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Sample records for brain metabolite markers

  1. Distribution of tamoxifen and metabolites into brain tissue and brain metastases in breast cancer patients.

    OpenAIRE

    Lien, E A; Wester, K.; Lønning, P. E.; Solheim, E; Ueland, P. M.

    1991-01-01

    We determined the amount of tamoxifen, N-desmethyltamoxifen (metabolite X), N-desdimethyltamoxifen (metabolite Z), and hydroxylated metabolites (Y, B, BX) in brain metastases from breast cancer and in the surrounding brain tissues. Specimens were collected from the breast cancer patients who received tamoxifen for 7-180 days and with the last dose taken within 28 h before surgical removal of the tumour. The concentrations of tamoxifen and its metabolites were up to 46-fold higher in the brain...

  2. Markers for blood-brain barrier integrity

    DEFF Research Database (Denmark)

    Saunders, Norman R; Dziegielewska, Katarzyna M; Møllgård, Kjeld;

    2015-01-01

    In recent years there has been a resurgence of interest in brain barriers and various roles their intrinsic mechanisms may play in neurological disorders. Such studies require suitable models and markers to demonstrate integrity and functional changes at the interfaces between blood, brain, and...... cerebrospinal fluid. Studies of brain barrier mechanisms and measurements of plasma volume using dyes have a long-standing history, dating back to the late nineteenth-century. Their use in blood-brain barrier studies continues in spite of their known serious limitations in in vivo applications. These were well...... known when first introduced, but seem to have been forgotten since. Understanding these limitations is important because Evans blue is still the most commonly used marker of brain barrier integrity and those using it seem oblivious to problems arising from its in vivo application. The introduction of...

  3. Clincal Aspects of Biological Brain Damage Markers

    OpenAIRE

    Undén, Johan

    2006-01-01

    Biomarkers for organ damage and/or dysfuntion are used in almost all areas of medicine. The brain has eluded this technological development for some time. Recently, the S100B protein has been shown to be a promising marker of brain damage. However, before S100S can reach clinical reality, several problems must be solved. The specificity of S100B requires special investigative attention. Although the sensitivity has seldom been criticised in the literature and assumed to be very high for S100B...

  4. Embedding filtering criteria into a wrapper marker selection method for brain tumor classification: an application on metabolic peak area ratios

    International Nuclear Information System (INIS)

    The purpose of this study is to identify reliable sets of metabolic markers that provide accurate classification of complex brain tumors and facilitate the process of clinical diagnosis. Several ratios of metabolites are tested alone or in combination with imaging markers. A wrapper feature selection and classification methodology is studied, employing Fisher's criterion for ranking the markers. The set of extracted markers that express statistical significance is further studied in terms of biological behavior with respect to the brain tumor type and grade. The outcome of this study indicates that the proposed method by exploiting the intrinsic properties of data can actually reveal reliable and biologically relevant sets of metabolic markers, which form an important adjunct toward a more accurate type and grade discrimination of complex brain tumors

  5. Tryptophan, kynurenine, and kynurenine metabolites: Relationship to lifetime aggression and inflammatory markers in human subjects.

    Science.gov (United States)

    Coccaro, Emil F; Lee, Royce; Fanning, Jennifer R; Fuchs, Dietmar; Goiny, Michel; Erhardt, Sophie; Christensen, Kyle; Brundin, Lena; Coussons-Read, Mary

    2016-09-01

    Inflammatory proteins are thought to be causally involved in the generation of aggression, possibly due to direct effects of cytokines in the central nervous system and/or by generation of inflammatory metabolites along the tryptophan-kynurenine (TRP/KYN) pathway, including KYN and its active metabolites kynurenic acid (KA), quinolinic acid (QA), and picolinic acid (PA). We examined plasma levels of TRP, KYN, KA, QA, and PA in 172 medication-free, medically healthy, human subjects to determine if plasma levels of these substances are altered as a function of trait aggression, and if they correlate with current plasma levels of inflammatory markers. Plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble interleukin-1 receptor-II (sIL-1RII) protein were also available in these subjects. We found normal levels of TRP but reduced plasma levels of KYN (by 48%), QA (by 6%), and a QA/KA (by 5%) ratio in subjects with Intermittent Explosive Disorder (IED) compared to healthy controls and psychiatric controls. Moreover, the metabolites were not associated with any of the inflammatory markers studied. These data do not support the hypothesis that elevated levels of KYN metabolites would be present in plasma of subjects with IED, and associated with plasma inflammation. However, our data do point to a dysregulation of the KYN pathway metabolites in these subjects. Further work will be necessary to replicate these findings and to understand their role in inflammation and aggression in these subjects. PMID:27318828

  6. Role of nitric oxide and its metabolites as potential markers in lung cancer

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    Masri Fares

    2010-01-01

    Full Text Available Nitric oxide (NO and reactive oxygen species (ROS play important physiologic roles as mediators of signaling processes. However, high concentrations of NO and ROS result in damage to cellular and extracellular components. Excessive production of endogenous and/or exogenous ROS and NO is implicated in the pathogenesis of lung cancer. NO and its metabolites interact with ROS to generate potent nitrating agents leading to protein nitration, which is one of the several chemical modifications that occur during oxidative/nitrosative stress. Although there is considerable evidence in support of a role for NO in protein modifications and carcinogenesis, recent data suggest that NO has antagonistic cellular effects, leading to either promotion or inhibition of tumor growth. However, the role of NO in tumor biology is still poorly understood. This review demonstrates the role of NO and its metabolites as potential markers in lung cancer.

  7. In Vivo Detection of Perinatal Brain Metabolite Changes in a Rabbit Model of Intrauterine Growth Restriction (IUGR.

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    Rui V Simões

    Full Text Available Intrauterine growth restriction (IUGR is a risk factor for abnormal neurodevelopment. We studied a rabbit model of IUGR by magnetic resonance imaging (MRI and spectroscopy (MRS, to assess in vivo brain structural and metabolic consequences, and identify potential metabolic biomarkers for clinical translation.IUGR was induced in 3 pregnant rabbits at gestational day 25, by 40-50% uteroplacental vessel ligation in one horn; the contralateral horn was used as control. Fetuses were delivered at day 30 and weighted. A total of 6 controls and 5 IUGR pups underwent T2-w MRI and localized proton MRS within the first 8 hours of life, at 7T. Changes in brain tissue volumes and respective contributions to each MRS voxel were estimated by semi-automated registration of MRI images with a digital atlas of the rabbit brain. MRS data were used for: (i absolute metabolite quantifications, using linear fitting; (ii local temperature estimations, based on the water chemical shift; and (iii classification, using spectral pattern analysis.Lower birth weight was associated with (i smaller brain sizes, (ii slightly lower brain temperatures, and (iii differential metabolite profile changes in specific regions of the brain parenchyma. Specifically, we found estimated lower levels of aspartate and N-acetylaspartate (NAA in the cerebral cortex and hippocampus (suggesting neuronal impairment, and higher glycine levels in the striatum (possible marker of brain injury. Our results also suggest that the metabolic changes in cortical regions are more prevalent than those detected in hippocampus and striatum.IUGR was associated with brain metabolic changes in vivo, which correlate well with the neurostructural changes and neurodevelopment problems described in IUGR. Metabolic parameters could constitute non invasive biomarkers for the diagnosis and abnormal neurodevelopment of perinatal origin.

  8. Circadian Rhythms of Oxidative Stress Markers and Melatonin Metabolite in Patients with Xeroderma Pigmentosum Group A

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    Rie Miyata

    2016-01-01

    Full Text Available Xeroderma pigmentosum group A (XPA is a genetic disorder in DNA nucleotide excision repair (NER with severe neurological disorders, in which oxidative stress and disturbed melatonin metabolism may be involved. Herein we confirmed the diurnal variation of melatonin metabolites, oxidative stress markers, and antioxidant power in urine of patients with XPA and age-matched controls, using enzyme-linked immunosorbent assay (ELISA. The peak of 6-sulfatoxymelatonin, a metabolite of melatonin, was seen at 6:00 in both the XPA patients and controls, though the peak value is lower, specifically in the younger age group of XPA patients. The older XPA patients demonstrated an increase in the urinary levels of 8-hydroxy-2′-deoxyguanosine and hexanoyl-lysine, a marker of oxidative DNA damage and lipid peroxidation, having a robust peak at 6:00 and 18:00, respectively. In addition, the urinary level of total antioxidant power was decreased in the older XPA patients. Recently, it is speculated that oxidative stress and antioxidant properties may have a diurnal variation, and the circadian rhythm is likely to influence the NER itself. We believe that the administration of melatonin has the possibility of ameliorating the augmented oxidative stress in neurodegeneration, especially in the older XPA patients, modulating the melatonin metabolism and the circadian rhythm.

  9. Circadian Rhythms of Oxidative Stress Markers and Melatonin Metabolite in Patients with Xeroderma Pigmentosum Group A.

    Science.gov (United States)

    Miyata, Rie; Tanuma, Naoyuki; Sakuma, Hiroshi; Hayashi, Masaharu

    2016-01-01

    Xeroderma pigmentosum group A (XPA) is a genetic disorder in DNA nucleotide excision repair (NER) with severe neurological disorders, in which oxidative stress and disturbed melatonin metabolism may be involved. Herein we confirmed the diurnal variation of melatonin metabolites, oxidative stress markers, and antioxidant power in urine of patients with XPA and age-matched controls, using enzyme-linked immunosorbent assay (ELISA). The peak of 6-sulfatoxymelatonin, a metabolite of melatonin, was seen at 6:00 in both the XPA patients and controls, though the peak value is lower, specifically in the younger age group of XPA patients. The older XPA patients demonstrated an increase in the urinary levels of 8-hydroxy-2'-deoxyguanosine and hexanoyl-lysine, a marker of oxidative DNA damage and lipid peroxidation, having a robust peak at 6:00 and 18:00, respectively. In addition, the urinary level of total antioxidant power was decreased in the older XPA patients. Recently, it is speculated that oxidative stress and antioxidant properties may have a diurnal variation, and the circadian rhythm is likely to influence the NER itself. We believe that the administration of melatonin has the possibility of ameliorating the augmented oxidative stress in neurodegeneration, especially in the older XPA patients, modulating the melatonin metabolism and the circadian rhythm. PMID:27213030

  10. Proton spectroscopic imaging of brain metabolites in basal ganglia of healthy older adults

    OpenAIRE

    Parikh, Jehill; Thrippleton, Michael J.; Murray, Catherine; Armitage, Paul A.; Harris, Bridget A.; Andrews, Peter J D; Wardlaw, Joanna M.; Starr, John M.; Deary, Ian J.; Marshall, Ian

    2014-01-01

    Object We sought to measure brain metabolite levels in healthy older people. Materials and methods Spectroscopic imaging at the level of the basal ganglia was applied in 40 participants aged 73–74 years. Levels of the metabolites N-acetyl aspartate (NAA), choline, and creatine were determined in "institutional units" (IU) corrected for T1 and T2 relaxation effects. Structural imaging enabled determination of grey matter (GM), white matter (WM), and cerebrospinal fluid content. ANOVA analysis ...

  11. Pharmacokinetic modeling of subcutaneous heroin and its metabolites in blood and brain of mice.

    Science.gov (United States)

    Boix, Fernando; Andersen, Jannike M; Mørland, Jørg

    2013-01-01

    High blood-brain permeability and effective delivery of morphine to the brain have been considered as explanations for the high potency of heroin. Results from Andersen et al. indicate that 6-monoacetylmorphine (6-MAM), and not morphine, is the active metabolite responsible for the acute effects observed for heroin. Here, we use pharmacokinetic modeling on data from the aforementioned study to calculate parameters of the distribution of heroin, 6-MAM and morphine in blood and brain tissue after subcutaneous heroin administration in mice. The estimated pharmacokinetic parameters imply that the very low heroin and the high 6-MAM levels observed both in blood and brain in the original experiment are likely to be caused by a very high metabolic rate of heroin in blood. The estimated metabolic rate of heroin in brain was much lower and cannot account for the low heroin and high 6-MAM levels in the brain, which would primarily reflect the concentrations of these compounds in blood. The very different metabolic rates for heroin in blood and brain calculated by the model were confirmed by in vitro experiments. These results show that heroin's fast metabolism in blood renders high concentrations of 6-MAM which, due to its relatively good blood-brain permeability, results in high levels of this metabolite in the brain. Thus, it is the high blood metabolism rate of heroin and the blood-brain permeability to 6-MAM, and not to heroin, which could account for the highly efficient delivery of active metabolites to the brain after heroin administration. PMID:21481103

  12. Depression of brain dopamine and its metabolite after mating in European honeybee (Apis mellifera) queens

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    Harano, Ken-Ichi; Sasaki, Ken; Nagao, Takashi

    2005-07-01

    To explore neuro-endocrinal changes in the brain of European honeybee (Apis mellifera) queens before and after mating, we measured the amount of several biogenic amines, including dopamine and its metabolite in the brain of 6- and 12-day-old virgins and 12-day-old mated queens. Twelve-day-old mated queens showed significantly lower amounts of dopamine and its metabolite (N-acetyldopamine) than both 6- and 12-day-old virgin queens, whereas significant differences in the amounts of these amines were not detected between 6- and 12-day-old virgin queens. These results are explained by down-regulation of both synthesis and secretion of brain dopamine after mating. It is speculated that higher amounts of brain dopamine in virgin queens might be involved in activation of ovarian follicles arrested in previtellogenic stages, as well as regulation of their characteristic behaviors.

  13. The role of markers of inflammation in traumatic brain injury

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    Thomas eWoodcock

    2013-03-01

    Full Text Available Within minutes of a traumatic impact, a robust inflammatory response is elicited in the injured brain. The complexity of this post-traumatic squeal involves a cellular component, comprising the activation of resident glial cells, microglia and astrocytes, and the infiltration of blood leukocytes. The second component regards the secretion immune mediators, which can be divided into the following sub-groups: the archetypal pro-inflammatory cytokines (IL-1, TNF, IL-6, the anti-inflammatory cytokines (IL-4, IL-10 and TGF-beta and the chemotactic cytokines or chemokines, which specifically drive the accumulation of parenchymal and peripheral immune cells in the injured brain region. Such mechanisms have been demonstrated in animal models, mostly in rodents, as well as in human brain. Whilst the humoral immune response is particularly pronounced in the acute phase following TBI, the activation of glial cells seems to be a rather prolonged effect lasting for several months. The complex interaction of cytokines and cell types installs a network of events, which subsequently intersect with adjacent pathological cascades including oxidative stress, excitotoxicity, or reparative events including angiogenesis, scarring and neurogenesis. It is well accepted that neuroinflammation is responsible of beneficial and detrimental effects, contributing to secondary brain damage but also facilitating neurorepair.Although such mediators are clear markers of immune activation, to what extent cytokines can be defined as diagnostic factors reflecting brain injury or as predictors of long term outcome needs to be further substantiated. In clinical studies some groups reported a proportional cytokine production in either the cerebrospinal fluid or intraparenchymal tissue with initial brain damage, mortality or poor outcome scores. However, the validity of cytokines as biomarkers is not broadly accepted. This review article will discuss the evidence from both clinical and

  14. Quantification of brain metabolites in amyotrophic lateral sclerosis by localized proton magnetic resonance spectroscopy

    DEFF Research Database (Denmark)

    Gredal, O; Rosenbaum, S; Topp, S;

    1997-01-01

    We performed proton magnetic resonance spectroscopy (1H-MRS) in patients with motor neuron disease (MND) to determine the absolute in vivo concentrations in the brain of the metabolites N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr/PCr). We examined the spectra acquired from a 20 x 20 x...

  15. Multiple Brain Markers are Linked to Age-Related Variation in Cognition.

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    Hedden, Trey; Schultz, Aaron P; Rieckmann, Anna; Mormino, Elizabeth C; Johnson, Keith A; Sperling, Reisa A; Buckner, Randy L

    2016-04-01

    Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65-90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70-80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health. PMID:25316342

  16. A 'complex' of brain metabolites distinguish altered chemistry in the cingulate cortex of episodic migraine patients.

    Science.gov (United States)

    Becerra, L; Veggeberg, R; Prescot, A; Jensen, J E; Renshaw, P; Scrivani, S; Spierings, E L H; Burstein, R; Borsook, D

    2016-01-01

    Despite the prevalence of migraine, the pathophysiology of the disease remains unclear. Current understanding of migraine has alluded to the possibility of a hyperexcitable brain. The aim of the current study is to investigate human brain metabolite differences in the anterior cingulate cortex (ACC) during the interictal phase in migraine patients. We hypothesized that there may be differences in levels of excitatory neurotransmitters and/or their derivatives in the migraine cohort in support of the theory of hyperexcitability in migraine. 2D J-resolved proton magnetic resonance spectroscopy ((1)H-MRS) data were acquired on a 3 Tesla (3 T) MRI from a voxel placed over the ACC of 32 migraine patients (MP; 23 females, 9 males, age 33 ± 9.6 years) and 33 healthy controls (HC; 25 females, 8 males, age 32 ± 9.6 years). Amplitude correlation matrices were constructed for each subject to evaluate metabolite discriminability. ProFit-estimated metabolite peak areas were normalized to a water reference signal to assess subject differences. The initial analysis of variance (ANOVA) was performed to test for group differences for all metabolites/creatine (Cre) ratios between healthy controls and migraineurs but showed no statistically significant differences. In addition, we used a multivariate approach to distinguish migraineurs from healthy subjects based on the metabolite/Cre ratio. A quadratic discriminant analysis (QDA) model was used to identify 3 metabolite ratios sufficient to minimize minimum classification error (MCE). The 3 selected metabolite ratios were aspartate (Asp)/Cre, N-acetyl aspartate (NAA)/Cre, and glutamine (Gln)/Cre. These findings are in support of a 'complex' of metabolite alterations, which may underlie changes in neuronal chemistry in the migraine brain. Furthermore, the parallel changes in the three-metabolite 'complex' may confer more subtle but biological processes that are ongoing. The data also support the current theory that the

  17. Ex-vivo HRMAS of adult brain tumours: metabolite quantification and assignment of tumour biomarkers

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    Wilson M

    2010-03-01

    Full Text Available Abstract Background High-resolution magic angle spinning (HRMAS NMR spectroscopy allows detailed metabolic analysis of whole biopsy samples for investigating tumour biology and tumour classification. Accurate biochemical assignment of small molecule metabolites that are "NMR visible" will improve our interpretation of HRMAS data and the translation of NMR tumour biomarkers to in-vivo studies. Results 1D and 2D 1H HRMAS NMR was used to determine that 29 small molecule metabolites, along with 8 macromolecule signals, account for the majority of the HRMAS spectrum of the main types of brain tumour (astrocytoma grade II, grade III gliomas, glioblastomas, metastases, meningiomas and also lymphomas. Differences in concentration of 20 of these metabolites were statistically significant between these brain tumour types. During the course of an extended 2D data acquisition the HRMAS technique itself affects sample analysis: glycine, glutathione and glycerophosphocholine all showed small concentration changes; analysis of the sample after HRMAS indicated structural damage that may affect subsequent histopathological analysis. Conclusions A number of small molecule metabolites have been identified as potential biomarkers of tumour type that may enable development of more selective in-vivo 1H NMR acquisition methods for diagnosis and prognosis of brain tumours.

  18. In vivo quantitation of metabolite concentrations in the brain by means of proton MRS

    DEFF Research Database (Denmark)

    Henriksen, O

    1995-01-01

    MRS offers unique possibilities for non-invasive studies of biochemistry in the human brain in vivo. A growing body of evidence suggests that proton MRS may contribute to the clinical evaluation of a number of pathologies including ischaemia, tumours, epilepsy, metabolic and neuropaediatric...... both, or may simply be due to changes in relaxation behaviour. Absolute quantitation of metabolite concentrations is therefore warranted. A number of studies using single volume proton MRS indicate that absolute quantitation of metabolite concentration is possible with respect to N-acetyl aspartate...... results are promising and encourage further exploitation of the utility of quantitative proton MRS in clinical practise....

  19. Faster metabolite (1H transverse relaxation in the elder human brain.

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    Małgorzata Marjańska

    Full Text Available (1H magnetic resonance spectroscopy (MRS is unique among imaging modalities because signals from several metabolites are measured during a single examination period. Each metabolite reflects a distinct intracellular process. Furthermore transverse (T2 relaxation times probe the viability of the cell microenvironment, e.g., the viscosity of the cellular fluids, the microscopic susceptibility distribution within the cells, and the iron content. In this study, T2s of brain metabolites were measured in the occipital lobe of eighteen young and fourteen elderly subjects at a field strength of 4 tesla. The T2s of N-acetylaspartate, total creatine, and total choline were 23%, 16% and 10% shorter in elderly than in young subjects. The findings of this study suggest that noninvasive detection of T2 provides useful biological information on changes in the cellular microenvironment that take place during aging.

  20. Exploration of oxidative stress and inflammatory markers in relation to urinary phthalate metabolites: NHANES 1999–2006

    OpenAIRE

    Ferguson, Kelly K.; Loch-Caruso, Rita; John D. Meeker

    2011-01-01

    Phthalate exposure has been associated with a wide range of adverse health outcomes in limited epidemiologic studies, and inflammation and oxidative stress have been hypothesized as potential mechanisms involved. In the present study we investigated associations between urinary concentrations of phthalate metabolites and potential blood markers of oxidative stress (bilirubin) and inflammation (alkaline phosphatase [ALP], absolute neutrophil count [ANC], ferritin [adjusted for iron status] and...

  1. Regional Metabolite T2 in the Healthy Rhesus Macaque Brain at 7T

    OpenAIRE

    Liu, Songtao; Gonen, Oded; Fleysher, Lazar; Fleysher, Roman; Soher, Brian J.; Pilkenton, Sarah; Lentz, Margaret R.; Ratai, Eva-Maria; González, R. Gilberto

    2008-01-01

    Although the rhesus macaque brain is an excellent model system for the study of neurological diseases and their responses to treatment, its small size requires much higher spatial resolution, motivating use of ultra-high-field (B0) imagers. Their weaker radio-frequency fields, however, dictate longer pulses; hence longer TE localization sequences. Due to the shorter transverse relaxation time (T2) at higher B0s, these longer TEs subject metabolites to T2-weighting, that decrease their quantif...

  2. Excretion of metabolites of biogenic amines in patients with irradiated brain tumours

    International Nuclear Information System (INIS)

    The metabolites of biogenic amines were determined in the 24-hour urine samples of patients submitted to surgical removal of a malignant brain tumour and subsequently to telecobalt therapy of the corresponding head region. A significant increase in the excretion of 5-hydroxyindoleasetic acid (5-HIAA), vanillinmandelic acid (VMA) as well as of free 3-methoxy-4-hydroxy-phenylglycol (MHPG) during the period of irradiation was found. This increase is presumably the result of radiation induced release of their parent amines from the brain; in the case of VMA the secondary response of the peripheral sympathetic system might occur. (author)

  3. MR spectroscopy-based brain metabolite profiling in propionic acidaemia: metabolic changes in the basal ganglia during acute decompensation and effect of liver transplantation

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    McKiernan Patrick J

    2011-05-01

    Full Text Available Abstract Background Propionic acidaemia (PA results from deficiency of Propionyl CoA carboxylase, the commonest form presenting in the neonatal period. Despite best current management, PA is associated with severe neurological sequelae, in particular movement disorders resulting from basal ganglia infarction, although the pathogenesis remains poorly understood. The role of liver transplantation remains controversial but may confer some neuro-protection. The present study utilises quantitative magnetic resonance spectroscopy (MRS to investigate brain metabolite alterations in propionic acidaemia during metabolic stability and acute encephalopathic episodes. Methods Quantitative MRS was used to evaluate brain metabolites in eight children with neonatal onset propionic acidaemia, with six elective studies acquired during metabolic stability and five studies during acute encephalopathic episodes. MRS studies were acquired concurrently with clinically indicated MR imaging studies at 1.5 Tesla. LCModel software was used to provide metabolite quantification. Comparison was made with a dataset of MRS metabolite concentrations from a cohort of children with normal appearing MR imaging. Results MRI findings confirm the vulnerability of basal ganglia to infarction during acute encephalopathy. We identified statistically significant decreases in basal ganglia glutamate+glutamine and N-Acetylaspartate, and increase in lactate, during encephalopathic episodes. In white matter lactate was significantly elevated but other metabolites not significantly altered. Metabolite data from two children who had received liver transplantation were not significantly different from the comparator group. Conclusions The metabolite alterations seen in propionic acidaemia in the basal ganglia during acute encephalopathy reflect loss of viable neurons, and a switch to anaerobic respiration. The decrease in glutamine + glutamate supports the hypothesis that they are consumed to

  4. Quantitation of normal metabolite concentrations in six brain regions by in-vivoH-MR spectroscopy.

    Science.gov (United States)

    Minati, Ludovico; Aquino, Domenico; Bruzzone, Maria Grazia; Erbetta, Alessandra

    2010-07-01

    This study examined the concentrations of brain metabolites visible to in-vivo(1)H-Magnetic Resonance Spectroscopy ((1)H-MRS) at 1.5 T in a sample of 28 normal subjects. Quantitation was attempted for inositol compounds, choline units, total creatine and N-acetyl moieties, using open-source software. Six brain regions were considered: frontal and parietal white matter, medial temporal lobe, thalamus, pons and cerebellum. Absolute concentrations were derived using tissue water as an internal reference and using an external reference; metabolite signal intensity ratios with respect to creatine were also calculated. The inter-individual variability was smaller for absolute concentrations (internal reference) as compared to that for signal intensity ratios. Significant regional variability in concentration was found for all metabolites, indicating that separate normative values are needed for different brain regions. The values obtained in this study can be used as reference in future studies, provided the same methodology is followed; it is confirmed that despite unsuccessful attempts in the past, smaller coefficients of variation can indeed be obtained through absolute quantification. PMID:20927223

  5. Metabolite profiling identifies candidate markers reflecting the clinical adaptations associated with Roux-en-Y gastric bypass surgery.

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    David M Mutch

    Full Text Available BACKGROUND: Roux-en-Y gastric bypass (RYGB surgery is associated with weight loss, improved insulin sensitivity and glucose homeostasis, and a reduction in co-morbidities such as diabetes and coronary heart disease. To generate further insight into the numerous metabolic adaptations associated with RYGB surgery, we profiled serum metabolites before and after gastric bypass surgery and integrated metabolite changes with clinical data. METHODOLOGY AND PRINCIPAL FINDINGS: Serum metabolites were detected by gas and liquid chromatography-coupled mass spectrometry before, and 3 and 6 months after RYGB in morbidly obese female subjects (n = 14; BMI = 46.2+/-1.7. Subjects showed decreases in weight-related parameters and improvements in insulin sensitivity post surgery. The abundance of 48% (83 of 172 of the measured metabolites changed significantly within the first 3 months post RYGB (p<0.05, including sphingosines, unsaturated fatty acids, and branched chain amino acids. Dividing subjects into obese (n = 9 and obese/diabetic (n = 5 groups identified 8 metabolites that differed consistently at all time points and whose serum levels changed following RYGB: asparagine, lysophosphatidylcholine (C18:2, nervonic (C24:1 acid, p-Cresol sulfate, lactate, lycopene, glucose, and mannose. Changes in the aforementioned metabolites were integrated with clinical data for body mass index (BMI and estimates for insulin resistance (HOMA-IR. Of these, nervonic acid was significantly and negatively correlated with HOMA-IR (p = 0.001, R = -0.55. CONCLUSIONS: Global metabolite profiling in morbidly obese subjects after RYGB has provided new information regarding the considerable metabolic alterations associated with this surgical procedure. Integrating clinical measurements with metabolomics data is capable of identifying markers that reflect the metabolic adaptations following RYGB.

  6. Quantitative analysis of brain metabolites in patients,with non-dementia vascular cognitive impairment and mild cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    刘艳艳

    2013-01-01

    Objective To investigate metabolite changes in the brain of patients with non-dementia vascular cognitive impairment(VCIND) and mild cognitive impairment(MCI) using magnetic resonance spectroscopy(MRS)

  7. Evaluation of brain metabolite in patients with complex regional pain syndrome by MR spectroscopy

    International Nuclear Information System (INIS)

    Recently brain imaging studies have shown that patients with chronic pain have an altered cortical processing of nociceptive inputs. We evaluated brain metabolites in patients with complex regional pain syndrome (CRPS) using MR spectroscopy. Absolute concentrations of N-acetylaspartate (NAA) and choline (Cho) were measured in anterior cingulate (ACC) and prefrontal cortices (PFC) of patients and volunteers as matched control. Psychological aspects of patients were also evaluated with Hospital Anxiety and Depression (HAD) scale, in addition to the intensity of pain by visual analog scale. In the ACC, CRPS patients had a significant decrease of NAA and a significant increase of Cho compared to the control. Furthermore, patients with anxiety scored by HAD scale had reduced NAA concentration in ACC compared to the patients without anxiety. In the PFC, there was a reduction of NAA in the patients compared with that in control. No correlation was observed between intensity of pain and these metabolites. These results suggest that metabolite changes in ACC and PFC could reflect the pathogenesis of CRPS. (author)

  8. The transport of L-6-fluorodopa and its metabolites from blood to cerebrospinal fluid and brain.

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    Hammerstad, J P; Pate, B D; Hewitt, K A; Chan, G L; Ruth, T J; Calne, D B

    1993-10-01

    The transport of L-6-fluorodopa and its major metabolites from the blood to the brain, cerebrospinal fluid (CSF), and muscle was studied in carbidopa-pretreated cynomolgus monkeys. A bolus intravenous injection of 18F-L-6-fluorodopa was followed by serial positron emission tomography scans and sampling of cisternal CSF and arterial blood. The relative concentrations of L-6-fluorodopa and its metabolites were determined in blood plasma and CSF by high-performance liquid chromatography. Raising the blood concentration of phenylalanine by intraperitoneal injection markedly reduced the accumulation of tracer in the brain. This indicates that L-6-fluorodopa and 3-O-methylfluorodopa, like native L-dopa and its O-methylated derivative, are transported at the brain capillary by the large neutral amino acid carrier-mediated system, which is subject to saturation and competition by other large neutral amino acids (such as phenylalanine) at physiological plasma concentrations. In contrast, administration of phenylalanine had no effect on the accumulation of tracer either in muscle, or as L-6-fluorodopa and 3-O-methylfluorodopa, in CSF. This suggests that the transport of L-dopa and its derivatives at the blood-CSF barrier differs from the transport at the blood-brain barrier and also that measurement of CSF L-dopa is not a good index of the transport and pharmacokinetics of L-dopa in the brain. However, the effect of phenylalanine administration in reducing the concentration of fluorohomovanillic acid in the CSF suggests that the concentration of homovanillic acid in the CSF is an accurate reflection of dopamine turnover in the brain. PMID:8215248

  9. Effects of Various Kynurenine Metabolites on Respiratory Parameters of Rat Brain, Liver and Heart Mitochondria

    Science.gov (United States)

    Baran, Halina; Staniek, Katrin; Bertignol-Spörr, Melanie; Attam, Martin; Kronsteiner, Carina; Kepplinger, Berthold

    2016-01-01

    Previously, we demonstrated that the endogenous glutamate receptor antagonist kynurenic acid dose-dependently and significantly affected rat heart mitochondria. Now we have investigated the effects of L-tryptophan, L-kynurenine, 3-hydroxykynurenine and kynurenic, anthranilic, 3-hydroxyanthranilic, xanthurenic and quinolinic acids on respiratory parameters (ie, state 2, state 3), respiratory control index (RC) and ADP/oxygen ratio in brain, liver and heart mitochondria of adult rats. Mitochondria were incubated with glutamate/malate (5 mM) or succinate (10 mM) and in the presence of L-tryptophan metabolites (1 mM) or in the absence, as control. Kynurenic and anthranilic acids significantly reduced RC values of heart mitochondria in the presence of glutamate/malate. Xanthurenic acid significantly reduced RC values of brain mitochondria in the presence of glutamate/malate. Furthermore, 3-hydroxykynurenine and 3-hydroxyanthranilic acid decreased RC values of brain, liver and heart mitochondria using glutamate/malate. In the presence of succinate, 3-hydroxykynurenine and 3-hydroxyanthranilic acid affected RC values of brain mitochondria, whereas in liver and heart mitochondria only 3-hydroxykynurenine lowered RC values significantly. Furthermore, lowered ADP/oxygen ratios were observed in brain mitochondria in the presence of succinate with 3-hydroxykynurenine and 3-hydroxyanthranilic acid, and to a lesser extent with glutamate/malate. In addition, 3-hydroxyanthranilic acid significantly lowered the ADP/oxygen ratio in heart mitochondria exposed to glutamate/malate, while in the liver mitochondria only a mild reduction was found. Tests of the influence of L-tryptophan and its metabolites on complex I in liver mitochondria showed that only 3-hydroxykynurenine, 3-hydroxyanthranilic acid and L-kynurenine led to a significant acceleration of NADH-driven complex I activities. The data indicate that L-tryptophan metabolites had different effects on brain, liver and heart

  10. Quantitative analysis of brain metabolites concentrations using MR spectroscopy in acute hypoxia ischemic encephalopathy

    International Nuclear Information System (INIS)

    Objective: To evaluate the absolute quantification of brain metabolites concentrations using external standard MRS in acute hypoxia ischemia encephalopathy (HIE) piglet model. Method: Eight 7-day-old healthy piglets were subjected to insult of hypoxia ischemia (HI). The animals and an external standard phantom containing detectable metabolites of known concentrations were studied on a 1.5 T GE Signa scanner. The single-voxel proton magnetic resonance spectroscopy (1H-MRS) data were processed using LCModel software, and the quantification of N-acetylaspartate (NAA), creatine (Cr) and lactate (Lac) were accomplished. Multivariate analysis of variance was performed to compare the NAA, Cr, Lac concentration differences in the brains of piglets pre- and post-HI (0h). In addition, the dynamic changes of brain metabolites concentrations of 2 HIE piglets were observed at the time points of 0 h and 2 h. Results: One piglet was excluded because it was over anesthetized to death. Seven piglets' data were analyzed. The concentrations of NAA pre- and post-HI were (6.86±0.49) mmol/kg and (5.73±0.88) mmol/kg respectively, they were (4.65±0.73) mmol/kg and (4.40±0.80) mmol/kg for Cr; and were 0.00 mmol/kg and (0.43±0.39) mmol/kg for Lac. After HI, decreased NAA concentration immediately was observed, and it was of statistical significance (F=8.608, P=0.013). The concentration of Cr was insignificantly decreased (F=0.379, P=0.550). The concentration of Lac was increased, and the difference was of statistical significance (F=8.600, P=0.013). Dynamic observation showed a Lac peak immediately after HI and it decreased after 2 h post-HI. Conclusions: External standard MRS using LCModel has great value in the quantitative analysis of brain metabolites. The changes of NAA and Lac concentrations are sensitive to reflect the early metabolic change of acute HIE. (authors)

  11. Pre-analytical sample quality: metabolite ratios as an intrinsic marker for prolonged room temperature exposure of serum samples.

    Directory of Open Access Journals (Sweden)

    Gabriele Anton

    Full Text Available Advances in the "omics" field bring about the need for a high number of good quality samples. Many omics studies take advantage of biobanked samples to meet this need. Most of the laboratory errors occur in the pre-analytical phase. Therefore evidence-based standard operating procedures for the pre-analytical phase as well as markers to distinguish between 'good' and 'bad' quality samples taking into account the desired downstream analysis are urgently needed. We studied concentration changes of metabolites in serum samples due to pre-storage handling conditions as well as due to repeated freeze-thaw cycles. We collected fasting serum samples and subjected aliquots to up to four freeze-thaw cycles and to pre-storage handling delays of 12, 24 and 36 hours at room temperature (RT and on wet and dry ice. For each treated aliquot, we quantified 127 metabolites through a targeted metabolomics approach. We found a clear signature of degradation in samples kept at RT. Storage on wet ice led to less pronounced concentration changes. 24 metabolites showed significant concentration changes at RT. In 22 of these, changes were already visible after only 12 hours of storage delay. Especially pronounced were increases in lysophosphatidylcholines and decreases in phosphatidylcholines. We showed that the ratio between the concentrations of these molecule classes could serve as a measure to distinguish between 'good' and 'bad' quality samples in our study. In contrast, we found quite stable metabolite concentrations during up to four freeze-thaw cycles. We concluded that pre-analytical RT handling of serum samples should be strictly avoided and serum samples should always be handled on wet ice or in cooling devices after centrifugation. Moreover, serum samples should be frozen at or below -80°C as soon as possible after centrifugation.

  12. Schizophrenia: from the brain to peripheral markers. A consensus paper of the WFSBP task force on biological markers

    DEFF Research Database (Denmark)

    Stober, Gerald; Ben-Shachar, Dorit; Cardon, M;

    2009-01-01

    traits that are specific to particular conditions. An important aim of biomarker discovery is the detection of disease correlates that can be used as diagnostic tools. Method. A selective review of the WFSBP Task Force on Biological Markers in schizophrenia is provided from the central nervous system to...... phenotypes, functional brain systems, chromosomal loci with potential genetic markers to the peripheral systems. Results. A number of biological measures have been proposed to be correlated with schizophrenia. At present, not a single biological trait in schizophrenia is available which achieves sufficient...

  13. Lower glial metabolite levels in brains of young children with prenatal nicotine exposure.

    Science.gov (United States)

    Chang, Linda; Cloak, Christine C; Jiang, Caroline S; Hoo, Aaron; Hernandez, Antonette B; Ernst, Thomas M

    2012-03-01

    Many pregnant women smoke cigarettes during pregnancy, but the effect of nicotine on the developing human brain is not well understood, especially in young children. This study aims to determine the effects of prenatal nicotine exposure (PNE) on brain metabolite levels in young (3-4 years old) children, using proton magnetic resonance spectroscopy ((1)H MRS). Twenty-six children with PNE and 24 nicotine-unexposed children (controls) were evaluated with a structured examination, a battery of neuropsychological tests, and MRI/(1)H MRS (without sedation). Concentrations of N-acetyl compounds (NA), total creatine (tCR), choline-containing compounds (CHO), myo-inositol (MI), and glutamate+glutamine (GLX) were measured in four brain regions. Children with PNE had similar performance to controls on neuropsychological testing. However, compared to controls, the PNE group had lower MI (repeated measures ANOVA-p = 0.03) and tCr levels (repeated measures ANOVA-p = 0.003), especially in the basal ganglia of the girls (-19.3%, p = 0.01). In contrast, GLX was elevated in the anterior cingulate cortex of the PNE children (+9.4%, p = 0.03), and those with the highest GLX levels had the poorest performance on vocabulary (r = -0.67; p metabolite concentrations. These findings suggest that PNE may lead to subclinical abnormalities in glial development, especially in the basal ganglia, and regionally specific changes in other neurometabolites. These alterations were not influenced by the amount of nicotine exposure prenatally. However, the effects of PNE on energy metabolism may be sex specific, with greater alterations in girls. PMID:21912896

  14. Marker-guided multimodality matching of the brain

    International Nuclear Information System (INIS)

    This paper describes a method for matching any combination of CT, MRI, single-photon emission CT (SPECT), and electroencephalography (EEG) or magnetoencephalography (MEG) derived dipole estimations, based on external markers which are easy to apply to the skin. A marker design for CT and MRI is presented which allows sub-slice accuracy in indicating points, and can also be used to pinpoint reference points slightly outside the scanned volume. Accurate registration is thus provided even in standard imaging protocols employing thick slices and/or large interslice gaps. While a similar triangular marker can be used for SPECT imaging, point-like radioactive markers have been considered instead because of their simplicity. Results of the method are presented by means of two- and three-dimensional visualisations. (orig.)

  15. Neurotransmitter and their metabolite concentrations in different areas of the HPRT knockout mouse brain.

    Science.gov (United States)

    Tschirner, Sarah K; Gutzki, Frank; Schneider, Erich H; Seifert, Roland; Kaever, Volkhard

    2016-06-15

    Lesch-Nyhan syndrome (LNS) is characterized by uric acid overproduction and severe neurobehavioral symptoms, such as recurrent self-mutilative behavior. To learn more about the pathophysiology of the disease, we quantified neurotransmitters and their metabolites in the cerebral hemisphere, cerebellum and the medulla oblongata of HPRT knockout mice, an animal model for LNS, in comparison to the corresponding wild-type. Our analyses included l-glutamate, 4-aminobutanoic acid (GABA), acetylcholine, serotonin, 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine, l-normetanephrine, epinephrine and l-metanephrine and were conducted via high performance liquid chromatography (HPLC) coupled to tandem mass spectrometry (MS/MS). Among these neurotransmitter systems, we did not find any abnormalities in the HPRT knockout mouse brains. On one side, this might indicate that HPRT deficiency most severely affects dopamine signaling, while brain functioning based on other neurotransmitters is more or less spared. On the other hand, our findings may reflect a compensating mechanism for impaired purine salvage that protects the brain in HPRT-deficient mice but not in LNS patients. PMID:27206901

  16. Quantitation of normal metabolite concentrations in six brain regions by in-vivo 1H-MR spectroscopy

    OpenAIRE

    Minati, Ludovico; Aquino, Domenico; Bruzzone, Maria Grazia; Erbetta, Alessandra

    2010-01-01

    This study examined the concentrations of brain metabolites visible to in-vivo 1H-Magnetic Resonance Spectroscopy (1H-MRS) at 1.5 T in a sample of 28 normal subjects. Quantitation was attempted for inositol compounds, choline units, total creatine and N-acetyl moieties, using open-source software. Six brain regions were considered: frontal and parietal white matter, medial temporal lobe, thalamus, pons and cerebellum. Absolute concentrations were derived using tissue water as an internal refe...

  17. Vitamin D metabolites as clinical markers in autoimmune and chronic disease.

    Science.gov (United States)

    Blaney, Greg P; Albert, Paul J; Proal, Amy D

    2009-09-01

    Recent research has implicated vitamin D deficiency (serum levels of 25-hydroxyvitamin D fibromyalgia and chronic fatigue syndrome. It has been assumed that low levels of 25-hydroxyvitamin D (25-D) accurately indicate vitamin D storage and vitamin D receptor (VDR)-mediated control of calcium metabolism and innate immunity. To evaluate this assumption, 25-D and 1,25-dihydroxyvitamin D3 (1,25-D) levels were measured in 100 Canadian patients with these conditions. Additionally, other inflammatory markers (CK, CRP) were measured. Results showed a strong positive association between these autoimmune conditions and levels of 1,25-D >110 pmol/L. However, there was little association with vitamin D deficiency or the other inflammatory markers, meaning that the results challenge the assumption that serum levels of 25-D are a sensitive measure of the autoimmune disease state. Rather, these findings support the use of 1,25-D as a clinical marker in autoimmune conditions. High levels of 1,25-D may result when dysregulation of the VDR by bacterial ligands prevents the receptor from expressing enzymes necessary to keep 1,25-D in a normal range. PMID:19758177

  18. Development and validation of a reliable method for studying the distribution pattern for opiates metabolites in brain.

    Science.gov (United States)

    Guerrini, Katia; Argo, Antonella; Borroni, Cristina; Catalano, Daria; Dell'acqua, Lucia; Farè, Fiorenza; Procaccianti, Paolo; Roda, Gabriella; Gambaro, Veniero

    2013-01-25

    Brain distribution pattern of "street" heroin metabolites (morphine and codeine) was investigated in two fatalities due to "acute narcotism". A suitable sample pretreatment prior to solid-phase-extraction was developed to achieve a good recovery of the analytes and to eliminate the interfering species. After derivatization with MSTFA, samples were analyzed by GC/MS. Specificity, accuracy, precision and linearity of the method were evaluated; LOD and LOQ were, respectively, 10ng/25ng for morphine and 5ng/10ng for codeine. This method was applied to the analysis of six brain areas (hippocampus, frontal lobe, occipital lobe, nuclei, bulb and pons) coming from two cases of heroin-related deaths. No evidence of accumulation of metabolites in a specific brain region was found. PMID:22541710

  19. Neurobiological markers of exercise-related brain plasticity in older adults

    OpenAIRE

    Voss, Michelle W.; Erickson, Kirk I.; Prakash, Ruchika Shaurya; Chaddock, Laura; Kim, Jennifer S; Alves, Heloisa; Szabo, Amanda; White, Siobhan M.; Wójcicki, Thomas R.; Mailey, Emily L; Olson, Erin A.; Gothe, Neha; Potter, Vicki V.; Martin, Stephen A.; Pence, Brandt D.

    2012-01-01

    The current study examined how a randomized one-year aerobic exercise program for healthy older adults would affect serum levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor type 1 (IGF-1), and vascular endothelial growth factor (VEGF) - putative markers of exercise-induced benefits on brain function. The study also examined whether (a) change in the concentration of these growth factors was associated with alterations in functional connectivity following exercise, ...

  20. Collagen cross-link metabolites in urine as markers of bone metastases in prostatic carcinoma.

    Science.gov (United States)

    Miyamoto, K K; McSherry, S A; Robins, S P; Besterman, J M; Mohler, J L

    1994-04-01

    The efficacy of radionuclide bone scans in monitoring metastatic bone activity remains controversial. Objective measurement of bone tumor burden would be useful for the evaluation of new therapies for metastatic carcinoma of the prostate. The recent discovery of the urinary excretion of pyridinoline (cross-link of mature collagen found in cartilage and bone) and deoxypyridinoline (collagen cross-link specific to bone) measured by high pressure liquid chromatography has provided sensitive specific indexes of cartilage and bone breakdown in rheumatoid arthritis, osteoporosis and metabolic bone diseases. We compared the urinary excretion of deoxypyridinoline,pyridinoline and hydroxyproline relative to urinary creatinine (nmol./mmol.creatinine) in 27 patients with benign prostatic hyperplasia (patient age 70.0 +/- 8.5 years, standard deviation), 29 with clinically confined prostate cancer (age 70.2 +/- 9.7 years), and 26 with prostate cancer and bone metastases (age 71.1 +/- 7.7 years). No diurnal variation of deoxypyridinoline or pyridinoline urinary excretion was detected in 5 patients with metastases. Urinary excretion of pyridinoline and deoxypyridinoline was significantly greater in patients with metastatic carcinoma of the prostate compared with patients with either benign prostatic hyperplasia (Mann-Whitney-Wilcoxon rank sum analysis, p r = 0.55, p r = 0.57, p r = 0.36, p = 0.08). Serial measurements of pyridinoline and deoxypyridinoline progressively increased in 3 patients with clinical progression documented by new metastatic lesions by bone scan. Measurement of pyridinoline and deoxypyridinoline excretion cannot diagnose metastatic disease. However, these markers should be evaluated further for quantitative assessment of bone metastases. PMID:7510346

  1. [Effect of phenibut on the content of monoamines, their metabolites, and neurotransmitter amino acids in rat brain structures].

    Science.gov (United States)

    Borodkina, L E; Kudrin, V S; Klodt, P M; Narkevich, V B; Tiurenkov, I N

    2009-01-01

    Effects of the nootropic drug phenibut, which is a structural analog of gamma-aminobutyric acid (GABA), on the content of monoamines, their metabolites, and neurotransmitter amino acids in brain structures have been studied on Wistar rats. It is established that a single administration of phenibut in a dose of 25 mg/kg (i.p.) produces a statistically significant increase in the content of dopamine metabolite (3,4-dioxyphenylacetic acid) and the retarding amino acid taurine in striatum. At the same time, phenibut did not significantly influence the levels of GABA, serotonin, and dopamine in various brain structures and produce a moderate decrease in the level of norepinephrine in the hippocampus. PMID:19334514

  2. Plasma based markers of [11C] PiB-PET brain amyloid burden.

    Directory of Open Access Journals (Sweden)

    Steven John Kiddle

    Full Text Available Changes in brain amyloid burden have been shown to relate to Alzheimer's disease pathology, and are believed to precede the development of cognitive decline. There is thus a need for inexpensive and non-invasive screening methods that are able to accurately estimate brain amyloid burden as a marker of Alzheimer's disease. One potential method would involve using demographic information and measurements on plasma samples to establish biomarkers of brain amyloid burden; in this study data from the Alzheimer's Disease Neuroimaging Initiative was used to explore this possibility. Sixteen of the analytes on the Rules Based Medicine Human Discovery Multi-Analyte Profile 1.0 panel were found to associate with [(11C]-PiB PET measurements. Some of these markers of brain amyloid burden were also found to associate with other AD related phenotypes. Thirteen of these markers of brain amyloid burden--c-peptide, fibrinogen, alpha-1-antitrypsin, pancreatic polypeptide, complement C3, vitronectin, cortisol, AXL receptor kinase, interleukin-3, interleukin-13, matrix metalloproteinase-9 total, apolipoprotein E and immunoglobulin E--were used along with co-variates in multiple linear regression, and were shown by cross-validation to explain >30% of the variance of brain amyloid burden. When a threshold was used to classify subjects as PiB positive, the regression model was found to predict actual PiB positive individuals with a sensitivity of 0.918 and a specificity of 0.545. The number of APOE [Symbol: see text] 4 alleles and plasma apolipoprotein E level were found to contribute most to this model, and the relationship between these variables and brain amyloid burden was explored.

  3. Cross-sectional and Longitudinal Reproducibility of Rhesus Macaque Brain Metabolites: A Proton MR Spectroscopy Study at 3 T

    OpenAIRE

    Wu, William E.; Kirov, Ivan I.; Zhang, Ke; Babb, James S.; Joo, Chan-Gyu; Ratai, Eva-Maria; González, R. Gilberto; Gonen, Oded

    2011-01-01

    Non-human primates are often used as preclinical model systems for (mostly diffuse or multi-focal) neurological disorders and their experimental treatment. Due to cost considerations, such studies frequently utilize non-destructive imaging modalities, MRI and proton MR spectroscopy (1H-MRS). Cost may explain why the inter- and intra-animal reproducibility of the 1H-MRS-observed brain metabolites, is not reported. To this end, we performed test-retest three-dimensional brain 1H-MRS in five hea...

  4. Brain metabolite changes in subcortical regions after exposure to cuprizone for 6 weeks: potential implications for schizophrenia.

    Science.gov (United States)

    Yan, Gen; Xuan, Yinghua; Dai, Zhuozhi; Shen, Zhiwei; Zhang, Guishan; Xu, Haiyun; Wu, Renhua

    2015-01-01

    Cuprizone is a copper chelating agent able to selectively damage the white matter in the mouse brain. Recent studies have reported behavioral abnormalities relevant to some of schizophrenia symptoms. While associating white matter damage to the behavioral abnormalities, these previous studies did not rule out the possible impairment in neuronal functions in cuprizone-exposed mice. The aim of this study was to examine brain metabolites of the cuprizone-exposed mice by proton magnetic resonance spectroscopy ((1)H-MRS). The examined brain regions were the caudoputamen, midbrain, and thalamus; these subcortical regions showed different susceptibilities to cuprizone in terms of demyelination and oligodendrocyte loss in previous studies. Young C57BL/6 mice were fed a standard rodent chow without or with cuprizone (0.2 %) for 6 weeks. At the end, open-field and Y-maze tests were performed to measure the emotional and cognitive behaviors of the animals, followed by (1)H-MRS procedure to evaluate the brain metabolites. Cuprizone-exposure increased anxiety levels and impaired spatial working memory. The same treatment increased T2 signal intensity in the cerebral cortex, hippocampus, and caudoputamen, but not in the thalamus. Cuprizone-exposure decreased the concentrations of NAA and NAA+NAAG in caudoputamen, but not in thalamus and midbrain. It decreased levels of Cr+PCr, GPC+PCh and myo-inositol in all the three brain regions. These results provided neurochemical evidence for the impairment in neuronal functions by cuprizone treatment. PMID:25347963

  5. Quantitation of normal metabolite concentrations in six brain regions by in-vivo 1 H-MR spectroscopy

    Directory of Open Access Journals (Sweden)

    Minati Ludovico

    2010-01-01

    Full Text Available This study examined the concentrations of brain metabolites visible to in-vivo 1 H-Magnetic Resonance Spectroscopy ( 1 H-MRS at 1.5 T in a sample of 28 normal subjects. Quantitation was attempted for inositol compounds, choline units, total creatine and N-acetyl moieties, using open-source software. Six brain regions were considered: frontal and parietal white matter, medial temporal lobe, thalamus, pons and cerebellum. Absolute concentrations were derived using tissue water as an internal reference and using an external reference; metabolite signal intensity ratios with respect to creatine were also calculated. The inter-individual variability was smaller for absolute concentrations (internal reference as compared to that for signal intensity ratios. Significant regional variability in concentration was found for all metabolites, indicating that separate normative values are needed for different brain regions. The values obtained in this study can be used as reference in future studies, provided the same methodology is followed; it is confirmed that despite unsuccessful attempts in the past, smaller coefficients of variation can indeed be obtained through absolute quantification.

  6. Quantitation of normal metabolite concentrations in six brain regions by in-vivo 1H-MR spectroscopy

    Science.gov (United States)

    Minati, Ludovico; Aquino, Domenico; Bruzzone, Maria Grazia; Erbetta, Alessandra

    2010-01-01

    This study examined the concentrations of brain metabolites visible to in-vivo 1H-Magnetic Resonance Spectroscopy (1H-MRS) at 1.5 T in a sample of 28 normal subjects. Quantitation was attempted for inositol compounds, choline units, total creatine and N-acetyl moieties, using open-source software. Six brain regions were considered: frontal and parietal white matter, medial temporal lobe, thalamus, pons and cerebellum. Absolute concentrations were derived using tissue water as an internal reference and using an external reference; metabolite signal intensity ratios with respect to creatine were also calculated. The inter-individual variability was smaller for absolute concentrations (internal reference) as compared to that for signal intensity ratios. Significant regional variability in concentration was found for all metabolites, indicating that separate normative values are needed for different brain regions. The values obtained in this study can be used as reference in future studies, provided the same methodology is followed; it is confirmed that despite unsuccessful attempts in the past, smaller coefficients of variation can indeed be obtained through absolute quantification. PMID:20927223

  7. Phospholipid metabolites in recurrent glioblastoma: in vivo markers detect different tumor phenotypes before and under antiangiogenic therapy.

    Directory of Open Access Journals (Sweden)

    Elke Hattingen

    Full Text Available PURPOSE: Metabolic changes upon antiangiogenic therapy of recurrent glioblastomas (rGBMs may provide new biomarkers for treatment efficacy. Since in vitro models showed that phospholipid membrane metabolism provides specific information on tumor growth we employed in-vivo MR-spectroscopic imaging (MRSI of human rGBMs before and under bevacizumab (BVZ to measure concentrations of phosphocholine (PCho, phosphoethanolamine (PEth, glycerophosphocholine (GPC, and glyceroethanolamine (GPE. METHODS: (1H and (31P MRSI was prospectively performed in 32 patients with rGBMs before and under BVZ therapy at 8 weeks intervals until tumor progression. Patients were dichotomized into subjects with long overall survival (OS (>median OS and short OS (Metabolite concentrations from tumor tissue and their ratios were compared to contralateral normal-appearing tissue (control. RESULTS: Before BVZ, (1H-detectable choline signals (total GPC and PCho in rGBMs were elevated but significance failed after dichotomizing. For metabolite ratios obtained by (31P MRSI, the short-OS group showed higher PCho/GPC (p = 0.004 in rGBMs compared to control tissue before BVZ while PEth/GPE was elevated in rGBMs of both groups (long-OS p = 0.04; short-OS p = 0.003. Under BVZ, PCho/GPC and PEth/GPE in the tumor initially decreased (p = 0.04 but only PCho/GPC re-increased upon tumor progression (p = 0.02. Intriguingly, in normal-appearing tissue an initial PEth/GPE decrease (p = 0.047 was followed by an increase at the time of tumor progression (p = 0.031. CONCLUSION: An elevated PCho/GPC ratio in the short-OS group suggests that it is a negative predictive marker for BVZ efficacy. These gliomas may represent a malignant phenotype even growing under anti-VEGF treatment. Elevated PEth/GPE may represent an in-vivo biomarker more sensitive to GBM infiltration than MRI.

  8. Inflammatory transcription factors as activation markers and functional readouts in immune-to-brain communication.

    Science.gov (United States)

    Rummel, Christoph

    2016-05-01

    Immune-to-brain communication pathways involve humoral mediators, including cytokines, central modulation by neuronal afferents and immune cell trafficking to the brain. During systemic inflammation these pathways contribute to mediating brain-controlled sickness symptoms including fever. Experimentally, activation of these signaling pathways can be mimicked and studied when injecting animals with pathogen associated molecular patterns (PAMPS). One central component of the brain inflammatory response, which leads, for example, to fever induction, is transcriptional activation of brain cells via cytokines and PAMPS. We and others have studied the spatiotemporal activation and the physiological significance of transcription factors for the induction of inflammation within the brain and the manifestation of fever. Evidence has revealed a role of nuclear factor (NF)κB in the initiation, signal transducer and activator of transcription (STAT)3 in the maintenance and NF-interleukin (IL)6 in the maintenance or even termination of brain-inflammation and fever. Moreover, psychological stressors, such as exposure to a novel environment, leads to increased body core temperature and genomic NF-IL6-activation, suggesting a potential use of NF-IL6-immunohistochemistry as a multimodal brain cell activation marker and a role for NF-IL6 for differential brain activity. In addition, the nutritional status, as reflected by circulating levels of the cytokine-like hormone leptin, influence immune-to-brain communication and age-dependent changes in LPS-induced fever. Overall, transcription factors remain therapeutically important targets for the treatment of brain-inflammation and fever induction during infectious/non-infectious inflammatory and psychological stress. However, the exact physiological role and significance of these transcription factors requires to be further investigated. PMID:26348582

  9. Statistical mapping of metabolites in the medial wall of the brain: a proton echo planar spectroscopic imaging study.

    Science.gov (United States)

    Niddam, David M; Tsai, Shang-Yueh; Lin, Yi-Ru

    2015-03-01

    With magnetic resonance spectroscopic imaging (MRSI), it is possible to simultaneously map distributions of several brain metabolites with relatively good spatial resolution in a short time. Although other functional imaging modalities have taken advantage of population-based inferences using spatially extended statistics, this approach remains little utilized for MRSI. In this study, statistical nonparametric mapping (SnPM) was applied to two-dimensional MRSI data from the medial walls of the human brain to assess the effect of normal aging on metabolite concentrations. The effects of different preprocessing steps on these results were then explored. Short echo time MRSI of left and right medial walls was acquired in conjunction with absolute quantification of total choline, total creatine (tCr), glutamate and glutamine, myo-inositol, and N-acetyl-aspartate. Individual images were spatially warped to a common anatomical frame of reference. Age effects were assessed within SnPM as were the effects of voxel subsampling, variance smoothing, and spatial smoothing. The main findings were: (1) regions in the bilateral dorsal anterior cingulate and in the left posterior cingulate exhibited higher tCr concentrations with age; (2) voxel subsampling but not spatial smoothing enhanced the cluster-level statistical sensitivity; and (3) variance smoothing was of little benefit in this study. Our study shows that spatially extended statistics can yield information about regional-specific changes in metabolite concentrations obtained by short echo time MRSI. This opens up the possibility for systematic comparisons of metabolites in the medial wall of the brain. PMID:25338521

  10. Markers

    Science.gov (United States)

    Healthy Schools Network, Inc., 2011

    2011-01-01

    Dry erase whiteboards come with toxic dry erase markers and toxic cleaning products. Dry erase markers labeled "nontoxic" are not free of toxic chemicals and can cause health problems. Children are especially vulnerable to environmental health hazards; moreover, schools commonly have problems with indoor air pollution, as they are more densely…

  11. The influence of X-irradiation on diazepam and its metabolites (nordazepam, temazepam and oxazepam) content in plasma, liver and brain in the rats

    International Nuclear Information System (INIS)

    The influence of whole-body X-ray irradiation (6.7 Gy) on pharmacokinetics of diazepam (DZP) and its metabolites (nordazepam, temazepam and oxazepam) was examined in male Wistar rats. DZP (5 mg/kg iv) was administered at day 7 after irradiation, and the content of the drug and its metabolites was measured by reversed-phase HPLC/UV in the serum, liver and brain at defined time points during eight hours. Concentrations of DZP were reduced in serum, liver and brain of irradiated rats, comparing to control, but the difference was significant during 2 hours after application only. On the other hand, concentrations of DZP metabolites were significantly reduced in the liver and brain of irradiated animals, but not in the serum. Our results suggest that acute radiation injury has altered the pharmacokinetics of DZP and its metabolites in the rats, preferentially affecting its distribution. (author)

  12. Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury

    Science.gov (United States)

    De Simoni, Maria-Grazia

    2013-01-01

    After brain stroke microglia/macrophages (M/M) undergo rapid activation with dramatic morphological and phenotypic changes that include expression of novel surface antigens and production of mediators that build up and maintain the inflammatory response. Emerging evidence indicates that M/M are highly plastic cells that can assume classic pro-inflammatory (M1) or alternative anti-inflammatory (M2) activation after acute brain injury. However a complete characterization of M/M phenotype marker expression, their colocalization and temporal evolution in the injured brain is still missing. Immunofluorescence protocols specifically staining relevant markers of M/M activation can be performed in the ischemic brain. Here we present immunofluorescence-based protocols followed by three-dimensional confocal analysis as a powerful approach to investigate the pattern of localization and co-expression of M/M phenotype markers such as CD11b, CD68, Ym1, in mouse model of focal ischemia induced by permanent occlusion of the middle cerebral artery (pMCAO). Two-dimensional analysis of the stained area reveals that each marker is associated to a defined M/M morphology and has a given localization in the ischemic lesion. Patterns of M/M phenotype marker co-expression can be assessed by three-dimensional confocal imaging in the ischemic area. Images can be acquired over a defined volume (10 μm z-axis and a 0.23 μm step size, corresponding to a 180 x 135 x 10 μm volume) with a sequential scanning mode to minimize bleed-through effects and avoid wavelength overlapping. Images are then processed to obtain three-dimensional renderings by means of Imaris software. Solid view of three dimensional renderings allows the definition of marker expression in clusters of cells. We show that M/M have the ability to differentiate towards a multitude of phenotypes, depending on the location in the lesion site and time after injury. PMID:24056862

  13. Brain metabolites in the hippocampus-amygdala region and cerebellum in autism: an {sup 1}H-MR spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, H.; Harada, M.; Hisaoka, S.; Nishitani, H. [Dept. of Radiology, Univ. of Tokushima, Tokushima City (Japan); Mori, K. [Dept. of Pediatrics, Univ. of Tokushima (Japan)

    1999-07-01

    Histological abnormalities of the brain in autism have been investigated extensively. We studied metabolites in the hippocampusamygdala (HA) region and cerebellum. We examined the right HA region and left cerebellar hemisphere of 27 autistic patients 2-18 years old, 21 boys and 6 girls and 10 normal children 6-14 years old, 4 boys and 6 girls, using the STEAM sequence. This sequence was used to minimise the influence of relaxation times. The N-acetyl aspartate (NAA) concentration was significantly lower (P=0.042) in autistic patients than in normal children (9.37 and 10.95 mM, respectively). There was no significant difference in other metabolites. The correlation coefficient (r value) of NAA between the HA region and cerebellum was 0.616. The decreased NAA concentration may be due to neuronal hypofunction or immature neurons. The NAA concentration in the HA region and cerebellum may be related, because of neuronal circuits or networks. (orig.)

  14. Brain metabolites in the hippocampus-amygdala region and cerebellum in autism: an 1H-MR spectroscopy study

    International Nuclear Information System (INIS)

    Histological abnormalities of the brain in autism have been investigated extensively. We studied metabolites in the hippocampusamygdala (HA) region and cerebellum. We examined the right HA region and left cerebellar hemisphere of 27 autistic patients 2-18 years old, 21 boys and 6 girls and 10 normal children 6-14 years old, 4 boys and 6 girls, using the STEAM sequence. This sequence was used to minimise the influence of relaxation times. The N-acetyl aspartate (NAA) concentration was significantly lower (P=0.042) in autistic patients than in normal children (9.37 and 10.95 mM, respectively). There was no significant difference in other metabolites. The correlation coefficient (r value) of NAA between the HA region and cerebellum was 0.616. The decreased NAA concentration may be due to neuronal hypofunction or immature neurons. The NAA concentration in the HA region and cerebellum may be related, because of neuronal circuits or networks. (orig.)

  15. Effects of chronic clozapine administration on markers of arachidonic acid cascade and synaptic integrity in rat brain

    OpenAIRE

    Kim, Hyung-Wook; Cheon, Yewon; Modi, Hiren R.; Rapoport, Stanley I; Rao, Jagadeesh S.

    2012-01-01

    The mode of action of clozapine, an atypical antipsychotic approved for treating schizophrenia and bipolar disorder (BD) mania, remains unclear. We tested for overlap with the actions of the mood stabilizers, lithium, carbamazepine and valproate, which downregulate arachidonic acid (AA) cascade markers in rat brain and upregulate BDNF. AA cascade markers are upregulated in the postmortem BD brain in association with neuroinflammation and synaptic loss, while BDNF is decreased. Rats were injec...

  16. Ex-vivo HRMAS of adult brain tumours: metabolite quantification and assignment of tumour biomarkers.

    NARCIS (Netherlands)

    Wright, A.J.; Fellows, G.A.; Griffiths, J.R.; Wilson, M.; Bell, B.A.; Howe, F.A.

    2010-01-01

    BACKGROUND: High-resolution magic angle spinning (HRMAS) NMR spectroscopy allows detailed metabolic analysis of whole biopsy samples for investigating tumour biology and tumour classification. Accurate biochemical assignment of small molecule metabolites that are "NMR visible" will improve our inter

  17. Multimodal MR imaging of acute and subacute experimental traumatic brain injury: Time course and correlation with cerebral energy metabolites

    International Nuclear Information System (INIS)

    Traumatic brain injury (TBI) is one of the leading causes of death and permanent disability world-wide. The predominant cause of death after TBI is brain edema which can be quantified by non-invasive diffusion-weighted magnetic resonance imaging (DWI). To provide a better understanding of the early onset, time course, spatial development, and type of brain edema after TBI and to correlate MRI data and the cerebral energy state reflected by the metabolite adenosine triphosphate (ATP). The spontaneous development of lateral fluid percussion-induced TBI was investigated in the acute (6 h), subacute (48 h), and chronic (7 days) phase in rats by MRI of quantitative T2 and apparent diffusion coefficient (ADC) mapping as well as perfusion was combined with ATP-specific bioluminescence imaging and histology. An induced TBI led to moderate to mild brain damages, reflected by transient, pronounced development of vasogenic edema and perfusion reduction. Heterogeneous ADC patterns indicated a parallel, but mixed expression of vasogenic and cytotoxic edema. Cortical ATP levels were reduced in the acute and subacute phase by 13% and 27%, respectively, but were completely normalized at 7 days after injury. The partial ATP reduction was interpreted to be partially caused by a loss of neurons in parallel with transient dilution of the regional ATP concentration by pronounced vasogenic edema. The normalization of energy metabolism after 7 days was likely due to infiltrating glia and not to recovery. The MRI combined with metabolite measurement further improves the understanding and evaluation of brain damages after TBI

  18. Corpus callosum thickness on mid-sagittal MRI as a marker of brain volume: a pilot study in children with HIV-related brain disease and controls

    Energy Technology Data Exchange (ETDEWEB)

    Andronikou, Savvas [University of the Witwatersrand, Department of Radiology, Faculty of Health Sciences, Cape Town (South Africa); Ackermann, Christelle [University of Stellenbosch, Department of Radiology, Stellenbosch (South Africa); Laughton, Barbara; Cotton, Mark [Stellenbosch University and Tygerberg Children' s Hospital, Children' s Infectious Diseases Research Unit, Stellenbosch (South Africa); Tomazos, Nicollette [University of Cape Town, Faculty of Commerce, Department of Management Studies, Cape Town (South Africa); Spottiswoode, Bruce [University of Cape Town, MRC/UCT Medical Imaging Research Unit, Department of Human Biology, Cape Town (South Africa); Mauff, Katya [University of Cape Town, Department of Statistical Sciences, Cape Town (South Africa); Pettifor, John M. [University of the Witwatersrand, MRC/Wits Developmental Pathways for Health Research Unit, Department of Paediatrics, Faculty of Health Sciences, Witwatersrand (South Africa)

    2015-07-15

    Corpus callosum thickness measurement on mid-sagittal MRI may be a surrogate marker of brain volume. This is important for evaluation of diseases causing brain volume gain or loss, such as HIV-related brain disease and HIV encephalopathy. To determine if thickness of the corpus callosum on mid-sagittal MRI is a surrogate marker of brain volume in children with HIV-related brain disease and in controls without HIV. A retrospective MRI analysis in children (<5 years old) with HIV-related brain disease and controls used a custom-developed semi-automated tool, which divided the midline corpus callosum and measured its thickness in multiple locations. Brain volume was determined using volumetric analysis. Overall corpus callosum thickness and thickness of segments of the corpus callosum were correlated with overall and segmented (grey and white matter) brain volume. Forty-four children (33 HIV-infected patients and 11 controls) were included. Significant correlations included overall corpus callosum (mean) and total brain volume (P = 0.05); prefrontal corpus callosum maximum with white matter volume (P = 0.02); premotor corpus callosum mean with total brain volume (P = 0.04) and white matter volume (P = 0.02), premotor corpus callosum maximum with white matter volume (P = 0.02) and sensory corpus callosum mean with total brain volume (P = 0.02). Corpus callosum thickness correlates with brain volume both in HIV-infected patients and controls. (orig.)

  19. Corpus callosum thickness on mid-sagittal MRI as a marker of brain volume: a pilot study in children with HIV-related brain disease and controls

    International Nuclear Information System (INIS)

    Corpus callosum thickness measurement on mid-sagittal MRI may be a surrogate marker of brain volume. This is important for evaluation of diseases causing brain volume gain or loss, such as HIV-related brain disease and HIV encephalopathy. To determine if thickness of the corpus callosum on mid-sagittal MRI is a surrogate marker of brain volume in children with HIV-related brain disease and in controls without HIV. A retrospective MRI analysis in children (<5 years old) with HIV-related brain disease and controls used a custom-developed semi-automated tool, which divided the midline corpus callosum and measured its thickness in multiple locations. Brain volume was determined using volumetric analysis. Overall corpus callosum thickness and thickness of segments of the corpus callosum were correlated with overall and segmented (grey and white matter) brain volume. Forty-four children (33 HIV-infected patients and 11 controls) were included. Significant correlations included overall corpus callosum (mean) and total brain volume (P = 0.05); prefrontal corpus callosum maximum with white matter volume (P = 0.02); premotor corpus callosum mean with total brain volume (P = 0.04) and white matter volume (P = 0.02), premotor corpus callosum maximum with white matter volume (P = 0.02) and sensory corpus callosum mean with total brain volume (P = 0.02). Corpus callosum thickness correlates with brain volume both in HIV-infected patients and controls. (orig.)

  20. Frontal brain asymmetry as a marker of depression and effectiveness of TMS therapy

    International Nuclear Information System (INIS)

    Full text: Resting frontal brain electroencephalography (EEG) asymmetry has been hypothesi sed as a diagnostic marker for depression. A number of studies have shown that depressed individuals are characterised by diminished left sided activation of the prefrontal cortex, which is indicated by greater left than right alpha-band power. Relative left frontal region activity is believed to be associated with positive approach related behaviour and relative right frontal activity is seen to be linked to negative withdrawal related behaviour. In this study, frontal brain EEG was recorded from 17 depressed and 19 control subjects, from which frontal brain asymmetry ratios were calculated. The results confirmed the trend of relative left anterior hypoaclivation for individuals with depression compared to the healthy controls. This study also looked at beta and theta band ratios and found theta for depressed is predominantly negative, while the control group dis played mainly positive values. Beta comparison showed little significant difference between control and depressed groups. In addition, there have been few studies that examined frontal brain asymmetry in depression soon after treatment to gauge its effectiv ness. In a very preliminary study, the effect of Transcranial Magnetic Stimulation (TMS) therapy on the alpha band frontal brain asymmetry ratio for 5 depl'essed subjects before and after treatment found a slight increase in FBA ratio for 4 subjects. Further research and a larger subject group is required to validate these results.

  1. The effect of experimentally-induced renal failure on accumulation of bupropion and its major basic metabolites in plasma and brain of guinea pigs.

    Science.gov (United States)

    DeVane, C L; Laizure, S C; Cameron, D F

    1986-01-01

    Dosage regimen adjustments because of poor renal function are often assumed to be unnecessary for extensively metabolized antidepressants. This assumption is being increasingly questioned in recognition of the role of active drug metabolites. The purpose of this study was to assess the steady-state accumulation of the new antidepressant bupropion and its three major basic metabolites in guinea pigs, with and without experimentally-induced renal failure. Two groups of guinea pigs were treated by intraperitoneal (IP) implantation of mini-osmotic pumps containing bupropion hydrochloride. Immediately after surgery, one group of animals received an injection of uranyl nitrate. After 4 days, all animals were sacrificed by decapitation following blood removal by cardiac puncture. Analysis of plasma and brain samples by high performance liquid chromatography (HPLC) for concentrations of bupropion (BUP) and its major basic metabolites, the erythro-amino alcohol (EB), the threo-amino alcohol (TB) and the hydroxy metabolite (HB) revealed greater accumulation of BUP, TB, and HB in plasma and brain of the animals with renal failure compared to controls. No difference was found between groups in the concentrations of the EB metabolite. As the guinea pig shows a BUP and metabolite plasma concentration profile similar to that seen in human studies, these results suggest that further studies of bupropion and its major metabolites are warranted in patients with impaired renal function to assess possible excessive drug and metabolite accumulation. PMID:3092270

  2. Cerebrospinal Fluid Markers of Neurodegeneration and Rates of Brain Atrophy in Early Alzheimer Disease

    Science.gov (United States)

    Tarawneh, Rawan; Head, Denise; Allison, Samantha; Buckles, Virginia; Fagan, Anne M.; Ladenson, Jack H.; Morris, John C.; Holtzman, David M.

    2015-01-01

    IMPORTANCE Measures of neuronal loss are likely good surrogates for clinical and radiological disease progression in Alzheimer disease (AD). Cerebrospinal fluid (CSF) markers of neuronal injury or neurodegeneration may offer usefulness in predicting disease progression and guiding outcome assessments and prognostic decisions in clinical trials of disease-modifying therapies. Visinin-like protein 1 (VILIP-1) has demonstrated potential usefulness as a marker of neuronal injury in AD. OBJECTIVE To investigate the usefulness of CSF VILIP-1, tau, p-tau181, and Aβ42 levels in predicting rates of whole-brain and regional atrophy in early AD and cognitively normal control subjects over time. DESIGN, SETTING, AND PARTICIPANTS Longitudinal observational study of brain atrophy in participants with early AD and cognitively normal controls. Study participants had baseline CSF biomarker measurements and longitudinal magnetic resonance imaging assessments for a mean follow-up period of 2 to 3 years. Mixed linear models assessed the ability of standardized baseline CSF biomarker measures to predict rates of whole-brain and regional atrophy over the follow-up period. The setting was The Charles F. and Joanne Knight Alzheimer’s Disease Research Center, Washington University School of Medicine in St Louis. Participants (mean age, 72.6 years) were individuals with a clinical diagnosis of very mild AD (n = 23) and cognitively normal controls (n = 64) who were enrolled in longitudinal studies of healthy aging and dementia. The study dates were 2000 to 2010. MAIN OUTCOMES AND MEASURES Correlations between baseline CSF biomarker measures and rates of whole-brain or regional atrophy in the AD and control cohorts over the follow-up period. RESULTS Baseline CSF VILIP-1, tau, and p-tau181 levels (but not Aβ42 levels) predicted rates of whole-brain and regional atrophy in AD over the follow-up period. Baseline CSF VILIP-1 levels predicted whole-brain (P = .006), hippocampal (P = .01), and

  3. Reversal of glial and neurovascular markers of unhealthy brain aging by exercise in middle-aged female mice.

    Directory of Open Access Journals (Sweden)

    Caitlin S Latimer

    Full Text Available Healthy brain aging and cognitive function are promoted by exercise. The benefits of exercise are attributed to several mechanisms, many which highlight its neuroprotective role via actions that enhance neurogenesis, neuronal morphology and/or neurotrophin release. However, the brain is also composed of glial and vascular elements, and comparatively less is known regarding the effects of exercise on these components in the aging brain. Here, we show that aerobic exercise at mid-age decreased markers of unhealthy brain aging including astrocyte hypertrophy, a hallmark of brain aging. Middle-aged female mice were assigned to a sedentary group or provided a running wheel for six weeks. Exercise decreased hippocampal astrocyte and myelin markers of aging but increased VEGF, a marker of angiogenesis. Brain vascular casts revealed exercise-induced structural modifications associated with improved endothelial function in the periphery. Our results suggest that age-related astrocyte hypertrophy/reactivity and myelin dysregulation are aggravated by a sedentary lifestyle and accompanying reductions in vascular function. However, these effects appear reversible with exercise initiated at mid-age. As this period of the lifespan coincides with the appearance of multiple markers of brain aging, including initial signs of cognitive decline, it may represent a window of opportunity for intervention as the brain appears to still possess significant vascular plasticity. These results may also have particular implications for aging females who are more susceptible than males to certain risk factors which contribute to vascular aging.

  4. Relationship between opioid therapy, tissue-damaging procedures, and brain metabolites as measured by proton MRS in asphyxiated term neonates.

    Science.gov (United States)

    Angeles, Danilyn M; Ashwal, Stephen; Wycliffe, Nathaniel D; Ebner, Charlotte; Fayard, Elba; Sowers, Lawrence; Holshouser, Barbara A

    2007-05-01

    To examine the effects of opioid and tissue-damaging procedures (TDPs) [i.e. procedures performed in the neonatal intensive care unit (NICU) known to result in pain, stress, and tissue damage] on brain metabolites, we reviewed the medical records of 28 asphyxiated term neonates (eight opioid-treated, 20 non-opioid treated) who had undergone magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) within the first month of life as well as eight newborns with no clinical findings of asphyxial injury. We found that lower creatine (Cr), myoinositol (Ins), and N-acetylaspartate (NAA)/choline (Cho) (p OGM) NAA/Cr was decreased (p = 0.03) and lactate (Lac) was present in a significantly higher amount (40%; p = 0.03) in non-opioid-treated neonates compared with opioid-treated neonates. Compared with controls, untreated neonates showed larger changes in more metabolites in basal ganglia (BG), thalami (TH), and OGM with greater significance than treated neonates. Our data suggest that TDPs affect spectral metabolites and that opioids do not cause harm in asphyxiated term neonates exposed to repetitive TDPs in the first 2-4 DOL and may provide a degree of neuroprotection. PMID:17413864

  5. Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats

    OpenAIRE

    Harry Gaylia; Kraft Andrew; Chen Mei; Greenstein Dede; Kellom Matthew; Kim Hyung-Wook; Rao Jagadeesh; Rapoport Stanley; Basselin Mireille

    2011-01-01

    Abstract Background Cognitive impairment has been reported in human immune deficiency virus-1- (HIV-1-) infected patients as well as in HIV-1 transgenic (Tg) rats. This impairment has been linked to neuroinflammation, disturbed brain arachidonic acid (AA) metabolism, and synapto-dendritic injury. We recently reported upregulated brain AA metabolism in 7- to 9-month-old HIV-1 Tg rats. We hypothesized that these HIV-1 Tg rats also would show upregulated brain inflammatory and AA cascade markers...

  6. Validation of UHPLC-MS/MS methods for the determination of kaempferol and its metabolite 4-hydroxyphenyl acetic acid, and application to in vitro blood-brain barrier and intestinal drug permeability studies.

    Science.gov (United States)

    Moradi-Afrapoli, Fahimeh; Oufir, Mouhssin; Walter, Fruzsina R; Deli, Maria A; Smiesko, Martin; Zabela, Volha; Butterweck, Veronika; Hamburger, Matthias

    2016-09-01

    Sedative and anxiolytic-like properties of flavonoids such as kaempferol and quercetin, and of some of their intestinal metabolites, have been demonstrated in pharmacological studies. However, routes of administration were shown to be critical for observing in vivo activity. Therefore, the ability to cross intestinal and blood-brain barriers was assessed in cell-based models for kaempferol (KMF), and for the major intestinal metabolite of KMF, 4-hydroxyphenylacetic acid (4-HPAA). Intestinal transport studies were performed with Caco-2 cells, and blood-brain barrier transport studies with an immortalized monoculture human model and a primary triple-co-culture rat model. UHPLC-MS/MS methods for KMF and 4-HPAA in Ringer-HEPES buffer and in Hank's balanced salt solution were validated according to industry guidelines. For all methods, calibration curves were fitted by least-squares quadratic regression with 1/X(2) as weighing factor, and mean coefficients of determination (R(2)) were >0.99. Data obtained with all barrier models showed high intestinal and blood-brain barrier permeation of KMF, and no permeability of 4-HPAA, when compared to barrier integrity markers. PMID:27281582

  7. Regional brain metabolite abnormalities in inherited prion disease and asymptomatic gene carriers demonstrated in vivo by quantitative proton magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Inherited prion diseases are caused by mutations in the gene which codes for prion protein (PrP), leading to proliferation of abnormal PrP isomers in the brain and neurodegeneration; they include Gerstmann-Straeussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). We studied two patients with symptomatic inherited prion disease (P102L) and two pre-symptomatic P102L gene carriers using quantitative magnetic resonance spectroscopy (MRS). Short echo time spectra were acquired from the thalamus, caudate region and frontal white matter, metabolite levels and ratios were measured and z-scores calculated for individual patients relative to age-matched normal controls. MRS data were compared with structural magnetic resonance imaging. One fCJD case had generalised atrophy and showed increased levels of myo-inositol (MI) in the thalamus (z=3.7). The other had decreased levels of N-acetylaspartate (z=4) and diffuse signal abnormality in the frontal white matter. Both asymptomatic gene carriers had normal imaging, but increased frontal white matter MI (z=4.3, 4.1), and one also had increased MI in the caudate (z=5.3). Isolated MI abnormalities in asymptomatic gene carriers are a novel finding and may reflect early glial proliferation, prior to significant neuronal damage. MRS provides potential non-invasive surrogate markers of early disease and progression in inherited prion disease. (orig.)

  8. Regional brain metabolite abnormalities in inherited prion disease and asymptomatic gene carriers demonstrated in vivo by quantitative proton magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Waldman, A.D.; Cordery, R.J.; Godbolt, A.; Rossor, M.N. [University College London, Dementia Research Group, Department of Neurodegenerative Disease, Institute of Neurology, London (United Kingdom); Imperial College of Science, Technology and Medicine, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, London (United Kingdom); MacManus, D.G. [University College London, NMR Research Unit, Department of Clinical Neurology, Institute of Neurology, London (United Kingdom); Collinge, J. [University College London, MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, London (United Kingdom)

    2006-06-15

    Inherited prion diseases are caused by mutations in the gene which codes for prion protein (PrP), leading to proliferation of abnormal PrP isomers in the brain and neurodegeneration; they include Gerstmann-Straeussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). We studied two patients with symptomatic inherited prion disease (P102L) and two pre-symptomatic P102L gene carriers using quantitative magnetic resonance spectroscopy (MRS). Short echo time spectra were acquired from the thalamus, caudate region and frontal white matter, metabolite levels and ratios were measured and z-scores calculated for individual patients relative to age-matched normal controls. MRS data were compared with structural magnetic resonance imaging. One fCJD case had generalised atrophy and showed increased levels of myo-inositol (MI) in the thalamus (z=3.7). The other had decreased levels of N-acetylaspartate (z=4) and diffuse signal abnormality in the frontal white matter. Both asymptomatic gene carriers had normal imaging, but increased frontal white matter MI (z=4.3, 4.1), and one also had increased MI in the caudate (z=5.3). Isolated MI abnormalities in asymptomatic gene carriers are a novel finding and may reflect early glial proliferation, prior to significant neuronal damage. MRS provides potential non-invasive surrogate markers of early disease and progression in inherited prion disease. (orig.)

  9. Influence of different TE on reliability of brain metabolites quantification in high field 1H MRS

    Czech Academy of Sciences Publication Activity Database

    Rackayová, V.; Cudalbu, C.; Xin, L.; Kunz, N.; Starčuková, Jana; Starčuk jr., Zenon; Gruetter, R.

    Vol. 23. Berkeley: Society of Magnetic Resonance, 2015. s. 1945. [ISMRM. Annual Meeting and Exhibition /23./. 30.05.2015-05.06.2015, Toronto] Institutional support: RVO:68081731 Keywords : MRS * metabolites * quantitation * short TE * simulation Subject RIV: BH - Optics, Masers, Lasers

  10. Naloxone-precipitated changes in biogenic amines and their metabolites in various brain regions of butorphanol-dependent rats.

    Science.gov (United States)

    Tokuyama, S; Wakabayashi, H; Hoskins, B; Ho, I K

    1996-06-01

    Influence of a naloxone (an opioid receptor antagonist) challenge (5 mg/kg, IP) on levels of biogenic amines and their metabolites in various brain regions of rats infused continuously with butorphanol (a mu/delta/kappa mixed opioid receptor agonist; 26 nmol/microliter/h) or morphine (a mu-opioid receptor agonist; 26 nmol/microliter/h) was investigated using high-performance liquid chromatography with electrochemical detection (HPLC-ED). Naloxone precipitated a withdrawal syndrome and decreased the levels of: dopamine (DA) in the cortex and striatum, 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum, homovanilic acid (HVA) in the striatum, limbic, midbrain, and pons/medulla regions in butorphanol-dependent rats. However, the levels of norepinephrine (NE), serotonin (5-hydroxytryptamine; 5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the regions studied were not affected by naloxone-precipitated withdrawal. In addition, naloxone increased the HVA/DA ratio in the cortex, while this ratio was reduced in the limbic, midbrain, and pons/medulla. The reduction of 5-HIAA/5-HT ratio was also detected in the limbic area. In the animals rendered dependent on morphine, the results obtained were similar to those of butorphanol-dependent rats except for changes of 5-HIAA levels in some brain regions. These results suggest that an alteration of dopaminergic neuron activity following a reduction of DA and its metabolites in specific brain regions (e.g., striatum, limbic, midbrain, and pons/medulla) play an important role in the expression of the opioid withdrawal syndrome. PMID:8743609

  11. Fatty acid amide hydrolase-dependent generation of antinociceptive drug metabolites acting on TRPV1 in the brain.

    Directory of Open Access Journals (Sweden)

    David A Barrière

    Full Text Available The discovery that paracetamol is metabolized to the potent TRPV1 activator N-(4-hydroxyphenyl-5Z,8Z,11Z,14Z-eicosatetraenamide (AM404 and that this metabolite contributes to paracetamol's antinociceptive effect in rodents via activation of TRPV1 in the central nervous system (CNS has provided a potential strategy for developing novel analgesics. Here we validated this strategy by examining the metabolism and antinociceptive activity of the de-acetylated paracetamol metabolite 4-aminophenol and 4-hydroxy-3-methoxybenzylamine (HMBA, both of which may undergo a fatty acid amide hydrolase (FAAH-dependent biotransformation to potent TRPV1 activators in the brain. Systemic administration of 4-aminophenol and HMBA led to a dose-dependent formation of AM404 plus N-(4-hydroxyphenyl-9Z-octadecenamide (HPODA and arvanil plus olvanil in the mouse brain, respectively. The order of potency of these lipid metabolites as TRPV1 activators was arvanil = olvanil>>AM404> HPODA. Both 4-aminophenol and HMBA displayed antinociceptive activity in various rodent pain tests. The formation of AM404, arvanil and olvanil, but not HPODA, and the antinociceptive effects of 4-aminophenol and HMBA were substantially reduced or disappeared in FAAH null mice. The activity of 4-aminophenol in the mouse formalin, von Frey and tail immersion tests was also lost in TRPV1 null mice. Intracerebroventricular injection of the TRPV1 blocker capsazepine eliminated the antinociceptive effects of 4-aminophenol and HMBA in the mouse formalin test. In the rat, pharmacological inhibition of FAAH, TRPV1, cannabinoid CB1 receptors and spinal 5-HT3 or 5-HT1A receptors, and chemical deletion of bulbospinal serotonergic pathways prevented the antinociceptive action of 4-aminophenol. Thus, the pharmacological profile of 4-aminophenol was identical to that previously reported for paracetamol, supporting our suggestion that this drug metabolite contributes to paracetamol's analgesic activity via

  12. Fatty Acid Amide Hydrolase-Dependent Generation of Antinociceptive Drug Metabolites Acting on TRPV1 in the Brain

    Science.gov (United States)

    Blomgren, Anders; Simonsen, Charlotte; Daulhac, Laurence; Libert, Frédéric; Chapuy, Eric; Etienne, Monique; Högestätt, Edward D.; Zygmunt, Peter M.; Eschalier, Alain

    2013-01-01

    The discovery that paracetamol is metabolized to the potent TRPV1 activator N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (AM404) and that this metabolite contributes to paracetamol’s antinociceptive effect in rodents via activation of TRPV1 in the central nervous system (CNS) has provided a potential strategy for developing novel analgesics. Here we validated this strategy by examining the metabolism and antinociceptive activity of the de-acetylated paracetamol metabolite 4-aminophenol and 4-hydroxy-3-methoxybenzylamine (HMBA), both of which may undergo a fatty acid amide hydrolase (FAAH)-dependent biotransformation to potent TRPV1 activators in the brain. Systemic administration of 4-aminophenol and HMBA led to a dose-dependent formation of AM404 plus N-(4-hydroxyphenyl)-9Z-octadecenamide (HPODA) and arvanil plus olvanil in the mouse brain, respectively. The order of potency of these lipid metabolites as TRPV1 activators was arvanil = olvanil>>AM404> HPODA. Both 4-aminophenol and HMBA displayed antinociceptive activity in various rodent pain tests. The formation of AM404, arvanil and olvanil, but not HPODA, and the antinociceptive effects of 4-aminophenol and HMBA were substantially reduced or disappeared in FAAH null mice. The activity of 4-aminophenol in the mouse formalin, von Frey and tail immersion tests was also lost in TRPV1 null mice. Intracerebroventricular injection of the TRPV1 blocker capsazepine eliminated the antinociceptive effects of 4-aminophenol and HMBA in the mouse formalin test. In the rat, pharmacological inhibition of FAAH, TRPV1, cannabinoid CB1 receptors and spinal 5-HT3 or 5-HT1A receptors, and chemical deletion of bulbospinal serotonergic pathways prevented the antinociceptive action of 4-aminophenol. Thus, the pharmacological profile of 4-aminophenol was identical to that previously reported for paracetamol, supporting our suggestion that this drug metabolite contributes to paracetamol’s analgesic activity via activation

  13. Metabolite Profiling of Diverse Rice Germplasm and Identification of Conserved Metabolic Markers of Rice Roots in Response to Long-Term Mild Salinity Stress

    Directory of Open Access Journals (Sweden)

    Myung Hee Nam

    2015-09-01

    Full Text Available The sensitivity of rice to salt stress greatly depends on growth stages, organ types and cultivars. Especially, the roots of young rice seedlings are highly salt-sensitive organs that limit plant growth, even under mild soil salinity conditions. In an attempt to identify metabolic markers of rice roots responding to salt stress, metabolite profiling was performed by 1H-NMR spectroscopy in 38 rice genotypes that varied in biomass accumulation under long-term mild salinity condition. Multivariate statistical analysis showed separation of the control and salt-treated rice roots and rice genotypes with differential growth potential. By quantitative analyses of 1H-NMR data, five conserved salt-responsive metabolic markers of rice roots were identified. Sucrose, allantoin and glutamate accumulated by salt stress, whereas the levels of glutamine and alanine decreased. A positive correlation of metabolite changes with growth potential and salt tolerance of rice genotypes was observed for allantoin and glutamine. Adjustment of nitrogen metabolism in rice roots is likely to be closely related to maintain the growth potential and increase the stress tolerance of rice.

  14. Brain Levels of the Neurotoxic Pyridinium Metabolite HPP+ and Extrapyramidal Symptoms in Haloperidol-Treated Mice

    OpenAIRE

    Crowley, James J; Ashraf-Khorassani, Mehdi; Castagnoli, Neal; Sullivan, Patrick F.

    2013-01-01

    The typical antipsychotic haloperidol is a highly effective treatment for schizophrenia but its use is limited by a number of serious, and often irreversible, motor side effects. These adverse drug reactions, termed extrapyramidal syndromes (EPS), result from an unknown pathophysiological mechanism. One theory relates to the observation that the haloperidol metabolite HPP+ (4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-pyridinium) is structurally similar to MPP+ (1-methyl-4-phenylpyrid...

  15. Herbal Extracts and Phytochemicals: Plant Secondary Metabolites and the Enhancement of Human Brain Function1

    OpenAIRE

    David O. Kennedy; Wightman, Emma L.

    2011-01-01

    Humans consume a wide range of foods, drugs, and dietary supplements that are derived from plants and which modify the functioning of the central nervous sytem (CNS). The psychoactive properties of these substances are attributable to the presence of plant secondary metabolites, chemicals that are not required for the immediate survival of the plant but which are synthesized to increase the fitness of the plant to survive by allowing it to interact with its environment, including pathogens an...

  16. Regional brain volumes, diffusivity, and metabolite changes after electroconvulsive therapy for severe depression

    DEFF Research Database (Denmark)

    Jørgensen, A.; Magnusson, P.; Hanson, Lars G.;

    2016-01-01

    , and metabolite changes in 19 patients receiving ECT for severe depression. Other regions of interest included the amygdala, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex, and hypothalamus. Patients received a 3T MR scan before ECT (TP1), 1 week (TP2), and 4 weeks (TP3) after ECT...... regulation, but due to their lack of correlation with the antidepressant effect, this remodeling does not appear to be directly underlying the antidepressant action of ECT...

  17. Shared Immune and Repair Markers During Experimental Toxoplasma Chronic Brain Infection and Schizophrenia.

    Science.gov (United States)

    Tomasik, Jakub; Schultz, Tracey L; Kluge, Wolfgang; Yolken, Robert H; Bahn, Sabine; Carruthers, Vern B

    2016-03-01

    Chronic neurologic infection with Toxoplasma gondii is relatively common in humans and is one of the strongest known risk factors for schizophrenia. Nevertheless, the exact neuropathological mechanisms linking T gondii infection and schizophrenia remain unclear. Here we utilize a mouse model of chronic T gondii infection to identify protein biomarkers that are altered in serum and brain samples at 2 time points during chronic infection. Furthermore, we compare the identified biomarkers to those differing between "postmortem" brain samples from 35 schizophrenia patients and 33 healthy controls. Our findings suggest that T gondii infection causes substantial and widespread immune activation indicative of neural damage and reactive tissue repair in the animal model that partly overlaps with changes observed in the brains of schizophrenia patients. The overlapping changes include increases in C-reactive protein (CRP), interleukin-1 beta (IL-1β), interferon gamma (IFNγ), plasminogen activator inhibitor 1 (PAI-1), tissue inhibitor of metalloproteinases 1 (TIMP-1), and vascular cell adhesion molecule 1 (VCAM-1). Potential roles of these factors in the pathogenesis of schizophrenia and toxoplasmosis are discussed. Identifying a defined set of markers shared within the pathophysiological landscape of these diseases could be a key step towards understanding their specific contributions to pathogenesis. PMID:26392628

  18. Will Posttranslational Modifications of Brain Proteins Provide Novel Serological Markers for Dementias?

    Directory of Open Access Journals (Sweden)

    Y. Wang

    2012-01-01

    Full Text Available Drug development for dementias is significantly hampered by the lack of easily accessible biomarkers. Fluid biomarkers of dementias provide indications of disease stage, but have little prognostic value, cannot detect early pathological changes, and can only be measured in CSF (cerebrospinal fluid which significantly limits their applicability. In contrast, imaging based biomarkers can provide indications of probability of disease progression, yet are limited in applicability due to cost, radiation and radio-tracers. These aspects highlight the need for other approaches to the development of biomarkers of dementia, which should focus on not only providing information about pathological changes, but also on being measured easily and reproducibly. For other diseases, focus on development of assays monitoring highly specific protease-generated cleavage fragments of proteins has provided assays, which in serum or plasma have the ability to predict early pathological changes. Proteolytic processing of brain proteins, such as tau, APP, and α-synuclein, is a key pathological event in dementias. Here, we speculate that aiming biomarker development for dementias at detecting small brain protein degradation fragments of generated by brain-derived proteases specifically in blood samples could lead to the development of novel markers of disease progression, stage and importantly of treatment efficacy.

  19. Quantitation of normal metabolite concentrations in six brain regions by in-vivo 1 H-MR spectroscopy

    OpenAIRE

    Minati Ludovico; Aquino Domenico; Bruzzone Maria; Erbetta Alessandra

    2010-01-01

    This study examined the concentrations of brain metabolites visible to in-vivo 1 H-Magnetic Resonance Spectroscopy ( 1 H-MRS) at 1.5 T in a sample of 28 normal subjects. Quantitation was attempted for inositol compounds, choline units, total creatine and N-acetyl moieties, using open-source software. Six brain regions were considered: frontal and parietal white matter, medial temporal lobe, thalamus, pons and cerebellum. Absolute concentrations were derived using tissue water as an internal r...

  20. Brain metabolite levels in recently sober individuals with alcohol use disorder: Relation to drinking variables and relapse.

    Science.gov (United States)

    Zahr, Natalie M; Carr, Rebecca A; Rohlfing, Torsten; Mayer, Dirk; Sullivan, Edith V; Colrain, Ian M; Pfefferbaum, Adolf

    2016-04-30

    Magnetic resonance spectroscopy (MRS) studies in alcohol use disorder (AUD) typically report lower levels of N-acetylaspartate (NAA) and choline-containing compounds (Cho) in several brain regions. Metabolite levels, however, are labile and can be affected by several competing factors, some related to drinking variables.. This in vivo MRS study included 20 recently sober (19.6±12.6 days) individuals with AUD and 15 controls. MRS was performed in single voxels placed in frontal white matter and thalamic regions using Constant-Time Point Resolved Spectroscopy (CT-PRESS) for absolute quantification of NAA, Cho, total creatine (tCr), and glutamate (Glu). A trend toward a thalamic NAA deficit in the total AUD group compared with controls was attributable to the subgroup of alcoholics who relapsed 3 or so months after scanning. In the total AUD group, frontal and thalamic NAA and Cho levels were lower with more recent drinking; frontal and thalamic Cho levels were also lower in AUD individuals with past stimulant abuse. Thalamic Cho levels were higher in binge-drinking AUD individuals and in those with longer length of alcohol dependence. MRS-visible metabolite peaks appear to be modulated by variables related to drinking behaviors, suggesting a sensitivity of MRS in tracking and predicting the dynamic course of alcoholism. PMID:27035062

  1. Motion compensation for brain PET imaging using wireless MR active markers in simultaneous PET-MR: phantom and non-human primate studies

    OpenAIRE

    Huang, Chuan; Ackerman, Jerome L.; Petibon, Yoann; Normandin, Marc D.; Brady, Thomas J.; El Fakhri, Georges; Ouyang, Jinsong

    2014-01-01

    Brain PET scanning plays an important role in the diagnosis, prognostication and monitoring of many brain diseases. Motion artifacts from head motion are one of the major hurdles in brain PET. In this work, we propose to use wireless MR active markers to track head motion in real time during a simultaneous PET-MR brain scan and incorporate the motion measured by the markers in the listmode PET reconstruction.

  2. TTF-1 may not be a Reliable Marker for Differentiating Metastasis from Brain Tumors

    Directory of Open Access Journals (Sweden)

    Betül ÜNAL

    2014-09-01

    Full Text Available Objective: TTF-1 is widely used as an immunohistochemical marker of lung and thyroid tumors. However, TTF-1 expression has been described in tumors from other sites. The presence of TTF-1 expression in primary brain tumors is largely unclear and has not been clearly specified yet. We characterized expression of two TTF-1 clones in primary brain tumors with relevance to tumor types and grades. Material and Method: We studied immunohistochemistry with tissue micro-array, using both clones (8G7G3/1 and SPT24 in 45 primary brain tumors of different types and grades. Our cases consisted of 1 grade I, 7 grade II, 4 grade III, 20 grade IV astrocytic tumors; 9 meningiomas, 2 oligodendrogliomas, 1 schwannoma and 1 medulloblastoma. Results: We have found TTF-1 nuclear staining using the SPT24 clone in 4 cases (3 cases were grade IV and 1 was grade III. Focal and weak staining was seen in three cases and moderate-strong and diffuse staining was seen in one case. All the tumors were negative with clone 8G7G3/1. Clone SPT24 was more sensitive but less specific. Conclusion: TTF-1 can also be expressed in primary brain tumors, particularly grade III to IV tumors. TTF-1 expression was a rare finding in previous studies, however strong and diffuse staining was not observed until today. We think that TTF-1 nuclear expression in high-grade astrocytic tumors cannot rule out primaries even when diffuse and strong staining. Clinical and pathological parameters should be evaluated together.

  3. Brain metabolite changes on proton magnetic resonance spectroscopy in children with poorly controlled type 1 diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Sarac, K.; Alkan, A.; Baysal, T. [Inonu University School of Medicine, Department of Radiology, Malatya (Turkey); Akinci, A.; Aslan, M. [Inonu University School of Medicine, Department of Paediatric Endocrinology, Malatya (Turkey); Oezcan, C. [Inonu University School of Medicine, Department of Neurology, Malatya (Turkey)

    2005-07-01

    The metabolite changes in the brains of children with poorly controlled type 1 diabetes mellitus (DM) were investigated by proton magnetic resonance spectroscopy (MRS). A total of 30 subjects and 14 age-matched healthy volunteers underwent single-voxel MRS (TE: 136). The duration of disease, medication, presence of hypoglycaemia episodes and the level of haemoglobin A1C (HbA1C) in the patients were noted. Voxels were placed in the pons, left basal ganglion (LBG) and left posterior parietal white matter (PPWM). N-acetylaspartate (NAA)/creatinine (Cr) and choline (Cho)/Cr ratios were calculated. The average HbA1c level was 11.9{+-}3.4 (8.2-19.4). The average number of keto-acidosis episodes was 1.9{+-}2.2 (0-9) and the average number of daily insulin injections was 2.8{+-}0.97 (2-4). MRS revealed lower NAA/Cr and Cho/Cr ratios in the pons and lower NAA/Cr ratio in the PPWM of patients with DM than in control subjects. No significant correlation was observed between the number of hypoglycaemia episodes and metabolite ratios. Metabolic abnormalities have been observed by MRS in the brain of poorly controlled type 1 DM children. These metabolic changes, in particular in the pons region, include a decrease in NAA, indicating neuronal loss or functional impairment, and likely explanations for a decrease in Cho may be dynamic changes in membrane lipids and/or decreased membrane turnover. (orig.)

  4. Brain metabolite changes on proton magnetic resonance spectroscopy in children with poorly controlled type 1 diabetes mellitus

    International Nuclear Information System (INIS)

    The metabolite changes in the brains of children with poorly controlled type 1 diabetes mellitus (DM) were investigated by proton magnetic resonance spectroscopy (MRS). A total of 30 subjects and 14 age-matched healthy volunteers underwent single-voxel MRS (TE: 136). The duration of disease, medication, presence of hypoglycaemia episodes and the level of haemoglobin A1C (HbA1C) in the patients were noted. Voxels were placed in the pons, left basal ganglion (LBG) and left posterior parietal white matter (PPWM). N-acetylaspartate (NAA)/creatinine (Cr) and choline (Cho)/Cr ratios were calculated. The average HbA1c level was 11.9±3.4 (8.2-19.4). The average number of keto-acidosis episodes was 1.9±2.2 (0-9) and the average number of daily insulin injections was 2.8±0.97 (2-4). MRS revealed lower NAA/Cr and Cho/Cr ratios in the pons and lower NAA/Cr ratio in the PPWM of patients with DM than in control subjects. No significant correlation was observed between the number of hypoglycaemia episodes and metabolite ratios. Metabolic abnormalities have been observed by MRS in the brain of poorly controlled type 1 DM children. These metabolic changes, in particular in the pons region, include a decrease in NAA, indicating neuronal loss or functional impairment, and likely explanations for a decrease in Cho may be dynamic changes in membrane lipids and/or decreased membrane turnover. (orig.)

  5. Association of white-matter lesions with brain atrophy markers: the three-city Dijon MRI study

    International Nuclear Information System (INIS)

    Background: Brain atrophy and white-matter lesions (WML) are common features at cerebral MRI of both normal and demented elderly people. In a population-based study of 1, 792 elderly subjects aged 65-80 years, free of dementia, who had a cerebral MRI at entry, we investigated the relationship between WML volume and brain atrophy markers estimated by hippocampal, gray matter (GM) and cerebrospinal fluid (CSF) volumes. Methods: An automated algorithm of detection and quantification of WML was developed, and voxel-based morphometry methods were used to estimate GM, CSF and hippocampal volumes. To evaluate the relation between those volumes and WML load, we used analysis of covariance and multiple linear regression models adjusting for potential confounders and total intracranial volumes. Results: Age was highly correlated with WML load and all brain atrophy markers. Total WML volume was negatively associated with both GM (β = -0.03, p ≤ 0.0001) and hippocampal volumes (β = -0.75, p = 0.0009) and positively with CSF volumes (beta 0.008, p = 0.02) after controlling for sex, age, education level, hypertension and apolipoprotein E genotype. Evidence for a relationship between brain atrophy markers and WML was stronger for periventricular WML. We found that the relationship between WML and hippocampal volumes was independent of other brain tissue volumes. Conclusion: These results suggest that, in the brain of non demented elderly subjects, degenerative processes and vascular changes co-occur and are related independently of vascular risk factors. (authors)

  6. Association between brain natriuretic peptide, markers of inflammation and the objective and subjective response to cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Brouwers, Corline; Versteeg, Henneke; Meine, Mathias;

    2014-01-01

    Introduction: Studies suggest that cardiac resynchronization therapy (CRT) can induce a decrease in brain natriuretic peptide (BNP) and systemic inflammation, which may be associated with CRT-response. However, the evidence is inconclusive. We examined levels of BNP and inflammatory markers from ...

  7. Somatic transposition in the brain has the potential to influence the biosynthesis of metabolites involved in Parkinson’s disease and schizophrenia

    Directory of Open Access Journals (Sweden)

    Abrusán György

    2012-11-01

    Full Text Available Abstract It has been recently discovered that transposable elements show high activity in the brain of mammals, however, the magnitude of their influence on its functioning is unclear so far. In this paper, I use flux balance analysis to examine the influence of somatic retrotransposition on brain metabolism, and the biosynthesis of its key metabolites, including neurotransmitters. The analysis shows that somatic transposition in the human brain can influence the biosynthesis of more than 250 metabolites, including dopamine, serotonin and glutamate, shows large inter-individual variability in metabolic effects, and may contribute to the development of Parkinson’s disease and schizophrenia. Reviewers This article was reviewed by Dr Kenji Kojima (nominated by Dr Jerzy Jurka and Dr Eugene Koonin.

  8. Effects of Various Kynurenine Metabolites on Respiratory Parameters of Rat Brain, Liver and Heart Mitochondria

    OpenAIRE

    Baran, Halina; Staniek, Katrin; Bertignol-Spörr, Melanie; Attam, Martin; Kronsteiner, Carina; Kepplinger, Berthold

    2016-01-01

    Previously, we demonstrated that the endogenous glutamate receptor antagonist kynurenic acid dose-dependently and significantly affected rat heart mitochondria. Now we have investigated the effects of L-tryptophan, L-kynurenine, 3-hydroxykynurenine and kynurenic, anthranilic, 3-hydroxyanthranilic, xanthurenic and quinolinic acids on respiratory parameters (ie, state 2, state 3), respiratory control index (RC) and ADP/oxygen ratio in brain, liver and heart mitochondria of adult rats. Mitochond...

  9. Effects of traumatic brain injury on cognitive functioning and cerebral metabolites in HIV-infected individuals

    OpenAIRE

    Lin, Kenny; Taylor, Michael J.; Heaton, Robert; Franklin, Donald; Jernigan, Terry; Fennema-Notestine, Christine; McCutchan, Allen; Atkinson, J. Hampton; Ellis, Ronald J.; McArthur, Justin; Morgello, Susan; Simpson, David; Collier, Ann C.; Marra, Christina; Gelman, Benjamin

    2011-01-01

    We explored the possible augmenting effect of traumatic brain injury (TBI) history on HIV (human immunodeficiency virus) associated neurocognitive complications. HIV-infected participants with self-reported history of definite TBI were compared to HIV patients without TBI history. Groups were equated for relevant demographic and HIV-associated characteristics. The TBI group evidenced significantly greater deficits in executive functioning and working memory. N-acetylaspartate, a putative mark...

  10. Boron neutron capture therapy of brain tumors: investigation of urinary metabolites and oxidation products of sodium borocaptate by electrospray ionization mass spectrometry.

    Science.gov (United States)

    Gibson, C R; Staubus, A E; Barth, R F; Yang, W; Kleinholz, N M; Jones, R B; Green-Church, K; Tjarks, W; Soloway, A H

    2001-12-01

    Boron neutron capture therapy (BNCT) is based on a nuclear capture reaction that occurs when boron-10, a stable isotope, is irradiated with low energy neutrons to produce high-energy alpha particles and recoiling lithium-7 nuclei. The purpose of the present study was to determine what urinary metabolites, if any, could be detected in patients with brain tumors who were given sodium borocaptate (BSH), a drug that has been used clinically for BNCT. BSH was infused intravenously over a 1-h time period at doses of 26.5, 44.1, or 88.2 mg/kg of body weight to patients with high-grade brain tumors. Electrospray ionization mass spectrometry has been used to investigate possible urinary metabolites of BSH. Chemical and instrument conditions were established to detect BSH and its possible metabolites in both positive and negative electrospray ionization modes. Using this methodology, boronated ions were found in patients' urine samples that appeared to be consistent with the following chemical structures: BSH sulfenic acid (BSOH), BSH sulfinic acid (BSO(2)H), BSH disulfide (BSSB), BSH thiosulfinate (BSOSB), and a BSH-S-cysteine conjugate (BSH-CYS). Although BSH has been used clinically for BNCT since the late 1960s, this is the first report of specific biotransformation products following administration to patients. Further studies will be required to determine both the biological significance of these metabolites and whether any of these accumulate in significant amounts in brain tumors. PMID:11717178

  11. Quantitative multivoxel proton MR spectroscopy study of brain metabolites in patients with amnestic mild cognitive impairment: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Zhong-Xian; Cheng, Xiao-Fang; Xu, Zhi-Feng; Cao, Zhen; Xiao, Ye-Yu; You, Ke-Zeng; Liu, Yan-Yan [Medical College of Shantou University, Department of Medical Imaging, The Second Affiliated Hospital, Shantou (China); Huo, Shan-Shan [Science College of Shantou University, Department of Physics, Shantou (China); Zeng, Jie-Xia; Chen, Wei [Medical College of Shantou University, Department of Neurology, The Second Affiliated Hospital, Shantou (China); Wu, Ren-Hua [Medical College of Shantou University, Department of Medical Imaging, The Second Affiliated Hospital, Shantou (China); Medical College of Shantou University, Provincial Key Laboratory of Medical Molecular Imaging, Guangdong, Shantou (China)

    2012-05-15

    The purpose of this study is to investigate brain metabolic changes in patients with amnestic mild cognitive impairment (aMCI) using multivoxel proton MR spectroscopy ({sup 1}H-MVS). Fourteen aMCI patients and fifteen healthy control subjects participated in this experiment. All MR measurements were acquired using a 1.5-T GE scanner. {sup 1}H-MVS point resolved spectroscopy (2D PROBE-CSI PRESS) pulse sequence (TE = 35 ms; TR = 1,500 ms; phase x frequency, 18 x 18) was used for acquiring MRS data. All data were post-processed using Spectroscopy Analysis by General Electric software and linear combination of model (LCModel). The absolute concentrations of N-acetylaspartate (NAA), choline (Cho), myoinositol (MI), creatine (Cr), and the metabolite ratios of NAA/Cr, Cho/Cr, MI/Cr, and NAA/MI were measured bilaterally in the posterior cingulate gyrus (PCG), inferior precuneus (Pr), paratrigonal white matter (PWM), dorsal thalamus (DT), and lentiform nucleus (LN). Patients with aMCI displayed significantly lower NAA levels in the bilateral PCG (p < 0.01), PWM (p < 0.05), and left inferior Pr (p < 0.05). The metabolite ratio of NAA/MI was decreased in the bilateral PCG (p < 0.01) and PWM (p < 0.05) and in the left DT (p < 0.01). NAA/Cr was decreased in the left PCG (p < 0.01), DT (p < 0.05), right PWM (p < 0.05), and LN (p < 0.05). However, MI/Cr was elevated in the right PCG (p < 0.01) and left PWM (p < 0.05). Significantly increased Cho level was also evident in the left PWM (p < 0.05). Our observations of decreased NAA, NAA/Cr, and NAA/MI, in parallel with increased Cho and MI/Cr might be characteristic of aMCI patients. (orig.)

  12. Quantitative multivoxel proton MR spectroscopy study of brain metabolites in patients with amnestic mild cognitive impairment: a pilot study

    International Nuclear Information System (INIS)

    The purpose of this study is to investigate brain metabolic changes in patients with amnestic mild cognitive impairment (aMCI) using multivoxel proton MR spectroscopy (1H-MVS). Fourteen aMCI patients and fifteen healthy control subjects participated in this experiment. All MR measurements were acquired using a 1.5-T GE scanner. 1H-MVS point resolved spectroscopy (2D PROBE-CSI PRESS) pulse sequence (TE = 35 ms; TR = 1,500 ms; phase x frequency, 18 x 18) was used for acquiring MRS data. All data were post-processed using Spectroscopy Analysis by General Electric software and linear combination of model (LCModel). The absolute concentrations of N-acetylaspartate (NAA), choline (Cho), myoinositol (MI), creatine (Cr), and the metabolite ratios of NAA/Cr, Cho/Cr, MI/Cr, and NAA/MI were measured bilaterally in the posterior cingulate gyrus (PCG), inferior precuneus (Pr), paratrigonal white matter (PWM), dorsal thalamus (DT), and lentiform nucleus (LN). Patients with aMCI displayed significantly lower NAA levels in the bilateral PCG (p < 0.01), PWM (p < 0.05), and left inferior Pr (p < 0.05). The metabolite ratio of NAA/MI was decreased in the bilateral PCG (p < 0.01) and PWM (p < 0.05) and in the left DT (p < 0.01). NAA/Cr was decreased in the left PCG (p < 0.01), DT (p < 0.05), right PWM (p < 0.05), and LN (p < 0.05). However, MI/Cr was elevated in the right PCG (p < 0.01) and left PWM (p < 0.05). Significantly increased Cho level was also evident in the left PWM (p < 0.05). Our observations of decreased NAA, NAA/Cr, and NAA/MI, in parallel with increased Cho and MI/Cr might be characteristic of aMCI patients. (orig.)

  13. Simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell cultures and in sub-regions of guinea pig brain

    DEFF Research Database (Denmark)

    Schou-Pedersen, Anne Marie Voigt; Hansen, Stine Normann; Tveden-Nyborg, Pernille;

    2016-01-01

    In the present paper, we describe a validated chromatographic method for the simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell culture and in sub-regions of the guinea pig brain. Electrochemical...... intracellular and extracellular amounts of monoamine neurotransmitters and their metabolites in guinea pig frontal cortex and hippocampal primary neuronal cell cultures. Noradrenaline, dopamine and serotonin were found to be in a range from 0.31 to 1.7 pmol per 2 million cells intracellularly, but only the...

  14. CT scanning of the brain and lumbar CSF monoamine metabolites in spinocerebellar degenerative disorders

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Hidenao; Kanazawa, Ichiro; Nakanishi, Takao; Kuramoto, Kenmei (Tsukuba Univ., Sakura, Ibaraki (Japan))

    1984-08-01

    Eight patients with parenchymatous cerebellar degeneration (PCD) group (3 with late cortical cerebellar atrophy and 5 with Holmes' hereditary ataxia), 14 with olivo-ponto-cerebellar atrophy (OPCA) group (4 with Shy-Drager syndrome, 6 with OPCA without family history and 4 with Menzel type SCS), 15 with Parkinson's disease and 44 control with other neurological diseases were studied. In all the spinocerebellar degenerative disorders (SCD) cases, CVI values corresponding to the cerebellar atrophy were definitely reduced. On the other hand, PVI values corresponding to the pontine atrophy were only significantly decreased in OPCA group. However, since there were several cases showing only questionable pontine atrophy, it seems difficult to clearly differentiate individual OPCA cases from other SCD cases on CT films alone. Concerning monoamine metabolites in CSF, it was noted that a significant reduction of HVA and total MHPG was found in the OPCA group. Among them, the patients with overt autonomic failure showed the lowest HVA level and the cases of Menzel type of SCD showed a slight reduction of HVA but an unexpected elevation of free MHPG values. The cases of Parkinson's disease showed a definite reduction of HVA. On the other hand, the cases of PCD group showed no significant difference against controls. 5-HIAA levels were not significantly different among the SCD subgroups.

  15. CT scanning of the brain and lumber CSF monoamine metabolites in spinocerebellar degenerative disorders

    International Nuclear Information System (INIS)

    Eight patients with parenchymatous cerebellar degeneration (PCD) group (3 with late cortical cerebellar atrophy and 5 with Holmes' hereditary ataxia), 14 with olivo-ponto-cerebellar atrophy (OPCA) group (4 with Shy-Drager syndrome, 6 with OPCA without family history and 4 with Menzel type SCS), 15 with Parkinson's disease and 44 control with other neurological diseases were studied. In all the spinocerebellar degenerative disorder s (SCD) cases, CVI values corresponding to the cerebellar atrophy were definitely reduced. On the other hand, PVI values corresponding to the pontine atrophy were only significantly decreased in OPCA group. However, since there were several cases showing only questionable pontine atrpphy, it seems difficult to clearly differentiate individual OPCA cases from other SCD cases on CT films alone. Concerning monoamine metabolites in CSF, it was noted that a significant reduction of HVA and total MHPG was found in the OPCA group. Among them, the patients with overt autonomic failure showed the lowest HVA level and the cases of Menzel type of SCD showed a slight reduction of HVA but an unexpected elevation of free MHPG values. The cases of Parkinson's disease showed a definite reduction of HVA. On the other hand, the cases of PCD group showed no significant difference against controls. 5-HIAA levels were not significantly different among the SCD subgroups. (J.P.N.)

  16. Brain metabolite changes in alcoholism: Localized proton magnetic resonance spectroscopy study of the occipital lobe

    Energy Technology Data Exchange (ETDEWEB)

    Modi, Shilpi; Bhattacharya, Manisha; Kumar, Pawan [NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences (DRDO), Lucknow Road, Timarpur, Delhi 110054 (India); Deshpande, Smita N. [Department of Psychiatry, Dr. Ram Manohar Lohia Hospital, New Delhi (India); Tripathi, Rajendra Prasad [NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences (DRDO), Lucknow Road, Timarpur, Delhi 110054 (India); Khushu, Subash, E-mail: skhushu@yahoo.com [NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences (DRDO), Lucknow Road, Timarpur, Delhi 110054 (India)

    2011-07-15

    Chronic alcoholism is associated with altered brain metabolism, morphology and cognitive abilities. Besides deficits in higher order cognitive functions, alcoholics also show a deficit in the processing of basic sensory information viz. visual stimulation. To assess the metabolic changes associated with this deficit, {sup 1}H MRS was carried out in the occipital lobe of alcohol dependents. A significant increase in Cho/Cr ratio (p < 0.015) was observed in occipital lobe in the alcoholic group indicating altered cell membrane metabolism, which may probably be associated with the alterations in the cognitive abilities associated with vision.

  17. Region-specific effects on brain metabolites of hypoxia and hyperoxia overlaid on cerebral ischemia in young and old rats: a quantitative proton magnetic resonance spectroscopy study

    Directory of Open Access Journals (Sweden)

    Giuliani Patricia

    2010-02-01

    Full Text Available Abstract Background Both hypoxia and hyperoxia, deregulating the oxidative balance, may play a role in the pathology of neurodegenerative disorders underlain by cerebral ischemia. In the present study, quantitative proton magnetic resonance spectroscopy was used to evaluate regional metabolic alterations, following a 24-hour hypoxic or hyperoxic exposure on the background of ischemic brain insult, in two contrasting age-groups of rats: young - 3 months old and aged - 24 months old. Methods Cerebral ischemia was induced by ligation of the right common carotid artery. Concentrations of eight metabolites (alanine, choline-containing compounds, total creatine, γ-aminobutyric acid, glutamate, lactate, myo-inositol and N-acetylaspartate were quantified from extracts in three different brain regions (fronto-parietal and occipital cortices and the hippocampus from both hemispheres. Results In the control normoxic condition, there were significant increases in lactate and myo-inositol concentrations in the hippocampus of the aged rats, compared with the respective values in the young ones. In the ischemia-hypoxia condition, the most prevalent changes in the brain metabolites were found in the hippocampal regions of both young and aged rats; but the effects were more evident in the aged animals. The ischemia-hyperoxia procedure caused less dedicated changes in the brain metabolites, which may reflect more limited tissue damage. Conclusions We conclude that the hippocampus turns out to be particularly susceptible to hypoxia overlaid on cerebral ischemia and that old age further increases this susceptibility.

  18. The prognostic value of multivoxel magnetic resonance spectroscopy determined metabolite levels in white and grey matter brain tissue for adverse outcome in term newborns following perinatal asphyxia

    Energy Technology Data Exchange (ETDEWEB)

    Doormaal, Pieter Jan van [University Medical Center Groningen and University of Groningen, Department of Pediatrics, Division of Neonatology, Groningen (Netherlands); Meander Medical Center Amersfoort, Department of Radiology, PO Box 1502, Amersfoort (Netherlands); Meiners, Linda C.; Sijens, Paul E. [University Medical Center Groningen and University of Groningen, Department of Radiology, Groningen (Netherlands); Horst, Hendrik J. ter; Veere, Christa N. van der [University Medical Center Groningen and University of Groningen, Department of Pediatrics, Division of Neonatology, Groningen (Netherlands)

    2012-04-15

    Magnetic resonance spectroscopy can identify brain metabolic changes in perinatal asphyxia by providing ratios of metabolites, such as choline (Cho), creatine (Cr), N-acetyl aspartate (NAA) and lactate (Lact) [Cho/Cr, Lact/NAA, etc.]. The purpose of this study was to quantify the separate white and grey matter metabolites in a slab cranial to the ventricles and relate these to the outcome. A standard 2D-chemical shift imaging protocol was used for measuring a transverse volume of interest located cranial to the ventricles allowing for direct comparison of the metabolites in white and grey matter brain tissue in 24 term asphyxiated newborns aged 3 to 16 days. Cho, NAA and Lact showed significant differences between four subgroups of asphyxiated infants with more and less favourable outcomes. High levels of Cho and Lact in the grey matter differentiated non-survivors from survivors (P = 0.003 and P = 0.017, respectively). In perinatal asphyxia the levels of Cho, NAA and Lact in both white and grey matter brain tissue are affected. The levels of Cho and Lact measured in the grey matter are the most indicative of survival. It is therefore advised to include grey matter brain tissue in the region of interest examined by multivoxel MR spectroscopy. (orig.)

  19. Identification of brain metabolites by magnetic resonance spectroscopy in MND/ALS.

    Science.gov (United States)

    Knight, J M; Jones, A P; Redmond, J P; Shaw, I C

    1996-08-01

    Magnetic resonance spectroscopy (MRS) has provided a novel means of studying the brain biochemistry of motor neurone disease/amyotrophic lateral sclerosis (MND/ALS) patients in vivo in situ. Previous studies have demonstrated changes in the ratios of areas under specific spectral peaks in MND/ALS patients (Jones et al., 1995). However, the significance of such findings cannot be fully elucidated without first ascertaining the biochemical identity of each peak. Each peak in a MRS spectrum corresponds to the resonance of specific protons in a particular chemical environment. Many biochemicals contain similar protons in similar environments so it is possible that a single spectral peak could represent protons from more than one biochemical. In this study of major brain MRS peaks we have demonstrated that peaks are potentially composed of a number of protons from different chemicals. For example, the peak at chemical shift 2.01 ppm, conventionally recognised as the neurotransmitter N-acetyl aspartate, may actually be a result of the protons of the N-acetyl moiety (Frahm et al., 1991). We have consequently shown that other N-acetylated compounds such as N-acetyl glutamate are also capable of producing a peak here, whereas their non-acetylated derivatives are not. We have also shown GABA is capable of producing a peak at chemical shift 3.00 ppm, a peak which is generally assigned to creatine/phosphocreatine. These findings have important implications in the identification of spectral peaks in MRS studies and in the interpretation of spectral differences between MND patients and controls. PMID:8899668

  20. Age-related differences in metabolites in the posterior cingulate cortex and hippocampus of normal ageing brain: A 1H-MRS study

    International Nuclear Information System (INIS)

    Objective: To study age-related metabolic changes in N-acetylaspartate (NAA), total creatine (tCr), choline (Cho) and myo-inositol (Ins). Materials and methods: Proton magnetic resonance spectroscopy (1H-MRS) was performed in the posterior cingulate cortex (PCC) and the left hippocampus (HC) of 90 healthy subjects (42 women and 48 men aged 18–76 years, mean ± SD, 48.4 ± 16.8 years). Both metabolite ratios and absolute metabolite concentrations were evaluated. Analysis of covariance (ANCOVA) and linear regression were used for statistical analysis. Results: Metabolite ratios Ins/tCr and Ins/H2O were found significantly increased with age in the PCC (P 2O was only observed in the PCC (P 1H-MRS results in these specific brain regions can be important to differentiate normal ageing from age-related pathologies such as mild cognitive impairment (MCI) and Alzheimer's disease.

  1. Data supporting the rat brain sample preparation and validation assays for simultaneous determination of 8 neurotransmitters and their metabolites using liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Wojnicz, Aneta; Ortiz, José Avendaño; Casas, Ana I; Freitas, Andiara E; López, Manuela G; Ruiz-Nuño, Ana

    2016-06-01

    The data presented in this article supports the rat brain sample preparation procedure previous to its injection into the liquid chromatography-tandem mass spectrometry (LC-MS/MS) system to monitor levels of adrenaline, noradrenaline, glutamic acid, γ-aminobutyric acid, dopamine, 5-hydroxytryptamine, 5-hydroxyindole acetic acid, and 3-methoxy-4-hydroxyphenylglycol. In addition, we describe the method validation assays (such as calibration curve, lower limit of quantification, precision and accuracy intra- and inter-day, selectivity, extraction recovery and matrix effect, stability, and carry-over effect) according to the United States Food and Drug Administration and European Medicine Agency to measure in one step different neurotransmitters and their metabolites. The data supplied in this article is related to the research study entitled: "Simultaneous determination of 8 neurotransmitters and their metabolite levels in rat brain using liquid chromatography in tandem with mass spectrometry: application to the murine Nrf2 model of depression" (Wojnicz et al. 2016) [1]. PMID:27054183

  2. Biogenic amines and their metabolites are differentially affected in the Mecp2-deficient mouse brain

    Directory of Open Access Journals (Sweden)

    Villard Laurent

    2011-05-01

    Full Text Available Abstract Background Rett syndrome (RTT, MIM #312750 is a severe neurological disorder caused by mutations in the X-linked methyl-CpG binding protein 2 (MECP2 gene. Female patients are affected with an incidence of 1/15000 live births and develop normally from birth to 6-18 months of age before the onset of deficits in autonomic, cognitive, motor functions (stereotypic hand movements, impaired locomotion and autistic features. Studies on Mecp2 mouse models, and specifically null mice, revealed morphological and functional alterations of neurons. Several functions that are regulated by bioaminergic nuclei or peripheral ganglia are impaired in the absence of Mecp2. Results Using high performance liquid chromatography, combined with electrochemical detection (HPLC/EC we found that Mecp2-/y mice exhibit an alteration of DA metabolism in the ponto-bulbar region at 5 weeks followed by a more global alteration of monoamines when the disease progresses (8 weeks. Hypothalamic measurements suggest biphasic disturbances of norepinephrine and serotonin at pathology onset (5 weeks that were found stabilized later on (8 weeks. Interestingly, the postnatal nigrostriatal dopaminergic deficit identified previously does not parallel the reduction of the other neurotransmitters investigated. Finally, dosage in cortical samples do not suggest modification in the monoaminergic content respectively at 5 and 8 weeks of age. Conclusions We have identified that the level of catecholamines and serotonin is differentially affected in Mecp2-/y brain areas in a time-dependent fashion.

  3. Early-life exercise may promote lasting brain and metabolic health through gut bacterial metabolites.

    Science.gov (United States)

    Mika, Agnieszka; Fleshner, Monika

    2016-02-01

    The 100 trillion microorganisms residing within our intestines contribute roughly 5 million additional genes to our genetic gestalt, thus posing the potential to influence many aspects of our physiology. Microbial colonization of the gut shortly after birth is vital for the proper development of immune, neural and metabolic systems, while sustaining a balanced, diverse gut flora populated with beneficial bacteria is necessary for maintaining optimal function of these systems. Although symbiotic host-microbial interactions are important throughout the lifespan, these interactions can have greater and longer lasting impacts during certain critical developmental periods. A better understanding of these sensitive periods is necessary to improve the impact and effectiveness of health-promoting interventions that target the microbial ecosystem. We have recently reported that exercise initiated in early life increases gut bacterial species involved in promoting psychological and metabolic health. In this review, we emphasize the ability of exercise during this developmentally receptive time to promote optimal brain and metabolic function across the lifespan through microbial signals. PMID:26647967

  4. (S)- and (R)-[11C]nicotine and the metabolite (R/S)-[11C]cotinine. Preparation, metabolite studies and in vivo distribution in the human brain using PET

    International Nuclear Information System (INIS)

    In order to investigate [11C]nicotine binding and metabolism in the living human brain by PET, routine protocols were developed for the preparation and purification of (S)-and (R)-[11C]nicotine and the metabolite (R/S)-[11C]cotinine. (S)- and (R)-[11C]nicotine were prepared by N-methylation with [11C]methyl iodide of the appropriate secondary amine, which was liberated in situ by 2,2,6,6,-tetramethylpiperidine (TMP) from its corresponding biscamsylate-salt. (R/S)-[11C]Cotinine was prepared by N-methylation of the amide precursor using tetrabutylammonium hydroxide as a phase transfer catalyst. Straight-phase semipreparative HPLC was in all purifications found to be superior to reversed-phase since the contamination by the norcompounds was eliminated. Reaction in acetonitrile for both (S)- and (R)-[11C]nicotine and (R/S)-[11C]cotinine with subsequent straight-phase HPLC purification resulted in 35-45% radiochemical yield with a total synthesis time of 30-35 min, a specific radioactivity of 1000-1500 Ci/mmol (37-55 GBq/μmol, EOS) and a radiochemical purity >99%. The uptake and distribution of these tracers in the human brain was studied in healthy volunteers by PET. The metabolite (R/S)-[11C]cotinine did not cross the blood-brain barrier to any significant degree. (author)

  5. Measuring multiple neurochemicals and related metabolites in blood and brain of the rhesus monkey by using dual microdialysis sampling and capillary hydrophilic interaction chromatography–mass spectrometry

    OpenAIRE

    Li, Juan; Pföstl, Veronika von; Zaldivar, Daniel; Zhang, Xiaozhe; Logothetis, Nikos; Rauch, Alexander

    2012-01-01

    In vivo measurement of multiple functionally related neurochemicals and metabolites (NMs) is highly interesting but remains challenging in the field of basic neuroscience and clinical research. We present here an analytical method for determining five functionally and metabolically related polar substances, including acetylcholine (quaternary ammonium), lactate and pyruvate (organic acids), as well as glutamine and glutamate (amino acids). These NMs are acquired from samples of the brain and ...

  6. Detection of Amide and Aromatic Proton Resonances of Human Brain Metabolites Using Localized Correlated Spectroscopy Combined with Two Different Water Suppression Schemes

    Directory of Open Access Journals (Sweden)

    Rajakumar Nagarajan

    2010-06-01

    Full Text Available The purpose of the study was to demonstrate the J-coupling connectivity network between the amide, aliphatic, and aromatic proton resonances of metabolites in human brain using two-dimensional (2D localized correlated spectroscopy (L-COSY. Two different global water suppression techniques were combined with L-COSY, one before and another after localizing the volume of interest (VOI. Phantom solutions containing several cerebral metabolites at physiological concentrations were evaluated initially for sequence optimization. Nine healthy volunteers were scanned using a 3T whole body MRI scanner. The VOI for 2D L-COSY was placed in the right occipital white/gray matter region. The 2D cross and diagonal peak volumes were measured for several metabolites such as N-acetyl aspartate (NAA, creatine (Cr, free choline (Ch, glutamate/glutamine (Glx, aspartate (Asp, myo-inositol (mI, GABA, glutathione (GSH, phosphocholine (PCh, phosphoethanolamine (PE, tyrosine (Tyr, lactate (Lac, macromolecules (MM and homocarnosine (Car. Using the pre-water suppression technique with L-COSY, the above mentioned metabolites were clearly identifiable and the relative ratios of metabolites were calculated. In addition to detecting multitude of aliphatic resonances in the high field region, we have demonstrated that the amide and aromatic resonances can also be detected using 2D L-COSY by pre water suppression more reliably than the post-water suppression.

  7. Quantification of metabolites from single-voxel in vivo 1H NMR data of normal human brain by means of time-domain data analysis.

    Science.gov (United States)

    Ala-Korpela, M; Usenius, J P; Keisala, J; van den Boogaart, A; Vainio, P; Jokisaari, J; Soimakallio, S; Kauppinen, R

    1995-01-01

    We present here a combination of time-domain signal analysis procedures for quantification of human brain in vivo 1H NMR spectroscopy (MRS) data. The method is based on a separate removal of a residual water resonance followed by a frequency-selective time-domain line-shape fitting analysis of metabolite signals. Calculation of absolute metabolite concentrations was based on the internal water concentration as a reference. The estimated average metabolite concentrations acquired from six regions of normal human brain with a single-voxel spin-echo technique for the N-acetylaspartate, creatine, and choline-containing compounds were 11.4 +/- 1.0, 6.5 +/- 0.5, and 1.7 +/- 0.2 mumol kg-1 wet weight, respectively. The time-domain analyses of in vivo 1H MRS data from different brain regions with their specific characteristics demonstrate a case in which the use of frequency-domain methods pose serious difficulties. PMID:8749730

  8. Markers of anthropogenic contamination: A validated method for quantification of pharmaceuticals, illicit drug metabolites, perfluorinated compounds, and plasticisers in sewage treatment effluent and rain runoff.

    Science.gov (United States)

    Wilkinson, John L; Swinden, Julian; Hooda, Peter S; Barker, James; Barton, Stephen

    2016-09-01

    An effective, specific and accurate method is presented for the quantification of 13 markers of anthropogenic contaminants in water using solid phase extraction (SPE) followed by high performance liquid chromatography (HPLC) tandem mass spectrometry (MS/MS). Validation was conducted according to the International Conference on Harmonisation (ICH) guidelines. Method recoveries ranged from 77 to 114% and limits of quantification between 0.75 and 4.91 ng/L. A study was undertaken to quantify the concentrations and loadings of the selected contaminants in 6 sewage treatment works (STW) effluent discharges as well as concentrations in 5 rain-driven street runoffs and field drainages. Detection frequencies in STW effluent ranged from 25% (ethinylestradiol) to 100% (benzoylecgonine, bisphenol-A (BPA), bisphenol-S (BPS) and diclofenac). Average concentrations of detected compounds in STW effluents ranged from 3.62 ng/L (ethinylestradiol) to 210 ng/L (BPA). Levels of perfluorinated compounds (PFCs) perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) as well as the plasticiser BPA were found in street runoff at maximum levels of 1160 ng/L, 647 ng/L and 2405 ng/L respectively (8.52, 3.09 and 2.7 times more concentrated than maximum levels in STW effluents respectively). Rain-driven street runoff may have an effect on levels of PFCs and plasticisers in receiving rivers and should be further investigated. Together, this method with the 13 selected contaminants enables the quantification of various markers of anthropogenic pollutants: inter alia pharmaceuticals, illicit drugs and their metabolites from humans and improper disposal of drugs, while the plasticisers and perfluorinated compounds may also indicate contamination from industrial and transport activity (street runoff). PMID:27348563

  9. Validated methods for determination of neurotransmitters and metabolites in rodent brain tissue and extracellular fluid by reversed phase UHPLC-MS/MS.

    Science.gov (United States)

    Bergh, Marianne Skov-Skov; Bogen, Inger Lise; Lundanes, Elsa; Øiestad, Åse Marit Leere

    2016-08-15

    Fast and sensitive methods for simultaneous determination of dopamine (DA), the two DA-metabolites homovanillic acid (HVA) and 3-methoxytyramine (3-MT), serotonin (5-HT) and the 5-HT-metabolite 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE), acetylcholine (ACh), glutamic acid (Glu) and γ-aminobutyric acid (GABA) in rodent brain tissue (1.0-4000nM) and extracellular fluid (ECF) (0.5-2000nM) based on ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) have been developed. Of the three different sample preparation methods for brain tissue samples tested, a simple and rapid protein precipitation procedure with formic acid was found to give the best results. The neurotransmitters (NTs) and NT metabolites were separated using UHPLC with an Acquity UPLC HSS T3 C18 column (2.1×100mm, 1.8μm particle size) with acidic mobile phase. Gradient elution with methanol was used and quantification was performed using multiple reaction monitoring (MRM). The total run time was 5.2min including equilibration time. The methods were validated by determining calibration model, intra- and inter-day precision and accuracy, limit of detection (LOD), lower limit of quantification (LLOQ), matrix effects (ME), carry-over and stability. Surrogate analytes were used to enable determination of the recovery and ME of the endogenous analytes in brain tissue. The methods were applied for determination of NTs at basal levels in rodent brain ECF and brain tissue homogenate. The developed methods are valuable tools in the studies of mechanisms of drugs of abuse, and neurologic and psychiatric disease. PMID:27336704

  10. In vivo quantification of brain metabolites by 1H-MRS using water as an internal standard

    DEFF Research Database (Denmark)

    Christiansen, P; Henriksen, O; Stubgaard, M; Gideon, P; Larsson, H B

    1993-01-01

    SP 63/84 wholebody MR-scanner operating at 1.5 T using a STEAM sequence. In vitro studies indicate a very high correlation between metabolite signals (area under peaks) and concentration, R = 0.99 as well as between metabolite signals and the volume of the selected voxel, R = 1.00. The error in...

  11. Do the metabolites of 6-[F-18]fluoro-L-dopa and of [F-18]fluoro-meta-L-tyrosine contribute to the F-18 accumulation in the human brain?

    International Nuclear Information System (INIS)

    The purpose of this study was to determine if the metabolites of 6-[F-18]fluoro-L-dopa (F-dopa) and of [F-18]fluoro-meta-L-tyrosine (FmLtyr) contribute to the accumulation of fluorine-18 in the brain through unspecific retention. PET studies were conducted on a healthy human subject who was treated with both of the radiopharmaceuticals and their labelled metabolites. Results indicated that in contrast to F-dopa, the metabolite of FmLtyr does not 'contaminate' the brain with extraneous fluorine-18

  12. Prism Adaptation Alters Electrophysiological Markers of Attentional Processes in the Healthy Brain.

    Science.gov (United States)

    Martín-Arévalo, Elisa; Laube, Inga; Koun, Eric; Farnè, Alessandro; Reilly, Karen T; Pisella, Laure

    2016-01-20

    Neglect patients typically show a rightward attentional orienting bias and a strong disengagement deficit, such that they are especially slow in responding to left-sided targets after right-sided cues (Posner et al., 1984). Prism adaptation (PA) can reduce diverse debilitating neglect symptoms and it has been hypothesized that PA's effects are so generalized that they might be mediated by attentional mechanisms (Pisella et al., 2006; Redding and Wallace, 2006). In neglect patients, performance on spatial attention tasks improves after rightward-deviating PA (Jacquin-Courtois et al., 2013). In contrast, in healthy subjects, although there is evidence that leftward-deviating PA induces neglect-like performance on some visuospatial tasks, behavioral studies of spatial attention tasks have mostly yielded negative results (Morris et al., 2004; Bultitude et al., 2013). We hypothesized that these negative behavioral findings might reflect the limitations of behavioral measures in healthy subjects. Here we exploited the sensitivity of event-related potentials to test the hypothesis that electrophysiological markers of attentional processes in the healthy human brain are affected by PA. Leftward-deviating PA generated asymmetries in attentional orienting (reflected in the cue-locked N1) and in attentional disengagement for invalidly cued left targets (reflected in the target-locked P1). This is the first electrophysiological demonstration that leftward-deviating PA in healthy subjects mimics attentional patterns typically seen in neglect patients. Significance statement: Prism adaptation (PA) is a promising tool for ameliorating many deficits in neglect patients and inducing neglect-like behavior in healthy subjects. The mechanisms underlying PA's effects are poorly understood but one hypothesis suggests that it acts by modulating attention. To date, however, there has been no successful demonstration of attentional modulation in healthy subjects. We provide the first

  13. Simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell cultures and in sub-regions of guinea pig brain.

    Science.gov (United States)

    Schou-Pedersen, Anne Marie V; Hansen, Stine N; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2016-08-15

    In the present paper, we describe a validated chromatographic method for the simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell culture and in sub-regions of the guinea pig brain. Electrochemical detection provided limits of quantifications (LOQs) between 3.6 and 12nM. Within the linear range, obtained recoveries were from 90.9±9.9 to 120±14% and intra-day and inter-day precisions found to be less than 5.5% and 12%, respectively. The analytical method was applicable for quantification of intracellular and extracellular amounts of monoamine neurotransmitters and their metabolites in guinea pig frontal cortex and hippocampal primary neuronal cell cultures. Noradrenaline, dopamine and serotonin were found to be in a range from 0.31 to 1.7pmol per 2 million cells intracellularly, but only the biogenic metabolites could be detected extracellularly. Distinct differences in monoamine concentrations were observed when comparing concentrations in guinea pig frontal cortex and cerebellum tissue with higher amounts of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid in frontal cortex, as compared to cerebellum. The chemical turnover in frontal cortex tissue of guinea pig was for serotonin successfully predicted from the turnover observed in the frontal cortex cell culture. In conclusion, the present analytical method shows high precision, accuracy and sensitivity and is broadly applicable to monoamine measurements in cell cultures as well as brain biopsies from animal models used in preclinical neurochemistry. PMID:27379407

  14. Fatty Acid Amide Hydrolase-Dependent Generation of Antinociceptive Drug Metabolites Acting on TRPV1 in the Brain

    OpenAIRE

    Barriere, David A.; Mallet, Christophe; Blomgren, Anders; Simonsen, Charlotte; Daulhac, Laurence; Libert, Frederic; Chapuy, Eric; Etienne, Monique; Högestätt, Edward; Zygmunt, Peter; Eschalier, Alain

    2013-01-01

    The discovery that paracetamol is metabolized to the potent TRPV1 activator N-(4-hydroxyphenyl)-5Z, 8Z, 11Z, 14Z-eicosatetraenamide (AM404) and that this metabolite contributes to paracetamol's antinociceptive effect in rodents via activation of TRPV1 in the central nervous system (CNS) has provided a potential strategy for developing novel analgesics. Here we validated this strategy by examining the metabolism and antinociceptive activity of the de-acetylated paracetamol metabolite 4-ami...

  15. EEG Oscillatory Phase-Dependent Markers of Corticospinal Excitability in the Resting Brain

    Directory of Open Access Journals (Sweden)

    Barbara Berger

    2014-01-01

    Full Text Available Functional meaning of oscillatory brain activity in various frequency bands in the human electroencephalogram (EEG is increasingly researched. While most research focuses on event-related changes of brain activity in response to external events there is also increasing interest in internal brain states influencing information processing. Several studies suggest amplitude changes of EEG oscillatory activity selectively influencing cortical excitability, and more recently it was shown that phase of EEG activity (instantaneous phase conveys additional meaning. Here we review this field with many conflicting findings and further investigate whether corticospinal excitability in the resting brain is dependent on a specific spontaneously occurring brain state reflected by amplitude and instantaneous phase of EEG oscillations. We applied single pulse transcranial magnetic stimulation (TMS over the left sensorimotor cortex, while simultaneously recording ongoing oscillatory activity with EEG. Results indicate that brain oscillations reflect rapid, spontaneous fluctuations of cortical excitability. Instantaneous phase but not amplitude of oscillations at various frequency bands at stimulation site at the time of TMS-pulse is indicative for brain states associated with different levels of excitability (defined by size of the elicited motor evoked potential. These results are further evidence that ongoing brain oscillations directly influence neural excitability which puts further emphasis on their role in orchestrating neuronal firing in the brain.

  16. Further evaluation of [11C]MP-10 as a radiotracer for phosphodiesterase 10A: PET imaging study in rhesus monkeys and brain tissue metabolite analysis.

    Science.gov (United States)

    Lin, Shu-Fei; Labaree, David; Chen, Ming-Kai; Holden, Daniel; Gallezot, Jean-Dominique; Kapinos, Michael; Teng, Jo-Ku; Najafzadeh, Soheila; Plisson, Christophe; Rabiner, Eugenii A; Gunn, Roger N; Carson, Richard E; Huang, Yiyun

    2015-02-01

    [(11)C]MP-10 is a potent and specific PET tracer previously shown to be suitable for imaging the phosphodiesterase 10A (PDE10A) in baboons with reversible kinetics and high specific binding. However, another report indicated that [(11)C]MP-10 displayed seemingly irreversible kinetics in rhesus monkeys, potentially due to the presence of a radiolabeled metabolite capable of penetrating the blood-brain-barrier (BBB) into the brain. This study was designed to address the discrepancies between the species by re-evaluating [(11)C]MP-10 in vivo in rhesus monkey with baseline scans to assess tissue uptake kinetics and self-blocking scans with unlabeled MP-10 to determine binding specificity. Ex vivo studies with one rhesus monkey and 4 Sprague-Dawley rats were also performed to investigate the presence of radiolabeled metabolites in the brain. Our results indicated that [(11)C]MP-10 displayed reversible uptake kinetics in rhesus monkeys, albeit slower than in baboons. Administration of unlabeled MP-10 reduced the binding of [(11)C]MP-10 in a dose-dependent manner in all brain regions including the cerebellum. Consequently, the cerebellum appeared not to be a suitable reference tissue in rhesus monkeys. Regional volume of distribution (VT) was mostly reliably derived with the multilinear analysis (MA1) method. In ex vivo studies in the monkey and rats only negligible amount of radiometabolites was seen in the brain of either species. In summary, results from the present study strongly support the suitability of [(11)C]MP-10 as a radiotracer for PET imaging and quantification of PDE10A in nonhuman primates. PMID:25450608

  17. 1H-Magnetic resonance spectroscopy study of stimulant medication effect on brain metabolites in French Canadian children with attention deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    BenAmor L

    2014-01-01

    Full Text Available Leila BenAmor1,21Department of Psychiatry Sainte-Justine Hospital, Montreal, Quebec, Canada; 2Department of Psychiatry, University of Montreal, Montreal, Quebec, CanadaBackground: Attention deficit hyperactivity disorder (ADHD is a common neurodevelopmental disorder in school aged children. Functional abnormalities have been reported in brain imaging studies in ADHD populations. Psychostimulants are considered as the first line treatment for ADHD. However, little is known of the effect of stimulants on brain metabolites in ADHD patients.Objectives: To compare the brain metabolite concentrations in children with ADHD and on stimulants with those of drug naïve children with ADHD, versus typically developed children, in a homogenous genetic sample of French Canadians.Methods: Children with ADHD on stimulants (n=57 and drug naïve children with ADHD (n=45 were recruited, as well as typically developed children (n=38. The presence or absence of ADHD diagnosis (Diagnostic and Statistical Manual of Mental Disorders IV criteria was based on clinical evaluation and The Diagnostic Interview Schedule for Children IV. All children (n=140 underwent a proton magnetic resonance spectroscopy session to measure the ratio of N-acetyl-aspartate, choline, glutamate, and glutamate–glutamine to creatine, respectively, in the left and right prefrontal and striatal regions of the brain, as well as in the left cerebellum.Results: When compared with drug naïve children with ADHD, children with ADHD on stimulants and children typically developed were found to have higher choline ratios in the left prefrontal region (P=0.04 and lower N-acetyl-aspartate ratios in the left striatum region (P=0.01, as well as lower glutamate–glutamine ratios in the left cerebellum (P=0.05. In these three regions, there was no difference between children with ADHD on stimulants and typically developed children.Conclusion: Therapeutic psychostimulant effects in children with ADHD may be

  18. Absolute quantitative proton NMR spectroscopy based on the amplitude of the local water suppression pulse. Quantification of brain water and metabolites

    DEFF Research Database (Denmark)

    Danielsen, E R; Henriksen, O

    1994-01-01

    Quantification in localized proton NMR spectroscopy has been achieved by various methods in recent years. A new method for absolute quantification is described in this paper. The method simultaneously rules out problems with B1 field inhomogeneity and coil loading, utilizing a relation between the...... locally optimized amplitude of a chemical shift selective water suppression pulse and the acquired signal. Validity and feasibility of quantification using the method of the water suppression pulse is demonstrated. Brain water and cerebral metabolites have been quantified in a study of 12 healthy...

  19. Identifying markers of pathology in SAXS data of malignant tissues of the brain

    International Nuclear Information System (INIS)

    Conventional neuropathological analysis for brain malignancies is heavily reliant on the observation of morphological abnormalities, observed in thin, stained sections of tissue. Small Angle X-ray Scattering (SAXS) data provide an alternative means of distinguishing pathology by examining the ultra-structural (nanometer length scales) characteristics of tissue. To evaluate the diagnostic potential of SAXS for brain tumors, data was collected from normal, malignant and benign tissues of the human brain at station 2.1 of the Daresbury Laboratory Synchrotron Radiation Source and subjected to data mining and multivariate statistical analysis. The results suggest SAXS data may be an effective classifier of malignancy

  20. Sex differences in the effects of adolescent stress on adult brain inflammatory markers in rats

    OpenAIRE

    Pyter, Leah M.; Kelly, Sean D.; Harrell, Constance S; Neigh, Gretchen N.

    2013-01-01

    Both basic and clinical research indicates that females are more susceptible to stress-related affective disorders than males. One of the mechanisms by which stress induces depression is via inflammatory signaling in the brain. Stress during adolescence, in particular, can also disrupt the activation and continued development of both the hypothalamic–pituitary–adrenal (HPA) and –gonadal (HPG) axes, both of which modulate inflammatory pathways and brain regions involved in affective behavior. ...

  1. Data supporting the rat brain sample preparation and validation assays for simultaneous determination of 8 neurotransmitters and their metabolites using liquid chromatography–tandem mass spectrometry

    Science.gov (United States)

    Wojnicz, Aneta; Ortiz, José Avendaño; Casas, Ana I.; Freitas, Andiara E.; López, Manuela G.; Ruiz-Nuño, Ana

    2016-01-01

    The data presented in this article supports the rat brain sample preparation procedure previous to its injection into the liquid chromatography–tandem mass spectrometry (LC–MS/MS) system to monitor levels of adrenaline, noradrenaline, glutamic acid, γ-aminobutyric acid, dopamine, 5-hydroxytryptamine, 5-hydroxyindole acetic acid, and 3-methoxy-4-hydroxyphenylglycol. In addition, we describe the method validation assays (such as calibration curve, lower limit of quantification, precision and accuracy intra- and inter-day, selectivity, extraction recovery and matrix effect, stability, and carry-over effect) according to the United States Food and Drug Administration and European Medicine Agency to measure in one step different neurotransmitters and their metabolites. The data supplied in this article is related to the research study entitled: “Simultaneous determination of 8 neurotransmitters and their metabolite levels in rat brain using liquid chromatography in tandem with mass spectrometry: application to the murine Nrf2 model of depression” (Wojnicz et al. 2016) [1]. PMID:27054183

  2. Data supporting the rat brain sample preparation and validation assays for simultaneous determination of 8 neurotransmitters and their metabolites using liquid chromatography–tandem mass spectrometry

    Directory of Open Access Journals (Sweden)

    Aneta Wojnicz

    2016-06-01

    Full Text Available The data presented in this article supports the rat brain sample preparation procedure previous to its injection into the liquid chromatography–tandem mass spectrometry (LC–MS/MS system to monitor levels of adrenaline, noradrenaline, glutamic acid, γ-aminobutyric acid, dopamine, 5-hydroxytryptamine, 5-hydroxyindole acetic acid, and 3-methoxy-4-hydroxyphenylglycol. In addition, we describe the method validation assays (such as calibration curve, lower limit of quantification, precision and accuracy intra- and inter-day, selectivity, extraction recovery and matrix effect, stability, and carry-over effect according to the United States Food and Drug Administration and European Medicine Agency to measure in one step different neurotransmitters and their metabolites. The data supplied in this article is related to the research study entitled: “Simultaneous determination of 8 neurotransmitters and their metabolite levels in rat brain using liquid chromatography in tandem with mass spectrometry: application to the murine Nrf2 model of depression” (Wojnicz et al. 2016 [1].

  3. The interference of ethanol with heroin-stimulated psychomotor activation in mice is not related to changed brain concentrations of the active metabolites 6MAM or morphine.

    Science.gov (United States)

    Andersen, Jannike M; Haugen, Karianne S; Ripel, Ase; Mørland, Jørg

    2014-02-01

    It has been suggested that the potentiating effect observed in human beings when combining alcohol and heroin may be due to an interference of ethanol with the pharmacokinetics of heroin, leading to accumulation of the biologically active metabolites, 6-monoacetylmorphine (6MAM) and morphine. However, experimental evidence for this hypothesis is lacking. In this study, we used mice and examined the effect of ethanol on the metabolism of heroin by combining a locomotor activity test, which is a behaviour model representative of psychomotor stimulation, with pharmacokinetic studies in blood and brain tissue. Pre-treatment with ethanol (1 and 2.5 g/kg, po) affected heroin-stimulated (2.5 and 15 μmol/kg, sc) locomotor activation significantly, resulting in a dose-dependent reduction in run distance. However, the change in the activity profiles did not indicate any increase in the concentration of active metabolites. Pharmacokinetic studies in blood and brain supported the behavioural findings, showing no change in the time-versus-concentration curves of either 6MAM or morphine after administration of heroin (15 μmol/kg, sc) to mice pre-treated with ethanol (2.5 g/kg, po). The concentration of heroin itself was elevated, but is probably of minor importance because heroin has low biological activity by itself. The in vivo pharmacokinetic findings were supported by experiments in vitro. In conclusion, studies in mice do not support the hypothesis from epidemiological studies of a pharmacokinetic interaction between alcohol and heroin. PMID:24102968

  4. Upregulated expression of brain enzymatic markers of arachidonic and docosahexaenoic acid metabolism in a rat model of the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Taha Ameer Y

    2012-10-01

    Full Text Available Abstract Background In animal models, the metabolic syndrome elicits a cerebral response characterized by altered phospholipid and unesterified fatty acid concentrations and increases in pro-apoptotic inflammatory mediators that may cause synaptic loss and cognitive impairment. We hypothesized that these changes are associated with phospholipase (PLA2 enzymes that regulate arachidonic (AA, 20:4n-6 and docosahexaenoic (DHA, 22:6n-6 acid metabolism, major polyunsaturated fatty acids in brain. Male Wistar rats were fed a control or high-sucrose diet for 8 weeks. Brains were assayed for markers of AA metabolism (calcium-dependent cytosolic cPLA2 IVA and cyclooxygenases, DHA metabolism (calcium-independent iPLA2 VIA and lipoxygenases, brain-derived neurotrophic factor (BDNF, and synaptic integrity (drebrin and synaptophysin. Lipid concentrations were measured in brains subjected to high-energy microwave fixation. Results The high-sucrose compared with control diet induced insulin resistance, and increased phosphorylated-cPLA2 protein, cPLA2 and iPLA2 activity and 12-lipoxygenase mRNA, but decreased BDNF mRNA and protein, and drebrin mRNA. The concentration of several n-6 fatty acids in ethanolamine glycerophospholipids and lysophosphatidylcholine was increased, as was unesterified AA concentration. Eicosanoid concentrations (prostaglandin E2, thromboxane B2 and leukotriene B4 did not change. Conclusion These findings show upregulated brain AA and DHA metabolism and reduced BDNF and drebrin, but no changes in eicosanoids, in an animal model of the metabolic syndrome. These changes might contribute to altered synaptic plasticity and cognitive impairment in rats and humans with the metabolic syndrome.

  5. The cell birth marker BrdU does not affect recruitment of subsequent cell divisions in the adult avian brain.

    Science.gov (United States)

    Cattan, Anat; Ayali, Amir; Barnea, Anat

    2015-01-01

    BrdU is commonly used to quantify neurogenesis but also causes mutation and has mitogenic, transcriptional, and translational effects. In mammalian studies, attention had been given to its dosage, but in birds such examination was not conducted. Our previous study suggested that BrdU might affect subsequent cell divisions and neuronal recruitment in the brain. Furthermore, this effect seemed to increase with time from treatment. Accordingly, we examined whether BrdU might alter neurogenesis in the adult avian brain. We compared recruitment of [(3)H]-thymidine(+) neurons in brains of zebra finches (Taeniopygia guttata) when no BrdU was involved and when BrdU was given 1 or 3 months prior to [(3)H]-thymidine. In nidopallium caudale, HVC, and hippocampus, no differences were found between groups in densities and percentages of [(3)H]-thymidine(+) neurons. The number of silver grains per [(3)H]-thymidine(+) neuronal nucleus and their distribution were similar across groups. Additionally, time did not affect the results. The results indicate that the commonly used dosage of BrdU in birds has no long-term effects on subsequent cell divisions and neuronal recruitment. This conclusion is also important in neuronal replacement experiments, where BrdU and another cell birth marker are given, with relatively long intervals between them. PMID:25759813

  6. The Disrupted-in-Schizophrenia-1 Ser704Cys polymorphism and brain neurodevelopmental markers in schizophrenia and healthy subjects.

    Science.gov (United States)

    Takahashi, Tsutomu; Nakamura, Mihoko; Nakamura, Yukako; Aleksic, Branko; Kido, Mikio; Sasabayashi, Daiki; Takayanagi, Yoichiro; Furuichi, Atsushi; Nishikawa, Yumiko; Noguchi, Kyo; Ozaki, Norio; Suzuki, Michio

    2015-01-01

    Increasing evidence has implicated the role of Disrupted-in-Schizophrenia-1 (DISC1), a potential susceptibility gene for schizophrenia, in early neurodevelopmental processes. However, the effect of its genotype variation on brain morphologic changes related to neurodevelopmental abnormalities in schizophrenia remains largely unknown. This magnetic resonance imaging study examined the association between DISC1 Ser704Cys polymorphism and a range of brain neurodevelopmental markers [cavum septi pellucidi (CSP), adhesio interthalamica (AI), olfactory sulcus depth, and sulcogyral pattern (Types I, II, III, and IV) in the orbitofrontal cortex (OFC)] in an all Japanese sample of 75 schizophrenia patients and 87 healthy controls. The Cys carriers had significantly larger CSP than the Ser homozygotes for both schizophrenia patients and healthy controls. The Cys carriers also exhibited a reduction in the Type I pattern of the right OFC in the healthy controls, but not in the schizophrenia patients. The DISC1 Ser704Cys polymorphism did not affect the AI and olfactory sulcus depth in either group. These results suggested a possible role of the DISC1 genotype in the early neurodevelopment of human brains, but failed to show its specific role in the neurodevelopmental pathology of schizophrenia. PMID:25092219

  7. Inter-relationships among behavioral markers, genes, brain and treatment in dyslexia and dysgraphia.

    Science.gov (United States)

    Berninger, Virginia; Richards, Todd

    2010-07-01

    Cross-country, longitudinal twin studies provide strong evidence for both the biological and environmental basis of dyslexia, and the stability of genetic influences on reading and spelling, even when skills improve in response to instruction. Although DNA studies aimed at identifying gene candidates in dyslexia and related phenotypes (behavioral expression of underlying genotypes); and imaging studies of brain differences between individuals with and without dyslexia and the brain's response to instructional treatment are increasing, this review illustrates, with the findings of one multidisciplinary research center, an emerging trend to investigate the inter-relationships among genetic, brain and instructional treatment findings in the same sample, which are interpreted in reference to a working-memory architecture, for dyslexia (impaired decoding and spelling) and/or dysgraphia (impaired handwriting). General principles for diagnosis and treatment, based on research with children who failed to respond to the regular instructional program, are summarized for children meeting research criteria for having or being at risk for dyslexia or dysgraphia. Research documenting earlier emerging specific oral language impairment during preschool years associated with reading and writing disabilities during school years is also reviewed. Recent seminal advances and projected future trends are discussed for linking brain endophenotypes and gene candidates, identifying transchromosomal interactions, and exploring epigenetics (chemic al modifications of gene expression in response to developmental or environmental changes). Rather than providing final answers, this review highlights past, current and emerging issues in dyslexia research and practice. PMID:20953351

  8. Brain region's relative proximity as marker for Alzheimer's disease based on structural MRI

    DEFF Research Database (Denmark)

    Erleben, Lene Lillemark; Sørensen, Lauge Emil Borch Laurs; Pai, Akshay Sadananda Uppinakudru;

    2014-01-01

    BACKGROUND:Alzheimer's disease (AD) is a progressive, incurable neurodegenerative disease and the most common type of dementia. It cannot be prevented, cured or drastically slowed, even though AD research has increased in the past 5-10 years. Instead of focusing on the brain volume or on the single...

  9. EEG Delta Band as a Marker of Brain Damage in Aphasic Patients after Recovery of Language

    Science.gov (United States)

    Spironelli, Chiara; Angrilli, Alessandro

    2009-01-01

    In this study spectral delta percentage was used to assess both brain dysfunction/inhibition and functional linguistic impairment during different phases of word processing. To this aim, EEG delta amplitude was measured in 17 chronic non-fluent aphasic patients while engaged in three linguistic tasks: Orthographic, Phonological and Semantic.…

  10. Brain antioxidant markers, cognitive performance and acetylcholinesterase activity of rats: efficiency of Sonchus asper

    Directory of Open Access Journals (Sweden)

    Khan Rahmat

    2012-05-01

    Full Text Available Abstract Background Sonchus asper (SA is traditionally used as a folk medicine to treat mental disorders in Pakistan. The aim of this study was to investigate the effect of polyphenolic rich methanolic fraction of SA on cognitive performance, brain antioxidant activities and acetylcholinesterase activity in male rats. Methods 30 male Sprague–Dawley rats were equally divided into three groups in this study. Animals of group I (control received saline (vehicle, group II received SA (50 mg/kg body weight (b.w., and group III treated with SA (100 mg/kg b.w., orally in dimethyl sulphoxide (DMSO for 7 days. The effect of SA was checked on rat cognitive performance, brain antioxidatant and acetylcholinesterase activities. Evaluation of learning and memory was assessed by a step-through a passive avoidance test on day 6 after two habituation trials and an initial acquisition trial on day 5. Antioxidant potential was determined by measuring activities of superoxide dismutase (SOD, catalase (CAT, contents of thiobarbituric acid reactive substances (TBARS and reduced glutathione (GSH in whole-brain homogenates. Acetylcholinesterase (AChE activity was determined by the colorimetric method. Results Results showed that 100 mg/kg b.w., SA treated rats exhibited a significant improvement in learning and memory (step-through latency time. SA administration reduced lipid peroxidation products and elevated glutathione levels in the SA100-treated group. Furthermore, salt and detergent soluble AChE activity was significantly decreased in both SA-treated groups. Short-term orally supplementation of SA showed significant cognitive enhancement as well as elevated brain antioxidant enzymes and inhibited AChE activity. Conclusion These findings stress the critical impact of Sonchus asper bioactive components on brain function.

  11. The enteric bacterial metabolite propionic acid alters brain and plasma phospholipid molecular species: further development of a rodent model of autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Thomas Raymond H

    2012-07-01

    Full Text Available Abstract Gastrointestinal symptoms and altered blood phospholipid profiles have been reported in patients with autism spectrum disorders (ASD. Most of the phospholipid analyses have been conducted on the fatty acid composition of isolated phospholipid classes following hydrolysis. A paucity of information exists on how the intact phospholipid molecular species are altered in ASD. We applied ESI/MS to determine how brain and blood intact phospholipid species were altered during the induction of ASD-like behaviors in rats following intraventricular infusions with the enteric bacterial metabolite propionic acid. Animals were infused daily for 8 days, locomotor activity assessed, and animals killed during the induced behaviors. Propionic acid infusions increased locomotor activity. Lipid analysis revealed treatment altered 21 brain and 30 blood phospholipid molecular species. Notable alterations were observed in the composition of brain SM, diacyl mono and polyunsaturated PC, PI, PS, PE, and plasmalogen PC and PE molecular species. These alterations suggest that the propionic acid rat model is a useful tool to study aberrations in lipid metabolism known to affect membrane fluidity, peroxisomal function, gap junction coupling capacity, signaling, and neuroinflammation, all of which may be associated with the pathogenesis of ASD.

  12. Association of Alzheimer disease GWAS loci with MRI-markers of brain aging

    Science.gov (United States)

    Chauhan, Ganesh; Adams, Hieab H.H.; Bis, Joshua C; Weinstein, Galit; Yu, Lei; Töglhofer, Anna Maria; Smith, Albert Vernon; van der Lee, Sven; Gottesman, Rebecca F; Thomson, Russell; Wang, Jing; Yang, Qiong; Niessen, Wiro J.; Lopez, Oscar L; Becker, James T; Phan, Thanh G; Beare, Richard J; Arfanakis, Konstantinos; Fleischman, Debra; Vernooij, Meike W.; Mazoyer, Bernard; Schmidt, Helena; Srikanth, Velandai; Knopman, Dave S; Jack, Clifford R; Amouyel, Philippe; Hofman, Albert; DeCarli, Charlie; Tzourio, Christophe; van Duijn, Cornelia M; Bennett, David A; Schmidt, Reinhold; Longstreth, William T; Mosley, Thomas H; Fornage, Myriam; Launer, Lenore J; Seshadri, Sudha; Ikram, M Arfan; Debette, Stephanie

    2015-01-01

    Whether novel risk variants of Alzheimer’s disease (AD) identified through genome-wide association studies (GWAS) also influence MRI-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume (ICV), total brain volume (TBV), hippocampal volume (HV), white matter hyperintensity (WMH) burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N=8,175–11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p=0.0054) and CD33 (rs3865444) with smaller ICV (p=0.0058) In gene-based tests, there was associations of HLA-DRB1 with TBV (p=0.0006) and BIN1 with HV (p=0.00089). A weighted AD genetic risk score was associated with smaller HV (beta±SE=−0.047±0.013, p=0.00041), even after excluding the APOE locus (p=0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in non-demented older community persons. PMID:25670335

  13. Analysis of metabolites in human brain tumors and cerebral infarctions using 31P- and 1H-magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    31P- and 1H-MRS with a 2.0 tesla MRI/S system was used to monitor the cerebral energy levels, phospholipid metabolism, intracellular pH, and lactate and amino acid levels in patients with brain tumors and cerebral infarctions. Studies of human brain tumors have suggested that the 31P-MRS of malignant brain tumors show low concentrations of phosphocreatine (PCr) and β-ATP, high levels of phosphomonoester (PME) and inorganic Pi, and an alkaline pH. The Pi, PME, and intracellular pH of malignant lymphoma were higher than those of other brain tumors. 1H-MRS showed an increase of lactate in malignant brain tumors and epidermoids. After ACNU administration, the tumor 31P-MRS showed transient reduction and elevation of Pi on five patients with malignant gliomas. Intracellular pH also showed a transient reduction during radiotherapy. 1H-MRS showed a reduction of lactate at the beginning of therapy and showed a marked re-elevation of lactate with tumor regrowth. After radiotherapy, the normal brain 31P-MRS showed transient elevation and reduction of Pi. Intracellular pH also showed a transient elevation during radiotherapy. To investigate the mechanism of hyperbaric oxygen therapy (HBO) in cerebral ischemia, changes of brain lactate level were estimated by 1H-MRS. Although the Lactate/Creatine ratio decreased consistently over time in all patients, it decreased more rapidly in the patients receiving HBO therapy than in those without such therapy. 1H-MRS demonstrated that HBO therapy may improve metabolism in the ischemic brain and reduces the lactate levels. 31P- and 1H-MRS are practical tools for the clinical analysis of cerebral disorders as well as for deciding on therapeutic procedures and evaluating the response. (K.H.)

  14. Determination of monoamine neurotransmitters and their metabolites in a mouse brain microdialysate by coupling high-performance liquid chromatography with gold nanoparticle-initiated chemiluminescence

    Energy Technology Data Exchange (ETDEWEB)

    Li Na; Guo Jizhao; Liu Bo; Yu Yuqi [Department of Chemistry, University of Science and Technology of China (USTC), JinZhai Road No: 96, 230026 Hefei, Anhui (China); Cui Hua, E-mail: hcui@ustc.edu.cn [Department of Chemistry, University of Science and Technology of China (USTC), JinZhai Road No: 96, 230026 Hefei, Anhui (China); Mao Lanqun; Lin Yuqing [Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences (CAS), 100080 Beijing (China)

    2009-07-10

    Our previous work showed that gold nanoparticles could trigger chemiluminescence (CL) between luminol and AgNO{sub 3}. In the present work, the effect of some biologically important reductive compounds, including monoamine neurotransmitters and their metabolites, reductive amino acids, ascorbic acid, uric acid, and glutathione, on the novel CL reaction were investigated for analytical purpose. It was found that all of them could inhibit the CL from the luminol-AgNO{sub 3}-Au colloid system. Among them, monoamine neurotransmitters and their metabolites exhibited strong inhibition effect. Taking dopamine as a model compound, the CL mechanism was studied by measuring absorption spectra during the CL reaction and the reaction kinetics via stopped-flow technique. The CL inhibition mechanism is proposed to be due to that these tested compounds competed with luminol for AgNO{sub 3} to inhibit the formation of luminol radicals and to accelerate deposition of Ag atoms on surface of gold nanoparticles, leading to a decrease in CL intensity. Based on the inhibited CL, a novel method for simultaneous determination of monoamine neurotransmitters and their metabolites was developed by coupling high-performance liquid chromatography with this CL reaction. The new method was successfully applied to determine the compounds in a mouse brain microdialysate. Compared with the reported HPLC-CL methods, the proposed method is simple, fast, and could determine more analytes. Moreover, the limits of linear ranges for NE, E, and DA using the proposed method were one order of magnitude lower than the luminol system without gold nanoparticles.

  15. Multi-slice echo-planar spectroscopic MR imaging provides both global and local metabolite measures in multiple sclerosis

    DEFF Research Database (Denmark)

    Mathiesen, Henrik Kahr; Tscherning, Thomas; Sorensen, Per Soelberg;

    2005-01-01

    MR spectroscopy (MRS) provides information about neuronal loss or dysfunction by measuring decreases in N-acetyl aspartate (NAA), a metabolite widely believed to be a marker of neuronal viability. In multiple sclerosis (MS), whole-brain NAA (WBNAA) has been suggested as a marker of disease...... longitudinal studies have often been hampered by standardization and reproducibility problems. Multi-slice echo-planar spectroscopic imaging (EPSI) is presented as a promising alternative to single-voxel or nonlocalized spectroscopy for obtaining global metabolite estimates in MS. In the same session...

  16. Effect of prolonged exposure to diesel engine exhaust on proinflammatory markers in different regions of the rat brain

    Directory of Open Access Journals (Sweden)

    Wang Kate

    2010-05-01

    Full Text Available Abstract Background The etiology and progression of neurodegenerative disorders depends on the interactions between a variety of factors including: aging, environmental exposures, and genetic susceptibility factors. Enhancement of proinflammatory events appears to be a common link in different neurological impairments, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Studies have shown a link between exposure to particulate matter (PM, present in air pollution, and enhancement of central nervous system proinflammatory markers. In the present study, the association between exposure to air pollution (AP, derived from a specific source (diesel engine, and neuroinflammation was investigated. To elucidate whether specific regions of the brain are more susceptible to exposure to diesel-derived AP, various loci of the brain were separately analyzed. Rats were exposed for 6 hrs a day, 5 days a week, for 4 weeks to diesel engine exhaust (DEE using a nose-only exposure chamber. The day after the final exposure, the brain was dissected into the following regions: cerebellum, frontal cortex, hippocampus, olfactory bulb and tubercles, and the striatum. Results Baseline levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α and interleukin-1 alpha (IL-1α were dependent on the region analyzed and increased in the striatum after exposure to DEE. In addition, baseline level of activation of the transcription factors (NF-κB and (AP-1 was also region dependent but the levels were not significantly altered after exposure to DEE. A similar, though not significant, trend was seen with the mRNA expression levels of TNF-α and TNF Receptor-subtype I (TNF-RI. Conclusions Our results indicate that different brain regions may be uniquely responsive to changes induced by exposure to DEE. This study once more underscores the role of neuroinflammation in response to ambient air pollution

  17. Tackling the 'dyslexia paradox': reading brain and behavior for early markers of developmental dyslexiax.

    Science.gov (United States)

    Ozernov-Palchik, Ola; Gaab, Nadine

    2016-03-01

    Developmental dyslexia is an unexplained inability to acquire accurate or fluent reading that affects approximately 5-17% of children. Dyslexia is associated with structural and functional alterations in various brain regions that support reading. Neuroimaging studies in infants and pre-reading children suggest that these alterations predate reading instruction and reading failure, supporting the hypothesis that variant function in dyslexia susceptibility genes lead to atypical neural migration and/or axonal growth during early, most likely in utero, brain development. Yet, dyslexia is typically not diagnosed until a child has failed to learn to read as expected (usually in second grade or later). There is emerging evidence that neuroimaging measures, when combined with key behavioral measures, can enhance the accuracy of identification of dyslexia risk in pre-reading children but its sensitivity, specificity, and cost-efficiency is still unclear. Early identification of dyslexia risk carries important implications for dyslexia remediation and the amelioration of the psychosocial consequences commonly associated with reading failure. WIREs Cogn Sci 2016, 7:156-176. doi: 10.1002/wcs.1383 For further resources related to this article, please visit the WIREs website. PMID:26836227

  18. Morphological and behavioral markers of environmentally induced retardation of brain development: an animal model

    International Nuclear Information System (INIS)

    In most neurotoxicological studies morphological assessment focuses on pathological effects, like degenerative changes in neuronal perikarya, axonopathy, demyelination, and glial and endothelial cell reactions. Similarly, the assessment of physiological and behavioral effects center on evident neurological symptoms, like EEG and EMG abnormalities, resting and intention tremor, abnormal gait, and abnormal reflexes. This paper reviews briefly another central nervous system target of harmful environmental agents, which results in behavioral abnormalities without any qualitatively evident neuropathology. This is called microneuronal hypoplasia, a retardation of brain development characterized by a quantitative reduction in the normal population of late-generated, short-axoned neurons in specific brain regions. Correlated descriptive and experimental neurogenetic studies in the rat have established that all the cerebellar granule cells and a very high proportion of hippocampal granule cells are produced postnatally, and that focal, low-dose X-irradiation either of the cerebellum or of the hippocampus after birth selectively interferes with the acquisition of the full complement of granule cells (microneuronal hypoplasia). Subsequent behavioral investigations showed that cerebellar microneuronal hypoplasia results in profound hyperactivity without motor abnormalities, while hippocampal microneuronal hypoplasia results in hyperactivity, as well as attentional and learning deficits. There is much indirect clinical evidence that various harmful environmental agents affecting the pregnant mother and/or the infant lead to such childhood disorders as hyperactivity and attentional and learning disorders. 109 references

  19. Radiation-induced inflammatory markers of brain injury are modulated by PPARdelta activation in vitro and in vivo

    Science.gov (United States)

    Schnegg, Caroline Isabel

    microglia in vitro. To extend our in vitro findings in vivo, we investigated whether administration of the peroxisomal proliferator-activated receptor (PPAR)ä agonist, GW0742, prevented radiation-induced brain injury in C57Bl/6 WT mice. Our data demonstrate that GW0742 prevented the radiation-induced increase in the number of activated microglia (CD68+ cells) in wild-type (WT) mice 1 week following 10 Gy WBI. Furthermore, GW0742 inhibited the WBI-induced increase in IL-1β message levels and ERK phosphorylation observed 3 h post-irradiation. In contrast, GW0742 administration failed to modulate the radiation-induced decrease in hippocampal neurogenesis (NeuN+/BrdU+ cells) determined 2 months after irradiation, or mitigate hippocampal-dependent spatial memory impairment observed 3 months post-irradiation using the Barnes Maze task. We used PPARō knockout (KO) mice to examine if the effects of GW0742 are PPARō-dependent. Unexpectedly, PPARō KO mice exhibited a differential response following WBI compared to WT mice; therefore, we were unable to make mechanistic conclusions about GW0742. KO mice do not exhibit a WBI-induced increase in activated microglia; however, they appeared to display a pronounced astrocytic response. In particular, PPARō KO but not WT mice displayed increased GFAP message levels 2 months after WBI. Additionally, the number of GFAP+ cells was reduced significantly in the WT mice 2 months after WBI, but it was not in the PPARō KO mice. These results demonstrate that: i) GW0742 prevents the radiation-induced increase in microglial activation and inflammatory markers, and ii) WT and PPARō KO mice have a differential response to WBI.

  20. Serum metabolites from walnut-fed aged rats attenuate stress-induced neurotoxicity in brain cells in vitro

    Science.gov (United States)

    The shift in equilibrium towards excess reactive oxygen or nitrogen species production from innate antioxidant defense in brain is a critical factor in the declining neural functions and cognitive deficits accompanying age. In aging, there are noticeable alterations in the membrane microenvironment,...

  1. Specifically progressive deficits of brain functional marker in amnestic type mild cognitive impairment.

    Directory of Open Access Journals (Sweden)

    Feng Bai

    Full Text Available BACKGROUND: Deficits of the default mode network (DMN have been demonstrated in subjects with amnestic type mild cognitive impairment (aMCI who have a high risk of developing Alzheimer's disease (AD. However, no longitudinal study of this network has been reported in aMCI. Identifying links between development of DMN and aMCI progression would be of considerable value in understanding brain changes underpinning aMCI and determining risk of conversion to AD. METHODOLOGY/PRINCIPAL FINDINGS: Resting-state fMRI was acquired in aMCI subjects (n = 26 and controls (n = 18 at baseline and after approximately 20 months follow up. Independent component analysis was used to isolate the DMN in each participant. Differences in DMN between aMCI and controls were examined at baseline, and subsequent changes between baseline and follow-up were also assessed in the groups. Posterior cingulate cortex/precuneus (PCC/PCu hyper-functional connectivity was observed at baseline in aMCI subjects, while a substantial decrement of these connections was evident at follow-up in aMCI subjects, compared to matched controls. Specifically, PCC/PCu dysfunction was positively related to the impairments of episodic memory from baseline to follow up in aMCI group. CONCLUSIONS/SIGNIFICANCE: The patterns of longitudinal deficits of DMN may assist investigators to identify and monitor the development of aMCI.

  2. Medroxyprogesterone acetate and the nuclear uptake of testosterone and its metabolites by brain, pituitary gland and genital tract in male cynomolgus monkeys.

    Science.gov (United States)

    Michael, R P; Bonsall, R W; Zumpe, D

    1991-01-01

    The synthetic progestin, medroxyprogesterone acetate (MPA), is used to treat male sex offenders, and it is also suppresses sexual activity in male monkeys. To examine the possibility that MPA may act as an anti-androgen in the primate brain, 4 intact male cynomolgus monkeys were given MPA (40 mg i.m.) once a week for 16 weeks, while 4 control males received i.m. injections of vehicle. All males were then castrated and 3 days later were given 3 mCi [3H]testosterone ([3H]T) i.v.; 1 h after injection males were killed, and radioactivity in nuclear pellets obtained from the hypothalamus (HYP), preoptic area (POA), amygdala (AMG), septum, pituitary gland and genital tract was analyzed by HPLC. Concentrations of [3H]T and [3H]dihydrotestosterone in nuclear pellets were 65-96% lower in MPA-treated males than in controls (P less than 0.001), but the aromatized metabolite, [3H]estradiol, which was the major form of radioactivity present in nuclear pellets from HYP, POA and AMG, was unchanged. There were no differences in concentrations of [3H]T in supernatants from the tissues of MPA-treated and control males. Because the reduced nuclear uptake of androgen in brain occurred in males whose androgen-dependent behavior had been suppressed by MPA treatments, it is proposed that MPA may have anti-androgenic effects at the level of the cell nucleus in brain regions that control behavior. PMID:1825470

  3. A population of human brain cells expressing phenotypic markers of more than one lineage can be induced in vitro to differentiate into mesenchymal cells

    International Nuclear Information System (INIS)

    Proliferating astrocytic cells from germinal, as well as mature areas of brain parenchyma, have the characteristics of neural stem/progenitor cells and are capable of generating both neurons and glia. We previously reported that primary fetal human brain cells, designated as Normal Human Astrocytes (NHA), expressed, in addition to GFAP, Vimentin and Nestin, low levels of βIII-Tubulin, an early neuronal marker, and differentiated into neurons and astrocytes in vitro. Here, we showed that primary NHA cells co-express low levels of mesenchymal markers Fibronectin and Collagen-1 in culture. These cells transitioned into mesenchymal-like cells when cultured in adherent conditions in serum containing media. The mesenchymal-like derivatives of these cells were characterized based on their morphological changes, high expression of Vimentin and extracellular matrix (ECM) proteins, Collagen-1 and Fibronectin, and decline of neural markers. When incubated in osteogenic and adipogenic induction media, the mesenchymal-like cells differentiated into osteoblasts and adipocytes. Furthermore, NHA cells express markers of neural crest cells, SOX-10 and p75. These data support the idea of ectoderm-derived mesenchymal lineages. These findings suggest that a population of primitive fetal brain cells with neural/neural crest/mesenchymal phenotype, resembles the remarkable phenotypic plasticity of neural crest cells, and differentiates into adipocytes and osteocytes under the influence of environmental factors

  4. Brain

    Science.gov (United States)

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  5. Effects of diltiazem, a Ca2+ channel blocker, on naloxone-precipitated changes in dopamine and its metabolites in the brains of opioid-dependent rats.

    Science.gov (United States)

    Tokuyama, S; Ho, I K

    1996-05-01

    The effects of diltiazem, an L-type Ca2+ channel blocker, on naloxone (an opioid receptor antagonist)-precipitated withdrawal signs and changes in extracellular levels of dopamine (DA) and its metabolites in various brain regions of morphine (a mu-opioid receptor agonist) or butorphanol (a mu/delta/kappa mixed opioid receptor agonist) dependent rats were investigated using high performance liquid chromatography fitted with an electrochemical detector (HPLC-ED). Rats were rendered opioid-dependent by continuous intracerebroventricular (i.c.v.) infusion with morphine (26 nmol/microliters per h) or butorphanol (26 nmol/microliters per h) for 3 days. The expression of physical dependence produced by these opioids, as evaluated by naloxone (5 mg/kg. i.p.)-precipitated withdrawal signs, was reduced by concomitant infusion of diltiazem (10 and 100 nmol/microliters per h). Under the same condition, naloxone decreased the levels of: DA in the cortex, striatum, and midbrain; 3,4-dihydroxyphenylacetic acid (DOPAC) in the cortex, striatum, limbic areas, and midbrain: and homovanilic acid (HVA) in the striatum, limbic areas, and midbrain regions. In animals rendered dependent on butorphanol, the results obtained were similar to those of morphine-dependent rats except for the changes in DOPAC levels. Furthermore, concomitant infusion of diltiazem and opioids blocked the decreases in levels of DA, DOPAC, and HVA in a dose-dependent manner. These results suggest that the augmentation of intracellular Ca2+ mediated through L-type Ca2+ channels during continuous opioid infusion results in a decrease in extracellular levels of DA and its metabolites in some specific regions, which are intimately involved in the expression of withdrawal syndrome precipitated by naloxone. PMID:8783387

  6. Functional definition of the N450 event-related brain potential marker of conflict processing: a numerical stroop study

    Directory of Open Access Journals (Sweden)

    Szűcs Dénes

    2012-03-01

    Full Text Available Abstract Background Several conflict processing studies aimed to dissociate neuroimaging phenomena related to stimulus and response conflict processing. However, previous studies typically did not include a paradigm-independent measure of either stimulus or response conflict. Here we have combined electro-myography (EMG with event-related brain potentials (ERPs in order to determine whether a particularly robust marker of conflict processing, the N450 ERP effect usually related to the activity of the Anterior Cingulate Cortex (ACC, is related to stimulus- or to response-conflict processing. EMG provided paradigm-independent measure of response conflict. In a numerical Stroop paradigm participants compared pairs of digits and pressed a button on the side where they saw the larger digit. 50% of digit-pairs were preceded by an effective cue which provided accurate information about the required response. 50% of trials were preceded by a neutral cue which did not communicate the side of response. Results EMG showed that response conflict was significantly larger in neutrally than in effectively cued trials. The N450 was similar when response conflict was high and when it was low. Conclusions We conclude that the N450 is related to stimulus or abstract, rather than to response conflict detection/resolution. Findings may enable timing ACC conflict effects.

  7. [Brain neurotransmitter systems gene Polymorphism: the Search for pharmacogenetic markers of efficacy of haloperidol in Russians and Tatars].

    Science.gov (United States)

    Gareeva, A E; Kinyasheva, K O; Galaktionova, D Yu; Sabirov, E T; Valinourov, R G; Chudinov, A V; Zasedatelev, A S; Nasedkina, T V; Khusnutdinova, E K

    2015-01-01

    Antipsychotics are the main drugs for the treatment of severe mental illness--schizophrenia affects about 1% of the population. The mechanism of action of neuroleptics is still up to the end. Several studies in the field of pharmacogenetics confirm enourmous influence of several neurotransmitter systems in the brain on the efficiency and the development of side effects. In this paper, we analyzed the association of nine polymorphic variants of five genes of dopaminergic and serotonergic systems DRD4, HTR2A, TPH1, SLC18A1, COMT in Russian and Tatars patients living in the Republic of Bashkortostan (RB) with the efficiency of a typical antipsychotic haloperidol on the scale of positive and negative systems of PANSS. The study established pharmacogenetic markers of increased and decreased effectiveness of therapy with haloperidol in the treatment groups. The results of this study confirm the importance of changes in the nucleotide sequences of the studied genes of the serotoninergic and dopaminergic systems (HTR2A, TPH1, SLC18A1 COMT, DRD4) in the formation of individual sensitivity to haloperidol. The results of our work considered as preliminary contact, requires an increase in the number of samples studied. PMID:26710776

  8. Multi-slice echo-planar spectroscopic MR imaging provides both global and local metabolite measures in multiple sclerosis

    DEFF Research Database (Denmark)

    Mathiesen, Henrik Kahr; Tscherning, Thomas; Sorensen, Per Soelberg;

    2005-01-01

    MR spectroscopy (MRS) provides information about neuronal loss or dysfunction by measuring decreases in N-acetyl aspartate (NAA), a metabolite widely believed to be a marker of neuronal viability. In multiple sclerosis (MS), whole-brain NAA (WBNAA) has been suggested as a marker of disease...... progression and treatment efficacy in treatment trials, and the ability to measure NAA loss in specific brain regions early in the evolution of this disease may have prognostic value. Most spectroscopic studies to date have been limited to single voxels or nonlocalized measurements of WBNAA only...

  9. The Effect of Oral Feeding of Tribulus Terrestris Fruit on Some Markers of Oxidative Stress in the Brain of Diabetic Rats

    OpenAIRE

    M. Roghani; S Arbab-Soleymani

    2013-01-01

    Introduction: Chronic diabetes mellitus in the long run accompanies enhanced oxidative stress burden and decreases activity of antioxidant defense system. Due to significant role of these factors in development of some neurological disorders and with regard to antidiabetic and antioxidant effect of Tribulus terrestris (TT), this study was conducted to evaluate the effect of its oral administration on brain tissue level of some markers of lipid peroxidation and oxidative stress in diabetic rat...

  10. Target-based metabolomics for the quantitative measurement of 37 pathway metabolites in rat brain and serum using hydrophilic interaction ultra-high-performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Chen, Jiahui; Hou, Waner; Han, Bo; Liu, Guanghui; Gong, Jin; Li, Yemeng; Zhong, Danmin; Liao, Qiongfeng; Xie, Zhiyong

    2016-04-01

    Amino acids, neurotransmitters, purines, and pyrimidines are bioactive molecules that play fundamental roles in maintaining various physiological functions. Their metabolism is closely related to the health, growth, development, reproduction, and homeostasis of organisms. Most recently, comprehensive measurements of these metabolites have shown their potential as innovative approaches in disease surveillance or drug intervention. However, simultaneous measurement of these metabolites presents great difficulties. Here, we report a novel quantitative method that uses hydrophilic interaction ultra-high-performance liquid chromatography-tandem mass spectrometry (HILIC-UPLC-MS/MS), which is highly selective, high throughput, and exhibits better chromatographic behavior than existing methods. The developed method enabled the rapid quantification of 37 metabolites, spanning amino acids, neurotransmitters, purines, and pyrimidines pathways, within 6.5 min. The compounds were separated on an ACQUITY UPLC® BEH Amide column. Serum and brain homogenate were extracted by protein precipitation. The intra- and interday precision of all of the analytes was less than 11.34 %, and the accuracy was between -11.74 and 11.51 % for all quality control (QC) levels. The extraction recoveries of serum ranged from 84.58 % to 116.43 % and those of brain samples from 80.80 % to 119.39 %, while the RSD was 14.61 % or less for all recoveries. This method was used to successfully characterize alterations in the rat brain and, in particular, their dynamics in serum. The following study was performed to simultaneously test global changes of these metabolites in a serotonin antagonist p-chlorophenylalanine (PCPA)-induced anxiety and insomnia rat model to understand the effect and mechanism of PCPA. Taken together, these results show that the method is able to simultaneously monitor a large panel of metabolites and that this protocol may represent a metabolomic method to diagnose

  11. [Effect of the novel dipeptide nootropic agent noopept and its metabolite cyclo-L-prolylglycine on the transcallosal evoked potential in the rat brain].

    Science.gov (United States)

    Molodavkin, G M; Borlikova, G G; Voronina, T A; Gudasheva, T A; Ostrovskaia, R U; Tushmalova, N A; Seredenin, S B

    2002-01-01

    The effect of new nootropic dipeptides--noopept (N-phenylacetyl-L-prolylglycine, GVS-111) and its metabolite (cyclo-L-prolylglycine)--and a standard nootrope piracetam on the transcallosal evoked potential (TEP) in rat brain was studied. In the dose range from 150 to 300 mg/kg, piracetam increased the TEP amplitude, which exhibited a maximum after 1.5-2 h and then gradually decreased. Both noopept and cyclo-L-prolylglycine also increased the TEP amplitude, which attained a plateau and retained this level over the entire observation time (above 3.5 h). All the nootropes studied increased both components of the evoked potential. Piracetam and cyclo-L-prolylglycine led to an approximately equal increase in both waves, while noopept induced a somewhat greater increase in the negative TEP wave amplitude. It is suggested that the positive effect of noopept and cyclo-L-prolylglycine upon the interhemispheric signal transfer (indicated by the improved transcallosal response) can be considered as a potential neurophysiological basis for a positive drug influence on the behavioral level. PMID:12109288

  12. Measuring levels of biogenic amines and their metabolites in rat brain tissue using high-performance liquid chromatography with photodiode array detection.

    Science.gov (United States)

    Gu, Min-Jung; Jeon, Ji-Hyun; Oh, Myung Sook; Hong, Seon-Pyo

    2016-01-01

    We developed a method to detect biogenic amines and their metabolites in rat brain tissue using simultaneous high-performance liquid chromatography and a photodiode array detection. Measurements were made using a Hypersil Gold C-18 column (250 × 2.1 mm, 5 µm). The mobile phase was 5 mM perchloric acid containing 5 % acetonitrile. The correlation coefficient was 0.9995-0.9999. LODs (S/N = 3) and LOQs (S/N = 10) were as follows: dopamine 0.4 and 1.3 pg, 3, 4-dihydroxyphenylacetic acid 8.4 and 28.0 pg, serotonin 0.4 and 1.3 pg, 5-hydroxyindolacetic acid 3.4 and 11.3 pg, and homovanillic acid 8.4 and 28.0 pg. This method does not require derivatization steps, and is more sensitive than the widely used HPLC-UV method. PMID:26463700

  13. Brain-Specific Cytoskeletal Damage Markers in Cerebrospinal Fluid: Is There a Common Pattern between Amyotrophic Lateral Sclerosis and Primary Progressive Multiple Sclerosis?

    Science.gov (United States)

    Abdelhak, Ahmed; Junker, Andreas; Brettschneider, Johannes; Kassubek, Jan; Ludolph, Albert C; Otto, Markus; Tumani, Hayrettin

    2015-01-01

    Many neurodegenerative disorders share a common pathophysiological pathway involving axonal degeneration despite different etiological triggers. Analysis of cytoskeletal markers such as neurofilaments, protein tau and tubulin in cerebrospinal fluid (CSF) may be a useful approach to detect the process of axonal damage and its severity during disease course. In this article, we review the published literature regarding brain-specific CSF markers for cytoskeletal damage in primary progressive multiple sclerosis and amyotrophic lateral sclerosis in order to evaluate their utility as a biomarker for disease progression in conjunction with imaging and histological markers which might also be useful in other neurodegenerative diseases associated with affection of the upper motor neurons. A long-term benefit of such an approach could be facilitating early diagnostic and prognostic tools and assessment of treatment efficacy of disease modifying drugs. PMID:26263977

  14. Measurement of brain metabolites by 1H-MR spectroscopy in patients with alzheimer disease: a Meta analysis

    International Nuclear Information System (INIS)

    Objective: To have a systemic review of the association between relative ratio in proton magnetic resonance spectroscopy (1H-MRS) and Alzheimer's disease (AD). Methods: A search in Medline and China National Knowledge Infrastructure (CNKI) was performed, and relevant English and Chinese-language articles about assessing AD with 1H-MRS were identified. The data of relative metabolic ratios (NAA/Cr, Cho/Cr, mI/Cr) from different brain regions (hippocampus, posterior cingulate gyrus, temporal lobe, parietal lobe, frontal lobe, occipital lobe) were extracted from the articles. The quality of the articles was evaluated according to the standard recommended by Newcastle-Ottawa criteria. The Meta-analysis was done with the Review Manager 4.2 to calculate pooled weighted mean difference (WMD) with 95% confidence interval (95% CI), and linear correlation analysis between NAA/Cr ratio and mI/Cr ratio was done by SPSS 17.0. Results: Thirty six articles (27 English articles, 9 Chinese articles) were included. After heterogeneity test was done,fixed effects model or random effects model was selected. The meta-analysis showed that the NAA/Cr ratio in patients with AD was higher than that in controls (WMD:-0.14, 95% CI: -0.17 to -0.11). The mI/Cr ratio in patients with AD was lower than that in controls (WMD: 0.10, 95% CI: 0.07 to 0.13). There were greatest changes in NAA/Cr ratio and mI/Cr ratio on the hippocampus (WMD of NAA/Cr: -0.27,95% CI: -0.36 to -0.19; WMD of mI/Cr: 0.21, 95% CI: 0.10 to 0.33). There were also no differences between patients with AD and controls with respect to the Cho/Cr ratio (WMD: 0.01, 95% CI:0.00 to 0.01, P>0.05). The NAA/Cr and mI/Cr changes are markedly correlated with each other in different brain regions (r=0.947, P=0.004). Conclusion: The hippocampus region is the first to present neuropathological changes in AD and the changes of NAA/Cr and MI/Cr might reflect the neurodegenerative process of AD. (authors)

  15. Identification of pro-angiogenic markers in blood vessels from stroked-affected brain tissue using laser-capture microdissection

    Directory of Open Access Journals (Sweden)

    Baldellou Maribel

    2009-03-01

    Full Text Available Abstract Background Angiogenesis correlates with patient survival following acute ischaemic stroke, and survival of neurons is greatest in tissue undergoing angiogenesis. Angiogenesis is critical for the development of new microvessels and leads to re-formation of collateral circulation, reperfusion, enhanced neuronal survival and improved recovery. Results Here, we have isolated active (CD105/Flt-1 positive and inactive (CD105/Flt-1 minus (n=5 micro-vessel rich-regions from stroke-affected and contralateral tissue of patients using laser-capture micro-dissection. Areas were compared for pro- and anti-angiogenic gene expression using targeted TaqMan microfluidity cards containing 46 genes and real-time PCR. Further analysis of key gene de-regulation was performed by immunohistochemistry to define localization and expression patterns of identified markers and de novo synthesis by human brain microvessel endothelial cells (HBMEC was examined following oxygen-glucose deprivation (OGD. Our data revealed that seven pro-angiogenic genes were notably up-regulated in CD105 positive microvessel rich regions. These were, beta-catenin, neural cell adhesion molecule (NRCAM, matrix metalloproteinase-2 (MMP-2, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1, hepatocyte growth factor-alpha (HGF-alpha, monocyte chemottractant protein-1 (MCP-1 and and Tie-2 as well as c-kit. Immunohistochemistry demonstrated strong staining of MMP-2, HGF-alpha, MCP-1 and Tie-2 in stroke-associated regions of active remodeling in association with CD105 positive staining. In vitro, OGD stimulated production of Tie-2, MCP-1 and MMP-2 in HBMEC, demonstrated a de novo response to hypoxia. Conclusion In this work we have identified concurrent activation of key angiogenic molecules associated with endothelial cell migration, differentiation and tube-formation, vessel stabilization and stem cell homing mechanisms in areas of revascularization. Therapeutic stimulation of these

  16. HPLC-ESI-MS/MS assessment of the tetrahydro-metabolites of cortisol and cortisone in bovine urine: promising markers of dexamethasone and prednisolone treatment.

    Science.gov (United States)

    Chiesa, Luca; Panseri, Sara; Pavlovic, Radmila; Cannizzo, Francesca Tiziana; Biolatti, Bartolomeo; Divari, Sara; Villa, Roberto; Arioli, Francesco

    2016-07-01

    The effects of long-term administration of low doses of dexamethasone (DX) and prednisolone (PL) on the metabolism of endogenous corticosteroids were investigated in veal calves. In addition to cortisol (F) and cortisone (E), whose interconversion is regulated by 11β-hydroxysteroid dehydrogenases (11βHSDs), special attention was paid to tetrahydrocortisol (THF), allo-tetrahydrocortisol (aTHF), tetrahydrocortisone (THE) and allo-tetrahydrocortisone (aTHE), which are produced from F and E by catalytic activity of 5α and 5β-reductases. A specifically developed HPLC-ESI-MS/MS method achieved the complete chromatographic separation of two pairs of diastereoisomers (THF/aTHF and THE/aTHE), which, with appropriate mass fragmentation patterns, provided an unambiguous conformation. The method was linear (r(2) > 0.9905; 0.5-25 ng ml(-1)), with LOQQ of 0.5 ng ml(-1). Recoveries were in range 75-114%, while matrix effects were minimal. The experimental study was carried out on three groups of male Friesian veal calves: group PL (n = 6, PL acetate 15 mg day(-1) p.o. for 31 days); group DX (n = 5, 5 mg of estradiol (E2) i.m., weekly, and 0.4 mg day(-1) of DX p.o. for 31 days) and a control group (n = 8). Urine was collected before, during (twice) and at the end of treatment. During PL administration, the tetrahydro-metabolite levels decreased gradually and remained low after the suspension of treatment. DX reduced urinary THF that persisted after the treatment, while THE levels decreased during the experiment, but rebounded substantially after the DX was withdrawn. Both DX and PL significantly interfered with the production of F and E, leading to their complete depletion. Taken together, the results demonstrate the influence of DX and PL administration on 11βHSD activity and their impact on dysfunction of the 5-reductase pathway. In conclusion, profiling tetrahydro-metabolites of F and E might serve as an alternative, indirect but reliable, non

  17. Metabolite profiles of essential oils and molecular markers analysis to explore the biodiversity of Ferula communis: Towards conservation of the endemic giant fennel.

    Science.gov (United States)

    Rahali, Fatma Zohra; Lamine, Myriam; Gargouri, Mahmoud; Rebey, Iness Bettaieb; Hammami, Majdi; Sellami, Ibtissem Hamrouni

    2016-04-01

    Giant fennel (Ferula communis L.) is well known in folk medicine for the treatment of various organ disorders. The biological importance of members of genus Ferula prompted us to investigate the leaves of the endangered Tunisian medicinal plant F. communis L. not previously investigated. An estimate of genetic diversity and differentiation between genotypes of breeding germplasm is of key importance for its improvement. Thus, four F. communis populations were RAPD fingerprinted (63 RAPD markers generated by 7 primers) and the composition of their leaf essential oils (EO) (134 EO compounds) was characterized by GC-MS. Cluster analysis based on the leaf volatiles chemical composition of F. communis accessions defined three chemotypes according to main compounds have been distinguished: α-eudesmol/β-eudesmol/γ-terpinene; α-eudesmol/α-pinene/caryophyllene oxide and chamazulene/α-humulene chemotypes. A high genetic diversity within population and high genetic differentiation among them, based on RAPDs, were revealed (H(pop)=0.320 and GST=0.288) caused both by the habitat fragmentation, the low size of most populations and the low level of gene flow among them. The RAPD dendrogram showed separation of three groups. Populations dominated by individuals from the β-eudesmol/γ-terpinene; chemotype showed the lowest gene diversity (H=0.104), while populations with exclusively α-pinene/caryophyllene oxide chemotype showed the highest value (H=0.285). The UPGMA dendrogram and PCA analysis based on volatiles yielded higher separation among populations, indicated specific adaptation of populations to the local environments. Correlation analysis showed a non-significant association between the distance matrices based on the genetic markers (RAPD) and chemical compounds of essential oil (P>0.05) indicating no influence of genetic background on the observed chemical profiles. These results reinforce the use of both volatile compounds and RAPD markers as a starting point for

  18. Evaluation of pro-inflammatory markers plasma C-reactive protein and urinary prostaglandin-E2 metabolite in colorectal adenoma risk.

    Science.gov (United States)

    Davenport, James R; Cai, Qiuyin; Ness, Reid M; Milne, Ginger; Zhao, Zhiguo; Smalley, Walter E; Zheng, Wei; Shrubsole, Martha J

    2016-08-01

    C-reactive protein (CRP) is a pro-inflammatory protein with potential as a biomarker in predicting colon cancer risk. However, little is known regarding its association with risk of colorectal adenomas, particularly by subtypes. We conducted a colonoscopy-based matched case-control study to assess whether elevated plasma CRP levels may be associated with colorectal adenoma risk and further whether this association may be modified by urinary prostaglandin E2 metabolite (PGE-M), a biomarker of systemic prostaglandin E2 production. Included in the study were 226 cases with a single small tubular adenoma, 198 cases with multiple small tubular adenomas, 283 cases with at least one advanced adenoma, and 395 polyp-free controls. No apparent association between CRP level and risk of single small tubular adenomas was found (ptrend  = 0.59). A dose-response relationship with CRP level was observed for risk of either multiple small tubular adenomas (OR = 2.01, 95%CI = 1.10-3.68 for the highest versus lowest tertile comparison; ptrend   = 0.03) or advanced adenomas (OR = 1.81, 95%CI = 1.10-2.96 for the highest versus lowest tertile comparison; ptrend  = 0.02). In a joint analysis of CRP level and PGE-M, risk of multiple or advanced adenoma was greatest among those with highest levels of both CRP and PGE-M in comparison to those with low CRP and low PGE-M (OR = 3.72, 95%CI = 1.49-9.72). Our results suggest that elevated CRP, particularly in the context of concurrent elevated PGE-M, may be a biomarker of multiple or advanced adenoma risk in a screening age population. © 2015 Wiley Periodicals, Inc. PMID:26333108

  19. Brain N-acetylaspartate levels correlate with motor function in metachromatic leukodystrophy

    DEFF Research Database (Denmark)

    i Dali, C; Hanson, L G; Barton, N W;

    2010-01-01

    known as a marker for neuronal and axonal loss. NAA and other metabolite levels measured by proton magnetic resonance spectroscopy (MRS) correlate with performance of the brain in normal children. There is a need for sensitive measures of disease progression in patients with MLD to enable development of...

  20. Expression pattern of neural synaptic plasticity marker-Arc in different brain regions induced by conditioned drug withdrawal from acute morphine-dependent rats

    Institute of Scientific and Technical Information of China (English)

    Mu LI; Yuan-yuan HOU; Bin LU; Jie CHEN; Zhi-qiang CHI; Jing-gen LIU

    2009-01-01

    Aim: The immediate early gene Arc (activity-regulated cytoskeletal-associated protein) mRNA and protein are induced by strong synaptic activation and rapidly transported into dendrites, where they localize at active synaptic sites. Thus, the Arc mRNA and protein are proposed as a marker of neuronal reactivity to map the neural substrates that are recruited by vari-ous stimuli. In the present study, we examined the expression of Arc protein induced by conditioned naloxone-precipitated drug withdrawal in different brain regions of acute morphine-dependent rats. The objective of the present study was to address the specific neural circuits involved in conditioned place aversion (CPA) that has not yet been well characterized. Methods: Place aversion was elicited by conditioned naloxone-precipitated drug withdrawal following exposure to a single dose of morphine. An immunohistochemical method was employed to detect the expression of Arc, which was used as a plasticity marker to trace the brain areas that contribute to the formation of the place aversion. Results: Marked increases in Arc protein levels were found in the medial and lateral prefrontal cortex, the sensory cortex, the lateral striatum and the amygdala. This effect was more pronounced in the basolateral arnygdala (BLA), the central nucleus of the amygdala (CeA), and the bed nucleus of the striatal terminals (BNST) when compared with the control group.Conclusion: Our results suggest that these brain regions may play key roles In mediating the negative motivational compo-nent of opiate withdrawal.

  1. Acute and subchronic toxicity of inhaled toluene in male Long Evans rats: oxidative stress markers in brain

    Data.gov (United States)

    U.S. Environmental Protection Agency — Research interested in oxidative stress markers following exposure to VOCs This dataset is associated with the following publication: Kodavanti , P., J. Royland ,...

  2. Effect of Short Periods of Normobaric Hyperoxia on Local Brain Tissue Oxygenation and Cerebrospinal Fluid Oxidative Stress Markers in Severe Traumatic Brain Injury

    OpenAIRE

    Puccio, Ava M.; Hoffman, Leslie A.; Bayir, Hülya; Zullo, Thomas G.; Fischer, Michael; Darby, Joseph; Alexander, Sheila; Dixon, C. Edward; Okonkwo, David O.; Kochanek, Patrick M.

    2009-01-01

    Preliminary evidence suggests local brain tissue oxygenation (PbtO2) values of ≤15 mm Hg following severe traumatic brain injury (TBI) represent brain tissue hypoxia. Accordingly, many neurotrauma units attempt to maintain PbtO2 ≥20 mm Hg to avoid hypoxia. This study tested the impact of a short (2 h) trial of normobaric hyperoxia on measures of oxidative stress. We hypothesized this treatment would positively affect cerebral oxygenation but negatively affect the cellular environment via oxid...

  3. Expression of c-fos in Rat Brain as a Prelude Marker of Central Nervous System Injury in Response to Methylmercury-stimulation

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To probe into the prelude marker of central nervous system injury in response to methyl mercury chloride (MMC) stimulation and the signal transduction molecular mechanism of injury in rat brain induced by MMC. Methods The expression of c-fos mRNA in brain and the expression of c-FOS protein in cortex, hippocampus and ependyma were observed using reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemical methods. The control group was injected with physiological saline of 0.9%, while the concentrations for the exposure groups were 0.05 and 0.5,5 mg/kg MMC respectively, and the sampling times points were 20, 60, 240, 1440 min. Results The expression of c-FOS protein in cortex and hippocampus increased significantly, the accumulation of mercury in the brain induced by 0.05 mg/Kg MMC for 20 min had no significant difference compared with the control group. The mean value was 0.0044 mg/Kg, while the protein c-FOS expression had significant difference compared with the control group (P<0.01). More sensitive expression occurred in hippocampus and cortex, but not in ependyma. Conclusion The expression of c-FOS protein in cortex and hippocampus can predict the neurotoxicity of MMC in the early time, and immediately early gene (IEG) c-fos participates in the process of brain injury induced by MMC.

  4. Integrative genomic analyses identify LIN28 and OLIG2 as markers of survival and metastatic potential in childhood central nervous system primitive neuro-ectodermal brain tumours

    Science.gov (United States)

    Picard, Daniel; Miller, Suzanne; Hawkins, Cynthia E; Bouffet, Eric; Rogers, Hazel A; Chan, Tiffany SY; Kim, Seung-Ki; Ra, Young-Shin; Fangusaro, Jason; Korshunov, Andrey; Toledano, Helen; Nakamura, Hideo; Hayden, James T; Chan, Jennifer; Lafay-Cousin, Lucie; Hu, Ping X; Fan, Xing; Muraszko, Karin M; Pomeroy, Scott L; Lau, Ching C; Ng, Ho-Keung; Jones, Chris; Meter, Timothy Van; Clifford, Steven C; Eberhart, Charles; Gajjar, Amar; Pfister, Stefan M; Grundy, Richard G; Huang, Annie

    2013-01-01

    Background Childhood Central Nervous System Primitive Neuro-Ectodermal brain Tumours (CNS-PNETs) are highly aggressive brain tumours for which molecular features and best therapeutic strategy remains unknown. We interrogated a large cohort of these rare tumours in order to identify molecular markers that will enhance clinical management of CNS-PNET. Methods Transcriptional and copy number profiles from primary hemispheric CNS-PNETs were examined using clustering, gene and pathways enrichment analyses to discover tumour sub-groups and group-specific molecular markers. Immuno-histochemical and/or gene expression analyses were used to validate and examine the clinical significance of novel sub-group markers in 123 primary CNS-PNETs. Findings Three molecular sub-groups of CNS-PNETs distinguished by primitive neural (Group 1), oligo-neural (Group 2) and mesenchymal lineage (Group 3) gene expression signature were identified. Tumour sub-groups exhibited differential expression of cell lineage markers, LIN28 and OLIG2, and correlated with distinct demographics, survival and metastatic incidence. Group 1 tumours affected primarily younger females; male: female ratios were respectively 0.61 (median age 2.9 years; 95% CI: 2.4–5.2; p≤ 0.005), 1.25 (median age 7.9 years; 95% CI: 6–9.7) and 1.63 (median age 5.9 years; 95% CI: 4.9–7.8) for group 1, 2 and 3 patients. Overall outcome was poorest in group 1 patients which had a median survival of 0.8 years (95% CI: 0.47–1.2; p=0.019) as compared to 1.8 years (95% CI: 1.4–2.3) and 4.3 years; (95% CI: 0.82–7.8) respectively for group 2 and 3 patients. Group 3 tumours had the highest incidence of metastases at diagnosis; M0: M+ ratio were respectively 0.9 and 3.9 for group 3, versus group 1 and 2 tumours combined (p=0.037). Interpretation LIN28 and OLIG2 represent highly promising, novel diagnostic and prognostic molecular markers for CNS PNET that warrants further evaluation in prospective clinical trials. PMID:22691720

  5. The Effect of Oral Feeding of Tribulus Terrestris Fruit on Some Markers of Oxidative Stress in the Brain of Diabetic Rats

    Directory of Open Access Journals (Sweden)

    M Roghani

    2013-06-01

    Full Text Available Introduction: Chronic diabetes mellitus in the long run accompanies enhanced oxidative stress burden and decreases activity of antioxidant defense system. Due to significant role of these factors in development of some neurological disorders and with regard to antidiabetic and antioxidant effect of Tribulus terrestris (TT, this study was conducted to evaluate the effect of its oral administration on brain tissue level of some markers of lipid peroxidation and oxidative stress in diabetic rats. Methods: In this experimental study, rats were divided into 4 groups, i.e. control, TT-treated control, diabetic, and TT-treated diabetic groups. For induction of diabetes, streptozotcin (STZ was intraperitoneally administered (60mg/Kg. In addition, TT-treated groups received TT mixed with standard pelleted food at a weight ratio of 3% for 5 weeks. Level of malondialdehyde (MDA and nitrite as well as activity of superoxide dismutase (SOD in brain tissue were measured at the end of the study. Results: Diabetic rats showed a significant increase in tissue level of MDA (p<0.01 and nitrite (p<0.01 and a non-significant reduction of SOD activity. Furthermore, TT treatment significantly reduced level of MDA p<0.01 and nitrite (p<0.05. Also, SOD activity in treated-diabetic group was non-significantly higher as compared to diabetics. Conclusion: Chronic oral treatment with TT could attenuate some markers of lipid peroxidation and oxidative stress in brain tissue in diabetic rats which this could possibly prevent some neurological disorders due to enhanced oxidative stress.

  6. Hippocampal kindling alters the concentration of glial fibrillary acidic protein and other marker proteins in rat brain

    DEFF Research Database (Denmark)

    Hansen, A; Jørgensen, Ole Steen; Bolwig, T G;

    1990-01-01

    The effect of hippocampal kindling on neuronal and glial marker proteins was studied in the rat by immunochemical methods. In hippocampus, pyriform cortex and amygdala there was an increase in glial fibrillary acidic protein (GFAP), indicating reactive gliosis, and an increase in the glycolytic e...

  7. N-terminal pro brain natriuretic peptide in arterial hypertension--a marker for left ventricular dimensions and prognosis

    DEFF Research Database (Denmark)

    Hildebrandt, Per; Boesen, Mikael; Olsen, Michael;

    2004-01-01

    In arterial hypertension risk factor evaluation, including LV mass measurements, and risk stratification using risk charts or programs, is generally recommended. In heart failure NT-proBNP has been shown to be a marker of LV dimensions and of prognosis. If the same diagnostic and prognostic value...... no CV disease, while patients with either high NT-proBNP or CV disease had a three-four-fold increased risk. In conclusion NT-proBNP predicts LV mass in hypertensive patients and is a very strong prognostic marker in these patients. This could indicate a use of NT-proBNP in the future for risk...... is present in arterial hypertension, risk factor evaluation would be easier. In 36 patients with arterial hypertension, electrocardiographic LV hypertrophy and preserved left ventricular function, NT-proBNP was eight-fold higher than in healthy subjects. The log NT-proBNP correlated with LV mass...

  8. Association of Metabolic Dysregulation With Volumetric Brain Magnetic Resonance Imaging and Cognitive Markers of Subclinical Brain Aging in Middle-Aged Adults

    OpenAIRE

    Beiser, Alexa S; Au, Rhoda; Himali, Jayandra J.; Debette, Stephanie; DeCarli, Charles; Vasan, Ramachandran S.; Wolf, Philip A.; Seshadri, Sudha; Tan, Zaldy S.; Fox, Caroline

    2011-01-01

    Objective: Diabetic and prediabtic states, including insulin resistance, fasting hyperglycemia, and hyperinsulinemia, are associated with metabolic dysregulation. These components have been individually linked to increased risks of cognitive decline and Alzheimer’s disease. We aimed to comprehensively relate all of the components of metabolic dysregulation to cognitive function and brain magnetic resonance imaging (MRI) in middle-aged adults. Research Design and Methods: Framingham Offspring ...

  9. Novel and sensitive reversed-phase high-pressure liquid chromatography method with electrochemical detection for the simultaneous and fast determination of eight biogenic amines and metabolites in human brain tissue.

    Science.gov (United States)

    Van Dam, Debby; Vermeiren, Yannick; Aerts, Tony; De Deyn, Peter Paul

    2014-08-01

    A fast and simple RP-HPLC method with electrochemical detection (ECD) and ion pair chromatography was developed, optimized and validated in order to simultaneously determine eight different biogenic amines and metabolites in post-mortem human brain tissue in a single-run analytical approach. The compounds of interest are the indolamine serotonin (5-hydroxytryptamine, 5-HT), the catecholamines dopamine (DA) and (nor)epinephrine ((N)E), as well as their respective metabolites, i.e. 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), 5-hydroxy-3-indoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG). A two-level fractional factorial experimental design was applied to study the effect of five experimental factors (i.e. the ion-pair counter concentration, the level of organic modifier, the pH of the mobile phase, the temperature of the column, and the voltage setting of the detector) on the chromatographic behaviour. The cross effect between the five quantitative factors and the capacity and separation factors of the analytes were then analysed using a Standard Least Squares model. The optimized method was fully validated according to the requirements of SFSTP (Société Française des Sciences et Techniques Pharmaceutiques). Our human brain tissue sample preparation procedure is straightforward and relatively short, which allows samples to be loaded onto the HPLC system within approximately 4h. Additionally, a high sample throughput was achieved after optimization due to a total runtime of maximally 40min per sample. The conditions and settings of the HPLC system were found to be accurate with high intra and inter-assay repeatability, recovery and accuracy rates. The robust analytical method results in very low detection limits and good separation for all of the eight biogenic amines and metabolites in this complex mixture of biological analytes. PMID:24857034

  10. BDNF Val66met and 5-HTTLPR polymorphisms predict a human in vivo marker for brain serotonin levels

    DEFF Research Database (Denmark)

    Fisher, Patrick M; Holst, Klaus K; Adamsen, Dea; Klein, Anders Bue; Frokjaer, Vibe G; Jensen, Peter S; Svarer, Claus; Gillings, Nic; Baare, William F C; Mikkelsen, Jens D; Knudsen, Gitte M

    2015-01-01

    BDNF val66met significantly predicted a LV reflecting [(11) C]SB207145 binding across regions (P = 0.005). BDNF val66met met-carriers showed 2-9% higher binding relative to val/val homozygotes. In contrast, 5-HTTLPR did not predict the LV but S-carriers showed 7% lower neocortical binding relative to...... LL homozygotes (P = 7.3 × 10(-6) ). We observed no evidence for genetic interaction. Our findings indicate that BDNF val66met significantly predicts a common regulator of brain [(11) C]SB207145 binding, which we hypothesize reflects brain serotonin levels. In contrast, our data indicate that 5-HTTLPR...

  11. Gene expression analysis of neuronal precursors from adult mouse brain and differential screen for neural stem cell markers

    OpenAIRE

    Pennartz, Sandra

    2004-01-01

    In the adult mouse brain, neuronal precursor cells continuously emanate from neural stem cells (NSC) in the subventricular zone (SVZ) and migrate into the olfactory bulb (OB) where they differentiate to serve as replenishment for GABAergic interneurons. During the migration process, PSA-NCAM (Polysialic acid-Neural cell adhesion molecule) specifically marks the neuronal precursors (PSA+ cells). This phenomenon was exploited in the framework of this doctoral thesis to isolate a homogeneous cel...

  12. Reaction time impairments in decision-making networks as a diagnostic marker for traumatic brain injuries and neurodegenerative diseases

    OpenAIRE

    Maia, Pedro D; Kutz, J Nathan

    2016-01-01

    The presence of diffuse Focal Axonal Swellings (FAS) is a hallmark cellular feature in many neurodegenerative diseases and traumatic brain injury. Among other things, the FAS have a significant impact on spike-train encodings that propagate through the affected neurons, leading to compromised signal processing on a neuronal network level. This work merges, for the first time, three fields of study: (i) signal processing in excitatory-inhibitory (EI) networks of neurons via population codes, (...

  13. Brain-type and liver-type fatty acid-binding proteins: new tumor markers for renal cancer?

    OpenAIRE

    Moch Holger; Miller Kurt; Johannsen Manfred; Lein Michael; Jung Monika; Tölle Angelika; Jung Klaus; Kristiansen Glen

    2009-01-01

    Abstract Background Renal cell carcinoma (RCC) is the most common renal neoplasm. Cancer tissue is often characterized by altered energy regulation. Fatty acid-binding proteins (FABP) are involved in the intracellular transport of fatty acids (FA). We examined the level of brain-type (B) and liver-type (L) FABP mRNA and the protein expression profiles of both FABPs in renal cell carcinoma. Methods Paired tissue samples of cancerous and noncancerous kidney parts were investigated. Quantitative...

  14. Altered protein markers related to neural plasticity and motor function following electro-acupuncture treatment in rat model of ischemic-hypoxic brain injury

    Institute of Scientific and Technical Information of China (English)

    Liping Zhang; Liping Zou

    2008-01-01

    BACKGROUND: Previous studies have demonstrated that acupuncture treatment could ameliorate impaired motor function, and these positive effects might be due to neural plasticity. OBJECTIVE: Myelin basic protein (MBP), microtubule-associated protein 2 (MAP2), growth-associated protein-43 (GAP-43), and synaptophysin (SYN) were selected as markers of neural remodeling, and expression of these markers was evaluated with regard to altered motor function following brain injury and acupuncture treatment. DESIGN, TIME AND SETTING: A completely randomized experiment was performed at the Central Laboratory of Peking University First Hospital from November 2006 to May 2007. MATERIALS: Twenty-four Sprague Dawley rat pups, aged 7 days, were selected for the present experiment. The left common carotid artery was ligated to establish a rat model of ischemic-hypoxic brain injury.METHODS: All animals were randomly divided into three groups: sham operation, model, and electro-acupuncture treatment, with 8 rats in each group. Rats in the model and electro-acupuncture treatment group underwent establishment of ischemic-hypoxic brain injury. Upon model established, rats underwent hypobaric oxygen intervention for 24 hours. Only the left common carotid artery was exposed in rats of the sham operation group, without model establishment or oxygen intervention. The rats in the electro-acupuncture treatment group were treated with electro-acupuncture. One acupuncture needle electrode was inserted into the subcutaneous layer at the Baihui and Dazhui acupoint. The stimulation condition of the electro-acupuncture simulator was set to an amplitude-modulated wave of 0-100% and alternative frequency of 100 cycles/second, as well as frequency-modulated wave of 2-100 Hz and an alternative frequency of 3 cycles/second. Maximal current through the two dectrodes was limited to 3-5 mA. The stimulation lasted for 30 minutes per day for 2 weeks. Rats in the sham operation and model groups were not treated

  15. Volatile Metabolites

    Directory of Open Access Journals (Sweden)

    Daryl D. Rowan

    2011-11-01

    Full Text Available Volatile organic compounds (volatiles comprise a chemically diverse class of low molecular weight organic compounds having an appreciable vapor pressure under ambient conditions. Volatiles produced by plants attract pollinators and seed dispersers, and provide defense against pests and pathogens. For insects, volatiles may act as pheromones directing social behavior or as cues for finding hosts or prey. For humans, volatiles are important as flavorants and as possible disease biomarkers. The marine environment is also a major source of halogenated and sulfur-containing volatiles which participate in the global cycling of these elements. While volatile analysis commonly measures a rather restricted set of analytes, the diverse and extreme physical properties of volatiles provide unique analytical challenges. Volatiles constitute only a small proportion of the total number of metabolites produced by living organisms, however, because of their roles as signaling molecules (semiochemicals both within and between organisms, accurately measuring and determining the roles of these compounds is crucial to an integrated understanding of living systems. This review summarizes recent developments in volatile research from a metabolomics perspective with a focus on the role of recent technical innovation in developing new areas of volatile research and expanding the range of ecological interactions which may be mediated by volatile organic metabolites.

  16. Neural markers of negative symptom outcomes in distributed working memory brain activity of antipsychotic-naive schizophrenia patients

    DEFF Research Database (Denmark)

    Nejad, Ayna B.; Madsen, Kristoffer H.; Ebdrup, Bjørn H.;

    2013-01-01

    Since working memory deficits in schizophrenia have been linked to negative symptoms, we tested whether features of the one could predict the treatment outcome in the other. Specifically, we hypothesized that working memory-related functional connectivity at pre-treatment can predict improvement of......-back task. Spatial independent component analysis identified task-modulated brain networks. A linear support vector machine was trained with these components to discriminate six patients who showed improvement in negative symptoms from eight non-improvers. Classification accuracy and significance was...

  17. γ-H2AX as a marker for dose deposition in the brain of wistar rats after synchrotron microbeam radiation.

    Directory of Open Access Journals (Sweden)

    Cristian Fernandez-Palomo

    Full Text Available Synchrotron radiation has shown high therapeutic potential in small animal models of malignant brain tumours. However, more studies are needed to understand the radiobiological effects caused by the delivery of high doses of spatially fractionated x-rays in tissue. The purpose of this study was to explore the use of the γ-H2AX antibody as a marker for dose deposition in the brain of rats after synchrotron microbeam radiation therapy (MRT.Normal and tumour-bearing Wistar rats were exposed to 35, 70 or 350 Gy of MRT to their right cerebral hemisphere. The brains were extracted either at 4 or 8 hours after irradiation and immediately placed in formalin. Sections of paraffin-embedded tissue were incubated with anti γ-H2AX primary antibody.While the presence of the C6 glioma does not seem to modulate the formation of γ-H2AX in normal tissue, the irradiation dose and the recovery versus time are the most important factors affecting the development of γ-H2AX foci. Our results also suggest that doses of 350 Gy can trigger the release of bystander signals that significantly amplify the DNA damage caused by radiation and that the γ-H2AX biomarker does not only represent DNA damage produced by radiation, but also damage caused by bystander effects.In conclusion, we suggest that the γ-H2AX foci should be used as biomarker for targeted and non-targeted DNA damage after synchrotron radiation rather than a tool to measure the actual physical doses.

  18. Lateral ventricular cerebrospinal fluid diffusivity as a potential neuroimaging marker of brain temperature in multiple sclerosis: a hypothesis and implications.

    Science.gov (United States)

    Hasan, Khader M; Lincoln, John A; Nelson, Flavia M; Wolinsky, Jerry S; Narayana, Ponnada A

    2015-04-01

    In this retrospective study we tested the hypothesis that the net effect of impaired electrical conduction and therefore increased heat dissipation in multiple sclerosis (MS) results in elevated lateral ventricular (LV) cerebrospinal fluid (CSF) diffusivity as a measure of brain temperature estimated in vivo using diffusion tensor imaging (DTI). We used validated DTI-based segmentation methods to obtain normalized LV-CSF volume and its corresponding CSF diffusivity in 108 MS patients and 103 healthy controls in the age range of 21-63 years. The LV CSF diffusivity was ~2% higher in MS compared to controls that correspond to a temperature rise of ~1°C that could not be explained by changes in the CSF viscosity due to altered CSF protein content in MS. The LV diffusivity decreased with age in healthy controls (r=-0.29; p=0.003), but not in MS (r=0.15; p=0.11), possibly related to MS pathology. Age-adjusted LV diffusivity increased with lesion load (r=0.518; p=1×10(-8)). Our data suggest that the total brain lesion load is the primary contributor to the increase in LV CSF diffusivity in MS. These findings suggest that LV diffusivity is a potential in vivo biomarker of the mismatch between heat generation and dissipation in MS. We also discuss limitations and possible confounders. PMID:25485790

  19. Analysis of metabolites in human brain tumors and cerebral infarctions using {sup 31}P- and {sup 1}H-magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Hirakawa, Wataru [Kagoshima Univ. (Japan). Faculty of Medicine

    1996-08-01

    {sup 31}P- and {sup 1}H-MRS with a 2.0 tesla MRI/S system was used to monitor the cerebral energy levels, phospholipid metabolism, intracellular pH, and lactate and amino acid levels in patients with brain tumors and cerebral infarctions. Studies of human brain tumors have suggested that the {sup 31}P-MRS of malignant brain tumors show low concentrations of phosphocreatine (PCr) and {beta}-ATP, high levels of phosphomonoester (PME) and inorganic Pi, and an alkaline pH. The Pi, PME, and intracellular pH of malignant lymphoma were higher than those of other brain tumors. {sup 1}H-MRS showed an increase of lactate in malignant brain tumors and epidermoids. After ACNU administration, the tumor {sup 31}P-MRS showed transient reduction and elevation of Pi on five patients with malignant gliomas. Intracellular pH also showed a transient reduction during radiotherapy. {sup 1}H-MRS showed a reduction of lactate at the beginning of therapy and showed a marked re-elevation of lactate with tumor regrowth. After radiotherapy, the normal brain {sup 31}P-MRS showed transient elevation and reduction of Pi. Intracellular pH also showed a transient elevation during radiotherapy. To investigate the mechanism of hyperbaric oxygen therapy (HBO) in cerebral ischemia, changes of brain lactate level were estimated by {sup 1}H-MRS. Although the Lactate/Creatine ratio decreased consistently over time in all patients, it decreased more rapidly in the patients receiving HBO therapy than in those without such therapy. {sup 1}H-MRS demonstrated that HBO therapy may improve metabolism in the ischemic brain and reduces the lactate levels. {sup 31}P- and {sup 1}H-MRS are practical tools for the clinical analysis of cerebral disorders as well as for deciding on therapeutic procedures and evaluating the response. (K.H.)

  20. 1H chemical shift imaging characterization of human brain tumor and edema

    International Nuclear Information System (INIS)

    Longitudinal (T1) and transverse (T2) relaxation times of metabolites in human brain tumor, peritumoral edema, and unaffected brain tissue were assessed from point resolved spectroscopy (PRESS) 1H chemical shift imaging results at different repetition times (TR=1500 and 5000 ms; T1: n=19) and echo times (TE=135 and 270 ms; T2: n=7). Metabolite T1 and T2 relaxation times in unaffected brain tissue corresponded with those published for healthy volunteers. T2 relaxation times were reduced in tumor (choline, N-acetyl aspartate) and edema (choline, creatine) compared with unaffected brain tissue (p1H chemical shift imaging is most suited in the use of choline elevation as tumor marker. (orig.)

  1. Magnetic microparticle-based SELEX process for the identification of highly specific aptamers of heart marker--brain natriuretic peptide

    International Nuclear Information System (INIS)

    The brain natriuretic peptide (BNP) is known to be an effective indicator of heart failure. It has been widely adopted as a parameter for the evaluation of heart function of cardiovascular and cerebrovascular diseases (CVDs). Current immune-recognition based methods for the detection of BNP are limited, to a certain extent, by the poor stability of the antibody and by high costs. The availability of an aptamer specific for BNP would greatly assist in the rapid and early diagnosis of CVDs. In order to screen for such an aptamer by the SELEX method, we have used magnetic microparticles (m-MPs) as the separation substrate for immobilization of target BNP. The use of m-MPs for rapid separation of combined aptamers enables bound oligonucleotides to be separated directly, quickly, and with high efficiency. After 14 rounds of selection, a panel of six aptamers against BNP was identified. Their dissociation constants range from 12.5 to 139 nM. The classical technique for conjugation of a target to m-MPs is known to be applicable to various fields, and we conclude that this m-MP-based SELEX process provides a general strategy for screening of specific aptamers against various analytes. (author)

  2. Exercise-induced motor improvement after complete spinal cord transection and its relation to expression of brain-derived neurotrophic factor and presynaptic markers

    Directory of Open Access Journals (Sweden)

    Sulejczak Dorota

    2009-12-01

    Full Text Available Abstract Background It has been postulated that exercise-induced activation of brain-derived neurotrophic factor (BDNF may account for improvement of stepping ability in animals after complete spinal cord transection. As we have shown previously, treadmill locomotor exercise leads to up-regulation of BDNF protein and mRNA in the entire neuronal network of intact spinal cord. The questions arise: (i how the treadmill locomotor training, supplemented with tail stimulation, affects the expression of molecular correlates of synaptic plasticity in spinal rats, and (ii if a response is related to BDNF protein level and distribution. We investigated the effect of training in rats spinalized at low thoracic segments on the level and distribution of BDNF immunoreactivity (IR in ventral quadrants of the lumbar segments, in conjunction with markers of presynaptic terminals, synaptophysin and synaptic zinc. Results Training improved hindlimb stepping in spinal animals evaluated with modified Basso-Beattie-Bresnahan scale. Grades of spinal trained animals ranged between 5 and 11, whereas those of spinal were between 2 and 4. Functional improvement was associated with changes in presynaptic markers and BDNF distribution. Six weeks after transection, synaptophysin IR was reduced by 18% around the large neurons of lamina IX and training elevated its expression by over 30%. The level of synaptic zinc staining in the ventral horn was unaltered, whereas in ventral funiculi it was decreased by 26% postlesion and tended to normalize after the training. Overall BDNF IR levels in the ventral horn, which were higher by 22% postlesion, were unchanged after the training. However, training modified distribution of BDNF in the processes with its predominance in the longer and thicker ones. It also caused selective up-regulation of BDNF in two classes of cells (soma ranging between 100-400 μm2 and over 1000 μm2 of the ventrolateral and laterodorsal motor nuclei

  3. Effect of vitamin B deprivation during pregnancy and lactation on homocysteine metabolism and related metabolites in brain and plasma of mice offspring.

    Directory of Open Access Journals (Sweden)

    Vanessa Cavalcante da Silva

    Full Text Available Epidemiological and experimental studies indicate that the altered fetal and neonatal environment influences physiological functions and may increase the risk of developing chronic diseases in adulthood. Because homocysteine (Hcy metabolic imbalance is considered a risk factor for neurodegenerative diseases, we investigated whether maternal Vitamin B deficiency during early development alters the offspring's methionine-homocysteine metabolism in their brain. To this end, the dams were submitted to experimental diet one month before and during pregnancy or pregnancy/lactation. After birth, the offspring were organized into the following groups: control (CT, deficient diet during pregnancy and lactation (DPL and deficient diet during pregnancy (DP. The mice were euthanized at various stages of development. Hcy, cysteine, glutathione (GSH, S-adenosylmethionine (SAM, S-adenosylhomocysteine (SAH, folate and cobalamin concentrations were measured in the plasma and/or brain. At postnatal day (PND 0, total brain of female and male offspring exhibited decreased SAM/SAH ratios. Moreover, at PND 28, we observed decreased GSH/GSSG ratios in both females and males in the DPL group. Exposure to a Vitamin B-deficient diet during the ontogenic plasticity period had a negative impact on plasma folate and brain cortex SAM concentrations in aged DPL males. We also observed decreased plasma GSH concentrations in both DP and DPL males (PND 210. Additionally, this manipulation seemed to affect the female and male offspring differently. The decreased plasma GSH concentration may reflect redox changes in tissues and the decreased brain cortex SAM may be involved in changes of gene expression, which could contribute to neurodegenerative diseases over the long term.

  4. Effect of vitamin B deprivation during pregnancy and lactation on homocysteine metabolism and related metabolites in brain and plasma of mice offspring.

    Science.gov (United States)

    da Silva, Vanessa Cavalcante; Fernandes, Leandro; Haseyama, Eduardo Jun; Agamme, Ana Luiza Dias Abdo; Guerra Shinohara, Elvira Maria; Muniz, Maria Tereza Cartaxo; D'Almeida, Vânia

    2014-01-01

    Epidemiological and experimental studies indicate that the altered fetal and neonatal environment influences physiological functions and may increase the risk of developing chronic diseases in adulthood. Because homocysteine (Hcy) metabolic imbalance is considered a risk factor for neurodegenerative diseases, we investigated whether maternal Vitamin B deficiency during early development alters the offspring's methionine-homocysteine metabolism in their brain. To this end, the dams were submitted to experimental diet one month before and during pregnancy or pregnancy/lactation. After birth, the offspring were organized into the following groups: control (CT), deficient diet during pregnancy and lactation (DPL) and deficient diet during pregnancy (DP). The mice were euthanized at various stages of development. Hcy, cysteine, glutathione (GSH), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), folate and cobalamin concentrations were measured in the plasma and/or brain. At postnatal day (PND) 0, total brain of female and male offspring exhibited decreased SAM/SAH ratios. Moreover, at PND 28, we observed decreased GSH/GSSG ratios in both females and males in the DPL group. Exposure to a Vitamin B-deficient diet during the ontogenic plasticity period had a negative impact on plasma folate and brain cortex SAM concentrations in aged DPL males. We also observed decreased plasma GSH concentrations in both DP and DPL males (PND 210). Additionally, this manipulation seemed to affect the female and male offspring differently. The decreased plasma GSH concentration may reflect redox changes in tissues and the decreased brain cortex SAM may be involved in changes of gene expression, which could contribute to neurodegenerative diseases over the long term. PMID:24695104

  5. Brain-type and liver-type fatty acid-binding proteins: new tumor markers for renal cancer?

    Directory of Open Access Journals (Sweden)

    Moch Holger

    2009-07-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is the most common renal neoplasm. Cancer tissue is often characterized by altered energy regulation. Fatty acid-binding proteins (FABP are involved in the intracellular transport of fatty acids (FA. We examined the level of brain-type (B and liver-type (L FABP mRNA and the protein expression profiles of both FABPs in renal cell carcinoma. Methods Paired tissue samples of cancerous and noncancerous kidney parts were investigated. Quantitative RT-PCR, immunohistochemistry and western blotting were used to determine B- and L-FABP in tumor and normal tissues. The tissue microarray (TMA contained 272 clinico-pathologically characterized renal cell carcinomas of the clear cell, papillary and chromophobe subtype. SPSS 17.0 was used to apply crosstables (χ2-test, correlations and survival analyses. Results B-FABP mRNA was significantly up-regulated in renal cell carcinoma. In normal tissue B-FABP mRNA was very low or often not detectable. RCC with a high tumor grading (G3 + G4 showed significantly lower B-FABP mRNA compared with those with a low grading (G1 + G2. Western blotting analysis detected B-FABP in 78% of the cases with a very strong band but in the corresponding normal tissue it was weak or not detectable. L-FABP showed an inverse relationship for mRNA quantification and western blotting. A strong B-FABP staining was present in 52% of the tumor tissues contained in the TMA. In normal renal tissue, L-FABP showed a moderate to strong immunoreactivity in proximal tubuli. L-FABP was expressed at lower rates compared with the normal tissues in 30.5% of all tumors. There was no correlation between patient survival times and the staining intensity of both FABPs. Conclusion While B-FABP is over expressed in renal cell carcinoma in comparison to normal renal tissues L-FABP appears to be reduced in tumor tissue. Although the expression behavior was not related to the survival outcome of the RCC patients

  6. Brain-type and liver-type fatty acid-binding proteins: new tumor markers for renal cancer?

    International Nuclear Information System (INIS)

    Renal cell carcinoma (RCC) is the most common renal neoplasm. Cancer tissue is often characterized by altered energy regulation. Fatty acid-binding proteins (FABP) are involved in the intracellular transport of fatty acids (FA). We examined the level of brain-type (B) and liver-type (L) FABP mRNA and the protein expression profiles of both FABPs in renal cell carcinoma. Paired tissue samples of cancerous and noncancerous kidney parts were investigated. Quantitative RT-PCR, immunohistochemistry and western blotting were used to determine B- and L-FABP in tumor and normal tissues. The tissue microarray (TMA) contained 272 clinico-pathologically characterized renal cell carcinomas of the clear cell, papillary and chromophobe subtype. SPSS 17.0 was used to apply crosstables (χ2-test), correlations and survival analyses. B-FABP mRNA was significantly up-regulated in renal cell carcinoma. In normal tissue B-FABP mRNA was very low or often not detectable. RCC with a high tumor grading (G3 + G4) showed significantly lower B-FABP mRNA compared with those with a low grading (G1 + G2). Western blotting analysis detected B-FABP in 78% of the cases with a very strong band but in the corresponding normal tissue it was weak or not detectable. L-FABP showed an inverse relationship for mRNA quantification and western blotting. A strong B-FABP staining was present in 52% of the tumor tissues contained in the TMA. In normal renal tissue, L-FABP showed a moderate to strong immunoreactivity in proximal tubuli. L-FABP was expressed at lower rates compared with the normal tissues in 30.5% of all tumors. There was no correlation between patient survival times and the staining intensity of both FABPs. While B-FABP is over expressed in renal cell carcinoma in comparison to normal renal tissues L-FABP appears to be reduced in tumor tissue. Although the expression behavior was not related to the survival outcome of the RCC patients, it can be assumed that these changes indicate fundamental

  7. Morphine metabolites

    DEFF Research Database (Denmark)

    Christrup, Lona Louring

    1997-01-01

    systemic administration reflect hepatic metabolism of morphine and that the morphine glucuronides, despite their high polarity, can penetrate into the brain. Like morphine, M6G has been shown to be relatively more selective for mu-receptors than for delta- and kappa-receptors while M3G does not appear to...... morphine, M6G and M3G has revealed that M6G and M3G were present in abundance after chronic oral morphine administration and that the area under the plasma concentration-time curve exceeded that of morphine. M3G has been found to antagonise morphine and M6G induced analgesia and ventilatory depression in...

  8. A liquid chromatography/mass spectrometric method for simultaneous analysis of arachidonic acid and its endogenous eicosanoid metabolites prostaglandins, dihydroxyeicosatrienoic acids, hydroxyeicosatetraenoic acids, and epoxyeicosatrienoic acids in rat brain tissue.

    Science.gov (United States)

    Yue, Hongfei; Jansen, Susan A; Strauss, Kenneth I; Borenstein, Michael R; Barbe, Mary F; Rossi, Luella J; Murphy, Elise

    2007-02-19

    A sensitive, specific, and robust liquid chromatography/mass spectrometric (LC/MS) method was developed and validated that allows simultaneous analysis of arachidonic acid (AA) and its cyclooxygenase, cytochrome P450, and lipoxygenase pathway metabolites prostaglandins (PGs), dihydroxyeicosatrienoic acids (DiHETrEs), hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs), including PGF(2alpha), PGE(2), PGD(2), PGJ(2), 14,15-DiHETrE, 11,12-DiHETrE, 8,9-DiHETrE, 5,6-DiHETrE, 20-HETE, 15-HETE, 12-HETE, 9-HETE, 8-HETE, 5-HETE, 14,15-EET, 11,12-EET, 8,9-EET, and 5,6-EET in rat brain tissues. Deuterium labeled PGF(2alpha)-d(4), PGD(2)-d(4), 15(S)-HETE-d(8), 14,15-EET-d(8), 11,12-EET-d(8), 8,9-EET-d(8), and AA-d(8) were used as internal standards. Solid phase extraction was used for sample preparation. A gradient LC/MS method using a C18 column and electrospray ionization source under negative ion mode was optimized for the best sensitivity and separation within 35 min. The method validation, including LC/MS instrument qualification, specificity, calibration model, accuracy, precision (without brain matrix and with brain matrix), and extraction efficiency were performed. The linear ranges of the calibration curves were 2-1000 pg for PGs, DiHETrEs, HETEs, and EETs, 10-2400 pg for PGE(2) and PGD(2), and 20-2000 ng for AA, respectively. PMID:17125954

  9. Disposition of Cannabichromene, Cannabidiol, and Δ9-Tetrahydrocannabinol and its Metabolites in Mouse Brain following Marijuana Inhalation Determined by High-Performance Liquid Chromatography–Tandem Mass Spectrometry

    OpenAIRE

    Poklis, Justin L.; Thompson, Candace C.; Long, Kelly A.; Lichtman, Aron H.; Poklis, Alphonse

    2010-01-01

    A liquid chromatography–tandem mass spectrometry (LC–MS–MS) method was developed for the analysis of marijuana cannabinoids in mouse brain tissue using an Applied Biosystems 3200 Q trap with a turbo V source for TurbolonSpray attached to a Shimadzu SCL HPLC system. The method included cannabichromene (CBC), cannabidiol (CBD), D9-tetrahydrocannabinol (THC), 11-hydroxytetrahydrocannabinol (11-OH-THC), and 11-nor-D9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH). These compounds were isolated...

  10. Effect of Vitamin B Deprivation during Pregnancy and Lactation on Homocysteine Metabolism and Related Metabolites in Brain and Plasma of Mice Offspring

    OpenAIRE

    da Silva, Vanessa Cavalcante; Fernandes, Leandro; Haseyama, Eduardo Jun; Agamme, Ana Luiza Dias Abdo; Shinohara, Elvira Maria Guerra; Muniz, Maria Tereza Cartaxo; D'Almeida, Vânia

    2014-01-01

    Epidemiological and experimental studies indicate that the altered fetal and neonatal environment influences physiological functions and may increase the risk of developing chronic diseases in adulthood. Because homocysteine (Hcy) metabolic imbalance is considered a risk factor for neurodegenerative diseases, we investigated whether maternal Vitamin B deficiency during early development alters the offspring's methionine-homocysteine metabolism in their brain. To this end, the dams were submit...

  11. Correlation of Ultrastructural Changes of Endothelial Cells and Astrocytes Occurring during Blood Brain Barrier Damage after Traumatic Brain Injury with Biochemical Markers of Blood Brain Barrier Leakage and Inflammatory Response

    Czech Academy of Sciences Publication Activity Database

    Vajtr, D.; Benada, Oldřich; Kukačka, J.; Průša, R.; Houšťava, L.; Toupalík, P.; Kizek, R.

    2009-01-01

    Roč. 58, č. 2 (2009), s. 263-268. ISSN 0862-8408 Institutional research plan: CEZ:AV0Z50200510 Keywords : Blood brain barrier * Expansive contusion * Metalloproteinases Subject RIV: EE - Microbiology, Virology Impact factor: 1.430, year: 2009

  12. Urine albumin/creatinine ratio, high sensitivity C-reactive protein and N-terminal pro brain natriuretic peptide--three new cardiovascular risk markers--do they improve risk prediction and influence treatment?

    DEFF Research Database (Denmark)

    Olsen, Michael H; Sehestedt, Thomas; Lyngbaek, Stig; Hansen, Tine W; Rasmussen, Susanne; Wachtell, Kristian; Torp-Pedersen, Christian; Hildebrandt, Per R; Ibsen, Hans

    2010-01-01

    In order to prioritize limited health resources in a time of increasing demands optimal cardiovascular risk stratification is essential. We tested the additive prognostic value of 3 relatively new, but established cardiovascular risk markers: N-terminal pro brain natriuretic peptide (Nt-proBNP), ......In order to prioritize limited health resources in a time of increasing demands optimal cardiovascular risk stratification is essential. We tested the additive prognostic value of 3 relatively new, but established cardiovascular risk markers: N-terminal pro brain natriuretic peptide (Nt...... death lower than 5% based on HeartScore and therefore not eligible for primary prevention, the actual 10-year risk of cardiovascular death exceeded 5% in a small subgroup of subjects with UACR higher than the 95-percentile of approximately 1.6 mg/mmol. Combined use of high UACR or high hsCRP identified...

  13. Can low brain-derived neurotrophic factor levels be a marker of the presence of depression in obese women?

    Directory of Open Access Journals (Sweden)

    Celik Guzel E

    2014-11-01

    levels lower than 70.2 pg/mL were associated with a higher prevalence of depressive symptoms. Conclusion: The results of our study suggest that the decrease in BDNF levels can be used as a marker for depression diagnosis in obese patients. Keywords: obesity, brain-derived neurotrophic factor, comorbidity

  14. Prehospital resuscitation with hypertonic saline-dextran modulates inflammatory, coagulation and endothelial activation marker profiles in severe traumatic brain injured patients

    Directory of Open Access Journals (Sweden)

    Morrison Laurie J

    2010-01-01

    Full Text Available Abstract Background Traumatic brain injury (TBI initiates interrelated inflammatory and coagulation cascades characterized by wide-spread cellular activation, induction of leukocyte and endothelial cell adhesion molecules and release of soluble pro/antiinflammatory cytokines and thrombotic mediators. Resuscitative care is focused on optimizing cerebral perfusion and reducing secondary injury processes. Hypertonic saline is an effective osmotherapeutic agent for the treatment of intracranial hypertension and has immunomodulatory properties that may confer neuroprotection. This study examined the impact of hypertonic fluids on inflammatory/coagulation cascades in isolated head injury. Methods Using a prospective, randomized controlled trial we investigated the impact of prehospital resuscitation of severe TBI (GCS vs 0.9% normal saline (NS, on selected cellular and soluble inflammatory/coagulation markers. Serial blood samples were drawn from 65 patients (30 HSD, 35 NS at the time of hospital admission and at 12, 24, and 48-h post-resuscitation. Flow cytometry was used to analyze leukocyte cell-surface adhesion (CD62L, CD11b and degranulation (CD63, CD66b molecules. Circulating concentrations of soluble (sL- and sE-selectins (sL-, sE-selectins, vascular and intercellular adhesion molecules (sVCAM-1, sICAM-1, pro/antiinflammatory cytokines [tumor necrosis factor (TNF-α and interleukin (IL-10], tissue factor (sTF, thrombomodulin (sTM and D-dimers (D-D were assessed by enzyme immunoassay. Twenty-five healthy subjects were studied as a control group. Results TBI provoked marked alterations in a majority of the inflammatory/coagulation markers assessed in all patients. Relative to control, NS patients showed up to a 2-fold higher surface expression of CD62L, CD11b and CD66b on polymorphonuclear neutrophils (PMNs and monocytes that persisted for 48-h. HSD blunted the expression of these cell-surface activation/adhesion molecules at all time-points to

  15. NMDA Receptors and Oxidative Stress Induced by the Major Metabolites Accumulating in HMG Lyase Deficiency Mediate Hypophosphorylation of Cytoskeletal Proteins in Brain From Adolescent Rats: Potential Mechanisms Contributing to the Neuropathology of This Disease.

    Science.gov (United States)

    Fernandes, Carolina Gonçalves; Pierozan, Paula; Soares, Gilberto Machado; Ferreira, Fernanda; Zanatta, Ângela; Amaral, Alexandre Umpierrez; Borges, Clarissa Günther; Wajner, Moacir; Pessoa-Pureur, Regina

    2015-10-01

    Neurological symptoms and cerebral abnormalities are commonly observed in patients with 3-hydroxy-3-methylglutaryl-CoA lyase (HMG lyase) deficiency, which is biochemically characterized by predominant tissue accumulation of 3-hydroxy-3-methylglutaric (HMG), 3-methylglutaric (MGA), and 3-methylglutaconic (MGT) acids. Since the pathogenesis of this disease is poorly known, the present study evaluated the effects of these compounds on the cytoskeleton phosphorylating system in rat brain. HMG, MGA, and MGT caused hypophosphorylation of glial fibrillary acidic protein (GFAP) and of the neurofilament subunits NFL, NFM, and NFH. HMG-induced hypophosphorylation was mediated by inhibiting the cAMP-dependent protein kinase (PKA) on Ser55 residue of NFL and c-Jun kinase (JNK) by acting on KSP repeats of NFM and NFH subunits. We also evidenced that the subunit NR2B of NMDA receptor and Ca(2+) was involved in HMG-elicited hypophosphorylation of cytoskeletal proteins. Furthermore, the antioxidants L-NAME and TROLOX fully prevented both the hypophosphorylation and the inhibition of PKA and JNK caused by HMG, suggesting that oxidative damage may underlie these effects. These findings indicate that the main metabolites accumulating in HMG lyase deficiency provoke hypophosphorylation of cytoskeleton neural proteins with the involvement of NMDA receptors, Ca(2+), and reactive species. It is presumed that these alterations may contribute to the neuropathology of this disease. PMID:26174040

  16. Metabolomics of Neurotransmitters and Related Metabolites in Post-Mortem Tissue from the Dorsal and Ventral Striatum of Alcoholic Human Brain.

    Science.gov (United States)

    Kashem, Mohammed Abul; Ahmed, Selina; Sultana, Nilufa; Ahmed, Eakhlas U; Pickford, Russell; Rae, Caroline; Šerý, Omar; McGregor, Iain S; Balcar, Vladimir J

    2016-02-01

    We report on changes in neurotransmitter metabolome and protein expression in the striatum of humans exposed to heavy long-term consumption of alcohol. Extracts from post mortem striatal tissue (dorsal striatum; DS comprising caudate nucleus; CN and putamen; P and ventral striatum; VS constituted by nucleus accumbens; NAc) were analysed by high performance liquid chromatography coupled with tandem mass spectrometry. Proteomics was studied in CN by two-dimensional gel electrophoresis followed by mass-spectrometry. Proteomics identified 25 unique molecules expressed differently by the alcohol-affected tissue. Two were dopamine-related proteins and one a GABA-synthesizing enzyme GAD65. Two proteins that are related to apoptosis and/or neuronal loss (BiD and amyloid-β A4 precursor protein-binding family B member 3) were increased. There were no differences in the levels of dopamine (DA), 3,4-dihydrophenylacetic acid (DOPAC), serotonin (5HT), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (HIAA), histamine, L-glutamate (Glu), γ-aminobutyric acid (GABA), tyrosine (Tyr) and tryptophan (Tryp) between the DS (CN and P) and VS (NAc) in control brains. Choline (Ch) and acetylcholine (Ach) were higher and norepinephrine (NE) lower, in the VS. Alcoholic striata had lower levels of neurotransmitters except for Glu (30 % higher in the alcoholic ventral striatum). Ratios of DOPAC/DA and HIAA/5HT were higher in alcoholic striatum indicating an increase in the DA and 5HT turnover. Glutathione was significantly reduced in all three regions of alcohol-affected striatum. We conclude that neurotransmitter systems in both the DS (CN and P) and the VS (NAc) were significantly influenced by long-term heavy alcohol intake associated with alcoholism . PMID:26801172

  17. Traffic pollution exposure is associated with altered brain connectivity in school children.

    Science.gov (United States)

    Pujol, Jesus; Martínez-Vilavella, Gerard; Macià, Dídac; Fenoll, Raquel; Alvarez-Pedrerol, Mar; Rivas, Ioar; Forns, Joan; Blanco-Hinojo, Laura; Capellades, Jaume; Querol, Xavier; Deus, Joan; Sunyer, Jordi

    2016-04-01

    Children are more vulnerable to the effects of environmental elements due to their active developmental processes. Exposure to urban air pollution has been associated with poorer cognitive performance, which is thought to be a result of direct interference with brain maturation. We aimed to assess the extent of such potential effects of urban pollution on child brain maturation using general indicators of vehicle exhaust measured in the school environment and a comprehensive imaging evaluation. A group of 263 children, aged 8 to 12years, underwent MRI to quantify regional brain volumes, tissue composition, myelination, cortical thickness, neural tract architecture, membrane metabolites, functional connectivity in major neural networks and activation/deactivation dynamics during a sensory task. A combined measurement of elemental carbon and NO2 was used as a putative marker of vehicle exhaust. Air pollution exposure was associated with brain changes of a functional nature, with no evident effect on brain anatomy, structure or membrane metabolites. Specifically, a higher content of pollutants was associated with lower functional integration and segregation in key brain networks relevant to both inner mental processes (the default mode network) and stimulus-driven mental operations. Age and performance (motor response speed) both showed the opposite effect to that of pollution, thus indicating that higher exposure is associated with slower brain maturation. In conclusion, urban air pollution appears to adversely affect brain maturation in a critical age with changes specifically concerning the functional domain. PMID:26825441

  18. Tumor Markers

    Science.gov (United States)

    ... guidelines on a variety of topics, including tumor markers for breast cancer, colorectal cancer, lung cancer, and others. The ... of recurrence 70-Gene signature (Mammaprint®) Cancer type: Breast ... Can tumor markers be used in cancer screening? Because tumor markers ...

  19. Optimal voxel size for measuring global gray and white matter proton metabolite concentrations using chemical shift imaging

    DEFF Research Database (Denmark)

    Hanson, Lars Peter Grüner; Adalsteinsson, E; Pfefferbaum, A;

    2000-01-01

    Quantification of gray and white matter levels of spectroscopically visible metabolites can provide important insights into brain development and pathological conditions. Chemical shift imaging offers a gain in efficiency for estimation of global gray and white matter metabolite concentrations co...

  20. Silica stationary phase-based on-line sample enrichment coupled with LC-MS/MS for the quantification of dopamine, serotonin and their metabolites in rat brain microdialysates.

    Science.gov (United States)

    Kim, Minjeong; Lee, Jin-Gyeom; Yang, Chae Ha; Lee, Sooyeun

    2016-06-01

    Accurate measurement of trace levels of endogenous compounds remains challenging despite advancements in analytical technologies. In particular, monoamine neurotransmitters such as dopamine (DA) and serotonin (5-HT) are polar compounds with low molecular weights, which complicates the optimization of retention and detection on liquid chromatography-mass spectrometry (LC-MS). Microdialysis is an important sampling technique to collect extracellular fluid from the brain of living animals. However, the very low basal concentrations of the neurotransmitters, small sample volume (maximum 30 μL) and the absence of matrix-matching calibrators are limitations of a microdialysate as an analytical sample. In the present study, an LC-MS/MS method was developed and fully validated for the quantification of DA, 5-HT and their main metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), in microdialysates from the rat nucleus accumbens shell. To improve the method sensitivity and accuracy, on-line sample enrichment using silica stationary phase was employed, before which any other sample pretreatment was not performed. The validation results proved the method to be selective, sensitive, accurate and precise, with acceptable linearity within calibration ranges. The lower limits of quantification were 0.025, 0.1, 0.5, 25 and 2.5 ng/mL for 5-HT, DA, 5-HIAA, HVA and DOPAC, respectively. This is a powerful analytical method to determine endogenous concentrations of those compounds in microdialysates from the rat nucleus accumbens and will be very useful to further study on the pathophysiological functions of monoamine neurotramsmitters in vivo. PMID:27155302

  1. Simultaneous analysis of gemfibrozil, morphine, and its two active metabolites in different mouse brain structures using solid-phase extraction with ultra-high performance liquid chromatography and tandem mass spectrometry with a deuterated internal standard.

    Science.gov (United States)

    Yang, Zizhao; Wang, Lu; Xu, Mingcheng; Gu, Jingkai; Yu, Lushan; Zeng, Su

    2016-06-01

    A rapid and sensitive bioassay was established and validated to simultaneously determine gemfibrozil, morphine, morphine-3β-glucuronide, and morphine-6β-glucuronide in mouse cerebrum, epencephalon, and hippocampus based on ultra-high performance liquid chromatography and tandem mass spectrometry. The deuterated internal standard, M6G-d3, was mixed with the prepared samples at 10 ng/mL as the final concentration. The samples were transferred into the C18 solid-phase extraction columns with gradient elution for solid-phase extraction. The mobile phase consisted of methanol and 0.05% formic acid (pH 3.2). Multiple reaction monitoring has been applied to analyze gemfibrozil (m/z 249.0 → 121.0) in anion mode, and M6G-d3 (m/z 465.1 → 289.1), morphine (m/z 286.0 → 200.9), and M3G and M6G (m/z 462.1 → 286.1) in the positive ion mode. The method has a linear calibration range from 0.05 to 10 ng for gemfibrozil, morphine, and M3G and M6G with correlation coefficients >0.993. The lower limit of quantitation for all four analytes was 0.05 ng/mL, relative standard deviation of intra- and interday precision was less than 10.5%, and the relative error of accuracy was from -8.2 to 8.3% at low, medium, and high concentrations for all the analytes. In conclusion, gemfibrozil can influence the morphine antinociception after coronary heart disease induced chronic angina by the change in one of morphine metabolites', M3G, distribution in mouse brain. PMID:27060926

  2. Disruption of non-enzymatic antioxidant defense systems in the brain of rats with water-immersion restraint stress

    OpenAIRE

    Ohta, Yoshiji; Yashiro, Koji; Ohashi, Koji; Imai, Yoichiro

    2012-01-01

    We examined whether non-enzymatic antioxidant defense systems are disrupted in the brain of rats with water-immersion restraint stress. When rats were exposed to water-immersion restraint stress for 1.5, 3 or 6 h, the brain had decreased ascorbic acid and reduced glutathione contents and increased lipid peroxide and nitric oxide metabolites contents at 3 h and showed further changes in these components with a reduction of vitamin E content at 6 h. Increased serum levels of stress markers were...

  3. Prehospital resuscitation with hypertonic saline-dextran modulates inflammatory, coagulation and endothelial activation marker profiles in severe traumatic brain injured patients

    OpenAIRE

    Morrison Laurie J; Baker Andrew J; Crnko Naomi T; Rhind Shawn G; Shek Pang N; Scarpelini Sandro; Rizoli Sandro B

    2010-01-01

    Abstract Background Traumatic brain injury (TBI) initiates interrelated inflammatory and coagulation cascades characterized by wide-spread cellular activation, induction of leukocyte and endothelial cell adhesion molecules and release of soluble pro/antiinflammatory cytokines and thrombotic mediators. Resuscitative care is focused on optimizing cerebral perfusion and reducing secondary injury processes. Hypertonic saline is an effective osmotherapeutic agent for the treatment of intracranial ...

  4. Bacopa monniera (CDRI-08 Upregulates the Expression of Neuronal and Glial Plasticity Markers in the Brain of Scopolamine Induced Amnesic Mice

    Directory of Open Access Journals (Sweden)

    Arpita Konar

    2015-01-01

    Full Text Available Preclinical studies on animal models have discerned the antiamnesic and memory-enhancing potential of Bacopa monniera (Brahmi crude extract and standardized extracts. These studies primarily focus on behavioral consequences. However, lack of information on molecular underpinnings has limited the clinical trials of the potent herb in human subjects. In recent years, researchers highlight plasticity markers as molecular correlates of amnesia and being crucial to design therapeutic targets. In the present report, we have investigated the effect of a special extract of B. monniera (CDRI-08 on the expression of key neuronal (BDNF and Arc and glial (GFAP plasticity markers in the cerebrum of scopolamine induced amnesic mice. Pre- and postadministration of CDRI-08 ameliorated amnesic effect of scopolamine by decreasing acetyl cholinesterase activity and drastically upregulating the mRNA and protein expression of BDNF, Arc, and GFAP in mouse cerebrum. Interestingly, the plant extract per se elevated BDNF and Arc expression as compared to control but GFAP was unaltered. In conclusion, our findings provide the first molecular evidence for antiamnesic potential of CDRI-08 via enhancement of both neuronal and glial plasticity markers. Further investigations on detailed molecular pathways would encourage therapeutic application of the extract in memory disorders.

  5. Enhanced metabolite generation

    Science.gov (United States)

    Chidambaram, Devicharan

    2012-03-27

    The present invention relates to the enhanced production of metabolites by a process whereby a carbon source is oxidized with a fermentative microbe in a compartment having a portal. An electron acceptor is added to the compartment to assist the microbe in the removal of excess electrons. The electron acceptor accepts electrons from the microbe after oxidation of the carbon source. Other transfers of electrons can take place to enhance the production of the metabolite, such as acids, biofuels or brewed beverages.

  6. Loss of metabolites from monkey striatum during PET with FDOPA

    DEFF Research Database (Denmark)

    Cumming, P; Munk, O L; Doudet, D

    2001-01-01

    The decarboxylation of 6-[(18)F]fluorodopa (FDOPA) and retention of the product [(18)F]fluorodopamine within vesicles of catecholamine fibers results in the labeling of dopamine-rich brain regions during FDOPA/PET studies. However, this metabolic trapping is not irreversible due to the eventual...... diffusion of [(18)F]fluorodopamine metabolites from brain. Consequently, time-radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K(D)(i), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate...... constant k(Lin)(cl) (min(-1)). Similarly, the DOPA decarboxylation rate constant (k(D)(3), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(DA)(9) (min(-1)). To compare the two methods, we calculated the two elimination rate...

  7. Cation shifts as markers in neurodegenerative diseases: correlations with transmitter deficts in Alzheimer and Huntington disease and imaging of excitoxic brain damage

    OpenAIRE

    Gramsbergen, Jan Bert Paul

    1988-01-01

    The clinical syndrome of dementia is best defined as an - usually at advanced age - acquired global impairment of intellect, memory and personality, but without impairment of consciousness, prominent causes of dementia are certain intrinsic degenerative diseases of the brain. The most common of these diseases is Alzheimer's disease (AD) . The pathological hallmark of AD is the presence of large amounts of so called plaques extracellular structures which involve processes of different neurons ...

  8. Over-estimation of glucose-6-phosphatase activity in brain in vivo. Apparent difference in rates of [2-3H]glucose and [U-14C]glucose utilization is due to contamination of precursor pool with 14C-labeled products and incomplete recovery of 14C-labeled metabolites

    International Nuclear Information System (INIS)

    Significant dephosphorylation of glucose 6-phosphate due to glucose-6-phosphatase activity in rat brain in vivo was recently reported. The evidence was an apparent more rapid 3H than 14C loss from the glucose pool and faster [2-3H]glucose than [U-14C]glucose utilization following pulse labeling of the brain with [2-3H,U-14C]glucose. Radiochemical purity of the glucose and quantitative recovery of the labeled products of glucose metabolism isolated from the brain were obviously essential requirements of their study, but no evidence for purity and recovery was provided. When we repeated these experiments with the described isolation procedures, we replicated the results, but found that: 1) the precursor glucose pool contained detritiated, 14C-labeled contaminants arising from glucose metabolism, particularly 2-pyrrolidone-5-carboxylic acid derived from [14C]glutamine; 2) [14C]glucose metabolite were not quantitatively recovered; 3) the procedure used to isolate the glucose itself produced detritiated, 14C-labeled derivatives of [2-3H,U-14C]glucose. These deficiencies in the isolation procedures could fully account for the observations that were interpreted as evidence of significant glucose 6-phosphate dephosphorylation by glucose-6-phosphatase activity. When glucose was isolated by more rigorous procedures and its purity verified in the present studies, no evidence for such activity in rat brain was found

  9. Raised dopamine metabolites in a case of malignant paraganglioma.

    OpenAIRE

    Florkowski, C M; Fairlamb, D J; Freeth, M. G.; Taylor, S A; Taylor, A; Weinkove, C; Jacobs, A G

    1990-01-01

    This paper describes the case of a malignant retroperitoneal paraganglioma with extensive metastases. The patient presented with a supraclavicular mass and an absence of hypertension. Exclusively raised dopamine metabolites were detected which may be a marker of a malignant process and account for the lack of hypertension.

  10. Bone Markers

    Science.gov (United States)

    ... bone turnover: C-telopeptide (C-terminal telopeptide of type 1 collagen (CTx)) – a marker for bone resorption. It is ... resorption include: N-telopeptide (N-terminal telopeptide of type 1 collagen (NTx)) – a peptide fragment from the amino terminal ...

  11. Spatial Elucidation of Spinal Cord Lipid- and Metabolite- Regulations in Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Hanrieder, Jörg; Ewing, Andrew G.

    2014-06-01

    Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressing disease of the central nervous system that is characterized by motor neuron degeneration in the brain stem and the spinal cord. We employed time of flight secondary ion mass spectrometry (ToF-SIMS) to profile spatial lipid- and metabolite- regulations in post mortem human spinal cord tissue from ALS patients to investigate chemical markers of ALS pathogenesis. ToF-SIMS scans and multivariate analysis of image and spectral data were performed on thoracic human spinal cord sections. Multivariate statistics of the image data allowed delineation of anatomical regions of interest based on their chemical identity. Spectral data extracted from these regions were compared using two different approaches for multivariate statistics, for investigating ALS related lipid and metabolite changes. The results show a significant decrease for cholesterol, triglycerides, and vitamin E in the ventral horn of ALS samples, which is presumably a consequence of motor neuron degeneration. Conversely, the biogenic mediator lipid lysophosphatidylcholine and its fragments were increased in ALS ventral spinal cord, pointing towards neuroinflammatory mechanisms associated with neuronal cell death. ToF-SIMS imaging is a promising approach for chemical histology and pathology for investigating the subcellular mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis.

  12. Brain oxidative stress: detection and mapping of anti-oxidant marker 'Glutathione' in different brain regions of healthy male/female, MCI and Alzheimer patients using non-invasive magnetic resonance spectroscopy.

    Science.gov (United States)

    Mandal, Pravat K; Tripathi, Manjari; Sugunan, Sreedevi

    2012-01-01

    Glutathione (GSH) serves as an important anti-oxidant in the brain by scavenging harmful reactive oxygen species that are generated during different molecular processes. The GSH level in the brain provides indirect information on oxidative stress of the brain. We report in vivo detection of GSH non-invasively from various brain regions (frontal cortex, parietal cortex, hippocampus and cerebellum) in bilateral hemispheres of healthy male and female subjects and from bi-lateral frontal cortices in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). All AD patients who participated in this study were on medication with cholinesterase inhibitors. Healthy young male (age 26.4±3.0) and healthy young female (age 23.6±2.1) subjects have higher amount of GSH in the parietal cortical region and a specific GSH distribution pattern (parietal cortex>frontal cortex>hippocampus ~ cerebellum) has been found. Overall mean GSH content is higher in healthy young female compared to healthy young male subjects and GSH is distributed differently in two hemispheres among male and female subjects. In both young female and male subjects, statistically significant (p=0.02 for young female and p=0.001 for young male) difference in mean GSH content is found when compared between left frontal cortex (LFC) and right frontal cortex (RFC). In healthy young female subjects, we report statistically significant positive correlation of GSH content between RFC and LFC (r=0.641, p=0.004) as well as right parietal cortex (RPC) and left parietal cortex (LPC) (r=0.797, p=0.000) regions. In healthy young male subjects, statistically significant positive correlation of GSH content was observed between LFC and LPC (r=0.481, p=0.032) regions. This statistical analysis implicates that in case of a high GSH content in LPC of a young male, his LFC region would also contain high GSH and vice versa. The difference in mean of GSH content between healthy young female control and female AD

  13. Repeat variation in the human PER2 gene as a new genetic marker associated with cocaine addiction and brain dopamine D2 receptor availability

    Science.gov (United States)

    Shumay, E; Fowler, J S; Wang, G-J; Logan, J; Alia-Klein, N; Goldstein, R Z; Maloney, T; Wong, C; Volkow, N D

    2012-01-01

    Low dopamine D2 receptor (D2R) levels in the striatum are consistently reported in cocaine abusers; inter-individual variations in the degree of the decrease suggest a modulating effect of genetic makeup on vulnerability to addiction. The PER2 (Period 2) gene belongs to the clock genes family of circadian regulators; circadian oscillations of PER2 expression in the striatum was modulated by dopamine through D2Rs. Aberrant periodicity of PER2 contributes to the incidence and severity of various brain disorders, including drug addiction. Here we report a newly identified variable number tandem repeat (VNTR) polymorphism in the human PER2 gene (VNTR in the third intron). We found significant differences in the VNTR alleles prevalence across ethnic groups so that the major allele (4 repeats (4R)) is over-represented in non-African population (4R homozygosity is 88%), but not in African Americans (homozygosity 51%). We also detected a biased PER2 genotype distribution among healthy controls and cocaine-addicted individuals. In African Americans, the proportion of 4R/three repeat (3R) carriers in healthy controls is much lower than that in cocaine abusers (23% vs 39%, P=0.004), whereas among non-Africans most 3R/4R heterozygotes are healthy controls (10.5% vs 2.5%, P=0.04). Analysis of striatal D2R availability measured with positron emission tomography and [11C]raclopride revealed higher levels of D2R in carriers of 4R/4R genotype (P<0.01). Taken together, these results provide preliminary evidence for the role of the PER2 gene in regulating striatal D2R availability in the human brain and in vulnerability for cocaine addiction. PMID:22832851

  14. The association of betaine, homocysteine and related metabolites with cognitive function in Dutch elderly people

    OpenAIRE

    Eussen, S.J.P.M.; Ueland, P. M.; Clarke, R; Blom, H.J.; Hoefnagels, W.H.L.; Staveren, van, R.; Groot, de, W.T.

    2007-01-01

    The importance of the one-carbon metabolites, choline and homocysteine, to brain function is well known. However, the associations between the one-carbon metabolites choline, betaine, methionine and dimethylglycine with cognition in elderly are unclear. We therefore examined the associations of these metabolites with cognition in a double-blind, placebo-controlled trial. Individuals (n 195) were randomized to receive daily oral capsules with either 1000 ¿g cobalamin (vitamin B12), or 1000 ¿g ...

  15. Changes in mouse brain metabolism following a convulsive dose of soman: A proton HRMAS NMR study

    International Nuclear Information System (INIS)

    Soman, an irreversible organophosphorus cholinesterase inhibitor, induces status epilepticus and, in sensitive brain areas, seizure-related brain damage (e.g. brain edema and neuronal loss). The brain metabolic disturbances associated with these events are ill known. In the present study, we thus evaluated these changes in a murine model of soman-induced status epilepticus up to 7 days after intoxication. Mice, protected by HI-6 and atropine methyl nitrate, were poisoned with soman (172 μg/kg) and then sacrificed at set time points, from 1 h to 7 days. Brain biopsies from the piriform cortex (Pir) and cerebellum (Cer) were analyzed by 1H HRMAS NMR spectroscopy. Spectra were then analyzed using both a supervised multivariate analysis and the QUEST procedure of jMRUI for the quantification of 17 metabolites. The multivariate analysis clearly showed the metabolic differences between a damaged structure (Pir) and a structure with less prominent changes (cerebellum) and helped to globally assess the time course of metabolic changes. Analysis of the individual metabolites showed that the major changes took place in the piriform cortex but that cerebellum was not change-free. The most prominent changes in the former were an early (1-4 h) increase in alanine and acetate, a delayed increase in lactate, glycerophosphocholine and glutamine as well as a delayed decrease in myo-inositol and N-acetylaspartate. A week after poisoning, some metabolic disturbances were still present. Further research will be necessary to clarify what could be the involvement of these metabolites in physiological processes and how they might become useful surrogate markers of brain damage and repair.

  16. The association of betaine, homocysteine and related metabolites with cognitive function in Dutch elderly people

    NARCIS (Netherlands)

    Eussen, S.J.P.M.; Ueland, P.M.; Clarke, R.; Blom, H.J.; Hoefnagels, W.H.L.; Staveren, van W.A.; Groot, de C.P.G.M.

    2007-01-01

    The importance of the one-carbon metabolites, choline and homocysteine, to brain function is well known. However, the associations between the one-carbon metabolites choline, betaine, methionine and dimethylglycine with cognition in elderly are unclear. We therefore examined the associations of thes

  17. The association of betaine, homocysteine and related metabolites with cognitive function in Dutch elderly people.

    NARCIS (Netherlands)

    Eussen, S.; Ueland, P.M.; Clarke, R.; Blom, H.J.; Hoefnagels, W.H.L.; Staveren, W.A. van; Groot, L.C. de

    2007-01-01

    The importance of the one-carbon metabolites, choline and homocysteine, to brain function is well known. However, the associations between the one-carbon metabolites choline, betaine, methionine and dimethylglycine with cognition in elderly are unclear. We therefore examined the associations of thes

  18. Circulating exosomes as new biomarkers for brain disease and injury

    Science.gov (United States)

    Graner, Michael W.; Epple, Laura M.; Dusto, Nathaniel L.; Lencioni, Alex M.; Nega, Meheret; Herring, Matthew; Winston, Ben; Madsen, Helen; Bemis, Lynne T.; Anchordoquy, Thomas J.

    2013-05-01

    Brain diseases such as cancers, neurodegenerative disorders, or trauma are frequently diagnosed with imaging modalities and sometimes with intracranial biopsies. Treatment response is similarly monitored, along with clinical indications. While these technologies provide important windows into the disease state, they fail to provide us a detailed molecular portrait of the disease and of the changes taking place during therapy. Exosomes are virus-sized nanovesicles derived from the endosomal system and are released extracellularly from essentially all cell types. Exosomes contain intracellular entities (proteins, nucleic acids, metabolites), membrane proteins and lipids, and even extracellular proteins bound to them. Exosomes may be considered as mini-surrogates of their cells of origin, with some content common to all cells/exosomes, but some of the content would be cell-specific. These vesicles are found in all biofluids in humans, and are thus accessible to "liquid biopsy" with harvest of vesicles from such fluids. Current challenges are to identify disease-related markers or panels of markers to distinguish the disease state. Here we will show examples of brain tumor markers found in/on exosomes from cell culture and patient sera, and we will suggest that aspects of the biology of disease may have a relevant place in the search for biomarkers.

  19. Metabolomics for Secondary Metabolite Research

    Directory of Open Access Journals (Sweden)

    Eriko Takano

    2013-11-01

    Full Text Available Metabolomics, the global characterization of metabolite profiles, is becoming an increasingly powerful tool for research on secondary metabolite discovery and production. In this review we discuss examples of recent technological advances and biological applications of metabolomics in the search for chemical novelty and the engineered production of bioactive secondary metabolites.

  20. Effect of cheese and butter intake on metabolites in urine using an untargeted metabolomics approach

    DEFF Research Database (Denmark)

    Hjerpsted, Julie Bousgaard; Ritz, Christian; Schou, Simon Stubbe; Tholstrup, Tine; Dragsted, Lars Ove

    2014-01-01

    Cheese intake has been shown to decrease total cholesterol and LDL cholesterol concentrations when compared to butter of equal fat content. An untargeted metabolite profiling may reveal exposure markers of cheese but may also contribute with markers which can help explain how the intake of cheese...

  1. Accumulation in murine amniotic fluid of halothane and its metabolites.

    Science.gov (United States)

    Danielsson, B R; Ghantous, H; Dencker, L

    1984-11-01

    The distribution of radioactivity in pregnant mice was registered at 0, 4, and 24 hrs after a 10 min. period of inhalation of 14C-halothane. Autoradiographic methods were used to allow to distinguish between the distribution of volatile (non-metabolize) halothane, water-soluble metabolites, and firmly tissue-bound metabolites. While volatile radioactivity was seen predominantly at short survival intervals, e.g. in body fat, blood, brain and liver, metabolites accumulated with time. Peak values occurred at 4 hrs in most organs (measured with liquid scintillation as well). The most remarkable findings were the high concentrations of radioactivity in amniotic fluid (and the ocular fluids of adults) with peak values at 4 hrs and rather high concentrations still prevailing at 24 hrs after inhalation. It is assumed that this activity represents only partly volaile halothane and mostly non-volatile metabolites. High activity of metabolites was seen in the neuroepithelium of the embryo in early gestation. Firmly tissue-bound metabolites, still remaining after washing the tissues with trichloroacetic acid and organic solvents, were found in the nasal mucosa, trachea and bronchial tree and in (presumably centrilobular) zones of the liver of adults after inhalation and 5-day old mice after intraperitoneal injection, indicating the formation of reactive metabolites in these organs. Firmly tissue-bound activity was not observed in the corresponding foetal organs. PMID:6528811

  2. [Neurochemical study of effects of the new anxiolytic drugs afobazol and ladasten on the synthesis and metabolism of monoamines and their metabolites in the brain structures of Wistar rat on the model of monoamine synthesis blockade induced by aromatic amino acid decarboxylase inhibitor NSD-1015].

    Science.gov (United States)

    Davydova, A I; Klodt, P M; Kudrin, V S; Kuznetsova, E A; Narkevich, V B

    2010-03-01

    Results of a neurochemical study of the effects of the new anxiolytic drugs afobazole and ladasten on the synthesis and metabolism of monoamines and their metabolites determined by HPLC on the model of monoamine synthesis blockade induced by NSD-1015 (aromatic L-amino acid decarboxylase) in the brain structures of Wistar rats are reported. A decrease in the levels of DOPAC in hypothalamus and HVA in striatum after afobazole injection may be evidence of an inhibitory action of this drug on the activity of monoamine oxidase (MAO-A), which is the main enzyme involved in dopamine biodegradation. Afobazole was also found to increase the content of serotonin (5-HT) as well as its precursor (5-OTP) and its main metabolite (5-HIAA) in hypothalamus by up to 50, 60 and 50%, respectively, which confirms a hypothesis that this anxiolytic drug can modulate the activity of tryptophan hydroxylase (5-OTP synthesis enzyme). In contrast to afobazole, ladasten demonstrated the ability to increase the level of L-DOPA (a dopamine precursor) in virtually all functional structures of the brain (except for hippocamp), which may support the hypothesis suggestion concerning a predominant action of this drug on the activity of tyrosine hydroxylase. Ladasten exhibited selectivity with respect to the dopaminergic system and affected only parameters of the dopamine metabolism, in particular, by increasing the HVA content in nucleus accumbens and decreasing it in the hypothalamus. The drug also affected the dopamine turnover parameters, producing an increase in both HVA/dopamine ratio in nucleus accumbens and DOPAC/dopamine ratio in hippocamp. PMID:20408420

  3. Over-estimation of glucose-6-phosphatase activity in brain in vivo. Apparent difference in rates of [2-3H]glucose and [U-14C]glucose utilization is due to contamination of precursor pool with 14C-labeled products and incomplete recovery of 14C-labeled metabolites.

    Science.gov (United States)

    Dienel, G A; Nelson, T; Cruz, N F; Jay, T; Crane, A M; Sokoloff, L

    1988-12-25

    Significant dephosphorylation of glucose 6-phosphate due to glucose-6-phosphatase activity in rat brain in vivo was recently reported (Huang, M., and Veech, R.L. (1982) J. Biol. Chem. 257, 11358-11363). The evidence was an apparent more rapid 3H than 14C loss from the glucose pool and faster [2-3H]glucose than [U-14C]glucose utilization following pulse labeling of the brain with [2-3H,U-14C]glucose. Radiochemical purity of the glucose and quantitative recovery of the labeled products of glucose metabolism isolated from the brain were obviously essential requirements of their study, but no evidence for purity and recovery was provided. When we repeated these experiments with the described isolation procedures, we replicated the results, but found that: 1) the precursor glucose pool contained detritiated, 14C-labeled contaminants arising from glucose metabolism, particularly 2-pyrrolidone-5-carboxylic acid derived from [14C]glutamine; 2) [14C]glucose metabolite were not quantitatively recovered; 3) the procedure used to isolate the glucose itself produced detritiated, 14C-labeled derivatives of [2-3H,U-14C]glucose. These deficiencies in the isolation procedures could fully account for the observations that were interpreted as evidence of significant glucose 6-phosphate dephosphorylation by glucose-6-phosphatase activity. When glucose was isolated by more rigorous procedures and its purity verified in the present studies, no evidence for such activity in rat brain was found. PMID:2848837

  4. Production of Metabolites

    DEFF Research Database (Denmark)

    2011-01-01

    A recombinant micro-organism such as Saccharomyces cerevisiae which produces and excretes into culture medium a stilbenoid metabolite product when grown under stilbenoid production conditions, which expresses in above native levels a ABC transporter which transports said stilbenoid out of said...... micro-organism cells to the culture medium. The genome of the Saccharomyces cerevisiae produces an auxotrophic phenotype which is compensated by a plasmid which also expresses one or more of said enzymes constituting said metabolic pathway producing said stilbenoid, an expression product of the plasmid...

  5. [Antiviral properties of basidiomycetes metabolites].

    Science.gov (United States)

    Avtonomova, A V; Krasnopolskaya, L M

    2014-01-01

    The data on the antiviral action of the Ganoderma lucidum, Lentinus edodes, Grifola frondosa, Agaricus brasiliensis and other basidiomycetes metabolites are summurized. The metabolites of these species of basidiomycetes exhibit a direct antiviral effect on herpes simplex virus types I and II, human immunodeficiency virus (HIV), hepatitis B virus, vesicular stomatitis virus, influenza virus, Epstein-Barr virus, and others. Moreover, metabolites of basidiomycetes increased antiviral immunity. PMID:25975107

  6. Metabolites of Siamenoside I and Their Distributions in Rats.

    Science.gov (United States)

    Yang, Xue-Rong; Xu, Feng; Li, Dian-Peng; Lu, Feng-Lai; Liu, Guang-Xue; Wang, Lei; Shang, Ming-Ying; Huang, Yong-Lin; Cai, Shao-Qing

    2016-01-01

    Siamenoside I is the sweetest mogroside that has several kinds of bioactivities, and it is also a constituent of Siraitiae Fructus, a fruit and herb in China. Hitherto the metabolism of siamenoside I in human or animals remains unclear. To reveal its metabolic pathways, a high-performance liquid chromatography-electrospray ionization-ion trap-time of flight-multistage mass spectrometry (HPLC-ESI-IT-TOF-MS(n)) method was used to profile and identify its metabolites in rats. Altogether, 86 new metabolites were identified or tentatively identified, and 23 of them were also new metabolites of mogrosides. In rats, siamenoside I was found to undergo deglycosylation, hydroxylation, dehydrogenation, deoxygenation, isomerization, and glycosylation reactions. Among them, deoxygenation, pentahydroxylation, and didehydrogenation were novel metabolic reactions of mogrosides. The distributions of siamenoside I and its 86 metabolites in rat organs were firstly reported, and they were mainly distributed to intestine, stomach, kidney, and brain. The most widely distributed metabolite was mogroside IIIE. In addition, eight metabolites were bioactive according to literature. These findings would help to understand the metabolism and effective forms of siamenoside I and other mogrosides in vivo. PMID:26840289

  7. Metabolites of Siamenoside I and Their Distributions in Rats

    Directory of Open Access Journals (Sweden)

    Xue-Rong Yang

    2016-01-01

    Full Text Available Siamenoside I is the sweetest mogroside that has several kinds of bioactivities, and it is also a constituent of Siraitiae Fructus, a fruit and herb in China. Hitherto the metabolism of siamenoside I in human or animals remains unclear. To reveal its metabolic pathways, a high-performance liquid chromatography-electrospray ionization-ion trap-time of flight-multistage mass spectrometry (HPLC-ESI-IT-TOF-MSn method was used to profile and identify its metabolites in rats. Altogether, 86 new metabolites were identified or tentatively identified, and 23 of them were also new metabolites of mogrosides. In rats, siamenoside I was found to undergo deglycosylation, hydroxylation, dehydrogenation, deoxygenation, isomerization, and glycosylation reactions. Among them, deoxygenation, pentahydroxylation, and didehydrogenation were novel metabolic reactions of mogrosides. The distributions of siamenoside I and its 86 metabolites in rat organs were firstly reported, and they were mainly distributed to intestine, stomach, kidney, and brain. The most widely distributed metabolite was mogroside IIIE. In addition, eight metabolites were bioactive according to literature. These findings would help to understand the metabolism and effective forms of siamenoside I and other mogrosides in vivo.

  8. Two Domains of Vimentin Are Expressed on the Surface of Lymph Node, Bone and Brain Metastatic Prostate Cancer Lines along with the Putative Stem Cell Marker Proteins CD44 and CD133

    International Nuclear Information System (INIS)

    Vimentin was originally identified as an intermediate filament protein present only as an intracellular component in many cell types. However, this protein has now been detected on the surface of a number of different cancer cell types in a punctate distribution pattern. Increased vimentin expression has been indicated as an important step in epithelial-mesenchymal transition (EMT) required for the metastasis of prostate cancer. Here, using two vimentin-specific monoclonal antibodies (SC5 and V9 directed against the coil one rod domain and the C-terminus of the vimentin protein, respectively), we examined whether either of these domains would be displayed on the surface of three commonly studied prostate cancer cell lines isolated from different sites of metastases. Confocal analysis of LNCaP, PC3 and DU145 prostate cancer cell lines (derived from lymph node, bone or brain prostate metastases, respectively) demonstrated that both domains of vimentin are present on the surface of these metastatic cancer cell types. In addition, flow cytometric analysis revealed that vimentin expression was readily detected along with CD44 expression but only a small subpopulation of prostate cancer cells expressed vimentin and the putative stem cell marker CD133 along with CD44. Finally, Cowpea mosaic virus (CPMV) nanoparticles that target vimentin could bind and internalize into tested prostate cancer cell lines. These results demonstrate that at least two domains of vimentin are present on the surface of metastatic prostate cancer cells and suggest that vimentin could provide a useful target for nanoparticle- or antibody- cancer therapeutic agents directed against highly invasive cancer and/or stem cells

  9. Mitochondrial Dysfunction in Bipolar Disorder: Lessons from Brain Imaging and Molecular Markers Disfunción mitocondrial en el trastorno bipolar: lecciones de las imágenes cerebrales y los marcadores moleculares

    Directory of Open Access Journals (Sweden)

    Luciano Minuzzi

    2011-10-01

    Full Text Available Bipolar disorder (BD is a chronic major mental illness characterized by extreme mood episodes, cognitive impairment, and high rates of disability. Several lines of evidence suggest that BD may be associated with abnormalities in mitochondrial function. Here we critically review findings from brain imaging and from preclinical studies that investigated markers of energy metabolism in BD. Research with postmortem brain and peripheral tissue revealed changes in size and distribution of mitochondria, as well as decreased mitochondrial electron transport chain function, increased oxidative stress, and increased lipid and protein damage. PET imaging studies revealed decreased glucose metabolism in sub-areas of the prefrontal cortex, amygdala, and hippocampus structures in BD. On the other hand, increased lactate levels in BD have been found in cerebrospinal fluid and in gray matter by magnetic resonance spectroscopy, which suggest that distinct pathophysiological processes may be region-specific. Resting state fMRI studies have demonstrated decreased functional connectivity between fronto-limbic circuits. In conclusion, these results support the hypothesis of mitochondrial dysfunction in BD and suggest that BD is associated with decreased energy production and a shift towards anaerobic glycolysis. Such changes in energy metabolism can potentially decrease cell plasticity and ultimately disrupt brain circuits associated with mood and cognitive control.El trastorno bipolar (TB es una enfermedad mental crónica grave caracterizada por episodios de ánimo extremo, trastornos cognitivos y altas tasas de discapacidad. Varias líneas de evidencia sugieren que el TB puede estar asociado con anormalidades en la función mitocondrial. Aquí analizamos críticamente los hallazgos de las imágenes cerebrales y de los estudios preclínicos que han investigado los marcadores del metabolismo de energía en TB. Las investigaciones post mórtem basadas en tejidos

  10. Sun, shade, and secondary metabolites

    Science.gov (United States)

    My research program focuses on understanding plant primary and secondary metabolites. Grape secondary metabolites, such as phenolics, have long been valuable for the organoleptic properties they impart to fruit and wine, and, more recently, for their possible health benefits. These compounds develop...

  11. Secondary metabolites from Eremostachys laciniata

    DEFF Research Database (Denmark)

    Calis, Ihsan; Güvenc, Aysegül; Armagan, Metin;

    2008-01-01

    metabolites were elucidated from spectroscopic (UV, IR, 1D- and 2D-NMR) and ESI-MS evidence, as well as from their specific optical rotation. The presence of these metabolites of three different classes strongly supports the close relationship of the genera Eremostachys and Phlomis....

  12. Aspartame and the rat brain monoaminergic system.

    Science.gov (United States)

    Perego, C; De Simoni, M G; Fodritto, F; Raimondi, L; Diomede, L; Salmona, M; Algeri, S; Garattini, S

    1988-12-01

    A high dose of aspartame (APM) was administered to rats to study possible effects on brain monoaminergic systems. APM and its metabolite phenylalanine (Phe) were given orally at doses of 1000 and 500 mg/kg, respectively. Significant increases were seen in brain Phe and tyrosine (Tyr) levels. Two different approaches were used to study monoaminergic systems: whole tissue measurements by HPLC-ED and in vivo voltammetry in freely moving rats. Dopamine, serotonin and their metabolites were taken as indexes of neuronal activity. In spite of the high dose used, no modification was found in monoamines or their metabolites in striatum, hippocampus and nucleus accumbens. PMID:2464204

  13. A chiral HPLC-UV method for the quantification of dibenz[b,f]azepine-5-carboxamide derivatives in mouse plasma and brain tissue: eslicarbazepine acetate, carbamazepine and main metabolites.

    Science.gov (United States)

    Fortuna, Ana; Bicker, Joana; Alves, Gilberto; Falcão, Amílcar; Soares-da-Silva, Patrício

    2011-06-01

    For the first time, a selective and sensitive chiral HPLC-UV method was developed and fully validated for the simultaneous quantification of eslicarbazepine acetate (ESL), carbamazepine (CBZ), S-licarbazepine (S-Lic), R-licarbazepine (R-Lic), oxcarbazepine (OXC) and carbamazepine-10,11-epoxide (CBZ-E), in mouse plasma and brain homogenate supernatant. After the addition of chloramphenicol as the internal standard, samples were processed using an SPE procedure. The chiral chromatographic analysis was carried out on a LiChroCART 250-4 ChiraDex column, employing a mobile phase of water and methanol (88:12, v/v) pumped at 0.9 mL/min and the UV detector set at 235 nm. The assay was linear (r(2) ≥0.995) for ESL, CBZ, OXC, S-Lic, R-Lic and CBZ-E in the range of, respectively, 0.2-4, 0.4-30, 0.1-60, 0.2-60, 0.2-60 and 0.2-30 μg/mL, in plasma, and of 0.06-1.5 μg/mL for ESL, 0.12-15 μg/mL for CBZ and CBZ-E and 0.06-15 μg/mL for OXC and both licarbazepine (Lic) enantiomers in brain homogenate supernatant. The overall precision was within 8.71% and accuracy ranged from -7.55 to 8.97%. The recoveries of all the compounds were over 92.1%. Afterwards, the application of the method was demonstrated using real plasma and brain samples obtained from mice administered simultaneously with ESL and CBZ. PMID:21557472

  14. Optimal voxel size for measuring global gray and white matter proton metabolite concentrations using chemical shift imaging

    DEFF Research Database (Denmark)

    Hanson, Lars Peter Grüner; Adalsteinsson, E; Pfefferbaum, A; Spielman, D.M.

    2000-01-01

    Quantification of gray and white matter levels of spectroscopically visible metabolites can provide important insights into brain development and pathological conditions. Chemical shift imaging offers a gain in efficiency for estimation of global gray and white matter metabolite concentrations co...... concentration error (<15%). Magn Reson Med 44:10-18, 2000....

  15. Effects of cerebrovascular disease on amyloid precursor protein metabolites in cerebrospinal fluid

    Directory of Open Access Journals (Sweden)

    Rosengren Lars

    2010-07-01

    Full Text Available Abstract Background Alzheimer's disease (AD and cerebrovascular disease (CVD including chronic small vessel disease of the brain (SVD are the most frequent causes of dementia. AD is associated with metabolism of amyloid precursor protein (APP and low levels of amyloid-β peptide (Aβ X-42 in the cerebrospinal fluid (CSF. CVD and SVD are established risk factors for AD, brain white matter lesions (WML are established surrogate markers for SVD and are also associated with reduced CSF AβX-42. A cohort survey was performed to examine whether SVD or acute CVD affects APP metabolism and to explore a potential association between WML and APP metabolism in two groups; cognitively impaired patients, subjective and mild (SCI and MCI and stroke patients. Through measurements of CSF APP metabolite levels in patients with a wide range of WML volumes, this study aimed to determine how SVD influences APP metabolism. Methods Sixty-three patients were included: 37 with subjective cognitive impairment (SCI or mild cognitive impairment (MCI without stroke, and 26 after acute stroke. Chronic and acute WML volume and infarct volume were determined by magnetic resonance imaging (MRI post-scan processing, and CSF levels of α- and β-cleaved soluble APP (sAPP-α and sAPP-β, AβX-38, AβX-40 and AβX-42 were determined. The Mann-Whitney test was used to compare the patient groups. Chronic and acute WML volumes, infarct volume, age, and sex were used as predictors for CSF biomarker levels in linear regression analysis. Results CSF levels of sAPP-α and sAPP-β were strongly correlated (r = 0.95, p p p p ≤ 0.005; p ≤ 0.01; p ≤ 0.01; p ≤ 0.05; p ≤ 0.05 respectively, but not with acute WML or infarct volumes. Conclusions Lower CSF levels of sAPP-α and sAPP-β in the stroke group than in the SCI/MCI group and an inverse correlation with chronic WML indicate that ischemia lowers the levels of CSF sAPP metabolites and suggests that APP axonal transport or

  16. Metabolomics profiling reveals novel markers for leukocyte telomere length.

    Science.gov (United States)

    Zierer, Jonas; Kastenmüller, Gabi; Suhre, Karsten; Gieger, Christian; Codd, Veryan; Tsai, Pei-Chien; Bell, Jordana; Peters, Annette; Strauch, Konstantin; Schulz, Holger; Weidinger, Stephan; Mohney, Robert P; Samani, Nilesh J; Spector, Tim; Mangino, Massimo; Menni, Cristina

    2016-01-01

    Leukocyte telomere length (LTL) is considered one of the most predictive markers of biological aging. The aim of this study was to identify novel pathways regulating LTL using a metabolomics approach. To this end, we tested associations between 280 blood metabolites and LTL in 3511 females from TwinsUK and replicated our results in the KORA cohort. We furthermore tested significant metabolites for associations with several aging-related phenotypes, gene expression markers and epigenetic markers to investigate potential underlying pathways. Five metabolites were associated with LTL: Two lysolipids, 1-stearoylglycerophosphoinositol (P=1.6×10(-5)) and 1-palmitoylglycerophosphoinositol (P=1.6×10(-5)), were found to be negatively associated with LTL and positively associated with phospholipase A2 expression levels suggesting an involvement of fatty acid metabolism and particularly membrane composition in biological aging. Moreover, two gamma-glutamyl amino acids, gamma-glutamyltyrosine (P=2.5×10(-6)) and gamma-glutamylphenylalanine (P=1.7×10(-5)), were negatively correlated with LTL. Both are products of the glutathione cycle and markers for increased oxidative stress. Metabolites were also correlated with functional measures of aging, i.e. higher blood pressure and HDL cholesterol levels and poorer lung, liver and kidney function. Our results suggest an involvement of altered fatty acid metabolism and increased oxidative stress in human biological aging, reflected by LTL and age-related phenotypes of vital organ systems. PMID:26797767

  17. Brain injury markers (S100B and NSE in chronic cocaine dependents Marcadores de lesão cerebral (S100B e NSE em dependentes crônicos de cocaína

    Directory of Open Access Journals (Sweden)

    Felix Henrique Paim Kessler

    2007-06-01

    Full Text Available OBJECTIVE: Studies have shown signs of brain damage caused by different mechanisms in cocaine users. The serum neuron specific enolase and S100B protein are considered specific biochemical markers of neuronal and glial cell injury. This study aimed at comparing blood levels of S100B and NSE in chronic cocaine users and in volunteers who did not use cocaine or other illicit drugs. METHOD: Twenty subjects dependent on cocaine but not on alcohol or marijuana, and 20 non-substance using controls were recruited. Subjects were selected by consecutive and non-probabilistic sampling. Neuron specific enolase and S100B levels were determined by luminescence assay. RESULTS: Cocaine users had significantly higher scores than controls in all psychiatric dimensions of the SCL-90 and had cognitive deficits in the subtest cubes of WAIS and the word span. Mean serum S100B level was 0.09 ± 0.04 µg/l among cocaine users and 0.08 ± 0.04 µg/l among controls. Mean serum neuron specific enolase level was 9.7 ± 3.5 ng/l among cocaine users and 8.3 ± 2.6 ng/l among controls. CONCLUSIONS: In this first study using these specific brain damage markers in cocaine users, serum levels of S100B and neuron specific enolase were not statistically different between cocaine dependent subjects and controls.OBJETIVO: Estudos têm demonstrado sinais de lesão cerebral causadas por diferentes mecanismos em usuários de cocaína. A enolase sérica neurônio-específica e a proteína S100B são consideradas marcadores bioquímicos específicos de lesão neuronal e glial. Este estudo objetivou comparar os níveis sangüíneos de S100B e enolase sérica neurônio-específica em usuários crônicos de cocaína e em voluntários que não usam cocaína ou outras drogas ilícitas. MÉTODO: Vinte sujeitos dependentes de cocaína, mas não dependentes de álcool, maconha ou outra droga, e 20 sujeitos controles não usuários de drogas foram recrutados. Os sujeitos foram selecionados por

  18. Secondary metabolites from marine microorganisms

    Directory of Open Access Journals (Sweden)

    KELECOM ALPHONSE

    2002-01-01

    Full Text Available After 40 years of intensive research, chemistry of marine natural products has become a mature field. Since 1995, there are signals of decreased interest in the search of new metabolites from traditional sources such as macroalgae and octocorals, and the number of annual reports on marine sponges stabilized. On the contrary, metabolites from microorganisms is a rapidly growing field, due, at least in part, to the suspicion that a number of metabolites obtained from algae and invertebrates may be produced by associated microorganisms. Studies are concerned with bacteria and fungi, isolated from seawater, sediments, algae, fish and mainly from marine invertebrates such as sponges, mollusks, tunicates, coelenterates and crustaceans. Although it is still to early to define tendencies, it may be stated that the metabolites from microorganisms are in most cases quite different from those produced by the invertebrate hosts. Nitrogenated metabolites predominate over acetate derivatives, and terpenes are uncommon. Among the latter, sesquiterpenes, diterpenes and carotenes have been isolated; among nitrogenated metabolites, amides, cyclic peptides and indole alkaloids predominate.

  19. Brain Basics

    Medline Plus

    Full Text Available ... News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  20. Brain Basics

    Science.gov (United States)

    ... News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  1. Brain Basics

    Medline Plus

    Full Text Available ... Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ... learning more about how the brain grows and works in healthy people, and how normal brain development ...

  2. Study on the radiation-induced biological responses based on the analysis of metabolites

    International Nuclear Information System (INIS)

    1. Objectives □ Establishment of basis of biological radiation response study by metabolite analysis 2. Project results □ Establishment of analytical basis of radiation-responsive metabolites in biological samples - Large scale collection of tissue samples from irradiated animal for radiation metabolomics research - Establishment of mass spectromety (GC MS, LC MS-MS) analysis methods of biological samples - 3 Standard Operation Protocols (SOP) for ultra high resolution mass spectrometry (FT-ICR MS, Q-TOF MS) analysis of metabolites from biological samples - Establishment of database for radiation metabolites □ Basic research on radiation-responsive metabolites and the interpretation of their functions - Validation of spermidine as a candidate biomarker of acute radiation response in mouse blood - Verification of 5 radiation-responsive steroid hormones and alteration of their metabolic enzyme activities in mouse blood - Verification of 13 radiation-responsive amino acids (related to oxidative stress, neurotransmission, energy metabolism) in regional mouse brain -Verification of 10 radiation-responsive amino acids (related to oxidative stress, neurotransmission, energy metabolism) in regional mouse brain - Verification of 74 radiation-responsive metabolites in whole rat brain by ultra high resolution FT-ICR MS and Q-TOF MS analysis 3. Expected benefits and plan of application □ Establishment of research basis of radiation metabolomics in Korea □ Provision of core technology in radiation bioscience and safety field by application of radiation metabolomics results to the technology development in radiation biodosimetry, and radiation response evaluation and modulation

  3. Study on the radiation-induced biological responses based on the analysis of metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Sungkee; Jung, Uhee; Park, Haeran; Roh, Changhyun; Shin, Heejune; Ryu, Dongkyoung

    2013-01-15

    1. Objectives □ Establishment of basis of biological radiation response study by metabolite analysis 2. Project results □ Establishment of analytical basis of radiation-responsive metabolites in biological samples - Large scale collection of tissue samples from irradiated animal for radiation metabolomics research - Establishment of mass spectromety (GC MS, LC MS-MS) analysis methods of biological samples - 3 Standard Operation Protocols (SOP) for ultra high resolution mass spectrometry (FT-ICR MS, Q-TOF MS) analysis of metabolites from biological samples - Establishment of database for radiation metabolites □ Basic research on radiation-responsive metabolites and the interpretation of their functions - Validation of spermidine as a candidate biomarker of acute radiation response in mouse blood - Verification of 5 radiation-responsive steroid hormones and alteration of their metabolic enzyme activities in mouse blood - Verification of 13 radiation-responsive amino acids (related to oxidative stress, neurotransmission, energy metabolism) in regional mouse brain -Verification of 10 radiation-responsive amino acids (related to oxidative stress, neurotransmission, energy metabolism) in regional mouse brain - Verification of 74 radiation-responsive metabolites in whole rat brain by ultra high resolution FT-ICR MS and Q-TOF MS analysis 3. Expected benefits and plan of application □ Establishment of research basis of radiation metabolomics in Korea □ Provision of core technology in radiation bioscience and safety field by application of radiation metabolomics results to the technology development in radiation biodosimetry, and radiation response evaluation and modulation.

  4. Characterization of Behavioral, Neuropathological, Brain Metabolic and Key Molecular Changes in zQ175 Knock-In Mouse Model of Huntington's Disease.

    Directory of Open Access Journals (Sweden)

    Qi Peng

    Full Text Available Huntington's disease (HD is caused by an expansion of the trinucleotide poly (CAG tract located in exon 1 of the huntingtin (Htt gene leading to progressive neurodegeneration in selected brain regions, and associated functional impairments in motor, cognitive, and psychiatric domains. Since the discovery of the gene mutation that causes the disease, mouse models have been developed by different strategies. Recently, a new model, the zQ175 knock-in (KI line, was developed in an attempt to have the Htt gene in a context and causing a phenotype that more closely mimics HD in humans. The behavioral phenotype was characterized across the independent laboratories and important features reminiscent of human HD are observed in zQ175 mice. In the current study, we characterized the zQ175 model housed in an academic laboratory under reversed dark-light cycle, including motor function, in vivo longitudinal structural MRI imaging for brain volume, MRS for striatal metabolites, neuropathology, as well as a panel of key disease marker proteins in the striatum at different ages. Our results suggest that homozygous zQ175 mice exhibited significant brain atrophy before the motor deficits and brain metabolite changes. Altered striatal medium spiny neuronal marker, postsynaptic marker protein and complement component C1qC also characterized zQ175 mice. Our results confirmed that the zQ175 KI model is valuable in understanding of HD-like pathophysiology and evaluation of potential therapeutics. Our data also provide suggestions to select appropriate outcome measurements in preclinical studies using the zQ175 mice.

  5. Neurochemical and structural markers in the brain predicting best choice-of-treatment in patients with schizophrenia - The Pan European Collaboration on Antipsychotic Naïve Schizophrenia II (PECANS II) study

    DEFF Research Database (Denmark)

    Jessen, Kasper; Bojesen, Kirsten Borup; Sigvard, Anne Mette;

    disturbances with positron emission tomography (PET) scanning, and loss of brain tissue with analysis of a structural MR-scanning revealing loss of cortical thickness and surface area. Neurochemical and structural disturbances are compared with treatment response and level of function as measured by various...... the progressive loss of brain tissue and social functions seen in many patients. Aim of PECANS II: To test if persistently high levels of glutamate and loss of brain tissue and social functions characterize a subgroup of patients with poor treatment response, while dopaminergic disturbances characterize another......: Inclusion started 1 January 2014 and is ongoing until the end of 2016. Conclusion: Identification of subgroups of patients with schizophrenia with distinct pathophysiological disturbances is clinically crucial, since brain levels of glutamate, loss of brain tissue, and dopaminergic disturbances may serve...

  6. Differentiating Hepatocellular Carcinoma from Hepatitis C Using Metabolite Profiling

    Directory of Open Access Journals (Sweden)

    Siwei Wei

    2012-10-01

    Full Text Available Hepatocellular carcinoma (HCC accounts for most liver cancer cases worldwide. Contraction of the hepatitis C virus (HCV is considered a major risk factor for liver cancer. In order to identify the risk of cancer, metabolic profiling of serum samples from patients with HCC (n=40 and HCV (n=22 was performed by 1H nuclear magnetic resonance spectroscopy. Multivariate statistical analysis showed a distinct separation of the two patient cohorts, indicating a distinct metabolic difference between HCC and HCV patient groups based on signals from lipids and other individual metabolites. Univariate analysis showed that three metabolites (choline, valine and creatinine were significantly altered in HCC. A PLS-DA model based on these three metabolites showed a sensitivity of 80%, specificity of 71% and an area under the receiver operating curve of 0.83, outperforming the clinical marker alpha-fetoprotein (AFP. The robustness of the model was tested using Monte-Carlo cross validation (MCCV. This study showed that metabolite profiling could provide an alternative approach for HCC screening in HCV patients, many of whom have high risk for developing liver cancer.

  7. Analysis of naltrexone urinary metabolites.

    Science.gov (United States)

    Ventura, R; de la Torre, R; Segura, J

    1988-01-01

    A reversed-phase HPLC method using ion-pair formation has been developed for the simultaneous determination of naltrexone and three urinary metabolites. The extraction of the free and conjugated metabolites was studied by liquid-solid procedures using styrene-divinylbenzene copolymers (Amberlite XAD-2) and bonded octadecyl silica supports (ODS-silica). Optimum recovery was obtained with ODS-silica extraction using 25% acetonitrile in a 5 mM diammonium phosphate buffer pH 2.1 as elution solvent. The chromatographic behaviour of naltrexone metabolites and naloxone (internal standard) was examined by varying the mobile phase composition. Increments of both the diammonium phosphate buffer concentration and the percentage of organic solvent in the eluent decreases the retention of compounds in a non-linear manner. Increments of the dodecyl sulphate (counter-ion) concentration, increases the retention time. The method was applied to determine the urinary levels of major naltrexone metabolites in a volunteer receiving a 50 mg oral dose. This is the first method reported which permits the simultaneous quantitative determination of naltrexone and its metabolites, 6beta-naltrexol, naltrexone glucuronide and 6beta-naltrexol glucuronide, in urine. PMID:16867358

  8. Metabolic Profiling and Quantification of Neurotransmitters in Mouse Brain by Gas Chromatography-Mass Spectrometry.

    Science.gov (United States)

    Jäger, Christian; Hiller, Karsten; Buttini, Manuel

    2016-01-01

    Metabolites are key mediators of cellular functions, and have emerged as important modulators in a variety of diseases. Recent developments in translational biomedicine have highlighted the importance of not looking at just one disease marker or disease inducing molecule, but at populations thereof to gain a global understanding of cellular function in health and disease. The goal of metabolomics is the systematic identification and quantification of metabolite populations. One of the most pressing issues of our times is the understanding of normal and diseased nervous tissue functions. To ensure high quality data, proper sample processing is crucial. Here, we present a method for the extraction of metabolites from brain tissue, their subsequent preparation for non-targeted gas chromatography-mass spectrometry (GC-MS) measurement, as well as giving some guidelines for processing of raw data. In addition, we present a sensitive screening method for neurotransmitters based on GC-MS in selected ion monitoring mode. The precise multi-analyte detection and quantification of amino acid and monoamine neurotransmitters can be used for further studies such as metabolic modeling. Our protocol can be applied to shed light on nervous tissue function in health, as well as neurodegenerative disease mechanisms and the effect of experimental therapeutics at the metabolic level. © 2016 by John Wiley & Sons, Inc. PMID:27584556

  9. Nitric oxide metabolites in goldfish under normoxic and hypoxic conditions

    DEFF Research Database (Denmark)

    Hansen, Marie N.; Jensen, Frank Bo

    2010-01-01

    Nitric oxide (NO), produced by nitric oxide synthases (NOS enzymes), regulates multiple physiological functions in animals. NO exerts its effects by binding to iron (Fe) of heme groups (exemplified by the activation of soluble guanylyl cyclase) and by S-nitrosylation of proteins – and it is...... metabolized to nitrite and nitrate. Nitrite is used as a marker for NOS activity but it is also a NO donor that can be activated by various cellular proteins under hypoxic conditions. Here, we report the first systematic study of NO metabolites (nitrite, nitrate, S-nitroso, N-nitroso and Fe-nitrosyl compounds...... hypoxia levels was assessed from metabolic and respiratory variables. In normoxic goldfish, the concentrations of NO metabolites in plasma and tissues were comparable with values reported in mammals, indicative of similar NOS activity. Exposure to hypoxia [at PO2 (partial pressure of O2) values close to...

  10. Serum estrogen and its metabolites in pregnant women exposed to dioxins and polychlorinated biphenyls (PCBs)

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shuli; Chang, Y.C.; Li, C.M.; Chou, W.L. [National Health Research Insts., Kaohsiung (Taiwan). Div. of Environmental Health and Occupational Medicine; Chao, H.R.; Guo, Y.L. [National Chung Kung Univ., Tainan (Taiwan). Inst. of Environmental Medicine

    2004-09-15

    Dioxins and PCBs are environmental endocrine disruptors that have half-life of 7-10 years in human bodies and have toxicities including carcinogenesis. Studies showed a high estrogen 4-/2- hydroxylation ratio appears to be a marker for neoplasm. The aim is to examine dioxin and PCBs body burden1 in relation to estrogen metabolites and catabolites.

  11. Brain herniation

    Science.gov (United States)

    ... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

  12. Enuresis as a Premorbid Developmental Marker of Schizophrenia

    Science.gov (United States)

    Hyde, Thomas M.; Deep-Soboslay, Amy; Iglesias, Bianca; Callicott, Joseph H.; Gold, James M.; Meyer-Lindenberg, Andreas; Honea, Robyn A.; Bigelow, Llewellyn B.; Egan, Michael F.; Emsellem, Esther M.; Weinberger, Daniel R.

    2008-01-01

    There is comparatively little information about premorbid maturational brain abnormalities in schizophrenia (SCZ). We investigated whether a history of childhood enuresis, a well-established marker of neurodevelopmental delay, is associated with SCZ and with measures of brain abnormalities also associated with SCZ. A Diagnostic and Statistical…

  13. Proton MR spectroscopy in mild traumatic brain injury

    International Nuclear Information System (INIS)

    To assess the role of 1H MRS in the detection of changes in cerebral metabolite levels in pyramidal tracts after mild traumatic brain injury (MTBI) and to compare metabolite alterations to the clinical status (Glasgow Coma Scale). Study group consisted of 25 patients after mild traumatic brain injury, with a score of 11 to 15 in GCS. The MR studies were performed with a 1.5 T scanner. The results of spectra approximation (presented as metabolite ratios: NAA/Cr, NAA/Cho, Cho/Cr, lac/Cr, lip/Cr, Glx/Cr) were subjected to statistical analysis. MR spectra were recorded from a normal-appearing brain region: internal capsules and cerebral peduncles. Spectra from traumatic patients were compared with a control group including 34 healthy volunteers recorded with the same techniques. The statistical analysis revealed significant differences between the data obtained from various brain regions of the same patients after an MTBI and between the study and the control group. Proton MR spectroscopy detects changes in cerebral metabolite levels in apparently normal regions. In pyramidal tracts (internal capsules, cerebral peduncles), we noticed a significant reduction of NAA /Cho, lip/Cr, lac/Cr and Glx/Cr. In patients with mild brain injury, we can detect some metabolite abnormalities in normal-appearing brain structures. Proton MRS is a very useful tool for evaluation of major changes in metabolite levels in pyramidal tracts after mild traumatic brain injury

  14. Correlations between phthalate metabolites in urine, serum, and seminal plasma from young Danish men determined by isotope dilution liquid chromatography tandem mass spectrometry

    DEFF Research Database (Denmark)

    Frederiksen, Hanne; Jørgensen, Niels; Andersson, Anna-Maria

    2010-01-01

    , correlations between urine and serum levels were only observed for mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(4-methyl-7-carboxyheptyl) phthalate (MCiOP), indicating that these secondary carboxylated metabolites were better serum markers than primary metabolites [mono(2-ethylhexyl) phthalate......Phthalates are suspected of endocrine disrupting effects. We aimed to develop an analytical method for simultaneous determination of several phthalate metabolites in human urine, serum, and seminal plasma and to study correlations between levels of metabolites in these matrices. Thirteen...... metabolites were determined in samples from 60 young Danish men. Metabolites of common di-ester phthalates were detected in most urine samples. Summed di-(2-ethylhexyl) phthalate (DEHP) metabolites were excreted in urine in the highest amount (median = 91.1 ng/mL), followed by monoethyl phthalate (MEP), mono...

  15. Profiling of metabolites in oil palm mesocarp at different stages of oil biosynthesis.

    Science.gov (United States)

    Neoh, Bee Keat; Teh, Huey Fang; Ng, Theresa Lee Mei; Tiong, Soon Huat; Thang, Yin Mee; Ersad, Mohd Amiron; Mohamed, Mohaimi; Chew, Fook Tim; Kulaveerasingam, Harikrishna; Appleton, David R

    2013-02-27

    Oil palm is one of the most productive oil producing crops and can store up to 90% oil in its fruit mesocarp. However, the biosynthetic regulation and drivers of palm mesocarp development are still not well understood. Multiplatform metabolomics technology was used to profile palm metabolites during six critical stages of fruit development in order to better understand lipid biosynthesis. Significantly higher amino acid levels were observed in palm mesocarp preceding lipid biosynthesis. Nucleosides were found to be in high concentration during lipid biosynthesis, whereas levels of metabolites involved in the tricarboxylic acid cycle were more concentrated during early fruit development. Apart from insights into the regulation of metabolites during fruit development in oil palm, these results provide potentially useful metabolite yield markers and genes of interest for use in breeding programs. PMID:23384169

  16. Enuresis as a premorbid developmental marker of schizophrenia*

    OpenAIRE

    Hyde, Thomas M.; Deep-Soboslay, Amy; Iglesias, Bianca; Callicott, Joseph H.; Gold, James M.; Meyer-Lindenberg, Andreas; Robyn A Honea; Bigelow, Llewellyn B.; Egan, Michael F.; Emsellem, Esther M.; Weinberger, Daniel R.

    2008-01-01

    There is comparatively little information about premorbid maturational brain abnormalities in schizophrenia (SCZ). We investigated whether a history of childhood enuresis, a well-established marker of neurodevelopmental delay, is associated with SCZ and with measures of brain abnormalities also associated with SCZ. A Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) based history of enuresis, volumetric brain MRI scans and neuropsychological testing were obtained in patients with...

  17. Brain Basics

    Medline Plus

    Full Text Available ... Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies show that brain growth in children with autism ...

  18. Rapid comparison of metabolites in humans and rats of different sexes using untargeted UPLC-TOFMS and an in-house software platform.

    Science.gov (United States)

    Liang, Qiande; Xu, Wangyanjun; Hong, Qian; Xiao, Chengrong; Yang, Liang; Ma, Zengchun; Wang, Yuguang; Tan, Hongling; Tang, Xianglin; Gao, Yue

    2015-01-01

    Metabolite differences between sexes have rarely been observed in a global manner, but it has recently been made possible by the advancement in metabolomics techniques. In this study, untargeted ultraperformance liquid chromatography coupled to time-of-flight mass spectrometry and an in-house software platform were used for a rapid comparison of sex differences in urinary metabolites in humans and in urinary and serum metabolites in Sprague Dawley (SD) rats. In addition, the species differences of urinary metabolites between humans and SD rats were also observed. Principle component analysis showed that all the observed metabolite sex differences were more distinct in SD rats than in humans, indicating that the sex differences of human urinary metabolites is small compared with that of SD rats. In SD rats, the observed metabolite sex differences were more distinct in urine than in serum, indicating the importance of urine analysis for metabolomics studies. The species differences in the urinary metabolites of humans and SD rats were much more distinct than any of the observed sex differences. Many sex- and species-related markers were discovered and putatively identified. In both humans and SD rats, steroid metabolites appeared to constitute a major sex difference in urinary metabolites. This provides new proof of the special importance of steroid metabolites in sex differences from an untargeted metabolomics investigation, which is rare for sex differences. Contrary patterns involving adrenocortical activity appeared to exist between rodents and humans, which agrees with previous reports. In the serum metabolites of SD rats, sex differences in ascorbic acid or its isomer and pantothenic acid or its isomer, but not in steroid metabolites, were prominent. Human-specific α-N- phenylacetyl-l-glutamine and androsterone glucuronide were among the putative identities of the markers discriminating humans and SD rats. This study demonstrated the feasibility of an in

  19. Seed metabolomic study reveals significant metabolite variations and correlations among different soybean cultivars

    Institute of Scientific and Technical Information of China (English)

    Hong Lin; Jun Rao; Jianxin Shi; Chaoyang Hu; Fang Cheng; Zoe AWilson; Dabing Zhang; Sheng Quan

    2014-01-01

    Soybean [Glycine max (L.) Merr.] is one of the world’s major crops, and soybean seeds are a rich and important resource for proteins and oils. While “omics”studies, such as genomics, transcriptomics, and proteomics, have been widely applied in soybean molecular research, fewer metabolomic studies have been conducted for large-scale detection of low molecular weight metabolites, especial y in soybean seeds. In this study, we investigated the seed metabolomes of 29 common soybean cultivars through combined gas chromatography-mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry. One hundred sixty-nine named metabolites were identified and subsequently used to construct a metabolic network of mature soybean seed. Among the 169 detected metabolites, 104 were found to be significantly variable in their levels across tested cultivars. Metabolite markers that could be used to distinguish genetical y related soybean cultivars were also identified, and metabolite-metabolite correlation analysis revealed some significant associations within the same or among different metabolite groups. Findings from this work may potentially provide the basis for further studies on both soybean seed metabolism and metabolic engineering to improve soybean seed quality and yield.

  20. Natural products: Hunting microbial metabolites

    Science.gov (United States)

    Schmidt, Eric W.

    2015-05-01

    Symbiotic bacteria synthesize many specialized small molecules; however, establishing the role these chemicals play in human health and disease has been difficult. Now, the chemical structure and mechanism of the Escherichia coli product colibactin provides insight into the link between this secondary metabolite and colorectal cancer.

  1. Primary expectations of secondary metabolites

    Science.gov (United States)

    Plant secondary metabolites (e.g., phenolics) are important for human health, in addition to the organoleptic properties they impart to fresh and processed foods. Consumer expectations such as appearance, taste, or texture influence their purchasing decisions. Thorough identification of phenolic com...

  2. The secondary metabolite bioinformatics portal

    DEFF Research Database (Denmark)

    Weber, Tilmann; Kim, Hyun Uk

    2016-01-01

    . In this context, this review gives a summary of tools and databases that currently are available to mine, identify and characterize natural product biosynthesis pathways and their producers based on ‘omics data. A web portal called Secondary Metabolite Bioinformatics Portal (SMBP at http...

  3. Whole Mouse Brain Image Reconstruction from Serial Coronal Sections Using FIJI (ImageJ).

    Science.gov (United States)

    Paletzki, Ronald; Gerfen, Charles R

    2015-01-01

    Whole-brain reconstruction of the mouse enables comprehensive analysis of the distribution of neurochemical markers, the distribution of anterogradely labeled axonal projections or retrogradely labeled neurons projecting to a specific brain site, or the distribution of neurons displaying activity-related markers in behavioral paradigms. This unit describes a method to produce whole-brain reconstruction image sets from coronal brain sections with up to four fluorescent markers using the freely available image-processing program FIJI (ImageJ). PMID:26426384

  4. Identification of Epoxide-Derived Metabolite(s) of Benzbromarone.

    Science.gov (United States)

    Wang, Kai; Wang, Hui; Peng, Ying; Zheng, Jiang

    2016-04-01

    Benzbromarone (BBR) is a benzofuran derivative that has been quite useful for the treatment of gout; however, it was withdrawn from European markets in 2003 because of reported serious incidents of drug-induced liver injury. BBR-induced hepatotoxicity has been suggested to be associated with the formation of a quinone intermediate. The present study reported epoxide-derived intermediate(s) of BBR. An N-acetylcysteine (NAC) conjugate derived from epoxide metabolite(s) was detected in both microsomal incubations of BBR and urine samples of mice treated with BBR. The NAC conjugate was identified as 6-NAC BBR. Ketoconazole suppressed the bioactivation of BBR to the epoxide intermediate(s), and the CYP3A subfamily was the primary enzyme responsible for the formation of the epoxide(s). The present study provided new information on metabolic activation of BBR. PMID:26792818

  5. EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain), 2015. Scientific Opinion on nitrofurans and their metabolites in food

    DEFF Research Database (Denmark)

    Petersen, Annette

    .0 µg/kg in foods of animal origin, excluding milk and dairy products. The mean chronic dietary exposure for this worst-case scenario would range from 3.3 to 8.0 and 1.9 to 4.3 ng/kg b.w. per day for toddlers and adults, respectively. Nitrofurans and their marker metabolites, generally, are genotoxic......Nitrofurans are antimicrobial agents not authorised for use in food-producing animals in the European Union. Nitrofurans are rapidly metabolised, occurring in animal tissues as protein-bound metabolites. The European Commission requested EFSA to provide a scientific opinion on the risks to human...... health related to the presence of nitrofurans in food and whether a reference point for action (RPA) of 1.0 µg/kg for the marker metabolites is adequate to protect public health. Data on occurrence of nitrofuran marker metabolites in food were extracted from the national residue monitoring plan results...

  6. Brain N-acetylaspartate levels correlate with motor function in metachromatic leukodystrophy

    DEFF Research Database (Denmark)

    í Dali, Christine; Hanson, Lars G.; Barton, N. W.;

    2010-01-01

    oligodendrocytes and is known as a marker for neuronal and axonal loss. NAA and other metabolite levels measured by proton magnetic resonance spectroscopy (MRS) correlate with performance of the brain in normal children. There is a need for sensitive measures of disease progression in patients with MLD to enable...... development of future reatments. Methods: A cross-section of 13 children with late infantile MLD were examined by proton MRS. Signals from NAA, total choline, and total creatine in the deep white matter were measured and correlated with the results of cognitive and motor function tests. Results: The NAA...... observed in cognitive function. We report strong positive correlations between standardized measures of motor and cognitive function and NAA levels in the deep white matter. Conclusions: We suggest that NAA levels could serve as a sensitive biomarker in children with MLD. Proton MRS may provide a valuable...

  7. Analysis of P-31 metabolite images of arm and brain

    International Nuclear Information System (INIS)

    There is no reliable clinical test that predicts the viability of ischemic limbs; therefore, revascularization may be performed when primary amputation may be preferable. The aim of this paper is to assessthe ability of phosphorus-31 MR images to detect irreversible tissue changes at rest. The authors examined 18 patients with severs ischimia (24 studies) and six control subjects. A 1.6-T prototype whole-body spectrometer was used. Two-dimensional chemical shift imaging was performed in the vertical axis of the foot at 2-cm intervals. Spectra from the plane containing maximal muscle bulk were analyzed. On the basis of surgical management and outcome at 6 months, the patients were divided into four groups: group 1, no surgical intervention; group 2, sucessful revascularization before surgery or after surgery; group 3, failure of revascularization; and group 4, immediately prior to amputation

  8. Effect of feed restriction on metabolites in cerebrospinal fluid and plasma of dairy cows.

    Science.gov (United States)

    Laeger, T; Görs, S; Metges, C C; Kuhla, B

    2012-03-01

    Endocrines and metabolites in the circulation act as long-term hunger or satiety signals in the brain during negative energy balance and play an important role in the control of feed intake. These signals also occur in the cerebrospinal fluid (CSF), which surrounds the hypothalamus and brainstem: 2 major centers of feed intake regulation. Thus CSF functions as a transport medium for fuel signals between blood and brain. The CSF metabolite concentrations are mainly under control of the blood-brain barriers, which provide specific carrier molecules facilitating the entry of substances required by the brain and protect the brain from factors that could impair neuronal function. The transport of small molecules such as amino acids (AA) across the blood-brain barriers may be limited by competing AA that share a common transporter for the uptake into brain. Consequently, CSF metabolite concentrations differ from those in blood. Thus it appears likely that central (CSF) rather than peripheral (blood) metabolites act as pivotal signals for the control of feed intake. However, the contribution of putative orexigenic and anorexigenic signals in CSF of cows has not been studied so far. Therefore, the aim of this study was to elucidate associations existing between both plasma and CSF metabolites, each in response to feed restriction-induced negative energy balance. Seven German Holstein dairy cows, between 87 and 96 DIM of the second lactation (milk yield, 27.9 L/d) were fed ad libitum (AL) for 4 d and CSF from the spinal cord and blood from the jugular vein was withdrawn before morning feeding at the fifth day. Subsequently, animals were feed restricted (R) to 50% of the previous AL intake for 4 d and CSF and plasma were collected at the ninth day. Body weight, feed intake, water intake, and milk production were determined. Thirty-one AA, β-hydroxybutyric acid, cholesterol, glucose, lactate, nonesterified fatty acids, urea, and osmolality were measured in both CSF and

  9. Embryonic Stem Cell Markers

    OpenAIRE

    Lan Ma; Liang Li; Wenxiu Zhao; Xiang Ji; Fangfang Zhang

    2012-01-01

    Embryonic stem cell (ESC) markers are molecules specifically expressed in ES cells. Understanding of the functions of these markers is critical for characterization and elucidation for the mechanism of ESC pluripotent maintenance and self-renewal, therefore helping to accelerate the clinical application of ES cells. Unfortunately, different cell types can share single or sometimes multiple markers; thus the main obstacle in the clinical application of ESC is to purify ES cells from other type...

  10. Antioxidant activity of nimesulide and its main metabolites.

    Science.gov (United States)

    Facino, R M; Carini, M; Aldini, G

    1993-01-01

    The antioxidant activity of nimesulide and its main metabolites, 4'-hydroxynimesulide (M1) and 2-(4'-hydroxyphenoxy)-4-N-acetylamino-methansulfonanilide (M2), was investigated using 2 in vitro models: NADPH-supported lipid peroxidation in rat liver microsomes (marker MDA formation) and xanthine/xanthine oxidase, iron-promoted depolymerisation of hyaluronic acid, determined by gel permeation chromatographic analysis (marker molecular weight distribution). In the lipid peroxidation model, all the compounds inhibited MDA formation in a concentration-dependent manner, although with different potencies; the maximum scavenging effect was observed for M1 [50% inhibitory concentration (IC50) = 30 mumol/L; M2 IC50 = 0.5 mmol/L; nimesulide = 0.8 mmol/L]. Nimesulide was more active than its metabolites in preventing OH-induced depolymerisation of hyaluronic acid, with a 50% effective concentration of approximately 230 mumol/L, which was fairly comparable to that of tenoxicam. This protective effect was due to the OH.-entrapping capacity of the drug, which, in the Fenton-driven model, is easily converted, via OH. attack, to M1 and putatively to 2-hydroxy-4-nitro-methansulfonanilide. PMID:7506157

  11. Secondary Metabolites from Rubiaceae Species

    OpenAIRE

    Daiane Martins; Cecilia Veronica Nunez

    2015-01-01

    This study describes some characteristics of the Rubiaceae family pertaining to the occurrence and distribution of secondary metabolites in the main genera of this family. It reports the review of phytochemical studies addressing all species of Rubiaceae, published between 1990 and 2014. Iridoids, anthraquinones, triterpenes, indole alkaloids as well as other varying alkaloid subclasses, have shown to be the most common. These compounds have been mostly isolated from the genera Uncaria, Psych...

  12. Autism and Phthalate Metabolite Glucuronidation

    OpenAIRE

    Stein, T. Peter; Schluter, Margaret D.; Steer, Robert A.; Ming, Xue

    2013-01-01

    Exposure to environmental chemicals may precipitate autism spectrum disorders (ASD) in genetically susceptible children. Differences in the efficiency of the glucuronidation process may substantially modulate substrate concentrations and effects. To determine whether the efficiency of this pathway is compromised in children with ASD, we measured the efficiency of glucuronidation for a series of metabolites derived from the commonly used plasticizer, diethylhexyl phthalate. Spot urines were co...

  13. Epigenome targeting by probiotic metabolites

    OpenAIRE

    Licciardi Paul V; Wong Sook-San; Tang Mimi LK; Karagiannis Tom C

    2010-01-01

    Abstract Background The intestinal microbiota plays an important role in immune development and homeostasis. A disturbed microbiota during early infancy is associated with an increased risk of developing inflammatory and allergic diseases later in life. The mechanisms underlying these effects are poorly understood but are likely to involve alterations in microbial production of fermentation-derived metabolites, which have potent immune modulating properties and are required for maintenance of...

  14. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, or ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are metastatic, ...

  15. Brain Basics

    Medline Plus

    Full Text Available ... Basics will introduce you to some of this science, such as: How the brain develops How genes and the environment affect the brain The basic structure of the brain How different parts of the brain communicate and work with each other How changes in the brain ...

  16. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  17. Brain Fingerprinting

    Directory of Open Access Journals (Sweden)

    ravi kumar

    2012-12-01

    Full Text Available Brain Fingerprinting is a scientific technique to determine whether or not specific information is stored in an individual's brain by measuring a electrical brain wave response to Word, phrases, or picture that are presented on computer screen. Brain Fingerprinting is a controversial forensic science technique that uses electroencephalograph y (EEG to determine whether specific information is stored in a subject's brain

  18. Metabolite quantitation in breast cancer by in vivo MR spectroscopy

    International Nuclear Information System (INIS)

    A large number of biochemical and imaging investigations are available for the diagnosis of cancer but detection is still a challenging task. Various magnetic resonance imaging (MRI) methods are used for the detection of tumors that gives morphological and functional details. On the other hand, magnetic resonance spectroscopy (MRS) provides metabolites or biochemicals at the molecular level. With technological advancement in MR, it is possible to detect in vivo metabolites from normal and pathological tissues that are present in millimolar concentrations and there are several localization methods available for the same. The commonest cancer in women is the breast cancer and is a leading cause of death among the female population worldwide. The in vivo localized proton MR spectroscopy of normal breast tissues is dominated by a huge lipid with little contribution from water while malignant breast tissues contain high water content. By suppressing the water and fat contribution, it is possible to detect choline containing compounds (tCho) in malignant breast tissues. The parameters obtained from in vivo proton MRS of breast tissues are water-to-fat (W-F) ratio and detection of tCho. tCho has been documented by many workers as a potential marker of breast malignancy. Recently, quantitative assessment of tCho concentration has been reported. There are two methods that are used for quantification of tCho: (a) semi-quantitative method that calculates the signal-to-noise ratio (SNR) of the choline signal; and (b) determination of the absolute concentration of tCho using water as an internal and external reference. Both W-F ratio and tCho concentration have been evaluated as markers for assessment of tumor response to therapy. This talk would cover various MRS methods used for the diagnosis of breast cancer together with the details of the determination of the absolute and relative concentrations of metabolites. (author)

  19. Activation of Astroglial Calcium Signaling by Endogenous Metabolites Succinate and Gamma-Hydroxybutyrate in the Nucleus Accumbens

    OpenAIRE

    Molnár, Tünde; Héja, László; Emri, Zsuzsa; Simon, Ágnes; Nyitrai, Gabriella; Pál, Ildikó; Kardos, Julianna

    2011-01-01

    Accumulating evidence suggests that different energy metabolites play a role not only in neuronal but also in glial signaling. Recently, astroglial Ca2+ transients evoked by the major citric acid cycle metabolite succinate (SUC) and gamma-hydroxybutyrate (GHB) that enters the citric acid cycle via SUC have been described in the brain reward area, the nucleus accumbens (NAc). Cells responding to SUC by Ca2+ transient constitute a subset of ATP-responsive astrocytes that are activated in a neur...

  20. Activation of astroglial calcium signaling by endogenous metabolites succinate and gamma-hydroxybutyrate in the nucleus accumbens

    OpenAIRE

    Zsuzsa Emri; Julianna Kardos

    2011-01-01

    Accumulating evidence suggests that different energy metabolites play a role not only in neuronal but also in glial signalling. Recently, astroglial Ca2+ transients evoked by the major citric acid cycle metabolite succinate (SUC) and gamma-hydroxybutyrate (GHB) that enters the citric acid cycle via SUC have been described in the brain reward area, the nucleus accumbens (NAc). Cells responding to SUC by Ca2+ transient constitute a subset of ATP-responsive astrocytes that are activated in a neu...

  1. Targeted serum metabolite profiling and sequential metabolite ratio analysis for colorectal cancer progression monitoring.

    Science.gov (United States)

    Zhu, Jiangjiang; Djukovic, Danijel; Deng, Lingli; Gu, Haiwei; Himmati, Farhan; Abu Zaid, Mohammad; Chiorean, Elena Gabriela; Raftery, Daniel

    2015-10-01

    Colorectal cancer (CRC) is one of the most prevalent cancers worldwide and a major cause of human morbidity and mortality. In addition to early detection, close monitoring of disease progression in CRC can be critical for patient prognosis and treatment decisions. Efforts have been made to develop new methods for improved early detection and patient monitoring; however, research focused on CRC surveillance for treatment response and disease recurrence using metabolomics has yet to be reported. In this proof of concept study, we applied a targeted liquid chromatography tandem mass spectrometry (LC-MS/MS) metabolic profiling approach focused on sequential metabolite ratio analysis of serial serum samples to monitor disease progression from 20 CRC patients. The use of serial samples reduces patient to patient metabolic variability. A partial least squares-discriminant analysis (PLS-DA) model using a panel of five metabolites (succinate, N2, N2-dimethylguanosine, adenine, citraconic acid, and 1-methylguanosine) was established, and excellent model performance (sensitivity = 0.83, specificity = 0.94, area under the receiver operator characteristic curve (AUROC) = 0.91 was obtained, which is superior to the traditional CRC monitoring marker carcinoembryonic antigen (sensitivity = 0.75, specificity = 0.76, AUROC = 0.80). Monte Carlo cross validation was applied, and the robustness of our model was clearly observed by the separation of true classification models from the random permutation models. Our results suggest the potential utility of metabolic profiling for CRC disease monitoring. PMID:26342311

  2. TETX: a novel nuclear selection marker for Chlamydomonas reinhardtii transformation

    OpenAIRE

    Garcia-Echauri, Sergio A; Cardineau, Guy A.

    2015-01-01

    Background Transformation of microalgae to obtain recombinant proteins, lipids or metabolites of economic value is of growing interest due to low costs associated with culture growth and scaling up. At present there are only three stable nuclear selection markers for the transformation of Chlamydomonas reinhardtii, which is the most commonly transformed microalgae, specifically: the aminoglycoside phosphotransferaseses aph7and aphVIII and the phleomycin resistance ble gene. As several microal...

  3. Brain Basics

    Medline Plus

    Full Text Available ... The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit of the ... distant nerve cells (via axons) to form brain circuits. These circuits control specific body functions such as ...

  4. Brain Basics

    Medline Plus

    Full Text Available ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies ...

  5. Brain Basics

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    Full Text Available ... Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ... others live with symptoms of mental illness every day. They can be moderate, or serious and cause ...

  6. Brain Basics

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    Full Text Available ... helps Sarah to better cope with her feelings. Brain Research Modern research tools and techniques are giving scientists ... the treatment for a person's specific conditions. Such brain research help increase the understanding of how the brain ...

  7. Brain Basics

    Medline Plus

    Full Text Available ... little dopamine or problems using dopamine in the thinking and feeling regions of the brain may play ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses ...

  8. Brain Basics

    Medline Plus

    Full Text Available ... as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit of the brain ... specialized for the function of conducting messages. A neuron has three basic parts: Cell body which includes ...

  9. Brain Malformations

    Science.gov (United States)

    Most brain malformations begin long before a baby is born. Something damages the developing nervous system or causes it ... medicines, infections, or radiation during pregnancy interferes with brain development. Parts of the brain may be missing, ...

  10. Brain Basics

    Medline Plus

    Full Text Available ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as ... grow there are differences in brain development in children who develop bipolar disorder than children who do ...

  11. Brain Basics

    Medline Plus

    Full Text Available ... Basics will introduce you to some of this science, such as: How the brain develops How genes and the environment affect the brain The basic structure of the brain How different parts of ...

  12. Brain Basics

    Medline Plus

    Full Text Available ... understanding of the brain than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures ...

  13. Brain Basics

    Medline Plus

    Full Text Available ... science, such as: How the brain develops How genes and the environment affect the brain The basic ... that with brain development in people mental disorders. Genes and environmental cues both help to direct this ...

  14. Brain surgery

    Science.gov (United States)

    Craniotomy; Surgery - brain; Neurosurgery; Craniectomy; Stereotactic craniotomy; Stereotactic brain biopsy; Endoscopic craniotomy ... cut depends on where the problem in the brain is located. The surgeon creates a hole in ...

  15. Radiopaque anastomosis marker

    International Nuclear Information System (INIS)

    This invention relates to split ring markers fabricated in whole or in part from a radiopaque material, usually metal, having the terminal ends thereof and a medial portion formed to define eyelets by means of which said marker can be sutured to the tissue at the site of an anastomosis to provide a visual indication of its location when examined fluoroscopically

  16. Non-invasive Assessment of Neonatal Brain Oxygen Metabolism: A Review of Newly Available Techniques

    OpenAIRE

    Liu, Peiying; Chalak, Lina F.; Lu, Hanzhang

    2014-01-01

    Because oxidative metabolism is the primary form of energy production in the brain, the amount of oxygen consumed by the brain, denoted by a physiological parameter termed cerebral metabolic rate of oxygen (CMRO2), represents a key marker for tissue viability and brain function. Quantitative assessment of cerebral oxygen metabolism in the neonate may provide an important marker in better understanding normal brain development and in making diagnosis and treatment decisions in neonatal brain i...

  17. The cerebral metabolism of amino acids and related metabolites as studied by {sup 13}C and {sup 14}C labelling

    Energy Technology Data Exchange (ETDEWEB)

    Hassel, B.

    1995-11-01

    The present investigations show the feasibility of analyzing the cerebral metabolism of amino acids and related metabolites by {sup 13}C-and {sup 14}C-labelling using labelled acetate and glucose as markers for glial and neuronal metabolism, respectively. Using [{sup 13}C]acetate, it was shown that glial cells export {approx}60% of their TCA cycle intermediates, mostly as glutamine, and that this glutamine is used by neurons partly as an energy reserve, and partly it is converted directly to glutamate and GABA. Using [{sup 13}C]glucose, the glial process or pyruvate carboxylation was shown to compensate fully for the loss of glutamine. The mechanism of action of two neurotoxins, fluorocitrate and 3-nitropropionate was elucidated. The latter toxin was shown to inhibit the TCA cycle of GABAergic neurons selectively. Formation of pyruvate and lactate from glial TCA cycle intermediates was demonstrated in vivo. This pathway may be important for glial inactivation of transmitter glutamate and GABA. The results illustrate glianeuronal interactions, and they suggest the applicability of {sup 13}CNMR spectroscopy to the detailed study of the cerebral metabolism of amino acids in the intact, unanesthetized human brain. 174 refs.

  18. The cerebral metabolism of amino acids and related metabolites as studied by 13C and 14C labelling

    International Nuclear Information System (INIS)

    The present investigations show the feasibility of analyzing the cerebral metabolism of amino acids and related metabolites by 13C-and 14C-labelling using labelled acetate and glucose as markers for glial and neuronal metabolism, respectively. Using [13C[acetate, it was shown that glial cells export ∼60% of their TCA cycle intermediates, mostly as glutamine, and that this glutamine is used by neurons partly as an energy reserve, and partly it is converted directly to glutamate and GABA. Using [13C[glucose, the glial process or pyruvate carboxylation was shown to compensate fully for the loss of glutamine. The mechanism of action of two neurotoxins, fluorocitrate and 3-nitropropionate was elucidated. The latter toxin was shown to inhibit the TCA cycle of GABAergic neurons selectively. Formation of pyruvate and lactate from glial TCA cycle intermediates was demonstrated in vivo. This pathway may be important for glial inactivation of transmitter glutamate and GABA. The results illustrate glianeuronal interactions, and they suggest the applicability of 13CNMR spectroscopy to the detailed study of the cerebral metabolism of amino acids in the intact, unanesthetized human brain. 174 refs

  19. Brain mapping

    OpenAIRE

    Blaž Koritnik

    2004-01-01

    Cartography of the brain ("brain mapping") aims to represent the complexities of the working brain in an understandable and usable way. There are four crucial steps in brain mapping: (1) acquiring data about brain structure and function, (2) transformation of data into a common reference, (3) visualization and interpretation of results, and (4) databasing and archiving. Electrophysiological and functional imaging methods provide information about function of the human brain. A prere...

  20. Amino Acid and Secondary Metabolite Production in Embryogenic and Non-Embryogenic Callus of Fingerroot Ginger (Boesenbergia rotunda.

    Directory of Open Access Journals (Sweden)

    Theresa Lee Mei Ng

    Full Text Available Interest in the medicinal properties of secondary metabolites of Boesenbergia rotunda (fingerroot ginger has led to investigations into tissue culture of this plant. In this study, we profiled its primary and secondary metabolites, as well as hormones of embryogenic and non-embryogenic (dry and watery callus and shoot base, Ultra Performance Liquid Chromatography-Mass Spectrometry together with histological characterization. Metabolite profiling showed relatively higher levels of glutamine, arginine and lysine in embryogenic callus than in dry and watery calli, while shoot base tissue showed an intermediate level of primary metabolites. For the five secondary metabolites analyzed (ie. panduratin, pinocembrin, pinostrobin, cardamonin and alpinetin, shoot base had the highest concentrations, followed by watery, dry and embryogenic calli. Furthermore, intracellular auxin levels were found to decrease from dry to watery calli, followed by shoot base and finally embryogenic calli. Our morphological observations showed the presence of fibrils on the cell surface of embryogenic callus while diphenylboric acid 2-aminoethylester staining indicated the presence of flavonoids in both dry and embryogenic calli. Periodic acid-Schiff staining showed that shoot base and dry and embryogenic calli contained starch reserves while none were found in watery callus. This study identified several primary metabolites that could be used as markers of embryogenic cells in B. rotunda, while secondary metabolite analysis indicated that biosynthesis pathways of these important metabolites may not be active in callus and embryogenic tissue.

  1. Amino Acid and Secondary Metabolite Production in Embryogenic and Non-Embryogenic Callus of Fingerroot Ginger (Boesenbergia rotunda).

    Science.gov (United States)

    Ng, Theresa Lee Mei; Karim, Rezaul; Tan, Yew Seong; Teh, Huey Fang; Danial, Asma Dazni; Ho, Li Sim; Khalid, Norzulaani; Appleton, David Ross; Harikrishna, Jennifer Ann

    2016-01-01

    Interest in the medicinal properties of secondary metabolites of Boesenbergia rotunda (fingerroot ginger) has led to investigations into tissue culture of this plant. In this study, we profiled its primary and secondary metabolites, as well as hormones of embryogenic and non-embryogenic (dry and watery) callus and shoot base, Ultra Performance Liquid Chromatography-Mass Spectrometry together with histological characterization. Metabolite profiling showed relatively higher levels of glutamine, arginine and lysine in embryogenic callus than in dry and watery calli, while shoot base tissue showed an intermediate level of primary metabolites. For the five secondary metabolites analyzed (ie. panduratin, pinocembrin, pinostrobin, cardamonin and alpinetin), shoot base had the highest concentrations, followed by watery, dry and embryogenic calli. Furthermore, intracellular auxin levels were found to decrease from dry to watery calli, followed by shoot base and finally embryogenic calli. Our morphological observations showed the presence of fibrils on the cell surface of embryogenic callus while diphenylboric acid 2-aminoethylester staining indicated the presence of flavonoids in both dry and embryogenic calli. Periodic acid-Schiff staining showed that shoot base and dry and embryogenic calli contained starch reserves while none were found in watery callus. This study identified several primary metabolites that could be used as markers of embryogenic cells in B. rotunda, while secondary metabolite analysis indicated that biosynthesis pathways of these important metabolites may not be active in callus and embryogenic tissue. PMID:27258536

  2. The profiling and identification of the metabolites of (+)-catechin and study on their distribution in rats by HPLC-DAD-ESI-IT-TOF-MS(n) technique.

    Science.gov (United States)

    Liang, Jing; Xu, Feng; Zhang, Ya-Zhou; Zang, Xin-Yu; Wang, Dan; Shang, Ming-Ying; Wang, Xuan; Chui, De-Hua; Cai, Shao-Qing

    2014-03-01

    (+)-Catechin, a potential beneficial compound to human health, is widely distributed in plants and foods. A high-performance liquid chromatography with diode array detector and combined with electrospray ionization ion trap time-of-flight multistage mass spectrometry method was applied to profile and identify the metabolites of (+)-catechin in rats and to study the distribution of these metabolites in rat organs for the first time. In total, 51 phase II metabolites (44 new) and three phase I metabolites were tentatively identified, comprising 16 (+)-catechin conjugates, 14 diarylpropan-2-ol metabolites, 6 phenyl valerolactone metabolites and 18 aromatic acid metabolites. Further, 19 phase II metabolites were new compounds. The in vivo metabolic reactions of (+)-catechin in rats were found to be ring-cleavage, sulfation, glucuronidation, methylation, dehydroxylation and dehydrogenation. The numbers of detected metabolites in urine, plasma, small intestine, kidney, liver, lung, heart, brain and spleen were 53, 23, 27, 9, 7, 5, 3, 2 and 1, respectively. This indicated that small intestine, kidney and liver were the major organs for the distribution of (+)-catechin metabolites. In addition, eight metabolites were found to possess bioactivities according to literature. These results are very helpful for better comprehension of the in vivo metabolism of (+)-catechin and its pharmacological actions, and also can give strong indications on the effective forms of (+)-catechin in vivo. PMID:24105958

  3. Metabolite pattern of Cysticercus cellulosae metacestode from different predilection sites of swine using proton magnetic resonance spectroscopy

    Directory of Open Access Journals (Sweden)

    Chawla S.

    2004-06-01

    Full Text Available Cysticercosis due to Taenia solium is one of the most common public health problems in various regions of the world. We have performed proton magnetic resonance spectroscopy (1H MRS experiments of the fluid aspirated from cysticerci excised from skeletal muscle (n = 16 and brain (n = 9 of infected swine to compare the metabolite pattern of cysticerci in different predilection sites. Perchloric acid extract of cysticercus cysts excised from skeletal muscles (n = 16was also prepared to ascertain water-soluble, low molecular weight metabolites using1H MRS. Absolute quantification and statistical analysis of different metabolites was done to look for any significant differences in different locations of cysts. The metabolite pattern of cysticerci was found to be similar in the various predilection sites. Metabolites observed were leucine, valine, alanine, lysine, glycine, lipid contents, lactate, glutamate, acetate, succinate, creatine, choline, and glucose. Concentration of creatine in cysticercus fluid of cysts removed from the muscle was found to be significantly higher (p = 0.001 than the cysts located in the brain. We conclude that the metabolite pattern in the cysticerci is not influenced by the surrounding tissue location; however concentration of certain metabolites may depend upon the tissue location.

  4. Human brain : biochemical lateralization in normal subjects.

    Directory of Open Access Journals (Sweden)

    Jayasundar R

    2002-07-01

    Full Text Available Chemical asymmetries in normal human brain were studied using the non-invasive technique of volume localized proton magnetic resonance spectroscopy (MRS. The technique of STEAM was used to acquire water-suppressed proton spectra from 8 ml voxels placed in bilaterally symmetrical positions in the two hemispheres of the brain. One hundred and sixty eight right-handed male volunteers were studied for six different regions in the brain (n=28, for each region. Parietal, occipital, temporal, frontal, thalamus and cerebellum regions were studied. The focus was on metabolites such as N-acetyl aspartate (NAA, creatine/phosphocreatine (Cr/PCr and choline (Cho containing compounds. Ratios of the peak areas were calculated for them. Quantitation of the metabolites were carried for data on 18 volunteers. Significant interhemispheric differences in the distribution of metabolites were observed for all the regions studied. There were statistically significant differences on right and left side for the metabolite ratios in all the regions studied. The study has shown the existence of significant lateralization in the distribution of proton MR visible metabolites for all the regions studied.

  5. Cerebral SPECT, a new diagnostic marker in depression

    International Nuclear Information System (INIS)

    Over the past twenty years the functional brain imagenology has improved greatly. Today the diagnostic, prognostic and therapeutic response are possible in psychiatry and neurology. The functional denomination in psychiatry has been known for more than a 100 years and it can be evident in the brain images. The relation between the blood brain flux and the brain can be seen as pictures in the Brain SPECT as hyper and hypo function areas. To carry out SPECT a venous injection of Tc-99m Technetium and (HMPAO) or (ECD) is applied in the arm. The images correspond to a period of two minutes after injection. The exam can be done until six hours after the brain fixation. The study is carried out in conditions, with the patient in repose, relaxed and without medication. The final result is an brain in colors. The yellow color gives us 95% of decrease and white color 95% of increase of the brain function. The red color gives a normal perfusion. The object of the study is to find that the Brain SPECT could be used as a new diagnostic marker of depression. The sample was 73 outpatients with major depression Our diagnostic marker is the prefrontal cortex ventral hypoperfusion (orbit frontal) in almost 100% of the patients and only 32% dorsal hypoperfusion (executive area), unlike most authors (Au)

  6. Epigenome targeting by probiotic metabolites

    Directory of Open Access Journals (Sweden)

    Licciardi Paul V

    2010-12-01

    Full Text Available Abstract Background The intestinal microbiota plays an important role in immune development and homeostasis. A disturbed microbiota during early infancy is associated with an increased risk of developing inflammatory and allergic diseases later in life. The mechanisms underlying these effects are poorly understood but are likely to involve alterations in microbial production of fermentation-derived metabolites, which have potent immune modulating properties and are required for maintenance of healthy mucosal immune responses. Probiotics are beneficial bacteria that have the capacity to alter the composition of bacterial species in the intestine that can in turn influence the production of fermentation-derived metabolites. Principal among these metabolites are the short-chain fatty acids butyrate and acetate that have potent anti-inflammatory activities important in regulating immune function at the intestinal mucosal surface. Therefore strategies aimed at restoring the microbiota profile may be effective in the prevention or treatment of allergic and inflammatory diseases. Presentation of the hypothesis Probiotic bacteria have diverse effects including altering microbiota composition, regulating epithelial cell barrier function and modulating of immune responses. The precise molecular mechanisms mediating these probiotic effects are not well understood. Short-chain fatty acids such as butyrate are a class of histone deacetylase inhibitors important in the epigenetic control of host cell responses. It is hypothesized that the biological function of probiotics may be a result of epigenetic modifications that may explain the wide range of effects observed. Studies delineating the effects of probiotics on short-chain fatty acid production and the epigenetic actions of short-chain fatty acids will assist in understanding the association between microbiota and allergic or autoimmune disorders. Testing the hypothesis We propose that treatment with

  7. Embryonic Stem Cell Markers

    Directory of Open Access Journals (Sweden)

    Lan Ma

    2012-05-01

    Full Text Available Embryonic stem cell (ESC markers are molecules specifically expressed in ES cells. Understanding of the functions of these markers is critical for characterization and elucidation for the mechanism of ESC pluripotent maintenance and self-renewal, therefore helping to accelerate the clinical application of ES cells. Unfortunately, different cell types can share single or sometimes multiple markers; thus the main obstacle in the clinical application of ESC is to purify ES cells from other types of cells, especially tumor cells. Currently, the marker-based flow cytometry (FCM technique and magnetic cell sorting (MACS are the most effective cell isolating methods, and a detailed maker list will help to initially identify, as well as isolate ESCs using these methods. In the current review, we discuss a wide range of cell surface and generic molecular markers that are indicative of the undifferentiated ESCs. Other types of molecules, such as lectins and peptides, which bind to ESC via affinity and specificity, are also summarized. In addition, we review several markers that overlap with tumor stem cells (TSCs, which suggest that uncertainty still exists regarding the benefits of using these markers alone or in various combinations when identifying and isolating cells.

  8. Metabolomic method: UPLC-q-ToF polar and non-polar metabolites in the healthy rat cerebellum using an in-vial dual extraction.

    Directory of Open Access Journals (Sweden)

    Amera A Ebshiana

    Full Text Available Unbiased metabolomic analysis of biological samples is a powerful and increasingly commonly utilised tool, especially for the analysis of bio-fluids to identify candidate biomarkers. To date however only a small number of metabolomic studies have been applied to studying the metabolite composition of tissue samples, this is due, in part to a number of technical challenges including scarcity of material and difficulty in extracting metabolites. The aim of this study was to develop a method for maximising the biological information obtained from small tissue samples by optimising sample preparation, LC-MS analysis and metabolite identification. Here we describe an in-vial dual extraction (IVDE method, with reversed phase and hydrophilic liquid interaction chromatography (HILIC which reproducibly measured over 4,000 metabolite features from as little as 3mg of brain tissue. The aqueous phase was analysed in positive and negative modes following HILIC separation in which 2,838 metabolite features were consistently measured including amino acids, sugars and purine bases. The non-aqueous phase was also analysed in positive and negative modes following reversed phase separation gradients respectively from which 1,183 metabolite features were consistently measured representing metabolites such as phosphatidylcholines, sphingolipids and triacylglycerides. The described metabolomics method includes a database for 200 metabolites, retention time, mass and relative intensity, and presents the basal metabolite composition for brain tissue in the healthy rat cerebellum.

  9. A study of ICAM expression in brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chang Hoon; Lee, Seung Hoon; Hong, Seok Il [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1995-12-01

    The purpose of this study is to test the possibility of using sICAM-1 as a marker for follow-up of treatment. The micro-ELISA method was adopted. The brain stem gliomas showed positive results in 67%. Overall, 23% of brain tumors showed positive results. It is possible that we can use sICAM-1 as a marker for metastatic brain tumors, and measurement after radiation therapy is not reliable. 6 refs. (Author) (Author).

  10. In vivo 1H MR spectroscopic findings in traumatic contusion of ICR mouse brain induced by fluid percussion injury

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study was to investigate the proton metabolic differences of the right parietal cortex with experimental brain contusions of ICR mouse induced by fluid percussion injury (FPI) compared to normal controls and to test the possibility that 1H magnetic resonance spectroscopy (MRS) findings could provide neuropathologic criteria in the diagnosis and monitoring of traumatic brain contusions. Materials and methods: A homogeneous group of 20 ICR male mice was used for MRI and in vivo 1H MRS. Using image-guided, water-suppressed in vivo 1H MRS with a 4.7 T MRI/MRS system, we evaluated the MRS measurement of the relative proton metabolite ratio between experimental brain contusion of ICR mouse and healthy control subjects. Results: After trauma, NAA/Cr ratio, as a neuronal marker decreased significantly versus controls, indicating neuronal loss. The ratio of NAA/Cr in traumatic brain contusions was 0.90 ± 0.11, while that in normal control subjects was 1.13 ± 0.12 (P = 0.001). The Cho/Cr ratio had a tendency to rise in experimental brain contusions (P = 0.02). The Cho/Cr ratio was 0.91 ± 0.17, while that of the normal control subjects was 0.76 ± 0.15. However, no significant difference of Glx/Cr was established between the experimental traumatic brain injury models and the normal controls. Discussion and conclusions: The present 1H MRS study shows significant proton metabolic changes of parietal cortex with experimental brain contusions of ICR mouse induced by FPI compared to normal controls. In vivo 1H MRS may be a useful modality for the clinical evaluation of traumatic contusions and could aid in better understanding the neuropathologic process of traumatic contusions induced by FPI

  11. Antifungal Activity of Microbial Secondary Metabolites

    OpenAIRE

    Jeffrey J Coleman; Ghosh, Suman; Okoli, Ikechukwu; Mylonakis, Eleftherios

    2011-01-01

    Secondary metabolites are well known for their ability to impede other microorganisms. Reanalysis of a screen of natural products using the Caenorhabditis elegans-Candida albicans infection model identified twelve microbial secondary metabolites capable of conferring an increase in survival to infected nematodes. In this screen, the two compound treatments conferring the highest survival rates were members of the epipolythiodioxopiperazine (ETP) family of fungal secondary metabolites, acetylg...

  12. Secondary metabolites in fungus-plant interactions

    OpenAIRE

    Pusztahelyi, Tünde; Holb, Imre J.; Pócsi, István (1961-) (biológus)

    2015-01-01

    Fungi and plants are rich sources of thousands of secondary metabolites. The genetically coded possibilities for secondary metabolite production, the stimuli of the production, and the special phytotoxins basically determine the microscopic fungi-host plant interactions and the pathogenic lifestyle of fungi. The review introduces plant secondary metabolites usually with antifungal effect as well as the importance of signaling molecules in induced systemic resistance and systemic acquired resi...

  13. Probabilistic Approach for Evaluating Metabolite Sample Integrity

    OpenAIRE

    Slaff, Barry M.; Jensen, Shane T.; Weljie, Aalim M.

    2015-01-01

    The success of metabolomics studies depends upon the "fitness" of each biological sample used for analysis: it is critical that metabolite levels reported for a biological sample represent an accurate snapshot of the studied organism's metabolite profile at time of sample collection. Numerous factors may compromise metabolite sample fitness, including chemical and biological factors which intervene during sample collection, handling, storage, and preparation for analysis. We propose a probabi...

  14. Experimental Periodontitis Results in Prediabetes and Metabolic Alterations in Brain, Liver and Heart: Global Untargeted Metabolomic Analyses

    Science.gov (United States)

    Ilievski, Vladimir; Kinchen, Jason M; Prabhu, Ramya; Rim, Fadi; Leoni, Lara; Unterman, Terry G.; Watanabe, Keiko

    2016-01-01

    Results from epidemiological studies suggest that there is an association between periodontitis and prediabetes, however, causality is not known. The results from our previous studies suggest that induction of periodontitis leads to hyperinsulinemia glucose intolerance and insulin resistance, all hallmarks of prediabetes. However, global effects of periodontitis on critical organs in terms of metabolic alterations are unknown. We determined the metabolic effects of periodontitis on brain, liver, heart and plasma resulting from Porphyromonas gingivalis induced periodontitis in mice. Periodontitis was induced by oral application of the periodontal pathogen, Porphyromonas gingivalis for 22 weeks. Global untargeted biochemical profiles in samples from these organs/plasma were determined by liquid and gas chromatography/mass spectrometry and compared between controls and animals with periodontitis. Oral application of Porphyromonas gingivalis induced chronic periodontitis and hallmarks of prediabetes. The results of sample analyses indicated a number of changes in metabolic readouts, including changes in metabolites related to glucose and arginine metabolism, inflammation and redox homeostasis. Changes in biochemicals suggested subtle systemic effects related to periodontal disease, with increases in markers of inflammation and oxidative stress most prominent in the liver. Signs of changes in redox homeostasis were also seen in the brain and heart. Elevated bile acids in liver were suggestive of increased biosynthesis, which may reflect changes in liver function. Interestingly, signs of decreasing glucose availability were seen in the brain. In all three organs and plasma, there was a significant increase in the microbiome-derived bioactive metabolite 4-ethylphenylsulfate sulfate in animals with periodontitis. The results of metabolic profiling suggest that periodontitis/bacterial products alter metabolomic signatures of brain, heart, liver, and plasma in the

  15. Differential metabolite profiles during fruit development in high-yielding oil palm mesocarp.

    Directory of Open Access Journals (Sweden)

    Huey Fang Teh

    Full Text Available To better understand lipid biosynthesis in oil palm mesocarp, in particular the differences in gene regulation leading to and including de novo fatty acid biosynthesis, a multi-platform metabolomics technology was used to profile mesocarp metabolites during six critical stages of fruit development in comparatively high- and low-yielding oil palm populations. Significantly higher amino acid levels preceding lipid biosynthesis and nucleosides during lipid biosynthesis were observed in a higher yielding commercial palm population. Levels of metabolites involved in glycolysis revealed interesting divergence of flux towards glycerol-3-phosphate, while carbon utilization differences in the TCA cycle were proven by an increase in malic acid/citric acid ratio. Apart from insights into the regulation of enhanced lipid production in oil palm, these results provide potentially useful metabolite yield markers and genes of interest for use in breeding programmes.

  16. Differential metabolite profiles during fruit development in high-yielding oil palm mesocarp.

    Science.gov (United States)

    Teh, Huey Fang; Neoh, Bee Keat; Hong, May Ping Li; Low, Jaime Yoke Sum; Ng, Theresa Lee Mei; Ithnin, Nalisha; Thang, Yin Mee; Mohamed, Mohaimi; Chew, Fook Tim; Yusof, Hirzun Mohd; Kulaveerasingam, Harikrishna; Appleton, David R

    2013-01-01

    To better understand lipid biosynthesis in oil palm mesocarp, in particular the differences in gene regulation leading to and including de novo fatty acid biosynthesis, a multi-platform metabolomics technology was used to profile mesocarp metabolites during six critical stages of fruit development in comparatively high- and low-yielding oil palm populations. Significantly higher amino acid levels preceding lipid biosynthesis and nucleosides during lipid biosynthesis were observed in a higher yielding commercial palm population. Levels of metabolites involved in glycolysis revealed interesting divergence of flux towards glycerol-3-phosphate, while carbon utilization differences in the TCA cycle were proven by an increase in malic acid/citric acid ratio. Apart from insights into the regulation of enhanced lipid production in oil palm, these results provide potentially useful metabolite yield markers and genes of interest for use in breeding programmes. PMID:23593468

  17. Temporal variability in urinary phthalate metabolite excretion based on spot, morning, and 24-h urine samples: Considerations for epidemiological studies

    DEFF Research Database (Denmark)

    Frederiksen, Hanne; Kranich, Selma K.; Jørgensen, Niels; Taboureau, Olivier; Petersen, Jørgen H.; Andersson, Anna-Maria

    2013-01-01

    Urinary phthalate excretion is used as marker of phthalate exposure in epidemiological studies. Here we examine the reliability of urinary phthalate levels in exposure classification by comparing the inter- and intrasubject variation of urinary phthalate metabolite levels. Thirty-three young heal...

  18. Occipital Proton Magnetic Resonance Spectroscopy ((1)H-MRS) Reveals Normal Metabolite Concentrations in Retinal Visual Field Defects

    NARCIS (Netherlands)

    Boucard, Christine C.; Hoogduin, Johannes M.; van der Grond, Jeroen; Cornelissen, Frans W.

    2007-01-01

    Background. Progressive visual field defects, such as age-related macular degeneration and glaucoma, prevent normal stimulation of visual cortex. We investigated whether in the case of visual field defects, concentrations of metabolites such as N-acetylaspartate (NAA), a marker for degenerative proc

  19. Brain Basics

    Medline Plus

    Full Text Available ... in Real Life Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video ... early brain development, and may also assist in learning and memory. ... rise to disabilities or diseases. neural circuit —A network of neurons ...

  20. Brain Basics

    Medline Plus

    Full Text Available ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies show that brain growth in children with autism appears to peak early. And as ...

  1. Brain Basics

    Medline Plus

    Full Text Available ... Research Modern research tools and techniques are giving scientists a more detailed understanding of the brain than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies ...

  2. Brain Basics

    Medline Plus

    Full Text Available ... Welcome. Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ... highly developed area at the front of the brain that, in humans, plays a role in executive functions such as ...

  3. Metabolites from Alternaria Fungi and Their Bioactivities

    Directory of Open Access Journals (Sweden)

    Ligang Zhou

    2013-05-01

    Full Text Available Alternaria is a cosmopolitan fungal genus widely distributing in soil and organic matter. It includes saprophytic, endophytic and pathogenic species. At least 268 metabolites from Alternaria fungi have been reported in the past few decades. They mainly include nitrogen-containing metabolites, steroids, terpenoids, pyranones, quinones, and phenolics. This review aims to briefly summarize the structurally different metabolites produced by Alternaria fungi, as well as their occurrences, biological activities and functions. Some considerations related to synthesis, biosynthesis, production and applications of the metabolites from Alternaria fungi are also discussed.

  4. Brain mapping

    Directory of Open Access Journals (Sweden)

    Blaž Koritnik

    2004-08-01

    Full Text Available Cartography of the brain ("brain mapping" aims to represent the complexities of the working brain in an understandable and usable way. There are four crucial steps in brain mapping: (1 acquiring data about brain structure and function, (2 transformation of data into a common reference, (3 visualization and interpretation of results, and (4 databasing and archiving. Electrophysiological and functional imaging methods provide information about function of the human brain. A prerequisite for multisubject, multidimensional and multimodal mapping is transformation of individual images to match a standard brain template. To produce brain maps, color, contours, and other visual cues are used to differentiate metabolic rates, electrical field potentials, receptor densities, and other attributes of structure or function. Databases are used to organize and archive data records. By relating the maps to cognitive functions and psychological models, brain mapping offers a prerequisite for the understanding of organizational principles of the human brain.

  5. 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites

    International Nuclear Information System (INIS)

    This study examines the effects of repeated systemic administration (20 mg/kg s.c., twice daily for 4 days) of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) on levels of brain monoamines, their metabolites and on the density of monoamine uptake sites in various regions of rat brain. Marked reductions (30-60%) in the concentration of 5-hydroxyindoleacetic acid were observed in cerebral cortex, hippocampus, striatum, hypothalamus and midbrain at 2 weeks after a 4-day treatment regimen of MDMA or MDA; less consistent reductions in serotonin (5-HT) content were observed in these brain regions. In addition, both MDMA and MDA caused comparable and substantial reductions (50-75%) in the density of [3H]paroxetine-labeled 5-HT uptake sites in all brain regions examined. In contrast, neither MDMA nor MDA caused any widespread or long-term changes in the content of the catecholaminergic markers (i.e., norepinephrine, dopamine, 3,4 dihydroxyphenylacetic acid and homovanillic acid) or in the number of [3H]mazindol-labeled norepinephrine or dopamine uptake sites in the brain regions examined. These data demonstrate that MDMA and MDA cause long-lasting neurotoxic effects with respect to both the functional and structural integrity of serotonergic neurons in brain. Furthermore, our measurement of reductions in the density of 5-HT uptake sites provides a means for quantification of the neurodegenerative effects of MDMA and MDA on presynaptic 5-HT terminals

  6. 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of (/sup 3/H)paroxetine-labeled serotonin uptake sites

    Energy Technology Data Exchange (ETDEWEB)

    Battaglia, G.; Yeh, S.Y.; O' Hearn, E.; Molliver, M.E.; Kuhar, M.J.; De Souza, E.B.

    1987-09-01

    This study examines the effects of repeated systemic administration (20 mg/kg s.c., twice daily for 4 days) of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) on levels of brain monoamines, their metabolites and on the density of monoamine uptake sites in various regions of rat brain. Marked reductions (30-60%) in the concentration of 5-hydroxyindoleacetic acid were observed in cerebral cortex, hippocampus, striatum, hypothalamus and midbrain at 2 weeks after a 4-day treatment regimen of MDMA or MDA; less consistent reductions in serotonin (5-HT) content were observed in these brain regions. In addition, both MDMA and MDA caused comparable and substantial reductions (50-75%) in the density of (/sup 3/H)paroxetine-labeled 5-HT uptake sites in all brain regions examined. In contrast, neither MDMA nor MDA caused any widespread or long-term changes in the content of the catecholaminergic markers (i.e., norepinephrine, dopamine, 3,4 dihydroxyphenylacetic acid and homovanillic acid) or in the number of (/sup 3/H)mazindol-labeled norepinephrine or dopamine uptake sites in the brain regions examined. These data demonstrate that MDMA and MDA cause long-lasting neurotoxic effects with respect to both the functional and structural integrity of serotonergic neurons in brain. Furthermore, our measurement of reductions in the density of 5-HT uptake sites provides a means for quantification of the neurodegenerative effects of MDMA and MDA on presynaptic 5-HT terminals.

  7. A Preliminary Link between Hydroxylated Metabolites of Polychlorinated Biphenyls and Free Thyroxin in Humans

    OpenAIRE

    Eveline Dirinck; Dirtu, Alin C.; Govindan Malarvannan; Adrian Covaci; Jorens, Philippe G.; Van Gaal, Luc F.

    2016-01-01

    Background: Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (HO-PCBs) interfere with thyroid hormone action both in vitro and in vivo. However, epidemiologic studies on the link between PCB exposure and thyroid function have yielded discordant results, while very few data are available for HO-PCBs. Objectives: Our study aimed at investigating the relationship between clinically available markers of thyroid metabolism and serum levels of both PCBs and HO-PCBs. Subjects and ...

  8. Quantification of glucuronide metabolites in biological matrices by LC-MS/MS

    OpenAIRE

    Trontelj, Jurij

    2015-01-01

    The glucuronide metabolites are important both for toxicology and for pharmacokinetics of many drugs and xenobiotics. Even though glucuronides oftenlack the pharmacological activity, after de-conjugation, the free aglycone can regain that activity and may present an environmental burden. Furthermore, glucuronides may be used as markers of the past substance exposure, like for example the ethyl-glucuronide in body hair for alcohol abuse or the cannabinoid-glucuronides for cannabis abuse. There...

  9. Adding Sarcosine to Antipsychotic Treatment in Patients with Stable Schizophrenia Changes the Concentrations of Neuronal and Glial Metabolites in the Left Dorsolateral Prefrontal Cortex.

    Science.gov (United States)

    Strzelecki, Dominik; Podgórski, Michał; Kałużyńska, Olga; Stefańczyk, Ludomir; Kotlicka-Antczak, Magdalena; Gmitrowicz, Agnieszka; Grzelak, Piotr

    2015-01-01

    The glutamatergic system is a key point in pathogenesis of schizophrenia. Sarcosine (N-methylglycine) is an exogenous amino acid that acts as a glycine transporter inhibitor. It modulates glutamatergic transmission by increasing glycine concentration around NMDA (N-methyl-d-aspartate) receptors. In patients with schizophrenia, the function of the glutamatergic system in the prefrontal cortex is impaired, which may promote negative and cognitive symptoms. Proton nuclear magnetic resonance (¹H-NMR) spectroscopy is a non-invasive imaging method enabling the evaluation of brain metabolite concentration, which can be applied to assess pharmacologically induced changes. The aim of the study was to evaluate the influence of a six-month course of sarcosine therapy on the concentration of metabolites (NAA, N-acetylaspartate; Glx, complex of glutamate, glutamine and γ-aminobutyric acid (GABA); mI, myo-inositol; Cr, creatine; Cho, choline) in the left dorso-lateral prefrontal cortex (DLPFC) in patients with stable schizophrenia. Fifty patients with schizophrenia, treated with constant antipsychotics doses, in stable clinical condition were randomly assigned to administration of sarcosine (25 patients) or placebo (25 patients) for six months. Metabolite concentrations in DLPFC were assessed with 1.5 Tesla ¹H-NMR spectroscopy. Clinical symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS). The first spectroscopy revealed no differences in metabolite concentrations between groups. After six months, NAA/Cho, mI/Cr and mI/Cho ratios in the left DLPFC were significantly higher in the sarcosine than the placebo group. In the sarcosine group, NAA/Cr, NAA/Cho, mI/Cr, mI/Cho ratios also significantly increased compared to baseline values. In the placebo group, only the NAA/Cr ratio increased. The addition of sarcosine to antipsychotic therapy for six months increased markers of neurons viability (NAA) and neurogilal activity (mI) with simultaneous improvement

  10. Altered Arachidonic Acid Cascade Enzymes in Postmortem Brain from Bipolar Disorder Patients

    OpenAIRE

    Kim, Hyung-Wook; Rapoport, Stanley I.; Rao, Jagadeesh S.

    2009-01-01

    Mood stabilizers that are approved for treating bipolar disorder (BD), when given chronically to rats, decrease expression of markers of the brain arachidonic metabolic cascade, and reduce excitotoxicity and neuroinflammation-induced upregulation of these markers. These observations, plus evidence for neuroinflammation and excitotoxicity in BD, suggest that AA cascade markers are upregulated in the BD brain. To test this hypothesis, these markers were measured in postmortem frontal cortex fro...

  11. Malignancy markers in the cerebrospinal fluid.

    Science.gov (United States)

    Koskiniemi, M

    1988-10-01

    The specificity and sensitivity of malignancy marker determinations in cerebrospinal fluid (CSF) are often insufficient. Even at the subclinical stage of the disease the marker should be present. The effect of therapy should be monitored and relapses noted. Thus high standards of methodology are required. There are many substances that may indicate a malignant process in the central nervous system. However, there are many pitfalls in their determination. Malignant cells may occur in CSF via processes involving leptomeningeal structures such as metastases and leukaemia, but primary brain tumours seldom show cells in CSF. Human chorionic gonadotrophin and alpha-fetoprotein determinations assist in the early detection of cerebral germ cell tumours and of relapses, even in the subclinical stage. Desmosterol may aid in the diagnosis of medulloblastomas and malignant gliomas and in monitoring therapy. Putrescine levels are elevated in CSF of patients with medulloblastoma and correlate with the clinical state, and serial analyses may reveal relapses. Fibronectin, when determined in CSF at the time of diagnosis, appears to be of great significance for the prognosis of acute lymphoblastic leukaemia. Ferritin and beta-2-microglobulin may help in some well-defined conditions. Brain-specific proteins and antibodies to them are non-specific markers whereas tumour-specific antigens and growth factors may be more significant. PMID:3058481

  12. Protective Effects of Dihydrocaffeic Acid, a Coffee Component Metabolite, on a Focal Cerebral Ischemia Rat Model

    Directory of Open Access Journals (Sweden)

    Kyungjin Lee

    2015-06-01

    Full Text Available We recently reported the protective effects of chlorogenic acid (CGA in a transient middle cerebral artery occlusion (tMCAo rat model. The current study further investigated the protective effects of the metabolites of CGA and dihydrocaffeic acid (DHCA was selected for further study after screening using the same tMCAo rat model. In the current study, tMCAo rats (2 h of MCAo followed by 22 h of reperfusion were injected with various doses of DHCA at 0 and 2 h after onset of ischemia. We assessed brain damage, functional deficits, brain edema, and blood-brain barrier damage at 24 h after ischemia. For investigating the mechanism, in vitro zymography and western blotting analysis were performed to determine the expression and activation of matrix metalloproteinase (MMP-2 and -9. DHCA (3, 10, and 30 mg/kg, i.p. dose-dependently reduced brain infarct volume, behavioral deficits, brain water content, and Evans Blue (EB leakage. DHCA inhibited expression and activation of MMP-2 and MMP-9. Therefore, DHCA might be one of the important metabolites of CGA and of natural products, including coffee, with protective effects on ischemia-induced neuronal damage and brain edema.

  13. Secondary metabolites from marine Penicillium brevicompactum

    OpenAIRE

    2006-01-01

    In a screening of Basidiomycete cultures isolated from marine invertebrates collected along the Chilean coastline for the production of antibiotics we identified a Penicillium brevicompactum strain as a producer of metabolites inhibiting the growth of bacteria and fungi. Bioactivity guided purification resulted in the isolation of four known metabolites. Their structures were elucidated by spectroscopic methods.

  14. Elevation of brain glucose and polyol-pathway intermediates with accompanying brain-copper deficiency in patients with Alzheimer’s disease: metabolic basis for dementia

    OpenAIRE

    Jingshu Xu; Paul Begley; Stephanie J. Church; Stefano Patassini; Selina McHarg; Nina Kureishy; Hollywood, Katherine A; Waldvogel, Henry J; Hong Liu; Shaoping Zhang; Wanchang Lin; Karl Herholz; Clinton Turner; Synek, Beth J.; Curtis, Maurice A.

    2016-01-01

    Impairment of brain-glucose uptake and brain-copper regulation occurs in Alzheimer’s disease (AD). Here we sought to further elucidate the processes that cause neurodegeneration in AD by measuring levels of metabolites and metals in brain regions that undergo different degrees of damage. We employed mass spectrometry (MS) to measure metabolites and metals in seven post-mortem brain regions of nine AD patients and nine controls, and plasma-glucose and plasma-copper levels in an ante-mortem cas...

  15. An isotope dilution gas chromatography/mass spectrometry method for trace analysis of xylene and its metabolites in tissues following threshold limit value exposures

    Energy Technology Data Exchange (ETDEWEB)

    Pyon, K.H.; Kracko, D.A.; Strunk, M.R. [and others

    1995-12-01

    The existence of a nose-brain barrier that functions to protect the central nervous system (CNS) from inhaled toxicants has been postulated. Just as a blood-brain barrier protects the CNS from systemic toxicants, the nose-brain barrier may have similar characteristic functions. One component of interest is nasal xenobiotic metabolism and its effect on the transport of pollutants into the CNS at environmentally plausible levels of exposure. Previous results have shown that inhaled xylene are dimethyl phenol (DMP) and methyl benzyl alcohol (MBA), and the nonvolatile metabolites are toluic acid (TA) and methyl hippuric acid (MHA). The nonvolatile metabolites of xylene, along with a small quantity of volatiles, representing either parent xylene or volatile metabolites, are transported via the olfactory epithelium to the glomeruli within the olfactory bulbs of the brain. Further work will be done to establish the linearity for each analyte at the actual highest detection limit of the GC/MS.

  16. Brain hypoxia imaging

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ho Chun [Chonnam National University Medical School, Gwangju (Korea, Republic of)

    2007-04-15

    The measurement of pathologically low levels of tissue pO{sub 2} is an important diagnostic goal for determining the prognosis of many clinically important diseases including cardiovascular insufficiency, stroke and cancer. The target tissues nowadays have mostly been tumors or the myocardium, with less attention centered on the brain. Radiolabelled nitroimidazole or derivatives may be useful in identifying the hypoxic cells in cerebrovascular disease or traumatic brain injury, and hypoxic-ischemic encephalopathy. In acute stroke, the target of therapy is the severely hypoxic but salvageable tissue. {sup 18}F-MISO PET and {sup 99m}Tc-EC-metronidazole SPECT in patients with acute ischemic stroke identified hypoxic tissues and ischemic penumbra, and predicted its outcome. A study using {sup 123}I-IAZA in patient with closed head injury detected the hypoxic tissues after head injury. Up till now these radiopharmaceuticals have drawbacks due to its relatively low concentration with hypoxic tissues associated with/without low blood-brain barrier permeability and the necessity to wait a long time to achieve acceptable target to background ratios for imaging in acute ischemic stroke. It is needed to develop new hypoxic marker exhibiting more rapid localization in the hypoxic region in the brain. And then, the hypoxic brain imaging with imidazoles or non-imidazoles may be very useful in detecting the hypoxic tissues, determining therapeutic strategies and developing therapeutic drugs in several neurological disease, especially, in acute ischemic stroke.

  17. Tumour markers in urology

    International Nuclear Information System (INIS)

    The same applies essentially also for the bladder carcinomas: There is no reliable marker for these cancers which would be useful for clinical purposes. TPA has proven to be too non-specific in malignoma-detection and therefore hardly facilitates clinical decision-making in individual cases. The CEA is not sensitive enough to be recommendable for routine application. However, in advanced stages a CEA examination may be useful if applied within the scope of therapeutic efforts made to evaluate efficacy. In cases of carcinomas of the prostate the sour prostate-specific phosphatase (SPP) and, more recently, especially the prostate-specific antigen (PSA) have proven in follow-up and therapy monitoring, whereby the PSA is superior to the SPP. Nevertheless, both these markers should be employed in therapy monitoring because differences in behaviour will be observed when the desired treatment effect is only achieved in one of the two markers producing tumour cell clonuses. Both markers, but especially the PSA, are quite reliably in agreement with the result of the introduced chemo-/hormone therapy, whereby an increase may be a sure indicator of relapse several months previous to clinical symptoms, imaging procedures, so-called routine laboratory results and subjective complaints. However, none of the 2 markers is appropriate for the purposes of screening or early diagnosis of carcinomas of the prostate. (orig.)

  18. A New Paradigm for Known Metabolite Identification in Metabonomics/Metabolomics: Metabolite Identification Efficiency

    Directory of Open Access Journals (Sweden)

    Jeremy R. Everett

    2015-01-01

    Full Text Available A new paradigm is proposed for assessing confidence in the identification of known metabolites in metabonomics studies using NMR spectroscopy approaches. This new paradigm is based upon the analysis of the amount of metabolite identification information retrieved from NMR spectra relative to the molecular size of the metabolite. Several new indices are proposed including: metabolite identification efficiency (MIE and metabolite identification carbon efficiency (MICE, both of which can be easily calculated. These indices, together with some guidelines, can be used to provide a better indication of known metabolite identification confidence in metabonomics studies than existing methods. Since known metabolite identification in untargeted metabonomics studies is one of the key bottlenecks facing the science currently, it is hoped that these concepts based on molecular spectroscopic informatics, will find utility in the field.

  19. Metabolic fingerprints of altered brain growth, osmoregulation and neurotransmission in a Rett syndrome model.

    Directory of Open Access Journals (Sweden)

    Angèle Viola

    Full Text Available BACKGROUND: Rett syndrome (RS is the leading cause of profound mental retardation of genetic origin in girls. Since RS is mostly caused by mutations in the MECP2 gene, transgenic animal models such as the Mecp2-deleted ("Mecp2-null" mouse have been employed to study neurological symptoms and brain function. However, an interdisciplinary approach drawing from chemistry, biology and neuroscience is needed to elucidate the mechanistic links between the genotype and phenotype of this genetic disorder. METHODOLOGY/PRINCIPAL FINDINGS: We performed, for the first time, a metabolomic study of brain extracts from Mecp2-null mice by using high-resolution magnetic resonance spectroscopy. A large number of individual water-soluble metabolites and phospholipids were quantified without prior selection for specific metabolic pathways. Results were interpreted in terms of Mecp2 gene deletion, brain cell function and brain morphology. This approach provided a "metabolic window" to brain characteristics in Mecp2-null mice (n = 4, revealing (i the first metabolic evidence of astrocyte involvement in RS (decreased levels of the astrocyte marker, myo-inositol, vs. wild-type mice; p = 0.034; (ii reduced choline phospholipid turnover in Mecp2-null vs. wild-type mice, implying a diminished potential of cells to grow, paralleled by globally reduced brain size and perturbed osmoregulation; (iii alterations of the platelet activating factor (PAF cycle in Mecp2-null mouse brains, where PAF is a bioactive lipid acting on neuronal growth, glutamate exocytosis and other processes; and (iv changes in glutamine/glutamate ratios (p = 0.034 in Mecp2-null mouse brains potentially indicating altered neurotransmitter recycling. CONCLUSIONS/SIGNIFICANCE: This study establishes, for the first time, detailed metabolic fingerprints of perturbed brain growth, osmoregulation and neurotransmission in a mouse model of Rett syndrome. Combined with morphological and neurological findings

  20. Effects of conditioned running on plasma, liver and brain tryptophan and on brain 5-hydroxytryptamine metabolism of the rat.

    OpenAIRE

    Chaouloff, F; Elghozi, J. L.; Guezennec, Y.; Laude, D.

    1985-01-01

    An investigation was made into the effects of conditioned running (1 h and 2 h at 20 m min-1), which accelerates lipolysis, on the concentrations of tryptophan (Trp) in plasma, liver and brain and on 5-hydroxytrptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in brain. Running caused time-dependent increases in plasma free Trp and brain Trp of the rat, leading to increased brain 5-HT turnover as revealed by higher amounts of its metabolite, 5-HIAA. The ratio of brain Trp to plasm...

  1. Biochemical responses and mitochondrial mediated activation of apoptosis on long-term effect of aspartame in rat brain

    Directory of Open Access Journals (Sweden)

    Iyaswamy Ashok

    2014-01-01

    Full Text Available Aspartame, an artificial sweetener, is very widely used in many foods and beverages. But there are controversies about its metabolite which is marked for its toxicity. Hence it is believed to be unsafe for human use. Previous studies have reported on methanol exposure with involvements of free radicals on excitotoxicity of neuronal apoptosis. Hence, this present study is proposed to investigate whether or not chronic aspartame (FDA approved Daily Acceptable Intake (ADI,40 mg/kg bwt administration could release methanol, and whether or not it can induce changes in brain oxidative stress status and gene and protein expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax and caspase-3 in the rat brain region. To mimic the human methanol metabolism, Methotrexate (MTX-treated Wistar strain male albino rats were used and after the oral administration of aspartame, the effects were studied along with controls and MTX-treated controls. Aspartame exposure resulted with a significant increase in the enzymatic activity in protein carbonyl, lipid peroxidation levels, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase and catalase activity in (aspartame MTX-treated animals and with a significant decrease in reduced glutathione, glutathione reductase and protein thiol, pointing out the generation of free radicals. The gene and protein expression of pro apoptotic marker Bax showed a marked increase whereas the anti-apoptotic marker Bcl-2 decreased markedly indicating the aspartame is harmful at cellular level. It is clear that long term aspartame exposure could alter the brain antioxidant status, and can induce apoptotic changes in brain.

  2. Gut-Microbiota-Metabolite Axis in Early Renal Function Decline.

    Directory of Open Access Journals (Sweden)

    Clara Barrios

    Full Text Available Several circulating metabolites derived from bacterial protein fermentation have been found to be inversely associated with renal function but the timing and disease severity is unclear. The aim of this study is to explore the relationship between indoxyl-sulfate, p-cresyl-sulfate, phenylacetylglutamine and gut-microbial profiles in early renal function decline.Indoxyl-sulfate (Beta(SE = -2.74(0.24; P = 8.8x10-29, p-cresyl-sulfate (-1.99(0.24, P = 4.6x10-16, and phenylacetylglutamine(-2.73 (0.25, P = 1.2x10-25 were inversely associated with eGFR in a large population base cohort (TwinsUK, n = 4439 with minimal renal function decline. In a sub-sample of 855 individuals, we analysed metabolite associations with 16S gut microbiome profiles (909 profiles, QIIME 1.7.0. Three Operational Taxonomic Units (OTUs were significantly associated with indoxyl-sulfate and 52 with phenylacetylglutamine after multiple testing; while one OTU was nominally associated with p-cresyl sulfate. All 56 microbial members belong to the order Clostridiales and are represented by anaerobic Gram-positive families Christensenellaceae, Ruminococcaceae and Lachnospiraceae. Within these, three microbes were also associated with eGFR.Our data suggest that indoxyl-sulfate, p-cresyl-sulfate and phenylacetylglutamine are early markers of renal function decline. Changes in the intestinal flora associated with these metabolites are detectable in early kidney disease. Future efforts should dissect this relationship to improve early diagnostics and therapeutics strategies.

  3. Lichen Secondary Metabolite, Physciosporin, Inhibits Lung Cancer Cell Motility.

    Science.gov (United States)

    Yang, Yi; Park, So-Yeon; Nguyen, Thanh Thi; Yu, Young Hyun; Nguyen, Tru Van; Sun, Eun Gene; Udeni, Jayalal; Jeong, Min-Hye; Pereira, Iris; Moon, Cheol; Ha, Hyung-Ho; Kim, Kyung Keun; Hur, Jae-Seoun; Kim, Hangun

    2015-01-01

    Lichens produce various unique chemicals that can be used for pharmaceutical purposes. To screen for novel lichen secondary metabolites showing inhibitory activity against lung cancer cell motility, we tested acetone extracts of 13 lichen samples collected in Chile. Physciosporin, isolated from Pseudocyphellaria coriacea (Hook f. & Taylor) D.J. Galloway & P. James, was identified as an effective compound and showed significant inhibitory activity in migration and invasion assays against human lung cancer cells. Physciosporin treatment reduced both protein and mRNA levels of N-cadherin with concomitant decreases in the levels of epithelial-mesenchymal transition markers such as snail and twist. Physciosporin also suppressed KITENIN (KAI1 C-terminal interacting tetraspanin)-mediated AP-1 activity in both the absence and presence of epidermal growth factor stimulation. Quantitative real-time PCR analysis showed that the expression of the metastasis suppressor gene, KAI1, was increased while that of the metastasis enhancer gene, KITENIN, was dramatically decreased by physciosporin. Particularly, the activity of 3'-untranslated region of KITENIN was decreased by physciosporin. Moreover, Cdc42 and Rac1 activities were decreased by physciosporin. These results demonstrated that the lichen secondary metabolite, physciosporin, inhibits lung cancer cell motility through novel mechanisms of action. PMID:26371759

  4. Lichen Secondary Metabolite, Physciosporin, Inhibits Lung Cancer Cell Motility.

    Directory of Open Access Journals (Sweden)

    Yi Yang

    Full Text Available Lichens produce various unique chemicals that can be used for pharmaceutical purposes. To screen for novel lichen secondary metabolites showing inhibitory activity against lung cancer cell motility, we tested acetone extracts of 13 lichen samples collected in Chile. Physciosporin, isolated from Pseudocyphellaria coriacea (Hook f. & Taylor D.J. Galloway & P. James, was identified as an effective compound and showed significant inhibitory activity in migration and invasion assays against human lung cancer cells. Physciosporin treatment reduced both protein and mRNA levels of N-cadherin with concomitant decreases in the levels of epithelial-mesenchymal transition markers such as snail and twist. Physciosporin also suppressed KITENIN (KAI1 C-terminal interacting tetraspanin-mediated AP-1 activity in both the absence and presence of epidermal growth factor stimulation. Quantitative real-time PCR analysis showed that the expression of the metastasis suppressor gene, KAI1, was increased while that of the metastasis enhancer gene, KITENIN, was dramatically decreased by physciosporin. Particularly, the activity of 3'-untranslated region of KITENIN was decreased by physciosporin. Moreover, Cdc42 and Rac1 activities were decreased by physciosporin. These results demonstrated that the lichen secondary metabolite, physciosporin, inhibits lung cancer cell motility through novel mechanisms of action.

  5. Metabolite Profiling of Italian Tomato Landraces with Different Fruit Types

    Science.gov (United States)

    Baldina, Svetlana; Picarella, Maurizio E.; Troise, Antonio D.; Pucci, Anna; Ruggieri, Valentino; Ferracane, Rosalia; Barone, Amalia; Fogliano, Vincenzo; Mazzucato, Andrea

    2016-01-01

    Increased interest toward traditional tomato varieties is fueled by the need to rescue desirable organoleptic traits and to improve the quality of fresh and processed tomatoes in the market. In addition, the phenotypic and genetic variation preserved in tomato landraces represents a means to understand the genetic basis of traits related to health and organoleptic aspects and improve them in modern varieties. To establish a framework for this approach, we studied the content of several metabolites in a panel of Italian tomato landraces categorized into three broad fruit type classes (flattened/ribbed, pear/oxheart, round/elongate). Three modern hybrids, corresponding to the three fruit shape typologies, were included as reference. Red ripe fruits were morphologically characterized and biochemically analyzed for their content in glycoalkaloids, phenols, amino acids, and Amadori products. The round/elongate types showed a higher content in glycoalkaloids, whereas flattened types had higher levels of phenolic compounds. Flattened tomatoes were also rich in total amino acids and in particular in glutamic acid. Multivariate analysis of amino acid content clearly separated the three classes of fruit types. Making allowance of the very low number of genotypes, phenotype-marker relationships were analyzed after retrieving single nucleotide polymorphisms (SNPs) among the landraces available in the literature. Sixty-six markers were significantly associated with the studied traits. The positions of several of these SNPs showed correspondence with already described genomic regions and QTLs supporting the reliability of the association. Overall the data indicated that significant changes in quality-related metabolites occur depending on the genetic background in traditional tomato germplasm, frequently according to specific fruit shape categories. Such a variability is suitable to harness association mapping for metabolic quality traits using this germplasm as an experimental

  6. Metabolite Profiling of Italian Tomato Landraces with Different Fruit Types

    Directory of Open Access Journals (Sweden)

    Svetlana eBaldina

    2016-05-01

    Full Text Available Increased interest towards traditional tomato varieties is fueled by the need to rescue desirable organoleptic traits and to improve the quality of fresh and processed tomatoes in the market. In addition, the phenotypic and genetic variation preserved in tomato landraces represents a means to understand the genetic basis of traits related to health and organoleptic aspects and improve them in modern varieties. To establish a framework for this approach, we studied the content of several metabolites in a panel of Italian tomato landraces categorized into three broad fruit type classes (flattened/ribbed, pear/oxheart, round/elongate. Three modern hybrids, corresponding to the three fruit shape typologies, were included as reference. Red ripe fruits were morphologically characterized and biochemically analyzed for their content in glycoalkaloids, phenols, amino acids and Amadori products. The round/elongate types showed a higher content in glycoalkaloids, whereas flattened types had higher levels of phenolic compounds. Flattened tomatoes were also rich in total amino acids and in particular in glutamic acid. Multivariate analysis of amino acid content clearly separated the three classes of fruit types. Making allowance of the very low number of genotypes, phenotype-marker relationships were analyzed after retrieving single nucleotide polymorphisms (SNPs among the landraces available in the literature. Sixty-six markers were significantly associated with the studied traits. The positions of several of these SNPs showed correspondence with already described genomic regions and QTLs supporting the reliability of the association. Overall the data indicated that significant changes in quality-related metabolites occur depending on the genetic background in traditional tomato germplasm, frequently according to specific fruit shape categories. Such a variability is suitable to harness association mapping for metabolic quality traits using this germplasm

  7. Tissue distribution of berberine and its metabolites after oral administration in rats.

    Science.gov (United States)

    Tan, Xiang-Shan; Ma, Jing-Yi; Feng, Ru; Ma, Chao; Chen, Wen-Jing; Sun, Yu-Peng; Fu, Jie; Huang, Min; He, Chi-Yu; Shou, Jia-Wen; He, Wen-Yi; Wang, Yan; Jiang, Jian-Dong

    2013-01-01

    Berberine (BBR) has been confirmed to have multiple bioactivities in clinic, such as cholesterol-lowering, anti-diabetes, cardiovascular protection and anti- inflammation. However, BBR's plasma level is very low; it cannot explain its pharmacological effects in patients. We consider that the in vivo distribution of BBR as well as of its bioactive metabolites might provide part of the explanation for this question. In this study, liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MS(n)-IT-TOF) as well as liquid chromatography that coupled with tandem mass spectrometry (LC-MS/MS) was used for the study of tissue distribution and pharmacokinetics of BBR in rats after oral administration (200 mg/kg). The results indicated that BBR was quickly distributed in the liver, kidneys, muscle, lungs, brain, heart, pancreas and fat in a descending order of its amount. The pharmacokinetic profile indicated that BBR's level in most of studied tissues was higher (or much higher) than that in plasma 4 h after administration. BBR remained relatively stable in the tissues like liver, heart, brain, muscle, pancreas etc. Organ distribution of BBR's metabolites was also investigated paralleled with that of BBR. Thalifendine (M1), berberrubine (M2) and jatrorrhizine (M4), which the metabolites with moderate bioactivity, were easily detected in organs like the liver and kidney. For instance, M1, M2 and M4 were the major metabolites in the liver, among which the percentage of M2 was up to 65.1%; the level of AUC (0-t) (area under the concentration-time curve) for BBR or the metabolites in the liver was 10-fold or 30-fold higher than that in plasma, respectively. In summary, the organ concentration of BBR (as well as its bioactive metabolites) was higher than its concentration in the blood after oral administration. It might explain BBR's pharmacological effects on human diseases in clinic. PMID:24205048

  8. Tissue distribution of berberine and its metabolites after oral administration in rats.

    Directory of Open Access Journals (Sweden)

    Xiang-Shan Tan

    Full Text Available Berberine (BBR has been confirmed to have multiple bioactivities in clinic, such as cholesterol-lowering, anti-diabetes, cardiovascular protection and anti- inflammation. However, BBR's plasma level is very low; it cannot explain its pharmacological effects in patients. We consider that the in vivo distribution of BBR as well as of its bioactive metabolites might provide part of the explanation for this question. In this study, liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MS(n-IT-TOF as well as liquid chromatography that coupled with tandem mass spectrometry (LC-MS/MS was used for the study of tissue distribution and pharmacokinetics of BBR in rats after oral administration (200 mg/kg. The results indicated that BBR was quickly distributed in the liver, kidneys, muscle, lungs, brain, heart, pancreas and fat in a descending order of its amount. The pharmacokinetic profile indicated that BBR's level in most of studied tissues was higher (or much higher than that in plasma 4 h after administration. BBR remained relatively stable in the tissues like liver, heart, brain, muscle, pancreas etc. Organ distribution of BBR's metabolites was also investigated paralleled with that of BBR. Thalifendine (M1, berberrubine (M2 and jatrorrhizine (M4, which the metabolites with moderate bioactivity, were easily detected in organs like the liver and kidney. For instance, M1, M2 and M4 were the major metabolites in the liver, among which the percentage of M2 was up to 65.1%; the level of AUC (0-t (area under the concentration-time curve for BBR or the metabolites in the liver was 10-fold or 30-fold higher than that in plasma, respectively. In summary, the organ concentration of BBR (as well as its bioactive metabolites was higher than its concentration in the blood after oral administration. It might explain BBR's pharmacological effects on human diseases in clinic.

  9. Brain Basics

    Medline Plus

    Full Text Available ... the anatomy, physiology, and chemistry of the nervous system. When the brain cannot effectively coordinate the billions ... basic working unit of the brain and nervous system. These cells are highly specialized for the function ...

  10. Brain Basics

    Medline Plus

    Full Text Available ... the brain cannot effectively coordinate the billions of cells in the body, the results can affect many ... unit of the brain and nervous system. These cells are highly specialized for the function of conducting ...

  11. Brain Basics

    Medline Plus

    Full Text Available ... Neurons & Neural Circuits Neurons are the basic working unit of the brain and nervous system. These cells ... A nerve cell that is the basic, working unit of the brain and nervous system, which processes ...

  12. Brain Basics

    Medline Plus

    Full Text Available ... Trials — Participants Statistics Help for Mental Illnesses Outreach Research Priorities Funding Labs at NIMH News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The ...

  13. Brain Basics

    Medline Plus

    Full Text Available ... brain may play a role in disorders like schizophrenia or attention deficit hyperactivity disorder (ADHD) . Glutamate —the ... mental disorders, including autism , obsessive compulsive disorder (OCD) , schizophrenia , and depression . Brain Regions Just as many neurons ...

  14. Brain Basics

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    Full Text Available ... medical professionals who can diagnose mental disorders are psychologists or clinical social workers. The psychiatrist asked Sarah ... important research tool in understanding how the brain functions. Another type of brain scan called magnetoencephalography, or ...

  15. Brain Basics

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    Full Text Available ... normal brain development and function can go awry, leading to mental illnesses. Brain Basics will introduce you ... of DNA. Sometimes this copying process is imperfect, leading to a gene mutation that causes the gene ...

  16. Brain Basics

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    Full Text Available ... and epigenetic changes can be passed on to future generations. Further understanding of genes and epigenetics may ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses ...

  17. Brain Basics

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  18. Brain Basics

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  19. Brain Basics

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    Full Text Available ... problems using dopamine in the thinking and feeling regions of the brain may play a role in ... obsessive compulsive disorder (OCD) , schizophrenia , and depression . Brain Regions Just as many neurons working together form a ...

  20. Brain Basics

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    Full Text Available ... medications could reduce the amount of trial and error and frustration that many people with depression experience ... early brain development, and may also assist in learning and memory. hippocampus —A portion of the brain ...

  1. Brain Basics

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    Full Text Available ... Brain Basics will introduce you to some of this science, such as: How the brain develops How ... cell, and responds to signals from the environment; this all helps the cell maintain its balance with ...

  2. Brain Basics

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    Full Text Available ... Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle- ... However, recent research points to a possible new class of antidepressants that can relieve symptoms of the ...

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    Full Text Available ... body, the results can affect many aspects of life. Scientists are continually learning more about how the brain grows and works in healthy people, and how normal brain development ...

  6. Brain Diseases

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    The brain is the control center of the body. It controls thoughts, memory, speech, and movement. It regulates the function of many organs. When the brain is healthy, it works quickly and automatically. However, ...

  7. Brain Basics

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    Full Text Available ... working unit of the brain and nervous system. These cells are highly specialized for the function of ... nerve cells (via axons) to form brain circuits. These circuits control specific body functions such as sleep ...

  8. Brain Basics

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    Full Text Available ... mainly involved in controlling movement and aiding the flow of information to the front of the brain, ... the neuron will fire. This enhances the electrical flow among brain cells required for normal function and ...

  9. Brain Basics

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    Full Text Available ... speech. The brain continues maturing well into a person's early 20s. Knowing how the brain is wired ... in Parkinson's disease, a disorder that affects a person's ability to move as they want to, resulting ...

  10. Brain Basics

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    Full Text Available ... of brain scan called magnetoencephalography, or MEG, can capture split-second changes in the brain. Using MEG, ... The study of how environmental factors like diet, stress and post-natal care can change gene expression ( ...

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    Full Text Available ... neurons, the most highly specialized cells of all, conduct messages. Every cell in our bodies contains a ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as ...

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    Full Text Available ... how the brain works, how mental illnesses are disorders of the brain, and ongoing research that helps us better understand and treat disorders. Mental disorders are common. You may have a ...

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    Full Text Available ... affect many aspects of life. Scientists are continually learning more about how the brain grows and works ... early brain development. It may also assist in learning and memory. Problems in making or using glutamate ...

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    Full Text Available ... may help improve treatments for anxiety disorders like phobias or post-traumatic stress disorder (PTSD) . Prefrontal cortex ( ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as ...

  20. Brain Basics

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    Full Text Available ... Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a ... blues" from time to time. In contrast, major depression is a serious disorder that lasts for weeks. ...

  1. Quantitative evaluation of the changes of brain metabolits in rats with focal cerebral ischemia by using 1H magnetic resonance spectrum%1H磁共振波谱对局灶性脑缺血大鼠脑内代谢物变化的定量评估

    Institute of Scientific and Technical Information of China (English)

    周仁兰; 谢鹏; 罗天友; 吕发金; 牟君; 王运良

    2005-01-01

    BACKGROUND: Brain metabolic abnormality can be observed after cerebral ischemia.OBJECTIVE: To observe the changes of biochemical metabolism of rats with focal cerebral ischemia with 1H magnetic resonance spectroscopy (MRS) in order to reflect the metabolite abnormalities of rats during cerebral ischemic recovery phase.DESIGN: Randomized controlled study.SETTING: Departments of Neurology and department of Radiology of First Affiliated Hospital of Chongqing Medical University.MATERIALS: The experiment was conducted at the Radiological Department of First Affiliated Hospital of Chongqing Medical University from April to July 2004. Totally 24 adult Wistar rats with clean grade were randomly divided into three groups, namely: control group, sham operation group and cerebral ischemia group, with 8 rats in each group.METHODS: The focal cerebral ischemic model was established by occluding the right internal carotid artery in cerebral ischemia group and the filament were just inserted into the internal carotid artery not into the middle cerebral artery in sham operation group, nothing was done except for anesthetizing in the control group. 1H MRS was performed within the area of cerebral infarction and the homologous area of the contralateral hemisphere using 1.5T GE signa Highspeed MRI spectrometer in cerebral ischemic and shamed operation group at the following time point of 30 minutes, 1, 3, 6, 12, 24 hours, 3, 7, 15 days, 1 and 2 months after cerebral ischemia, and in the control group at the same time point.MAIN OUTCOME MEASURES: Changes of lactate, N-acetyl-aspartate (NAA), choline and creatine in infarct hemisphere and contralateral hemisphere.RESULTS: Totally 24 rats were selected in the study, but two died of anesthesia in sham operation group and four of serious brain edema in cerebral ischemia group, only 18 rats entered the final analysis with 8 in normal control group, 6 in sham operation group and 4 in cerebral isThe marked increase in NAA, choline and

  2. Memory Impairment in Korsakoff's Psychosis: A Correlation with Brain Noradrenergic Activity.

    Science.gov (United States)

    McEntee, William J.; Mair, Robert G.

    1978-01-01

    The concentration of the primary brain metabolite of norepinephrine is diminished in the lumbar spinal fluid of patients with Korsakoff's syndrome. The extent of its reduction is correlated with measures of memory impairment. (BB)

  3. Brain Basics

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    Full Text Available ... pituitary-adrenal (HPA) axis. Brain Basics in Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah ... having trouble coping with the stresses in her life. She began to think of suicide because she ...

  4. Brain Basics

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    Full Text Available ... Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle-aged woman ... new memories. hypothalmic-pituitary-adrenal (HPA) axis —A brain-body ... stress. impulse —An electrical communication signal sent between neurons ...

  5. Brain Aneurysm

    Science.gov (United States)

    A brain aneurysm is an abnormal bulge or "ballooning" in the wall of an artery in the brain. They are sometimes called berry aneurysms because they ... often the size of a small berry. Most brain aneurysms produce no symptoms until they become large, ...

  6. Brain Basics

    Medline Plus

    Full Text Available ... other cells guide neurons in forming various brain structures. Neighboring neurons make connections with each other and with distant nerve cells (via axons) to form brain circuits. These circuits control specific body functions such as sleep and speech. The brain continues ...

  7. Synthesis and features of the pharmacokinetics of the 14C metabolite of peptidobenzophenones and some preparations of the benzodiazepine series

    International Nuclear Information System (INIS)

    The authors study the derivatives of peptidobenzophenones (I) which are converted to the corresponding 1,4-benzodiazepine (II) in the animal organism. The authors accomplished the synthesis of 7-bromo-5-phenyl-1,2-dihydro-3H-1,4-benzodizepam-2-one-(2-14C) (II) and its potential metabolites to determine the contribution of (II) to the pharmacological activity of (I) and to study the secondary metabolites. Data on the kinetics of the content of the initial compound and its metabolites in the mouse brain are presented. Optimal conditions for the kinetics of extraction of the investigated biological samples and the quantitative determination of (II) and its metabolites were studied. Glycine-(I-14C) of specific radioactivity 1 Ci/mole was taken as the initial compound for the synthesis of (II)

  8. Prepuberal stimulation of 5-HT7-R by LP-211 in a rat model of hyper-activity and attention-deficit: permanent effects on attention, brain amino acids and synaptic markers in the fronto-striatal interface.

    Directory of Open Access Journals (Sweden)

    Lucia A Ruocco

    Full Text Available The cross-talk at the prefronto-striatal interface involves excitatory amino acids, different receptors, transducers and modulators. We investigated long-term effects of a prepuberal, subchronic 5-HT7-R agonist (LP-211 on adult behaviour, amino acids and synaptic markers in a model for Attention-Deficit/Hyperactivity Disorder (ADHD. Naples High Excitability rats (NHE and their Random Bred controls (NRB were daily treated with LP-211 in the 5th and 6th postnatal week. One month after treatment, these rats were tested for indices of activity, non selective (NSA, selective spatial attention (SSA and emotionality. The quantity of L-Glutamate (L-Glu, L-Aspartate (L-Asp and L-Leucine (L-Leu, dopamine transporter (DAT, NMDAR1 subunit and CAMKIIα, were assessed in prefrontal cortex (PFC, dorsal (DS and ventral striatum (VS, for their role in synaptic transmission, neural plasticity and information processing. Prepuberal LP-211 (at lower dose reduced horizontal activity and (at higher dose increased SSA, only for NHE but not in NRB rats. Prepuberal LP-211 increased, in NHE rats, L-Glu in the PFC and L-Asp in the VS (at 0.250 mg/kg dose, whereas (at 0.125 mg/kg dose it decreased L-Glu and L-Asp in the DS. The L-Glu was decreased, at 0.125 mg/kg, only in the VS of NRB rats. The DAT levels were decreased with the 0.125 mg/kg dose (in the PFC, and increased with the 0.250 mg/kg dose (in the VS, significantly for NHE rats. The basal NMDAR1 level was higher in the PFC of NHE than NRB rats; LP-211 treatment (at 0.125 mg/kg dose decreased NMDAR1 in the VS of NRB rats. This study represents a starting point about the impact of developmental 5-HT7-R activation on neuro-physiology of attentive processes, executive functions and their neural substrates.

  9. Application of mass spectrometry for metabolite identification.

    Science.gov (United States)

    Ma, Shuguang; Chowdhury, Swapan K; Alton, Kevin B

    2006-06-01

    Metabolism studies play a pivotal role in drug discovery and development. Characterization of metabolic "hot-spots" as well as reactive and pharmacologically active metabolites is critical to designing new drug candidates with improved metabolic stability, toxicological profile and efficacy. Metabolite identification in the preclinical species used for safety evaluation is required in order to determine whether human metabolites have been adequately tested during non-clinical safety assessment. From an instrumental standpoint, high performance liquid chromatography (HPLC) coupled with mass spectrometry (MS) dominates all analytical tools used for metabolite identification. The general strategies employed for metabolite identification in both drug discovery and drug development settings together with sample preparation techniques are reviewed herein. These include a discussion of the various ionization methods, mass analyzers, and tandem mass spectrometry (MS/MS) techniques that are used for structural characterization in a modern drug metabolism laboratory. Mass spectrometry-based techniques, such as stable isotope labeling, on-line H/D exchange, accurate mass measurement to enhance metabolite identification and recent improvements in data acquisition and processing for accelerating metabolite identification are also described. Rounding out this review, we offer additional thoughts about the potential of alternative and less frequently used techniques such as LC-NMR/MS, CRIMS and ICPMS. PMID:16787159

  10. Left Brain. Right Brain. Whole Brain

    Science.gov (United States)

    Farmer, Lesley S. J.

    2004-01-01

    As the United States student population is becoming more diverse, library media specialists need to find ways to address these distinctive needs. However, some of these differences transcend culture, touching on variations in the brain itself. Most people have a dominant side of the brain, which can affect their personality and learning style.…

  11. Magik Markers Trehvis

    Index Scriptorium Estoniae

    2008-01-01

    Müra-rock'i viljelevast USA duost Magik Markers (ansambel osaleb režissöör Veiko Õunapuu uue mängufilmi "Püha Tõnu kiusamine" võtetel, kontsert 15. nov. Tartus klubis Trehv, vt. www.magikmarkers.audiosport.org.)

  12. Accuracy of MR markers for differentiating Progressive Supranuclear Palsy from Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Stefano Zanigni

    2016-01-01

    Conclusion: Although several quantitative brain MR markers provided high diagnostic accuracy in differentiating Progressive Supranuclear Palsy-Richardson's Syndrome from Parkinson's disease, the morphometric assessment of midbrain area is the best single diagnostic marker and should be routinely included in the neuroradiological work-up of parkinsonian patients.

  13. Tissue distribution of naringenin conjugated metabolites following repeated dosing of naringin to rats

    OpenAIRE

    Lin, Shiuan-Pey; Hou, Yu-Chi; Tsai, Shang-Yuan; Wang, Meng-Ju; Chao, Pei-Dawn Lee

    2014-01-01

    Background: Naringin is a major antioxidant in Citrus fruits and herbs. To clarify molecular forms distributed to various tissues, we investigated tissue distribution of naringin and relevant metabolites in rats after repeated dosing. Methods: Male Sprague-Dawley rats were orally administered naringin (210 mg/kg) twice daily for eight days. At 6 h post the 17th dose, various tissues including liver, kidney, heart, spleen and brain were collected and analyzed by HPLC method before and after hy...

  14. A wood preservative metabolite in river water.

    Science.gov (United States)

    Khoroshko, Larisa O; Petrova, Varvara N; Viktorovskii, Igor V; Lahtiperä, Mirja; Sinkkonen, Seija; Paasivirta, Jaakko

    2005-01-01

    A previously unknown pollutant in river water was identified to be 2-mercaptobenzothiazole (2-MBT) by interpretation and simulation of its GC/LRMS spectrum. Further GC/HRMS measurement of the isotope composition of the molecular ion verified this structure. 2-MBT is a well-known agent for corrosion inhibition and a stable metabolite of several other benzothiazoles. The present 2-MBT trace was most probably a metabolite of the wood preservative TCMTB which leaked from an upstream sawmill. The metabolite had been detected earlier in urine of the sawmill workers, but now was identified in the recipient water environment for the first time. PMID:15768735

  15. Tumor Microenvironment in the Brain

    International Nuclear Information System (INIS)

    In addition to malignant cancer cells, tumors contain a variety of different stromal cells that constitute the tumor microenvironment. Some of these cell types provide crucial support for tumor growth, while others have been suggested to actually inhibit tumor progression. The composition of tumor microenvironment varies depending on the tumor site. The brain in particular consists of numerous specialized cell types such as microglia, astrocytes, and brain endothelial cells. In addition to these brain-resident cells, primary and metastatic brain tumors have also been shown to be infiltrated by different populations of bone marrow-derived cells. The role of different cell types that constitute tumor microenvironment in the progression of brain malignancies is only poorly understood. Tumor microenvironment has been shown to be a promising therapeutic target and diagnostic marker in extracranial malignancies. A better understanding of tumor microenvironment in the brain would therefore be expected to contribute to the development of improved therapies for brain tumors that are urgently required due to a poor availability of treatments for these malignancies. This review summarizes some of the known interactions between brain tumors and different stromal cells, and also discusses potential therapeutic approaches within this context

  16. Tumor Microenvironment in the Brain

    Energy Technology Data Exchange (ETDEWEB)

    Lorger, Mihaela [Leeds Institute of Molecular Medicine, University of Leeds, St. James’s University Hospital, Beckett Street, Leeds, LS9 7TF (United Kingdom)

    2012-02-22

    In addition to malignant cancer cells, tumors contain a variety of different stromal cells that constitute the tumor microenvironment. Some of these cell types provide crucial support for tumor growth, while others have been suggested to actually inhibit tumor progression. The composition of tumor microenvironment varies depending on the tumor site. The brain in particular consists of numerous specialized cell types such as microglia, astrocytes, and brain endothelial cells. In addition to these brain-resident cells, primary and metastatic brain tumors have also been shown to be infiltrated by different populations of bone marrow-derived cells. The role of different cell types that constitute tumor microenvironment in the progression of brain malignancies is only poorly understood. Tumor microenvironment has been shown to be a promising therapeutic target and diagnostic marker in extracranial malignancies. A better understanding of tumor microenvironment in the brain would therefore be expected to contribute to the development of improved therapies for brain tumors that are urgently required due to a poor availability of treatments for these malignancies. This review summarizes some of the known interactions between brain tumors and different stromal cells, and also discusses potential therapeutic approaches within this context.

  17. Secondary Metabolites from Rubiaceae Species

    Directory of Open Access Journals (Sweden)

    Daiane Martins

    2015-07-01

    Full Text Available This study describes some characteristics of the Rubiaceae family pertaining to the occurrence and distribution of secondary metabolites in the main genera of this family. It reports the review of phytochemical studies addressing all species of Rubiaceae, published between 1990 and 2014. Iridoids, anthraquinones, triterpenes, indole alkaloids as well as other varying alkaloid subclasses, have shown to be the most common. These compounds have been mostly isolated from the genera Uncaria, Psychotria, Hedyotis, Ophiorrhiza and Morinda. The occurrence and distribution of iridoids, alkaloids and anthraquinones point out their chemotaxonomic correlation among tribes and subfamilies. From an evolutionary point of view, Rubioideae is the most ancient subfamily, followed by Ixoroideae and finally Cinchonoideae. The chemical biosynthetic pathway, which is not so specific in Rubioideae, can explain this and large amounts of both iridoids and indole alkaloids are produced. In Ixoroideae, the most active biosysthetic pathway is the one that produces iridoids; while in Cinchonoideae, it produces indole alkaloids together with other alkaloids. The chemical biosynthetic pathway now supports this botanical conclusion.

  18. Secondary metabolites from Rubiaceae species.

    Science.gov (United States)

    Martins, Daiane; Nunez, Cecilia Veronica

    2015-01-01

    This study describes some characteristics of the Rubiaceae family pertaining to the occurrence and distribution of secondary metabolites in the main genera of this family. It reports the review of phytochemical studies addressing all species of Rubiaceae, published between 1990 and 2014. Iridoids, anthraquinones, triterpenes, indole alkaloids as well as other varying alkaloid subclasses, have shown to be the most common. These compounds have been mostly isolated from the genera Uncaria, Psychotria, Hedyotis, Ophiorrhiza and Morinda. The occurrence and distribution of iridoids, alkaloids and anthraquinones point out their chemotaxonomic correlation among tribes and subfamilies. From an evolutionary point of view, Rubioideae is the most ancient subfamily, followed by Ixoroideae and finally Cinchonoideae. The chemical biosynthetic pathway, which is not so specific in Rubioideae, can explain this and large amounts of both iridoids and indole alkaloids are produced. In Ixoroideae, the most active biosysthetic pathway is the one that produces iridoids; while in Cinchonoideae, it produces indole alkaloids together with other alkaloids. The chemical biosynthetic pathway now supports this botanical conclusion. PMID:26205062

  19. Positive association between concentration of phthalate metabolites in urine and microparticles in adolescents and young adults.

    Science.gov (United States)

    Lin, Chien-Yu; Hsieh, Chia-Jung; Lo, Shyh-Chyi; Chen, Pau-Chung; Torng, Pao-Ling; Hu, Anren; Sung, Fung-Chang; Su, Ta-Chen

    2016-01-01

    Di-(2-ethylhexyl) phthalate (DEHP) has been used worldwide in various products for many years. In vitro studies have shown that exposure to DEHP and its metabolite mono(2-ethylhexyl) phthalate (MEHP) induces endothelial cell apoptosis. Moreover, exposure to DEHP had been linked to cardiovascular risk factors and cardiovascular diseases in epidemiological studies. Circulating microparticles have been known to be indicators of vascular injury. However, whether DEHP or its metabolites are independently associated with microparticles in humans remains unknown. From 2006 to 2008, we recruited 793 subjects (12-30years) from a population-based sample to participate in this cardiovascular disease prevention examination. Each participant was subjected to interviews and biological sample collection to determine the relationship between concentrations of DEHP metabolites MEHP, mono(ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethly-5-oxoheyl) phthalate in urine and concentrations of endothelial microparticles (CD62E and CD31+/CD42a-), platelet microparticles (CD62P and CD31+/CD42a+), and CD14 in serum. Multiple linear regression analysis revealed that an ln-unit increase in MEHP concentration in urine was positively associated with an increase in serum microparticle counts/μL of 0.132 (±0.016) in CD31+/CD42a- (endothelial apoptosis marker), 0.117 (±0.023) in CD31+/CD42a+ (platelet apoptosis marker), and 0.026 (±0.007) in CD14 (monocyte, macrophage, and neutrophil activation marker). There was no association between DEHP metabolite concentration and CD62E or CD62P. In conclusion, a higher MEHP concentration in urine was associated with an increase in endothelial and platelet microparticles in this cohort of adolescents and young adults. Further studies are warranted to clarify the causal relationship between exposure to DEHP and atherosclerosis. PMID:27104673

  20. Development of Marker-Free Transgenic Potato Tubers Enriched in Caffeoylquinic Acids and Flavonols.

    Science.gov (United States)

    Li, Yang; Tang, Wenzhao; Chen, Jing; Jia, Ru; Ma, Lianjie; Wang, Shaoli; Wang, Jiao; Shen, Xiangling; Chu, Zhaohui; Zhu, Changxiang; Ding, Xinhua

    2016-04-13

    Potato (Solanum tuberosum L.) is a major crop worldwide that meets human economic and nutritional requirements. Potato has several advantages over other crops: easy to cultivate and store, cheap to consume, and rich in a variety of secondary metabolites. In this study, we generated three marker-free transgenic potato lines that expressed the Arabidopsis thaliana flavonol-specific transcriptional activator AtMYB12 driven by the tuber-specific promoter Patatin. Marker-free potato tubers displayed increased amounts of caffeoylquinic acids (CQAs) (3.35-fold increases on average) and flavonols (4.50-fold increase on average). Concentrations of these metabolites were associated with the enhanced expression of genes in the CQA and flavonol biosynthesis pathways. Accumulation of CQAs and flavonols resulted in 2-fold higher antioxidant capacity compared to wild-type potatoes. Tubers from these marker-free transgenic potatoes have therefore improved antioxidant properties. PMID:27019017

  1. Metabolite profiles of common Stemphylium species

    DEFF Research Database (Denmark)

    Andersen, Birgitte; Solfrizzo, Michelle; Visconti, Angelo

    1995-01-01

    identified by their chromatographic and spectroscopic data (Rf values, reflectance spectrum, retention index and ultraviolet spectrum). These metabolites have been used for the chemotaxonomical characterization of Stemphylium botryosum, S. herbarum, S. alfalfae, S. majusculum, S. sarciniforme, S. vesicarium...

  2. Secondary metabolites of slime molds (myxomycetes)

    Czech Academy of Sciences Publication Activity Database

    Dembitsky, V. M.; Řezanka, Tomáš; Spížek, Jaroslav; Hanuš, L. O.

    2005-01-01

    Roč. 66, - (2005), s. 747-769. ISSN 0031-9422 Institutional research plan: CEZ:AV0Z50200510 Keywords : slime molds * myxomycetes * metabolites Subject RIV: EE - Microbiology, Virology Impact factor: 2.780, year: 2005

  3. Metabolism and metabolites of polychlorinated biphenyls (PCBs)

    OpenAIRE

    Grimm, FA; Hu, D.; Kania-Korwel, I.; Lehmler, HJ; Ludewig, G; Hornbuckle, KC; Duffel, MW; Bergman, A; Robertson, LW

    2015-01-01

    The metabolism of polychlorinated biphenyls (PCBs) is complex and has an impact on toxicity and thereby assessment of PCB risks. A large number of reactive and stable metabolites are formed in the processes of biotransformation in biota in general and in humans in particular. The aim of this document is to provide an overview of PCB metabolism and to identify metabolites of concern and their occurrence. Emphasis is given to mammalian metabolism of PCBs and their hydroxyl, methylsulfonyl, and ...

  4. Biologically active secondary metabolites from marine cyanobacteria

    OpenAIRE

    Nunnery, Joshawna K.; Mevers, Emily; Gerwick, William H

    2010-01-01

    Marine cyanobacteria are a rich source of complex bioactive secondary metabolites which derive from mixed biosynthetic pathways. Recently, several marine cyanobacterial natural products have garnered much attention due to their intriguing structures and exciting anti-proliferative or cancer cell toxic activities. Several other recently discovered secondary metabolites exhibit insightful neurotoxic activities whereas others are showing pronounced anti-inflammatory activity. A number of anti-in...

  5. Low-molecular-weight metabolite systems chemistry

    OpenAIRE

    Hadacek, Franz; Bachmann, Gert

    2015-01-01

    Low-molecular-weight metabolites (LMWMs) comprise primary or central and a plethora of intermediary or secondary metabolites, all of which are characterized by a molecular weight below 900 Dalton. The latter are especially prominent in sessile higher organisms, such as plants, corals, sponges and fungi, but are produced by all types of microbial organisms too. Common to all of these carbon molecules are oxygen, nitrogen and, to a lesser extent, sulfur, as heteroatoms. The latter can contribut...

  6. Analytical strategies for identifying drug metabolites.

    Science.gov (United States)

    Prakash, Chandra; Shaffer, Christopher L; Nedderman, Angus

    2007-01-01

    With the dramatic increase in the number of new chemical entities (NCEs) arising from combinatorial chemistry and modern high-throughput bioassays, novel bioanalytical techniques are required for the rapid determination of the metabolic stability and metabolites of these NCEs. Knowledge of the metabolic site(s) of the NCEs in early drug discovery is essential for selecting compounds with favorable pharmacokinetic credentials and aiding medicinal chemists in modifying metabolic "soft spots". In development, elucidation of biotransformation pathways of a drug candidate by identifying its circulatory and excretory metabolites is vitally important to understand its physiological effects. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) have played an invaluable role in the structural characterization and quantification of drug metabolites. Indeed, liquid chromatography (LC) coupled with atmospheric pressure ionization (API) MS has now become the most powerful tool for the rapid detection, structure elucidation, and quantification of drug-derived material within various biological fluids. Often, however, MS alone is insufficient to identify the exact position of oxidation, to differentiate isomers, or to provide the precise structure of unusual and/or unstable metabolites. In addition, an excess of endogenous material in biological samples often suppress the ionization of drug-related material complicating metabolite identification by MS. In these cases, multiple analytical and wet chemistry techniques, such as LC-NMR, enzymatic hydrolysis, chemical derivatization, and hydrogen/deuterium-exchange (H/D-exchange) combined with MS are used to characterize the novel and isomeric metabolites of drug candidates. This review describes sample preparation and introduction strategies to minimize ion suppression by biological matrices for metabolite identification studies, the application of various LC-tandem MS (LC-MS/MS) techniques for the rapid quantification and

  7. Synthesis of the major metabolites of Tolvaptan

    Institute of Scientific and Technical Information of China (English)

    Wei Li Wan; Jian Bo Wu; Fan Lei; Xiao Long Li; Li Hai; Yong Wu

    2012-01-01

    Tolvaptan is a nonpeptide arginine vasopressin (AVP) V2-receptor antagonist and used in the treatment of heart failure,cirrhosis,syndrome of inappropriate antidiuretic hormone secretion or other high-volume capacity of hyponatremia.The metabolites of tolvaptan are mainly produced by CYP3A4,including two major compounds named DM-4103 and DM-4107.Herein,the chemical synthesis of those two metabolites is described in this article for further study.

  8. The urine marker test

    DEFF Research Database (Denmark)

    Elbe, Anne-Marie; Jensen, Stine Nylandsted; Elsborg, Peter;

    2016-01-01

    BACKGROUND: Urine sample collection for doping control tests is a key component of the World Anti-Doping Agency's fight against doping in sport. However, a substantial number of athletes experience difficulty when having to urinate under supervision. Furthermore, it cannot always be ensured...... that athletes are actually delivering their own urine. A method that can be used to alleviate the negative impact of a supervised urination procedure and which can also identify urine as coming from a specific athlete is the urine marker test. Monodisperse low molecular weight polyethylene glycols (PEGs......) are given orally prior to urination. Urine samples can be traced to the donor by analysis of the PEGs previously given. OBJECTIVE: The objective of this study was to investigate the use of the urine marker during urine doping control testing. METHODS: Two studies investigated athletes' acceptance...

  9. Urinary Phthalate Metabolites and Biomarkers of Oxidative Stress in a Mexican-American Cohort: Variability in Early and Late Pregnancy

    Directory of Open Access Journals (Sweden)

    Nina Holland

    2016-03-01

    Full Text Available People are exposed to phthalates through their wide use as plasticizers and in personal care products. Many phthalates are endocrine disruptors and have been associated with adverse health outcomes. However, knowledge gaps exist in understanding the molecular mechanisms associated with the effects of exposure in early and late pregnancy. In this study, we examined the relationship of eleven urinary phthalate metabolites with isoprostane, an established marker of oxidative stress, among pregnant Mexican-American women from an agricultural cohort. Isoprostane levels were on average 20% higher at 26 weeks than at 13 weeks of pregnancy. Urinary phthalate metabolite concentrations suggested relatively consistent phthalate exposures over pregnancy. The relationship between phthalate metabolite concentrations and isoprostane levels was significant for the sum of di-2-ethylhexyl phthalate and the sum of high molecular weight metabolites with the exception of monobenzyl phthalate, which was not associated with oxidative stress at either time point. In contrast, low molecular weight metabolite concentrations were not associated with isoprostane at 13 weeks, but this relationship became stronger later in pregnancy (p-value = 0.009 for the sum of low molecular weight metabolites. Our findings suggest that prenatal exposure to phthalates may influence oxidative stress, which is consistent with their relationship with obesity and other adverse health outcomes.

  10. Lipoprotein marker for hypertriglyceridemia

    Science.gov (United States)

    Cubicciotti, Roger S.; Karu, Alexander E.; Krauss, Ronald M.

    1986-01-01

    Methods and compositions are provided for the detection of a particular low density lipoprotein which has been found to be a marker for patients suffering from type IV hypertriglyceridemia. A monoclonal antibody capable of specifically binding to a characteristic epitopic site on this LDL subspecies can be utilized in a wide variety of immunoassays. Hybridoma cell line SPL.IVA5A1 was deposited at the American Type Culture Collection on Mar. 29, 1984, and granted accession no. HB 8535.

  11. Urinary Phthalate Metabolites and Biomarkers of Oxidative Stress in Pregnant Women: A Repeated Measures Analysis

    Science.gov (United States)

    Ferguson, Kelly K.; McElrath, Thomas F.; Chen, Yin-Hsiu; Mukherjee, Bhramar

    2014-01-01

    Background Phthalate exposure occurs readily in the environment and has been associated with an array of health end points, including adverse birth outcomes. Some of these may be mediated by oxidative stress, a proposed mechanism for phthalate action. Objectives In the present study, we explored the associations between phthalate metabolites and biomarkers of oxidative stress measured in urine samples from multiple time points during pregnancy. Methods Women were participants in a nested case–control study of preterm birth (n = 130 cases, n = 352 controls). Each was recruited early in pregnancy and followed until delivery, providing urine samples at up to four visits. Nine phthalate metabolites were measured to assess exposure, and 8-hydroxydeoxyguanosine and 8-isoprostane were also measured in urine as markers of oxidative stress. Associations were assessed using linear mixed models to account for intraindividual correlation, with inverse selection probability weightings based on case status to allow for greater generalizability. Results Interquartile range increases in phthalate metabolites were associated with significantly higher concentrations of both biomarkers. Estimated differences were greater in association with monobenzyl phthalate (MBzP), mono-n-butyl phthalate (MBP), and monoisobutyl phthalate (MiBP), compared with di(2-ethylhexyl) phthalate (DEHP) metabolites. Conclusions Urinary phthalate metabolites were associated with increased oxidative stress biomarkers in our study population of pregnant women. These relationships may be particularly relevant to the study of birth outcomes linked to phthalate exposure. Although replication is necessary in other populations, these results may also be of great importance for a range of other health outcomes associated with phthalates. Citation Ferguson KK, McElrath TF, Chen YH, Mukherjee B, Meeker JD. 2015. Urinary phthalate metabolites and biomarkers of oxidative stress in pregnant women: a repeated measures

  12. Tissue metabolite profiling identifies differentiating and prognostic biomarkers for prostate carcinoma.

    Science.gov (United States)

    Jung, Klaus; Reszka, Regina; Kamlage, Beate; Bethan, Bianca; Stephan, Carsten; Lein, Michael; Kristiansen, Glen

    2013-12-15

    Metabolomic research offers a deeper insight into biochemical changes in cancer metabolism and is a promising tool for identifying novel biomarkers. We aimed to evaluate the diagnostic and prognostic potential of metabolites in prostate cancer (PCa) tissue after radical prostatectomy. In matched malignant and nonmalignant prostatectomy samples from 95 PCa patients, aminoadipic acid, cerebronic acid, gluconic acid, glycerophosphoethanolamine, 2-hydroxybehenic acid, isopentenyl pyrophosphate, maltotriose, 7-methylguanine and tricosanoic acid were determined within a global metabolite profiling study using gas chromatography/liquid chromatography-mass spectrometry. The data were related to clinicopathological variables like prostate volume, tumor stage, Gleason score, preoperative prostate-specific antigen and disease recurrence in the follow-up. All nine metabolites showed higher concentrations in malignant than in nonmalignant samples except for gluconic acid and maltotriose, which had lower levels in tumors. Receiver -operating characteristics analysis demonstrated a significant discrimination for all metabolites between malignant and nonmalignant tissue with a maximal area under the curve of 0.86 for tricosanoic acid, whereas no correlation was observed between the metabolite levels and the Gleason score or tumor stage except for gluconic acid. Univariate Cox regression and Kaplan-Meier analyses showed that levels of aminoadipic acid, gluconic acid and maltotriose were associated with the biochemical tumor recurrence (prostate-specific antigen > 0.2 ng/mL). In multivariate Cox regression analyses, aminoadipic acid together with tumor stage and Gleason score remained in a model as independent marker for prediction of biochemical recurrence. This study proved that metabolites in PCa tissue can be used, in combination with traditional clinicopathological factors, as promising diagnostic and prognostic tools. PMID:23737455

  13. Synthesis and positron emission tomography studies of C-11-labeled isotopomers and metabolites of GTS-21, a partial {alpha}7 nicotinic cholinergic agonist drug

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Won [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States) and Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400 (United States)]. E-mail: swkim@bnl.gov; Ding Yushin [Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400 (United States); Department of Radiology, Yale University School of Medicine, New Haven, CT 06520-8048 (United States); Alexoff, David [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Patel, Vinal [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Logan, Jean [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Lin, K.-S. [Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Shea, Colleen [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Muench, Lisa [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Xu Youwen [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Carter, Pauline [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); King, Payton [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Constanzo, Jasmine R. [Department of Chemistry, Fordham University, Bronx, NY 10458 (United States); Ciaccio, James A. [Department of Chemistry, Fordham University, Bronx, NY 10458 (United States); Fowler, Joanna S. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400 (United States); Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029 (United States)

    2007-07-15

    Introduction: (3E)-3-[(2,4-dimethoxyphenyl)methylene]-3,4,5,6-tetrahydro-2,3'-bipyridine (GTS-21), a partial {alpha}7 nicotinic acetylcholine receptor agonist drug, has recently been shown to improve cognition in schizophrenia and Alzheimer's disease. One of its two major demethylated metabolites, 4-OH-GTS-21, has been suggested to contribute to its therapeutic effects. Methods: We labeled GTS-21 in two different positions with carbon-11 ([2-methoxy-{sup 11}C]GTS-21 and [4-{sup 11}C]GTS-21) along with two corresponding demethylated metabolites ([2-methoxy-{sup 11}C]4-OH-GTS-21 and [4-methoxy-{sup 11}C]2-OH-GTS-21) for pharmacokinetic studies in baboons and mice with positron emission tomography (PET). Results: Both [2-{sup 11}C]GTS-21 and [4-methoxy-{sup 11}C]GTS-21 showed similar initial high rapid uptake in baboon brain, peaking from 1 to 3.5 min (0.027-0.038%ID/cc) followed by rapid clearance (t {sub 1/2}<15 min), resulting in low brain retention by 30 min. However, after 30 min, [2-methoxy-{sup 11}C]GTS-21 continued to clear while [4-methoxy-{sup 11}C]GTS-21 plateaued, suggesting the entry of a labeled metabolite into the brain. Comparison of the pharmacokinetics of the two labeled metabolites confirmed expected higher brain uptake and retention of [4-methoxy-{sup 11}C]2-OH-GTS-21 (the labeled metabolite of [4-methoxy-{sup 11}C]GTS-21) relative to [2-methoxy-{sup 11}C]4-OH-GTS-21 (the labeled metabolite of [2-methoxy-{sup 11}C]GTS-21), which had negligible brain uptake. Ex vivo studies in mice showed that GTS-21 is the major chemical form in the mouse brain. Whole-body dynamic PET imaging in baboon and mouse showed that the major route of excretion of C-11 is through the gallbladder. Conclusions: The major findings are as follows: (a) extremely rapid uptake and clearance of [2-methoxy-{sup 11}C]GTS-21 from the brain, which may need to be considered in developing optimal dosing of GTS-21 for patients, and (b) significant brain uptake of 2-OH-GTS-21

  14. Brain glycogen

    DEFF Research Database (Denmark)

    Obel, Linea Lykke Frimodt; Müller, Margit S; Walls, Anne B;

    2012-01-01

    Glycogen is a complex glucose polymer found in a variety of tissues, including brain, where it is localized primarily in astrocytes. The small quantity found in brain compared to e.g., liver has led to the understanding that brain glycogen is merely used during hypoglycemia or ischemia....... In this review evidence is brought forward highlighting what has been an emerging understanding in brain energy metabolism: that glycogen is more than just a convenient way to store energy for use in emergencies-it is a highly dynamic molecule with versatile implications in brain function, i.e., synaptic...... activity and memory formation. In line with the great spatiotemporal complexity of the brain and thereof derived focus on the basis for ensuring the availability of the right amount of energy at the right time and place, we here encourage a closer look into the molecular and subcellular mechanisms...

  15. Brain Basics

    Medline Plus

    Full Text Available ... as they grow there are differences in brain development in children who develop bipolar disorder than children who do not. Studies comparing such children to those with normal brain development may help scientists to pinpoint when and where ...

  16. Brain Basics

    Medline Plus

    Full Text Available ... PTSD) . Prefrontal cortex (PFC) —Seat of the brain's executive functions, such as judgment, decision making, and problem solving. ... brain that, in humans, plays a role in executive functions such as judgment, decision making and problem solving, ...

  17. Brain Basics

    Medline Plus

    Full Text Available ... Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take ... to slow or stop them from progressing. Functional magnetic resonance imaging (fMRI) is another important research tool in ...

  18. Brain Basics

    Medline Plus

    Full Text Available ... in brain development in children who develop bipolar disorder than children who do not. Studies comparing such children to those with normal brain development may help scientists to pinpoint when and where mental disorders begin and perhaps how to slow or stop ...

  19. Brain Basics

    Medline Plus

    Full Text Available ... and are working to compare that with brain development in people mental disorders. Genes and environmental cues both help to direct ... as they grow there are differences in brain development in children who develop bipolar disorder than children who do not. Studies comparing such ...

  20. Brain Basics

    Medline Plus

    Full Text Available ... her symptoms were not caused by a stroke, brain tumor, or similar conditions, Sarah's doctor referred her to a psychiatrist, a type of medical doctor who is an expert on mental ... of serotonin in the brain and help reduce symptoms of depression. Sarah also ...

  1. Brain Basics

    Medline Plus

    Full Text Available ... the brain, which is linked to thought and emotion. It is also linked to reward systems in the brain. Problems in producing dopamine can result in Parkinson's disease, a disorder that affects a person's ability to move as they want to, resulting ...

  2. Brain imaging

    International Nuclear Information System (INIS)

    The techniques of brain imaging and results in perfusion studies and delayed images are outlined. An analysis of the advantages and disadvantages of the brain scan in a variety of common problems is discussed, especially as compared with other available procedures. Both nonneoplastic and neoplastic lesions are considered. (Auth/C.F.)

  3. Brain Basics

    Medline Plus

    Full Text Available ... will fire. This enhances the electrical flow among brain cells required for normal function and plays an important ... of neurons and their interconnections. neuron —A nerve cell that is the basic, working unit of the brain and nervous system, which processes and transmits information. ...

  4. Brain surgery

    Science.gov (United States)

    ... piece of tumor for a biopsy Remove abnormal brain tissue Drain blood or an infection Free a nerve The bone flap is usually replaced after surgery, using small metal ... or if the brain was swollen. (This is called a craniectomy.) The ...

  5. Brain Basics

    Medline Plus

    Full Text Available ... little dopamine or problems using dopamine in the thinking and feeling regions of the brain may play ... axis —A brain-body circuit which plays a critical role in the body's response to stress. impulse — ...

  6. Brain Basics

    Medline Plus

    Full Text Available ... Basics in Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle-aged woman who seemed to have it all. She was happily married and successful in business. Then, after a serious setback at work, she lost interest ...

  7. Brain Basics

    Medline Plus

    Full Text Available ... Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of ... to slow or stop them from progressing. Functional magnetic resonance imaging (fMRI) is another important research tool in understanding ...

  8. Brain Basics

    Medline Plus

    Full Text Available ... Basics in Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a ... medical history. Epigenetic changes from stress or early-life experiences ... In contrast, major depression is a serious disorder that lasts for weeks. ...

  9. Brain Basics

    Medline Plus

    Full Text Available ... her feelings. Brain Research Modern research tools and techniques are giving scientists a more detailed understanding of the brain than ... a person responds to a certain medication. This information may someday ... is allowing scientists to make important discoveries that could change the ...

  10. Brain Diseases

    Science.gov (United States)

    ... know what causes some brain diseases, such as Alzheimer's disease. The symptoms of brain diseases vary widely depending on the specific problem. In some cases, damage is permanent. In other cases, treatments such as surgery, medicines, or physical therapy can correct the source of the problem or ...

  11. Multi-voxel magnetic resonance spectroscopy of cerebral metabolites in healthy dogs at 1.5 Tesla

    Science.gov (United States)

    Choi, Sooyoung; Song, Yumi; Lee, Kija; Lee, Youngwon

    2016-01-01

    This study was conducted to measure the difference in levels of cerebral metabolites in the right and left hemispheres, gray (GM) and white matter (WM), imaging planes, and anatomical regions of healthy dogs to establish normal variations. Eight male Beagle dogs (1 to 4 years of age; mean age, 2 years) with no evidence of neurologic disease were studied. Using the multi-voxel technique on a 1.5 Tesla magnetic resonance imaging scanner, metabolite values (N-acetyl aspartate [NAA], choline [Cho], creatine [Cr]) were obtained from the frontoparietal WM, parietal GM, temporal GM, occipital GM, thalamus, cerebellum, mid-brain, and pons. There was no significant difference in levels of these metabolites between the right and left in any locations or between the GM and WM in the cerebral hemispheres. However, there were significant differences in metabolite ratios within imaging planes. The NAA/Cr was lower in the cerebellum than other regions and the thalamus had a higher Cho/Cr and lower NAA/Cho ratio than in other regions. The spectral and metabolic values will provide a useful internal reference for clinical practice and research involving multi-voxel magnetic resonance spectroscopy. Measurement of metabolite values in the transverse plane is recommended for comparing levels of regional metabolites. PMID:26645339

  12. Multi-voxel magnetic resonance spectroscopy of cerebral metabolites in healthy dogs at 1.5 Tesla.

    Science.gov (United States)

    Choi, Sooyoung; Song, Yumi; Lee, Kija; Lee, Youngwon; Choi, Hojung

    2016-06-30

    This study was conducted to measure the difference in levels of cerebral metabolites in the right and left hemispheres, gray (GM) and white matter (WM), imaging planes, and anatomical regions of healthy dogs to establish normal variations. Eight male Beagle dogs (1 to 4 years of age; mean age, 2 years) with no evidence of neurologic disease were studied. Using the multi-voxel technique on a 1.5 Tesla magnetic resonance imaging scanner, metabolite values (N-acetyl aspartate [NAA], choline [Cho], creatine [Cr]) were obtained from the frontoparietal WM, parietal GM, temporal GM, occipital GM, thalamus, cerebellum, mid-brain, and pons. There was no significant difference in levels of these metabolites between the right and left in any locations or between the GM and WM in the cerebral hemispheres. However, there were significant differences in metabolite ratios within imaging planes. The NAA/Cr was lower in the cerebellum than other regions and the thalamus had a higher Cho/Cr and lower NAA/Cho ratio than in other regions. The spectral and metabolic values will provide a useful internal reference for clinical practice and research involving multi-voxel magnetic resonance spectroscopy. Measurement of metabolite values in the transverse plane is recommended for comparing levels of regional metabolites. PMID:26645339

  13. The noradrenaline metabolite MHPG is a candidate biomarker from the manic to the remission state in bipolar disorder I: a clinical naturalistic study.

    Directory of Open Access Journals (Sweden)

    Masatake Kurita

    Full Text Available Remission is the primary goal of treatment for bipolar disorder I (BDI. Metabolites of noradrenaline and dopamine, 3-methoxy-4-hydroxyphenylglycol (MHPG and homovanillic acid (HVA, respectively, are reduced by treatment with antipsychotics, but whether these phenomena are caused by antipsychotics or by the pathophysiology of BDI is not known. Interactions between brain-derived neurotrophic factor (BDNF and mood disorders have also been suggested. We conducted a multifaceted study in BDI patients to ascertain if biological markers are associated with the manic state. Patients with Young Mania Rating Scale (YMRS scores >20 participated in the study. Final analyses involved 24 BDI patients (13 men and 11 women. We used YMRS scores to identify mania stages in individual BDI patients (i.e., manic syndrome, response and remission stages. Statistical analyses were done using one-way repeated-measures analyses of variance (rep-ANOVA throughout manic syndrome, response and remission stages. Plasma concentrations of MHPG and HVA were analyzed by high-performance liquid chromatography with electrochemical detection. Plasma levels of BDNF were measured by sandwich enzyme-linked immunosorbent assay. BDI patients had significantly reduced plasma levels of MHPG throughout manic syndrome, response and remission stages (rep-ANOVA, p = 0.002. Without a case of response state, there was a significant positive correlation between YMRS scores and plasma levels of MHPG (ρ = 0.33, p = 0.033, n = 48. Plasma levels of HVA and BDNF were not significantly altered throughout manic syndrome, response and remission stages. These data suggest that the peripheral level of MHPG (which is associated with noradrenaline levels in the brain could be used as a biomarker for the manic state in BDI. The MHPG level is likely to reflect the clinical characteristics of the manic syndrome in BDI, and noradrenaline may reflect the pathophysiology from manic to remission

  14. Brain plasticity of rats exposed to prenatal immobilization stress

    OpenAIRE

    Badalyan B. Yu.; Tumasyan N. V.; Meliksetyan I. B.; Sahakyan I. K.; Abrahamyan S. S.; Galoyan A. A.

    2011-01-01

    Aim. This histochemical and immunohistochemical study was aimed at examining the brain cellular structures of newborn rats exposed to prenatal immobilization (IMO) stress. Methods. Histochemical method on detection of Ca2+-dependent acid phosphatase activity and ABC immunohistochemical technique. Results. Cell structures with radial astrocytes marker GFAP, neuroepithelial stem cell marker gene nestin, stem-cells marker and the hypothalamic neuroprotective proline-rich polypeptide PRP-1 (Galar...

  15. Gender-specific impact of personal health parameters on individual brain aging in cognitively unimpaired elderly subjects

    OpenAIRE

    Katja Franke; Michael Ristow

    2014-01-01

    Aging alters brain structure and function. Personal health markers and modifiable lifestyle factors are related to individual brain aging as well as to the risk of developing Alzheimer’s disease (AD). This study uses a novel magnetic resonance imaging (MRI)-based biomarker to assess the effects of 17 health markers on individual brain aging in cognitively unimpaired elderly subjects. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estim...

  16. Gender-specific impact of personal health parameters on individual brain aging in cognitively unimpaired elderly subjects

    OpenAIRE

    Franke, Katja; Ristow, Michael; Gaser, Christian

    2014-01-01

    Aging alters brain structure and function. Personal health markers and modifiable lifestyle factors are related to individual brain aging as well as to the risk of developing Alzheimer's disease (AD). This study used a novel magnetic resonance imaging (MRI)-based biomarker to assess the effects of 17 health markers on individual brain aging in cognitively unimpaired elderly subjects. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estim...

  17. Metabolic drift in the aging brain.

    Science.gov (United States)

    Ivanisevic, Julijana; Stauch, Kelly L; Petrascheck, Michael; Benton, H Paul; Epstein, Adrian A; Fang, Mingliang; Gorantla, Santhi; Tran, Minerva; Hoang, Linh; Kurczy, Michael E; Boska, Michael D; Gendelman, Howard E; Fox, Howard S; Siuzdak, Gary

    2016-05-01

    Brain function is highly dependent upon controlled energy metabolism whose loss heralds cognitive impairments. This is particularly notable in the aged individuals and in age-related neurodegenerative diseases. However, how metabolic homeostasis is disrupted in the aging brain is still poorly understood. Here we performed global, metabolomic and proteomic analyses across different anatomical regions of mouse brain at different stages of its adult lifespan. Interestingly, while severe proteomic imbalance was absent, global-untargeted metabolomics revealed an energymetabolic drift or significant imbalance in core metabolite levels in aged mouse brains. Metabolic imbalance was characterized by compromised cellular energy status (NAD decline, increased AMP/ATP, purine/pyrimidine accumulation) and significantly altered oxidative phosphorylation and nucleotide biosynthesis and degradation. The central energy metabolic drift suggests a failure of the cellular machinery to restore metabostasis (metabolite homeostasis) in the aged brain and therefore an inability to respond properly to external stimuli, likely driving the alterations in signaling activity and thus in neuronal function and communication. PMID:27182841

  18. Urinary estrogen metabolites and breast cancer

    DEFF Research Database (Denmark)

    Dallal, Cher M; Stone, Roslyn A; Cauley, Jane A;

    2013-01-01

    Background: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16a-hydroxyestrone (16a-OHE1), and their...... ratio (2:16a-OHE1) in relation to breast cancer risk. ¿Methods: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using...... enzyme linked immunosorbent assays. Study-specific and combined multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated based on tertiles of estrogen metabolites. Multinomial logistic regression models were fit according to hormone receptor status.¿Results: Higher...

  19. Patterns of Brain Injury in Inborn Errors of Metabolism

    OpenAIRE

    Gropman, Andrea L.

    2012-01-01

    Many inborn errors of metabolism (IEMs) are associated with irreversible brain injury. For many, it is unclear how metabolite intoxication or substrate depletion accounts for the specific neurologic findings observed. IEM-associated brain injury patterns are characterized by whether the process involves gray matter, white matter, or both, and beyond that, whether subcortical or cortical gray matter nuclei are involved. Despite global insults, IEMs may result in selective injury to deep gray m...

  20. Liraglutide, a long-acting GLP-1 mimetic, and its metabolite attenuate inflammation after intracerebral hemorrhage

    DEFF Research Database (Denmark)

    Hou, Jack; Manaenko, Anatol; Hakon, Jakob;

    2012-01-01

    The inflammatory response plays a pivotal role in propagating injury of intracerebral hemorrhage (ICH). Glucagon-like-peptide-1 (GLP-1) is a hormone with antidiabetic effect and may also have antiinflammatory properties. Despite consensus that the glucoregulatory action is mediated by the GLP-1...... receptor (GLP-1R), mechanisms in the brain remain unclear. We investigated the effect of a long-acting GLP-1 analog, liraglutide, and its truncated metabolite, GLP-1(9-36)a from dipeptidyl peptidase-4 (DPP-4) cleavage in ICH-induced brain injury. Primary outcomes were cerebral edema formation......, neurobehavior, and inflammatory parameters. GLP-1(9-36)a, GLP-1R inhibitor, adenosine monophosphate-activated protein kinase (AMPK) phosphorylation inhibitor and DPP-4 inhibitor were administered to examine the mechanisms of action. Liraglutide suppressed neuroinflammation, prevented brain edema and neurologic...

  1. Determination of Urine 3-HPMA, a Stable Acrolein Metabolite in a Rat Model of Spinal Cord Injury

    OpenAIRE

    Zheng, Lingxing; Park, Jonghyuck; Walls, Michael; Tully, Melissa; Jannasch, Amber; Cooper, Bruce; Shi, Riyi

    2013-01-01

    Acrolein has been suggested to be involved in a variety of pathological conditions. The monitoring of acrolein is of significant importance in delineating the pathogenesis of various diseases. Aimed at overcoming the reactivity and volatility of acrolein, we describe a specific and stable metabolite of acrolein in urine, N-acetyl-S-3-hydroxypropylcysteine (3-HPMA), as a potential surrogate marker for acrolein quantification. Using the LC/MS/MS method, we demonstrated that 3-HPMA was significa...

  2. Transporter and its engineering for secondary metabolites.

    Science.gov (United States)

    Lv, Huajun; Li, Jianhua; Wu, Yingying; Garyali, Sanjog; Wang, Yong

    2016-07-01

    Secondary metabolites possess a lot of biological activities, and to achieve their functions, transmembrane transportation is crucial. Elucidation of their transport mechanisms in the cell is critical for discovering ways to improve the production. Here, we have summarized the recent progresses for representative secondary metabolite transporters and also the strategies for uncovering the transporter systems in plants and microbes. We have also discussed the transporter engineering strategies being utilized for improving the heterologous natural product production, which exhibits promising future under the guide of synthetic biology. PMID:27209041

  3. [Autism and Autism-associated Metabolites].

    Science.gov (United States)

    Watanabe, Kunitomo

    2016-06-01

    Gene-microbiota interactions are now proposed to be a special case of gene-environmental interaction. Preclinical and clinical data summarized in this article reveal that a specific serum metabolite, associated with alterations in gut microbiome composition, might have an emerging role in the onset and pathogenesis of autism. Altered level of this specified metabolite may induce perturbations in the epigenome and modulate the expression of key disease susceptible genes in neurons and their associated cells during critical periods of neurodevelopment. The gut microbiota itself is now regarded as a reservoir for environmental epigenetic factors. PMID:27279160

  4. Animal bioavailability of defined xenobiotic lignin metabolites

    International Nuclear Information System (INIS)

    Lignin has been recognized as a major component of bound pesticide residues in plants and is thought to be undigestible in animals. Two defined ring-U-14C-labeled chloroaniline/lignin metabolites have now been fed to rats, where a release of ∼66% of the bound xenobiotic occurred in the form of simple chloroaniline derivatives. The observed high degree of bioavailability indicates that bound pesticidal residues may possess ecotoxicological significance. In parallel studies, the white-rot fungus Phanerochaete chrysosporium was more efficient, and a soil system was much less efficient, in the degradation of the [ring-U-14C]chloroaniline/lignin metabolites

  5. Metabolites from mangrove endophytic fungus Dothiorella sp.

    Institute of Scientific and Technical Information of China (English)

    XUQingyan; WANGJianfeng; HUANGYaojian; ZHENGZhonghui; SONGSiyang; ZHANGYongmin; SUWenjin

    2004-01-01

    Mangroves are special woody plant communities in the intertidal zone of tropical and subtropical coasts. They prove to be a natural microorganisms and new metabolites storage. In the study of mangrove endophytic fungi metabolites, four new compounds, Compounds 1, 2, 3 and 4, as well as a known octaketide, cytosporone B (5), are isolated from an endophytic fungus, Dothiorella sp., HTF3. They all show cytotoxic activities. The elucidation of these structures is mainly based on 1D/2D NMR and ESI-MS spectral analyses.

  6. Blood-Brain Barrier Effects of the Fusarium Mycotoxins Deoxynivalenol, 3 Acetyldeoxynivalenol, and Moniliformin and Their Transfer to the Brain

    OpenAIRE

    Behrens, Matthias; Hüwel, Sabine; Galla, Hans-Joachim; Humpf, Hans-Ulrich

    2015-01-01

    Background Secondary metabolites produced by Fusarium fungi frequently contaminate food and feed and have adverse effects on human and animal health. Fusarium mycotoxins exhibit a wide structural and biosynthetic diversity leading to different toxicokinetics and toxicodynamics. Several studies investigated the toxicity of mycotoxins, focusing on very specific targets, like the brain. However, it still remains unclear how fast mycotoxins reach the brain and if they impair the integrity of the ...

  7. [Biochemical markers for acute and chronic alcohol consumption].

    Science.gov (United States)

    Geppert, Bogna; Tezyk, Artur; Zaba, Czesław

    2012-01-01

    In spite of the fact, that ethyl alcohol is a legal and socially accepted recreational drug its abuse may cause numerous problems for the individual and society. Casualties of car accidents caused by drunk drivers, aggressive behavior, family problems and effective less work are the main problems connected with alcohol abuse. The easiest and most effective way of proving recent alcohol consumption is confirming its presence in biological samples taken from the individual. However, the main disadvantage of this method is a short window detection for ethanol, because of its high speed of elimination process. Nowadays, in order to prevent and have a better control of alcohol abuse, markers that could provide a better view of short and long term ethanol consumption are in frequent use. Ethyl alcohol present in the body cause many qualitative and quantitative disturbances in biochemical metabolites that could be used as markers of its consumption. In practice markers of ethanol consumption are usually divided into acute (tests confirm single alcohol intake) and chronic (confirm long term alcohol consumption or lack of teetotalism). Markers of ethanol consumption are valuable alternative and complementation to customary examinations performed in medical practice and forensic medicine. PMID:23421117

  8. Increased plasma concentrations of vitamin D metabolites and vitamin D binding protein in women using hormonal contraceptives: a cross-sectional study

    DEFF Research Database (Denmark)

    Liendgaard, Ulla Kristine Møller; við Streym, Susanna; Jensen, Lars Thorbjørn; Mosekilde, Leif; Schoenmakers, Inez; Nigdikar, Shailja; Rejnmark, Lars

    2013-01-01

    Use of hormonal contraceptives (HC) may influence total plasma concentrations of vitamin D metabolites. A likely cause is an increased synthesis of vitamin D binding protein (VDBP). Discrepant results are reported on whether the use of HC affects free concentrations of vitamin D metabolites. Aim......: In a cross-sectional study, plasma concentrations of vitamin D metabolites, VDBP, and the calculated free vitamin D index in users and non-users of HC were compared and markers of calcium and bone metabolism investigated. Results: 75 Caucasian women aged 25-35 years were included during winter season....../creatinine ratio) between groups. In conclusion: Use of HC is associated with 13%-25% higher concentrations of total vitamin D metabolites and VDBP. This however is not reflected in indices of calcium or bone metabolism. Use of HC should be considered in the interpretation of plasma concentrations vitamin D...

  9. Brain tumor

    International Nuclear Information System (INIS)

    BNCT in the past was not widely accepted because of poor usability of a nuclear reactor as a neutron source. Recently, technical advancements in the accelerator field have made accelerator-based BNCT feasible. Consequently, clinical trials of intractable brain tumors have started using it since 2012. In this review, our clinical results obtained from conventional reactor-based BNCT for treatment of brain tumors are introduced. It is strong hope that accelerator-based BNCT becomes a standard therapy for current intractable brain tumors. (author)

  10. Brain and Addiction

    Science.gov (United States)

    ... Teens / Drug Facts / Brain and Addiction Brain and Addiction Print Your Brain Your brain is who you ... is taken over and over. What Is Drug Addiction? Addiction is a chronic brain disease that causes ...

  11. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  12. Cancer and tumour markers

    International Nuclear Information System (INIS)

    Cancer has been a major cause of death world wide and in Nigeria there are six commonest forms of manifestation of cancer known. Of these prostrate cancer is the highest with 16% occurrence of all known cancers according to a study by the Histopathology Department of the UCH. Many factors, amongst them dietary, environmental, lifestyle, age and sedentary work are possible causes. With the global rise in incidents, the IAEA initiated the Tumour Marker Project as a means of screening cancers in 15 African countries including Nigeria. In Nigeria, 4 groups of the commonest cancers have been chosen for screening. These are prostrate cancer, primary liver cancer, cancer of the GI tract and trophoblastic cancer

  13. Male Microchimerism in the Human Female Brain

    OpenAIRE

    Chan, William F. N.; Gurnot, Cécile; Montine, Thomas J.; Sonnen, Joshua A.; Guthrie, Katherine A.; Nelson, J. Lee

    2012-01-01

    In humans, naturally acquired microchimerism has been observed in many tissues and organs. Fetal microchimerism, however, has not been investigated in the human brain. Microchimerism of fetal as well as maternal origin has recently been reported in the mouse brain. In this study, we quantified male DNA in the human female brain as a marker for microchimerism of fetal origin (i.e. acquisition of male DNA by a woman while bearing a male fetus). Targeting the Y-chromosome-specific DYS14 gene, we...

  14. Simultaneous quantification of multiple urinary naphthalene metabolites by liquid chromatography tandem mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Daniel C Ayala

    Full Text Available Naphthalene is an environmental toxicant to which humans are exposed. Naphthalene causes dose-dependent cytotoxicity to murine airway epithelial cells but a link between exposure and human pulmonary disease has not been established. Naphthalene toxicity in rodents depends on P450 metabolism. Subsequent biotransformation results in urinary elimination of several conjugated metabolites. Glucuronide and sulfate conjugates of naphthols have been used as markers of naphthalene exposure but, as the current studies demonstrate, these assays provide a limited view of the range of metabolites generated from the parent hydrocarbon. Here, we present a liquid chromatography tandem mass spectrometry method for measurement of the glucuronide and sulfate conjugates of 1-naphthol as well as the mercapturic acids and N-acetyl glutathione conjugates from naphthalene epoxide. Standard curves were linear over 2 log orders. On column detection limits varied from 0.91 to 3.4 ng; limits of quantitation from 1.8 to 6.4 ng. The accuracy of measurement of spiked urine standards was -13.1 to + 5.2% of target and intra-day and inter-day variability averaged 7.2 (± 4.5 and 6.8 (± 5.0 %, respectively. Application of the method to urine collected from mice exposed to naphthalene at 15 ppm (4 hrs showed that glutathione-derived metabolites accounted for 60-70% of the total measured metabolites and sulfate and glucuronide conjugates were eliminated in equal amounts. The method is robust and directly measures several major naphthalene metabolites including those derived from glutathione conjugation of naphthalene epoxide. The assays do not require enzymatic deconjugation, extraction or derivatization thus simplifying sample work up.

  15. POPULAR MOLECULAR MARKERS IN BACTERIA

    OpenAIRE

    Weilong, Liu; Lv, Li; MD. ASADUZZAMAN KHAN AND FEIZHOU ZHU

    2012-01-01

    Molecular markers are defined as the fragments of DNA sequence associated with a genome, which are used to identify a particular DNA sequence. Nowadays, with the explosive growth of genetic research and bacterial classification, molecular marker is an important tool to identify bacterial species. Taking account to its significant roles in clinic, medicine and food industry, in this review article, we summarize the traditional research and new development about molecular markers (also called g...

  16. Blood-brain distribution of morphine-6-glucuronide in sheep

    DEFF Research Database (Denmark)

    Villesen, H H; Foster, D J R; Upton, R N;

    2006-01-01

    At present there are few data regarding the rate and extent of brain-blood partitioning of the opioid active metabolite of morphine, morphine-6-glucuronide (M6G). In this study the cerebral kinetics of M6G were determined, after a short-term intravenous infusion, in chronically instrumented...

  17. Gender-specific impact of personal health parameters on individual brain aging in cognitively unimpaired elderly subjects

    Directory of Open Access Journals (Sweden)

    Katja eFranke

    2014-05-01

    Full Text Available Aging alters brain structure and function. Personal health markers and modifiable lifestyle factors are related to individual brain aging as well as to the risk of developing Alzheimer’s disease (AD. This study uses a novel magnetic resonance imaging (MRI-based biomarker to assess the effects of 17 health markers on individual brain aging in cognitively unimpaired elderly subjects. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE score indicates accelerated atrophy and is considered a risk factor for developing AD. Within this cross-sectional, multi-center study 228 cognitively unimpaired elderly subjects (118 males completed an MRI at 1.5T, physiological and blood parameter assessments. The multivariate regression model combining all measured parameters was capable of explaining 39% of BrainAGE variance in males (p < 0.001 and 32% in females (p < 0.01. Furthermore, markers of the metabolic syndrome as well as markers of liver and kidney functions were profoundly related to BrainAGE scores in males (p < 0.05. In females, markers of liver and kidney functions as well as supply of vitamin B12 were significantly related to BrainAGE (p < 0.05. In conclusion, in cognitively unimpaired elderly subjects several clinical markers of poor health were associated with subtle structural changes in the brain that reflect accelerated aging, whereas protective effects on brain aging were observed for markers of good health. Additionally, the relations between individual brain aging and miscellaneous health markers show gender-specific patterns. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of subtly abnormal patterns of brain aging probably preceding cognitive decline and development of AD.

  18. Minocycline Attenuates Iron-Induced Brain Injury.

    Science.gov (United States)

    Zhao, Fan; Xi, Guohua; Liu, Wenqaun; Keep, Richard F; Hua, Ya

    2016-01-01

    Iron plays an important role in brain injury after intracerebral hemorrhage (ICH). Our previous study found minocycline reduces iron overload after ICH. The present study examined the effects of minocycline on the subacute brain injury induced by iron. Rats had an intracaudate injection of 50 μl of saline, iron, or iron + minocycline. All the animals were euthanized at day 3. Rat brains were used for immunohistochemistry (n = 5-6 per each group) and Western blotting assay (n = 4). Brain swelling, blood-brain barrier (BBB) disruption, and iron-handling proteins were measured. We found that intracerebral injection of iron resulted in brain swelling, BBB disruption, and brain iron-handling protein upregulation (p < 0.05). The co-injection of minocycline with iron significantly reduced iron-induced brain swelling (n = 5, p < 0.01). Albumin, a marker of BBB disruption, was measured by Western blot analysis. Minocycline significantly decreased albumin protein levels in the ipsilateral basal ganglia (p < 0.01). Iron-handling protein levels in the brain, including ceruloplasmin and transferrin, were reduced in the minocycline co-injected animals. In conclusion, the present study suggests that minocycline attenuates brain swelling and BBB disruption via an iron-chelation mechanism. PMID:26463975

  19. Brain Basics

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  1. Brain Health

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    ... Love Your Brain Stay Physically Active Adopt a Healthy Diet Stay Mentally and Socially Active We Can Help ... of any wellness plan. Learn More Adopt a Healthy Diet > Eat a heart-healthy diet that benefits both ...

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