Effect of Sucralfate on the Relative Bioavailability of Enrofloxacin and Ciprofloxacin in Healthy Fed Dogs

Background: Sucralfate impairs absorption of ciprofloxacin and other fluoroquinolones in humans, but no sucralfate-fluoroquinolone interaction has been reported in dogs. Veterinary formularies recommend avoiding concurrent administration of these medications, which might impact compliance, therapeutic success, and resistance selection from fluoroquinolones. Objectives: To determine whether a drug interaction exists when sucralfate is administered to fed dogs concurrently with ciprofloxacin or enrofloxacin, and whether a 2 hour delay between fluoroquinolone and sucralfate affects fluoroquinolone absorption. Animals: Five healthy Greyhounds housed in a research colony. Methods: This was a randomized crossover study. Treatments included oral ciprofloxacin (C) or oral enrofloxacin (E) alone, each fluoroquinolone concurrently with an oral suspension of sucralfate (CS, ES), and sucralfate suspension 2 hours after each fluoroquinolone (C2S, E2S). Fluoroquinolone concentrations were evaluated using liquid chromatography with mass spectrometry. Results: Drug exposure of ciprofloxacin was highly variable (AUC 5.52-22.47 h ?g/mL) compared to enrofloxacin (AUC 3.86-7.50 h ?g/mL). The mean relative bioavailability for ciprofloxacin and concurrent sucralfate was 48% (range 8-143%) compared to ciprofloxacin alone. Relative bioavailability of ciprofloxacin improved to 87% (range 37-333%) when sucralfate was delayed by 2 hours. By contrast, relative bioavailability for enrofloxacin and concurrent sucralfate was 104% (94-115%).Citation: KuKanich, K., KuKanich, B., Guess, S. and Heinrich, E. (2015), Effect of Sucralfate on the Relative Bioavailability of Enrofloxacin and Ciprofloxacin in Healthy Fed Dogs. Journal of Veterinary Internal Medicine. doi: 10.1111/jvim.1379

Insulin-associated weight gain in obese type 2 diabetes mellitus patients: What can be done?

Insulin therapy (IT ) is initiated for patients with type 2 diabetes mellitus when glycaemic targets are not met with diet and other hypoglycaemic agents. The initiation of IT improves glycaemic control and reduces the risk of microvascular complications. There is, however, an associated weight gain following IT , which may adversely affect diabetic and cardiovascular morbidity and mortality. A 3 to 9 kg insulin‐associated weight gain (IAWG ) is reported to occur in the first year of initiating IT , predominantly caused by adipose tissue. The potential causes for this weight gain include an increase in energy intake linked to a fear of hypoglycaemia, a reduction in glycosuria, catch‐up weight, and central effects on weight and appetite regulation. Patients with type 2 diabetes who are receiving IT often have multiple co‐morbidities, including obesity, that are exacerbated by weight gain, making the management of their diabetes and obesity challenging. There are several treatment strategies for patients with type 2 diabetes, who require IT , that attenuate weight gain, help improve glycaemic control, and help promote body weight homeostasis. This review addresses the effects of insulin initiation and intensification on IAWG , and explores its potential underlying mechanisms, the predictors for this weight gain, and the available treatment options for managing and limiting weight gain

Intratumoral Delivery of Interferon\u3b3-Secreting Mesenchymal Stromal Cells Repolarizes Tumor-Associated Macrophages and Suppresses Neuroblastoma Proliferation In Vivo

Neuroblastoma, the most common extracranial solid tumor in childhood, remains a therapeutic challenge. However, one promising patient treatment strategy is the delivery of anti-tumor therapeutic agents via mesenchymal stromal cell (MSC) therapy. MSCs have been safely used to treat genetic bone diseases such as osteogenesis imperfecta, cardiovascular diseases, autoimmune diseases, and cancer. The pro-inflammatory cytokine interferon-gamma (IFN\u3b3) has been shown to decrease tumor proliferation by altering the tumor microenvironment (TME). Despite this, clinical trials of systemic IFN\u3b3 therapy have failed due to the high blood concentration required and associated systemic toxicities. Here, we developed an intra-adrenal model of neuroblastoma, characterized by liver and lung metastases. We then engineered MSCs to deliver IFN\u3b3 directly to the TME. In vitro, these MSCs polarized murine macrophages to the M1 phenotype. In vivo, we attained a therapeutically active TME concentration of IFN\u3b3 without increased systemic concentration or toxicity. The TME-specific IFN\u3b3 reduced tumor growth rate and increased survival in two models of T cell deficient athymic nude mice. Absence of this benefit in NOD SCID gamma (NSG) immunodeficient mouse model indicates a mechanism dependent on the innate immune system. IL-17 and IL-23p19, both uniquely M1 polarization markers, transiently increased in the tumor interstitial fluid. Finally, the MSC vehicle did not promote tumor growth. These findings reveal that MSCs can deliver effective cytokine therapy directly to the tumor while avoiding systemic toxicity. This method transiently induces inflammatory M1 macrophage polarization, which reduces tumor burden in our novel neuroblastoma murine model

Analysis of Web Browsing Data: A Guide

The use of individual-level browsing data, that is, the records of a person’s visits to online content through a desktop or mobile browser, is of increasing importance for social scientists. Browsing data have characteristics that raise many questions for statistical analysis, yet to date, little hands-on guidance on how to handle them exists. Reviewing extant research, and exploring data sets collected by our four research teams spanning seven countries and several years, with over 14,000 participants and 360 million web visits, we derive recommendations along four steps: preprocessing the raw data; filtering out observations; classifying web visits; and modelling browsing behavior. The recommendations we formulate aim to foster best practices in the field, which so far has paid little attention to justifying the many decisions researchers need to take when analyzing web browsing data.Die Verwendung von Browsing-Daten auf individueller Ebene, d.h. die Aufzeichnungen der Besuche einer Person bei Online-Inhalten über einen Desktop- oder mobilen Browser, ist für Sozialwissenschaftler*innen von zunehmender Bedeutung. Browsing-Daten haben Eigenschaften, die viele Fragen für die statistische Analyse aufwerfen, doch bisher gibt es nur wenige praktische Anleitungen für den Umgang mit ihnen. Nach Durchsicht bestehender Forschungsarbeiten und der Untersuchung von Datensätzen, die von vier Forschungsteams in sieben Ländern und über mehrere Jahre hinweg gesammelt wurden, mit über 14.000 Teilnehmenden und 360 Millionen Webbesuchen, leiten die Autor*innen Empfehlungen in vier Schritten ab: Vorverarbeitung der Rohdaten, Herausfiltern von Beobachtungen, Klassifizierung von Webbesuchen und Modellierung des Surfverhaltens

Spectroscopy of 13B via the 13C(t,3He) reaction at 115 AMeV

Gamow-Teller and dipole transitions to final states in 13B were studied via the 13C(t,3He) reaction at Et = 115 AMeV. Besides the strong Gamow-Teller transition to the 13B ground state, a weaker Gamow-Teller transition to a state at 3.6 MeV was found. This state was assigned a spin-parity of 3/2- by comparison with shell-model calculations using the WBP and WBT interactions which were modified to allow for mixing between nhw and (n+2)hw configurations. This assignment agrees with a recent result from a lifetime measurement of excited states in 13B. The shell-model calculations also explained the relatively large spectroscopic strength measured for a low-lying 1/2+ state at 4.83 MeV in 13B. The cross sections for dipole transitions up to Ex(13B)= 20 MeV excited via the 13C(t,3He) reaction were also compared with the shell-model calculations. The theoretical cross sections exceeded the data by a factor of about 1.8, which might indicate that the dipole excitations are "quenched". Uncertainties in the reaction calculations complicate that interpretation.Comment: 11 pages, 6 figure

Identification of a murine CD45-F4/80lo HSC-derived marrow endosteal cell associated with donor stem cell engraftment

Hematopoietic stem cells (HSCs) reside in specialized microenvironments within the marrow designated as stem cell niches, which function to support HSCs at homeostasis and promote HSC engraftment after radioablation. We previously identified marrow space remodeling after hematopoietic ablation, including osteoblast thickening, osteoblast proliferation, and megakaryocyte migration to the endosteum, which is critical for effective engraftment of donor HSCs. To further evaluate the impact of hematopoietic cells on marrow remodeling, we used a transgenic mouse model (CD45Cre/iDTR) to selectively deplete hematopoietic cells in situ. Depletion of hematopoietic cells immediately before radioablation and hematopoietic stem cell transplantation abrogated donor HSC engraftment and was associated with strikingly flattened endosteal osteoblasts with preserved osteoblast proliferation and megakaryocyte migration. Depletion of monocytes, macrophages, or megakaryocytes (the predominant hematopoietic cell populations that survive short-term after irradiation) did not lead to an alteration of osteoblast morphology, suggesting that a hematopoietic-derived cell outside these lineages regulates osteoblast morphologic adaptation after irradiation. Using 2 lineage-tracing strategies, we identified a novel CD45-F4/80lo HSC-derived cell that resides among osteoblasts along the endosteal marrow surface and, at least transiently, survives radioablation. This newly identified marrow cell may be an important regulator of HSC engraftment, possibly by influencing the shape and function of endosteal osteoblasts

Rethinking globalised resistance : feminist activism and critical theorising in international relations

This article argues that a feminist approach to the 'politics of resistance' offers a number of important empirical insights which, in turn, open up lines of theoretical inquiry which critical theorists in IR would do well to explore. Concretely, we draw on our ongoing research into feminist 'anti-globalisation' activism to rethink the nature of the subject of the politics of resistance, the conditions under which resistance emerges and how resistance is enacted and expressed. We begin by discussing the relationship of feminism to critical IR theory as a way of situating and explaining the focus and approach of our research project. We then summarise our key empirical arguments regarding the emergence, structure, beliefs, identities and practices of feminist 'anti-globalisation' activism before exploring the implications of these for a renewed critical theoretical agenda in IR

On the extraction of weak transition strengths via the (3He,t) reaction at 420 MeV

Differential cross sections for transitions of known weak strength were measured with the (3He,t) reaction at 420 MeV on targets of 12C, 13C, 18O, 26Mg, 58Ni, 60Ni, 90Zr, 118Sn, 120Sn and 208Pb. Using this data, it is shown the proportionalities between strengths and cross sections for this probe follow simple trends as a function of mass number. These trends can be used to confidently determine Gamow-Teller strength distributions in nuclei for which the proportionality cannot be calibrated via beta-decay strengths. Although theoretical calculations in distorted-wave Born approximation overestimate the data, they allow one to understand the main experimental features and to predict deviations from the simple trends observed in some of the transitions.Comment: 4 pages, 2 figure

Beta-delayed proton emission in the 100Sn region

Beta-delayed proton emission from nuclides in the neighborhood of 100Sn was studied at the National Superconducting Cyclotron Laboratory. The nuclei were produced by fragmentation of a 120 MeV/nucleon 112Sn primary beam on a Be target. Beam purification was provided by the A1900 Fragment Separator and the Radio Frequency Fragment Separator. The fragments of interest were identified and their decay was studied with the NSCL Beta Counting System (BCS) in conjunction with the Segmented Germanium Array (SeGA). The nuclei 96Cd, 98Ing, 98Inm and 99In were identified as beta-delayed proton emitters, with branching ratios bp = 5.5(40)%, 5.5+3 -2%, 19(2)% and 0.9(4)%, respectively. The bp for 89Ru, 91,92Rh, 93Pd and 95Ag were deduced for the first time with bp = 3+1.9 -1.7%, 1.3(5)%, 1.9(1)%, 7.5(5)% and 2.5(3)%, respectively. The bp = 22(1)% for 101Sn was deduced with higher precision than previously reported. The impact of the newly measured bp values on the composition of the type-I X-ray burst ashes was studied.Comment: 15 pages, 14 Figures, 4 Table