Disparate effects of chronic and acute theophylline on cyclosporine A nephrotoxicity

Abstract : We previously developed a model of acute cyclosporine A (CsA)-induced vasomotor nephrotoxicity in rabbits. As exogenous adenosine infusion mimics the haemodynamic changes that characterize acute renal failure (ARF), we wanted to know whether adenosine was a mediator in this model and whether an adenosine receptor blocker could prevent the CsA-induced ARF. Group 1 were untreated controls. Group 2 received CsA (25 mg/kg per day) for 5 days. Renal function parameters were measured, showing ARF in all animals compared to controls. Theophylline (1 mg/kg i.v. bolus) was then administered and renal function was reassessed. Theophylline significantly reduced renal vascular resistance (-8%) and increased renal blood flow (RBF) (+20%), glomerular filtration rate (GFR) (+50%), filtration fraction (+24%) and diuresis (+73%), suggesting that adenosine was involved in the CsA-induced ARF. In group 3, theophylline (30 mg/kg per day) was given concomitantly with CsA for 5 days. GFR was normalized, but theophylline did not hinder the drop in RBF seen with CsA alone in group 2. Microscopy observation of the kidneys showed that chronic theophylline administration aggravated the morphological changes induced by CsA alone. We conclude that CsA administration for 5 days induced a vasomotor nephropathy with an adenosine-mediated afferent arteriolar constriction which cannot be prevented by concomitant theophylline administratio

Making science at home: visual displays of space science and nuclear physics at the Science Museum and on television in postwar Britain

The public presentation of science and technology in postwar Britain remains a field open to exploration. Current scholarship on the topic is growing but still tends to concentrate on the written word, thus making theorizing, at this stage, difficult. This paper is an attempt to expand the literature through two case studies that compare and synthesize displays of scientific and technological knowledge in two visual media, the Science Museum and television, in the 1950s and 1960s. The topics of these case studies are space exploration and nuclear energy. The thesis this paper explores is that both media fleshed out strategies of displays based on the use of categories from everyday life. As a result, outcomes of large-scale public scientific and technological undertakings were interwoven within audiences’ daily life experiences, thus appearing ordinary rather than extraordinary. This use of symbols and values drawn from private life worked to alleviate fears of risk associated with these new fields of technological exploration and at the same time give them widespread currency in the public sphere

Vers un changement de pratique dans une filière céréalière : apport de la modélisation de l’environnement

National audienceProject management, especially in the field of sustainable development, requires to take into account not only the working environment stricto sensu, but also supra components of environmental, social, economic, legislative, etc. Ergonomists and psychologists are then led to be interested in, and to develop modeling frameworks to better understand and to make more intelligible this complex environment. The study presented here, which requires taking into account this environment, aims at setting up a novel practice for improving the food safety of a cereal chain in a global context of sustainable development: protection of the environment (flora and fauna) and the health of farmers and consumers. As part of this study, a quick fungal contamination diagnostic tool and a corresponding decontamination process have been developed for an application in the barley-malt-beer food chain. However, the use of these processes may change the agricultural practices in antifungal treatments with the regular and high dose treatments replaced by fine targeted applications only where and when necessary. In relation with this technological development, the challenge is to identify the components of the environment that may become brakes and levers to the implementation of this new practice. In this scope, this investigation mobilizes the modeling of the environment of Thatcher and Yeow (2016). This paper is consequently aimed at presenting the underlying process to this construction, and this in relation with the characteristics of the study. At last, a discussion is initiated concerning the further use of such modelling practices for purposes other than the decision-making processes on ergonomic intervention purposes.L’intervention ergonomique dans le champ du développement durable requiert la prise en compte d’un environnement dépassant largement l’environnement de travail afin d’y intégrer des composants relevant de dimensions environnementales, économique, législative, etc. Les ergonomes et psychologues ergonomes sont alors conduits à développer des cadres de modélisation permettant d’appréhender et de rendre davantage intelligible cet environnement complexe. L’étude sur laquelle nous nous basons ici s’inscrit dans ce cadre et vise l’identification des freins et leviers à la mise en place d’une nouvelle pratique en matière de traitement antifongique pour la filière orge-malt-bière. Pour cette investigation, nous nous référons notamment à la modélisation de Thatcher et Yeow (2016). L’enjeu est de présenter le processus de recueil et d’analyse sous-jacente à la modélisation et de poursuivre par une réflexion quant à l’emploi de ces formes de modélisation au cours d’un processus d’intervention

Microtiming patterns and interactions with musical properties in Samba music

In this study, we focus on the interaction between microtiming patterns and several musical properties: intensity, meter and spectral characteristics. The data-set of 106 musical audio excerpts is processed by means of an auditory model and then divided into several spectral regions and metric levels. The resulting segments are described in terms of their musical properties, over which patterns of peak positions and their intensities are sought. A clustering algorithm is used to systematize the process of pattern detection. The results confirm previously reported anticipations of the third and fourth semiquavers in a beat. We also argue that these patterns of microtiming deviations interact with different profiles of intensities that change according to the metrical structure and spectral characteristics. In particular, we suggest two new findings: (i) a small delay of microtiming positions at the lower end of the spectrum on the first semiquaver of each beat and (ii) systematic forms of accelerando and ritardando at a microtiming level covering two-beat and four-beat phrases. The results demonstrate the importance of multidimensional interactions with timing aspects of music. However, more research is needed in order to find proper representations for rhythm and microtiming aspects in such contexts

Variations in Multiple Birth Rates and Impact on Perinatal Outcomes in Europe

Objective Infants from multiple pregnancies have higher rates of preterm birth, stillbirth and neonatal death and differences in multiple birth rates (MBR) exist between countries. We aimed to describe differences in MBR in Europe and to investigate the impact of these differences on adverse perinatal outcomes at a population level. Methods We used national aggregate birth data on multiple pregnancies, maternal age, gestational age (GA), stillbirth and neonatal death collected in the Euro-Peristat project (29 countries in 2010, N = 5 074 643 births). We also used European Society of Human Reproduction and Embryology (ESHRE) data on assisted conception and single embryo transfer (SET). The impact of MBR on outcomes was studied using meta-analysis techniques with random-effects models to derive pooled risk ratios (pRR) overall and for four groups of country defined by their MBR. We computed population attributable risks (PAR) for these groups. Results In 2010, the average MBR was 16.8 per 1000 women giving birth, ranging from 9.1 (Romania) to 26.5 (Cyprus). Compared to singletons, multiples had a nine-fold increased risk (pRR 9.4, 95% Cl 9.1–9.8) of preterm birth (<37 weeks GA), an almost 12-fold increased risk (pRR 11.7, 95% CI 11.0–12.4) of very preterm birth (<32 weeks GA). Pooled RR were 2.4 (95% Cl 1.5–3.6) for fetal mortality at or after 28 weeks GA and 7.0 (95% Cl 6.1–8.0) for neonatal mortality. PAR of neonatal death and very preterm birth were higher in countries with high MBR compared to low MBR (17.1% (95% CI 13.8–20.2) versus 9.8% (95% Cl 9.6–11.0) for neonatal death and 29.6% (96% CI 28.5–30.6) versus 17.5% (95% CI 15.7–18.3) for very preterm births, respectively). Conclusions Wide variations in MBR and their impact on population outcomes imply that efforts by countries to reduce MBR could improve perinatal outcomes, enabling better long-term child health

Acute kidney injury in children

Acute kidney injury (AKI) (previously called acute renal failure) is characterized by a reversible increase in the blood concentration of creatinine and nitrogenous waste products and by the inability of the kidney to regulate fluid and electrolyte homeostasis appropriately. The incidence of AKI in children appears to be increasing, and the etiology of AKI over the past decades has shifted from primary renal disease to multifactorial causes, particularly in hospitalized children. Genetic factors may predispose some children to AKI. Renal injury can be divided into pre-renal failure, intrinsic renal disease including vascular insults, and obstructive uropathies. The pathophysiology of hypoxia/ischemia-induced AKI is not well understood, but significant progress in elucidating the cellular, biochemical and molecular events has been made over the past several years. The history, physical examination, and laboratory studies, including urinalysis and radiographic studies, can establish the likely cause(s) of AKI. Many interventions such as ‘renal-dose dopamine’ and diuretic therapy have been shown not to alter the course of AKI. The prognosis of AKI is highly dependent on the underlying etiology of the AKI. Children who have suffered AKI from any cause are at risk for late development of kidney disease several years after the initial insult. Therapeutic interventions in AKI have been largely disappointing, likely due to the complex nature of the pathophysiology of AKI, the fact that the serum creatinine concentration is an insensitive measure of kidney function, and because of co-morbid factors in treated patients. Improved understanding of the pathophysiology of AKI, early biomarkers of AKI, and better classification of AKI are needed for the development of successful therapeutic strategies for the treatment of AKI

Apical and basolateral localisation of GLUT2 transporters in human lung epithelial cells

Glucose concentrations of normal human airway surface liquid are ~12.5 times lower than blood glucose concentrations indicating that glucose uptake by epithelial cells may play a role in maintaining lung glucose homeostasis. We have therefore investigated potential glucose uptake mechanisms in non-polarised and polarised H441 human airway epithelial cells and bronchial biopsies. We detected mRNA and protein for glucose transporter type 2 (GLUT2) and glucose transporter type 4 (GLUT4) in non-polarised cells but GLUT4 was not detected in the plasma membrane. In polarised cells, GLUT2 protein was detected in both apical and basolateral membranes. Furthermore, GLUT2 protein was localised to epithelial cells of human bronchial mucosa biopsies. In non-polarised H441 cells, uptake of d-glucose and deoxyglucose was similar. Uptake of both was inhibited by phloretin indicating that glucose uptake was via GLUT-mediated transport. Phloretin-sensitive transport remained the predominant route for glucose uptake across apical and basolateral membranes of polarised cells and was maximal at 5–10 mM glucose. We could not conclusively demonstrate sodium/glucose transporter-mediated transport in non-polarised or polarised cells. Our study provides the first evidence that glucose transport in human airway epithelial cells in vitro and in vivo utilises GLUT2 transporters. We speculate that these transporters could contribute to glucose uptake/homeostasis in the human airway