Effects of creatine supplementation on muscle weakness in patients with rheumatoid arthritis

Background and objectives. Patients with rheumatoid arthritis (RA) frequently suffer from muscle weakness. Oral administration of creatine has been shown to improve muscle strength in healthy subjects. The objective of this study was to examine the effect of oral creatine supplementation on muscle weakness, disease activity and activities of daily living in patients with RA. Methods. During a period of 3 weeks, 12 patients with RA were treated with creatine monohydrate (20 g/day for 5 days followed by 2 g/day for 16 days). They were examined on entry and at the end of the study. The patients were investigated clinically, blood and urine samples were obtained, muscle biopsies were performed before and after treatment, muscle strength was determined, and self‐administered patient questionnaires were completed. Results. From all patients we were able to obtain full clinical and questionnaire data, while biopsies were taken from 12 patients at the start and from nine patients at the end of the study. Muscle strength, as determined by the muscle strength index, increased in eight of 12 patients. In contrast, physical functional ability and disease activity did not change significantly. The creatine concentration in serum and skeletal muscle increased significantly, while creatine phosphate and total creatine did not increase in skeletal muscle. The skeletal muscle creatine content was associated with muscle strength at baseline but not after administration of creatine. The changes in muscle strength were not associated with the changes in skeletal muscle creatine or creatine phosphate. Conclusion. Although the skeletal muscle creatine content and muscle strength increased with creatine administration in some patients with RA, a clear clinical benefit could not be demonstrated for this treatment when the patients were considered as one grou

Pharmacological manipulation of L-carnitine transport into L6 cells with stable overexpression of human OCTN2

Abstract.: The high-affinity Na+-dependent carnitine transporter OCTN2 (SLC22A5) has a high renal expression and reabsorbs most filtered carnitine. To gain more insight into substrate specificity of OCTN2, we overexpressed hOCTN2 in L6 cells and characterized the structural requirements of substances acting as human OCTN2 (hOCTN2) inhibitors. A 1905-bp fragment containing the hOCTN2 complete coding sequence was introduced into the pWpiresGFP vector, and L6 cells were stably transduced using a lentiviral system. The transduced L6 cells revealed increased expression of hOCTN2 on the mRNA, protein and functional levels. Structural requirements for hOCTN2 inhibition were predicted in silico and investigated in vitro. Essential structural requirements for OCTN2 inhibition include a constantly positively charged nitrogen atom and a carboxyl, nitrile or ester group connected by a 2-4-atom linker. Our cell system is suitable for studying in vitro interactions with OCTN2, which can subsequently be investigated in viv

FACT -- the First Cherenkov Telescope using a G-APD Camera for TeV Gamma-ray Astronomy (HEAD 2010)

Geiger-mode Avalanche Photodiodes (G-APD) bear the potential to significantly improve the sensitivity of Imaging Air Cherenkov Telescopes (IACT). We are currently building the First G-APD Cherenkov Telescope (FACT) by refurbishing an old IACT with a mirror area of 9.5 square meters and construct a new, fine pixelized camera using novel G-APDs. The main goal is to evaluate the performance of a complete system by observing very high energy gamma-rays from the Crab Nebula. This is an important field test to check the feasibility of G-APD-based cameras to replace at some time the PMT-based cameras of planned future IACTs like AGIS and CTA. In this article, we present the basic design of such a camera as well as some important details to be taken into account.Comment: Poster shown at HEAD 2010, Big Island, Hawaii, March 1-4, 201

FACT -- The G-APD revolution in Cherenkov astronomy

Since two years, the FACT telescope is operating on the Canary Island of La Palma. Apart from its purpose to serve as a monitoring facility for the brightest TeV blazars, it was built as a major step to establish solid state photon counters as detectors in Cherenkov astronomy. The camera of the First G-APD Cherenkov Telesope comprises 1440 Geiger-mode avalanche photo diodes (G-APD), equipped with solid light guides to increase the effective light collection area of each sensor. Since no sense-line is available, a special challenge is to keep the applied voltage stable although the current drawn by the G-APD depends on the flux of night-sky background photons significantly varying with ambient light conditions. Methods have been developed to keep the temperature and voltage dependent response of the G-APDs stable during operation. As a cross-check, dark count spectra with high statistics have been taken under different environmental conditions. In this presentation, the project, the developed methods and the experience from two years of operation of the first G-APD based camera in Cherenkov astronomy under changing environmental conditions will be presented.Comment: Proceedings of the Nuclear Science Symposium and Medical Imaging Conference (IEEE-NSS/MIC), 201

MAGIC Upper Limits for two Milagro-detected, Bright Fermi Sources in the Region of SNR G65.1+0.6

We report on the observation of the region around supernova remnant G65.1+0.6 with the stand-alone MAGIC-I telescope. This region hosts the two bright GeV gamma-ray sources 1FGL J1954.3+2836 and 1FGL J1958.6+2845. They are identified as GeV pulsars and both have a possible counterpart detected at about 35 TeV by the Milagro observatory. MAGIC collected 25.5 hours of good quality data, and found no significant emission in the range around 1 TeV. We therefore report differential flux upper limits, assuming the emission to be point-like (<0.1 deg) or within a radius of 0.3 deg. In the point-like scenario, the flux limits around 1 TeV are at the level of 3 % and 2 % of the Crab Nebula flux, for the two sources respectively. This implies that the Milagro emission is either extended over a much larger area than our point spread function, or it must be peaked at energies beyond 1 TeV, resulting in a photon index harder than 2.2 in the TeV band.Comment: 8 pages, 3 figures, 1 tabl