High intensity exercise downregulates FTO mRNA expression during the early stages of recovery in young males and females.

BACKGROUND: Physical exercise and activity status may modify the effect of the fat mass- and obesity-associated (FTO) genotype on body weight and obesity risk. To understand the interaction between FTO's effect and physical activity, the present study investigated the effects of high and low intensity exercise on FTO mRNA and protein expression, and potential modifiers of exercise-induced changes in FTO in healthy-weighted individuals. METHODS: Twenty-eight untrained males and females (25.4 ± 1.1 years; 73.1 ± 2.0 kg; 178.8 ± 1.4 cm; 39.0 ± 1.2 ml.kg.min- 1 VO2peak) were genotyped for the FTO rs9939609 (T > A) polymorphism and performed isocaloric (400 kcal) cycle ergometer exercise on two separate occasions at different intensities: 80% (High Intensity (HI)) and 40% (Low Intensity (LO)) VO2peak. Skeletal muscle biopsies (vastus lateralis) and blood samples were taken pre-exercise and following 10 and 90 mins passive recovery. RESULTS: FTO mRNA expression was significantly decreased after HI intensity exercise (p = 0.003). No differences in basal and post-exercise FTO protein expression were evident between FTO genotypes. Phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and Akt substrate of 160 kDa (AS160) were significantly increased following HI intensity exercise (p < 0.05). Multivariate models of metabolomic data (orthogonal two partial least squares discriminant analysis (O2PLS-DA)) were unable to detect any significant metabolic differences between genotypes with either exercise trial (p > 0.05). However, skeletal muscle glucose accumulation at 10 mins following HI (p = 0.021) and LO (p = 0.033) intensity exercise was greater in AA genotypes compared to TT genotypes. CONCLUSION: Our novel data provides preliminary evidence regarding the effects of exercise on FTO expression in skeletal muscle. Specifically, high intensity exercise downregulates expression of FTO mRNA and suggests that in addition to nutritional regulation, FTO could also be regulated by exercise. TRIAL REGISTRATION: ACTRN12612001230842. Registered 21 November 2012 - Prospectively registered, https://www.anzctr.org.au/.

Application of Metabolomics to Osteoarthritis: from Basic Science to the Clinical Approach.

PURPOSE OF THE REVIEW: Osteoarthritis (OA) is a multifactorial and progressive disease affecting whole synovial joint. The extract pathogenic mechanisms and diagnostic biomarkers of OA remain unclear. In this article, we review the studies related to metabolomics of OA, discuss the biomarkers as a tool for early OA diagnosis. Furthermore, we examine the major studies on the application of metabolomics methodology in the complex context of OA and create a bridge from findings in basic science to their clinical utility. RECENT FINDINGS: Recently, the tissue metabolomics signature permits a view into transitional phases between the healthy and OA joint. Both nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry-based metabolomics approaches have been used to interrogate the metabolic alterations that may indicate the complex progression of OA. Specifically, studies on alterations pertaining to lipids, glucose, and amino acid metabolism have aided in the understanding of the complex pathogenesis of OA. The discovery of identified metabolites could be important for diagnosis and staging of OA, as well as for the assessment of efficacy of new drugs.

Biofabricated soft network composites for cartilage tissue engineering.

Articular cartilage from a material science point of view is a soft network composite that plays a critical role in load-bearing joints during dynamic loading. Its composite structure, consisting of a collagen fiber network and a hydrated proteoglycan matrix, gives rise to the complex mechanical properties of the tissue including viscoelasticity and stress relaxation. Melt electrospinning writing allows the design and fabrication of medical grade polycaprolactone (mPCL) fibrous networks for the reinforcement of soft hydrogel matrices for cartilage tissue engineering. However, these fiber-reinforced constructs underperformed under dynamic and prolonged loading conditions, suggesting that more targeted design approaches and material selection are required to fully exploit the potential of fibers as reinforcing agents for cartilage tissue engineering. In the present study, we emulated the proteoglycan matrix of articular cartilage by using highly negatively charged star-shaped poly(ethylene glycol)/heparin hydrogel (sPEG/Hep) as the soft matrix. These soft hydrogels combined with mPCL melt electrospun fibrous networks exhibited mechanical anisotropy, nonlinearity, viscoelasticity and morphology analogous to those of their native counterpart, and provided a suitable microenvironment for in vitro human chondrocyte culture and neocartilage formation. In addition, a numerical model using the p-version of the finite element method (p-FEM) was developed in order to gain further insights into the deformation mechanisms of the constructs in silico, as well as to predict compressive moduli. To our knowledge, this is the first study presenting cartilage tissue-engineered constructs that capture the overall transient, equilibrium and dynamic biomechanical properties of human articular cartilage.

Nickel(II) meso-Hydroxyporphyrin Complexes Revisited: Palladium-Catalysed Synthesis, Electronic Structures of Derived Oxy Radicals, and Oxidative Coupling to a Dioxoporphodimethene Dyad.

We report the synthesis and characterisation of new examples of meso-hydroxynickel(II) porphyrins with 5,15-diphenyl and 10-phenyl-5,15-diphenyl/diaryl substitution. The OH group was introduced by using carbonate or hydroxide as nucleophile by using palladium/phosphine catalysis. The NiPor-OHs exist in solution in equilibrium with the corresponding oxy radicals NiPor-O. . The 15-phenyl group stabilises the radicals, so that the 1 H NMR spectra of {NiPor-OH} are extremely broad due to chemical exchange with the paramagnetic species. The radical concentration for the diphenylporphyrin analogue is only 1 %, and its NMR line-broadening was able to be studied by variable-temperature NMR spectroscopy. The EPR signals of NiPor-O. are consistent with somewhat delocalised porphyrinyloxy radicals, and the spin distributions calculated by using density functional theory match the EPR and NMR spectroscopic observations. Nickel(II) meso-hydroxy-10,20-diphenylporphyrin was oxidatively coupled to a dioxo-terminated porphodimethene dyad, the strongly red-shifted electronic spectrum of which was successfully modelled by using time-dependent DFT calculations.

The effect of ß-alanine and NaHCO3 co-ingestion on buffering capacity and exercise performance with high-intensity exercise in healthy males.

INTRODUCTION: ß-alanine (BAl) and NaHCO3 (SB) ingestion may provide performance benefits by enhancing concentrations of their respective physiochemical buffer counterparts, muscle carnosine and blood bicarbonate, counteracting acidosis during intense exercise. This study examined the effect of BAl and SB co-supplementation as an ergogenic strategy during high-intensity exercise. METHODS: Eight healthy males ingested either BAl (4.8 g day(-1) for 4 weeks, increased to 6.4 g day(-1) for 2 weeks) or placebo (Pl) (CaCO3) for 6 weeks, in a crossover design (6-week washout between supplements). After each chronic supplementation period participants performed two trials, each consisting of two intense exercise tests performed over consecutive days. Trials were separated by 1 week and consisted of a repeated sprint ability (RSA) test and cycling capacity test at 110 % Wmax (CCT110 %). Placebo (Pl) or SB (300 mg kgbw(-1)) was ingested prior to exercise in a crossover design to creating four supplement conditions (BAl-Pl, BAl-SB, Pl-Pl, Pl-SB). RESULTS: Carnosine increased in the gastrocnemius (n = 5) (p = 0.03) and soleus (n = 5) (p = 0.02) following BAl supplementation, and Pl-SB and BAl-SB ingestion elevated blood HCO3 (-) concentrations (p < 0.01). Although buffering capacity was elevated following both BAl and SB ingestion, performance improvement was only observed with BAl-Pl and BAl-SB increasing time to exhaustion of the CCT110 % test 14 and 16 %, respectively, compared to Pl-Pl (p < 0.01). CONCLUSION: Supplementation of BAl and SB elevated buffering potential by increasing muscle carnosine and blood bicarbonate levels, respectively. BAl ingestion improved performance during the CCT110 %, with no aggregating effect of SB supplementation (p > 0.05). Performance was not different between treatments during the RSA test.

Neurological consequences of diabetic ketoacidosis at initial presentation of type 1 diabetes in a prospective cohort study of children.

OBJECTIVE: To investigate the impact of new-onset diabetic ketoacidosis (DKA) during childhood on brain morphology and function. RESEARCH DESIGN AND METHODS: Patients aged 6-18 years with and without DKA at diagnosis were studied at four time points: <48 h, 5 days, 28 days, and 6 months postdiagnosis. Patients underwent magnetic resonance imaging (MRI) and spectroscopy with cognitive assessment at each time point. Relationships between clinical characteristics at presentation and MRI and neurologic outcomes were examined using multiple linear regression, repeated-measures, and ANCOVA analyses. RESULTS: Thirty-six DKA and 59 non-DKA patients were recruited between 2004 and 2009. With DKA, cerebral white matter showed the greatest alterations with increased total white matter volume and higher mean diffusivity in the frontal, temporal, and parietal white matter. Total white matter volume decreased over the first 6 months. For gray matter in DKA patients, total volume was lower at baseline and increased over 6 months. Lower levels of N-acetylaspartate were noted at baseline in the frontal gray matter and basal ganglia. Mental state scores were lower at baseline and at 5 days. Of note, although changes in total and regional brain volumes over the first 5 days resolved, they were associated with poorer delayed memory recall and poorer sustained and divided attention at 6 months. Age at time of presentation and pH level were predictors of neuroimaging and functional outcomes. CONCLUSIONS: DKA at type 1 diabetes diagnosis results in morphologic and functional brain changes. These changes are associated with adverse neurocognitive outcomes in the medium term.

Age-related loss of brain volume and T2 relaxation time in youth with type 1 diabetes.

OBJECTIVE: 2 Childhood-onset type 1 diabetes is associated with neurocognitive deficits, but there is limited evidence to date regarding associated neuroanatomical brain changes and their relationship to illness variables such as age at disease onset. This report examines age-related changes in volume and T2 relaxation time (a fundamental parameter of magnetic resonance imaging that reflects tissue health) across the whole brain. RESEARCH DESIGN AND METHODS: Type 1 diabetes, N = 79 (mean age 20.32 ± 4.24 years), and healthy control participants, N = 50 (mean age 20.53 ± 3.60 years). There were no substantial group differences on socioeconomic status, sex ratio, or intelligence quotient. RESULTS: Regression analyses revealed a negative correlation between age and brain changes, with decreasing gray matter volume and T2 relaxation time with age in multiple brain regions in the type 1 diabetes group. In comparison, the age-related decline in the control group was small. Examination of the interaction of group and age confirmed a group difference (type 1 diabetes vs. control) in the relationship between age and brain volume/T2 relaxation time. CONCLUSIONS: We demonstrated an interaction between age and group in predicting brain volumes and T2 relaxation time such that there was a decline in these outcomes in type 1 diabetic participants that was much less evident in control subjects. Findings suggest the neurodevelopmental pathways of youth with type 1 diabetes have diverged from those of their healthy peers by late adolescence and early adulthood but the explanation for this phenomenon remains to be clarified.

Renal bioenergetics during early gram-negative mammalian sepsis and angiotensin II infusion.

PURPOSE: To measure renal adenosine triphosphate (ATP) (bioenergetics) during hypotensive sepsis with or without angiotensin II (Ang II) infusion. METHODS: In anaesthetised sheep implanted with a renal artery flow probe and a magnetic resonance coil around one kidney, we induced hypotensive sepsis with intravenous Escherichia coli injection. We measured mean arterial pressure (MAP), heart rate, renal blood flow RBF and renal ATP levels using magnetic resonance spectroscopy. After 2 h of sepsis, we randomly assigned sheep to receive an infusion of Ang II or vehicle intravenously and studied the effect of treatment on the same variables. RESULTS: After E. coli administration, the experimental animals developed hypotensive sepsis (MAP from 92 ± 9 at baseline to 58 ± 4 mmHg at 4 h). Initially, RBF increased, then, after 4 h, it decreased below control levels (from 175 ± 28 at baseline to 138 ± 27 mL/min). Despite decreased RBF and hypotension, renal ATP was unchanged (total ATP to inorganic phosphate ratio from 0.69 ± 0.02 to 0.70 ± 0.02). Ang II infusion restored MAP but caused significant renal vasoconstriction. However, it induced no changes in renal ATP (total ATP to inorganic phosphate ratio from 0.79 ± 0.03 to 0.80 ± 0.02). CONCLUSIONS: During early hypotensive experimental gram-negative sepsis, there was no evidence of renal bioenergetic failure despite decreased RBF. In this setting, the addition of a powerful renal vasoconstrictor does not lead to deterioration in renal bioenergetics.

Neuroprotective effects of low-dose lithium in individuals at ultra-high risk for psychosis. A longitudinal MRI/MRS study.

OBJECTIVES: To investigate if low-dose lithium may counteract the microstructural and metabolic brain changes proposed to occur in individuals at ultra-high risk (UHR) for psychosis. METHODS: Hippocampal T2 relaxation time (HT2RT) and proton magnetic resonance spectroscopy ((1)H-MRS) measurements were performed prior to initiation and following three months of treatment in 11 UHR patients receiving low-dose lithium and 10 UHR patients receiving treatment as usual (TAU). HT2RT and (1)H-MRS percentage change scores between scans were compared using repeated measures ANOVA and correlated with behavioural change scores. RESULTS: Low-dose lithium significantly reduced HT2RT compared to TAU (p=0.018). No significant group by time effects was seen for any brain metabolites as measured with (1)H-MRS, although myo-inositol, creatine, choline-containing compounds and NAA increased in the group receiving low-dose lithium and decreased or remained unchanged in subjects receiving TAU. CONCLUSIONS: This pilot study suggests that low-dose lithium may protect the microstructure of the hippocampus in UHR states as reflected by significantly decreasing HT2RT. Larger scale replication studies in UHR states using T2 relaxation time as a proxy for emerging brain pathology seem a feasible mean to test neuroprotective strategies such as low-dose lithium as potential treatments to delay or even prevent the progression to full-blown disorder.

Magnetic resonance spectroscopy and neurocognitive dysfunction in obstructive sleep apnea before and after CPAP treatment.

STUDY OBJECTIVES: To determine whether cerebral metabolite changes may underlie abnormalities of neurocognitive function and respiratory control in OSA. DESIGN: Observational, before and after CPAP treatment. SETTING: Two tertiary hospital research institutes. PARTICIPANTS: 30 untreated severe OSA patients, and 25 age-matched healthy controls, all males free of comorbidities, and all having had detailed structural brain analysis using voxel-based morphometry (VBM). MEASUREMENTS AND RESULTS: Single voxel bilateral hippocampal and brainstem, and multivoxel frontal metabolite concentrations were measured using magnetic resonance spectroscopy (MRS) in a high resolution (3T) scanner. Subjects also completed a battery of neurocognitive tests. Patients had repeat testing after 6 months of CPAP. There were significant differences at baseline in frontal N-acetylaspartate/choline (NAA/Cho) ratios (patients [mean (SD)] 4.56 [0.41], controls 4.92 [0.44], P = 0.001), and in hippocampal choline/creatine (Cho/Cr) ratios (0.38 [0.04] vs 0.41 [0.04], P = 0.006), (both ANCOVA, with age and premorbid IQ as covariates). No longitudinal changes were seen with treatment (n = 27, paired t tests), however the hippocampal differences were no longer significant at 6 months, and frontal NAA/Cr ratios were now also significantly different (patients 1.55 [0.13] vs control 1.65 [0.18] P = 0.01). No significant correlations were found between spectroscopy results and neurocognitive test results, but significant negative correlations were seen between arousal index and frontal NAA/Cho (r = -0.39, corrected P = 0.033) and between % total sleep time at SpO(2) < 90% and hippocampal Cho/Cr (r = -0.40, corrected P = 0.01). CONCLUSIONS: OSA patients have brain metabolite changes detected by MRS, suggestive of decreased frontal lobe neuronal viability and integrity, and decreased hippocampal membrane turnover. These regions have previously been shown to have no gross structural lesions using VBM. Little change was seen with treatment with CPAP for 6 months. No correlation of metabolite concentrations was seen with results on neurocognitive tests, but there were significant negative correlations with OSA severity as measured by severity of nocturnal hypoxemia.

Reduced variance in monozygous twins for multiple MR parameters: implications for disease studies and the genetic basis of brain structure.

Twin studies offer the opportunity to determine the relative contribution of genes versus environment in traits of interest. Here, we investigate the extent to which variance in brain structure is reduced in monozygous twins with identical genetic make-up. We investigate whether using twins as compared to a control population reduces variability in a number of common magnetic resonance (MR) structural measures, and we investigate the location of areas under major genetic influences. This is fundamental to understanding the benefit of using twins in studies where structure is the phenotype of interest. Twenty-three pairs of healthy MZ twins were compared to matched control pairs. Volume, T2 and diffusion MR imaging were performed as well as spectroscopy (MRS). Images were compared using (i) global measures of standard deviation and effect size, (ii) voxel-based analysis of similarity and (iii) intra-pair correlation. Global measures indicated a consistent increase in structural similarity in twins. The voxel-based and correlation analyses indicated a widespread pattern of increased similarity in twin pairs, particularly in frontal and temporal regions. The areas of increased similarity were most widespread for the diffusion trace and least widespread for T2. MRS showed consistent reduction in metabolite variation that was significant in the temporal lobe N-acetylaspartate (NAA). This study has shown the distribution and magnitude of reduced variability in brain volume, diffusion, T2 and metabolites in twins. The data suggest that evaluation of twins discordant for disease is indeed a valid way to attribute genetic or environmental influences to observed abnormalities in patients since evidence is provided for the underlying assumption of decreased variability in twins.

Silylation of layered double hydroxides via a calcination-rehydration route.

Silylated layered double hydroxides (LDHs) were synthesized through a surfactant-free method involving an in situ condensation of silane with the surface hydroxyl group of LDHs during its reconstruction in carbonate solution. X-ray diffraction (XRD) patterns showed the silylation reaction occurred on the external surfaces of LDHs layers. The successful silylation was evidenced by (29)Si cross-polarization magic-angle spinning nuclear magnetic resonance ((29)Si CP/MAS NMR) spectroscopy, attenuated total reflection Fourier transform infrared (ATR FTIR) spectroscopy, and infrared emission spectroscopy (IES). The ribbon shaped crystallites with a "rodlike" aggregation were observed through transmission electron microscopy (TEM) images. The aggregation was explained by the T(2) and T(3) types of linkage between adjacent silane molecules as indicated in the (29)Si NMR spectrum. In addition, the silylated products show high thermal stability by maintained Si related bands even when the temperature was increased to 1000 degrees C as observed in IES spectra.

Anisotropy of spin relaxation of water protons in cartilage and tendon.

Transverse spin relaxation rates of water protons in articular cartilage and tendon depend on the orientation of the tissue relative to the applied static magnetic field. This complicates the interpretation of magnetic resonance images of these tissues. At the same time, relaxation data can provide information about their organisation and microstructure. We present a theoretical analysis of the anisotropy of spin relaxation of water protons observed in fully hydrated cartilage. We demonstrate that the anisotropy of transverse relaxation is due almost entirely to intramolecular dipolar coupling modulated by a specific mode of slow molecular motion: the diffusion of water molecules in the hydration shell of a collagen fibre around the fibre, such that the molecular director remains perpendicular to the fibre. The theoretical anisotropy arising from this mechanism follows the 'magic-angle' dependence observed in magnetic-resonance measurements of cartilage and tendon and is in good agreement with the available experimental results. We discuss the implications of the theoretical findings for MRI of ordered collagenous tissues.

Medial temporal lobe glutathione concentration in first episode psychosis: a 1H-MRS investigation.

Glutathione (GSH) is implicated in the pathophysiology of schizophrenia. Previous brain spectroscopy studies, however, have been inconsistent, and there is little data available from first episode psychosis patients. This study compared brain GSH in a first episode cohort (n=30) to controls (n=18), using magnetic resonance spectroscopy (MRS), examining a temporal lobe voxel. Short-echo (TE 30 ms) acquisition proton MRS was performed on a 3T clinical magnetic resonance scanner. Comparison of the first-episode and control groups' GSH concentrations revealed a significant main effect of group (F(1,46)=4.7, p=0.035), but no main effect of hemisphere (F(1,46)=2.3, p=0.137) or group-by-side interactions (F(1,46)=0.4, p=0.513). Medial temporal lobe GSH concentrations in the first episode group were 22% higher than those in the control group. This study provides further evidence of significant perturbations in brain GSH in first episode psychosis, and supports a broader involvement of GSH in the pathophysiology of schizophrenia.

Central nervous system function in youth with type 1 diabetes 12 years after disease onset.

OBJECTIVE: In this study, we used neurocognitive assessment and neuroimaging to examine brain function in youth with type 1 diabetes studied prospectively from diagnosis. RESEARCH DESIGN AND METHODS: We studied type 1 diabetic (n = 106) and control subjects (n = 75) with no significant group difference on IQ at baseline 12 years previously by using the Wechsler Abbreviated Scale of General Intelligence, magnetic resonance spectroscopy and imaging, and metabolic control data from diagnosis. RESULTS: Type 1 diabetic subjects had lower verbal and full scale IQs than control subjects (both P < 0.05). Type 1 diabetic subjects had lower N-acetylaspartate in frontal lobes and basal ganglia and higher myoinositol and choline in frontal and temporal lobes and basal ganglia than control subjects (all P < 0.05). Type 1 diabetic subjects, relative to control subjects, had decreased gray matter in bilateral thalami and right parahippocampal gyrus and insular cortex. White matter was decreased in bilateral parahippocampi, left temporal lobe, and middle frontal area (all P < 0.0005 uncorrected). T2 in type 1 diabetic subjects was increased in left superior temporal gyrus and decreased in bilateral lentiform nuclei, caudate nuclei and thalami, and right insular area (all P < 0.0005 uncorrected). Early-onset disease predicted lower performance IQ, and hypoglycemia was associated with lower verbal IQ and volume reduction in thalamus; poor metabolic control predicted elevated myoinositol and decreased T2 in thalamus; and older age predicted volume loss and T2 change in basal ganglia. CONCLUSIONS: This study documents brain effects 12 years after diagnosis in a type 1 diabetic sample whose IQ at diagnosis matched that of control subjects. Findings suggest several neuropathological processes including gliosis, demyelination, and altered osmolarity.

A 1H-MRS investigation of the medial temporal lobe in antipsychotic-naïve and early-treated first episode psychosis.

Schizophrenia is associated with significant brain abnormalities, including changes in brain metabolites as measured by proton magnetic resonance spectroscopy (MRS). What remains unclear is the extent to which these changes are a consequence of the emergence of psychotic disorders or the result of treatment with antipsychotic medication. We assessed 34 patients with first episode psychosis (15 antipsychotic naïve) and 19 age- and gender-matched controls using short-echo MRS in the medial temporal lobe bilaterally. Overall, there were no differences in any metabolite, regardless of treatment status. However, when the analysis was limited to patients with a diagnosis of schizophrenia, schizophreniform or schizoaffective disorder, significant elevations of creatine/phosphocreatine (Cr/PCr) and myo-inositol (mI) were found in the treated group. These data indicate a relative absence of temporal lobe metabolic abnormalities in first episode psychosis, but suggest that some treatment-related changes in mI might be apparent in patients with schizophrenia-spectrum diagnoses. Seemingly illness-related Cr/PCr elevations were also specific to the diagnosis of schizophrenia-spectrum disorder and seem worthy of future study.

Anterior cingulate glutamate-glutamine levels predict symptom severity in women with obsessive-compulsive disorder.

OBJECTIVE: Abnormalities of the anterior cingulate cortex (ACC) have consistently been identified in obsessive-compulsive disorder (OCD), but very few studies have examined the biochemical basis of such changes. The purpose of the present study was to investigate how ACC biochemistry in OCD varies as a function of gender, hemisphere, subregion, and symptomatology. METHOD: 3 T proton-magnetic resonance spectroscopy (MRS) was used to probe ACC biochemistry in 20 OCD patients (10 male, 10 female) and a comparable group of 26 healthy comparison subjects. Data were acquired from the left and right dorsal and rostral subregions of the ACC. Metabolites assessed included N-acetylaspartate (NAA), glutamate-glutamine (Glx), choline-containing compounds (Cho), creatine/phosphocreatine (Cr), and myoinositol-containing compounds (mI). RESULTS: Female OCD patients had significantly reduced levels of Glx in all but one subregion of the ACC when compared to matched controls. Levels of Glx were correlated with clinical measures of symptom severity in female but not male patients. State levels of anxiety and depression did not explain this association. In addition, both male and female OCD patients had relatively higher concentrations of mI in their right ACC (rostral and dorsal) compared with healthy controls. No other compounds had any statistically significant group differences, nor were the concentrations of any other compounds correlated with symptom measures. CONCLUSIONS: To the authors' knowledge this is the first study to demonstrate gender-specific neurochemical changes in OCD. Although these findings are tentative and require replication, they raise the possibility that MRS techniques may be of use in objectively monitoring patient progress and assessing the effectiveness of various treatments.

Ethyl-eicosapentaenoic acid in first-episode psychosis. A 1H-MRS study.

Ethyl-eicosapentaenoic acid (E-EPA) is an omega-3 fatty acid that has been used in a range of neuropsychiatric conditions with some benefits. However, its mechanism of action is unknown. Here, we investigate its effects on in vivo brain metabolism in first-episode psychosis (FEP). Proton magnetic resonance spectroscopy at 3 T was performed in the temporal lobes of 24 FEP patients before and after 12 weeks of treatment in the context of a larger double-blind, placebo-controlled E-EPA augmentation study. Treatment group effects for glutathione (F1,12=6.1, p=0.03), and a hemisphere-by-group interaction for glutamine/glutamate (F1,20=4.4, p=0.049) were found. Glutathione increased bilaterally and glutamate/glutamine increased in the left hemisphere following E-EPA administration. Improvement in negative symptoms correlated with metabolic brain changes, particularly glutathione (r=-0.57). These results suggest that E-EPA augmentation alters glutathione availability and modulates the glutamine/glutamate cycle in early psychosis, with some of the metabolic brain changes being correlated with negative symptom improvement. Larger confirmatory studies of these postulated metabolic brain effects of E-EPA are warranted.

Liver transplantation for argininosuccinic aciduria: clinical, biochemical, and metabolic outcome.

We report successful liver transplantation in a young adult with argininosuccinic aciduria but without cirrhosis. Plasma amino acid profile normalized and brain magnetic resonance spectroscopy indicated improved metabolism after transplantation. The general well-being of the patient and his quality of life improved. We suggest that orthotopic liver transplantation should be considered for patients with argininosuccinic aciduria even in the absence of cirrhosis, with the aim of correcting (at least in part) central nervous system metabolism, thereby preventing further neurological deterioration.