Overlapping roles of NADPH oxidase 4 for diabetic and gadolinium-based contrast agent-induced systemic fibrosis.

Dozens of millions of people are exposed to gadolinium-based contrast agents annually for enhanced magnetic resonance imaging. Gadolinium-based contrast agents are known nephrotoxins and can trigger the potentially fatal condition of systemic fibrosis. Risk factors are practically entirely undefined. We examined the role of NADPH oxidase 4 (Nox4) in gadolinium-induced systemic disease. Age- and weight-matched mice were randomized to experimental diabetes (streptozotocin) and control groups followed by systemic gadolinium-based contrast agent treatment. Nox4-deficient mice were randomized to experimental diabetes and gadolinium-based contrast agent treatment. Skin fibrosis and cellular infiltration were apparent in both gadolinium-based contrast agent-treated and experimental diabetes groups. Similarly, both groups demonstrated renal pathologies with evidence of reactive oxygen species generation. Deletion of Nox4 abrogated both skin and renal pathology, whether from diabetes or gadolinium-based contrast agent treatment. These discoveries demonstrate the importance of Nox4 in gadolinium-based contrast agent- and diabetes-induced fibrosis.NEW & NOTEWORTHY A mouse model of gadolinium-based contrast agent- and diabetes-induced fibrosis was used to demonstrate the role of NADPH oxidase 4 (Nox4) in gadolinium-induced systemic disease. Using these models, we established the role of Nox4 as a mediator of reactive oxygen species generation and subsequent skin and kidney fibrosis. These novel findings have defined Nox-4-mediated mechanisms by which gadolinium-based contrast agents induce systemic diseases.

Mouse Metanephric Mesenchymal Cell-Derived Angioblasts Undergo Vasculogenesis in Three-Dimensional Culture.

In vitro models for the investigation of renal vascular development are limited. We previously showed that isolated metanephric mesenchymal (MM) and ureteric bud (UB) cells grown in three-dimensional (3D) matrices formed organoids that consisted of primitive vascular structures surrounding a polarized epithelium. Here, we examined the potential of two principal effectors of vasculogenesis, vascular endothelial growth factor A (VEGF-A), and platelet-derived growth factor B chain (PDGF-BB), to stimulate MM cell differentiation. The results showed that MM cells possess angioblast characteristics by expressing phenotypic markers for endothelial and mesenchymal cells. UB cells synthesize VEGF-A and PDGF-BB proteins and RNA, whereas the MM cells express the respective cognate receptors, supporting their role in directional induction of vasculogenesis. VEGF-A stimulated proliferation of MM cells in monolayer and in 3D sponges but did not affect MM cell migration, organization, or vasculogenesis. However, PDGF-BB stimulated MM cell proliferation, migration, and vasculogenesis in monolayer and organization of the cells into primitive capillary-like assemblies in 3D sea sponge scaffolds in vitro. A role for PDGF-BB in vasculogenesis in the 3D MM/UB co-culture system was validated by direct interference with PDGF-BB or PDGF receptor-ß cell interactions to implicate PDGF-BB as a primary effector of MM cell vasculogenesis. Thus, MM cells resemble early renal angioblasts that may provide an ideal platform for the investigation of renal vasculogenesis in vitro.

Gadolinium-based contrast agents: why nephrologists need to be concerned.

PURPOSE OF REVIEW: The hegemony of gadolinium-based contrast agent-induced adverse events stretches beyond those who have renal impairment. 'Nephrogenic' systemic fibrosis is a misnomer: gadolinium-based contrast agents are the known trigger for the disease; kidney impairment is a risk factor. Impaired (true) glomerular filtration may be one catalyst for gadolinium-based contrast agent-induced adverse events, but it is increasingly evident that the same cluster of symptoms occurs in patients with normal renal function. RECENT FINDINGS: It has been known for nearly 30 years that gadolinium-based contrast agents distribute and are cleared according to a three compartment model. Single doses of gadolinium-based contrast agents can trigger 'nephrogenic' systemic fibrosis in nondialysis dependent patients. Manifestations have occurred years after exposure. Renal insufficiency alone is not an adequate explanation for 'nephrogenic' systemic fibrosis, and the continuum of its symptoms with the adverse events reported by patients with normal renal function clearly indicate that the physiologic reactions are largely undefined. SUMMARY: Gadolinium-based contrast agents should be used with extreme caution.

Gadolinium-based contrast agents: Stimulators of myeloid-induced renal fibrosis and major metabolic disruptors.

Evidence for gadolinium-based contrast agent- (GBCA-) induced disease continues to mount. Risk factors for gadolinium-induced systemic fibrosis are entirely unexplored. Obesity-related renal injury is characterized by activation of glomerular mesangial cells and podocyte damage with alteration of lipid metabolism/lipid accumulation in both cell types resulting in matrix accumulation and eventual progression to glomerulosclerosis. We examined the consequences of GBCA treatment in the kidneys from mice with normal kidney function and the potential interplay between obesity and gadolinium exposure. We found that administration of GBCA (4 weeks) causes significant renal fibrosis and podocyte injury that are associated with metabolic disorders as evidenced by dyslipidemia. Metabolomic analysis demonstrated that renal lipid metabolism and metabolic markers of collagen turnover are significantly altered by gadolinium. GBCA stimulates myeloid-derived fibrocytes to the kidney. Obesity was induced by feeding a group of mice a high fat diet (HFD) for 22 weeks. Groups were sub-randomized to GBCA treatment versus none for 4 weeks before sacrifice. HFD-induced fibrosis and podocyte injury were worsened by GBCA. Similarly, HFD-mediated hyperlipidemia and lipid metabolites were exacerbated by gadolinium. This is the first evidence that GBCA causes significant metabolic disorders and kidney injury in mice without renal insufficiency and that the injurious actions of GBCA are amplified by obesity. The understanding of the functional interplay between gadolinium and obesity will allow the development of therapeutic interventions or the establishment of effective preventive measures to reduce gadolinium- and obesity-mediated renal pathologies.

Survey of gastrointestinal nematodes in breeding-age heifers on 6 Saskatchewan dairy farms.

To determine the prevalence, mean fecal egg count intensities, and predominant gastrointestinal nematode species, fresh environmental fecal samples were collected from 30 grazing heifers at monthly intervals (June, July, and August) on 6 Saskatchewan dairy farms in 2016. The population average strongylid prevalence ranged from 67.2% [95% confidence interval (CI): 49.5% to 84.9%] in June to 88.3% (95% CI: 76.7% to 100.0%) in August (P = 0.05) while the mean fecal egg count ranged from 1.7 in June to 9.3 eggs/g of feces in August (P < 0.003). The predominant nematode species were identified using a deep-sequencing nemabiome assay targeting the internal transcribed spacer rDNA genomic locus of both L1 and L3-stage larvae. Cooperia oncophora and Ostertagia ostertagi were predominant on all farms, accounting for > 85% of the species. The results provide important previously unavailable data on the epidemiology of gastrointestinal nematodes (GIN) in fecal samples from these grazing heifers in Saskatchewan.

Examen des nématodes gastro-intestinaux chez les génisses en âge de se reproduire sur six fermes laitières de la Saskatchewan. Afin de déterminer la prévalence, l'intensité du dénombrement moyen d'oeufs dans les fèces et les espèces de nématodes gastro-intestinaux prédominants, des échantillons environnementaux de fèces fraîches furent prélevés de 30 génisses au pâturage à un intervalle mensuel (juin, juillet, et août) sur six fermes laitières de la Saskatchewan en 2016. La prévalence de la population moyenne de strongyles variait de 67,2 % [intervalle de confiance de 95 % (CI) : 49,5 % à 84,9 %] en juin à 88,3 % (CI 95 % : 76,7 % à 100,0 %) en août (P = 0,05) alors que le dénombrement moyen des oeufs dans les fèces variait de 1,7 en juin à 9,3 oeufs/g de fèces en août (P < 0,003). Les espèces de nématodes prédominantes furent identifiées à l'aide d'un test de séquençage profond du némabiome visant l'ADNr du locus génomique de l'espaceur interne transcrit des stades larvaires L1 et L3. Cooperia oncophora et Ostertagia ostertagi étaient prédominants sur toutes les fermes, représentant > 85 % des espèces. Ces résultats fournissent des données importantes non-disponibles auparavant sur l'épidémiologie de GIN dans des échantillons de fèces provenant de ces génisses au pâturage en Saskatchewan.(Traduit par Dr Serge Messier).

Characteristics of parasitic egg shedding over a 1-year period in foals and their dams in 2 farms in central Saskatchewan.

The goals of this study were to report the seasonal shedding patterns of strongyle and Parascaris spp. eggs in repeated fecal samples for mares (n = 38) and foals (n = 39), and to evaluate the efficacy of ivermectin treatment in mares from 2 selected horse breeding farms in central Saskatchewan. Median strongyle fecal egg counts (FEC) peaked in July and August in adult horses. The farms differed significantly (P = 0.0005) in regard to strongyle shedding categories (< 200; 200 to 500; and > 500 eggs/g) over time, but for each individual horse (both farms combined) these categories did not differ over time (P = 0.13) on samples collected in grazing season. When evaluating 3 samples collected fall, summer and fall in 2 consecutive grazing seasons, 94% of horses that shed < 200 eggs/g on 2 initial samples, remained in the same category on the third sample. Mares on each farm didn't differ statistically in shedding categories when comparing September samples from 2 consecutive years (Farm A: P = 0.56, Farm B: P = 0.06). Peak strongyle shedding occurred late fall in the first year of life for foals on Farm A, and in July in the second year of life for foals on Farm B. Parascaris spp. FEC were greatest in foals ≤ 6 months of age, with peak observed when foals were 5 to 6 months old. Ivermectin was 100% effective at reducing strongyle FEC 2 weeks after treatment in adult horses. Horses in Saskatchewan had relatively high strongyle shedding levels, which were significantly different between the farms, and high prevalence of Oxyuris equi. Strongyle shedding consistency was observed for FECs collected from mares in grazing season (July to September).

Caractéristiques de l'excrétion des oeufs de parasites pendant une période de 1 an chez les poulains et leurs mères dans deux fermes du centre de la Saskatchewan. Cette étude avait pour but de dresser un rapport sur les tendances d'excrétion saisonnière des oeufs des strongyles et de Parascaris spp. dans des prélèvements fécaux répétés pour les juments (n = 38) et les poulains (n = 39) et d'évaluer l'efficacité du traitement à l'ivermectine chez deux juments provenant de deux fermes d'élevage de chevaux dans le centre de la Saskatchewan. Les comptes médians d'oeufs fécaux des strongyles ont culminé en juillet et en août chez les chevaux adultes. Les fermes présentaient des différences significatives (P = 0,0005) à l'égard des catégories d'excrétion des strongyles (< 200; de 200 à 500; et > 500 oeufs/g) dans le temps, mais, pour chaque cheval individuel (les deux fermes combinées), ces catégories ne présentaient pas de différences à la longue (P = 0,13) pour les échantillons prélevés durant la saison de pâturage. Lors de l'évaluation des reois échantillons prélevés à l'automne, à l'été et à l'automne pendant deux saisons de pâturage consécutives, 94 % des chevaux qui avaient excrété < 200 oeufs/g pour deux prélèvements initiaux, sont demeurés dans la même catégorie pour le troisième échantillon. Les juments de chaque ferme ne présentaient pas de différences statistiques pour les catégories d'excrétion lorsque l'on comparait les échantillons de septembre provenant de deux années consécutives (Ferme A : P = 0,56, Ferme B : P = 0,06). L'excrétion des strongyles a culminé à la fin de l'automne pendant la première année de vie pour les poulains de la Ferme A et en juillet de la deuxième année de vie pour les poulains de la Ferme B. Les comptes d'oeufs fécaux de Parascaris spp. étaient les plus importants chez les poulains âgés de ≤ 6 mois et le point culminant était observé lorsque les poulains étaient âgés de 5 ou 6 mois. L'ivermectine était efficace à 100 % pour réduire les comptes d'oeufs fécaux 2 semaines après le traitement chez les chevaux adultes. Les chevaux de la Saskatchewan ont présenté des taux d'excrétion relativement élevés de strongyles, qui étaient significativement différents entre les fermes, et une forte prévalence d'Oxyuris equi. La constance de l'excrétion des strongyles a été observée pour les comptes d'oeufs fécaux obtenus auprès des juments pendant la saison de pâturage (de juillet à septembre).(Traduit par Isabelle Vallières).

Design and fabrication of distributed Bragg reflector multilayers for dynamic pressure sensing.

A novel 2D-surface shock pressure sensor is designed and tested based on 1D-Photonic Crystal, i.e., Distributed Bragg Reflector Multilayer (DBR/ML) structures. The fast opto-mechanical response of these structures to changes in layer thicknesses and refractive indices are ideally suited for dynamic pressure sensing. They offer the potential to minimize acoustic impedance mismatch between the material layers, and most importantly, the potential to monitor both temporal and spatial (lateral) variations during shock compression. In this feasibility study, different materials and device designs are investigated to identify material/device design combinations with optimum response to dynamic loading. Structural and material effects are studied in terms of spectral and mechanical properties, structure stability, and the ease of fabrication process. Structures comprising of different numbers of SiO1.5/SiO1.7 bilayer stacks are modeled, and fabricated. A 10-bilayer structure placed under a dynamic compressive load of ~7.2 GPa, exhibits a blueshift of 29 nm with a response time of ~5 ns which is well within the shock pressure rise time measured with PDV velocimetry. This promising result successfully demonstrates the feasibility of the specifically designed DBR/ML structure as a dynamic pressure sensor.

Centrality of bone marrow in the severity of gadolinium-based contrast-induced systemic fibrosis.

Systemic fibrosis can be induced in humans with gadolinium-based contrast, and cumulative doses correlate with severity. Bone marrow-derived fibrocytes accumulate in the dermis. Whether target organs liberate chemokines to recruit these fibrocytes or whether fibrocytes are stimulated to home to the affected tissue is unknown. Transgenic (tagged) donor rats were treated with gadolinium-based contrast. Bone marrow was obtained from diseased animals and age-matched controls. Rats with subtotal nephrectomies were lethally irradiated and underwent salvage transplantation with either the contrast-naïve or contrast-exposed bone marrow. Groups were randomly assigned to control or contrast treatment. Contrast treatment led to dermal fibrosis, and this was exacerbated in recipients of contrast-exposed marrow. Fibronectin, C-C chemokine receptors (CCRs)2 and 7, and oxidative stress were all increased in skin from contrast-treated animals-all parameters more severe in recipients of contrast-treated animals. The respective ligands, monocyte chemoattractant protein and C-C motif ligand 19, were both elevated in skin from contrast-treated animals. Coadministration of gadolinium-based contrast and a CCR2 inhibitor reduced the severity of skin disease as well as dermal cellularity. The functional role of chemokines in the effects of gadolinium-based contrast was further confirmed in in situ coculture studies using neutralizing CCR2 antibodies. These data implicate dermal liberation of specific chemokines in the recruitment of circulating bone marrow-derived cells. The disease is augmented by bone marrow exposure to contrast, which explains why multiple exposures correlate with severity.-Drel, V. R., Tan, C., Barnes, J. L., Gorin, Y., Lee, D.-Y., Wagner, B. Centrality of bone marrow in the severity of gadolinium-based contrast-induced systemic fibrosis.

Pathophysiology of gadolinium-associated systemic fibrosis.

Systemic fibrosis from gadolinium-based magnetic resonance imaging contrast is a scourge for the afflicted. Although gadolinium-associated systemic fibrosis is a rare condition, the threat of litigation has vastly altered clinical practice. Most theories concerning the etiology of the fibrosis are grounded in case reports rather than experiment. This has led to the widely accepted conjecture that the relative affinity of certain contrast agents for the gadolinium ion inversely correlates with the risk of succumbing to the disease. How gadolinium-containing contrast agents trigger widespread and site-specific systemic fibrosis and how chronicity is maintained are largely unknown. This review highlights experimentally-derived information from our laboratory and others that pertain to our understanding of the pathophysiology of gadolinium-associated systemic fibrosis.

Synthesis and characterization of a BaGdF5:Tb glass ceramic as a nanocomposite scintillator for x-ray imaging.

Transparent glass ceramics with embedded light-emitting nanocrystals show great potential as low-cost nanocomposite scintillators in comparison to single crystal and transparent ceramic scintillators. In this study, cubic structure BaGdF5:Tb nanocrystals embedded in an aluminosilicate glass matrix are reported for potential high performance MeV imaging applications. Scintillator samples with systematically varied compositions were prepared by a simple conventional melt-quenching method followed by annealing. Optical, structural and scintillation properties were characterized to guide the design and optimization of selected material systems, aiming at the development of a system with higher crystal volume and larger crystal size for improved luminosity. It is observed that enhanced scintillation performance was achieved by tuning the glass matrix composition and using GdF3 in the raw materials, which served as a nucleation agent. A 26% improvement in light output was observed from a BaGdF5:Tb glass ceramic with addition of GdF3.

Negative covariance between parasite load and body condition in a population of feral horses.

In wild and domestic animals, gastrointestinal parasites can have significant impacts on host development, condition, health, reproduction and longevity. Improving our understanding of the causes and consequences of individual-level variation in parasite load is therefore of prime interest. Here we investigated the relationship between strongyle fecal egg count (FEC) and body condition in a unique, naturalized population of horses that has never been exposed to anthelmintic drugs (Sable Island, Nova Scotia, Canada). We first quantified variation in FEC and condition for 447 individuals according to intrinsic (sex, age, reproductive status, social status) and extrinsic (group size, location, local density) variables. We then quantified the repeatability of measurements obtained over a field season and tested for covariance between FEC and condition. FECs were high relative to other horse populations (mean eggs per gram ± SD = 1543·28 ± 209·94). FECs generally decreased with age, were higher in lactating vs non-lactating females, and unexpectedly lower in males in some part of the island. FECs and condition were both spatially structured, with patterns depending on age, sex and reproductive status. FECs and condition were both repeatable. Most notably, FECs and condition were negatively correlated, especially in adult females.

Synthesis and luminescence properties of Tb doped LaBGeO5 and GdBGeO5 glass scintillators.

Borogermanate glasses show promise as scintillators due to their ability to incorporate high levels of heavy metal oxides without excessive loss of luminescent output intensity. Heavy metal oxide scintillating glasses of 50GeO2-25B2O3-(25-x)La2O3/Gd2O3-xTb2O3 (x=1,2,3,4) with the same stoichiometric composition of crystalline Tb doped LaBGeO5/GdBGeO5 were synthesized via the melt-quench method. Three times of higher light output under gamma ray excitation was observed from Tb doped GdBGeO5 based glass compared to LaBGeO5 glass due to efficient energy transfer between Gd-Tb pairs and higher luminescence efficiency in the GdBGeO5 glasses. The potential to form LaBGeO5/GdBGeO5 glass ceramic scintillators was also discussed and preliminarily investigated.

Identification of microfilaria in a mammary mass aspirate from a female dog.

A filarial nematode larva (microfilaria) was found in an aspirate of a mammary mass from a dog imported to Saskatchewan from Myanmar. This was an unusual location for a microfilaria and numerous filarial nematodes infecting dogs in Asia had to be considered. This report describes the laboratory diagnosis of canine heartworm disease in this dog.

Identification de la microfilaire dans le prélèvement par aspiration d'une masse mammaire chez une chienne. Une larve de nématode filaire (microfilaire) a été trouvée dans un prélèvement par aspiration d'une masse mammaire chez un chien importé en Saskatchewan en provenance du Myanmar. Il s'agissait d'un emplacement inhabituel pour une microfilaire et plusieurs nématodes filaires infectant les chiens en Asie ont dû être considérés. Ce rapport décrit le diagnostic de laboratoire de la maladie du ver du coeur canin chez ce chien.(Traduit par Isabelle Vallières).

Multiple liver abscesses in a dog secondary to the liver fluke Metorchis conjunctus treated by percutaneous transhepatic drainage and alcoholization.

A 1-year-old German shepherd × husky cross dog was diagnosed with multiple liver abscesses and severe cholangitis secondary to the liver fluke Metorchis conjunctus. The dog was successfully treated with 2 percutaneous transhepatic drainage and alcoholization procedures, and a prolonged course of antibiotics and praziquantel.

Abcès hépatiques multiples chez un chien secondaire à une douve du foieMetorchis conjunctustraitée par drainage transhépatique percutané et alcoolisation. Un chien de race croisée Berger allemand et Husky âgé de 1 an a été diagnostiqué avec des abcès hépatiques multiples et une cholangite grave secondaire à la douve du foie Metorchis conjunctus. Le chien a été traité avec succès à l'aide de deux interventions de drainage transhépatique percutané et d'alcoolisation ainsi que d'un traitement prolongé aux antibiotiques et au praziquantel.(Traduit par Isabelle Vallières).

Enteric parasites of free-roaming, owned, and rural cats in prairie regions of Canada.

The objective of this study was to determine prevalence, intensity, and zoonotic potential of gastrointestinal parasites in free-roaming and pet cats in urban areas of Saskatchewan (SK) and a rural region in southwestern Alberta (AB). Fecal samples were analyzed using a modified double centrifugation sucrose flotation to detect helminth eggs and coccidian oocysts, and an immunofluorescence assay to detect Giardia and Cryptosporidium. Endoparasite prevalence was higher in samples from rural AB cats (41% of 27) and free-roaming SK cats (32% of 161) than client-owned SK cats (6% of 31). Parasites identified using morphological and molecular techniques included Toxocara cati, Toxascaris leonina, Baylisascaris-type eggs, Eucoleus aerophilus, Taenia taeniaeformis, Isospora spp., Cryptosporidium spp., and zoonotic genotype A of Giardia duodenalis. This study demonstrates significant differences in endoparasite prevalence in feline populations, and the value of molecular techniques in fecal-based surveys to identify and determine parasite zoonotic potential.

Parasites entériques des chats errants, des chats avec propriétaire et des chats ruraux dans les régions des Prairies du Canada. Cette étude avait pour but de déterminer la prévalence, l'intensité et le potentiel zoonotique des parasites gastro-intestinaux chez les chats errants et les chats animaux de compagnie dans les régions urbaines de la Saskatchewan et une région rurale du Sud-Ouest de l'Alberta. Des échantillons de fèces ont été analysés à l'aide d'une méthode modifiée de flottaison au sucrose à double centrifugation afin de détecter les œufs d'helminthe et les ookystes coccidiens et une épreuve d'immunofluorescence a été réalisée pour détecter Giardia et Cryptosporidium. La prévalence des endoparasites était supérieure dans les échantillons provenant de chats ruraux de l'Alberta (41 % de 27) et de chats errants de la Saskatchewan (32 % de 161) que dans ceux de chats appartenant à des clients (6 % de 31). Les parasites identifiés à l'aide de techniques morphologiques et moléculaires incluaient Toxocara cati, Toxascaris leonina, des œufs de type Baylisascaris, Eucoleus aerophilus, Taenia taeniaeformis, Isospora spp., Cryptosporidium spp., et un génotype zoonotique A de Giardia duodenalis. Cette étude démontre les différences significatives dans la prévalence des endoparasites chez les populations félines et la valeur des techniques moléculaires dans les études basées sur les fèces afin d'identifier et de déterminer le potentiel zoonotique.(Traduit par Isabelle Vallières).

Src tyrosine kinase mediates platelet-derived growth factor BB-induced and redox-dependent migration in metanephric mesenchymal cells.

The adult kidney is derived from the interaction between the metanephric blastema and the ureteric bud. Platelet-derived growth factor (PDGF) receptor ß is essential for the development of the mature glomerular tuft, as mice deficient for this receptor lack mesangial cells. This study investigated the role of Src tyrosine kinase in PDGF-mediated reactive oxygen species (ROS) generation and migration of metanephric mesenchymal cells (MMCs). Cultured embryonic MMCs from wild-type and PDGF receptor-deficient embryos were established. Migration was determined via wound-healing assay. Unlike PDGF AA, PDGF BB-induced greater migration in MMCs with respect to control. This was abrogated by neutralizing an antibody to PDGF BB. Phosphatidylinositol 3-kinase (PI3K) inhibitors suppressed PDGF BB-induced migration. Conversely, mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) inhibitors had no effect. Src inhibitors inhibited PDGF-induced cell migration, PI3K activity, and Akt phosphorylation. Adenoviral dominant negative Src (AD DN Src) abrogated PDGF BB-induced Akt phosphorylation. Hydrogen peroxide stimulated cell migration. PDGF BB-induced wound closure was inhibited by the antioxidants N-acetyl-l-cysteine, tiron, and the flavoprotein inhibitor diphenyleneiodonium. These cells express the NADPH oxidase homolog Nox4. Inhibiting Nox4 with antisense oligonucleotides or small interfering RNA (siRNA) suppressed PDGF-induced wound closure. Inhibition of Src with siRNA reduced PDGF BB-induced ROS generation as assessed by 2',7'-dichlorodihydrofluorescein diacetate fluorescence. Furthermore, PDGF BB-stimulated ROS generation and migration were similarly suppressed by Ad DN Src. In MMCs, PDGF BB-induced migration is mediated by PI3K and Src in a redox-dependent manner involving Nox4. Src may be upstream to PI3K and Nox4.

Type of MRI contrast, tissue gadolinium, and fibrosis.

It has been presupposed that the thermodynamic stability constant (K(therm)) of gadolinium-based MRI chelates relate to the risk of precipitating nephrogenic systemic fibrosis. The present study compared low-K(therm) gadodiamide with high-K(therm) gadoteridol in cultured fibroblasts and rats with uninephrectomies. Gadolinium content was assessed using scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy in paraffin-embedded tissues. In vitro, fibroblasts demonstrated dose-dependent fibronectin generation, transforming growth factor-ß production, and expression of activated myofibroblast stress fiber protein α-smooth muscle actin. There were negligible differences with respect to toxicity or proliferation between the two contrast agents. In the rodent model, gadodiamide treatment led to greater skin fibrosis and dermal cellularity than gadoteridol. In the kidney, both contrast agents led to proximal tubule vacuolization and increased fibronectin accumulation. Despite large detectable gadolinium signals in the spleen, skin, muscle, and liver from the gadodiamide-treated group, contrast-induced fibrosis appeared to be limited to the skin and kidney. These findings support the hypothesis that low-K(therm) chelates have a greater propensity to elicit nephrogenic systemic fibrosis and demonstrate that certain tissues are resistant to these effects.

Composition optimization of scintillating rare-earth nanocrystals in oxide glass-ceramics for radiation spectroscopy.

Glass-ceramic nanocomposites comprising GdBr3/CeBr3 loaded sodium-aluminosilicate glasses in which scintillating crystallites are precipitated in situ from a host glass matrix were studied. This materials system shows promise as an alternative to single-crystal scintillators, with potential to be fabricated into a wide variety of sizes, shapes, and compositions. Batch compositions containing 15-18 mol. % GdBr3 and 3-4 mol. % CeBr3 were prepared and analyzed for photoluminescent light yield. Light yield peaked with rare-earth content of 15 mol. % GdBr3 and 4 mol. % CeBr3. Preliminary ceramization studies on this composition found that the precipitated phase more closely matched a Gd2O3-CeO2 mixture rather than the GdBr3(Ce) that was targeted.