Study of Coronary Flow Reserve with Intravenous Use of Microbubbles (Contrast Echocardiography) and Adenosine: Protocol for Clinical Application in Patients Suspected of Having Coronary Heart Disease

OBJECTIVE: To test the feasibility, safety and accuracy of the adenosine protocol in the study of myocardial perfusion with microbubbles contrast echocardiography. METHODS: 81 pts (64 male, 60+11 years) were submitted to contrast echocardiography with PESDA (sonicated solution of albumin 20%-1ml, dextrose 5%-12ml and deca-fluorobutane gas-8ml) to study the myocardial perfusion at rest and after bolus injection of adenosine (6 to 18mg) and to coronary angiography within 1 month each other. For each patient 3 left ventricle perfusion beds were considered (total of 243 territories). 208 territories were analyzed and 35 territories were excluded. PESDA was continuously infused (1-2ml/min), titrated for best myocardial contrast. Triggered (1:1) second harmonic imaging was used. RESULTS: Coronary angiography showed 70 flow limiting (> 75%) lesions and 138 no flow limiting lesions. At rest an obvious myocardium contrast enhancement was seen in at least 1 segment of a territory in all patients. After adenosine injection an unquestionable further increase in myocardial contrast was observed in 136 territories (99%) related to no flow limiting lesions, lasting < 10 s, and a myocardial perfusion defect was detected in 68 territories (97%) related to flow limiting lesions. It was observed only 4 false results. There were no serious complications. CONCLUSION: Myocardial perfusion study with PESDA and adenosine protocol is a practical, safe and accurate method to analyze the coronary flow reserve.

The Irish pub as a third place : a sociological exploration of people, place and identity

There is considerable interest in alcohol in Irish society, yet minimal sociologcial understanding of its consumption, particularly of the sites where most drinking occurs: the country's 8750 pubs. Despite widespread public discussions on the role of the pub, there is scant social science evidence to better inform debate. Pubs are central to Irish community and are key sites of social interaction. American sociologist Ray Oldenburg has argued that "third places" (neither workplace nor home) are crucial to the maintenance of the community and the enhancement of social capital. According to Oldenburg, the role of the third place in the community is to provide continuity, regularity, a sense of place - all of which conceptually contribute to the construction of the self, the projection of the self within the public sphere, the distribution of social capital and the generation of a collective identity. The pub is the archetypal third place, but Oldenburg is concerned that modern pubs are less able to provide this vital function. Social scientists have suggested that community is in a state of fragmentation and decline due to changes in modes of social interaction and a decrease in shared spaces, resulting in a weakened connection to place. Community without propinquity has been characterised by social alienation, fragmentation and what Oldenburg refers to as the "problem of place" (13). Third places, and thus the Irish pub, have been particularly affected. In order to increase the sociological knowledge of the pub in Ireland, this project critically engages with the pub to assess the importance that public drinking houses have in the everyday. Moreover, this research sets out to investigate the people/place relationship using the pub as an investigative lens and examine the ways in which people shape place, place shapes people and how that relationship is implicated in the construction of irish identities. Furthermore, this is also an articulation of a cultural shift within Ireland and Irish places whose effects are deep and multi-layered. This project aims to explore the development of the contemporary geography of identity as the irish pub as a third place is transformed or disappears from the social landscape.

Einfluss der Mikrokonvektion auf Selektivität und Stofftransport während der Verdunstung binärer Flüssigkeiten aus porösen Schichten

Interfacial convection, enhancement of mass transfer, packed beds, evaporation, selectivity

Prognostic Value of Pulmonary Vascular Resistance by Magnetic Resonance in Systolic Heart Failure

Abstract Background: Pulmonary hypertension is associated with poor prognosis in heart failure. However, non-invasive diagnosis is still challenging in clinical practice. Objective: We sought to assess the prognostic utility of non-invasive estimation of pulmonary vascular resistances (PVR) by cardiovascular magnetic resonance to predict adverse cardiovascular outcomes in heart failure with reduced ejection fraction (HFrEF). Methods: Prospective registry of patients with left ventricular ejection fraction (LVEF) < 40% and recently admitted for decompensated heart failure during three years. PVRwere calculated based on right ventricular ejection fraction and average velocity of the pulmonary artery estimated during cardiac magnetic resonance. Readmission for heart failure and all-cause mortality were considered as adverse events at follow-up. Results: 105 patients (average LVEF 26.0 ±7.7%, ischemic etiology 43%) were included. Patients with adverse events at long-term follow-up had higher values of PVR (6.93 ± 1.9 vs. 4.6 ± 1.7estimated Wood Units (eWu), p < 0.001). In multivariate Cox regression analysis, PVR ≥ 5 eWu(cutoff value according to ROC curve) was independently associated with increased risk of adverse events at 9 months follow-up (HR2.98; 95% CI 1.12-7.88; p < 0.03). Conclusions: In patients with HFrEF, the presence of PVR ≥ 5.0 Wu is associated with significantly worse clinical outcome at follow-up. Non-invasive estimation of PVR by cardiac magnetic resonance might be useful for risk stratification in HFrEF, irrespective of etiology, presence of late gadolinium enhancement or LVEF.

Weak systems of Gandy, Jensen and Devlin

In Part I, we formulate and examine some systems that have arisen in the study of the constructible hierarchy; we find numerous transitive models for them, among which are supertransitive models containing all ordinals that show that Devlin's system BS lies strictly between Gandy's systems PZ and BST'; and we use our models to show that BS fails to handle even the simplest rudimentary functions, and is thus inadequate for the use intended for it in Devlin's treatise. In Part II we propose and study an enhancement of the underlying logic of these systems, build further models to show where the previous hierarchy of systems is preserved by our enhancement; and consider three systems that might serve for Devlin's purposes: one the enhancement of a version of BS, one a formulation of Gandy-Jensen set theory, and the third a subsystem common to those two. In Part III we give new proofs of results of Boffa by constructing three models in which, respectively, TCo, AxPair and AxSing fail; we give some sufficient conditions for a set not to belong to the rudimentary closure of another set, and thus answer a question of McAloon; and we comment on Gandy's numerals and correct and sharpen other of his observations.

Propietats d'absorció bifotònica del tetrafenilporficè i el seu complex de palladi: potencials sensibilitzadors per a Teràpia Fotodinàmica bifotònica.

Estudi elaborat a partir d’una estada a la Universitat de Aarhus, Dinamarca, durant juliol 2006. En el present treball s’investiguen, per primer cop, les propietats de absorció bifotòniques del fotosensibilitzador 2,7,12,17-tetrafenilporficè (TPPo) i del seu complex de pal•ladi (II) (PdTPPo). Ambos compostos han rebut molta atenció com a possibles otosensibilitzadors per a Teràpia Fotodinàmica (TFD). S’utilitza la detecció de la fosforescència de l’oxigen singlet, centrada a 1270 nm i produïda per l’absorció de dos fotons, per quantificar la magnitud de la secció d’absorció bifotònica, "delta", dels porficèns estudiats. Els experiments se han dut a terme en el marge espectral 750-850 nm i a l’infraroig proper a 1100nm. Aquestes longituds d’ona corresponen a les zones d’absorció bifotònica en les bandes de Soret i Q. Les propietats bifotòniques obtingudes es comparen i contrasten amb les dades conegudes de la tetrafenilporfirina (TPP), isòmer estructural del tetrafenilporficè però amb més gran simetria, i es troba que en la banda de Soret (que coincideix amb la regió de la pell més transparent) els valors de delta per el TPPo i PdTPPo son aproximadament 2000 GM en el màxim, pràcticament cent vegades més grans que per la TPP. A més a més, aquestos valors son dos ordres de magnitud més grans que els obtinguts a l’irradiar a 1100 nm (bandes Q). Aquestes observacions es poden explicar mitjançant la amplificació per ressonància deguda a la presència de transicions monofotòniques ressonants en la regió de les bandes Q. Els elevats valors de "delta" obtinguts per els tetrafenilporficèns estudiats junt a les principals característiques que aquestos presenten (elevat rendiment de formació d’oxigen singlet, estabilitat química i fotoquímica, absència de citotoxicitat,...) qualifiquen al TPPo y PdTPPo com a possibles fotosensibilitzadors per a Teràpia Fotodinàmica Bifotònica.

Evolution of sarcoma 180 in mice treated with hyperchlorinated water

Mice treated with hyperchlorinated water (50 ppm of chlorine) and control mice, drinking tap water (1-3 ppm of chlorine) were inoculated with 2.5 x 10 [raised to the power of 6] sarcoma 180 cells, by intraperitoneal route. Tumor evolution was measured by enumeration of tumor cells in peritoneal cavity and by evaluation of weight gain at different time intervals after tumor implantation. In mice treated with excessive amounts of chlorine there was enhancement of tumor growth demonstrated by: (a) shorter incubation period and increased weight gain (ascites formation) after tumor implantation; (b) increased number of tumor cells in the peritoneal cavity 2, 3 and 4 days after tumor challenge. The number of peritoneal cells exsudated after tumor implantation was lower in mice treated with hyperchlorinated water than in controls. The tumor enhancement observed after excessive chlorine ingestion would be due to: (a) reduction of the number of peritoneal macrophages that migrate to the peritoneal cavity and (b) reduction of the tumoricidal capacity of peritonela macrophages induced by the direct effect of chlorine or by the reduction of the amount of endogenous endotoxins due to the bactericidal effect of chlorine.

Glucose-dependent insulinotropic polypeptide receptor deficiency leads to modifications of trabecular bone volume and quality in mice.

A role for the gastro-intestinal tract in controlling bone remodeling is suspected since serum levels of bone remodeling markers are affected rapidly after a meal. Glucose-dependent insulinotropic polypeptide (GIP) represents a suitable candidate in mediating this effect. The aim of the present study was to investigate the effect of total inhibition of GIP signaling on trabecular bone volume, microarchitecture and quality. We used GIP receptor (GIPR) knockout mice and investigated trabecular bone volume and microarchitecture by microCT and histomorphometry. GIPR-deficient animals at 16 weeks of age presented with a significant (20%) increase in trabecular bone mass accompanied by an increase (17%) in trabecular number. In addition, the number of osteoclasts and bone formation rate was significantly reduced and augmented, respectively in these animals when compared with wild-type littermates. These modifications of trabecular bone microarchitecture are linked to a remodeling in the expression pattern of adipokines in the GIPR-deficient mice. On the other hand, despite significant enhancement in bone volume, intrinsic mechanical properties of the bone matrix was reduced as well as the distribution of bone mineral density and the ratio of mature/immature collagen cross-links. Taken together, these results indicate an increase in trabecular bone volume in GIPR KO animals associated with a reduction in bone quality.

High-resolution magnetic resonance imaging quantitatively detects individual pancreatic islets.

OBJECTIVE-We studied whether manganese-enhanced high-field magnetic resonance (MR) imaging (MEHFMRI) could quantitatively detect individual islets in situ and in vivo and evaluate changes in a model of experimental diabetes.RESEARCH DESIGN AND METHODS-Whole pancreata from untreated (n = 3), MnCl(2) and glucose-injected mice (n = 6), and mice injected with either streptozotocin (STZ; n = 4) or citrate buffer (n = 4) were imaged ex vivo for unambiguous evaluation of islets. Exteriorized pancreata of MnCl(2) and glucose-injected mice (n = 6) were imaged in vivo to directly visualize the gland and minimize movements. In all cases, MR images were acquired in a 14.1 Testa scanner and correlated with the corresponding (immuno)histological sections.RESULTS-In ex vivo experiments, MEHFMRI distinguished different pancreatic tissues and evaluated the relative abundance of islets in the pancreata of normoglycemic mice. MEHFMRI also detected a significant decrease in the numerical and volume density of islets in STZ-injected mice. However, in the latter measurements the loss of beta-cells was undervalued under the conditions tested. The experiments on the externalized pancreata confirmed that MEHFMRI could visualize native individual islets in living, anesthetized mice.CONCLUSIONS-Data show that MEHFMRI quantitatively visualizes individual islets in the intact mouse pancreas, both ex vivo and in vivo. Diabetes 60:2853-2860, 2011

Ultra high performance supercritical fluid chromatography coupled with tandem mass spectrometry for screening of doping agents. II: Analysis of biological samples.

The potential and applicability of UHPSFC-MS/MS for anti-doping screening in urine samples were tested for the first time. For this purpose, a group of 110 doping agents with diverse physicochemical properties was analyzed using two separation techniques, namely UHPLC-MS/MS and UHPSFC-MS/MS in both ESI+ and ESI- modes. The two approaches were compared in terms of selectivity, sensitivity, linearity and matrix effects. As expected, very diverse retentions and selectivities were obtained in UHPLC and UHPSFC, proving a good complementarity of these analytical strategies. In both conditions, acceptable peak shapes and MS detection capabilities were obtained within 7min analysis time, enabling the application of these two methods for screening purposes. Method sensitivity was found comparable for 46% of tested compounds, while higher sensitivity was observed for 21% of tested compounds in UHPLC-MS/MS and for 32% in UHPSFC-MS/MS. The latter demonstrated a lower susceptibility to matrix effects, which were mostly observed as signal suppression. In the case of UHPLC-MS/MS, more serious matrix effects were observed, leading typically to signal enhancement and the matrix effect was also concentration dependent, i.e., more significant matrix effects occurred at the lowest concentrations.

A review of achievements of the national schistosomiasis control program in middle and upper Egypt areas

In Egypt the "national schistosomiasis control program" was formulated to control transmission by reduction of prevalence and intensity of current infections, and thereby achieve an acceptable level of schistosomiasis disease control. The program was implemented foremost in Middle Egypt (1977) and Upper Egypt (1980), collectively extending 800 km alongside of the River Nile and accommodate about 10.5 million people. Schistosoma haematobium has been essentially the prevailing species infection in both areas. The strategy of control entailed both area-wide mollusciciding with niclosamide, and selective population chemotherapy with metrifonate. Evaluation in 1986 showed that prevalence dropped from pre-control 29.4% in Middle Egypt and 26.3% in Upper Egypt to 6% and 7.8% respectively, together with a remarkable drop of infections among children. Also mean intensity attained low levels consistent of low grade infections. It is evident therefore that in these areas where an enhancement of schistosomiasis infections had been anticipated the employment of the twofold strategy effected a state of low-prevalence/low-intensity signifying a lowered reservoir of infection and a substantial interference with the potentials of transmission.

Setting boundaries: brain dynamics of modal and amodal illusory shape completion in humans.

Normal visual perception requires differentiating foreground from background objects. Differences in physical attributes sometimes determine this relationship. Often such differences must instead be inferred, as when two objects or their parts have the same luminance. Modal completion refers to such perceptual "filling-in" of object borders that are accompanied by concurrent brightness enhancement, in turn termed illusory contours (ICs). Amodal completion is filling-in without concurrent brightness enhancement. Presently there are controversies regarding whether both completion processes use a common neural mechanism and whether perceptual filling-in is a bottom-up, feedforward process initiating at the lowest levels of the cortical visual pathway or commences at higher-tier regions. We previously examined modal completion (Murray et al., 2002) and provided evidence that the earliest modal IC sensitivity occurs within higher-tier object recognition areas of the lateral occipital complex (LOC). We further proposed that previous observations of IC sensitivity in lower-tier regions likely reflect feedback modulation from the LOC. The present study tested these proposals, examining the commonality between modal and amodal completion mechanisms with high-density electrical mapping, spatiotemporal topographic analyses, and the local autoregressive average distributed linear inverse source estimation. A common initial mechanism for both types of completion processes (140 msec) that manifested as a modulation in response strength within higher-tier visual areas, including the LOC and parietal structures, is demonstrated, whereas differential mechanisms were evident only at a subsequent time period (240 msec), with amodal completion relying on continued strong responses in these structures.

Role of microRNAs in the pathogenesis of Ewing's sarcoma

SummaryEwing's sarcoma family tumors (ESFT) are the second most frequent cancer of bone in adolescents and young adults. ESFT are characterized by a chromosomal translocation that involves the 5' segment of the EWSR1 gene and the 3' segment of an ets transcription factor family member gene. In 85% of cases the chromosomal translocation generates the fusion protein EWSR1-FLI-1. Recent work from our laboratory identified mesenchymal stem cells (MSC) as the putative cell of origin of ESFT and characterized a CD133+ subpopulation of ESFT cells with tumor initating and self-renewal capacity, known as cancer stem cells (CSC). MicroRNAs (miRNAs) are small non-coding RNA that regulate protein expression at the post-transcriptional level by either repressing translation or destabilizing mRNA. MiRNAs participate in several biological processes including cell proliferation and differentiation. We used miRNA expression profile comparison between MSC and ESFT cell lines and CD133+ ESFT cells and CD133" ESFT cells to investigate the role of miRNAs in ESFT pathogenesis. MiRNA expression profile comparison of MSC and ESFT cell lines identified 35 differentially expressed miRNAs. Among these was down-regulation of let-7a which results, in part, by the direct repression of let-7a-l promoter by EWSR1-FLI-1. Overexpression of let-7a in ESFT cells blocked ESFT tumorigenesis through an High-motility group AT-hook2 (HMGA2)-mediated mechanism.MiRNA profiling of CD133+ ESFT and CD 133" ESFT cells revealed a broad repression of miRNAs in CD133+ ESFT mediated by down-regulation of TARBP2, a central regulator of the miRNA maturation pathway. Down-regulation of TARBP2 in ESFT cell lines results in a miRNA expression profile reminescent of that observed in CD133+ ESFT and associated with increased tumorigenicity. Enhancement of TARBP2 activity using the antibiotic enoxacin or overexpression of miRNA-143 or miRNA-145, two targets of TARBP2, impaired ESFT CSC self-renewal and block ESFT tumorigenicity. Moreover in vivo administration of synthetic let- 7a, miRNA-143 or miRNA-145 blocks ESFT tumor growth.Thus, dysregulation of miRNA expression is a key feature in ESFT pathogenesis and restoration of their expressions might be used as a new therapeutic tool.RésuméLe sarcome d'Ewing est la deuxième tumeur osseuse la plus fréquente chez l'enfant et le jeune adolescent. Le sarcome d'Ewing est caractérisé par une translocation chromosomique qui produit une protéine de fusion EWSR1-FLI-1. Des récents travaux ont identifié les cellules mésenchymateuses souches (MSC) comme étant les cellules à l'origine du sarcome d'Ewing ainsi qu'une sous-population de cellules exprimant le marqueur CD 133, dans le sarcome d'Ewing connu comme les cellules cancéreuses souches (CSC). Ces cellules ont la capacité d'initier la croissance tumorale et possèdent des propriétés d'auto-renouvellement. Les microRNAs (miRNAs) sont de petits ARN qui ne codent pas pour des protéines et qui contrôlent l'expression des protéines en bloquant la traduction ou en dégradant l'ARNm. Les miRNAs participent à différents processus biologiques comme la prolifération et la différenciation cellulaires.Le but de ce travail est d'étudier le rôle des miRNAs dans le sarcome d'Ewing. Un profil d'expression de miRNAs entre les MSC et des lignées cellulaires de sarcome d'Ewing a mis en évidence 35 miRNAs différemment exprimés. Parmi ceux-ci, la répression de let-7a est liée à la répression directe du promoteur de let-7a-l par EWSR-FLI-1. La sur-expression de let-7a dans des lignées cellulaires de sarcome d'Ewing inhibe leur croissance tumorale. Cette inhibition de croissance tumorale est régulée par la protéine high-motility group AT-hook2 (HMGA2).Un profil d'expression de miRNAs entre les cellules du sarcome d'Ewing CD133+ et CD133" montre une sous-expression d'un grand nombre de miRNAs dans les cellules CD133+ par rapport aux cellules CD133". Cette différence d'expression de miRNAs est due à la répression du gène TARBP2 qui participe à la maturation des miRNAs. La suppression de TARBP2 dans des cellules d'Ewing induit un profil d'expression de miRNAs similaire aux cellules CD133+ du sarcome d'Ewing et augmente la tumorigenèse des lignées cellulaires. De plus l'utilisation d'enoxacin, une molécule qui augmente l'activité de TARBP2 ou la sur- expression des miRNA143 ou miRNA-145 dans les CSC du sarcome d'Ewing bloque l'auto- renouvellement des cellules et la croissance tumorale. Finalement, l'administration de let-7a, miRNA-143 ou miRNA-145, dans des souris bloque la croissance du sarcome d'Ewing. Ces résultats indiquent que la dysrégulation des miRNAs participe à la pathogenèse du sarcome d'Ewing et que les miRNAs peuvent être utilisés comme des agents thérapeutiques.

Brain-derived neurotrophic factor enhances the hippocampal expression of key postsynaptic proteins in vivo including the monocarboxylate transporter MCT2.

Brain-derived neurotrophic factor (BDNF) promotes synaptic plasticity via an enhancement in expression of specific synaptic proteins. Recent results suggest that the neuronal monocarboxylate transporter MCT2 is a postsynaptic protein critically involved in synaptic plasticity and long-term memory. To investigate in vivo whether BDNF can modulate the expression of MCT2 as well as other proteins involved in synaptic plasticity, acute injection of BDNF was performed in mouse dorsal hippocampal CA1 area. Using immunohistochemistry, it was found that MCT2 expression was enhanced in part of the CA1 area and in the dentate gyrus 6 h after a single intrahippocampal injection of BDNF. Similarly, expression of the immediate early genes Arc and Zif268 was enhanced in the same hippocampal areas, in accordance with their role in synaptic plasticity. Immunoblot analysis confirmed the significant enhancement in MCT2 protein expression. In contrast, no changes were observed for the glial monocarboxylate transporters MCT1 and MCT4. When other synaptic proteins were investigated, it was found that postsynaptic density 95 (PSD95) and glutamate receptor 2 (GluR2) protein levels were significantly enhanced while no effect could be detected for synaptophysin, synaptosomal-associated protein 25 (SNAP25), αCaMKII and GluR1. These results demonstrate that MCT2 expression can be upregulated together with other key postsynaptic proteins in vivo under conditions related to synaptic plasticity, further suggesting the importance of energetics for memory formation.

Treatment of acute experimental schistosomiasis

A model of acute schistosomiasis of the mouse was used to observe whether curative treatment would be followed by an enhancement of the hepatic and splenic lesions, as a consequence of the massive destruction of worms and eggs within the portal system. Mice infected with 50 cercariae of Schistosoma mansoni were treated with both oxamniquine and praziquantel on the 50th day of infection and submitted to a sequential histologic examination from the 2nd to the 45th day after treatment. Although severe focal lesions due to dead and disintegranting worms were present in the livers of the treated animals, no aggravation of the general changes (reative hepatitis and splenitis, or periovular granulomas) was seen in comparison with a control non-treated group. Of 50 animals treated during the acute phase of schistosomiasis only one died espontaneously, while 16 ou of 30 infected controls died before the end of the experiment. The present investigation indicates that curative treatment during the acute phase of schistosomiasis does not enhance previous lesions at first and results in progressive disappearance of the lesions starting six days following chemotherapy.