An Octopus-Derived Peptide with Antidiuretic Activity in Rats.

Discovering new drug candidates with high efficacy and few side effects is a major challenge in new drug development. The two evolutionarily related peptides oxytocin (OXT) and arginine vasopressin (AVP) are known to be associated with a variety of physiological and psychological processes via the association of OXT with three types of AVP receptors. Over decades, many synthetic analogs of these peptides have been designed and tested for therapeutic applications; however, only a few studies of their natural analogs have been performed. In this study, we investigated the bioactivity and usefulness of two natural OXT/AVP analogs that originate from the marine invertebrate Octopus vulgaris, named octopressin (OTP) and cephalotocin (CPT). By measuring the intracellular Ca2+ or cyclic AMP increase in each OXT/AVP receptor subtype-overexpressing cell, we found that CPT, but not OTP, acts as a selective agonist of human AVP type 1b and 2 receptors. This behavior is reminiscent of desmopressin, the most widely prescribed antidiuretic drug in the world. Similar to the case for desmopressin, a single intravenous tail injection of CPT into Sprague-Dawley rats reduced urine output and increased urinary osmolality. In conclusion, we suggest that CPT has a significant antidiuretic effect and that CPT might be beneficial for treating urological conditions such as nocturia, enuresis, and diabetes insipidus.

Spatiotemporal characterisation of ischaemic lesions in transient stroke animal models using diffusion free water elimination and mapping MRI with echo time dependence.

BACKGROUND AND PURPOSE: The excess fluid as a result of vasogenic oedema and the subsequent tissue cavitation obscure the microstructural characterisation of ischaemic tissue by conventional diffusion and relaxometry MRI. They lead to a pseudo-normalisation of the water diffusivity and transverse relaxation time maps in the subacute and chronic phases of stroke. Within the context of diffusion MRI, the free water elimination and mapping method (FWE) with echo time dependence has been proposed as a promising approach to measure the amount of free fluid in brain tissue robustly and to eliminate its biasing effect on other biomarkers. In this longitudinal study of transient middle cerebral artery occlusion (MCAo) in the rat brain, we investigated the use of FWE MRI with echo time dependence for the characterisation of the tissue microstructure and explored the potential of the free water fraction as a novel biomarker of ischaemic tissue condition. METHODS: Adult rats received a transient MCAo. Diffusion- and transverse relaxation-weighted MRI experiments were performed longitudinally, pre-occlusion and on days 1, 3, 4, 5, 6, 7 and 10 after MCAo on four rats. Histology was performed for non-stroke and 1, 3 and 10 days after MCAo on three different rats at each time point. RESULTS: The free water fraction was homogeneously increased in the ischaemic cortex one day after stroke. Between three and ten days after stroke, the core of the ischaemic tissue showed a progressive normalisation in the amount of free water, whereas the inner and outer border zones of the ischaemic cortex depicted a large, monotonous increase with time. The specific lesions in brain sections were verified by H&E and immunostaining. The tissue-specific diffusion and relaxometry MRI metrics in the ischaemic cortex were significantly different compared to their conventional counterpart. CONCLUSIONS: Our results demonstrate that the free water fraction in FWE MRI with echo time dependence is a valuable biomarker, sensitive to the progressive degeneration in ischaemic tissue. We showed that part of the heterogeneity previously observed in conventional parameter maps can be accounted for by a heterogeneous distribution of free water in the tissue. Our results suggest that the temporal evolution of the free fluid fraction map at the core and inner border zone can be associated with the pathological changes linked to the evolution of vasogenic oedema. Namely, the homogeneous increase in free water one day after stroke and its tendency to normalise in the core of the ischaemic cortex starting three days after stroke, followed by a progressive increase in free water at the inner border zone from three to ten days after stroke. Finally, the monotonous increase in free fluid in the outer border zone of the cortex reflects the formation of fluid-filled cysts.

Magnetic resonance spectroscopy with transcranial direct current stimulation to explore the underlying biochemical and physiological mechanism of the human brain: A systematic review.

A large body of molecular and neurophysiological evidence connects synaptic plasticity to specific functions and energy metabolism in particular areas of the brain. Furthermore, altered plasticity and energy regulation has been associated with a number of neuropsychiatric disorders. A favourable approach enabling the modulation of neuronal excitability and energy in humans is to stimulate the brain using transcranial direct current stimulation (tDCS) and then to observe the effect on neurometabolites using magnetic resonance spectroscopy (MRS). In this way, a well-defined modulation of brain energy and excitability can be achieved using a dedicated tDCS protocol to a predetermined brain region. This systematic review was guided by the preferred reporting items for systematic reviews and meta-analysis and summarises recent literature studying the effect of tDCS on neurometabolites in the human brain as measured by proton or phosphorus MRS. Limitations and recommendations are discussed for future research. The findings of this review provide clear evidence for the potential of using tDCS and MRS to examine and understand the effect of neurometabolites in the in vivo human brain.

Dedicated diffusion phantoms for the investigation of free water elimination and mapping: insights into the influence of T2 relaxation properties.

Conventional diffusion-weighted (DW) MRI suffers from free water contamination due to the finite voxel size. The most common case of free water contamination occurs with cerebrospinal fluid (CSF) in voxels located at the CSF-tissue interface, such as at the ventricles in the human brain. Another case refers to intra-tissue free water as in vasogenic oedema. In order to avoid the bias in diffusion metrics, several multi-compartment methods have been introduced, which explicitly model the presence of a free water compartment. However, fitting multi-compartment models in DW MRI represents a well known ill conditioned problem. Although during the last decade great effort has been devoted to mitigating this estimation problem, the research field remains active. The aim of this work is to introduce the design, characterise the NMR properties and demonstrate the use of two dedicated anisotropic diffusion fibre phantoms, useful for the study of free water elimination (FWE) and mapping models. In particular, we investigate the recently proposed FWE diffusion tensor imaging approach, which takes explicit account of differences in the transverse relaxation times between the free water and tissue compartments.

9.4 T small animal MRI using clinical components for direct translational studies.

BACKGROUND: Magnetic resonance is a major preclinical and clinical imaging modality ideally suited for longitudinal studies, e.g. in pharmacological developments. The lack of a proven platform that maintains an identical imaging protocol between preclinical and clinical platforms is solved with the construction of an animal scanner based on clinical hard- and software. METHODS: A small animal magnet and gradient system were connected to a clinical MR system. Several hardware components were either modified or built in-house to achieve compatibility. The clinical software was modified to account for the different field-of-view of a preclinical MR system. The established scanner was evaluated using clinical QA protocols, and platform compatibility for translational research was verified against clinical scanners of different field strength. RESULTS: The constructed animal scanner operates with the majority of clinical imaging sequences. Translational research is greatly facilitated as protocols can be shared between preclinical and clinical platforms. Hence, when maintaining sequences parameters, maximum similarity between pulses played out on a human or an animal system is maintained. CONCLUSION: Coupling of a small animal magnet with a clinical MR system is a flexible, easy to use way to establish and advance translational imaging capability. It provides cost and labor efficient translational capability as no tedious sequence reprogramming between moieties is required and cross-platform compatibility of sequences facilitates multi-center studies.

Catastrophic failure of a monolithic zirconia prosthesis.

Recently, monolithic zirconia restorations have received attention as an alternative to zirconia veneered with feldspathic porcelain to eliminate chipping failures of veneer ceramics. In this clinical report, a patient with mandibular edentulism received 4 dental implants in the interforaminal area, and a screw-retained monolithic zirconia prosthesis was fabricated. The patient also received a maxillary complete removable dental prosthesis over 4 anterior roots. At the 18-month follow-up, all of the zirconia cylinders were seen to be fractured, and the contacting abutment surfaces had lost structural integrity. The damaged abutments were replaced with new abutments, and a new prosthesis was delivered with a computer-assisted design and computer-assisted manufacturing fabricated titanium framework with denture teeth and denture base resins. At the 6-month recall, the patient did not have any problems. Dental zirconia has excellent physical properties; however, care should be taken to prevent excessive stresses on the zirconia cylinders when a screw-retained zirconia restoration is planned as a definitive prosthesis.

Phosphorylation of actin-related protein 2 (Arp2) is required for normal development and cAMP chemotaxis in Dictyostelium.

Phosphorylation of the actin-related protein 2 (Arp2) subunit of the Arp2/3 complex on evolutionarily conserved threonine and tyrosine residues was recently identified and shown to be necessary for nucleating activity of the Arp2/3 complex and membrane protrusion of Drosophila cells. Here we use the Dictyostelium diploid system to replace the essential Arp2 protein with mutants that cannot be phosphorylated at Thr-235/6 and Tyr-200. We found that aggregation of the resulting mutant cells after starvation was substantially slowed with delayed early developmental gene expression and that chemotaxis toward a cAMP gradient was defective with loss of polarity and attenuated F-actin assembly. Chemotaxis toward cAMP was also diminished with reduced cell speed and directionality and shorter pseudopod lifetime when Arp2 phosphorylation mutant cells were allowed to develop longer to a responsive state similar to that of wild-type cells. However, clathrin-mediated endocytosis and chemotaxis under agar to folate in vegetative cells were only subtly affected in Arp2 phosphorylation mutants. Thus, phosphorylation of threonine and tyrosine is important for a subset of the functions of the Arp2/3 complex, in particular an unexpected major role in regulating development.

A Review of Parallel Transmit Arrays for Ultra-High Field MR Imaging.

Parallel transmission (pTX) techniques are required to tackle a number of challenges, e.g., the inhomogeneous distribution of the transmit field and elevated specific absorption rate (SAR), in ultra-high field (UHF) MR imaging. Additionally, they offer multiple degrees of freedom to create temporally- and spatially-tailored transverse magnetization. Given the increasing availability of MRI systems at 7 T and above, it is anticipated that interest in pTX applications will grow accordingly. One of the key components in MR systems capable of pTX is the design of the transmit array, as this has a major impact on performance in terms of power requirements, SAR and RF pulse design. While several reviews on pTX pulse design and the clinical applicability of UHF exist, there is currently no systematic review of pTX transmit/transceiver coils and their associated performance. In this article, we analyze transmit array concepts to determine the strengths and weaknesses of different types of design. We systematically review the different types of individual antennas employed for UHF, their combination into pTX arrays, and methods to decouple the individual elements. We also reiterate figures-of-merit (FoMs) frequently employed to describe the performance of pTX arrays and summarize published array designs in terms of these FoMs.

Near ultraviolet InGaN/AlGaN-based light-emitting diodes with highly reflective tin-doped indium oxide/Al-based reflectors.

The enhanced light output power of a InGaN/AlGaN-based light-emitting diodes (LEDs) using three different types of highly reflective Sn-doped indium oxide (ITO)/Al-based p-type reflectors, namely, ITO/Al, Cu-doped indium oxide (CIO)/s-ITO(sputtered)/Al, and Ag nano-dots(n-Ag)/CIO/s-ITO/Al, is presented. The ITO/Al-based reflectors exhibit lower reflectance (76 - 84% at 365 nm) than Al only reflector (91.1%). However, unlike Al only n-type contact, the ITO/Al-based contacts to p-GaN show good ohmic characteristics. Near-UV (365 nm) InGaN/AlGaN-based LEDs with ITO/Al, CIO/s-ITO/Al, and n-Ag/CIO/s-ITO/Al reflectors exhibit forward-bias voltages of 3.55, 3.48, and 3.34 V at 20 mA, respectively. The LEDs with the ITO/Al and CIO/s-ITO/Al reflectors exhibit 9.5% and 13.5% higher light output power (at 20 mA), respectively, than the LEDs with the n-Ag/CIO/s-ITO/Al reflector. The improved performance of near UV LEDs is attributed to the high reflectance and low contact resistivity of the ITO/Al-based reflectors, which are better than those of conventional Al-based reflectors.

Design of a Folded, Double-Tuned Loop Coil for ¹H/X-Nuclei MRI Applications.

MR measurement using a combination of X-nuclei and proton MRI is of great interest as the information provided by the two nuclei is highly complementary, with the X-nuclei signal giving metabolic data relating to potential biomarkers and the proton signal affording anatomical details. Due to the relatively weak signal obtained from X-nuclei, combining an X-nuclei coil with a proton coil is also advantageous for [Formula: see text] shimming and scout images. One approach to building a double-resonant coil is to modify the coil geometry. Here, to achieve double-resonance, a 2× 1 ladder network was designed and tuned at both proton and X-nuclei frequencies successfully. Due to coupling between closed wires, the double-tuned coil generates a shifted transmit efficiency pattern compared to that of the single-tuned loop at the 7T MRI proton frequency. To compensate for the shifted pattern, one part of the 2× 1 ladder network was folded, and the tuning and performance of the folded double-tuned coil were evaluated in simulations and MR measurements. The proposed structure was further evaluated with overlapped decoupling in a receive-only array. The results show that our proposed folded double-tuned coil moderated the shifted pattern of a straight double-tuned loop coil and provided minimum losses at both proton and X-nuclei frequencies. The proposed folded double-tuned loop coil has also been further extended to a receive-only array.

MRI Coil Development Strategies for Hybrid MR-PET Systems: A Review.

Simultaneously operating MR-PET systems have the potential to provide synergetic multi-parametric information, and, as such, interest surrounding their use and development is increasing. However, despite the potential advantages offered by fully combined MR-PET systems, implementing this hybrid integration is technically laborious, and any factors degrading the quality of either modality must be circumvented to ensure optimal performance. In order to attain the best possible quality from both systems, most full MR-PET integrations tend to place the shielded PET system inside the MRI system, close to the target volume of the subject. The radiofrequency (RF) coil used in MRI systems is a key factor in determining the quality of the MR images, and, in simultaneous acquisition, it is generally positioned inside the PET system and PET imaging region, potentially resulting in attenuation and artefacts in the PET images. Therefore, when designing hybrid MR-PET systems, it is imperative that consideration be given to the RF coils inside the PET system. In this review, we present current state-of-the-art RF coil designs used for hybrid MR-PET experiments and discuss various design strategies for constructing PET transparent RF coils.

A Novel J-Shape Antenna Array for Simultaneous MR-PET or MR-SPECT Imaging.

Simultaneous MR-PET/-SPECT is an emerging technology that capitalises on the invaluable advantages of both modalities, allowing access to numerous sensitive tracers and superior soft-tissue contrast alongside versatile functional imaging capabilities. However, to optimise these capabilities, concurrent acquisitions require the MRI antenna located inside the PET/SPECT field-of-view to be operated without compromising any aspects of system performance or image quality compared to the stand-alone instrumentation. Here, we report a novel gamma-radiation-transparent antenna concept. The end-fed J-shape antenna is particularly adept for hybrid ultra-high field MR-PET/-SPECT applications as it enables all highly attenuating materials to be placed outside the imaging field-of-view. Furthermore, this unique configuration also provides advantages in stand-alone MR applications by reducing the amount of coupling between the cables and the antenna elements, and by lowering the potential specific absorption rate burden. The use of this new design was experimentally verified according to the important features for both ultra-high field MRI and the 511 keV transmission scan. The reconstructed attenuation maps evidently showed much lower attenuation (  âˆ¼ 15 %) for the proposed array when compared to the conventional dipole antenna array since there were no high-density components. In MR, it was observed that the signal-to-noise ratio from the whole volume obtained using the proposed array was comparable to that acquired by the conventional array which was also in agreement with the simulation results. The unique feature, J-shape array, would enable simultaneous MR-PET/-SPECT experiments to be conducted without unduly compromising any aspects of system performance and image quality compared to the stand-alone instrumentation.

Design and Construction of a PET-Compatible Double-Tuned 1H/31P MR Head Coil.

Simultaneous MR-PET is an increasingly popular multimodal imaging technique that is able to combine metabolic information obtained from PET with anatomical/functional information from MRI. One of the key technological challenges of the technique is the integration of a PET-transparent MR coil system, a solution to which is demonstrated here for a double-tuned 1H/31P head coil at 3 T. Two single-resonant birdcage coils tuned to the 1H and 31P resonances were arranged in an interleaved fashion and electrically decoupled with the use of trap circuits. All high 511 keV quanta absorbing components were arranged outside the PET field-of-view in order to minimize count rate reduction. The materials inside the PET field-of-view were carefully evaluated and chosen for minimum impact on the PET image quality. As far as possible, the coil case was geometrically optimized to avoid sharp transitions in attenuation, which may potentially result in streaking artefacts during PET image reconstruction. The coil caused a count rate loss of just above 5% when inserted into the PET detector ring. Except for the anterior region, which was designed to maintain free openings for increased patient comfort, an almost uniform distribution of 511 keV attenuation was maintained around the circumference of the coil. MR-related performance for both nuclei was similar or slightly better than that of a commercial double-tuned coil, despite the MR-PET coil having a close-fitting RF screen to shield the PET and MR electronics from possible electromagnetic interferences.

Combined electrochemical surface plasmon resonance for angle spread imaging of multielement electrode arrays.

A surface plasmon resonance imaging system combined with a multielement electrode array is described. An optical system with shaping optics is used to direct a wedge of light onto a gold-coated sample. The reflected light is detected in the form of an angle-spread image of the surface, with one direction denoting a variable incident angle and the other showing a span of locations along one lateral direction of the sample surface. At the proper incident angle, the angle-spread image shows the complete surface plasmon resonance curve over a span of locations on the surface. This imaging system is combined with a sample configuration consisting of a series of gold microelectrode bands, each with independent electrochemical control. In solution, this system can be used to perform high-throughput and dynamic electrochemical experiments. Simultaneous measurement of electrochemical and surface plasmon resonance can be quantitatively performed on each of the electrode surfaces either by holding each electrode at a different potential value or by scanning the applied potential. The sensitivity of this configuration is demonstrated by monitoring oxide formation and removal at a gold electrode in an aqueous electrolyte. A second example, with the use of a thin poly(aniline) coating, illustrates the ability to monitor film changes, including thickness, dielectric properties, and associated electrochemically induced polymer oxidation/reduction on multiple electrodes. This represents a simple and compact method for combining the sensitivity of surface plasmon resonance into an array-based, high-throughput electrochemical system.

Optimization of high-channel count, switch matrices for multinuclear, high-field MRI.

Modern magnetic resonance imaging systems are equipped with a large number of receive connectors in order to optimally support a large field-of-view and/or high acceleration in parallel imaging using high-channel count, phased array coils. Given that the MR system is equipped with a limited number of digitizing receivers and in order to support operation of multinuclear coil arrays, these connectors need to be flexibly routed to the receiver outside the RF shielded examination room. However, for a number of practical, economic and safety reasons, it is better to only route a subset of the connectors. This is usually accomplished with the use of switch matrices. These exist in a variety of topologies and differ in routing flexibility and technological implementation. A highly flexible implementation is a crossbar topology that allows to any one input to be routed to any one output and can use single PIN diodes as active elements. However, in this configuration, long open-ended transmission lines can potentially remain connected to the signal path leading to high transmission losses. Thus, especially for high-field systems compensation mechanisms are required to remove the effects of open-ended transmission line stubs. The selection of a limited number of lumped element reactance values to compensate for the for the effect of transmission line stubs in large-scale switch matrices capable of supporting multi-nuclear operation is non-trivial and is a combinatorial problem of high order. Here, we demonstrate the use of metaheuristic approaches to optimize the circuit design of these matrices that additionally carry out the optimization of distances between the parallel transmission lines. For a matrix with 128 inputs and 64 outputs a realization is proposed that displays a worst-case insertion loss of 3.8 dB.

The state-of-the-art and emerging design approaches of double-tuned RF coils for X-nuclei, brain MR imaging and spectroscopy: A review.

With the increasing availability of ultra-high field MRI systems, studying non-proton nuclei (X-nuclei), such as 23Na and 31P has received great interest. X-nuclei are able to provide insight into important cellular processes and energy metabolism in tissues and by monitoring these nuclei closely it is possible to establish links to pathological conditions and neurodegenerative diseases. In order to investigate X-nuclei, a well-designed radiofrequency (RF) system with a multi-tuned RF coil is required. However, as the intrinsic sensitivity of non-proton nuclei is lower compared to 1H, it is important to ensure that the signal-to-noise ratio (SNR) of the X-nuclei is as high as possible. This review aims to give a comprehensive overview of previous efforts, with particular focus on the design concept of multi-tuned coils, predominantly for brain applications. In order to guide the readers, the main body of the review is categorised into two parts: state-of-the art according to the single or multiple design structures and emerging technologies. A more detailed description is given in each subsection relating to the specific design approaches of, mostly, double-tuned coils, including using traps, PIN-diodes, nested and metamaterial, together with explanations of their novelties, optimal solutions and trade-offs.

Design, evaluation and comparison of endorectal coils for hybrid MR-PET imaging of the prostate.

Prostate cancer is one of the most common cancers among men and its early detection is critical for its successful treatment. The use of multimodal imaging, such as MR-PET, is most advantageous as it is able to provide detailed information about the prostate. However, as the human prostate is flexible and can move into different positions under external conditions, it is important to localise the focused region-of-interest using both MRI and PET under identical circumstances. In this work, we designed five commonly used linear and quadrature radiofrequency surface coils suitable for hybrid MR-PET use in endorectal applications. Due to the endorectal design and the shielded PET insert, the outer face of the coils investigated was curved and the region to be imaged was outside the volume of the coil. The tilting angles of the coils were varied with respect to the main magnetic field direction. This was done to approximate the various positions from which the prostate could be imaged. The transmit efficiencies and safety excitation efficiencies from simulations, together with the signal-to-noise ratios from the MR images were calculated and analysed. Overall, it was found that the overlapped loops driven in quadrature were superior to the other types of coils we tested. In order to determine the effect of the different coil designs on PET, transmission scans were carried out, and it was observed that the differences between attenuation maps with and without the coils were negligible. The findings of this work can provide useful guidance for the integration of such coil designs into MR-PET hybrid systems in the future.

An in vivo multimodal feasibility study in a rat brain tumour model using flexible multinuclear MR and PET systems.

BACKGROUND: In addition to the structural information afforded by 1H MRI, the use of X-nuclei, such as sodium-23 (23Na) or phosphorus-31 (31P), offers important complementary information concerning physiological and biochemical parameters. By then combining this technique with PET, which provides valuable insight into a wide range of metabolic and molecular processes by using of a variety of radioactive tracers, the scope of medical imaging and diagnostics can be significantly increased. While the use of multimodal imaging is undoubtedly advantageous, identifying the optimal combination of these parameters to diagnose a specific dysfunction is very important and is advanced by the use of sophisticated imaging techniques in specific animal models. METHODS: In this pilot study, rats with intracerebral 9L gliosarcomas were used to explore a combination of sequential multinuclear MRI using a sophisticated switchable coil set in a small animal 9.4 T MRI scanner and, subsequently, a small animal PET with the tumour tracer O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET). This made it possible for in vivo multinuclear MR-PET experiments to be conducted without compromising the performance of either multinuclear MR or PET. RESULTS: High-quality in vivo images and spectra including high-resolution 1H imaging, 23Na-weighted imaging, detection of 31P metabolites and [18F]FET uptake were obtained, allowing the characterisation of tumour tissues in comparison to a healthy brain. It has been reported in the literature that these parameters are useful in the identification of the genetic profile of gliomas, particularly concerning the mutation of the isocitrate hydrogenase gene, which is highly relevant for treatment strategy. CONCLUSIONS: The combination of multinuclear MR and PET in, for example, brain tumour models with specific genetic mutations will enable the physiological background of signal alterations to be explored and the identification of the optimal combination of imaging parameters for the non-invasive characterisation of the molecular profile of tumours.

Investigation of Cerebral O-(2-[18F]Fluoroethyl)-L-Tyrosine Uptake in Rat Epilepsy Models.

PURPOSE: A recent study reported on high, longer lasting and finally reversible cerebral uptake of O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) induced by epileptic activity. Therefore, we examined cerebral [18F]FET uptake in two chemically induced rat epilepsy models and in patients with focal epilepsy to further investigate whether this phenomenon represents a major pitfall in brain tumor diagnostics and whether [18F]FET may be a potential marker to localize epileptic foci. PROCEDURES: Five rats underwent kainic acid titration to exhibit 3 to 3.5 h of class IV-V motor seizures (status epilepticus, SE). Rats underwent 4× [18F]FET PET and 4× MRI on the following 25 days. Six rats underwent kindling with pentylenetetrazol (PTZ) 3 to 8×/week over 10 weeks, and hence, seizures increased from class I to class IV. [18F]FET PET and MRI were performed regularly on days with and without seizures. Four rats served as healthy controls. Additionally, five patients with focal epilepsy underwent [18F]FET PET within 12 days after the last documented seizure. RESULTS: No abnormalities in [18F]FET PET or MRI were detected in the kindling model. The SE model showed significantly decreased [18F]FET uptake 3 days after SE in all examined brain regions, and especially in the amygdala region, which normalized within 2 weeks. Corresponding signal alterations in T2-weighted MRI were noted in the amygdala and hippocampus, which recovered 24 days post-SE. No abnormality of cerebral [18F]FET uptake was noted in the epilepsy patients. CONCLUSIONS: There was no evidence for increased cerebral [18F]FET uptake after epileptic seizures neither in the rat models nor in patients. The SE model even showed decreased [18F]FET uptake throughout the brain. We conclude that epileptic seizures per se do not cause a longer lasting increased [18F]FET accumulation and are unlikely to be a major cause of pitfall for brain tumor diagnostics.

Methylglyoxal accumulation by glutathione depletion leads to cell cycle arrest in Dictyostelium.

Reduced glutathione (GSH) serves as a primary redox buffer and its depletion causes growth inhibition or apoptosis in many organisms. In Dictyostelium discoideum, the null mutant (gcsA(-)) of gcsA encoding gamma-glutamylcysteine synthetase shows growth arrest and developmental defect when GSH is depleted. To investigate the mechanism by which GSH depletion induces growth arrest, a proteomic analysis was performed and aldose reductase (AlrA) was identified as the most prominently induced protein in gcsA(-) cells. Induction of AlrA was dependent on GSH concentration and was repressed by GSH but not effectively by either the reducing agent such as dithiothreitol or overexpression of superoxide dismutase. Methylglyoxal (MG), a toxic alpha-ketoaldehyde, strongly induced alrA expression and AlrA catalysed MG reduction efficiently. The alrA knockdown gcsA(-) cells (gcsA(-)/alrA(as)) exhibited more decreased growth rate than gcsA(-) cells, whereas the gcsA(-) cells overexpressing alrA (gcsA(-)/alrA(oe)) showed the recovery of growth rate. Interestingly, intracellular MG levels were significantly augmented in gcsA(-)/alrA(as) cells compared with gcsA(-) cells following GSH depletion. By contrast, gcsA(-)/alrA(oe) cells showed repression of MG induction. Furthermore, MG treatment inhibited growth of wild-type KAx3 cells, inducing G1 phase arrest. Thus, our findings suggest that MG accumulated by GSH depletion inhibits cell growth in Dictyostelium.