Valutazione di marker diagnostici, epidemiologia e nuove prospettive terapeutiche nell' avvelenamento da rodenticidi anticoagulanti nel cane.

In Medicina Veterinaria l'avvelenamento da rodenticidi anticoagulanti è conosciuto e studiato ormai da anni, essendo una delle intossicazioni più comunemente riscontrate nelle specie non target. In letteratura si rinvengono numerose pubblicazioni ma alcuni aspetti sono rimasti ancora inesplorati.Questo studio si propone di valutare il processo infiammatorio, mediante le proteine di fase acuta (APPs), in corso di fenomeni emorragici, prendendo come modello reale un gruppo di soggetti accidentalmente avvelenati da rodenticidi anticoagulanti. I 102 soggetti avvelenati presentano un valore più elevato di proteina C reattiva (CRP)con una mediana di 4.77 mg/dl statisticamente significativo rispetto alla mediana delle due popolazioni di controllo di pari entità numerica create con cross match di sesso, razza ed età; rispettivamente 0.02 mg/dl dei soggetti sani e 0.37 mg/dl dei soggetti malati di altre patologie. Inoltre all'interno del gruppo dei soggetti avvelenati un valore di CRP elevato all'ammissione può predisporre al decesso. La proteina C reattiva assume quindi un ruolo diagnostico e prognostico in questo avvelenamento. Un'altra finalità, di non inferiore importanza, è quella di definire una linea guida terapeutica con l'ausilio di biomarker coagulativi e di valutare la sicurezza della vitamina K per via endovenosa: in 73 cani, non in terapia con vitamina k, intossicati da rodenticidi anticoagulanti, i tempi della coagulazione (PT ed aPTT) ritornano nel range di normalità dopo 4 ore dalla prima somministrazione di 5 mg/kg di vitamina k per via endovenosa e nessun soggetto durante e dopo il trattamento ha manifestato reazioni anafilattiche, nessuno dei pazienti ha necessitato trasfusione ematica e tutti sono sopravvissuti. Infine si è valutata l'epidemiologia dell'ingestione dei prodotti rodenticidi nella specie oggetto di studio e la determinazione dei principi attivi mediante cromatografia liquida abbinata a spettrofotometria di massa (UPLC-MS/MS).

Expression of cartilage-related genes in bovine synovial tissue

The synovium contains mesenchymal stem cells with chondrogenic potential. Although synovial and articular cartilage tissue develop from a common pool of mesenchymal cells, little is known about their genetic commonalities. In the present study, the mRNA levels for several cartilage-related proteins, namely, cartilage oligomeric matrix protein (COMP), Sox9, aggrecan, and collagen types I, II, IX, X, and XI, were measured using the real-time polymerase chain reaction. Our data reveal the synovium of calf metacarpal joints to physiologically express not only type I collagen but also COMP, Sox9, aggrecan, and collagen types X and XI. The mRNA levels for the latter five proteins lie between 2% and 15% of those in articular cartilage. We speculate that these genes are being expressed by chondroprogenitor cells, whose presence in the synovium reflects a common ontogenetic phase in the fetal development of this tissue and of articular cartilage.

Variability between laboratories performing coagulation tests with identical platforms: a nationwide evaluation study.

BACKGROUND While the assessment of analytical precision within medical laboratories has received much attention in scientific enquiry, the degree of as well as the sources causing variation between them remains incompletely understood. In this study, we quantified the variance components when performing coagulation tests with identical analytical platforms in different laboratories and computed intraclass correlations coefficients (ICC) for each coagulation test. METHODS Data from eight laboratories measuring fibrinogen twice in twenty healthy subjects with one out of 3 different platforms and single measurements of prothrombin time (PT), and coagulation factors II, V, VII, VIII, IX, X, XI and XIII were analysed. By platform, the variance components of (i) the subjects, (ii) the laboratory and the technician and (iii) the total variance were obtained for fibrinogen as well as (i) and (iii) for the remaining factors using ANOVA. RESULTS The variability for fibrinogen measurements within a laboratory ranged from 0.02 to 0.04, the variability between laboratories ranged from 0.006 to 0.097. The ICC for fibrinogen ranged from 0.37 to 0.66 and from 0.19 to 0.80 for PT between the platforms. For the remaining factors the ICC's ranged from 0.04 (FII) to 0.93 (FVIII). CONCLUSIONS Variance components that could be attributed to technicians or laboratory procedures were substantial, led to disappointingly low intraclass correlation coefficients for several factors and were pronounced for some of the platforms. Our findings call for sustained efforts to raise the level of standardization of structures and procedures involved in the quantification of coagulation factors.

Micro-granulometry of sedimentary dykes, Kathmandu basin, Nepal

Soft-sediment deformation structures have been analyzed at six sites of the Kathmandu valley. Microgranulometric study (this Supplement and Fig. 3B of Mugnier et al., Tectonophysics, 2011) reveals that silty levels (60 to 80% silt) favor the development of soft-sediment deformation structures, while sandy levels (60 to 80% sand) are passively deformed. Nonetheless well sorted sand levels (more than 80% sand) generate over-fluid pressure during compaction if located beneath a silty cap, leading to fluidization and dike development. 3-D geometry of seismites indicates a very strong horizontal shearing during their development. Using a physical approach based on soil liquefaction during horizontal acceleration, we show that the fluidization zone progressively grows down-section during the shaking, but does not exactly begin at the surface. The comparison of bed-thickness and strength/depth evolution indicates three cases: i) no soft-sediment deformation occurs for thin (few centimeters) silty beds; ii) the thickness of soft-sediment deformation above sandy beds is controlled by the lithological contrast; iii) the thickness of soft-sediment deformation depends on the shaking intensity for very thick silty beds. These 3 cases are evidenced in the Kathmandu basin. We use the 30 cm-thick soft-sediment deformation level formed during the 1833 earthquake as a reference: the 1833 earthquake rupture zone extended very close to Kathmandu, inducing there MMI IX-X damages. A 90 cm-thick sediment deformation has therefore to be induced by an event greater than MMI X. From a compilation of paleo and historic seismology studies, it is found that the great (M ~ 8.1) historical earthquakes are not characteristic of the greatest earthquakes of Himalaya; hence earthquakes greater than M ~ 8.6 occurred. Kathmandu is located above one of the asperities that laterally limits the extent of mega-earthquake ruptures and two successive catastrophic events already affected Kathmandu, in 1255 located to the west of this asperity and in ~ 1100 to the east.

Composition of sediments and cores from DSDP Legs 54 and 61-63

The monograph gives results of studies of sediments and rocks collected from D/S Glomar Challenger in the Pacific Ocean. These studies have been based on the lithological facial analysis applied for the first time for identificating genesis of ocean sediments. These results include new ideas on formation of the Earth's sedimentary cover and can be used for constructing regional and global schemes of ocean paleogeography, reconstructing some structures, correlating sedimentation on continents and in oceans, estimating perspectives of oil- and gas-bearing deposits and ore formation. The monograph also gives the first petrographic classification of organic matter in black shales.

Las estructuras

La afirmación de que las primeras realizaciones arquitectónicas y de ingeniería estructural son tan antiguas como la civilización no es gratuita. En efecto, tan pronto como se desea cubrir un espacio, salvar un vano o transmitir un empuje (vertical u horizontal), es preciso el desarrollo de un conocimiento específico. El dominio de las técnicas para resolver,en particular, tales problemas ha sido transmitido a través de construcciones religiosas o áulicas que han permanecido a través de los siglos como puntos de referencia y muestra de la habilidad, el ingenio y la audacia de las generaciones predecesoras. Obras como el puente de Alcántara (Cáceres), la mezquita de Córdoba y el monasterio de El Escorial (Madrid) -de los siglos I, X y XVI, respectivamente- demuestran la personalidad de sus proyectistas pero también sus conocimientos constructivos, su capacidad organizadora y la ambición y poderío económico de sus promotores. De hecho, aunque la habilidad para combinar mecanismos estructurales se encuentra en todos los artefactos manejados por el hombre, es en el ámbito de la edificación y de las obras públicas donde, hasta épocas relativamente recientes, se encuentran los ejemplos más espectaculares de estructuras resistentes. Éstos sólo aparecen, sin embargo, cuando coincide la calidad de cada uno de los tres factores que intervienen en la obra, es decir, un proyectista con imaginación y conocimientos, una industria de la construcción capaz de ofrecerle los materiales más adecuados y de llevar a cabo los procesos constructivos que aquél imagine, y un promotor con solvencia económica pero también capaz de calibrar las ventajas de las soluciones que se ofrecen y apreciar factores imponderables como la innovación o la estética, que tanto añaden al cumplimiento de los factores utilitarios que se encuentran en la motivación de las construcciones. A lo largo de la historia los proyectistas españoles han dado pruebas de calidad en algunas realizaciones que se comentarán a continuación y siempre han demostrado un buen conocimiento del estado del arte en el exterior.Sin embargo, no puede decirse que ése haya sido el caso de los promotores o de la industria que, por uno u otro motivo, se ha visto muy afectada por avatares políticos o decisiones económicas equivocadas. Las quejas de Pablo Alzola sobre el "espíritu cosmopolita con que abrimos nuestras puertas a quienes nos las cierran herméticamente", el cual, en el siglo XIX, facilitó las franquicias a la importación de materiales relacionados con la industria ferroviaria, condenando esta importación "a muerte el porvenir de la industria española de hierro y acero, base muy principal de prosperidad en todas las naciones juntas", resuenan de nuevo en relación con la integración europea. Ello se explica por la tendencia general hacia el rendimiento inmediato de las capitales con la consiguiente destecnificación propia y penetración de productos extranjeros conseguidos mediante una investigación coordinada entre administración, industria y universidad. La falta de grupos organizados, de lo que es una interesante excepción la industria del hormigón, ha provocado en muchos ámbitos una ausencia de legislación propia que la industria nacional actualmente echa en falta como defensa específica en términos técnicos.

Defects in embryonic hindbrain development and fetal resorption resulting from vitamin A deficiency in the rat are prevented by feeding pharmacological levels of all-trans-retinoic acid

Vitamin A is required for reproduction and normal embryonic development. We have determined that all-trans-retinoic acid (atRA) can support development of the mammalian embryo to parturition in vitamin A-deficient (VAD) rats. At embryonic day (E) 0.5, VAD dams were fed purified diets containing either 12 μg of atRA per g of diet (230 μg per rat per day) or 250 μg of atRA per g of diet (4.5 mg per rat per day) or were fed the purified diet supplemented with a source of retinol (100 units of retinyl palmitate per day). An additional group was fed both 250 μg of atRA per g of diet in combination with retinyl palmitate. Embryonic survival to E12.5 was similar for all groups. However, embryonic development in the group fed 12 μg of atRA per g of diet was grossly abnormal. The most notable defects were in the region of the hindbrain, which included a loss of posterior cranial nerves (IX, X, XI, and XII) and postotic pharyngeal arches as well as the presence of ectopic otic vesicles and a swollen anterior cardinal vein. All embryonic abnormalities at E12.5 were prevented by feeding pharmacological amounts of atRA (250 μg/g diet) or by supplementation with retinyl palmitate. Embryos from VAD dams receiving 12 μg of atRA per g of diet were resorbed by E18.5, whereas those in the group fed 250 μg of atRA per g of diet survived to parturition but died shortly thereafter. Equivalent results were obtained by using commercial grade atRA or atRA that had been purified to eliminate any potential contamination by neutral retinoids, such as retinol. Thus, 250 μg of atRA per g of diet fed to VAD dams (≈4.5 mg per rat per day) can prevent the death of embryos at midgestation and prevents the early embryonic abnormalities that arise when VAD dams are fed insufficient amounts of atRA.

Demonstration of the extrinsic coagulation pathway in teleostei: Identification of zebrafish coagulation factor VII

It is not known whether the mammalian mechanism of coagulation initiation is conserved in fish. Identification of factor VII is critical in providing evidence for such a mechanism. A cDNA was cloned from a zebrafish (teleost) library that predicted a protein with sequence similarity to human factor VII. Factor VII was shown to be present in zebrafish blood and liver by Western blot analysis and immunohistochemistry. Immunodepletion of factor VII from zebrafish plasma selectively inhibited thromboplastin-triggered thrombin generation. Heterologous expression of zebrafish factor VII demonstrated a secreted protein (50 kDa) that reconstituted thromboplastin-triggered thrombin generation in immunodepleted zebrafish plasma. These results suggest conservation of the extrinsic coagulation pathway between zebrafish and humans and add credence to the zebrafish as a model for mammalian hemostasis. The structure of zebrafish factor VIIa predicted by homology modeling was consistent with the overall three-dimensional structure of human factor VIIa. However, amino acid disparities were found in the epidermal growth factor-2/serine protease regions that are present in the human tissue factor–factor VIIa contact surface, suggesting a structural basis for the species specificity of this interaction. In addition, zebrafish factor VII demonstrates that the Gla-EGF-EGF-SP domain structure, which is common to coagulation factors VII, IX, X, and protein C, was present before the radiation of the teleosts from the tetrapods. Identification of zebrafish factor VII significantly narrows the evolutionary window for development of the vertebrate coagulation cascade and provides insight into the structural basis for species specificity in the tissue factor–factor VIIa interaction.

Una nueva rábita en la playa de Guardamar del Segura: la rábita de El Moncayo

Se publican las noticias que ha arrojado la excavación en 2004 de unos muros situados en la denominada playa de El Moncayo. Los hallazgos se sitúan a unos 3 kilómetros al Sur del casco urbano de Guardamar del Segura; a unos 135 m. en dirección Norte está la Torre del Descargador (torre almenara de los siglos IV/X y V/XI), a unos 3,5 kilómetros se localiza El Castillo de Guardamar (de los siglos VIII a.C. al XIX) y, un poco más al Norte, a unos 4 kilómetros, en las proximidades de la desembocadura del Segura, los oratorios o rábitas de las dunas de Guardamar. Se dan a conocer los restos arquitectónicos y cerámicos aparecidos en la excavación del 2004 que se interpretan como de restos del recinto de una rábita o mezquitilla (cuando se excave más se verá si está aislada o hay más edificios similares), se presentan unos apuntes al hilo de la orientación de la rábita de El Moncayo y un estudio de la moneda andalusí hallada en la excavación de El Moncayo (datables entre en 429/1037-8 y 433/1041-2).

L’assentament ibèric del Cabeçó de Mariola (Alfafara, Alacant; Bocairent, València): plantejaments i primers resultats de la recerca

S’hi presenten les recerques realitzades a l’assentament fortificat ibèric del Cabeçó de Mariola (Alfafara, Alacant; Bocairent, València). S’hi han realitzat prospeccions superficials, geofísica i sondejos arqueològics assistits amb tecnologies geoespacials, a més de la inserció del lloc en el seu entorn territorial mitjançant els SIG. Els resultats mostren una àmplia seqüència d’ocupació, datada entre els segles IX i I aC, d’un important centre fortificat que controla un pas estratègic per a les comunicacions comarcals. Durant el període Ibèric tardà, en els segles II-I, presenta una intensa reestructuració de l’habitatge i les fortificacions que acabarà amb una violenta destrucció en el primer terç del s. I aC.

Papyri in the Princeton University collections.

Vol. II, edited with notes by Edmund Harris Kase.

Die ältere Romantik und die Kunst des jungen Goethe /

Appeared also as author's inaugural dissertation, Marburg.

Anna Karenina,

Translated by Rochelle S. Townsend.

Effective speech, including public speaking, mental training and the development of personality /

v. 1. Manual I-II. -- v. 2. Manual III-IV. -- v. 3. Manual V-VI. -- v. 4. Manual VII-VIII. -- v. 5. Manual IX-X. -- v. 6. Manual XI-XII.