Spontaneous combined rupture of a pelvicalyceal cyst into the collector system and retroperitoneal space during the acquisition of computed tomography scan images: a case report

Abstract Introduction Pelvicalyceal cysts are common findings in autopsies and can manifest with a variety of patterns. These cystic lesions are usually a benign entity with no clinical significance unless they enlarge enough to cause compression of the adjacent collecting system and consequently obstructive uropathy. Few cases of the spontaneous rupture of pelvicalyceal renal cysts have been published and to the best of our knowledge there is no report of a combined rupture to collector system and retroperitoneal space documented during a multiphase computed tomography. Case presentation We report a case of a ‘real-time’ spontaneous rupture of a pelvicalyceal cyst into the collecting system with fistulization into the retroperitoneum. The patient was a 78-year-old Caucasian man with a previous history of renal stones and a large pelvicalyceal renal cyst who was admitted to our Emergency department with acute right flank pain. A multiphase computed tomography was performed and the pre-contrast images demonstrated a right pelvicalyceal renal cyst measuring 12.0 × 6.1cm in the lower pole causing moderate dilation of the upper right renal collection system. In addition, a partially obstructive stone on the left distal ureter with mild left hydronephrosis was noted. The nephrographic phase did not add any new information. The excretory phase (10-minute delay) demonstrated a spontaneous rupture of the cyst into the pelvicalyceal system with posterior fistulization into the retroperitoneal space. Conclusion In this case study we present time-related changes of a rare pelvicalyceal cyst complication, which to the best of our knowledge has fortunately not been previously documented. Analysis of the sequential images and comparison with an earlier scan allowed us to better understand the physiopathological process of the rupture, the clinical presentation and to elaborate hypotheses for its etiopathogenesis.

Animal models of prenatal immune challenge and their contribution to the study of schizophrenia: a systematic review

Prenatal immune challenge (PIC) in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism. Based on this, the goal of this article was to review the main contributions of PIC models, especially the one using the viral-mimetic particle polyriboinosinic-polyribocytidylic acid (poly-I:C), to the understanding of the etiology, biological basis and treatment of schizophrenia. This systematic review consisted of a search of available web databases (PubMed, SciELO, LILACS, PsycINFO, and ISI Web of Knowledge) for original studies published in the last 10 years (May 2001 to October 2011) concerning animal models of PIC, focusing on those using poly-I:C. The results showed that the PIC model with poly-I:C is able to mimic the prodrome and both the positive and negative/cognitive dimensions of schizophrenia, depending on the specific gestation time window of the immune challenge. The model resembles the neurobiology and etiology of schizophrenia and has good predictive value. In conclusion, this model is a robust tool for the identification of novel molecular targets during prenatal life, adolescence and adulthood that might contribute to the development of preventive and/or treatment strategies (targeting specific symptoms, i.e., positive or negative/cognitive) for this devastating mental disorder, also presenting biosafety as compared to viral infection models. One limitation of this model is the incapacity to model the full spectrum of immune responses normally induced by viral exposure.

The Azores Current System and the Canary Current from CTD and ADCP data

Se han eliminado páginas en blanco

Effect of culture system and diet in early larval stages over skeletal deformities development in gilthead sea bream

[ES] Main deformities such as lordosis, opercular deformities and upper/lower jaws shortening are considered as quality descriptors in commercial marine fish fry production and seem to be related with larval culture conditions in early larval stages. The aim of this work was to obtain information about the contribution of the diet and rearing system to the apparition of these abnormalities in gilthead sea bream (Sparus aurata) larvae in semi-industrial scale facilities. For that purpose, two different larval rearing systems semi-intensive and intensive were compared; besides, two different rotifer enrichments, DHA Protein Selco, (Inve Aquaculture, Dendermonde, Belgium) (R1) and Red Pepper Paste, (Bernaqua bvba, Turnhout, Belgium) were tested in the intensive system. Biochemical composition of larvae, preys and commercial products was analysed. At 50 days post hatching six hundred fish per treatment were individually studied under stereoscope and deformity frequency recorded. Besides at 95 days post hatching fry were soft X ray monitored. Both rotifer enrichment and rearing system affected survival, growth and deformity frequency. Rearing system did not affect total larvae fatty acid content except at 20 dah, where DHA were significantly higher and EPA significantly lower in Semi-intensive system. A significantly lower percentage of deformity rates together with better survival and growth were obtained in the semi-intensive system. In dietary treatment, rotifer enrichment significantly affected larval survival. R1 rotifers enrichment significantly (P<0.05) improved survival when compared to fed R2 larvae. The content of DPA was significantly (P<0.05) higher in R2 fed larvae reflecting the R2 rotifers content of this fatty acid. The level of this FA tended to decrease in concordance with the rotifers replacement by artemia in the diet. The effects n-3-HUFA and DPA (22:5n-6) over larval survival and skeletal deformities development is discussed.

Transcriptional regulation of human mu-opioid receptor gene: functional characterization of activating and inhibitory transcription factors

The organization of the nervous and immune systems is characterized by obvious differences and striking parallels. Both systems need to relay information across very short and very long distances. The nervous system communicates over both long and short ranges primarily by means of more or less hardwired intercellular connections, consisting of axons, dendrites, and synapses. Longrange communication in the immune system occurs mainly via the ordered and guided migration of immune cells and systemically acting soluble factors such as antibodies, cytokines, and chemokines. Its short-range communication either is mediated by locally acting soluble factors or transpires during direct cell–cell contact across specialized areas called “immunological synapses” (Kirschensteiner et al., 2003). These parallels in intercellular communication are complemented by a complex array of factors that induce cell growth and differentiation: these factors in the immune system are called cytokines; in the nervous system, they are called neurotrophic factors. Neither the cytokines nor the neurotrophic factors appear to be completely exclusive to either system (Neumann et al., 2002). In particular, mounting evidence indicates that some of the most potent members of the neurotrophin family, for example, nerve growth factor (NGF) and brainderived neurotrophic factor (BDNF), act on or are produced by immune cells (Kerschensteiner et al., 1999) There are, however, other neurotrophic factors, for example the insulin-like growth factor-1 (IGF-1), that can behave similarly (Kermer et al., 2000). These factors may allow the two systems to “cross-talk” and eventually may provide a molecular explanation for the reports that inflammation after central nervous system (CNS) injury has beneficial effects (Moalem et al., 1999). In order to shed some more light on such a cross-talk, therefore, transcription factors modulating mu-opioid receptor (MOPr) expression in neurons and immune cells are here investigated. More precisely, I focused my attention on IGF-I modulation of MOPr in neurons and T-cell receptor induction of MOPr expression in T-lymphocytes. Three different opioid receptors [mu (MOPr), delta (DOPr), and kappa (KOPr)] belonging to the G-protein coupled receptor super-family have been cloned. They are activated by structurallyrelated exogenous opioids or endogenous opioid peptides, and contribute to the regulation of several functions including pain transmission, respiration, cardiac and gastrointestinal functions, and immune response (Zollner and Stein 2007). MOPr is expressed mainly in the central nervous system where it regulates morphine-induced analgesia, tolerance and dependence (Mayer and Hollt 2006). Recently, induction of MOPr expression in different immune cells induced by cytokines has been reported (Kraus et al., 2001; Kraus et al., 2003). The human mu-opioid receptor gene (OPRM1) promoter is of the TATA-less type and has clusters of potential binding sites for different transcription factors (Law et al. 2004). Several studies, primarily focused on the upstream region of the OPRM1 promoter, have investigated transcriptional regulation of MOPr expression. Presently, however, it is still not completely clear how positive and negative transcription regulators cooperatively coordinate cellor tissue-specific transcription of the OPRM1 gene, and how specific growth factors influence its expression. IGF-I and its receptors are widely distributed throughout the nervous system during development, and their involvement in neurogenesis has been extensively investigated (Arsenijevic et al. 1998; van Golen and Feldman 2000). As previously mentioned, such neurotrophic factors can be also produced and/or act on immune cells (Kerschenseteiner et al., 2003). Most of the physiologic effects of IGF-I are mediated by the type I IGF surface receptor which, after ligand binding-induced autophosphorylation, associates with specific adaptor proteins and activates different second messengers (Bondy and Cheng 2004). These include: phosphatidylinositol 3-kinase, mitogen-activated protein kinase (Vincent and Feldman 2002; Di Toro et al. 2005) and members of the Janus kinase (JAK)/STAT3 signalling pathway (Zong et al. 2000; Yadav et al. 2005). REST plays a complex role in neuronal cells by differentially repressing target gene expression (Lunyak et al. 2004; Coulson 2005; Ballas and Mandel 2005). REST expression decreases during neurogenesis, but has been detected in the adult rat brain (Palm et al. 1998) and is up-regulated in response to global ischemia (Calderone et al. 2003) and induction of epilepsy (Spencer et al. 2006). Thus, the REST concentration seems to influence its function and the expression of neuronal genes, and may have different effects in embryonic and differentiated neurons (Su et al. 2004; Sun et al. 2005). In a previous study, REST was elevated during the early stages of neural induction by IGF-I in neuroblastoma cells. REST may contribute to the down-regulation of genes not yet required by the differentiation program, but its expression decreases after five days of treatment to allow for the acquisition of neural phenotypes. Di Toro et al. proposed a model in which the extent of neurite outgrowth in differentiating neuroblastoma cells was affected by the disappearance of REST (Di Toro et al. 2005). The human mu-opioid receptor gene (OPRM1) promoter contains a DNA sequence binding the repressor element 1 silencing transcription factor (REST) that is implicated in transcriptional repression. Therefore, in the fist part of this thesis, I investigated whether insulin-like growth factor I (IGF-I), which affects various aspects of neuronal induction and maturation, regulates OPRM1 transcription in neuronal cells in the context of the potential influence of REST. A series of OPRM1-luciferase promoter/reporter constructs were transfected into two neuronal cell models, neuroblastoma-derived SH-SY5Y cells and PC12 cells. In the former, endogenous levels of human mu-opioid receptor (hMOPr) mRNA were evaluated by real-time PCR. IGF-I upregulated OPRM1 transcription in: PC12 cells lacking REST, in SH-SY5Y cells transfected with constructs deficient in the REST DNA binding element, or when REST was down-regulated in retinoic acid-differentiated cells. IGF-I activates the signal transducer and activator of transcription-3 (STAT3) signaling pathway and this transcription factor, binding to the STAT1/3 DNA element located in the promoter, increases OPRM1 transcription. T-cell receptor (TCR) recognizes peptide antigens displayed in the context of the major histocompatibility complex (MHC) and gives rise to a potent as well as branched intracellular signalling that convert naïve T-cells in mature effectors, thus significantly contributing to the genesis of a specific immune response. In the second part of my work I exposed wild type Jurkat CD4+ T-cells to a mixture of CD3 and CD28 antigens in order to fully activate TCR and study whether its signalling influence OPRM1 expression. Results were that TCR engagement determined a significant induction of OPRM1 expression through the activation of transcription factors AP-1, NF-kB and NFAT. Eventually, I investigated MOPr turnover once it has been expressed on T-cells outer membrane. It turned out that DAMGO induced MOPr internalisation and recycling, whereas morphine did not. Overall, from the data collected in this thesis we can conclude that that a reduction in REST is a critical switch enabling IGF-I to up-regulate human MOPr, helping these findings clarify how human MOPr expression is regulated in neuronal cells, and that TCR engagement up-regulates OPRM1 transcription in T-cells. My results that neurotrophic factors a and TCR engagement, as well as it is reported for cytokines, seem to up-regulate OPRM1 in both neurons and immune cells suggest an important role for MOPr as a molecular bridge between neurons and immune cells; therefore, MOPr could play a key role in the cross-talk between immune system and nervous system and in particular in the balance between pro-inflammatory and pro-nociceptive stimuli and analgesic and neuroprotective effects.

Crack measurements in structural concrete with D.I.C. system and validation of a tensile constitutive law

Compared with other mature engineering disciplines, fracture mechanics of concrete is still a developing field and very important for structures like bridges subject to dynamic loading. An historical point of view of what done in the field is provided and then the project is presented. The project presents an application of the Digital Image Correlation (DIC) technique for the detection of cracks at the surface of concrete prisms (500mmx100mmx100mm) subject to flexural loading conditions (Four Point Bending test). The technique provide displacement measurements of the region of interest and from this displacement field information about crack mouth opening (CMOD) are obtained and related to the applied load. The evolution of the fracture process is shown through graphs and graphical maps of the displacement at some step of the loading process. The study shows that it is possible with the DIC system to detect the appearance and evolution of cracks, even before the cracks become visually detectable.

The Enhanced Single-dish Control System and wide surveys of compact sources

The Italian radio telescopes currently undergo a major upgrade period in response to the growing demand for deep radio observations, such as surveys on large sky areas or observations of vast samples of compact radio sources. The optimised employment of the Italian antennas, at first constructed mainly for VLBI activities and provided with a control system (FS – Field System) not tailored to single-dish observations, required important modifications in particular of the guiding software and data acquisition system. The production of a completely new control system called ESCS (Enhanced Single-dish Control System) for the Medicina dish started in 2007, in synergy with the software development for the forthcoming Sardinia Radio Telescope (SRT). The aim is to produce a system optimised for single-dish observations in continuum, spectrometry and polarimetry. ESCS is also planned to be installed at the Noto site. A substantial part of this thesis work consisted in designing and developing subsystems within ESCS, in order to provide this software with tools to carry out large maps, spanning from the implementation of On-The-Fly fast scans (following both conventional and innovative observing strategies) to the production of single-dish standard output files and the realisation of tools for the quick-look of the acquired data. The test period coincided with the commissioning phase for two devices temporarily installed – while waiting for the SRT to be completed – on the Medicina antenna: a 18-26 GHz 7-feed receiver and the 14-channel analogue backend developed for its use. It is worth stressing that it is the only K-band multi-feed receiver at present available worldwide. The commissioning of the overall hardware/software system constituted a considerable section of the thesis work. Tests were led in order to verify the system stability and its capabilities, down to sensitivity levels which had never been reached in Medicina using the previous observing techniques and hardware devices. The aim was also to assess the scientific potential of the multi-feed receiver for the production of wide maps, exploiting its temporary availability on a mid-sized antenna. Dishes like the 32-m antennas at Medicina and Noto, in fact, offer the best conditions for large-area surveys, especially at high frequencies, as they provide a suited compromise between sufficiently large beam sizes to cover quickly large areas of the sky (typical of small-sized telescopes) and sensitivity (typical of large-sized telescopes). The KNoWS (K-band Northern Wide Survey) project is aimed at the realisation of a full-northern-sky survey at 21 GHz; its pilot observations, performed using the new ESCS tools and a peculiar observing strategy, constituted an ideal test-bed for ESCS itself and for the multi-feed/backend system. The KNoWS group, which I am part of, supported the commissioning activities also providing map-making and source-extraction tools, in order to complete the necessary data reduction pipeline and assess the general system scientific capabilities. The K-band observations, which were carried out in several sessions along the December 2008-March 2010 period, were accompanied by the realisation of a 5 GHz test survey during the summertime, which is not suitable for high-frequency observations. This activity was conceived in order to check the new analogue backend separately from the multi-feed receiver, and to simultaneously produce original scientific data (the 6-cm Medicina Survey, 6MS, a polar cap survey to complete PMN-GB6 and provide an all-sky coverage at 5 GHz).

Spinal cord injury: assessment of autonomic state-dependent control of cardiovascular system and body core temperature

Spinal cord injury (SCI) results not only in paralysis; but it is also associated with a range of autonomic dysregulation that can interfere with cardiovascular, bladder, bowel, temperature, and sexual function. The entity of the autonomic dysfunction is related to the level and severity of injury to descending autonomic (sympathetic) pathways. For many years there was limited awareness of these issues and the attention given to them by the scientific and medical community was scarce. Yet, even if a new system to document the impact of SCI on autonomic function has recently been proposed, the current standard of assessment of SCI (American Spinal Injury Association (ASIA) examination) evaluates motor and sensory pathways, but not severity of injury to autonomic pathways. Beside the severe impact on quality of life, autonomic dysfunction in persons with SCI is associated with increased risk of cardiovascular disease and mortality. Therefore, obtaining information regarding autonomic function in persons with SCI is pivotal and clinical examinations and laboratory evaluations to detect the presence of autonomic dysfunction and quantitate its severity are mandatory. Furthermore, previous studies demonstrated that there is an intimate relationship between the autonomic nervous system and sleep from anatomical, physiological, and neurochemical points of view. Although, even if previous epidemiological studies demonstrated that sleep problems are common in spinal cord injury (SCI), so far only limited polysomnographic (PSG) data are available. Finally, until now, circadian and state dependent autonomic regulation of blood pressure (BP), heart rate (HR) and body core temperature (BcT) were never assessed in SCI patients. Aim of the current study was to establish the association between the autonomic control of the cardiovascular function and thermoregulation, sleep parameters and increased cardiovascular risk in SCI patients.

Development of an X-ray spectrometric system and feasibility tests of Silicon Drift Detector for medical and space applications

The thesis work concerns X-ray spectrometry for both medical and space applications and is divided into two sections. The first section addresses an X-ray spectrometric system designed to study radiological beams and is devoted to the optimization of diagnostic procedures in medicine. A parametric semi-empirical model capable of efficiently reconstructing diagnostic X-ray spectra in 'middle power' computers was developed and tested. In addition, different silicon diode detectors were tested as real-time detectors in order to provide a real-time evaluation of the spectrum during diagnostic procedures. This project contributes to the field by presenting an improved simulation of a realistic X-ray beam emerging from a common X-ray tube with a complete and detailed spectrum that lends itself to further studies of added filtration, thus providing an optimized beam for different diagnostic applications in medicine. The second section describes the preliminary tests that have been carried out on the first version of an Application Specific Integrated Circuit (ASIC), integrated with large area position-sensitive Silicon Drift Detector (SDD) to be used on board future space missions. This technology has been developed for the ESA project: LOFT (Large Observatory for X-ray Timing), a new medium-class space mission that the European Space Agency has been assessing since February of 2011. The LOFT project was proposed as part of the Cosmic Vision Program (2015-2025).

Involvement of the opioid system and BDNF in neuroplastic alterations occurring in neuropathic pain conditions

Chronic pain affects one in five adults, reducing quality of life and increasing risk of developing co-morbidities such as depression. Neuropathic pain results by lesions to the nervous system that alter its structure and function leading to spontaneous pain and amplified responses to noxious and innocuous stimuli. The Opioid System is probably the most important system involved in control of nociceptive transmission. Dynorphin and nociceptin systems have been suggested key mediators of some neuropathic pain aspects. An important role also for BDNF has been recently suggested since its involvement in the peripheral and central sensitization phenomena is known. We studied neuroplastic alterations occurring in chronic pain in mice subjected to the chronic constriction injury (CCI). We investigated gene expression alterations of both BDNF and Opioid System at spinal level at different intervals of time. A transient upregulation of pBDNF and pDYN was observed in spinal cord, while increasing upregulation of ppN/OFQ was found in the DRGs of injured mice. Development of neuropathic behavioral signs has been observed in ICR/CD-1 and BDNF+/+ mice, subjected to CCI. A different development of these signs was observed in BDNF+/-. We also studied gene expression changes of investigated systems in different brain areas fourteen days after surgery. We found pBDNF, pDYN, pKOP, ppN/OFQ and pNOP gene expression alterations in several areas of CCI mice. In the same brain regions we also determined bioactive nociceptin peptide levels, and elevated N/OFQ levels were observed in the amygdala area. Histone modifications studies have been performed in BDNF and DYN gene promoters of CCI animal spinal cord showing selected alterations in pDYN gene promoter. In addition, a preliminary characterization of the innovative NOP-EGFP mice was performed. Overall, our results could be useful to understand which and how neuropeptidergic systems are involved in neuroplastic mechanism occurring in neuropathic pain.

Intraoperative kinematic evaluation with navigation system and postoperative kinematic evaluation with dynamic RSA of total knee arthroplasty

Restoring a correct implant kinematics and providing a good ligament balance and patellar tracking is mandatory to improve clinical and functional outcome after a Total Knee Replacement. Surgical navigation systems are a reliable and accurate tool to help the surgeon in achieving these goals. The aim of the present study was to use navigation system with an intra-operative surgical protocol to evaluate and determine an optimal implant kinematics during a Total Knee Replacement.

The role of B cells during acute and latent infections with murine cytomegalovirus and Leishmania major

This thesis focuses on the role of B cells in mCMV and Leishmania major infection. B cells are an essential component of the adaptive immune system and play a key role in the humoral immune response. In mCMV infection we analyzed the influence of B cells on the virus-specific CD8 T cell response, in detail the role of B cells as IL-10 secreting cells, as source of immunoglobulin (Ig) and as antigen presenting cells. In Leishmania major infection we investigated the role of Ig in Th1 and Th2 directed disease.rnWe found in mCMV infection that the B cell secreted IL-10 suppresses effectively the acute virus-specific CD8 T cell response, while the IL-10 secreted by dendritic cell has no obvious effect. Ig has no effect in the acute virus-specific CD8 T cell response, but in memory response Ig is essential. If Ig is missing the CD8 T cell population remains high in memory response 135 days post infection. The complete absence of B cells dramatically reduces the acute virus-specific CD8 T cell response, while B cell reconstitution just partially rescues this dramatic reduction. A comparison of this reduction in a B cell free organism to an organism with depleted dendritic cells gave a similar result. To exclude a malfunction of the CD8 T cells in the B cell deficient mice, the decreased virus-specific CD8 T cell population was confirmed in a B cell depletion model. Further, bone marrow chimeras with a B cell compartment deficient for CD40-/- showed a decrease of the virus-specific response and an involvement of CD40 on B cells. Taken together these results suggest a role for B cells in antigen presentation during mCMV infection.rnFurther we took advantage of the altered mCMV specific CD8 T cell memory response in mice without Ig to investigate the memory inflation of CD8 T cells specific for distinct mCMV specifc peptides. Using a SIINFEKL-presenting virus system, we were able to shorten the time until the memory inflation occurs and show that direct presentation stimulates the memory inflation. rnIn Leishmania major infection, Ig of Th2 balanced BALB/c mice has a central role in preventing a systemic infection, although the ear lesions are smaller in IgMi mice without specific Ig. Here the parasite loads of ears and spleen are elevated, and an IMS-reconstitution does not affect the parasite load. In contrast in Th1 balanced C57BL/6 mice, reconstitution of IgMi mice with serum of either untreated or immunized mice decreased the parasite load of spleen and ear, further IMS treatment reduces the size of the spleen and the cytokine-levels of IL-10, IL-4, IL-2 and IFN-γ to a level comparable to wt mice. rn

Synthesis in millireactor system and stability of intermediates for the functionalization of imidazole

This Master thesis presents the results obtained in the curricular traineeship, carried out within the laboratories of the Department of Chemistry of the University of Bergen, during the Erasmus period, and within the Department of Industrial Chemistry of the University of Bologna. The project followed in Bergen concerned the synthesis of key intermediates used for the functionalization of the backbone of imidazole, using N,N'- diiodo-5,5-dimethylhydantoin (“DIH”) as an iodinating agent, and employing an innovative kind of chemical reactor: the “Multijet Oscillating Disc Millireactor” (MJOD Reactor). Afterwards, the work performed in Bologna consisted in verifying the stability in solution of the above mentioned N,N'-diiodo-5,5-dimethylhydantoin utilising spectrophotometric techniques and High Performance Liquid Chromatography analyses (HPLC).

Detection and identification of 700 drugs by multi-target screening with a 3200 Q TRAP LC-MS/MS system and library searching

The multi-target screening method described in this work allows the simultaneous detection and identification of 700 drugs and metabolites in biological fluids using a hybrid triple-quadrupole linear ion trap mass spectrometer in a single analytical run. After standardization of the method, the retention times of 700 compounds were determined and transitions for each compound were selected by a "scheduled" survey MRM scan, followed by an information-dependent acquisition using the sensitive enhanced product ion scan of a Q TRAP hybrid instrument. The identification of the compounds in the samples analyzed was accomplished by searching the tandem mass spectrometry (MS/MS) spectra against the library we developed, which contains electrospray ionization-MS/MS spectra of over 1,250 compounds. The multi-target screening method together with the library was included in a software program for routine screening and quantitation to achieve automated acquisition and library searching. With the help of this software application, the time for evaluation and interpretation of the results could be drastically reduced. This new multi-target screening method has been successfully applied for the analysis of postmortem and traffic offense samples as well as proficiency testing, and complements screening with immunoassays, gas chromatography-mass spectrometry, and liquid chromatography-diode-array detection. Other possible applications are analysis in clinical toxicology (for intoxication cases), in psychiatry (antidepressants and other psychoactive drugs), and in forensic toxicology (drugs and driving, workplace drug testing, oral fluid analysis, drug-facilitated sexual assault).