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Creatine
Kinds of Creatine Terms modified by Creatine Selected AbstractsImpact of cerebrospinal fluid contamination on brain metabolites evaluation with 1H-MR spectroscopy: A single voxel study of the cerebellar vermis in patients with degenerative ataxiasJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 1 2009Laura Guerrini MD PhD Abstract Purpose To investigate the impact of cerebrospinal fluid (CSF) contamination on metabolite evaluation in the superior cerebellar vermis with single-voxel 1H-MRS in normal subjects and patients with degenerative ataxias. Materials and Methods Twenty-nine healthy volunteers and 38 patients with degenerative ataxias and cerebellar atrophy were examined on a 1.5 Tesla scanner. Proton spectra of a volume of interest placed in the superior vermis were acquired using a four TE PRESS technique. We calculated N-acetyl aspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and NAA/Cho ratios, T2 relaxation times and concentrations of the same metabolites using the external phantom method. Finally, concentrations were corrected taking into account the proportion of nervous tissue and CSF, that was determined as Volume Fraction (VF). Results In healthy subjects, a significant difference was observed between metabolite concentrations with and without correction for VF. As compared to controls, patients with ataxias showed significantly reduced NAA/Cr and NAA concentrations, while only corrected Cr concentration was significantly increased. The latter showed an inverse correlation with VF. Conclusion CSF contamination has a not negligible effect on the estimation of brain metabolites. The increase of Cr concentration in patients with cerebellar atrophy presumably reflects the substitutive gliosis which takes place along with loss of neurons. J. Magn. Reson. Imaging 2009;30:11,17. © 2009 Wiley-Liss, Inc. [source] A multi-center 1H MRS study of the AIDS dementia complex: Validation and preliminary analysisJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2003Patricia Lani Lee PhD Abstract Purpose To demonstrate the technical feasibility and reliability of a multi-center study characterizing regional levels of the brain metabolite ratios choline (Cho)/creatine (Cr) and myoinositol (MI)/Cr, markers of glial cell activity, and N-acetyl aspartate (NAA)/Cr, a marker of mature neurons, in subjects with AIDS dementia complex (ADC). Materials and Methods Using an automated protocol (GE PROBE-P), short echo time spectra (TE = 35 msec) were obtained at eight sites from uniformly prepared phantoms and from three brain regions (frontal white matter, basal ganglia, and parietal cortex) of normal volunteers and ADC and HIV-negative subjects. Results A random-effects model of the phantom and volunteer data showed no significant inter-site differences. Feasibility of a multi-center study was further validated by detection of significant differences between the metabolite ratios of ADC subjects and HIV-negative controls. ADC subjects exhibited significantly higher Cho/Cr and MI/Cr in the basal ganglia and significantly reduced NAA/Cr and significantly higher MI/Cr in the frontal white matter. These results are consistent with the predominantly subcortical distribution of the pathologic abnormalities associated with ADC. Conclusion This is the first study to ascertain and validate the reliability and reproducibility of a short echo time 1H-MRS acquisition sequence from multiple brain regions in a multi-center setting. It should now be possible to examine the regional effects of HIV infection in the brain in a large number of subjects and to study the metabolic effects of new therapies for the treatment of ADC in a clinical trial setting. J. Magn. Reson. Imaging 2003;17:625,633. © 2003 Wiley-Liss, Inc. [source] Mechanism of the protective effect of hypothermia on ammonia toxicity in astrocytesJOURNAL OF NEUROCHEMISTRY, Issue 2002C. Zwingmann Ammonia is a key factor in the pathogenesis of hepatic encephalopathy (HE). Acute ammonia treatment causes energy failure of astrocytes, which are able to compensate partly by increased anaerobic metabolism as a means of making up for the energetic shortfall. As hypothermia offers protection from severe encephalopathy and lactate accumulation in liver failure, we investigated the mechanism by which hypothermia protects against ammonia toxicity by multinuclear NMR spectroscopy. 12 h exposure to 5 mm NH4CL decreased the phosphocreatine (PCr)/creatine (Cr) and ATP/ADP ratios to 65 and 76% of control, increased synthesis and release of glutamine to 200,250% and led to a significant stimulation of glycolytic activity reflected by increased uptake and consumption of glucose and accumulation of de novo synthesized intra- and extracellular lactate to 161 and 230% of control. The protective effect of mild hypothermia was evident from inhibiton of lactate accumulation and restoration of ammonia-induced depletion of PCr/Cr. Moderate hypothermia led to an increase of PCr/Cr ratio and inhibited lactate synthesis to 14% of normothermic control, but did not prevent the ATP decrease. While hypothermia inhibited glycolytic flux, intracellular glutamine remained elevated. The results suggest that hypothermia-induced protection against ammonia toxicity results from reduction of cellular energy demand leading to inhibition of anaerobic glucose metabolism and a compensatory stimulation of mitochondrial energy production. Acknowledgements:, Funded by CIHR Canada. [source] Delayed changes in T1 -weighted signal intensity in a rat model of 15-minute transient focal ischemia studied by magnetic resonance imaging/spectroscopy and synchrotron radiation X-ray fluorescenceMAGNETIC RESONANCE IN MEDICINE, Issue 3 2006Xuxia Wang Abstract Previous studies have found that rats subjected to 15-min transient middle cerebral artery occlusion (MCAO) show neurodegeneration in the dorsolateral striatum only, and the resulting striatal lesion is associated with increased T1 -weighted (T1W) signal intensity (SI) and decreased T2 -weighted (T2W) SI at 2,8 weeks after the initial ischemia. It has been shown that the delayed increase in T1W SI in the ischemic region is associated with deposition of paramagnetic manganese ions. However, it has been suggested that other mechanisms, such as tissue calcification and lipid accumulation, also contribute to the relaxation time changes. To clarify this issue, we measured changes in relaxation times, lipid accumulation, and elemental distributions in the brain of rats subjected to 15-min MCAO using MRI, in vivo 1H MR spectroscopy (MRS), and synchrotron radiation X-ray fluorescence (SRXRF). The results show that a delayed (2 weeks after ischemia) increase in T1W SI in the ischemic striatum is associated with significant increases in manganese, calcium, and iron, but without evident accumulation of MRS-visible lipids or hydroxyapatite precipitation. It was also found that 15-min MCAO results in acutely reduced N-acetylaspartate (NAA)/creatine (Cr) ratio in the ipsilateral striatum, which recovers to the control level at 2 weeks after ischemia. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc. [source] Cerebellar metabolic symmetry in essential tremor studied with 1H magnetic resonance spectroscopic imaging: Implications for disease pathologyMOVEMENT DISORDERS, Issue 6 2004Elan D. Louis MD Abstract The pathological basis for essential tremor (ET) is not known; however, metabolic changes in the cerebellum can be observed in positron emission tomography (PET) and 1H magnetic resonance spectroscopic imaging (MRSI) studies. Tremor is relatively symmetric in ET, suggesting that underlying metabolic changes could be also symmetric. The degree of metabolic asymmetry in the cerebellum, however, has not yet been studied in ET, and knowledge about distribution and laterality of metabolic changes might shed some light on basic disease mechanisms. We measured brain metabolism (N -acetylaspartate[NAA]/creatine [tCR]) to obtain an asymmetry index for cerebellar cortical metabolism ET patients compared with that in controls. This index, a percentage, was calculated as |(value right , value left)|/(value right + value left) × 100. Multislice 1H MRSI data were acquired for 20 patients and 11 controls. In ET patients, mean right and left cerebellar cortical NAA/tCR values were 1.61 ± 0.42 and 1.55 ± 0.38, respectively, compared with 1.81 ± 0.62 and 1.87 ± 0.49 in controls. The difference between right and left cerebellar cortical NAA/tCR was also calculated for each subject. In ET patients, the mean right-left difference was 0.14 ± 0.11, compared with 0.32 ± 0.27 in controls (P = 0.016). The mean cerebellar cortical asymmetry index was low in ET (8.8 ± 6.1%), one-half of that in controls (17.0 ± 13.7%, P = 0.027). These data suggest that pathological lesions in ET patients, which remain elusive, might be distributed similarly in each cerebellar cortex. Postmortem studies are needed to confirm these preliminary imaging results. © 2004 Movement Disorder Society [source] Temporal lobe magnetic resonance spectroscopic imaging following selective amygdalohippocampectomy for treatment-resistant epilepsyACTA NEUROLOGICA SCANDINAVICA, Issue 1 2005D. C. Spencer Objectives,,, Magnetic resonance spectroscopic imaging (MRSI) may show circumscribed or extensive decreased brain N -acetyl aspartate (NAA)/creatine and phosphocreatine (Cr) in epilepsy patients. We compared temporal lobe MRSI in patients seizure-free (SzF) or with persistent seizures (PSz) following selective amygdalohippocampectomy (SAH) for medically intractable mesial temporal lobe epilepsy (mTLE). We hypothesized that PSz patients had more extensive temporal lobe metabolite abnormalities than SzF patients. Materials and methods,,, MRSI was used to study six regions of interest (ROI) in the bilateral medial and lateral temporal lobes in 14 mTLE patients following SAH and 11 controls. Results,,, PSz patients had more temporal lobe ROI with abnormally low NAA/Cr than SzF patients, including the unoperated hippocampus and ipsilateral lateral temporal lobe. Conclusion,,, Postoperative temporal lobe MRSI abnormalities are more extensive if surgical outcome following SAH is poor. MRSI may be a useful tool to improve selection of appropriate candidates for SAH by identifying patients requiring more intensive investigation prior to epilepsy surgery. Future prospective studies are needed to evaluate the utility of MRSI, a predictor of successful outcome following SAH. [source] Creatine has no beneficial effect on skeletal muscle energy metabolism in patients with single mitochondrial DNA deletions: a placebo-controlled, double-blind 31P-MRS crossover studyEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2005C. Kornblum The purpose of our randomized, double-blind, placebo-controlled crossover study in 15 patients with chronic progressive external ophthalmoplegia (CPEO) or Kearns,Sayre syndrome (KSS) because of single large-scale mitochondrial (mt) DNA deletions was to determine whether oral creatine (Cr) monohydrate can improve skeletal muscle energy metabolism in vivo. Each treatment phase with Cr in a dosage of 150 mg/kg body weight/day or placebo lasted 6 weeks. The effect of Cr was estimated by phosphorus-31 magnetic resonance spectroscopy (31P-MRS), clinical and laboratory tests. 31P-MRS analysis prior to treatment showed clear evidence of severe mitochondrial dysfunction. However, there were no relevant changes in 31P-MRS parameters under Cr. In particular, phosphocreatine (PCr)/ATP at rest did not increase, and there was no facilitation of post-exercise PCr recovery. Clinical scores and laboratory tests did not alter significantly under Cr, which was tolerated without major side-effects in all patients. Cr supplementation did not improve skeletal muscle oxidative phosphorylation in our series of patients. However, one explanation for our negative findings may be the short study duration or the limited number of patients included. [source] The distribution, metabolism and function of creatine in the male mammalian reproductive tract: a reviewINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 1 2000N. P. Moore Creatine is widely distributed throughout the male reproductive system in several mammalian species, and proteins involved in its metabolism and transport have been reported in a number of cell and tissue types. Creatine is synthesized within some organs, incorporating nitrogen from amino acid metabolism. Although creatine metabolism is obligatory for the motility of sea urchin spermatozoa, this does not appear to be the case for mammals. The possible functions of creatine within the reproductive tract are discussed. [source] Bioenergetics in the pathogenesis of neurodegenerationJOURNAL OF NEUROCHEMISTRY, Issue 2001M. Flint Beal Evidence implicating both mitochondria and bioenergetics as playing a crucial role in necrotic and apoptotic cell death is rapidly accumulating. Mitochondria are essential in controlling specific apoptosis cell death pathways and they are the major source of free radicals in the cell. Direct evidence for a role of mitochondria in neurodegenerative diseases comes from studies in Friedreich's Ataxia. Mutations in frataxin lead to an accumulation of iron within mitochondria. We found a three-fold increase in a marker of oxidative damage to DNA in the urine of patients with Friedreich's Ataxia. There is evidence for mitochondrial defects in patients with amyotrophic lateral sclerosis (ALS). There are mitochondrial abnormalities in liver biopsies and muscle biopsies from individuals with sporadic ALS. Muscle biopsies have shown reduced complex I activity in patients with sporadic ALS. A study of ALS cybrids showed a significant decrease in complex I activity as well as trends towards reduced complex 3 and 4 activities. We found increased levels of 8-hydroxy-2-deoxyguanosine, a marker of oxidative damage to DNA in the plasma, urine and CSF of sporadic ALS patients and increased numbers of point mutations in mtDNA of ALS spinal cord tissue. There is mitochondrial vacuolization in transgenic mouse models of ALS. We found substantial evidence for mitochondrial dysfunction in Huntington's Disease (HD). In HD postmortem brain tissue, there are significant reductions in complex 2, 3 activity. We also demonstrated increased brain lactate concentrations as well as reduced phosphocreatine to inorganic phosphate ratio in the resting muscle of patients with HD. More recent studies have demonstrated that there is abnormal depolarization of mitochondria of HD lymphoblasts, which directly correlates with CAG repeat length. There are reductions in ATP production in muscle are both presymptomatic and symptomatic HD patients. Transgenic mouse models of HD show significant reductions in N-acetylaspartate concentrations, which precede the onset of neuronal degeneration. We investigated a number of therapeutic interventions in both transgenic mouse models of ALS and HD. In transgenic ALS mice we found that oral administration of creatine dose-dependently extends survival and reduces the neuronal degeneration in the spinal cord. We found modest protection with ginkgo biloba and lipoic acid. In the HD mice we found significant improvement with oral administration of creatine in two different transgenic mouse models. Creatine not only extended survival but it also improved motor performance, delayed weight loss and attenuated striatal atrophy. Creatine significantly attenuated reductions in N-acetylaspartate concentrations as assessed using magnetic resonance spectroscopy. We also found significant neuroprotective effects with dichloroacetate, which stimulates pyruvate dehydrogenase. These findings implicate bioenergetic dysfunction in transgenic mouse models of both ALS and HD, and they suggest several novel therapeutic strategies aimed at energy replenishment. [source] Evaluation of creatine transport using Caco-2 monolayers as an in vitro model for intestinal absorptionJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2001Alekha K. Dash Abstract Creatine is a nutraceutical that has gained popularity in both well-trained and casual athletes for its performance-enhancing or ergogenic properties. The major disadvantages of creatine monohydrate formulations are poor solubility and oral bioavailability. In the present study, creatine transport was examined using Caco-2 monolayers as an in vitro model for intestinal absorption. Confluent monolayers of Caco-2 cells (passage 25,35) were used for the permeability studies. Monolayers were placed in side-by-side diffusion chambers. 14C-Creatine (0.1,0.5 ,Ci/mL) was added to either the apical or basolateral side, and the transport of the creatine across the Caco-2 monolayer was measured over a 90-min period. The apical to basolateral transport of 14C-creatine was small, ranging from 0.2,3% of the original amount appearing on the receiver side in a 90-min period. Interestingly, the basolateral to apical permeability of radiolabeled creatine was substantially greater than that observed in the apical to basolateral direction. Studies with drug efflux transport inhibitors indicate that neither the P-glycoprotein nor multidrug resistance-associated protein is involved in the enhanced basolateral to apical transport of creatine. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1593,1598, 2001 [source] Creatine supplementation for patients with COPD receiving pulmonary rehabilitation: A systematic review and meta-analysisRESPIROLOGY, Issue 5 2010Fahad AL-GHIMLAS ABSTRACT Background and objective: Creatine improves muscle strength in exercising healthy individuals, and in patients with neuromuscular disease and heart failure. The aim of this study was to assess whether creatine supplementation improves pulmonary rehabilitation (PR) outcomes in patients with COPD. Methods: A systematic review and meta-analysis was performed of randomized controlled trials published between January 1966 and February 2009 that evaluated the effect of creatine compared with placebo on exercise capacity, muscle strength and health-related quality of life (HR-QoL) in patients undergoing PR for COPD. The pooled estimates were expressed as mean differences (MD) or standardized mean differences (SMD). Results: Four randomized controlled trials that included 151 patients were identified. There was no effect of creatine supplementation on exercise capacity (SMD ,0.01, 95% CI: ,0.42 to 0.22, n = 151). Creatine supplementation did not improve lower extremity muscle strength (SMD 0.03, 95% CI: ,0.55 to 0.61, n = 140) or upper limb muscular strength (SMD 0.02, 95% CI: ,0.33 to 0.38, n = 128) compared with placebo. Two studies (n = 48) assessed quality of life using the St. George's Respiratory Disease Questionnaire. There were no differences in HR-QoL according to domain or total scores. Overall, creatine appeared to be safe and was well tolerated. Quality assessment of the studies showed important limitations. Conclusions: Creatine supplementation does not improve exercise capacity, muscle strength or HR-QoL in patients with COPD receiving PR. However, important limitations were identified in the quality of the available evidence, suggesting that further research is required in this area. [source] Clinical applications of 1H-MR spectroscopy in the evaluation of epilepsies , What do pathological spectra stand for with regard to current results and what answers do they give to common clinical questions concerning the treatment of epilepsies?ACTA NEUROLOGICA SCANDINAVICA, Issue 4 2003T. Hammen Nuclear magnetic resonance spectroscopy (1H-MRS) is a non-invasive method in detecting abnormal spectra of various brain metabolites containing N -acetylaspartate (NAA), Choline (Cho), Creatine (Cr), , -Aminobutyric acid (GABA) and Glutamate. Technical processing of the MR-systems, improved automated shimming methods and further development of special shim coils increase the magnetic field homogeneity and lead to a better spectral quality and spectral resolution. The handling of the systems becomes more user-friendly and is more likely to be used in routine diagnostics. The 1H-MRS has become a diagnostic tool for assessing a number of diseases of the central nervous system mainly including epilepsies and brain tumours. The role of 1H-MRS in the assessment of epilepsies will probably increase in future. In the following article, the principles of 1H-MRS and an overview of it in the evaluation and treatment of epilepsies with special regard to temporal lobe epilepsies (TLE) has been illustrated. [source] MRI white matter hyperintensities, 1H-MR spectroscopy and cognitive function in geriatric depression: a comparison of early- and late-onset casesINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 12 2001Tetsuhito Murata Abstract Background and Objectives Geriatric depression is often thought to differ from that at other times of adulthood. Recently, several studies have shown that the incidence of white matter hyperintense lessions identified by brain MRI is higher in patients with geriatric depression than in healthy elderly subjects, but a consensus has not yet been reached on the relationship between the severity of white matter lesions and either cognitive impairment or depressive symptoms. Method Forty-seven patients aged 50 to 75 years with major depression were divided into two groups based on age at onset of depression: early-onset (<,50 years) group (20 patients; mean age, 62.7,±,6.7) and late-onset (,50 years) group (27 patients; mean age, 65.6,±,5.4). The severity of hyperintense white matter lesions on MRI was classified by region, then a proton magnetic resonance spectroscopy (1H-MRS) focusing on the white matter of the frontal lobes, multidimensional neuropsychological tests and evaluation of depressive symptoms were conducted. Results The severity of the deep white matter lesions, the deterioration of cognitive function related to subcortical/frontal brain system and clinician-rated depressive symptoms were all more pronounced in the late-onset group compared with those in the early-onset group. It was further observed that the more severe the deep white matter lesions, the lower the levels of N-acetylaspartate/creatine. With the age of onset as the covariate, the patients with moderate deep white matter lesions had more pronounced cognitive impairment and clinician-rated depressive symptoms than those with none and/or mild lesions. Conclusion These results suggest that subcortical/frontal type cognitive impairment and the persistence of depressive symptoms in geriatric depression is related to moderate deep white matter lesions more often complicated in the late-onset group. The 1H-MRS findings were suggested to be a useful indicator of neuronal/axonal loss in the white matter of the frontal lobes which precedes cognitive impairment. Copyright © 2001 John Wiley & Sons, Ltd. [source] Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 14JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2003A Toscano Transthyretin-derived familial amyloid polyneuropathy (TTR-FAP) is the most common form of hereditary amyloidosis, often associated with multisystemic involvement and a poor prognosis. We studied four patients, aged between 43 and 68 yrs, with TTR-FAP. A severe somatic and autonomic polyneuropathy was seen in three patients, whereas one was at onset of the disease. In addition 2/4, aged 43 and 63 years old, had a mild central nervous system (CNS) involvement. Neurophysiological studies showed an axonal polyneuropathy and amyloid deposits were found in all sural nerve biopsies. Combined conventional MRI and proton MR spectroscopic imaging (MRSI) were performed in our patients and in 14 age-matched normal controls. Conventional MRI was normal in two patients and showed minimal white matter and subcortical lesions in the other two, who were 63 and 68 years old. Proton MRSI of the periventricular brain regions showed a large reduction in N-acetylaspartate/creatine (NAA/Cr) resonance intensity (mean NAA/Cr in patients: 2.45 ± 0.04; mean NAA/Cr in normal controls: 2.9 ± 0.1; p < 0.003). Our findings suggest that, despite minimal or no abnormalities on conventional MRI, evidence of diffuse axonal damage can be demonstrated in brain of patients with TTR-FAP by proton MRSI examination, even in patients with no or mild CNS involvement. [source] Proton magnetic resonance spectroscopic imaging to differentiate between nonneoplastic lesions and brain tumors in children,JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 2 2006Roula Hourani MD Abstract Purpose To investigate whether in vivo proton magnetic resonance spectroscopic imaging (MRSI) can differentiate between 1) tumors and nonneoplastic brain lesions, and 2) high- and low-grade tumors in children. Materials and Methods Thirty-two children (20 males and 12 females, mean age = 10 ± 5 years) with primary brain lesions were evaluated retrospectively. Nineteen patients had a neuropathologically confirmed brain tumor, and 13 patients had a benign lesion. Multislice proton MRSI was performed at TE = 280 msec. Ratios of N-acetyl aspartate/choline (NAA/Cho), NAA/creatine (Cr), and Cho/Cr were evaluated in the lesion and the contralateral hemisphere. Normalized lesion peak areas (Chonorm, Crnorm, and NAAnorm) expressed relative to the contralateral hemisphere were also calculated. Discriminant function analysis was used for statistical evaluation. Results Considering all possible combinations of metabolite ratios, the best discriminant function to differentiate between nonneoplastic lesions and brain tumors was found to include only the ratio of Cho/Cr (Wilks' lambda, P = 0.012; 78.1% of original grouped cases correctly classified). The best discriminant function to differentiate between high- and low-grade tumors included the ratios of NAA/Cr and Chonorm (Wilks' lambda, P = 0.001; 89.5% of original grouped cases correctly classified). Cr levels in low-grade tumors were slightly lower than or comparable to control regions and ranged from 53% to 165% of the control values in high-grade tumors. Conclusion Proton MRSI may have a promising role in differentiating pediatric brain lesions, and an important diagnostic value, particularly for inoperable or inaccessible lesions. J. Magn. Reson. Imaging 2006. Published 2005 Wiley-Liss, Inc. [source] Relative increase in choline in the occipital cortex in chronic fatigue syndromeACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2002B. K. Puri Puri BK, Counsell SJ, Zaman R, Main J, Collins AG, Hajnal JV, Davey NJ. Relative increase in choline in the occipital cortex in chronic fatigue syndrome. Acta Psychiatr Scand 2002: 106: 224,226. © Blackwell Munksgaard 2002. Objective:,To test the hypothesis that chronic fatigue syndrome (CFS) is associated with altered cerebral metabolites in the frontal and occipital cortices. Method:,Cerebral proton magnetic resonance spectroscopy (1H MRS) was carried out in eight CFS patients and eight age- and sex-matched healthy control subjects. Spectra were obtained from 20 × 20 × 20 mm3 voxels in the dominant motor and occipital cortices using a point-resolved spectroscopy pulse sequence. Results:,The mean ratio of choline (Cho) to creatine (Cr) in the occipital cortex in CFS (0.97) was significantly higher than in the controls (0.76; P=0.008). No other metabolite ratios were significantly different between the two groups in either the frontal or occipital cortex. In addition, there was a loss of the normal spatial variation of Cho in CFS. Conclusion:,Our results suggest that there may be an abnormality of phospholipid metabolism in the brain in CFS. [source] On-line automatic SPE-CE coupling for the determination of biological markers in urineELECTROPHORESIS, Issue 5 2007José Ruiz-Jiménez Abstract Automatic SPE has been coupled on-line to CE by a transfer tube and the replenishment system of the CE instrument. The approach allows the target analytes (viz. creatinine, creatine, xanthine, hypoxanthine, uric acid, p -aminohippuric acid and ascorbic acid in urine samples) to be removed from the sample matrix, cleaned up, preconcentrated and injected into the capillary. The detection limits range between 0.14 and 4.50,,g/mL, the quantification limits between 0.45 and 15.0,,g/mL, and linear dynamic ranges , which include the reference healthy human values , from the quantification limits to 1332,,g/mL. The precision, expressed as RSD, ranges between 0.38 and 2.22% for repeatability and between 1.79 and 7.61% for within-laboratory reproducibility. The errors, expressed as RSD for all compounds, range between 0.20 and 6.90%. The time for automatic SPE and that necessary for the individual separation,detection of the target analytes are 13 and 12,min, respectively; the analysis frequency is 5,h,1. The accuracy of the method and potential matrix effects were studied by using spiked samples and recoveries between 96.00 and 103.07 % were obtained. The proposed method was applied to samples from healthy young students. [source] A Short-echo-time Proton Magnetic Resonance Spectroscopic Imaging Study of Temporal Lobe EpilepsyEPILEPSIA, Issue 9 2002Robert J. Simister Summary: ,Purpose: We used short-echo-time proton magnetic resonance spectroscopy imaging (MRSI) to study metabolite concentration variation through the temporal lobe in patients with temporal lobe epilepsy (TLE) with and without abnormal MRI. Methods: MRSI was performed at TE = 30 ms to study 10 control subjects, 10 patients with TLE and unilateral hippocampal sclerosis, and 10 patients with TLE and unremarkable MRI (MRI negative). We measured the concentrations of N -acetyl aspartate +N -acetyl aspartyl-glutamate (NAAt), creatine (Cr), choline (Cho), glutamate + glutamine (Glx), and myoinositol, in the anterior, middle, and posterior medial temporal lobe (MTL), and in the posterior lateral temporal lobe. Segmented volumetric T1 -weighted MRIs gave the tissue composition of each MRSI voxel. Normal ranges were defined as the control mean ± 3 SD. Results: In the hippocampal sclerosis group, seven of 10 had abnormally low NAAt in the ipsilateral anterior MTL. In the MRI-negative group, four of 10 had low NAAt in the middle MTL voxel ipsilateral to seizure onset. Metabolite ratios were less sensitive to abnormality than was the NAAt concentration. Group analysis showed low NAAt, Cr, and Cho in the anterior MTL in hippocampal sclerosis. Glx was elevated in the anterior voxel contralateral to seizure onset in the MRI-negative group. Metabolite concentrations were influenced by voxel position and tissue composition. Conclusions: (a) Low NAAt, Cr, and Cho were features of the anterior sclerotic hippocampus, whereas low NAAt was observed in the MRI-negative group in the middle MTL region. The posterior temporal lobe regions were not associated with significant metabolite abnormality; (b) The two patient groups demonstrated different metabolite profiles across the temporal lobe, with elevated Glx a feature of the MRI-negative group; and (c) Voxel tissue composition and position influenced obtained metabolite concentrations. [source] Creatine has no beneficial effect on skeletal muscle energy metabolism in patients with single mitochondrial DNA deletions: a placebo-controlled, double-blind 31P-MRS crossover studyEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2005C. Kornblum The purpose of our randomized, double-blind, placebo-controlled crossover study in 15 patients with chronic progressive external ophthalmoplegia (CPEO) or Kearns,Sayre syndrome (KSS) because of single large-scale mitochondrial (mt) DNA deletions was to determine whether oral creatine (Cr) monohydrate can improve skeletal muscle energy metabolism in vivo. Each treatment phase with Cr in a dosage of 150 mg/kg body weight/day or placebo lasted 6 weeks. The effect of Cr was estimated by phosphorus-31 magnetic resonance spectroscopy (31P-MRS), clinical and laboratory tests. 31P-MRS analysis prior to treatment showed clear evidence of severe mitochondrial dysfunction. However, there were no relevant changes in 31P-MRS parameters under Cr. In particular, phosphocreatine (PCr)/ATP at rest did not increase, and there was no facilitation of post-exercise PCr recovery. Clinical scores and laboratory tests did not alter significantly under Cr, which was tolerated without major side-effects in all patients. Cr supplementation did not improve skeletal muscle oxidative phosphorylation in our series of patients. However, one explanation for our negative findings may be the short study duration or the limited number of patients included. [source] Contractile Properties, Fatigue and Recovery are not Influenced by Short-Term Creatine Supplementation in Human MuscleEXPERIMENTAL PHYSIOLOGY, Issue 4 2000J. M. Jakobi There have been several studies on the effect of short-term creatine (Cr) supplementation on exercise performance, but none have investigated both voluntary and stimulated muscle contractions in the same experiment. Fourteen moderately active young men (19-28 years) were randomly assigned, in a double blind manner, to either a creatine (Cr) or placebo (P) group. The subjects supplemented their regular diet 4 times a day for 5 days with either 5 g Cr + 5 g maltodextrin (Cr group), or 5 g maltodextrin (P group). Isometric maximal voluntary contraction (MVC), muscle activation, as assessed using the modified twitch interpolation technique, electrically stimulated contractile properties, electromyography (EMG), endurance time and recovery from fatigue were measured in the elbow flexors. The fatigue protocol involved both voluntary and stimulated contractions. Following supplementation there was a significant weight gain in the Cr group (1.0 kg), whereas the P group did not change. For each group, pre-supplementation measures were not significantly different from post-supplementation for MVC, twitch and tetanic tensions at rest, time to peak tension, half-relaxation time and contraction duration. Prior to Cr supplementation time to fatigue was 10 ± 4 min (mean ± S.E.M.) for both groups, and following supplementation there was a non-significant increase of 1 min in each group. MVC force, muscle activation, EMG, stimulated tensions and durations were similar for the Cr and P groups over the course of the fatigue protocol and did not change after supplementation. Furthermore, recovery of MVC, stimulated tensions and contractile speeds did not differ as a result of Cr supplementation. These results indicate that short-term Cr supplementation does not influence isometric elbow flexion force, muscle activation, stimulated contractile properties, or delay time to fatigue or improve recovery. [source] The distribution, metabolism and function of creatine in the male mammalian reproductive tract: a reviewINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 1 2000N. P. Moore Creatine is widely distributed throughout the male reproductive system in several mammalian species, and proteins involved in its metabolism and transport have been reported in a number of cell and tissue types. Creatine is synthesized within some organs, incorporating nitrogen from amino acid metabolism. Although creatine metabolism is obligatory for the motility of sea urchin spermatozoa, this does not appear to be the case for mammals. The possible functions of creatine within the reproductive tract are discussed. [source] Improving cellular function through modulation of energy metabolismINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 5 2004D. Maes The ambivalent consequences of mitochondrial stimulation on cellular activity have been well established. Mitochondria supply the cell with energy through a process of oxidative phosphorylation but thereby generate free radicals, resulting in the accumulation of hydrogen peroxide in the cytoplasm. We have investigated the impact of cellular senescence as well as UV irradiation, on the balance between these two activities. The adenosine triphosphate (ATP) level, DNA and protein synthesis in fibroblasts obtained from donors between 30 and 90 years of age appeared to be significantly influenced by the aging process. Both DNA and protein synthesis could be stimulated by increasing intracellular ATP levels. In-vitro senescent fibroblasts showed a reduction in the level of ATP as well as a shift in mitochondrial membrane potential. At the same time, there was an increase in intracellular hydrogen peroxide with increasing population doubling, indicating a clear dysfunction of the metabolic machinery in the mitochondria of senescent cells. To counteract this degradation of the energy pool, we treated cells with creatine, which is known to restore the pool of phosphocreatine in the mitochondria. Creatine treatment significantly increased cell survival after UV exposure, stimulated the repair of UVB-induced DNA damage in keratinocytes and caused a significant reduction in the number of sunburn cells in a UVB-exposed reconstituted skin model. These results clearly indicate that restoration of the energy pool in mitochondria increased cellular self-defense mechanism. These data show the important role played by the mitochondrial energy metabolism on the aging process, and indicate a possible therapy that can be used to counteract this negative effect. Treatment with creatine seems to provide the necessary boost to the cellular metabolism, which leads to an induction of a significant amount of protection and repair to human skin cells. [source] A child with spider bite and glomerulonephritis: a diagnostic challengeINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 4 2000Jennifer M. Lung MD A previously healthy 7-year-old white boy presented to St. Louis Children's Hospital with a 1-day history of headache, malaise, temperature of 38.7 °C, and a progressively erythematous, tender calf with central dusky purpura. On the morning of admission, his mother noticed a 2-mm crust on the patient's right calf with a 3-cm × 3-cm area of surrounding erythema. No history of recent trauma or bite was obtained. He had suffered two episodes of nonbloody, nonbilious emesis during the last day. In addition, over the previous 12 h, he presented brown urine without dysuria. His mother and brother had suffered from gastroenteritis over the previous week without bloody diarrhea. On initial physical examination, there was a 6-cm × 11-cm macular tender purpuric plaque with a central punctum on the right inner calf, which was warm and tender to the touch, with erythematous streaking towards the popliteal fossa ( Fig. 1). The inguinal area was also erythematous with tender lymphadenopathy and induration, but without fluctuance. Laboratory studies included an elevated white blood cell count of 20,800/,L with 6% bands, 86% segs, and 7% lymphocytes, hemoglobin of 12.5 g/dL, hematocrit of 35.1%, and platelets of 282,000/,L. The prothrombin time/activated partial tissue thromboplastin was 10.4/28.0 s (normal PT, 9.3,12.3 s; normal PTT, 21.3,33.7 s) and fibrinogen was 558 mg/dL (normal, 192,379 mg/dL). Urinalysis showed 1+ protein, 8,10 white blood cells, too numerous to count red blood cells, and no hemoglobinuria. His electrolytes, blood urea nitrogen (BUN), and creatine were normal. The urine culture was negative. Blood culture after 24 h showed one out of two bottles of coagulase negative Staphylococcus epidermidis. Figure 1. (A) 7-year-old boy with painful purpura of the calf The patient's physical examination was highly suggestive of a brown recluse spider bite with surrounding purpura. Over the next 2 days, the surrounding rim of erythema expanded. The skin within the plaque cleared and peeled at the periphery. The coagulase negative staphylococci in the blood culture were considered to be a contaminant. Cefotaxime and oxacillin were given intravenously. His leg was elevated and cooled with ice packs. The patient's fever resolved within 24 h. The lesion became less erythematous and nontender with decreased warmth and lymphadenopathy. The child was discharged on Duricef for 10 days. Because the patient experienced hematuria rather than hemoglobinuria, nephritis was suggested. In this case, poststreptococcal glomerulonephritis was the most likely cause. His anti-streptolysin-O titer was elevated at 400 U (normal, <200 U) and C3 was 21.4 mg/dL (normal, 83,177 mg/dL). His urine lightened to yellow,brown in color. His blood pressure was normal. Renal ultrasound showed severe left hydronephrosis with cortical atrophy, probably secondary to chronic/congenital ureteropelvic junction obstruction. His right kidney was normal. [source] Preparation and adsorption characteristic of polymeric microsphere with strong adsorbability for creatinineJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2008Baojiao Gao Abstract Cross-linking terpolymer microspheres (HEMA/NVP/MBA; it can also be designated as HEMA/NVP because HEMA and NVP are main components) with an average diameter of 180 µm, were prepared via inverse suspension copolymerization by using 2-hydroxyethyl methacrylate (HEMA) and N -vinylpyrrolidone (NVP) as monomers and N,N,-methylene bisacrylamide (MBA) as cross-linked agent. The microsphere HEMA/NVP was chemically modified with 3,5-dinitrobenzoyl chloride (DNBC), and the functional microsphere DNBZ-HEMA/NVP, on which a great number of 3,5-dinitrobenzoate group (DNBZ) were bound, was obtained. The functional microsphere DNBZ-HEMA/NVP were characterized with FTIR and the chemical analysis method. The adsorption characteristics and mechanism of the absorption of DNBZ-HEMA/NVP for creatine was mainly studied. The results of static adsorption experiments show that the functional microsphere DNBZ-HEMA/NVP has very strong adsorption ability for creatinine, and the saturated adsorption amount is 25 mg/g. The adsorption capacity of the functional microsphere DNBZ-HEMA/NVP for creatinine is enhanced 20 times as against unmodified microsphere HEMA/NVP. The adsorption capacity is smaller, at lower and higher pH, and has a maximum as pH 8.5. The higher the salinity of the medium, the smaller the adsorption capacity. The adsorption capacity decreases with increasing temperature. The study results show that the adsorption of the microsphere DNBZ-HEMA/NVP for creatinine is ascribed to a chemical adsorption by driving of electrostatic interaction. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:166,174, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20221 [source] Thermal and Storage Stability of Nutraceuticals in a Milk Beverage Dietary SupplementJOURNAL OF FOOD SCIENCE, Issue 3 2007M. Uzzan ABSTRACT:, Under the Dietary Supplement Health and Education Act (DSHEA), fluid skim milk can be used to serve as a vehicle to deliver certain metabolites (nutraceuticals or new dietary ingredients), which provide health benefits as related to aging problems for those over 55. This opens a new avenue for an increase in milk consumption and may replace taking pills. Milk beverages enriched with various nutraceutical ingredients (soy isoflavones, glucosamine, chondroitin sulfate, creatine, and lactoferrin) were thermally processed at different combinations of temperatures from 72 to 138 °C for different holding times using a Microthermics pilot plant thermal processing unit and were incubated at refrigeration, room, or elevated storage temperatures. Residual concentrations of the active compounds were measured by high performance liquid chromatography or by immunodifusion (for lactoferrin) and degradation kinetics were determined. Results showed a very good stability of isoflavones and chondroitin sulfate in the milk environment while glucosamine, lactoferrin, and creatin showed only limited stability at either processing or storage. Glucosamine destabilized the milk protein system at boiling temperature or higher, which caused drastic precipitation in the heat exchangers. Nevertheless, all the tested nutraceutical compounds can be used to design milk beverage dietary supplements but an overrun of over 25% may be required for some of them. [source] Quantitative multivoxel proton spectroscopy of the brain in developmental delayJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2009Krijn T. Verbruggen MD Abstract Purpose To assess whether proton MR spectroscopy of the brain in children with developmental delay reveals a consistent pattern of abnormalities. Materials and Methods Eighty-eight patients (median age, 4.6 years; interquartile range, 3.1,8.1 years) with unexplained developmental delay, were compared with 48 normally developing age-matched controls. Patients and controls were assigned to five age-groups. Multivoxel MR spectroscopy was performed on a volume of interest superior to the lateral ventricles. The relative levels of choline, creatine, N-acetyl aspartate, and glutamate/glutamine in 24 voxels containing white matter and 12 voxels containing gray matter were quantified in an operator-independent manner and expressed in proportion to the total metabolite peak area in the volume of interest. Results White matter choline in DD showed less decrease with age. Mean choline levels, compared with mean control levels, increased from 99 to 111% with increasing age. This was statistically significant in the highest age groups (P = 0.015 [7 < yr , 12.8] and P = 0.039 [12.8 < yr]). Other metabolites did not show clear alterations. Conclusion Proton MR spectroscopy in a group of patients with unexplained DD shows small differences in the metabolite pattern, compared with normally developing controls, that is, higher choline in the white matter. The pathophysiological origin and significance may relate to myelination and maturation of the white matter. J. Magn. Reson. Imaging 2009;30:716,721. © 2009 Wiley-Liss, Inc. [source] 1H spectroscopic imaging of human brain at 3 Tesla: Comparison of fast three-dimensional magnetic resonance spectroscopic imaging techniquesJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 3 2009Matthew L. Zierhut PhD Abstract Purpose To investigate the signal-to-noise-ratio (SNR) and data quality of time-reduced three-dimensional (3D) proton magnetic resonance spectroscopic imaging (1H MRSI) techniques in the human brain at 3 Tesla. Materials and Methods Techniques that were investigated included ellipsoidal k -space sampling, parallel imaging, and echo-planar spectroscopic imaging (EPSI). The SNR values for N-acetyl aspartate, choline, creatine, and lactate or lipid peaks were compared after correcting for effective spatial resolution and acquisition time in a phantom and in the brains of human volunteers. Other factors considered were linewidths, metabolite ratios, partial volume effects, and subcutaneous lipid contamination. Results In volunteers, the median normalized SNR for parallel imaging data decreased by 34,42%, but could be significantly improved using regularization. The normalized signal to noise loss in flyback EPSI data was 11,18%. The effective spatial resolutions of the traditional, ellipsoidal, sensitivity encoding (SENSE) sampling scheme, and EPSI data were 1.02, 2.43, 1.03, and 1.01 cm3, respectively. As expected, lipid contamination was variable between subjects but was highest for the SENSE data. Patient data obtained using the flyback EPSI method were of excellent quality. Conclusion Data from all 1H 3D-MRSI techniques were qualitatively acceptable, based upon SNR, linewidths, and metabolite ratios. The larger field of view obtained with the EPSI methods showed negligible lipid aliasing with acceptable SNR values in less than 9.5 min without compromising the point-spread function. J. Magn. Reson. Imaging 2009;30:473,480. © 2009 Wiley-Liss, Inc. [source] MRI of late microstructural and metabolic alterations in radiation-induced brain injuriesJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 5 2009Kevin C. Chan BEng Abstract Purpose To evaluate the late effects of radiation-induced damages in the rat brain by means of in vivo multiparametric MRI. Materials and Methods The right hemibrains of seven Sprague-Dawley rats were irradiated with a highly collimated 6 MV photon beam at a single dose of approximately 28 Gy. Diffusion tensor imaging (DTI), proton MR spectroscopy (1H-MRS), T2-weighted imaging, and T1-weighted imaging were performed to the same animals 12 months after radiation treatment. Results Compared with the contralateral side, a significantly higher percentage decrease in fractional anisotropy was observed in the ipsilateral fimbria of hippocampus (29%) than the external capsule (8%) in DTI, indicating the selective vulnerability of fimbria to radiation treatment. Furthermore, in 1H-MRS, significantly higher choline, glutamate, lactate, and taurine peaks by 24%, 25%, 87%, and 58%, respectively, were observed relative to creatine in the ipsilateral brain. Postmortem histology confirmed these white matter degradations as well as glial fibrillary acidic protein and glutamine synthetase immunoreactivity increase in the ipsilateral brain. Conclusion The microstructural and metabolic changes in late radiation-induced brain injuries were documented in vivo. These multiparametric MRI measurements may help understand the white matter changes and neurotoxicity upon radiation treatment in a single setting. J. Magn. Reson. Imaging 2009;29:1013,1020. © 2009 Wiley-Liss, Inc. [source] Proton MR spectroscopic imaging of the medulla and cervical spinal cord,JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2007Richard A.E. Edden PhD Abstract Purpose To demonstrate the feasibility of quantitative, one-dimensional proton MR spectroscopic imaging (1D-MRSI) of the upper cervical spine and medulla at 3.0 Tesla. Materials and Methods A method was developed for 1D-point-resolved spectroscopy sequence (PRESS)-MRSI, exciting signal in five voxels extending from the pontomedullary junction to the level of the C3 vertebra, and performed in 10 healthy volunteers to generate control data. Results High-resolution 1D-MRSI data were obtained from all 10 subjects. Upper cervical spine concentrations of choline, creatine, and N-acetyl aspartate were estimated to be 2.8 ± 0.5, 8.8 ± 1.8, and 10.9 ± 2.7 mM, respectively, while in the medulla they were 2.6 ± 0.5, 9.1 ± 1.7, and 10.8 ± 0.9 mM. Conclusion Quantitative 1D-MRSI of the upper cervical spine has been shown to be feasible at 3.0 Tesla. J. Magn. Reson. Imaging 2007;26:1101,1105. © 2007 Wiley-Liss, Inc. [source] Proton spectroscopic metabolite signal relaxation times in preterm infants: A prerequisite for quantitative spectroscopy in infant brainJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2003Harald Kugel PhD Abstract Purpose To determine relaxation times of metabolite signals in proton magnetic resonance (MR) spectra of immature brain, which allow a correction of relaxation that is necessary for a quantitative evaluation of spectra acquired with long TE. Proton MR spectra acquired with long TE allow a better definition of metabolites as N-acetyl aspartate (NAA) and lactate especially in children. Materials and Methods Relaxation times were determined in the basal ganglia of 84 prematurely born infants at a postconceptional age of 37.8 ± 2.2 (mean ± SD) weeks. Metabolite resonances were investigated using the double-spin-echo volume selection method (PRESS) at 1.5 T. T1 was determined from intensity ratios of signals obtained with TRs of 1884 and 6000 msec, measured at 3 TEs (25 msec, 136 msec, 272 msec). T2 was determined from signal intensity ratios obtained with TEs of 136 msec and 272 msec, measured at 2 TR. Taking only long TEs reduced baseline distortions by macromolecules and lipids. For myo-inositol (MI), an apparent T2 for short TE was determined from the ratio of signals obtained with TE = 25 msec and 136 msec. Intensities were determined by fitting a Lorentzian to the resonance, and by integration. Results Relaxation times were as follows: trimethylamine-containing compounds (Cho): T1 = 1217 msec/T2 = 273 msec; total creatine (Cr) at 3.9 ppm: 1010 msec/111 msec; Cr at 3.0 ppm: 1388 msec/224 msec; NAA: 1171 msec/499 msec; Lac: 1820 msec/1022 msec; MI: 1336 msec/173 msec; apparent T2 at short TE: 68 msec. Conclusion T1 and T2 in the basal ganglia of premature infants do not differ much from previously published data from basal ganglia of older children and adults. T2 of Cho was lower than previous values. T2 of Cr at 3.9 ppm and Lac have been measured under different conditions before, and present values differ from these data. J. Magn. Reson. Imaging 2003;17:634,640. © 2003 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||