteins related to cellular migration, transformation, and apoptosis. On the other hand, Kaplan-Meier analysis exhibited that low expression of TRPM2 could be used to predict poor outcome in ER- and HER2+ breast carcinoma patients. Conclusions: TRPM2 is a promising biomarker for aggressiveness of breast cancer, and a potential target for the development of new therapies.

Resumen: Introducción: El cáncer de mama es la neoplasia maligna más común que afecta a mujeres. Estudios recientes han revelado un papel importante de los canales iónicos en el cáncer. El receptor de potencial transitorio melastatin-2 (TRPM2) es un canal que se expresa en la membrana plasmática y en los lisosomas; posee funciones importantes en la migración y muerte celular de células inmunes y tumorales. Métodos: En este estudio se investigó el valor pronóstico del canal TRPM2 en cáncer mama. Se realizó el análisis de bases de datos públicos empleando las plataformas OncomineTM (Thermo Fisher, Ann Arbor, MI) y Kaplan-Meier Plotter. Resultados: Los resultados mostraron que el mRNA de TRPM2 se sobreexpresa significativamente en los carcinomas de mama in situ e invasivo en comparación con el tejido mamario normal. Además, la validación de múltiples genes empleando OncomineTM reveló que este canal se coexpresa con proteínas relacionadas con la migración celular, la transformación celular y apoptosis. Por otra lado, el análisis de la sobrevivencia promedio usando curvas Kaplan-Meier mostró que la baja expresión de TRPM2 podría utilizarse como un marcador de pronóstico pobre en pacientes con carcinoma de mama receptor de estrógeno negativo (ER-) y receptor 2 del factor de crecimiento epidermal positivo (HER2+). Conclusiones: El TRPM2 podría emplearse como biomarcador de agresividad en cáncer de mama, y como blanco para el desarrollo de nuevas terapias.

Evaluation of the TRPM2 channel as a biomarker in breast cancer using public databases analysis.

BACKGROUND: Breast cancer is one of the most common malignancies affecting women. Recent investigations have revealed a major role of ion channels in cancer. The transient receptor potential melastatin-2 (TRPM2) is a plasma membrane and lysosomal channel with important roles in cell migration and cell death in immune cells and tumor cells. METHODS: In this study, we investigated the prognostic value of TRPM2 channel in breast cancer, analyzing public databases compiled in Oncomine™ (Thermo Fisher, Ann Arbor, MI) and online Kaplan-Meier Plotter platforms. RESULTS: The results revealed that TRPM2 mRNA overexpression is significant in situ and invasive breast carcinoma compared to normal breast tissue. Furthermore, multi-gene validation using Oncomine™ showed that this channel is coexpressed with proteins related to cellular migration, transformation, and apoptosis. On the other hand, Kaplan-Meier analysis exhibited that low expression of TRPM2 could be used to predict poor outcome in ER- and HER2+ breast carcinoma patients. CONCLUSIONS: TRPM2 is a promising biomarker for aggressiveness of breast cancer, and a potential target for the development of new therapies.

Discovery of small molecules with vasodilating characteristics and adjustable hydrolytic behavior.

In this contribution the development of a new class of vasodilating compounds obtained by lead structure optimization is described. Three groups of compounds were synthesized and tested for their activity on various smooth muscle preparations of the guinea pig. Beside the lead compound 3a, the most interesting derivative was 1H-imidazole-1-carbothioic acid O-cyclohexyl ester hydrochloride (5b) with a good selective vasodilating potential on aorta and pulmonary artery rings (EC50 14 µM and 24 µM, respectively). Due to the properties of small molecules the hydrolysis behavior of the compounds can be easily adapted hence opening a new route in terms of duration of the agent's effect. With the aid of structure-activity relationship studies, structural motifs influencing the biological activity on isolated smooth muscle cell preparations of the synthesized compounds were proposed. The presented compounds offer good tools in identifying promising molecules as emergency therapy in myocardial infarction.

A novel prodrug-based strategy to increase effects of bumetanide in epilepsy.

OBJECTIVE: There is considerable interest in using bumetanide, a chloride importer Na-K-Cl cotransporter antagonist, for treatment of neurological diseases, such as epilepsy or ischemic and traumatic brain injury, that may involve deranged cellular chloride homeostasis. However, bumetanide is heavily bound to plasma proteins (~98%) and highly ionized at physiological pH, so that it only poorly penetrates into the brain, and chronic treatment with bumetanide is compromised by its potent diuretic effect. METHODS: To overcome these problems, we designed lipophilic and uncharged prodrugs of bumetanide that should penetrate the blood-brain barrier more easily than the parent drug and are converted into bumetanide in the brain. The feasibility of this strategy was evaluated in mice and rats. RESULTS: Analysis of bumetanide levels in plasma and brain showed that administration of 2 ester prodrugs of bumetanide, the pivaloyloxymethyl (BUM1) and N,N-dimethylaminoethylester (BUM5), resulted in significantly higher brain levels of bumetanide than administration of the parent drug. BUM5, but not BUM1, was less diuretic than bumetanide, so that BUM5 was further evaluated in chronic models of epilepsy in mice and rats. In the pilocarpine model in mice, BUM5, but not bumetanide, counteracted the alteration in seizure threshold during the latent period. In the kindling model in rats, BUM5 was more efficacious than bumetanide in potentiating the anticonvulsant effect of phenobarbital. INTERPRETATION: Our data demonstrate that the goal of designing bumetanide prodrugs that specifically target the brain is feasible and that such drugs may resolve the problems associated with using bumetanide for treatment of neurological disorders.

Foam cell specific LXRα ligand.

OBJECTIVE: The liver X receptor α (LXRα) is a ligand-dependent nuclear receptor and the major regulator of reverse cholesterol transport in macrophages. This makes it an interesting target for mechanistic study and treatment of atherosclerosis. METHODS AND RESULTS: We optimized a promising stilbenoid structure (STX4) in order to reach nanomolar effective concentrations in LXRα reporter-gene assays. STX4 displayed the unique property to activate LXRα effectively but not its subtype LXRß. The potential of STX4 to increase transcriptional activity as an LXRα ligand was tested with gene expression analyses in THP1-derived human macrophages and oxLDL-loaded human foam cells. Only in foam cells but not in macrophage cells STX4 treatment showed athero-protective effects with similar potency as the synthetic LXR ligand T0901317 (T09). Surprisingly, combinatorial treatment with STX4 and T09 resulted in an additive effect on reporter-gene activation and target gene expression. In physiological tests the cellular content of total and esterified cholesterol was significantly reduced by STX4 without the undesirable increase in triglyceride levels as observed for T09. CONCLUSIONS: STX4 is a new LXRα-ligand to study transcriptional regulation of anti-atherogenic processes in cell or ex vivo models, and provides a promising lead structure for pharmaceutical development.

Estrategias de enseñanza para el abordaje de imágenes en anatomía patológica, Facultad de Odontología, Universidad Nacional de Córdoba, Argentina / Strategies of education for the study of images in pathology, School of Dentistry, Universidad Nacional de Córdoba, Argentina

La enseñanza universitaria de las ciencias morfológicas suele presentar dificultades en la comprensión de sus imágenes, dada una aparente limitación de los estudiantes para la percepción eficiente de éstas. Estudios sobre las capacidades y especializaciones cognitivas asimétricas cerebrales, han evidenciado una actividad preponderante del hemisferio derecho en el procesamiento de las formas, colores y en el reconocimiento de sus patrones. Se analizaron las cohortes 1990 a 2004 (Grupo 1) y 2005 a 2009 (Grupo 2) de la asignatura Anatomía Patológica, Cátedra B, Facultad de Odontología de la Universidad Nacional de Córdoba, Argentina. En el Grupo 1 se implementó una metodología de exposición de imágenes en soporte póster y dibujo de las mismas, mientras que el Grupo 2 se aplicaron las técnicas de visualización de Edwards (bloqueo del hemisferio cerebral izquierdo y activación del derecho) modificadas para la exposición de imágenes en soporte guía impresa. Mientras que la estructura lógico-matemática de las preparaciones en el Grupo 1 indujo al estudiante a memorizar una determinada posición de la fotografía ó a desarrollar destrezas no competentes a los contenidos procedimentales de esta asignatura, las técnicas empleadas en el Grupo 2 permitieron potenciar la observación de formas, texturas y colores y las relaciones espaciales entre las estructuras, elementos inherentes a la exploración de imágenes en Anatomía Patológica. Se concluye que el abordaje de imágenes desde esta perspectiva neurobiológica y como estrategia de enseñanza, favorece y estimula el aprendizaje significativo en esta asignatura morfológica.

University education of the morphological sciences presents difficulties in the comprehension of its images because of an apparent limitation of the students to efficiently perceive these images. Studies on the capacities and cognitive asymmetric cerebral specializations, have demonstrated a preponderant activity of the right hemisphere in the processing of forms, colors, and in the recognition of their patterns. The 1990-2009 (Group 1) and 2005-2009 (Group 2) cohorts and B Department of Pathology of the School of Dentistry, National University of Cordoba, Argentina were studied. In Group 1 a methodology was implemented including exhibition and drawing of images in support poster and drawing of the same, whereas in Group 2 the modified Edwards techniques of visualization were applied, (blocking of the cerebral left hemisphere and the activation of the right hemisphere, for the exhibition of images in support printed guide. Whereas the logical mathematical structure of the preparation in Group 1 led the student to memorize a certain position of the photography, or to develop skills unrelated to the procedural contents of this subject, the techniques used in Group 2 allowed the development of observation of forms , textures and colors, and the spatial relations between the structures and elements inherent in the exploration of images in pathology. In conclusion, the discussion of images viewed from this neurobiological perspective and as a strategy of education, favors and stimulates significant learning of this morphological subject.

Método forense para determinar sexo en individuos subadultos usando odontometría de la dentición / Forensic method to determine gender in sub adult subjets using odontometrics in the deciduous dentition

Introducción: por muchos años, los estudios antropológicos de muestras contemporáneas de subadultos han sugerido poco dimorfismo sexual expresado en los patrones morfológicos convencionales. El objetivo fue evaluar el dimorfismo sexual en una muestra de subadultos de la población de la ciudad de Córdoba, Argentina, usando dimensiones de la dentición decidua. Métodos: este artículo describe el dimorfismo dental en una muestra de 98 subadultos con dentición temporal provenientes de la Ciudad de Córdoba, Argentina. Se tomaron las medidas mesiodistal y bucolingual de la dentición temporal y los datos arrojados se procesaron con el índice Weighted Boundary (WB) y análisis discriminante stepwise. Resultados y conclusiones: se propone una técnica alternativa de determinación de sexo usando dentición temporal. Se seleccionaron nueve variables que expresaron diferencias altamente significativas; entre ellas la BL UM1 predice correctamente el sexo masculino en el 90,9% y el femenino en un 93,7% de los casos.

Introduction: for many years, anthropological studies of sub-adult contemporary samples suggest that a low sex dimorphism expressed in morphology patterns exist. The objective was to evaluate the sex dimorphism in a sample of sub adults from Cordoba City, Argentina using dental dimensions in deciduous teeth. Methods: this article describes the dental dimorphism in a sample of 98 sub-adults with deciduous dentition from Córdoba City, Argentina. Mesial -distal and buccal-lingual diameters of the deciduous dentition were taken and the data was analyzed with Weighted Boundary (WB) index and multivariate discriminate stepwise analysis. Results and conclusion: an alternative technique for gender determination using the deciduous dentition is proposed. Nine variables that expressed highly significant differences were selected, among them, BL UM1 correctly predicting male gender in 90.9% and female gender in 93.7% of the cases.

Comparative photophysical investigation of oxygen and sulfur as covalent linkers on octaalkylamino substituted zinc(II) phthalocyanines.

This work describes a systematic comparison of oxygen and sulfur as covalent linkers on octasubstituted zinc(II) phthalocyaninates. Most photophysical parameters that make phthalocyanines technologically relevant, e.g. molar absorption coefficients, fluorescence, triplet and singlet oxygen quantum yields, are essentially unaffected by the substitution. The energy content of the first triplet state was observed to be close to the first singlet state of molecular oxygen for both spacers, as follows from photoacoustic determinations. Nonetheless, a bathochromic shift of 30 nm in the absorption and emission maxima, and of 60 nm in the triplet-triplet absorption spectra were observed when alkyloxyl and alkylsulfanyl moieties were alternatively present. Fluorescence quantum yields proved to be much more sensitive towards aggregation than the absorption spectra. Therefore, a novel fluorescence data analysis provided aggregation parameters and photophysical properties of the monomeric species. It was observed that the tendency towards dimerization is slightly higher with sulfur linkers. These results set a foundation for the rational design of conveniently substituted phthalocyaninates with different connectors between the macrocycle and the side chains.

Esmalte aprismático yuxtadentinario y caries, en dientes permanentes / Yuxta-dentinal aprismatic enamel and caries in permanent teeth

Se describen las características del esmalte aprismático yuxtadentinario, empleando microscopía de transparencia, incidencia y polarización. Su presencia es constante, su espesor uniforme y por setores esfumado, adoptando una configuración estructural particular identificada por la microscopía de polarización y es travesado por laminillas, penachos y husos adamantinos. Su comportamiento ante la progresión de la caries, es similar a una barrera natural, ofreciendo resistencia a la desmineralización cariogénica

Esmalte aprismático yuxtadentinario y caries, en dientes permanentes / Yuxta-dentinal aprismatic enamel and caries in permanent teeth

Se describen las características del esmalte aprismático yuxtadentinario, empleando microscopía de transparencia, incidencia y polarización. Su presencia es constante, su espesor uniforme y por setores esfumado, adoptando una configuración estructural particular identificada por la microscopía de polarización y es travesado por laminillas, penachos y husos adamantinos. Su comportamiento ante la progresión de la caries, es similar a una barrera natural, ofreciendo resistencia a la desmineralización cariogénica (AU)

Esmalte aprismático en surcos de dientes permanentes y caries incipientes / Prismless enamel in grooves from permanent teeth and incipient caries

En 50 dientes permanentes extraídos por diferentes razones, se demuestra la presencia de esmalte aprismático en un 60 por ciento de los mismos, en las vertientes que configuran fosas y surcos oclusales. En un 22 por ciento guardan relación con las estrías de Retzius de los surcos, en forma imbricada, y en un 78 por ciento, la forma laminar. La metodología empleada: microscopía de polarización y microscopía electrónica de barrido (M.E.B.), permiten determinar su aspecto irregular cuando esta zona es afectada por la caries incipiente. Los procesos de pérdida de sales minerales y remineralización se dan principalmente en esta zona

Esmalte aprismático en surcos de dientes permanentes y caries incipientes / Prismless enamel in grooves from permanent teeth and incipient caries

En 50 dientes permanentes extraídos por diferentes razones, se demuestra la presencia de esmalte aprismático en un 60 por ciento de los mismos, en las vertientes que configuran fosas y surcos oclusales. En un 22 por ciento guardan relación con las estrías de Retzius de los surcos, en forma imbricada, y en un 78 por ciento, la forma laminar. La metodología empleada: microscopía de polarización y microscopía electrónica de barrido (M.E.B.), permiten determinar su aspecto irregular cuando esta zona es afectada por la caries incipiente. Los procesos de pérdida de sales minerales y remineralización se dan principalmente en esta zona (AU)

Relación esmalte-cemento y presencia de caries / Relationship between enamel-cementum and caries presence

Choquet describió 4 casos de relaciones entre esmalte y cemento. En este trabajo se estudia en qué porcentaje se encuentran estas relaciones y las probables variaciones individuales y por caras en una misma pieza dentaria. La posibilidad de que la caries guarde alguna vinculación con un determinado caso. Se estudiaron 140 piezas dentarias las que fueron cortadas axialmente buscando que el corte, adecuadamente refrigerado, se oriente por sectores indemnes o sanos. Lectura con lupa de gran aumento en ambos límites cemento-adamantinos, completando las lecturas con otro corte perpendicular sobre los ya realizados. Los cortes, pulimentados, se observaron con lupa y aquellos de importancia diagnóstica fueron desgastados para observar por transparencia. Aquellos fijados en formol al 10 por ciento fueron sometidos a la reacción de PAS para interpretar el cemento PAS positivo y el proceso de descalcificación cariogénica. Se encontró al cemento cubriendo al esmalte en un 23,57 por ciento, al esmalte contactando con cemento en un 35 por ciento, al esmalte y cemento sin contactar en un 39,29 por ciento y al esmalte sobre cemento en un 2,14 por ciento. La caries en estadíos iniciales estuvo presente en un 37 por ciento del total de casos estudiados, iniciándose en cemento (15,20 por ciento), en dentina (9,60 por ciento), en la unión de esmalte y cemento (9,20 por ciento) o en esmalte (2 por ciento). Existieron variaciones individuales y topográficas por pieza dentaria (AU)

Relación esmalte-cemento y presencia de caries / Relationship between enamel-cementum and caries presence

Choquet describió 4 casos de relaciones entre esmalte y cemento. En este trabajo se estudia en qué porcentaje se encuentran estas relaciones y las probables variaciones individuales y por caras en una misma pieza dentaria. La posibilidad de que la caries guarde alguna vinculación con un determinado caso. Se estudiaron 140 piezas dentarias las que fueron cortadas axialmente buscando que el corte, adecuadamente refrigerado, se oriente por sectores indemnes o sanos. Lectura con lupa de gran aumento en ambos límites cemento-adamantinos, completando las lecturas con otro corte perpendicular sobre los ya realizados. Los cortes, pulimentados, se observaron con lupa y aquellos de importancia diagnóstica fueron desgastados para observar por transparencia. Aquellos fijados en formol al 10 por ciento fueron sometidos a la reacción de PAS para interpretar el cemento PAS positivo y el proceso de descalcificación cariogénica. Se encontró al cemento cubriendo al esmalte en un 23,57 por ciento, al esmalte contactando con cemento en un 35 por ciento, al esmalte y cemento sin contactar en un 39,29 por ciento y al esmalte sobre cemento en un 2,14 por ciento. La caries en estadíos iniciales estuvo presente en un 37 por ciento del total de casos estudiados, iniciándose en cemento (15,20 por ciento), en dentina (9,60 por ciento), en la unión de esmalte y cemento (9,20 por ciento) o en esmalte (2 por ciento). Existieron variaciones individuales y topográficas por pieza dentaria