MR Imaging Findings of Iron Overload

Hemochromatosis can be classified as (a) primary, when it originates from a genetic disturbance that promotes the increase of iron absorption, or (b) secondary, when it relates to chronic diseases or to multiple transfusions. The distribution of iron accumulation differs between these two forms; therefore, they can be distinguished by using imaging methods in the majority of cases. Magnetic resonance (MR) imaging is the most sensitive and specific imaging modality in the diagnosis of hemochromatosis. The susceptibility effect caused by the accumulation of iron leads to signal loss in the affected tissues, particularly with the T2*-weighted sequences, which makes the diagnosis of iron overload possible. By using MR imaging techniques, it is possible to estimate the hepatic iron concentration in a noninvasive way, thereby avoiding repeated biopsies. Hemochromatosis can lead to complications, such as a higher frequency of neoplasia, particularly the development of hepatocellular carcinoma. Other neoplasms, such as colorectal tumors, are also associated. Complications related to the treatment of chronic anemia include the appearance of peliosis hepatis and tumors, which can regress after the suspension of treatment with drugs. Knowledge of the disease and of the patterns of iron deposition in patients with iron overload enables not only diagnosis, but also treatment, follow-up, and the detection of possible complications by using imaging methods. (C) RSNA, 2009 . radiographics.rsna.org

Fluoxetine effect on kidney water reabsorption

Background. The pathogenesis of hyponatraemia caused by fluoxetine (Fx) use in the treatment of depression is not well understood. It has been attributed to a SIADH, although ADH-enhanced plasma level has not yet been demonstrated in all the cases reported in humans. This experiment aimed at investigating the effect of fluoxetine on the kidney and more specifically in the inner medullary collecting duct (IMCD). Methods. ( 1) In vivo study: ( a) 10 rats were injected daily i. p. with 10 mg/kg fluoxetine doses. After 10 days, rats were sacrificed and blood and kidneys were collected. (b) Immunoblotting studies for AQP2 protein expression in the IMCD from injected rats and in IMCD tubules suspension from 10 normal rats incubated with 10(-7) M fluoxetine. ( 2) In vitro microperfusion study: The osmotic water permeability (P-f, mu m/s) was determined in normal rats IMCD (n = 6), isolated and perfused by the standard methods. Results. In vivo study: ( a) Injected rats with fluoxetine lost about 12% body weight; Na+ plasma level decreased from 139.3 +/- 0.78 mEq/1 to 134.9 +/- 0.5 mEq/1 ( p < 0.01) and K+ and ADH plasma levels remained unchanged. ( b) Immunoblotting densitometric analysis of the assays showed an increase in AQP2 protein abundance of about 40%, both in IMCDs from injected rats [ control period (cont) 99.6 +/- 5.2 versus Fx 145.6 +/- 16.9, p < 0.05] and in tubule suspension incubated with fluoxetine ( cont 100.0 +/- 3.5 versus 143.0 +/- 2.0, p < 0.01). In vitro microperfusion study fluoxetine increased Pf in the IMCD in the absence of ADH from the cont 7.24 +/- 2.07 to Fx 15.77 +/- 3.25 ( p < 0.01). Conclusion. After fluoxetine use, the weight and plasma Na+ level decreased, and the K+ and ADH plasma levels remained unchanged, whereas the AQP2 protein abundance and water absorption in the IMCD increased, leading us to conclude that the direct effect of fluoxetine in the IMCD could explain at least in part, the hyponatraemia found sometime after this drug use in humans.

A fructan: fructan fructosyltransferase activity from Lolium rigidum

Fructan:fructan fructosyltransferase (FFT) activity was purified about 300-fold from leaves of Lolium rigidura Gaudin by a combination of affinity chromatography, gel filtration, anion exchange and isoelectric focusing. The FFT activity was free of sucrose:sucrose fructosyltransferase and invertase activities. It had an apparent pI of 4.7 as determined by isoelectric focusing, and a molecular mass of about 50000 (gel filtration). The FFT activity utilized the trisaccharides 1-kestose and 6(G)-kestose as sole substrates, but was not able to use 6-kestose as sole substrate. The FFT activity was not saturated when assayed at concentrations of 1-kestose, 6(G)-kestose or (1,1)-kestotetraose of up to 400 mM The rate of reaction of the FFT activity was most rapid when assayed with 1-kestose and was less rapid when assayed with 6(G)-kestose, (1,1)-kestotetraose or (1,1,1)-kestopentaose. The FFT activity when assayed at a relatively high concentration of enzyme activity (approximately equivalent to about half the activity in crude extracts per gram fresh mass) did not synthesize fructan of degree of polymerization > 6, even during extended assays of up to 10 h. When assayed with a combination of 1-kestose and uniformly labelled [C-14]sucrose as substrates, the major reaction was the transfer of a fructosyl residue from 1-kestose to sucrose resulting in the re-synthesis of 1-kestose. Tetrasaccharide and 6(G)-kestose were also synthesized. When assayed with 6(G)-kestose and [C-14]sucrose as substrates, the major reaction of the FFT activity was the synthesis of tetrasaccharide. However, some synthesis of 1-kestose and re-synthesis of 6(G)-kestose also occurred. When 6, kestose was the sole substrate for the FFT activity, synthesis of tetrasaccharide was 2.7 to 3.4-fold slower than when 1-kestose was used as the sole substrate. Owing to differences in the fructan:sucrose fructosyltransferase activity of the FFT with each of the trisaccharides, net synthesis of tetrasaccharide by the FFT was altered significantly in the presence of sucrose. The magnitude of this effect depended on the concentration of the trisaccharides. In the presence of sucrose, 6(G)-kestose could be a substrate of equivalent importance to 1-kestose for synthesis of tetrasaccharide.

Identification of products formed by a fructan:fructan fructosyltransferase activity from Lolium rigidum

The products formed by a fructan:fructan fructosyltransferase (FFT) activity purified from Lolium rigidum Gaudin were identified after gas chromatography-mass spectrometry of partially methylated alditol acetates, electrospray ionization-mass spectrometry and reversed-phase high-performance liquid chromatography. The FFT activity synthesized oligofructans up to degree of polymerization (DP) 6, but did not synthesize fructans of DP > 6 even when assayed with (1,1,1)-kestopentaose for up to 10 h. The FFT activity when assayed with 1-kestose or 6(G)-kestose synthesized fructan with fructosyl residues almost exclusively linked by beta-2,1-glycosidic linkages. When assayed with 1-kestose, the FFT activity synthesized tetrasaccharides and pentasaccharides with an internal glucosyl residue. The predominant tetrasaccharide was (1&6(G))-kestotetraose and the predominant pentasaccharide was (1&6(G),1)-kestopentaose. By comparison, tetrasaccharides and pentasaccharides extracted from L. rigidum also contained predominantly beta-2,1-glycosidic linked fructans with an internal glucosyl residue. The only exception was that one of the pentasaccharides contained beta-2,1- and beta-2,6-glycosidic linked fructosyl residues. This pentasaccharide was not synthesized by the FFT activity. The role of this FFT activity in formation of oligofructans in L. rigidum is discussed.

Usefulness of a quick decalcification of bone sections embedded in methyl metacrylate: an improved method for immunohistochemistry

Immunohistochemistry of undecalcified bone sections embedded in methyl methacrylate (MMA) is not commonly employed because of potential destruction of tissue antigenicity by highly exothermic polymerization. The aim of the present study was to describe a new technique in which a quick decalcification of bone sections embedded in MMA improves the results for immunohistochemistry. The quality of interleukin 1 alpha (IL-1 alpha) immunostaining according to the present method was better than the conventional one. Immunostaining for osteoprotegerin (OPG) and the receptor activator of NF-kappa B ligand (RANKL) in bone sections of chronic kidney disease patients with mineral bone disorders (CKD-MBD) was stronger than in controls (postmortem healthy subjects). The present study suggested that this method is easy, fast, and effective to perform both histomorphometry and immunohistochemistry in the same bone fragment, yielding new insights into pathophysiological aspects and therapeutic approaches in bone disease.

Annexin 1 mimetic peptide protects against renal ischemia/reperfusion injury in rats

Inflammation is currently recognized as a key mechanism in the pathogenesis of renal ischemia-reperfusion (I/R) injury. The importance of infiltrating neutrophil, lymphocytes, and macrophage in this kind of injury has been assessed with conflicting results. Annexin 1 is a protein with potent neutrophil anti-migratory activity. In order to evaluate the effects of annexin A1 on renal I/R injury, uninephrectomized rats received annexin A1 mimetic peptide Ac2-26 (100 mu g) or vehicle before 30 min of renal artery clamping and were compared to sham surgery animals. Annexin A1 mimetic peptide granted a remarkable protection against I/R injury, preventing glomerular filtration rate and urinary osmolality decreases and acute tubular necrosis development. Annexin A1 infusion aborted neutrophil extravasation and attenuated macrophage infiltration but did not prevent tissue lymphocyte traffic. I/R increased annexin A1 expression (assessed by transmission electron microscopy) in renal epithelial cells, which was attenuated by exogenous annexin A1 infusion. Additionally, annexin A1 reduced I/R injury in isolated proximal tubules suspension. Annexin A1 protein afforded striking functional and structural protection against renal I/R. These results point to an important role of annexin A1 in the epithelial cells defense against I/R injury and indicate that neutrophils are key mediators for the development of tissue injury after renal I/R. If these results were confirmed in clinical studies, annexin A1 might emerge as an important tool to protect against I/R injury in renal transplantation and in vascular surgery.

Studies on the gelation of photocatalysed dicyanate ester resins

The gel point of a dicyanate ester resin (Arocy B-10 (4-4'-dicyanato-2,2'-diphenylpropane)) heated following irradiation in the presence of the catalyst tricarbonyl cyclopentadienyl manganese (CpMn(CO)(3)) was studied using differential scanning calorimetry (d.s.c.) and dynamic rheological techniques over the temperature range 110-140 degrees C. The gel times of another commercial cyanate ester (RTX366) were also studied using independent rheological techniques, and the results agreed within experimental error. Gel times decreased linearly with increasing catalyst level and with increasing temperature according to an Arrhenius relation with activation energy of 68 +/- 6 kJmol(-1). The gel conversion was calculated by correlation of the rheological gel data to d.s.c. data to be 0.57 +/- 0.02, and differences between techniques, and between theoretical predictions, are discussed. Evidence is produced that the photocatalysed polymerization results in a greater rate of cyclotrimerization, less intramolecular cyclization and a more rigid network than the uncatalysed or metal salt-catalysed high-temperature polymerization. (C) 1997 Elsevier Science Ltd.

Synthesis of fructans by partially purified fructosyltransferase activities from Lolium rigidum

Sucrose:sucrose fructosyltransferase (SST) activity was partially purified from whole shoots of Lolium rigidum by a combination of affinity chromatography, gel filtration and anion-exchange chromatography. The SST activity co-eluted with some fructan:fructan fructosyltransferase (FFT) and invertase activities and consequently the partially purified preparation was termed the fructosyltransferase (FT) preparation. The SST-like activity in the FT preparation was purified 214-fold and had an apparent molecular mass of 84 000. The FT preparation contained several peptides with an apparent pI of 4.6-4.7. When assayed with sucrose concentrations up to 600 mM, the FT preparation synthesized 1-kestose at all concentrations, and synthesized 6-kestose at concentrations of 150 mM and greater. The K-m of 1-kestose production was 0.2 M. When the FT preparation was assayed at a concentration of activity approximately half that measured in fresh tissue with 100 mM sucrose, 1-kestose, or 6(G)-kestose as substrates, fructans of degree of polymerization (DP) less than or equal to 5 were synthesized. A partially purified FFT activity, free of SST and invertase activities, which synthesized beta-2,1-glycosidic linked oligofructans of DP less than or equal to 6, was combined in vitro with the FT preparation (FFT-FT preparation) to give a ratio of SST:FFT activities similar to that measured in crude enzyme extracts from L. rigidum. The FFT-FT preparation synthesized oligofructans when assayed with 100 mM concentrations of sucrose, 1-kestose or 6(G)-kestose, but was not able to synthesize fructans of DP greater than or equal to 6 even after extended assays of up to 10 h. The FFT-FT preparation was also assayed with 100 mM sucrose with small amounts of concentrated sucrose added periodically during the assay to maintain the substrate concentration. In this assay, the FFT-FT preparation synthesized fructans up to an apparent DP of 17 or greater. The fructans of DP greater than or equal to 6 synthesized in the assay appeared to form two molecular series containing both beta-2,1- and beta-2,6-glycosidic linked fructosyl residues with terminal or internal glucosyl residues. The apparent rate of SST activity in the assay of the FFT-FT preparation was greater than that measured in a similar assay of the FT preparation alone which did not result in fructans with DP greater than or equal to 6. It was concluded that the FFT-FT preparation, when assayed with a continual supply of sucrose, contained a factor which promoted synthesis of fructans of DP greater than or equal to 6 and synthesis of beta-2,B-glycosidic linkages between fructosyl residues.

Characterization of the Biocompatible Magnetic Colloid on the Basis of Fe(3)O(4) Nanoparticles Coated with Dextran, Used as Contrast Agent in Magnetic Resonance Imaging

The magnetic resonance imaging contrast agent, the so-called Endorem (TM) colloidal suspension on the basis of superparamagnetic iron oxide nanoparticles (mean diameter of 5.5 nm) coated with dextran, were characterized on the basis of several measurement techniques to determine the parameters of their most important physical and chemical properties. It is assumed that each nanoparticle is consisted of Fe(3)O(4) monodomain and it was observed that its oxidation to gamma-Fe(2)O(3) occurs at 253.1 degrees C. The Mossbauer spectroscopy have shown a superparamagnetic behavior of the magnetic nanoparticles. The Magnetic Resonance results show an increase of the relaxation times T(1), T(2), and T(2)* with decreasing concentration of iron oxide nanoparticles. The relaxation effects of SPIONs contrast agents are influenced by their local concentration as well as the applied field strength and the environment in which these agents interact with surrounding protons. The proton relaxation rates presented a linear behavior with concentration. The measured values of thermooptic coefficient partial derivative n/partial derivative T, thermal conductivity K, optical birefringence Delta n(0), nonlinear refractive index n(2), nonlinear absorption beta` and third-order nonlinear susceptibility vertical bar chi((3))vertical bar are also reported.

Pulmonary function and histological impairment in mice after acute exposure to aluminum dust

Along the aluminum refining process, alumina (Al(2)O(3)) constitutes the main source of dust. Although aluminum refinery workers present respiratory symptoms with lung functional changes, no conclusive data about lung function impairment after alumina exposure has been so far reported. We examined the pulmonary alterations of exposure to material collected in an aluminum refinery in Brazil. BALB/c mice were exposed in a whole-body chamber for 1 h to either saline (CTRL, n = 11) or to a suspension (in saline) of 8 mg/m(3) of the dust (ALUM, n = 11) both delivered by an ultrasonic nebulizer. Twenty-four hours after exposure lung mechanics were measured by the end-inflation method. Lungs were prepared for histology. ALUM showed significantly higher static elastance (34.61 +/- 5.76 cmH(2)O/mL), elastic component of viscoelasticity (8.16 +/- 1.20 cmH(2)O/mL), pressure used to overcome the resistive component of viscoelasticity (1.62 +/- 0.24 cmH(2)O), and total resistive pressure (2.21 +/- 0.49 cmH(2)O) than CTRL (27.95 +/- 3.63 cmH(2)O/mL, 6.12 +/- 0.99 cmH(2)O/mL, 1.23 +/- 0.19 cmH(2)O, and 1.68 +/- 0.23 cmH(2)O, respectively). ALUM also presented significantly higher fraction area of alveolar collapse (69.7 +/- 1.2%) and influx of polymorphonuclear cells (27.5 +/- 1.1%) in lung parenchyma than CTRL (27.2 +/- 1.1% and 14.6 +/- 0.7%, respectively). The composition analysis of the particulate matter showed high concentrations of aluminum. For the first time it was demonstrated in an experimental model that an acute exposure to dust collected in an aluminum producing facility impaired lung mechanics that could be associated with inflammation.

Statins withdrawal, vascular complications, rebound effect and similitude

Hahnemann considered the secondary action of medicines to be a law of nature and reviewed the conditions under which it occurs. It is closely related to the rebound effects observed with many modern drugs. I review the evidence of the rebound effect of statins that support the similitude principle. In view of their indications in primary and secondary prevention of cardiovascular diseases, statins are widely prescribed. Besides reducing cholesterol biosynthesis, they provide vasculoprotective effects (pleiotropic effects), including improvement of endothelial function, increased nitric oxide bioavailability, antioxidant properties, inhibition of inflammatory and thrombogenic responses, stabilisation of atherosclerotic plaques, and others. Recent studies suggest that suspension of statin treatment leads to a rebound imparing of vascular function, and increasing morbidity and mortality in patients with vascular diseases. Similarly to other classes of modern palliative drugs, this rebound effect is the same as a secondary action or vital reaction described by Samuel Hahnemann, and used in homeopathy in a therapeutic sense. Homeopathy (2010) 99, 255-262.

Antidepressants, suicidality and rebound effect: evidence of similitude?

Background: Samuel Hahnemann noticed that palliative treatments for the symptoms of chronic diseases, after an initial improvement, provoked symptoms similar but stronger symptoms to those initially suppressed. He regarded this as a consequence of the vital reaction of the organism: an automatic and instinctive capacity to return to the initial health condition altered by medicines. Using this homeostatic conception of the organism as a treatment rationale, Hahnemann proposed the therapy of similarity, administering to the patients medicines capable of causing, in healthy individuals, similar symptoms to the natural disease. Based on experimental observations, he proposed that the primary action of the drug was followed by the secondary and opposite action of the organism, inaugurating homeopathic pharmacology, and alerting to the harmful consequences of palliative medicines in susceptible individuals. Such liatrogenic events can be observed in contemporary medicine, after the withdrawal of modern enantiopathic medicines, according to the study of the rebound effect or paradoxical reaction of the organism. Method. This study reviews the recent studies which describe suicidallity after the suspension or discontinuation of second generation antidepressants according to the hypothesis of the paradoxical reaction of the organism. Conclusions: Rebound and withdrawal effects, including suicidality occur with antidepressant drugs. They are relatively rare but more intense than the primary action of the drug. The probability of such effects is influenced by patient factors including age and diagnosis, and drug factors including half-life. Homeopathy (2009) 98, 114-121.

Browlifting as an Alternative Procedure for Apraxia of Eyelid Opening

Essential blepharospasm is an idiopathic disorder that consists of spontaneous, spasmodic, and involuntary eyelid closure in the absence of ocular disease. Some patients develop an inability to open their eyelids in the absence of orbicularis spasms. These patients have essential blepharospasm combined with apraxia of eyelid opening. Botulinum toxin injections are the treatment of choice for blepharospasm but results may be insufficient, especially in cases associated with apraxia. Apraxia can be treated surgically by levator aponeurosis advancement, frontalis suspension, and upper myectomy. The authors report the first browlift using polypropylene suture to manage eyelid apraxia associated with blepharospasm as an alternative and minimally invasive procedure.

Poly(ethylene glycol) decorated poly(methylmethacrylate) nanoparticles for protein adsorption

Poly(ethylene glycol) decorated poly( methyl methacrylate) particles were synthesized by means of emulsion polymerization using poly(ethylene glycol) sorbitan monolaurate (Tween-20) as surfactant. PMMA/PEG particles presented mean diameter (195 +/- 15) nm, indicating narrow size distribution. The adsorption behavior of bovine serum albumin (BSA) and concanavalin A (ConA) onto PMMA/PEG particles was investigated by means of spectrophotometry. Adsorption isotherms obtained for BSA onto PMMA/PEG particles fitted well sigmoidal function, which is typical for multilayer adsorption. Con A adsorbed irreversibly onto PMMA/PEG particles. The efficiency of ConA covered particles to induce dengue virus quick agglutination was evaluated. (C) 2010 Elsevier B.V. All rights reserved.

Regulation of chemokine receptor by Toll-like receptor 2 is critical to neutrophil migration and resistance to polymicrobial sepsis

Patients with sepsis have a marked defect in neutrophil migration. Here we identify a key role of Toll-like receptor 2 (TLR2) in the regulation of neutrophil migration and resistance during polymicrobial sepsis. We found that the expression of the chemokine receptor CXCR2 was dramatically down-regulated in circulating neutrophils from WT mice with severe sepsis, which correlates with reduced chemotaxis to CXCL2 in vitro and impaired migration into an infectious focus in vivo. TLR2 deficiency prevented the down-regulation of CXCR2 and failure of neutrophil migration. Moreover, TLR2(-/-) mice exhibited higher bacterial clearance, lower serum inflammatory cytokines, and improved survival rate during severe sepsis compared with WT mice. In vitro, the TLR2 agonist lipoteichoic acid (LTA) down-regulated CXCR2 expression and markedly inhibited the neutrophil chemotaxis and actin polymerization induced by CXCL2. Moreover, neutrophils activated ex vivo by LTA and adoptively transferred into naive WT recipient mice displayed a significantly reduced competence to migrate toward thioglycolate-induced peritonitis. Finally, LTA enhanced the expression of G protein-coupled receptor kinases 2 (GRK2) in neutrophils; increased expression of GRK2 was seen in blood neutrophils from WT mice, but not TLR2(-/-) mice, with severe sepsis. Our findings identify an unexpected detrimental role of TLR2 in polymicrobial sepsis and suggest that inhibition of TLR2 signaling may improve survival from sepsis.