Retention of Gadolinium in Brain Parenchyma: Pathways for Speciation, Access, and Distribution. A Critical Review.

The unexpected appearance of T hyperintensities, mostly in the dentate nucleus and the globus pallidus, during nonenhanced MRI was reported in 2014. This effect is associated with prior repeated administrations of gadolinium (Gd)-based contrast agents (GBCAs) in patients with a functional blood-brain barrier (BBB). It is widely assumed that GBCAs do not cross the intact BBB, but the observation of these hypersignals raises questions regarding this assumption.

Multimodal Imaging Study of Gadolinium Presence in Rat Cerebellum: Differences Between Gd Chelates, Presence in the Virchow-Robin Space, Association With Lipofuscin, and Hypotheses About Distribution Pathway.

Purpose: The aim of this study was to investigate, based on in-depth multimodal imaging, the presence of Gd deposits, their ultrastructure, location, and co-location with endogenous elements, in the cerebellum, after repeated administrations of gadolinium-based contrast agents (GBCAs).

Methods: Rats sensitized by subtotal nephrectomy received 20 daily intravenous injections of 0.6 mmol Gd/kg for 5 weeks of commercial forms of either gadoterate, gadobenate or gadodiamide, or saline (n = 2/group).

Application of laboratory and digital techniques for visual enhancement during the ultrastructural assessment of cilia.

Routine diagnostic electron microscopy of primary ciliary dyskinesia (PCD) is based on the findings of ultrastructural defects of axonemal components. Assessment of the typical abnormalities can be enhanced by improving the sample preservation status using tannic acid (TA) as additive in the biopsy fixation or processing steps. Another option is the implementation of computer-assisted image analysis tools.

Distribution profile of gadolinium in gadolinium chelate-treated renally-impaired rats: role of pharmaceutical formulation.

While not acutely toxic, chronic hepatic effect of certain gadolinium chelates (GC), used as contrast agent for magnetic resonance imaging, might represent a risk in renally-impaired patients due to free gadolinium accumulation in the liver. To answer this question, this study investigated the consequences of the presence of small amounts of either a soluble gadolinium salt ("free" Gd) or low-stability chelating impurity in the pharmaceutical solution of gadoteric acid, a macrocyclic GC with high thermodynamic and kinetic stabilities, were investigated in renally-impaired rats. Renal failure was induced by adding 0.

Tumor-Induced Osteomalacia: Increased Level of FGF-23 in a Patient with a Phosphaturic Mesenchymal Tumor at the Tibia Expressing Periostin.

In our case, a 45-year-old male patient had multiple fractures accompanied by hypophosphatemia. FGF-23 levels were significantly increased, and total body magnetic resonance imaging (MRI) revealed a tumor mass located at the distal tibia leading to the diagnosis of tumor-induced osteomalacia (TIO). After resection of the tumor, hypophosphatemia and the increased levels of FGF-23 normalized within a few days.

Endothelial dysfunction and altered mechanical and structural properties of resistance arteries in a murine model of graft-versus-host disease.

A putative involvement of the vasculature seems to play a critical role in the pathophysiology of graft-versus-host disease (GVHD). We aimed to characterize alterations of mesenteric resistance arteries in GVHD in a fully MHC-mismatched model of BALB/c mice conditioned with total body irradiation that underwent transplantation with bone marrow cells and splenocytes from syngeneic (BALB/c) or allogeneic (C57BL/6) donors. After 4 weeks, animals were sacrificed and mesenteric resistance arteries were studied in a pressurized myograph.

Inadequate corticosterone levels relative to arthritic inflammation are accompanied by altered mitochondria/cholesterol breakdown in adrenal cortex: a steroid-inhibiting role of IL-1β in rats.

Objectives: In rheumatoid arthritis, inadequate cortisol secretion was observed relative to inflammation, but reasons are unknown. Human adrenal glands cannot be investigated due to ethical reasons. Thus, a model of arthritis was studied to test inadequate glucocorticoid secretion and adrenocortical alterations.

Mistargeting of peroxisomal EHHADH and inherited renal Fanconi's syndrome.

Background: In renal Fanconi's syndrome, dysfunction in proximal tubular cells leads to renal losses of water, electrolytes, and low-molecular-weight nutrients. For most types of isolated Fanconi's syndrome, the genetic cause and underlying defect remain unknown.

Methods: We clinically and genetically characterized members of a five-generation black family with isolated autosomal dominant Fanconi's syndrome.

Male infertility: assessment of juvenile testicular dysfunction and risk for malignancy in cryptorchid boys based on resin section evaluation.

Infertility is sometimes more a man's problem than a woman's, failure of one or both of the testes to descend (cryptorchidism) being the most frequent genital malformation in boys. Untreated, the undescended testis impairs germ cell development and significantly reduces adult fertility. A-dark spermatogonia are the stem cells for all future spermatozoa, and their depletion can be reliably estimated in resin semithin sections.

Lipid-labeling facilitates a novel magnetic isolation procedure to characterize pathogen-containing phagosomes.

Here we describe a novel approach for the isolation and biochemical characterization of pathogen-containing compartments from primary cells: We developed a lipid-based procedure to magnetically label the surface of bacteria and visualized the label by scanning and transmission electron microscopy (SEM, TEM). We performed infection experiments with magnetically labeled Mycobacterium avium, M. tuberculosis and Listeria monocytogenes and isolated magnetic bacteria-containing phagosomes using a strong magnetic field in a novel free-flow system.

Recessive HYDIN mutations cause primary ciliary dyskinesia without randomization of left-right body asymmetry.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder characterized by defective cilia and flagella motility. Chronic destructive-airway disease is caused by abnormal respiratory-tract mucociliary clearance. Abnormal propulsion of sperm flagella contributes to male infertility.

Follicular thyroid adenoma dominated by spindle cells: report of two unusual cases and literature review.

Primary spindle cell neoplasms of the thyroid gland are quite rare. They encompass a heterogeneous group of benign and malignant lesions of mesenchymal and epithelial origin. We herein describe two unusual follicular thyroid adenomas dominated by spindle cells with occasional areas of colloid-forming follicular differentiation.

Skin gadolinium following use of MR contrast agents in a rat model of nephrogenic systemic fibrosis.

Purpose: To detect the ultrastructural site of gadolinium retention in skin by using an animal model of nephrogenic systemic fibrosis and compare a linear, low-stability gadolinium chelate (formulated gadodiamide) with a macrocylic, high-stability gadolinium chelate (gadoterate meglumine).

Materials And Methods: Experimental procedures were performed according to rules and regulations laid down by the UK Home Office (Animal Procedures Act of 1986). Male Wistar rats were subjected to 5/6 subtotal nephrectomy (creatinine clearance, 25% normal).

Cutaneous amyloidoses and systemic amyloidoses with cutaneous involvement.

Extracellular deposition of altered autologous protein (amyloid protein) within the dermis is the hallmark of cutaneous amyloidoses and systemic amyloidoses with cutaneous involvement. Amyloidoses may be acquired or hereditary in nature and subclassification differentiates between primary amyloidosis (no obvious predisposing disease) and secondary amyloidosis (specific underlying disease). More than 26 different proteins and peptides have been identified as amyloid precursors and these proteins are used to subclassify this heterogeneous group of diseases.

Absence of gadolinium deposits in the peritoneal membrane of patients with encapsulating peritoneal sclerosis.

Unlabelled: Background. Encapsulating peritoneal sclerosis (EPS) is a severe complication of long-term peritoneal dialysis (PD) characterized by the development of an extensive fibrosis of the visceral peritoneum that may eventually lead to intestinal constriction. Its cause remains elusive.

Electron microscopic documentation of late changes in permanent fillers and clinical management of granulomas in affected patients.

Background: The manufacturers of permanent injectable fillers claim that their products are widely inert, biocompatible, atoxic, and nonimmunogenic. There are polymer gels without microparticles on the market and combination products that use collagen suspension or a hyaluronic acid gel as a vector to which polymer microspheres or polygonal particles are added. The filling effect of the polymer gels is based on the volume injected and, for the combination gels, partly on the volume injected and partly on the intended host foreign-body reaction to the microparticles.

Alterations in mechanical properties of mesenteric resistance arteries in experimental portal hypertension.

Splanchnic vasodilation is the pathophysiological hallmark in the development of the hyperdynamic circulatory syndrome in liver cirrhosis and portal hypertension. This has been attributed so far mainly to a marked vascular hyporeactivity to endogenous vasoconstrictors. However, myogenic tone and vessel stiffness have not been addressed in mesenteric arteries in liver cirrhosis.

Hyaline globules in paucicellular leiomyomas of the gastrointestinal tract are distinct from skeinoid fibers and represent degenerating smooth muscle cells.

Skeinoid fibers are globular, brightly eosinophilic periodic Schiff stain (PAS)-positive extracellular collagen deposits commonly seen in gastrointestinal stromal tumors (GIST) of the small bowel. However, smooth-surfaced hyaline globules are occasionally encountered in leiomyomatous GI neoplasms and may be mistaken for true skeinoid fibers. We investigated a total of 93 histologically and immunohistochemically well-characterized true smooth muscle neoplasms of the GI tract for the presence of hyaline globules.

Detection of intact rAAV particles up to 6 years after successful gene transfer in the retina of dogs and primates.

Gene transfer to the retina using recombinant adeno-associated viral (rAAV) vectors has proven to be an effective option for the treatment of retinal degenerative diseases in several animal models and has recently advanced into clinical trials in humans. To date, intracellular trafficking of AAV vectors and subsequent capsid degradation has been studied only in vitro, but the fate of AAV particles in transduced cells following subretinal injection has yet to be elucidated. Using electron microscopy and western blot, we analyzed retinas of one primate and four dogs that had been subretinally injected with AAV2/4, -2/5, or -2/2 serotypes and that displayed efficient gene transfer over several years.

Human immunodeficiency virus type-1 (HIV-1) Pr55gag virus-like particles are potent activators of human monocytes.

Human immunodeficiency virus type-1 (HIV-1) Pr55(Gag) virus-like particles (VLP) represent an interesting HIV vaccine component since they stimulate strong humoral and cellular immune responses. We demonstrated that VLP expressed by recombinant baculoviruses activate human PBMC to release pro-inflammatory (lL-6, TNF-alpha), anti-inflammatory (IL-10) and Th1-polarizing (IFN-gamma) cytokines as well as GM-CSF and MIP-1alpha in a dose-and time-dependent manner. Herein, residual baculoviruses within the VLP preparations showed no or minor effects.

CD4+ T helper cell responses against human bocavirus viral protein 2 viruslike particles in healthy adults.

Background: Human bocavirus (HBoV) was recently described as a new member of the Parvoviridae family, and its possible association with respiratory illness in infants has been discussed. To date, HBoV genomes have been detected worldwide in respiratory tract samples obtained from children with pulmonary diseases, whereas only limited data on virus-specific immunity are available, mainly because of the lack of recombinant viral antigens.

Methods: HBoV viruslike particles (VLPs) were produced in insect cells and characterized by electron microscopy and cesium chloride gradient centrifugation.