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Sample records for cerebral metabolic abnormalities

  1. Cerebral glucose metabolic abnormality in patients with congenital scoliosis

    Nam, H. Y.; Seo, G. T.; Lee, J. S.; Kim, S. C.; Kim, I. J.; Kim, Y. K.; Jeon, S. M.

    2007-01-01

    A possible association between congenital scoliosis and low mental status has been recognized, but there are no reports describing the mental status or cerebral metabolism in patients with congenital scoliosis in detail. We investigated the mental status using a mini-mental status exam as well as the cerebral glucose metabolism using F-18 fluorodeoxyglucose brain positron emission tomography in 12 patients with congenital scoliosis and compared them with those of 14 age-matched patients with adolescent idiopathic scoliosis. The mean mini-mental status exam score in the congenital scoliosis group was significantly lower than that in the adolescent idiopathic scoliosis group. Group analysis found that various brain areas of patients with congenital scoliosis showed glucose hypometabolisms in the left prefrontal cortex (Brodmann area 10), right orbitofrontal cortex (Brodmann area 11), left dorsolateral prefrontal cortex (Brodmann area 9), left anterior cingulate gyrus (Brodmann area 24) and pulvinar of the left thalamus. From this study, we could find the metabolic abnormalities of brain in patients with congenital scoliosis and suggest the possible role of voxel-based analysis of brain fluorodeoxyglucose positron emission tomography

  2. Cerebral glucose metabolic abnormality in patients with congenital scoliosis

    Nam, H. Y.; Seo, G. T.; Lee, J. S.; Kim, S. C.; Kim, I. J.; Kim, Y. K.; Jeon, S. M. [Pusan National University Hospital, Pusan (Korea, Republic of)

    2007-07-01

    A possible association between congenital scoliosis and low mental status has been recognized, but there are no reports describing the mental status or cerebral metabolism in patients with congenital scoliosis in detail. We investigated the mental status using a mini-mental status exam as well as the cerebral glucose metabolism using F-18 fluorodeoxyglucose brain positron emission tomography in 12 patients with congenital scoliosis and compared them with those of 14 age-matched patients with adolescent idiopathic scoliosis. The mean mini-mental status exam score in the congenital scoliosis group was significantly lower than that in the adolescent idiopathic scoliosis group. Group analysis found that various brain areas of patients with congenital scoliosis showed glucose hypometabolisms in the left prefrontal cortex (Brodmann area 10), right orbitofrontal cortex (Brodmann area 11), left dorsolateral prefrontal cortex (Brodmann area 9), left anterior cingulate gyrus (Brodmann area 24) and pulvinar of the left thalamus. From this study, we could find the metabolic abnormalities of brain in patients with congenital scoliosis and suggest the possible role of voxel-based analysis of brain fluorodeoxyglucose positron emission tomography.

  3. Cerebral blood flow and metabolic abnormalities in Alzheimer's disease

    Matsuda, Hiroshi

    2001-01-01

    In this review I summarize observations of PET and SPECT studies about cerebral blood flow and metabolic abnormalities in Alzheimer's disease (AD). In very early AD flow or metabolism reduces first in the posterior cingulate gyrus and precuneus. This reduction may arise from functional deafferentation caused by primary neural degeneration in the remote area of the entorhinal cortex that is the first to be pathologically affected in AD. Then medial temporal structures and parietotemporal association cortex show flow or metabolic reduction as disease processes. The reason why flow or metabolism in medial temporal structures shows delay in starting to reduce in spite of the earliest pathological affection remains to be elucidated. It is likely that anterior cingulate gyrus is functionally involved, since attention is the first non-memory domain to be affected, before deficits in language and visuospatial functions. However few reports have described involvement in the anterior cingulate gyrus. Relationship between cerebral blood flow or metabolism and apolipoprotein E (APOE) genotype has been investigated. Especially, the APOEε4 allele has been reported to increase risk and to lower onset age as a function of the inherited dose of the ε4 allele. Reduction of flow or metabolism in the posterior cingulate gyrus and precuneus has been reported even in presymptomatic nondemented subjects who were cognitively normal and had at least a single ε4 allele. On the contrary the relation of ε4 allele to the progression rate of AD has been controversial from neuroimaging approaches. PET and SPECT imaging has become to be quite useful for assessing therapeutical effects of newly introduced treatment for AD. Recent investigations observed significant regional flow increase after donepezil hydrochloride treatment. Most of these observations have been made by applying computer assisted analysis of three-dimensional stereotactic surface projection or statistical parametric mapping

  4. Cerebral glucose metabolic abnormality in patients with congenital scoliosis

    Park, Weon Wook; Suh, Kuen Tak; Kim, Jeung Il; Ku, Ja Gyung; Lee, Hong Seok; Kim, Seong-Jang; Kim, In-Ju; Kim, Yong-Ki; Lee, Jung Sub

    2008-01-01

    A possible association between congenital scoliosis and low mental status has been recognized, but there are no reports describing the mental status or cerebral metabolism in patients with congenital scoliosis in detail. We investigated the mental status using a mini-mental status exam as well as the cerebral glucose metabolism using F-18 fluorodeoxyglucose brain positron emission tomography in 12 patients with congenital scoliosis and compared them with those of 14 age-matched patients with ...

  5. Asymmetry of cerebral glucose metabolism in very low-birth-weight infants without structural abnormalities.

    Jae Hyun Park

    Full Text Available Thirty-six VLBW infants who underwent F-18 fluorodeoxyglucose (F-18 FDG brain PET and MRI were prospectively enrolled, while infants with evidence of parenchymal brain injury on MRI were excluded. The regional glucose metabolic ratio and asymmetry index were calculated. The asymmetry index more than 10% (right > left asymmetry or less than -10% (left > right asymmetry were defined as abnormal. Regional cerebral glucose metabolism were compared between right and left cerebral hemispheres, and between the following subgroups: multiple gestations, premature rupture of membrane, bronchopulmonary dysplasia, and low-grade intraventricular hemorrhage.In the individual analysis, 21 (58.3% of 36 VLBW infants exhibited asymmetric cerebral glucose metabolism. Fifteen infants (41.7% exhibited right > left asymmetry, while six (16.7% exhibited left > right asymmetry. In the regional analysis, right > left asymmetry was more extensive than left > right asymmetry. The metabolic ratio in the right frontal, temporal, and occipital cortices and right thalamus were significantly higher than those in the corresponding left regions. In the subgroup analyses, the cerebral glucose metabolism in infants with multiple gestations, premature rupture of membrane, bronchopulmonary dysplasia, or low-grade intraventricular hemorrhage were significantly lower than those in infants without these.VLBW infants without structural abnormalities have asymmetry of cerebral glucose metabolism. Decreased cerebral glucose metabolism are noted in infants with neurodevelopmental risk factors. F-18 FDG PET could show microstructural abnormalities not detected by MRI in VLBW infants.

  6. Cerebral metabolic abnormalities in congestive heart failure detected by proton magnetic resonance spectroscopy.

    Lee, C W; Lee, J H; Kim, J J; Park, S W; Hong, M K; Kim, S T; Lim, T H; Park, S J

    1999-04-01

    Using proton magnetic resonance spectroscopy, we investigated cerebral metabolism and its determinants in congestive heart failure (CHF), and the effects of cardiac transplantation on these measurements. Few data are available about cerebral metabolism in CHF. Fifty patients with CHF (ejection fraction OGM) and parietal white matter (PWM). Absolute levels of the metabolites (N-acetylaspartate, creatine, choline, myo-inositol) were calculated. In PWM only creatine level was significantly lower in CHF than in control subjects, but in OGM all four metabolite levels were decreased in CHF. The creatine level was independently correlated with half-recovery time and duration of heart failure symptoms in PWM (r = -0.56, p OGM (r = 0.58, p < 0.05). Cerebral metabolic abnormalities were improved after successful cardiac transplantation. This study shows that cerebral metabolism is abnormally deranged in advanced CHF and it may serve as a potential marker of the disease severity.

  7. Persistence of cerebral metabolic abnormalities in chronic schizophrenia as determined by positron emission tomography

    Wolkin, A.; Jaeger, J.; Brodie, J.D.; Wolf, A.P.; Fowler, J.; Rotrosen, J.; Gomez-Mont, F.; Cancro, R.

    1985-01-01

    Local cerebral metabolic rates were determined by positron emission tomography and the deoxyglucose method in a group of 10 chronic schizophrenic subjects before and after somatic treatment and in eight normal subjects. Before treatment, schizophrenic subjects had markedly lower absolute metabolic activity than did normal controls in both frontal and temporal regions and a trend toward relative hyperactivity in the basal ganglia area. After treatment, their metabolic rates approached those seen in normal subjects in nearly all regions except frontal. Persistence of diminished frontal metabolism was manifested as significant relative hypofrontality. These findings suggest specific loci of aberrant cerebral functioning in chronic schizophrenia and the utility of positron emission tomography in characterizing these abnormalities

  8. Cerebral blood flow and metabolic abnormalities in Alzheimer's disease

    Matsuda, Hiroshi [National Center of Neurology and Psychiatry, Kodaira, Tokyo (Japan). National Center Hospital for Mental, Nervous, and Muscular Disorders

    2001-04-01

    In this review I summarize observations of PET and SPECT studies about cerebral blood flow and metabolic abnormalities in Alzheimer's disease (AD). In very early AD flow or metabolism reduces first in the posterior cingulate gyrus and precuneus. This reduction may arise from functional deafferentation caused by primary neural degeneration in the remote area of the entorhinal cortex that is the first to be pathologically affected in AD. Then medial temporal structures and parietotemporal association cortex show flow or metabolic reduction as disease processes. The reason why flow or metabolism in medial temporal structures shows delay in starting to reduce in spite of the earliest pathological affection remains to be elucidated. It is likely that anterior cingulate gyrus is functionally involved, since attention is the first non-memory domain to be affected, before deficits in language and visuospatial functions. However few reports have described involvement in the anterior cingulate gyrus. Relationship between cerebral blood flow or metabolism and apolipoprotein E (APOE) genotype has been investigated. Especially, the APOE{epsilon}4 allele has been reported to increase risk and to lower onset age as a function of the inherited dose of the {epsilon}4 allele. Reduction of flow or metabolism in the posterior cingulate gyrus and precuneus has been reported even in presymptomatic nondemented subjects who were cognitively normal and had at least a single {epsilon}4 allele. On the contrary the relation of {epsilon}4 allele to the progression rate of AD has been controversial from neuroimaging approaches. PET and SPECT imaging has become to be quite useful for assessing therapeutical effects of newly introduced treatment for AD. Recent investigations observed significant regional flow increase after donepezil hydrochloride treatment. Most of these observations have been made by applying computer assisted analysis of three-dimensional stereotactic surface projection

  9. Abnormality of cerebral cortical glucose metabolism in temporal lobe epilepsy with cognitive function impairment

    Bang-Hung Yang; Tsung-Szu Yeh; Tung-Ping Su; Jyh-Cheng Chen; Ren-Shyan Liu

    2004-01-01

    =95). Significantly negative correlation was demonstrated in superior temporal gyms of right temporal lobe (corrected p = 0.003, voxel size 113). Significantly positive correlation between PIQ and rCMRglc was shown in posterior lobe of cerebellum (corrected p < 0.001, voxel size =244). There was no significantly negative correlation between PIQ and rCMRglc. Conclusions: This study provided neuroimaging evidence of cerebral metabolic abnormalities which was related to cognition function impairment in temporal lobe epilepsy patient. All lesions were located with ipislateral hemisphere but outside the seizure foci. This may suggest that cognition impairment is not directly related to seizure foci but may be related with remoting areas. The epilepsy patients whose seizures will prove to be refractory should be identified as early as possible, and thus the need for new prognostic factors of intractable epilepsy is evident. Since multiple seizure foci indicated poor prognosis, quantification of Brodmann area 4, 32, 18 and cerebellum in FDG PET images may be a prognostic factor. (authors)

  10. Cerebral ketone body metabolism.

    Morris, A A M

    2005-01-01

    Ketone bodies (KBs) are an important source of energy for the brain. During the neonatal period, they are also precursors for the synthesis of lipids (especially cholesterol) and amino acids. The rate of cerebral KB metabolism depends primarily on the concentration in blood; high concentrations occur during fasting and on a high-fat diet. Cerebral KB metabolism is also regulated by the permeability of the blood-brain barrier (BBB), which depends on the abundance of monocarboxylic acid transporters (MCT1). The BBB's permeability to KBs increases with fasting in humans. In rats, permeability increases during the suckling period, but human neonates have not been studied. Monocarboxylic acid transporters are also present in the plasma membranes of neurons and glia but their role in regulating KB metabolism is uncertain. Finally, the rate of cerebral KB metabolism depends on the activities of the relevant enzymes in brain. The activities vary with age in rats, but reliable results are not available for humans. Cerebral KB metabolism in humans differs from that in the rat in several respects. During fasting, for example, KBs supply more of the brain's energy in humans than in the rat. Conversely, KBs are probably used more extensively in the brain of suckling rats than in human neonates. These differences complicate the interpretation of rodent studies. Most patients with inborn errors of ketogenesis develop normally, suggesting that the only essential role for KBs is as an alternative fuel during illness or prolonged fasting. On the other hand, in HMG-CoA lyase deficiency, imaging generally shows asymptomatic white-matter abnormalities. The ability of KBs to act as an alternative fuel explains the effectiveness of the ketogenic diet in GLUT1 deficiency, but its effectiveness in epilepsy remains unexplained.

  11. In vivo measurements of cerebral metabolic abnormalities by proton spectroscopy after a transient ischemic attack revealing an internal carotid stenosis > 70%

    Giroud, M.; Becker, F.; Lemesle, M.; Walker, P.; Guy, F.; Martin, D.; Baudouin, N.; Brunotte, F.; Dumas, R.

    1996-01-01

    Aims: The aim of this work is to look for cerebral metabolic abnormalities within the first 3 days after a transient ischemic attack revealing an internal carotid stenosis > 70 %. Methods: Five patients with a transient ischemic attack lasting between 30 and 180 minutes, affecting sensory and motor brachio-facial territory, with or without aphasia. Were studied. A CT-scan, an EEG, a cervical Doppler ultrasound, a standard arteriography, a magnetic resonance imaging and a proton spectroscopy were performed within the cerebral area affected by the transient ischemic attack. We measured 2 markers: N-acetyl-aspartate, the marker of the neuronal mass, and lactate, the marker of anaerobe metabolism. In each case, a contralateral internal stenosis was diagnosed by cervical Doppler ultrasound and standard arteriography. No cerebral infarction was observed. Results: With the affected cerebral area defined according to clinical and EEG features, proton spectroscopy showed a significant rise of lactate, without any change in N-acetyl-aspartate levels. Conclusions: Within the first 3 days after a transient ischemic attack, there is a significant risk of lactate inside the affected cerebral area. This change may reflect a localized and transient hypoperfusion, but long enough to induce a rise of lactate but not sufficient to produce a cerebral infarct. This area is probably at risk to induce cerebral infarct. This data lead us to study the metabolic change induced by the asymptomatic internal carotid stenosis. (authors). 18 refs

  12. MR imaging of cerebral abnormalities in utero.

    Thickman, D; Mintz, M; Mennuti, M; Kressel, H Y

    1984-12-01

    In view of the lack of ionizing radiation, ability to image in a variety of planes, and high contrast resolution, magnetic resonance (MR) imaging may have a role in obstetrical management. Three fetuses with severe cerebral abnormalities were studied by MR in utero. The findings were correlated with ultrasound examinations and with autopsy results. Ventricular dilatation and progression of hydrocephalus were detected by MR. Although fetal motion may affect image quality, diagnostically useful images were obtained with imaging times of 2.5 min.

  13. Cerebral FDG-PET scanning abnormalities in optimally treated HIV patients

    Andersen, Åse Bengård; Law, Ian; Krabbe, Karen Suarez

    2010-01-01

    The long-term neurological consequences of HIV infection and treatment are not yet completely understood. In this study we examined the prevalence of cerebral metabolic abnormalities among a cohort of neurologically intact HIV patients with fully suppressed HIV viral loads. Concomitant analyses...

  14. Acute hypoxia increases the cerebral metabolic rate

    Vestergaard, Mark Bitsch; Lindberg, Ulrich; Aachmann-Andersen, Niels Jacob

    2016-01-01

    The aim of the present study was to examine changes in cerebral metabolism by magnetic resonance imaging of healthy subjects during inhalation of 10% O2 hypoxic air. Hypoxic exposure elevates cerebral perfusion, but its effect on energy metabolism has been less investigated. Magnetic resonance im...

  15. Cerebral energy metabolism during induced mitochondrial dysfunction

    Nielsen, T H; Bindslev, TT; Pedersen, S M

    2013-01-01

    In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes...... in brain tissue oxygen tension (PbtO(2)) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets....

  16. In vivo measurements of cerebral metabolic abnormalities by proton spectroscopy after a transient ischemic attack revealing an internal carotid stenosis > 70%; Anomalies metaboliques cerebrales mesurees in vivo par la spectroscopie du proton dans les accidents ischemiques transitoires revelant une stenose de la carotide interne superieure a 70%

    Giroud, M.; Becker, F.; Lemesle, M.; Walker, P.; Guy, F.; Martin, D.; Baudouin, N.; Brunotte, F.; Dumas, R. [Centre Hospitalier Universitaire, 21 -Dijon (France)

    1996-06-01

    Aims: The aim of this work is to look for cerebral metabolic abnormalities within the first 3 days after a transient ischemic attack revealing an internal carotid stenosis > 70 %. Methods: Five patients with a transient ischemic attack lasting between 30 and 180 minutes, affecting sensory and motor brachio-facial territory, with or without aphasia. Were studied. A CT-scan, an EEG, a cervical Doppler ultrasound, a standard arteriography, a magnetic resonance imaging and a proton spectroscopy were performed within the cerebral area affected by the transient ischemic attack. We measured 2 markers: N-acetyl-aspartate, the marker of the neuronal mass, and lactate, the marker of anaerobe metabolism. In each case, a contralateral internal stenosis was diagnosed by cervical Doppler ultrasound and standard arteriography. No cerebral infarction was observed. Results: With the affected cerebral area defined according to clinical and EEG features, proton spectroscopy showed a significant rise of lactate, without any change in N-acetyl-aspartate levels. Conclusions: Within the first 3 days after a transient ischemic attack, there is a significant risk of lactate inside the affected cerebral area. This change may reflect a localized and transient hypoperfusion, but long enough to induce a rise of lactate but not sufficient to produce a cerebral infarct. This area is probably at risk to induce cerebral infarct. This data lead us to study the metabolic change induced by the asymptomatic internal carotid stenosis. (authors). 18 refs.

  17. Cerebral FDG-PET scanning abnormalities in optimally treated HIV patients

    Andersen, Ase B; Law, Ian; Krabbe, Karen S

    2010-01-01

    with no history of virological failure, a CD4 count above 200 x 106 cells/l and no other co-morbidities. The distribution of the regional cerebral metabolic rate of glucose metabolism was measured using fluorine-18-flourodeoxyglucose positron emission tomography (FDG-PET) scanning. The PET scans were evaluated...... in the relative metabolic rate of glucose. Compared to healthy subjects, the patients with abnormal FDG-PET scanning results had a shorter history of known HIV infection, fewer years on antiretroviral therapy and higher levels of circulating TNF alpha and IL-6 (p = 0.08). CONCLUSION: A large proportion...... of optimally treated HIV patients exhibit cerebral FDG-PET scanning abnormalities and elevated TNF alpha and IL-6 levels, which may indicate imminent neuronal damage. The neuroprotective effect of early ARV treatment should be considered in future prospective follow-up studies....

  18. Abnormal radionuclide cerebral angiograms and scans due to seizures

    Stevens, J.S.; Mishkin, F.S.

    1975-01-01

    The effect of recent seizures on the brain scan was determined in a retrospective study of patients who had had seizures. All patients who underwent brain scanning within eight days of seizures and who did not have a specific intracranial lesion were included. The /sup 99m/Tc-pertechnetate cerebral angiogram and/or delayed scan was abnormal in 73 percent of 22 patients. The data suggest that if seizures occur within six days of the brain imaging, the image is likely to be abnormal. (auth)

  19. Purine Metabolism in Acute Cerebral Ischemia

    Ye. V. Oreshnikov

    2008-01-01

    Full Text Available Objective: to study the specific features of purine metabolism in clinically significant acute cerebral ischemia. Subjects and materials. Three hundred and fifty patients with the acutest cerebral ischemic stroke were examined. The parameters of gas and electrolyte composition, acid-base balance, the levels of malonic dialdehyde, adenine, guanine, hypox-anthine, xanthine, and uric acid, and the activity of xanthine oxidase were determined in arterial and venous bloods and spinal fluid. Results. In ischemic stroke, hyperuricemia reflects the severity of cerebral metabolic disturbances, hemodynamic instability, hypercoagulation susceptiility, and the extent of neurological deficit. In ischemic stroke, hyperuri-corachia is accompanied by the higher spinal fluid levels of adenine, guanine, hypoxanthine, and xanthine and it is an indirect indicator of respiratory disorders of central genesis, systemic acidosis, hypercoagulation susceptibility, free radical oxidation activation, the intensity of a stressor response to cerebral ischemia, cerebral metabolic disturbances, the depth of reduced consciousness, and the severity of neurological deficit. Conclusion. The high venous blood activity of xanthine oxidase in ischemic stroke is associated with the better neurological parameters in all follow-up periods, the better early functional outcome, and lower mortality rates. Key words: hyperuricemia, stroke, xanthine oxidase, uric acid, cerebral ischemia.

  20. Epileptiform abnormalities predict delayed cerebral ischemia in subarachnoid hemorrhage.

    Kim, J A; Rosenthal, E S; Biswal, S; Zafar, S; Shenoy, A V; O'Connor, K L; Bechek, S C; Valdery Moura, J; Shafi, M M; Patel, A B; Cash, S S; Westover, M B

    2017-06-01

    To identify whether abnormal neural activity, in the form of epileptiform discharges and rhythmic or periodic activity, which we term here ictal-interictal continuum abnormalities (IICAs), are associated with delayed cerebral ischemia (DCI). Retrospective analysis of continuous electroencephalography (cEEG) reports and medical records from 124 patients with moderate to severe grade subarachnoid hemorrhage (SAH). We identified daily occurrence of seizures and IICAs. Using survival analysis methods, we estimated the cumulative probability of IICA onset time for patients with and without delayed cerebral ischemia (DCI). Our data suggest the presence of IICAs indeed increases the risk of developing DCI, especially when they begin several days after the onset of SAH. We found that all IICA types except generalized rhythmic delta activity occur more commonly in patients who develop DCI. In particular, IICAs that begin later in hospitalization correlate with increased risk of DCI. IICAs represent a new marker for identifying early patients at increased risk for DCI. Moreover, IICAs might contribute mechanistically to DCI and therefore represent a new potential target for intervention to prevent secondary cerebral injury following SAH. These findings imply that IICAs may be a novel marker for predicting those at higher risk for DCI development. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  1. Cerebral blood flow and metabolism during sleep

    Madsen, Peter Lund; Vorstrup, S

    1991-01-01

    A review of the current literature regarding sleep-induced changes in cerebral blood flow (CBF) and cerebral metabolic rate (CMR) is presented. Early investigations have led to the notion that dreamless sleep was characterized by global values of CBF and CMR practically at the level of wakefulness......, while rapid eye movement (REM) sleep (dream sleep) was a state characterized by a dramatically increased level of CBF and possibly also of CMR. However, recent investigations firmly contradict this notion. Investigations on CBF and CMR performed during non-REM sleep, taking the effect of different...... current state identify the physiological processes involved in sleep or the physiological role of sleep....

  2. Normal and abnormal neuronal migration in the developing cerebral cortex.

    Sun, Xue-Zhi; Takahashi, Sentaro; Cui, Chun; Zhang, Rui; Sakata-Haga, Hiromi; Sawada, Kazuhiko; Fukui, Yoshihiro

    2002-08-01

    Neuronal migration is the critical cellular process which initiates histogenesis of cerebral cortex. Migration involves a series of complex cell interactions and transformation. After completing their final mitosis, neurons migrate from the ventricular zone into the cortical plate, and then establish neuronal lamina and settle onto the outermost layer, forming an "inside-out" gradient of maturation. This process is guided by radial glial fibers, requires proper receptors, ligands, other unknown extracellular factors, and local signaling to stop neuronal migration. This process is also highly sensitive to various physical, chemical and biological agents as well as to genetic mutations. Any disturbance of the normal process may result in neuronal migration disorder. Such neuronal migration disorder is believed as major cause of both gross brain malformation and more special cerebral structural and functional abnormalities in experimental animals and in humans. An increasing number of instructive studies on experimental models and several genetic model systems of neuronal migration disorder have established the foundation of cortex formation and provided deeper insights into the genetic and molecular mechanisms underlying normal and abnormal neuronal migration.

  3. Cerebral glucose metabolism in Parkinson's disease

    Martin, W R.W.; Beckman, J H; Calne, D B; Adam, M J; Harrop, R; Rogers, J G; Ruth, T J; Sayre, C I; Pate, B D [British Columbia Univ., Vancouver (Canada). TRIUMF Facility

    1984-02-01

    Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using sup(18)F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra.

  4. Cerebral glucose metabolism in Parkinson's disease

    Martin, W.R.W.; Beckman, J.H.; Calne, D.B.; Adam, M.J.; Harrop, R.; Rogers, J.G.; Ruth, T.J.; Sayre, C.I.; Pate, B.D.

    1984-01-01

    Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using sup(18)F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra

  5. Diabetic patients have abnormal cerebral autoregulation during cardiopulmonary bypass

    Croughwell, N.; Lyth, M.; Quill, T.J.; Newman, M.; Greeley, W.J.; Smith, L.R.; Reves, J.G.

    1990-01-01

    We tested the hypothesis that insulin-dependent diabetic patients with coronary artery bypass graft surgery experience altered coupling of cerebral blood flow and oxygen consumption. In a study of 23 patients (11 diabetics and 12 age-matched controls), cerebral blood flow was measured using 133Xe clearance during nonpulsatile, alpha-stat blood gas managed cardiopulmonary bypass at the conditions of hypothermia and normothermia. In diabetic patients, the cerebral blood flow at 26.6 +/- 2.42 degrees C was 25.3 +/- 14.34 ml/100 g/min and at 36.9 +/- 0.58 degrees C it was 27.3 +/- 7.40 ml/100 g/min (p = NS). The control patients increased cerebral blood flow from 20.7 +/- 6.78 ml/100 g/min at 28.4 +/- 2.81 degrees C to 37.6 +/- 8.81 ml/100 g/min at 36.5 +/- 0.45 degrees C (p less than or equal to 0.005). The oxygen consumption was calculated from jugular bulb effluent and increased from hypothermic values of 0.52 +/- 0.20 ml/100 g/min in diabetics to 1.26 +/- 0.28 ml/100 g/min (p = 0.001) at normothermia and rose from 0.60 +/- 0.27 to 1.49 +/- 0.35 ml/100 g/min (p = 0.0005) in the controls. Thus, despite temperature-mediated changes in oxygen consumption, diabetic patients did not increase cerebral blood flow as metabolism increased. Arteriovenous oxygen saturation gradients and oxygen extraction across the brain were calculated from arterial and jugular bulb blood samples. The increase in arteriovenous oxygen difference between temperature conditions in diabetic patients and controls was significantly different (p = 0.01). These data reveal that diabetic patients lose cerebral autoregulation during cardiopulmonary bypass and compensate for an imbalance in adequate oxygen delivery by increasing oxygen extraction

  6. Metabolic abnormalities in Williams-Beuren syndrome.

    Palacios-Verdú, María Gabriela; Segura-Puimedon, Maria; Borralleras, Cristina; Flores, Raquel; Del Campo, Miguel; Campuzano, Victoria; Pérez-Jurado, Luis Alberto

    2015-04-01

    Williams-Beuren syndrome (WBS, OMIM-194050) is a neurodevelopmental disorder with multisystemic manifestations caused by a 1.55-1.83 Mb deletion at 7q11.23 including 26-28 genes. Reported endocrine and metabolic abnormalities include transient hypercalcaemia of infancy, subclinical hypothyroidism in ∼ 30% of children and impaired glucose tolerance in ∼ 75% of adult individuals. The purpose of this study was to further study metabolic alterations in patients with WBS, as well as in several mouse models, to establish potential candidate genes. We analysed several metabolic parameters in a cohort of 154 individuals with WBS (data available from 69 to 151 cases per parameter), as well as in several mouse models with complete and partial deletions of the orthologous WBS locus, and searched for causative genes and potential modifiers. Triglyceride plasma levels were significantly decreased in individuals with WBS while cholesterol levels were slightly decreased compared with controls. Hyperbilirubinemia, mostly unconjugated, was found in 18.3% of WBS cases and correlated with subclinical hypothyroidism and hypotriglyceridemia, suggesting common pathogenic mechanisms. Haploinsufficiency at MLXIPL and increased penetrance for hypomorphic alleles at the UGT1A1 gene promoter might underlie the lipid and bilirubin alterations. Other disturbances included increased protein and iron levels, as well as the known subclinical hypothyroidism and glucose intolerance. Our results show that several unreported biochemical alterations, related to haploinsufficiency for specific genes at 7q11.23, are relatively common in WBS. The early diagnosis, follow-up and management of these metabolic disturbances could prevent long-term complications in this disorder. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  7. Frequency of metabolic abnormalities in urinary stones patients.

    Ahmad, Iftikhar; Pansota, Mudassar Saeed; Tariq, Muhammad; Tabassum, Shafqat Ali

    2013-11-01

    To determine the frequency of metabolic abnormalities in the serum and urine of patients with urinary stones disease. Two hundred patients with either multiple or recurrent urolithiasis diagnosed on ultrasonography and intravenous urography were included in this study. 24 hour urine sample were collected from each patient and sent for PH, specific gravity, Creatinine, uric acid, calcium, phosphate, oxalate, citrate and magnesium. In addition, blood sample of each patient was also sent for serum levels of urea, creatinine, uric acid, phosphate and calcium. Mean age of patients was 38 ± 7.75 years with male to female ratio of 2:1. The main presenting complaint was lumber pain and 82.5% patients were found to have calcium oxalate stones on chemical analysis. Metabolic abnormalities were found in 90.5% patients, whereas there were no metabolic abnormalities in 19 (9.5%) patients. Forty patients (21.5%) only had one metabolic abnormality and 157 (78.5%) patients had multiple metabolic abnormalities. Hyperoxaluria was the most commonly observed metabolic abnormality and was found in 64.5% patients. Other significant metabolic abnormalities were hypercalciuria, Hypercalcemia, hypocitraturia and hyperuricemia. This study concludes that frequency of metabolic abnormalities is very high in patients with urolithiasis and hyperoxaluria, hypercalciuria and hypocitraturia are the most important metabolic abnormalities observed in these patients.

  8. Regional cerebral blood flow abnormalities in patients with primary hyperparathyroidism

    Cermik, Tevfik F.; Kaya, Meryem; Bedel, Deniz; Berkarda, Sakir; Yigitbasi, Oemer N.; Ugur-Altun, Betuel

    2007-01-01

    We assessed the alterations in regional cerebral blood flow (rCBF) in patients with primary hyperparathyroidism (PHP) before parathyroidectomy by semiquantitative analysis of brain single photon emission computed tomography (SPECT) images. Included in this prospective study were 14 patients (mean age 47.6 ± 10.4 years; 3 male, 11 female) and 10 control subjects (mean age 36.0 ± 8.5 years, 6 male, 4 female) were SPECT imaging was performed using a dual-headed gamma camera 60-90 min after intravenous administration of 925 MBq Tc-99m HMPAO. The corticocerebellar rCBF ratios were calculated from 52 brain areas and reference lower values (RLVs) were calculated from the rCBF ratios of control subjects. The regional ratios that were below the corresponding RLV were considered abnormal (hypoperfused). Hypoperfusion was shown in 171 out of 728 regions (23%) and there was a significant correlation between serum calcium, PTH levels and the sum of hypoperfused regions in the patient group (R = 0.75 and P = 0.001, and R = 0.75, P = 0.001, respectively). Significantly reduced rCBF were found in the following cortical regions: bilateral cingulate cortex, superior and inferior frontal cortex, anterior temporal cortex, precentral gyrus, postcentral gyrus and parietal cortex, and right posterior temporal cortex. Our results indicate that alterations in rCBF in patients with PHP can be demonstrated with brain SPECT. The correlation between serum calcium, PTH levels and the sum of hypoperfused regions indicates that there may be a strong relationship between rCBF abnormalities and increased levels of serum calcium and PTH. In addition, the degree of rCBF abnormalities could be determined by brain SPECT in PHP patients with or without psychiatric symptoms. (orig.)

  9. Regional cerebral blood flow abnormalities in patients with primary hyperparathyroidism

    Cermik, Tevfik F. [Hospital of the University of Trakya, Department of Nuclear Medicine, Edirne (Turkey); Trakya Universitesi Hastanesi, Nukleer Tip Anabilim Dali, Gullapoglu Yerleskesi, Edirne (Turkey); Kaya, Meryem; Bedel, Deniz; Berkarda, Sakir; Yigitbasi, Oemer N. [Hospital of the University of Trakya, Department of Nuclear Medicine, Edirne (Turkey); Ugur-Altun, Betuel [Hospital of the University of Trakya, Department of Internal Medicine, Division of Endocrinology, Edirne (Turkey)

    2007-04-15

    We assessed the alterations in regional cerebral blood flow (rCBF) in patients with primary hyperparathyroidism (PHP) before parathyroidectomy by semiquantitative analysis of brain single photon emission computed tomography (SPECT) images. Included in this prospective study were 14 patients (mean age 47.6 {+-} 10.4 years; 3 male, 11 female) and 10 control subjects (mean age 36.0 {+-} 8.5 years, 6 male, 4 female) were SPECT imaging was performed using a dual-headed gamma camera 60-90 min after intravenous administration of 925 MBq Tc-99m HMPAO. The corticocerebellar rCBF ratios were calculated from 52 brain areas and reference lower values (RLVs) were calculated from the rCBF ratios of control subjects. The regional ratios that were below the corresponding RLV were considered abnormal (hypoperfused). Hypoperfusion was shown in 171 out of 728 regions (23%) and there was a significant correlation between serum calcium, PTH levels and the sum of hypoperfused regions in the patient group (R = 0.75 and P = 0.001, and R = 0.75, P = 0.001, respectively). Significantly reduced rCBF were found in the following cortical regions: bilateral cingulate cortex, superior and inferior frontal cortex, anterior temporal cortex, precentral gyrus, postcentral gyrus and parietal cortex, and right posterior temporal cortex. Our results indicate that alterations in rCBF in patients with PHP can be demonstrated with brain SPECT. The correlation between serum calcium, PTH levels and the sum of hypoperfused regions indicates that there may be a strong relationship between rCBF abnormalities and increased levels of serum calcium and PTH. In addition, the degree of rCBF abnormalities could be determined by brain SPECT in PHP patients with or without psychiatric symptoms. (orig.)

  10. Positron emission tomography and cerebral metabolism

    Comar, D.; Maziere, M.; Zarifian, E.; Naquet, R.

    1979-01-01

    The association of new methods of labelling with short lived radioisotopes and of visualisation 'in vivo' of these labelled molecules by emission tomography, provide the possibility of studying brain metabolism at different levels. Two examples will illustrate the possibilities of this methodology. Cerebral metabolism of methionine- 11 C in phenylketonutic patients: The cerebral uptake of methionine was measured in 24 PKU children aged 1 to 40 months on a low protein diet. Ten of them were examined twice at intervals of several months. Stopping the diet for one week leads to an increase in blood phenylalanine and to a significant important decrease in brain uptake of labelled methionine. Futhermore, for children under treatment having a low phenylalanine blood concentration, brain uptake of methionine decreases with age between 1 and 40 months. These results suggest that the treatment of this disease should be started as soon as possible after birth. Cerebral metabolism of psychoactive drugs: The study of the brain distribution and kinetics of psychoactive drugs may help in understanding their mode of action. Chlorpromazine- 11 C was administered i.v. to schyzophrenic patients not previously treated with neuroleptics. In all patients the brain uptake of the drug was high and rapid, and was localized mainly in the grey matter, probably in proportion to the blood flow. Non-specific binding of this drug to brain proteins prevented visualization of specific binding to dopaminergic or αnor-adrenergic receptors. Specific receptor binding of benzodiazepines was however visualized in the brain of baboons after injection of 11 C-flunitrazepam (specific activity = 600 Ci/μmole) and subsequent displacement of this radioactive ligand by a pharmacological dose of Lorazepam

  11. Correlations between cerebral glucose metabolism and neuropsychological test performance in nonalcoholic cirrhotics.

    Lockwood, Alan H; Weissenborn, Karin; Bokemeyer, Martin; Tietge, U; Burchert, Wolfgang

    2002-03-01

    Many cirrhotics have abnormal neuropsychological test scores. To define the anatomical-physiological basis for encephalopathy in nonalcoholic cirrhotics, we performed resting-state fluorodeoxyglucose positron emission tomographic scans and administered a neuropsychological test battery to 18 patients and 10 controls. Statistical parametric mapping correlated changes in regional glucose metabolism with performance on the individual tests and a composite battery score. In patients without overt encephalopathy, poor performance correlated with reductions in metabolism in the anterior cingulate. In all patients, poor performance on the battery was positively correlated (p glucose metabolism in bifrontal and biparietal regions of the cerebral cortex and negatively correlated with metabolism in hippocampal, lingual, and fusiform gyri and the posterior putamen. Similar patterns of abnormal metabolism were found when comparing the patients to 10 controls. Metabolic abnormalities in the anterior attention system and association cortices mediating executive and integrative function form the pathophysiological basis for mild hepatic encephalopathy.

  12. Selective cerebral perfusion prevents abnormalities in glutamate cycling and neuronal apoptosis in a model of infant deep hypothermic circulatory arrest and reperfusion.

    Kajimoto, Masaki; Ledee, Dolena R; Olson, Aaron K; Isern, Nancy G; Robillard-Frayne, Isabelle; Des Rosiers, Christine; Portman, Michael A

    2016-11-01

    Deep hypothermic circulatory arrest is often required for the repair of complex congenital cardiac defects in infants. However, deep hypothermic circulatory arrest induces neuroapoptosis associated with later development of neurocognitive abnormalities. Selective cerebral perfusion theoretically provides superior neural protection possibly through modifications in cerebral substrate oxidation and closely integrated glutamate cycling. We tested the hypothesis that selective cerebral perfusion modulates glucose utilization, and ameliorates abnormalities in glutamate flux, which occur in association with neuroapoptosis during deep hypothermic circulatory arrest. Eighteen infant male Yorkshire piglets were assigned randomly to two groups of seven (deep hypothermic circulatory arrest or deep hypothermic circulatory arrest with selective cerebral perfusion for 60 minutes at 18℃) and four control pigs without cardiopulmonary bypass support. Carbon-13-labeled glucose as a metabolic tracer was infused, and gas chromatography-mass spectrometry and nuclear magnetic resonance were used for metabolic analysis in the frontal cortex. Following 2.5 h of cerebral reperfusion, we observed similar cerebral adenosine triphosphate levels, absolute levels of lactate and citric acid cycle intermediates, and carbon-13 enrichment among three groups. However, deep hypothermic circulatory arrest induced significant abnormalities in glutamate cycling resulting in reduced glutamate/glutamine and elevated γ-aminobutyric acid/glutamate along with neuroapoptosis, which were all prevented by selective cerebral perfusion. The data suggest that selective cerebral perfusion prevents these modifications in glutamate/glutamine/γ-aminobutyric acid cycling and protects the cerebral cortex from apoptosis. © The Author(s) 2016.

  13. Evaluation of regional metabolic abnormality and treatment effect in patients with narcolepsy

    Kim, Yu Kyeong; Yoon, In Young; Shin, Youn Kyung; Eo, Jae Sean; Won, Oh So; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-07-01

    The aim of the present study was to evaluated regional metabolic abnormalities in untreated narcoleptic patients and the changes in regional cerebral metabolism after treatment with modafinil. Eight drug free narcoleptic patients (mean age of 17{+-}1 yr) participated in this study. Two [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans before and after a 2-week titrated modafinil treatment (target dose = 100{approx}400 mg/day). The PET data were analyzed by using statistical parametric mapping methods to identify the regional cerebral abnormalities compared with those of healthy young controls. In addition, treatment effect was evaluated by comparison between before and after treatment scan. In narcolepsy patients, a significant reduction of regional metabolism was demonstrated in the brain stem, bilateral hypothalamus, posterior thalamus, hippocampus, parahippocampal gyrus, and adjacent perihinal area on pretreatment scans compared with those of healthy subjects. The decrease glucose metabolism was also found in the occipital cortex and cerebellum. The patients could control daytime sleepiness after treatment. Posttreatment scan showed a significant increase in regional metabolism in the left hippocampus. This study demonstrated the metabolic abnormalities and the effect of modafinil treatment in narcoleptic patients in the sleep associated regions. This results could be helpful to understand the pathophysiology of the narcolepsy and treatment mechanism.

  14. Cerebral oxygen metabolism and cerebral blood flow in man during light sleep (stage 2)

    Madsen, P L; Schmidt, J F; Holm, S

    1991-01-01

    . They differ in respect of arousal threshold as a stronger stimulus is required to awaken a subject from deep sleep as compared to light sleep. Our results suggest that during non-rapid eye movement sleep cerebral metabolism and thereby cerebral synaptic activity is correlated to cerebral readiness rather than...

  15. Cerebral ammonia metabolism in hyperammonemic rats

    Cooper, A J; Mora, S N; Cruz, N F; Gelbard, A S

    1985-06-01

    The short-term metabolic fate of blood-borne (/sup 13/N)ammonia was determined in the brains of chronically (8- or 14-week portacaval-shunted rats) or acutely (urease-treated) hyperammonemic rats. Using a freeze-blowing technique it was shown that the overwhelming route for metabolism of blood-borne (/sup 13/N)ammonia in normal, chronically hyperammonemic and acutely hyperammonemic rat brain was incorporation into glutamine (amide). However, the rate of turnover of (/sup 13/N)ammonia to L-(amide-/sup 13/N)glutamine was slower in the hyperammonemic rat brain than in the normal rat brain. The activities of several enzymes involved in cerebral ammonia and glutamate metabolism were also measured in the brains of 14-week portacaval-shunted rats. The rat brain appears to have little capacity to adapt to chronic hyperammonemia because there were no differences in activity compared with those of weight-matched controls for the following brain enzymes involved in glutamate/ammonia metabolism: glutamine synthetase, glutamate dehydrogenase, aspartate aminotransferase, glutamine transaminase, glutaminase, and glutamate decarboxylase. The present findings are discussed in the context of the known deleterious effects on the CNS of high ammonia levels in a variety of diseases.

  16. Cerebral circulation and metabolism with recovery of chronic poststroke aphasia

    Yamada, Tomoyuki; Kabasawa, Hidehiro; Matsubara, Michitaka; Hibino, Hiroaki; Kamimoto, Kaoru; Fukagawa, Kazutoshi

    2004-01-01

    The recruitment of cerebral circulation and oxygen metabolism in the particular brain areas responsible for poststroke aphasia are necessary for recovery. This study was undertaken to investigate changes in cerebral circulation and oxygen metabolism corresponding to improvement of aphasia. Twenty-nine right-handed chronic aphasic patients with left hemispheric stroke were studied. Aphasia was evaluated as the score of fluency, comprehension, repetition and naming by the Western Aphasia Battery (Japanese version). Concurrent with the evaluation of aphasia, positron emission tomography (PET) scans were performed. After several months of speech therapy, PET scans and evaluation of aphasia were reperformed. Both regional cerebral blood flow and the cerebral metabolic rate for oxygen significantly increased in the left upper superior and middle temporal gyri, and in the left upper inferior frontal gyrus in the fair recovery group for comprehension, repetition and naming. In the fair recovery group for fluency, the cerebral metabolic rate for oxygen significantly increased in the left upper superior and middle temporal gyri, but regional cerebral blood flow increased insignificantly in these areas. In the lower white matter of the right parietal lobe, both the regional cerebral blood flow and the cerebral metabolic rate for oxygen were significantly increased in the fair recovery group for all aphasic features. The recruitment of cerebral circulation and oxygen metabolism in the left temporo-parietal area, in the left inferior frontal area, and in the right deep parietal area are essentially responsible for the recovery of aphasia. (author)

  17. Self-reported fatigue common among optimally treated HIV patients: no correlation with cerebral FDG-PET scanning abnormalities

    Andersen, Ase B; Law, Ian; Ostrowski, Sisse R

    2006-01-01

    patients (n = 95), known to be HIV positive for 5 years, on anti-retroviral therapy for a minimum of 3 years and with CD4 counts above 0.2 x 10(9) cells/l, completed a validated fatigue inventory, and plasma was analysed for pro-inflammatory markers including tumour necrosis factor-alpha, interleukin 6......-PET) scanning. RESULTS: Fifteen percent suffered from severe fatigue, but no association with pro-inflammatory markers was found. About 50% of the FDG-PET-scanned patients showed minor abnormalities in the relative cerebral metabolic rate of glucose. These abnormalities were not associated with fatigue...

  18. Radiotherapy-induced cerebral abnormalities in patients with low-grade glioma

    Postma, TJ; Klein, M; Verstappen, CCP; Bromberg, JEC; Swennen, M; Langendijk, JA; Taphoorn, MJB; Scheltens, P; Slotman, BJ; van der Ploeg, HM; Aaronson, NK; Heimans, JJ

    2002-01-01

    Abnormalities on CT or MRI and neuropsychological performance in patients with low-grade glioma, with (n = 23) or without (n = 16) prior cerebral radiotherapy, were evaluated. Cerebral atrophy was observed in 14 of 23 patients (61%) treated with prior radiotherapy, and in 1 of 16 patients (6%)

  19. Cerebral blood flow and metabolism during exercise: implications for fatigue

    Seifert, T.; Lieshout, J.J. van; Secher, Niels

    2008-01-01

    During exercise: the Kety-Schmidt-determined cerebral blood flow (CBF) does not change because the jugular vein is collapsed in the upright position. In contrast, when CBF is evaluated by (133)Xe clearance, by flow in the internal carotid artery, or by flow velocity in basal cerebral arteries......, a approximately 25% increase is detected with a parallel increase in metabolism. During activation, an increase in cerebral O(2) supply is required because there is no capillary recruitment within the brain and increased metabolism becomes dependent on an enhanced gradient for oxygen diffusion. During maximal...... whole body exercise, however, cerebral oxygenation decreases because of eventual arterial desaturation and marked hyperventilation-related hypocapnia of consequence for CBF. Reduced cerebral oxygenation affects recruitment of motor units, and supplemental O(2) enhances cerebral oxygenation and work...

  20. Normal and abnormal lipid and lipoprotein metabolism

    2009-03-20

    Mar 20, 2009 ... This article focuses on lipid and lipoprotein metabolism and introduces a range of genetic ... spherical structures that are suspended in the plasma and whose ..... atherosclerosis. Table II suggests a simple classification of.

  1. Low cerebral blood flow after cardiac arrest is not associated with anaerobic cerebral metabolism

    Hoedemaekers, C.W.E.; Ainslie, Philip N.; Hinssen, S.; Aries, M.J.; Bisschops, Laurens L.; Hofmeijer, Jeannette; van der Hoeven, J.G.

    2017-01-01

    Aim of the study Estimation of cerebral anaerobic metabolism in survivors and non-survivors after cardiac arrest. Methods We performed an observational study in twenty comatose patients after cardiac arrest and 19 healthy control subjects. We measured mean flow velocity in the middle cerebral artery

  2. Cerebral oxygen metabolism and cerebral blood flow in man during light sleep (stage 2)

    Madsen, P L; Schmidt, J F; Holm, S

    1991-01-01

    We measured cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) during light sleep (stage 2) in 8 young healthy volunteers using the Kety-Schmidt technique with 133Xe as the inert gas. Measurements were performed during wakefulness and light sleep as verified by standard...... polysomnography. Unlike our previous study in man showing a highly significant 25% decrease in CMRO2 during deep sleep (stage 3-4) we found a modest but statistically significant decrease of 5% in CMRO2 during stage 2 sleep. Deep and light sleep are both characterized by an almost complete lack of mental activity....... They differ in respect of arousal threshold as a stronger stimulus is required to awaken a subject from deep sleep as compared to light sleep. Our results suggest that during non-rapid eye movement sleep cerebral metabolism and thereby cerebral synaptic activity is correlated to cerebral readiness rather than...

  3. Hypothermia reduces cerebral metabolic rate and cerebral blood flow in newborn pigs

    Busija, D.W.; Leffler, C.W.

    1987-01-01

    The authors examined effects of hypothermia on cerebral metabolic rate and cerebral blood flow in anesthetized, newborn pigs (1-4 days old). Cerebral blood flow (CBF) was determined with 15-μm radioactive microspheres. Regional CBF ranged from 44 to 66 ml·min -1 ·100 g -1 , and cerebral metabolic rate was 1.94 ± 0.23 ml O 2 ·100 g -1 ·min -1 during normothermia (39 degree C). Reduction of rectal temperature to 34-35 degree C decreased CBF and cerebral metabolic rate 40-50%. In another group of piglets, they examined responsiveness of the cerebral circulation to arterial hypercapnia during hypothermia. Although absolute values for normocapnic and hypercapnic CBF were reduced by hypothermia and absolute values for normocapnic and hypercapnic cerebrovascular resistance were increased, the percentage changes from control in these variables during hypercapnia were similar during normothermia and hypothermia. In another group of animals that were maintained normothermic and exposed to two episodes of hypercapnia, there was no attenuation of cerebrovascular dilation during the second episode. They conclude that hypothermia reduces CBF secondarily to a decrease in cerebral metabolic rate and that percent dilator responsiveness to arterial hypercapnia is unaltered when body temperature is reduced

  4. Dynamic change in cerebral microcirculation and focal cerebral metabolism in experimental subarachnoid hemorrhage in rabbits.

    Song, Jin-Ning; Chen, Hu; Zhang, Ming; Zhao, Yong-Lin; Ma, Xu-Dong

    2013-03-01

    Regional cerebral blood flow (rCBF) in the cerebral metabolism and energy metabolism measurements can be used to assess blood flow of brain cells and to detect cell activity. Changes of rCBF in the cerebral microcirculation and energy metabolism were determined in an experimental model of subarachnoid hemorrhage (SAH) model in 56 large-eared Japanese rabbits about 12 to 16-month old. Laser Doppler flowmetry was used to detect the blood supply to brain cells. Internal carotid artery and vein blood samples were used for duplicate blood gas analysis to assess the energy metabolism of brain cells. Cerebral blood flow (CBF) was detected by single photon emission computed tomography (SPECT) perfusion imaging using Tc-99m ethyl cysteinate dimer (Tc-99m ECD) as an imaging reagent. The percentage of injected dose per gram of brain tissue was calculated and analyzed. There were positive correlations between the percentage of radionuclide injected per gram of brain tissue and rCBF supply and cerebral metabolic rate for oxygen (P brain cells after SAH, and also found that deterioration of energy metabolism of brain cells played a significant role in the development of SAH. There are matched reductions in CBF and metabolism. Thus, SPECT imaging could be used as a noninvasive method to detect CBF.

  5. Cerebral blood flow and cerebral oxygen metabolism in thalamic hemorrhage

    Yasui, Nobuyuki; Asakura, Ken

    1987-01-01

    Cerebral blood flow (CBF), cerebral oxygen consumption (CMRO 2 ), oxygen extraction fraction (OEF) and cerebral blood volume (CBV) were studied in 20 cases of thalamic hemorrhage using positron CT and 15 O labeled gas steady-state inhalation method. CBF reduction was limited around the thalamus in the small sized hematoma. CBF were significantly diminished in the mean cortical, parietal, temporal, basal ganglia and thalamic area ipsilateral and cerebellar cortex contralateral to the medium sized hematoma. There was bilateral and diffuse CBF reduction in the large sized hematoma which was caused by increased intracranial pressure. CMRO 2 value were similary changed as CBF. OEF change showed within normal limit. Diffuse CBV reduction was observed in the large sized hematoma. This reduction was the result of decreased vascular bed caused by mass effect of the hematoma and hydrocephalus. Effect of surgical treatment such as ventricular drainage and hematoma evacuation were also discussed in correlation to CBF in some case using positron and single photon ECT. (author)

  6. PET imaging of cerebral perfusion and oxygen metabolism in stroke

    Pointon, O.; Yasaka, M.; Berlangieri, S.U.; Newton, M.R.; Thomas, D.L.; Chan, C.G.; Egan, G.F.; Tochon-Danguy, H.J.; O``Keefe, G.; Donnan, G.A.; McKay, W.J. [Austin Hospital, Melbourne, VIC (Australia). Centre for PET and Depts of Nuclear Medicine and Neurology

    1998-03-01

    Full text: Stroke remains a devastating clinical event with few therapeutic options. In patients with acute stroke, we studied the cerebral perfusion and metabolic patterns with {sup 15}O-CO{sub 2} or H{sub 2}O and {sup 15}O-O{sub 2} positron emission tomography and correlated these findings to the clinical background. Forty three patients underwent 45 studies 0-23 days post-stroke (mean 7 days). Fifteen patients showed luxury perfusion (Group A), 10 had matched low perfusion and metabolism (B) and 3 showed mixed pattern including an area of misery perfusion (C). Seventeen showed no relevant abnormality (D) and there were no examples of isolated misery perfusion. Twelve of the 15 in Group A had either haemorrhagic transformation on CT, re-opening on angiography, or a cardioembolic mechanism. In contrast only 5/10 in Group B, 0/3 in Group C and 2/17 in Group D had these features. Although 7/10 in group B had moderate or large size infarcts on CT the incidence of haemorrhagic transformation was low (2/10) and significant carotid stenoses were more common in those studied (5/8) compared with the other groups. Misery perfusion was not seen beyond five days. Thus, luxury perfusion seems to be related to a cardio-embolic mechanism or reperfusion. Matched low perfusion and metabolism was associated with a low rate of haemorrhagic transformation despite a high incidence of moderate to large size infarcts. Misery perfusion is an early phenomenon in the evolution of ischaemic stroke.

  7. Normal and abnormal neuronal migration in the developing cerebral cortex

    Sun, Xue-Zhi; Takahashi, Sentaro; Cui, Chun; Zhang, Rui; Sakata-Haga, Hiromi; Sawada, Kazuhiko; Fukui, Yoshihiro

    2002-01-01

    Neuronal migration is the critical cellular process which initiates histogenesis of cerebral cortex. Migration involves a series of complex cell interactions and transformation. After completing their final mitosis, neurons migrate from the ventricular zone into the cortical plate, and then establish neuronal lamina and settle onto the outermost layer, forming an “inside-out” gradient of maturation. This process is guided by radial glial fibers, requires proper receptors, ligands, other unkno...

  8. Metabolic abnormalities in cachexia and anorexia.

    Tisdale, M J

    2000-10-01

    An increased glucose requirement by many solid tumors produces an increased metabolic demand on the liver, resulting in an increased energy expenditure. In addition, several cytokines and tumor catabolic products have been suggested as being responsible for the depletion of adipose tissue and skeletal-muscle mass in cachexia. A sulphated glycoprotein of molecular mass 24 kDa, produced by cachexia-inducing tumors and present in the urine of cancer patients actively losing weight, has been shown to be capable of inducing direct muscle catabolism in vitro and a state of cachexia in vivo, with specific loss of the non-fat carcass mass. In vitro studies have shown the bioactivity of this proteolysis-inducing factor to be attenuated by the polyunsaturated fatty acid, eicosapentaenoic acid. Preliminary clinical studies have shown that eicosapentaenoic acid stabilizes body weight and protein and fat reserves in patients with pancreatic carcinoma. Further trials are required to confirm the efficacy of eicosapentaenoic acid and to determine the anticachectic activity in other types of cancer.

  9. Cerebral abnormalities: use of calculated T1 and T2 magnetic resonance images for diagnosis

    Mills, C.M.; Crooks, L.E.; Kaufman, L.; Brant-Zawadzki, M.

    1984-01-01

    The potential clinical importance of T1 and T2 relaxation times in distinguishing normal and pathologic tissue with magnetic resonance (MR) is discussed and clinical examples of cerebral abnormalities are given. Five patients with cerebral infarction, 15 with multiple sclerosis, two with Wilson disease, and four with tumors were imaged. Hemorrhagic and ischemic cerebrovascular accidents were distinguished using the spin echo technique. In the patients with multiple sclerosis, lesions had prolonged T1 and T2 times, but the definition of plaque was limited by spatial resolution. No abnormalities in signal intensity were seen in the patient with Wilson disease who was no longer severly disabled; abnormal increased signal intensity in the basal ganglia was found in the second patient with Wilson disease. Four tumors produced abnormal T1 and T2 relaxation times but these values alone were not sufficient for tumor characterization

  10. Cerebral blood flow and oxygen metabolism after subarachnoid hemorrhage

    Ito, Hidemichi; Sakurai, Takashi; Hayashi, Tatsuo; Hashimoto, Takuo

    2004-01-01

    The mechanism of reduction of cerebral circulation in the early phase of aneurysmal subarachnoid hemorrhage (SAH) has not yet been clarified. Previous studies have variously indicated that cerebral blood flow (CBF) reduction may be due to cerebral vasospasm, an elevation in intracranial pressure (ICP), constriction of intraparenchymal arterioles, or metabolic reduction. The aim of this study is to investigate the relationship between cerebral circulation and oxygen metabolism. In 36 patients with aneurysmal SAH, the values of mean cerebral blood flow (mCBF), cerebral metabolic rate of oxygen (GMRO 2 ) and oxygen extraction fraction (OEF) were measured by using single photon emission computed tomography (SPECT) with arterial blood drawing and oxygen saturation of internal jugular bulb blood (SjO 2 ) in the acute stage (1-3 days after onset) and the spasm stage (7-10 days after onset). The patients in our study were selected by using the following criteria: no history of cerebrovascular or cardiopulmonary diseases; under the age of 70; the ruptured aneurysm was treated by clipping or coil embolization within 72 hours after onset; no symptoms of cerebral vasospasm; no signs of cerebral ischemic change on CT scans. These patients were divided into 2 groups according to the World Federation of Neurological Surgeons (WFNS) grading classification; the mild group (Grades I and II) consisted of 27 cases and the severe group (Grade IV) consisted of 9 cases. We studied differences in mCBF CMRO 2 , and OEF between the mild group and severe group. In the mild group, mCBF, CMRO 2 , and OEF were significantly higher than in the severe group during both the acute and the spasm stage. Also mCBF showed a direct correlation with CMRO 2 . All the patients were kept under the following conditions: the bed was positioned so that the upper body was raised at an angle at 30 deg; blood pressure was maintained at 130-150 mmHg and PaCO 2 of arterial blood was maintained at 35-40 mmHg; ICP

  11. Cerebral biochemical abnormalities in experimental maternal phenylketonuria: gangliosides and sialoglycoproteins

    Loo, Y.H.; Hyde, K.R.; Lin, F.H.; Wisniewski, H.M.

    1985-01-01

    The present study sought a biochemical explanation for retarded brain development in the heterozygous offspring of the phenylketonuric (PKU) mother. Two rat models of simulated maternal PKU, one induced by p-chloropheylalanine and phenylalanine and the other by phenylacetate, were employed in this investigation. Maternal PKU had no influence on cerebral concentrations of DNA, protein, and cholesterol, which were normal in the 2 d old pup. However, there was a noticeable disruption of the normal ganglioside pattern and a significant reduction of sialoglycoproteins. Concomitant with a delayed drop in the gangliosides Q/sub 1b/ and D 3 , was a slower rise in M 1 and D/sub 1a/. At least 66% of sialoglycoproteins located on SDS-PAGE gel chromatograms, by radioactivity incorporated in vivo from radiolabeled N-acetylmannosamine and by ( 3 H) sialic acid released by neuraminidase from periodate-( 3 H) borohydride labeled glycoproteins, have mobilites of the cell adhesion molecules N-CAM and D-CAM. Whether the reduction of the sialogylcoproteins induced by maternal PKU is mainly in these cell adhesion molecules requires further investigation. Interference with the function of gangliosides and certain sialoglycoproteins during cerebral development may contribute to the brain dysfunction observed in the offspring of PKU mothers not on diet control during pregnancy. 49 references, 2 figures, 3 tables

  12. A case of glutaric aciduria type I with unique abnormalities in the cerebral CT findings

    Yamaguchi, Seiji; Orii, Tadao; Yasuda, Kanji; Kohno, Yoshinori

    1987-01-01

    A first Japanese case of glutaric aciduria type I (GA-I) was described. She was a 7-month-old girl presenting with poor head control, irritability and sleeplessness. The profile of urinary organic acids by gas chromatography mass spectrometry (GC/MS) suggesting GA-I were confirmed by no activity of glutaryl-CoA dehydrogenase in the fibroblasts. The cerebral computer tomography (CT) showed marked changes such as large fluid collections on bilateral frontotemporal regions and a slight enlargement of bilateral ventricles. The amounts of urinary glutarate excretion decreased after restriction of lysine and tryptophan in her diet and administration of carnitine improved the carnitine levels in blood and urine, while these were less effective for the neurological symptoms. On the other hand, oral administration of lioresal, an analogue of gamma-aminobutyrate (GABA), cleared her symptoms such as ill temper, irritability and sleeplessness dramatically, and the abnormalities of the CT examinations were not more deteriorative until 2 years of her age at least. The neurological manifestations of GA-I seemed to be affected by the unusual metabolism of GABA in the central nervous system. (author)

  13. Cerebral blood flow in normal and abnormal sleep and dreaming

    Meyer, J.S.; Ishikawa, Y.; Hata, T.; Karacan, I.

    1987-01-01

    Measurements of regional or local cerebral blood flow (CBF) by the xenon-133 inhalation method and stable xenon computerized tomography CBF (CTCBF) method were made during relaxed wakefulness and different stages of REM and non-REM sleep in normal age-matched volunteers, narcoleptics, and sleep apneics. In the awake state, CBF values were reduced in both narcoleptics and sleep apneics in the brainstem and cerebellar regions. During sleep onset, whether REM or stage I-II, CBF values were paradoxically increased in narcoleptics but decreased severely in sleep apneics, while in normal volunteers they became diffusely but more moderately decreased. In REM sleep and dreaming CBF values greatly increased, particularly in right temporo-parietal regions in subjects experiencing both visual and auditory dreaming

  14. Cerebral blood flow and metabolism during exercise: implications for fatigue.

    Secher, Neils H; Seifert, Thomas; Van Lieshout, Johannes J

    2008-01-01

    During exercise: the Kety-Schmidt-determined cerebral blood flow (CBF) does not change because the jugular vein is collapsed in the upright position. In contrast, when CBF is evaluated by (133)Xe clearance, by flow in the internal carotid artery, or by flow velocity in basal cerebral arteries, a approximately 25% increase is detected with a parallel increase in metabolism. During activation, an increase in cerebral O(2) supply is required because there is no capillary recruitment within the brain and increased metabolism becomes dependent on an enhanced gradient for oxygen diffusion. During maximal whole body exercise, however, cerebral oxygenation decreases because of eventual arterial desaturation and marked hyperventilation-related hypocapnia of consequence for CBF. Reduced cerebral oxygenation affects recruitment of motor units, and supplemental O(2) enhances cerebral oxygenation and work capacity without effects on muscle oxygenation. Also, the work of breathing and the increasing temperature of the brain during exercise are of importance for the development of so-called central fatigue. During prolonged exercise, the perceived exertion is related to accumulation of ammonia in the brain, and data support the theory that glycogen depletion in astrocytes limits the ability of the brain to accelerate its metabolism during activation. The release of interleukin-6 from the brain when exercise is prolonged may represent a signaling pathway in matching the metabolic response of the brain. Preliminary data suggest a coupling between the circulatory and metabolic perturbations in the brain during strenuous exercise and the ability of the brain to access slow-twitch muscle fiber populations.

  15. Selective cerebral perfusion prevents abnormalities in glutamate cycling and neuronal apoptosis in a model of infant deep hypothermic circulatory arrest and reperfusion

    Kajimoto, Masaki; Ledee, Dolena R.; Olson, Aaron K.; Isern, Nancy G.; Robillard-Frayne, Isabelle; Des Rosiers, Christine; Portman, Michael A.

    2016-10-01

    Rationale: Deep hypothermic circulatory arrest (DHCA) is often required for the repair of complex congenital cardiac defects in infants. However, DHCA induces neuroapoptosis associated with later development of neurocognitive abnormalities. Selective cerebral perfusion (SCP) theoretically provides superior neural protection possibly through modifications in cerebral substrate oxidation and closely integrated glutamate cycling. Objectives: We tested the hypothesis that SCP modulates glucose entry into the citric acid cycle, and ameliorates abnormalities in glutamate flux which occur in association neuroapoptosis during DHCA. Methods and Results: Eighteen male Yorkshire piglets (age 34-44 days) were assigned randomly to 2 groups of 7 (DHCA or DHCA with SCP for 60 minutes at 18 °C) and 4 control pigs without cardiopulmonary bypass support. After the completion of rewarming from DHCA, 13-Carbon-labeled (13C) glucose as a metabolic tracer was infused. We used gas chromatography-mass spectrometry (GCMS) and nuclear magnetic resonance for metabolic analysis in the frontal cortex. Following 2.5 hours of cerebral reperfusion, we observed similar cerebral ATP levels, absolute levels of lactate and citric acid cycle intermediates, and 13C-enrichment. However, DHCA induced significant abnormalities in glutamate cycling resulting in reduced glutamate/glutamine and elevated γ-aminobutyric acid (GABA)/glutamate along with neuroapoptosis (TUNEL), which were all prevented by SCP. Conclusions: DHCA alone induces abnormalities in cycling of the major neurotransmitters in association with neuroapoptosis, but does not alter cerebral glucose utilization during reperfusion. The data suggest that SCP prevents these modifications in glutamate/glutamine/GABA cycling and protects the cerebral cortex from neuroapoptosis.

  16. Correlation of glucose metabolism in brain cells and brain morphological changes with clinical typing in children with cerebral palsy

    Qiongxiang Zhai; Huixian Qiao; Jiqing Liu

    2006-01-01

    BACKGROUND:It is widely known that fluorino-18-fluorodeoxyglucose positron emission tomography(18F-FDG PET)is commonly used to evaluate and diagnose epilepsy;however,whether it is beneficial to understand functional metabolism of bra in cells so as to reflect injured site and degree of brain cells or not should be studied further.OBJECTIVE:To evaluate the correlation between glucose metabolism and clinical typling as well as the conelation between active function of brain cells and degree of brain injury among children with cerbral palsy with 18F-FDG PET and MRI and compare the results of them.DESIGN:Case analysis.SETTING:Department of Pediatrics,People's Hospital of Guangdong Province.PARTICIPANTS:A total of 31 children with cerebral palsy were selected from Out-patient Clinic and In-patient Department of People's Hospital of Guangdong Province from July 2001 to August 2004.Based on clinical criteria of cerebral palsy,patients were classified into spasm(n=10),gradual movement(n=4),mixed type(n =13)and ataxia(n=4).There were 18 boys and 13 girls aged from 10 months to 4 years.All of them were met the diagnostic criteria of cerebral palsy and all parents of them were told the facts.Exclusion cdteria:Patients who had cerebral palsy caused by genetic metabolism disease were excluded.METHODS:①All children accepted MRI examination after hospitalization with Philips Acs NT 15T superconductling magnetic resonance scanner.②All children were fasted for 4 hours.And then,PET image of brain was collected based on T+EID type.If obvious hypermetabolism or hypometabolism region successively occurred on two layers, the image was regarded as abnormality. ③Different correlations of various abnormal greups of MRI and vadous types of cerebral palsy with PET image were compared and analyzed with Erusal-Willas rank sum test.MAIN OUTCOME MEASURES:①Results of 18F-FDG PET;②Results of MRI examination;③Correlation of variously abnormal groups of MRI and various types of cerebral

  17. Cerebral Metabolic Changes Related to Oxidative Metabolism in a Model of Bacterial Meningitis Induced by Lipopolysaccharide

    Munk, Michael; Rom Poulsen, Frantz; Larsen, Lykke

    2018-01-01

    BACKGROUND: Cerebral mitochondrial dysfunction is prominent in the pathophysiology of severe bacterial meningitis. In the present study, we hypothesize that the metabolic changes seen after intracisternal lipopolysaccharide (LPS) injection in a piglet model of meningitis is compatible...... with mitochondrial dysfunction and resembles the metabolic patterns seen in patients with bacterial meningitis. METHODS: Eight pigs received LPS injection in cisterna magna, and four pigs received NaCl in cisterna magna as a control. Biochemical variables related to energy metabolism were monitored by intracerebral...... dysfunction with increasing cerebral LPR due to increased lactate and normal pyruvate, PbtO2, and ICP. The metabolic pattern resembles the one observed in patients with bacterial meningitis. Metabolic monitoring in these patients is feasible to monitor for cerebral metabolic derangements otherwise missed...

  18. Cerebral perfusion abnormalities in therapy-resistant epilepsy in mentally retarded pediatric patients

    Abdel-Dayem, H.M.; Nawaz, K.; Hassoon, M.; Rahman, M.; Olofsson, O.E.

    1990-01-01

    This paper identifies sites of cerebral perfusion abnormalities in therapy-resistant epilepsy in mentally retarded pediatric patients (TREMRPP) using Tc-99m HMPAO and to compare it with the results of electroencephalography (EEG) and fluorographic CT. Thirteen children underwent Tc-99m HMPAO single photon emission CT (SPECT) studies; 11 had fluorographic CT, and 12 had EEG (four had EEG twice). All studies for same patients were within 2 weeks of each other. SPECT studies were reviewed twice by two nuclear medicine physicians without any knowledge of the results of other tests. Fluorographic CT results showed cerebral atrophy in only three and were normal in eight. EEG results were abnormal in all 12 patients examined. Epileptogenic spikes (EPS) were seen in eight patients only. Tc-99m HMPAO SPECT studies were abnormal in all patients; they showed 21 foci of decreased perfusion on nine patients and nine foci of increased perfusion in seven patients (three patients had mixed lesions)

  19. A study of cerebral circulation, metabolism and MRI findings in patients with chronic cerebral circulatory insufficiency

    Kondo, Susumu

    1995-01-01

    Chronic cerebral circulatory insufficiency (CCCI) is a recently proposed clinical entity characterized by symptoms such as dizziness, a feeling of heavy-headedness or vague numbness without any neurological signs or organic vascular lesions on CT. In order to elucidate its pathogenesis, ultrasonic quantitative blood flow measurement system, positron emission tomography (PET) and MRI were employed to study three groups of subjects: 60 subjects with CCCI (group A), 44 subjects with risk factors for cerebrovascular disease but without neurological abnormalities (group B), and 40 normal healthy volunteers (group C). The results are summarized as follows: Mean common carotid blood flow decreased with age in all groups. Common carotid blood flow was lowest in group A and second lowest in group B in every decade of patient age. PET study revealed that CBF and CMRO 2 in all regions examined were significantly lower in group A than in group C. The incidence of MR signal abnormalities in the white matter increased with age. Group A had the highest incidence, and group C had the lowest. Reduction in mean common carotid blood flow and cerebral blood flow was associated with increasing incidence and severity of MR signal abnormalities. These findings indicate that CCCI is a pathologic condition closely related to diffuse cerebral low perfusion resulting from cerebral arteriosclerosis. The symptoms seen in this condition, which are apt to be taken lightly, may warn of impending ischemic stroke. (author)

  20. Cerebral energy metabolism in streptozotocin-diabetic rats

    Biessels, G.J.; Braun, K.P.J.; Graaf, de R.A.; Eijsden, van P.; Gispen, W.H.; Nicolaij, K.

    2001-01-01

    Aims/hypothesis. It is increasingly evident that the brain is another site of diabetic end-organ damage. The pathogenesis has not been fully explained, but seems to involve an interplay between aberrant glucose metabolism and vascular changes. Vascular changes, such as deficits in cerebral blood

  1. Persistent abnormal coronary flow reserve in association with abnormal glucose metabolism affects prognosis in acute myocardial infarction

    Løgstrup, Brian B; Høfsten, Dan E; Christophersen, Thomas B

    2011-01-01

    baseline CFR (P = 0.004), S' (P = 0.045) and abnormal glucose metabolism (P = 0.001) were predictors of a decreased CFR at 3 months of follow-up. In multivariate analyses abnormal glucose metabolism (OR: 5.3; 95%CI: 1.9-14.4; P = 0.001) remained a predictor of decreased CFR at follow-up, furthermore...

  2. Cerebral glucose metabolism in Wernicke's, Broca's, and conduction aphasia

    Metter, E.J.; Kempler, D.; Jackson, C.; Hanson, W.R.; Mazziotta, J.C.; Phelps, M.E.

    1989-01-01

    Cerebral glucose metabolism was evaluated in patients with either Wernicke's (N = 7), Broca's (N = 11), or conduction (N = 10) aphasia using 18 F-2-fluoro-2-deoxy-D-glucose with positron emission tomography. The three aphasic syndromes differed in the degree of left-to-right frontal metabolic asymmetry, with Broca's aphasia showing severe asymmetry and Wernicke's aphasia mild-to-moderate metabolic asymmetry, while patients with conduction aphasia were metabolically symmetric. On the other hand, the three syndromes showed the same degree of metabolic decline in the left temporal region. The parietal region appeared to separate conduction aphasia from both Broca's and Wernicke's aphasias. Common aphasic features in the three syndromes appear to be due to common changes in the temporal region, while unique features were associated with frontal and parietal metabolic differences

  3. Arginase Inhibition Ameliorates Hepatic Metabolic Abnormalities in Obese Mice

    Moon, Jiyoung; Do, Hyun Ju; Cho, Yoonsu; Shin, Min-Jeong

    2014-01-01

    Objectives We examined whether arginase inhibition influences hepatic metabolic pathways and whole body adiposity in diet-induced obesity. Methods and Results After obesity induction by a high fat diet (HFD), mice were fed either the HFD or the HFD with an arginase inhibitor, Nω-hydroxy-nor-L-arginine (nor-NOHA). Nor-NOHA significantly prevented HFD-induced increases in body, liver, and visceral fat tissue weight, and ameliorated abnormal lipid profiles. Furthermore, nor-NOHA treatment reduced lipid accumulation in oleic acid-induced hepatic steatosis in vitro. Arginase inhibition increased hepatic nitric oxide (NO) in HFD-fed mice and HepG2 cells, and reversed the elevated mRNA expression of hepatic genes in lipid metabolism. Expression of phosphorylated 5′ AMPK-activated protein kinase α was increased by arginase inhibition in the mouse livers and HepG2 cells. Conclusions Arginase inhibition ameliorated obesity-induced hepatic lipid abnormalities and whole body adiposity, possibly as a result of increased hepatic NO production and subsequent activation of metabolic pathways involved in hepatic triglyceride metabolism and mitochondrial function. PMID:25057910

  4. Cerebral blood flow and oxygen metabolism in the Rett syndrome

    Yoshikawa, Hideto; Fueki, Noboru; Suzuki, Hisaharu; Sakuragawa, Norio; Iio, Masaaki

    1992-01-01

    Positron emission tomography (PET) was performed on six patients with the Rett syndrome and the results were compared with the concurrent clinical status of the patients. The cerebral metabolic rate of oxygen (CMRO 2 ) was low in five patients, and oxygen extraction fraction (OEF) was low in four patients; both had a tendency to decline with advancing age. Although the cause is unknown, it is suggested that impaired oxidative metabolism exists in the Rett syndrome. An analysis of the distribution among brain regions showed that the ratios of values for the frontal cortex to those for the temporal cortex for both the cerebral blood flow (CBF) and CMRO 2 were lower than those for the controls, which may indicate the loss of of hyperfrontality in the Rett syndrome. Distribution of brain metabolism may be immature in the Rett syndrome. (author)

  5. Determination of cerebral metabolic patterns in dementia using positron emission tomography

    Kuhl, D.E.

    1986-01-01

    With the introduction of the Kety-Schmidt method whole brain measurements of blood flow and metabolism were first applied to normal aged and demented patients. Chronically demented patients were consistently found to have marked reductions in cerebral blood flow, oxygen utilization, and glucose utilization when dementia was severe, and lesser reductions when it was mild. Others found that cerebral blood flow, oxygen utilization, and glucose utilization were decreased in parallel in late stages of Alzheimer's disease (AD) and multiple infarct dementia (MID). The intraarterial /sup 133/Xe method has been used to determine abnormalities in regional cerebral blood flow that correlate with cognitive deficits in patients with organic dementia, mostly Alzheimer's cases. Positron emission tomography (PET) and the /sup 18/F fluorodeoxyglycose (FDG) method have been applied to small numbers of demented patients with advanced AD. In general, decreases were found in global cerebral glucose utilization, but especially in temporal and parietal cortex. Others, using PET and the /sup 15/O/sub 2/ steady-state method, found a coupled decline in global cerebral blood flow and oxygen utilization that was correlated with increasing severity of dementia in both AD and MID, but there was no increase in oxygen extraction ratio, and therefore no evidence to support the existence of a chronic ischemic brain process. In this chapter, the author reviews some of the recent findings at UCLA using PET and the method in the study of normal aging and dementing disorders

  6. Cerebral blood flow and metabolism during isoflurane-induced hypotension in patients subjected to surgery for cerebral aneurysms

    Madsen, J B; Cold, G E; Hansen, E S

    1987-01-01

    Cerebral blood flow and cerebral metabolic rate for oxygen were measured during isoflurane-induced hypotension in 10 patients subjected to craniotomy for clipping of a cerebral aneurysm. Flow and metabolism were measured 5-13 days after the subarachnoid haemorrhage by a modification of the classi......Cerebral blood flow and cerebral metabolic rate for oxygen were measured during isoflurane-induced hypotension in 10 patients subjected to craniotomy for clipping of a cerebral aneurysm. Flow and metabolism were measured 5-13 days after the subarachnoid haemorrhage by a modification......). Controlled hypotension to an average MAP of 50-55 mm Hg was induced by increasing the dose of isoflurane, and maintained at an inspired concentration of 2.2 +/- 0.2%. This resulted in a significant decrease in CMRO2 (to 1.73 +/- 0.16 ml/100 g min-1), while CBF was unchanged. After the clipping...

  7. Cerebral hemodynamic and metabolic changes in fulminant hepatic failure

    Fernando Mendes Paschoal Junior

    Full Text Available ABSTRACT Intracranial hypertension and brain swelling are a major cause of morbidity and mortality of patients suffering from fulminant hepatic failure (FHF. The pathogenesis of these complications has been investigated in man, in experimental models and in isolated cell systems. Currently, the mechanism underlying cerebral edema and intracranial hypertension in the presence of FHF is multi-factorial in etiology and only partially understood. The aim of this paper is to review the pathophysiology of cerebral hemodynamic and metabolism changes in FHF in order to improve understanding of intracranial dynamics complication in FHF.

  8. The Coupling of Cerebral Metabolic Rate of Glucose and Cerebral Blood Flow In Vivo

    Hasselbalch, Steen; Paulson, Olaf Bjarne

    2012-01-01

    The energy supplied to the brain by metabolic substrate is largely utilized for maintaining synaptic transmission. In this regulation cerebral blood flow and glucose consumption is tightly coupled as well in the resting condition as during activation. Quantification of cerebral blood flow...... not used for aerobic metabolism. Although some of the excess glucose uptake can be explained by lactate production, this phenomenon can still not account for the excess glucose uptake. Thus, more complex metabolic patterns in the brain might be reflected in the excess glucose uptake during activation......, and especially temporal relationships must be taken into account. What triggers the flow increase during functional brain activation is not entirely elucidated. The demand for excess glucose uptake may be important and a possible oxygen deficit in tissue distant from the capillaries is probably of minor...

  9. Local cerebral metabolism during partial seizures

    Engel, J. Jr.; Kuhl, D.E.; Phelps, M.E.; Rausch, R.; Nuwer, M.

    1983-01-01

    Interictal and ictal fluorodeoxyglucose scans were obtained with positron CT from four patients with spontaneous recurrent partial seizures, one with epilepsia partialis continua, and one with a single partial seizure induced by electrical stimulation of the hippocampus. Ictal metabolic patterns were different for each patient studied. Focal and generalized increased and decreased metabolism were observed. Ictal hypermetabolism may exceed six times the interictal rate and could represent activation of excitatory or inhibitory synapses in the epileptogenic region and its projection fields. Hypometabolism seen on ictal scans most likely reflects postictal depression and may indicate projection fields of inhibited neurons. No quantitative relationship between alterations in metabolism and EEG or behavioral measurements of ictal events could be demonstrated

  10. Local cerebral metabolism during partial seizures

    Engel, J. Jr.; Kuhl, D.E.; Phelps, M.E.; Rausch, R.; Nuwer, M.

    1983-04-01

    Interictal and ictal fluorodeoxyglucose scans were obtained with positron CT from four patients with spontaneous recurrent partial seizures, one with epilepsia partialis continua, and one with a single partial seizure induced by electrical stimulation of the hippocampus. Ictal metabolic patterns were different for each patient studied. Focal and generalized increased and decreased metabolism were observed. Ictal hypermetabolism may exceed six times the interictal rate and could represent activation of excitatory or inhibitory synapses in the epileptogenic region and its projection fields. Hypometabolism seen on ictal scans most likely reflects postictal depression and may indicate projection fields of inhibited neurons. No quantitative relationship between alterations in metabolism and EEG or behavioral measurements of ictal events could be demonstrated.

  11. Computerized system for measuring cerebral metabolism

    McGlone, J.S.; Hibbard, L.S.; Hawkins, R.A.; Kasturi, R.

    1987-01-01

    A computerized stereotactic measurement system for evaluating rat brain metabolism was developed to utilize the large amount of data generated by quantitative autoradiography. Conventional methods of measurement only analyze a small percent of these data because these methods are limited by instrument design and the subjectiveness of the investigator. However, a computerized system allows digital images to be analyzed by placing data at their appropriate three-dimensional stereotactic coordinates. The system automatically registers experimental data to a standard three-dimensional image using alignment, scaling, and matching operations. Metabolic activity in different neuronal structures is then measured by generating digital masks and superimposing them on to experimental data. Several experimental data sets were evaluated and it was noticed that the structures measured by the computerized system, had in general, lower metabolic activity than manual measurements had indicated. This was expected because the computerized system measured the structure over its volume while the manual readings were taken from the most active metabolic area of a particular structure

  12. Cerebral oxygenation and energy metabolism in bacterial meningitis

    Larsen, Lykke

    Introduction: In a recent retrospective study of patients with severe bacterial meningitis we demonstrated that cerebral oxidative metabolism was affected in approximately 50% of the cases. An increase of lactate/pyruvate (LP) ratio above the upper normal limit, defined according to according...... bacterial meningitis; secondly to examine whether it is correct to separate the diagnosis of cerebral ischemia from mitochondrial dysfunction based exclusively on the biochemical pattern obtained during intracerebral microdialysis. Method: A prospective clinical study including patients with severe...... community acquired bacterial meningitis admitted to the Department of Infectious Diseases, Odense University Hospital, during the period January 2014 to June 2016. We relate data from measurements of brain tissue oxygen tension (PbtO2) to simultaneously recorded data reflecting cerebral cytoplasmic redox...

  13. Abnormal islet sphingolipid metabolism in type 1 diabetes.

    Holm, Laurits J; Krogvold, Lars; Hasselby, Jane P; Kaur, Simranjeet; Claessens, Laura A; Russell, Mark A; Mathews, Clayton E; Hanssen, Kristian F; Morgan, Noel G; Koeleman, Bobby P C; Roep, Bart O; Gerling, Ivan C; Pociot, Flemming; Dahl-Jørgensen, Knut; Buschard, Karsten

    2018-04-18

    Sphingolipids play important roles in beta cell physiology, by regulating proinsulin folding and insulin secretion and in controlling apoptosis, as studied in animal models and cell cultures. Here we investigate whether sphingolipid metabolism may contribute to the pathogenesis of human type 1 diabetes and whether increasing the levels of the sphingolipid sulfatide would prevent models of diabetes in NOD mice. We examined the amount and distribution of sulfatide in human pancreatic islets by immunohistochemistry, immunofluorescence and electron microscopy. Transcriptional analysis was used to evaluate expression of sphingolipid-related genes in isolated human islets. Genome-wide association studies (GWAS) and a T cell proliferation assay were used to identify type 1 diabetes related polymorphisms and test how these affect cellular islet autoimmunity. Finally, we treated NOD mice with fenofibrate, a known activator of sulfatide biosynthesis, to evaluate the effect on experimental autoimmune diabetes development. We found reduced amounts of sulfatide, 23% of the levels in control participants, in pancreatic islets of individuals with newly diagnosed type 1 diabetes, which were associated with reduced expression of enzymes involved in sphingolipid metabolism. Next, we discovered eight gene polymorphisms (ORMDL3, SPHK2, B4GALNT1, SLC1A5, GALC, PPARD, PPARG and B4GALT1) involved in sphingolipid metabolism that contribute to the genetic predisposition to type 1 diabetes. These gene polymorphisms correlated with the degree of cellular islet autoimmunity in a cohort of individuals with type 1 diabetes. Finally, using fenofibrate, which activates sulfatide biosynthesis, we completely prevented diabetes in NOD mice and even reversed the disease in half of otherwise diabetic animals. These results indicate that islet sphingolipid metabolism is abnormal in type 1 diabetes and suggest that modulation may represent a novel therapeutic approach. The RNA expression data is

  14. Regional cerebral glucose metabolism in patients with alcoholic Korsakoff's syndrome

    Kessler, R.M.; Parker, E.S.; Clark, C.M.; Martin, P.R.; George, D.T.; Weingartner, H.; Sokoloff, L.; Ebert, M.H.; Mishkin, M.

    1985-01-01

    Seven alcoholic male subjects diagnosed as having Korsakoff's syndrome and eight age-matched male normal volunteers were studied with /sup 18/F 2-fluoro-2-deoxy-D-glucose (2/sup 18/FDG). All subjects were examined at rest with eyes covered in a quiet, darkened room. Serial plasma samples were obtained following injection of 4 to 5 mCi of 2/sup 18/FDG. Tomographic slices spaced at 10mm axial increments were obtained (in-plane resolution = 1.75 cm, axial resolution = 1.78 cm). Four planes were selected from each subject, and a total of 46 regions of interest were sampled and glucose metabolic rates for each region calculated. The mean glucose metalbolic rate for the 46 regions in the Korsakoff subjects was significantly lower than that in the normal controls (5.17 +- .43 versus 6.6 +- 1.31). A Q-component analysis, which examined each subject's regional rates relative to his mean rate, revealed two distinct patterns in the Korsakoff group. Glucose metabolism was significantly reduced in 37 of the 46 regions sampled. Reduced cerebral glucose metabolism in a nondemented group of subjects has not previously been reported. The reduction in cortical metabolism may be the result of damage to sub-cortical projecting systems. The differing patterns of cerebral metabolism in Korsakoff's syndrome suggests subgroups with differing neuropathology. Regions implicated in memory function, medial temporal, thalamic and medial prefrontal were among the regions reduced in metabolism

  15. Regional effects of craniotomy on cerebral circulation and metabolism

    Abumiya, Takeo; Sayama, Ichiro; Asakura, Ken; Hadeishi, Hiromu; Mizuno, Makoto; Suzuki, Akifumi; Yasui, Nobuyuki; Shishido, Fumio; Uemura, Kazuo

    1990-01-01

    Regional effects of craniotomy on cerebral circulation and metabolism, such as regional cerebral blood flow (rCBF), regional cerebral oxygen consumption (rCMRO 2 ), regional oxygen extraction fraction (rOEF), and regional cerebral blood volume (rCBV) were examined by a PET (positron emission tomography) study concerning surgery that was performed on un-ruptured aneurysm patients. Eight patients with intracranial un-ruptured aneurysms were studied pre- and post-operatively by the 15 O labelled-gas steady-state method, using HEADTOME-III. All patients underwent aneurysmal surgery performed by the transsylvian approach. There was a significant increase in the mean OEF values taken from the whole-brains of 8 patients, but there was not a significant change in CBF, CMRO 2 or CBV. The increase in OEF was caused by decrease of O 2 content, which was caused by post-operative decrease in the Hb value. So, this OEF increase was not the direct effect of craniotomy. In 2 patients, the rCBF and rCMRO 2 , in the fronto-temporal region (where craniotomy was performed) increased post-operatively. This regional effect suggests transient reactive hyperemia following compressive ischemia during the operative procedure, and metabolic demands for recovery of brain function. In 2 other patients, who had relatively low rCBFs during the pre-operative study, rCBF and rCMRO 2 in the bi-frontal region had decreased more at the post-operative study. This change appears to have been caused by removal of cerebrospinal fluid and depression of the frontal lobe. From this study, it becomes evident that the regional effect of craniotomy on cerebral circulation and metabolism is not so great, when adequate microsurgical techniques are used. (author)

  16. Plasma pH does not influence the cerebral metabolic ratio during maximal whole body exercise

    Volianitis, Stefanos; Rasmussen, Peter; Seifert, Thomas

    2011-01-01

    .05) following the Sal and Bicarb trials, respectively. Accordingly, the cerebral metabolic ratio decreased equally during the Sal and Bicarb trials: from 5.8 ± 0.6 at rest to 1.7 ± 0.1 and 1.8 ± 0.2, respectively. The enlarged blood-buffering capacity after infusion of Bicarb eliminated metabolic acidosis......Exercise lowers the cerebral metabolic ratio of O2 to carbohydrate (glucose + 1/2 lactate) and metabolic acidosis appears to promote cerebral lactate uptake. However, the influence of pH on cerebral lactate uptake and, in turn, on the cerebral metabolic ratio during exercise is not known. Sodium...... during maximal exercise but that did not affect the cerebral lactate uptake and, therefore, the decrease in the cerebral metabolic ratio....

  17. THE ROLE OF NUTRIGENOMICS IN CORRECTION OF METABOLIC ABNORMALITIES

    I. V. Misnikova

    2015-01-01

    Full Text Available In some patients, diet and increased physical exercise are not effective enough to prevent the development of type 2 diabetes mellitus. At present, a  new approach is proposed to elaborate the diet with consideration of specific need of an individual. Food components can cause changes in metabolism through their influence on activity of certain genes that subsequently influence human proteome and metabolome. It is assumed that nutrients may influence methylation of deoxyribonucleic acid. A number of studies established an interaction between some foods and genes associated with obesity and type 2 diabetes mellitus. Diet recommendations based on presence of certain gene polymorphisms have been developed. The spectrum of gene polymorphisms that is necessary to assess in individuals with metabolic abnormalities or with high risk of their development has been also defined.

  18. Swedish Massage and Abnormal Reflexes of Children with Spastic Cerebral Palsy

    Vida Alizad

    2007-09-01

    Full Text Available Objectives: Massage therapy is one of the most widely used complementary and alternative medicine therapies for children. This study was conducted to determine the effect of wedish massage on abnormal reflexes in children with spastic cerebral palsy (CP. Methods: This study was a single blind clinical trial conducted on forty children with spastic CP who were recruited from clinics of the University of Social Welfare & Rehabilitation Sciences. They were randomly assigned to intervention and control groups. The routine occupational therapy (OT techniques were performed during a 3 month-period in both groups. The intervention group also received Swedish massage for 30 minutes before every OT session. Primary, spinal, brain stem, midbrain, cortical and automatic reflexes were evaluated at the beginning of the study and 3 months later. The data analysis was done by parametric and nonparametric tests. Results: Finally, thirteen subjects in the intervention group and 14 subjects in the control group were remained and studied. The average ages in the intervention and control groups were 49.5 and 42.1 months respectively. There were no statistically significant differences in abnormal reflexes in the intervention group in comparison to the control (P>0.05. Discussion: Adding Swedish massage to traditional OT techniques had no significant effects on abnormal reflexes in children with spastic cerebral palsy. Evidently more research is required in order to completely reject the effects of Swedish massage on abnormal reflexes of children with CP.

  19. PET measurements of cerebral metabolism corrected for CSF contributions

    Chawluk, J.; Alavi, A.; Dann, R.; Kushner, M.J.; Hurtig, H.; Zimmerman, R.A.; Reivich, M.

    1984-01-01

    Thirty-three subjects have been studied with PET and anatomic imaging (proton-NMR and/or CT) in order to determine the effect of cerebral atrophy on calculations of metabolic rates. Subgroups of neurologic disease investigated include stroke, brain tumor, epilepsy, psychosis, and dementia. Anatomic images were digitized through a Vidicon camera and analyzed volumetrically. Relative areas for ventricles, sulci, and brain tissue were calculated. Preliminary analysis suggests that ventricular volumes as determined by NMR and CT are similar, while sulcal volumes are larger on NMR scans. Metabolic rates (18F-FDG) were calculated before and after correction for CSF spaces, with initial focus upon dementia and normal aging. Correction for atrophy led to a greater increase (%) in global metabolic rates in demented individuals (18.2 +- 5.3) compared to elderly controls (8.3 +- 3.0,p < .05). A trend towards significantly lower glucose metabolism in demented subjects before CSF correction was not seen following correction for atrophy. These data suggest that volumetric analysis of NMR images may more accurately reflect the degree of cerebral atrophy, since NMR does not suffer from beam hardening artifact due to bone-parenchyma juxtapositions. Furthermore, appropriate correction for CSF spaces should be employed if current resolution PET scanners are to accurately measure residual brain tissue metabolism in various pathological states

  20. Frontiers in optical imaging of cerebral blood flow and metabolism.

    Devor, Anna; Sakadžić, Sava; Srinivasan, Vivek J; Yaseen, Mohammad A; Nizar, Krystal; Saisan, Payam A; Tian, Peifang; Dale, Anders M; Vinogradov, Sergei A; Franceschini, Maria Angela; Boas, David A

    2012-07-01

    In vivo optical imaging of cerebral blood flow (CBF) and metabolism did not exist 50 years ago. While point optical fluorescence and absorption measurements of cellular metabolism and hemoglobin concentrations had already been introduced by then, point blood flow measurements appeared only 40 years ago. The advent of digital cameras has significantly advanced two-dimensional optical imaging of neuronal, metabolic, vascular, and hemodynamic signals. More recently, advanced laser sources have enabled a variety of novel three-dimensional high-spatial-resolution imaging approaches. Combined, as we discuss here, these methods are permitting a multifaceted investigation of the local regulation of CBF and metabolism with unprecedented spatial and temporal resolution. Through multimodal combination of these optical techniques with genetic methods of encoding optical reporter and actuator proteins, the future is bright for solving the mysteries of neurometabolic and neurovascular coupling and translating them to clinical utility.

  1. Propofol Compared to Isoflurane Inhibits Mitochondrial Metabolism in Immature Swine Cerebral Cortex

    Kajimoto, Masaki; Atkinson, D. B.; Ledee, Dolena R.; Kayser, Ernst-Bernhard; Morgan, Phil G.; Sedensky, Margaret M.; Isern, Nancy G.; Des Rosiers, Christine; Portman, Michael A.

    2014-01-08

    Anesthetics used in infants and children are implicated in development of neurocognitive disorders. Although propofol induces neuroapoptosis in developing brain, the underlying mechanisms require elucidation and may have an energetic basis. We studied substrate utilization in an immature swine model anesthetized with either propofol or isoflurane for 4 hours. Piglets were infused with 13-Carbon labeled glucose and leucine in the common carotid artery in order to assess citric acid cycle (CAC) metabolism in the parietal cortex. The anesthetics produced similar systemic hemodynamics and cerebral oxygen saturation by near-infrared-spectroscopy. Compared to isoflurane, propofol depleted ATP and glycogen stores. Propofol also decreased pools of the CAC intermediates, citrate and α-ketoglutarate, while markedly increasing succinate along with decreasing mitochondrial complex II activity. Propofol also inhibited acetyl-CoA entry into the CAC through pyruvate dehydrogenase, while promoting glycolytic flux with marked accumulation of lactate. Although oxygen supply appeared similar between the anesthetic groups, propofol yielded a metabolic phenotype which resembled a hypoxic state. Propofol impairs substrate flux through the CAC in the immature cerebral cortex. These impairments occurred without systemic metabolic perturbations which typically accompany propofol infusion syndrome. These metabolic abnormalities may play a role in neurotoxity observed with propofol in the vulnerable immature brain.

  2. The cerebral blood flow and metabolism for Broca's aphasia using positron emission tomography

    Kato, Toshiaki

    1987-01-01

    A total of 11 patients with Broca's aphasia (BA) underwent positron emission tomography (PET) with the purpose of investigating the responsible region and the symptomatic flow and metabolism thresholds for BA. Computed tomography (CT) was concurrently performed. In the group of 3 patients undergoing PET with C-11 glucose, both PET and CT provided abnormal findings in the region that is thought to be responsible for BA (Broca's area), including the cortex and subcortex in the anterior region to Sylvian fissure. The Broca's area in the remaining one was shown as low C-11 accumulation area on PET and as isodensity on CT. The second group, consisting of 8 BA patients and 30 control patients without BA, underwent PET using O-15 steady method. PET showed reduction of regional cerebral blood flow (rCBF) and oxygen metabolic rate (rCMRO 2 ) in the Broca's area in all BA patients. Computed tomography showed abnormal low density in the Broca's area in 3 patients, and abnormal findings in the basal ganglionic region and subcortex without evidence for abnormal low density in the Broca's area in the other 5 patients. Comparison of rCBF and rCMRO 2 in BA patients with those in control patients may show the symptomatic thresholds to be 20 - 27 ml/100 g/min for rCBF and 2.0 ml/100 g/min for rCMRO 2 . (Namekawa, K.)

  3. The relationship between the cerebral blood flow, oxygen consumption and glucose metabolism in primary degenerative dementia

    Kuwabara, Yasuo; Ichiya, Yuichi; Ichimiya, Atsushi; Sasaki, Masayuki; Akashi, Yuko; Yoshida, Tsuyoshi; Fukumura, Toshimitsu; Masada, Kouji

    1995-01-01

    The CBF, CMRO 2 and CMRGlu were measured in patients with primary degenerative dementia including 5 patients with dementia of Alzheimer's type and 4 patients with Pick's disease, and then the correlation between the cerebral blood flow and energy metabolism was evaluated. The control subjects consisted of 5 age-matched normal volunteers. The CBF, CMRO 2 and CMRGlu decreased in the bilateral frontal, temporal and parietal regions in the patients with Alzheimer's dementia, while they decreased in the bilateral frontal and temporal regions in the patients with Pick's disease. Both the CBF and CMRO 2 were closely correlated with each other. However, the CMRGlu was more severely impaired than the CBF or CMRO 2 in both pathological conditions. These results suggested that CMRGlu began to decrease before the reduction of the aerobic metabolism and thus measuring the CMRGlu is considered to be the most sensitive method for detecting abnormal regions in primary degenerative dementia. (author)

  4. Effect of anxiety on cortical cerebral blood flow and metabolism

    Gur, R.C.; Gur, R.E.; Resnick, S.M.; Skolnick, B.E.; Alavi, A.; Reivich, M.

    1987-01-01

    The relation between anxiety and cortical activity was compared in two samples of normal volunteers. One group was studied with the noninvasive xenon-133 inhalation technique for measuring cerebral blood flow (CBF) and the other with positron emission tomography (PET) using 18 Flurodeoxyglucose ( 18 FDG) for measuring cerebral metabolic rates (CMR) for glucose. The inhalation technique produced less anxiety than the PET procedure, and for low anxiety subjects, there was a linear increase in CBF with anxiety. For higher anxiety subjects, however, there was a linear decrease in CBF with increased anxiety. The PET group manifested a linear decrease in CMR with increased anxiety. The results indicate that anxiety can have systematic effects on cortical activity, and this should be taken into consideration when comparing data from different procedures. They also suggest a physiologic explanation of a fundamental behavioral law that stipulates a curvilinear, inverted-U relationship between anxiety and performance

  5. Embryologic Association of Tornwaldt's Cyst with Cerebral Artery Abnormalities and Infarction: A Case Report

    Michael F. Osborn

    2012-01-01

    Full Text Available Background and Purpose. Tornwaldt's cysts are rare nasopharyngeal lesions that develop from remnants of the embryonic notochord. Summary of Case. We reported a twelve-year-old female stroke patient with Tornwaldt's cysts, whose father also suffered a stroke at age fifty two with the presence of an abdominal aortic aneurysm, suggesting a genetic influence in this case. Conclusions. This paper suggests an etiologic connection between Tornwaldt's cysts and cerebral vasculature abnormalities by way of notochordal dysfunction during development, likely the result of perturbation of notochord-derived molecular cues during development or biogenesis.

  6. Cerebral metabolism, anatomy, and cognition in monozygotic twins discordant for dementia of the Alzheimer type.

    Luxenberg, J S; May, C; Haxby, J V; Grady, C; Moore, A; Berg, G; White, B J; Robinette, D; Rapoport, S I

    1987-03-01

    One pair of monozygotic twins discordant for dementia of the Alzheimer type (DAT) was studied using neuropsychological testing, quantitative x-ray computed tomography (QCT) and magnetic resonance imaging (MRI) of the brain. Cerebral glucose metabolism was measured using positron emission tomography (PET) and 2-[18-F]fluoro-2-deoxy-D-glucose (FDG). The affected twin had a seven year history of progressive cognitive impairment and was severely demented. Neuropsychological testing of the affected twin demonstrated marked deficits in all areas of cognitive function. The asymptomatic twin showed some impairment on tests of perceptual organisation and delayed recall. The affected twin had loss of gray matter and ventricular enlargement on QCT and MRI compared with healthy controls (p less than 0.05). He also had frontal and parietal lobe hypometabolism and increased asymmetry of metabolism on PET compared to both his twin and healthy age-matched controls (p less than 0.05). PET, QCT, and MRI distinguished changes in the twin with DAT compared with his brother and healthy controls. Although the subtle neuropsychological abnormalities of the asymptomatic twin may be signs of early DAT, they were not accompanied by any changes in regional cerebral metabolism or brain structure.

  7. Atrioventricular conduction abnormality and hyperchloremic metabolic acidosis in toluene sniffing

    Jian-Hsiung Tsao

    2011-10-01

    Full Text Available Toluene is an aromatic hydrocarbon with widespread industrial use as an organic solvent. As a result of the euphoric effect and availability of these substances, inhalation of toluene-based products is popular among young adults and children. Chronic or acute exposure is known to cause acid–base and electrolyte disorders, and to be toxic to the nervous and hematopoietic systems. We report a 38-year-old man who suffered from general muscular weakness of all extremities after toluene sniffing, which was complicated with hypokalemic paralysis, atrioventricular conduction abnormality, and normal anion gap hyperchloremic metabolic acidosis. Renal function, serum potassium and acid–base status normalized within 3 days after aggressive potassium chloride and intravenous fluid replacement. Electrocardiography showed regression of first-degree atrioventricular block. Exposure to toluene can lead to cardiac arrhythmias and sudden sniffing death syndrome. Tachyarrhythmia is the classical manifestation of toluene cardiotoxicity. Atrioventricular conduction abnormalities have been rarely mentioned in the literature. Knowledge of the toxicology and medical complications associated with toluene sniffing is essential for clinical management of these patients.

  8. Abnormal metabolic network activity in REM sleep behavior disorder.

    Holtbernd, Florian; Gagnon, Jean-François; Postuma, Ron B; Ma, Yilong; Tang, Chris C; Feigin, Andrew; Dhawan, Vijay; Vendette, Mélanie; Soucy, Jean-Paul; Eidelberg, David; Montplaisir, Jacques

    2014-02-18

    To determine whether the Parkinson disease-related covariance pattern (PDRP) expression is abnormally increased in idiopathic REM sleep behavior disorder (RBD) and whether increased baseline activity is associated with greater individual risk of subsequent phenoconversion. For this cohort study, we recruited 2 groups of RBD and control subjects. Cohort 1 comprised 10 subjects with RBD (63.5 ± 9.4 years old) and 10 healthy volunteers (62.7 ± 8.6 years old) who underwent resting-state metabolic brain imaging with (18)F-fluorodeoxyglucose PET. Cohort 2 comprised 17 subjects with RBD (68.9 ± 4.8 years old) and 17 healthy volunteers (66.6 ± 6.0 years old) who underwent resting brain perfusion imaging with ethylcysteinate dimer SPECT. The latter group was followed clinically for 4.6 ± 2.5 years by investigators blinded to the imaging results. PDRP expression was measured in both RBD groups and compared with corresponding control values. PDRP expression was elevated in both groups of subjects with RBD (cohort 1: p abnormalities in subjects with idiopathic RBD are associated with a greater likelihood of subsequent phenoconversion to a progressive neurodegenerative syndrome.

  9. Evolution of Metabolic Abnormalities in Alcoholic Patients during Withdrawal

    X. Vandemergel

    2015-01-01

    Full Text Available Chronic alcohol intoxication is accompanied by metabolic abnormalities. Evolution during the early withdrawal period has been poorly investigated. The aim of this study was to determine the evolution of metabolic parameters during alcohol withdrawal. Patients and Methods. Thirty-three patients admitted in our department for alcohol withdrawal were prospectively included. Results. Baseline hypophosphatemia was found in 24% of cases. FEPO4 was reduced from 14.2 ± 9% at baseline to 7.3 ± 4.2% at day 3 (Pnl, respectively. No correlation was found between the sodium and CPK levels (P=0.75 nor between the CPK level and the amount of alcohol ingested (rs = 0.084, P=0.097. Baseline urate level was elevated and returned to normal after three days. Baseline magnesium concentration was normal and stable over time. Conclusion. Chronic alcohol intoxication was accompanied by phosphaturia, rapidly reversible after alcohol withdrawal and inversely correlated with albuminemia, slight hyponatremia, low levels of 25 hydroxy vitamin D, elevated CPK level in about 30% of women, and hyperuricemia with rapid normalization.

  10. Mineral Metabolic Abnormalities and Mortality in Dialysis Patients

    Masanori Abe

    2013-03-01

    Full Text Available The survival rate of dialysis patients, as determined by risk factors such as hypertension, nutritional status, and chronic inflammation, is lower than that of the general population. In addition, disorders of bone mineral metabolism are independently related to mortality and morbidity associated with cardiovascular disease and fracture in dialysis patients. Hyperphosphatemia is an important risk factor of, not only secondary hyperparathyroidism, but also cardiovascular disease. On the other hand, the risk of death reportedly increases with an increase in adjusted serum calcium level, while calcium levels below the recommended target are not associated with a worsened outcome. Thus, the significance of target levels of serum calcium in dialysis patients is debatable. The consensus on determining optimal parathyroid function in dialysis patients, however, is yet to be established. Therefore, the contribution of phosphorus and calcium levels to prognosis is perhaps more significant. Elevated fibroblast growth factor 23 levels have also been shown to be associated with cardiovascular events and death. In this review, we examine the associations between mineral metabolic abnormalities including serum phosphorus, calcium, and parathyroid hormone and mortality in dialysis patients.

  11. Evaluation of cerebral blood flow, cerebral metabolism and cerebral function by magnetic resonance imaging

    Tanaka, Chuzo; Higuchi, Toshihiro; Umeda, Masahiro; Naruse, Shoji; Horikawa, Yoshiharu; Ueda, Satoshi; Furuya, Seiichi.

    1995-01-01

    The magnetic resonance (MR) method has the unique potentiality of detecting cerebral metabolites, cerebral blood flow and brain functions in a noninvasive fashion. We have developed several MR techniques to detect these cerebral parameters with the use of clinical MRI scanners. By modifying the MR spectroscopy (MRS) technique, both 31 P- and 1 H-MRS data can be obtained from multiple, localized regions (multi-voxel method) of the brain, and the distribution of each metabolite in the brain can be readily visualized by metabolite mapping. The use of diffusion weighted images (DWI) permits visualization of the anisotropy of water diffusion in white matter, and based on the difference of diffusion coefficiency, the differential diagnosis between epidermoid tumor and arachnoid cyst can be made. By employing dynamic-MRI (Dyn-MRI) with Gd-DTPA administration, it is possible to examine the difference in blood circulation between brain tumor tissue and normal tissue, as well as among different types of brain tumors. By using magnetization transfer contrast (MTC) imaging, it has become possible to detect brain tumors, and with a small dose of Gd-DTPA, to visualize the vascular system. Functional MRI (fMRI) visualizes the activated brain by using conventional gradient echo technique on conventional MRI scanners. This method has the unique characteristic of detecting a brain function with high spatial and temporal resolution by using the intrinsic substance. Moreover, the localization of motor and sensory areas was detected by noninvasive means within few minutes. The fMRI procedure will be used in the future to analyze the higher and complex brain functions. In conclusion, multi-modality MR is a powerful technique that is useful for investigating the pathogenesis of many diseases, and provides a noninvasive analytic modality for studying brain function. (author)

  12. Cerebral metabolism in experimental hydrocephalus: an in vivo 1H and 31P magnetic resonance spectroscopy study

    Braun, K. P.; van Eijsden, P.; Vandertop, W. P.; de Graaf, R. A.; Gooskens, R. H.; Tulleken, K. A.; Nicolay, K.

    1999-01-01

    Brain damage in patients with hydrocephalus is caused by mechanical forces and cerebral ischemia. The severity and localization of impaired cerebral blood flow and metabolism are still largely unknown. Magnetic resonance (MR) spectroscopy offers the opportunity to investigate cerebral energy

  13. Parenchymal abnormalities in cerebral venous thrombosis: findings of magnetic resonance imaging and magnetic resonance angiography

    Ferreira, Clecia Santos; Pellini, Marcos; Boasquevisque, Edson; Souza, Luis Alberto M. de

    2006-01-01

    Objective: to determine the frequency and localization of parenchymal abnormalities in cerebral venous thrombosis on magnetic resonance imaging and magnetic resonance angiography as well as their correlation with the territory and affected venous drainage. Materials and methods: retrospective analysis (1996 to 2004) of 21 patients (3 male and 18 female) age range between 3 and 82 years (mean 40 years, median 36 years) with clinical and radiological diagnosis of cerebral venous thrombosis on magnetic resonance imaging and magnetic resonance angiography in 2D PC, 3D PC and contrast-enhanced 3D TOF sequences. The statistical analysis was performed with the qui-square test. Four patients had follow-up exams and three patients underwent digital subtraction angiography. Results: main predisposing factors were: infection, use of oral contraceptives, hormone replacement therapy and collagenosis. Predominant symptoms included: focal deficit, headache, alteration of consciousness level and seizures. Most frequent parenchymal manifestations were: cortical/subcortical edema or infarct, venous congestion and collateral circulation, meningeal enhancement and thalamic and basal ganglia edema or infarct. Occlusion occurred mainly in superior sagittal, left transverse, left sigmoid and straight sinuses. Cavernous sinus and cortical veins thrombosis are uncommon events. Conclusion: cerebral venous thrombosis is an uncommon cause of stroke, with favorable prognosis because of its reversibility. Diagnosis is highly dependent on the radiologist capacity to recognize the presentations of this disease, principally in cases where the diagnosis is suggested by parenchymal abnormalities rather than necessarily by visualization of the thrombus itself. An accurate and rapid diagnosis allows an immediate treatment, reducing the morbidity and mortality rates. (author)

  14. Abnormal excitability and episodic low-frequency oscillations in the cerebral cortex of the tottering mouse.

    Cramer, Samuel W; Popa, Laurentiu S; Carter, Russell E; Chen, Gang; Ebner, Timothy J

    2015-04-08

    The Ca(2+) channelopathies caused by mutations of the CACNA1A gene that encodes the pore-forming subunit of the human Cav2.1 (P/Q-type) voltage-gated Ca(2+) channel include episodic ataxia type 2 (EA2). Although, in EA2 the emphasis has been on cerebellar dysfunction, patients also exhibit episodic, nonmotoric abnormalities involving the cerebral cortex. This study demonstrates episodic, low-frequency oscillations (LFOs) throughout the cerebral cortex of tottering (tg/tg) mice, a widely used model of EA2. Ranging between 0.035 and 0.11 Hz, the LFOs in tg/tg mice can spontaneously develop very high power, referred to as a high-power state. The LFOs in tg/tg mice are mediated in part by neuronal activity as tetrodotoxin decreases the oscillations and cortical neuron discharge contain the same low frequencies. The high-power state involves compensatory mechanisms because acutely decreasing P/Q-type Ca(2+) channel function in either wild-type (WT) or tg/tg mice does not induce the high-power state. In contrast, blocking l-type Ca(2+) channels, known to be upregulated in tg/tg mice, reduces the high-power state. Intriguingly, basal excitatory glutamatergic neurotransmission constrains the high-power state because blocking ionotropic or metabotropic glutamate receptors results in high-power LFOs in tg/tg but not WT mice. The high-power LFOs are decreased markedly by acetazolamide and 4-aminopyridine, the primary treatments for EA2, suggesting disease relevance. Together, these results demonstrate that the high-power LFOs in the tg/tg cerebral cortex represent a highly abnormal excitability state that may underlie noncerebellar symptoms that characterize CACNA1A mutations. Copyright © 2015 the authors 0270-6474/15/355664-16$15.00/0.

  15. Cerebral blood flow and metabolism in multi-infarct dementia

    Ujike, Takashi; Terashi, Akiro; Soeda, Toshiyuki; Kitamura, Shin; Kato, Toshiaki; Iio, Masaaki.

    1985-01-01

    Cerebral blood flow and oxygen metabolism were studied in three aged normal volunteers and 10 patients with multi-infarct dementia (MID) by Positron Emission Tomography using O-15. The diagnosis of MID was done according to the Loeb's modified ischemic score and X-ray CT findings. The MID patients, whose X-ray CT showed localized low density areas in the subcortical white matter and basal ganglia and thalamus, were studied. No occulusion was observed at anterior cerebral artery and/or middle cerebral artery on cerebral angiography. All cases of MID were mild dementias. Regional CBF, rOEF and rCMRO 2 were measured by the steady state technique described by Terry Jones et al. The values of rCBF in MID patients were significantly low compared with those of aged normal subjects in frontal, temporal, occipital, parietal cortices and thalamus. The values of CMRO 2 in MID were significantly low in frontal, temporal, occipital cortices and thalamus compared with normal subjects'. The OEF was 0.46 in aged normal subjects, and 0.52 in MID patients. The MID patients in the early stage of dementia showed the increased oxygen extraction fraction, and this fact suggests that ischemia is a significant pathogenic mechanism in the production and progression of multi-infarct dementia. The decrease of CBF and CMRO 2 in MID compared from normal subjects' were most remarkable in frontal cortex. The impairment of mental functions in MID should be caused by the decreased neuronal activities in frontal association cortex. (author)

  16. Cerebrospinal fluid ionic regulation, cerebral blood flow, and glucose use during chronic metabolic alkalosis

    Schroeck, H.K.; Kuschinsky, W.

    1989-01-01

    Chronic metabolic alkalosis was induced in rats by combining a low K+ diet with a 0.2 M NaHCO3 solution as drinking fluid for either 15 or 27 days. Local cerebral blood flow and local cerebral glucose utilization were measured in 31 different structures of the brain in conscious animals by means of the iodo-[14C]antipyrine and 2-[14C]deoxy-D-glucose method. The treatment induced moderate [15 days, base excess (BE) 16 mM] to severe (27 days, BE 25 mM) hypochloremic metabolic alkalosis and K+ depletion. During moderate metabolic alkalosis no change in cerebral glucose utilization and blood flow was detectable in most brain structures when compared with controls. Cerebrospinal fluid (CSF) K+ and H+ concentrations were significantly decreased. During severe hypochloremic alkalosis, cerebral blood flow was decreased by 19% and cerebral glucose utilization by 24% when compared with the control values. The decrease in cerebral blood flow during severe metabolic alkalosis is attributed mainly to the decreased cerebral metabolism and to a lesser extent to a further decrease of the CSF H+ concentration. CSF K+ concentration was not further decreased. The results show an unaltered cerebral blood flow and glucose utilization together with a decrease in CSF H+ and K+ concentrations at moderate metabolic alkalosis and a decrease in cerebral blood flow and glucose utilization together with a further decreased CSF H+ concentration at severe metabolic alkalosis

  17. Bedside Evaluation of Cerebral Energy Metabolism in Severe Community-Acquired Bacterial Meningitis

    Rom Poulsen, Frantz; Schulz, Mette; Jacobsen, Anne

    2015-01-01

    BACKGROUND: Mortality and morbidity have remained high in bacterial meningitis. Impairment of cerebral energy metabolism probably contributes to unfavorable outcome. Intracerebral microdialysis is routinely used to monitor cerebral energy metabolism, and recent experimental studies indicate...... that this technique may separate ischemia and non-ischemic mitochondrial dysfunction. The present study is a retrospective interpretation of biochemical data obtained in a series of patients with severe community-acquired meningitis. METHODS: Cerebral energy metabolism was monitored in 15 patients with severe...... community-acquired meningitis utilizing intracerebral microdialysis and bedside biochemical analysis. According to previous studies, cerebral ischemia was defined as lactate/pyruvate (LP) ratio >30 with intracerebral pyruvate level

  18. Metabolic, Reproductive, and Neurologic Abnormalities in Agpat1-Null Mice.

    Agarwal, Anil K; Tunison, Katie; Dalal, Jasbir S; Nagamma, Sneha S; Hamra, F Kent; Sankella, Shireesha; Shao, Xinli; Auchus, Richard J; Garg, Abhimanyu

    2017-11-01

    Defects in the biosynthesis of phospholipids and neutral lipids are associated with cell membrane dysfunction, disrupted energy metabolism, and diseases including lipodystrophy. In these pathways, the 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) enzymes transfer a fatty acid to the sn-2 carbon of sn-1-acylglycerol-3-phosphate (lysophosphatidic acid) to form sn-1, 2-acylglycerol-3-phosphate [phosphatidic acid (PA)]. PA is a precursor for key phospholipids and diacylglycerol. AGPAT1 and AGPAT2 are highly homologous isoenzymes that are both expressed in adipocytes. Genetic defects in AGPAT2 cause congenital generalized lipodystrophy, indicating that AGPAT1 cannot compensate for loss of AGPAT2 in adipocytes. To further explore the physiology of AGPAT1, we characterized a loss-of-function mouse model (Agpat1-/-). The majority of Agpat1-/- mice died before weaning and had low body weight and low plasma glucose levels, independent of plasma insulin and glucagon levels, with reduced percentage of body fat but not generalized lipodystrophy. These mice also had decreased hepatic messenger RNA expression of Igf-1 and Foxo1, suggesting a decrease in gluconeogenesis. In male mice, sperm development was impaired, with a late meiotic arrest near the onset of round spermatid production, and gonadotropins were elevated. Female mice showed oligoanovulation yet retained responsiveness to gonadotropins. Agpat1-/- mice also demonstrated abnormal hippocampal neuron development and developed audiogenic seizures. In summary, Agpat1-/- mice developed widespread disturbances of metabolism, sperm development, and neurologic function resulting from disrupted phospholipid homeostasis. AGPAT1 appears to serve important functions in the physiology of multiple organ systems. The Agpat1-deficient mouse provides an important model in which to study the contribution of phospholipid and triacylglycerol synthesis to physiology and diseases. Copyright © 2017 Endocrine Society.

  19. SU-E-J-122: Detecting Treatment-Induced Metabolic Abnormalities in Craniopharyngioma Patients Undergoing Surgery and Proton Therapy

    Hua, C; Shulkin, B; Li, Y; LI, X; Merchant, T [St. Jude Children' s Research Hospital, Memphis, TN (United States); Indelicato, D [University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Boop, F [Semmes-Murphey Neurologic and Spine Institute, Memphis, TN (United States)

    2014-06-01

    Purpose: To identify treatment-induced defects in the brain of children with craniopharyngioma receiving surgery and proton therapy using fluorodeoxyglucose positron emission tomography (FDG PET). Methods: Forty seven patients were enrolled on a clinical trial for craniopharyngioma with serial imaging and functional evaluations. Proton therapy was delivered using the double-scattered beams with a prescribed dose of 54 Cobalt Gray Equivalent. FDG tracer uptake in each of 63 anatomical regions was computed after warping PET images to a 3D reference template in Talairach coordinates. Regional uptake was deemed significantly low or high if exceeding two standard deviations of normal population from the mean. For establishing the normal ranges, 132 children aged 1–20 years with noncentral nervous system related diseases and normal-appearing cerebral PET scans were analyzed. Age- and gender-dependent regional uptake models were developed by linear regression and confidence intervals were calculated. Results: Most common PET abnormality before proton therapy was significantly low uptake in the frontal lobe, the occipital lobe (particularly in cuneus), the medial and ventral temporal lobe, cingulate gyrus, caudate nuclei, and thalamus. They were related to injury from surgical corridors, tumor mass effect, insertion of a ventricular catheter, and the placement of an Ommaya reservoir. Surprisingly a significantly high uptake was observed in temporal gyri and the parietal lobe. In 13 patients who already completed 18-month PET scans, metabolic abnormalities improved in 11 patients from baseline. One patient had persistent abnormalities. Only one revealed new uptake abnormalities in thalamus, brainstem, cerebellum, and insula. Conclusion: Postoperative FDG PET of craniopharyngioma patients revealed metabolic abnormalities in specific regions of the brain. Proton therapy did not appear to exacerbate these surgery- and tumor-induced defects. In patients with persistent and

  20. SU-E-J-122: Detecting Treatment-Induced Metabolic Abnormalities in Craniopharyngioma Patients Undergoing Surgery and Proton Therapy

    Hua, C; Shulkin, B; Li, Y; LI, X; Merchant, T; Indelicato, D; Boop, F

    2014-01-01

    Purpose: To identify treatment-induced defects in the brain of children with craniopharyngioma receiving surgery and proton therapy using fluorodeoxyglucose positron emission tomography (FDG PET). Methods: Forty seven patients were enrolled on a clinical trial for craniopharyngioma with serial imaging and functional evaluations. Proton therapy was delivered using the double-scattered beams with a prescribed dose of 54 Cobalt Gray Equivalent. FDG tracer uptake in each of 63 anatomical regions was computed after warping PET images to a 3D reference template in Talairach coordinates. Regional uptake was deemed significantly low or high if exceeding two standard deviations of normal population from the mean. For establishing the normal ranges, 132 children aged 1–20 years with noncentral nervous system related diseases and normal-appearing cerebral PET scans were analyzed. Age- and gender-dependent regional uptake models were developed by linear regression and confidence intervals were calculated. Results: Most common PET abnormality before proton therapy was significantly low uptake in the frontal lobe, the occipital lobe (particularly in cuneus), the medial and ventral temporal lobe, cingulate gyrus, caudate nuclei, and thalamus. They were related to injury from surgical corridors, tumor mass effect, insertion of a ventricular catheter, and the placement of an Ommaya reservoir. Surprisingly a significantly high uptake was observed in temporal gyri and the parietal lobe. In 13 patients who already completed 18-month PET scans, metabolic abnormalities improved in 11 patients from baseline. One patient had persistent abnormalities. Only one revealed new uptake abnormalities in thalamus, brainstem, cerebellum, and insula. Conclusion: Postoperative FDG PET of craniopharyngioma patients revealed metabolic abnormalities in specific regions of the brain. Proton therapy did not appear to exacerbate these surgery- and tumor-induced defects. In patients with persistent and

  1. Effects of CDP-choline on neurologic deficits and cerebral glucose metabolism in a rat model of cerebral ischemia

    Kakihana, M.; Fukuda, N.; Suno, M.; Nagaoka, A.

    1988-02-01

    The effects of cytidine 5'-diphosphocholine (CDP-choline) on neurologic deficits and cerebral glucose metabolism were studied in a rat model of transient cerebral ischemia. Cerebral ischemia was induced by occluding both common carotid arteries for 20 or 30 minutes 24 hours after the vertebral arteries were permanently occluded by electrocautery. CDP-choline was administered intraperitoneally twice daily for 4 days after reestablishing carotid blood flow. CDP-choline at two dosages (50 and 250 mg/kg) shortened the time required for recovery of spontaneous motor activity in a dose-related manner; recovery time was measured early after reperfusion. Neurologic signs were observed for 10 days. High-dose CDP-choline improved neurologic signs in the rats within 20-30 minutes of ischemia. When cerebral glucose metabolism was assessed on Day 4, increases in the levels of glucose and pyruvate were accompanied by decreases in the synthesis of labeled acetylcholine from uniformly labeled (/sup 14/C)glucose measured in the cerebral cortex of rats with 30 minutes of ischemia. High-dose CDP-choline also attenuated changes in these variables. CDP-(1,2-/sup 14/C)choline injected intravenously 10 minutes after reperfusion was used for membrane lipid biosynthesis. These results indicate that CDP-choline has beneficial effects on brain dysfunction induced by cerebral ischemia, which may be due in part to the restorative effects of CDP-choline on disturbed cerebral glucose metabolism, probably by stimulating phospholipid biosynthesis.

  2. Effects of CDP-choline on neurologic deficits and cerebral glucose metabolism in a rat model of cerebral ischemia

    Kakihana, M.; Fukuda, N.; Suno, M.; Nagaoka, A.

    1988-01-01

    The effects of cytidine 5'-diphosphocholine (CDP-choline) on neurologic deficits and cerebral glucose metabolism were studied in a rat model of transient cerebral ischemia. Cerebral ischemia was induced by occluding both common carotid arteries for 20 or 30 minutes 24 hours after the vertebral arteries were permanently occluded by electrocautery. CDP-choline was administered intraperitoneally twice daily for 4 days after reestablishing carotid blood flow. CDP-choline at two dosages (50 and 250 mg/kg) shortened the time required for recovery of spontaneous motor activity in a dose-related manner; recovery time was measured early after reperfusion. Neurologic signs were observed for 10 days. High-dose CDP-choline improved neurologic signs in the rats within 20-30 minutes of ischemia. When cerebral glucose metabolism was assessed on Day 4, increases in the levels of glucose and pyruvate were accompanied by decreases in the synthesis of labeled acetylcholine from uniformly labeled [ 14 C]glucose measured in the cerebral cortex of rats with 30 minutes of ischemia. High-dose CDP-choline also attenuated changes in these variables. CDP-[1,2- 14 C]choline injected intravenously 10 minutes after reperfusion was used for membrane lipid biosynthesis. These results indicate that CDP-choline has beneficial effects on brain dysfunction induced by cerebral ischemia, which may be due in part to the restorative effects of CDP-choline on disturbed cerebral glucose metabolism, probably by stimulating phospholipid biosynthesis

  3. Similarities of cerebral glucose metabolism in Alzheimer's and Parkinsonian dementia

    Kuhl, D.E.; Metter, E.J.; Benson, D.F.; Ashford, J.W.; Riege, W.H.; Fujikawa, D.G.; Markham, C.H.; Maltese, A.

    1985-01-01

    In the dementia of probable Alzheimer's Disease (AD), there is a decrease in the metabolic ratio of parietal cortex/caudate-thalamus which relates measures in the most and in the least severely affected locations. Since some demented patients with Parkinson's Disease (PDD) are known to share pathological and neurochemical features with AD patients, the authors evaluated if the distribution of cerebral hypometabolism in PDD and AD were the same. Local cerebral metabolic rates were determined using the FDG method and positron tomography in subjects with AD (N=23), and PDD (N=7), multiple infarct dementia (MID)(N=6), and controls (N=10). In MID, the mean par/caudthal ratio was normal (0.79 +- 0.9, N=6). In AD and PDD patients, this ratio correlated negatively with both the severity (r=-0.624, rho=0.001) and duration (r=-0.657, rho=0.001) of dementia. The ratio was markedly decreased in subjects with mild to severe dementia (0.46 +- 0.09, N=21) and with dementia duration greater than two years (0.44 +- 0.08, N=18), but the ratio was also significantly decreased in patients with less advanced disease, i.e., when dementia was only questionable (0.64 +- 0.14, N=9) (t=2.27, rho<0.037) and when duration was two years or less (0.62 +- 0.13, N=12)(t=2.88, rho<0.009). This similarity of hypometabolism in AD and PDD is additional evidence that a common mechanism may operate in both disorders. The par/caud-thal metabolic ratio may be an index useful in the differential diagnosis of early dementia

  4. Fatty liver as a risk factor for progression from metabolically healthy to metabolically abnormal in non-overweight individuals.

    Hashimoto, Yoshitaka; Hamaguchi, Masahide; Fukuda, Takuya; Ohbora, Akihiro; Kojima, Takao; Fukui, Michiaki

    2017-07-01

    Recent studies identified that metabolically abnormal non-obese phenotype is a risk factor for cardiovascular diseases. However, little is known about risk factor for progression from metabolically healthy non-overweight to metabolically abnormal phenotype. We hypothesized that fatty liver had a clinical impact on progression from metabolically healthy non-overweight to metabolically abnormal phenotype. In this retrospective cohort study, 14,093 Japanese (7557 men and 6736 women), who received the health-checkup program from 2004 to 2012, were enrolled. Overweight and obesity were defined as body mass index 23.0-25.0 and ≥25.0 kg/m 2 . Four metabolic factors (impaired fasting glucose, hypertension, hypertriglyceridemia and low high density lipoprotein-cholesterol concentration) were used for definition of metabolically healthy (less than two factors) or metabolically abnormal (two or more). We divided the participants into three groups: metabolically healthy non-overweight (9755 individuals, men/women = 4290/5465), metabolically healthy overweight (2547 individuals, 1800/747) and metabolically healthy obesity (1791 individuals, 1267/524). Fatty liver was diagnosed by ultrasonography. Over the median follow-up period of 5.3 years, 873 metabolically healthy non-overweight, 512 metabolically healthy overweight and 536 metabolically healthy obesity individuals progressed to metabolically abnormal. The adjusted hazard risks of fatty liver on progression were 1.49 (95% confidence interval 1.20-1.83, p = 0.005) in metabolically healthy non-overweight, 1.37 (1.12-1.66, p = 0.002) in metabolically healthy overweight and 1.38 (1.15-1.66, p overweight individuals.

  5. Regional cerebral metabolic rate for glucose and cerebrospinal fluid monoamine metabolites in subacute sclerosing panencephalitis

    Yanai, Kazuhiko; Miyabayashi, Shigeaki; Iinuma, Kazuie; Tada, Keiya; Fukuda, Hiroshi; Ito, Masatoshi; Matsuzawa, Taiju.

    1987-01-01

    Regional cerebral metabolic rate for glucose (rCMRglu) and cerebrospinal fluid monoamine metabolites were measured in two cases of subacute sclerosing panencephalitis (SSPE) with different clinical courses. A marked decrease in rCMRglu was found in the cortical gray matter of a patient with rapidly developing SSPE (3.6 - 4.2 mg/100 g brain tissue/min). However, the rCMRglu was preserved in the caudate and lenticular nuclei of the patient (7.7 mg/100 g/min). The rCMRglu in a patient with slowly developing SSPE revealed patterns and values similar to those of the control. Cerebrospinal fluid monoamine metabolites ; homovanilic acid and 5-hydroxyindoleacetic acid, were decreased in both rapidly and slowly developing SSPE. These data indicated that rCMRglu correlated better with the neurological and psychological status and that dopaminergic and serotonergic abnormalities have been implicated in pathophysiology of SSPE. (author)

  6. Prevalence of Metabolic Abnormalities and Association with Obesity among Saudi College Students

    Abolfotouh, Mostafa A.; Al-Alwan, Ibrahim A.; Al-Rowaily, Mohammed A.

    2012-01-01

    Aim. (i) To estimate the prevalence of the metabolic abnormalities among Saudi college students in Riyadh, Saudi Arabia, and (ii) to investigate the association between different indicators of body composition and these abnormalities. Methods. A total of 501 college students participated in a cross-sectional study. Anthropometric assessments, BP measurements, and biochemical assessment were done. Metabolic abnormalities were identified. Results. Applying BMI, 21.9 % and 20.6% of students were...

  7. Cerebral white matter changes are associated with abnormalities on neurological examination in non-disabled elderly

    Poggesi, Anna; Gouw, Alida; van der Flier, Wiesje

    2013-01-01

    Cerebral white matter changes (WMC) are associated with motor, cognitive, mood, urinary disturbances, and disability, but little is known about the prevalence of neurological signs in patients with these brain lesions. We assessed the presence and occurrence of neurological abnormalities over a 3......-year period and their possible associations with WMC in a cohort of initially non-disabled elderly subjects. Data from the multicenter Leukoaraiosis And DISability study were used. A standard neurological examination was performed at baseline and at each of the annual follow-up visits. A standard MRI...... associated with the presence and the occurrence of neurological signs, independently of other vascular brain lesions, confirming that these lesions have clinical relevance....

  8. Cerebral abnormalities in cocaine abusers: Demonstration by SPECT perfusion brain scintigraphy. Work in progress

    Tumeh, S.S.; Nagel, J.S.; English, R.J.; Moore, M.; Holman, B.L.

    1990-01-01

    Single photon emission computed tomography (SPECT) perfusion brain scans with iodine-123 isopropyl iodoamphetamine (IMP) were obtained in 12 subjects who acknowledged using cocaine on a sporadic to a daily basis. The route of cocaine administration varied from nasal to intravenous. Concurrent abuse of other drugs was also reported. None of the patients were positive for human immunodeficiency virus. Brain scans demonstrated focal defects in 11 subjects, including seven who were asymptomatic, and no abnormality in one. Among the findings were scattered focal cortical deficits, which were seen in several patients and which ranged in severity from small and few to multiple and large, with a special predilection for the frontal and temporal lobes. No perfusion deficits were seen on I-123 SPECT images in five healthy volunteers. Focal alterations in cerebral perfusion are seen commonly in asymptomatic drug users, and these focal deficits are readily depicted by I-123 IMP SPECT

  9. Regional cerebral blood flow abnormalities in late-life depression. Relation to refractoriness and chronification

    Awata, Shuichi; Konno, Michiko; Sato, Mitsumoto; Ito, Hiroshi; Ono, Shuichi; Kawashima, Ryuta; Fukuda, Hiroshi

    1998-01-01

    We examined patterns of regional cerebral blood flow (rCBF) abnormalities in 18 patients with major depressive disorder in late life using single photon emission computed tomography (SPECT) and 99m Tc-hexamethyl-propylenamine oxime ( 99m Tc-HMPAO). Compared with 13 age-matched controls, relative rCBF was significantly decreased bilaterally in the anterior cingulate gyrus, the prefrontal cortex, the temporal cortex, the parietal cortex, the hippocampus and the caudate nucleus. However, it was not correlated with the severity of depression or global cognitive dysfunction. In 10 patients with a prolonged depressive episode or prolonged residual symptoms (the refractory subgroup), robust and extensive decreases in rCBF were found compared with controls and the rCBF decreased significantly in the anterior cingulate gyrus and the prefrontal cortex compared with that in the non-refractory subgroup. In the non-reflactory subgroup, rCBF decreased significantly in the caudate nucleus and tended to decrease in the anterior cingulate gyrus compared with controls. These findings indicate that dysfunction of the limbic system, the cerebral association cortex and the caudate nucleus may be implicated in late-life depression and that robust and extensive hypoperfusion, especially in the anterior cingulate and the prefrontal regions, may relate to refractoriness or chronification of depression. (author). 60 refs

  10. Regional cerebral blood flow abnormalities in late-life depression. Relation to refractoriness and chronification

    Awata, Shuichi; Konno, Michiko; Sato, Mitsumoto [Tohoku Univ., Sendai (Japan). School of Medicine; Ito, Hiroshi; Ono, Shuichi; Kawashima, Ryuta; Fukuda, Hiroshi

    1998-02-01

    We examined patterns of regional cerebral blood flow (rCBF) abnormalities in 18 patients with major depressive disorder in late life using single photon emission computed tomography (SPECT) and {sup 99m}Tc-hexamethyl-propylenamine oxime ({sup 99m}Tc-HMPAO). Compared with 13 age-matched controls, relative rCBF was significantly decreased bilaterally in the anterior cingulate gyrus, the prefrontal cortex, the temporal cortex, the parietal cortex, the hippocampus and the caudate nucleus. However, it was not correlated with the severity of depression or global cognitive dysfunction. In 10 patients with a prolonged depressive episode or prolonged residual symptoms (the refractory subgroup), robust and extensive decreases in rCBF were found compared with controls and the rCBF decreased significantly in the anterior cingulate gyrus and the prefrontal cortex compared with that in the non-refractory subgroup. In the non-reflactory subgroup, rCBF decreased significantly in the caudate nucleus and tended to decrease in the anterior cingulate gyrus compared with controls. These findings indicate that dysfunction of the limbic system, the cerebral association cortex and the caudate nucleus may be implicated in late-life depression and that robust and extensive hypoperfusion, especially in the anterior cingulate and the prefrontal regions, may relate to refractoriness or chronification of depression. (author). 60 refs.

  11. Unchanged cerebral blood flow and oxidative metabolism after acclimatization to high altitude

    Møller, Kirsten; Paulson, Olaf B; Hornbein, Thomas F.

    2002-01-01

    The authors investigated the effect of acclimatization to high altitude on cerebral blood flow and oxidative metabolism at rest and during exercise. Nine healthy, native sea-level residents were studied 3 weeks after arrival at Chacaltaya, Bolivia (5,260 m) and after reacclimatization to sea level....... At high altitude at rest, arterial carbon dioxide tension, oxygen saturation, and oxygen tension were significantly reduced, and arterial oxygen content was increased because of an increase in hemoglobin concentration. Global cerebral blood flow was similar in the four conditions. Cerebral oxygen delivery...... and cerebral metabolic rates of oxygen and glucose also remained unchanged, whereas cerebral metabolic rates of lactate increased slightly but nonsignificantly at high altitude during exercise compared with high altitude at rest. Reaction time was unchanged. The data indicate that cerebral blood flow...

  12. Cerebral Metabolic Differences Associated with Cognitive Impairment in Parkinson's Disease.

    Yilin Tang

    Full Text Available To characterize cerebral glucose metabolism associated with different cognitive states in Parkinson's disease (PD using 18F-fluorodeoxyglucose (FDG and Positron Emission Tomography (PET.Three groups of patients were recruited in this study including PD patients with dementia (PDD; n = 10, with mild cognitive impairment (PD-MCI; n = 20, and with no cognitive impairment (PD-NC; n = 30. The groups were matched for age, sex, education, disease duration, motor disability, levodopa equivalent dose and Geriatric Depression Rating Scale (GDS score. All subjects underwent a FDG-PET study. Maps of regional metabolism in the three groups were compared using statistical parametric mapping (SPM5.PD-MCI patients exhibited limited areas of hypometabolism in the frontal, temporal and parahippocampal gyrus compared with the PD-NC patients (p < 0.01. PDD patients had bilateral areas of hypometabolism in the frontal and posterior parietal-occipital lobes compared with PD-MCI patients (p < 0.01, and exhibited greater metabolic reductions in comparison with PD-NC patients (p < 0.01.Compared with PD-NC patients, hypometabolism was much higher in the PDD patients than in PD-MCI patients, mainly in the posterior cortical areas. The result might suggest an association between posterior cortical hypometabolism and more severe cognitive impairment. PD-MCI might be important for early targeted therapeutic intervention and disease modification.

  13. Hepatic and cerebral energy metabolism after neonatal canine alimentation.

    Kliegman, R M; Miettinen, E L; Morton, S K

    1983-04-01

    Intrahepatic and intracerebral metabolic responses to neonatal fasting or enteric carbohydrate alimentation were investigated among newborn dogs. Pups were either fasted or given an intravenous glucose infusion (alimented) before an enteric feeding of physiologic quantities of either glucose or galactose. These pups were also compared to another group which was completely starved throughout the study period. Gastrointestinal carbohydrate feeding resulted in enhanced hepatic glycogen content among pups after a prior state of fasting. Though there were no differences of glycogen content between glucose or galactose feeding in this previously fasted group, combined intravenous glucose and enteric galactose administration produced the greatest effect on hepatic glycogen synthesis. Intrahepatic fructose 1, 6-diphosphate and phosphoenolpyruvate levels were increased among previously fasted pups fed enteric monosaccharides compared to completely starved control pups, whereas intrahepatic phosphoenolpyruvate and pyruvate levels were elevated after combined intravenous and enteric carbohydrate administration. Of greater interest was the observation that hepatic levels of ATP were significantly elevated among all groups given exogenous carbohydrates compared to the completely starved control group. In contrast to the augmented hepatic glycogen and ATP levels, there were no alterations of cerebral glycogen or ATP after alimentation. Nevertheless, cerebral pyruvate and/or phosphoenolpyruvate concentrations were elevated after enteric or combined intravenous and enteric alimentation compared to the totally starved control pups.

  14. Sympathetic influence on cerebral blood flow and metabolism during exercise in humans

    Seifert, Thomas; Secher, Niels H

    2011-01-01

    This review focuses on the possibility that autonomic activity influences cerebral blood flow (CBF) and metabolism during exercise in humans. Apart from cerebral autoregulation, the arterial carbon dioxide tension, and neuronal activation, it may be that the autonomic nervous system influences CBF...... perfusion and reduces the near-infrared determined cerebral oxygenation at rest, but not during exercise associated with an increased cerebral metabolic rate for oxygen (CMRO(2)), suggesting competition between CMRO(2) and sympathetic control of CBF. CMRO(2) does not change during even intense handgrip...

  15. Cerebral white matter changes are associated with abnormalities on neurological examination in non-disabled elderly: the LADIS study

    Poggesi, A.; Gouw, A.A.; van der Flier, W.M.; Pracucci, G.; Chabriat, H.; Erkinjuntti, T.; Fazekas, F.; Ferro, J.M.; Hennerici, M.; Langhorne, P.; O'Brien, J. T.; Visser, M.C.; Wahlund, L.O.; Waldemar, G.; Wallin, A.; Scheltens, P.; Inzitari, D.; Pantoni, L.

    2013-01-01

    Cerebral white matter changes (WMC) are associated with motor, cognitive, mood, urinary disturbances, and disability, but little is known about the prevalence of neurological signs in patients with these brain lesions. We assessed the presence and occurrence of neurological abnormalities over a

  16. ELECTROCARDIOGRAPHIC ABNORMALITIES AMONG MEXICAN AMERICANS: CORRELATIONS WITH DIABETES, OBESITY, AND THE METABOLIC SYNDROME.

    Queen, Saulette R; Smulevitz, Beverly; Rentfro, Anne R; Vatcheva, Kristina P; Kim, Hyunggun; McPherson, David D; Hanis, Craig L; Fisher-Hoch, Susan P; McCormick, Joseph B; Laing, Susan T

    2012-04-01

    Resting ischemic electrocardiographic abnormalities have been associated with cardiovascular mortality. Simple markers of abnormal autonomic tone have also been associated with diabetes, obesity, and the metabolic syndrome in some populations. Data on these electrocardiographic abnormalities and correlations with coronary risk factors are lacking among Mexican Americans wherein these conditions are prevalent. This study aimed to evaluate the prevalent resting electrocardiographic abnormalities among community-dwelling Mexican Americans, and correlate these findings with coronary risk factors, particularly diabetes, obesity, and the metabolic syndrome. Study subjects (n=1280) were drawn from the Cameron County Hispanic Cohort comprised of community-dwelling Mexican Americans living in Brownsville, Texas at the United States-Mexico border. Ischemic electrocardiographic abnormalities were defined as presence of ST/T wave abnormalities suggestive of ischemia, abnormal Q waves, and left bundle branch block. Parameters that reflect autonomic tone, such as heart rate-corrected QT interval and resting heart rate, were also measured. Ischemic electrocardiographic abnormalities were more prevalent among older persons and those with hypertension, diabetes, obesity, and the metabolic syndrome. Subjects in the highest quartiles of QTc interval and resting heart rate were also more likely to be diabetic, hypertensive, obese, or have the metabolic syndrome. Among Mexican Americans, persons with diabetes, obesity, and the metabolic syndrome were more likely to have ischemic electrocardiographic abnormalities, longer QTc intervals, and higher resting heart rates. A resting electrocardiogram can play a complementary role in the comprehensive evaluation of cardiovascular risk in this minority population.

  17. Brain 18F-FDG PET Metabolic Abnormalities in Patients with Long-Lasting Macrophagic Myofascitis.

    Van Der Gucht, Axel; Aoun Sebaiti, Mehdi; Guedj, Eric; Aouizerate, Jessie; Yara, Sabrina; Gherardi, Romain K; Evangelista, Eva; Chalaye, Julia; Cottereau, Anne-Ségolène; Verger, Antoine; Bachoud-Levi, Anne-Catherine; Abulizi, Mukedaisi; Itti, Emmanuel; Authier, François-Jérôme

    2017-03-01

    The aim of this study was to characterize brain metabolic abnormalities in patients with macrophagic myofascitis (MMF) and the relationship with cognitive dysfunction through the use of PET with 18 F-FDG. Methods: 18 F-FDG PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (age [mean ± SD], 45.9 ± 12 y; 74% women). Images were analyzed with statistical parametric mapping (SPM12). Through the use of analysis of covariance, all 18 F-FDG PET brain images of MMF patients were compared with those of a reference population of 44 healthy subjects similar in age (45.4 ± 16 y; P = 0.87) and sex (73% women; P = 0.88). The neuropsychological assessment identified 4 categories of patients: those with no significant cognitive impairment ( n = 42), those with frontal subcortical (FSC) dysfunction ( n = 29), those with Papez circuit dysfunction ( n = 22), and those with callosal disconnection ( n = 7). Results: In comparison with healthy subjects, the whole population of patients with MMF exhibited a spatial pattern of cerebral glucose hypometabolism ( P glucose hypometabolism that was most marked in MMF patients with FSC dysfunction. Further studies are needed to determine whether this pattern could represent a diagnostic biomarker of MMF in patients with chronic fatigue syndrome and cognitive dysfunction. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  18. In vivo imaging of cerebral energy metabolism with two-photon fluorescence lifetime microscopy of NADH.

    Yaseen, Mohammad A; Sakadžić, Sava; Wu, Weicheng; Becker, Wolfgang; Kasischke, Karl A; Boas, David A

    2013-02-01

    Minimally invasive, specific measurement of cellular energy metabolism is crucial for understanding cerebral pathophysiology. Here, we present high-resolution, in vivo observations of autofluorescence lifetime as a biomarker of cerebral energy metabolism in exposed rat cortices. We describe a customized two-photon imaging system with time correlated single photon counting detection and specialized software for modeling multiple-component fits of fluorescence decay and monitoring their transient behaviors. In vivo cerebral NADH fluorescence suggests the presence of four distinct components, which respond differently to brief periods of anoxia and likely indicate different enzymatic formulations. Individual components show potential as indicators of specific molecular pathways involved in oxidative metabolism.

  19. Age differences in intercorrelations between regional cerebral metabolic rates for glucose

    Horwitz, B.; Duara, R.; Rapoport, S.I.

    1986-01-01

    Patterns of cerebral metabolic intercorrelations were compared in the resting state in 15 healthy young men (ages 20 to 32 years) and 15 healthy elderly men (ages 64 to 83 years). Controlling for whole-brain glucose metabolism, partial correlation coefficients were determined between pairs of regional cerebral metabolic rates for glucose determined by positron emission tomography using [18F]fluorodeoxyglucose and obtained in 59 brain regions. Compared with the young men, the elderly men had fewer statistically significant correlations, with the most notable reductions observed between the parietal lobe regions, and between the parietal and frontal lobe regions. These results suggest that cerebral functional interactions are reduced in healthy elderly men

  20. R6/2 Huntington's disease mice develop early and progressive abnormal brain metabolism and seizures.

    Cepeda-Prado, Efrain; Popp, Susanna; Khan, Usman; Stefanov, Dimitre; Rodríguez, Jorge; Menalled, Liliana B; Dow-Edwards, Diana; Small, Scott A; Moreno, Herman

    2012-05-09

    A hallmark feature of Huntington's disease pathology is the atrophy of brain regions including, but not limited to, the striatum. Though MRI studies have identified structural CNS changes in several Huntington's disease (HD) mouse models, the functional consequences of HD pathology during the progression of the disease have yet to be investigated using in vivo functional MRI (fMRI). To address this issue, we first established the structural and functional MRI phenotype of juvenile HD mouse model R6/2 at early and advanced stages of disease. Significantly higher fMRI signals [relative cerebral blood volumes (rCBVs)] and atrophy were observed in both age groups in specific brain regions. Next, fMRI results were correlated with electrophysiological analysis, which showed abnormal increases in neuronal activity in affected brain regions, thus identifying a mechanism accounting for the abnormal fMRI findings. [(14)C] 2-deoxyglucose maps to investigate patterns of glucose utilization were also generated. An interesting mismatch between increases in rCBV and decreases in glucose uptake was observed. Finally, we evaluated the sensitivity of this mouse line to audiogenic seizures early in the disease course. We found that R6/2 mice had an increased susceptibility to develop seizures. Together, these findings identified seizure activity in R6/2 mice and show that neuroimaging measures sensitive to oxygen metabolism can be used as in vivo biomarkers, preceding the onset of an overt behavioral phenotype. Since fMRI-rCBV can also be obtained in patients, we propose that it may serve as a translational tool to evaluate therapeutic responses in humans and HD mouse models.

  1. Depressed cerebral oxygen metabolism in patients with chronic renal failure. A positron emission tomography study

    Hirakata, Hideki; Kanai, Hidetoshi; Nakane, Hiroshi; Fujii, Ken-ichiro; Hirakata, Eriko; Ibayashi, Setsuro; Kuwabara, Yasuo; Deenitchna, S.S.; Fujishima, Masatoshi

    2001-01-01

    In order to elucidate brain oxygen metabolism in uremic patients, the regional cerebral blood flow (rCBF), oxygen extraction (rOEF) and oxygen metabolism (rCMRO 2 ) were measured by positron emission tomography (PET) in both 10 hemodialysis patients (HD: male [m]/female [f]=2/8, age of 49±3 [SEM] years old, HD duration of 113±26 months) and 13 pre-dialysis renal failure patients (CRF: m/f=10/3, age of 61±2 years old, serum creatinine (SCr) of 6.3±1.0 mg/dl). Data were compared with 20 non-uremic subjects (Control: m/f=7/13, age of 62±2 years old, SCr of 0.9±0.1 mg/dl). They had no neurological abnormalities, congestive heart failure, history of cerebrovascular accident, diabetes mellitus, or symptomatic brain lesion on magnetic resonance imaging. The age of HD was significantly younger than the other groups (p 2 in both HD (1.82±0.10 ml/min/100 g) and CRF (1.95±0.09) showed significantly lower values as compared to Control (2.23±0.05) (p<0.01, respectively). Hemispheric rCBF in HD (35.6±2.1 ml/100 g/min) and in CRF (36.1±2.1) were not different from that in Control (31.8±1.4). Hemispheric rOEF in CRF (45.7±1.6%) was significantly higher than that in Control (40.5±1.2%) (p<0.02), but that in HD (43.7±1.9%) did not increase significantly. These tendencies were similar in all regions of interest, especially in the cerebral cortices, but not in the cerebellum. All PET parameters in the frontal cortices tended to show the lowest value in renal failure patients. For all HD patients, rCBF in both the frontal cortex and the white matter correlated inversely with HD duration (frontal cortex: r=-0.649, p<0.05; white matter: r=-0.706, p<0.02). Based on these data, it is concluded that brain oxygen metabolism is depressed in renal failure patients on or before hemodialysis treatment. The cause for the depressed brain oxygen metabolism is considered to be due either to the dysregulation of cerebral circulation or to lower brain cell activity. (author)

  2. Sympathetic influence on cerebral blood flow and metabolism during exercise in humans

    Seifert, Thomas; Secher, Niels H

    2011-01-01

    This review focuses on the possibility that autonomic activity influences cerebral blood flow (CBF) and metabolism during exercise in humans. Apart from cerebral autoregulation, the arterial carbon dioxide tension, and neuronal activation, it may be that the autonomic nervous system influences CBF...... perfusion and reduces the near-infrared determined cerebral oxygenation at rest, but not during exercise associated with an increased cerebral metabolic rate for oxygen (CMRO(2)), suggesting competition between CMRO(2) and sympathetic control of CBF. CMRO(2) does not change during even intense handgrip......-oxidative carbohydrate uptake during exercise. Adrenaline appears to accelerate cerebral glycolysis through a beta2-adrenergic receptor mechanism since noradrenaline is without such an effect. In addition, the exercise-induced cerebral non-oxidative carbohydrate uptake is blocked by combined beta 1/2-adrenergic blockade...

  3. Cerebral vascular control and metabolism in heat stress

    Bain, Anthony R; Nybo, Lars; Ainslie, Philip N

    2015-01-01

    implications and pathologies known to confound cerebral functioning during hyperthermia. A reduction in cerebral blood flow (CBF), derived primarily from a respiratory-induced alkalosis, underscores the cerebrovascular changes to hyperthermia. Arterial pressures may also become compromised because of reduced...

  4. Prevalence of Metabolic Abnormalities and Association with Obesity among Saudi College Students

    Mostafa A. Abolfotouh

    2012-01-01

    Full Text Available Aim. (i To estimate the prevalence of the metabolic abnormalities among Saudi college students in Riyadh, Saudi Arabia, and (ii to investigate the association between different indicators of body composition and these abnormalities. Methods. A total of 501 college students participated in a cross-sectional study. Anthropometric assessments, BP measurements, and biochemical assessment were done. Metabolic abnormalities were identified. Results. Applying BMI, 21.9 % and 20.6% of students were classified as overweight and obese, respectively. Central obesity was prevalent in 26.9% and 42.2% of students based on WC and WHtR, respectively. Other metabolic abnormalities were hypertension (23.6% and abnormal FPG level (22.6%. Three or more abnormalities were prevalent in 7.8% of students and increased significantly to 26.4%, 20%, and 17.6 in obese subjects based on BMI, WC, and WHtR, respectively. With the exception of abnormal FPG, prevalence of individual metabolic abnormalities as well as the number of these abnormalities significantly increased with increasing BMI, WC, and WHtR (P<0.001 each. Conclusion. Our findings provide evidence for the presence of MS in Saudi college students. Central adiposity contributes to the high incidence of individual MS components. College health programs that promote healthful lifestyle and avoidance of adult weight gain are recommended.

  5. Global cerebral blood flow and metabolism during acute hyperketonemia in the awake and anesthetized rat

    Linde, Rasmus; Hasselbalch, Steen G.; Topp, Simon

    2006-01-01

    and cerebral metabolism could not be explained by alterations in blood pH or arterial CO2 tension. By measuring cerebral intracellular pH by 31P nuclear magnetic resonance spectroscopy, it could further be concluded that the brain pH was unchanged during acute hyperketonemia. These observations indicate......In the human setting, it has been shown that acute increase in the concentration of ketone bodies by infusion of beta-hydroxybutyrate increased the cerebral blood flow (CBF) without affecting the overall cerebral metabolic activity. The mechanism by which this effect of ketone bodies was mediated...... that the mechanism responsible for the increase in CBF is rather a direct effect on the cerebral endothelium than via some metabolic interactions...

  6. Cerebral perfusion, oxygenation and metabolism during exercise in young and elderly individuals

    Fisher, James P; Hartwich, Doreen; Seifert, Thomas

    2013-01-01

    )), glucose and lactate across the brain. The molar ratio between the cerebral uptake of O(2) versus carbohydrate (O(2)-carbohydrate index; O(2) / [glucose + 0.5 lactate]; OCI), the cerebral metabolic rate of O(2) (CMRO(2)) and changes in mitochondrial O(2) tension (P(mito)O(2)) were calculated. W...

  7. Acute effects of thalamotomy and pallidotomy on regional cerebral metabolism, evaluated by PET

    Henselmans, JML; de Jong, BM; Pruim, J; Staal, MJ; Rutgers, AWF; Haaxma, R

    The subacute effect of thalamotomy and pallidotomy on regional cerebral metabolism was studied by means of Positron Emission Tomography (PET). In this way we aimed to identify the pattern of functional deafferentiation following a specific lesion in the basal ganglia. The cerebral distribution of

  8. Regional cerebral glucose metabolism in patients with Parkinson's disease with or without dementia

    Sasaki, Masayuki; Ichiya, Yuichi; Hosokawa, Shinichi; Otsuka, Makoto; Kuwabara, Yasuo; Fukumura, Toshimitsu; Kato, Motohiro; Goto, Ikuo; Masuda, Kouji [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1992-11-01

    By means of positron emission tomography, the cerebral glucose metabolism in 5 patients with Parkinson's disease with dementia was compared with that in 9 patients without dementia, and that in 5 normal volunteers. The metabolic rates for glucose were measured by placing one hundred regions of interest. In the demented patients, cerebral glucose metabolism was diffusely decreased compared with that of the non-demented patients and the normal controls. The most significant decrease in glucose metabolism was observed in the angular gyrus (49.7% of the normal controls). The glucose metabolism in the cingulate, pre- and postcentral, occipital and subcortical regions was relatively spared (62.1 to 85.5% of the normal controls). In the patients without dementia, the glucose metabolism in each region was not significantly different from that in the normal controls. These results suggest that diffuse glucose hypometabolism in the cerebral cortex may correlate with that of patients with Parkinson's disease with dementia. (author).

  9. Metabolic abnormalities and genitourinary tract anatomical alternations in patients with recurrent urolithiasis

    John Neil

    2017-06-01

    Conclusions: 80% of patients with recurrent stone disease had some measure of metabolic abnormality to account for the disease. The use of two 24-hour urine samples significantly improved the detection rate of metabolic abnormalities compared to a single sample. The major limitation of this study was the small number of patients as well as the short study duration. [Arch Clin Exp Surg 2017; 6(2.000: 81-85

  10. Abnormal Responses of the Human Cerebral Microcirculation to Papaverin During Aneurysm Surgery

    Pennings, Frederik A.; Albrecht, Kees W.; Muizelaar, J. Paul; Schuurman, P. Richard; Bouma, Gerrit J.

    2009-01-01

    BACKGROUND AND PURPOSE: The role of the cerebral microcirculation in delayed ischemia after subarachnoid hemorrhage remains obscure. To test the hypothesis that cerebral arterioles have a reduced capacity to dilate after subarachnoid hemorrhage, we studied the microvascular responses to papaverine

  11. Decreased cerebral glucose metabolism associated with mental deterioration in multi-infarct dementia

    Meguro, K.; Doi, C.; Yamaguchi, T.; Sasaki, H.; Matsui, H.; Yamada, K.; Kinomura, S.; Tohoku Univ.; Itoh, M.

    1991-01-01

    Cerebral glucose metabolism of 18 patients with multi-infarct dementia (MID) and 10 age-matched normal subjects were examined with positron emission tomography and the 18 -F-fluoro-deoxy-glucose technique. MID patients had significantly lower glucose metabolsim in all the grey matter regions measured and were also characterized by more individuality in metabolic pattern. MID patients were also evaluated as to intelligence quotient (IQ). A positive correlation between IQ as shown by the Tanaka-Binet test and glucose metabolism for the entire grey matter was found. The clinical applicability of this test for predicting cerebral metabolism is discussed. (orig.)

  12. The relationship between the cerebral blood flow, oxygen consumption and glucose metabolism in primary degenerative dementia

    Kuwabara, Yasuo; Ichiya, Yuichi; Ichimiya, Atsushi; Sasaki, Masayuki; Akashi, Yuko; Yoshida, Tsuyoshi; Fukumura, Toshimitsu; Masada, Kouji [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1995-03-01

    The CBF, CMRO{sub 2} and CMRGlu were measured in patients with primary degenerative dementia including 5 patients with dementia of Alzheimer`s type and 4 patients with Pick`s disease, and then the correlation between the cerebral blood flow and energy metabolism was evaluated. The control subjects consisted of 5 age-matched normal volunteers. The CBF, CMRO{sub 2} and CMRGlu decreased in the bilateral frontal, temporal and parietal regions in the patients with Alzheimer`s dementia, while they decreased in the bilateral frontal and temporal regions in the patients with Pick`s disease. Both the CBF and CMRO{sub 2} were closely correlated with each other. However, the CMRGlu was more severely impaired than the CBF or CMRO{sub 2} in both pathological conditions. These results suggested that CMRGlu began to decrease before the reduction of the aerobic metabolism and thus measuring the CMRGlu is considered to be the most sensitive method for detecting abnormal regions in primary degenerative dementia. (author).

  13. Effect of the acquisition enhancing drug piracetam on rat cerebral energy metabolism. Comparison with naftidrofuryl and methamphetamine

    Nickolson, V.J.; Wolthuis, O.L.

    1976-01-01

    The effects of Piracetam, Naftidrofuryl and methamphetamine on several parameters of cerebral energy metabolism have been studied. At variance with some reports in the literature neither Piracetam nor Naftidrofuryl affected the cerebral contents of adenine nucleotides and, accordingly, both

  14. Influence of abnormal glucose metabolism on coronary microvascular function after a recent myocardial infarction

    Løgstrup, Brian B; Høfsten, Dan E; Christophersen, Thomas B

    2009-01-01

    OBJECTIVES: This study sought to assess the association between abnormal glucose metabolism and abnormal coronary flow reserve (CFR) in patients with a recent acute myocardial infarction (AMI). BACKGROUND: Mortality and morbidity after AMI is high among patients with abnormal glucose metabolism, ...... (140 microg/kg/min) to obtain the hyperemic flow profiles. The CFR was defined as the ratio of hyperemic to baseline peak diastolic coronary flow velocities. RESULTS: Median CFR was 1.9 (interquartile range [IQR] 1.4 to 2.4], and 109 (60%) patients had a CFR...

  15. Cerebral blood flow and oxygen metabolism in patients with Parkinson's disease

    Kitamura, Shin; Ujike, Takashi; Kuroki, Soemu; Sakamoto, Shizuki; Soeda, Toshiyuki; Terashi, Akiro; Iio, Masaaki

    1988-10-01

    The purpose of this study was to determine functional changes in the cerebral cortex and basal ganglia in Parkinson's disease (PD). Cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO/sub 2/) were determined using 0-15 positron emission tomography in 10 PD patients and five age-matched healthy volunteers. There was a tendency among PD patients towards a decreased CBF and CMRO/sub 2/ in the cerebral cortex and basal ganglia. These values were significantly lower in the frontal cortex in the PD group than the control group. There was no difference in OEF between the groups. A more decreased cerebral oxygen metabolism was observed in patients staged as severer on the scale of Hoehn and Yahr. There was no correlation between cerebral oxygen metabolism and tremor, rigidity, or bradykinesis. A decreased cerebral oxygen metabolism was associated with mental disorders, such as depression, hallucination, and dementia. These results may provide an important clue for the understanding of mesocortical dopaminergic pathway and the relationship between PD and dementia. (N.K.).

  16. Cerebral blood flow and oxygen metabolism in patients with Parkinson's disease

    Kitamura, Shin; Ujike, Takashi; Kuroki, Soemu; Sakamoto, Shizuki; Soeda, Toshiyuki; Terashi, Akiro; Iio, Masaaki.

    1988-01-01

    The purpose of this study was to determine functional changes in the cerebral cortex and basal ganglia in Parkinson's disease (PD). Cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO 2 ) were determined using 0-15 positron emission tomography in 10 PD patients and five age-matched healthy volunteers. There was a tendency among PD patients towards a decreased CBF and CMRO 2 in the cerebral cortex and basal ganglia. These values were significantly lower in the frontal cortex in the PD group than the control group. There was no difference in OEF between the groups. A more decreased cerebral oxygen metabolism was observed in patients staged as severer on the scale of Hoehn and Yahr. There was no correlation between cerebral oxygen metabolism and tremor, rigidity, or bradykinesis. A decreased cerebral oxygen metabolism was associated with mental disorders, such as depression, hallucination, and dementia. These results may provide an important clue for the understanding of mesocortical dopaminergic pathway and the relationship between PD and dementia. (N.K.)

  17. Cerebral Metabolism and the Role of Glucose Control in Acute Traumatic Brain Injury.

    Buitrago Blanco, Manuel M; Prashant, Giyarpuram N; Vespa, Paul M

    2016-10-01

    This article reviews key concepts of cerebral glucose metabolism, neurologic outcomes in clinical trials, the biology of the neurovascular unit and its involvement in secondary brain injury after traumatic brain insults, and current scientific and clinical data that demonstrate a better understanding of the biology of metabolic dysfunction in the brain, a concept now known as cerebral metabolic energy crisis. The use of neuromonitoring techniques to better understand the pathophysiology of the metabolic crisis is reviewed and a model that summarizes the triphasic view of cerebral metabolic disturbance supported by existing scientific data is outlined. The evidence is summarized and a template for future research provided. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Clinical significance of brain SPECT abnormalities of thalami and cerebellum in cerebral palsy with normal MRI

    Park, C. H.; Lim, S. Y.; Lee, I. Y.; Kim, O. H.; Bai, M. S.; Kim, S. J.; Yoon, S. N.; Cho, C. W.

    1997-01-01

    The cerebral palsy(CP) encephalopathies are often of uncertain etiology and various functional image findings comparing with anatomical image findings have been reported. However, only a few have mentioned its clinical implications. The purpose of our report is to compare clinical severity and functional SPECT abnormalities of thalami and cerebellum in CP patients with normal MRI. Thirty six CP patients with bilateral spastic palsy who had normal MRI and brain SPECT were studied from July 1996 to September 1997. The patients' age at the time of SPECT was 22.84±17.69 months. The patients were divided into two groups according to motor quotient(MQ); moderate defect (>50MQ : n=27 MQ=22.78±10.36), mild defect ( 2 test. Brain SPECT was performed following IV administration of 0.05-0.1 mCi/kg (minimum 2.0 mCi) of Tc-99m ECD and chloral hydrate sedation (50-80 mg/kg p.o) using a triple head system (MS 3, Siemens). Interpretation of brain SPECT was visual analysis: severe decrease is defined when the defect is moderate to marked and mild decrease in rCBF as mild. Seven of 36 (19.4%) showed unilateral or bilateral moderate decrease in rCBF in thalami, 20(55.6%) showed mild decrease, and 9(25.0%) showed no decreased rCBF. All 7 who had moderate thalamic defect reveled moderate motor defect clinically. Ten of 36(27.9%) revealed unilateral or bilateral moderate rCBF defect, 23 (63.9%) depicted mild defect, and 3(8.3%) showed no defect. Sixteen with moderate thalamic rCBF defect showed moderate motor defect in 15 patients. There was statistically significant (p=0.02605) relationship between rCBF defect and motor defect in our CP patients. In conclusion, brain SPECT appears sensitive, non-invasive tool in the evaluation as well as in the prognostication of bilateral spastic cerebral palsy patients and deserves further study using larger number of patients

  19. Clinical significance of brain SPECT abnormalities of thalami and cerebellum in cerebral palsy with normal MRI

    Park, C. H.; Lim, S. Y.; Lee, I. Y.; Kim, O. H.; Bai, M. S.; Kim, S. J.; Yoon, S. N.; Cho, C. W. [College of Medicine, Ajou Univ., Suwon (Korea, Republic of)

    1997-07-01

    The cerebral palsy(CP) encephalopathies are often of uncertain etiology and various functional image findings comparing with anatomical image findings have been reported. However, only a few have mentioned its clinical implications. The purpose of our report is to compare clinical severity and functional SPECT abnormalities of thalami and cerebellum in CP patients with normal MRI. Thirty six CP patients with bilateral spastic palsy who had normal MRI and brain SPECT were studied from July 1996 to September 1997. The patients' age at the time of SPECT was 22.84{+-}17.69 months. The patients were divided into two groups according to motor quotient(MQ); moderate defect (>50MQ : n=27 MQ=22.78{+-}10.36), mild defect (<50MQ : n=9, MQ=66.11{+-}13.87). The degree of rCBF decrease between the two groups was evaluated by {chi}{sup 2} test. Brain SPECT was performed following IV administration of 0.05-0.1 mCi/kg (minimum 2.0 mCi) of Tc-99m ECD and chloral hydrate sedation (50-80 mg/kg p.o) using a triple head system (MS 3, Siemens). Interpretation of brain SPECT was visual analysis: severe decrease is defined when the defect is moderate to marked and mild decrease in rCBF as mild. Seven of 36 (19.4%) showed unilateral or bilateral moderate decrease in rCBF in thalami, 20(55.6%) showed mild decrease, and 9(25.0%) showed no decreased rCBF. All 7 who had moderate thalamic defect reveled moderate motor defect clinically. Ten of 36(27.9%) revealed unilateral or bilateral moderate rCBF defect, 23 (63.9%) depicted mild defect, and 3(8.3%) showed no defect. Sixteen with moderate thalamic rCBF defect showed moderate motor defect in 15 patients. There was statistically significant (p=0.02605) relationship between rCBF defect and motor defect in our CP patients. In conclusion, brain SPECT appears sensitive, non-invasive tool in the evaluation as well as in the prognostication of bilateral spastic cerebral palsy patients and deserves further study using larger number of patients.

  20. Effects of hyperthermia on cerebral blood flow and metabolism during prolonged exercise in humans

    Nybo, Lars; Møller, Kirsten; Volianitis, Stefanos

    2002-01-01

    The development of hyperthermia during prolonged exercise in humans is associated with various changes in the brain, but it is not known whether the cerebral metabolism or the global cerebral blood flow (gCBF) is affected. Eight endurance-trained subjects completed two exercise bouts on a cycle...... ergometer. The gCBF and cerebral metabolic rates of oxygen, glucose, and lactate were determined with the Kety-Schmidt technique after 15 min of exercise when core temperature was similar across trials, and at the end of exercise, either when subjects remained normothermic (core temperature = 37.9 degrees C...... with control at the end of exercise (43 +/- 4 vs. 51 +/- 4 ml. 100 g(-1). min(-1); P glucose, and the cerebral metabolic rate was therefore higher at the end...

  1. Associations between Zinc Deficiency and Metabolic Abnormalities in Patients with Chronic Liver Disease

    Takashi Himoto

    2018-01-01

    Full Text Available Zinc (Zn is an essential trace element which has favorable antioxidant, anti-inflammatory, and apoptotic effects. The liver mainly plays a crucial role in maintaining systemic Zn homeostasis. Therefore, the occurrence of chronic liver diseases, such as chronic hepatitis, liver cirrhosis, or fatty liver, results in the impairment of Zn metabolism, and subsequently Zn deficiency. Zn deficiency causes plenty of metabolic abnormalities, including insulin resistance, hepatic steatosis and hepatic encephalopathy. Inversely, metabolic abnormalities like hypoalbuminemia in patients with liver cirrhosis often result in Zn deficiency. Recent studies have revealed the putative mechanisms by which Zn deficiency evokes a variety of metabolic abnormalities in chronic liver disease. Zn supplementation has shown beneficial effects on such metabolic abnormalities in experimental models and actual patients with chronic liver disease. This review summarizes the pathogenesis of metabolic abnormalities deriving from Zn deficiency and the favorable effects of Zn administration in patients with chronic liver disease. In addition, we also highlight the interactions between Zn and other trace elements, vitamins, amino acids, or hormones in such patients.

  2. Abnormal islet sphingolipid metabolism in type 1 diabetes

    Holm, Laurits J; Krogvold, Lars; Hasselby, Jane P

    2018-01-01

    AIMS/HYPOTHESIS: Sphingolipids play important roles in beta cell physiology, by regulating proinsulin folding and insulin secretion and in controlling apoptosis, as studied in animal models and cell cultures. Here we investigate whether sphingolipid metabolism may contribute to the pathogenesis....... Transcriptional analysis was used to evaluate expression of sphingolipid-related genes in isolated human islets. Genome-wide association studies (GWAS) and a T cell proliferation assay were used to identify type 1 diabetes related polymorphisms and test how these affect cellular islet autoimmunity. Finally, we...... diabetes, which were associated with reduced expression of enzymes involved in sphingolipid metabolism. Next, we discovered eight gene polymorphisms (ORMDL3, SPHK2, B4GALNT1, SLC1A5, GALC, PPARD, PPARG and B4GALT1) involved in sphingolipid metabolism that contribute to the genetic predisposition to type 1...

  3. Quantification of structural cerebral abnormalities on MRI 18 months after aneurysmal subarachnoid hemorrhage in patients who received endovascular treatment

    Bresser, Jeroen de [University Medical Center Utrecht, Department of Radiology, P.O. Box 85500, Utrecht (Netherlands); Schaafsma, Joanna D.; Luitse, Merel J.A.; Rinkel, Gabriel J.E.; Biessels, Geert Jan [University Medical Center Utrecht, Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, Utrecht (Netherlands); Viergever, Max A. [University Medical Center Utrecht, Image Sciences Institute, Utrecht (Netherlands)

    2015-03-01

    Volume measurements performed on brain MRI after aneurysmal subarachnoid hemorrhage (aSAH) may provide insight into the structural abnormalities that underlie the commonly occurring and persistent long-term functional deficits after aSAH. We examined the pattern of long-term cerebral structural changes on MRI in relation to known risk factors for poor functional outcome. We studied MRI scans from 38 patients who received endovascular treatment and were not dependent for activities of daily life at 18 months after aSAH. Risk factors for poor functional outcome (clinical condition, Hijdra score, and bicaudate index on admission; occurrence of hydrocephalus or delayed cerebral infarction during hospitalization) were related to supratentorial cerebral parenchymal and lateral ventricular volumes on MRI with linear regression analyses adjusted for age, sex, and intracranial volume. Clinical condition, Hijdra score, and bicaudate index on admission were not related to cerebral parenchymal volume at 18 months. A higher bicaudate index on admission was related to lateral ventricular enlargement at 18 months after aSAH (Beta; 95%CI: 0.51; 0.14<->0.88). Delayed cerebral infarction was related to smaller cerebral parenchymal volumes (-0.14; -0.25<->-0.04) and to lateral ventricular enlargement (0.49; 0.16<->0.83) at 18 months. Volume measurements of the brain are able to quantify patterns of long-term cerebral damage in relation to different risk factors after aSAH. Application of volumetric techniques may provide more insight into the heterogeneous underlying pathophysiological processes. After confirmation of these results in larger studies, volumetric measures might even be used as outcome measures in future treatment studies. (orig.)

  4. Altered carbon dioxide metabolism and creatine abnormalities in rett syndrome

    Halbach, Nicky S J; Smeets, Eric E J; Bierau, Jörgen; Keularts, Irene M L W; Plasqui, Guy; Julu, Peter O O; Engerström, Ingegerd Witt; Bakker, Jaap A.; Curfs, Leopold M G

    2012-01-01

    Despite their good appetite, many females with Rett syndrome (RTT) meet the criteria for moderate to severe malnutrition. Although feeding difficulties may play a part in this, other constitutional factors such as altered metabolic processes are suspected. Irregular breathing is a common clinical

  5. A study on cognitive impairment and gray matter volume abnormalities in silent cerebral infarction patients

    Luo, Wei; Wei, Xiaofeng; Li, Mengxiong; Jiang, Xun; Li, Shanshan

    2015-01-01

    The relationship between silent cerebral infarction (SCI) and the integrity of cognitive function is unknown. We intended to investigate whether cognitive impairment is associated with gray matter volume (GMV) in the SCI patients. Sixty-two patients with SCI and 62 age- and gender-matched healthy controls (HC) were evaluated with P300 test, Montreal Cognitive Assessment (MoCA) test, Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HDRS). Whole brain high-resolution T1-weighted images were processed with SPM12b software and analyzed by voxel-based morphometry (VBM). Correlation analysis was performed between the GMV and the scores of MoCA Scale, P300 latency, P300 amplitude, HAMA, HDRS, age, and educational level. The brains of the SCI patients have a significant reduction in GMV in the left superior and inferior frontal gyrus, left superior temporal gyrus, right middle temporal gyrus, and bilateral hippocampus gyrus (p < 0.01, FDR correction). No significant increase of GMV was detected. The GMV of their frontal and temporal lobes is positively correlated with the score of MoCA scale and P300 amplitude (r ≥ 0.62, p < 0.01). The GMV of frontal, temporal, and hippocampus is negatively correlated with P300 latency (r ≤ -0.71, p < 0.05). No significant correlation between the GMV of abnormal brain regions and another two clinical characteristics was found. SCI patients have impaired cognitive function and reduced GMV compared to the HC subjects. The neuropathological basis of such cognitive deficits in SCI patients might be a reduced GMV. (orig.)

  6. A study on cognitive impairment and gray matter volume abnormalities in silent cerebral infarction patients

    Luo, Wei; Wei, Xiaofeng; Li, Mengxiong [The First Affiliated Hospital of Yangtze University, Biomedical Engineering Laboratory, Jingzhou, Hubei (China); Jiang, Xun [Renmin Hospital of Wuhan University, Biomedical Engineering Laboratory, Wuhan, Hubei (China); Li, Shanshan [JingZhou City Central Blood Bank, Jingzhou, Hubei (China)

    2015-08-15

    The relationship between silent cerebral infarction (SCI) and the integrity of cognitive function is unknown. We intended to investigate whether cognitive impairment is associated with gray matter volume (GMV) in the SCI patients. Sixty-two patients with SCI and 62 age- and gender-matched healthy controls (HC) were evaluated with P300 test, Montreal Cognitive Assessment (MoCA) test, Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HDRS). Whole brain high-resolution T1-weighted images were processed with SPM12b software and analyzed by voxel-based morphometry (VBM). Correlation analysis was performed between the GMV and the scores of MoCA Scale, P300 latency, P300 amplitude, HAMA, HDRS, age, and educational level. The brains of the SCI patients have a significant reduction in GMV in the left superior and inferior frontal gyrus, left superior temporal gyrus, right middle temporal gyrus, and bilateral hippocampus gyrus (p < 0.01, FDR correction). No significant increase of GMV was detected. The GMV of their frontal and temporal lobes is positively correlated with the score of MoCA scale and P300 amplitude (r ≥ 0.62, p < 0.01). The GMV of frontal, temporal, and hippocampus is negatively correlated with P300 latency (r ≤ -0.71, p < 0.05). No significant correlation between the GMV of abnormal brain regions and another two clinical characteristics was found. SCI patients have impaired cognitive function and reduced GMV compared to the HC subjects. The neuropathological basis of such cognitive deficits in SCI patients might be a reduced GMV. (orig.)

  7. Abnormal regional cerebral blood flow in systemic lupus erythematosus patients with psychiatric symptoms.

    Oda, Kenji; Matsushima, Eisuke; Okubo, Yoshiro; Ohta, Katsuya; Murata, Yuji; Koike, Ryuji; Miyasaka, Nobuyuki; Kato, Motoichiro

    2005-07-01

    Single-photon emission computed tomography (SPECT) studies have demonstrated decreased regional cerebral blood flow (rCBF) in systemic lupus erythematosus (SLE) patients. However, no study has done voxel-based analysis using statistical parametric mapping (SPM) that can evaluate rCBF objectively, and the relationship between rCBF and psychiatric symptoms has not been well investigated. Using L,L-ethyl cysteinate dimer (99mTc ECD) SPECT and SPM, we aimed to clarify the association of rCBF changes with psychiatric symptoms in SLE patients whose magnetic resonance imaging (MRI) showed no morphological abnormalities. Twenty SLE patients and 19 healthy volunteers underwent 99mTc ECD SPECT. Data were collected from August 2000 to March 2003. SLE was diagnosed according to American College of Rheumatology criteria, and psychiatric symptoms were diagnosed according to ICD-10 criteria. On the basis of the modified Carbotte, Denburg, and Denburg method, the patients were classified into 3 groups: a group with major psychiatric symptoms (hallucinosis, delusional disorder, and mood disorder), a group with minor psychiatric symptoms (anxiety disorder, dissociative disorder, and emotionally labile disorder), and a group without psychiatric symptoms. Gross organic lesions were ruled out by brain MRI. Group comparisons of rCBF were performed with analysis using SPM99. SLE patients without MRI lesions showed decreased rCBF in the posterior cingulate gyrus and thalamus. The reduction in rCBF was overt in patients with major psychiatric symptoms. Our study indicated that SLE patients may have dysfunction in the posterior cingulate gyrus and thalamus and that this may be associated with the severity of psychiatric symptoms.

  8. Cerebral O2 metabolism and cerebral blood flow in humans during deep and rapid-eye-movement sleep

    Madsen, P L; Schmidt, J F; Wildschiødtz, Gordon

    1991-01-01

    on examination of this question. We have now measured CBF and CMRO2 in young healthy volunteers using the Kety-Schmidt technique with 133Xe as the inert gas. Measurements were performed during wakefulness, deep sleep (stage 3/4), and rapid-eye-movement (REM) sleep as verified by standard polysomnography...... associated with light anesthesia. During REM sleep (dream sleep) CMRO2 was practically the same as in the awake state. Changes in CBF paralleled changes in CMRO2 during both deep and REM sleep.......It could be expected that the various stages of sleep were reflected in variation of the overall level of cerebral activity and thereby in the magnitude of cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF). The elusive nature of sleep imposes major methodological restrictions...

  9. Comparison of cerebral metabolism of glucose in normal human and cancer patients

    Si, M.

    2007-01-01

    )) (p<0.01), with especially apparent in the prefrontal cortex (BA9) and sensory-motor cortex (BA5, 7)(p<0.001), while characteristic hypometabolism in anterior cingulate (BA24, BA30,BA32) and bilateral cerebellum are only seen in 'cancer group'. 2. Compared to the same interval of 'normal subgroup', each 'cancer subgroup' shows remarkable/significant hypometabolism in anterior cingulate (BA24, BA30, BA32) (p<0.001), as well as bilateral parahippocampal gyrus, basal ganglia (lentiform nucleus, thalamus) and bilateral cerebellum (p<0.01) Conclusions:Regional cerebral metabolism of glucose shows a descent tendency with aging, especially in the prefrontal cortex (BA9) and sensory-motor cortex (BA5, 7) in both normal samples and cancer patients. In spite of the cerebral atrophy of aging, these relative hypometabolic brain areas are considered to be correlated with structural and functional cerebral deficit in the process of normal brain aging thus the influence of aging can be omitted. Relative hypometabolism in limbic system such as cingulate gyrus, parahippocampal gyrus and basal ganglia (lentiform nucleus and thalamus) as well as bilateral cerebellum are only found among cancer patients, and we consider that these abnormalities in regional brain metabolism are correlated with the existence of the cancer, especially correlated with patients' negative mood, such as anxiety and depression. (author)

  10. Metabolic and circulatory evaluation of acute cerebral ischaemic accidents in man by positron emission tomography

    Depresseux, J C; Franck, G., Van Cauwenberge, H.

    1987-06-18

    Positron emission tomography and oxygen-15 were used to evaluate the effects of an almitrine-raubasine combination on cerebral blood flow and oxydative metabolism in patients with acute cerebral ischaemia. In 5 patients, aged between 58 and 74 years, with cerebral ischaemic accident in the territory of the middle cerebral artery, blood flow rate, oxygen consumption and brain oxygen extraction were measured before and after a 90-min intravenous infusion of almitrine bismesilate 15 mg and raubasine 5 mg. Only one patient presented with initial relative luxury perfusion, the intensity of which was reduced by the combined treatment. The other 4 patients had focal reduction of cerebral blood flow and oxygen consumption prior to treatment. Satistical analysis conducted on three cerebral areas (epicentre of the lesion, anterior and posterior juxtalesional areas and homologous heterolateral areas) showed a significant 3.6% increase of oxygen consumption in the epicentre, both hemispheres included, and a significant increase of cerebral blood flow in all three areas (3% on the healthy side, 13% on the diseased side). No significant change in oxygen extraction was demonstrated. The authors conclude that acute almitrine-raubasine treatment has beneficial effects on the brain immediately after a cerebral vascular accident, reflecting respect of the circulation-metabolism couple.

  11. Metabolic and circulatory evaluation of acute cerebral ischaemic accidents in man by positron emission tomography

    Depresseux, J.C.; Franck, G.; Van Cauwenberge, H.

    1987-01-01

    Positron emission tomography and oxygen-15 were used to evaluate the effects of an almitrine-raubasine combination on cerebral blood flow and oxydative metabolism in patients with acute cerebral ischaemia. In 5 patients, aged between 58 and 74 years, with cerebral ischaemic accident in the territory of the middle cerebral artery, blood flow rate, oxygen consumption and brain oxygen extraction were measured before and after a 90-min intravenous infusion of almitrine bismesilate 15 mg and raubasine 5 mg. Only one patient presented with initial relative luxury perfusion, the intensity of which was reduced by the combined treatment. The other 4 patients had focal reduction of cerebral blood flow and oxygen consumption prior to treatment. Satistical analysis conducted on three cerebral areas (epicentre of the lesion, anterior and posterior juxtalesional areas and homologous heterolateral areas) showed a significant 3.6% increase of oxygen consumption in the epicentre, both hemispheres included, and a significant increase of cerebral blood flow in all three areas (3% on the healthy side, 13% on the diseased side). No significant change in oxygen extraction was demonstrated. The authors conclude that acute almitrine-raubasine treatment has beneficial effects on the brain immediately after a cerebral vascular accident, reflecting respect of the circulation-metabolism couple [fr

  12. Impact of maternal metabolic abnormalities in pregnancy on human milk and subsequent infant metabolic development: methodology and design

    Hamilton Jill K

    2010-10-01

    Full Text Available Abstract Background Childhood obesity is on the rise and is a major risk factor for type 2 diabetes later in life. Recent evidence indicates that abnormalities that increase risk for diabetes may be initiated early in infancy. Since the offspring of women with diabetes have an increased long-term risk for obesity and type 2 diabetes, the impact of maternal metabolic abnormalities on early nutrition and infant metabolic trajectories is of considerable interest. Human breast milk, the preferred food during infancy, contains not only nutrients but also an array of bioactive substances including metabolic hormones. Nonetheless, only a few studies have reported concentrations of metabolic hormones in human milk specifically from women with metabolic abnormalities. We aim to investigate the impact of maternal metabolic abnormalities in pregnancy on human milk hormones and subsequently on infant development over the first year of life. The objective of this report is to present the methodology and design of this study. Methods/Design The current investigation is a prospective study conducted within ongoing cohort studies of women and their offspring. Pregnant women attending outpatient obstetrics clinics in Toronto, Canada were recruited. Between April 2009 and July 2010, a total of 216 pregnant women underwent a baseline oral glucose tolerance test and provided medical and lifestyle history. Follow-up visits and telephone interviews are conducted and expected to be completed in October 2011. Upon delivery, infant birth anthropometry measurements and human breast milk samples are collected. At 3 and 12 months postpartum, mothers and infants are invited for follow-up assessments. Interim telephone interviews are conducted during the first year of offspring life to characterize infant feeding and supplementation behaviors. Discussion An improved understanding of the link between maternal metabolic abnormalities in pregnancy and early infant nutrition may

  13. Impact of maternal metabolic abnormalities in pregnancy on human milk and subsequent infant metabolic development: methodology and design.

    Ley, Sylvia H; O'Connor, Deborah L; Retnakaran, Ravi; Hamilton, Jill K; Sermer, Mathew; Zinman, Bernard; Hanley, Anthony J

    2010-10-06

    Childhood obesity is on the rise and is a major risk factor for type 2 diabetes later in life. Recent evidence indicates that abnormalities that increase risk for diabetes may be initiated early in infancy. Since the offspring of women with diabetes have an increased long-term risk for obesity and type 2 diabetes, the impact of maternal metabolic abnormalities on early nutrition and infant metabolic trajectories is of considerable interest. Human breast milk, the preferred food during infancy, contains not only nutrients but also an array of bioactive substances including metabolic hormones. Nonetheless, only a few studies have reported concentrations of metabolic hormones in human milk specifically from women with metabolic abnormalities. We aim to investigate the impact of maternal metabolic abnormalities in pregnancy on human milk hormones and subsequently on infant development over the first year of life. The objective of this report is to present the methodology and design of this study. The current investigation is a prospective study conducted within ongoing cohort studies of women and their offspring. Pregnant women attending outpatient obstetrics clinics in Toronto, Canada were recruited. Between April 2009 and July 2010, a total of 216 pregnant women underwent a baseline oral glucose tolerance test and provided medical and lifestyle history. Follow-up visits and telephone interviews are conducted and expected to be completed in October 2011. Upon delivery, infant birth anthropometry measurements and human breast milk samples are collected. At 3 and 12 months postpartum, mothers and infants are invited for follow-up assessments. Interim telephone interviews are conducted during the first year of offspring life to characterize infant feeding and supplementation behaviors. An improved understanding of the link between maternal metabolic abnormalities in pregnancy and early infant nutrition may assist in the development of optimal prevention and intervention

  14. Fluorescence lifetime microscopy of NADH distinguishes alterations in cerebral metabolism in vivo.

    Yaseen, Mohammad A; Sutin, Jason; Wu, Weicheng; Fu, Buyin; Uhlirova, Hana; Devor, Anna; Boas, David A; Sakadžić, Sava

    2017-05-01

    Evaluating cerebral energy metabolism at microscopic resolution is important for comprehensively understanding healthy brain function and its pathological alterations. Here, we resolve specific alterations in cerebral metabolism in vivo in Sprague Dawley rats utilizing minimally-invasive 2-photon fluorescence lifetime imaging (2P-FLIM) measurements of reduced nicotinamide adenine dinucleotide (NADH) fluorescence. Time-resolved fluorescence lifetime measurements enable distinction of different components contributing to NADH autofluorescence. Ostensibly, these components indicate different enzyme-bound formulations of NADH. We observed distinct variations in the relative proportions of these components before and after pharmacological-induced impairments to several reactions involved in glycolytic and oxidative metabolism. Classification models were developed with the experimental data and used to predict the metabolic impairments induced during separate experiments involving bicuculline-induced seizures. The models consistently predicted that prolonged focal seizure activity results in impaired activity in the electron transport chain, likely the consequence of inadequate oxygen supply. 2P-FLIM observations of cerebral NADH will help advance our understanding of cerebral energetics at a microscopic scale. Such knowledge will aid in our evaluation of healthy and diseased cerebral physiology and guide diagnostic and therapeutic strategies that target cerebral energetics.

  15. Relation of EEG alpha background to cognitive fuction, brain atrophy, and cerebral metabolism in Down's syndrome. Age-specific changes

    Devinsky, O.; Sato, S.; Conwit, R.A.; Schapiro, M.B.

    1990-01-01

    We studied 19 young adults (19 to 37 years old) and 9 older patients (42 to 66 years old) with Down's syndrome (DS) and a control group of 13 healthy adults (22 to 38 years old) to investigate the relation of electroencephalographic (EEG) alpha background to cognitive function and cerebral metabolism. Four of the older patients with DS had a history of mental deterioration, disorientation, and memory loss and were demented. Patients and control subjects had EEGs, psychometric testing, quantitative computed tomography, and positron emission tomography with fludeoxyglucose F 18. A blinded reader classified the EEGs into two groups--those with normal alpha background or those with abnormal background. All the control subjects, the 13 young adult patients with DS, and the 5 older patients with DS had normal EEG backgrounds. In comparison with the age-matched patients with DS with normal alpha background, older patients with DS with decreased alpha background had dementia, fewer visuospatial skills, decreased attention span, larger third ventricles, and a global decrease in cerebral glucose utilization with parietal hypometabolism. In the young patients with DS, the EEG background did not correlate with psychometric or positron emission tomographic findings, but the third ventricles were significantly larger in those with abnormal EEG background. The young patients with DS, with or without normal EEG background, had positron emission tomographic findings similar to those of the control subjects. The mechanism underlying the abnormal EEG background may be the neuropathologic changes of Alzheimer's disease in older patients with DS and may be cerebral immaturity in younger patients with DS

  16. Transcriptional abnormalities of hamstring muscle contractures in children with cerebral palsy.

    Smith, Lucas R; Chambers, Henry G; Subramaniam, Shankar; Lieber, Richard L

    2012-01-01

    Cerebral palsy (CP) is an upper motor neuron disease that results in a spectrum of movement disorders. Secondary to the neurological lesion, muscles from patients with CP are often spastic and form debilitating contractures that limit range of motion and joint function. With no genetic component, the pathology of skeletal muscle in CP is a response to aberrant complex neurological input in ways that are not fully understood. This study was designed to gain further understanding of the skeletal muscle response in CP using transcriptional profiling correlated with functional measures to broadly investigate muscle adaptations leading to mechanical deficits.Biopsies were obtained from both the gracilis and semitendinosus muscles from a cohort of patients with CP (n = 10) and typically developing patients (n = 10) undergoing surgery. Biopsies were obtained to define the unique expression profile of the contractures and passive mechanical testing was conducted to determine stiffness values in previously published work. Affymetrix HG-U133A 2.0 chips (n = 40) generated expression data, which was validated for selected transcripts using quantitative real-time PCR. Chips were clustered based on their expression and those from patients with CP clustered separately. Significant genes were determined conservatively based on the overlap of three summarization algorithms (n = 1,398). Significantly altered genes were analyzed for over-representation among gene ontologies and muscle specific networks.The majority of altered transcripts were related to increased extracellular matrix expression in CP and a decrease in metabolism and ubiquitin ligase activity. The increase in extracellular matrix products was correlated with mechanical measures demonstrating the importance in disability. These data lay a framework for further studies and development of novel therapies.

  17. Transcriptional abnormalities of hamstring muscle contractures in children with cerebral palsy.

    Lucas R Smith

    Full Text Available Cerebral palsy (CP is an upper motor neuron disease that results in a spectrum of movement disorders. Secondary to the neurological lesion, muscles from patients with CP are often spastic and form debilitating contractures that limit range of motion and joint function. With no genetic component, the pathology of skeletal muscle in CP is a response to aberrant complex neurological input in ways that are not fully understood. This study was designed to gain further understanding of the skeletal muscle response in CP using transcriptional profiling correlated with functional measures to broadly investigate muscle adaptations leading to mechanical deficits.Biopsies were obtained from both the gracilis and semitendinosus muscles from a cohort of patients with CP (n = 10 and typically developing patients (n = 10 undergoing surgery. Biopsies were obtained to define the unique expression profile of the contractures and passive mechanical testing was conducted to determine stiffness values in previously published work. Affymetrix HG-U133A 2.0 chips (n = 40 generated expression data, which was validated for selected transcripts using quantitative real-time PCR. Chips were clustered based on their expression and those from patients with CP clustered separately. Significant genes were determined conservatively based on the overlap of three summarization algorithms (n = 1,398. Significantly altered genes were analyzed for over-representation among gene ontologies and muscle specific networks.The majority of altered transcripts were related to increased extracellular matrix expression in CP and a decrease in metabolism and ubiquitin ligase activity. The increase in extracellular matrix products was correlated with mechanical measures demonstrating the importance in disability. These data lay a framework for further studies and development of novel therapies.

  18. The effects of incretin hormones on cerebral glucose metabolism in health and disease

    Nilsson, Malin; Gjedde, Albert; Brock, Birgitte

    2017-01-01

    Incretin hormones, notably glucagon-like peptide-1 (GLP-1), are gluco-regulatory hormones with pleiotropic effects also in the central nervous system. Apart from a local production of GLP-1, systemic administration of the hormone has been shown to influence a number of cerebral pathologies......, including neuroinflammation. Given the brains massive dependence on glucose as its major fuel, we here review the mechanistics of cerebral glucose transport and metabolism, focusing on the deleterious effects of both hypo- and hyperglycaemia. GLP-1, when administered as long-acting analogues...... or intravenously, appears to decrease transport of glucose in normoglycaemic conditions, without affecting the total cerebral glucose content. During hypoglycaemia this effect seems abated, whereas during hyperglycaemia GLP-1 regulates cerebral glucose metabolism towards stable levels resembling normoglycaemia...

  19. [The lipid metabolism abnormality in patients administered with olanzapine].

    Amano, Taku; Hosaka, Shigetoshi; Takami, Hiroshi; Sugiyama, Chie; Oda, Kazue; Morikawa, Ryuichi

    2012-11-01

    The atypical antipsychotic medication olanzapine is a useful agent in acute and maintenance treatment of schizophrenia and related disorders. It has beneficial effects on both positive and negative symptoms, an early onset of antipsychotic action and a favourable side effect profile. On the other hand, olanzapine has many reports of causing weight gain, glucose metabolism disturbances and lipidosis. We carried out blood tests (leptin, adiponectin, remnant-like lipoprotein cholesterol (RLP-C), total cholesterol, HbA1C, 75-OGTT and etc.) on patients with schizophrenia who had taken olanzapine. As a result, leptin, neutral lipid and RLP-C were significantly correlated by BMI. (The average blood test data and BMI revealed a normal range). Most analysis results of the lipoprotein fraction by a polyacrylamide-gel-electrophoresis method were normal patterns. Furthermore, the serum insulin concentrations from 75 g glucose tolerance (75 g-OGTT) 30 minutes later, in one third of patients receiving olanzapine, registered more than 100 microU/ml. The mechanism of the insulin secretion rise by olannzapine is unknown. Olanzapine may impair glucose tolerance due in part to increased insulin resistance. These findings do not necessarily imply that olanzapine is directly associated with a risk of impairment of weight gain, glucose metabolism disturbances and lipidosis. These results suggest that it is useful to promote diet cure and exercise therapy with patients with high BMI levels.

  20. Regional cerebral glucose metabolism during sevoflurane anaesthesia in healthy subjects studied with positron emission tomography

    Schlünzen, L; Juul, N; Hansen, K V

    2010-01-01

    BACKGROUND: The precise mechanism by which sevoflurane exerts its effects in the human brain remains unknown. In the present study, we quantified the effects of sevoflurane on regional cerebral glucose metabolism (rGMR) in the human brain measured with positron emission tomography. METHODS: Eight...... areas by 48-71% of the baseline (Pbrain metabolic reduction of GMR in all regions...... of the human brain, with the most marked metabolic suppression in the lingual gyrus, thalamus and occipital lobe....

  1. Imaging cerebral 2-ketoisocaproate metabolism with hyperpolarized (13)C Magnetic Resonance Spectroscopic Imaging

    Butt, Sadia Asghar; Søgaard, Lise Vejby-Christensen; Magnusson, Peter O.

    2012-01-01

    The branched chain amino acid transaminase (BCAT) has an important role in nitrogen shuttling and glutamate metabolism in the brain. The purpose of this study was to describe the cerebral distribution and metabolism of hyperpolarized 2-keto[1-(13)C]isocaproate (KIC) in the normal rat using magnet...... & Metabolism advance online publication, 28 March 2012; doi:10.1038/jcbfm.2012.34....

  2. Improved cerebral energetics and ketone body metabolism in db/db mice

    Andersen, Jens V; Christensen, Sofie K; Nissen, Jakob D

    2017-01-01

    It is becoming evident that type 2 diabetes mellitus is affecting brain energy metabolism. The importance of alternative substrates for the brain in type 2 diabetes mellitus is poorly understood. The aim of this study was to investigate whether ketone bodies are relevant candidates to compensate...... metabolism in type 2 diabetes mellitus. The increased hippocampal ketone body utilization and improved mitochondrial function in db/db mice, may act as adaptive mechanisms in order to maintain cerebral energetics during hampered glucose metabolism....

  3. Current concepts of metabolic abnormalities in HIV patients: focus on lipodystrophy.

    Kolter, Donald P

    2003-12-01

    HIV infection is associated with a number of metabolic abnormalities, including lipodystrophy, a difficult-to-define disorder whose characteristics include hyperlipidemia, insulin resistance, and fat redistribution. Current data suggest that lipodystrophy is caused by multiple factors. Dual-nucleoside reverse transcriptase inhibitor therapy combined with protease inhibitor therapy has been shown to increase the risk of metabolic abnormalities, but susceptibility independent of drug effects has also been shown. While many of the treatments for the broad range of signs and symptoms of lipodystrophy bring about improvements in patient status, none have been demonstrated to bring about a return to baseline levels.

  4. Effect of graded hyperventilation on cerebral metabolism in a cisterna magna blood injection model of subarachnoid hemorrhage in rats

    Ma, Xiaodong; Bay-Hansen, Rikke; Hauerberg, John

    2006-01-01

    In subarachnoid hemorrhage (SAH) with cerebrovascular instability, hyperventilation may induce a risk of inducing or aggravating cerebral ischemia. We measured cerebral blood flow (CBF) and cerebral metabolic rates of oxygen (CMRO2), glucose (CMRglc), and lactate (CMRlac) at different PaCO2 level...

  5. Protein metabolism in the rat cerebral cortex in vivo and in vitro as affected by the acquisition enhancing drug piracetam

    Nickolson, V.J.; Wolthuis, O.L.

    1976-01-01

    The effect of Piracetam on rat cerebral protein metabolism in vivo and in vitro was studied. It was found that the drug stimulates the uptake of labelled leucine by cerebral cortex slices, has no effect on the incorporation of leucine into cerebral protein, neither in slices nor in vivo, but

  6. The importance of sensitive screening for abnormal glucose metabolism in patients with IgA nephropathy.

    Jia, Xiaoyuan; Pan, Xiaoxia; Xie, Jingyuan; Shen, Pingyan; Wang, Zhaohui; Li, Ya; Wang, Weiming; Chen, Nan

    2016-01-01

    To investigate the prevalence of abnormal glucose metabolism, insulin resistance (IR) and the related risk factors in IgA nephropathy (IgAN) patients. We analyzed oral glucose tolerance test (OGTT) and clinical data of 107 IgAN patients and 106 healthy controls. Glucose metabolism, homeostasis model assessment of insulin resistance (HOMA-IR) and the insulin sensitivity index (ISI) of both groups were evaluated. The prevalence of abnormal glucose metabolism was significantly higher in the IgAN group than in the control group (41.12% vs. 9.43%, p glucose, fasting insulin, OGTT 2-hour blood glucose, OGTT 2-hour insulin, HOMA-IR, and lower ISI than healthy controls. Triglyceride (OR = 2.55), 24-hour urine protein excretion (OR = 1.39), and age (OR = 1.06) were independent risk factors for abnormal glucose metabolism in IgAN patients. BMI, eGFR, 24-hour urine protein excretion, triglyceride, fasting blood glucose, fasting insulin, OGTT 2-hour blood glucose, and OGTT 2-hour insulin were significantly higher in IgAN patients with IR than in IgAN patients without IR, while HDL and ISI were significantly lower. BMI, serum albumin, and 24-hour urine protein excretion were correlated factors of IR in IgAN patients. Our study highlighted that abnormal glucose metabolism was common in IgAN patients. Triglyceride and 24-hour urine protein excretion were significant risk factors for abnormal glucose metabolism. Therefore, sensitive screening for glucose metabolism status and timely intervention should be carried out in clinical work.

  7. Regional cerebral blood flow and oxygen metabolism in normal pressure hydrocephalus after subarachnoid hemorrhage

    Ishikawa, Masatsune; Kikuchi, Haruhiko; Taki, Waro; Kobayashi, Akira; Nishizawa, Sadahiko; Yonekura, Yoshiharu; Konishi, Junji [Kyoto Univ. (Japan). Faculty of Medicine

    1989-05-01

    To clarify the pathophysiology of normal pressure hydrocephalus (NPH) after subarachnoid hemorrhage, the authors measured cerebral blood flow (CBF), cerebral oxygen metabolic rates (CMRO{sub 2}), the cerebral oxygen extraction fraction (OEF), and cerebral blood volume (CBV) in eight normal volunteers, six SAH patients with NPH, and seven patients without NPH by {sup 15}O-labeled gas and positron emission tomography (PET). In the NPH group, PET revealed a decrease in CBF in the lower regions of the cerebral cortex and a diffuse decrease in CMRO{sub 2}. The decrease in CBF in the lower frontal, temporal, and occipital cortices was significantly greater in the NPH than in the non-NPH group. Reduction of CMRO{sub 2} was also more extensive in the NPH group, and both CBF and CMRO{sub 2} were more markedly decreased in the lower frontal region. OEF was increased in all areas in both of the patient groups, but the increase was not significant in most areas. CBF, CMRO{sub 2} and OEF did not significantly differ between the non-NPH group and the normal volunteers. There was no significant difference in CBV among the three groups. These results indicate that NPH involves impairment of cerebral oxygen metabolism in the lower regions of the cerebral cortex, particularly in the lower frontal region. (author).

  8. Relationships among smoking habits, airflow limitations, and metabolic abnormalities in school workers.

    Horie, Masafumi; Noguchi, Satoshi; Tanaka, Wakae; Goto, Yasushi; Yoshihara, Hisanao; Kawakami, Masaki; Suzuki, Masaru; Sakamoto, Yoshio

    2013-01-01

    Chronic obstructive pulmonary disease is caused mainly by habitual smoking and is common among elderly individuals. It involves not only airflow limitation but also metabolic disorders, leading to increased cardiovascular morbidity and mortality. We evaluated relationships among smoking habits, airflow limitation, and metabolic abnormalities. Between 2001 and 2008, 15,324 school workers (9700 males, 5624 females; age: ≥ 30 years) underwent medical checkups, including blood tests and spirometry. They also responded to a questionnaire on smoking habits and medical history. Airflow limitation was more prevalent in current smokers than in ex-smokers and never-smokers in men and women. The frequency of hypertriglyceridemia was higher in current smokers in all age groups, and those of low high-density-lipoprotein cholesterolemia and diabetes mellitus were higher in current smokers in age groups ≥ 40 s in men, but not in women. There were significant differences in the frequencies of metabolic abnormalities between subjects with airflow limitations and those without in women, but not in men. Smoking index was an independent factor associated with increased frequencies of hypertriglyceridemia (OR 1.015; 95% CI: 1.012-1.018; psmoking cessation was an independent factor associated with a decreased frequency of hypertriglyceridemia (0.984; 0.975-0.994; p = 0.007). Habitual smoking causes high incidences of airflow limitation and metabolic abnormalities. Women, but not men, with airflow limitation had higher frequencies of metabolic abnormalities.

  9. Cerebral blood flow, oxygen and glucose metabolism with PET in progressive supranuclear palsy

    Otsuka, Makoto; Ichiya, Yuici; Kuwabara, Yasuo

    1989-01-01

    Cerebral blood flow, cerebral oxygen metabolic rate and cerebral glucose metabolic rate were measured with positron emission tomography (PET) in four patients with progressive supranuclear palsy (PSP). Decreased blood flow and hypometabolism of oxygen and glucose were found in both subcortical and cortical regions, particularly in the striatum including the head of the caudate nucleus and the frontal cortex. The coupling between blood flow and metabolism was preserved even in the regions which showed decreased blood flow and hypometabolism. These findings indicated the hypofunction, as revealed by decreased blood flow and hypometablolism on PET, both in the striatum and the frontal cortex, and which may underlie the pathophysiological mechanism of motor and mental disturbance in PSP. (author)

  10. Parenchymal abnormalities in cerebral venous thrombosis: findings of magnetic resonance imaging and magnetic resonance angiography; Alteracoes parenquimatosas na trombose venosa cerebral: aspectos da ressonancia magnetica e da angiorressonancia

    Ferreira, Clecia Santos; Pellini, Marcos [Universidade Federal, Rio de Janeiro, RJ (Brazil). Faculdade de Medicina. Dept. de Radiologia]. E-mail: csferreira@superig.com.br; Boasquevisque, Edson [Universidade do Estado do Rio de Janeiro, (UERJ), RJ (Brazil). Faculdade de Medicina. Dept. de Patologia; Souza, Luis Alberto M. de [Hospital da Beneficencia Portuguesa do Rio de Janeiro, RJ (Brazil). Servico de Imagem. Setor de Ressonancia Magnetica

    2006-09-15

    Objective: to determine the frequency and localization of parenchymal abnormalities in cerebral venous thrombosis on magnetic resonance imaging and magnetic resonance angiography as well as their correlation with the territory and affected venous drainage. Materials and methods: retrospective analysis (1996 to 2004) of 21 patients (3 male and 18 female) age range between 3 and 82 years (mean 40 years, median 36 years) with clinical and radiological diagnosis of cerebral venous thrombosis on magnetic resonance imaging and magnetic resonance angiography in 2D PC, 3D PC and contrast-enhanced 3D TOF sequences. The statistical analysis was performed with the qui-square test. Four patients had follow-up exams and three patients underwent digital subtraction angiography. Results: main predisposing factors were: infection, use of oral contraceptives, hormone replacement therapy and collagenosis. Predominant symptoms included: focal deficit, headache, alteration of consciousness level and seizures. Most frequent parenchymal manifestations were: cortical/subcortical edema or infarct, venous congestion and collateral circulation, meningeal enhancement and thalamic and basal ganglia edema or infarct. Occlusion occurred mainly in superior sagittal, left transverse, left sigmoid and straight sinuses. Cavernous sinus and cortical veins thrombosis are uncommon events. Conclusion: cerebral venous thrombosis is an uncommon cause of stroke, with favorable prognosis because of its reversibility. Diagnosis is highly dependent on the radiologist capacity to recognize the presentations of this disease, principally in cases where the diagnosis is suggested by parenchymal abnormalities rather than necessarily by visualization of the thrombus itself. An accurate and rapid diagnosis allows an immediate treatment, reducing the morbidity and mortality rates. (author)

  11. Depressed cerebral oxygen metabolism in patients with chronic renal failure. A positron emission tomography study

    Hirakata, Hideki; Kanai, Hidetoshi; Nakane, Hiroshi; Fujii, Ken-ichiro; Hirakata, Eriko; Ibayashi, Setsuro; Kuwabara, Yasuo; Deenitchna, S.S.; Fujishima, Masatoshi [Kyushu Univ., Fukuoka (Japan). Graduate School of Medical Sciences

    2001-07-01

    In order to elucidate brain oxygen metabolism in uremic patients, the regional cerebral blood flow (rCBF), oxygen extraction (rOEF) and oxygen metabolism (rCMRO{sub 2}) were measured by positron emission tomography (PET) in both 10 hemodialysis patients (HD: male [m]/female [f]=2/8, age of 49{+-}3 [SEM] years old, HD duration of 113{+-}26 months) and 13 pre-dialysis renal failure patients (CRF: m/f=10/3, age of 61{+-}2 years old, serum creatinine (SCr) of 6.3{+-}1.0 mg/dl). Data were compared with 20 non-uremic subjects (Control: m/f=7/13, age of 62{+-}2 years old, SCr of 0.9{+-}0.1 mg/dl). They had no neurological abnormalities, congestive heart failure, history of cerebrovascular accident, diabetes mellitus, or symptomatic brain lesion on magnetic resonance imaging. The age of HD was significantly younger than the other groups (p<0.02) and the hemoglobin (Hb) levels in both HD (10.5{+-}0.5 g/dl) and CRF (9.8{+-}0.9) were significantly lower than that in Control (13.3{+-}0.3) (p<0.02). In the hemisphere, rCMRO{sub 2} in both HD (1.82{+-}0.10 ml/min/100 g) and CRF (1.95{+-}0.09) showed significantly lower values as compared to Control (2.23{+-}0.05) (p<0.01, respectively). Hemispheric rCBF in HD (35.6{+-}2.1 ml/100 g/min) and in CRF (36.1{+-}2.1) were not different from that in Control (31.8{+-}1.4). Hemispheric rOEF in CRF (45.7{+-}1.6%) was significantly higher than that in Control (40.5{+-}1.2%) (p<0.02), but that in HD (43.7{+-}1.9%) did not increase significantly. These tendencies were similar in all regions of interest, especially in the cerebral cortices, but not in the cerebellum. All PET parameters in the frontal cortices tended to show the lowest value in renal failure patients. For all HD patients, rCBF in both the frontal cortex and the white matter correlated inversely with HD duration (frontal cortex: r=-0.649, p<0.05; white matter: r=-0.706, p<0.02). Based on these data, it is concluded that brain oxygen metabolism is depressed in renal failure

  12. A reduced cerebral metabolic ratio in exercise reflects metabolism and not accumulation of lactate within the human brain

    Dalsgaard, Mads K; Quistorff, Bjørn; Danielsen, Else R

    2003-01-01

    During maximal exercise lactate taken up by the human brain contributes to reduce the cerebral metabolic ratio, O(2)/(glucose + 1/2 lactate), but it is not known whether the lactate is metabolized or if it accumulates in a distribution volume. In one experiment the cerebral arterio-venous differe......During maximal exercise lactate taken up by the human brain contributes to reduce the cerebral metabolic ratio, O(2)/(glucose + 1/2 lactate), but it is not known whether the lactate is metabolized or if it accumulates in a distribution volume. In one experiment the cerebral arterio......-venous differences (AV) for O(2), glucose (glc) and lactate (lac) were evaluated in nine healthy subjects at rest and during and after exercise to exhaustion. The cerebrospinal fluid (CSF) was drained through a lumbar puncture immediately after exercise, while control values were obtained from six other healthy.......0 to 0.9 +/- 0.1 mM (P ratio from 6.0 +/- 0.3 to 2.8 +/- 0.2 (P

  13. Regional cerebral glucose metabolism in systemic lupus erythematosus patients with major depressive disorder.

    Saito, Tomoyuki; Tamura, Maasa; Chiba, Yuhei; Katsuse, Omi; Suda, Akira; Kamada, Ayuko; Ikura, Takahiro; Abe, Kie; Ogawa, Matsuyoshi; Minegishi, Kaoru; Yoshimi, Ryusuke; Kirino, Yohei; Ihata, Atsushi; Hirayasu, Yoshio

    2017-08-15

    Depression is frequently observed in patients with systemic lupus erythematosus (SLE). Neuropsychiatric SLE (NPSLE) patients often exhibit cerebral hypometabolism, but the association between cerebral metabolism and depression remains unclear. To elucidate the features of cerebral metabolism in SLE patients with depression, we performed brain 18F-fluoro-d-glucose positron emission tomography (FDG-PET) on SLE patients with and without major depressive disorder. We performed brain FDG-PET on 20 SLE subjects (5 male, 15 female). The subjects were divided into two groups: subjects with major depressive disorder (DSLE) and subjects without major depressive disorder (non-DSLE). Cerebral glucose metabolism was analyzed using the three-dimensional stereotactic surface projection (3D-SSP) program. Regional metabolism was evaluated by stereotactic extraction estimation (SEE), in which the whole brain was divided into segments. Every SLE subject exhibited cerebral hypometabolism, in contrast to the normal healthy subjects. Regional analysis revealed a significantly lower ER in the left medial frontal gyrus (p=0.0055) and the right medial frontal gyrus (p=0.0022) in the DSLE group than in the non-DSLE group. Hypometabolism in the medial frontal gyrus may be related to major depressive disorder in SLE. Larger studies are needed to clarify this relationship. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Abnormal fetal cerebral laminar organization in cobblestone complex as seen on post-mortem MRI and DTI

    Widjaja, Elysa; Geibprasert, Sasikhan; Blaser, Susan; Rayner, Tammy; Shannon, Patrick

    2009-01-01

    We report a unique case of cobblestone complex using post-mortem MR and diffusion tensor imaging to assess the laminar organization of the fetal cerebrum. The imaging findings were correlated with autopsy findings. Abnormal cortical development in cobblestone complex resulted in disruption of normal laminar organization of the fetal brain, which was seen as interruption and nodularity of the high-signal T1 cortical band with increased anisotropy and medium diffusivity extending beyond the cortical band into the cerebral mantle on post-mortem MR and diffusion tensor imaging. (orig.)

  15. Abnormal fetal cerebral laminar organization in cobblestone complex as seen on post-mortem MRI and DTI

    Widjaja, Elysa; Geibprasert, Sasikhan; Blaser, Susan; Rayner, Tammy [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); Shannon, Patrick [University of Toronto, Department of Pathology, Mount Sinai Hospital, Toronto (Canada)

    2009-08-15

    We report a unique case of cobblestone complex using post-mortem MR and diffusion tensor imaging to assess the laminar organization of the fetal cerebrum. The imaging findings were correlated with autopsy findings. Abnormal cortical development in cobblestone complex resulted in disruption of normal laminar organization of the fetal brain, which was seen as interruption and nodularity of the high-signal T1 cortical band with increased anisotropy and medium diffusivity extending beyond the cortical band into the cerebral mantle on post-mortem MR and diffusion tensor imaging. (orig.)

  16. Neonatal lactic acidosis, complex I/IV deficiency, and fetal cerebral disruption

    van Straaten, H. L. M.; van Tintelen, J. P.; Trijbels, J. M. F.; van den Heuvel, L. P.; Troost, D.; Rozemuller, J. M.; Duran, M.; de Vries, L. S.; Schuelke, M.; Barth, P. G.

    2005-01-01

    Cerebral developmental abnormalities occur in various inborn errors of metabolism including peroxisomal deficiencies, pyruvate dehydrogenase complex deficiency and others. Associations with abnormalities of the respiratory chain are rare. Here we report male and female siblings with microcephaly, a

  17. Neonatal lactic acidosis, complex I/IV deficiency, and fetal cerebral disruption

    van Straaten, HLM; van Tintelen, JP; Trijbels, JMF; van den Heuvel, LP; Troost, D; Rozemuller, JM; Duran, M; de Vries, LS; Schuelke, M; Barth, PG

    Cerebral developmental abnormalities occur in various inborn errors of metabolism including peroxisomal deficiencies, pyruvate dehydrogenase complex deficiency and others. Associations with abnormalities of the respiratory chain are rare. Here we report male and female siblings with microcephaly, a

  18. Neonatal lactic acidosis, complex I/IV deficiency, and fetal cerebral disruption.

    Straaten, H.L.M. van; Tintelen, J.P. van; Trijbels, J.M.F.; Heuvel, L.P.W.J. van den; Troost, D.; Rozemuller, J.M.; Duran, M.; Vries, L.S. de; Schuelke, M.; Barth, P.G.

    2005-01-01

    Cerebral developmental abnormalities occur in various inborn errors of metabolism including peroxisomal deficiencies, pyruvate dehydrogenase complex deficiency and others. Associations with abnormalities of the respiratory chain are rare. Here we report male and female siblings with microcephaly, a

  19. Abnormal Transmethylation/Transsulfuration Metabolism and DNA Hypomethylation among Parents of Children with Autism

    James, S. Jill; Melnyk, Stepan; Jernigan, Stefanie; Hubanks, Amanda; Rose, Shannon; Gaylor, David W.

    2008-01-01

    An integrated metabolic profile reflects the combined influence of genetic, epigenetic, and environmental factors that affect the candidate pathway of interest. Recent evidence suggests that some autistic children may have reduced detoxification capacity and may be under chronic oxidative stress. Based on reports of abnormal methionine and…

  20. Correlations between abnormal iron metabolism and non-motor symptoms in Parkinson's disease.

    Xu, Wu; Zhi, Yan; Yuan, Yongsheng; Zhang, Bingfeng; Shen, Yuting; Zhang, Hui; Zhang, Kezhong; Xu, Yun

    2018-07-01

    Despite a growing body of evidence suggests that abnormal iron metabolism plays an important role in the pathogenesis of Parkinson's disease (PD), few studies explored its role in non-motor symptoms (NMS) of PD. The present study aimed to investigate the relationship between abnormal iron metabolism and NMS of PD. Seventy PD patients and 64 healthy controls were consecutively recruited to compare serum iron, ceruloplasmin, ferritin, and transferrin levels. We evaluated five classic NMS, including depression, anxiety, pain, sleep disorder, and autonomic dysfunction in PD patients using the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA), the short form of the McGill Pain Questionnaire, the Pittsburgh Sleep Quality Index and the Scale for Outcomes in Parkinson's disease for Autonomic Symptoms, respectively. Hierarchical multiple regression analysis was used to investigate the correlations between abnormal iron metabolism and NMS. No differences in serum ceruloplasmin and ferritin levels were examined between PD patients and healthy controls, but we observed significantly decreased serum iron levels and increased serum transferrin levels in PD patients in comparison with healthy controls. After eliminating confounding factors, HAMD scores and HAMA scores were both negatively correlated with serum iron levels and positively correlated with serum transferrin levels. In summary, abnormal iron metabolism might play a crucial role in the pathogenesis of depression and anxiety in PD. Serums levels of iron and transferrin could be peripheral markers for depression and anxiety in PD.

  1. Abnormalities in Human Brain Creatine Metabolism in Gulf War Illness Probed with MRS

    2014-12-01

    TYPE Final 3. DATES COVERED 30 Sep 2012 - 29 Sep 2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Abnormalities in Human Brain Creatine Metabolism in...levels of total creatine (tCr) in veterans with Gulf War Illness have been observed in prior studies. The goal of this research is to estimate amounts and

  2. Local cerebral blood flow and glucose metabolism during seizure in spontaneously epileptic El mice

    Hosokawa, Chisa; Ochi, Hironobu; Yamagami, Sakae; Kawabe, Joji; Kobashi, Toshiko; Okamura, Terue; Yamada, Ryusaku

    1995-01-01

    Local cerebral blood flow and glucose metabolism were examined in spontaneously epileptic El mice using autoradiography with 125 I-IMP and 14 C-DG in the interictal phase and during seizure. El (+) mice that developed generalized tonic-clonic convulsions and El (-) mice that received no stimulation and had no history of epileptic seizures were examined. The seizure non-susceptible, maternal strain ddY mice were used as control. Uptake ratios for IMP and DG in mouse brain were calculated using the autoradiographic density. In the interictal phase, the pattern of local cerebral blood flow of El (+) mice was similar to that of ddY and El (-) mice, and glucose metabolism in the hippocampus was higher in El (+) mice than in El (-) and ddY mice, but flow and metabolism were nearly matched. During seizure, no significant changed blood flow and increased glucose metabolism in the hippocampus, the epileptic focus, and no markedly changed blood flow and depressed glucose metabolism in other brain regions were observed and considered to be flow-metabolism uncoupling. These observations have never been reported in clinical or experimental studies of epilepsy. Seizures did not cause large regional differences in cerebral blood flow. Therefore, only glucose metabolism is useful for detection of the focus of secondary generalized seizures in El mice, and appeared possibly to be related to the pathophysiology of secondary generalized epilepsy in El mice. (author)

  3. Resveratrol Ameliorates the Depressive-Like Behaviors and Metabolic Abnormalities Induced by Chronic Corticosterone Injection

    Yu-Cheng Li

    2016-10-01

    Full Text Available Chronic glucocorticoid exposure is known to cause depression and metabolic disorders. It is critical to improve abnormal metabolic status as well as depressive-like behaviors in patients with long-term glucocorticoid therapy. This study aimed to investigate the effects of resveratrol on the depressive-like behaviors and metabolic abnormalities induced by chronic corticosterone injection. Male ICR mice were administrated corticosterone (40 mg/kg by subcutaneous injection for three weeks. Resveratrol (50 and 100 mg/kg, fluoxetine (20 mg/kg and pioglitazone (10 mg/kg were given by oral gavage 30 min prior to corticosterone administration. The behavioral tests showed that resveratrol significantly reversed the depressive-like behaviors induced by corticosterone, including the reduced sucrose preference and increased immobility time in the forced swimming test. Moreover, resveratrol also increased the secretion of insulin, reduced serum level of glucose and improved blood lipid profiles in corticosterone-treated mice without affecting normal mice. However, fluoxetine only reverse depressive-like behaviors, and pioglitazone only prevent the dyslipidemia induced by corticosterone. Furthermore, resveratrol and pioglitazone decreased serum level of glucagon and corticosterone. The present results indicated that resveratrol can ameliorate depressive-like behaviors and metabolic abnormalities induced by corticosterone, which suggested that the multiple effects of resveratrol could be beneficial for patients with depression and/or metabolic syndrome associated with long-term glucocorticoid therapy.

  4. Relation of metabolic syndrome with endometrial pathologies in patients with abnormal uterine bleeding.

    Özdemir, Suna; Batmaz, Gonca; Ates, Seda; Celik, Cetin; Incesu, Feyzanur; Peru, Celalettin

    2015-01-01

    We aimed to investigate the association of metabolic syndrome and metabolic risk factors with endometrial hyperplasia and carcinoma among women with abnormal uterine bleeding (AUB). This study included 199 patients who had undergone endometrial curettage due to abnormal uterine bleeding. We divided the patients into two groups according to whether they had an abnormal (n = 53) or normal endometrium (n = 146). Waist circumference, blood pressure, fasting glucose and serum lipid levels were measured and statistically analyzed. The women in each group were matched with regard to mean age, gravidity, parity and menopausal status. We found increased prevalence of metabolic syndrome, diabetes, general and abdominal obesity, hypertension, elevated levels of glucose, total cholesterol and LDL-cholesterol and reduced levels of HDL-cholesterol among women with endometrial carcinoma and hyperplasia. These results were detected particularly in postmenopausal (>50 years) women compared to pre-menopausal cases (<50 years). All metabolic parameters were similar between hyperplasia and cancer groups. Metabolic syndrome and its components have been shown to have profound impacts on initiation and progession of endometrial pathology, particularly during post-menopausal period.

  5. Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition

    Zhu Zhu

    2016-01-01

    Full Text Available Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice by altering exposure to light. C57 BL/6J mice (C57 mice and ApoE-KO mice (ApoE-KO mice exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1 levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

  6. Abnormalities of Microcirculation and Intracranial and Cerebral Perfusion Pressures in Severe Brain Injury

    Yu. A. Churlyaev

    2008-01-01

    Full Text Available Objective: to evaluate the states of microcirculation, cerebral perfusion intracranial pressures in patients with isolated severe brain injury (SBI and to determine their possible relationships. Subjects and methods. 148 studies were performed in 16 victims with SBI. According to the outcome of brain traumatic disease, the patients were divided into two groups: 1 those who had a good outcome (n=8 and 2 those who had a fatal outcome (n=8. Microcirculation was examined by skin laser Doppler flowmetry using a LAKK-01 capillary blood flow laser analyzer (LAZMA Research-and-Production Association, Russian Federation. All the victims underwent surgical interventions to remove epi-, subdural, and intracerebral hematomas. A Codman subdural/intraparenchymatous intracranial pressure (ICD sensor (Johnson & Johnson, United Kingdom was intraoperatively inserted in the victims. Cerebral perfusion pressure (CPP was calculated using the generally accepted formula: CPP = MBP (mean blood pressure — ICD. ICD, CPP, and microcirculation were studied on postoperative days 1, 3, 5, and 7. Their values were recorded simultaneously. Ninety and 58 studies were conducted in the group of patients with good and fatal outcomes, respectively. Results. No correlation between the changes in MBP, ICD, and microcirculatory parameters suggested that the value of ICD was determined by the nature of brain damage and it was the leading and determining indicator in the diagnosis and treatment of secondary cerebral lesions. The amplitude of low-frequency fluctuations directly correlated with ICD, which indicated that they might be used to evaluate cerebral perfusion and impaired cerebral circulation indirectly in victims with severe brain injury. Conclusion. The laser Doppler flowmetric technique makes it possible not only to qualitatively, but also quantitatively determine changes in the tissue blood flow system in severe brain injury. With this technique, both the local and central

  7. Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized C-13 magnetic resonance

    Mishkovsky, Mor; Anderson, Brian; Karlsson, Magnus

    2017-01-01

    The mammalian brain relies primarily on glucose as a fuel to meet its high metabolic demand. Among the various techniques used to study cerebral metabolism, C-13 magnetic resonance spectroscopy (MRS) allows following the fate of C-13-enriched substrates through metabolic pathways. We herein...... glucose is split into 3-carbon intermediates by aldolase. This unique method allows direct detection of glycolysis in vivo in the healthy brain in a noninvasive manner....... demonstrate that it is possible to measure cerebral glucose metabolism in vivo with sub-second time resolution using hyperpolarized C-13 MRS. In particular, the dynamic C-13-labeling of pyruvate and lactate formed from C-13-glucose was observed in real time. An ad-hoc synthesis to produce [2,3,4,6,6-H-2(5), 3...

  8. Program for PET image alignment: Effects on calculated differences in cerebral metabolic rates for glucose

    Phillips, R.L.; London, E.D.; Links, J.M.; Cascella, N.G.

    1990-01-01

    A program was developed to align positron emission tomography images from multiple studies on the same subject. The program allowed alignment of two images with a fineness of one-tenth the width of a pixel. The indications and effects of misalignment were assessed in eight subjects from a placebo-controlled double-blind crossover study on the effects of cocaine on regional cerebral metabolic rates for glucose. Visual examination of a difference image provided a sensitive and accurate tool for assessing image alignment. Image alignment within 2.8 mm was essential to reduce variability of measured cerebral metabolic rates for glucose. Misalignment by this amount introduced errors on the order of 20% in the computed metabolic rate for glucose. These errors propagate to the difference between metabolic rates for a subject measured in basal versus perturbed states

  9. Anormalidades de fluxo sangüíneo cerebral em indivíduos dependentes de cocaína Cerebral blood flow abnormalities in cocaine dependent subjects

    Sergio Nicastri

    2000-06-01

    Full Text Available INTRODUÇÃO: Nos últimos anos, tem havido relatos de anormalidades do fluxo sanguíneo cerebral em indivíduos com o abuso de cocaína, detectadas por meio de tomografia computadorizada por emissão de fóton único (SPECT. Esse padrão anormal de perfusão cerebral tem sido associado a prejuízos cognitivos mas não a alterações observáveis por meio de exames de neuroimagem estrutural. Um problema envolvendo a maioria dos trabalhos publicados sobre esse tema é a inclusão de um grande número de usuários de heroína nas amostras estudadas. Essa outra droga também parece afetar o padrão de perfusão cerebral, particularmente durante estados de abstinência. MÉTODOS: Quatorze pacientes dependentes de cocaína (nenhum com uso de opióides e 14 voluntários normais (grupo controle foram submetidos a exames de SPECT com dímero de etil-cisteína marcado com tecnécio-99m. A análise dos exames de SPECT foi realizada por meio de análise visual qualitativa das imagens obtidas (procedimento padrão na prática clínica, realizada por um radiologista não informado sobre o diagnóstico dos indivíduos avaliados. RESULTADOS: A análise visual revelou um padrão sugestivo de irregularidades do fluxo sangüíneo cerebral em nove pacientes, mas em apenas dois controles (p = 0,018; teste exato de Fisher bicaudal. CONCLUSÕES: Anormalidades de circulação cerebral podem ter relação com prejuízos cognitivos relatados em populações de dependentes de cocaína. Embora déficits de perfusão cerebral associados ao uso de cocaína possam ser irreversíveis, têm surgido relatos na literatura de tratamentos para essas anormalidades de fluxo sangüíneo. Alterações de fluxo sangüíneo cerebral associadas à dependência de cocaína ocorrem mesmo na ausência de abuso ou dependência de opióides.INTRODUCTION: In the last years, there have been reports of abnormalities in brain blood flow of cocaine abusers, detected by single photon computed

  10. Effects of head-up vs. supine CPR on cerebral oxygenation and cerebral metabolism - a prospective, randomized porcine study.

    Putzer, Gabriel; Braun, Patrick; Martini, Judith; Niederstätter, Ines; Abram, Julia; Lindner, Andrea Katharina; Neururer, Sabrina; Mulino, Miriam; Glodny, Bernhard; Helbok, Raimund; Mair, Peter

    2018-05-01

    Recent studies have shown that during cardiopulmonary resuscitation (CPR) head-up position (HUP) as compared to standard supine position (SUP) decreases intracranial pressure (ICP) and increases cerebral perfusion pressure (CPP). The impact of this manoeuvre on brain oxygenation and metabolism is not clear. We therefore investigated HUP as compared to SUP during basic life support (BLS) CPR for their effect on brain oxygenation and metabolism. Twenty pigs were anaesthetized and instrumented. After 8 min of cardiac arrest (CA) pigs were randomized to either HUP or SUP and resuscitated mechanically for 20 min. Mean arterial pressure (MAP), ICP, CPP, cerebral regional oxygen saturation (rSO 2 ) and brain tissue oxygen tension (P bt O 2 ) were measured at baseline, after CA and every 5 min during CPR. Cerebral venous oxygen saturation (S cv O 2 ) was measured at baseline, after CA and after 20 min of CPR. Cerebral microdialysis parameters, e.g. lactate/pyruvate ratio (L/P ratio) were taken at baseline and the end of the experiment. ICP was significantly lower in HUP compared to SUP animals after 5 min (18.0 ± 4.5 vs. 24.1 ± 5.2 mmHg; p = 0.033) and 20 min (12.0 ± 3.4 vs. 17.8 ± 4.3 mmHg; p = 0.023) of CPR. Accordingly, CPP was significantly higher in the HUP group after 5 min (11.2 ± 9.5 vs. 1.0 ± 9.2 mmHg; p = 0.045) and 20 min (3.4 ± 6.4 vs. -3.8 ± 2.8 mmHg; p = 0.023) of CPR. However, no difference was found in rSO 2 , P bt O 2 , S cv O 2 and L/P ratio between groups after 20 min of CPR. In this animal model of BLS CPR, HUP as compared to SUP did not improve cerebral oxygenation or metabolism. Copyright © 2018. Published by Elsevier B.V.

  11. Effect of NMDA Receptor Antagonist on Local Cerebral Glucose Metabolic Rate in Focal Cerebral Ischemia

    Kim, Sang Eun; Hong, Seung Bong; Yoon, Byung Woo

    1995-01-01

    There has recently been increasing interest in the use of NMDA receptor antagonists as potential neuroprotective agents for the treatment of ischemic stroke. To evaluate the neuroprotective effect of the selective non-competitive NMDA receptor antagonist MK-801 in focal cerebral ischemia, local cerebral glucose utilization (1CGU) was examined in 15 neuroanatomically discrete regions of the conscious rat brain using the 2-deoxy-D[14C]glucose quantitative autoradiographic technique 24 hr after left middle cerebral artery occlusion (MCAO). Animals received MK-801 (5 mg/kg i.v.) or saline vehicle before (20-30 min) or after (30 min) MCAO. Both pretreatment and posttreatment of MK-801 increased occluded/non-occluded 1CGU ratio in 7 and 5 of the 15 regions measured, respectively(most notably in cortical structures). Following MK-801 pretreatment, there was evidence of widespread increases in 1CCPU not only in the non-occluded hemisphere (12 of the 15 areas studied) but also in the occluded hemisphere (13 of the 15 areas studied), while MK-801 posttreatment did not significantly increase 1CGU both in the normal and occluded hemispheres. These data indicate that MK-801 has a neuroprotective effect in focal cerebral ischemia and demonstrate that MK-801 provides widespread alterations of glucose utilization in conscious animals.

  12. A community-based exercise intervention transitions metabolically abnormal obese adults to a metabolically healthy obese phenotype

    Dalleck, Lance C; Van Guilder, Gary P; Richardson, Tara B; Bredle, Donald L; Janot, Jeffrey M

    2014-01-01

    Background Lower habitual physical activity and poor cardiorespiratory fitness are common features of the metabolically abnormal obese (MAO) phenotype that contribute to increased cardiovascular disease risk. The aims of the present study were to determine 1) whether community-based exercise training transitions MAO adults to metabolically healthy, and 2) whether the odds of transition to metabolically healthy were larger for obese individuals who performed higher volumes of exercise and/or experienced greater increases in fitness. Methods and results Metabolic syndrome components were measured in 332 adults (190 women, 142 men) before and after a supervised 14-week community-based exercise program designed to reduce cardiometabolic risk factors. Obese (body mass index ≥30 kg · m2) adults with two to four metabolic syndrome components were classified as MAO, whereas those with no or one component were classified as metabolically healthy but obese (MHO). After community exercise, 27/68 (40%) MAO individuals (Pmetabolically healthy, increasing the total number of MHO persons by 73% (from 37 to 64). Compared with the lowest quartiles of relative energy expenditure and change in fitness, participants in the highest quartiles were 11.6 (95% confidence interval: 2.1–65.4; Pexercise transitions MAO adults to metabolically healthy. MAO adults who engaged in higher volumes of exercise and experienced the greatest increase in fitness were significantly more likely to become metabolically healthy. Community exercise may be an effective model for primary prevention of cardiovascular disease. PMID:25120373

  13. Metabolic response of the cerebral cortex following gentle sleep deprivation and modafinil administration.

    Petit Jean-Marie; Tobler Irene; Kopp Caroline; Morgenthaler Florence; Borbély Alexander A; Magistretti Pierre J

    2010-01-01

    STUDY OBJECTIVES The main energy reserve of the brain is glycogen which is almost exclusively localized in astrocytes. We previously reported that cerebral expression of certain genes related to glycogen metabolism changed following instrumental sleep deprivation in mice. Here we extended our investigations to another set of genes related to glycogen and glucose metabolism. We also compared the effect of instrumentally and pharmacologically induced prolonged wakefulness followed (or not) by 3...

  14. Effects of nitrous oxide on cerebral haemodynamics and metabolism during isoflurane anaesthesia in man

    Algotsson, L.; Messeter, K.; Rosen, I.; Holmin. T.

    1992-01-01

    Seven normoventilated and five hyperventilated healthy adults undergoing cholecystectomy and anaesthetized with methohexitone, fentanyl and pancuronium were studied with measurement of cerebral blood flow (CBF), cereal metabolic rate of oxygen (CMRo 2 ), and quantified electroencephalography (EEG) under two sets of conditions: 1) 1.7% end-tidal concentration of isoflurane in air/oxygen: 2) 0.85% end-tidal concentration of isoflurane in nitrous oxide (N 2 O)/oxygen. The object was to study the effects of N 2 O during isoflurane anaesthesia on cerebral circulation, metabolism and neuroelectric activity. N 2 O in the anaesthetic gas mixture caused a 43% (P 2 was not significantly altered by N 2 O. EEG demonstrated an activated pattern with decreased low frequency activity and increased high frequency activity. The results confirm that N 2 O is a potent cerebral vasodilator in man, although the mechanisms underlying the effects on CBF are still unclear. (au)

  15. Weight-adjusted lean body mass and calf circumference are protective against obesity-associated insulin resistance and metabolic abnormalities

    Toshinari Takamura

    2017-07-01

    Interpretation: Weight-adjusted lean body mass and skeletal muscle area are protective against weight-associated insulin resistance and metabolic abnormalities. The calf circumference reflects lean body mass and may be useful as a protective marker against obesity-associated metabolic abnormalities.

  16. Cerebral oxygen metabolism in patients with early Parkinson's disease

    Borghammer, Per; Cumming, Paul; Østergaard, Karen

    2012-01-01

    ) and cerebral blood flow (CBF) PET scans from PD patients and healthy controls. MATERIALS AND METHODS: Nine early-stage PD patients and 15 healthy age-matched controls underwent PET scans for quantitative mapping of CMRO(2) and CBF. Between-group differences were evaluated for absolute data and intensity...... in spatially contiguous cortical regions in early PD, and support the hypothesis that ETC dysfunction could be a primary pathogenic mechanism in early PD....

  17. Brain Size and Cerebral Glucose Metabolic Rate in Nonspecific Retardation and Down Syndrome.

    Haier, Richard J.; And Others

    1995-01-01

    Brain size and cerebral glucose metabolic rate were determined for 10 individuals with mild mental retardation (MR), 7 individuals with Down syndrome (DS), and 10 matched controls. MR and DS groups both had brain volumes of about 80% compared to controls, with variance greatest within the MR group. (SLD)

  18. PET-imaging of cerebral glucose metabolism during sleep and dreaming

    Heiss, W.D.; Pawlik, G.; Herholz, K.; Wagner, R.; Wienhard, K.

    1985-01-01

    Positron emission tomography (PET) of ( 18 F)-2-fluoro-2-deoxyglucose (FDG) affording non-invasive repeatable quantification of local cerebral glucose utilization was employed to determine possible differential effects of sleep, with and without dreaming, on regional brain metabolism of normal volunteers also measured during wakefulness. (author). 7 refs.; 1 tab

  19. Comparison Between Cerebral Tissue Oxygen Tension and Energy Metabolism in Experimental Subdural Hematoma

    Nielsen, Troels Halfeld; Engell, Susanne I; Johnsen, Rikke Aagaard

    2011-01-01

    BACKGROUND: An experimental swine model (n = 7) simulating an acute subdural hematoma (ASDH) was employed (1) to explore the relation between the brain tissue oxygenation (PbtO(2)) and the regional cerebral energy metabolism as obtained by microdialysis, and (2) to define the lowest level of PbtO(2...

  20. Photoacoustic microscopy of cerebral hemodynamic and oxygen-metabolic responses to anesthetics

    Cao, Rui; Li, Jun; Ning, Bo; Sun, Naidi; Wang, Tianxiong; Zuo, Zhiyi; Hu, Song

    2017-02-01

    General anesthetics are known to have profound effects on cerebral hemodynamics and neuronal activities. However, it remains a challenge to directly assess anesthetics-induced hemodynamic and oxygen-metabolic changes from the true baseline under wakefulness at the microscopic level, due to the lack of an enabling technology for high-resolution functional imaging of the awake mouse brain. To address this challenge, we have developed head-restrained photoacoustic microscopy (PAM), which enables simultaneous imaging of the cerebrovascular anatomy, total concentration and oxygen saturation of hemoglobin (CHb and sO2), and blood flow in awake mice. From these hemodynamic measurements, two important metabolic parameters, oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2), can be derived. Side-by-side comparison of the mouse brain under wakefulness and anesthesia revealed multifaceted cerebral responses to isoflurane, a volatile anesthetic widely used in preclinical research and clinical practice. Key observations include elevated cerebral blood flow (CBF) and reduced oxygen extraction and metabolism.

  1. Pattern of cerebral glucose metabolism on F-18 FDG brain PET during vomiting and symptom free periods in cyclic vomiting syndrome

    Kim, Yu Kyeong; Lee, Dong Soo; Kang, Eun Joo; Seo, Jeong Kee; Yeo, Jeong Seok; Chung, June Key; Lee, Myung Chul

    2001-01-01

    Cyclic Vomiting Syndrome (CVS) is characterized by recurrent, periodic, self-limiting vomiting. However, its pathogenesis is not yet established. We investigated the changes of the cerebral glucose metabolism using F-18 FDG during the vomiting attack and symptom free period in two children with CVS. FDG PET study showed the markedly increased metabolism in both temporal lobes and also in the medulla and cerebellum during the vomiting period. Also, FDG PET showed the decreased metabolism in the parieto-occipital and occipital areas during the in vomiting period. The area with decreased metabolism seemed to be related with the region showing abnormalities in EEG and perfusion SPECT studies. We expect that what we observed would be a helpful finding in clarifying the pathogenesis of the CVS

  2. Metabolic abnormalities associated with renal calculi in patients with horseshoe kidneys.

    Raj, Ganesh V; Auge, Brian K; Assimos, Dean; Preminger, Glenn M

    2004-03-01

    Horseshoe kidneys are a complex anatomic variant of fused kidneys, with a 20% reported incidence of associated calculi. Anatomic causes such as high insertion of the ureter on the renal pelvis and obstruction of the ureteropelvic junction are thought to contribute to stone formation via impaired drainage, with urinary stasis, and an increased incidence of infection. In this multi-institutional study, we evaluated whether metabolic factors contributed to stone development in patients with horseshoe kidneys. A retrospective review of 37 patients with horseshoe kidneys was performed to determine if these patients had metabolic derangements that might have contributed to calculus formation. Stone compositions as well as 24-hour urine collections were examined. Specific data points of interest were total urine volume; urine pH; urine concentrations of calcium, sodium, uric acid, oxalate, and citrate; and number of abnormalities per patient per 24-hour urine collection. These data were compared with those of a group of 13 patients with stones in caliceal diverticula as well as 24 age-, race-, and sex-matched controls with stones in anatomically normal kidneys. Eleven (9 men and 2 women) of the 37 patients (30%) with renal calculi in horseshoe kidneys had complete metabolic evaluations available for review. All patients were noted to have at least one abnormality, with an average of 2.68 abnormalities per 24-hour urine collection (range 1-4). One patient had primary hyperparathyroidism and underwent a parathyroidectomy. Low urine volumes were noted in eight patients on at least one of the two specimens (range 350-1640 mL/day). Hypercalciuria, hyperoxaluria, hyperuricosuria, and hypocitraturia were noted in seven, three, six, and six patients, respectively. No patients were found to have gouty diathesis or developed cystine stones. Comparative metabolic analyses of patients with renal calculi in caliceal diverticula or normal kidneys revealed a distinct profile in patients

  3. Slowed EEG rhythmicity in patients with chronic pancreatitis: evidence of abnormal cerebral pain processing?

    Olesen, Søren Schou; Hansen, Tine Maria; Gravesen, Carina

    2011-01-01

    Intractable pain usually dominates the clinical presentation of chronic pancreatitis (CP). Slowing of electroencephalogram (EEG) rhythmicity has been associated with abnormal cortical pain processing in other chronic pain disorders. The aim of this study was to investigate the spectral distribution...

  4. Comparison of cerebral blood flow and metabolism to flumazenil binding potential in patients with hemodynamic ischemia

    Yukawa, Hirotsugu; Ogasawara, Kuniaki

    2003-01-01

    Because benzodiazepine receptors (BZR) are abundant in the cortex, an accumulation of 11 C-flumazenil which selectively bind to BZR may be useful as markers of neuron density. The aims of this study were to clarify the relationship between neuron density and cerebral oxygen metabolism and to investigate the usefulness of 11 C-flumazenil PET for detecting misery perfusion. The subjects were 16 patients with either internal carotid or middle cerebral arterial occlusive disease who underwent PET. Regional cerebral blood flow (CBF), regional cerebral oxygen extraction fraction (OEF), regional cerebral metabolic rate for oxygen (CMRO 2 ) and regional cerebrovascular reserve capacity (CVRC) to acetazolamide were calculated. After CBF study, flumazenil binding potential was measured using the [ 11 C] flumazenil bolus injection method. Forty-eight regions of interests (ROIs) were obtained in 16 patients. Flumazenil binding potential was correlated to CMRO 2 (r=0.337, p=0.0069), but in 7 of 48 ROIs, CMRO 2 decreased, whereas flumazenil binding potential did not change. Seventeen of 29 ROIs with decreased CVRC showed high OEF and the remaining 12 showed normal OEF. Flumazenil binding potential in ROIs with normal OEF was significantly lower than in those with high OEF (p=0.0003). This study demonstrated that 11 C-flumazenil PET is useful for detecting misery perfusion in patients with hemodynamic ischemia. (author)

  5. Demonstration of cerebral abnormalities in cocaine abusers with SPECT perfusion brain scans

    Nagel, J.S.; Tumeh, S.S.; English, R.J.; Moore, M.; Lee, V.W.; Holman, L.B.

    1989-01-01

    This paper reports I-123 isopropyl iodoamphetamine (IMP) single-photon emission CT (SPECT) brain scans performed on cocaine users to investigate the effects of cocaine on the cerebral perfusion in a manner similar to previous CT, angiographic and positron-emission tomographic (PET) studies. Ten asymptomatic or mildly symptomatic cocaine users, two users with major neurovascular complications, and five normal subjects were studied with IMP SPECT. Rotating-brain images of the cerebral IMP uptake were displayed by using a distance-weighted surface-projection technique and were visually analyzed for focal cortical perfusion deficits. Eleven cocaine users had multiple scattered cortical IMP defects. Frontal lobe defects were most prominent. One user had confluent defects resembling swiss cheese. Concurrent CT scans available in nine patients were negative in seven and showed infarcts in two. No similar focal findings were visible in normals

  6. Cerebral glucose metabolism in Wernicke's, Broca's, and conduction aphasia

    Metter, E.J.; Kempler, D.; Jackson, C.; Hanson, W.R.; Mazziotta, J.C.; Phelps, M.E.

    1989-01-01

    Cerebral glucose metabolism was evaluated in patients with either Wernicke's (N = 7), Broca's (N = 11), or conduction (N = 10) aphasia using /sup 18/F-2-fluoro-2-deoxy-D-glucose with positron emission tomography. The three aphasic syndromes differed in the degree of left-to-right frontal metabolic asymmetry, with Broca's aphasia showing severe asymmetry and Wernicke's aphasia mild-to-moderate metabolic asymmetry, while patients with conduction aphasia were metabolically symmetric. On the other hand, the three syndromes showed the same degree of metabolic decline in the left temporal region. The parietal region appeared to separate conduction aphasia from both Broca's and Wernicke's aphasias. Common aphasic features in the three syndromes appear to be due to common changes in the temporal region, while unique features were associated with frontal and parietal metabolic differences.

  7. Cerebral glucose metabolic differences in patients with panic disorder

    Nordahl, T.E.; Semple, W.E.; Gross, M.; Mellman, T.A.; Stein, M.B.; Goyer, P.; King, A.C.; Uhde, T.W.; Cohen, R.M. (NIMH, Bethesda, MD (USA))

    1990-08-01

    Regional glucose metabolic rates were measured in patients with panic disorder during the performance of auditory discrimination. Those regions examined by Reiman and colleagues in their blood flow study of panic disorder were examined with a higher resolution positron emission tomography (PET) scanner and with the tracer (F-18)-2-fluoro-2-deoxyglucose (FDG). In contrast to the blood flow findings of Reiman et al., we did not find global gray metabolic differences between patients with panic disorder and normal controls. Consistent with the findings of Reiman et al., we found hippocampal region asymmetry. We also found metabolic decreases in the left inferior parietal lobule and in the anterior cingulate (trend), as well as an increase in the metabolic rate of the medial orbital frontal cortex (trend) of panic disorder patients. It is unclear whether the continuous performance task (CPT) enhanced or diminished findings that would have been noted in a study performed without task.

  8. Cerebral glucose metabolic differences in patients with panic disorder

    Nordahl, T.E.; Semple, W.E.; Gross, M.; Mellman, T.A.; Stein, M.B.; Goyer, P.; King, A.C.; Uhde, T.W.; Cohen, R.M.

    1990-01-01

    Regional glucose metabolic rates were measured in patients with panic disorder during the performance of auditory discrimination. Those regions examined by Reiman and colleagues in their blood flow study of panic disorder were examined with a higher resolution positron emission tomography (PET) scanner and with the tracer [F-18]-2-fluoro-2-deoxyglucose (FDG). In contrast to the blood flow findings of Reiman et al., we did not find global gray metabolic differences between patients with panic disorder and normal controls. Consistent with the findings of Reiman et al., we found hippocampal region asymmetry. We also found metabolic decreases in the left inferior parietal lobule and in the anterior cingulate (trend), as well as an increase in the metabolic rate of the medial orbital frontal cortex (trend) of panic disorder patients. It is unclear whether the continuous performance task (CPT) enhanced or diminished findings that would have been noted in a study performed without task

  9. APP Metabolism Regulates Tau Proteostasis in Human Cerebral Cortex Neurons

    Steven Moore

    2015-05-01

    Full Text Available Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer’s disease (AD. To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons.

  10. Regional Cerebral Glucose Metabolism in Novelty Seeking and Antisocial Personality: A Positron Emission Tomography Study.

    Park, So Hyeon; Park, Hyun Soo; Kim, Sang Eun

    2016-08-01

    Novelty seeking (NS) and antisocial personality (ASP) are commonly exhibited by those who suffer from addictions, such as substance abuse. NS has been suggested to be a fundamental aspect of ASP. To investigate the neurobiological substrate of NS and ASP, we tested the relationship between regional cerebral glucose metabolism and the level of NS, determining the differences between individuals with and without ASP. Seventy-two healthy adults (43 males, mean age±SD=38.8±16.6 years, range=20~70 years; 29 females, 44.2±20.1 years, range=19~72 years) underwent resting-state brain positron emission tomography (PET) 40 minutes after (18)F-fluorodeoxyglucose (FDG) injection. Within 10 days of the FDG PET study, participants completed Cloninger's 240-item Temperament and Character Inventory (TCI) to determine NS scores. Participants with and without ASP were grouped according to their TCI profiles. Statistical parametric mapping analysis was performed using the FDG PET and TCI profile data. NS scores positively correlated with metabolism in the left anterior cingulate gyrus and the insula on both sides of the brain and negatively correlated with metabolism in the right pallidum and putamen. Participants with ASP showed differences in cerebral glucose metabolism across various cortical and subcortical regions, mainly in the frontal and prefrontal areas. These data demonstrate altered regional cerebral glucose metabolism in individuals with NS and ASP and inform our understanding of the neurobiological substrates of problematic behaviors and personality disorders.

  11. Marked reduction of cerebral oxygen metabolism in patients with advanced cirrhosis

    Kawatoko, Toshiharu; Murai, Koichiro; Ibayashi, Setsurou; Tsuji, Hiroshi; Nomiyama, Kensuke; Sadoshima, Seizo; Eujishima, Masatoshi; Kuwabara, Yasuo; Ichiya, Yuichi

    1992-01-01

    Regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (rCMRO 2 ), and oxygen extraction fraction (rOEF) were measured using positron emission tomography (PET) in four patients with cirrhosis (two males and two females, aged 57 to 69 years) in comparison with those in five age matched controls with previous transient global amnesia. PET studies were carried out when the patients were fully alert and oriented after the episodes of encephalopathy. In the patients, rCBF tended to be lower, while rCMRO 2 was significantly lowered in almost all hemisphere cortices, more markedly in the frontal cortex. Our results suggest that the brain oxygen metabolism is diffusely impaired in patients with advanced cirrhosis, and the frontal cortex seems to be more susceptible to the systemic metabolic derangements induced by chronic liver disease. (author)

  12. Marked reduction of cerebral oxygen metabolism in patients with advanced cirrhosis; A positron emission tomography study

    Kawatoko, Toshiharu; Murai, Koichiro; Ibayashi, Setsurou; Tsuji, Hiroshi; Nomiyama, Kensuke; Sadoshima, Seizo; Eujishima, Masatoshi; Kuwabara, Yasuo; Ichiya, Yuichi (Kyushu Univ., Fukuoka (Japan). Faculty of Medicine)

    1992-01-01

    Regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (rCMRO{sub 2}), and oxygen extraction fraction (rOEF) were measured using positron emission tomography (PET) in four patients with cirrhosis (two males and two females, aged 57 to 69 years) in comparison with those in five age matched controls with previous transient global amnesia. PET studies were carried out when the patients were fully alert and oriented after the episodes of encephalopathy. In the patients, rCBF tended to be lower, while rCMRO{sub 2} was significantly lowered in almost all hemisphere cortices, more markedly in the frontal cortex. Our results suggest that the brain oxygen metabolism is diffusely impaired in patients with advanced cirrhosis, and the frontal cortex seems to be more susceptible to the systemic metabolic derangements induced by chronic liver disease. (author).

  13. Clustered metabolic abnormalities blunt regression of hypertensive left ventricular hypertrophy: the LIFE study

    de Simone, G; Okin, P M; Gerdts, E

    2009-01-01

    BACKGROUND AND AIMS: Clusters of metabolic abnormalities resembling phenotypes of metabolic syndrome predicted outcome in the LIFE study, independently of single risk markers, including obesity, diabetes and baseline ECG left ventricular hypertrophy (LVH). We examined whether clusters of two......-duration product (CP) over 5 years was assessed using a quadratic polynomial contrast, adjusting for age, sex, prevalent cardiovascular disease and treatment arm (losartan or atenolol). At baseline, despite similar blood pressures, CP was greater in the presence than in the absence of MetAb (p

  14. Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects

    Fox, P.T.; Raichle, M.E.

    1986-01-01

    Coupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO 2 ) was studied using multiple sequential administrations of 15 O-labeled radiotracers and positron emission tomography. In the resting state an excellent correlation between CBF and CMRO 2 was found when paired measurements of CBF and CMRO 2 from multiple (30-48) brain regions were tested in each of 33 normal subjects. Regional uncoupling of CBF and CMRO 2 was found, however, during neuronal activation induced by somatosensory stimulation. Stimulus-induced focal augmentation of cerebral blood flow (29% mean) far exceeded the concomitant local increase in tissue metabolic rate (mean, 5%), when resting-state and stimulated-state measurements were obtained in each of 9 subjects. Stimulus duration had no significant effect on response magnitude or on the degree of CBF-CMRO 2 uncoupling observed. Dynamic, physiological regulation of CBF by a mechanism (neuronal or biochemical) dependent on neuronal firing per se, but independent of the cerebral metabolic rate of oxygen, is hypothesized

  15. How Energy Metabolism Supports Cerebral Function: Insights from 13C Magnetic Resonance Studies In vivo

    Sarah Sonnay

    2017-05-01

    Full Text Available Cerebral function is associated with exceptionally high metabolic activity, and requires continuous supply of oxygen and nutrients from the blood stream. Since the mid-twentieth century the idea that brain energy metabolism is coupled to neuronal activity has emerged, and a number of studies supported this hypothesis. Moreover, brain energy metabolism was demonstrated to be compartmentalized in neurons and astrocytes, and astrocytic glycolysis was proposed to serve the energetic demands of glutamatergic activity. Shedding light on the role of astrocytes in brain metabolism, the earlier picture of astrocytes being restricted to a scaffold-associated function in the brain is now out of date. With the development and optimization of non-invasive techniques, such as nuclear magnetic resonance spectroscopy (MRS, several groups have worked on assessing cerebral metabolism in vivo. In this context, 1H MRS has allowed the measurements of energy metabolism-related compounds, whose concentrations can vary under different brain activation states. 1H-[13C] MRS, i.e., indirect detection of signals from 13C-coupled 1H, together with infusion of 13C-enriched glucose has provided insights into the coupling between neurotransmission and glucose oxidation. Although these techniques tackle the coupling between neuronal activity and metabolism, they lack chemical specificity and fail in providing information on neuronal and glial metabolic pathways underlying those processes. Currently, the improvement of detection modalities (i.e., direct detection of 13C isotopomers, the progress in building adequate mathematical models along with the increase in magnetic field strength now available render possible detailed compartmentalized metabolic flux characterization. In particular, direct 13C MRS offers more detailed dataset acquisitions and provides information on metabolic interactions between neurons and astrocytes, and their role in supporting neurotransmission. Here

  16. Inhibition of Endothelial p53 Improves Metabolic Abnormalities Related to Dietary Obesity

    Masataka Yokoyama

    2014-06-01

    Full Text Available Accumulating evidence has suggested a role for p53 activation in various age-associated conditions. Here, we identified a crucial role of endothelial p53 activation in the regulation of glucose homeostasis. Endothelial expression of p53 was markedly upregulated when mice were fed a high-calorie diet. Disruption of endothelial p53 activation improved dietary inactivation of endothelial nitric oxide synthase that upregulated the expression of peroxisome proliferator-activated receptor-γ coactivator-1α in skeletal muscle, thereby increasing mitochondrial biogenesis and oxygen consumption. Mice with endothelial cell-specific p53 deficiency fed a high-calorie diet showed improvement of insulin sensitivity and less fat accumulation, compared with control littermates. Conversely, upregulation of endothelial p53 caused metabolic abnormalities. These results indicate that inhibition of endothelial p53 could be a novel therapeutic target to block the vicious cycle of cardiovascular and metabolic abnormalities associated with obesity.

  17. Abnormal bone and mineral metabolism in kidney transplant patients--a review

    Sprague, S.M.; Belozeroff, V.; Danese, M.D.

    2008-01-01

    BACKGROUND/AIMS: Abnormal bone and mineral metabolism is common in patients with kidney failure and often persists after successful kidney transplant. METHODS: To better understand the natural history of this disease in transplant patients, we reviewed the literature by searching MEDLINE...... within 2 months. Low levels of 1,25(OH)2 vitamin D typically did not reach normal values until almost 18 months after transplant. CONCLUSION: This review provides evidence demonstrating that abnormal bone and mineral metabolism exists in patients after kidney transplant and suggests the need...... for English language articles published between January 1990 and October 2006 that contained Medical Subject Headings and key words related to secondary or persistent hyperparathyroidism and kidney transplant. RESULTS: Parathyroid hormone levels decreased significantly during the first 3 months after...

  18. Cerebral blood flow, oxidative metabolism and cerebrovascular carbon dioxide reactivity in patients with acute bacterial meningitis

    Møller, Kirsten; Strauss, Gitte Irene; Thomsen, Gerda

    2002-01-01

    BACKGROUND: The optimal arterial carbon dioxide tension (P(a)CO(2)) in patients with acute bacterial meningitis (ABM) is unknown and controversial. The objective of this study was to measure global cerebral blood flow (CBF), cerebrovascular CO(2) reactivity (CO(2)R), and cerebral metabolic rates...... and hyperventilation with single-photon emission computed tomography (SPECT) (14 patients) and/or the Kety-Schmidt technique (KS) (11 patients and all controls). In KS studies, CMR was measured by multiplying the arterial to jugular venous concentration difference (a-v D) by CBF. RESULTS: CBF did not differ...

  19. Cerebral haemodynamic and metabolic changes in carotid artery occlusion: a PET study

    Samson, Y.; Loc'h, C.; Ottaviani, M.; Baron, J.C.; Bousser, M.

    1984-09-01

    Using the positron emission tomography, with the O 15 inhalation technique, the cerebral blood flow (CBF), the oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO 2 ) were studied in 37 patients with internal carotid artery (ICA) occlusion. In the territory of the occluded ICA, two pattern of focal anomaly have been observed: a CBF decrease with a ''compensatory'' OEF increase or a matched CBF and CMRO 2 decrease. On the other hand, as compared to age matched control values, CMRO 2 is significantly decreased in the territory of the occluded carotid only in patients with extensive neck vessels obstructive disease

  20. The responsible region and the symptomatic threshold of cerebral blood flow and oxygen metabolism for Broca's aphasia using positron emission tomography

    Kato, Toshiaki; Ujike, Takashi; Kitamura, Shin; Soeda, Toshiyuki; Terashi, Akiro

    1987-01-01

    This study was designed to investigate the responsible region and the symptomatic flow and metabolism threshold for Broca's aphasia. Regional cerebral blood flow (CBF) and oxygen metabolism (CMRO 2 ) were measured by positron emission tomography (PET) using 15 O steady state method in eight patients with Broca's aphasia due to cerebral infarction and thirty patients without aphasia. During scanning, patients closed their eyes and were kept free from any stimuration. X-CT scan revealed abnormal low density in Broca's area which includes cortex and subcortex in the anterior region to Sylvian fissure in three patients with aphasia. In the other five patients with aphasia X-CT scan showed no abnormal low density in Broca's area, showed it in basal ganglionic region and subcortex. PET study revealed reduction of CBF and CMRO 2 in Broca's area in all cases with Broca's aphasia. CBF and CMRO 2 of Broca's area of aphasic patients were compared to those of non aphasic patients to obtain the symptomatic threshold in CBF and CMRO 2 . The values of symptomatic threshold were 20 - 27 ml/100 g/min in CBF and 2.0 ml/100 g/min in CMRO 2 . The symptomatic threshold differed from the threshold for development of abnormal low density on X-CT, therefore the measurement of CBF and CMRO 2 were useful in studying the responsible region for aphasia. (author)

  1. Reduced brain/serum glucose ratios predict cerebral metabolic distress and mortality after severe brain injury.

    Kurtz, Pedro; Claassen, Jan; Schmidt, J Michael; Helbok, Raimund; Hanafy, Khalid A; Presciutti, Mary; Lantigua, Hector; Connolly, E Sander; Lee, Kiwon; Badjatia, Neeraj; Mayer, Stephan A

    2013-12-01

    The brain is dependent on glucose to meet its energy demands. We sought to evaluate the potential importance of impaired glucose transport by assessing the relationship between brain/serum glucose ratios, cerebral metabolic distress, and mortality after severe brain injury. We studied 46 consecutive comatose patients with subarachnoid or intracerebral hemorrhage, traumatic brain injury, or cardiac arrest who underwent cerebral microdialysis and intracranial pressure monitoring. Continuous insulin infusion was used to maintain target serum glucose levels of 80-120 mg/dL (4.4-6.7 mmol/L). General linear models of logistic function utilizing generalized estimating equations were used to relate predictors of cerebral metabolic distress (defined as a lactate/pyruvate ratio [LPR] ≥ 40) and mortality. A total of 5,187 neuromonitoring hours over 300 days were analyzed. Mean serum glucose was 133 mg/dL (7.4 mmol/L). The median brain/serum glucose ratio, calculated hourly, was substantially lower (0.12) than the expected normal ratio of 0.40 (brain 2.0 and serum 5.0 mmol/L). In addition to low cerebral perfusion pressure (P = 0.05) and baseline Glasgow Coma Scale score (P brain/serum glucose ratios below the median of 0.12 were independently associated with an increased risk of metabolic distress (adjusted OR = 1.4 [1.2-1.7], P brain/serum glucose ratios were also independently associated with in-hospital mortality (adjusted OR = 6.7 [1.2-38.9], P brain/serum glucose ratios, consistent with impaired glucose transport across the blood brain barrier, are associated with cerebral metabolic distress and increased mortality after severe brain injury.

  2. Regional cerebral glucose metabolism in frontotemporal lobar degeneration

    Park, J.M.; Cho, S.S.; Lee, K.-H.; Choi, Y.; Choe, Y.S.; Kim, B.-T.; Kim, S.E.; Kwon, J.C.; Na, D.L.

    2002-01-01

    Purpose: Frontotemporal lobar degeneration (FTLD) is the third most common cause of dementia, following Alzheimer's disease and Lewy body disease. Four prototypic neuro behavioral syndromes can be produced by FTLD: frontotemporal dementia (FTD), frontotemporal dementia with motor neuron disease (MND), semantic dementia (SD), and progressive aphasia (PA). We investigated patterns of metabolic impairment in patients with FTLD presented with four different clinical syndromes. Methods: We analyzed glucose metabolic patterns on FDG PET images obtained from 34 patients with a clinical diagnosis of FTLD (19 FTD, 6 MND, 6 SD, and 3 PA, according to a consensus criteria for clinical syndromes associated with FTLD) and 7 age-matched healthy controls using SPM99. Results: Patients with FTD had metabolic deficit in the left frontal cortex and bilateral anterior temporal cortex. Hypometabolism in the bilateral pre-motor area was shown in patients with MND. Patients with SD had metabolic deficit in the left posterior temporal cortex including Wernicke's area, while hypometabolism in the bilateral inferior frontal gyrus including Broca's area and left angular gyrus was seen in patients with PA. These metabolic patterns were well correlated with clinical and neuropsychological features of FTLD syndromes. Conclusion: These data provide a biochemical basis of clinical classification of FTLD. FDG PET may help evaluate and classify patients with FTLD

  3. Relationship between relative cerebral blood flow, relative cerebral blood volume, and relative cerebral metabolic rate of oxygen in the preterm neonatal brain.

    Nourhashemi, Mina; Kongolo, Guy; Mahmoudzadeh, Mahdi; Goudjil, Sabrina; Wallois, Fabrice

    2017-04-01

    The mechanisms responsible for coupling between relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and relative cerebral metabolic rate of oxygen ([Formula: see text]), an important function of the microcirculation in preterm infants, remain unclear. Identification of a causal relationship between rCBF-rCBV and [Formula: see text] in preterms may, therefore, help to elucidate the principles of cortical hemodynamics during development. We simultaneously recorded rCBF and rCBV and estimated [Formula: see text] by two independent acquisition systems: diffuse correlation spectroscopy and near-infrared spectroscopy, respectively, in 10 preterms aged between 28 and 35 weeks of gestational age. Transfer entropy was calculated in order to determine the directionality between rCBF-rCBV and [Formula: see text]. The surrogate method was applied to determine statistical significance. The results show that rCBV and [Formula: see text] have a predominant driving influence on rCBF at the resting state in the preterm neonatal brain. Statistical analysis robustly detected the correct directionality of rCBV on rCBF and [Formula: see text] on rCBF. This study helps to clarify the early organization of the rCBV-rCBF and [Formula: see text] inter-relationship in the immature cortex.

  4. Migration abnormalities in cerebral malformations - evaluation of CT and MR examinations

    Uhlenbrock, D.; Sehlen, S.; Terwey, B.

    1991-01-01

    Twenty-eight patients with abnormalities of migration were examined with CT and MRI. Thirteen patients had heterotopia, ten patients had agyria/pachygyria, two with unilateral schizencephaly and three with hemimegalencephaly. MRI proved markedly superior because of its wider contrast range and its ability to obtain various imaging planes. The various conditions are described in detail. (orig.) [de

  5. Non-invasive optical measurement of cerebral metabolism and hemodynamics in infants.

    Lin, Pei-Yi; Roche-Labarbe, Nadege; Dehaes, Mathieu; Carp, Stefan; Fenoglio, Angela; Barbieri, Beniamino; Hagan, Katherine; Grant, P Ellen; Franceschini, Maria Angela

    2013-03-14

    Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO₂). Thus, measures of CMRO₂ are reflective of neuronal viability and provide critical diagnostic information, making CMRO₂ an ideal target for bedside measurement of brain health. Brain-imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) yield measures of cerebral glucose and oxygen metabolism, but these techniques require the administration of radionucleotides, so they are used in only the most acute cases. Continuous-wave near-infrared spectroscopy (CWNIRS) provides non-invasive and non-ionizing radiation measures of hemoglobin oxygen saturation (SO₂) as a surrogate for cerebral oxygen consumption. However, SO₂ is less than ideal as a surrogate for cerebral oxygen metabolism as it is influenced by both oxygen delivery and consumption. Furthermore, measurements of SO₂ are not sensitive enough to detect brain injury hours after the insult, because oxygen consumption and delivery reach equilibrium after acute transients. We investigated the possibility of using more sophisticated NIRS optical methods to quantify cerebral oxygen metabolism at the bedside in healthy and brain-injured newborns. More specifically, we combined the frequency-domain NIRS (FDNIRS) measure of SO2 with the diffuse correlation spectroscopy (DCS) measure of blood flow index (CBFi) to yield an index of CMRO₂ (CMRO₂i). With the combined FDNIRS/DCS system we are able to quantify cerebral metabolism and hemodynamics. This represents an improvement over CWNIRS for detecting brain health, brain

  6. Lactate storm marks cerebral metabolism following brain trauma.

    Lama, Sanju; Auer, Roland N; Tyson, Randy; Gallagher, Clare N; Tomanek, Boguslaw; Sutherland, Garnette R

    2014-07-18

    Brain metabolism is thought to be maintained by neuronal-glial metabolic coupling. Glia take up glutamate from the synaptic cleft for conversion into glutamine, triggering glial glycolysis and lactate production. This lactate is shuttled into neurons and further metabolized. The origin and role of lactate in severe traumatic brain injury (TBI) remains controversial. Using a modified weight drop model of severe TBI and magnetic resonance (MR) spectroscopy with infusion of (13)C-labeled glucose, lactate, and acetate, the present study investigated the possibility that neuronal-glial metabolism is uncoupled following severe TBI. Histopathology of the model showed severe brain injury with subarachnoid and hemorrhage together with glial cell activation and positive staining for Tau at 90 min post-trauma. High resolution MR spectroscopy of brain metabolites revealed significant labeling of lactate at C-3 and C-2 irrespective of the infused substrates. Increased (13)C-labeled lactate in all study groups in the absence of ischemia implied activated astrocytic glycolysis and production of lactate with failure of neuronal uptake (i.e. a loss of glial sensing for glutamate). The early increase in extracellular lactate in severe TBI with the injured neurons rendered unable to pick it up probably contributes to a rapid progression toward irreversible injury and pan-necrosis. Hence, a method to detect and scavenge the excess extracellular lactate on site or early following severe TBI may be a potential primary therapeutic measure. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Re-establishment of cerebral metabolism after carotid endarterectomy

    Balm, R.; van der Grond, J.; Mali, W. P.; Eikelboom, B. C.

    1995-01-01

    OBJECTIVES: The purpose of this study was to evaluate the metabolic changes that occur in the human brain in patients with a symptomatic carotid artery stenosis. MATERIALS AND METHODS: N-acetyl-aspartate (NAA), choline, creatine and lactate were measured both before, and 4 days after, carotid

  8. APP metabolism regulates tau proteostasis in human cerebral cortex neurons.

    Moore, Steven; Evans, Lewis D B; Andersson, Therese; Portelius, Erik; Smith, James; Dias, Tatyana B; Saurat, Nathalie; McGlade, Amelia; Kirwan, Peter; Blennow, Kaj; Hardy, John; Zetterberg, Henrik; Livesey, Frederick J

    2015-05-05

    Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer's disease (AD). To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Regional cerebral metabolic correlates of WASO during NREM sleep in insomnia.

    Nofzinger, Eric A; Nissen, Christoph; Germain, Anne; Moul, Douglas; Hall, Martica; Price, Julie C; Miewald, Jean M; Buysse, Daniel J

    2006-07-15

    To investigate the non-rapid eye movement (NREM) sleep-related regional cerebral metabolic correlates of wakefulness after sleep onset (WASO) in patients with primary insomnia. Fifteen patients who met DSM-IV criteria for primary insomnia completed 1-week sleep diary (subjective) and polysomnographic (objective) assessments of WASO and regional cerebral glucose metabolic assessments during NREM sleep using [18F] fluoro-2-deoxy-D-glucose positron emission tomography. Whole-brain voxel-by-voxel correlations, as well as region of interest analyses, were performed between subjective and objective WASO and relative regional cerebral metabolism using the statistical software SPM2. Subjective WASO was significantly greater than objective WASO, but the 2 measures were positively correlated. Objective WASO correlated positively with the percentage of stage 2 sleep and negatively with the percentage of stages 3 and 4 sleep. Both subjective and objective WASO positively correlated with NREM sleep-related cerebral glucose metabolism in the pontine tegmentum and in thalamocortical networks in a frontal, anterior temporal, and anterior cingulate distribution. Increased relative metabolism in these brain regions during NREM sleep in patients with insomnia is associated with increased WASO measured either subjectively or objectively. These effects are related to the lighter sleep stages of patients with more WASO and may result from increased activity in arousal systems during sleep and or to activity in higher-order cognitive processes related to goal-directed behavior, conflict monitoring, emotional awareness, anxiety, and fear. Such changes may decrease arousal thresholds and/or increase perceptions of wakefulness in insomnia.

  10. Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder

    Swedo, S.E.; Schapiro, M.B.; Grady, C.L.; Cheslow, D.L.; Leonard, H.L.; Kumar, A.; Friedland, R.; Rapoport, S.I.; Rapoport, J.L.

    1989-01-01

    The cerebral metabolic rate for glucose was studied in 18 adults with childhood-onset obsessive-compulsive disorder (OCD) and in age- and sex-matched controls using positron emission tomography and fludeoxyglucose F 18. Both groups were scanned during rest, with reduced auditory and visual stimulation. The group with OCD showed an increased glucose metabolism in the left orbital frontal, right sensorimotor, and bilateral prefrontal and anterior cingulate regions as compared with controls. Ratios of regional activity to mean cortical gray matter metabolism were increased for the right prefrontal and left anterior cingulate regions in the group with OCD as a whole. Correlations between glucose metabolism and clinical assessment measures showed a significant relationship between metabolic activity and both state and trait measurements of OCD and anxiety as well as the response to clomipramine hydrochloride therapy. These results are consistent with the suggestion that OCD may result from a functional disturbance in the frontal-limbic-basal ganglia system

  11. [Joint effect of birth weight and obesity measures on abnormal glucose metabolism at adulthood].

    Xi, Bo; Cheng, Hong; Chen, Fangfang; Zhao, Xiaoyuan; Mi, Jie

    2016-01-01

    To investigate the joint effect of birth weight and each of obesity measures (body mass index (BMI) and waist circumference (WC)) on abnormal glucose metabolism (including diabetes) at adulthood. Using the historical cohort study design and the convenience sampling method, 1 921 infants who were born in Beijing Union Medical College Hospital from June 1948 to December 1954 were selected to do the follow-up in 1995 and 2001 respectively. Through Beijing Household Registration and Management System, they were invited to participate in this study. A total of 972 subjects (627 were followed up in 1995 and 345 were followed up in 2001) with complete information on genders, age, birth weight, family history of diabetes, BMI, WC, fasting plasma glucose (FPG) and 2-hour plasma glucose (2 h PG) met the study inclusion criteria at the follow-up visits. In the data analysis, they were divided into low, normal, and high birth weight, respectively. The ANOVA and Chi-squared tests were used to compare the differences in their characteristics by birth weight group. In addition, multiple binary Logistic regression model was used to investigate the single effect of birth weight, BMI, and waist circumference on abnormal glucose metabolism at adulthood. Stratification analysis was used to investigate the joint effect of birth weight and each of obesity measures (BMI and WC) on abnormal glucose metabolism. There were 972 subjects (males: 50.7%, mean age: (46.0±2.2) years) included in the final data analysis. The 2 h PG in low birth weight group was (7.6±3.2) mmol/L , which was higher than that in normal birth weight group (6.9±2.1) mmol/L and high birth weight group (6.4±1.3) mmol/L (F=3.88, P=0.021). After adjustment for genders, age, body length, gestation age, family history of diabetes, physical activity, smoking and alcohol consumption, and duration of follow-up, subjects with overweight and obesity at adulthood had 2.73 (95% confidence interval (CI) =2.06- 3.62) times risk

  12. Effects of Metformin on the Cerebral Metabolic Changes in Type 2 Diabetic Patients

    Yung-Cheng Huang

    2014-01-01

    Full Text Available Metformin, a widely used antidiabetic drug, has numerous effects on human metabolism. Based on emerging cellular, animal, and epidemiological studies, we hypothesized that metformin leads to cerebral metabolic changes in diabetic patients. To explore metabolism-influenced foci of brain, we used 2-deoxy-2-[18F]fluoro-D-glucose (FDG positron emission tomography for type 2 diabetic patients taking metformin (MET, n=18, withdrawing from metformin (wdMET, n=13, and not taking metformin (noMET, n=9. Compared with the noMET group, statistical parametric mapping showed that the MET group had clusters with significantly higher metabolism in right temporal, right frontal, and left occipital lobe white matter and lower metabolism in the left parahippocampal gyrus, left fusiform gyrus, and ventromedial prefrontal cortex. In volume of interest (VOI- based group comparisons, the normalized FDG uptake values of both hypermetabolic and hypometabolic clusters were significantly different between groups. The VOI-based correlation analysis across the MET and wdMET groups showed a significant negative correlation between normalized FDG uptake values of hypermetabolic clusters and metformin withdrawal durations and a positive but nonsignificant correlation in the turn of hypometabolic clusters. Conclusively, metformin affects cerebral metabolism in some white matter and semantic memory related sites in patients with type 2 diabetes.

  13. Cerebral blood flow and metabolism in patients with aphasia due to basal ganglionic lesion

    Kitamura, Shin; Kato, Toshiaki; Ujike, Takashi; Kuroki, Soemu; Terashi, Akiro

    1987-01-01

    Cerebral blood flow and metabolism in right handed eight patients with subcortical lesion and aphasia were measured to investigate the correlation between aphasia and functional changes in cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO 2 ) in the cortex and the basal ganglionic region. All patients had no lesion in the cortex, but in the basal ganglionic region (putamen, caudate nucleus, internal capsule, and periventricular white matter) on CT images. Patients with bilateral lesion were excluded in this study. Six patients with cerebral infarction in the left basal ganglionic region and two patients with the left putammal hemorrhage were examined. Five patients had non fluent Broca's type speech, two patients had poor comprehension, fluent Wernicke-type speech and one patient was globally aphasic. CBF, CMRO 2 , and oxygen extraction fraction were measured by the positron emission tomography using 15 O 2 , C 15 O 2 inhalation technique. In addition to reduction of CBF and CMRO 2 in the basal ganglionic region, CBF and CMRO 2 decreased in the left frontal cortex especially posterior part in four patients with Broca's aphasia. In two patients with Wernicke type aphasia, CBF and CMRO 2 decreased in the basal ganglionic region and the left temporal cortex. In a globally aphasic patient, marked reduction of CBF and CMRO 2 was observed in the left frontal and temporal cortex, in addition to the basal ganglionic region. These results suggest that dysfunction of cortex as well as that of basal ganglionic region might be related to the occurence of aphasia. However, in one patient with Broca's ahasia, CBF and CMRO 2 were preserved in the cortex and metabolic reduction was observed in only basal ganglia. This case indicates the relation between basal ganglionic lesion and the occurrence of aphasia. These results suggest that measurements of cerebral blood flow and metabolism were necessary to study the responsible lesion for aphasia. (author)

  14. Regional cerebral blood flow and metabolism in patients with transient global amnesia. A study using SPECT and {sup 1}H-MRS

    Ishihara, Tetsuya; Hirata, Koichi; Tatsumoto, Muneto; Yamazaki, Kaoru [Dokkyo Univ., Tochigi (Japan). School of Medicine; Sato, Toshihiko

    1997-06-01

    In 13 patients with transient global amnesia (TGA), we studied the clinical course and changes over time by means of imaging techniques such as SPECT. MRI, and proton MR spectroscopy ({sup 1}H-MRS). In the case of SPECT, a cerebral blood flow decrease at the time center of the temporal lobe persisted at least for more than one month. In many patients, no abnormal signs were found on MRI. Despite the presence of intracranial impairment of energy metabolism, no evidence of cerebral ischemia was obtained using {sup 1}H-MRS at the acute and subacute stages. There were thus discrepancies between the symptoms and the findings of SPECT as well as the findings of {sup 1}H-MRS. These data suggest that TGA may not necessarily be caused by cerebra1 ischemia. (author)

  15. Regional cerebral blood flow and metabolism in patients with transient global amnesia. A study using SPECT and 1H-MRS

    Ishihara, Tetsuya; Hirata, Koichi; Tatsumoto, Muneto; Yamazaki, Kaoru; Sato, Toshihiko.

    1997-01-01

    In 13 patients with transient global amnesia (TGA), we studied the clinical course and changes over time by means of imaging techniques such as SPECT. MRI, and proton MR spectroscopy ( 1 H-MRS). In the case of SPECT, a cerebral blood flow decrease at the time center of the temporal lobe persisted at least for more than one month. In many patients, no abnormal signs were found on MRI. Despite the presence of intracranial impairment of energy metabolism, no evidence of cerebral ischemia was obtained using 1 H-MRS at the acute and subacute stages. There were thus discrepancies between the symptoms and the findings of SPECT as well as the findings of 1 H-MRS. These data suggest that TGA may not necessarily be caused by cerebra1 ischemia. (author)

  16. Differential effects of gaseous versus injectable anesthetics on changes in regional cerebral blood flow and metabolism induced by l-DOPA in a rat model of Parkinson's disease.

    Bimpisidis, Zisis; Öberg, Carl M; Maslava, Natallia; Cenci, M Angela; Lundblad, Cornelia

    2017-06-01

    Preclinical imaging of brain activity requires the use of anesthesia. In this study, we have compared the effects of two widely used anesthetics, inhaled isoflurane and ketamine/xylazine cocktail, on cerebral blood flow and metabolism in a rat model of Parkinson's disease and l-DOPA-induced dyskinesia. Specific tracers were used to estimate regional cerebral blood flow (rCBF - [ 14 C]-iodoantipyrine) and regional cerebral metabolic rate (rCMR - [ 14 C]-2-deoxyglucose) with a highly sensitive autoradiographic method. The two types of anesthetics had quite distinct effects on l-DOPA-induced changes in rCBF and rCMR. Isoflurane did not affect either the absolute rCBF values or the increases in rCBF in the basal ganglia after l-DOPA administration. On the contrary, rats anesthetized with ketamine/xylazine showed lower absolute rCBF values, and the rCBF increases induced by l-DOPA were masked. We developed a novel improved model to calculate rCMR, and found lower metabolic activities in rats anesthetized with isoflurane compared to animals anesthetized with ketamine/xylazine. Both anesthetics prevented changes in rCMR upon l-DOPA administration. Pharmacological challenges in isoflurane-anesthetized rats indicated that drugs mimicking the actions of ketamine/xylazine on adrenergic or glutamate receptors reproduced distinct effects of the injectable anesthetics on rCBF and rCMR. Our results highlight the importance of anesthesia in studies of cerebral flow and metabolism, and provide novel insights into mechanisms mediating abnormal neurovascular responses to l-DOPA in Parkinson's disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. [Cerebral and ocular abnormalities with anterior pituitary insufficiency of familial nature].

    Weill, J; Boudailliez, B; Piussan, C; Ponte, C

    1985-01-01

    Three families presenting one or several cases of brain or ophthalmic abnormalities and an hypopituitarism at least by one of the members have been observed. In the first family, the mother and one of her sons present bilateral choroidoretineal coloboma with amblyopia; one of these two suffers as well from panhypopituitarism. In the second family two premature twins, a brother and his sister, present a syndrome with hypophyseal dwarfism and ophthalmic abnormalities, consisting in the boy's case in an peripapillary depigmentation with no visible sight trouble whereas girl's is showing an extreme microphthalmia with major mental retardation. In the third family two 2nd degree cousins present a panhypopituitarism but only one of the two reveals through neuroradiological investigations corpus callosum and septum lucidum agenesia. The karyotype is normal in all the cases. An hereditary mechanism appears clearly in the first family. It is possible in the second, probable in the third one.

  18. Global reduction of cerebral glucose metabolism in persons with symptomatic as well as asymptomatic lacunar infarction

    Takahashi, Wakoh; Takagi, Shigeharu; Shinohara, Yukito; Ide, Michiru; Shohtsu, Akira

    2000-01-01

    To clarify the hemodynamic changes in lacunar infarction, we evaluated cerebral glucose metabolism by using positron emission tomography with 18 F-fluorodeoxyglucose (FDG-PET) in patients with asymptomatic and symptomatic lacunar infarction and in persons without cerebral infarction on MRI. Subjects in this study were 27 patients with symptomatic lacunar infarction (SCI group), 73 subjects with asymptomatic lacunar infarction (ACI group), and 134 persons without infarction (NC group). CMRgI in the ACI group was significantly lower than that in the NC group in the cerebral cortex (P<0.05) and thalamus (P<0.05). CMRgI in the SCI group was significantly reduced from that in the NC group in the cerebral cortex (P<0.005), basal ganglia (P<0.001), thalamus (P<0.05) and white matter (P<0.005). The reduction in CMRgI in the SCI group was more severe than that in the ACI group in basal ganglia (P<0.05) and thalamus (P<0.05). Our results indicated that glucose metabolism in patients with asymptomatic lacunar infarction is reduced throughout the whole brain as compared with non-infarcted elderly persons. Follow-up and treatment of risk factors if present, may be necessary in such patients. (author)

  19. Effects of hyperbaric treatment in cerebral air embolism on intracranial pressure, brain oxygenation, and brain glucose metabolism in the pig

    van Hulst, Robert A.; Drenthen, Judith; Haitsma, Jack J.; Lameris, Thomas W.; Visser, Gerhard H.; Klein, Jan; Lachmann, Burkhard

    2005-01-01

    OBJECTIVE: To evaluate the effects of hyperbaric oxygen treatment after cerebral air embolism on intracranial pressure, brain oxygenation, brain glucose/lactate metabolism, and electroencephalograph. DESIGN: Prospective animal study. SETTING: Hyperbaric chamber. SUBJECTS: Eleven Landrace/Yorkshire

  20. Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury.

    Moro, Nobuhiro; Ghavim, Sima; Harris, Neil G; Hovda, David A; Sutton, Richard L

    2013-10-16

    Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients' remain under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. In Experiment 1, a single episode of hyperglycemia (50% glucose at 2 g/kg, i.p.) initiated immediately after CCI was found to significantly attenuate a TBI-induced depression of glucose metabolism in cerebral cortex (4 of 6 regions) and subcortical regions (2 of 7) as well as to significantly reduce the number of dead/dying neurons in cortex and hippocampus at 24 h post-CCI. Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2 g/kg, i.p.) at 0, 1, 3 and 6h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand. © 2013 Elsevier B.V. All rights reserved.

  1. Energy metabolism of rat cerebral cortex, hypothalamus and hypophysis during ageing.

    Villa, R F; Ferrari, F; Gorini, A

    2012-12-27

    Ageing is one of the main risk factors for brain disorders. According to the neuroendocrine theory, ageing modifies the sensitivity of hypothalamus-pituitary-adrenal axis to homoeostatic signals coming from the cerebral cortex. The relationships between the energy metabolism of these areas have not been considered yet, in particular with respect to ageing. For these reasons, this study was undertaken to systematically investigate in female Sprague-Dawley rats aged 4, 6, 12, 18, 24, 28 months and in 4-month-old male ones, the catalytic properties of energy-linked enzymes of the Krebs' cycle, electron transport chain, glutamate and related amino acids on different mitochondrial subpopulations, i.e. non-synaptic perikaryal and intra-synaptic (two types) mitochondria. The biochemical enzymatic pattern of these mitochondria shows different expression of the above-mentioned enzymatic activities in the investigated brain areas, including frontal cerebral cortex, hippocampus, striatum, hypothalamus and hypophysis. The study shows that: (i) the energy metabolism of the frontal cerebral cortex is poorly affected by physiological ageing; (ii) the biochemical machinery of non-synaptic perikaryal mitochondria is differently expressed in the considered brain areas; (iii) at 4-6 months, hypothalamus and hypophysis possess lower oxidative metabolism with respect to the frontal cerebral cortex while (iv), during ageing, the opposite situation occurs. We hypothesised that these metabolic modifications likely try to grant HPA functionality in response to the incoming external stress stimuli increased during ageing. It is particularly notable that age-related changes in brain bioenergetics and in mitochondrial functionality may be considered as remarkable factors during physiological ageing and should play important roles in predisposing the brain to physiopathological events, tightly related to molecular mechanisms evoked for pharmacological treatments. Copyright © 2012 IBRO

  2. Hepatic encephalopathy is associated with decreased cerebral oxygen metabolism and blood flow, not increased ammonia uptake

    Dam, Gitte; Keiding, Susanne; Munk, Ole Lajord

    2013-01-01

    Studies have shown decreased cerebral oxygen metabolism (CMRO(2)) and blood flow (CBF) in patients with cirrhosis with hepatic encephalopathy (HE). It remains unclear, however, whether these disturbances are associated with HE or with cirrhosis itself and how they may relate to arterial blood...... associated with HE rather than the liver disease as such. The changes in CMRO(2) and CBF could not be linked to blood ammonia concentration or CMRA....

  3. The effects of abnormalities of glucose homeostasis on the expression and binding of muscarinic receptors in cerebral cortex of rats.

    Sherin, Antony; Peeyush, Kumar T; Naijil, George; Nandhu, Mohan Sobhana; Jayanarayanan, Sadanandan; Jes, Paul; Paulose, Cheramadathikudiyil Skaria

    2011-01-25

    Glucose homeostasis in humans is an important factor for the functioning of nervous system. Both hypo and hyperglycemia contributes to neuronal functional deficit. In the present study, effect of insulin induced hypoglycemia and streptozotocin induced diabetes on muscarinic receptor binding, cholinergic enzymes; AChE, ChAT expression and GLUT3 in the cerebral cortex of experimental rats were analysed. Total muscarinic, muscarinic M(1) receptor showed a significant decrease and muscarinic M(3) receptor subtype showed a significant increased binding in the cerebral cortex of hypoglycemic rats compared to diabetic and control. Real-Time PCR analysis of muscarinic M(1), M(3) receptor subtypes confirmed the receptor binding studies. Immunohistochemistry of muscarinic M(1), M(3) receptors using specific antibodies were also carried out. AChE and GLUT3 expression up regulated and ChAT expression down regulated in hypoglycemic rats compared to diabetic and control rats. Our results showed that hypo/hyperglycemia caused impaired glucose transport in neuronal cells as shown by altered expression of GLUT3. Increased AChE and decreased ChAT expression is suggested to alter cortical acetylcholine metabolism in experimental rats along with altered muscarinic receptor binding in hypo/hyperglycemic rats, impair cholinergic transmission, which subsequently lead to cholinergic dysfunction thereby causing learning and memory deficits. We observed a prominent cholinergic functional disturbance in hypoglycemic condition than in hyperglycemia. Hypoglycemia exacerbated the neurochemical changes in cerebral cortex induced by hyperglycemia. These findings have implications for both therapy and identification of causes contributing to neuronal dysfunction in diabetes. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. Clinical features of male patients with alcoholic liver cirrhosis or hepatitis B cirrhosis complicated by abnormal glucose metabolism

    CHEN Qidan

    2016-02-01

    Full Text Available ObjectiveTo investigate the clinical features of male patients with alcoholic liver cirrhosis (ALC or hepatitis B cirrhosis (HBC complicated by abnormal glucose metabolism. MethodsA total of 287 patients with liver cirrhosis who were admitted to Guangzhou Panyu Central Hospital from January 2008 to September 2013 were selected. Among these patients, 74 had ALC and were all male, including 54 with abnormal glucose metabolism; the other 213 had HBC, including 97 with abnormal glucose metabolism (69 male patients and 28 female patients. A controlled study was performed for the clinical data of ALC and HBC patients with abnormal glucose metabolism, to investigate the association of patients′ clinical manifestations with the indices for laboratory examination, insulin resistance index, incidence rate of abnormal glucose metabolism, and Child-Pugh class. The t-test was applied for comparison of continuous data between groups, the chi-square test was applied for comparison of categorical data between groups, and the Spearman rank correlation was applied for correlation analysis. ResultsCompared with HBC patients, ALC patients had significantly higher incidence rates of abnormal glucose metabolism (730% vs 32.4%, hepatogenous diabetes (35.1% vs 14.6%, fasting hypoglycemia (27.0% vs 10.3%, and impaired glucose tolerance (31.1% vs 14.1% (χ2=4.371, 3.274, 4.784, and 1.633, all P<0.05. The Spearman correlation analysis showed that in ALC and HBC patients, the incidence rate of abnormal glucose metabolism was positively correlated with Child-Pugh class (rs=0.41, P<005. Compared with the HBC patients with abnormal glucose metabolism, the ALC patients with abnormal glucose metabolism had a significantly higher incidence rate of Child-Pugh class A (χ2=7.520, P=0.001, and a significantly lower incidence rate of Child-Pugh class C (χ2=6.542, P=0.003. There were significant differences in the incidence rates of dim complexion, telangiectasia of the

  5. Acute effect of glucose on cerebral blood flow, blood oxygenation, and oxidative metabolism.

    Xu, Feng; Liu, Peiying; Pascual, Juan M; Xiao, Guanghua; Huang, Hao; Lu, Hanzhang

    2015-02-01

    While it is known that specific nuclei of the brain, for example hypothalamus, contain glucose-sensing neurons thus their activity is affected by blood glucose level, the effect of glucose modulation on whole-brain metabolism is not completely understood. Several recent reports have elucidated the long-term impact of caloric restriction on the brain, showing that animals under caloric restriction had enhanced rate of tricarboxylic acid cycle (TCA) cycle flux accompanied by extended life span. However, acute effect of postprandial blood glucose increase has not been addressed in detail, partly due to a scarcity and complexity of measurement techniques. In this study, using a recently developed noninvasive MR technique, we measured dynamic changes in global cerebral metabolic rate of O2 (CMRO2 ) following a 50 g glucose ingestion (N = 10). A time dependent decrease in CMRO2 was observed, which was accompanied by a reduction in oxygen extraction fraction (OEF) with unaltered cerebral blood flow (CBF). At 40 min post-ingestion, the amount of CMRO2 reduction was 7.8 ± 1.6%. A control study without glucose ingestion was performed (N = 10), which revealed no changes in CMRO2 , CBF, or OEF, suggesting that the observations in the glucose study was not due to subject drowsiness or fatigue after staying inside the scanner. These findings suggest that ingestion of glucose may alter the rate of cerebral metabolism of oxygen in an acute setting. © 2014 Wiley Periodicals, Inc.

  6. The effect of enzymes upon metabolism, storage, and release of carbohydrates in normal and abnormal endometria.

    Hughes, E C

    1976-07-01

    This paper presents preliminary data concerning the relationship of various components of glandular epithelium and effect of enzymes on metabolism, storage, and release of certain substances in normal and abnormal endometria. Activity of these endometrial enzymes has been compared between two groups: 252 patients with normal menstrual histories and 156 patients, all over the age of 40, with abnormal uterine bleeding. Material was obtained by endometrial biopsy or curettage. In the pathologic classification of the group of 156, 30 patients had secretory endometria, 88 patients had endometria classified as proliferative, 24 were classified as endometrial hyperplasia, and 14 were classified as adenocarcinoma. All tissue was studied by histologic, histochemical, and biochemical methods. Glycogen synthetase activity caused synthesis of glucose to glycogen, increasing in amount until midcycle, when glycogen phosphorylase activity caused the breakdown to glucose during the regressive stage of endometrial activity. This normal cyclic activity did not occur in the abnormal endometria, where activity of both enzymes continued at low constant tempo. Only the I form of glycogen synthetase increased as the tissue became more hyperplastic. With the constant glycogen content and the increased activity of both the TPN isocitric dehydrogenase and glucose-6-phosphate dehydrogenase in the hyperplastic and cancerous endometria, tissue energy was created, resulting in abnormal cell proliferation. These altered biochemical and cellular activities may be the basis for malignant cell growth.

  7. Alleviation of metabolic abnormalities induced by excessive fructose administration in Wistar rats by Spirulina maxima.

    Jarouliya, Urmila; Zacharia, J Anish; Kumar, Pravin; Bisen, P S; Prasad, G B K S

    2012-03-01

    Diabetes mellitus is a metabolic disorder characterized by hyperglycaemia. Several natural products have been isolated and identified to restore the complications of diabetes. Spirulina maxima is naturally occurring fresh water cyanobacterium, enriched with proteins and essential nutrients. The aim of the study was to determine whether S. maxima could serve as a therapeutic agent to correct metabolic abnormalities induced by excessive fructose administration in Wistar rats. Oral administration of 10 per cent fructose solution to Wistar rats (n = 5 in each group) for 30 days resulted in hyperglycaemia and hyperlipidaemia. Aqueous suspension of S. maxima (5 or 10%) was also administered orally once daily for 30 days. The therapeutic potential of the preparation with reference to metformin (500 mg/kg) was assessed by monitoring various biochemical parameters at 10 day intervals during the course of therapy and at the end of 30 days S. maxima administration. Significant (Pmaxima aquous extract. Co-administration of S. maxima extract (5 or 10% aqueous) with 10 per cent fructose solution offered a significant protection against fructose induced metabolic abnormalities in Wistar rats. The present findings showed that S. maxima exhibited anti-hyperglycaemic, anti-hyperlipidaemic and hepatoprotective activity in rats fed with fructose. Further studies are needed to understand the mechanisms.

  8. ACE Reduces Metabolic Abnormalities in a High-Fat Diet Mouse Model

    Seong-Jong Lee

    2015-01-01

    Full Text Available The medicinal plants Artemisia iwayomogi (A. iwayomogi and Curcuma longa (C. longa radix have been used to treat metabolic abnormalities in traditional Korean medicine and traditional Chinese medicine (TKM and TCM. In this study we evaluated the effect of the water extract of a mixture of A. iwayomogi and C. longa (ACE on high-fat diet-induced metabolic syndrome in a mouse model. Four groups of C57BL/6N male mice (except for the naive group were fed a high-fat diet freely for 10 weeks. Among these, three groups (except the control group were administered a high-fat diet supplemented with ACE (100 or 200 mg/kg or curcumin (50 mg/kg. Body weight, accumulation of adipose tissues in abdomen and size of adipocytes, serum lipid profiles, hepatic steatosis, and oxidative stress markers were analyzed. ACE significantly reduced the body and peritoneal adipose tissue weights, serum lipid profiles (total cholesterol and triglycerides, glucose levels, hepatic lipid accumulation, and oxidative stress markers. ACE normalized lipid synthesis-associated gene expressions (peroxisome proliferator-activated receptor gamma, PPARγ; fatty acid synthase, FAS; sterol regulatory element-binding transcription factor-1c, SREBP-1c; and peroxisome proliferator-activated receptor alpha, PPARα. The results from this study suggest that ACE has the pharmaceutical potential reducing the metabolic abnormalities in an animal model.

  9. Abnormal metabolic brain networks in Parkinson's disease from blackboard to bedside.

    Tang, Chris C; Eidelberg, David

    2010-01-01

    Metabolic imaging in the rest state has provided valuable information concerning the abnormalities of regional brain function that underlie idiopathic Parkinson's disease (PD). Moreover, network modeling procedures, such as spatial covariance analysis, have further allowed for the quantification of these changes at the systems level. In recent years, we have utilized this strategy to identify and validate three discrete metabolic networks in PD associated with the motor and cognitive manifestations of the disease. In this chapter, we will review and compare the specific functional topographies underlying parkinsonian akinesia/rigidity, tremor, and cognitive disturbance. While network activity progressed over time, the rate of change for each pattern was distinctive and paralleled the development of the corresponding clinical symptoms in early-stage patients. This approach is already showing great promise in identifying individuals with prodromal manifestations of PD and in assessing the rate of progression before clinical onset. Network modulation was found to correlate with the clinical effects of dopaminergic treatment and surgical interventions, such as subthalamic nucleus (STN) deep brain stimulation (DBS) and gene therapy. Abnormal metabolic networks have also been identified for atypical parkinsonian syndromes, such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Using multiple disease-related networks for PD, MSA, and PSP, we have developed a novel, fully automated algorithm for accurate classification at the single-patient level, even at early disease stages. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. The Severity of Fatty Liver Disease Relating to Metabolic Abnormalities Independently Predicts Coronary Calcification

    Lee, Ying-Hsiang; Wu, Yih-Jer; Liu, Chuan-Chuan; Hou, Charles Jia-Yin; Yeh, Hung-I.; Tsai, Cheng-Ho; Shih, Shou-Chuan; Hung, Chung-Lieh

    2011-01-01

    Background. Nonalcoholic fatty liver disease (NAFLD) is one of the metabolic disorders presented in liver. The relationship between severity of NAFLD and coronary atherosclerotic burden remains largely unknown. Methods and Materials. We analyzed subjects undergoing coronary calcium score evaluation by computed tomography (MDCT) and fatty liver assessment using abdominal ultrasonography. Framingham risk score (FRS) and metabolic risk score (MRS) were obtained in all subjects. A graded, semiquantitative score was established to quantify the severity of NAFLD. Multivariate logistic regression analysis was used to depict the association between NAFLD and calcium score. Results. Of all, 342 participants (female: 22.5%, mean age: 48.7 ± 7.0 years) met the sufficient information rendering detailed analysis. The severity of NAFLD was positively associated with MRS (X 2 = 6.12, trend P < 0.001) and FRS (X 2 = 5.88, trend P < 0.001). After multivariable adjustment for clinical variables and life styles, the existence of moderate to severe NAFLD was independently associated with abnormal calcium score (P < 0.05). Conclusion. The severity of NAFLD correlated well with metabolic abnormality and was independently predict coronary calcification beyond clinical factors. Our data suggests that NAFLD based on ultrasonogram could positively reflect the burden of coronary calcification

  11. Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography

    Buchsbaum, M.S.; Wu, J.; Hazlett, E.; Sicotte, N.; Bunney, W.E. Jr.; Gillin, J.C.

    1989-01-01

    The cerebral metabolic rate of glucose was measured during nighttime sleep in 36 normal volunteers using positron emission tomography and fluorine-18-labeled 2-deoxyglucose (FDG). In comparison to waking controls, subjects given FDG during non-rapid eye movement (NREM) sleep showed about a 23% reduction in metabolic rate across the entire brain. This decrease was greater for the frontal than temporal or occipital lobes, and greater for basal ganglia and thalamus than cortex. Subjects in rapid eye movement (REM) sleep tended to have higher cortical metabolic rates than walking subjects. The cingulate gyrus was the only cortical structure to show a significant increase in glucose metabolic rate in REM sleep in comparison to waking. The basal ganglia were relatively more active on the right in REM sleep and symmetrical in NREM sleep

  12. Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography

    Rumsey, J.M.; Duara, R.; Grady, C.; Rapoport, J.L.; Margolin, R.A.; Rapoport, S.I.; Cutler, N.R.

    1985-05-01

    The cerebral metabolic rate for glucose was studied in ten men (mean age = 26 years) with well-documented histories of infantile autism and in 15 age-matched normal male controls using positron emission tomography and (F-18) 2-fluoro-2-deoxy-D-glucose. Positron emission tomography was completed during rest, with reduced visual and auditory stimulation. While the autistic group as a whole showed significantly elevated glucose utilization in widespread regions of the brain, there was considerable overlap between the two groups. No brain region showed a reduced metabolic rate in the autistic group. Significantly more autistic, as compared with control, subjects showed extreme relative metabolic rates (ratios of regional metabolic rates to whole brain rates and asymmetries) in one or more brain regions.

  13. Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography

    Rumsey, J.M.; Duara, R.; Grady, C.; Rapoport, J.L.; Margolin, R.A.; Rapoport, S.I.; Cutler, N.R.

    1985-01-01

    The cerebral metabolic rate for glucose was studied in ten men (mean age = 26 years) with well-documented histories of infantile autism and in 15 age-matched normal male controls using positron emission tomography and (F-18) 2-fluoro-2-deoxy-D-glucose. Positron emission tomography was completed during rest, with reduced visual and auditory stimulation. While the autistic group as a whole showed significantly elevated glucose utilization in widespread regions of the brain, there was considerable overlap between the two groups. No brain region showed a reduced metabolic rate in the autistic group. Significantly more autistic, as compared with control, subjects showed extreme relative metabolic rates (ratios of regional metabolic rates to whole brain rates and asymmetries) in one or more brain regions

  14. Branched-chain amino acid metabolism in rat muscle: abnormal regulation in acidosis

    May, R.C.; Hara, Y.; Kelly, R.A.; Block, K.P.; Buse, M.G.; Mitch, W.E.

    1987-06-01

    Branched-chain amino acid (BCAA) metabolism is frequently abnormal in pathological conditions accompanied by chronic metabolic acidosis. To study how metabolic acidosis affects BCAA metabolism in muscle, rats were gavage fed a 14% protein diet with or without 4 mmol NH/sub 4/Cl x 100 g body wt/sup -1/ x day/sup -1/. Epitrochlearis muscles were incubated with L-(1-/sup 14/C)-valine and L-(1-/sup 14/C)leucine, and rates of decarboxylation, net transamination, and incorporation into muscle protein were measured. Plasma and muscle BCAA levels were lower in acidotic rats. Rates of valine and leucine decarboxylation and net transamination were higher in muscles from acidotic rats; these differences were associated with a 79% increase in the total activity of branched-chain ..cap alpha..-keto acid dehydrogenase and a 146% increase in the activated form of the enzyme. They conclude that acidosis affects the regulation of BCAA metabolism by enhancing flux through the transaminase and by directly stimulating oxidative catabolism through activation of branched-chain ..cap alpha..-keto acid dehydrogenase.

  15. Prevalence and predictors of metabolic abnormalities in Chinese women with PCOS: a cross- sectional study

    2014-01-01

    Background Polycystic ovary syndrome (PCOS) is a common condition estimated to affect 5.61% of Chinese women of reproductive age, but little is known about the prevalence and predictors in Chinese PCOS patients. This study aimed to determine the prevalence and predictors of the metabolic abnormalities in Chinese women with and without PCOS. Methods A large-scale national epidemiological investigation was conducted in reproductive age women (19 to 45 years) across China. 833 reproductive aged PCOS women, who participated in the healthcare screening, were recruited from ten provinces in China. Clinical history, ultrasonographic exam (ovarian follicle), hormonal and metabolic parameters were the main outcome measures. Results The prevalence of metabolic syndrome (MetS) as compared in PCOS and non-PCOS women from community were 18.2% vs 14.7%, and IR (insulin resistance) were 14.2% vs 9.3% (p PCOS than in non-PCOS groups. Using multivariate logistic regression, central obesity and FAI were risk factors, while SHBG was a protective factor on the occurrence of Mets and IR in PCOS women (OR: 1.132, 1.105 and 0.995). Conclusions The risk factors of the metabolic syndrome and insulin resistance were BMI and FAI for PCOS women, respectively. The decrease of SHBG level was also a risk factor for insulin resistance in both PCOS and metabolic disturbance. PMID:25223276

  16. Branched-chain amino acid metabolism in rat muscle: abnormal regulation in acidosis

    May, R.C.; Hara, Y.; Kelly, R.A.; Block, K.P.; Buse, M.G.; Mitch, W.E.

    1987-01-01

    Branched-chain amino acid (BCAA) metabolism is frequently abnormal in pathological conditions accompanied by chronic metabolic acidosis. To study how metabolic acidosis affects BCAA metabolism in muscle, rats were gavage fed a 14% protein diet with or without 4 mmol NH 4 Cl x 100 g body wt -1 x day -1 . Epitrochlearis muscles were incubated with L-[1- 14 C]-valine and L-[1- 14 C]leucine, and rates of decarboxylation, net transamination, and incorporation into muscle protein were measured. Plasma and muscle BCAA levels were lower in acidotic rats. Rates of valine and leucine decarboxylation and net transamination were higher in muscles from acidotic rats; these differences were associated with a 79% increase in the total activity of branched-chain α-keto acid dehydrogenase and a 146% increase in the activated form of the enzyme. They conclude that acidosis affects the regulation of BCAA metabolism by enhancing flux through the transaminase and by directly stimulating oxidative catabolism through activation of branched-chain α-keto acid dehydrogenase

  17. Neonatal seizures: the overlap between diagnosis of metabolic disorders and structural abnormalities. Case report

    Freitas Alessandra

    2003-01-01

    Full Text Available Inborn metabolic errors (IME and cortical developmental malformations are uncommon etiologies of neonatal seizures, however they may represent treatable causes of refractory epilepsy and for this reason must be considered as possible etiological factors. This case report aims to demonstrate the importance of neuroimaging studies in one patient with neonatal seizures, even when there are clues pointing to a metabolic disorder. CASE REPORT: A previously healthy 14 day-old child started presenting reiterated focal motor seizures (FMS which evolved to status epilepticus. Exams showed high serum levels of ammonia and no other abnormalities. A metabolic investigation was conducted with normal results. During follow-up, the patient presented developmental delay and left side hemiparesia. Seizures remained controlled with anti-epileptic drugs for four months, followed by relapse with repetitive FMS on the left side. Temporary improvement was obtained with anti-epileptic drug adjustment. At the age of 6 months, during a new episode of status epilepticus, high ammonia levels were detected. Other metabolic exams remained normal. The child was referred to a video-electroencephalographic monitoring and continuous epileptiform discharges were recorded over the right parasagittal and midline regions, with predominance over the posterior quadrant. A new neuroimaging study was performed and displayed a malformation of cortical development. Our case illustrates that because newborns are prone to present metabolic disarrangement, an unbalance such as hyperammonemia may be a consequence of acute events and conduct to a misdiagnosis of IME.

  18. Cerebral metabolic and structural alterations in hereditary spastic paraplegia with thin corpus callosum assessed by MRS and DTI

    Dreha-Kulaczewski, Steffi; Dechent, Peter; Helms, Gunther; Frahm, Jens; Gaertner, Jutta; Brockmann, Knut

    2006-01-01

    Hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is a complicated form of autosomal-recessive hereditary spastic paraplegia. Characteristic clinical features comprise progressive spastic gait, cognitive impairment, and ataxia. Diagnostic MRI findings include thinning of the corpus callosum and non-progressive white matter (WM) alterations. To study the extent of axonal involvement, we performed localized proton magnetic resonance spectroscopy (MRS) of the cerebral WM and cortical grey matter (GM) in a patient with HSP-TCC at 20 and 25 years of age. The second investigation included diffusion tensor imaging (DTI). While MRS of the GM was normal, affected WM was characterized by major metabolic alterations such as reduced concentrations of N-acetylaspartate and N-acetylaspartyl-glutamate, creatine and phosphocreatine, and choline-containing compounds as well as elevated levels of myo-inositol. These abnormalities showed progression over a period of 5 years. DTI revealed increased mean diffusivity as well as reduced fractional anisotropy in periventricular WM. The metabolic and structural findings are consistent with progressive neuroaxonal loss in the WM accompanied by astrocytic proliferation - histopathological changes known to occur in HSP-TCC. Our results are in agreement with the hypothesis that the primary pathological process in HSP-TCC affects the axon, possibly due to impaired axonal trafficking. (orig.)

  19. Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer's disease: a PET follow-up study

    Drzezga, Alexander; Willoch, Frode; Schwaiger, Markus [Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675, Muenchen (Germany); Lautenschlager, Nicola; Riemenschneider, Matthias; Kurz, Alexander [Department of Psychiatry and Psychotherapy, Technische Universitaet Muenchen, Muenchen (Germany); Siebner, Hartwig [Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London (United Kingdom); Minoshima, Satoshi [Department of Radiology, University of Washington, Seattle, WA (United States)

    2003-08-01

    A high percentage of patients with mild cognitive impairment (MCI) develop clinical dementia of the Alzheimer type (AD) within 1 year. The aim of this longitudinal study was to identify characteristic patterns of cerebral metabolism at baseline in patients converting from MCI to AD, and to evaluate the changes in these patterns over time. Baseline and follow-up examinations after 1 year were performed in 22 MCI patients (12 males, 10 females, aged 69.8{+-}5.8 years); these examinations included neuropsychological testing, structural cranial magnetic resonance imaging and fluorine-18 fluorodeoxyglucose positron emission tomography (PET) evaluation of relative cerebral glucose metabolic rate (rCMRglc). Individual PET scans were stereotactically normalised with NEUROSTAT software (Univ. of Michigan, Ann Arbor, USA). Subsequently, statistical comparison of PET data with an age-matched healthy control population and between patient subgroups was performed using SPM 99 (Wellcome Dept. of Neuroimaging Sciences, London, UK). After 1 year, eight patients (36%) had developed probable AD (referred to as MCI{sub AD}), whereas 12 (55%) were still classified as having stable MCI (referred to as MCI{sub MCI}). Compared with the healthy control group, a reduced rCMRglc in AD-typical regions, including the temporoparietal and posterior cingulate cortex, was detected at baseline in patients with MCI{sub AD}. Abnormalities in the posterior cingulate cortex reached significance even in comparison with the MCI{sub MCI} group. After 1 year, MCI{sub AD} patients demonstrated an additional bilateral reduction of rCMRglc in prefrontal areas, along with a further progression of the abnormalities in the parietal and posterior cingulate cortex. No such changes were observed in the MCI{sub MCI} group. In patients with MCI, characteristic cerebral metabolic differences can be delineated at the time of initial presentation, which helps to define prognostic subgroups. A newly emerging reduction

  20. Abnormal cerebral functional connectivity in esophageal cancer patients with theory of mind deficits in resting state.

    Cao, Yin; Xiang, JianBo; Qian, Nong; Sun, SuPing; Hu, LiJun; Yuan, YongGui

    2015-01-01

    To explore the function of the default mode network (DMN) in the psychopathological mechanisms of theory of mind deficits in patients with an esophageal cancer concomitant with depression in resting the state. Twenty-five cases of esophageal cancer with theory of mind deficits (test group) that meet the diagnostic criteria of esophageal cancer and neuropsychological tests, including Beck depression inventory, reading the mind in the eyes, and Faux pas, were included, Another 25 cases of esophageal cancer patients but without theory of mind deficits (control group) were enrolled. Each patient completed a resting-state functional magnetic resonance imaging. The functional connectivity intensities within the cerebral regions in the DMN of all the enrolled patients were analyzed. The results of each group were compared. The functional connectivity of the bilateral prefrontal central region with the precuneus, bilateral posterior cingulate gyrus and bilateral ventral anterior cingulate gyrus in the patients of the test group were all reduced significantly (P theory of mind deficits. The theory of mind deficits might have an important function in the pathogenesis of esophageal cancer.

  1. Changes of regional cerebral glucose metabolism in normal aging process : A study with FDG PET

    Yoon, Joon Kee; Kim, Sang Eun; Lee, Kyung Han; Choi, Yong; Choe, Yearn Seong; Kim, Byung Tae [Sungkyunkwan Univ., School of Medicine, Seoul (Korea, Republic of)

    2001-08-01

    Normal aging results in detectable changes in the brain structure and function. We evaluated the changes of regional cerebral glucose metabolism in the normal aging process with FDG PET. Brain PET images were obtained in 44 healthy volunteers (age range 20-69'y'; M:F = 29:15) who had no history of neuropsychiatric disorders. On 6 representative transaxial images, ROls were drawn in the cortical and subcortical areas. Regional FDG uptake was normalized using whole brain uptake to adjust for the injection dose and correct for nonspecific declines of glucose metabolism affecting all brain areas equally. In the prefrontal, temporoparietal and primary sensorimotor cortex, the normalized FDG uptake (NFU) reached a peak In subjects in their 30s. The NFU in the prefrontal and primary sensorimotor cortex declined with age after 30s at a rate of 3.15%/decade and 1.93%/decade, respectively. However, the NFU in the lernporoparietal cortex did not change significantly with age after 30s. The anterior (prefrontal) posterior (temporoparietal) gradient peaked in subjects in their 30s and declined with age the reafter at a rate of 35%/decade. The NFU in the caudate nucleus was decreased with age after 20s at a rate of 2.39%/decade. In the primary visual cortex, putamen, and thalamus, the NFU values did not change significantly throughout the ages covered. These patterns were not significantly different between right and left cerebral hemispheres. Of interest was that the NFU in the left cerebellar cortex was increased with age after 20s at a rate of 2.86%/decade. These data demonstrate regional variation of the age-related changes in the cerebral glucose metabolism, with the most prominent age-related decline of metabolism in the prefrontal cortex. The increase in the cerebellar metabolism with age might reflect a process of neuronal plasticity associated with aging.

  2. Changes of regional cerebral glucose metabolism in normal aging process : A study with FDG PET

    Yoon, Joon Kee; Kim, Sang Eun; Lee, Kyung Han; Choi, Yong; Choe, Yearn Seong; Kim, Byung Tae

    2001-01-01

    Normal aging results in detectable changes in the brain structure and function. We evaluated the changes of regional cerebral glucose metabolism in the normal aging process with FDG PET. Brain PET images were obtained in 44 healthy volunteers (age range 20-69'y'; M:F = 29:15) who had no history of neuropsychiatric disorders. On 6 representative transaxial images, ROls were drawn in the cortical and subcortical areas. Regional FDG uptake was normalized using whole brain uptake to adjust for the injection dose and correct for nonspecific declines of glucose metabolism affecting all brain areas equally. In the prefrontal, temporoparietal and primary sensorimotor cortex, the normalized FDG uptake (NFU) reached a peak In subjects in their 30s. The NFU in the prefrontal and primary sensorimotor cortex declined with age after 30s at a rate of 3.15%/decade and 1.93%/decade, respectively. However, the NFU in the lernporoparietal cortex did not change significantly with age after 30s. The anterior (prefrontal) posterior (temporoparietal) gradient peaked in subjects in their 30s and declined with age the reafter at a rate of 35%/decade. The NFU in the caudate nucleus was decreased with age after 20s at a rate of 2.39%/decade. In the primary visual cortex, putamen, and thalamus, the NFU values did not change significantly throughout the ages covered. These patterns were not significantly different between right and left cerebral hemispheres. Of interest was that the NFU in the left cerebellar cortex was increased with age after 20s at a rate of 2.86%/decade. These data demonstrate regional variation of the age-related changes in the cerebral glucose metabolism, with the most prominent age-related decline of metabolism in the prefrontal cortex. The increase in the cerebellar metabolism with age might reflect a process of neuronal plasticity associated with aging

  3. Study of cerebral metabolism of glucose in normal human brain correlated with age

    Si, M.

    2007-01-01

    Full text: The objective was to determine whether cerebral metabolism in various regions of the brain differs with advancing age by using 18F-FDG PET instrument and SPM software. Materials and Methods We reviewed clinical information of 295 healthy normal samples who were examined by a whole body GE Discovery LS PET-CT instrument in our center from Aug. 2004 to Dec. 2005.They (with the age ranging from 21 to 88; mean age+/-SD: 49.77+/-13.51) were selected with: (i)absence of clear focal brain lesions (epilepsy.cerebrovascular diseases etc);(ii) absence of metabolic diseases, such as hyperthyroidism, hypothyroidism and diabetes;(iii) absence of psychiatric disorders and abuse of drugs and alcohol. They were sub grouped into six groups with the interval of 10 years old starting from 21, and the gender, educational background and serum glucose were matched. All subgroups were compared to the control group of 31-40 years old (84 samples; mean age+/-SD: 37.15+/-2.63). All samples were injected with 18F-FDG (5.55MBq/kg), 45-60 minutes later, their brains were scanned for 10min. Pixel-by-pixel t-statistic analysis was applied to all brain images using the Statistical parametric mapping (SPM2) .The hypometabolic areas (p < 0. 01 or p<0.001, uncorrected) were identified in the Stereotaxic coordinate human brain atlas and three-dimensional localized by MNI Space utility (MSU) software. Results:Relative hypometabolic brain areas detected are mainly in the cortical structures such as bilateral prefrontal cortex, superior temporal gyrus(BA22), parietal cortex (inferior parietal lobule and precuneus(BA40, insula(BA13)), parahippocampal gyrus and amygdala (p<0.01).It is especially apparent in the prefrontal cortex (BA9)and sensory-motor cortex(BA5, 7) (p<0.001), while basal ganglia and cerebellum remained metabolically unchanged with advancing age. Conclusions Regional cerebral metabolism of glucose shows a descent tendency with aging, especially in the prefrontal cortex (BA9)and

  4. Abnormal glucose metabolism in acute myocardial infarction: influence on left ventricular function and prognosis

    Høfsten, Dan E; Løgstrup, Brian B; Møller, Jacob E

    2009-01-01

    tolerance test before discharge. LV function was assessed using echocardiographic measurements (LV end-diastolic volume, LV end-systolic volume, LV ejection fraction, restrictive diastolic filling pattern, early transmitral flow velocity to early diastolic mitral annular velocity ratio [E/e'], and left...... atrial volume index) and by measuring plasma N-terminal pro-B-type natriuretic peptide levels. RESULTS: After adjustment for age and gender, a linear relationship between the degree of abnormal glucose metabolism was observed for each marker of LV dysfunction (p(trend)

  5. Phenobarbital and neonatal seizures affect cerebral oxygen metabolism: a near-infrared spectroscopy study.

    Sokoloff, Max D; Plegue, Melissa A; Chervin, Ronald D; Barks, John D E; Shellhaas, Renée A

    2015-07-01

    Near-infrared spectroscopy (NIRS) measures oxygen metabolism and is increasingly used for monitoring critically ill neonates. The implications of NIRS-recorded data in this population are poorly understood. We evaluated NIRS monitoring for neonates with seizures. In neonates monitored with video-electroencephalography, NIRS-measured cerebral regional oxygen saturation (rSO2) and systemic O2 saturation were recorded every 5 s. Mean rSO2 was extracted for 1-h blocks before, during, and after phenobarbital doses. For each electrographic seizure, mean rSO2 was extracted for a period of three times the duration of the seizure before and after the ictal pattern, as well as during the seizure. Linear mixed models were developed to assess the impact of phenobarbital administration and of seizures on rSO2 and fractional tissue oxygen extraction. For 20 neonates (estimated gestational age: 39.6 ± 1.5 wk), 61 phenobarbital doses and 40 seizures were analyzed. Cerebral rSO2 rose (P = 0.005), and fractional tissue oxygen extraction declined (P = 0.018) with increasing phenobarbital doses. rSO2 declined during seizures, compared with baseline and postictal phases (baseline 81.2 vs. ictal 77.7 vs. postictal 79.4; P = 0.004). Fractional tissue oxygen extraction was highest during seizures (P = 0.002). Cerebral oxygen metabolism decreases after phenobarbital administration and increases during seizures. These small, but clear, changes in cerebral oxygen metabolism merit assessment for potential clinical impact.

  6. Cerebral Correlates of Abnormal Emotion Conflict Processing in Euthymic Bipolar Patients: A Functional MRI Study.

    Favre, Pauline; Polosan, Mircea; Pichat, Cédric; Bougerol, Thierry; Baciu, Monica

    2015-01-01

    Patients with bipolar disorder experience cognitive and emotional impairment that may persist even during the euthymic state of the disease. These persistent symptoms in bipolar patients (BP) may be characterized by disturbances of emotion regulation and related fronto-limbic brain circuitry. The present study aims to investigate the modulation of fronto-limbic activity and connectivity in BP by the processing of emotional conflict. Fourteen euthymic BP and 13 matched healthy subjects (HS) underwent functional magnetic resonance imaging (fMRI) while performing a word-face emotional Stroop task designed to dissociate the monitoring/generation of emotional conflict from its resolution. Functional connectivity was determined by means of psychophysiological interaction (PPI) approach. Relative to HS, BP were slower to process incongruent stimuli, reflecting higher amount of behavioral interference during emotional Stroop. Furthermore, BP showed decreased activation of the right dorsolateral prefrontal cortex (DLPFC) during the monitoring and a lack of bilateral amygdala deactivation during the resolution of the emotional conflict. In addition, during conflict monitoring, BP showed abnormal positive connectivity between the right DLPFC and several regions of the default mode network. Overall, our results highlighted dysfunctional processing of the emotion conflict in euthymic BP that may be subtended by abnormal activity and connectivity of the DLPFC during the conflict monitoring, which, in turn, leads to failure of amygdala deactivation during the resolution of the conflict. Emotional dysregulation in BP may be underpinned by a lack of top-down cognitive control and a difficulty to focus on the task due to persistent self-oriented attention.

  7. Cerebral circulation, metabolism, and blood-brain barrier of rats in hypocapnic hypoxia

    Beck, T.; Krieglstein, J.

    1987-01-01

    The effects of hypoxic hypoxia on physiological variables, cerebral circulation, cerebral metabolism, and blood-brain barrier were investigated in conscious, spontaneously breathing rats by exposing them to an atmosphere containing 7% O 2 . Hypoxia affected a marked hypotension, hypocapnia and alkalosis. Cortical tissue high-energy phosphates and glucose content were not affected by hypoxia, glucose 6-phosphate lactate, and pyruvate levels were significantly increased. Blood-brain barrier permeability, regional brain glucose content and lumped constant were not changed by hypoxia. Local cerebral glucose utilization (LCGU) rose by 40-70% of control values in gray matter and by 80-90% in white matter. Under hypoxia, columns of increased and decreased LCGU and were detectable in cortical gray matter. Color-coded [ 14 C]2-deoxy-D-glucose autoradiograms of rat brain are shown. Local cerebral blood flow (LCBF) increased by 50-90% in gray matter and by up to 180% in white matter. Coupling between LCGU and LCBF in hypoxia remained unchanged. The data suggests a stimulation of glycolysis, increased glucose transport into the cell, and increased hexokinase activity. The physiological response of gray and white matter to hypoxia obviously differs. Uncoupling of the relation between LCGU and LCBF does not occur

  8. Regional cerebral metabolic changes after acupuncture by FDG PET: effects and methodology

    Guan Yihui; Li Ji; Zuo Chuantao; Dong Jincheng; Zhao Jun; Lin Xiangtong

    2002-01-01

    In order to investigate the therapeutic mechanisms of acupuncture pints in cerebrovascular ischemic patients and normal volunteers, FDG PET was adopted. Changes in cerebral glucose metabolism and cerebral functional activity before and after electro-acupuncture treatment were studied in 12 normal volunteers and 11 cerebrovascular ischemic patients. The PET imaging was read by visual interpretation and calculated by semi-quantitative analysis. After acupuncture, cerebral glucose metabolism of the normal group is higher in the frontal lobe, temporal lobe, thalamus bilaterally and cerebellum contralaterally. The cerebrovascular ischemic patients had manifested greater response in their lesions than in their normal regions of the two tested groups, as well as than in their normal regions of the whole brain, after acupuncture treatment. The study shows that the regulatory effects of acupuncture on the central nervous system influence the brain at multiple-sections, multiple-directions and multiple-levels of brain function. It conforms to the holistic and bi-directions regulatory laws of acupuncture

  9. Effects of nitrous oxide on cerebral haemodynamics and metabolism during isoflurane anaesthesia in man

    Algotsson, L.; Messeter, K. (Department of Anaesthesiology, University Hospital, Lund (Sweden)); Rosen, I. (Department of Clinical Neurophysiology, University Hospital, Lund (Sweden)); Holmin, T. (Department of Surgery, University Hospital, Lund (Sweden))

    1992-01-01

    Seven normoventilated and five hyperventilated healthy adults undergoing cholecystectomy and anaesthetized with methohexitone, fentanyl and pancuronium were studied with measurement of cerebral blood flow (CBF), cereal metabolic rate of oxygen (CMRo[sub 2]), and quantified electroencephalography (EEG) under two sets of conditions: (1) 1.7% end-tidal concentration of isoflurane in air/oxygen: (2) 0.85% end-tidal concentration of isoflurane in nitrous oxide (N[sub 2]O)/oxygen. The object was to study the effects of N[sub 2]O during isoflurane anaesthesia on cerebral circulation, metabolism and neuroelectric activity. N[sub 2]O in the anaesthetic gas mixture caused a 43% (P<0.05) increase in CBF during normocarbic conditions but no significant change during hypocapnia. CMRo[sub 2] was not significantly altered by N[sub 2]O. EEG demonstrated an activated pattern with decreased low frequency activity and increased high frequency activity. The results confirm that N[sub 2]O is a potent cerebral vasodilator in man, although the mechanisms underlying the effects on CBF are still unclear. (au).

  10. Clinical significance of reduced cerebral metabolism in multiple sclerosis. A combined PET and MRI study

    Sun, Xiayan; Tanaka, Makoto; Kondo, Susumu; Okamoto, Koichi; Hirai, Shunsaku

    1998-01-01

    Magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) has provided major insights into the disease's natural history, and many studies have focussed on possible correlations between MRI findings and the clinical manifestations of MS. In contrast, there are few reports on possible relationships between functional imaging data and cognitive function. The present study assessed the relationship between clinical presentation and combined anatomical and functional imaging data in MS. Twenty patients with definite MS underwent MRI and positron emission tomography (PET) to evaluate cerebral blood flow (rCBF) and oxygen metabolism (rCMRO 2 ). The relationships between these neuroimaging findings and clinical data, including the Expanded Disability Status Scale (EDSS), Mini-mental status scale, Hasegawa Dementia Scale and relapse time, were evaluated with Spearman's rank correlation coefficients. A general reduction in rCBF and rCMRO 2 in the gray and white matter were found in the MS patients. EDSS was correlated with the number and size of the lesions on MRI and was negatively correlated with rCMRO 2 . A correlation between the decrease in rCMRO 2 and the level of cognitive impairment was also found. The severity of cerebral hypometabolism was also related to the number of relapses. Morphological and functional findings obtained by MRI and PET are closely related to the clinical status in MS. Our results suggest that measurement of cerebral metabolism in MS has the potential to be an objective marker for monitoring disease activity and to provide prognostic information. (author)

  11. Regional cerebral metabolic changes after acupuncture by FDG PET: Effects and methodology

    Guan, Y.H.; Zuo, C.T.; Zhao, J.; Lin, X.T.; Li, J.; Dong, J.C.

    2002-01-01

    Abstract Objectives: To observe the regional cerebral metabolism changes in cerebrovascular ischemic patients and normal volunteers while acupuncture by using FDG PET. To definite the locations of the influence of these acupoints on brain function in certain regions of the cerebrum, as well as to explore the laws of therapeutic effects of acupuncture on subjects and established the One-day method for brain FDG PET scan. Methods and Materials Using FDG PET, cerebral glucose metabolism and cerebral functional changes before and after electro-acupuncture treatment were investigated in 12 normal volunteers and 8 cerebrovascular ischemic patients. These subjects were treated with acupuncture in the following points: Hegu (LI4) and Quchi (LI11) of Hand Yang-Ming meridian, Zusanli (ST36) and Shangjuxu (ST37) of Foot Yang-Ming meridian and added Motor Area and Fengchi (B20). Limbs points were contralateral to the brain points. In the normal group, the side of the body treated by acupuncture was randomly selected and in the patients groups, the sides treated were on the side of paralysis. PET imaging was read by visual interpretation and calculated in multiple ROI semi-quantitative analysis method. Therefore, the image subject method was used to demonstrate the variety of glucose metabolism after acupuncture. Results One-day method was established in these studies. PET imaging was read by visual interpretation in blind method and calculated by semi-quantitative analysis. This results shows that cerebral glucose metabolism and cerebral functional activity of the normal is higher in the frontal lobe, temporal lobe, thalamus, Sensorimotor, Parietal bilaterally and cerebellum contralaterally. After acupuncture, the increase ratio of ipslateral glucose metabolism was between 23% and 38%; while the contralateral increase ratio between 22% and 40%. Above all, the variation in cerebral glucose metabolism was predominantly contralateral cerebral regions. The cerebrovascular ischemic

  12. The exploration of the changes in bone metabolism in patients with abnormal thyroid function

    Chu Shaolin; Li Xiaohong; Lei Qiufang; Ye Peihong; Chai Luhua

    2001-01-01

    To explore the changes in bone metabolism with abnormal thyroid function, BGP and PTH in 91 patients with hyperthyroidism, 37 patients with hypothyroidism, 51 controls, were measured by means of IRMA, calcaneus heel bone density (BMD) was measured by means of 241 Am single photon absorptiometry. BGP levels in hyperthyroidism were significantly higher than those in controls (P < 0.001). BGP levels in hypothyroidism were significantly lower than those in controls (P < 0.001). PTH levels in hyperthyroidism were a little lower than those in controls (P < 0.05). PTH levels in hypothyroidism were significantly higher than those in controls (P < 0.001). The measurement of BMD showed that the prevalence rates of osteoporosis (OP) in hyperthyroidism and hypothyroidism were significantly higher than those in controls. In hyperthyroidism and hypothyroidism groups the age of OP tends to be younger. The patients with hyperthyroidism over 55 years of age were all suffered from OP. The changes in BGP and PTH were earlier than BMD, so BGP and PTH can be used as sensitive indicator of the changes in bone metabolism with abnormal thyroid function, especially for curative effect observations

  13. Serotonergic dysfunctions and abnormal iron metabolism: Relevant to mental fatigue of Parkinson disease.

    Zuo, Li-Jun; Yu, Shu-Yang; Hu, Yang; Wang, Fang; Piao, Ying-Shan; Lian, Teng-Hong; Yu, Qiu-Jin; Wang, Rui-Dan; Li, Li-Xia; Guo, Peng; Du, Yang; Zhu, Rong-Yan; Jin, Zhao; Wang, Ya-Jie; Wang, Xiao-Min; Chan, Piu; Chen, Sheng-Di; Wang, Yong-Jun; Zhang, Wei

    2016-12-21

    Fatigue is a very common non-motor symptom in Parkinson disease (PD) patients. It included physical fatigue and mental fatigue. The potential mechanisms of mental fatigue involving serotonergic dysfunction and abnormal iron metabolism are still unknown. Therefore, we evaluated the fatigue symptoms, classified PD patients into fatigue group and non-fatigue group, and detected the levels of serotonin, iron and related proteins in CSF and serum. In CSF, 5-HT level is significantly decreased and the levels of iron and transferrin are dramatically increased in fatigue group. In fatigue group, mental fatigue score is negatively correlated with 5-HT level in CSF, and positively correlated with the scores of depression and excessive daytime sleepiness, and disease duration, also, mental fatigue is positively correlated with the levels of iron and transferrin in CSF. Transferrin level is negatively correlated with 5-HT level in CSF. In serum, the levels of 5-HT and transferrin are markedly decreased in fatigue group; mental fatigue score exhibits a negative correlation with 5-HT level. Thus serotonin dysfunction in both central and peripheral systems may be correlated with mental fatigue through abnormal iron metabolism. Depression, excessive daytime sleepiness and disease duration were the risk factors for mental fatigue of PD.

  14. Carbon balance studies of glucose metabolism in rat cerebral cortical synaptosomes

    Bauer, U; Brand, K

    1982-07-01

    Synaptosomes were isolated from rat cerebral cortex and incubated with (U-/sup 14/C)-, (1-/sup 14/C)- or (6-/sup 14/C)glucose. Glucose utilization and the metabolic partitioning of glucose carbon in products were determined by isotopic methods. From the data obtained a carbon balance was constructed, showing lactate to be the main product of glucose metabolism, followed by CO/sup 2/, amino acids and pyruvate. Measuring the release of /sup 14/CO/sup 2/ from glucose labelled in three different positions allowed the construction of a flow diagram of glucose carbon atoms in synaptosomes, which provides information about the contribution of the various pathways of glucose metabolism. Some 2% of glucose utilized was calculated to be degraded via the pentose phosphate pathway. Addition of chlorpromazine, imipramine or haloperidol at concentrations of 10(-5) M reduced glucose utilisation by 30% without changing the distribution pattern of radioactivity in the various products.

  15. Investigation of cerebral metabolism by positron CT in Japanese following musical stimulation

    Wakasugi, Naotoshi

    1994-01-01

    Cerebral metabolic responses to Japanese and Western instrumental music were examined using 11 C-glucose and positron CT. Eight right-handed subjects were studied in both Japanese and Western music-stimulated states. Biaural musical stimulation with a Japanese instrument, the 'shakuhachi', produced diffuse metabolic changes in the left temporal lobe in all subjects. Biaural musical stimulation with a Western instrument, the 'violin', produced metabolic changes in the right temporal lobe in 3 subjects, changes in the left in 4, and changes on both sides in one. It was considered previously that all musical stimulation led to hypermetabolism in the right hemisphere of human beings. However, the present results indicated that Japanese music produced activation of the left hemisphere in Japanese. On the other hand, Western music produced right hemispheric hypermetabolism in Japanese with no emotion. The laterality of the hemisphere stimulated by Western music was apparently incidentally changed according to the state of mind the Japanese subjects. (author)

  16. In vivo neuro MR spectroscopy: a non-invasive insight into cerebral metabolism

    Rose, S.; De Zubicaray, G.; Wang, D.; Galloway, G.; Doddrell, D.; Chalk, J.; University of Queensland, Brisbane, QLD; Eagle, S.; Semple, J.

    1999-01-01

    In addition to conventional magnetic resonance imaging (MRI) for examining anatomical structure, in vivo proton magnetic resonance spectroscopy (MRS) is currently being used as a non-invasive clinical tool for monitoring altered brain metabolism. Conditions such as head injury, dementia, multiple sclerosis, tumour, stroke, epilepsy and inborn errors of metabolism are all presently being investigated with MRS. At the Centre for Magnetic Resonance, we are currently undertaking a longitudinal study of dementia progression in Alzheimer's disease (AD) utilising both MRS and volumetric MRI techniques. The aim is to identify metabolic differences between this patient group and normal older adults and to correlate these measures with cognitive function. Cerebral artrophy, or loss of brain matter, together with ventricular enlargement , or enlargement of normally occuring cavities, is clearly present on MRI exams in patients with moderate and severe AD

  17. Regional cerebral glucose metabolism in patients with alcoholic Korsakoff's syndrome

    Kessler, R.M.; Parker, E.S.; Clark, C.M.; Martin, P.R.; George, D.T.; Weingartner, H.; Sokoloff, L.; Ebert, M.H.; Mishkin, M.

    1985-05-01

    Seven alcoholic male subjects diagnosed as having Korsakoff's syndrome and eight age-matched male normal volunteers were studied with /sup 18/F 2-fluoro-2-deoxy-D-glucose (2/sup 18/FDG). All subjects were examined at rest with eyes covered in a quiet, darkened room. Serial plasma samples were obtained following injection of 4 to 5 mCi of 2/sup 18/FDG. Tomographic slices spaced at 10mm axial increments were obtained (in-plane resolution = 1.75 cm, axial resolution = 1.78 cm). Four planes were selected from each subject, and a total of 46 regions of interest were sampled and glucose metabolic rates for each region calculated. The mean glucose metalbolic rate for the 46 regions in the Korsakoff subjects was significantly lower than that in the normal controls (5.17 +- .43 versus 6.6 +- 1.31). A Q-component analysis, which examined each subject's regional rates relative to his mean rate, revealed two distinct patterns in the Korsakoff group. Glucose metabolism was significantly reduced in 37 of the 46 regions sampled. Reduced cerebral glucose metabolism in a nondemented group of subjects has not previously been reported. The reduction in cortical metabolism may be the result of damage to sub-cortical projecting systems. The differing patterns of cerebral metabolism in Korsakoff's syndrome suggests subgroups with differing neuropathology. Regions implicated in memory function, medial temporal, thalamic and medial prefrontal were among the regions reduced in metabolism.

  18. Cerebral blood flow and metabolism in patients with aphasia due to basal ganglionic lesion

    Kitamura, Shin; Kato, Toshiaki; Ujike, Takashi; Kuroki, Soemu; Terashi, Akiro

    1987-03-01

    Cerebral blood flow and metabolism in right handed eight patients with subcortical lesion and aphasia were measured to investigate the correlation between aphasia and functional changes in cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO/sub 2/) in the cortex and the basal ganglionic region. All patients had no lesion in the cortex, but in the basal ganglionic region (putamen, caudate nucleus, internal capsule, and periventricular white matter) on CT images. Patients with bilateral lesion were excluded in this study. Six patients with cerebral infarction in the left basal ganglionic region and two patients with the left putammal hemorrhage were examined. Five patients had non fluent Broca's type speech, two patients had poor comprehension, fluent Wernicke-type speech and one patient was globally aphasic. CBF, CMRO/sub 2/, and oxygen extraction fraction were measured by the positron emission tomography using /sup 15/O/sub 2/, C/sup 15/O/sub 2/ inhalation technique. In addition to reduction of CBF and CMRO/sub 2/ in the basal ganglionic region, CBF and CMRO/sub 2/ decreased in the left frontal cortex especially posterior part in four patients with Broca's aphasia. In two patients with Wernicke type aphasia, CBF and CMRO/sub 2/ decreased in the basal ganglionic region and the left temporal cortex. In a globally aphasic patient, marked reduction of CBF and CMRO/sub 2/ was observed in the left frontal and temporal cortex, in addition to the basal ganglionic region. These results suggest that dysfunction of cortex as well as that of basal ganglionic region might be related to the occurence of aphasia. However, in one patient with Broca's ahasia, CBF and CMRO/sub 2/ were preserved in the cortex and metabolic reduction was observed in only basal ganglia. This case indicates the relation between basal ganglionic lesion and the occurrence of aphasia.

  19. Aspirin suppresses the abnormal lipid metabolism in liver cancer cells via disrupting an NFκB-ACSL1 signaling.

    Yang, Guang; Wang, Yuan; Feng, Jinyan; Liu, Yunxia; Wang, Tianjiao; Zhao, Man; Ye, Lihong; Zhang, Xiaodong

    2017-05-06

    Abnormal lipid metabolism is a hallmark of tumorigenesis. Hence, the alterations of metabolism enhance the development of hepatocellular carcinoma (HCC). Aspirin is able to inhibit the growth of cancers through targeting nuclear factor κB (NF-κB). However, the role of aspirin in disrupting abnormal lipid metabolism in HCC remains poorly understood. In this study, we report that aspirin can suppress the abnormal lipid metabolism of HCC cells through inhibiting acyl-CoA synthetase long-chain family member 1 (ACSL1), a lipid metabolism-related enzyme. Interestingly, oil red O staining showed that aspirin suppressed lipogenesis in HepG2 cells and Huh7 cells in a dose-dependent manner. In addition, aspirin attenuated the levels of triglyceride and cholesterol in the cells, respectively. Strikingly, we identified that aspirin was able to down-regulate ACSL1 at the levels of mRNA and protein. Moreover, we validated that aspirin decreased the nuclear levels of NF-κB in HepG2 cells. Mechanically, PDTC, an inhibitor of NF-κB, could down-regulate ACSL1 at the levels of mRNA and protein in the cells. Functionally, PDTC reduced the levels of lipid droplets, triglyceride and cholesterol in HepG2 cells. Thus, we conclude that aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling. Our finding provides new insights into the mechanism by which aspirin inhibits abnormal lipid metabolism of HCC. Therapeutically, aspirin is potentially available for HCC through controlling abnormal lipid metabolism. Copyright © 2017. Published by Elsevier Inc.

  20. Weight-adjusted lean body mass and calf circumference are protective against obesity-associated insulin resistance and metabolic abnormalities.

    Takamura, Toshinari; Kita, Yuki; Nakagen, Masatoshi; Sakurai, Masaru; Isobe, Yuki; Takeshita, Yumie; Kawai, Kohzo; Urabe, Takeshi; Kaneko, Shuichi

    2017-07-01

    To test the hypothesis that preserved muscle mass is protective against obesity-associated insulin resistance and metabolic abnormalities, we analyzed the relationship of lean body mass and computed tomography-assessed sectional areas of specific skeletal muscles with insulin resistance and metabolic abnormalities in a healthy cohort. A total of 195 subjects without diabetes who had completed a medical examination were included in this study. Various anthropometric indices such as circumferences of the arm, waist, hip, thigh, and calf were measured. Body composition (fat and lean body mass) was determined by bioelectrical impedance analysis. Sectional areas of specific skeletal muscles (iliopsoas, erector spinae, gluteus, femoris, and rectus abdominis muscles) were measured using computed tomography. Fat and lean body mass were significantly correlated with metabolic abnormalities and insulin resistance indices. When adjusted by weight, relationships of fat and lean body mass with metabolic parameters were mirror images of each other. The weight-adjusted lean body mass negatively correlated with systolic and diastolic blood pressures; fasting plasma glucose, HbA1c, alanine aminotransferase, and triglyceride, and insulin levels; and hepatic insulin resistance indices, and positively correlated with HDL-cholesterol levels and muscle insulin sensitivity indices. Compared with weight-adjusted lean body mass, weight-adjusted sectional areas of specific skeletal muscles showed similar, but not as strong, correlations with metabolic parameters. Among anthropometric measures, the calf circumference best reflected lean body mass, and weight-adjusted calf circumference negatively correlated with metabolic abnormalities and insulin resistance indices. Weight-adjusted lean body mass and skeletal muscle area are protective against weight-associated insulin resistance and metabolic abnormalities. The calf circumference reflects lean body mass and may be useful as a protective

  1. Morphological and glucose metabolism abnormalities in alcoholic Korsakoff's syndrome: group comparisons and individual analyses.

    Anne-Lise Pitel

    Full Text Available BACKGROUND: Gray matter volume studies have been limited to few brain regions of interest, and white matter and glucose metabolism have received limited research attention in Korsakoff's syndrome (KS. Because of the lack of brain biomarkers, KS was found to be underdiagnosed in postmortem studies. METHODOLOGY/PRINCIPAL FINDINGS: Nine consecutively selected patients with KS and 22 matched controls underwent both structural magnetic resonance imaging and (18F-fluorodeoxyglucose positron emission tomography examinations. Using a whole-brain analysis, the between-group comparisons of gray matter and white matter density and relative glucose uptake between patients with KS and controls showed the involvement of both the frontocerebellar and the Papez circuits, including morphological abnormalities in their nodes and connection tracts and probably resulting hypometabolism. The direct comparison of the regional distribution and degree of gray matter hypodensity and hypometabolism within the KS group indicated very consistent gray matter distribution of both abnormalities, with a single area of significant difference in the middle cingulate cortex showing greater hypometabolism than hypodensity. Finally, the analysis of the variability in the individual patterns of brain abnormalities within our sample of KS patients revealed that the middle cingulate cortex was the only brain region showing significant GM hypodensity and hypometabolism in each of our 9 KS patients. CONCLUSIONS/SIGNIFICANCE: These results indicate widespread brain abnormalities in KS including both gray and white matter damage mainly involving two brain networks, namely, the fronto-cerebellar circuit and the Papez circuit. Furthermore, our findings suggest that the middle cingulate cortex may play a key role in the pathophysiology of KS and could be considered as a potential in vivo brain biomarker.

  2. Cerebral metabolic changes in neurologically presymptomatic patients undergoing haemodialysis: in vivo proton MR spectroscopic findings

    Chiu, Ming-Lun; Chiang, I. Chan; Li, Chun-Wei; Chang, Jer-Ming; Ko, Chih-Hung; Chuang, Hung-Yi; Sheu, Reu-Sheng; Lee, Chen-Chang; Hsieh, Tsyh-Jyi

    2010-01-01

    To prospectively investigate and detect early cerebral metabolic changes in patients with end-stage renal disease (ESRD) by using in vivo proton MR spectroscopy (MRS). We enrolled 32 patients with ESRD and 32 healthy controls between the ages of 26 and 50 years. Short echo time single-voxel proton MRS was acquired from volumes of interest (VOIs) located in the frontal grey and white matter, temporal white matter and basal ganglia. The choline/phospatidylcholine (Cho), myo-inositol (mI), N-acetylaspartate (NAA) and total creatine (tCr) peaks were measured and the metabolic ratios with respect to tCr were calculated. In the ESRD group, significant elevations of the Cho/tCr and mI/tCr ratios were observed for the frontal grey matter, frontal white matter, temporal white matter and basal ganglia as compared with controls. There was no significant difference in the NAA/tCr ratios at all VOIs between the ESRD patients and the healthy controls. Proton MRS is a useful and non-invasive imaging tool for the detection of early cerebral metabolic changes in neurologically presymptomatic ESRD patients. (orig.)

  3. Investigations on the effects of ''Ecstasy'' on cerebral glucose metabolism: an 18-FDG PET study

    Schreckenberger, M.; Sabri, O.; Arning, C.; Tuttass, T.; Schulz, G.; Kaiser, H.J.; Wagenknecht, G.; Buell, U.; Gouzoulis-Mayfrank, E.; Sass, H.

    1998-01-01

    Purpose: The aim of the present study was to determine the acute effects of the 'Ecstasy' analogue MDE (3,4-methylendioxyethamphetamine) on the cerebral glucose metabolism (rMRGlu) of healthy volunteers. Method: In a randomised double-blind trial, 16 healthy volunteers without a history of drug abuse were examined with 18-FDG PET 110-120 minutes after oral administration of 2 mg/kg MDE (n=8) or placebo (n=8). Beginning two minutes prior to radiotracer injection, a constant cognitive stimulation was maintained for 32 minutes using a word repetition paradigm in order to ensure constant and comparable mental conditions during cerebral 18-FDG uptake. Individual brain anatomy was represented using T1-weighted 3D flash MRI, followed by manual regionalisation into 108 regions-of-interest and PET/MRI overlay. Absolute quantification of rMRGlu and comparison of glucose metabolism under MDE versus placebo were performed using Mann-Whitney U-test. Results: Absolute global MRGlu was not significantly changed under MDE versus placebo (MDE: 41,8±11,1 μmol/min/100 g, placebo: 50,1±18,1 μmol/min/100 g, p=0,298). The normalised regional metabolic data showed a significantly decreased rMRGlu in the bilateral frontal cortex: Left frontal posterior (-7.1%, p [de

  4. Cerebral metabolic changes in neurologically presymptomatic patients undergoing haemodialysis: in vivo proton MR spectroscopic findings

    Chiu, Ming-Lun; Chiang, I. Chan [Kaohsiung Medical University Hospital, Department of Medical Imaging (China); Li, Chun-Wei [Kaohsiung Medical University, Department of Medical Imaging and Radiological Sciences, College of Health Science (China); Chang, Jer-Ming [Kaohsiung Medical University, Department of Internal Medicine, Kaohsiung Hsiao-Kang Municipal Hospital (China); Kaohsiung Medical University, Department of Nephrology, School of Medicine, College of Medicine (China); Ko, Chih-Hung [Kaohsiung Medical University, Department of Psychiatry, School of Medicine, College of Medicine (China); Kaohsiung Medical University Hospital, Department of Psychiatry (China); Chuang, Hung-Yi [Kaohsiung Medical University, Faculty of Public Health, College of Health Science (China); Kaohsiung Medical University Hospital, Department of Environmental and Occupational Medicine (China); Sheu, Reu-Sheng [Kaohsiung Medical University, Department of Radiology, Kaohsiung Municipal Hsiao-Kang Hospital (China); Kaohsiung Medical University, Department of Radiology, Faculty of Medicine, College of Medicine (China); Lee, Chen-Chang [Kaohsiung Medical University, Department of Medical Imaging and Radiological Sciences, College of Health Science (China); Kaohsiung Medical Centre, Department of Radiology, Chang Gung Memorial Hospital (China); Hsieh, Tsyh-Jyi [Kaohsiung Medical University Hospital, Department of Medical Imaging (China); Kaohsiung Medical University, Department of Radiology, Faculty of Medicine, College of Medicine (China); Kaohsiung Municipal Ta-Tung Hospital, Department of Medical Imaging (China)

    2010-06-15

    To prospectively investigate and detect early cerebral metabolic changes in patients with end-stage renal disease (ESRD) by using in vivo proton MR spectroscopy (MRS). We enrolled 32 patients with ESRD and 32 healthy controls between the ages of 26 and 50 years. Short echo time single-voxel proton MRS was acquired from volumes of interest (VOIs) located in the frontal grey and white matter, temporal white matter and basal ganglia. The choline/phospatidylcholine (Cho), myo-inositol (mI), N-acetylaspartate (NAA) and total creatine (tCr) peaks were measured and the metabolic ratios with respect to tCr were calculated. In the ESRD group, significant elevations of the Cho/tCr and mI/tCr ratios were observed for the frontal grey matter, frontal white matter, temporal white matter and basal ganglia as compared with controls. There was no significant difference in the NAA/tCr ratios at all VOIs between the ESRD patients and the healthy controls. Proton MRS is a useful and non-invasive imaging tool for the detection of early cerebral metabolic changes in neurologically presymptomatic ESRD patients. (orig.)

  5. The effect of glycerol on regional cerebral blood flow, blood volume and oxygen metabolism

    Ishikawa, Masatsune; Kikuchi, Haruhiko; Nagata, Izumi; Yamagata, Sen; Taki, Waro; Kobayashi, Akira; Yonekura, Yoshiharu; Nishizawa, Sadahiko.

    1989-01-01

    Using positron emission tomography with 15 O-labelled CO 2 , O 2 and CO gases, the effects of glycerol on regional cerebral blood flow (CBF), blood volume (CBV) and oxygen metabolism (CMRO 2 ) were investigated in 6 patients with meningioma accompanying peritumoral brain edema. The same study was done in 5 normal volunteers. The changes of blood gases, hematocrit and hemoglobin were also examined. After a drip infusion of glycerol, the regional CBF increased not only in the peritumoral cortex and white matter but also in the intact cortex and white matter on the contralateral side. The increase of CBF was extensive and substantially there were no regional differences. In contrast, the changes of CMRO 2 were not significant. This was derived from the increase in oxygen extraction fraction throughout extensive areas including the peritumoral area. There were no changes in CBV. Hematocrit and hemoglobin decreased to a small degree. In the normal volunteers, the same findings were noted. Thus, glycerol increases the functional reserve for cerebral oxygen metabolism, not only in the peritumoral regions but also in the intact regions. The effects of glycerol on hemodynamics and metabolism were discussed with reference to some differences from mannitol. (author)

  6. Regional cerebral glucose metabolism in frontotemporal dementia: a study with FDG PET

    Cho, S. S.; Jeong, J.; Kang, S. J.; Na, D. L.; Choe, Y. S.; Lee, K. H.; Choi, Y.; Kim, B. T.; Kim, S. E. [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2002-07-01

    Frontotemporal dementia (FTD) is a common cause of presenile dementia. We investigated the regional cerebral glucose metabolic impairments in patients with FTD using FDG PET. We analysed the regional metabolic patterns on FDG PET images obtained from 30 patients with FTD and age- and sex-matched 15 patients with Alzheimers disease (AD) and 11 healthy subjects using SPM99. We also compared the inter-hemispheric metabolic asymmetry among the three groups by counting the total metabolic activity of each hemisphere and computing asymmetry index (AL) between hemispheres. The hypometabolic brain regions in FTD patients compared with healthy controls were as follows: superior middle and medial frontal lobules, superior and middle temporal lobules, anterior and posterior cingulate gyri, uncus, insula, lateral globus pallidus and thalamus. The regions with decreased metabolism in FTD patients compared with AD patients were as follows: superior, inferior and medial frontal lobules, anterior cingulate gyrus, and caudate nucleus. Twenty-five (83%) out of the 30 FTD patients had AI values that was beyond the 95% confidence interval of the AI values obtained from healthy controls; 10 patients had hypometabolism more severe on the right and 15 patients had the opposite pattern. In comparison, 10 (67%) out of the 15 AD patients had asymmetric metabolism. Our SPM analysis of FDG PET revealed additional areas of decreased metabolism in FTD patients compared with prior studies using the ROI method, involving frontal, temporal, cingulate gyrus, corpus callosum, uncus, insula, and some subcortical areas. The inter-hemispheric metabolic asymmetry was common in FTD patients, which can be another metabolic feature that helps differentiate FTD from AD.

  7. Regional cerebral glucose metabolism in frontotemporal dementia: a study with FDG PET

    Cho, S. S.; Jeong, J.; Kang, S. J.; Na, D. L.; Choe, Y. S.; Lee, K. H.; Choi, Y.; Kim, B. T.; Kim, S. E.

    2002-01-01

    Frontotemporal dementia (FTD) is a common cause of presenile dementia. We investigated the regional cerebral glucose metabolic impairments in patients with FTD using FDG PET. We analysed the regional metabolic patterns on FDG PET images obtained from 30 patients with FTD and age- and sex-matched 15 patients with Alzheimers disease (AD) and 11 healthy subjects using SPM99. We also compared the inter-hemispheric metabolic asymmetry among the three groups by counting the total metabolic activity of each hemisphere and computing asymmetry index (AL) between hemispheres. The hypometabolic brain regions in FTD patients compared with healthy controls were as follows: superior middle and medial frontal lobules, superior and middle temporal lobules, anterior and posterior cingulate gyri, uncus, insula, lateral globus pallidus and thalamus. The regions with decreased metabolism in FTD patients compared with AD patients were as follows: superior, inferior and medial frontal lobules, anterior cingulate gyrus, and caudate nucleus. Twenty-five (83%) out of the 30 FTD patients had AI values that was beyond the 95% confidence interval of the AI values obtained from healthy controls; 10 patients had hypometabolism more severe on the right and 15 patients had the opposite pattern. In comparison, 10 (67%) out of the 15 AD patients had asymmetric metabolism. Our SPM analysis of FDG PET revealed additional areas of decreased metabolism in FTD patients compared with prior studies using the ROI method, involving frontal, temporal, cingulate gyrus, corpus callosum, uncus, insula, and some subcortical areas. The inter-hemispheric metabolic asymmetry was common in FTD patients, which can be another metabolic feature that helps differentiate FTD from AD

  8. Prevalence of type 2 diabetes mellitus and other abnormalities of carbohydrate metabolism depending on diagnostic criteria

    Alexander Vasil'evich Dreval'

    2010-03-01

    Full Text Available Aim. To assess current criteria for type 2 diabetes mellitus. Materials and methods. This screening study involving 2,368 residents of two municipal districts of the Moscow region was designed to elucidate differencesin the prevalence of abnormalities of carbohydrate metabolism depending on diagnostic criteria (WHO and ADA. Results. The prevalence of early disorders of carbohydrate metabolism and DM2 among the adult population of Moscow region is 17,1 and 7,2 respectivelyusing WHO criteria and 40,0 and 5,9% by ADA criteria. Conclusion. Refusal to undergo OGTT during screening decreases detectability of early metabolic disorders by 28,8 and 6,1% using WHO and ADAcriteria respectively. When screening is aimed to diagnose DM2 alone, OGTT can be omitted in subjects with fasting plasma glucose level below4,7 mmol/l. If it is aimed to diagnose both DM2 and impaired glucose tolerance, OGTT is not needed in subjects with fasting plasma glucose levelbelow 4,2 mmol/l. The use of ?combined? diagnostic criteria (i.e. OGTT according to ADA, but not WHO significantly increases the prevalence ofmetabolic disorders from 24,9 to 48,8%.

  9. Variants of Insulin-Signaling Inhibitor Genes in Type 2 Diabetes and Related Metabolic Abnormalities

    Carlo de Lorenzo

    2013-01-01

    Full Text Available Insulin resistance has a central role in the pathogenesis of several metabolic diseases, including type 2 diabetes, obesity, glucose intolerance, metabolic syndrome, atherosclerosis, and cardiovascular diseases. Insulin resistance and related traits are likely to be caused by abnormalities in the genes encoding for proteins involved in the composite network of insulin-signaling; in this review we have focused our attention on genetic variants of insulin-signaling inhibitor molecules. These proteins interfere with different steps in insulin-signaling: ENPP1/PC-1 and the phosphatases PTP1B and PTPRF/LAR inhibit the insulin receptor activation; INPPL1/SHIP-2 hydrolyzes PI3-kinase products, hampering the phosphoinositide-mediated downstream signaling; and TRIB3 binds the serine-threonine kinase Akt, reducing its phosphorylation levels. While several variants have been described over the years for all these genes, solid evidence of an association with type 2 diabetes and related diseases seems to exist only for rs1044498 of the ENPP1 gene and for rs2295490 of the TRIB3 gene. However, overall the data recapitulated in this Review article may supply useful elements to interpret the results of novel, more technically advanced genetic studies; indeed it is becoming increasingly evident that genetic information on metabolic diseases should be interpreted taking into account the complex biological pathways underlying their pathogenesis.

  10. Abnormal metabolism of glycogen phosphate as a cause for Lafora disease.

    Tagliabracci, Vincent S; Girard, Jean Marie; Segvich, Dyann; Meyer, Catalina; Turnbull, Julie; Zhao, Xiaochu; Minassian, Berge A; Depaoli-Roach, Anna A; Roach, Peter J

    2008-12-05

    Lafora disease is a progressive myoclonus epilepsy with onset in the teenage years followed by neurodegeneration and death within 10 years. A characteristic is the widespread formation of poorly branched, insoluble glycogen-like polymers (polyglucosan) known as Lafora bodies, which accumulate in neurons, muscle, liver, and other tissues. Approximately half of the cases of Lafora disease result from mutations in the EPM2A gene, which encodes laforin, a member of the dual specificity protein phosphatase family that is able to release the small amount of covalent phosphate normally present in glycogen. In studies of Epm2a(-/-) mice that lack laforin, we observed a progressive change in the properties and structure of glycogen that paralleled the formation of Lafora bodies. At three months, glycogen metabolism remained essentially normal, even though the phosphorylation of glycogen has increased 4-fold and causes altered physical properties of the polysaccharide. By 9 months, the glycogen has overaccumulated by 3-fold, has become somewhat more phosphorylated, but, more notably, is now poorly branched, is insoluble in water, and has acquired an abnormal morphology visible by electron microscopy. These glycogen molecules have a tendency to aggregate and can be recovered in the pellet after low speed centrifugation of tissue extracts. The aggregation requires the phosphorylation of glycogen. The aggregrated glycogen sequesters glycogen synthase but not other glycogen metabolizing enzymes. We propose that laforin functions to suppress excessive glycogen phosphorylation and is an essential component of the metabolism of normally structured glycogen.

  11. Pathophysiology and molecular basis of selected metabolic abnormalities in Huntington’s disease

    Jolanta Krzysztoń-Russjan

    2016-12-01

    Full Text Available Huntington’s disease (HD is an incurable, devastating neurodegenerative disease with a known genetic background and autosomally dominant inheritance pattern. HTT gene mutation (mHTT is associated with polymorphic fragment elongation above 35 repeats of the CAG triplet. The mHTT product is an altered protein with a poly-Q elongated fragment, with the highest expression determined in the central nervous system (CNS and with differentiated expression outside the CNS. A drastic loss of striatal and deeper layers of the cerebral cortex neurons was determined in the CNS, but muscle and body weight mass loss with dysfunction of many organs was also observed. HD symptoms include neurological disturbances, such as choreal movements with dystonia, speech and swallowing impairments, and additionally a variety of psychiatric and behavioral symptoms with cognitive decline have been described.They are the result of disturbances of several cellular pathways related to signal transmission, mitochondrial dysfunction and energy metabolism impairment shown by gene and protein expression and alteration of their functions. Impairment of energy processes demonstrated by a decrease of ATP production and increase of oxidative stress markers was determined in- and outside of the CNS in glycolysis, the Krebs cycle and the electron transport chain. A correlation between the increase of energy metabolism impairment level and the increase in number of CAG repeats in HTT has often been described. The energy metabolism study is an initial stage of sensitive biomarkers and a new therapeutic investigative option for early application in order to inhibit pathological processes in HD.Identification of pathological changes outside the CNS requires a reevaluation of diagnostic and therapeutic rules in HD.

  12. Pathophysiology and molecular basis of selected metabolic abnormalities in Huntington's disease.

    Krzysztoń-Russjan, Jolanta

    2016-12-30

    Huntington's disease (HD) is an incurable, devastating neurodegenerative disease with a known genetic background and autosomally dominant inheritance pattern. HTT gene mutation (mHTT) is associated with polymorphic fragment elongation above 35 repeats of the CAG triplet. The mHTT product is an altered protein with a poly-Q elongated fragment, with the highest expression determined in the central nervous system (CNS) and with differentiated expression outside the CNS. A drastic loss of striatal and deeper layers of the cerebral cortex neurons was determined in the CNS, but muscle and body weight mass loss with dysfunction of many organs was also observed. HD symptoms include neurological disturbances, such as choreal movements with dystonia, speech and swallowing impairments, and additionally a variety of psychiatric and behavioral symptoms with cognitive decline have been described. They are the result of disturbances of several cellular pathways related to signal transmission, mitochondrial dysfunction and energy metabolism impairment shown by gene and protein expression and alteration of their functions. Impairment of energy processes demonstrated by a decrease of ATP production and increase of oxidative stress markers was determined in- and outside of the CNS in glycolysis, the Krebs cycle and the electron transport chain. A correlation between the increase of energy metabolism impairment level and the increase in number of CAG repeats in HTT has often been described. The energy metabolism study is an initial stage of sensitive biomarkers and a new therapeutic investigative option for early application in order to inhibit pathological processes in HD. Identification of pathological changes outside the CNS requires a reevaluation of diagnostic and therapeutic rules in HD.

  13. [Characteristics of cerebral glucose metabolism in patients with cognitive impairment in Parkinson's disease].

    Homenko, Ju G; Susin, D S; Kataeva, G V; Irishina, Ju A; Zavolokov, I G

    To study the relationship between early cognitive impairment symptoms and cerebral glucose metabolism in different brain regions (according to the positron emission tomography (PET) data) in Parkinson's disease (PD) in order to increase the diagnostic and treatment efficacy. Two groups of patients with PD (stage I-III), including 11 patients without cognitive disorders and 13 with mild cognitive impairment (MCI), were examined. The control group included 10 age-matched people with normal cognition. To evaluate cognitive state, the Mini mental state examination (MMSE), the Frontal assessment battery (FAB) and the 'clock drawing test' were used. The regional cerebral glucose metabolism rate (CMRglu) was assessed using PET with 18F-fluorodeoxyglucose (FDG). In PD patients, CMRglu were decreased in the frontal (Brodmann areas (BA) 9, 10, 11, 46, 47), occipital (BA 19) and parietal (BA 39), temporal (BA 20, 37), and cingulate cortex (BA 32) compared to the control group. Cerebral glucose metabolism was decreased in the frontal (BA 8, 9, 10, 45, 46, 47), parietal (BA 7, 39, 40) and cingulate cortex (BA 23, 24, 31, 32) in the group of PD patients with MCI compared to PD patients with normal cognition. Hypometabolism in BA 7, 8, 23, 24, 31, 40 was revealed only in comparison of PD and PD-MCI groups, and did not appear in case of comparison of cognitively normal PD patients with the control group. It is possible to suggest that the mentioned above brain areas were associated with cognitive impairment. The revealed glucose hypometabolism pattern possibly has the diagnostic value for the early and preclinical diagnosis of MCI in PD and control of treatment efficacy.

  14. Cerebral oxygenation and metabolism during exercise following three months of endurance training in healthy overweight males

    Seifert, T; Rasmussen, P; Brassard, P

    2009-01-01

    /(glucose + (1/2) lactate); OCI], changes in mitochondrial oxygen tension (DeltaP(Mito)O(2)) and the cerebral metabolic rate of oxygen (CMRO(2)) were calculated. For all subjects, resting OCI was higher at the 3-mo follow-up (6.3 +/- 1.3 compared with 4.7 +/- 0.9 at baseline, mean +/- SD; P ... with a lower plasma epinephrine concentration (P Mito)O(2) (-22 mmHg) decreased (P ... +/- 53 micromol x 100 x g(-1) min(-1) (P Mito)O(2) (-7 +/- 13 mmHg) did not decrease significantly from rest and when compared with values before training (P

  15. A longitudinal study of cerebral glucose metabolism, MRI, and disability in patients with MS

    Blinkenberg, M; Jensen, C.V.; Holm, S

    1999-01-01

    OBJECTIVE: To study the time-related changes in cerebral metabolic rate of glucose (CMRglc) in MS patients and to correlate these with changes in MRI lesion load and disability. BACKGROUND: Measurements of MRI lesion load and neurologic disability are used widely to monitor disease progression...... and parietal cortical areas. There was a statistically significant increase of disability (pmetabolism in MS is decreased significantly during a 2......-year observation period, suggesting a deterioration of cortical activity with disease progression. The time-related changes of cortical CMRglc are statistically stronger than changes in TLA measurements and neurologic disability, and might be a useful secondary measure of treatment efficacy...

  16. Cerebral autoregulation and flow/metabolism coupling during cardiopulmonary bypass: the influence of PaCO/sub 2/

    Murkin, J.M.; Farrar, J.K.; Tweed, W.A.; McKenzie, F.N.; Guiraudon, G.

    1987-09-01

    Measurement of /sup 133/Xe clearance and effluent cerebral venous blood sampling were used in 38 patients to determine the effects of cardiopulmonary bypass, and of maintaining temperature corrected or noncorrected PaCO/sub 2/ at 40 mm Hg on regulation of cerebral blood flow (CBF) and flow/metabolism coupling. After induction of anesthesia with diazepam and fentanyl, mean CBF was 25 ml X 100 g-1 X min-1 and cerebral oxygen consumption, 1.67 ml X 100 g-1 X min-1. Cerebral oxygen consumption during nonpulsatile cardiopulmonary bypass at 26 degrees C was reduced to 0.42 ml X 100 g-1 X min-1 in both groups. CBF was reduced to 14-15 ml X 100 g-1 X min-1 in the non-temperature-corrected group (n = 21), was independent of cerebral perfusion pressure over the range of 20-100 mm Hg, but correlated with cerebral oxygen consumption. In the temperature-corrected group (n = 17), CBF varied from 22 to 32 ml X 100 g-1 X min-1, and flow/metabolism coupling was not maintained (i.e., CBF and cerebral oxygen consumption varied independently). However, variation in CBF correlated significantly with cerebral perfusion pressure over the pressure range of 15-95 mm Hg. This study demonstrates a profound reduction in cerebral oxygen consumption during hypothermic nonpulsatile cardiopulmonary bypass. When a non-temperature-corrected PaCO/sub 2/ of approximately 40 mm Hg was maintained, CBF was lower, and analysis of pooled data suggested that CBF regulation was better preserved, i.e., CBF was independent of pressure changes and dependent upon cerebral oxygen consumption.

  17. Cerebral autoregulation and flow/metabolism coupling during cardiopulmonary bypass: the influence of PaCO2

    Murkin, J.M.; Farrar, J.K.; Tweed, W.A.; McKenzie, F.N.; Guiraudon, G.

    1987-01-01

    Measurement of 133 Xe clearance and effluent cerebral venous blood sampling were used in 38 patients to determine the effects of cardiopulmonary bypass, and of maintaining temperature corrected or noncorrected PaCO 2 at 40 mm Hg on regulation of cerebral blood flow (CBF) and flow/metabolism coupling. After induction of anesthesia with diazepam and fentanyl, mean CBF was 25 ml X 100 g-1 X min-1 and cerebral oxygen consumption, 1.67 ml X 100 g-1 X min-1. Cerebral oxygen consumption during nonpulsatile cardiopulmonary bypass at 26 degrees C was reduced to 0.42 ml X 100 g-1 X min-1 in both groups. CBF was reduced to 14-15 ml X 100 g-1 X min-1 in the non-temperature-corrected group (n = 21), was independent of cerebral perfusion pressure over the range of 20-100 mm Hg, but correlated with cerebral oxygen consumption. In the temperature-corrected group (n = 17), CBF varied from 22 to 32 ml X 100 g-1 X min-1, and flow/metabolism coupling was not maintained (i.e., CBF and cerebral oxygen consumption varied independently). However, variation in CBF correlated significantly with cerebral perfusion pressure over the pressure range of 15-95 mm Hg. This study demonstrates a profound reduction in cerebral oxygen consumption during hypothermic nonpulsatile cardiopulmonary bypass. When a non-temperature-corrected PaCO 2 of approximately 40 mm Hg was maintained, CBF was lower, and analysis of pooled data suggested that CBF regulation was better preserved, i.e., CBF was independent of pressure changes and dependent upon cerebral oxygen consumption

  18. Preoperative cerebral metabolic difference related to the outcome of cochlear implantation in prelingually deaf children

    Lee, J. H.; Lim, G. C.; Ahn, J. H.; Lee, K. S.; Jeong, J. W.; Kim, J. S.

    2007-01-01

    The outcome of cochlear implantation (CI) has known to be variable. The aim of this study was to evaluate the preoperative regional glucose metabolism difference related to the speech perception outcome after CI in prelingually deaf children. Forty-one prelingually deaf children who underwent CI at age 2∼10 years were included. All patients underwent F-18 FDG brain PET within one month before CI and measured speech perception using the institute version of the CID at 2 years after CI. Patients were classified into younger (2∼6 years) and older (7∼10 years) groups. Each group was also divided into a GOOD (CID scores>80) and a BAD (CID scores<60) subgroup. We assessed regional metabolic difference according to CID scores and age by voxel based analysis (SPM2) comparing normal controls (n =8, 20∼30 years). Speech perception was good in 19 (68%) of 28 younger patients and 5 (38%) of 13 older patients after CI. Regional metabolism of both younger and older GOOD subgroup was significantly decreased in right temporal, left cerebellar and right frontal regions compared to normal controls (uncorrected p<0.001). In younger GOOD subgroup, left frontotemporal and both parietal regions showed decreased metabolism and right frontal, left temporal and anterior cingulate regions showed increased metabolism compared to BAD subgroup (uncorrected p<0.005). In younger group, regional metabolism in left superior frontal, right temporal and right occipital regions showed a significant negative correlation with CID scores (uncorrected p<0.005). In older group, the pattern of regional metabolic difference correlated with CID score was not similar to that of younger group. Preoperative regional cerebral metabolism is decreased in several brain regions related to the language in preligually deaf patients and the neuralplasty of younger patients are different according to the outcome of speech perception after CI

  19. Cerebral glucose metabolism and cognition in newly diagnosed Parkinson's disease: ICICLE-PD study.

    Firbank, M J; Yarnall, A J; Lawson, R A; Duncan, G W; Khoo, T K; Petrides, G S; O'Brien, J T; Barker, R A; Maxwell, R J; Brooks, D J; Burn, D J

    2017-04-01

    To assess reductions of cerebral glucose metabolism in Parkinson's disease (PD) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their associations with cognitive decline. FDG-PET was performed on a cohort of 79 patients with newly diagnosed PD (mean disease duration 8 months) and 20 unrelated controls. PD participants were scanned while on their usual dopaminergic medication. Cognitive testing was performed at baseline, and after 18 months using the Cognitive Drug Research (CDR) and Cambridge Neuropsychological Test Automated Battery (CANTAB) computerised batteries, the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). We used statistical parametric mapping (SPM V.12) software to compare groups and investigate voxelwise correlations between FDG metabolism and cognitive score at baseline. Linear regression was used to evaluate how levels of cortical FDG metabolism were predictive of subsequent cognitive decline rated with the MMSE and MoCA. PD participants showed reduced glucose metabolism in the occipital and inferior parietal lobes relative to controls. Low performance on memory-based tasks was associated with reduced FDG metabolism in posterior parietal and temporal regions, while attentional performance was associated with more frontal deficits. Baseline parietal to cerebellum FDG metabolism ratios predicted MMSE (β=0.38, p=0.001) and MoCA (β=0.3, p=0.002) at 18 months controlling for baseline score. Reductions in cortical FDG metabolism were present in newly diagnosed PD, and correlated with performance on neuropsychological tests. A reduced baseline parietal metabolism is associated with risk of cognitive decline and may represent a potential biomarker for this state and the development of PD dementia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  20. Preoperative cerebral metabolic difference related to the outcome of cochlear implantation in prelingually deaf children

    Lee, J. H.; Lim, G. C.; Ahn, J. H.; Lee, K. S.; Jeong, J. W.; Kim, J. S. [Asan Medical Center, Seoul (Korea, Republic of)

    2007-07-01

    The outcome of cochlear implantation (CI) has known to be variable. The aim of this study was to evaluate the preoperative regional glucose metabolism difference related to the speech perception outcome after CI in prelingually deaf children. Forty-one prelingually deaf children who underwent CI at age 2{approx}10 years were included. All patients underwent F-18 FDG brain PET within one month before CI and measured speech perception using the institute version of the CID at 2 years after CI. Patients were classified into younger (2{approx}6 years) and older (7{approx}10 years) groups. Each group was also divided into a GOOD (CID scores>80) and a BAD (CID scores<60) subgroup. We assessed regional metabolic difference according to CID scores and age by voxel based analysis (SPM2) comparing normal controls (n =8, 20{approx}30 years). Speech perception was good in 19 (68%) of 28 younger patients and 5 (38%) of 13 older patients after CI. Regional metabolism of both younger and older GOOD subgroup was significantly decreased in right temporal, left cerebellar and right frontal regions compared to normal controls (uncorrected p<0.001). In younger GOOD subgroup, left frontotemporal and both parietal regions showed decreased metabolism and right frontal, left temporal and anterior cingulate regions showed increased metabolism compared to BAD subgroup (uncorrected p<0.005). In younger group, regional metabolism in left superior frontal, right temporal and right occipital regions showed a significant negative correlation with CID scores (uncorrected p<0.005). In older group, the pattern of regional metabolic difference correlated with CID score was not similar to that of younger group. Preoperative regional cerebral metabolism is decreased in several brain regions related to the language in preligually deaf patients and the neuralplasty of younger patients are different according to the outcome of speech perception after CI.

  1. Subcortical cerebral blood flow and metabolic changes elicited by cortical spreading depression in rat

    Mraovitch, S.; Calando, Y.; Goadsby, P.J.; Seylaz, J. (Laboratoire de Recherches Cerebrovasculaire, Paris (France))

    1992-06-01

    Changes in cerebral cortical perfusion (CBF{sub LDF}), local cerebral blood flow (lCBF) and local cerebral glucose utilization (lCGU) elicited by unilateral cortical spreading depression (SD) were monitored and measured in separate groups of rats anesthetized with {alpha}-chloralose. CBF{sub LDF} was recorded with laser Doppler flowmetry, while lCBF and lCGU were measured by the quantitative autoradiographic ({sup 14}C)iodoantipyrine and ({sup 14}C)-2-deoxyglucose methods, respectively. SD elicited a wave of hyperemia after a latency of 2 to 3 min followed by an oligemic phase. Ninety minutes following the onset of SD cortical lCBF and lCGU were essentially the same as on the contralateral side and in sham-treated rats. However, alteration in the lCBF and lCGU in upper and lower brainstem persisted. The present results demonstrate that long-lasting cerebrovascular and metabolic alterations take place within the subcortical regions following SD. These regions provide an attractive site to integrate observations in man concerning spreading depression and the aura of migraine with the other features of the syndrome. 19 refs., 2 figs., 1 tab.

  2. A Giant Ureteral Stone without Underlying Anatomic or Metabolic Abnormalities: A Case Report

    Selcuk Sarikaya

    2013-01-01

    Full Text Available A 28-year old man presented with left flank pain and dysuria. Plain abdominal film and computed tomography showed a left giant ureteral stone measuring 11.5 cm causing ureteral obstruction and other stones 2.5 cm in size in the lower pole of ipsilateral kidney and 7 mm in size in distal part of right ureter. A left ureterolithotomy was performed and then a double J stent was inserted into the ureter. The patient was discharged from the hospital 4 days postoperatively with no complications. Stone analysis was consistent with magnesium ammonium phosphate and calcium oxalate. Underlying anatomic or metabolic abnormalities were not detected. One month after surgery, right ureteral stone passed spontaneously, left renal stone moved to distal ureter, and it was removed by ureterolithotomy. Control intravenous urography and cystography demonstrated unobstructed bilateral ureter and the absence of vesicoureteral reflux.

  3. New insights into coupling and uncoupling of cerebral blood flow and metabolism in the brain.

    Venkat, Poornima; Chopp, Michael; Chen, Jieli

    2016-06-30

    The brain has high metabolic and energy needs and requires continuous cerebral blood flow (CBF), which is facilitated by a tight coupling between neuronal activity, CBF, and metabolism. Upon neuronal activation, there is an increase in energy demand, which is then met by a hemodynamic response that increases CBF. Such regional CBF increase in response to neuronal activation is observed using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography. The mechanisms and mediators (eg, nitric oxide, astrocytes, and ion channels) that regulate CBF-metabolism coupling have been extensively studied. The neurovascular unit is a conceptual model encompassing the anatomical and metabolic interactions between the neurons, vascular components, and glial cells in the brain. It is compromised under disease states such as stroke, diabetes, hypertension, dementias, and with aging, all of which trigger a cascade of inflammatory responses that exacerbate brain damage. Hence, tight regulation and maintenance of neurovascular coupling is central for brain homeostasis. This review article also discusses the waste clearance pathways in the brain such as the glymphatic system. The glymphatic system is a functional waste clearance pathway that removes metabolic wastes and neurotoxins from the brain along paravascular channels. Disruption of the glymphatic system burdens the brain with accumulating waste and has been reported in aging as well as several neurological diseases.

  4. High-sugar intake does not exacerbate metabolic abnormalities or cardiac dysfunction in genetic cardiomyopathy.

    Hecker, Peter A; Galvao, Tatiana F; O'Shea, Karen M; Brown, Bethany H; Henderson, Reney; Riggle, Heather; Gupte, Sachin A; Stanley, William C

    2012-05-01

    A high-sugar intake increases heart disease risk in humans. In animals, sugar intake accelerates heart failure development by increased reactive oxygen species (ROS). Glucose-6-phosphate dehydrogenase (G6PD) can fuel ROS production by providing reduced nicotinamide adenine dinucleotide phosphate (NADPH) for superoxide generation by NADPH oxidase. Conversely, G6PD also facilitates ROS scavenging using the glutathione pathway. We hypothesized that a high-sugar intake would increase flux through G6PD to increase myocardial NADPH and ROS and accelerate cardiac dysfunction and death. Six-week-old TO-2 hamsters, a non-hypertensive model of genetic cardiomyopathy caused by a δ-sarcoglycan mutation, were fed a long-term diet of high starch or high sugar (57% of energy from sucrose plus fructose). After 24 wk, the δ-sarcoglycan-deficient animals displayed expected decreases in survival and cardiac function associated with cardiomyopathy (ejection fraction: control 68.7 ± 4.5%, TO-2 starch 46.1 ± 3.7%, P sugar 58.0 ± 4.2%, NS, versus TO-2 starch or control; median survival: TO-2 starch 278 d, TO-2 sugar 318 d, P = 0.133). Although the high-sugar intake was expected to exacerbate cardiomyopathy, surprisingly, there was no further decrease in ejection fraction or survival with high sugar compared with starch in cardiomyopathic animals. Cardiomyopathic animals had systemic and cardiac metabolic abnormalities (increased serum lipids and glucose and decreased myocardial oxidative enzymes) that were unaffected by diet. The high-sugar intake increased myocardial superoxide, but NADPH and lipid peroxidation were unaffected. A sugar-enriched diet did not exacerbate ventricular function, metabolic abnormalities, or survival in heart failure despite an increase in superoxide production. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Investigation on Abnormal Iron Metabolism and Related Inflammation in Parkinson Disease Patients with Probable RBD

    Hu, Yang; Yu, Shu-Yang; Zuo, Li-Jun; Piao, Ying-Shan; Cao, Chen-Jie; Wang, Fang; Chen, Ze-Jie; Du, Yang; Lian, Teng-Hong; Liu, Gai-Fen; Wang, Ya-Jie; Chan, Piu; Chen, Sheng-Di; Wang, Xiao-Min; Zhang, Wei

    2015-01-01

    Objective To investigate potential mechanisms involving abnormal iron metabolism and related inflammation in Parkinson disease (PD) patients with probable rapid eye movement sleep behavior disorder (PRBD). Methods Total 210 PD patients and 31 controls were consecutively recruited. PD patients were evaluated by RBD Screening Questionnaire (RBDSQ) and classified into PRBD and probable no RBD (NPRBD) groups. Demographics information were recorded and clinical symptoms were evaluated by series of rating scales. Levels of iron and related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum were detected. Comparisons among control, NPRBD and PRBD groups and correlation analyses between RBDSQ score and levels of above factors were performed. Results (1)The frequency of PRBD in PD patients is 31.90%. (2)PRBD group has longer disease duration, more advanced disease stage, severer motor symptoms and more non-motor symptoms than NPRBD group. (3)In CSF, levels of iron, transferrin, NO and IL–1β in PRBD group are prominently increased. RBDSQ score is positively correlated with the levels of iron, transferrin, NO and IL–1β in PD group. Iron level is positively correlated with the levels of NO and IL–1β in PD group. (4)In serum, transferrin level is prominently decreased in PRBD group. PGE2 level in PRBD group is drastically enhanced. RBDSQ score exhibits a positive correlation with PGE2 level in PD group. Conclusions PRBD is common in PD patients. PRBD group has severer motor symptoms and more non-motor symptoms. Excessive iron in brain resulted from abnormal iron metabolism in central and peripheral systems is correlated with PRBD through neuroinflammation. PMID:26431210

  6. The prevalence of abnormal metabolic parameters in obese and overweight children.

    Salvatore, Deborah; Satnick, Ava; Abell, Rebecca; Messina, Catherine R; Chawla, Anupama

    2014-09-01

    This retrospective study aimed to determine the prevalence of abnormal metabolic parameters in obese children and its correlation to the degree of obesity determined by body mass index (BMI). In total, 101 children seen at the Pediatric Gastroenterology Obesity Clinic at Stony Brook Children's University Hospital were enrolled in the study. The degree of obesity was characterized according to the following formula: (patient's BMI/BMI at 95th percentile) × 100%, with class I obesity >100%-120%, class II obesity >120%-140%, and class III obesity >140%. A set of metabolic parameters was evaluated in these patients. Frequency distributions of all study variables were examined using the χ(2) test of independence. Mean differences among the obesity classes and continuous measures were examined using 1-way analysis of variance. Within our study population, we found that 80% of our obese children had a low high-density lipoprotein (HDL) cholesterol level, 58% had elevated fasting insulin levels, and 32% had an elevated alanine aminotransferase (ALT) level. Class II obese children had a 2-fold higher ALT value when compared with class I children (P = .036). Fasting insulin, ALT, HDL cholesterol, and triglyceride levels trended with class of obesity. Obese children in classes II and III are at higher risk for developing abnormal laboratory values. We recommend obese children be further classified to reflect the severity of the obesity since this has predictive significance for comorbidities. Obesity classes I, II, and III could help serve as a screening tool to help communicate risk assessment. © 2013 American Society for Parenteral and Enteral Nutrition.

  7. Electrocardiographic left ventricular hypertrophy without echocardiographic abnormalities evaluated by myocardial perfusion and fatty acid metabolic imaging

    Narita, Michihiro; Kurihara, Tadashi

    2000-01-01

    The pathophysiologic process in patients with electrocardiographic left ventricular hypertrophy with ST, T changes but without echocardiographic abnormalities was investigated by myocardial perfusion imaging and fatty acid metabolic imaging. Exercise stress 99m Tc-methoxy-isobutyl isonitrile (MIBI) imaging and rest 123 I-beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP) imaging were performed in 59 patients with electrocardiographic hypertrophy including 29 without apparent cause including hypertension and echocardiographic hypertrophy, and 30 with essential hypertension. Coronary angiography was performed in 6 patients without hypertension and 4 with hypertension and biopsy specimens were obtained from the left ventricular apex from 6 patients without hypertension. Myocardial perfusion and 123 I-BMIPP images were classified into 3 types: normal, increased accumulation of the isotope at the left ventricular apex (high uptake) and defect. Transient perfusion abnormality and apical defect observed by 123 I-BMIPP imaging were more frequent in patients without hypertension than in patients with hypertension (32% vs. 17%, p=0.04671 in perfusion; 62% vs. 30%, p=0.0236 in 123 I-BMIPP). Eighteen normotensive patients with apical defect by 123 I-BMIPP imaging included 3 of 10 patients with normal perfusion at exercise, 6 of 10 patients with high uptake and 9 of 9 patients with perfusion defect. The defect size revealed by 123 I-BMIPP imaging was greater than that of the perfusion abnormality. Coronary stenoses were not observed and myocardial specimens showed myocardial disarray with hypertrophy. Moreover, 9 patients with hypertension and apical defects by 123 I-BMIPP showed 3 different types of perfusion. Many patients without hypertension show a pathologic process similar to hypertrophic cardiomyopathy. Perfusion and 123 I-BMIPP imaging are useful for the identification of these patients. (author)

  8. Reduced thalamic volume in preterm infants is associated with abnormal white matter metabolism independent of injury

    Wisnowski, Jessica L.; Ceschin, Rafael C.; Choi, So Young; Schmithorst, Vincent J.; Painter, Michael J.; Nelson, Marvin D.; Blueml, Stefan; Panigrahy, Ashok

    2015-01-01

    Altered thalamocortical development is hypothesized to be a key substrate underlying neurodevelopmental disabilities in preterm infants. However, the pathogenesis of this abnormality is not well-understood. We combined magnetic resonance spectroscopy of the parietal white matter and morphometric analyses of the thalamus to investigate the association between white matter metabolism and thalamic volume and tested the hypothesis that thalamic volume would be associated with diminished N-acetyl-aspartate (NAA), a measure of neuronal/axonal maturation, independent of white matter injury. Data from 106 preterm infants (mean gestational age at birth: 31.0 weeks ± 4.3; range 23-36 weeks) who underwent MR examinations under clinical indications were included in this study. Linear regression analyses demonstrated a significant association between parietal white matter NAA concentration and thalamic volume. This effect was above and beyond the effect of white matter injury and age at MRI and remained significant even when preterm infants with punctate white matter lesions (pWMLs) were excluded from the analysis. Furthermore, choline, and among the preterm infants without pWMLs, lactate concentrations were also associated with thalamic volume. Of note, the associations between NAA and choline concentration and thalamic volume remained significant even when the sample was restricted to neonates who were term-equivalent age or older. These observations provide convergent evidence of a neuroimaging phenotype characterized by widespread abnormal thalamocortical development and suggest that the pathogenesis may involve impaired axonal maturation. (orig.)

  9. Reduced thalamic volume in preterm infants is associated with abnormal white matter metabolism independent of injury

    Wisnowski, Jessica L. [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States); University of Pittsburgh, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States); University of Southern California, Brain and Creativity Institute, Los Angeles, CA (United States); Ceschin, Rafael C. [University of Pittsburgh, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States); University of Pittsburgh, Department of Biomedical Informatics, Pittsburgh, PA (United States); Choi, So Young [University of Southern California, Brain and Creativity Institute, Los Angeles, CA (United States); Schmithorst, Vincent J. [University of Pittsburgh, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States); Painter, Michael J. [University of Pittsburgh, Department of Pediatrics, Division of Neurology, Childrens Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States); Nelson, Marvin D. [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States); Blueml, Stefan [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States); Rudi Schulte Research Institute, Santa Barbara, CA (United States); Panigrahy, Ashok [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States); University of Pittsburgh, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States)

    2015-05-01

    Altered thalamocortical development is hypothesized to be a key substrate underlying neurodevelopmental disabilities in preterm infants. However, the pathogenesis of this abnormality is not well-understood. We combined magnetic resonance spectroscopy of the parietal white matter and morphometric analyses of the thalamus to investigate the association between white matter metabolism and thalamic volume and tested the hypothesis that thalamic volume would be associated with diminished N-acetyl-aspartate (NAA), a measure of neuronal/axonal maturation, independent of white matter injury. Data from 106 preterm infants (mean gestational age at birth: 31.0 weeks ± 4.3; range 23-36 weeks) who underwent MR examinations under clinical indications were included in this study. Linear regression analyses demonstrated a significant association between parietal white matter NAA concentration and thalamic volume. This effect was above and beyond the effect of white matter injury and age at MRI and remained significant even when preterm infants with punctate white matter lesions (pWMLs) were excluded from the analysis. Furthermore, choline, and among the preterm infants without pWMLs, lactate concentrations were also associated with thalamic volume. Of note, the associations between NAA and choline concentration and thalamic volume remained significant even when the sample was restricted to neonates who were term-equivalent age or older. These observations provide convergent evidence of a neuroimaging phenotype characterized by widespread abnormal thalamocortical development and suggest that the pathogenesis may involve impaired axonal maturation. (orig.)

  10. The influence of abnormal thyroid function on sex hormones and bone metabolism in female patients

    Li Xiaohong; Chu Shaolin; Lei Qiufang; Ye Peihong; Chai Luhua

    2001-01-01

    Objectives: To explore the influence of hyperthyroidism and hypothyroidism on sex hormones and bone metabolism in female patients. Method: A single photon bone absorptiometry was used to measure calcareous bone mineral density (BMD) in 91 female patients with hyperthyroidism, and 37 female patients with hypothyroidism caused by Hashimoto's thyroiditis and 51 healthy female subjects with euthyroid. In addition the serum levels of BGP and PTH were determined by means of IRMA. Serum levels of FSH and E 2 were determined by RIA. Results: Serum levels of FSH , E 2 and BGP in hyperthyroidism group were significantly higher than those in control group. The serum levels of PTH were slightly lower than that in control group (P 2 and BGP were significantly lower than those in control group. The assessment of BMD showed that the prevalence rate of osteoporosis (OP) both in hyperthyroidism groups and in hypothyroidism groups was significantly higher than control group. The peak bone density in young and middle-aged female was decreased, and OP was more common in over 60-year-aged female with hypothyroidism. Conclusions: Female patients with abnormal thyroid function are often associated with abnormality of sex hormones. It leads to increasing the incidence of OP. The attack age of OP tends to be younger, especially aged patients with lymphocytic hypothyroidism increases more markedly. Therefore, BMD should be measured in all female patients with a variety of thyroid diseases

  11. Marchiafava-Bignami disease with dementia: severe cerebral metabolic depression revealed by PET. Case report

    Pappata, S.; Chabriat, H.; Levasseur, M.; Legault-Demare, F.; Baron, J.C.

    1994-01-01

    The Cerebral Metabolic Rate of Glucose (CMRGlu) was measured with positron emission tomography and 18 F-FDG in a patient with Marchiafava-Bignami Disease (MBD)-related dementia. Despite MRI evidence of lesions essentially limited to the corpus callosum (CC), but consistent with the cognitive pattern of cortical dementia, the CMRGlu was markedly reduced in the frontal and temporo-parieto-occipital association cortices. Disruption of cortico-cortical networks crossing the CC presumably contributed to, but may not in and by itself explain, the severity of the clinical-metabolic findings in this patient. An additional role could be played by microscopic white matter lesions and/or neocortical neuronal loss, which have been occasionally observed in post-mortem studies of MBD patients. (authors)

  12. Evaluation of regional cerebral circulation and metabolism in moyamoya disease using positron emission computed tomography

    Kuwabara, Yasuo

    1986-01-01

    Regional cerebral blood flow, oxygen extraction fraction, metabolic rate of oxygen, blood volume and transit time were evaluated in 11 patients with moyamoya disease and 3 with suspected moyamoya disease using positron emission computed tomography. Eight of them were examined before and after EC-IC bypass surgery. Moyamoya patients were classified into four groups, namely, pediatric bilateral chronic type (over 5 years from onset), pediatric bilateral early type (within 5 years from onset), pediatric unilateral early type and adult type, according to age, duration of disease from onset and angiographic findings. These four groups showed different patterns on PET images; diffusely decreased CBF and CMRO2 in pediatric bilateral chronic type, decreased CBF and increased OEF in the frontal or temporoparietal region in pediatric bilateral early type, diffusely decreased CBF and increased OEF in the unilateral cerebral hemisphere in pediatric unilateral cerebral hemisphere in pediatric unilateral early type, and decreased CBF and CMRO2 in adult type. An increase of rCBV was demonstrated in frontal regions or basal ganglia in all groups, more prominently in pediatric patients. This was thought to be a common finding in moyamoya disease, corresponding to moyamoya vessels. Staging of moyamoya disease by PET was presented and compared to the angiographic staging. They were significantly correlated, and the stage 3 on PET image with decreased CMRO2 corresponded to the stage 3 or 4 on angiography, the most active stage of moyamoya disease. PET revealed increased CBF in the cortical area around EC-IC bypass but no remarkable changes in mean values of rCBF, OEF, CMRO2 and CBV in cerebral hemisphere. Some patients showed decreased rCBV in the basal ganglia. (J.P.N.)

  13. Multichannel optical brain imaging to separate cerebral vascular, tissue metabolic, and neuronal effects of cocaine

    Ren, Hugang; Luo, Zhongchi; Yuan, Zhijia; Pan, Yingtian; Du, Congwu

    2012-02-01

    Characterization of cerebral hemodynamic and oxygenation metabolic changes, as well neuronal function is of great importance to study of brain functions and the relevant brain disorders such as drug addiction. Compared with other neuroimaging modalities, optical imaging techniques have the potential for high spatiotemporal resolution and dissection of the changes in cerebral blood flow (CBF), blood volume (CBV), and hemoglobing oxygenation and intracellular Ca ([Ca2+]i), which serves as markers of vascular function, tissue metabolism and neuronal activity, respectively. Recently, we developed a multiwavelength imaging system and integrated it into a surgical microscope. Three LEDs of λ1=530nm, λ2=570nm and λ3=630nm were used for exciting [Ca2+]i fluorescence labeled by Rhod2 (AM) and sensitizing total hemoglobin (i.e., CBV), and deoxygenated-hemoglobin, whereas one LD of λ1=830nm was used for laser speckle imaging to form a CBF mapping of the brain. These light sources were time-sharing for illumination on the brain and synchronized with the exposure of CCD camera for multichannel images of the brain. Our animal studies indicated that this optical approach enabled simultaneous mapping of cocaine-induced changes in CBF, CBV and oxygenated- and deoxygenated hemoglobin as well as [Ca2+]i in the cortical brain. Its high spatiotemporal resolution (30μm, 10Hz) and large field of view (4x5 mm2) are advanced as a neuroimaging tool for brain functional study.

  14. Cocaine abstinence following chronic treatment alters cerebral metabolism in dopaminergic reward regions. Bromocriptine enhances recovery

    Clow, D.W.; Hammer, R.P. Jr.

    1991-01-01

    2-[14C]deoxyglucose autoradiography was used to determine local cerebral glucose utilization (lCGU) in rats following chronic cocaine treatment and subsequent abstinence. lCGU was examined in 43 discrete brain regions in animals which had received daily injections of cocaine for 14 days (10 mg/kg) followed by 3 days of saline or bromocriptine (10 mg/kg) treatment. Cocaine abstinence following chronic treatment significantly reduced lCGU in several regions including mesocorticolimbic structures such as ventral tegmental area, medial prefrontal cortex, and nucleus accumbens (NAc). Within the NAc, however, only the rostral pole showed significant reduction. In contrast, when bromocriptine treatment accompanied abstinence, lCGU was no longer reduced in mesocorticolimbic and most other regions, implying that metabolic recovery was enhanced by bromocriptine treatment during early abstinence following chronic cocaine treatment. These data suggest that cerebral metabolism is decreased during cocaine abstinence following chronic treatment in critical brain regions, and that this alteration can be prevented by treatment with direct-acting dopamine agonists such as bromocriptine

  15. Cocaine abstinence following chronic treatment alters cerebral metabolism in dopaminergic reward regions. Bromocriptine enhances recovery

    Clow, D.W.; Hammer, R.P. Jr. (Univ. of Hawaii School of Medicine, Honolulu (USA))

    1991-01-01

    2-(14C)deoxyglucose autoradiography was used to determine local cerebral glucose utilization (lCGU) in rats following chronic cocaine treatment and subsequent abstinence. lCGU was examined in 43 discrete brain regions in animals which had received daily injections of cocaine for 14 days (10 mg/kg) followed by 3 days of saline or bromocriptine (10 mg/kg) treatment. Cocaine abstinence following chronic treatment significantly reduced lCGU in several regions including mesocorticolimbic structures such as ventral tegmental area, medial prefrontal cortex, and nucleus accumbens (NAc). Within the NAc, however, only the rostral pole showed significant reduction. In contrast, when bromocriptine treatment accompanied abstinence, lCGU was no longer reduced in mesocorticolimbic and most other regions, implying that metabolic recovery was enhanced by bromocriptine treatment during early abstinence following chronic cocaine treatment. These data suggest that cerebral metabolism is decreased during cocaine abstinence following chronic treatment in critical brain regions, and that this alteration can be prevented by treatment with direct-acting dopamine agonists such as bromocriptine.

  16. Glucose and fatty acid metabolism in normal and diabetic rabbit cerebral microvessels

    Hingorani, V.; Brecher, P.

    1987-01-01

    Rabbit cerebral microvessels were used to study fatty acid metabolism and its utilization relative to glucose. Microvessels were incubated with either [6- 14 C]glucose or [1- 14 C]oleic acid and the incorporation of radioactivity into 14 CO 2 , lactate, triglyceride, cholesterol ester, and phospholipid was determined. The inclusion of 5.5 mM glucose in the incubation mixture reduced oleate oxidation by 50% and increased esterification into both phospholipid and triglyceride. Glucose oxidation to CO 2 was reduced by oleate addition, whereas lactate production was unaffected. 2'-Tetradecylglycidic acid, an inhibitor of carnitine acyltransferase I, blocked oleic acid oxidation in the presence and absence of glucose. It did not effect fatty acid esterification when glucose was absent and eliminated the inhibition of oleate on glucose oxidation. Glucose oxidation to 14 CO 2 was markedly suppressed in microvessels from alloxan-treated diabetic rabbits but lactate formation was unchanged. Fatty acid oxidation to CO 2 and incorporation into triglyceride, phospholipid, and cholesterol ester remained unchanged in the diabetic state. The experiments show that both fatty acid and glucose can be used as a fuel source by the cerebral microvessels, and the interactions found between fatty acid and glucose metabolism are similar to the fatty acid-glucose cycle, described previously

  17. Cerebral perfusion and glucose metabolism in Alzheimer's disease and frontotemporal dementia: two sides of the same coin?

    Verfaillie, Sander C.J.; Adriaanse, Sofie M.; Binnewijzend, Maja A.A.; Benedictus, Marije R.; Ossenkoppele, Rik [VU University Medical Centre, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); VU University Medical Centre, Alzheimer Centre and Department of Neurology, P.O. Box 7057, Amsterdam (Netherlands); Wattjes, Mike P.; Lammertsma, Adriaan A.; Boellaard, Ronald; Berckel, Bart N.M. van; Barkhof, Frederik [VU University Medical Centre, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); Pijnenburg, Yolande A.L.; Scheltens, Philip [VU University Medical Centre, Alzheimer Centre and Department of Neurology, P.O. Box 7057, Amsterdam (Netherlands); Flier, Wiesje M. van der [VU University Medical Centre, Alzheimer Centre and Department of Neurology, P.O. Box 7057, Amsterdam (Netherlands); VU University Medical Centre, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands); Kuijer, Joost P.A. [VU University Medical Centre, Department of Physics and Medical Technology, Amsterdam (Netherlands)

    2015-10-15

    Alzheimer's disease (AD) and frontotemporal (FTD) dementia can be differentiated using [{sup 18}F]-2-deoxy-2-fluoro-D-glucose (FDG)-PET. Since cerebral blood flow (CBF) is related to glucose metabolism, our aim was to investigate the extent of overlap of abnormalities between AD and FTD. Normalized FDG-PET and arterial spin labelling (ASL-MRI)-derived CBF was measured in 18 AD patients (age, 64 ± 8), 12 FTD patients (age, 61 ± 8), and 10 controls (age, 56 ± 10). Voxel-wise comparisons, region-of-interest (ROI), correlation, and ROC curve analyses were performed. Voxel-wise comparisons showed decreased CBF and FDG uptake in AD compared with controls and FTD in both precuneus and inferior parietal lobule (IPL). Compared with controls and AD, FTD patients showed both hypometabolism and hypoperfusion in medial prefrontal cortex (mPFC). ASL and FDG were related in precuneus (r = 0.62, p < 0.001), IPL (r = 0.61, p < 0.001), and mPFC across groups (r = 0.74, p < 001). ROC analyses indicated comparable performance of perfusion and metabolism in the precuneus (AUC, 0.72 and 0.74), IPL (0.85 and 0.94) for AD relative to FTD, and in the mPFC in FTD relative to AD (both 0.68). Similar patterns of hypoperfusion and hypometabolism were observed in regions typically associated with AD and FTD, suggesting that ASL-MRI provides information comparable to FDG-PET. (orig.)

  18. Cerebral perfusion and glucose metabolism in Alzheimer's disease and frontotemporal dementia: two sides of the same coin?

    Verfaillie, Sander C.J.; Adriaanse, Sofie M.; Binnewijzend, Maja A.A.; Benedictus, Marije R.; Ossenkoppele, Rik; Wattjes, Mike P.; Lammertsma, Adriaan A.; Boellaard, Ronald; Berckel, Bart N.M. van; Barkhof, Frederik; Pijnenburg, Yolande A.L.; Scheltens, Philip; Flier, Wiesje M. van der; Kuijer, Joost P.A.

    2015-01-01

    Alzheimer's disease (AD) and frontotemporal (FTD) dementia can be differentiated using [ 18 F]-2-deoxy-2-fluoro-D-glucose (FDG)-PET. Since cerebral blood flow (CBF) is related to glucose metabolism, our aim was to investigate the extent of overlap of abnormalities between AD and FTD. Normalized FDG-PET and arterial spin labelling (ASL-MRI)-derived CBF was measured in 18 AD patients (age, 64 ± 8), 12 FTD patients (age, 61 ± 8), and 10 controls (age, 56 ± 10). Voxel-wise comparisons, region-of-interest (ROI), correlation, and ROC curve analyses were performed. Voxel-wise comparisons showed decreased CBF and FDG uptake in AD compared with controls and FTD in both precuneus and inferior parietal lobule (IPL). Compared with controls and AD, FTD patients showed both hypometabolism and hypoperfusion in medial prefrontal cortex (mPFC). ASL and FDG were related in precuneus (r = 0.62, p < 0.001), IPL (r = 0.61, p < 0.001), and mPFC across groups (r = 0.74, p < 001). ROC analyses indicated comparable performance of perfusion and metabolism in the precuneus (AUC, 0.72 and 0.74), IPL (0.85 and 0.94) for AD relative to FTD, and in the mPFC in FTD relative to AD (both 0.68). Similar patterns of hypoperfusion and hypometabolism were observed in regions typically associated with AD and FTD, suggesting that ASL-MRI provides information comparable to FDG-PET. (orig.)

  19. Aspirin suppresses the abnormal lipid metabolism in liver cancer cells via disrupting an NFκB-ACSL1 signaling

    Yang, Guang; Wang, Yuan; Feng, Jinyan; Liu, Yunxia; Wang, Tianjiao; Zhao, Man; Ye, Lihong; Zhang, Xiaodong

    2017-01-01

    Abnormal lipid metabolism is a hallmark of tumorigenesis. Hence, the alterations of metabolism enhance the development of hepatocellular carcinoma (HCC). Aspirin is able to inhibit the growth of cancers through targeting nuclear factor κB (NF-κB). However, the role of aspirin in disrupting abnormal lipid metabolism in HCC remains poorly understood. In this study, we report that aspirin can suppress the abnormal lipid metabolism of HCC cells through inhibiting acyl-CoA synthetase long-chain family member 1 (ACSL1), a lipid metabolism-related enzyme. Interestingly, oil red O staining showed that aspirin suppressed lipogenesis in HepG2 cells and Huh7 cells in a dose-dependent manner. In addition, aspirin attenuated the levels of triglyceride and cholesterol in the cells, respectively. Strikingly, we identified that aspirin was able to down-regulate ACSL1 at the levels of mRNA and protein. Moreover, we validated that aspirin decreased the nuclear levels of NF-κB in HepG2 cells. Mechanically, PDTC, an inhibitor of NF-κB, could down-regulate ACSL1 at the levels of mRNA and protein in the cells. Functionally, PDTC reduced the levels of lipid droplets, triglyceride and cholesterol in HepG2 cells. Thus, we conclude that aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling. Our finding provides new insights into the mechanism by which aspirin inhibits abnormal lipid metabolism of HCC. Therapeutically, aspirin is potentially available for HCC through controlling abnormal lipid metabolism. - Highlights: • Aspirin inhibits the levels of liquid droplets, triglyceride and cholesterol in HCC cells. • Aspirin is able to down-regulate ACSL1 in HCC cells. • NF-κB inhibitor PDTC can down-regulate ACSL1 and reduces lipogenesis in HCC cells. • Aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling.

  20. Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities.

    Quintana, Anita M; Yu, Hung-Chun; Brebner, Alison; Pupavac, Mihaela; Geiger, Elizabeth A; Watson, Abigail; Castro, Victoria L; Cheung, Warren; Chen, Shu-Huang; Watkins, David; Pastinen, Tomi; Skovby, Flemming; Appel, Bruce; Rosenblatt, David S; Shaikh, Tamim H

    2017-08-01

    CblX (MIM309541) is an X-linked recessive disorder characterized by defects in cobalamin (vitamin B12) metabolism and other developmental defects. Mutations in HCFC1, a transcriptional co-regulator which interacts with multiple transcription factors, have been associated with cblX. HCFC1 regulates cobalamin metabolism via the regulation of MMACHC expression through its interaction with THAP11, a THAP domain-containing transcription factor. The HCFC1/THAP11 complex potentially regulates genes involved in diverse cellular functions including cell cycle, proliferation, and transcription. Thus, it is likely that mutation of THAP11 also results in biochemical and other phenotypes similar to those observed in patients with cblX. We report a patient who presented with clinical and biochemical phenotypic features that overlap cblX, but who does not have any mutations in either MMACHC or HCFC1. We sequenced THAP11 by Sanger sequencing and discovered a potentially pathogenic, homozygous variant, c.240C > G (p.Phe80Leu). Functional analysis in the developing zebrafish embryo demonstrated that both THAP11 and HCFC1 regulate the proliferation and differentiation of neural precursors, suggesting important roles in normal brain development. The loss of THAP11 in zebrafish embryos results in craniofacial abnormalities including the complete loss of Meckel's cartilage, the ceratohyal, and all of the ceratobranchial cartilages. These data are consistent with our previous work that demonstrated a role for HCFC1 in vertebrate craniofacial development. High throughput RNA-sequencing analysis reveals several overlapping gene targets of HCFC1 and THAP11. Thus, both HCFC1 and THAP11 play important roles in the regulation of cobalamin metabolism as well as other pathways involved in early vertebrate development. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Abnormalities in biomarkers of mineral and bone metabolism in kidney donors.

    Kasiske, Bertram L; Kumar, Rajiv; Kimmel, Paul L; Pesavento, Todd E; Kalil, Roberto S; Kraus, Edward S; Rabb, Hamid; Posselt, Andrew M; Anderson-Haag, Teresa L; Steffes, Michael W; Israni, Ajay K; Snyder, Jon J; Singh, Ravinder J; Weir, Matthew R

    2016-10-01

    Previous studies have suggested that kidney donors may have abnormalities of mineral and bone metabolism typically seen in chronic kidney disease. This may have important implications for the skeletal health of living kidney donors and for our understanding of the pathogenesis of long-term mineral and bone disorders in chronic kidney disease. In this prospective study, 182 of 203 kidney donors and 173 of 201 paired normal controls had markers of mineral and bone metabolism measured before and at 6 and 36 months after donation (ALTOLD Study). Donors had significantly higher serum concentrations of intact parathyroid hormone (24.6% and 19.5%) and fibroblast growth factor-23 (9.5% and 8.4%) at 6 and 36 months, respectively, as compared to healthy controls, and significantly reduced tubular phosphate reabsorption (-7.0% and -5.0%) and serum phosphate concentrations (-6.4% and -2.3%). Serum 1,25-dihydroxyvitamin D3 concentrations were significantly lower (-17.1% and -12.6%), while 25-hydroxyvitamin D (21.4% and 19.4%) concentrations were significantly higher in donors compared to controls. Moreover, significantly higher concentrations of the bone resorption markers, carboxyterminal cross-linking telopeptide of bone collagen (30.1% and 13.8%) and aminoterminal cross-linking telopeptide of bone collagen (14.2% and 13.0%), and the bone formation markers, osteocalcin (26.3% and 2.7%) and procollagen type I N-terminal propeptide (24.3% and 8.9%), were observed in donors. Thus, kidney donation alters serum markers of bone metabolism that could reflect impaired bone health. Additional long-term studies that include assessment of skeletal architecture and integrity are warranted in kidney donors. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  2. Cerebral glucose metabolic patterns in Alzheimer's disease. Effect of gender and age at dementia onset

    Small, G.W.; Kuhl, D.E.; Riege, W.H.; Fujikawa, D.G.; Ashford, J.W.; Metter, E.J.; Mazziotta, J.C.

    1989-01-01

    No previous study of Alzheimer's disease has, to our knowledge, assessed the effect of both age at dementia onset and gender on cerebral glucose metabolic patterns. To this end, we used positron emission tomography (fludeoxyglucose F 18 method) to study 24 patients with clinical diagnoses of probable Alzheimer's disease. Comparisons of the 13 patients with early-onset dementia (less than 65 years of age) with the 11 patients with late-onset dementia (greater than 65 years of age) revealed significantly lower left parietal metabolic ratios (left posterior parietal region divided by the hemispheric average) in the early-onset group. The metabolic ratio of posterior parietal cortex divided by the relatively disease-stable average of caudate and thalamus also separated patients with early-onset dementia from those with late-onset dementia, but not men from women. Further comparisons between sexes showed that, in all brain regions studied, the 9 postmenopausal women had higher nonweighted mean metabolic rates than the 15 men from the same age group, with hemispheric sex differences of 9% on the right and 7% on the left. These results demonstrate decreased parietal ratios in early-onset dementia of Alzheimer's disease, independent of a gender effect

  3. Positron computed tomography studies of cerebral metabolic responses to complex motor tasks

    Phelps, M.E.; Mazziotta, J.C.

    1984-01-01

    Human motor system organization was explored in 8 right-handed male subjects using /sup 18/F-fluorodeoxyglucose and positron computed tomography to measure cerebral glucose metabolism. Five subjects had triple studies (eyes closed) including: control (hold pen in right hand without moving), normal size writing (subject repeatedly writes name) and large (10-15 X normal) name writing. In these studies normal and large size writing had a similar distribution of metabolic responses when compared to control studies. Activations (percent change from control) were in the range of 12-20% and occurred in the striatum bilaterally > contralateral Rolandic cortex > contralateral thalamus. No significant activations were observed in the ipsilateral thalamus, Rolandic cortex or cerebellum (supplementary motor cortex was not examined). The magnitude of the metabolic response in the striatum was greater with the large versus normal sized writing. This differential response may be due to an increased number and topographic distribution of neurons responding with the same average activity between tasks or an increase in the functional activity of the same neuronal population between the two tasks (present spatial resolution inadequate to differentiate). When subjects (N=3) performed novel sequential finger movements, the maximal metabolic response was in the contralateral Rolandic cortex > striatum. Such studies provide a means of exploring human motor system organization, motor learning and provide a basis for examining patients with motor system disorders

  4. Early Cerebral Hemodynamic, Metabolic, and Histological Changes in Hypoxic-Ischemic Fetal Lambs during Postnatal Life.

    Rey-Santano, Carmen; Mielgo, Victoria E; Gastiasoro, Elena; Murgia, Xabier; Lafuente, Hector; Ruiz-Del-Yerro, Estibaliz; Valls-I-Soler, Adolf; Hilario, Enrique; Alvarez, Francisco J

    2011-01-01

    The hemodynamic, metabolic, and biochemical changes produced during the transition from fetal to neonatal life may be aggravated if an episode of asphyxia occurs during fetal life. The aim of the study was to examine regional cerebral blood flow (RCBF), histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress in the first hours of postnatal life following severe fetal asphyxia. Eighteen chronically instrumented newborn lambs were randomly assigned to either a control group or the hypoxic-ischemic (HI) group, in which case fetal asphyxia was induced just before delivery. All the animals were maintained on intermittent positive pressure ventilation for 3 h after delivery. During the HI insult, the injured group developed acidosis, hypoxia, hypercapnia, lactic acidosis, and tachycardia (relative to the control group), without hypotension. The intermittent positive pressure ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilatory support, there continued to be an increased RCBF in inner regions among the HI group, but no significant differences were detected in cortical flow compared to the control group. Also, the magnitude of the increase in TUNEL positive cells (apoptosis) and antioxidant enzymes, and decrease of ATP reserves was significantly greater in the brain regions where the RCBF was not higher. In conclusion, our findings identify early metabolic, histological, and hemodynamic changes involved in brain damage in premature asphyxiated lambs. Such changes have been described in human neonates, so our model could be useful to test the safety and the effectiveness of different neuroprotective or ventilation strategies applied in the first hours after fetal HI injury.

  5. Early cerebral hemodynamic, metabolic and histological changes in hypoxic-ischemic fetal lambs during postnatal life

    Carmen eRey-Santano

    2011-09-01

    Full Text Available The hemodynamic, metabolic and biochemical changes produce during transition from fetal to neonatal life could be aggravated if asphyctic event occur during fetal life. The aim of the study was to examine the regional cerebral blood flow (RCBF, histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress for the first hours of postnatal life following severe fetal asphyxia. 18 chronically instrumented fetal lambs were assigned to: hypoxic-ischemic group, following fetal asphyxia animals were delivered and maintained on intermittent-positive-pressure-ventilation for 3 hours, and non-injured animals that were managed similarly to the previous group and used as control group. During hypoxic-ischemic insult, injured group developed acidosis, hypoxia, hypercapnia, latacidaemia and tachycardia in comparison to control group, without hypotension. Intermittent-positive-pressure-ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilation-support, the increased RCBF in inner zones was maintained for hypoxic-ischemic group, but cortical flow did not exhibit differences compared to the control group. Also, the increase of TUNEL positive cells (apoptosis and antioxidant enzymes, and decrease of ATP reserves was significantly higher in the brain regions where the RCBF were not increased.In conclusion, early metabolic, histological and hemodynamic changes involved in brain damage have been intensively investigated and reported in premature asphyctic lambs for the first 3 hours of postnatal life. Those changes have been described in human neonates, so our model could be useful to test the security and the effectiveness of different neuroprotective or ventilatory strategies when are applied in the first hours after fetal hypoxic-ischemic injury.

  6. Daily consumption of white tea (Camellia sinensis (L.)) improves the cerebral cortex metabolic and oxidative profile in prediabetic Wistar rats.

    Nunes, Ana R; Alves, Marco G; Tomás, Gonçalo D; Conde, Vanessa R; Cristóvão, Ana C; Moreira, Paula I; Oliveira, Pedro F; Silva, Branca M

    2015-03-14

    Diabetes mellitus (DM) is a major public health problem and its incidence is rising dramatically. The brain, particularly the cerebral cortex, is very susceptible to glucose fluctuations and hyperglycaemia-induced oxidative stress. Tea (Camellia sinensis (L.)) is widely consumed; however, the antidiabetic properties of white tea remain largely unexplored. In the present study, we investigated the effects of daily consumption of white tea on the cerebral cortex of prediabetic rats. The cerebral cortex metabolic profile was evaluated, and the expression levels of GLUT, phosphofructokinase-1, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 were assessed. LDH activity was also determined. The cerebral cortex oxidative profile was determined by evaluating its antioxidant power, lipid peroxidation and protein oxidation levels. Catalase, glutathione, glutamate, N-acetylaspartate, aspartate, choline, γ-aminobutyric acid, taurine and valine contents were determined. Daily consumption of white tea ameliorated glucose tolerance and insulin sensitivity. Moreover, white tea altered the cortex glycolytic profile, modulating GLUT expression and lactate and alanine contents. Finally, white tea consumption restored protein oxidation and lipid peroxidation levels and catalase expression, and improved antioxidant capacity. In conclusion, daily consumption of white tea improved the cerebral cortex metabolic and oxidative profile in prediabetic rats, suggesting it as a good, safe and inexpensive strategy to prevent DM-related effects in the cerebral cortex.

  7. Cerebral blood flow and metabolism during cardiopulmonary bypass with special reference to effects of hypotension induced by prostacyclin

    Feddersen, K.; Aren, C.; Nilsson, N.J.; Radegran, K.

    1986-01-01

    Cerebral blood flow and metabolism of oxygen, glucose, and lactate were studied in 43 patients undergoing aortocoronary bypass. Twenty-five patients received prostacyclin infusion, 50 ng per kilogram of body weight per minute, during cardiopulmonary bypass (CPB), and 18 patients served as a control group. Regional cerebral blood flow (CBF) was studied by intraarterially injected xenon 133 and a single scintillation detector. Oxygen tension, carbon dioxide tension, oxygen saturation, glucose, and lactate were measured in arterial and cerebral venous blood. Mean arterial blood pressure decreased during hypothermia and prostacyclin infusion to less than 30 mm Hg. The regional CBF was, on average, 22 (standard deviation [SD] 4) ml/100 gm/min before CPB. It increased in the control group during hypothermia to 34 (SD 12) ml/100 gm/min, but decreased in the prostacyclin group to 15 (SD 5) ml/100 gm/min. It increased during rewarming in the prostacyclin group. After CPB, regional CBF was about 40 ml/100 gm/min in both groups. The cerebral arteriovenous oxygen pressure difference decreased more in the control group than in the prostacyclin group during hypothermia. The cerebral metabolic rate of oxygen decreased in both groups from approximately 2 ml/100 gm/min to about 1 ml/100 gm/min during hypothermia, increased again during rewarming, and after CPB was at the levels measured before bypass in both groups. There was no difference between the groups in regard to glucose and lactate metabolism

  8. Cerebral glucose metabolism change in patients with complex regional pain syndrome. A PET study

    Shiraishi, Satoe; Kobayashi, Hidetoshi; Nihashi, Takashi

    2006-01-01

    The aim of this study was to examine abnormalities of the central nervous system in patients with chronic pain who were diagnosed with complex regional pain syndrome (CRPS). Brain activity was assessed using 18 F-fluorodeoxyglucose positron emission tomography. The data collected from 18 patients were compared with data obtained from 13 normal age-matched controls. Our results showed that glucose metabolism was bilaterally increased in the secondary somatosensory cortex, mid-anterior cingulated cortex (ACC) or posterior cingulated cortex (PCC) (or both), parietal cortex, posterior parietal cortex (PPC), and cerebellum as well as in the right posterior insula and right thalamus in our patients. In contrast, glucose metabolism was reduced contralaterally in the dorsal prefrontal cortex and primary motor cortex. Glucose metabolism was bilaterally elevated in the mid-ACC/PCC and the PPC, which correlated with pain duration. These data suggested that glucose metabolism in the brains of patients with CRPS changes dramatically at each location. In particular, glucose metabolism was increased in the areas concerned with somatosensory perception, possibly due to continuous painful stimulation. (author)

  9. Abnormal brain glucose metabolism and depressive mood in patients with pre-dialytic chronic kidney disease: SPM analysis of F-18 FDG positron emission tomography

    Jun, Sung Min; Song, Sang Heon; Kim, Seong Jang; Kim, Ji Hoon; Kwak, Ihm Soo; Kim, In Ju; Kim, Yong Ki [Pusan National University Hospital, Pusan (Korea, Republic of)

    2007-07-01

    The aim of this study was to investigate the relationship between depressive mood and pre-dialytic CKD, to localize and quantify depressive mood -related lesions in pre-dialytic CKD patients through statistical parametric mapping (SPM) analysis of brain positron emission tomography (PET), and to examine the usefulness of brain PET for early detection and proper treatment of depressive mood. Twenty one patients with stage 5 CKD and 22 healthy volunteers were analyzed by depressive mood assessment and statistical parametric mapping (SPM) analysis of 18F-FDG PET. Depressive mood assessment was done by Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS). The largest clusters were areas including precentral gyrus, prefrontal cortex, and anterior cingulated cortex of left hemisphere. Other clusters were left transverse temporal gyrus, left superior temporal gyrus, right prefrontal cortex, right dorsolateral prefrontal cortex (BA 46, 44), right inferior frontal gyrus, right inferior parietal lobule, left angular gyrus. In addition, correlation was found between hypometabolized areas and HDRS scores of CKD patients in right prefrontal cortex (BA 11) and right anterior cingulated gyrus (BA 24). In conclusion, this study demonstrated specific depressive mood-related abnormal metabolic lesion. Interestingly, in CKD patients with severe depressive mood, cerebral metabolism was similar to that of MDD.

  10. Abnormal brain glucose metabolism and depressive mood in patients with pre-dialytic chronic kidney disease: SPM analysis of F-18 FDG positron emission tomography

    Jun, Sung Min; Song, Sang Heon; Kim, Seong Jang; Kim, Ji Hoon; Kwak, Ihm Soo; Kim, In Ju; Kim, Yong Ki

    2007-01-01

    The aim of this study was to investigate the relationship between depressive mood and pre-dialytic CKD, to localize and quantify depressive mood -related lesions in pre-dialytic CKD patients through statistical parametric mapping (SPM) analysis of brain positron emission tomography (PET), and to examine the usefulness of brain PET for early detection and proper treatment of depressive mood. Twenty one patients with stage 5 CKD and 22 healthy volunteers were analyzed by depressive mood assessment and statistical parametric mapping (SPM) analysis of 18F-FDG PET. Depressive mood assessment was done by Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS). The largest clusters were areas including precentral gyrus, prefrontal cortex, and anterior cingulated cortex of left hemisphere. Other clusters were left transverse temporal gyrus, left superior temporal gyrus, right prefrontal cortex, right dorsolateral prefrontal cortex (BA 46, 44), right inferior frontal gyrus, right inferior parietal lobule, left angular gyrus. In addition, correlation was found between hypometabolized areas and HDRS scores of CKD patients in right prefrontal cortex (BA 11) and right anterior cingulated gyrus (BA 24). In conclusion, this study demonstrated specific depressive mood-related abnormal metabolic lesion. Interestingly, in CKD patients with severe depressive mood, cerebral metabolism was similar to that of MDD

  11. Pharmacologic modulation of cerebral metabolic derangement and excitotoxicity in a porcine model of traumatic brain injury and hemorrhagic shock

    Hwabejire, John O; Jin, Guang; Imam, Ayesha M

    2013-01-01

    Cerebral metabolic derangement and excitotoxicity play critical roles in the evolution of traumatic brain injury (TBI). We have shown previously that treatment with large doses of valproic acid (VPA) decreases the size of brain lesion. The goal of this experiment was to determine whether...

  12. Cerebral metabolism and vascular reactivity during breath-hold and hypoxic challenge in freedivers and healthy controls

    Vestergaard, Mark B.; Larsson, Henrik B.W.

    2017-01-01

    blood flow (CBF) and metabolic rate of oxygen (CMRO2), and magnetic resonance spectroscopy was used to measure the cerebral lactate, glutamate+glutamine, N-acetylaspartate and phosphocreatine+creatine concentrations in the occipital lobe. Fifteen freedivers and seventeen non-diver controls participated...

  13. Regional cerebral energy metabolism during intravenous anesthesia with etomidate, ketamine or thiopental

    Davis, D.W.

    1987-01-01

    Regional brain glucose utilization (rCMRglc) was measured in rats during steady-state levels of intravenous anesthesia to determine if alterations in brain function due to anesthesia could provide information on the mechanisms of anesthesia. Intravenous anesthetics from three different chemical classes were studied: etomidate, ketamine and thiopental. All rCMRglc experiments were conducted in freely moving rats in isolation chambers, with the use of [6- 14 C] glucose and guantitative autoradiography. Etomidate caused a rostral-to-caudal gradient of depression of rCMRglc. The four doses of etomidate did not differ in their effects on energy metabolism. Sub-anesthetic (5 mg kg -1 ) and anesthetic (30 mg kg -1 ) doses of ketamine produced markedly different patterns of behavior. Brain energy metabolism during the sub-anesthetic dose was stimulated in most regions, while the anesthetic dose selectively stimulated the hippocampus, leaving most brain regions unaffected. Thiopental produced a dose-dependent reduction of rCMRglc in all gray matter regions. No brain region was selectively affected. Comparison of the drug-specific alterations of cerebral energy metabolism suggests these anesthetics do not act through a common mechanism. The hypothesis that each acts by binding to specific cell membrane receptors is consistent with these observations

  14. Investigation of cerebral metabolism by positron CT in Japanese following musical stimulation

    Wakasugi, Naotoshi (Nihon Univ., Tokyo (Japan). School of Medicine)

    1994-02-01

    Cerebral metabolic responses to Japanese and Western instrumental music were examined using [sup 11]C-glucose and positron CT. Eight right-handed subjects were studied in both Japanese and Western music-stimulated states. Biaural musical stimulation with a Japanese instrument, the 'shakuhachi', produced diffuse metabolic changes in the left temporal lobe in all subjects. Biaural musical stimulation with a Western instrument, the 'violin', produced metabolic changes in the right temporal lobe in 3 subjects, changes in the left in 4, and changes on both sides in one. It was considered previously that all musical stimulation led to hypermetabolism in the right hemisphere of human beings. However, the present results indicated that Japanese music produced activation of the left hemisphere in Japanese. On the other hand, Western music produced right hemispheric hypermetabolism in Japanese with no emotion. The laterality of the hemisphere stimulated by Western music was apparently incidentally changed according to the state of mind the Japanese subjects. (author).

  15. Cerebral metabolism, magnetic resonance spectroscopy and cognitive dysfunction in early multiple sclerosis: an exploratory study

    Blinkenberg, Morten; Mathiesen, Henrik K; Tscherning, Thomas

    2012-01-01

    and neurological disability. METHODS: We studied 20 recently diagnosed, clinically definite, relapsing-remitting MS patients. Global and cortical CMRglc was estimated using PET with 18-F-deoxyglucose and NAA/Cr ratio was measured using multislice echo-planar spectroscopic imaging. All subjects were neuro-psychologically......OBJECTIVES: Positron emission tomography (PET) studies have shown that cortical cerebral metabolic rate of glucose (CMRglc) is reduced in multiple sclerosis (MS). Quantitative magnetic resonance spectroscopy (MRS) measures of N-acetyl-aspartate (NAA) normalized to creatine (NAA/Cr) assess neuronal...... deterioration, and several studies have shown reductions in MS. Furthermore, both PET and MRS reductions correlate with cognitive dysfunction in MS. Our aim was to determine if changes in cortical CMRglc in early MS correlate with NAA/Cr measurements of neuronal deterioration, as well as cognitive dysfunction...

  16. Are barriers to physical activity similar for adults with and without abnormal glucose metabolism?

    Hume, Clare; Dunstan, David; Salmon, Jo; Healy, Genevieve; Andrianopoulos, Nick; Owen, Neville

    2010-01-01

    The purpose of this study was to examine perceived barriers to physical activity among adults with and without abnormal glucose metabolism (AGM), and whether barriers varied according to physical activity status. The 1999 to 2000 Australian Diabetes, Obesity, and Lifestyle Study (AusDiab) was a population-based cross-sectional study among adults aged > or =25 years. AGM was identified through an oral glucose tolerance test. The previous week's physical activity and individual, social, and environmental barriers to physical activity were self-reported. Logistic regression analyses examined differences in barriers to physical activity between those with and without AGM, and for those with and without AGM who did and did not meet the minimum recommendation of 150 minutes/week of moderate-to-vigorous intensity physical activity. Of the 7088 participants (47.5 +/- 12.7 years; 46% male), 18.5% had AGM. Approximately 47.5% of those with AGM met the physical activity recommendation, compared to 54.7% of those without AGM (P barriers to physical activity included lack of time, other priorities, and being tired. Following adjustment for sociodemographic and behavioral factors, there were few differences in barriers to physical activity between those with and without AGM, even after stratifying according to physical activity. Adults with AGM report similar barriers to physical activity, as do those without AGM. Programs for those with AGM can therefore focus on the known generic adult-reported barriers to physical activity.

  17. Alterations in cerebral metabolism observed in living rodents using fluorescence lifetime microscopy of intrinsic NADH (Conference Presentation)

    Yaseen, Mohammad A.; Sakadžić, Sava; Sutin, Jason; Wu, Weicheng; Fu, Buyin; Boas, David A.

    2017-02-01

    Monitoring cerebral energy metabolism at a cellular level is essential to improve our understanding of healthy brain function and its pathological alterations. In this study, we resolve specific alterations in cerebral metabolism utilizing minimally-invasive 2-Photon fluorescence lifetime imaging (2P-FLIM) measurements of reduced nicotinamide adenine dinucleotide (NADH) fluorescence, collected in vivo from anesthetized rats and mice. Time-resolved lifetime measurements enables distinction of different components contributing to NADH autofluorescence. These components reportedly represent different enzyme-bound formulations of NADH. Our observations from this study confirm the hypothesis that NADH FLIM can identify specific alterations in cerebral metabolism. Using time-correlated single photon counting (TCSPC) equipment and a custom-built multimodal imaging system, 2-photon fluorescence lifetime imaging (FLIM) was performed in cerebral tissue with high spatial and temporal resolution. Multi-exponential fits for NADH fluorescence lifetimes indicate 4 distinct components, or 'species.' We observed distinct variations in the relative proportions of these components before and after pharmacological-induced impairments to several reactions involved in anaerobic glycolysis and aerobic oxidative metabolism. Classification models developed with experimental data correctly predict the metabolic impairments associated with bicuculline-induced focal seizures in separate experiments. Compared to traditional intensity-based NADH measurements, lifetime imaging of NADH is less susceptible to the adverse effects of overlying blood vessels. Evaluating NADH measurements will ultimately lead to a deeper understanding of cerebral energetics and its pathology-related alterations. Such knowledge will likely aid development of therapeutic strategies for neurodegenerative diseases such as Alzheimer's Disease, Parkinson's disease, and stroke.

  18. Exenatide Regulates Cerebral Glucose Metabolism in Brain Areas Associated With Glucose Homeostasis and Reward System.

    Daniele, Giuseppe; Iozzo, Patricia; Molina-Carrion, Marjorie; Lancaster, Jack; Ciociaro, Demetrio; Cersosimo, Eugenio; Tripathy, Devjit; Triplitt, Curtis; Fox, Peter; Musi, Nicolas; DeFronzo, Ralph; Gastaldelli, Amalia

    2015-10-01

    Glucagon-like peptide 1 receptors (GLP-1Rs) have been found in the brain, but whether GLP-1R agonists (GLP-1RAs) influence brain glucose metabolism is currently unknown. The study aim was to evaluate the effects of a single injection of the GLP-1RA exenatide on cerebral and peripheral glucose metabolism in response to a glucose load. In 15 male subjects with HbA1c of 5.7 ± 0.1%, fasting glucose of 114 ± 3 mg/dL, and 2-h glucose of 177 ± 11 mg/dL, exenatide (5 μg) or placebo was injected in double-blind, randomized fashion subcutaneously 30 min before an oral glucose tolerance test (OGTT). The cerebral glucose metabolic rate (CMRglu) was measured by positron emission tomography after an injection of [(18)F]2-fluoro-2-deoxy-d-glucose before the OGTT, and the rate of glucose absorption (RaO) and disposal was assessed using stable isotope tracers. Exenatide reduced RaO0-60 min (4.6 ± 1.4 vs. 13.1 ± 1.7 μmol/min ⋅ kg) and decreased the rise in mean glucose0-60 min (107 ± 6 vs. 138 ± 8 mg/dL) and insulin0-60 min (17.3 ± 3.1 vs. 24.7 ± 3.8 mU/L). Exenatide increased CMRglu in areas of the brain related to glucose homeostasis, appetite, and food reward, despite lower plasma insulin concentrations, but reduced glucose uptake in the hypothalamus. Decreased RaO0-60 min after exenatide was inversely correlated to CMRglu. In conclusion, these results demonstrate, for the first time in man, a major effect of a GLP-1RA on regulation of brain glucose metabolism in the absorptive state. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  19. Positron emission tomography assessment of cerebral glucose metabolic rates in autism spectrum disorder and schizophrenia.

    Mitelman, Serge A; Bralet, Marie-Cecile; Mehmet Haznedar, M; Hollander, Eric; Shihabuddin, Lina; Hazlett, Erin A; Buchsbaum, Monte S

    2018-04-01

    Several models have been proposed to account for observed overlaps in clinical features and genetic predisposition between schizophrenia and autism spectrum disorder. This study assessed similarities and differences in topological patterns and vectors of glucose metabolism in both disorders in reference to these models. Co-registered 18 fluorodeoxyglucose PET and MRI scans were obtained in 41 schizophrenia, 25 ASD, and 55 healthy control subjects. AFNI was used to map cortical and subcortical regions of interest. Metabolic rates were compared between three diagnostic groups using univariate and multivariate repeated-measures ANOVA. Compared to controls, metabolic rates in schizophrenia subjects were decreased in the frontal lobe, anterior cingulate, superior temporal gyrus, amygdala and medial thalamic nuclei; rates were increased in the occipital cortex, hippocampus, basal ganglia and lateral thalamic nuclei. In ASD subjects metabolic rates were decreased in the parietal lobe, frontal premotor and eye-fields areas, and amygdala; rates were increased in the posterior cingulate, occipital cortex, hippocampus and basal ganglia. In relation to controls, subjects with ASD and schizophrenia showed opposite changes in metabolic rates in the primary motor and somatosensory cortex, anterior cingulate and hypothalamus; similar changes were found in prefrontal and occipital cortices, inferior parietal lobule, amygdala, hippocampus, and basal ganglia. Schizophrenia and ASD appear to be associated with a similar pattern of metabolic abnormalities in the social brain. Divergent maladaptive trade-offs, as postulated by the diametrical hypothesis of their evolutionary relationship, may involve a more circumscribed set of anterior cingulate, motor and somatosensory regions and the specific cognitive functions they subserve.

  20. Metabolic Abnormalities Are Common among South American Hispanics Subjects with Normal Weight or Excess Body Weight: The CRONICAS Cohort Study.

    Benziger, Catherine P; Bernabé-Ortiz, Antonio; Gilman, Robert H; Checkley, William; Smeeth, Liam; Málaga, Germán; Miranda, J Jaime

    2015-01-01

    We aimed to characterize metabolic status by body mass index (BMI) status. The CRONICAS longitudinal study was performed in an age-and-sex stratified random sample of participants aged 35 years or older in four Peruvian settings: Lima (Peru's capital, costal urban, highly urbanized), urban and rural Puno (both high-altitude), and Tumbes (costal semirural). Data from the baseline study, conducted in 2010, was used. Individuals were classified by BMI as normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (≥30 kg/m2), and as metabolically healthy (0-1 metabolic abnormality) or metabolically unhealthy (≥2 abnormalities). Abnormalities included individual components of the metabolic syndrome, high-sensitivity C-reactive protein, and insulin resistance. A total of 3088 (age 55.6±12.6 years, 51.3% females) had all measurements. Of these, 890 (28.8%), 1361 (44.1%) and 837 (27.1%) were normal weight, overweight and obese, respectively. Overall, 19.0% of normal weight in contrast to 54.9% of overweight and 77.7% of obese individuals had ≥3 risk factors (poverweight and 3.9% of obese individuals were metabolically healthy and, compared to Lima, the rural and urban sites in Puno were more likely to have a metabolically healthier profile. Most Peruvians with overweight and obesity have additional risk factors for cardiovascular disease, as well as a majority of those with a healthy weight. Prevention programs aimed at individuals with a normal BMI, and those who are overweight and obese, are urgently needed, such as screening for elevated fasting cholesterol and glucose.

  1. Relationship between salivary cortisol levels and regional cerebral glucose metabolism in nondemented elderly subjects

    Kwak, Young Bin; Cho, Sang Soo; Lee, Sung Ha; Chey, Jean Yung; Kim, Sang Eun

    2004-01-01

    Cortisol is a primary stress hormone for flight-or-fight response in human. Increased levels of cortisol have been associated with memory and learning impairments. However, little is known about the role of cortisol on brain/cognitive functions in older adults. We compared regional cerebral glucose metabolism between elderly subjects with high and low cortisol levels using FDG PET. Salivary cortisol levels were measured four times during a day, and an average of the four measurements was used as the standard cortisol level for the analyses. From a population of 120 nondemented elderly subjects, 19 (mean age, 70.1±4.9 y: 2 males and 17 females) were identified as the high (> mean + 1 SD of the total population) cortisol subjects (mean cortisol, 0.69±0.09 μ g/dL), while 14 (mean age, 67.2±4.5 y: all females) as the low (< mean 1 SD) cortisol (mean cortisol, 0.27±0.03 μ g/dL). A voxel-wise comparison of FDG PET images from the high and low cortisol subjects was performed using SPM99. When compared with the low cortisol group, the high cortisol group had significant hypometabolism in the right middle temporal gyrus, left precuneus, right parahippocampal gyrus, right inferior temporal and superior temporal gyri (P < 0.01 uncorrected, k = 100). There was no significant increase of glucose metabolism in the high cortisol group compared with the low cortisol group (P < 0.01 uncorrected, k = 100). The high cortisol elderly subjects had hypometabolism in the parahippocampal and temporal gyri and precuneus, regions involved in memory and other cognitive functions. This may represent the preclinical metabolic correlates of forthcoming cognitive dysfunction associated with stress in the elderly. Longitudinal studies of brain metabolism and cognitive function are warranted

  2. Decreased regional cerebral glucose metabolism in the prefrontal regions in adults' with internet game addiction

    Park, Hyun Soo; Bang, Soong Ae; Yoon, Eun Jin; Cho, Sang Soo; Kim, Sang Hee; Kim, Yu Kyeong; Kim, Sang Eun

    2007-01-01

    Internet Game Addiction (IGA) is known to be associated with poor decision-making and diminished impulse control; however, the underlying neural substrates of IGA have not been identified. To investigate the neural substrates of IGA, we compared regional cerebral glucose metabolism between adults with and without IGA, primarily in the prefrontal brain regions, which have been implicated in inhibitory control. We studied 10 right-handed participants (5 controls: male, 23.8±0.75 y, 5 IGAs: male, 22.6±2.42 y) with FDG PET. A standardized questionnaire was used to assess the severity of IGA. Before scanning, all subjects carried out a computerized version of the Iowa Gambling Task (IGT) and the Balloon Analogue Risk Task (BART), as measures of behavioral inhibitory control. Statistical Parametric Mapping 2 (SPM2) was used to analyze differences in regional brain glucose metabolism between adults with and without IGA. Consistent with our predictions, compared to controls, significant reductions in FDG uptake in individuals with IGA were found in the bilateral orbitofrontal gyrus (BA 11, 47), bilateral inferior frontal gyrus (BA 44, 48), cingulate cortex (BA 24), and bilateral supplementary motor area (SMA) (BA 6); whereas increases were found in the bilateral hippocampus. Correlation analyses within the IGA group further showed that the level of glucose metabolism in the right orbitofrontal gyrus was marginally positively correlated with task scores in BART. Our results showed that IGA is associated with reduced glucose metabolism in the prefrontal regions involved in inhibitory control. This finding highlights dysfunctional inhibitory brain systems in individuals with IGA and offers implications for the development for therapeutic paradigms for IGA

  3. Relationship between salivary cortisol levels and regional cerebral glucose metabolism in nondemented elderly subjects

    Kwak, Young Bin; Cho, Sang Soo; Lee, Sung Ha; Chey, Jean Yung; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2004-07-01

    Cortisol is a primary stress hormone for flight-or-fight response in human. Increased levels of cortisol have been associated with memory and learning impairments. However, little is known about the role of cortisol on brain/cognitive functions in older adults. We compared regional cerebral glucose metabolism between elderly subjects with high and low cortisol levels using FDG PET. Salivary cortisol levels were measured four times during a day, and an average of the four measurements was used as the standard cortisol level for the analyses. From a population of 120 nondemented elderly subjects, 19 (mean age, 70.1{+-}4.9 y: 2 males and 17 females) were identified as the high (> mean + 1 SD of the total population) cortisol subjects (mean cortisol, 0.69{+-}0.09 {mu} g/dL), while 14 (mean age, 67.2{+-}4.5 y: all females) as the low (< mean 1 SD) cortisol (mean cortisol, 0.27{+-}0.03 {mu} g/dL). A voxel-wise comparison of FDG PET images from the high and low cortisol subjects was performed using SPM99. When compared with the low cortisol group, the high cortisol group had significant hypometabolism in the right middle temporal gyrus, left precuneus, right parahippocampal gyrus, right inferior temporal and superior temporal gyri (P < 0.01 uncorrected, k = 100). There was no significant increase of glucose metabolism in the high cortisol group compared with the low cortisol group (P < 0.01 uncorrected, k = 100). The high cortisol elderly subjects had hypometabolism in the parahippocampal and temporal gyri and precuneus, regions involved in memory and other cognitive functions. This may represent the preclinical metabolic correlates of forthcoming cognitive dysfunction associated with stress in the elderly. Longitudinal studies of brain metabolism and cognitive function are warranted.

  4. Cerebral blood flow and metabolism of the patients with a carotid stenosis evaluated by SPECT and 1H-MRS

    Uno, Masaaki; Nishi, Kyouko; Shinno, Kiyohito; Nagahiro, Shinji; Ohtsuka, Hideki; Harada, Masafumi

    1998-01-01

    We examined cerebral blood flow (CBF) and metabolic states in patients with a severe carotid stenosis by SPECT and proton MRS ( 1 H-MRS). SPECT using 99m Tc-HMPAO and 1 H-MRS were performed in twenty five patients with over 70% carotid stenosis. Moreover, 10 patients were evaluated by these methods after carotid endarterectomy (CEA). N-acetyl-aspartate (NAA) on the ipsilateral side was reduced in 17 patients (Group A) while NAA of other 8 patients was not reduced (Group B). In Group A, although regional CBF was reduced in only 4 of 17 patients, 11 patients showed decline of cerebral vasoreactivity evaluated by acetazolamide injection. Concentration of NAA and regional CBF showed significant correlations. After CEA, ipsilateral NAA was increased significantly compared to preoperative NAA level. In 6 of 7 patients in Group A, cerebral vasoreactivity also improved postoperatively. These results indicated that ipsilatereal NAA metabolism and cerebral vasoreactivity can be improved after CEA. SPECT and 1 H-MRS were useful to evaluate CBF and metabolism in patients with carotid stenosis. (author)

  5. Cerebral blood flow abnormalities induced by transient hypothyroidism after thyroidectomy. Analysis by Tc-99m-HMPAO and SPM96

    Nagamachi, Shigeki; Jinnouchi, Seishi; Nishii, Ryuichi; Ishida, Yasushi; Fujita, Seigo; Futami, Shigemi; Kodama, Takao; Tamura, Shozo; Kawai, Keiichi

    2004-01-01

    The current study is an investigation of alterations in regional cerebral blood flow (rCBF) distribution in patients with transient hypothyroidism after thyroidectomy. In addition, the effects of thyroxine treatment on rCBF changes were studied. Noninvasive rCBF measurements using 99m Tc-HMPAO SPECT were performed on 24 post-thyroidectomy patients who were in a hypothyroidic state. The measurements were conducted before 131 I therapy and after thyroid hormone (thyroxine) replacement. We used adjusted rCBF images (normalization of global CBF for each subject to 50 ml/100 g/min with proportional scaling) to compare these data with age-matched normal control groups (n=15) using statistical parametric mapping (SPM) 96. We also compared the absolute rCBF value of hypothyroidic patients with those of normal control groups. In addition, the association between rCBF alteration and the severity of depression was also analyzed. Finally, the effect of thyroid hormone replacement on rCBF was investigated individually using the Jack-knife test, in which patient data were compared with those from healthy volunteers. According to the result of this test, all cases were categorized into three subgroups, namely, improved, unchanged group and normal. To prove the reversibility of rCBF alteration after thyroid hormone replacement, a group comparison test between the normal controls and the improved group was done before and after thyroid hormone replacement. Similarly a group comparison test between the unchanged group and normal controls was also performed. In the hypothyroidic condition, there was a significant decrease in the posterior part of the bilateral parietal lobes and in part of the bilateral occipital lobes, including the cuneus. These decreased rCBF areas extended to the bilateral prefrontal cortices as deterioration became more profound. On individual analysis, 16 of 24 patients (66.7%) demonstrated rCBF reduction, while 8 patient did not show significant rCBF change

  6. The regulation of cerebral glucose uptake and metabolism in normal and diabetic man

    Polonsky, K.

    1987-01-01

    The effects of changes in serum insulin and glucose on brain glucose metabolism using PET technology were investigated. Eight normal, right-handed, male subjects were studied on three separate occasions at least one week apart. In each subject a PET scan was performed under three different metabolic circumstances: basal conditions after an overnight fast, euglycemic clamp, and hypoglycemic clamp in which the plasma glucose was maintained at 55 mg/dl. Exogenous insulin was infused at the same rate in the euglycemic and hypoglycemic clamp studies. In the latter study, the concomitant glucose infusion rate was reduced to allow the plasma glucose concentration to fall to the desired level of mild hypoglycemia. During each study, dynamic positron emission tomography was used to characterize cerebral uptake and distribution of the Fluorine-18 2-deoxyglucose radiotracer as a function of time. Analysis of the brain uptake curve and tracer input function provided rate constants for transport and phosphorylation in accord with a 3 compartmental model (Sokoloff, 1979). Dynamic scans were performed on each study occasion allowing individual rate constants to be studied. In addition to the brain uptake curves, plasma glucose, F-18 2DG levels and counterregulatory hormone values were determined from frequent arterialized venous blood samples

  7. Altered cerebral blood flow and glucose metabolism in patients with liver disease and minimal encephalopathy

    Lockwood, A.H.; Yap, E.W.; Rhoades, H.M.; Wong, W.H.

    1991-01-01

    We measured CBF and the CMRglc in normal controls and in patients with severe liver disease and evidence for minimal hepatic encephalopathy using positron emission tomography. Regions were defined in frontal, temporal, parietal, and visual cortex; the thalamus; the caudate; the cerebellum; and the white matter along with a whole-slice value obtained at the level of the thalamus. There was no difference in whole-slice CBF and CMRglc values. Individual regional values were normalized to the whole-slice value and subjected to a two-way repeated measures analysis of variance. When normalized CBF and CMRglc values for regions were compared between groups, significant differences were demonstrated (F = 5.650, p = 0.00014 and F = 4.58, p = 0.0073, respectively). These pattern differences were due to higher CBF and CMRglc in the cerebellum, thalamus, and caudate in patients and lower values in the cortex. Standardized coefficients extracted from a discriminant function analysis permitted correct group assignment for 95.5% of the CBF studies and for 92.9% of the CMRglc studies. The similarity of the altered pattern of cerebral metabolism and flow in our patients to that seen in rats subjected to portacaval shunts or ammonia infusions suggests that this toxin may alter flow and metabolism and that this, in turn, causes the clinical expression of encephalopathy

  8. Acupuncture regulates the glucose metabolism in cerebral functional regions in chronic stage ischemic stroke patients---a PET-CT cerebral functional imaging study

    Huang Yong

    2012-06-01

    Full Text Available Abstract Background Acupuncture has been applied to aid in the recovery of post-stroke patients, but its mechanism is unclear. This study aims to analyze the relationship between acupuncture and glucose metabolism in cerebral functional regions in post-stroke patients using 18 FDG PET-CT techniques. Forty-three ischemic stroke patients were randomly divided into 5 groups: the Waiguan (TE5 needling group, the TE5 sham needling group, the sham point needling group, the sham point sham needling group and the non-needling group. Cerebral functional images of all patients were then acquired using PET-CT scans and processed by SPM2 software. Results Compared with the non-needling group, sham needling at TE5 and needling/sham needling at the sham point did not activate cerebral areas. However, needling at TE5 resulted in the activation of Brodmann Area (BA 30. Needling/sham needling at TE5 and needling at the sham point did not deactivate any cerebral areas, whereas sham needling at the sham point led to deactivation in BA6. Compared with sham needling at TE5, needling at TE5 activated BA13, 19 and 47 and did not deactivate any areas. Compared with needling at the sham point, needling at TE5 had no associated activation but a deactivating effect on BA9. Conclusion Needling at TE5 had a regulating effect on cerebral functional areas shown by PET-CT, and this may relate to its impact on the recovery of post-stroke patients.

  9. Gender differences in age-related decline in regional cerebral glucose metabolism

    Bang, Seong Ae; Cho, Sang Soo; Yoon, Eun Jin; Park, Hyun Soo; Lee, Eun Ju; Kim, Yu Kyeong; Kim, Sang Sun

    2007-01-01

    In this study, we investigated gender differences in age-related declines in regional cerebral glucose metabolism using FDG-PET in a large population sample with a broad age range. 230 healthy subjects (90 male; age: 34-80 y, 140 females; age: 33-82 y) participated. Correlation maps showing age related declines in glucose uptake were created separately for each gender in SPM2. Using population-based probabilistic volume of interests (VOIs), VOIs were defined for the regions showing significant decline with aging. Age related declines were separately assessed within each age range using analysis of covariate in SPSS 13.0. In the total population without gender effect, age-related negative correlation of glucose metabolism was found in the bilateral inferior frontal gyri, bilateral caudate, bilateral thalamus, left insula, left superior frontal gyrus, left uncus, right superior temporal gyrus, right medial frontal gyrus, right parahippocampal gyrus, right anterior cingulate gyrus (P < 0.001 corrected, extent threshold k = 100). 14 VOIs values of brain regions were calculated based on this negative correlation results. The rate of decline across all defined VOIs assessed in the age category of 'more than 70' referenced to the category of '30- 39years' were 7.85% in the entire sample; 7.62% in male and 8.09% in female. Detailed analyses of declines in each age range showed separable patterns of declines across gender. In males, greater decline was observed after the age 60 (20.45%) than the ages of 30 and 50(7.98%). Whereas in females, greater declines were found in age 60s (20.15%) compared to 50s, and in 40(14.84%) compared to 30s. Age-related decline in cerebral glucose metabolism was found in both genders. We further observed that males show a relatively constant pattern of decline across a life span; whereas, females show a pattern of steep changes aging to 60s and to 40s, which may be related to changes in sex hormone levels after menopause

  10. Gender differences in age-related decline in regional cerebral glucose metabolism

    Bang, Seong Ae; Cho, Sang Soo; Yoon, Eun Jin; Park, Hyun Soo; Lee, Eun Ju; Kim, Yu Kyeong; Kim, Sang Sun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    In this study, we investigated gender differences in age-related declines in regional cerebral glucose metabolism using FDG-PET in a large population sample with a broad age range. 230 healthy subjects (90 male; age: 34-80 y, 140 females; age: 33-82 y) participated. Correlation maps showing age related declines in glucose uptake were created separately for each gender in SPM2. Using population-based probabilistic volume of interests (VOIs), VOIs were defined for the regions showing significant decline with aging. Age related declines were separately assessed within each age range using analysis of covariate in SPSS 13.0. In the total population without gender effect, age-related negative correlation of glucose metabolism was found in the bilateral inferior frontal gyri, bilateral caudate, bilateral thalamus, left insula, left superior frontal gyrus, left uncus, right superior temporal gyrus, right medial frontal gyrus, right parahippocampal gyrus, right anterior cingulate gyrus (P < 0.001 corrected, extent threshold k = 100). 14 VOIs values of brain regions were calculated based on this negative correlation results. The rate of decline across all defined VOIs assessed in the age category of 'more than 70' referenced to the category of '30- 39years' were 7.85% in the entire sample; 7.62% in male and 8.09% in female. Detailed analyses of declines in each age range showed separable patterns of declines across gender. In males, greater decline was observed after the age 60 (20.45%) than the ages of 30 and 50(7.98%). Whereas in females, greater declines were found in age 60s (20.15%) compared to 50s, and in 40(14.84%) compared to 30s. Age-related decline in cerebral glucose metabolism was found in both genders. We further observed that males show a relatively constant pattern of decline across a life span; whereas, females show a pattern of steep changes aging to 60s and to 40s, which may be related to changes in sex hormone levels after menopause.

  11. Effects and mechanisms of caffeine to improve immunological and metabolic abnormalities in diet-induced obese rats.

    Liu, Chih-Wei; Tsai, Hung-Cheng; Huang, Chia-Chang; Tsai, Chang-Youh; Su, Yen-Bo; Lin, Ming-Wei; Lee, Kuei-Chuan; Hsieh, Yun-Cheng; Li, Tzu-Hao; Huang, Shiang-Fen; Yang, Ying-Ying; Hou, Ming-Chih; Lin, Han-Chieh; Lee, Fa-Yauh; Lee, Shou-Dong

    2018-05-01

    In obesity, there are no effective therapies for parallel immune and metabolic abnormalities, including systemic/tissue insulin-resistance/inflammation, adiposity and hepatic steatosis. Caffeine has anti-inflammation, antihepatic steatosis, and anti-insulin resistance effects. In this study, we evaluated the effects and molecular mechanisms of 6 wk of caffeine treatment (HFD-caf) on immunological and metabolic abnormalities of high-fat diet (HFD)-induced obese rats. Compared with HFD vehicle (HFD-V) rats, in HFD-caf rats the suppressed circulating immune cell inflammatory [TNFα, MCP-1, IL-6, intercellular adhesion molecule 1 (ICAM-1), and nitrite] profiles were accompanied by decreased liver, white adipose tissue (WAT), and muscle macrophages and their intracellular cytokine levels. Metabolically, the increase in metabolic rates reduced lipid accumulation in various tissues, resulting in reduced adiposity, lower fat mass, decreased body weight, amelioration of hepatic steatosis, and improved systemic/muscle insulin resistance. Further mechanistic approaches revealed an upregulation of tissue lipogenic [(SREBP1c, fatty acid synthase, acetyl-CoA carboxylase)/insulin-sensitizing (GLUT4 and p-IRS1)] markers in HFD-caf rats. Significantly, ex vivo experiments revealed that the cytokine release by the cocultured peripheral blood mononuclear cell (monocyte) and WAT (adipocyte), which are known to stimulate macrophage migration and hepatocyte lipogenesis, were lower in HFD-V groups than HFD-caf groups. Caffeine treatment simultaneously ameliorates immune and metabolic pathogenic signals present in tissue to normalize immunolgical and metabolic abnormalities found in HFD-induced obese rats.

  12. Cerebral vasculitis

    Greenan, T.J.; Grossman, R.I.

    1990-01-01

    This paper reviews retrospectively MR, CT, and angiographic findings in patients with cerebral vasculitis in order to understand the strengths and weaknesses of the various imaging modalities, as well as the spectrum of imaging abnormalities in this disease entity. Studies were retrospectively reviewed in 12 patients with cerebral vasculitis proved by means of angiography and/or brain biopsy

  13. Cerebral blood flow and metabolic patterns as predictors of response to bilateral anterior capsulotomy for obsessive-compulsive disorder: a retrospective study

    Borbely, K.; Babel, B.; Tron, L.; Nemeth, A.; Pataki, E.; Csigo, E.; Morocz, K.; Lukacs, E.

    2002-01-01

    Aims: Earlier Single Photon Emission Tomography (SPECT) and Positron Emission Tomography (PET) studies of patients with Obsessive-Compulsive Disorder (OCD) have demonstrated abnormal regional Cerebral Blood Flow (rCBF) and Cerebral Glucose Metabolic (rCGlM) pattern in the orbitofrontal-basal ganglia-thalamo-cortical circuits (OBgThC). OCD is characterized by intrusive, repetitive thoughts and/or behaviors that cause marked distress. In case of a severe, and medically and/or psycho therapeutically intractable disease surgical therapy remains the only possible solution. The purpose of this study was to evaluate rCBF and rCGlM patterns as potential predictors of treatment response to bilateral anterior capsulotomy. We performed rCBF SPECT and rCGlM PET studies in 5 patients with severe, intractable OCD before and after (3, 6 and 12 months) surgical therapy. Methods: The assessment included neurological, psychiatrical examination, CT, MRI, and neuropsychological evaluation. 99mTc-HMPAO-SPECT and 18F-FDG-PET studies were carried out with a standard technique for each patient. The data were analyzed visually and by a special region of interests (ROIs) program. The rCBF SPECT and glucose metabolic PET results were compared to clinical and neuropsychological findings. Results: The SPECT and PET measurements showed significant (p<0.05) rCBF and metabolic abnormalities in caudate nuclei, thalamus, singular and orbitofrontal cortex. There was a marked, but individually variable rCBF and rCGlM pattern before and after surgery. Additionally, the preoperative and postoperative rCBF and rCGlM data proved to be concordant with clinical and neuropsychological findings. Conclusion: Both SPECT and PET (before and after surgery) proved to be concordant with clinical and neuropsychological findings. However, rCGlM PET measurements had a higher sensitivity. Patients with higher preoperative rCBF and rCGlM rates of OBgThC circuits were associated with a better postoperative outcome. RCBF

  14. The number of metabolic abnormalities associated with the risk of gallstones in a non-diabetic population.

    Chung-Hung Tsai

    Full Text Available AIM: To evaluate whether metabolic syndrome is associated with gallstones, independent of hepatitis C infection or chronic kidney disease (CKD, in a non-diabetic population. MATERIALS AND METHODS: A total of 8,188 Chinese adult participants that underwent a self-motivated health examination were recruited into the final analysis after excluding the subjects who had a history of cholecystectomy, diabetes mellitus, or were currently using antihypertensive or lipid-lowering agents. Gallstones were defined by the presence of strong intraluminal echoes that were gravity-dependent or that attenuated ultrasound transmission. RESULTS: A total of 447 subjects (5.5% had gallstones, with 239 (5.1% men and 208 (6.0% women. After adjusting for age, gender, obesity, education level, and lifestyle factors, included current smoking, alcohol drinking, regular exercise, hepatitis B, hepatitis C, and CKD, there was a positive association between metabolic syndrome and gallstones. Moreover, as compared to subjects without metabolic abnormalities, subjects with one, two, and three or more suffered from a 35, 40, and 59% higher risk of gallstones, respectively. CONCLUSIONS: Non-diabetic subjects with metabolic syndrome had a higher risk of gallstones independent of hepatitis C or CKD, and a dose-dependent effect of metabolic abnormalities also exists.

  15. Comparison of Cerebral Glucose Metabolism between Possible and Probable Multiple System Atrophy

    Kyum-Yil Kwon

    2009-05-01

    Full Text Available Background: To investigate the relationship between presenting clinical manifestations and imaging features of multisystem neuronal dysfunction in MSA patients, using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET. Methods: We studied 50 consecutive MSA patients with characteristic brain MRI findings of MSA, including 34 patients with early MSA-parkinsonian (MSA-P and 16 with early MSA-cerebellar (MSA-C. The cerebral glucose metabolism of all MSA patients was evaluated in comparison with 25 age-matched controls. 18F-FDG PET results were assessed by the Statistic Parametric Mapping (SPM analysis and the regions of interest (ROI method. Results: The mean time from disease onset to 18F-FDG PET was 25.9±13.0 months in 34 MSA-P patients and 20.1±11.1 months in 16 MSA-C patients. Glucose metabolism of the putamen showed a greater decrease in possible MSA-P than in probable MSA-P (p=0.031. Although the Unified Multiple System Atrophy Rating Scale (UMSARS score did not differ between possible MSA-P and probable MSA-P, the subscores of rigidity (p=0.04 and bradykinesia (p= 0.008 were significantly higher in possible MSA-P than in probable MSA-P. Possible MSA-C showed a greater decrease in glucose metabolism of the cerebellum than probable MSA-C (p=0.016. Conclusions: Our results may suggest that the early neuropathological pattern of possible MSA with a predilection for the striatonigral or olivopontocerebellar system differs from that of probable MSA, which has prominent involvement of the autonomic nervous system in addition to the striatonigral or olivopontocerebellar system.

  16. Individual cerebral metabolic deficits in Alzheimer's disease and amnestic mild cognitive impairment: an FDG PET study

    Del Sole, Angelo; Lecchi, Michela; Lucignani, Giovanni; Clerici, Francesca; Mariani, Claudio; Maggiore, Laura; Chiti, Arturo; Mosconi, Lisa

    2008-01-01

    The purpose of the study was the identification of group and individual subject patterns of cerebral glucose metabolism (CMRGlu) in patients with Alzheimer's disease (AD) and with amnestic mild cognitive impairment (aMCI). [ 18 F]fluorodeoxyglucose positron emission tomography (PET) studies and neuropsychological tests were performed in 16 aMCI patients (ten women, age 75 ± 8 years) and in 14 AD patients (ten women, age 75 ± 9 years). Comparisons between patient subgroups and with a control population were performed using Statistical Parametric Mapping. Clusters of low CMRGlu were observed bilaterally in the posterior cingulate cortex (PCC), in the precuneus, in the inferior parietal lobule and middle temporal gyrus of AD patients. In aMCI patients, reduced CMRGlu was found only in PCC. Areas of low CMRGlu in PCC were wider in AD compared to aMCI and extended to the precuneus, while low CMRGlu was found in the lateral parietal cortex in AD but not in aMCI patients. Individual subject pattern analysis revealed that 86% of AD patients had low CMRGlu in the PCC (including the precuneus in 71%), 71% in the temporal cortex, 64% in the parietal cortex and 35% in the frontal cortex. Among the aMCI patients, 56% had low CMRGlu in the PCC, 44% in the temporal cortex, 18% in the frontal cortex and none in the parietal cortex. This study demonstrates that both AD and aMCI patients have highly heterogeneous metabolic impairment. This potential of individual metabolic PET imaging in patients with AD and aMCI may allow timely identification of brain damage on individual basis and possibly help planning tailored early interventions. (orig.)

  17. Revealing the cerebral regions and networks mediating vulnerability to depression: oxidative metabolism mapping of rat brain.

    Harro, Jaanus; Kanarik, Margus; Kaart, Tanel; Matrov, Denis; Kõiv, Kadri; Mällo, Tanel; Del Río, Joaquin; Tordera, Rosa M; Ramirez, Maria J

    2014-07-01

    The large variety of available animal models has revealed much on the neurobiology of depression, but each model appears as specific to a significant extent, and distinction between stress response, pathogenesis of depression and underlying vulnerability is difficult to make. Evidence from epidemiological studies suggests that depression occurs in biologically predisposed subjects under impact of adverse life events. We applied the diathesis-stress concept to reveal brain regions and functional networks that mediate vulnerability to depression and response to chronic stress by collapsing data on cerebral long term neuronal activity as measured by cytochrome c oxidase histochemistry in distinct animal models. Rats were rendered vulnerable to depression either by partial serotonergic lesion or by maternal deprivation, or selected for a vulnerable phenotype (low positive affect, low novelty-related activity or high hedonic response). Environmental adversity was brought about by applying chronic variable stress or chronic social defeat. Several brain regions, most significantly median raphe, habenula, retrosplenial cortex and reticular thalamus, were universally implicated in long-term metabolic stress response, vulnerability to depression, or both. Vulnerability was associated with higher oxidative metabolism levels as compared to resilience to chronic stress. Chronic stress, in contrast, had three distinct patterns of effect on oxidative metabolism in vulnerable vs. resilient animals. In general, associations between regional activities in several brain circuits were strongest in vulnerable animals, and chronic stress disrupted this interrelatedness. These findings highlight networks that underlie resilience to stress, and the distinct response to stress that occurs in vulnerable subjects. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism

    Trangmar, Steven J; Chiesa, Scott T; Llodio, Iñaki

    2015-01-01

    Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, whereas the cerebral metabolic rate for O2 (CMRO2 ) is preserved. It remains unknown whether CMRO2 is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled...... to fatigue. Two studies were undertaken. In study 1, 10 male cyclists cycled in the heat for ∼2 h with (control) and without fluid replacement (dehydration) while internal and external carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples...... were assessed with dehydration to evaluate CMRO2 . In study 2, in 8 male subjects, middle cerebral artery blood velocity was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, internal carotid artery flow declined...

  19. PGC-1alpha Deficiency Causes Multi-System Energy Metabolic Derangements: Muscle Dysfunction, Abnormal Weight Control and Hepatic Steatosis

    Leone Teresa C

    2005-01-01

    Full Text Available The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha was targeted in mice. PGC-1alpha null (PGC-1alpha-/- mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1alpha-/- mice. With age, the PGC-1alpha-/- mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1alpha-/- mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha-/- mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha-/- mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha-/- mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha-/- mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1alpha-/- mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.

  20. PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis.

    Teresa C Leone

    2005-04-01

    Full Text Available The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha was targeted in mice. PGC-1alpha null (PGC-1alpha(-/- mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1alpha(-/- mice. With age, the PGC-1alpha(-/- mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1alpha(-/- mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha(-/- mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha(-/- mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha(-/- mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha(-/- mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1alpha(-/- mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.

  1. A novel Bayesian approach to accounting for uncertainty in fMRI-derived estimates of cerebral oxygen metabolism fluctuations.

    Simon, Aaron B; Dubowitz, David J; Blockley, Nicholas P; Buxton, Richard B

    2016-04-01

    Calibrated blood oxygenation level dependent (BOLD) imaging is a multimodal functional MRI technique designed to estimate changes in cerebral oxygen metabolism from measured changes in cerebral blood flow and the BOLD signal. This technique addresses fundamental ambiguities associated with quantitative BOLD signal analysis; however, its dependence on biophysical modeling creates uncertainty in the resulting oxygen metabolism estimates. In this work, we developed a Bayesian approach to estimating the oxygen metabolism response to a neural stimulus and used it to examine the uncertainty that arises in calibrated BOLD estimation due to the presence of unmeasured model parameters. We applied our approach to estimate the CMRO2 response to a visual task using the traditional hypercapnia calibration experiment as well as to estimate the metabolic response to both a visual task and hypercapnia using the measurement of baseline apparent R2' as a calibration technique. Further, in order to examine the effects of cerebral spinal fluid (CSF) signal contamination on the measurement of apparent R2', we examined the effects of measuring this parameter with and without CSF-nulling. We found that the two calibration techniques provided consistent estimates of the metabolic response on average, with a median R2'-based estimate of the metabolic response to CO2 of 1.4%, and R2'- and hypercapnia-calibrated estimates of the visual response of 27% and 24%, respectively. However, these estimates were sensitive to different sources of estimation uncertainty. The R2'-calibrated estimate was highly sensitive to CSF contamination and to uncertainty in unmeasured model parameters describing flow-volume coupling, capillary bed characteristics, and the iso-susceptibility saturation of blood. The hypercapnia-calibrated estimate was relatively insensitive to these parameters but highly sensitive to the assumed metabolic response to CO2. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. A novel Bayesian approach to accounting for uncertainty in fMRI-derived estimates of cerebral oxygen metabolism fluctuations

    Simon, Aaron B.; Dubowitz, David J.; Blockley, Nicholas P.; Buxton, Richard B.

    2016-01-01

    Calibrated blood oxygenation level dependent (BOLD) imaging is a multimodal functional MRI technique designed to estimate changes in cerebral oxygen metabolism from measured changes in cerebral blood flow and the BOLD signal. This technique addresses fundamental ambiguities associated with quantitative BOLD signal analysis; however, its dependence on biophysical modeling creates uncertainty in the resulting oxygen metabolism estimates. In this work, we developed a Bayesian approach to estimating the oxygen metabolism response to a neural stimulus and used it to examine the uncertainty that arises in calibrated BOLD estimation due to the presence of unmeasured model parameters. We applied our approach to estimate the CMRO2 response to a visual task using the traditional hypercapnia calibration experiment as well as to estimate the metabolic response to both a visual task and hypercapnia using the measurement of baseline apparent R2′ as a calibration technique. Further, in order to examine the effects of cerebral spinal fluid (CSF) signal contamination on the measurement of apparent R2′, we examined the effects of measuring this parameter with and without CSF-nulling. We found that the two calibration techniques provided consistent estimates of the metabolic response on average, with a median R2′-based estimate of the metabolic response to CO2 of 1.4%, and R2′- and hypercapnia-calibrated estimates of the visual response of 27% and 24%, respectively. However, these estimates were sensitive to different sources of estimation uncertainty. The R2′-calibrated estimate was highly sensitive to CSF contamination and to uncertainty in unmeasured model parameters describing flow-volume coupling, capillary bed characteristics, and the iso-susceptibility saturation of blood. The hypercapnia-calibrated estimate was relatively insensitive to these parameters but highly sensitive to the assumed metabolic response to CO2. PMID:26790354

  3. The study of regional cerebral glucose metabolic change in human being normal aging process by using PET scanner

    Si Mingjue; Huang Gang

    2008-01-01

    Objective: With the technique development, PET has been more and more applied in brain function research. The aim of this study was to investigate the tendency of regional cerebral glucose metabolism changes in human being normal aging process by using 18 F-fluorodeoxyglucose (FDG) PET/CT and statistical parametric mapping (SPM) software. Methods: 18 F-FDG PET/CT brain imaging data acquired from 252 healthy normal subjects (age ranging: 21 to 88 years old) were divided into 6 groups according to their age: 21-30, 31-40, 41-50, 51-60, 61-70, 71-88. All 5 groups with age ≥31 years old were compared to the control group of 21-30 years old, and pixel-by-pixel t-statistic analysis was applied using the SPM2. The hypo-metabolic areas were identified by MNI space utility (MSU) software and the voxel value of each brain areas were calculated (P 60 years old showed significant metabolic decreases with aging mainly involved bilateral frontal lobe (pre-motto cortex, dorsolateral prefrontal cortex, frontal pole), temporal lobe (temporal pole), insula, anterior cingulate cortex and cerebellum. The most significant metabolic decrease area with aging was the frontal lobe , followed by the anterior cingulate cortex, temporal lobe, insula and cerebellum at predominance right hemisphere (P<0.0001). Parietal lobe, parahippocampal gyrus, basal ganglia and thalamus remain metabolically unchanged with advancing aging. Conclusions: Cerebral metabolic function decrease with normal aging shows an inconstant and unsymmetrical process. The regional cerebral metabolic decrease much more significantly in older than 60 years old healthy volunteers, mainly involving bilateral frontal lobe, temporal lobe, insula, anterior cingulate cortex and cerebellum at right predominance hemisphere. (authors)

  4. Do obese but metabolically normal women differ in intra-abdominal fat and physical activity levels from those with the expected metabolic abnormalities? A cross-sectional study

    Walker Mark

    2010-11-01

    Full Text Available Abstract Background Obesity remains a major public health problem, associated with a cluster of metabolic abnormalities. However, individuals exist who are very obese but have normal metabolic parameters. The aim of this study was to determine to what extent differences in metabolic health in very obese women are explained by differences in body fat distribution, insulin resistance and level of physical activity. Methods This was a cross-sectional pilot study of 39 obese women (age: 28-64 yrs, BMI: 31-67 kg/m2 recruited from community settings. Women were defined as 'metabolically normal' on the basis of blood glucose, lipids and blood pressure. Magnetic Resonance Imaging was used to determine body fat distribution. Detailed lifestyle and metabolic profiles of participants were obtained. Results Women with a healthy metabolic profile had lower intra-abdominal fat volume (geometric mean 4.78 l [95% CIs 3.99-5.73] vs 6.96 l [5.82-8.32] and less insulin resistance (HOMA 3.41 [2.62-4.44] vs 6.67 [5.02-8.86] than those with an abnormality. The groups did not differ in abdominal subcutaneous fat volume (19.6 l [16.9-22.7] vs 20.6 [17.6-23.9]. A higher proportion of those with a healthy compared to a less healthy metabolic profile met current physical activity guidelines (70% [95% CIs 55.8-84.2] vs 25% [11.6-38.4]. Intra-abdominal fat, insulin resistance and physical activity make independent contributions to metabolic status in very obese women, but explain only around a third of the variance. Conclusion A sub-group of women exists who are metabolically normal despite being very obese. Differences in fat distribution, insulin resistance, and physical activity level are associated with metabolic differences in these women, but account only partially for these differences. Future work should focus on strategies to identify those obese individuals most at risk of the negative metabolic consequences of obesity and on identifying other factors that

  5. Role of 99mTc-ECD brain SPECT in the detection of cerebral perfusion abnormality in cases of Attention Deficit Hyperactivity Disorder

    Kumar, A.; Phom, H.; Thomas, E.J.; Tripathi, M.; Chandrashekar, N.; Bal, C.S.; Zamir, H.; Gulati, S.; Kalra, V.

    2002-01-01

    Aim: A randomized placebo controlled drug trial with Mentat, a herbal pharmacological agent, was initiated in January 2000 in the department of pediatrics at AIIMS, New Delhi, to compare the efficacy of Mentat with a placebo in school children with Attention Deficit Hyperactivity Disorder (ADHD). Materials and Methods: Contact was established with 12 Public schools in Delhi, to identify poor performers in classes I-V (age 6-12 yrs.). About 195 children with poor school performance were recruited in the study. They were screened for causes of poor performance, which included attention problems, hyperactivity, behavior problems, emotional problems, mental sub-normality and learning disability. ADHD suspected children were identified using the Malin's WISC, Connor's rating scale, Problem Behavior checklist, Bender Gestalt test and some sub tests of the Kaufman's Assessment Battery for Children (K-ABC). Sixty children diagnosed as ADHD (using DSM-IV criteria), with an IQ between 90-110, were enrolled into the study. Of the 60 children randomized in the study, 30 received Mentat and 30 received an identical looking placebo. The drug/Placebo was given for a six-month period. 99mTC-ECD brain SPECT was performed in a subset of 34 children with ADHD. Results: Abnormal cerebral perfusion was seen in 23/34; thalamic hypoperfusion in 11, basal ganglia hypoperfusion in 9, thalamus and basal ganglia hypoperfusion in 2 and basifrontal hypoperfusion in 1. So far, in ten children with abnormal pretreatment scans, post treatment scans have also been done. In mentat group, 2/5 children showed normalization of perfusion abnormality after treatment whereas in placebo group, 1/5. Conclusion: This study suggests that there is selective focal cerebral hypoperfusion in cases of ADHD and 99mTc-ECD brain SPECT can be used for evaluation and further monitoring of therapeutic outcome in such cases

  6. PRECIPITATING FACTORS, CLINICAL PROFILE AND METABOLIC ABNORMALITIES OF DIABETIC KETOACIDOSIS IN CHILDREN WITH TYPE 1 DIABETES AND THEIR ROLE IN PREDICTING THE OUTCOME

    Madhava Vijaya Kumar

    2017-01-01

    Full Text Available BACKGROUND The aim of the study is to study the clinical profile of diabetic ketoacidosis in children with type 1 diabetes to identify the precipitating factors, to assess the metabolic alterations due to this illness and to correlate these parameters with the outcome. MATERIALS AND METHODS This was a prospective observational study and 33 children admitted in PICU during the study period were recruited for the study. RESULTS 24 children were newly-diagnosed cases and 9 children were already established cases of type 1 diabetes. Mean age group was 10.7 years. Major precipitating causes of DKA in established cases were intercurrent respiratory infections and omission of insulin. Nausea, vomiting, thirst and polyuria were the most common symptoms. Mean duration of symptoms before diagnosing DKA were 20 days in newly-diagnosed cases and 4 days in established cases. ¾ of children had dehydration at the time of admission. Severity was more in younger children. Commonest biochemical abnormality was hypokalaemia. Late diagnosis and delay in the initiation of treatment were the commonest predisposing factors for the development of cerebral oedema. CONCLUSION DKA is a life-threatening complication of type 1 diabetes and the red flag signs of bad outcome were young age, late diagnosis, late referral and late initiation of treatment. Hence, a high index of suspicion is necessary to diagnose DKA in first presentation of diabetes as well as in established cases.

  7. Prevalence of coronary artery disease in Japanese patients with cerebral infarction. Impact of metabolic syndrome and intracranial large artery atherosclerosis

    Hoshino, Atsushi; Enomoto, Satoko; Kawahito, Hiroyuki; Nakamura, Takashi; Kurata, Hiroyuki; Nakahara, Yoshifumi; Ijichi, Toshiharu

    2008-01-01

    Patients with cerebral infarction have a high prevalence of asymptomatic coronary artery disease (CAD) and other vascular diseases, but there is a lack of such data for Japanese patients, so the present study investigated the prevalence of cardiovascular disease (CVD) in Japanese patients and determined the predictors of CAD. The study group comprised 104 patients with cerebral infarction who had no history of CVD. All patients underwent coronary computed tomographic angiography, and systematic evaluation was done on the basis of the presence of other vascular diseases, CVD risk markers, and the degree of atherosclerosis. Of the total, 39 patients (37.5%) had CAD, 9 (8.7%) had carotid artery stenosis, 9 (8.7%) had peripheral artery disease of the lower limbs, and 3 (2.9%) had atherosclerotic renal artery stenosis. Multiple regression analysis showed that the presence of CAD was independently associated with metabolic syndrome (odds ratio (OR) 5.008, 95% confidence interval (CI) 1.538-16.309; p<0.01) and intracranial large artery atherosclerosis (OR 4.979, 95% CI 1.633-15.183; p<0.01). Japanese patients with cerebral infarction have a high prevalence of CVD, especially asymptomatic CAD. Both metabolic syndrome and intracranial large artery atherosclerosis may be potential predictors for identifying patients with cerebral infarction who are at the highest risk of asymptomatic CAD. (author)

  8. Effect of STA-proximal MCA bypass. Improvement of cerebral blood flow and metabolism and neuropsychological function

    Ogawa, Akira; Funayama, Masayuki; Miura, Kazuyuki; Ogasawara, Kuniaki; Suzuki, Michiyasu; Kuroda, Kiyoshi; Sasaki, Toshiaki

    1998-01-01

    We investigated cerebral blood flow (CBF) and metabolism in patients with hemodynamic ischemia by positron emission tomography (PET) and thermal diffusion flow meter. We also studied neuropsychological functions to evaluate the effects of surgical revascularization. Bypass surgery of the superficial temporal artery to the proximal middle cerebral artery was performed on 26 patients satisfying the following categories: stenosis or occlusive lesion in main cerebral arteries; no marked focus of infarction on CT or MRI. PET was performed before and 1 month after the operation, and CBF, the cerebral metabolic rate of oxygen (CMRO 2 ) and oxygen extraction fraction (OEF) were analyzed. Cerebrovascular reserve capacity (CVRC) was also calculated after acetazolamide challenge. CBF during the operation was continuously measured with a thermal diffusion flow meter. CO 2 response of CBF was analyzed before and after anastomosis. Neuropsychological functions were evaluated by Hasegawa dementia scale revised (HDS-R), mini-mental state examination (MMSE) and Wechsler adult intelligence scale revised (WAIS-R). Before the operation, increase in OEF accorded with the decrease in CBF, and a significant relationship between both CBF and CVRC, and OEF and CVRC was found. A decrease in CVRC was noted prior to a decrease in CBF and elevation of OEF. CVRC caused by acetazolamide might reflect CO 2 reactivity. Significant improvement of CBF and CVRC, and normalization of OEF were observed after the operation. Also, significant improvement of neuropsychological function was observed by HDS-R and WAIS-R. Disturbance in neuropsychological function might reflect elevation of OEF. (author)

  9. Positron emission tomography in cerebrovascular disease: The relationship between regional cerebral blood flow, blood volume and oxygen metabolism

    Herold, S.

    1985-03-01

    Positron emission tomography in cerebrovascular disease has demonstrated the importance of the relationship between regional cerebral blood flow and the cerebral metabolic activity. In acute stroke it has been found that within the first hours after the onset of symptoms cerebral blood flow in the affected area is more depressed than cerebral oxygen utilisation. This relative preservation of oxygen utilisation results from an increase in the oxygen extraction ratio far above its normal value. However, the oxygen extraction fraction subsequently falls in the following days indicating the transition from a situation of possibly reversible ischaemia to irreversible infarction. In patients with carotid occlusive disease an increase in the oxygen extraction ratio has been observed only in very few cases. It has been shown, however, that at an earlier stage the relationship between CBF and CBV (as CBF/CBV-ratio) provides a sensitive measure of diminished perfusion pressure which could be helpful for the selection of patients for EC-IC bypass surgery. In patients with sickle cell anaemia it has been found that oxygen delivery to the brain is maintained by an increase in cerebral blood flow, whereas the oxygen extraction ratio is not increased despite the presence of a low oxygen affinity haemoglobin. Preliminary observations in classical migraine suggest an ischaemic situation during the attack.

  10. Non-selective beta-adrenergic blockade prevents reduction of the cerebral metabolic ratio during exhaustive exercise in humans

    Larsen, T.S.; Rasmussen, P.; Overgaard, M.

    2008-01-01

    Intense exercise decreases the cerebral metabolic ratio of oxygen to carbohydrates [O(2)/(glucose + (1/2)lactate)], but whether this ratio is influenced by adrenergic stimulation is not known. In eight males, incremental cycle ergometry increased arterial lactate to 15.3 +/- 4.2 mm (mean +/- s.......d.) and the arterial-jugular venous (a-v) difference from -0.02 +/- 0.03 mm at rest to 1.0 +/- 0.5 mm (P cerebral metabolic ratio decreased from 5.5 +/- 1.4 to 3.0 +/- 0.3 (P ... of a non-selective beta-adrenergic (beta(1) + beta(2)) receptor antagonist (propranolol) reduced heart rate (69 +/- 8 to 58 +/- 6 beats min(-1)) and exercise capacity (239 +/- 42 to 209 +/- 31 W; P

  11. Local cerebral metabolic rate of glucose (lCMRGlc) in treated and untreated patients with Parkinson's disease

    Rougemont, D; Baron, J C; Collard, P; Bustany, P; Comar, D; Agid, Y

    1983-06-01

    Local cerebral metabolic rate of glucose (lCMRGlc) was measured twice, using positron emission tomography and /sup 18/F-Fluoro-2-deoxy-D-glucose (/sup 18/FDG), in 4 patients with Parkinson disease, first unmedicated and then treated with L-DOPA. Despite a dramatic clinical improvement, no significant changes in lCMRGlc could be detected. Moreover, no reproducible differences of lCMRGlc were found between patients with Parkinson disease and with normal brain.

  12. Local cerebral metabolic rate of glucose (lCMRGlc) in treated and untreated patients with Parkinson's disease

    Rougemont, D.; Baron, J.C.; Collard, P.; Bustany, P.; Comar, D.; Agid, Y.

    1983-06-01

    Local cerebral metabolic rate of glucose (lCMRGlc) was measured twice, using positron emission tomography and 18 F-Fluoro-2-deoxy-D-glucose ( 18 FDG), in 4 patients with Parkinson disease, first unmedicated and then treated with L-DOPA. Despite a dramatic clinical improvement, no significant changes in lCMRGlc could be detected. Moreover, no reproducible differences of lCMRGlc were found between patients with Parkinson disease and with normal brain

  13. Two patterns of cerebral metabolite abnormalities are detected on proton magnetic resonance spectroscopy in HIV-infected subjects commencing antiretroviral therapy

    Winston, Alan; Taylor-Robinson, Simon D.; Duncombe, Chris; Li, Patrick C.K.; Gill, John M.; Kerr, Stephen J.; Puls, Rebekah L.; Emery, Sean; Cooper, David A.

    2012-01-01

    Cerebral function impairment remains problematic in subjects with chronic human immunodeficiency virus (HIV) infection despite effective combination antiretroviral therapy (cART). Using cerebral proton magnetic resonance spectroscopy ( 1 H MRS), we aimed to determine if abnormalities could be detected in neurologically asymptomatic HIV-infected subjects electively commencing cART. Therapy-naive, HIV-infected individuals and HIV-uninfected controls underwent 1 H MRS in several anatomical voxels including the mid-frontal grey matter (FGM) and right basal ganglia (RBG). Differences in cerebral metabolite ratios between groups and correlations between immune and virological status were assessed. Forty-six subjects were recruited (26 HIV-infected and 20 control subjects). In the HIV-infected group, mean CD4+ count (SD, cells per microlitre) and plasma HIV RNA (SD, log10 copies per millilitre) were 192 (86) and 4.71 (0.64), respectively. Choline (Cho)/Creatine (Cr) and myoinositol (MI)/Cr ratios were significantly lower in the FGM in HIV-infected subjects compared to controls (0.67 (0.14) versus 0.88 (0.49), p = 0.036, and 0.94 (0.28) and 1.17 (0.26), p = 0.008, for Cho/Cr and MI/Cr, respectively) and Cho/Cr ratio associated with CD4+ lymphocyte count (p = 0.041). N-Acetyl-aspartate (NAA)/Cho ratio was significantly lower in the RBG in HIV-infected subjects compared to controls (2.27 (0.54) versus 2.63 (0.68), p = 0.002), and this was associated with greater plasma HIV RNA load (p = 0.014). Two patterns of cerebral metabolite abnormalities were observed in HIV-infected subjects electively commencing cART. Greater inflammatory metabolite ratios (Cho/Cr and MI/Cr) associated with lower markers of peripheral immune markers (CD4+ lymphocyte count) in the FGM and lower neuronal metabolite ratios (NAA/Cho) associated with greater HIV viraemia in the RBG were present in HIV-infected subjects. (orig.)

  14. Two patterns of cerebral metabolite abnormalities are detected on proton magnetic resonance spectroscopy in HIV-infected subjects commencing antiretroviral therapy

    Winston, Alan; Taylor-Robinson, Simon D. [Imperial College London, St. Mary' s Hospital, London (United Kingdom); Duncombe, Chris [HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok (Thailand); Li, Patrick C.K. [Queen Elizabeth Hospital, Hong Kong (China); Gill, John M. [Calgary Regional Health Authority, Calgary (Canada); Kerr, Stephen J. [HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok (Thailand); University of New South Wales, National Centre in HIV Epidemiology and Clinical Research, Sydney, NSW (Australia); Puls, Rebekah L.; Emery, Sean; Cooper, David A. [University of New South Wales, National Centre in HIV Epidemiology and Clinical Research, Sydney, NSW (Australia); Collaboration: for the Altair Study Group

    2012-12-15

    Cerebral function impairment remains problematic in subjects with chronic human immunodeficiency virus (HIV) infection despite effective combination antiretroviral therapy (cART). Using cerebral proton magnetic resonance spectroscopy ({sup 1}H MRS), we aimed to determine if abnormalities could be detected in neurologically asymptomatic HIV-infected subjects electively commencing cART. Therapy-naive, HIV-infected individuals and HIV-uninfected controls underwent {sup 1}H MRS in several anatomical voxels including the mid-frontal grey matter (FGM) and right basal ganglia (RBG). Differences in cerebral metabolite ratios between groups and correlations between immune and virological status were assessed. Forty-six subjects were recruited (26 HIV-infected and 20 control subjects). In the HIV-infected group, mean CD4+ count (SD, cells per microlitre) and plasma HIV RNA (SD, log10 copies per millilitre) were 192 (86) and 4.71 (0.64), respectively. Choline (Cho)/Creatine (Cr) and myoinositol (MI)/Cr ratios were significantly lower in the FGM in HIV-infected subjects compared to controls (0.67 (0.14) versus 0.88 (0.49), p = 0.036, and 0.94 (0.28) and 1.17 (0.26), p = 0.008, for Cho/Cr and MI/Cr, respectively) and Cho/Cr ratio associated with CD4+ lymphocyte count (p = 0.041). N-Acetyl-aspartate (NAA)/Cho ratio was significantly lower in the RBG in HIV-infected subjects compared to controls (2.27 (0.54) versus 2.63 (0.68), p = 0.002), and this was associated with greater plasma HIV RNA load (p = 0.014). Two patterns of cerebral metabolite abnormalities were observed in HIV-infected subjects electively commencing cART. Greater inflammatory metabolite ratios (Cho/Cr and MI/Cr) associated with lower markers of peripheral immune markers (CD4+ lymphocyte count) in the FGM and lower neuronal metabolite ratios (NAA/Cho) associated with greater HIV viraemia in the RBG were present in HIV-infected subjects. (orig.)

  15. Cerebral perfusion and metabolism in relation to the evolution of unilateral spatial neglect due to cerebral infarction. Contribution of bilateral hemispheres in appearance and recovery

    Kato, Haruhisa

    2006-01-01

    To investigate the mechanisms underlying the evolution of unilateral spatial neglect (USN) due to cerebral infarction, the cerebral oxygen metabolism was measured quantitatively by positron emission tomography (PET). Out of 189 consecutive patients with right hemisphere lesions who underwent PET, we recruited 13 patients (group A) who exhibited USN at the time of PET examination, 11 patients (group B) who had already recovered from USN, and 27 patients (group C) with right hemisphere infarction who failed to present with USN throughout. Eight normal volunteers (group NV) served as controls. Statistical comparisons were performed on the local values of the cerebral metabolic rate of oxygen (CMRO 2 ) from the region of interest (ROI) in the right dorsolateral frontal lobe, superior temporal gyrus, inferior parietal lobule, cingulate gyrus, basal ganglia and thalamus which are associated with USN. We also obtained CMRO 2 values for the contralateral areas. As compared with group C or NV, there were significant decreases in CMRO 2 in the right frontal, right temporal and right parietal lobes, right basal ganglia, right thalamus and bilateral cingulate gyri in groups A and B. Except for the left inferior parietal lobule, no significant differences in regional CMRO 2 were noted between groups A and B. These findings indicate that extensive right hemisphere lesions may produce USN, but no specific brain region is associated with its recovery. Different from aphasics, no definite relationship is evident between recovery from USN and the role of the contralateral left hemisphere. This could be explained partly by the complexity of the pathogenetic mechanisms underlying USN. (author)

  16. Evaluation of glucose metabolic abnormality in postlingually deaf patients using F-18-FDG positron emission tomography and statistical parametric mapping

    Lee, Jae Sung; Lee, Dong Soo; Oh, Seung Ha; Kim, Chong Sun; Park, Kwang Suk; Chung, June Key; Lee, Myung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    2000-07-01

    We have previously reported the prognostic relevance of cross-modal cortical plasticity in prelingual deaf patients revealed by F-18-FDG PET and SPM analysis. In this study, we investigated metabolic abnormality in postlingual deaf patients, whose clinical features are different from prelingual deafness. Nine postlingual deaf patients (age: 30.5 {+-}14.0) were performed on F-18-FDG brain PET. We compared their PET images with those of age-matched 20 normal controls (age: 27.1 {+-}8.6), and performed correlation analysis to investigate the relationship between glucose metabolism and deaf duration using SPM99. Glucose metabolism of deaf patients was significantly (p<0.05, corrected) decreased in both anterior cingulate, inferior frontal cortices, and superior temporal cortices, and left hippocampus. Metabolism in both superior temporal cortices and association area in inferior parietal cortices showed significant (p<0.01, uncorrected) positive correlation with deaf duration. Decreased metabolism in hippocampus accompanied with hypometabolism in auditory related areas can be explained by recent finding of anatomical connectivity between them, and may be the evidence indicating their functional connectivity. Metabolism recovery in auditory cortex after long deaf duration suggests that cortical plasticity takes place also in postlingual deafness.

  17. Evaluation of glucose metabolic abnormality in postlingually deaf patients using F-18-FDG positron emission tomography and statistical parametric mapping

    Lee, Jae Sung; Lee, Dong Soo; Oh, Seung Ha; Kim, Chong Sun; Park, Kwang Suk; Chung, June Key; Lee, Myung Chul

    2000-01-01

    We have previously reported the prognostic relevance of cross-modal cortical plasticity in prelingual deaf patients revealed by F-18-FDG PET and SPM analysis. In this study, we investigated metabolic abnormality in postlingual deaf patients, whose clinical features are different from prelingual deafness. Nine postlingual deaf patients (age: 30.5 ±14.0) were performed on F-18-FDG brain PET. We compared their PET images with those of age-matched 20 normal controls (age: 27.1 ±8.6), and performed correlation analysis to investigate the relationship between glucose metabolism and deaf duration using SPM99. Glucose metabolism of deaf patients was significantly (p<0.05, corrected) decreased in both anterior cingulate, inferior frontal cortices, and superior temporal cortices, and left hippocampus. Metabolism in both superior temporal cortices and association area in inferior parietal cortices showed significant (p<0.01, uncorrected) positive correlation with deaf duration. Decreased metabolism in hippocampus accompanied with hypometabolism in auditory related areas can be explained by recent finding of anatomical connectivity between them, and may be the evidence indicating their functional connectivity. Metabolism recovery in auditory cortex after long deaf duration suggests that cortical plasticity takes place also in postlingual deafness

  18. The Role of Exercise – Rehabilitation on Energy Cost and Metabolic Efficiency in Dipelegic Spastic Cerebral Palsy Children

    M. Izadi

    2005-07-01

    Full Text Available Introduction & Objective: The aim of this study was to compare the resting energy expenditure and metabolic efficiency before and after of aerobic exercise in spastic cerebral palsy children (mean age of 11 years and also to compare with those of normal children. Materials & Methods : Fifteen dipelegia spastic cerebral palsy children (experimental group participated in exercise–rehabilitation program by voluntarily and the peers eighteen able body children(control group were selected randomly. The experimental group(cp performed rehabilitation program for 3 months,3 session in week with work intensity(%HRR=462.5equal to144bpm of heart rate. The values were measured on tantory cycle ergometer according to Macmaster protocol.Results: Rest and exercise heart rate and exercise intensity(%HRR in patients decreased after rehabilitation program(P<0.05. The resting energy expenditure was similar in cp and normal groups. The rate of oxygen cost of patients decreased in post test(P<0.05 that showed increasing in metabolic efficiency.Conclusion: cerebral palsy children have greater exercise energy cost and lower cardiovascular fitness than normal children and exercise–rehabilitation leads to enhance of metabolic efficiency in this patients that is remarkable from clinical perception.

  19. Changes in cerebral glucose metabolism in patients with posttraumatic cognitive impairment after memantine therapy. A preliminary study

    Kim, Yong-Wook; Shin, Ji-Cheol; An, Young-Sil

    2010-01-01

    The objective of this study was to investigate the changes in cerebral glucose metabolism in patients with posttraumatic cognitive impairment after memantine therapy. We performed serial F-18 fluorodeoxyglucose positron emission tomography studies before and after memantine therapy (20 mg per day) on 17 patients with posttraumatic cognitive impairment using statistical parametric mapping analysis. In addition, covariance analysis was performed to identify regions, where changes in regional cerebral glucose metabolism correlated significantly with increased Mini-Mental Status Examination scores. Statistical parametric mapping analysis demonstrated that, compared with baseline, significantly increased cerebral glucose metabolism occurred in both inferior, middle and superior frontal gyri, both angular gyri, both precuneus, the right middle cingulum, the left inferior parietal lobule, the left fusiform gyrus, the left precentral gyrus, the left paracentral lobule, and the left lingual gyrus after memantine therapy (P uncorrected uncorrected corrected <0.0001). Our findings indicate that the prefrontal and the parietal association cortices may be the relevant structures for the pharmacological response to memantine therapy in patients with posttraumatic cognitive impairment. (author)

  20. Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study

    Phillips, P.C.; Dhawan, V.; Strother, S.C.; Sidtis, J.J.; Evans, A.C.; Allen, J.C.; Rottenberg, D.A.

    1987-01-01

    Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for 82 Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity

  1. Longitudinal PET evaluation of cerebral glucose metabolism in rivastigmine treated patients with mild Alzheimer's disease

    Stefanova, E.; Forsberg, A.; Wall, A.; Nilsson, A.; Langstroem, B.; Almkvist, O.; Nordberg, A.

    2006-01-01

    In this study 11 patients with mild Alzheimer's disease (AD) were treated with the cholinesterase inhibitor rivastigmine (mean dose 8.6 ± 1.3 mg) for 12 months and underwent positron emission tomography (PET) studies of cerebral glucose metabolism (CMRglc) and neuropsychological testing at baseline and after 12 months. An untreated group of 10 AD patients served as control group. While the untreated AD patients showed a significant decline of CMRglc in the temporo-parietal and frontal cortical regions after 12 months follow-up the rivastigmine-treated patients showed no decline in CMRglc in corresponding cortical brain regions. Furthermore, a significant dose-related increase in CMRglc was recorded in the right frontal association region after 12 months rivastigmine treatment. A positive correlation was observed between changes in CMRglc and several cognitive tests in patients receiving higher doses (10.5-12 mg) of rivastigmine. These results suggest a stabilization effect of rivastigmine on CMRglc in mild AD patients receiving long-term rivastigmine treatment. (author)

  2. 3-Hydroxybutyrate regulates energy metabolism and induces BDNF expression in cerebral cortical neurons.

    Marosi, Krisztina; Kim, Sang Woo; Moehl, Keelin; Scheibye-Knudsen, Morten; Cheng, Aiwu; Cutler, Roy; Camandola, Simonetta; Mattson, Mark P

    2016-12-01

    During fasting and vigorous exercise, a shift of brain cell energy substrate utilization from glucose to the ketone 3-hydroxybutyrate (3OHB) occurs. Studies have shown that 3OHB can protect neurons against excitotoxicity and oxidative stress, but the underlying mechanisms remain unclear. Neurons maintained in the presence of 3OHB exhibited increased oxygen consumption and ATP production, and an elevated NAD + /NADH ratio. We found that 3OHB metabolism increases mitochondrial respiration which drives changes in expression of brain-derived neurotrophic factor (BDNF) in cultured cerebral cortical neurons. The mechanism by which 3OHB induces Bdnf gene expression involves generation of reactive oxygen species, activation of the transcription factor NF-κB, and activity of the histone acetyltransferase p300/EP300. Because BDNF plays important roles in synaptic plasticity and neuronal stress resistance, our findings suggest cellular signaling mechanisms by which 3OHB may mediate adaptive responses of neurons to fasting, exercise, and ketogenic diets. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  3. Effects of nutritional education on weight change and metabolic abnormalities among patients with schizophrenia in Japan: A randomized controlled trial.

    Sugawara, Norio; Sagae, Toyoaki; Yasui-Furukori, Norio; Yamazaki, Manabu; Shimoda, Kazutaka; Mori, Takao; Sugai, Takuro; Matsuda, Hiroshi; Suzuki, Yutaro; Ozeki, Yuji; Okamoto, Kurefu; Someya, Toshiyuki

    2018-02-01

    Patients with schizophrenia have a higher prevalence of metabolic syndrome (MetS) than the general population. Minimizing weight gain and metabolic abnormalities in a population with an already high prevalence of obesity is of clinical and social importance. This randomized controlled trial investigated the effect of monthly nutritional education on weight change and metabolic abnormalities among patients with schizophrenia in Japan. From July 2014 to December 2014, we recruited 265 obese patients who had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder. Participants were randomly assigned to a standard care (A), doctor's weight loss advice (B), or an individual nutritional education group (C) for 12 months. The prevalence of MetS and body weight were measured at baseline and 12 months. After the 12-month treatment, 189 patients were evaluated, and the prevalence of MetS based on the ATP III-A definition in groups A, B, and C was 68.9%, 67.2%, and 47.5%, respectively. Group C showed increased weight loss (3.2 ± 4.5 kg) over the 12-month study period, and the change in weight differed significantly from that of group A; additionally, 26.2% of the participants in group C lost 7% or more of their initial weight, compared with 8.2% of those in group A. Individual nutrition education provided by a dietitian was highly successful in reducing obesity in patients with schizophrenia and could be the first choice to address both weight gain and metabolic abnormalities induced by antipsychotic medications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Cerebral metabolic rates for glucose in mood disorders. Studies with positron emission tomography and fluorodeoxyglucose F 18

    Baxter, L.R. Jr.; Phelps, M.E.; Mazziotta, J.C.; Schwartz, J.M.; Gerner, R.H.; Selin, C.E.; Sumida, R.M.

    1985-01-01

    Cerebral metabolic rates for glucose were examined in patients with unipolar depression (N = 11), bipolar depression (N = 5), mania (N = 5), bipolar mixed states (N = 3), and in normal controls (N = 9) using positron emission tomography and fluorodeoxyglucose F 18. All subjects were studied supine under ambient room conditions with eyes open. Bipolar depressed and mixed patients had supratentorial whole brain glucose metabolic rates that were significantly lower than those of the other comparison groups. The whole brain metabolic rates for patients with bipolar depression increased going from depression or a mixed state to a euthymic or manic state. Patients with unipolar depression showed a significantly lower ratio of the metabolic rate of the caudate nucleus, divided by that of the hemisphere as a whole, when compared with normal controls and patients with bipolar depression

  5. Regional cerebral blood flow and oxygen metabolism in patients with ischemic stroke studied with high resolution pet and the O-15 labelled gas steady-state method

    Uemura, K.; Shishido, F.; Inugami, A.; Yamaguchi, T.; Ogawa, T.; Murakami, M.; Kanno, I.; Tagawa, K.; Yasui, N.

    1986-01-01

    Although regional cerebral blood flow (rCBF) studies have considerably increased pathophysiological knowledge in ischemic cerebrovascular disease, sometimes the results of such studies do not correlate with neurological abnormalities observed in the subjects being examined. Because regional neuronal activities always couple to the regional energy metabolism of brain tissue, simultaneous observation of rCBF and regional energy metabolism, such as regional oxygen consumption (rCMRO/sub 2/) and regional glucose consumption (rCMRG1), will provide greater understanding of the pathophysiology of the disease than rCBF study alone. Positron emission tomography (PET) using the 0-15 labelled gas steady-state method offers simultaneous measurement of rCBF and rCMRO/sub 2/ in vivo, and demonstrates imbalance between rCBF and rCMRO/sub 2/ in an ischemic lesion in a human brain. However, clinical PET studies in ischemic cerebrovascular disease reported previously, have been carried out using low resolution (more than 15 mm in the full width at half maximum; FWHM) PET. This report presents preliminary results using a high resolution tomograph; Headtome III and 0-15 labelled gas steady state method to investigate ischemic cerebrovascular disease

  6. Different cerebral metabolic features in dementia with lewy bodies with/without visual hallucination

    Kim, Bom Sahn; Kim, Yu Kyeong; Yang, Young Soon; Park, Eun Kyung; Cho, Sang Soo; Kim, Sang Yun; Kim, Sang Eun

    2007-01-01

    Reduction of glucose metabolism in the occipital cortex is well known in dementia with Lewy Bodies (DLB). The aim of this study was to evaluate the different nature of FDG PET in DLB patients who had visual hallucination or not. Thirteen patients (729 yrs, m:f=6:7) with DLB participated. DLB patient were classified into two groups according to the presence of visual hallucination; seven DLB patients with visual hallucination and 6 patients without visual hallucination. No differences between patient with and without visual hallucination was found in their cognitive function measured by mini mental status exam (MMSE) and clinical dementia rating (CDR) scale. Age and gender matched 30 healthy subjects (age; 715 yrs, m: f = 13:17) served as controls for comparison purpose. Regional metabolic differences on FDG PET among the groups were tested using SPM. In DLB patients groups regardless of visual hallucination, significant regional hypometabolism were observed in the bilateral occipital cortices as well as bilateral parietotemporal and frontal association cortices when compared with healthy controls, as expected. In DLB patients with visual hallucination compared to patients without hallucination, regional hypometabolism over primary and secondary visual cortex (BA17, BA18) was more significant. Moreover, lower regional metabolism in the paracentral area (BA 6) and cerebellar vermis was also observed in DLB with visual hallucination than without hallucination. Profound hypometabolism in the visual cortex may be a feature in DLB patients with visual hallucination. Also, relative hypometabolism in the paracentral area and cerebellum could be neurobiological characteristics related with abnormal cognitive and motor process response to hallucination

  7. Insulin resistance and endocrine-metabolic abnormalities in polycystic ovarian syndrome: Comparison between obese and non-obese PCOS patients.

    Layegh, Parvin; Mousavi, Zohreh; Farrokh Tehrani, Donya; Parizadeh, Seyed Mohammad Reza; Khajedaluee, Mohammad

    2016-04-01

    Insulin resistance has an important role in pathophysiology of polycystic ovarian syndrome (PCOS). Yet there are certain controversies regarding the presence of insulin resistance in non-obese patients. The aim was to compare the insulin resistance and various endocrine and metabolic abnormalities in obese and non-obese PCOS women. In this cross-sectional study which was performed from 2007-2010, 115 PCOS patients, aged 16-45 years were enrolled. Seventy patients were obese (BMI ≥25) and 45 patients were non-obese (BMI 2.3) between two groups (p=0.357). Waist circumference (pPCOS patients. There was no significant difference in total testosterone (p=0.634) and androstenedione (p=0.736) between groups whereas Dehydroepiandrotendione sulfate (DHEAS) was significantly higher in non-obese PCOS women (p=0.018). There was no case of fatty liver and metabolic syndrome in non-obese patients, whereas they were seen in 31.3% and 39.4% of obese PCOS women, respectively. Our study showed that metabolic abnormalities are more prevalent in obese PCOS women, but adrenal axis activity that is reflected in higher levels of DHEAS was more commonly pronounced in our non-obese PCOS patients.

  8. Cerebral signal intensity abnormalities on T2-weighted MR images in HIV patients with highly active antiretroviral therapy: relationship with clinical parameters and interval changes.

    Hanning, Uta; Husstedt, Ingo W; Niederstadt, Thomas-Ulrich; Evers, Stefan; Heindel, Walter; Kloska, Stephan P

    2011-09-01

    The aim of this study was to assess the relationship between immune state and cerebral signal intensity abnormalities (SIAs) on T2-weighted magnetic resonance images in subjects with human immunodeficiency virus type 1 infection and highly active antiretroviral therapy. Thirty-two subjects underwent a total of 109 magnetic resonance studies. The presence of human immunodeficiency virus-associated neurocognitive disorder, categorized CD4(+) T lymphocyte count, and plasma viral load were assessed for relationship with the severity and interval change of SIAs for different anatomic locations of the brain. Subjects with multifocal patterns of SIAs had CD4(+) cell counts < 200 cells/μL in 66.0%, whereas subjects with diffuse patterns of SIAs had CD4(+) cell counts < 200 cells/μL in only 31.4% (P < .001). Subjects without SIAs in the basal ganglia had CD4(+) cell counts < 200 cells/μL in 37.0%, whereas subjects with minor and moderate SIAs in the basal ganglia had CD4(+) cell counts < 200 cells/μL in 78.3% and 80.0%, respectively (P < .005). The percentage of subjects with CD4(+) cell counts < 200 cells/μL was 85.7% when there were progressive periventricular SIA changes and 45.5% when periventricular SIA changes were stable in follow-up (P < .05). The presence and progression of cerebral SIAs on T2-weighted magnetic resonance images reflecting cerebral infection with human immunodeficiency virus are significantly related to impaired immune state as measured by CD4(+) cell count. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

  9. Dietary Tributyrin Supplementation Attenuates Insulin Resistance and Abnormal Lipid Metabolism in Suckling Piglets with Intrauterine Growth Retardation

    He, Jintian; Dong, Li; Xu, Wen; Bai, Kaiwen; Lu, Changhui; Wu, Yanan; Huang, Qiang; Zhang, Lili; Wang, Tian

    2015-01-01

    Intrauterine growth retardation (IUGR) is associated with insulin resistance and lipid disorder. Tributyrin (TB), a pro-drug of butyrate, can attenuate dysfunctions in body metabolism. In this study, we investigated the effects of TB supplementation on insulin resistance and lipid metabolism in neonatal piglets with IUGR. Eight neonatal piglets with normal birth weight (NBW) and 16 neonatal piglets with IUGR were selected, weaned on the 7th day, and fed basic milk diets (NBW and IUGR groups) or basic milk diets supplemented with 0.1% tributyrin (IT group, IUGR piglets) until day 21 (n = 8). Relative parameters for lipid metabolism and mRNA expression were measured. Piglets with IUGR showed higher (P insulin in the serum, higher (P insulin, HOMA-IR, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in the serum, and the concentrations of TG and NEFA in the liver, and increased (P insulin signal transduction pathway and hepatic lipogenic pathway (including transcription factors and nuclear factors) was significantly (P insulin resistance and abnormal lipid metabolism in IUGR piglets by increasing enzyme activities and upregulating mRNA expression, leading to an early improvement in the metabolic efficiency of IUGR piglets. PMID:26317832

  10. Cerebral glucose metabolism and the glutamine cycle as detected by in vivo and in vitro 13C NMR spectroscopy.

    García-Espinosa, María A; Rodrigues, Tiago B; Sierra, Alejandra; Benito, Marina; Fonseca, Carla; Gray, Heather L; Bartnik, Brenda L; García-Martín, María L; Ballesteros, Paloma; Cerdán, Sebastián

    2004-01-01

    We review briefly 13C NMR studies of cerebral glucose metabolism with an emphasis on the roles of glial energetics and the glutamine cycle. Mathematical modeling analysis of in vivo 13C turnover experiments from the C4 carbons of glutamate and glutamine are consistent with: (i) the glutamine cycle being the major cerebral metabolic route supporting glutamatergic neurotransmission, (ii) glial glutamine synthesis being stoichiometrically coupled to glycolytic ATP production, (iii) glutamine serving as the main precursor of neurotransmitter glutamate and (iv) glutamatergic neurotransmission being supported by lactate oxidation in the neurons in a process accounting for 60-80% of the energy derived from glucose catabolism. However, more recent experimental approaches using inhibitors of the glial tricarboxylic acid (TCA) cycle (trifluoroacetic acid, TFA) or of glutamine synthase (methionine sulfoximine, MSO) reveal that a considerable portion of the energy required to support glutamine synthesis is derived from the oxidative metabolism of glucose in the astroglia and that a significant amount of the neurotransmitter glutamate is produced from neuronal glucose or lactate rather than from glial glutamine. Moreover, a redox switch has been proposed that allows the neurons to use either glucose or lactate as substrates for oxidation, depending on the relative availability of these fuels under resting or activation conditions, respectively. Together, these results suggest that the coupling mechanisms between neuronal and glial metabolism are more complex than initially envisioned.

  11. Reduced cerebral blood flow and oxygen metabolism in extremely preterm neonates with low-grade germinal matrix- intraventricular hemorrhage

    Lin, Pei-Yi; Hagan, Katherine; Fenoglio, Angela; Grant, P. Ellen; Franceschini, Maria Angela

    2016-05-01

    Low-grade germinal matrix-intraventricular hemorrhage (GM-IVH) is the most common complication in extremely premature neonates. The occurrence of GM-IVH is highly associated with hemodynamic instability in the premature brain, yet the long-term impact of low-grade GM-IVH on cerebral blood flow and neuronal health have not been fully investigated. We used an innovative combination of frequency-domain near infrared spectroscopy and diffuse correlation spectroscopy (FDNIRS-DCS) to measure cerebral oxygen saturation (SO2) and an index of cerebral blood flow (CBFi) at the infant’s bedside and compute an index of cerebral oxygen metabolism (CMRO2i). We enrolled twenty extremely low gestational age (ELGA) neonates (seven with low-grade GM-IVH) and monitored them weekly until they reached full-term equivalent age. During their hospital stay, we observed consistently lower CBFi and CMRO2i in ELGA neonates with low-grade GM-IVH compared to neonates without hemorrhages. Furthermore, lower CBFi and CMRO2i in the former group persists even after the resolution of the hemorrhage. In contrast, SO2 does not differ between groups. Thus, CBFi and CMRO2i may have better sensitivity than SO2 in detecting GM-IVH-related effects on infant brain development. FDNIRS-DCS methods may have clinical benefit for monitoring the evolution of GM-IVH, evaluating treatment response, and potentially predicting neurodevelopmental outcome.

  12. Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities

    Quintana, Anita M; Yu, Hung-Chun; Brebner, Alison

    2017-01-01

    roles in normal brain development. The loss of THAP11 in zebrafish embryos results in craniofacial abnormalities including the complete loss of Meckel's cartilage, the ceratohyal, and all of the ceratobranchial cartilages. These data are consistent with our previous work that demonstrated a role...

  13. Can the cerebral metabolic rate of oxygen be estimated with near-infrared spectroscopy?

    Boas, D A; Strangman, G; Culver, J P; Hoge, R D; Jasdzewski, G; Poldrack, R A; Rosen, B R; Mandeville, J B

    2003-01-01

    We have measured the changes in oxy-haemoglobin and deoxy-haemoglobin in the adult human brain during a brief finger tapping exercise using near-infrared spectroscopy (NIRS). The cerebral metabolic rate of oxygen (CMRO 2 ) can be estimated from these NIRS data provided certain model assumptions. The change in CMRO 2 is related to changes in the total haemoglobin concentration, deoxy-haemoglobin concentration and blood flow. As NIRS does not provide a measure of dynamic changes in blood flow during brain activation, we relied on a Windkessel model that relates dynamic blood volume and flow changes, which has been used previously for estimating CMRO 2 from functional magnetic resonance imaging (fMRI) data. Because of the partial volume effect we are unable to quantify the absolute changes in the local brain haemoglobin concentrations with NIRS and thus are unable to obtain an estimate of the absolute CMRO 2 change. An absolute estimate is also confounded by uncertainty in the flow-volume relationship. However, the ratio of the flow change to the CMRO 2 change is relatively insensitive to these uncertainties. For the finger tapping task, we estimate a most probable flow-consumption ratio ranging from 1.5 to 3 in agreement with previous findings presented in the literature, although we cannot exclude the possibility that there is no CMRO 2 change. The large range in the ratio arises from the large number of model parameters that must be estimated from the data. A more precise estimate of the flow-consumption ratio will require better estimates of the model parameters or flow information, as can be provided by combining NIRS with fMRI

  14. Depressive disorder and gastrointestinal dysfunction after myocardial infarct are associated with abnormal tryptophan-5-hydroxytryptamine metabolism in rats.

    Lu, Xiaofang; Wang, Yuefen; Liu, Chunyan; Wang, Yangang

    2017-01-01

    In this study, we investigated the relationship between tryptophan-5-hydroxytryptamine metabolism, depressive disorder, and gastrointestinal dysfunction in rats after myocardial infarction. Our goal was to elucidate the physiopathologic bases of somatic/psychiatric depression symptoms after myocardial infarction. A myocardial infarction model was established by permanent occlusion of the left anterior descending coronary artery. Depression-like behavior was evaluated using the sucrose preference test, open field test, and forced swim test. Gastric retention and intestinal transit were detected using the carbon powder labeling method. Immunohistochemical staining was used to detect indoleamine 2,3-dioxygenase expression in the hippocampus and ileum. High-performance liquid chromatography with fluorescence and ultraviolet detection determined the levels of 5-hydroxytryptamine, its precursor tryptophan, and its metabolite 5-hydroxyindoleacetic acid in the hippocampus, distal ileum, and peripheral blood. All data were analyzed using one-way analyses of variance. Three weeks after arterial occlusion, rats in the model group began to exhibit depression-like symptoms. For example, the rate of sucrose consumption was reduced, the total and central distance traveled in the open field test were reduced, and immobility time was increased, while swimming, struggling and latency to immobility were decreased in the forced swim test. Moreover, the gastric retention rate and gastrointestinal transit rate were increased in the model group. Expression of indoleamine 2,3-dioxygenase was increased in the hippocampus and ileum, whereas 5-hydroxytryptamine metabolism was decreased, resulting in lower 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels in the hippocampus and higher levels in the ileum. Depressive disorder and gastrointestinal dysfunction after myocardial infarction involve abnormal tryptophan-5-hydroxytryptamine metabolism, which may explain the somatic, cognitive

  15. Depressive disorder and gastrointestinal dysfunction after myocardial infarct are associated with abnormal tryptophan-5-hydroxytryptamine metabolism in rats.

    Xiaofang Lu

    Full Text Available In this study, we investigated the relationship between tryptophan-5-hydroxytryptamine metabolism, depressive disorder, and gastrointestinal dysfunction in rats after myocardial infarction. Our goal was to elucidate the physiopathologic bases of somatic/psychiatric depression symptoms after myocardial infarction. A myocardial infarction model was established by permanent occlusion of the left anterior descending coronary artery. Depression-like behavior was evaluated using the sucrose preference test, open field test, and forced swim test. Gastric retention and intestinal transit were detected using the carbon powder labeling method. Immunohistochemical staining was used to detect indoleamine 2,3-dioxygenase expression in the hippocampus and ileum. High-performance liquid chromatography with fluorescence and ultraviolet detection determined the levels of 5-hydroxytryptamine, its precursor tryptophan, and its metabolite 5-hydroxyindoleacetic acid in the hippocampus, distal ileum, and peripheral blood. All data were analyzed using one-way analyses of variance. Three weeks after arterial occlusion, rats in the model group began to exhibit depression-like symptoms. For example, the rate of sucrose consumption was reduced, the total and central distance traveled in the open field test were reduced, and immobility time was increased, while swimming, struggling and latency to immobility were decreased in the forced swim test. Moreover, the gastric retention rate and gastrointestinal transit rate were increased in the model group. Expression of indoleamine 2,3-dioxygenase was increased in the hippocampus and ileum, whereas 5-hydroxytryptamine metabolism was decreased, resulting in lower 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels in the hippocampus and higher levels in the ileum. Depressive disorder and gastrointestinal dysfunction after myocardial infarction involve abnormal tryptophan-5-hydroxytryptamine metabolism, which may explain the

  16. Metabolic Characterization of Acutely Isolated Hippocampal and Cerebral Cortical Slices Using [U-(13)C]Glucose and [1,2-(13)C]Acetate as Substrates

    McNair, Laura F; Kornfelt, Rasmus; Walls, Anne B

    2017-01-01

    Brain slice preparations from rats, mice and guinea pigs have served as important tools for studies of neurotransmission and metabolism. While hippocampal slices routinely have been used for electrophysiology studies, metabolic processes have mostly been studied in cerebral cortical slices. Few...

  17. PET imaging of cerebral metabolic change in tinnitus using 18F-FDG

    Tian Jiahe; Wang Hongtian; Yin Dayi; Yao Shulin; Shao Mingzhe; Yang Weiyan; Jiang Sichang

    2000-01-01

    Tinnitus is an auditory disorder hardly assessable by clinical technology. PET imaging of the brain in 13 cases with and 10 without tinnitus was undertaken at 40 min after injection of 280-440 MBq 18 F-FDG. To ensure the quality of the PET study, all cases followed a normalized procedure with visual and auditory blockage. CT/MRI imaging and routine acoustic tests were carried out in all subjects. PET revealed that an increased uptake of 18 F-FDG at left med-temporal lobe (primary auditory center, PAC) present exclusively in tinnitus, regardless the side of hearing hallucination. Significant asymmetry was noted between left and right PAC, but not at other cortex area. While control cases showed no asymmetric uptake between two hemispheres. The abnormal PAC uptake did not respond to external pure sound stimulus, nor did it relate to the severity of hearing loss assessed by acoustic tests. No anatomical or morphological alteration could be proven on CT/MRI. In conclusion, PET/ 18 F-FDG objectively revealed an increased metabolic change at left PAC in tinnitus, which is of diagnostic value; and there is evidence suggesting tinnitus is most likely induced by a functional change in the brain

  18. PET imaging of cerebral metabolic change in tinnitus using {sup 18}F-FDG

    Jiahe, Tian; Hongtian, Wang; Dayi, Yin; Shulin, Yao; Mingzhe, Shao; Weiyan, Yang; Sichang, Jiang [The PLA General Hospital, Beijing (China)

    2000-11-01

    Tinnitus is an auditory disorder hardly assessable by clinical technology. PET imaging of the brain in 13 cases with and 10 without tinnitus was undertaken at 40 min after injection of 280-440 MBq {sup 18}F-FDG. To ensure the quality of the PET study, all cases followed a normalized procedure with visual and auditory blockage. CT/MRI imaging and routine acoustic tests were carried out in all subjects. PET revealed that an increased uptake of {sup 18}F-FDG at left med-temporal lobe (primary auditory center, PAC) present exclusively in tinnitus, regardless the side of hearing hallucination. Significant asymmetry was noted between left and right PAC, but not at other cortex area. While control cases showed no asymmetric uptake between two hemispheres. The abnormal PAC uptake did not respond to external pure sound stimulus, nor did it relate to the severity of hearing loss assessed by acoustic tests. No anatomical or morphological alteration could be proven on CT/MRI. In conclusion, PET/{sup 18}F-FDG objectively revealed an increased metabolic change at left PAC in tinnitus, which is of diagnostic value; and there is evidence suggesting tinnitus is most likely induced by a functional change in the brain.

  19. Effect of STA-proximal MCA bypass. Improvement of cerebral blood flow and metabolism and neuropsychological function

    Ogawa, Akira; Funayama, Masayuki; Miura, Kazuyuki; Ogasawara, Kuniaki; Suzuki, Michiyasu; Kuroda, Kiyoshi; Sasaki, Toshiaki [Iwate Medical Univ., Morioka (Japan). School of Medicine

    1998-11-01

    We investigated cerebral blood flow (CBF) and metabolism in patients with hemodynamic ischemia by positron emission tomography (PET) and thermal diffusion flow meter. We also studied neuropsychological functions to evaluate the effects of surgical revascularization. Bypass surgery of the superficial temporal artery to the proximal middle cerebral artery was performed on 26 patients satisfying the following categories: stenosis or occlusive lesion in main cerebral arteries; no marked focus of infarction on CT or MRI. PET was performed before and 1 month after the operation, and CBF, the cerebral metabolic rate of oxygen (CMRO{sub 2}) and oxygen extraction fraction (OEF) were analyzed. Cerebrovascular reserve capacity (CVRC) was also calculated after acetazolamide challenge. CBF during the operation was continuously measured with a thermal diffusion flow meter. CO{sub 2} response of CBF was analyzed before and after anastomosis. Neuropsychological functions were evaluated by Hasegawa dementia scale revised (HDS-R), mini-mental state examination (MMSE) and Wechsler adult intelligence scale revised (WAIS-R). Before the operation, increase in OEF accorded with the decrease in CBF, and a significant relationship between both CBF and CVRC, and OEF and CVRC was found. A decrease in CVRC was noted prior to a decrease in CBF and elevation of OEF. CVRC caused by acetazolamide might reflect CO{sub 2} reactivity. Significant improvement of CBF and CVRC, and normalization of OEF were observed after the operation. Also, significant improvement of neuropsychological function was observed by HDS-R and WAIS-R. Disturbance in neuropsychological function might reflect elevation of OEF. (author)

  20. Elevated global cerebral blood flow, oxygen extraction fraction and unchanged metabolic rate of oxygen in young adults with end-stage renal disease: an MRI study

    Zheng, Gang; Lou, Yaxian; Pan, Zhiying; Liu, Ya [Medical School of Nanjing University, Department of Medical Imaging, Jinling Hospital, Nanjing, Jiangsu (China); Nanjing University of Aeronautics and Astronautics, College of Aivil Aviation, Nanjing, Jiangsu (China); Wen, Jiqiu; Li, Xue; Zhang, Zhe [Medical School of Nanjing University, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing, Jiangsu (China); Lu, Hanzhang [University of Texas Southwestern Medical Center, Advanced Imaging Research Center, Dallas, TX (United States); Liu, Wei [Siemens Shenzhen Magnetic Resonance Ltd., Shenzhen, Guangdong (China); Liu, Hui [Siemens MR NEA Collaboration, Siemens Ltd., Shanghai (China); Chen, Huijuan; Kong, Xiang; Luo, Song; Jiang, Xiaolu; Zhang, Zongjun; Zhang, Long Jiang; Lu, Guang Ming [Medical School of Nanjing University, Department of Medical Imaging, Jinling Hospital, Nanjing, Jiangsu (China)

    2016-06-15

    To noninvasively assess global cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO{sub 2}) in young adults with end-stage renal disease (ESRD). Thirty-six patients and 38 healthy volunteers were included and took part in MR examinations, blood and neuropsychological tests. CBF and OEF were measured by phase-contrast and T2-relaxation-under-spin-tagging MRI techniques, respectively. CMRO{sub 2} was computed from CBF, OEF and hematocrit according to Fick's principle. Correlations were performed between MR measurements, blood biochemistry measurements and neuropsychological test scores. Compared with controls, ESRD patients had elevated CBF (72.9 ± 12.5 vs. 63.8 ± 8.5 ml min{sup -1} 100 g{sup -1}, P < 0.001), elevated OEF (47.2 ± 10.2 vs. 35.8 ± 5.4 %, P < 0.001), but unaffected CMRO{sub 2} (199.5 ± 36.4 vs. 193.8 ± 28.6 μmol O{sub 2} min{sup -1} 100 g{sup -1}, P = 0.879). Hematocrit negatively correlated with CBF (r = -0.640, P < 0.001) and OEF (r = -0.701, P < 0.001), but not with CMRO{sub 2}. Altered neuropsychological test scores of ESRD patients were associated with OEF and CBF, but not with CMRO{sub 2}. There were weak relationships between eGFR and hematocrit (r = 0.308, P = 0.068) or CBF (r = 0.318, P = 0.059). Our findings suggested that anaemic young adults with ESRD may afford higher CBF and OEF to maintain a normal CMRO{sub 2}. Despite this compensatory process, however, cognitive function was still impaired and its severity was correlated with their CBF and OEF abnormality. (orig.)

  1. Elevated global cerebral blood flow, oxygen extraction fraction and unchanged metabolic rate of oxygen in young adults with end-stage renal disease: an MRI study

    Zheng, Gang; Lou, Yaxian; Pan, Zhiying; Liu, Ya; Wen, Jiqiu; Li, Xue; Zhang, Zhe; Lu, Hanzhang; Liu, Wei; Liu, Hui; Chen, Huijuan; Kong, Xiang; Luo, Song; Jiang, Xiaolu; Zhang, Zongjun; Zhang, Long Jiang; Lu, Guang Ming

    2016-01-01

    To noninvasively assess global cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2 ) in young adults with end-stage renal disease (ESRD). Thirty-six patients and 38 healthy volunteers were included and took part in MR examinations, blood and neuropsychological tests. CBF and OEF were measured by phase-contrast and T2-relaxation-under-spin-tagging MRI techniques, respectively. CMRO 2 was computed from CBF, OEF and hematocrit according to Fick's principle. Correlations were performed between MR measurements, blood biochemistry measurements and neuropsychological test scores. Compared with controls, ESRD patients had elevated CBF (72.9 ± 12.5 vs. 63.8 ± 8.5 ml min -1 100 g -1 , P < 0.001), elevated OEF (47.2 ± 10.2 vs. 35.8 ± 5.4 %, P < 0.001), but unaffected CMRO 2 (199.5 ± 36.4 vs. 193.8 ± 28.6 μmol O 2 min -1 100 g -1 , P = 0.879). Hematocrit negatively correlated with CBF (r = -0.640, P < 0.001) and OEF (r = -0.701, P < 0.001), but not with CMRO 2 . Altered neuropsychological test scores of ESRD patients were associated with OEF and CBF, but not with CMRO 2 . There were weak relationships between eGFR and hematocrit (r = 0.308, P = 0.068) or CBF (r = 0.318, P = 0.059). Our findings suggested that anaemic young adults with ESRD may afford higher CBF and OEF to maintain a normal CMRO 2 . Despite this compensatory process, however, cognitive function was still impaired and its severity was correlated with their CBF and OEF abnormality. (orig.)

  2. Association of neural tube defects in children of mothers with MTHFR 677TT genotype and abnormal carbohydrate metabolism risk: a case-control study.

    Cadenas-Benitez, N M; Yanes-Sosa, F; Gonzalez-Meneses, A; Cerrillos, L; Acosta, D; Praena-Fernandez, J M; Neth, O; Gomez de Terreros, I; Ybot-González, P

    2014-03-26

    Abnormalities in maternal folate and carbohydrate metabolism have both been shown to induce neural tube defects (NTD) in humans and animal models. However, the relationship between these two factors in the development of NTDs remains unclear. Data from mothers of children with spina bifida seen at the Unidad de Espina Bífida del Hospital Infantil Virgen del Rocío (case group) were compared to mothers of healthy children with no NTD (control group) who were randomly selected from patients seen at the outpatient ward in the same hospital. There were 25 individuals in the case group and 41 in the control group. Analysis of genotypes for the methylenetetrahydrofolate reductase (MTHFR) 677CT polymorphism in women with or without risk factors for abnormal carbohydrate metabolism revealed that mothers who were homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism were more likely to have offspring with spina bifida and high levels of homocysteine, compared to the control group. The increased incidence of NTDs in mothers homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism stresses the need for careful metabolic screening in pregnant women, and, if necessary, determination of the MTHFR 677CT genotype in those mothers at risk of developing abnormal carbohydrate metabolism.

  3. A PET study of cerebellar metabolism in normal and abnormal states

    Kushner, M.; Alavi, A.; Chawluk, J.; Silver, F.; Dann, R.; Rosen, M.; Reivich, M.

    1985-01-01

    The authors studied cerebellar metabolism under varying conditions of sensory stimulation. Cerebellar glucose consumption was measured by positron emission scanning and 18F-fluorodeoxyglucose in 64 subjects. Cerebellar metabolism relative to the whole brain (CM), and the asymmetry of metabolism between the cerebellar hemispheres (CA) was determined. The lowest CM occurred with maximal sensory deprivation, eyes and ears closed, (CM=96%, n=6). CM increased nonsignificantly with visual stimulation (CM=99%,n=17) and was highest for auditory stimulation (CM=104%,n=10,p<.05). CA was unaffected by sensory input. Under ambient conditions the CM values were 101%, 113% and 135% respectively for young controls (n=9, age=22), old controls (n=8, age=61) and Alzheimer patients (SDAT, n=14, age=69). This difference was significant for SDAT vs young and old controls and was nearly significant for young vs old controls

  4. Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice

    Bing Han

    2017-03-01

    Full Text Available Background/Aims: Stress response is determined by the brain, and the brain is a sensitive target for stress. Our previous experiments have confirmed that once the stress response is beyond the tolerable limit of the brain, particularly that of the hippocampus, it will have deleterious effects on hippocampal structure and function; however, the metabolic mechanisms for this are not well understood. Methods: Here, we used morris water maze, elisa and gas chromatography-time of flight/mass spectrometry to observe the changes in cognition, neuropathology and metabolomics in the hippocampus of APP/PS1 mice and wild-type (C57 mice caused by chronic unpredictable mild stress (CUMS, we also further explored the correlation between cognition and metabolomics. Results: We found that 4 weeks of CUMS aggravated cognitive impairment and increased amyloid-β deposition in APP/PS1 mice, but did not affect C57 mice. Under non-stress conditions, compared with C57 mice, there were 8 different metabolites in APP/PS1 mice. However, following CUMS, 3 different metabolites were changed compared with untreated C57 mice. Compared to APP/PS1 mice, there were 7 different metabolites in APP/PS1+CUMS mice. Among these alterations, 3-hydroxybutyric acid, valine, serine, beta-alanine and o-phosphorylethanolamine, which are involved in sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism. Conclusion: The results indicate that APP/PS1 mice are more vulnerable to stress than C57 mice, and the metabolic mechanisms of stress-related cognitive impairment in APP/PS1 mice are related to multiple pathways and networks, including sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism.

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

    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.

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

    Hassel, B.

    1995-11-01

    The present investigations show the feasibility of analyzing the cerebral metabolism of amino acids and related metabolites by 13 C-and 14 C-labelling using labelled acetate and glucose as markers for glial and neuronal metabolism, respectively. Using [ 13 C[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 [ 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 13 CNMR spectroscopy to the detailed study of the cerebral metabolism of amino acids in the intact, unanesthetized human brain. 174 refs

  7. FDG PET in non-pharmacological therapy in Alzheimer's disease; cerebral metabolic increase correlates with clinical improvement after cognitive therapy

    Na, Hae Ri; Kim, Yu Kyeong; Park, Seong Min; Lee, Seung Hyun; Park, Eun Kyung; Lee, Jung Seok; Kim, Sang Yun; Kim, Sang Eun

    2007-01-01

    In management of AD, pharmacological treatment alone using acetylcholinesterase inhibitor (AChEI) is general consensus, and provides beneficial effect to prolong their progression. Combined non-pharmacological therapy, especially cognitive therapy is recently having attention with expectation of improvement in cognitive ability. This study examined the effect of combined cognitive therapy in AD patients who were maintaining AChEI using FDG PET. Four patients (689 yrs) who diagnosed as probable Alzheimer's disease based on the NINCDS-ADRDA criteria participated in this study. 12-week cognitive therapy comprised seven fields to enhance orientation, memory, recall, visuo-motor organization, categorization and behavior modification/sequencing. They received 45-minute sessions twice per week with maintaining their previous medication. Clinical improvement was assessed by comprehensive neuropsychological tests. Two FDG PET studies were performed before cognitive therapy and in the middle of the therapy, and compared to evaluate the effect of cognitive therapy to cerebral metabolism. Two of 4 patients whose initial cognitive impairment was milder had clinical improvement after 12 weeks, the rest who were more severely impaired failed to have clinical improvement. Regional cerebral hypometabolism on initial PET was correlated with their functional status. Follow up PET of two responders demonstrated the increases in regional metabolism in the temporal and/or frontal cortex, which was associated their functional improvement. Cerebral metabolism in poor responders were minimally increased or no changed. This preliminary data suggests that cognitive therapy is potentially useful to stabilize or improve cognitive and functional performance in AD patients with relatively mild cognitive dysfunction. And FDG PET could demonstrate possible candidates for cognitive therapy and the effect of the therapy

  8. Changes in cerebral oxidative metabolism in patients with acute liver failure

    Bjerring, P N; Larsen, F S

    2013-01-01

    acid cycle, induces substrate depletion through marked glutamate utilization for glutamine synthesis and leads to mitochondrial dysfunction. In patients with acute liver failure cerebral microdialysis studies show a linear correlation between the lactate to pyruvate ratio and the glutamine...

  9. Altered free radical metabolism in acute mountain sickness: implications for dynamic cerebral autoregulation and blood-brain barrier function

    Bailey, D M; Evans, K A; James, P E

    2008-01-01

    We tested the hypothesis that dynamic cerebral autoregulation (CA) and blood-brain barrier (BBB) function would be compromised in acute mountain sickness (AMS) subsequent to a hypoxia-mediated alteration in systemic free radical metabolism. Eighteen male lowlanders were examined in normoxia (21% O...... developed clinical AMS (AMS+) and were more hypoxaemic relative to subjects without AMS (AMS-). A more marked increase in the venous concentration of the ascorbate radical (A(*-)), lipid hydroperoxides (LOOH) and increased susceptibility of low-density lipoprotein (LDL) to oxidation was observed during...

  10. Effects of the intraoperative application of dexmedetomidine on hemodynamics and cerebral oxygen metabolism of patients with cerebrovascular malformations

    Liang Feng

    2017-01-01

    Full Text Available Circulatory stability of patients with cerebrovascular malformations during the surgery is critical to their prognosis. Anesthesia-induced intubation, tumor separation, clamping and other operations may cause severe fluctuations in blood pressure and even result in aneurysm rupture. As a highly efficient and selective adrenergic α2 receptor agonists, dexmedetomidine hydrochloride is able to regulate the release of catecholamine by means of negative feedback so as to control blood pressure. This study aims to assess the effects of dexmedetomidine hydrochloride on hemodynamics and cerebral oxygen metabolism of intraoperative patients with cerebrovascular malformations.

  11. Cerebral circulation and metabolism in the patients with higher brain dysfunction caused by chronic minor traumatic brain injury. A study by the positron emission tomography in twenty subjects with normal MRI findings

    Kabasawa, Hidehiro; Ogawa, Tetsuo; Iida, Akihiko; Matsubara, Michitaka [Nagoya City Rehabilitation and Sports Center (Japan)

    2002-06-01

    Many individuals are affected on their higher brain functions, such as intelligence, memory, and attention, even after minor traumatic brain injury (MTBI). Although higher brain dysfunction is based on impairment of the cerebral circulation and metabolism, the precise relationship between them remains unknown. This study was undertaken to investigate the relationship between the cerebral circulation or cerebral metabolism and higher brain dysfunction. Twenty subjects with higher brain dysfunction caused by chronic MTBI were studied. They had no abnormal MRI findings. The full-scale intelligence quotient (FIQ) were quantitatively evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-R), and the subjects were classified into the normal group and the impaired group. Concurrent with the evaluation of FIQ, positron emission tomography (PET) was performed by the steady state method with {sup 15}O gases inhalation. Regional cerebral blood flow (rCBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO{sub 2}) were calculated in the bilateral frontal, parietal, temporal, and occipital lobe. First, of all twenty subjects, we investigated rCBF, OEF and CMRO{sub 2} in all regions. Then we compared rCBF, OEF, and CMRO{sub 2} between the normal group and the impaired group based on FIQ score. We also studied the change of FIQ score of 13 subjects 9.3 months after the first evaluation. In addition, we investigated the change of rCBF, OEF and CMRO{sub 2} along with the improvement of FIQ score. Although rCBF and OEF of all subjects were within the normal range in all regions, CMRO{sub 2} of more than half of subjects was under the lower normal limit in all regions except in the right occipital lobe, showing the presence of ''relative luxury perfusion''. Comparison of rCBF, OEF and CMRO{sub 2} between normal group and impaired group revealed that CMRO{sub 2} of the impaired group was significantly lower than that of the

  12. Cerebral circulation and metabolism in the patients with higher brain dysfunction caused by chronic minor traumatic brain injury. A study by the positron emission tomography in twenty subjects with normal MRI findings

    Kabasawa, Hidehiro; Ogawa, Tetsuo; Iida, Akihiko; Matsubara, Michitaka

    2002-01-01

    Many individuals are affected on their higher brain functions, such as intelligence, memory, and attention, even after minor traumatic brain injury (MTBI). Although higher brain dysfunction is based on impairment of the cerebral circulation and metabolism, the precise relationship between them remains unknown. This study was undertaken to investigate the relationship between the cerebral circulation or cerebral metabolism and higher brain dysfunction. Twenty subjects with higher brain dysfunction caused by chronic MTBI were studied. They had no abnormal MRI findings. The full-scale intelligence quotient (FIQ) were quantitatively evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-R), and the subjects were classified into the normal group and the impaired group. Concurrent with the evaluation of FIQ, positron emission tomography (PET) was performed by the steady state method with 15 O gases inhalation. Regional cerebral blood flow (rCBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2 ) were calculated in the bilateral frontal, parietal, temporal, and occipital lobe. First, of all twenty subjects, we investigated rCBF, OEF and CMRO 2 in all regions. Then we compared rCBF, OEF, and CMRO 2 between the normal group and the impaired group based on FIQ score. We also studied the change of FIQ score of 13 subjects 9.3 months after the first evaluation. In addition, we investigated the change of rCBF, OEF and CMRO 2 along with the improvement of FIQ score. Although rCBF and OEF of all subjects were within the normal range in all regions, CMRO 2 of more than half of subjects was under the lower normal limit in all regions except in the right occipital lobe, showing the presence of ''relative luxury perfusion''. Comparison of rCBF, OEF and CMRO 2 between normal group and impaired group revealed that CMRO 2 of the impaired group was significantly lower than that of the normal group in the bilateral frontal, temporal, and occipital

  13. Local cerebral metabolic rate of /sup 11/C-L-Methionine in early stages of dementia, schizophrenia, Parkinson's disease

    Bustany, P; Henry, J F; de Rotrou, J; Signoret, J L; Ziegler, M; Zarifian, E; Soussaline, F; Comar, D

    1983-06-01

    A dynamic three-compartment model of methionine metabolism in brain was applied in human patients using /sup 11/C-L-methionine and positron emission tomography (P.E.T). Psychometric evaluations of demented patients were correlated with a significant diminution of protein synthesis in the frontal area. This diminution was lower in ebephrenic patients (-17%) but was consistent with the results obtained with /sup 18/F glucose. No significant abnormality was detected in patients with Parkinson disease.

  14. Local cerebral metabolic rate of 11C-L-Methionine in early stages of dementia, schizophrenia, Parkinson's disease

    Bustany, P.; Henry, J.F.; de Rotrou, J.; Signoret, J.L.; Ziegler, M.; Zarifian, E.; Soussaline, F.; Comar, D.

    1983-06-01

    A dynamic three-compartment model of methionine metabolism in brain was applied in human patients using 11 C-L-Methionine and positron emission tomography (P.E.T). Psychometric evaluations of demented patients were correlated with a significant diminution of protein synthesis in the frontal area. This diminution was lower in ebephrenic patients (-17%) but was consistent with the results obtained with 18 F glucose. No significant abnormality was detected in patients with Parkinson disease

  15. Myocardial metabolic abnormalities in hypertrophic cardiomyopathy assessed by iodine-123-labeled beta-methyl-branched fatty acid myocardial scintigraphy and its relation to exercise-induced ischemia

    Matsuo, Shinro; Nakamura, Yasuyuki; Takahashi, Masayuki; Mitsunami, Kenichi; Kinoshita, Masahiko

    1998-01-01

    Reversible thallium-201 ( 201 Tl) abnormalities during exercise stress have been used as markers of myocardial ischemia in hypertrophic cardiomyopathy (HCM) and are most likely to identify relatively underperfused myocardium. Although metabolic abnormalities in HCM were reported, the relationship between impaired energy metabolism and exercise-induced ischemia has not been fully elucidated as yet. To assess the relationship between myocardial perfusion abnormalities and fatty acid metabolic abnormalities, 28 patients with HCM underwent exercise 201 Tl and rest 123 I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) scintigraphy. Perfusion abnormalities were observed by exercise 201 Tl in 19/28 patients with HCM. 123 I-BMIPP uptake was decreased compared with delayed 201 Tl in 106/364 (29%) of the total myocardial segments (p 123 I-BMIPP and 201 Tl was observed more often in the 49/75 (65%) segments with reversible exercise 201 Tl defects (p 123 I-BMIPP and 201 Tl suggests that myocardial ischemia may play an important role in metabolic abnormalities in HCM. (author)

  16. [Metabolic abnormalities in polycystic ovary syndrome women: obese and non obese].

    Romano, Lucas Gabriel Maltoni; Bedoschi, Giuliano; Melo, Anderson Sanches; Albuquerque, Felipe Oliveira de; Rosa e Silva, Ana Carolina Japur de Sá; Ferriani, Rui Alberto; Navarro, Paula Andrea

    2011-06-01

    To compare the metabolic characteristics of obese and non-obese young women with polycystic ovary syndrome (POS) from the Brazilian Southeast. This was a cross-sectional study conducted on 218 women of reproductive age with a diagnosis of POS--90 non-obese women (BMI between 18.5 and 29.9 kg/m²), and 128 obese patients (BMI > 30 kg/m²) selected at the time of diagnosis. The frequency of insulin resistance (IR), glucose intolerance (GI), metabolic syndrome (MetS) and type 2 diabetes mellitus (DM2) and mean values of total cholesterol (TC), triglycerides (TG), high-density (HDL) and low-density lipoproteins (LDL), were compared between obese and non-obese patients with POS. The two groups were also compared in terms of clinical and hormonal characteristics (follicle stimulating hormone, prolactin, thyroid stimulating hormone, total testosterone, dihydroepiandrostenedione sulfate, and 17-hydroxyprogesterone). Statistical analysis was performed using the SAS 9.0 software. Quantitative variables were compared by the Student's t-test (data with normal distribution) or by the Mann-Whitney test (non-parametric distribution). Qualitative variables were compared by the Fisher test. The level of significance was set at 5% (p women with POS have a higher frequency of IR, GI and MS than non-obese. However, the occurrence of metabolic disorders is elevated also in the non-obese patients, suggesting that the presence of the syndrome may favor the development of metabolic comorbidities with potential medium- and long-term repercussions.

  17. Hydroxytyrosol prevents diet-induced metabolic syndrome and attenuates mitochondrial abnormalities in obese mice.

    Cao, Ke; Xu, Jie; Zou, Xuan; Li, Yuan; Chen, Cong; Zheng, Adi; Li, Hao; Li, Hua; Szeto, Ignatius Man-Yau; Shi, Yujie; Long, Jiangang; Liu, Jiankang; Feng, Zhihui

    2014-02-01

    A Mediterranean diet rich in olive oil has profound influence on health outcomes including metabolic syndrome. However, the active compound and detailed mechanisms still remain unclear. Hydroxytyrosol (HT), a major polyphenolic compound in virgin olive oil, has received increased attention for its antioxidative activity and regulation of mitochondrial function. Here, we investigated whether HT is the active compound in olive oil exerting a protective effect against metabolic syndrome. In this study, we show that HT could prevent high-fat-diet (HFD)-induced obesity, hyperglycemia, hyperlipidemia, and insulin resistance in C57BL/6J mice after 17 weeks supplementation. Within liver and skeletal muscle tissues, HT could decrease HFD-induced lipid deposits through inhibition of the SREBP-1c/FAS pathway, ameliorate HFD-induced oxidative stress by enhancing antioxidant enzyme activities, normalize expression of mitochondrial complex subunits and mitochondrial fission marker Drp1, and eventually inhibit apoptosis activation. Moreover, in muscle tissue, the levels of mitochondrial carbonyl protein were decreased and mitochondrial complex activities were significantly improved by HT supplementation. In db/db mice, HT significantly decreased fasting glucose, similar to metformin. Notably, HT decreased serum lipid, at which metformin failed. Also, HT was more effective at decreasing the oxidation levels of lipids and proteins in both liver and muscle tissue. Similar to the results in the HFD model, HT decreased muscle mitochondrial carbonyl protein levels and improved mitochondrial complex activities in db/db mice. Our study links the olive oil component HT to diabetes and metabolic disease through changes that are not limited to decreases in oxidative stress, suggesting a potential pharmaceutical or clinical use of HT in metabolic syndrome treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism.

    Trangmar, Steven J; Chiesa, Scott T; Llodio, Iñaki; Garcia, Benjamin; Kalsi, Kameljit K; Secher, Niels H; González-Alonso, José

    2015-11-01

    Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, whereas the cerebral metabolic rate for O2 (CMRO2 ) is preserved. It remains unknown whether CMRO2 is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled to fatigue. Two studies were undertaken. In study 1, 10 male cyclists cycled in the heat for ∼2 h with (control) and without fluid replacement (dehydration) while internal and external carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples were assessed with dehydration to evaluate CMRO2 . In study 2, in 8 male subjects, middle cerebral artery blood velocity was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, internal carotid artery flow declined to baseline with progressive dehydration (P dehydration accelerates the decline in CBF without affecting CMRO2 and also restricts extracranial perfusion. Thus, fatigue is related to a reduction in CBF and extracranial perfusion rather than CMRO2 . Copyright © 2015 the American Physiological Society.

  19. Cerebral blood flow and oxygen metabolism in senile dementia of Alzheimer's type and vascular dementia with deep white matter changes

    Tohgi, H.; Yonezawa, H.; Takahashi, S.; Sato, N.; Kato, E.; Kudo, M.; Hatano, K.; Sasaki, T.

    1998-01-01

    Regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (rCMRO 2 ), oxygen extraction fraction (rOEF), and cerebral blood volume (rCBV) were investigated using positron emission tomography (PET) in 16 patients with senile dementia of Alzheimer's type (SDAT), and compared with those of 6 nondemented and 3 demented patients with deep white matter high signal (DWMH) on T2-weighted MRI and 6 controls. rCBF, rCMRO 2 and rCBV were determined using C 15 O 2 , 15 O 2 and C 15 O, respectively. rCBF and CMRO 2 were significantly decreased in the frontal, parietal and temporal cortex (P 2 was significantly reduced in only the frontal and temporal cortex of demented patients (P < 0.05). rOEF was significantly increased in the parietal cortex of patients with SDAT and in the white matter of patients with SDAT or DWMH (P < 0.05), and the increase in the frontal white matter significantly paralleled the progression of dementia in patients with SDAT (P < 0.05). rCBV was significantly decreased in the parietal and temporal cortex of patients with SDAT (P < 0.05), but not in any areas of those with DWMH. (orig.)

  20. Lower aerobic capacity was associated with abnormal intramuscular energetics in patients with metabolic syndrome

    Yokota, Takashi; Kinugawa, Shintaro; Okita, Koichi

    2011-01-01

    Lower aerobic capacity is a strong and independent predictor of cardiovascular morbidity and mortality in patients with metabolic syndrome (MetS). However, the mechanisms are not fully elucidated. We tested the hypothesis that skeletal muscle dysfunction could contribute to the lower aerobic capacity in MetS patients. The incremental exercise tests with cycle ergometer were performed in 12 male patients with MetS with no habitual exercise and 11 age-, sex- and activity-matched control subjects to assess the aerobic capacity. We performed 31 phosphorus-magnetic resonance spectroscopy (MRS) to assess the high-energy phosphate metabolism in skeletal muscle during aerobic exercise. Proton-MRS was also performed to measure intramyocellular lipid (IMCL) content. Peak oxygen uptake (peak VO 2 ; 34.1±6.2 vs. 41.4±8.4 ml kg -1 min -1 , P -1 min -1 , P 2 (r=-0.64) and AT (r=-0.60), respectively. IMCL content was threefold higher in MetS and was inversely correlated with peak VO 2 (r=-0.47) and AT (r=-0.52), respectively. Moreover, there was a positive correlation between IMCL content and PCr loss (r=0.64). These results suggested that lean-body aerobic capacity in MetS patients was lower compared with activity-matched healthy subjects, which might be due to the reduced intramuscular fatty acid oxidative metabolism. (author)

  1. Regional differences of relationships between atrophy and glucose metabolism of cerebral cortex in patients with Alzheimer's disease

    Toyama, H.; Uemura, K.; Kanekiyo, S.; Ishii, K.; Ishii, K.

    2002-01-01

    Aim: The purpose of this paper is to estimate a correlation between the extent of atrophy and the decline in the brain function measured with PET study among the patients with Alzheimer's disease by each brain lobe. Materials and Methods: Two groups, the normal controls (male: 8, female: 22 age: 62.4±4.9) and the patients with Alzheimer's disease (male: 6, female: 24, age: 65.9±7.2) participated in this study. The extent of atrophy was evaluated from the extracted gyrus on 2D-projection magnetic resonance imaging (MRI) and the cerebral cortical glucose metabolism was assessed on 2D-projection positron emission tomography (PET) image, and then a relationship between the cerebral atrophy and the function was evaluated by each brain lobe extracted automatically. 2D-projection of PET and MR images were made by means of the Mollweide method which keeps the area of the brain surface. In order to extract brain lobes from each subject automatically, the bitmap with different value by each brain lobe was made from a standard brain image and was automatically transformed to match each subject's brain image by using SPM99. A correlation image was generated between 2D-projection images of glucose metabolism and the area of the sulcus and the gyrus extracted from the correlation between MR and PET images clustered by K-means method. Results: The glucose metabolism of Alzheimer's disease was lower than that of normal control subjects at the frontal, parietal, and temporal lobes with the same extent of atrophy as that of the normal. There was high correlation between the area of gyrus and the glucose metabolism, and the correlation tendency of the Alzheimer's disease was steeper than that of the normal control at the parietal lobe. Conclusions: Combined analysis of regional morphology and function may be useful to distinguish pathological process such as early stage of Alzheimer's disease from normal physiological aging

  2. Correlation of methylenetetrahydrofolate reductase polymorphism with Hcy metabolism and inflammatory response in patients with recurrent cerebral infarction

    Gai-Zhuang Liu

    2017-07-01

    Full Text Available Objective: To study the correlation of methylenetetrahydrofolate reductase (MTHFR polymorphism with Hcy metabolism and inflammatory response in patients with recurrent cerebral infarction. Methods: 40 patients with recurrent cerebral infarction who were treated in Yulin Third Hospital between December 2013 and December 2016 were selected as recurrent group, 58 patients with primary cerebral infarction were selected as primary group, and 60 healthy volunteers were selected as control group. Peripheral blood MTHFR gene C677T polymorphism and serum levels of Hcy metabolism indexes and inflammatory response indicators were determined. Results: CC genotype constituent ratio of recurrent group was significantly lower than that of primary group and control group while CT genotype and TT genotype constituent ratio were significantly higher than those of primary group and control group; serum Hcy, HMGB1, sCD40L, YKL-40, Lp-PLA2 and MMP-9 levels in recurrent group and primary group were significantly higher than those in control group while VitB12 and FA levels were significantly lower than those in control group; serum Hcy, HMGB1, sCD40L, YKL-40, Lp-PLA2 and MMP-9 levels in recurrent group were significantly higher than those in primary group while VitB12 and FA levels were significantly lower than those in primary group. Serum Hcy, HMGB1, sCD40L, YKL-40, Lp-PLA2 and MMP-9 levels in patients with CC genotype were significantly lower than those in patients with CT genotype and TT genotype while VitB12 and FA levels were significantly higher than those in patients with CT genotype and TT genotype; serum Hcy, HMGB1, sCD40L, YKL-40, Lp-PLA2 and MMP-9 levels in patients with CT genotype were significantly lower than those in patients with TT genotype while VitB12 and FA levels were significantly higher than those in patients with TT genotype. Conclusion: MTHFR gene C677T polymorphism is closely related to the recurrence of cerebral infarction, and allele C

  3. Short-Term Treatment with Bisphenol-A Leads to Metabolic Abnormalities in Adult Male Mice

    Batista, Thiago M.; Alonso-Magdalena, Paloma; Vieira, Elaine; Amaral, Maria Esmeria C.; Cederroth, Christopher R.; Nef, Serge; Quesada, Ivan; Carneiro, Everardo M.; Nadal, Angel

    2012-01-01

    Bisphenol-A (BPA) is one of the most widespread endocrine disrupting chemicals (EDC) used as the base compound in the manufacture of polycarbonate plastics. Although evidence points to consider exposure to BPA as a risk factor for insulin resistance, its actions on whole body metabolism and on insulin-sensitive tissues are still unclear. The aim of the present work was to study the effects of low doses of BPA in insulin-sensitive peripheral tissues and whole body metabolism in adult mice. Adult mice were treated with subcutaneous injection of 100 µg/kg BPA or vehicle for 8 days. Whole body energy homeostasis was assessed with in vivo indirect calorimetry. Insulin signaling assays were conducted by western blot analysis. Mice treated with BPA were insulin resistant and had increased glucose-stimulated insulin release. BPA-treated mice had decreased food intake, lower body temperature and locomotor activity compared to control. In skeletal muscle, insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit was impaired in BPA-treated mice. This impairment was associated with a reduced insulin-stimulated Akt phosphorylation in the Thr308 residue. Both skeletal muscle and liver displayed an upregulation of IRS-1 protein by BPA. The mitogen-activated protein kinase (MAPK) signaling pathway was also impaired in the skeletal muscle from BPA-treated mice. In the liver, BPA effects were of lesser intensity with decreased insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit. In conclusion, short-term treatment with low doses of BPA slows down whole body energy metabolism and disrupts insulin signaling in peripheral tissues. Thus, our findings support the notion that BPA can be considered a risk factor for the development of type 2 diabetes. PMID:22470480

  4. Metabolic Characterization of Acutely Isolated Hippocampal and Cerebral Cortical Slices Using [U-13C]Glucose and [1,2-13C]Acetate as Substrates.

    McNair, Laura F; Kornfelt, Rasmus; Walls, Anne B; Andersen, Jens V; Aldana, Blanca I; Nissen, Jakob D; Schousboe, Arne; Waagepetersen, Helle S

    2017-03-01

    Brain slice preparations from rats, mice and guinea pigs have served as important tools for studies of neurotransmission and metabolism. While hippocampal slices routinely have been used for electrophysiology studies, metabolic processes have mostly been studied in cerebral cortical slices. Few comparative characterization studies exist for acute hippocampal and cerebral cortical slices, hence, the aim of the current study was to characterize and compare glucose and acetate metabolism in these slice preparations in a newly established incubation design. Cerebral cortical and hippocampal slices prepared from 16 to 18-week-old mice were incubated for 15-90 min with unlabeled glucose in combination with [U- 13 C]glucose or [1,2- 13 C]acetate. Our newly developed incubation apparatus allows accurate control of temperature and is designed to avoid evaporation of the incubation medium. Subsequent to incubation, slices were extracted and extracts analyzed for 13 C-labeling (%) and total amino acid contents (µmol/mg protein) using gas chromatography-mass spectrometry and high performance liquid chromatography, respectively. Release of lactate from the slices was quantified by analysis of the incubation media. Based on the measured 13 C-labeling (%), total amino acid contents and relative activity of metabolic enzymes/pathways, we conclude that the slice preparations in the current incubation apparatus exhibited a high degree of metabolic integrity. Comparison of 13 C-labeling observed with [U- 13 C]glucose in slices from cerebral cortex and hippocampus revealed no significant regional differences regarding glycolytic or total TCA cycle activities. On the contrary, results from the incubations with [1,2- 13 C]acetate suggest a higher capacity of the astrocytic TCA cycle in hippocampus compared to cerebral cortex. Finally, we propose a new approach for assessing compartmentation of metabolite pools between astrocytes and neurons using 13 C-labeling (%) data obtained from

  5. Design of the NL-ENIGMA study: Exploring the effect of Souvenaid on cerebral glucose metabolism in early Alzheimer's disease.

    Scheltens, Nienke M E; Kuyper, Ingrid S; Boellaard, Ronald; Barkhof, Frederik; Teunissen, Charlotte E; Broersen, Laus M; Lansbergen, Marieke M; van der Flier, Wiesje M; van Berckel, Bart N M; Scheltens, Philip

    2016-11-01

    Alzheimer's disease is associated with early synaptic loss. Specific nutrients are known to be rate limiting for synapse formation. Studies have shown that administering specific nutrients may improve memory function, possibly by increasing synapse formation. This Dutch study explores the Effect of a specific Nutritional Intervention on cerebral Glucose Metabolism in early Alzheimer's disease (NL-ENIGMA, Dutch Trial Register NTR4718, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4718). The NL-ENIGMA study is designed to test whether the specific multinutrient combination Fortasyn Connect present in the medical food Souvenaid influences cerebral glucose metabolism as a marker for improved synapse function. This study is a double-blind, randomized controlled parallel-group single-center trial. Forty drug-naive patients with mild cognitive impairment or mild dementia with evidence of amyloid deposition are 1:1 randomized to receive either the multinutrient combination or placebo once daily. Main exploratory outcome parameters include absolute quantitative positron emission tomography with 18 F-fluorodeoxyglucose (including arterial sampling) and standard uptake value ratios normalized for the cerebellum or pons after 24 weeks. We expect the NL-ENIGMA study to provide further insight in the potential of this multinutrient combination to improve synapse function.

  6. [Prevalence of target organ damage and metabolic abnormalities in resistant hypertension].

    Armario, Pedro; Oliveras, Anna; Hernández Del Rey, Raquel; Ruilope, Luis Miguel; De La Sierra, Alejandro

    2011-10-15

    Patients with resistant hypertension (RH) are relatively frequently visited in specialized units of hypertension. The aim of this study was to assess the prevalence of target organ damage, central obesity and metabolic syndrome in a cohort of patients with RH consecutively included in the Register of Resistant Hypertension of the Spanish Society of Hypertension (SHE-LELHA). Cross-sectional, multicenter epidemiologic study in usual clinical practice conditions. Patients with clinical diagnosis of resistant hypertension, that is, office systolic and diastolic blood pressure ≥ 140 mm Hg and/or ≥ 90 mm Hg, respectively, despite a prescribed therapeutic schedule with an appropriate combination of three or more full-dose antihypertensive drugs, including a diuretic, were consecutively recruited from specialized hypertension units spread through Spain. Demographic and anthropometric characteristics as well as cardiovascular risk factors and associated conditions were recorded, and all the subjects underwent 24-h ambulatory blood pressure monitoring. Left ventricular hypertrophy was considered as a left ventricular mass index ≥ 125 g/m(2) in males and ≥ 110 g/m(2) in females. Left atrial enlargement was defined as an indexed left atrium diameter ≥ 26 mm/m(2). Microalbuminuria was defined as a urinary albumin/creatinine ratio ≥ 22 mg/g in males and ≥ 31 mg/g in females. 513 patients were included, aged 64±11 years old, 47% women. Central obesity was present in 65.7% (CI 95% 61.6-69.9), 38.6% (CI 95% 34.4-42.8) had diabetes and 63.7% (CI 95% 59.4-67.9) had metabolic syndrome. The prevalence of left ventricular hypertrophy and left atrial enlargement, determined by echocardiography was 57.1% (CI 95% 50.8-63.5) and 10.0% (CI 95% 6.3-13.7) respectively. Microalbuminuria was found in 46.6% (CI 95% 41.4-51.8) of the subjects. Patients with metabolic syndrome were significantly older (65.4±11 and 62.5±12 years; P=.0052), presented a higher prevalence of diabetes

  7. Late Antiretroviral Therapy (ART) Initiation Is Associated with Long-Term Persistence of Systemic Inflammation and Metabolic Abnormalities

    Ghislain, Mathilde; Bastard, Jean-Philippe; Meyer, Laurence; Capeau, Jacqueline; Fellahi, Soraya; Gérard, Laurence; May, Thierry; Simon, Anne; Vigouroux, Corinne; Goujard, Cécile

    2015-01-01

    Objectives HIV-induced immunodeficiency is associated with metabolic abnormalities and systemic inflammation. We investigated the effect of antiretroviral therapy (ART) on restoration of insulin sensitivity, markers of immune activation and inflammation. Methods Immunological, metabolic and inflammatory status was assessed at antiretroviral therapy initiation and three years later in 208 patients from the ANRS-COPANA cohort. Patients were compared according to their pre-ART CD4+ cell count (group 1: ≤ 200/mm3, n = 66 vs. group 2: > 200/mm3, n = 142). Results Median CD4+ cell count increased in both groups after 3 years of successful ART but remained significantly lower in group 1 than in group 2 (404 vs 572 cells/mm3). Triglyceride and insulin levels were higher or tended to be higher in group 1 than in group 2 at ART initiation (median: 1.32 vs 0.97 mmol/l, p = 0.04 and 7.6 vs 6.8 IU, p = 0.09, respectively) and remained higher after three years of ART (1.42 vs 1.16 mmol/L, p = 0.0009 and 8.9 vs 7.2 IU, p = 0.01). After adjustment for individual characteristics and antiretroviral therapy regimens (protease inhibitor (PI), zidovudine), insulin levels remained significantly higher in patients with low baseline CD4+ cell count. Baseline IL-6, sCD14 and sTNFR2 levels were higher in group 1 than in group 2. Most biomarkers of immune activation/inflammation declined during ART, but IL-6 and hsCRP levels remained higher in patients with low baseline CD4+ cell count than in the other patients (median are respectively 1.4 vs 1.1 pg/ml, p = 0.03 and 2.1 vs 1.3 mg/ml, p = 0.07). Conclusion After three years of successful ART, low pretreatment CD4+ T cell count remained associated with elevated insulin, triglyceride, IL-6 and hsCRP levels. These persistent metabolic and inflammatory abnormalities could contribute to an increased risk of cardiovascular and metabolic disease. PMID:26636578

  8. Metabolic Abnormalities Detected in Phase II Evaluation of Doxycycline in Dogs with Multicentric B-Cell Lymphoma.

    Hume, Kelly R; Sylvester, Skylar R; Borlle, Lucia; Balkman, Cheryl E; McCleary-Wheeler, Angela L; Pulvino, Mary; Casulo, Carla; Zhao, Jiyong

    2018-01-01

    Doxycycline has antiproliferative effects in human lymphoma cells and in murine xenografts. We hypothesized that doxycycline would decrease canine lymphoma cell viability and prospectively evaluated its clinical tolerability in client-owned dogs with spontaneous, nodal, multicentric, substage a, B-cell lymphoma, not previously treated with chemotherapy. Treatment duration ranged from 1 to 8 weeks (median and mean, 3 weeks). Dogs were treated with either 10 ( n  = 6) or 7.5 ( n  = 7) mg/kg by mouth twice daily. One dog had a stable disease for 6 weeks. No complete or partial tumor responses were observed. Five dogs developed grade 3 and/or 4 metabolic abnormalities suggestive of hepatopathy with elevations in bilirubin, ALT, ALP, and/or AST. To evaluate the absorption of oral doxycycline in our study population, serum concentrations in 10 treated dogs were determined using liquid chromatography tandem mass spectrometry. Serum levels were variable and ranged from 3.6 to 16.6 µg/ml (median, 7.6 µg/ml; mean, 8.8 µg/ml). To evaluate the effect of doxycycline on canine lymphoma cell viability in vitro , trypan blue exclusion assay was performed on canine B-cell lymphoma cell lines (17-71 and CLBL) and primary B-cell lymphoma cells from the nodal tissue of four dogs. A doxycycline concentration of 6 µg/ml decreased canine lymphoma cell viability by 80%, compared to matched, untreated, control cells (mixed model analysis, p  canine lymphoma, combination therapy may be worthwhile if future research determines that doxycycline can alter cell survival pathways in canine lymphoma cells. Due to the potential for metabolic abnormalities, close monitoring is recommended with the use of this drug in tumor-bearing dogs. Additional research is needed to assess the tolerability of chronic doxycycline therapy.

  9. Will acarbose improve the metabolic abnormalities of insulin-resistant type 2 diabetes mellitus?

    Scott, R; Lintott, C J; Zimmet, P; Campbell, L; Bowen, K; Welborn, T

    1999-03-01

    Individuals with type 2 diabetes mellitus (n = 105; age 36-71 years) on diet therapy alone, and with quite good glycaemic control (mean HbA1c approximately 7.0%) were randomized to receive acarbose (100 mg three times daily) or placebo for 16 weeks, and changes in clinical and metabolic parameters indicative of Syndrome X were monitored. Fasting levels of glucose, glycosylated haemoglobin (HbA1c), true insulin, proinsulin, fibrinogen and lipids were measured four times weekly, and glucose, insulin, proinsulin and triglyceride responses to a standardized 1.6 MJ breakfast were determined at 0, 1 and 2 h post meal. Analysis was on an intention-to-treat basis. Fasting levels of glucose (P fasting glucose and triglyceride levels, lowers HbA1c and limits the glycaemic and insulin response to food in individuals with type 2 diabetes mellitus with Syndrome X. Pharmacological agents that improve the metabolic environment and reduce insulin resistance have the potential to limit the progression of atherogenesis associated with type 2 diabetes mellitus.

  10. PM2.5-bound metal metabolic distribution and coupled lipid abnormality at different developmental windows.

    Ku, Tingting; Zhang, Yingying; Ji, Xiaotong; Li, Guangke; Sang, Nan

    2017-09-01

    Atmospheric fine particulate matter (PM 2.5 ) is a serious threat to human health. As a toxicant constituent, metal leads to significant health risks in a population, but exposure to PM 2.5 -bound metals and their biological impacts are not fully understood. In this study, we determined the metal contents of PM 2.5 samples collected from a typical coal-burning city and then investigated the metabolic distributions of six metals (Zn, Pb, Mn, As, Cu, and Cd) following PM 2.5 inhalation in mice in different developmental windows. The results indicate that fine particles were mainly deposited in the lung, but PM 2.5 -bound metals could reach and gather in secondary off-target tissues (the lung, liver, heart and brain) with a developmental window-dependent property. Furthermore, elevations in triglycerides and cholesterol levels in sensitive developmental windows (the young and elderly stages) occurred, and significant associations between metals (Pb, Mn, As and Cd) and cholesterol in the heart, brain, liver and lung were observed. These findings suggest that PM 2.5 inhalation caused selective metal metabolic distribution in tissues with a developmental window-dependent property and that the effects were associated with lipid alterations. This provides a foundation for the underlying systemic toxicity following PM 2.5 exposure based on metal components. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Amelioration of Abnormalities Associated with the Metabolic Syndrome by Spinacia oleracea (Spinach) Consumption and Aerobic Exercise in Rats.

    Panda, Vandana; Mistry, Kinjal; Sudhamani, S; Nandave, Mukesh; Ojha, Shreesh Kumar

    2017-01-01

    The present study evaluates the protective effects of an antioxidant-rich extract of Spinacea oleracea (NAOE) in abnormalities associated with the metabolic syndrome (MetS) in rats. HPTLC of NAOE revealed the presence of 13 total antioxidants, 14 flavonoids, and 10 phenolic acids. Rats administered with fructose (20%  w / v ) in drinking water for 45 days to induce abnormalities of MetS received NAOE (200 and 400 mg/kg, po), the standard drug gemfibrozil (60 mg/kg, po), aerobic exercise (AE), and a combination of NAOE 400 mg/kg and AE (NAOEAE) daily for 45 days. All treatments significantly altered the lipid profile and attenuated the fructose-elevated levels of uric acid, C-reactive protein, homocysteine, and marker enzymes (AST, LDH, and CK-MB) in serum and malondialdehyde in the heart and restored the fructose-depleted levels of glutathione and antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase). A significant decrease in blood glucose and insulin levels decreased insulin resistance, and improved glucose tolerance was observed in the treatment animals when compared with the fructose-fed animals. The best mitigation of MetS was shown by the NAOEAE treatment indicating that regular exercise along with adequate consumption of antioxidant-rich foods such as spinach in diet can help control MetS.

  12. Amelioration of Abnormalities Associated with the Metabolic Syndrome by Spinacia oleracea (Spinach Consumption and Aerobic Exercise in Rats

    Vandana Panda

    2017-01-01

    Full Text Available The present study evaluates the protective effects of an antioxidant-rich extract of Spinacea oleracea (NAOE in abnormalities associated with the metabolic syndrome (MetS in rats. HPTLC of NAOE revealed the presence of 13 total antioxidants, 14 flavonoids, and 10 phenolic acids. Rats administered with fructose (20% w/v in drinking water for 45 days to induce abnormalities of MetS received NAOE (200 and 400 mg/kg, po, the standard drug gemfibrozil (60 mg/kg, po, aerobic exercise (AE, and a combination of NAOE 400 mg/kg and AE (NAOEAE daily for 45 days. All treatments significantly altered the lipid profile and attenuated the fructose-elevated levels of uric acid, C-reactive protein, homocysteine, and marker enzymes (AST, LDH, and CK-MB in serum and malondialdehyde in the heart and restored the fructose-depleted levels of glutathione and antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. A significant decrease in blood glucose and insulin levels decreased insulin resistance, and improved glucose tolerance was observed in the treatment animals when compared with the fructose-fed animals. The best mitigation of MetS was shown by the NAOEAE treatment indicating that regular exercise along with adequate consumption of antioxidant-rich foods such as spinach in diet can help control MetS.

  13. Lack of significant metabolic abnormalities in mice with liver-specific disruption of 11β-hydroxysteroid dehydrogenase type 1.

    Lavery, Gareth G

    2012-07-01

    Glucocorticoids (GC) are implicated in the development of metabolic syndrome, and patients with GC excess share many clinical features, such as central obesity and glucose intolerance. In patients with obesity or type 2 diabetes, systemic GC concentrations seem to be invariably normal. Tissue GC concentrations determined by the hypothalamic-pituitary-adrenal (HPA) axis and local cortisol (corticosterone in mice) regeneration from cortisone (11-dehydrocorticosterone in mice) by the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme, principally expressed in the liver. Transgenic mice have demonstrated the importance of 11β-HSD1 in mediating aspects of the metabolic syndrome, as well as HPA axis control. In order to address the primacy of hepatic 11β-HSD1 in regulating metabolism and the HPA axis, we have generated liver-specific 11β-HSD1 knockout (LKO) mice, assessed biomarkers of GC metabolism, and examined responses to high-fat feeding. LKO mice were able to regenerate cortisol from cortisone to 40% of control and had no discernible difference in a urinary metabolite marker of 11β-HSD1 activity. Although circulating corticosterone was unaltered, adrenal size was increased, indicative of chronic HPA stimulation. There was a mild improvement in glucose tolerance but with insulin sensitivity largely unaffected. Adiposity and body weight were unaffected as were aspects of hepatic lipid homeostasis, triglyceride accumulation, and serum lipids. Additionally, no changes in the expression of genes involved in glucose or lipid homeostasis were observed. Liver-specific deletion of 11β-HSD1 reduces corticosterone regeneration and may be important for setting aspects of HPA axis tone, without impacting upon urinary steroid metabolite profile. These discordant data have significant implications for the use of these biomarkers of 11β-HSD1 activity in clinical studies. The paucity of metabolic abnormalities in LKO points to important compensatory effects by HPA

  14. Metabolic abnormalities associated with weight loss during chemoirradiation of head-and-neck cancer

    Lin, Alexander; Jabbari, Siavash; Worden, Francis P.; Bradford, Carol R.; Chepeha, Douglas B.; Teknos, Theodoros N.; Liao, Jay J.; Nyquist, Gurston G.; Tsien, Christina; Schipper, Matthew J.; Urba, Susan; Wolf, Gregory T.; Eisbruch, Avraham

    2005-01-01

    Purpose: Weight loss caused by acute mucositis and dysphagia is common during concurrent chemoirradiation (chemo-RT) of head-and-neck (HN) cancer. The metabolic consequences of weight loss during chemo-RT were investigated. Patients and Methods: Ninety-six patients with locally advanced HN cancer were treated from 1995 to 2001 on protocols that consisted of 1 to 2 cycles of induction cisplatin/5-fluorouracil followed by irradiation (70 Gy over 7 weeks) concurrent with cisplatin (100 mg/m 2 every 3 weeks). Body weights and metabolic evaluations were obtained before and during induction chemotherapy and chemo-RT. Greatest percent changes in weight and in the laboratory values were calculated for each phase of therapy. Results: During induction chemotherapy, significant changes were found in BUN, BUN:creatinine ratio, HCO 3 , Mg, and albumin, but not in creatinine, Na, K, or weight. During chemo-RT, significant additional changes were observed in all parameters measured, including increases in BUN, creatinine, BUN: creatinine ratio, and HCO 3 and decreases in Mg, albumin, Na, K, and weight. The magnitude of most of these changes was significantly greater during chemo-RT than during induction chemotherapy. During chemo-RT, 35% of the patients had more than 10% body weight loss and 6 patients had an increase in creatinine of more than 100%, including 5 patients with Grade 2 nephrotoxicity, all of whom had weight loss 10% or more. Significant correlations were found between weight loss and creatinine (p < 0.0001) or BUN (p = 0.0002) rises, but not with BUN:creatinine ratio or other metabolic changes. Age, gender, tobacco history, hypertension, and diabetes mellitus were not significant predictors of nephrotoxicity. Conclusions: Weight loss during cisplatin-containing chemo-RT was found to be associated with reduced kidney function. These findings do not establish cause-effect relationships; however, they highlight the importance of intensive supportive measures of

  15. Elevated levels of plasma phenylalanine in schizophrenia: a guanosine triphosphate cyclohydrolase-1 metabolic pathway abnormality?

    Olaoluwa Okusaga

    Full Text Available BACKGROUND: Phenylalanine and tyrosine are precursor amino acids required for the synthesis of dopamine, the main neurotransmitter implicated in the neurobiology of schizophrenia. Inflammation, increasingly implicated in schizophrenia, can impair the function of the enzyme Phenylalanine hydroxylase (PAH; which catalyzes the conversion of phenylalanine to tyrosine and thus lead to elevated phenylalanine levels and reduced tyrosine levels. This study aimed to compare phenylalanine, tyrosine, and their ratio (a proxy for PAH function in a relatively large sample of schizophrenia patients and healthy controls. METHODS: We measured non-fasting plasma phenylalanine and tyrosine in 950 schizophrenia patients and 1000 healthy controls. We carried out multivariate analyses to compare log transformed phenylalanine, tyrosine, and phenylalanine:tyrosine ratio between patients and controls. RESULTS: Compared to controls, schizophrenia patients had higher phenylalanine (p<0.0001 and phenylalanine: tyrosine ratio (p<0.0001 but tyrosine did not differ between the two groups (p = 0.596. CONCLUSIONS: Elevated phenylalanine and phenylalanine:tyrosine ratio in the blood of schizophrenia patients have to be replicated in longitudinal studies. The results may relate to an abnormal PAH function in schizophrenia that could become a target for novel preventative and interventional approaches.

  16. Mitochondrial dysfunction induced by frataxin deficiency is associated with cellular senescence and abnormal calcium metabolism

    Arantxa eBolinches-Amorós

    2014-05-01

    Full Text Available Friedreich ataxia is considered a neurodegenerative disorder involving both the peripheral and central nervous systems. Dorsal root ganglia (DRG are the major target tissue structures. This neuropathy is caused by mutations in the FXN gene that encodes frataxin. Here, we investigated the mitochondrial and cell consequences of frataxin depletion in a cellular model based on frataxin silencing in SH-SY5Y human neuroblastoma cells, a cell line that has been used widely as in vitro models for studies on neurological diseases. We showed that the reduction of frataxin induced mitochondrial dysfunction due to a bioenergetic deficit and abnormal Ca2+ homeostasis in the mitochondria that were associated with oxidative and endoplasmic reticulum stresses. The depletion of frataxin did not cause cell death but increased autophagy, which may have a cytoprotective effect against cellular insults such as oxidative stress. Frataxin silencing provoked slow cell growth associated with cellular senescence, as demonstrated by increased SA-βgal activity and cell cycle arrest at the G1 phase. We postulate that cellular senescence might be related to a hypoplastic defect in the DRG during neurodevelopment, as suggested by necropsy studies.

  17. Expression changes of hippocampal energy metabolism enzymes contribute to behavioural abnormalities during chronic morphine treatment

    Xiao-Lan Chen; Jing-Gen Liu; Gang Lu; Ying-Xia Gong; Liang-Cai Zhao; Jie Chen; Zhi-Qiang Chi; Yi-Ming Yang; Zhong Chen; Qing-lin Li

    2007-01-01

    Dependence and impairment of learning and memory are two well-established features caused by abused drugs such as opioids. The hippocampus is an important region associated with both drug dependence and learning and memory. However, the molecular events in hippocampus following exposure to abused drugs such as opioids are not well understood. Here we examined the effect of chronic morphine treatment on hippocampal protein expression by proteomic analyses. We found that chronic exposure of mice to morphine for 10 days produced robust morphine withdrawal jumping and memory impairment, and also resulted in a significant downregulation of hippocampal protein levels of three metabolic enzymes, including Fe-S protein 1 of NADH dehydrogenase, dihydrolipoamide acetyltransferase or E2 component of the pyruvate dehydrogenase complex and lactate dehydrogenase 2. Further real-time quantitative PCR analyses confirmed that the levels of the corresponding mRNAs were also remarkably reduced. Consistent with these findings, lower ATP levels and an impaired ability to convert glucose into ATP were also observed in the hippocampus of chronically treated mice. Opioid antagonist naltrexone administrated concomitantly with morphine significantly suppressed morphine withdrawal jumping and reversed the downregulation of these proteins. Acute exposure to morphine also produced robust morphine withdrawal jumping and significant memory impairment, but failed to decrease the expression of these three proteins. Intrahippocampal injection of D-glucose before morphine administration significantly enhanced ATP levels and suppressed morphine withdrawal jumping and memory impairment in acute morphine-treated but not in chronic morphine-treated mice. Intraperitoneal injection of high dose of D-glucose shows a similar effect on morphine-induced withdrawal jumping as the central treatment. Taken together, our results suggest that reduced expression of the three metabolic enzymes in the hippocampus as

  18. Evaluation of tributyltin toxicity in Chinese rare minnow larvae by abnormal behavior, energy metabolism and endoplasmic reticulum stress.

    Li, Zhi-Hua; Li, Ping

    2015-02-05

    Tributyltin (TBT) is a ubiquitous contaminant in aquatic environment, but the detailed mechanisms underlying the toxicity of TBT have not been fully understood. In this study, the effects of TBT on behavior, energy metabolism and endoplasmic reticulum (ER) stress were investigated by using Chinese rare minnow larvae. Fish larvae were exposed at sublethal concentrations of TBT (100, 400 and 800 ng/L) for 7 days. Compared with the control, energy metabolic parameters (RNA/DNA ratio, Na(+)-K(+)-ATPase) were significantly inhibited in fish exposed at highest concentration (800 ng/L), as well as abnormal behaviors observed. Moreover, we found that the PERK (PKR-like ER kinase)-eIF2α (eukaryotic translation initiation factor 2α) pathway, as the main branch was activated by TBT exposure in fish larvae. In short, TBT-induced physiological, biochemical and molecular responses in fish larvae were reflected in parameters measured in this study, which suggest that these biomarkers could be used as potential indicators for monitoring organotin compounds present in aquatic environment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. A combination of physical activity and computerized brain training improves verbal memory and increases cerebral glucose metabolism in the elderly.

    Shah, T; Verdile, G; Sohrabi, H; Campbell, A; Putland, E; Cheetham, C; Dhaliwal, S; Weinborn, M; Maruff, P; Darby, D; Martins, R N

    2014-12-02

    Physical exercise interventions and cognitive training programs have individually been reported to improve cognition in the healthy elderly population; however, the clinical significance of using a combined approach is currently lacking. This study evaluated whether physical activity (PA), computerized cognitive training and/or a combination of both could improve cognition. In this nonrandomized study, 224 healthy community-dwelling older adults (60-85 years) were assigned to 16 weeks home-based PA (n=64), computerized cognitive stimulation (n=62), a combination of both (combined, n=51) or a control group (n=47). Cognition was assessed using the Rey Auditory Verbal Learning Test, Controlled Oral Word Association Test and the CogState computerized battery at baseline, 8 and 16 weeks post intervention. Physical fitness assessments were performed at all time points. A subset (total n=45) of participants underwent [(18)F] fluorodeoxyglucose positron emission tomography scans at 16 weeks (post-intervention). One hundred and ninety-one participants completed the study and the data of 172 participants were included in the final analysis. Compared with the control group, the combined group showed improved verbal episodic memory and significantly higher brain glucose metabolism in the left sensorimotor cortex after controlling for age, sex, premorbid IQ, apolipoprotein E (APOE) status and history of head injury. The higher cerebral glucose metabolism in this brain region was positively associated with improved verbal memory seen in the combined group only. Our study provides evidence that a specific combination of physical and mental exercises for 16 weeks can improve cognition and increase cerebral glucose metabolism in cognitively intact healthy older adults.

  20. Reversal of brain metabolic abnormalities following treatment of AIDS dementia complex with 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine): a PET-FDG study

    Brunetti, A.; Berg, G.; Di Chiro, G.

    1989-01-01

    Brain glucose metabolism was evaluated in four patients with acquired immunodeficiency syndrome (AIDS) dementia complex using [ 18 F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) scans at the beginning of therapy with 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine), and later in the course of therapy. In two patients, baseline, large focal cortical abnormalities of glucose utilization were reversed during the course of therapy. In the other two patients, the initial PET study did not reveal pronounced focal alterations, while the post-treatment scans showed markedly increased cortical glucose metabolism. The improved cortical glucose utilization was accompanied in all patients by immunologic and neurologic improvement. PET-FDG studies can detect cortical metabolic abnormalities associated with AIDS dementia complex, and may be used to monitor the metabolic improvement in response to AZT treatment

  1. Regional Cerebral Perfusion in Progressive Supranuclear Palsy

    Lee, Won Yong; Lee, Ki Hyeong; Yoon, Byung Woo; Lee, Sang Bok; Jeon, Beom S. [Samsung Medical Center, Seoul (Korea, Republic of); Lee, Kyung Han; Lee, Myung Chul [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1996-03-15

    Progressive supranuclear palsy (PSP) is a Parkinson-plus syndrome characterized clinically by supranuclear ophthalmoplegia, pseudobulbar palsy, axial rigidity, bradykinesia, postural instability and dementia. Presence of dementia and lack of cortical histopathology suggest the derangement of cortical function by pathological changes in subcortical structures in PSP, which is supported by the pattern of behavioral changes and measurement of brain metabolism using positron emission tomography. This study was done to examine whether there are specific changes of regional cerebral perfusion in PSP and whether there is a correlation between severity of motor abnormaility and degree of changes in cerebral perfusion. We measured regional cerebral perfusion indices in 5 cortical and 2 subcortical areas in 6 patients with a clinical diagnosis of PSP and 6 healthy age and sex matched controls using Tc-99m-HMPAO SPECT. Compared with age and sex matched controls, only superior frontal regional perfusion index was significantly decreased in PSP (p<0.05). There was no correlation between the severity of the motor abnormality and any of the regional cerebral perfusion indices (p>0.05). We affirm the previous reports that perfusion in superior frontal cortex is decreased in PSP. Based on our results that there was no correlation between severity of motor abnormality and cerebral perfusion in the superior frontal cortex, nonmotoric symptoms including dementia needs to be looked at whether there is a correlation with the perfusion abnormality in superior frontal cortex

  2. [Abnormal metabolism of triglycerides fractions in chronic pancreatitis and results after the operation treatment].

    Diakowska, Dorota; Knast, Witold; Diakowski, Witold; Grabowski, Krzysztof; Szelachowski, Piotr; Pelczar, Piotr

    2005-06-01

    This study was undertaken to determine how fats digestion processes were damaged due to chronic pancreatitis, and identify, whether lipid metabolism improved after surgical treatment the patients with chronic pancreatitis. Total lipids, triglycerides, diglycerides and free fatty acids levels in serum and stool were analysed, using chemical tests, thin-layer chromatography and electrophoresis of serum lipoproteins. The patients before the operations showed higher total lipids and triglycerides concentrations, and lower concentrations of diglycerides and free fatty acids in stool. These patients had high triglycerides, chylomicrons, VLDL, LDL-CH concentrations, and low-diglycerides, free fatty acids, HDL-CH concentrations in serum. These data were statistically significant. After the operations and substitution therapy it was observed normalization of the total lipids and lipids fractions levels in stool and in serum. Concentrations of LDL-CH and HDL-CH fractions were irregular. We conclude, that these lipids parameters could be used in diagnosing and monitoring the results of chronic pancreatitis surgical treatment.

  3. Ultrasonographic Characterization of the db/db Mouse: An Animal Model of Metabolic Abnormalities

    Francesco Faita

    2018-01-01

    Full Text Available The availability of an animal model able to reliably mirror organ damage occurring in metabolic diseases is an urgent need. These models, mostly rodents, have not been fully characterized in terms of cardiovascular, renal, and hepatic ultrasound parameters, and only sparse values can be found in literature. Aim of this paper is to provide a detailed, noninvasive description of the heart, vessels, liver, and kidneys of the db/db mouse by ultrasound imaging. Sixteen wild type and thirty-four db/db male mice (11-week-old were studied. State-of-the-art ultrasound technology was used to acquire images of cardiovascular, renal, and hepatic districts. A set of parameters describing function of the selected organs was evaluated. db/db mice are characterized by systolic and diastolic dysfunction, confirmed by strain analysis. Abdominal aortic and carotid stiffness do not seem to be increased in diabetic rodents; furthermore, they are characterized by a smaller mean diameter for both vessels. Renal microcirculation is significantly compromised, while liver steatosis is only slightly higher in db/db mice than in controls. We offer here for the first time an in vivo detailed ultrasonographic characterization of the db/db mouse, providing a useful tool for a thoughtful choice of the right rodent model for any experimental design.

  4. Correction of metabolic abnormalities in a rodent model of obesity, metabolic syndrome, and type 2 diabetes mellitus by inhibitors of hepatic protein kinase C-ι

    Sajan, Mini P.; Nimal, Sonali; Mastorides, Stephen; Acevedo-Duncan, Mildred; Kahn, C. Ronald; Fields, Alan P.; Braun, Ursula; Leitges, Michael; Farese, Robert V.

    2013-01-01

    Excessive activity of hepatic atypical protein kinase (aPKC) is proposed to play a critical role in mediating lipid and carbohydrate abnormalities in obesity, the metabolic syndrome, and type 2 diabetes mellitus. In previous studies of rodent models of obesity and type 2 diabetes mellitus, adenoviral-mediated expression of kinase-inactive aPKC rapidly reversed or markedly improved most if not all metabolic abnormalities. Here, we examined effects of 2 newly developed small-molecule PKC-ι/λ inhibitors. We used the mouse model of heterozygous muscle-specific knockout of PKC-λ, in which partial deficiency of muscle PKC-λ impairs glucose transport in muscle and thereby causes glucose intolerance and hyperinsulinemia, which, via hepatic aPKC activation, leads to abdominal obesity, hepatosteatosis, hypertriglyceridemia, and hypercholesterolemia. One inhibitor, 1H-imidazole-4-carboxamide, 5-amino-1-[2,3-dihydroxy-4-[(phosphonooxy)methyl]cyclopentyl-[1R-(1a,2b,3b,4a)], binds to the substrate-binding site of PKC-λ/ι, but not other PKCs. The other inhibitor, aurothiomalate, binds to cysteine residues in the PBl-binding domains of aPKC-λ/ι/ζ and inhibits scaffolding. Treatment with either inhibitor for 7 days inhibited aPKC, but not Akt, in liver and concomitantly improved insulin signaling to Akt and aPKC in muscle and adipocytes. Moreover, both inhibitors diminished excessive expression of hepatic, aPKC-dependent lipogenic, proinflammatory, and gluconeogenic factors; and this was accompanied by reversal or marked improvements in hyperglycemia, hyperinsulinemia, abdominal obesity, hepatosteatosis, hypertriglyceridemia, and hypercholesterolemia. Our findings highlight the pathogenetic importance of insulin signaling to hepatic PKC-ι in obesity, the metabolic syndrome, and type 2 diabetes mellitus and suggest that 1H-imidazole-4-carboxamide, 5-amino-1-[2,3-dihydroxy-4-[(phosphonooxy)methyl]cyclopentyl-[1R-(1a,2b,3b,4a)] and aurothiomalate or similar agents that

  5. Abnormal metabolic brain network associated with Parkinson's disease: replication on a new European sample

    Tomse, Petra; Jensterle, Luka; Grmek, Marko; Zaletel, Katja; Pirtosek, Zvezdan; Trost, Maja; Dhawan, Vijay; Peng, Shichun; Eidelberg, David; Ma, Yilong

    2017-01-01

    The purpose of this study was to identify the specific metabolic brain pattern characteristic for Parkinson's disease (PD): Parkinson's disease-related pattern (PDRP), using network analysis of [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) brain images in a cohort of Slovenian PD patients. Twenty PD patients (age 70.1 ± 7.8 years, Movement Disorder Society Unified Parkinson's Disease Motor Rating Scale (MDS-UPDRS-III) 38.3 ± 12.2; disease duration 4.3 ± 4.1 years) and 20 age-matched normal controls (NCs) underwent FDG-PET brain imaging. An automatic voxel-based scaled subprofile model/principal component analysis (SSM/PCA) was applied to these scans for PDRP-Slovenia identification. The pattern was characterized by relative hypermetabolism in pallidum, putamen, thalamus, brain stem, and cerebellum associated with hypometabolism in sensorimotor cortex, posterior parietal, occipital, and frontal cortices. The expression of PDRP-Slovenia discriminated PD patients from NCs (p < 0.0001) and correlated positively with patients' clinical score (MDS-UPDRS-III, p = 0.03). Additionally, its topography agrees well with the original PDRP (p < 0.001) identified in American cohort of PD patients. We validated the PDRP-Slovenia expression on additional FDG-PET scans of 20 PD patients, 20 NCs, and 25 patients with atypical parkinsonism (AP). We confirmed that the expression of PDRP-Slovenia manifests good diagnostic accuracy with specificity and sensitivity of 85-90% at optimal pattern expression cutoff for discrimination of PD patients and NCs and is not expressed in AP. PDRP-Slovenia proves to be a robust and reproducible functional imaging biomarker independent of patient population. It accurately differentiates PD patients from NCs and AP and correlates well with the clinical measure of PD progression. (orig.)

  6. (1H-NMR spectroscopy revealed Mycobacterium tuberculosis caused abnormal serum metabolic profile of cattle.

    Yingyu Chen

    Full Text Available To re-evaluate virulence of Mycobacterium tuberculosis (M. tb in cattle, we experimentally infected calves with M. tb andMycobacterium bovisvia intratracheal injection at a dose of 2.0×10(7 CFU and observed the animals for 33 weeks. The intradermal tuberculin test and IFN-γin vitro release assay showed that both M. tb and M. bovis induced similar responses. Immunohistochemical staining of pulmonary lymph nodes indicated that the antigen MPB83 of both M. tb and M. bovis were similarly distributed in the tissue samples. Histological examinations showed all of the infected groups exhibited neutrophil infiltration to similar extents. Although the infected cattle did not develop granulomatous inflammation, the metabolic profiles changed significantly, which were characterized by a change in energy production pathways and increased concentrations of N-acetyl glycoproteins. Glycolysis was induced in the infected cattle by decreased glucose and increased lactate content, and enhanced fatty acid β-oxidation was induced by decreased TG content, and decreased gluconeogenesis indicated by the decreased concentration of glucogenic and ketogenic amino acids promoted utilization of substances other than glucose as energy sources. In addition, an increase in acute phase reactive serum glycoproteins, together with neutrophil infiltration and increased of IL-1β production indicated an early inflammatory response before granuloma formation. In conclusion, this study indicated that both M. tb and M.bovis were virulent to cattle. Therefore, it is likely that cattle with M. tb infections would be critical to tuberculosis transmission from cattle to humans. Nuclear magnetic resonance was demonstrated to be an efficient method to systematically evaluate M. tb and M. bovi sinfection in cattle.

  7. Urine Eicosanoids in the Metabolic Abnormalities, Telmisartan, and HIV Infection (MATH Trial.

    Catherine N Le

    Full Text Available Arachidonic acid metabolites (eicosanoids reflect oxidative stress and vascular health and have been associated with anthropometric measures and sex differences in cross-sectional analyses of HIV-infected (HIV+ persons. Telmisartan is an angiotensin receptor blocker and PPAR-γ agonist with potential anti-inflammatory and metabolic benefits. We assessed telmisartan's effects on urine eicosanoids among HIV+ adults with central adiposity on suppressive antiretroviral therapy enrolled in a prospective clinical trial.Thirty-five HIV+ adults (15 women; 20 men completed 24 weeks of open-label oral telmisartan 40mg daily. Lumbar computed tomography quantified visceral (VAT and subcutaneous (SAT abdominal adipose tissue. Urine F2-isoprostane (F2-IsoP, prostaglandin E2 (PGE-M, prostacyclin (PGI-M, and thromboxane B2 (TxB-M were quantified at baseline and 24 weeks using gas/liquid chromatography-mass spectroscopy. Mann-Whitney-U tests compared sub-group differences; Spearman's rho assessed correlations between clinical factors and eicosanoid levels.Median PGE-M increased on telmisartan (p5% VAT (+3.7 ng/mg cr, p5% SAT (+1.7 ng/mg cr, p = 0.04. Median baseline F2-IsoP and TxB-M were slightly higher in women (both between-group p = 0.08 and did not change on telmisartan.Urine PGE-M increased with 24 weeks of telmisartan in virally suppressed, HIV+ adults with central adiposity. Associations with favorable fat redistribution suggest increased PGE-M may reflect a beneficial response.

  8. The effects of anticholinergic drugs on regional cerebral blood flow, and oxygen metabolism in previously untreated patients with Parkinson's disease

    Obara, Satoko; Takahashi, Satoshi; Yonezawa, Hisashi; Sato, Yoshitomo

    1998-01-01

    Regional cerebral blood flow (rCBF) and oxygen metabolism (rCMRO 2 ) were measured using the steady-state 15 O technique and positron emission tomography (PET) in six previously untreated patients with Parkinson's disease before and after trihexyphenidyl (THP) treatment. The patients comprised of 4 men and 2 women with Hoehn-Yahr stage II-III. Their ages at the onset of the study ranged from 46 to 57 years (mean±SD, 51.8±3.7) and the duration of the illness ranged from 10 to 48 months (mean±SD, 28.8±15.5). The PET study, assessments of the disability and cognitive function were undergone twice. The first time assessments were done was when the patients were not receiving any drugs, and the second time was one to three months after administration of 6 mg THP. All patients showed clinical improvement after THP treatment. The mean disability score of Unified Parkinson's Disease Rating Scale decreased from 35.1 (SD±11.3) to 25.7 (SD±11.6). The cognitive function assessed by Hasegawa's dementia rating scale-revised, Mini-Mental State Examination, Wechsler Adult Intelligence Scale-Revised, and Wechsler Memory Scale-Revised, were not significantly different before and after the THP treatment. After the THP treatment, rCBF and rCMRO 2 decreased significantly in the striatum (about 15%) and all cerebral cortices (about 10%) on both sides contralateral and ipsilateral to the predominantly symptomatic limbs. We conclude that an anticholinergic THP decreases the rCBF and rCMRO 2 significantly in the cerebral cortices without cognitive impairment in early untreated patients with Parkinson's disease. (author)

  9. [Measurement of regional cerebral metabolism rate of glucose in patients with Alzheimer's disease in different levels of severity].

    Xiao, Shi-fu; Cao, Qiu-yun; Xue, Hai-bo; Liu, Yong-chang; Zuo, Chuan-tao; Jiang, Kai-da; Zhang, Ming-yuan

    2005-11-09

    To measure the changes of regional cerebral metabolism rate of glucose (rCMRglc) in patients with Alzheimer's disease (AD) and explore their value to diagnosis of AD. 10 patients with AD who met the diagnostic criteria of DSM-IV and 10 normal controls (NC) were assessed with (18)F-2-fluoro-deoxy-D-glucose positron emission tomography (PET). The two groups were matched in age, gender and education. The mean total scores of the mini-mental status examination (MMSE) were 16.5 +/- 6.1 for AD and 28.7 +/- 1.6 for NC. The mean total memory quotient of Wechsler Memory Scales (MQ) were 32.3 +/- 19.6 for AD and 93.1 +/- 9.0 for NC. Comparing to NC, the AD groups showed statistically significant decline of rCMRglc in frontal lobe, temporal lobe and the hippocampal formation with decreased rates ranged from 3.3% to 28.4% (P upper and middle frontal gyri, middle temporal gyrus, orbital gyrus and anterior cingulate gyrus, in which areas the metabolism decreased over 20% compared to NC. The hypo-metabolism was correlated to the severity of dementia. Discriminant analysis demonstrated that the variables of right inferior temporal gyrus, left upper temporal gyrus, left hippocampus and right insular lobe were entered into the discriminant functions and the total discriminant accuracy reached 100%. (18)F-FDG PET is a very sensitive tool in measurement of the changes of rCMRglc in patients with AD. The findings show a frontal-temporal type of metabolism in AD patients and suggest that hypo-metabolism in hippocampal formation and temporal lobe is helpful in early detection of AD.

  10. Influence of antihypertensive therapy on cerebral perfusion in patients with metabolic syndrome: relationship with cognitive function and 24-h arterial blood pressure monitoring.

    Efimova, Nataliya Y; Chernov, Vladimir I; Efimova, Irina Y; Lishmanov, Yuri B

    2015-08-01

    To investigate the regional cerebral blood flow, cognitive function, and parameters of 24-h arterial blood pressure monitoring in patients with metabolic syndrome before and after combination antihypertensive therapy. The study involved 54 patients with metabolic syndrome (MetS) investigated by brain single-photon emission computed tomography, 24-h blood pressure monitoring (ABPM), and comprehensive neuropsychological testing before and after 24 weeks of combination antihypertensive therapy. Patients with metabolic syndrome had significantly poorer regional cerebral blood flow compared with control group: by 7% (P = 0.003) in right anterior parietal cortex, by 6% (P = 0.028) in left anterior parietal cortex, by 8% (P = 0.007) in right superior frontal lobe, and by 10% (P = 0.00002) and 7% (P = 0.006) in right and left temporal brain regions, correspondingly. The results of neuropsychological testing showed 11% decrease in mentation (P = 0.002), and 19% (P = 0.011) and 20% (P = 0.009) decrease in immediate verbal and visual memory in patients with MetS as compared with control group. Relationships between the indices of ABPM, cerebral perfusion, and cognitive function were found. Data showed an improvement of regional cerebral blood flow, ABPM parameters, and indicators of cognitive functions after 6 months of antihypertensive therapy in patients with MetS. The study showed the presence of diffuse disturbances in cerebral perfusion is associated with cognitive disorders in patients with metabolic syndrome. Combination antihypertensive treatment exerts beneficial effects on the 24-h blood pressure profile, increases cerebral blood flow, and improves cognitive function in patients with MetS. © 2015 John Wiley & Sons Ltd.

  11. FDG-PET study of the bilateral subthalamic nucleus stimulation effects on the regional cerebral metabolism in advanced Parkinson disease

    Li, D.; Shen, J.; Zan, S.; Sun, B.; Zuo, C.; Guan, Y.; Zhao, Y.

    2006-01-01

    The aim of the study was to evaluate the changes in regional cerebral metabolic rate of glucose (rCMRGIu) induced by bilateral subthalamic nucleus (STN) stimulation in advanced Parkinson's disease (PD). 18 F-Fluorodeoxyglucose (FDG) PET data obtained before and one month after stimulation were analyzed with statistical parametric mapping (SPM). As a result of clinically effective bilateral STN stimulation, rCMRGIu increased in lateral globus pallidus (GP), upper brain stem, dorsolateral prefrontal cortex (DLPFC) and posterior parietal-occipital cortex, and decreased in the orbital frontal cortex and parahippocampus gyrus (p <0.001). We conclude that the alleviation of clinical symptoms in advanced PD by bilateral STN stimulation may be the result of activation of both ascending and descending pathways from STN and of restoration of the impaired higher-order cortex functions. (author)

  12. Metabolic Abnormalities Detected in Phase II Evaluation of Doxycycline in Dogs with Multicentric B-Cell Lymphoma

    Kelly R. Hume

    2018-02-01

    Full Text Available Doxycycline has antiproliferative effects in human lymphoma cells and in murine xenografts. We hypothesized that doxycycline would decrease canine lymphoma cell viability and prospectively evaluated its clinical tolerability in client-owned dogs with spontaneous, nodal, multicentric, substage a, B-cell lymphoma, not previously treated with chemotherapy. Treatment duration ranged from 1 to 8 weeks (median and mean, 3 weeks. Dogs were treated with either 10 (n = 6 or 7.5 (n = 7 mg/kg by mouth twice daily. One dog had a stable disease for 6 weeks. No complete or partial tumor responses were observed. Five dogs developed grade 3 and/or 4 metabolic abnormalities suggestive of hepatopathy with elevations in bilirubin, ALT, ALP, and/or AST. To evaluate the absorption of oral doxycycline in our study population, serum concentrations in 10 treated dogs were determined using liquid chromatography tandem mass spectrometry. Serum levels were variable and ranged from 3.6 to 16.6 µg/ml (median, 7.6 µg/ml; mean, 8.8 µg/ml. To evaluate the effect of doxycycline on canine lymphoma cell viability in vitro, trypan blue exclusion assay was performed on canine B-cell lymphoma cell lines (17-71 and CLBL and primary B-cell lymphoma cells from the nodal tissue of four dogs. A doxycycline concentration of 6 µg/ml decreased canine lymphoma cell viability by 80%, compared to matched, untreated, control cells (mixed model analysis, p < 0.0001; Wilcoxon signed rank test, p = 0.0313. Although the short-term administration of oral doxycycline is not associated with the remission of canine lymphoma, combination therapy may be worthwhile if future research determines that doxycycline can alter cell survival pathways in canine lymphoma cells. Due to the potential for metabolic abnormalities, close monitoring is recommended with the use of this drug in tumor-bearing dogs. Additional research is needed to assess the tolerability of chronic

  13. Sleep-Wake Differences in Relative Regional Cerebral Metabolic Rate for Glucose among Patients with Insomnia Compared with Good Sleepers

    Kay, Daniel B.; Karim, Helmet T.; Soehner, Adriane M.; Hasler, Brant P.; Wilckens, Kristine A.; James, Jeffrey A.; Aizenstein, Howard J.; Price, Julie C.; Rosario, Bedda L.; Kupfer, David J.; Germain, Anne; Hall, Martica H.; Franzen, Peter L.; Nofzinger, Eric A.; Buysse, Daniel J.

    2016-01-01

    Study Objectives: The neurobiological mechanisms of insomnia may involve altered patterns of activation across sleep-wake states in brain regions associated with cognition, self-referential processes, affect, and sleep-wake promotion. The objective of this study was to compare relative regional cerebral metabolic rate for glucose (rCMRglc) in these brain regions across wake and nonrapid eye movement (NREM) sleep states in patients with primary insomnia (PI) and good sleeper controls (GS). Methods: Participants included 44 PI and 40 GS matched for age (mean = 37 y old, range 21–60), sex, and race. We conducted [18F]fluoro-2-deoxy-d-glucose positron emission tomography scans in PI and GS during both morning wakefulness and NREM sleep at night. Repeated measures analysis of variance was used to test for group (PI vs. GS) by state (wake vs. NREM sleep) interactions in relative rCMRglc. Results: Significant group-by-state interactions in relative rCMRglc were found in the precuneus/posterior cingulate cortex, left middle frontal gyrus, left inferior/superior parietal lobules, left lingual/fusiform/occipital gyri, and right lingual gyrus. All clusters were significant at Pcorrected sleep and wakefulness. Significant group-by-state interactions in relative rCMRglc suggest that insomnia is associated with impaired disengagement of brain regions involved in cognition (left frontoparietal), self-referential processes (precuneus/posterior cingulate), and affect (left middle frontal, fusiform/lingual gyri) during NREM sleep, or alternatively, to impaired engagement of these regions during wakefulness. Citation: Kay DB, Karim HT, Soehner AM, Hasler BP, Wilckens KA, James JA, Aizenstein HJ, Price JC, Rosario BL, Kupfer DJ, Germain A, Hall MH, Franzen PL, Nofzinger EA, Buysse DJ. Sleep-wake differences in relative regional cerebral metabolic rate for glucose among patients with insomnia compared with good sleepers. SLEEP 2016;39(10):1779–1794. PMID:27568812

  14. Abnormalities in the Polysomnographic, Adenosine and Metabolic Response to Sleep Deprivation in an Animal Model of Hyperammonemia

    Selena Marini

    2017-08-01

    Full Text Available Patients with liver cirrhosis can develop hyperammonemia and hepatic encephalopathy (HE, accompanied by pronounced daytime sleepiness. Previous studies with healthy volunteers show that experimental increase in blood ammonium levels increases sleepiness and slows the waking electroencephalogram. As ammonium increases adenosine levels in vitro, and adenosine is a known regulator of sleep/wake homeostasis, we hypothesized that the sleepiness-inducing effect of ammonium is mediated by adenosine. Eight adult male Wistar rats were fed with an ammonium-enriched diet for 4 weeks; eight rats on standard diet served as controls. Each animal was implanted with electroencephalography/electromyography (EEG/EMG electrodes and a microdialysis probe. Sleep EEG recording and cerebral microdialysis were carried out at baseline and after 6 h of sleep deprivation. Adenosine and metabolite levels were measured by high-performance liquid chromatography (HPLC and targeted LC/MS metabolomics, respectively. Baseline adenosine and metabolite levels (12 of 16 amino acids, taurine, t4-hydroxy-proline, and acetylcarnitine were lower in hyperammonemic animals, while putrescine was higher. After sleep deprivation, hyperammonemic animals exhibited a larger increase in adenosine levels, and a number of metabolites showed a different time-course in the two groups. In both groups the recovery period was characterized by a significant decrease in wakefulness/increase in NREM and REM sleep. However, while control animals exhibited a gradual compensatory effect, hyperammonemic animals showed a significantly shorter recovery phase. In conclusion, the adenosine/metabolite/EEG response to sleep deprivation was modulated by hyperammonemia, suggesting that ammonia affects homeostatic sleep regulation and its metabolic correlates.

  15. Potential Adverse Effects of Prolonged Sevoflurane Exposure on Developing Monkey Brain: From Abnormal Lipid Metabolism to Neuronal Damage.

    Liu, Fang; Rainosek, Shuo W; Frisch-Daiello, Jessica L; Patterson, Tucker A; Paule, Merle G; Slikker, William; Wang, Cheng; Han, Xianlin

    2015-10-01

    Sevoflurane is a volatile anesthetic that has been widely used in general anesthesia, yet its safety in pediatric use is a public concern. This study sought to evaluate whether prolonged exposure of infant monkeys to a clinically relevant concentration of sevoflurane is associated with any adverse effects on the developing brain. Infant monkeys were exposed to 2.5% sevoflurane for 9 h, and frontal cortical tissues were harvested for DNA microarray, lipidomics, Luminex protein, and histological assays. DNA microarray analysis showed that sevoflurane exposure resulted in a broad identification of differentially expressed genes (DEGs) in the monkey brain. In general, these genes were associated with nervous system development, function, and neural cell viability. Notably, a number of DEGs were closely related to lipid metabolism. Lipidomic analysis demonstrated that critical lipid components, (eg, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol) were significantly downregulated by prolonged exposure of sevoflurane. Luminex protein analysis indicated abnormal levels of cytokines in sevoflurane-exposed brains. Consistently, Fluoro-Jade C staining revealed more degenerating neurons after sevoflurane exposure. These data demonstrate that a clinically relevant concentration of sevoflurane (2.5%) is capable of inducing and maintaining an effective surgical plane of anesthesia in the developing nonhuman primate and that a prolonged exposure of 9 h resulted in profound changes in gene expression, cytokine levels, lipid metabolism, and subsequently, neuronal damage. Generally, sevoflurane-induced neuronal damage was also associated with changes in lipid content, composition, or both; and specific lipid changes could provide insights into the molecular mechanism(s) underlying anesthetic-induced neurotoxicity and may be sensitive biomarkers for the early detection of anesthetic-induced neuronal damage. Published by Oxford University Press on behalf of the

  16. Elevated global cerebral blood flow, oxygen extraction fraction and unchanged metabolic rate of oxygen in young adults with end-stage renal disease: an MRI study.

    Zheng, Gang; Wen, Jiqiu; Lu, Hanzhang; Lou, Yaxian; Pan, Zhiying; Liu, Wei; Liu, Hui; Li, Xue; Zhang, Zhe; Chen, Huijuan; Kong, Xiang; Luo, Song; Jiang, Xiaolu; Liu, Ya; Zhang, Zongjun; Zhang, Long Jiang; Lu, Guang Ming

    2016-06-01

    To noninvasively assess global cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) in young adults with end-stage renal disease (ESRD). Thirty-six patients and 38 healthy volunteers were included and took part in MR examinations, blood and neuropsychological tests. CBF and OEF were measured by phase-contrast and T2-relaxation-under-spin-tagging MRI techniques, respectively. CMRO2 was computed from CBF, OEF and hematocrit according to Fick's principle. Correlations were performed between MR measurements, blood biochemistry measurements and neuropsychological test scores. Compared with controls, ESRD patients had elevated CBF (72.9 ± 12.5 vs. 63.8 ± 8.5 ml min(-1) 100 g(-1), P < 0.001), elevated OEF (47.2 ± 10.2 vs. 35.8 ± 5.4 %, P < 0.001), but unaffected CMRO2 (199.5 ± 36.4 vs. 193.8 ± 28.6 μmol O2 min(-1) 100 g(-1), P = 0.879). Hematocrit negatively correlated with CBF (r = -0.640, P < 0.001) and OEF (r = -0.701, P < 0.001), but not with CMRO2. Altered neuropsychological test scores of ESRD patients were associated with OEF and CBF, but not with CMRO2. There were weak relationships between eGFR and hematocrit (r = 0.308, P = 0.068) or CBF (r = 0.318, P = 0.059). Our findings suggested that anaemic young adults with ESRD may afford higher CBF and OEF to maintain a normal CMRO2. Despite this compensatory process, however, cognitive function was still impaired and its severity was correlated with their CBF and OEF abnormality. • Anaemic young adults with ESRD may afford higher CBF and OEF. • Anaemic young adults with ESRD maintain a normal CMRO 2 . • Cognitive function was still impaired in young ESRD adults. • The severity of cognitive dysfunction correlated with CBF and OEF changes.

  17. Apparent brain temperature imaging with multi-voxel proton magnetic resonance spectroscopy compared with cerebral blood flow and metabolism imaging on positron emission tomography in patients with unilateral chronic major cerebral artery steno-occlusive disease

    Nanba, Takamasa; Nishimoto, Hideaki; Murakami, Toshiyuki; Fujiwara, Shunrou; Ogasawara, Kuniaki [Iwate Medical University, Department of Neurosurgery, Iwate (Japan); Yoshioka, Yoshichika [Osaka University, Open and Transdisciplinary Research Initiatives, Osaka (Japan); Sasaki, Makoto; Uwano, Ikuko [Iwate Medical University, Institute for Biomedical Science, Iwate (Japan); Terasaki, Kazunori [Iwate Medical University, Cyclotron Research Center, Iwate (Japan)

    2017-09-15

    The purpose of the present study was to determine whether apparent brain temperature imaging using multi-voxel proton magnetic resonance (MR) spectroscopy correlates with cerebral blood flow (CBF) and metabolism imaging in the deep white matter of patients with unilateral chronic major cerebral artery steno-occlusive disease. Apparent brain temperature and CBF and metabolism imaging were measured using proton MR spectroscopy and {sup 15}O-positron emission tomography (PET), respectively, in 35 patients. A set of regions of interest (ROIs) of 5 x 5 voxels was placed on an MR image so that the voxel row at each edge was located in the deep white matter of the centrum semiovale in each cerebral hemisphere. PET images were co-registered with MR images with these ROIs and were re-sliced automatically using image analysis software. In 175 voxel pairs located in the deep white matter, the brain temperature difference (affected hemisphere - contralateral hemisphere: ΔBT) was correlated with cerebral blood volume (CBV) (r = 0.570) and oxygen extraction fraction (OEF) ratios (affected hemisphere/contralateral hemisphere) (r = 0.641). We excluded voxels that contained ischemic lesions or cerebrospinal fluid and calculated the mean values of voxel pairs in each patient. The mean ΔBT was correlated with the mean CBF (r = - 0.376), mean CBV (r = 0.702), and mean OEF ratio (r = 0.774). Apparent brain temperature imaging using multi-voxel proton MR spectroscopy was correlated with CBF and metabolism imaging in the deep white matter of patients with unilateral major cerebral artery steno-occlusive disease. (orig.)

  18. Cerebral blood flow and metabolism in a patient with motor aphasia by positron emission tomography using 15O2 and C15O2

    Kitamura, Shin; Terashi, Akiro; Kato, Toshiaki; Soeda, Toshiyuki; Iio, Masaaki.

    1986-01-01

    Cerebral blood flow and metabolism, in a patient with motor aphasia due to cerebral infarction of the left basal ganglionic region, were studied by positron emission tomography (PET) using 15 O 2 and C 15 O 2 . A 62-year-old woman, right handed, was admitted with a complaint of right hemiparesis. Motor aphasia developed on the following day of hospitalization. CT scan showed low density area in the left caduate nucleus, putamen, internal capsule, and centrum semiovale, but the cortex was intact on the images of CT scan. PET studies were performed 22 days and 92 days after onset of stroke. The first PET study revealed marked reduction of CBF (cerebral blood flow) in the left cortex and subcortex, but CMRO 2 (cerebral oxygen consumption) was relatively preserved and OEF (oxygen extraction fraction) increased. The second PET study showed recovery of CBF in the left cortex and increase of OEF vanished. CMRO 2 decreased in the left posterior frontal region and subcortex. Motor aphasia still continued at the time of the second PET study. Therefore, the left posterior frontal cortex lesion as well as the left subcortex lesion might be related to the occurrence of motor aphasia in this case. The thresholds of CBF and CMRO 2 for developing clinical symptoms are higher than those for developing low density on the images of CT scan. These results suggest the importance of the study of cerebral blood flow and metabolism in the study of the responsible lesion for aphasia. (author)

  19. Decreased regional cerebral glucose metabolism in the prefrontal regions in adults' with internet game addiction

    Park, Hyun Soo; Bang, Soong Ae; Yoon, Eun Jin; Cho, Sang Soo; Kim, Sang Hee; Kim, Yu Kyeong; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    Internet Game Addiction (IGA) is known to be associated with poor decision-making and diminished impulse control; however, the underlying neural substrates of IGA have not been identified. To investigate the neural substrates of IGA, we compared regional cerebral glucose metabolism between adults with and without IGA, primarily in the prefrontal brain regions, which have been implicated in inhibitory control. We studied 10 right-handed participants (5 controls: male, 23.8{+-}0.75 y, 5 IGAs: male, 22.6{+-}2.42 y) with FDG PET. A standardized questionnaire was used to assess the severity of IGA. Before scanning, all subjects carried out a computerized version of the Iowa Gambling Task (IGT) and the Balloon Analogue Risk Task (BART), as measures of behavioral inhibitory control. Statistical Parametric Mapping 2 (SPM2) was used to analyze differences in regional brain glucose metabolism between adults with and without IGA. Consistent with our predictions, compared to controls, significant reductions in FDG uptake in individuals with IGA were found in the bilateral orbitofrontal gyrus (BA 11, 47), bilateral inferior frontal gyrus (BA 44, 48), cingulate cortex (BA 24), and bilateral supplementary motor area (SMA) (BA 6); whereas increases were found in the bilateral hippocampus. Correlation analyses within the IGA group further showed that the level of glucose metabolism in the right orbitofrontal gyrus was marginally positively correlated with task scores in BART. Our results showed that IGA is associated with reduced glucose metabolism in the prefrontal regions involved in inhibitory control. This finding highlights dysfunctional inhibitory brain systems in individuals with IGA and offers implications for the development for therapeutic paradigms for IGA.

  20. Combined administration of hyperbaric oxygen and hydroxocobalamin improves cerebral metabolism after acute cyanide poisoning in rats

    Hansen, M B; Olsen, Niels Vidiendal; Hyldegaard, O

    2013-01-01

    -to-pyruvate ratio in rat brain by means of microdialysis during acute CN poisoning. Anesthetized rats were allocated to three groups: 1) vehicle (1.2 ml isotonic NaCl intra-arterially); 2) potassium CN (5.4 mg/kg intra-arterially); 3) potassium CN, OHCob (100 mg/kg intra-arterially) and subsequent HBOT (284 k......Pa in 90 min). OHCob and HBOT significantly attenuated the acute surges in interstitial cerebral lactate, glucose, and glycerol concentrations compared with the intoxicated rats given no treatment. Furthermore, the combined treatment resulted in consistent low lactate, glucose, and glycerol concentrations...

  1. Blood metabolomics analysis identifies abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism in bipolar disorder.

    Yoshimi, Noriko; Futamura, Takashi; Kakumoto, Keiji; Salehi, Alireza M; Sellgren, Carl M; Holmén-Larsson, Jessica; Jakobsson, Joel; Pålsson, Erik; Landén, Mikael; Hashimoto, Kenji

    2016-06-01

    Bipolar disorder (BD) is a severe and debilitating psychiatric disorder. However, the precise biological basis remains unknown, hampering the search for novel biomarkers. We performed a metabolomics analysis to discover novel peripheral biomarkers for BD. We quantified serum levels of 116 metabolites in mood-stabilized male BD patients (n = 54) and age-matched male healthy controls (n = 39). After multivariate logistic regression, serum levels of pyruvate, N-acetylglutamic acid, α-ketoglutarate, and arginine were significantly higher in BD patients than in healthy controls. Conversely, serum levels of β-alanine, and serine were significantly lower in BD patients than in healthy controls. Chronic (4-weeks) administration of lithium or valproic acid to adult male rats did not alter serum levels of pyruvate, N-acetylglutamic acid, β-alanine, serine, or arginine, but lithium administration significantly increased serum levels of α-ketoglutarate. The metabolomics analysis demonstrated altered serum levels of pyruvate, N-acetylglutamic acid, β-alanine, serine, and arginine in BD patients. The present findings suggest that abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism play a role in the pathogenesis of BD.

  2. Prevalence of metabolic syndrome and risks of abnormal serum alanine aminotransferase in Hispanics: a population-based study.

    Jen-Jung Pan

    Full Text Available Study the prevalence of metabolic syndrome (MS and risk factors for and association with elevated alanine aminotransferase (ALT as markers of hepatic injury in a large Hispanic health disparity cohort with high rates of obesity.Analysis of data from a prospective cross-sectional population based study. From 2004-7, we randomly recruited 2000 community participants to the Cameron County Hispanic Cohort collecting extensive socioeconomic, clinical and laboratory data. We excluded 153 subjects due to critical missing data. Pearson chi-square tests and Student's t-tests were used for categorical and continuous variable analysis, respectively. Logistic regression analysis was performed to determine the risk factors for elevated ALT.The mean age of the cohort was 45 years and 67% were females. The majority of the cohort was either overweight (32.4% or obese (50.7%. Almost half (43.7% had MS and nearly one-third diabetes. Elevated ALT level was more prevalent in males than females. Obesity was a strong risk for abnormal ALT in both genders. Hypertriglyceridemia, hypercholesterolemia and young age were risks for elevated ALT in males only, whereas increased fasting plasma glucose was associated with elevated ALT in females only.We identified high prevalence of MS and markers of liver injury in this large Mexican American cohort with gender differences in prevalence and risk factors, with younger males at greatest risk.

  3. Lipid metabolism abnormalities in alcohol-treated rabbits: a morphometric and haematologic study comparing high and low alcohol doses.

    Ikemura, Satoshi; Yamamoto, Takuaki; Motomura, Goro; Iwasaki, Kenyu; Yamaguchi, Ryosuke; Zhao, Garida; Iwamoto, Yukihide

    2011-08-01

    The pathogenesis of alcohol-induced osteonecrosis remains unclear. The purpose of the present study was to evaluate the morphological changes in bone marrow fat cells and the changes in the serum lipid levels in alcohol-treated rabbits. Fifteen rabbits were randomly assigned into three groups: Four rabbits intragastrically received low-dose alcohol (LDA) (15 ml/kg per day) containing 15% ethanol for 4 weeks, five rabbits received high-dose alcohol (HDA) (30 ml/kg per day) for 4 weeks and six rabbits received physiologic saline for 4 weeks as a control group. Six weeks after the initial alcohol administration, all rabbits were sacrificed. The mean size of the bone marrow fat cells in rabbits treated with HDA was significantly larger than that in the control group (P = 0.0001). Haematologically, the levels of triglycerides and free fatty acids in the rabbits treated with both low-dose and HDA were significantly higher than those in the control group (P = 0.001 for both comparisons). The results of this study are that there are lipid metabolism abnormalities, both morphologically and haematologically, after alcohol administration. Also these findings were more apparent in rabbits treated with HDA than those treated with LDA. © 2011 The Authors. International Journal of Experimental Pathology © 2011 International Journal of Experimental Pathology.

  4. Hepatitis B virus X protein (HBx)-induced abnormalities of nucleic acid metabolism revealed by (1)H-NMR-based metabonomics.

    Dan Yue; Zhang, Yuwei; Cheng, Liuliu; Ma, Jinhu; Xi, Yufeng; Yang, Liping; Su, Chao; Shao, Bin; Huang, Anliang; Xiang, Rong; Cheng, Ping

    2016-04-14

    Hepatitis B virus X protein (HBx) plays an important role in HBV-related hepatocarcinogenesis; however, mechanisms underlying HBx-mediated carcinogenesis remain unclear. In this study, an NMR-based metabolomics approach was applied to systematically investigate the effects of HBx on cell metabolism. EdU incorporation assay was conducted to examine the effects of HBx on DNA synthesis, an important feature of nucleic acid metabolism. The results revealed that HBx disrupted metabolism of glucose, lipids, and amino acids, especially nucleic acids. To understand the potential mechanism of HBx-induced abnormalities of nucleic acid metabolism, gene expression profiles of HepG2 cells expressing HBx were investigated. The results showed that 29 genes involved in DNA damage and DNA repair were differentially expressed in HBx-expressing HepG2 cells. HBx-induced DNA damage was further demonstrated by karyotyping, comet assay, Western blotting, immunofluorescence and immunohistochemistry analyses. Many studies have previously reported that DNA damage can induce abnormalities of nucleic acid metabolism. Thus, our results implied that HBx initially induces DNA damage, and then disrupts nucleic acid metabolism, which in turn blocks DNA repair and induces the occurrence of hepatocellular carcinoma (HCC). These findings further contribute to our understanding of the occurrence of HCC.

  5. Age- and Sex-Associated Changes in Cerebral Glucose Metabolism in Normal Healthy Subjects: Statistical Parametric Mapping Analysis of F-18 Fluorodeoxyglucose Brain Positron Emission Tomography

    Kim, In-Ju; Kim, Seong-Jang; Kim, Yong-Ki

    2009-01-01

    Background: The age- and sex-associated changes of brain development are unclear and controversial. Several previous studies showed conflicting results of a specific pattern of cerebral glucose metabolism or no differences of cerebral glucose metabolism in association with normal aging process and sex. Purpose: To investigate the effects of age and sex on changes in cerebral glucose metabolism in healthy subjects using fluorine-18 fluorodeoxyglucose (F-18 FDG) brain positron emission tomography (PET) and statistical parametric mapping (SPM) analysis. Material and Methods: Seventy-eight healthy subjects (32 males, mean age 46.6±18.2 years; 46 females, mean age 40.6±19.8 years) underwent F-18 FDG brain PET. Using SPM, age- and sex-associated changes in cerebral glucose metabolism were investigated. Results: In males, a negative correlation existed in several gray matter areas, including the right temporopolar (Brodmann area [BA] 38), right orbitofrontal (BA 47), left orbitofrontal gyrus (BA 10), left dorsolateral frontal gyrus (BA 8), and left insula (BA 13) areas. A positive relationship existed in the left claustrum and left thalamus. In females, negative changes existed in the left caudate body, left temporopolar area (BA 38), right orbitofrontal gyri (BA 47 and BA 10), and right dorsolateral prefrontal cortex (BA 46). A positive association was demonstrated in the left subthalamic nucleus and the left superior frontal gyrus. In white matter, an age-associated decrease in FDG uptake in males was shown in the left insula, and increased FDG uptake was found in the left corpus callosum. The female group had an age-associated negative correlation of FDG uptake only in