The significance of sigma neurofeedback training on sleep spindles and aspects of declarative memory.

The functional significance of sleep spindles for overnight memory consolidation and general learning aptitude as well as the effect of four 10-minute sessions of spindle frequency (11.6-16 Hz, sigma) neurofeedback-training on subsequent sleep spindle activity and overnight performance change was investigated. Before sleep, subjects were trained on a paired-associate word list task after having received either neurofeedback training (NFT) or pseudofeedback training (PFT). Although NFT had no significant impact on subsequent spindle activity and behavioral outcomes, there was a trend for enhanced sigma band-power during NREM (stage 2 to 4) sleep after NFT as compared to PFT. Furthermore, a significant positive correlation between spindle activity during slow wave sleep (in the first night half) and overall memory performance was revealed. The results support the view that the considerable inter-individual variance in sleep spindle activity can at least be partly explained by differences in the ability to acquire new declarative information. We conclude that the short NFT before sleep was not sufficient to efficiently enhance phasic spindle activity and/or to influence memory processing. NFT was, however, successful in increasing sigma power, presumably because sigma NFT effects become more easily evident in actually trained frequency bands than in associated phasic spindle activity.

[Gout]. / Rhumatologie. La goutte.

Gout must be regarded as a systemic and chronic disease with potentially serious sequelae. Hyperuricemia is probably an independent risk factor for cardiovascular diseases, at least in high-risk individuals. Nevertheless, current data do not justify for the moment the treatment of asymptomatic hyperuricemia. Finally, if allopurinol remains the only available agent in Switzerland for the treatment of chronic gout, new molecules, like febuxostat and pegylated uricase, are currently being evaluated.

[Clinical evaluation of rheumatoid arthritis in practice]. / Evaluation clinique d'une polyarthrite rhumatoïde en pratique quotidienne.

Clinical evaluation is an integral part of medical practice. However, recent data have demonstrated that a systematic and standardized evaluation modifies the prognosis of our rheumatoid arthritis patients. The systematic use of activity indexes allows us to better appreciate the needs of our patients and the necessity to optimize and intensifie treatment. Likewise, auto-evaluations tools bring useful information to patient management.

[Interest of magnetic resonance imaging in rheumatoid arthritis]. / Intérêt de l'imagerie par résonance magnétique dans l'évaluation de la polyarthrite rhumatoïde.

Magnetic Resonance Imaging (MRI) is the best imaging method in early detection and management of rheumatoid arthritis (RA). There are other imaging methods available as ultrasound, scintigraphy, computed tomography and plain radiography for imaging RA but MRI provides the best sensitivity in detecting inflammatory changes in the joints. MRI shows the best intra and interobserver reliability and low variation between repetitive examinations. MRI has shown the best visualisation and the greater sensitivity to detect erosion in early RA, compared to standard radiography. The use of a contrast agent further increases the sensitivity in detecting erosions and differentiate synovial proliferation from fluid collections. Otherwise, intraossous cyst, tenosynovitis, bone marrow edema, that are concomitant manifestations of the disease, are best imaged by MRI. MRI assists in the early detection of rheumatoid arthritis, which allows earlier initiation of treatment.

[Rheumatoid arthritis and pregnancy]. / Polyarthrite rhumatoïde et grossesse.

Rheumatoid arthritis occurs frequently in women in childbearing years. With the improvement of the treatments, more patients with rheumatoid arthritis consider a pregnancy. Close co-operation between the physician and the obstetrician caring for the mother and the foetus is necessary. The disease should be well controlled at the time of the conception, although an amelioration of rheumatoid arthritis occurs in about 75% of pregnancies, in the first trimester. Some medications can be used during pregnancy and lactation. There is no indication of any adverse effects of rheumatoid arthritis on pregnancy outcome. The mother needs to be followed up regularly after delivery because of the high risk of post-partum flare.

Ultrasound in emergency patients: better detection of free intraabdominal fluids by the use of tissue harmonic imaging.

BACKGROUND: Ultrasound examination is one of the main investigative procedures in emergency patients who are hospitalized due to abdominal pain. Detectable free fluid collections are important hints to the definite, sometimes life-threatening diagnosis, but their detection in cases of only small amounts is difficult to perform by conventional sonography. PATIENTS AND METHODS: We report about 25 cases of patients who suffered from acute abdominal pain and who were presented as emergency patients to our department of ultrasound. First, the examination was performed by conventional sonography (3.4 MHz). Only with the additional tissue harmonic imaging (THI, 2.3 MHz, pulse inversion) thin borders of free fluids around the liver or other abdominal organs (gallbladder, spleen, pancreas, bowel) could be detected leading to other important diagnostic or therapeutic steps. In this way, the diagnosis of pancreatitis, cholezystitis, peritonitis, peritoneal carcinosis, ascites (liver cirrhosis, serositis, postoperative status after laparotomy), bleeding or paralytic ileus could be elucidated. CONCLUSION: THI sonography improves the detection of small amounts of free abdominal fluid collections. Therefore, this technique is helpful in the diagnostic procedure of emergency patients.

RANTES production by cytokine-stimulated nasal fibroblasts: its inhibition by glucocorticoids.

Nasal fibroblasts play an important role in both nasal polyposis and nasal allergic diseases and they are known to release a number of proinflammatory cytokines, including GM-CSF, IL-8 and IL-6. The aim of this present work was to investigate whether cytokine-stimulated nasal fibroblasts release biologically active RANTES as well as to study the effect of corticosteroids on the ability of nasal fibroblasts to produce the cytokine. Measurements of RANTES by ELISA demonstrated that RANTES is constitutively secreted spontaneously (21+/-4 vs. 19+/-6 ng/ml, respectively p>0.05). Stimulation of these cells with either TNF-alpha, IL-1beta or IFN-gamma induce further release of RANTES in a dose-dependent manner with TNF-alpha being the most potent stimulus. RANTES mRNA expression in nasal fibroblasts correlated with the amount of protein released in the culture supernatant upon cytokine stimulation. Moreover, chemotaxis studies demonstrated that the nasal-derived RANTES was biologically active on eosinophils. Betamethasone and hydrocortisone were found to downregulate RANTES mRNA expression in TNF-alpha-stimulated fibroblasts. These observations suggest that RANTES released by nasal fibroblasts may regulate eosinophil recruitment in nasal disease while glucocorticoids may inhibit the influx of these cells by suppressing the production of RANTES.

Fibroblasts but not epithelial cells obtained from human nasal mucosa produce the chemokine RANTES.

RANTES is a chemokine that was already found in tissues obtained from nasal polyps of patients suffering from chronic polypous sinusitis. Its cellular origin is as yet unknown. The aim of this study was to investigate whether human nasal mucosa fibroblasts and epithelial cells are capable to produce RANTES. Fibroblasts and epithelial cells, obtained from healthy human nasal mucosa, were cultured. Expression of RANTES-mRNA and secretion of RANTES-protein in supernatants was investigated after stimulation with 50 ng/ml Tumour Necrosis Factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interferon-g (IFN-gamma), lipopolysaccharide (LPS), phorbolymyristate acetate (PMA) and serum-free medium (SFM) for 24 h. Cultivated nasal fibroblasts either expressed RANTES-mRNA or secreted RANTES protein upon TNF-alpha, IL-1 beta and IFN-gamma stimulation. The amounts of RANTES-protein production ranged from 23 ng/ml (PMA) to 198 ng/ml (TNF-alpha). Nasal epithelial cells expressed RANTES-mRNA only after stimulation with PMA. Secretion of significant amounts of RANTES protein were not detected in the supernatants from nasal epithelial cells. We conclude that nasal fibroblasts but not epithelial cells could be a cellular source of RANTES in nasal mucosa or in secretions of patients suffering from diseases, where eosinophilic tissue infiltration represents a characteristic histopathological feature.

Chiral linear hydroxamates as biomimetic analogues of ferrioxamine and coprogen and their use in probing siderophore-receptor specificity in bacteria and fungi.

Linear hydroxamate derivatives, possessing chiral alpha-amino acid moieties, were synthesized and their iron transport activities were studied in bacteria and fungi. No growth-promoting activity could be detected in the Gram-positive hydroxamate-auxotroph Aureobacterium flavescens JG9. However, Gram-negative enterobacteria, such as Escherichia coli, Pantoea agglomerans and Hafnia alvei were able to utilize iron from these analogues. Uptake of 55Fe-labeled analogues was inhibited by sodium azide, suggesting an active transport process. The receptors involved during uptake in enterobacteria were identified by using appropriate indicator organisms which are defective in the transport of either ferrioxamines (P. agglomerans FM13), coprogens (H. alvei), or both of these siderophore classes (E. coli fhuE). Our data suggest that the chiral hydroxamates are recognized by the ferrioxamine receptor (FoxA) and the coprogen receptor (FhuE) at a ratio which depends on the optical lambda/delta isomer fraction and the nature of side chains. Transport was also observed in the fungus Neurospora crassa, known to take up coprogen rather than ferrioxamines, suggesting that in this fungus the synthetic analogues behave like coprogen.

Transport and utilization of ferrioxamine-E-bound iron in Erwinia herbicola (Pantoea agglomerans).

We have analyzed ferrioxamine-E-mediated iron uptake and metabolization in Erwinia herbicola K4 (Pantoea agglomerans) by means of in vivo Mössbauer spectroscopy and radioactive labeling techniques. A comparison of cell spectra with the spectrum of ferrioxamine clearly demonstrates that ferrioxamine E is not accumulated in the cell, indicating a fast metal transfer. Only two major components of iron metabolism can be detected, a ferric and a ferrous species. At 30 min after uptake, 86% of the internalized metal corresponded to a ferrous ion compound and 14% to a ferric iron species. Metal transfer apparently involves a reductive process. With progressing growth, the oxidized species of the two major proteins becomes dominant. The two iron metabolites closely resemble species previously isolated from Escherichia coli. These components of iron metabolism differ from bacterio-ferritin, cytochromes and most iron-sulfur proteins. All other iron-containing cellular components are at least one order of magnitude lower in concentration. We suggest that the ferrous and ferric iron species correspond to two different oxidation states of a low-molecular mass protein.

Identification of enterobactin and linear dihydroxybenzoylserine compounds by HPLC and ion spray mass spectrometry (LC/MS and MS/MS).

The production of catecholate siderophores was studied in some selected species of Enterobacter (Enterobacteriaceae). The extracted catecholates were separated as iron-free compounds by HPLC on a C18 reversed-phase column using methanol/0.1% phosphoric acid or methanol/0.1% formic acid as a solvent system and identified by ion spray mass spectrometry (LC/MS, MS/MS). Five catecholate compounds were identified which include 2,3-dihydroxybenzoylserine, its linear dimer and trimer, the cyclic enterobactin and an unidentified isomer of enterobactin. In addition, a new large-scale method for the isolation of catecholate siderphores is described which is based on adsorption on XAD-2 and subsequent purification on Sephadex LH20.

Ferrioxamine transport mutants and the identification of the ferrioxamine receptor protein (FoxA) in Erwinia herbicola (Enterobacter agglomerans).

Iron deprivation of Erwinia herbicola (Enterobacter agglomerans) induces the biosynthesis of six high-Mr outer-membrane proteins and large amounts of ferrioxamine E. Mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine and selection with ferrimycin A yielded mutants of E. herbicola K4 (wild type), defective in the expression of a 76-kDa outer-membrane protein, as determined by SDS/polyacrylamide gel electrophoresis. While in bioassays wild-type cells showed growth promotion in the presence of ferrioxamines (B, D1, D2, E, G), enterobactin, citrate, ferrichrome and coprogen, these mutants failed to respond to ferrioxamines. Moreover, experiments with 55Fe-labelled siderophores confirmed that iron transport mediated by ferrioxamine E and B in the mutants was completely inhibited, whereas iron transport by other hydroxamate siderophores, such as ferrichrome and coprogen was unaffected. The results are evidence that the 76-kDa protein in the outer membrane represents the receptor protein (FoxA) for ferrioxamines in E. herbicola.

Characterization of ferrioxamine E as the principal siderophore of Erwinia herbicola (Enterobacter agglomerans).

Several strains of the enterobacterial group Erwinia herbicola (Enterobacter agglomerans) were screened for siderophore production. After 3 days of growth in a low-iron medium, all strains studied produced hydroxamate siderophores. The retention values of the main siderophore during thin-layer chromatography on silica gel plates and on HPLC reversed-phase columns were identical with those of an authentic sample of ferrioxamine E (norcardamine). Gas-chromatographic analysis of the HI hydrolyzate yielded succinic acid and 1,5-diaminopentane in equimolar amounts; fast-atom-bombardment (FAB) mass spectroscopy showed a molecular mass of 653 Da. Iron from 55Fe-labelled ferrioxamine E was well taken up by iron-starved cells of E. herbicola (Km = 0.1 microM, Vmax = 8 pmol mg-1 min-1). However, besides ferrioxamine E (100%), several exogenous siderophores such as enterobactin (94.5%), ferric citrate (78.5%), coprogen (63.5%) and ferrichrome (17.5%) served as siderophores, suggesting the presence of multiple siderophore receptors in the outer membrane of E. herbicola.