1,137 research outputs found

    Arachidonic Acid Metabolism In Murine Fibrosarcoma Cells With Differing In Vivo And In Vitro Characteristics

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144314/1/ijc1985363383.pd

    Vascular tube formation on matrix metalloproteinase-1-damaged collagen

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    Connective tissue damage and angiogenesis are both important features of tumour growth and invasion. Here, we show that endothelial cells maintained on a three-dimensional lattice of intact polymerised collagen formed a monolayer of cells with a cobblestone morphology. When the collagen was exposed to organ culture fluid from human basal cell tumours of the skin (containing a high level of active matrix metalloproteinase-1 (MMP-1)), degradation of the collagen matrix occurred. The major degradation products were the 3over43over 4- and 1over41over 4-sized fragments known to result from the action of MMP-1 on type I collagen. When endothelial cells were maintained on the partially degraded collagen, the cells organised into a network of vascular tubes. Pretreatment of the organ culture fluid with either tissue inhibitor of metalloproteinase-1 (TIMP-1) or neutralising antibody to MMP-1 prevented degradation of the collagen lattice and concomitantly inhibited endothelial cell organisation into the vascular network. Purified (activated) MMP-1 duplicated the effects of skin organ culture fluid, but other enzymes including MMP-9 (gelatinase B), elastase or trypsin failed to produce measurable fragments from intact collagen and also failed to promote vascular tube formation. Together, these studies suggest that damage to the collagenous matrix is itself an important inducer of new vessel formation

    Pain control in the continuity of care.

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    As cancer is earlier diagnosed and its treatments improve, palliative care is increasingly playing a vital role in the oncology population. The concept and the timing of application of palliative care have evolved in the last decades. The WHO pain ladder and the greater understanding of appropriate multimodal pain control treatments have dramatically improved the management of cancer pain. Integration of palliative care, which appears crucial for a proper management of patients, can be defined as the provision of palliative care both during curative cancer treatment and after curative treatment has ceased. Clinical assistance should be delivered by specialized physicians in different fields, psychologists and nurses, and should include all aspects of advanced cancer care, from diagnosis to the treatment of symptoms. A further aspect of integration of palliative care concerns the role of the continuity of care in acute or emergency contexts both for out- and inpatients. Further improvements in the management of cancer pain are needed. First, the WHO ladder should be modified with further steps, like those of interventional pain control procedures and techniques, with the aim of being effective also for the small proportion of nonresponsive patients. Second, more research is needed to find out which interventions aiming to improve continuity of care of cancer patients are beneficial to improve patient, provider and process of care outcomes and to identify which outcomes are the most sensitive to change. Of crucial importance would be the development of a standardised instrument to measure the continuity of care in cancer patients. This article is a brief overview on the management of cancer pain, from the pharmacological treatments reported by WHO ladder, to the need for integration and continuity of care

    Anomalous crossover between thermal and shot noise in macroscopic diffusive conductors

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    We predict the existence of an anomalous crossover between thermal and shot noise in macroscopic diffusive conductors. We first show that, besides thermal noise, these systems may also exhibit shot noise due to fluctuations of the total number of carriers in the system. Then we show that at increasing currents the crossover between the two noise behaviors is anomalous, in the sense that the low frequency current spectral density displays a region with a superlinear dependence on the current up to a cubic law. The anomaly is due to the non-trivial coupling in the presence of the long range Coulomb interaction among the three time scales relevant to the phenomenon, namely, diffusion, transit and dielectric relaxation time.Comment: 4 pages, 2 figure

    Serodiagnosis of visceral leishmaniasis in northeastern italy: Evaluation of seven serological tests

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    This study compares the performance of seven assays, including two ELISA (Leishmania ELISA IgG + IgM, Vircell Microbiologists; Leishmania infantum IgG ELISA, NovaTec), three rK39-based immunochromatographic tests (rK39-ICTs) (Leishmania Dipstick Rapydtest, Apacor; On Site Leishmania IgG/IgM Combo Rapid Test, CTK Biotech; LEISHMANIA Strip quick Test, Cypress Diagnostic), one indirect immunofluorescent antibody test (IFAT) (Leishmania-Spot IF, BioM\ue9rieux), and one western blot (WB) (Leishmania WESTERN BLOT IgG, LDBio Diagnostics) for serodiagnosis of visceral leishmaniasis (VL). Serum samples from 27 VL patients living in northeastern Italy were analyzed, as well as the serum samples from 50 individuals in whom VL diagnosis was excluded. The WB and the IFAT had 96% sensitivity, followed by the ELISA (63% and 74%, respectively). The rK39-ICT exhibited the worst performance among the serological tests, with sensitivities ranging from 52% to 70%. By combining selected ELISA/ICT, the sensitivity of VL detection reached 89%. IFAT and WB outperformed ELISA and rK39-ICT by possessing optimal sensitivity, but their high cost and complexity of execution would not allow their employment as screening tests. In conclusion, the combination of easy-to-perform tests, such as ICT and ELISA, could improve sensitivity in the serodiagnosis of Mediterranean VL

    Rapid communications Ongoing outbreak of visceral leishmaniasis in Bologna

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    (VL) cases has recently been reported in Bologna Province in northern Italy. Over six months from November 2012 to May 2013, 14 cases occurred, whereas the average number of cases per year was 2.6 (range: 0–8) in 2008 to 2012. VL was diagnosed in a median of 40 days (range: 15–120) from disease onset. This delay in diagnosis shows the need for heightened awareness of clinicians for autochthonous VL in Europe. From November 2012 to May 2013, public health authorities, microbiologists and clinicians in Bologna Province, northern Italy, noted an upsurge in human cases of visceral leishmaniasis. During these six months, 14 cases were notified, an over five-fold increase compared with the annual average of 2.

    Isolation and molecular typing of Leishmania infantum from Phlebotomus perfiliewi in a reemerging focus of leishmaniasis, Northeastern Italy

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    Visceral leishmaniasis (VL) caused by Leishmania (L.) infantum is a public health threat in the Emilia-Romagna region, northeastern Italy, but its epidemiology has not been fully elucidated in this area. The objective of this study was to characterize Leishmania infection in sand flies collected in a re-emerging focus of VL in the Bologna province. During the summer of 2016, 6114 sand flies were collected, identified, and tested for Leishmania detection. Of the identified sand flies, 96.5% were Phlebotomus (P.) perfiliewi and 3.5% were P. perniciosus. Detected parasites were characterized by biomolecular methods (multilocus microsatellite typing and characterization of repetitive region on chromosome 31), and quantified by real-time PCR. The prevalence of Leishmania infection in individually-tested P. perfiliewi sand flies varied from 6% to 10% with an increasing trend during the season. Promastigotes of L. infantum were isolated by dissection in one P. perfiliewi female; the isolated strain (Lein-pw) were closely related to Leishmania parasites from VL cases in northeastern Italy, but differed from strains isolated in dogs from the same area. Our findings strongly support the vector status of P. perfiliewi for human VL in the study area

    In vitro and in vivo evaluation of 99mTc-polymyxin B for specific targeting of gram-bacteria

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    Background: Infectious diseases are one of the main causes of morbidity and mortality worldwide. Nuclear molecular imaging would be of great help to non-invasively discriminate between septic and sterile inflammation through available radiopharmaceuticals, as none is currently available for clinical practice. Here, we describe the radiolabeling procedure and in vitro and in vivo studies of99mTc-polymyxin B sulfate (PMB) as a new single photon emission imaging agent for the characterization of infections due to Gram-negative bacteria. Results: Labeling efficiency was 97 ± 2% with an average molar activity of 29.5 ± 0.6 MBq/nmol. The product was highly stable in saline and serum up to 6 h. In vitro binding assay showed significant displaceable binding to Gram-negative bacteria but not to Gram-positive controls. In mice,99mTc-HYNIC-PMB was mainly taken up by liver and kidneys. Targeting studies confirmed the specificity of99mTc-HYNIC-PMB obtained in vitro, showing significantly higher T/B ratios for Gram-negative bacteria than Gram-positive controls. Conclusions: In vitro and in vivo results suggest that99mTc-HYNIC-PMB has a potential for in vivo identification of Gram-negative bacteria in patients with infections of unknown etiology. However, further investigations are needed to deeply understand the mechanism of action and behavior of99mTc-HYNIC-PMB in other animal models and in humans

    Shot-noise anomalies in nondegenerate elastic diffusive conductors

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    We present a theoretical investigation of shot-noise properties in nondegenerate elastic diffusive conductors. Both Monte Carlo simulations and analytical approaches are used. Two new phenomena are found: (i) the display of enhanced shot noise for given energy dependences of the scattering time, and (ii) the recovery of full shot noise for asymptotic high applied bias. The first phenomenon is associated with the onset of negative differential conductivity in energy space that drives the system towards a dynamical electrical instability in excellent agreement with analytical predictions. The enhancement is found to be strongly amplified when the dimensionality in momentum space is lowered from 3 to 2 dimensions. The second phenomenon is due to the suppression of the effects of long range Coulomb correlations that takes place when the transit time becomes the shortest time scale in the system, and is common to both elastic and inelastic nondegenerate diffusive conductors. These phenomena shed new light in the understanding of the anomalous behavior of shot noise in mesoscopic conductors, which is a signature of correlations among different current pulses.Comment: 9 pages, 6 figures. Final version to appear in Phys. Rev.
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