The val158met polymorphism of human catechol-O-methyltransferase (COMT) affects anterior cingulate cortex activation in response to painful laser stimulation

<p>Abstract</p> <p>Background</p> <p>Pain is a complex experience with sensory, emotional and cognitive aspects. Genetic and environmental factors contribute to pain-related phenotypes such as chronic pain states. Genetic variations in the gene coding for catechol-O-methyltransferase (<it>COMT</it>) have been suggested to affect clinical and experimental pain-related phenotypes including regional μ-opioid system responses to painful stimulation as measured by ligand-PET (positron emission tomography). The functional val¹⁵⁸met single nucleotide polymorphism has been most widely studied. However, apart from its impact on pain-induced opioid release the effect of this genetic variation on cerebral pain processing has not been studied with activation measures such as functional magnetic resonance imaging (fMRI), PET or electroencephalography. In the present fMRI study we therefore sought to investigate the impact of the <it>COMT </it>val¹⁵⁸met polymorphism on the blood oxygen level-dependent (BOLD) response to painful laser stimulation.</p> <p>Results</p> <p>57 subjects were studied. We found that subjects homozygous for the met158 allele exhibit a higher BOLD response in the anterior cingulate cortex (ACC), foremost in the mid-cingulate cortex, than carriers of the val158 allele.</p> <p>Conclusion</p> <p>This result is in line with previous studies that reported higher pain sensitivity in homozygous met carriers. It adds to the current literature in suggesting that this behavioral phenotype may be mediated by, or is at least associated with, increased ACC activity. More generally, apart from one report that focused on pain-induced opioid release, this is the first functional neuroimaging study showing an effect of the <it>COMT </it>val¹⁵⁸met polymorphism on cerebral pain processing.</p

Synovitis and bone inflammation in early rheumatoid arthritis: high-resolution multi-pinhole SPECT versus MRI

PURPOSEWe aimed to assess the relationship between bone inflammation in multi-pinhole single-photon emission computed tomography (MPH-SPECT) and synovitis detected by magnetic resonance imaging (MRI) in early rheumatoid arthritis patients. MATERIALS AND METHODSMPH-SPECT with technetium dicarboxypropanedisphosphonate (Tc-99mDPD) and 3 Tesla MRI were performed in 10 early rheumatoid arthritis patients. Eighty finger joint sites were assessed for increased osteoblastic activity using visual and region-of-interest (ROI) analysis. Presence of joint inflammation in MRI was investigated using the subscores of the rheumatoid arthritis MRI score. RESULTSTc-99mDPD uptake was increased in 38 (47.5%) and 22 (27.5%) joint sites as determined by visual and ROI analysis, respectively. A total of 32 (84.2%) sites with increased bone metabolism showed a normal MRI bone signal. The MPHSPECT uptake ratio was elevated only in the subgroup with severe synovitis (P < 0.001). CONCLUSIONIn early rheumatoid arthritis, molecular imaging with MPHSPECT detects higher rates of inflammatory bone involvement compared to MRI. Our preliminary data suggest that osteitis is related to severe synovitis

Toward Optimal Fitting Parameters for Multi-Exponential DWI Image Analysis of the Human Kidney: A Simulation Study Comparing Different Fitting Algorithms

In DWI, multi-exponential signal analysis can be used to determine signal underlying diffusion components. However, the approach is very complex due to the inherent low SNR, the limited number of signal decay data points, and the absence of appropriate acquisition parameters and standardized analysis methods. Within the scope of this work, different methods for multi-exponential analysis of the diffusion signal in the kidney were compared. To assess the impact of fitting parameters, a simulation was conducted comparing the free non-negative (NNLS) and rigid non-linear least square (NLLS) fitting methods. The simulation demonstrated improved accuracy for NNLS in combination with area-under-curve estimation. Furthermore, the accuracy and stability of the results were further enhanced utilizing optimized parameters, namely 350 logarithmically spaced diffusion coefficients within [0.7, 300] × 10−3 mm2/s and a minimal SNR of 100. The NNLS approach shows an improvement over the rigid NLLS method. This becomes apparent not only in terms of accuracy and omitting prior knowledge, but also in better representation of renal tissue physiology. By employing the determined fitting parameters, it is expected that more stable and reliable results for diffusion imaging in the kidney can be achieved. This might enable more accurate DWI results for clinical utilization

Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration

We previously reported that inactivation of the transmembrane taurine transporter (TauT or solute carrier 6a6) causes early retinal degeneration in mice. Compatible with taurine's indispensability for cell volume homeostasis, protein stabilization, cytoprotection, antioxidation, and immuno- and neuromodulation, mice develop multisystemic dysfunctions (hearing loss; liver fibrosis; and behavioral, heart, and skeletal muscle abnormalities) later on. Here, by genetic, cell biologic, in vivo H-1-magnetic resonance spectroscopy and molecular dynamics simulation studies, we conducted in-depth characterization of a novel disorder: human TAUT deficiency. Loss of TAUT function due to a homozygous missense mutation caused panretinal degeneration in 2 brothers. TAUT(p.A78E) still localized in the plasma membrane but is predicted to impact structural stabilization. H-3-taurine uptake by peripheral blood mononuclear cells was reduced by 95%, and taurine levels were severely reduced in plasma, skeletal muscle, and brain. Extraocular dysfunctions were not yet detected, but significantly increased urinary excretion of 8-oxo-7,8-dihydroguanosine indicated generally enhanced (yet clinically unapparent) oxidative stress and RNA oxidation, warranting continuous broad surveillance.-Preising, M. N., Gorg, B., Friedburg, C., Qvartskhava, N., Budde, B. S., Bonus, M., Toliat, M. R., Pfleger, C., Altmuller, J., Herebian, D., Beyer, M., Zollner, H. J., Wittsack, H.-J., Schaper, J., Klee, D., Zechner, U., Nurnberg, P., Schipper, J., Schnitzler, A., Gohlke, H., Lorenz, B., Haussinger, D., Bolz, H. J. Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration