Role of magnetic resonance in characterising extrahepatic cholangiocarcinomas

PURPOSE: The purpose of this study was to evaluate the accuracy of magnetic resonance (MR) in correctly locating and characterising biliary strictures in patients affected by extrahepatic cholangiocarcinoma, identify findings suggestive of the disease, identify lesions with similar MR features and possible criteria for differential diagnosis and establish prospective MR accuracy in diagnosis of malignant obstruction of extrahepatic bile ducts. MATERIALS AND METHODS: We retrospectively reviewed the MR examinations of 39 patients affected by extrahepatic cholangiocarcinoma confirmed by histology or cytology. The studies were evaluated for the following parameters: site of obstruction (hilar, proximal or distal), presence of intra- or extrahepatic dilation of bile ducts, morphology of ductal stenosis (gradual tapering or abrupt ending), morphology of the lesion (mass like or circumferential), dimension, signal intensity before contrast medium administration and lesion enhancement after administration of contrast medium. Finally, we assessed the most useful sequence for the diagnosis. In order to evaluate MR accuracy in the diagnosis of malignant obstruction of extrahepatic bile ducts, we prospectively reviewed MR examinations of 74 patients affected by obstructive jaundice (55 malignant lesions and 19 inflammatory lesions). MR diagnosis was compared with histology or cytology considered as the gold standard. RESULTS: MR allowed identification and localisation of 41/41 extrahepatic cholangiocarcinomas. Fifty-four percent of the lesions showed gradual duct tapering; the remaining lesions showed an abrupt ending. Fifty-six percent of the lesions appeared as a circumferential thickening (infiltrative growth); the remaining lesions had a mass-like appearance (expansile growth). Most lesions were hypo- (49%) or isointense (49%) in T1-weighted sequences and hyper- (49%) or isointense (51%) in T2-weighted sequences. Ninety-five percent of the lesions did not enhance significantly in the arterial phase while 98% showed late enhancement (10 min). The most diagnostic sequence (in 76% of cases) was the late-phase gradient-echo (GRE) T1 fat-saturated sequence. MR had good sensitivity (91%) but poor specificity (47%) in characterising stenosis as malignant, given the large number (10/19) of benign lesions evaluated as neoplastic lesions. CONCLUSIONS: MR almost always identified the cause of stenosis and suggested its neoplastic nature if it exhibited a mass-like appearance (extraductal or growing into the choledochus). On the other hand, lesions with parietal thickening, particularly if smaller than 1 cm, require endoscopic cytology or histology because of the high risk of unnecessary procedures for benign lesions

Examination of the Effects of Heterogeneous Organization of RyR Clusters, Myofibrils and Mitochondria on Ca2+ Release Patterns in Cardiomyocytes

Spatio-temporal dynamics of intracellular calcium, [Ca2+]i, regulate the contractile function of cardiac muscle cells. Measuring [Ca2+]i flux is central to the study of mechanisms that underlie both normal cardiac function and calcium-dependent etiologies in heart disease. However, current imaging techniques are limited in the spatial resolution to which changes in [Ca2+]i can be detected. Using spatial point process statistics techniques we developed a novel method to simulate the spatial distribution of RyR clusters, which act as the major mediators of contractile Ca2+ release, upon a physiologically-realistic cellular landscape composed of tightly-packed mitochondria and myofibrils.We applied this method to computationally combine confocal-scale (~ 200 nm) data of RyR clusters with 3D electron microscopy data (~ 30 nm) of myofibrils and mitochondria, both collected from adult rat left ventricular myocytes. Using this hybrid-scale spatial model, we simulated reaction-diffusion of [Ca2+]i during the rising phase of the transient (first 30 ms after initiation). At 30 ms, the average peak of the simulated [Ca2+]i transient and of the simulated fluorescence intensity signal, F/F0, reached values similar to that found in the literature ([Ca2+]i 1 μM; F/F0 5.5). However, our model predicted the variation in [Ca2+]i to be between 0.3 and 12.7 μM (~3 to 100 fold from resting value of 0.1 μM) and the corresponding F/F0 signal ranging from 3 to 9.5. We demonstrate in this study that: (i) heterogeneities in the [Ca2+]i transient are due not only to heterogeneous distribution and clustering of mitochondria; (ii) but also to heterogeneous local densities of RyR clusters. Further, we show that: (iii) these structureinduced heterogeneities in [Ca2+]i can appear in line scan data. Finally, using our unique method for generating RyR cluster distributions, we demonstrate the robustness in the [Ca2+]i transient to differences in RyR cluster distributions measured between rat and human cardiomyocytes

Transverse tubule remodelling: a cellular pathology driven by both sides of the plasmalemma?

Transverse (t)-tubules are invaginations of the plasma membrane that form a complex network of ducts, 200–400 nm in diameter depending on the animal species, that penetrates deep within the cardiac myocyte, where they facilitate a fast and synchronous contraction across the entire cell volume. There is now a large body of evidence in animal models and humans demonstrating that pathological distortion of the t-tubule structure has a causative role in the loss of myocyte contractility that underpins many forms of heart failure. Investigations into the molecular mechanisms of pathological t-tubule remodelling to date have focused on proteins residing in the intracellular aspect of t-tubule membrane that form linkages between the membrane and myocyte cytoskeleton. In this review, we shed light on the mechanisms of t-tubule remodelling which are not limited to the intracellular side. Our recent data have demonstrated that collagen is an integral part of the t-tubule network and that it increases within the tubules in heart failure, suggesting that a fibrotic mechanism could drive cardiac junctional remodelling. We examine the evidence that the linkages between the extracellular matrix, t-tubule membrane and cellular cytoskeleton should be considered as a whole when investigating the mechanisms of t-tubule pathology in the failing heart

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

3D Respiratory Triggered MRCP versus conventional MRCP in the evaluation of branch duct intraductal mucinous papillary tumors

ORAL COMMUNICATION

Three Dimensional Respiratory Triggered MRCP versus Conventional MRCP in the Evaluation of Branch Duct IPMTs

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Three-dimensional MRCP with respiratory triggering versus conventional MRCP in the evaluation of IPMT of the collateral branches

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Ceramic films on cast iron for high temperature treatments.

The research aims the deposition of low thickness ceramic films on the surface of cast iron forms that are used for recycled Pb moulding. The films will establish a thermal insulating coating to delate the metal solidification for a short time in order to complete an unforced mechanical scorification. Moreover the bars will assume a more uniform and market acceptable surface. The thermal conductivities of the cast iron (Meehanite HE type) and the ceramic material are 55 W/m°C and 2.2 W/m°C respectively. High temperature ceramic coating not suited to thin film production so the sol gel process seems appropriate to homogeneously apply a mixture of metal oxides at low temperature. To avoid the film shrinkage due to the phase evolution of the inorganic components, at first, we prepared the inorganic oxide mixture by the conventional frit manufacturing process; the mixture was homogenized in a water suspension, dried and melted at temperature between 1000 and 1200°C. Then the glass was quenched in air or poured in water; after it was milled and sieved at 325 mesh (< 40 µm). The powder was added to the sol-gel acid mixture (hydrolysis step) prepared from tetralkylalkoxysilanes, and applied on the cast iron surface by dipping, spraying or spreading with a blade. The cast iron surface was prepared by alternate washings with acids and bases followed by drying. To improve the adhesion largely influenced by the differences between the thermal expansion properties of the substrate and the film (the CTE, linear is 13.0 µm/m-°C for the cast iron and 2-5 µm/m-°C for the ceramic film) and corrosion resistance, the surface was treated with an activating agent like fluoro-metal acid (metal = Zr, Si) before the sol-gel colloid application. Thermal treatment at temperature between 750 and 930°C were adopted and the film evolution was investigated by SEM. The frits were characterized by XRD analysis checking the influence of annealing temperature on the film structure and the phase evolution was investigated, so as to obtain films with superior performance. GDOES analysis was used to characterized the film composition. The thickness was 100-150 µm with an adhesion value measured with the ASTM 3359-02 method of about 2B-3B probably due to an high hardness characteristic. More investigation on the metal oxide mixture and film properties are in course

Hybrid film: a case analysis of the sol-gel technology for improved mechanical properties application.

The paper deals with the analysis of the mechanical characteristics of hybrid coating obtained through the sol-gel synthesis starting from CH3Si(OCH3)3 and C6H5Si(OCH3)3 with colloidal silica, α-Al2O3, and HNO3 as catalyst. The experimental conditions refer to a not-optimized reaction parameters trying to obtain a greater sensibility on their variations. On the base of the kinetic reaction pathway the surface morphology, analysed by SEM, the hardness, the abrasion, the film porosity and the contact angles, are interpreted. Indeed the temperature appears a relevant parameter in the control of the surface aspect and the mechanical behaviour. The roles of the colloidal silica and of the nanometric α-Al2O3 were analysed. The results demonstrate the strong enclosing of the silica particle in the hybrid polymer network. On the contrary α-Al2O3 decreases the abrasion resistance due to the lack of chemical bonds with the network

Imaging pesato in diffusione nello studio dell\u2019addome: possibili applicazioni cliniche

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