Role of hemoclips in the management of acute bleeding from a gastric stromal tumor: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Though gastrointestinal stromal tumors (GISTs) frequently present with gastrointestinal bleeding, the guidelines for the management and control of bleeding are unclear especially in patients who are not appropriate for surgical resection.</p> <p>Case presentation</p> <p>We report a case of gastric GIST in an elderly patient who presented with bleeding. Homeostasis was achieved initially with the endoscopic placement of a hemoclip followed by treatment with the tyrosine kinase inhibitor, imatinib.</p> <p>Conclusion</p> <p>The management of bleeding GISTs in the elderly pose a challenging task to the gastroenterologist and treatment strategies should be tailored to the expertise of the endoscopist, surgeon and other supportive staff.</p

Raman vibrational dynamics of hydrated ions in the low-frequency spectral region

The hydration structure of ions in aqueous environments can have a significant influence on their chemical and biological properties. Due to its inherent dynamical character, determination of the hydration shell around dissolved ions has proved challenging, mainly so for cations such as sodium and potassium which form diffuse and dynamic hydrating structures. The low frequency polarized Raman spectrum, as retrieved by time resolved isotropic optical Kerr effect measurements, is sensitive to structural fluctuations and can reveal information about ion-water interactions through their Raman active vibrational modes. Here we study a series of mixtures of sodium, potassium and lithium hydroxide solutions by changing cation concentration pairwise (namely, sodium/potassium or sodium/lithium) while keeping constant the hydroxide concentration. The hydroxide-water hydrogen bond vibration, which produces a well-defined isotropic Raman mode, appears at higher frequencies from the cation-water Raman active vibrations. In addition to previously reported lithium-water low frequency vibrations, clear spectral features could be resolved from the concentration studies and assigned to sodium-water hydration shell vibrations. However, potassium related low frequency spectral features remain elusive. The same method was applied to mixtures of the same cations with a halide anion (chloride) in order to rule out any specific features related to the dissolved hydroxide anion. Comparison between halide and hydroxide measurements confirmed the presence of the cation modes and further revealed a low frequency spectral feature related to hydroxide induced changes in water polarizability

Solar interacting protons versus interplanetary protons in the core plus halo model of diffusive shock acceleration and stochastic re-acceleration

With the first observations of solar γ-rays from the decay of pions, the relationship of protons producing ground level enhancements (GLEs) on the Earth to those of similar energies producing the γ-rays on the Sun has been debated. These two populations may be either independent and simply coincident in large flares, or they may be, in fact, the same population stemming from a single accelerating agent and jointly distributed at the Sun and also in space. Assuming the latter, we model a scenario in which particles are accelerated near the Sun in a shock wave with a fraction transported back to the solar surface to radiate, while the remainder is detected at Earth in the form of a GLE. Interplanetary ions versus ions interacting at the Sun are studied for a spherical shock wave propagating in a radial magnetic field through a highly turbulent radial ray (the acceleration core) and surrounding weakly turbulent sector in which the accelerated particles can propagate toward or away from the Sun. The model presented here accounts for both the first-order Fermi acceleration at the shock front and the second-order, stochastic re-acceleration by the turbulence enhanced behind the shock. We find that the re-acceleration is important in generating the γ-radiation and we also find that up to 10% of the particle population can find its way to the Sun as compared to particles escaping to the interplanetary space

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel. In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime, compute the two-point correlation functions of these perturbations and prove that Minkowski spacetime is a stable solution of semiclassical gravity. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a black hole and describe the metric fluctuations near the event horizon of an evaporating black holeComment: 100 pages, no figures; an update of the 2003 review in Living Reviews in Relativity gr-qc/0307032 ; it includes new sections on the Validity of Semiclassical Gravity, the Stability of Minkowski Spacetime, and the Metric Fluctuations of an Evaporating Black Hol

HIV-1 Tat mimetic of VEGF correlates with increased microvessels density in AIDS-related diffuse large B-cell and Burkitt lymphomas

Angiogenic switch marks the beginning of tumor’s strategy to acquire independent blood supply. In some subtypes of non-Hodgkin’s lymphomas, higher local vascular endothelial growth factor (VEGF) expression correlates with increased microvessel density. However, this local VEGF expression is higher only in tumors with elevated expression of the receptors of the growth factor, suggesting an autocrine growth-promoting feedback loop. Several studies have indicated that VEGF receptors are also targeted by Tat protein from the HIV-1-infected cells. Given the similarity of the basic region of Tat to the angiogenic factors (basic fibroblast growth factor, VEGF), Tat mimics these proteins and binds to their receptors. We evaluated the role of HIV-1 Tat in regulating the level of VEGF expression and microvessel density in the AIDS-related diffuse large B-cell (DLBCL) and Burkitt lymphomas (BL). By luciferase assay, we showed that VEGF promoter activity was downregulated in vitro in cells transfected with Tat. Reduced VEGF protein expression in primary HIV-1 positive BL and DLBCL, compared to the negative cases, supported the findings of promoter downregulation from the cell lines. Microvascular density assessed by CD34 expression was, however, higher in HIV-1 positive than in HIV-1 negative tumors. These results suggest that Tat has a wider angiogenic role, besides the regulation of VEGF expression. Thus, targeting Tat protein itself and stabilizing transient silencing of VEGF expression or use of monoclonal antibodies against their receptors in the AIDS-associated tumors will open a window for future explorable pathways in the management of angiogenic phenotypes in the AIDS-associated non-Hodgkin’s lymphomas

Induction of PPM1D following DNA-damaging treatments through a conserved p53 response element coincides with a shift in the use of transcription initiation sites

PPM1D (Wip1), a type PP2C phosphatase, is expressed at low levels in most normal tissues but is overexpressed in several types of cancers. In cells containing wild-type p53, the levels of PPM1D mRNA and protein increase following exposure to genotoxic stress, but the mechanism of regulation by p53 was unknown. PPM1D also has been identified as a CREB-regulated gene due to the presence of a cyclic AMP response element (CRE) in the promoter. Transient transfection and chromatin immunoprecipitation experiments in HCT116 cells were used to characterize a conserved p53 response element located in the 5′ untranslated region (UTR) of the PPM1D gene that is required for the p53-dependent induction of transcription from the human PPM1D promoter. CREB binding to the CRE contributes to the regulation of basal expression of PPM1D and directs transcription initiation at upstream sites. Following exposure to ultraviolet (UV) or ionizing radiation, the abundance of transcripts with short 5′ UTRs increased in cells containing wild-type p53, indicating increased utilization of downstream transcription initiation sites. In cells containing wild-type p53, exposure to UV resulted in increased PPM1D protein levels even when PPM1D mRNA levels remained constant, indicating post-transcriptional regulation of PPM1D protein levels

Diffusion in crowded biological environments: applications of Brownian dynamics

Biochemical reactions in living systems occur in complex, heterogeneous media with total concentrations of macromolecules in the range of 50 - 400 mgml. Molecular species occupy a significant fraction of the immersing medium, up to 40% of volume. Such complex and volume-occupied environments are generally termed 'crowded' and/or 'confined'. In crowded conditions non-specific interactions between macromolecules may hinder diffusion - a major process determining metabolism, transport, and signaling. Also, the crowded media can alter, both qualitatively and quantitatively, the reactions in vivo in comparison with their in vitro counterparts. This review focuses on recent developments in particle-based Brownian dynamics algorithms, their applications to model diffusive transport in crowded systems, and their abilities to reproduce and predict the behavior of macromolecules under in vivo conditions

Stochastic Acceleration by Turbulence

The subject of this paper is stochastic acceleration by plasma turbulence, a process akin to the original model proposed by Fermi. We review the relative merits of different acceleration models, in particular the so called first order Fermi acceleration by shocks and second order Fermi by stochastic processes, and point out that plasma waves or turbulence play an important role in all mechanisms of acceleration. Thus, stochastic acceleration by turbulence is active in most situations. We also show that it is the most efficient mechanism of acceleration of relatively cool non relativistic thermal background plasma particles. In addition, it can preferentially accelerate electrons relative to protons as is needed in many astrophysical radiating sources, where usually there are no indications of presence of shocks. We also point out that a hybrid acceleration mechanism consisting of initial acceleration by turbulence of background particles followed by a second stage acceleration by a shock has many attractive features. It is demonstrated that the above scenarios can account for many signatures of the accelerated electrons, protons and other ions, in particular $^3$He and $^4$He, seen directly as Solar Energetic Particles and through the radiation they produce in solar flares.Comment: 29 pages 7 figures for proceedings of ISSI-Bern workshop on Particle Acceleration 201

Epigenetic polypharmacology: from combination therapy to multitargeted drugs

The modern drug discovery process has largely focused its attention in the so-called magic bullets, single chemical entities that exhibit high selectivity and potency for a particular target. This approach was based on the assumption that the deregulation of a protein was causally linked to a disease state, and the pharmacological intervention through inhibition of the deregulated target was able to restore normal cell function. However, the use of cocktails or multicomponent drugs to address several targets simultaneously is also popular to treat multifactorial diseases such as cancer and neurological disorders. We review the state of the art with such combinations that have an epigenetic target as one of their mechanisms of action. Epigenetic drug discovery is a rapidly advancing field, and drugs targeting epigenetic enzymes are in the clinic for the treatment of hematological cancers. Approved and experimental epigenetic drugs are undergoing clinical trials in combination with other therapeutic agents via fused or linked pharmacophores in order to benefit from synergistic effects of polypharmacology. In addition, ligands are being discovered which, as single chemical entities, are able to modulate multiple epigenetic targets simultaneously (multitarget epigenetic drugs). These multiple ligands should in principle have a lower risk of drug-drug interactions and drug resistance compared to cocktails or multicomponent drugs. This new generation may rival the so-called magic bullets in the treatment of diseases that arise as a consequence of the deregulation of multiple signaling pathways provided the challenge of optimization of the activities shown by the pharmacophores with the different targets is addressed