Transgenic mice expressing constitutive active MAPKAPK5 display gender-dependent differences in exploration and activity

Background  

The mitogen-activated protein kinases, MAPKs for short, constitute cascades of signalling pathways involved in the regulation of several cellular processes that include cell proliferation, differentiation and motility. They also intervene in neurological processes like fear conditioning and memory. Since little remains known about the MAPK-Activated Protein Kinase, MAPKAPK5, we constructed the first MAPKAPK knockin mouse model, using a constitutive active variant of MAPKAPK5 and analyzed the resulting mice for changes in anxiety-related behaviour.     

No regression of renal AL amyloid in monoclonal gammopathy after successful autologous blood stem cell transplantation and significant clinical improvement.

BACKGROUND: High-dose chemotherapy followed by autologous blood stem cell transplantation induces remission of plasma cell dyscrasia in patients with AL amyloidosis. The impact of this treatment on the glomerular amyloid mass is still unknown. METHODS: In the present study, the quantity of the renal amyloid mass before and more than 3 years after high-dose melphalan treatment and autologous blood stem cell transplantation was assessed in two patients. At the time of the second renal biopsy, both patients were in complete remission without detectable serum and urinary monoclonal IgA-lambda and a normal percentage of plasma cells in the bone marrow. RESULTS: In both patients with biopsy-proven AL amyloidosis, urinary protein excretion decreased from 7 g/24 h to <2 g/24 h more than 3 years after autologous blood stem cell transplantation. In contrast, glomerular amyloid deposits persisted, as shown in the second biopsy. CONCLUSION: Despite complete remission of the plasma cell dyscrasia and improvement of glomerular permeability, the amount of glomerular amyloid mass did not regress.     

In vivo measurements of fibrin formation and degradation in nephrotic patients

Summary Intraglomerular fibrin deposition has been implicated as an important pathogenetic mechanism in patients with glomerular diseases and the nephrotic syndrome. To investigate fibrin formation and degradation in nephrosis, we measured fibrinopeptide A by radio-immunoassay and D-dimer by enzyme-linked immunosorbent assay in the plasma of 30 consecutive adult patients with the nephrotic syndrome; in 10 the serum creatinine was more than 2 mg/dl. Both fibrinopeptide A and D-dimer were abnormally elevated in the majority of nephrotics (P<0.001 vs. healthy controls), providing evidence of increased fibrin generation and lysis “in vivo.” A positive correlation was found between fibrinopeptide A and D-dimer (correlation coefficient 0.64,P<0.001), suggesting a close relationship between fibrin formation and degradation. Calcium heparin, administered to 12 nephrotics, caused a marked decrease in plasma fibrinopeptide A, due to a reduction of in vivo thrombin activity. As enhanced thrombin activity can favor fibrin deposition within the renal parenchyma, as well as vascular complications, it is reasonable to assume that an antithrombotic treatment aimed at controlling thrombin generation may ameliorate the natural history of nephrosis.     

Stronger association of drug-induced progressive multifocal leukoencephalopathy (PML) with biological immunomodulating agents

Aim  

The aim of the present study was to collect and compare cases of drug-induced PML in order to contribute to the debate about the role of the underlying diseases and/or drug immunosuppression in PML occurrence.     

Fluorescein angiographic findings and results of laser treatment in circumscribed choroidal hemangioma

We studied retrospectively 12 eyes with a solitary choroidal hemangioma in 12 patients over a period of 13 years. A peculiar, even hyperfluorescence of the tumor within the retinal venous phases occurred in all 12 cases. In all but four patients, laser therapy was performed to reduce subretinal fluid and partially destroy the tumor. Two of the three eyes without extensive retinal detachment or cystoid macular edema at the initial visit regained a final vision of 20/30 or better. The remaining 5 patients with the two major complications had a final vision of 20/80 or worse due to degenerative retinal changes. We believe that laser treatment is definitely advisable in the early stages of a circumscribed choroidal hemangioma.The study was performed at the Institute of Ophthalmology, University of Nijmegen.     

Localization of parathyroid enlargement: experience with technetium-99m methoxyisobutylisonitrile and thallium-201 scintigraphy,ultrasonography and computed tomography

Technetium-99m methoxyisobutylisonitrile (MIBI), like thallium-201, has recently been introduced as a myocardial perfusion agent and is now also showing very promising results in parathyroid scintigrapy. The results of ²⁰¹Tl/^99mTc-pertechnetate and ^99mTc-MIBI/^99mTc-pertechnetate subtraction scintigraphy, ultrasonography and computed tomography are presented in a series of 43 patients operated on for hyperparathyroidism. All four imaging modalities were confirmed to be reliable, scintigraphy being the most accurate. Sensitivities ranged from 81% to 95%, that of ^99mTc-MIBI being the highest. Moreover this tracer, which has more favourable physical and also biochemical properties, yielded images of superior quality. This allowed localization of the lesion by visual inspection only in as many as 86% of the patients with positive ^99mTc-MIBI/^99mTc-pertechnetate subtraction scintigraphy. We believe that the higher sensitivity, superior image quality and lower cost of ^99mTc-MIBI imaging will make ^99mTc-MIBI the new radiopharmaceutical of choice for parathyroid scintigraphy (when one takes into account the stability of labelling with large activities it is possible to perform three or four cardiac studies together with one parathyroid scintigraphic examination using one lyophililzed vial).     

X-ray investigation on highly oriented polyacetylene, 3 Crystal structure of the iodine/trans-polyacetylene complex

The crystal structure of iodine/trans-polyacetylene complexes (CHI_y)_x (y = 0,009, 0,035, 0,17 and 0,30) was investigated by X-ray diffraction analysis of highly oriented samples. An iodine-containing phase (PAI) was observed in all cases, accompanied by residual crystallinity due to pristine polyacetylene (PA) for y < 0,17. A structural model is proposed for PAI, consisting of blocks of iodine-saturated PA (PAI_s) and blocks of PA, arranged in a mosaic-like lattice, paracrystalline in character. PAI_s, corresponding to (CHI_0,40)_x, is formed by layers of (CH)_x chains alternating with layers containing polyiodide chains, the latter being characterized by ordered stacking of sequentially disordered (I₃^?-I₅^?-I₃^?) groups. I… C non-bonded interactions are identified in the lattice, which may be responsible for the electron transfer from the polymer to the polyiodide anions. Short-range transverse correlation occurs within the polyiodide layers with a resulting quasi-regular two-dimensional lattice of iodines. The iodine and the polymer lattices are incommensurate along c. The model fits the experimental data from an X-ray fibre diagram. A mathematical expression is derived, which allows to evaluate the intensity scattered by the iodine lattice. An approximate expression of the non-equatorial intensity along the ξ reciprocal direction was obtained, which accounts for the modulation of the streaks observed in the fibre pattern.     

Development, characterization, and anti-microbial efficacy of hydroxyapatite-chlorhexidine coatings produced by surface-induced mineralization

The surface-induced mineralization (SIM) technique was used to produce hydroxyapatite (HAP) coatings on external fixation pins with the antimicrobial agent, chlorhexidine, incorporated within the coating. The SIM process involved surface modification of the substrate with organic functional groups followed by immersion in aqueous supersaturated calcium phosphate solutions. X-ray diffraction spectra confirmed that hydroxyapatite coatings were formed. Chlorhexidine was incorporated into the coating by placing the substrate into various chlorhexidine solutions in between mineralization cycles. Total uptake was measured by dissolution of the coating into a 0.1 M nitric acid solution and measuring the chlorhexidine concentration using UV spectroscopy at 251 nm. Release rates were measured by submersion of coated substrates into saline solutions and measuring chlorhexidine UV absorbency at 231 nm as a function of time. Results show an initial rapid release followed by a period of slower sustained release. The anti-microbial efficacy of the HAP-chlorhexidine coatings was evaluated in vitro using a Staphylococcus aureus cell culture. Initial results show a large "inhibition zone" formed around the chlorhexidine/HAP coating vs. coatings with HAP only. This preliminary work clearly demonstrates that SIM HAP coatings have great potential to locally deliver antimicrobial agents such as chlorhexidine at implantation sites, which may greatly reduce the incidence of pin tract infection that occurs in external fixation.