Science.gov

Sample records for metabolism neurological functions

  1. The radical scavenger edaravone improves neurologic function and perihematomal glucose metabolism after acute intracerebral hemorrhage.

    PubMed

    Shang, Hanbing; Cui, Derong; Yang, Dehua; Liang, Sheng; Zhang, Weifeng; Zhao, Weiguo

    2015-01-01

    Oxidative injury caused by reactive oxygen species plays an important role in the progression of intracerebral hemorrhage (ICH)-induced secondary brain injury. Previous studies have demonstrated that the free radical scavenger edaravone may prevent neuronal injury and brain edema after ICH. However, the influence of edaravone on cerebral metabolism in the early stages after ICH and the underlying mechanism have not been fully investigated. In the present study, we investigated the effect of edaravone on perihematomal glucose metabolism using (18)F-fluorordeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). Additionally, the neurologic deficits, brain edemas, and cell death that followed ICH were quantitatively analyzed. After blood infusion, the rats treated with edaravone showed significant improvement in both forelimb placing and corner turn tests compared with those treated with vehicle. Moreover, the brain water content of the edaravone-treated group was significantly decreased compared with that of the vehicle group on day 3 after ICH. PET/CT images of ICH rats exhibited obvious decreases in FDG standardized uptake values in perihematomal region on day 3, and the lesion-to-normal ratio of the edaravone-treated ICH rats was significantly increased compared with that of the control rats. Calculation of the brain injury volumes from the PET/CT images revealed that the volumes of the blood-induced injuries were significantly smaller in the edaravone group compared with the vehicle group. Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling assays performed 3 days after ICH revealed that the numbers of apoptotic cells in perihematomal region of edaravone-treated ICH rats were decreased relative to the vehicle group. Thus, the present study demonstrates that edaravone has scavenging properties that attenuate neurologic behavioral deficits and brain edema in the early period of ICH. Additionally, edaravone may improve

  2. Effects of copper metabolism on neurological functions in Wistar and Wilson's disease model rats.

    PubMed

    Fujiwara, Noriko; Iso, Hiroyuki; Kitanaka, Nobue; Kitanaka, Junichi; Eguchi, Hironobu; Ookawara, Tomomi; Ozawa, Keiichiro; Shimoda, Shigero; Yoshihara, Daisaku; Takemura, Motohiko; Suzuki, Keiichiro

    2006-10-27

    Behavioral functions of Wistar and Long-Evans Cinnamon (LEC) rats, Wilson's disease animal model, were compared by measuring the open-field, acoustic startle reflex and prepulse inhibition (PPI), and shuttle-box avoidance learning tests with or without oral supplementation with copper or D-penicillamine, copper chelator. All of the LEC rats, irrespective of the treatment, exhibited higher locomotor activity, a decreased habituation to startle response or a lower PPI, compared with Wistar rats. The copper content of all brain regions examined, except for the medulla oblongata of LEC rats, was significantly lower than those in Wistar rats. Besides, in the region of the striatum and the nucleus accumbens of the LEC rats, lower content of norepinephrine, and higher content of dopamine and serotonin were observed compared with Wistar rats. Although copper supplementation did not affect the brain copper content, it reduced the PPI in both Wistar and LEC rats. In contrast, D-penicillamine supplementation decreased both the brain copper content and locomotor activity, and enhanced the startle amplitude only in Wistar rats. These findings suggest that an imbalance in copper homeostasis affects monoamine metabolism and behavioral functions.

  3. Metabolic phenotyping and systems biology approaches to understanding neurological disorders.

    PubMed

    Dumas, Marc-Emmanuel; Davidovic, Laetitia

    2013-01-01

    The development of high-throughput metabolic profiling and the study of the metabolome are particularly important in brain research where small molecules or metabolites play fundamental signalling roles: neurotransmitters, signalling lipids, osmolytes and even ions. Metabolic profiling has shown that metabolic perturbations in the brain go beyond alterations of neurotransmission and that variations in brain metabolic homeostasis are associated with neurological disorders. In this report, we will focus on recent developments in the field of metabolic phenotyping that have contributed to unravelling the pathophysiology of neurological diseases. Also, we will highlight the necessity of implementing systems biology approaches to integrate metabolic data and tackle the structural and functional complexity of the brain in normal and pathological conditions. PMID:23755365

  4. [Inborn errors of metabolism in adult neurology].

    PubMed

    Sedel, F

    2013-02-01

    Inborn errors of metabolism (IEM) are caused by mutations in genes coding for enzymes and other proteins involved in cell metabolism. Many IEM can be treated effectively. Although IEM have usually been considered pediatric diseases, they can present at any age, mostly with neurological and psychiatric symptoms, and therefore constitute an integral subspeciality of neurology. However, although they are increasingly being recognized, IEM remain rare, and the care for patients should be optimized in specialized reference centers. Since the number of different diseases is very large, the diagnostic approach needs to be rigorous, starting at the clinics and calling upon the additional help of neuroradiology, biochemistry and molecular biology. In practice, it is important for the neurologist to recognize: (1) when to start suspecting an IEM; and (2) how to correlate a given clinical presentation with one of the five major groups of diseases affecting the nervous system. These five groups may be classified as: (a) energy metabolism disorders such as respiratory chain disorders, pyruvate dehydrogenase deficiency, GLUT1 deficiency, fatty-acid β-oxidation defects, and disorders involving key cofactors such as electron transfer flavoprotein, thiamine, biotin, riboflavin, vitamin E and coenzyme Q10; (b) intoxication syndromes such as porphyrias, urea-cycle defects, homocystinurias, organic acidurias and amino acidopathies; (c) lipid-storage disorders such as lysosomal storage disorders (Krabbe disease, metachromatic leukodystrophy, Niemann - Pick disease type C, Fabry disease and Gaucher's disease), peroxisomal disorders (adrenomyeloneuropathy, Refsum disease, disorders of pristanic acid metabolism, peroxisome biogenesis disorders), Tangier disease and cerebrotendinous xanthomatosis; (d) metal-storage diseases such as iron, copper and manganese metabolic disorders; and (e) neurotransmitter metabolism defects, including defects of serotonin, dopamine and glycine metabolism

  5. Metabolic Disturbances in Diseases with Neurological Involvement

    PubMed Central

    Duarte, João M. N.; Schuck, Patrícia F.; Wenk, Gary L.; Ferreira, Gustavo C.

    2014-01-01

    Degeneration of specific neuronal populations and progressive nervous system dysfunction characterize neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. These findings are also reported in inherited diseases such as phenylketonuria and glutaric aciduria type I. The involvement of mitochondrial dysfunction in these diseases was reported, elicited by genetic alterations, exogenous toxins or buildup of toxic metabolites. In this review we shall discuss some metabolic alterations related to the pathophysiology of diseases with neurological involvement and aging process. These findings may help identifying early disease biomarkers and lead to more effective therapies to improve the quality of life of the patients affected by these devastating illnesses. PMID:25110608

  6. Functional Disorders in Neurology: Case Studies.

    PubMed

    Stone, Jon; Hoeritzauer, Ingrid; Gelauff, Jeannette; Lehn, Alex; Gardiner, Paula; van Gils, Anne; Carson, Alan

    2016-08-01

    Functional, often called psychogenic, disorders are common in neurological practice. We illustrate clinical issues and highlight some recent research findings using six case studies of functional neurological disorders. We discuss dizziness as a functional disorder, describing the relatively new consensus term Persistent Posturo-Perceptual Dizziness (PPPD), axial jerking/myoclonus as a functional movement disorder, functional speech symptoms, post-concussion disorder with functional cognitive symptoms and finally advances in treatment of dissociative seizures and functional motor disorders. PMID:27445247

  7. Functional magnetic resonance imaging in neurology.

    PubMed

    Auer, Tibor; Schwarcz, Attila; Horváth, Réka A; Barsi, Péter; Janszky, József

    2008-01-30

    The present contribution discusses the clinical use of functional MRI (fMRI) and its role in the most common neurological diseases. FMRI was found a reliable and reproducible examination tool resulting in a wide distribution of fMRI methods in presurgical evaluation of epilepsy in determining the relationship of eloquent areas and the epileptic focus. Preliminary data suggest that fMRI using memory paradigms can predict the postoperative memory decline in epilepsy surgery by determining whether a reorganization of memory functions took place. Speech-activated fMRI became the most used tool in determining hemispheric dominance. Visual and sensory-motor cortex can also be routinely investigated by fMRI which helps in decision on epilepsy surgery. FMRI combined with EEG is a new diagnostic tool in epilepsy and sleep disorders. FMRI can identify the penumbra after stroke and can provide an additional information on metabolic state of the threatened brain tissue. FMRI has a predictive role in post-stroke recovery. In relapsing-remitting MS an adaptive reorganization can be demonstrated by fMRI affecting the visual, motor, and memory systems, despite preserved functional performance. Much more extensive reorganization can be demonstrated in secondary progressive MS. These findings suggest that the different stages of MS are related to different stages of the reorganization and MS becomes progressive when there is no more reserve capacity in the brain for reorganization. FMRI offers the capability of detecting early functional hemodynamic alterations in Alzheimer's disease before morphological changes. FMRI can be a valuable tool to test and monitor treatment efficacy in AD. FMRI can also provide information about the mechanisms of different therapeutic approaches in Parkinson disorder including drug treatment and deep brain stimulation.

  8. Update on 3-iodothyronamine and its neurological and metabolic actions

    PubMed Central

    Zucchi, Riccardo; Accorroni, Alice; Chiellini, Grazia

    2014-01-01

    3-iodothyronamine (T1AM) is an endogenous amine, that has been detected in many rodent tissues, and in human blood. It has been hypothesized to derive from thyroid hormone metabolism, but this hypothesis still requires validation. T1AM is not a ligand for nuclear thyroid hormone receptors, but stimulates with nanomolar affinity trace amine-associated receptor 1 (TAAR1), a G protein-coupled membrane receptor. With a lower affinity it interacts with alpha2A adrenergic receptors. Additional targets are represented by apolipoprotein B100, mitochondrial ATP synthase, and membrane monoamine transporters, but the functional relevance of these interactions is still uncertain. Among the effects reported after administration of exogenous T1AM to experimental animals, metabolic and neurological responses deserve special attention, because they were obtained at low dosages, which increased endogenous tissue concentration by about one order of magnitude. Systemic T1AM administration favored fatty acid over glucose catabolism, increased ketogenesis and increased blood glucose. Similar responses were elicited by intracerebral infusion, which inhibited insulin secretion and stimulated glucagon secretion. However, T1AM administration increased ketogenesis and gluconeogenesis also in hepatic cell lines and in perfused liver preparations, providing evidence for a peripheral action, as well. In the central nervous system, T1AM behaved as a neuromodulator, affecting adrenergic and/or histaminergic neurons. Intracerebral T1AM administration favored learning and memory, modulated sleep and feeding, and decreased the pain threshold. In conclusion T1AM should be considered as a component of thyroid hormone signaling and might play a significant physiological and/or pathophysiological role. T1AM analogs have already been synthetized and their therapeutical potential is currently under investigation. 3-iodothyronamine (T1AM) is a biogenic amine whose structure is closely related to that of

  9. Human neurologic function and the aging process.

    PubMed

    Potvin, A R; Syndulko, K; Tourtellotte, W W; Lemmon, J A; Potvin, J H

    1980-01-01

    Sixty-one normal men whose ages ranged from 20 to 80 years were evaluated on two occasions by means of a comprehensive series of 128 instrumented tests of neurologic function. The tests measured cognition, vision, strength, steadiness, reactions, speed, coordination, fatigue, gait, station, sensations, and tasks of daily living. The reliability of each test measured was determined, and any measure found unreliable (r less than or equal to 0.41) was not further analyzed. Significant age-related linear decreases were found for almost all neurologic functions. The declines over the age span varied from less than 10 percent to more than 90 percent for different functions. For the upper extremities, the largest declines (greater than 50 percent) were in hand-force steadiness, speed of hand-arm movements, and vibration sense; for the lower extremities, the largest declines were in one-legged balance with eyes closed and in vibration sense. For 13 of 14 tests in which significant dominant body-side effects were found, larger re-testing 7-10 days later, the subjects improved their scores by more than 5 percent on only 17 tests, 9 of which concerned the activities of daily living. No significant differential learning effects were found across age groups. The results point to the importance of developing a data bank on age-based neurologic function so that therapeutic effects can be evaluated in terms of age- and sex-matched normal functioning.

  10. The role of RNA metabolism in neurological diseases

    PubMed Central

    Abou Al-Shaar, H; Shariff, RK; Albakr, A

    2015-01-01

    Abstract Neurodegenerative disorders are commonly encountered in medical practices. Such diseases can lead to major morbidity and mortality among the affected individuals. The molecular pathogenesis of these disorders is not yet clear. Recent literature has revealed that mutations in RNA-binding proteins are a key cause of several human neuronal-based diseases. This review discusses the role of RNA metabolism in neurological diseases with specific emphasis on roles of RNA translation and microRNAs in neurodegeneration, RNA-mediated toxicity, repeat expansion diseases and RNA metabolism, molecular pathogenesis of amyotrophic lateral sclerosis and frontotemporal dementia, and neurobiology of survival motor neuron (SMN) and spinal muscular atrophy. PMID:27785391

  11. Sparring and Neurological Function in Professional Boxers

    PubMed Central

    Stiller, John W.; Yu, Steven S.; Brenner, Lisa A.; Langenberg, Patricia; Scrofani, Phillip; Pannella, Patrick; Hsu, Edbert B.; Roberts, Darryl W.; Monsell, Ray M. T.; Binks, Sidney W.; Guzman, Alvaro; Postolache, Teodor T.

    2014-01-01

    Despite increased interest regarding the potentially long-term negative impact of chronic traumatic brain injury, limited research has been conducted regarding such injuries and neurological outcomes in real world settings. To increase understanding regarding the relationship between sparring (e.g., training under the tutelage of an experienced boxing coach for the purpose of improving skills and/or fitness) and neurological functioning, professional boxers (n = 237) who competed in Maryland between 2003 and 2008 completed measures regarding sparring exposure (Cumulative Sparring Index, CSI) and performance on tests of cognition (Symbol Digit Modalities Test, SDMT) and balance (Sharpened Romberg Test, SRT). Measures were completed prior to boxing matches. Higher scores on the CSI (increased sparring exposure) were associated with poorer performance on both tests of cognition (SDMT) and balance (SRT). A threshold effect was noted regarding performance on the SDMT, with those reporting CSI values greater than about 150 experiencing a decline in cognition. A history of frequent and/or intense sparring may pose a significant risk for developing boxing associated neurological sequelae. Implementing administration of clinically meaningful tests before bouts, such as the CSI, SDMT, and/or the SRT, as well as documentation of results into the boxer’s physicals or medical profiles may be an important step for improving boxing safety. PMID:25101253

  12. Premature ovarian insufficiency and neurological function.

    PubMed

    Soni, M; Hogervorst, E

    2014-09-01

    Premature ovarian insufficiency (POI) involves loss of ovarian function before age 40. POI has been associated with neurological dysfunction and an increased risk of dementia, perhaps due to depletion in estrogen levels. The present review discusses the effects of POI caused by genetic disorder, natural premature menopause, surgical menopause, breast cancer treatment and gonadotropin-releasing hormone (GnRH) agonist treatment. Overall, data suggest an increased risk of neurological disorder where POI is due to premature menopause or induced from surgery. This increased risk appears to be most apparent on domains of global cognitive and verbal memory tests. Where POI is caused by genetic disorder, observed cognitive deficiencies may be more likely to have a genetic basis rather than being due to the effects of sex steroids on the brain. Findings related to loss of cognitive function after chemotherapy or GnRH treatments are mixed. There are also discrepant data related to use of hormone therapy after POI (particularly after surgical menopause). After surgery, hormone treatment appears to be most beneficial if initiated close to the average natural age of menopause.

  13. Functional Neuroanatomy and Neurophysiology of Functional Neurological Disorders (Conversion Disorder).

    PubMed

    Voon, Valerie; Cavanna, Andrea E; Coburn, Kerry; Sampson, Shirlene; Reeve, Alya; LaFrance, W Curt

    2016-01-01

    Much is known regarding the physical characteristics, comorbid symptoms, psychological makeup, and neuropsychological performance of patients with functional neurological disorders (FNDs)/conversion disorders. Gross neurostructural deficits do not account for the patients' deficits or symptoms. This review describes the literature focusing on potential neurobiological (i.e. functional neuroanatomic/neurophysiological) findings among individuals with FND, examining neuroimaging and neurophysiological studies of patients with the various forms of motor and sensory FND. In summary, neural networks and neurophysiologic mechanisms may mediate "functional" symptoms, reflecting neurobiological and intrapsychic processes.

  14. Functional Neuroanatomy and Neurophysiology of Functional Neurological Disorders (Conversion Disorder).

    PubMed

    Voon, Valerie; Cavanna, Andrea E; Coburn, Kerry; Sampson, Shirlene; Reeve, Alya; LaFrance, W Curt

    2016-01-01

    Much is known regarding the physical characteristics, comorbid symptoms, psychological makeup, and neuropsychological performance of patients with functional neurological disorders (FNDs)/conversion disorders. Gross neurostructural deficits do not account for the patients' deficits or symptoms. This review describes the literature focusing on potential neurobiological (i.e. functional neuroanatomic/neurophysiological) findings among individuals with FND, examining neuroimaging and neurophysiological studies of patients with the various forms of motor and sensory FND. In summary, neural networks and neurophysiologic mechanisms may mediate "functional" symptoms, reflecting neurobiological and intrapsychic processes. PMID:26900733

  15. Arsenic Exposure at Low-to-Moderate Levels and Skin Lesions, Arsenic Metabolism, Neurological Functions, and Biomarkers for Respiratory and Cardiovascular Diseases: Review of Recent Findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh

    PubMed Central

    Chen, Yu; Parvez, Faruque; Gamble, Mary; Islam, Tariqul; Ahmed, Alauddin; Argos, Maria; Graziano, Joseph H.; Ahsan, Habibul

    2012-01-01

    The contamination of groundwater by arsenic in Bangladesh is a major public health concern affecting 35–75 million people. Although it is evident that high levels (> 300 µg/L) of arsenic exposure from drinking water are related to adverse health outcomes, health effects of arsenic exposure at low-to-moderate levels (10–300 µg/L) are not well understood. We established the Health Effects of Arsenic Longitudinal Study (HEALS) with more than 20,000 men and women in Araihazar, Bangladesh, to prospectively investigate the health effects of arsenic predominately at low-to-moderate levels (0.1 to 864 µg/L, mean 99 µg/L) of arsenic exposure. Findings to date suggest adverse effects of low-to-moderate levels of arsenic exposure on the risk of pre-malignant skin lesions, high blood pressure, neurological dysfunctions, and all-cause and chronic disease mortality. In addition, the data also indicate that the risk of skin lesion due to arsenic exposure is modifiable by nutritional factors, such as folate and selenium status, lifestyle factors, including cigarette smoking and body mass index, and genetic polymorphisms in genes related to arsenic metabolism. The analyses of biomarkers for respiratory and cardiovascular functions support that there may be adverse effects of arsenic on these outcomes and call for confirmation in large studies. A unique strength of the HEALS is the availability of outcome data collected prospectively and data on detailed individual-level arsenic exposure estimated using water, blood and repeated urine samples. Future prospective analyses of clinical endpoints and related host susceptibility will enhance our knowledge on the health effects of low-to-moderate levels of arsenic exposure, elucidate disease mechanisms, and give directions for prevention. PMID:19371619

  16. Arsenic exposure at low-to-moderate levels and skin lesions, arsenic metabolism, neurological functions, and biomarkers for respiratory and cardiovascular diseases: Review of recent findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh

    SciTech Connect

    Chen Yu; Parvez, Faruque; Gamble, Mary; Islam, Tariqul; Ahmed, Alauddin; Argos, Maria; Graziano, Joseph H.; Ahsan, Habibul

    2009-09-01

    The contamination of groundwater by arsenic in Bangladesh is a major public health concern affecting 35-75 million people. Although it is evident that high levels (> 300 {mu}g/L) of arsenic exposure from drinking water are related to adverse health outcomes, health effects of arsenic exposure at low-to-moderate levels (10-300 {mu}g/L) are not well understood. We established the Health Effects of Arsenic Longitudinal Study (HEALS) with more than 20,000 men and women in Araihazar, Bangladesh, to prospectively investigate the health effects of arsenic predominately at low-to-moderate levels (0.1 to 864 {mu}g/L, mean 99 {mu}g/L) of arsenic exposure. Findings to date suggest adverse effects of low-to-moderate levels of arsenic exposure on the risk of pre-malignant skin lesions, high blood pressure, neurological dysfunctions, and all-cause and chronic disease mortality. In addition, the data also indicate that the risk of skin lesion due to arsenic exposure is modifiable by nutritional factors, such as folate and selenium status, lifestyle factors, including cigarette smoking and body mass index, and genetic polymorphisms in genes related to arsenic metabolism. The analyses of biomarkers for respiratory and cardiovascular functions support that there may be adverse effects of arsenic on these outcomes and call for confirmation in large studies. A unique strength of the HEALS is the availability of outcome data collected prospectively and data on detailed individual-level arsenic exposure estimated using water, blood and repeated urine samples. Future prospective analyses of clinical endpoints and related host susceptibility will enhance our knowledge on the health effects of low-to-moderate levels of arsenic exposure, elucidate disease mechanisms, and give directions for prevention.

  17. Arsenic exposure at low-to-moderate levels and skin lesions, arsenic metabolism, neurological functions, and biomarkers for respiratory and cardiovascular diseases: review of recent findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh.

    PubMed

    Chen, Yu; Parvez, Faruque; Gamble, Mary; Islam, Tariqul; Ahmed, Alauddin; Argos, Maria; Graziano, Joseph H; Ahsan, Habibul

    2009-09-01

    The contamination of groundwater by arsenic in Bangladesh is a major public health concern affecting 35-75 million people. Although it is evident that high levels (>300 microg/L) of arsenic exposure from drinking water are related to adverse health outcomes, health effects of arsenic exposure at low-to-moderate levels (10-300 microg/L) are not well understood. We established the Health Effects of Arsenic Longitudinal Study (HEALS) with more than 20,000 men and women in Araihazar, Bangladesh, to prospectively investigate the health effects of arsenic predominantly at low-to-moderate levels (0.1 to 864 microg/L, mean 99 microg/L) of arsenic exposure. Findings to date suggest adverse effects of low-to-moderate levels of arsenic exposure on the risk of pre-malignant skin lesions, high blood pressure, neurological dysfunctions, and all-cause and chronic disease mortality. In addition, the data also indicate that the risk of skin lesion due to arsenic exposure is modifiable by nutritional factors, such as folate and selenium status, lifestyle factors, including cigarette smoking and body mass index, and genetic polymorphisms in genes related to arsenic metabolism. The analyses of biomarkers for respiratory and cardiovascular functions support that there may be adverse effects of arsenic on these outcomes and call for confirmation in large studies. A unique strength of the HEALS is the availability of outcome data collected prospectively and data on detailed individual-level arsenic exposure estimated using water, blood and repeated urine samples. Future prospective analyses of clinical endpoints and related host susceptibility will enhance our knowledge on the health effects of low-to-moderate levels of arsenic exposure, elucidate disease mechanisms, and give directions for prevention. PMID:19371619

  18. Arsenic exposure at low-to-moderate levels and skin lesions, arsenic metabolism, neurological functions, and biomarkers for respiratory and cardiovascular diseases: review of recent findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh.

    PubMed

    Chen, Yu; Parvez, Faruque; Gamble, Mary; Islam, Tariqul; Ahmed, Alauddin; Argos, Maria; Graziano, Joseph H; Ahsan, Habibul

    2009-09-01

    The contamination of groundwater by arsenic in Bangladesh is a major public health concern affecting 35-75 million people. Although it is evident that high levels (>300 microg/L) of arsenic exposure from drinking water are related to adverse health outcomes, health effects of arsenic exposure at low-to-moderate levels (10-300 microg/L) are not well understood. We established the Health Effects of Arsenic Longitudinal Study (HEALS) with more than 20,000 men and women in Araihazar, Bangladesh, to prospectively investigate the health effects of arsenic predominantly at low-to-moderate levels (0.1 to 864 microg/L, mean 99 microg/L) of arsenic exposure. Findings to date suggest adverse effects of low-to-moderate levels of arsenic exposure on the risk of pre-malignant skin lesions, high blood pressure, neurological dysfunctions, and all-cause and chronic disease mortality. In addition, the data also indicate that the risk of skin lesion due to arsenic exposure is modifiable by nutritional factors, such as folate and selenium status, lifestyle factors, including cigarette smoking and body mass index, and genetic polymorphisms in genes related to arsenic metabolism. The analyses of biomarkers for respiratory and cardiovascular functions support that there may be adverse effects of arsenic on these outcomes and call for confirmation in large studies. A unique strength of the HEALS is the availability of outcome data collected prospectively and data on detailed individual-level arsenic exposure estimated using water, blood and repeated urine samples. Future prospective analyses of clinical endpoints and related host susceptibility will enhance our knowledge on the health effects of low-to-moderate levels of arsenic exposure, elucidate disease mechanisms, and give directions for prevention.

  19. Functional disorders in the Neurology section of ICD-11

    PubMed Central

    Hallett, Mark; Carson, Alan; Bergen, Donna; Shakir, Raad

    2014-01-01

    Functional disorders are one of the most common diagnoses in neurologic practice, but this is not reflected in current classification systems. The 11th revision of the World Health Organization's International Classification of Diseases (ICD-11) in 2017 offers an opportunity for these disorders to appear within both neurologic and psychiatric categories for the first time. We discuss the rationale for this proposal and highlight the potential benefits for health professionals and patients. PMID:25488992

  20. Phonatory Function of Neurologically Impaired Patients.

    ERIC Educational Resources Information Center

    Zwirner, Petra; And Others

    1991-01-01

    This investigation compared five parameters of phonatory function in an examination of the use of acoustic measures in differential diagnosis in 39 subjects in 3 neuropathological groups (Parkinson, Huntington, cerebellar ataxia) and a normal control group. Results indicated higher variability in perturbation in all the neuropathological groups.…

  1. Gene Therapy for the Treatment of Neurological Disorders: Metabolic Disorders

    PubMed Central

    Gessler, Dominic J.; Gao, Guangping

    2016-01-01

    Metabolic disorders comprise a large group of heterogeneous diseases ranging from very prevalent diseases such as diabetes mellitus to rare genetic disorders like Canavan Disease. Whether either of these diseases is amendable by gene therapy depends to a large degree on the knowledge of their pathomechanism, availability of the therapeutic gene, vector selection, and availability of suitable animal models. In this book chapter, we review three metabolic disorders of the central nervous system (CNS; Canavan Disease, Niemann–Pick disease and Phenylketonuria) to give examples for primary and secondary metabolic disorders of the brain and the attempts that have been made to use adeno-associated virus (AAV) based gene therapy for treatment. Finally, we highlight commonalities and obstacles in the development of gene therapy for metabolic disorders of the CNS exemplified by those three diseases. PMID:26611604

  2. Sleep and metabolic function

    PubMed Central

    Morselli, Lisa L.; Guyon, Aurore; Spiegel, Karine

    2012-01-01

    Evidence for the role of sleep on metabolic and endocrine function has been reported more than four decades ago. In the past 30 years, the prevalence of obesity and diabetes has greatly increased in industrialized countries, and self-imposed sleep curtailment, now very common, is starting to be recognized as a contributing factor, alongside with increased caloric intake and decreased physical activity. Furthermore, obstructive sleep apnea, a chronic condition characterized by recurrent upper airway obstruction leading to intermittent hypoxemia and sleep fragmentation, has also become highly prevalent as a consequence of the epidemic of obesity and has been shown to contribute, in a vicious circle, to the metabolic disturbances observed in obese patients. In this article, we summarize the current data supporting the role of sleep in the regulation of glucose homeostasis and the hormones involved in the regulation of appetite. We also review the results of the epidemiologic and laboratory studies that investigated the impact of sleep duration and quality on the risk of developing diabetes and obesity, as well as the mechanisms underlying this increased risk. Finally, we discuss how obstructive sleep apnea affects glucose metabolism and the beneficial impact of its treatment, the continuous positive airway pressure. In conclusion, the data available in the literature highlight the importance of getting enough good sleep for metabolic health. PMID:22101912

  3. Rett syndrome: disruption of epigenetic control of postnatal neurological functions.

    PubMed

    Pohodich, Amy E; Zoghbi, Huda Y

    2015-10-15

    Loss-of-function mutations in the X-linked gene Methyl-CpG-binding protein 2 (MECP2) cause a devastating pediatric neurological disorder called Rett syndrome. In males, these mutations typically result in severe neonatal encephalopathy and early lethality. On the other hand, owing to expression of the normal allele in ∼50% of cells, females do not suffer encephalopathy but instead develop Rett syndrome. Typically females with Rett syndrome exhibit a delayed onset of neurologic dysfunction that manifests around the child's first birthday and progresses over the next few years. Features of this disorder include loss of acquired language and motor skills, intellectual impairment and hand stereotypies. The developmental regression observed in patients with Rett syndrome arises from altered neuronal function and is not the result of neurodegeneration. Maintenance of an appropriate level of MeCP2 appears integral to the function of healthy neurons as patients with increased levels of MeCP2, owing to duplication of the Xq28 region encompassing the MECP2 locus, also present with intellectual disability and progressive neurologic symptoms. Despite major efforts over the past two decades to elucidate the molecular functions of MeCP2, the mechanisms underlying the delayed appearance of symptoms remain unclear. In this review, we will highlight recent findings that have expanded our knowledge of MeCP2's functions, and we will discuss how epigenetic regulation, chromatin organization and circuit dynamics may contribute to the postnatal onset of Rett syndrome.

  4. Leigh Syndrome in Childhood: Neurologic Progression and Functional Outcome

    PubMed Central

    Lee, Jin Sook; Kim, Hunmin; Lim, Byung Chan; Hwang, Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung

    2016-01-01

    Background and Purpose Few studies have analyzed the clinical course and functional outcome in Leigh syndrome (LS). The aim of this study was to determine the clinical, radiological, biochemical, and genetic features of patients with LS, and identify prognostic indicators of the disease progression and neurological outcome. Methods Thirty-nine patients who had been diagnosed with LS at the Seoul National University Children's Hospital were included. Their medical records, neuroimaging findings, and histological/biochemical findings of skeletal muscle specimens were reviewed. Targeted sequencing of mitochondrial DNA was performed based on mitochondrial respiratory chain (MRC) enzyme defects. Results Isolated complex I deficiency was the most frequently observed MRC defect (in 42% of 38 investigated patients). Mitochondrial DNA mutations were identified in 11 patients, of which 81.8% were MT-ND genes. The clinical outcome varied widely, from independent daily activity to severe disability. Poor functional outcomes and neurological deterioration were significantly associated with early onset (before an age of 1 year) and the presence of other lesions additional to basal ganglia involvement in the initial neuroimaging. Conclusions The neurological severity and outcome of LS may vary widely and be better than those predicted based on previous studies. We suggest that age at onset and initial neuroimaging findings are prognostic indicators in LS. PMID:27074294

  5. Invited article: inhibition of B cell functions: implications for neurology.

    PubMed

    Dalakas, Marinos C

    2008-06-01

    B cells are involved in the pathophysiology of many neurologic diseases, either in a causative or contributory role, via production of autoantibodies, cytokine secretion, or by acting as antigen-presenting cells leading to T cell activation. B cells are clonally expanded in various CNS disorders, such as multiple sclerosis (MS), paraneoplastic CNS disorders, or stiff-person syndrome, and are activated to produce pathogenic autoantibodies in demyelinating neuropathies and myasthenia. B cell activating factor (BAFF) and a proliferating inducing ligand (APRIL), key cytokines for B cell survival, are strongly unregulated in MS brain and in muscles of inflammatory myopathies. Modulation of B cell functions using a series of monoclonal antibodies against CD20+ B cells or the molecules that increase B cell survival, such as BAFF/APRIL and their receptors BAFF-R, TACI, and BCMA, provide a rational approach to the treatment of the aforementioned neurologic disorders. In controlled studies, rituximab, a B cell-depleting monoclonal antibody, has been encouraging in MS and paraproteinemic anti-MAG demyelinating neuropathy, exerting long-lasting remissions. In uncontrolled series, benefit has been reported in several disorders. B cell depletion is a well-tolerated therapeutic option currently explored in the treatment of several autoimmune neurologic disorders.

  6. Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features

    PubMed Central

    Ouyang, Qing; Nakayama, Tojo; Baytas, Ozan; Davidson, Shawn M.; Yang, Chendong; Schmidt, Michael; Lizarraga, Sofia B.; Mishra, Sasmita; EI-Quessny, Malak; Niaz, Saima; Gul Butt, Mirrat; Imran Murtaza, Syed; Javed, Afzal; Chaudhry, Haroon Rashid; Vaughan, Dylan J.; Hill, R. Sean; Partlow, Jennifer N.; Yoo, Seung-Yun; Lam, Anh-Thu N.; Nasir, Ramzi; Al-Saffar, Muna; Barkovich, A. James; Schwede, Matthew; Nagpal, Shailender; Rajab, Anna; DeBerardinis, Ralph J.; Housman, David E.; Mochida, Ganeshwaran H.; Morrow, Eric M.

    2016-01-01

    Mutations that cause neurological phenotypes are highly informative with regard to mechanisms governing human brain function and disease. We report autosomal recessive mutations in the enzyme glutamate pyruvate transaminase 2 (GPT2) in large kindreds initially ascertained for intellectual and developmental disability (IDD). GPT2 [also known as alanine transaminase 2 (ALT2)] is one of two related transaminases that catalyze the reversible addition of an amino group from glutamate to pyruvate, yielding alanine and α-ketoglutarate. In addition to IDD, all affected individuals show postnatal microcephaly and ∼80% of those followed over time show progressive motor symptoms, a spastic paraplegia. Homozygous nonsense p.Arg404* and missense p.Pro272Leu mutations are shown biochemically to be loss of function. The GPT2 gene demonstrates increasing expression in brain in the early postnatal period, and GPT2 protein localizes to mitochondria. Akin to the human phenotype, Gpt2-null mice exhibit reduced brain growth. Through metabolomics and direct isotope tracing experiments, we find a number of metabolic abnormalities associated with loss of Gpt2. These include defects in amino acid metabolism such as low alanine levels and elevated essential amino acids. Also, we find defects in anaplerosis, the metabolic process involved in replenishing TCA cycle intermediates. Finally, mutant brains demonstrate misregulated metabolites in pathways implicated in neuroprotective mechanisms previously associated with neurodegenerative disorders. Overall, our data reveal an important role for the GPT2 enzyme in mitochondrial metabolism with relevance to developmental as well as potentially to neurodegenerative mechanisms. PMID:27601654

  7. Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features.

    PubMed

    Ouyang, Qing; Nakayama, Tojo; Baytas, Ozan; Davidson, Shawn M; Yang, Chendong; Schmidt, Michael; Lizarraga, Sofia B; Mishra, Sasmita; Ei-Quessny, Malak; Niaz, Saima; Gul Butt, Mirrat; Imran Murtaza, Syed; Javed, Afzal; Chaudhry, Haroon Rashid; Vaughan, Dylan J; Hill, R Sean; Partlow, Jennifer N; Yoo, Seung-Yun; Lam, Anh-Thu N; Nasir, Ramzi; Al-Saffar, Muna; Barkovich, A James; Schwede, Matthew; Nagpal, Shailender; Rajab, Anna; DeBerardinis, Ralph J; Housman, David E; Mochida, Ganeshwaran H; Morrow, Eric M

    2016-09-20

    Mutations that cause neurological phenotypes are highly informative with regard to mechanisms governing human brain function and disease. We report autosomal recessive mutations in the enzyme glutamate pyruvate transaminase 2 (GPT2) in large kindreds initially ascertained for intellectual and developmental disability (IDD). GPT2 [also known as alanine transaminase 2 (ALT2)] is one of two related transaminases that catalyze the reversible addition of an amino group from glutamate to pyruvate, yielding alanine and α-ketoglutarate. In addition to IDD, all affected individuals show postnatal microcephaly and ∼80% of those followed over time show progressive motor symptoms, a spastic paraplegia. Homozygous nonsense p.Arg404* and missense p.Pro272Leu mutations are shown biochemically to be loss of function. The GPT2 gene demonstrates increasing expression in brain in the early postnatal period, and GPT2 protein localizes to mitochondria. Akin to the human phenotype, Gpt2-null mice exhibit reduced brain growth. Through metabolomics and direct isotope tracing experiments, we find a number of metabolic abnormalities associated with loss of Gpt2. These include defects in amino acid metabolism such as low alanine levels and elevated essential amino acids. Also, we find defects in anaplerosis, the metabolic process involved in replenishing TCA cycle intermediates. Finally, mutant brains demonstrate misregulated metabolites in pathways implicated in neuroprotective mechanisms previously associated with neurodegenerative disorders. Overall, our data reveal an important role for the GPT2 enzyme in mitochondrial metabolism with relevance to developmental as well as potentially to neurodegenerative mechanisms. PMID:27601654

  8. Total venous inflow occlusion in the normothermic dog: a study of haemodynamic, metabolic and neurological consequences.

    PubMed

    Hunt, G B; Malik, R; Bellenger, C R; Pearson, M R

    1992-05-01

    The acute haemodynamic and metabolic repercussions of total venous inflow occlusion were evaluated in six normal dogs, each of which underwent two four minute occlusions and one eight minute occlusion at normothermia. A further three dogs underwent a single eight minute period of occlusion and were allowed to recover from anaesthesia. Total venous inflow occlusion was well tolerated by all animals. They remained in sinus rhythm at the completion of occlusion, and unassisted haemodynamic recovery occurred rapidly. Recovery was quicker after four minutes than after eight minutes. There was no clinically detectable neurological impairment in three dogs which were allowed to recover.

  9. Analysis of abnormalities in purine metabolism leading to gout and to neurological dysfunctions in man.

    PubMed Central

    Curto, R; Voit, E O; Cascante, M

    1998-01-01

    A modelling approach is used to analyse diseases associated with purine metabolism in man. The specific focus is on deficiencies in two enzymes, hypoxanthine:guanine phosphoribosyltransferase and adenylosuccinate lyase. These deficiencies can lead to a number of symptoms, including neurological dysfunctions and mental retardation. Although the biochemical mechanisms of dysfunctions associated with adenylosuccinate lyase deficiency are not completely understood, there is at least general agreement in the literature about possible causes. Simulations with our model confirm that accumulation of the two substrates of the enzyme can lead to significant biochemical imbalance. In hypoxanthine:guanine phosphoribosyltransferase deficiency the biochemical mechanisms associated with neurological dysfunctions are less clear. Model analyses support some old hypotheses but also suggest new indicators for possible causes of neurological dysfunctions associated with this deficiency. Hypoxanthine:guanine phosphoribosyltransferase deficiency is known to cause hyperuricaemia and gout. We compare the relative importance of this deficiency with other known causes of gout in humans. The analysis suggests that defects in the excretion of uric acid are more consequential than defects in uric acid synthesis such as hypoxanthine:guanine phosphoribosyltransferase deficiency. PMID:9445373

  10. Kupffer Cell Metabolism and Function

    PubMed Central

    Nguyen-Lefebvre, Anh Thu; Horuzsko, Anatolij

    2015-01-01

    Kupffer cells are resident liver macrophages and play a critical role in maintaining liver functions. Under physiological conditions, they are the first innate immune cells and protect the liver from bacterial infections. Under pathological conditions, they are activated by different components and can differentiate into M1-like (classical) or M2-like (alternative) macrophages. The metabolism of classical or alternative activated Kupffer cells will determine their functions in liver damage. Special functions and metabolism of Kupffer cells suggest that they are an attractive target for therapy of liver inflammation and related diseases, including cancer and infectious diseases. Here we review the different types of Kupffer cells and their metabolism and functions in physiological and pathological conditions. PMID:26937490

  11. Neurological abnormalities and neurocognitive functions in healthy elder people: A structural equation modeling analysis

    PubMed Central

    2011-01-01

    Background/Aims Neurological abnormalities have been reported in normal aging population. However, most of them were limited to extrapyramidal signs and soft signs such as motor coordination and sensory integration have received much less attention. Very little is known about the relationship between neurological soft signs and neurocognitive function in healthy elder people. The current study aimed to examine the underlying relationships between neurological soft signs and neurocognition in a group of healthy elderly. Methods One hundred and eighty healthy elderly participated in the current study. Neurological soft signs were evaluated with the subscales of Cambridge Neurological Inventory. A set of neurocognitive tests was also administered to all the participants. Structural equation modeling was adopted to examine the underlying relationship between neurological soft signs and neurocognition. Results No significant differences were found between the male and female elder people in neurocognitive function performances and neurological soft signs. The model fitted well in the elderly and indicated the moderate associations between neurological soft signs and neurocognition, specifically verbal memory, visual memory and working memory. Conclusions The neurological soft signs are more or less statistically equivalent to capture the similar information done by conventional neurocognitive function tests in the elderly. The implication of these findings may serve as a potential neurological marker for the early detection of pathological aging diseases or related mental status such as mild cognitive impairment and Alzheimer's disease. PMID:21827719

  12. CD163 promotes hematoma absorption and improves neurological functions in patients with intracerebral hemorrhage

    PubMed Central

    Xie, Wen-jing; Yu, Hong-quan; Zhang, Yu; Liu, Qun; Meng, Hong-mei

    2016-01-01

    Clinical outcomes are positively associated with hematoma absorption. The monocyte-macrophage scavenger receptor, CD163, plays an important role in the metabolism of hemoglobin, and a soluble form of CD163 is present in plasma and other tissue fluids; therefore, we speculated that serum CD163 affects hematoma absorption after intracerebral hemorrhage. Patients with intracerebral hemorrhage were divided into high- and low-level groups according to the average CD163 level (1,977.79 ± 832.91 ng/mL). Compared with the high-level group, the low-level group had a significantly slower hematoma absorption rate, and significantly increased National Institutes of Health Stroke Scale scores and modified Rankin Scale scores. These results suggest that CD163 promotes hematoma absorption and the recovery of neurological function in patients with intracerebral hemorrhage.

  13. CD163 promotes hematoma absorption and improves neurological functions in patients with intracerebral hemorrhage.

    PubMed

    Xie, Wen-Jing; Yu, Hong-Quan; Zhang, Yu; Liu, Qun; Meng, Hong-Mei

    2016-07-01

    Clinical outcomes are positively associated with hematoma absorption. The monocyte-macrophage scavenger receptor, CD163, plays an important role in the metabolism of hemoglobin, and a soluble form of CD163 is present in plasma and other tissue fluids; therefore, we speculated that serum CD163 affects hematoma absorption after intracerebral hemorrhage. Patients with intracerebral hemorrhage were divided into high- and low-level groups according to the average CD163 level (1,977.79 ± 832.91 ng/mL). Compared with the high-level group, the low-level group had a significantly slower hematoma absorption rate, and significantly increased National Institutes of Health Stroke Scale scores and modified Rankin Scale scores. These results suggest that CD163 promotes hematoma absorption and the recovery of neurological function in patients with intracerebral hemorrhage. PMID:27630696

  14. CD163 promotes hematoma absorption and improves neurological functions in patients with intracerebral hemorrhage

    PubMed Central

    Xie, Wen-jing; Yu, Hong-quan; Zhang, Yu; Liu, Qun; Meng, Hong-mei

    2016-01-01

    Clinical outcomes are positively associated with hematoma absorption. The monocyte-macrophage scavenger receptor, CD163, plays an important role in the metabolism of hemoglobin, and a soluble form of CD163 is present in plasma and other tissue fluids; therefore, we speculated that serum CD163 affects hematoma absorption after intracerebral hemorrhage. Patients with intracerebral hemorrhage were divided into high- and low-level groups according to the average CD163 level (1,977.79 ± 832.91 ng/mL). Compared with the high-level group, the low-level group had a significantly slower hematoma absorption rate, and significantly increased National Institutes of Health Stroke Scale scores and modified Rankin Scale scores. These results suggest that CD163 promotes hematoma absorption and the recovery of neurological function in patients with intracerebral hemorrhage. PMID:27630696

  15. Neurologic function among termiticide applicators exposed to chlorpyrifos.

    PubMed Central

    Steenland, K; Dick, R B; Howell, R J; Chrislip, D W; Hines, C J; Reid, T M; Lehman, E; Laber, P; Krieg, E F; Knott, C

    2000-01-01

    Chlorpyrifos is a moderately toxic organophosphate pesticide. Houses and lawns in the United States receive a total of approximately 20 million annual chlorpyrifos treatments, and 82% of U.S. adults have detectable levels of a chlorpyrifos metabolite (3,5, 6-trichloro-2-pyridinol; TCP) in the urine. The U.S. Environmental Protection Agency has estimated that there are 5,000 yearly reported cases of accidental chlorpyrifos poisoning, and approximately one-fourth of these cases exhibit symptoms. Organophosphates affect the nervous system, but there are few epidemiologic data on chlorpyrifos neurotoxicity. We studied neurologic function in 191 current and former termiticide applicators who had an average of 2.4 years applying chlorpyrifos and 2.5 years applying other pesticides, and we compared them to 189 nonexposed controls. The average urinary TCP level for 65 recently exposed applicators was 629.5 microg/L, as compared to 4.5 microg/L for the general U.S. population. The exposed group did not differ significantly from the nonexposed group for any test in the clinical examination. Few significant differences were found in nerve conduction velocity, arm/hand tremor, vibrotactile sensitivity, vision, smell, visual/motor skills, or neurobehavioral skills. The exposed group did not perform as well as the nonexposed group in pegboard turning tests and some postural sway tests. The exposed subjects also reported significantly more symptoms, including memory problems, emotional states, fatigue, and loss of muscle strength; our more quantitative tests may not have been adequate to detect these symptoms. Eight men who reported past chlorpyrifos poisoning had a pattern of low performance on a number of tests, which is consistent with prior reports of chronic effects of organophosphate poisoning. Overall, the lack of exposure effects on the clinical examination was reassuring. The findings for self-reported symptoms raise some concern, as does the finding of low performance

  16. Neurological soft signs in children with attention deficit hyperactivity disorder: Their relationship to executive function and parental neurological soft signs.

    PubMed

    Gong, Jingbo; Xie, Jingtao; Chen, Gui; Zhang, Yajie; Wang, Suhong

    2015-07-30

    The correlations between neurological soft signs (NSS) in children with attention deficit hyperactivity disorder (ADHD) and their executive function, symptoms of inattention, and hyperactivity-impulsivity and the NSS of their parents remain unclear. This study aimed to examine: (1) the prevalence of NSS in children with ADHD and their parents; (2) the correlation between the NSS of children with ADHD and the NSS of their parents; and (3) the correlation between the NSS of children with ADHD and their executive function and symptoms. NSS were assessed with the Cambridge Neurological Inventory (CNI) in 57 children with ADHD (and 80 parents) and 60 healthy children (and 75 parents). Executive function was measured with the Behavioral Rating Inventory of Executive Function (BRIEF). Children with ADHD and their parents had significantly higher NSS than normal children and their parents, respectively, and the NSS of children with ADHD were correlated more strongly with the NSS of their fathers than their mothers. No correlation was found between NSS and BRIEF executive function, but Disinhibition in children with ADHD was significantly correlated with hyperactivity-impulsivity symptoms. Paternal and maternal NSS provided different predictions for child NSS. It may be that NSS are more likely to be genetically transmitted by fathers.

  17. Cognitive and motor function of neurologically impaired extremely low birth weight children

    PubMed Central

    Bernardo, Janine; Friedman, Harriet; Minich, Nori; Taylor, H Gerry; Wilson-Costello, Deanne; Hack, Maureen

    2015-01-01

    BACKGROUND: Rates of neurological impairment among extremely low birth weight children (ELBW [<1 kg]) have decreased since 2000; however, their functioning is unexamined. OBJECTIVE: To compare motor and cognitive functioning of ELBW children with neurological impairment, including cerebral palsy and severe hypotonia/hypertonia, between two periods: 1990 to 1999 (n=83) and 2000 to 2005 (n=34). METHODS: Measures of function at 20 months corrected age included the Mental and Psychomotor Developmental Indexes of the Bayley Scales of Infant Development and the Gross Motor Functional Classification System as primary outcomes and individual motor function items as secondary outcomes. RESULTS: Analysis failed to reveal significant differences for the primary outcomes, although during 2000 to 2005, sitting significantly improved in children with neurological impairment (P=0.003). CONCLUSION: Decreases in rates of neurological impairment among ELBW children have been accompanied by a suggestion of improved motor function, although cognitive function has not changed. PMID:26435676

  18. Intellectual and neurological functioning in Morquio syndrome (MPS IVa).

    PubMed

    Davison, J E; Kearney, S; Horton, J; Foster, K; Peet, A C; Hendriksz, C J

    2013-03-01

    Mucopolysaccharidosis type IVa (MPS IVa, Morquio syndrome OMIM #253000) is a lysosomal storage disease caused by deficiency in N-acetylgalactosamine-6-sulfatase (GALNS, EC 3.1.6.4; encoded by GALNS gene at 16q24.3). Unlike other MPS disorders involving excessive heparan and dermatan sulfate, Morquio syndrome has not been associated with neurological involvement nor with intellectual impairment as this disorder of keratan sulfate has been described as a purely visceral and skeletal disorder. Neurocognitive assessment was undertaken of MPS IVa patients with age appropriate intellectual tests as well as a Child Behaviour Checklist as part of clinical follow up. Available neuroimaging studies (MRI and MR spectroscopy) were reviewed. Whilst more than half of the overall IQ scores fell in the average range, scores for 3/8 children fell below average. A number of behavioural problems were highlighted, including anxiety/depression, attention and somatic complaints. Subtle neuroimaging abnormalities were demonstrated in over half of the children. These findings present a challenge to existing assumptions about the nature of Morquio A syndrome. A hypothesis regarding the potential role of calcium signalling is explored. PMID:22231379

  19. Functional disorders in the Neurology section of ICD-11: A landmark opportunity.

    PubMed

    Stone, Jon; Hallett, Mark; Carson, Alan; Bergen, Donna; Shakir, Raad

    2014-12-01

    Functional disorders are one of the most common diagnoses in neurologic practice, but this is not reflected in current classification systems. The 11th revision of the World Health Organization's International Classification of Diseases (ICD-11) in 2017 offers an opportunity for these disorders to appear within both neurologic and psychiatric categories for the first time. We discuss the rationale for this proposal and highlight the potential benefits for health professionals and patients.

  20. Designing and implementing a longitudinal study of children with neurological, genetic or metabolic conditions: charting the territory

    PubMed Central

    2010-01-01

    Background Children with progressive metabolic, neurological, or chromosomal conditions and their families anticipate an unknown lifespan, endure unstable and often painful symptoms, and cope with erratic emotional and spiritual crises as the condition progresses along an uncertain trajectory towards death. Much is known about the genetics and pathophysiology of these diseases, but very little has been documented about the trajectory of symptoms for children with these conditions or the associated experience of their families. A longitudinal study design will help to close this gap in knowledge. Methods/Design Charting the Territory is a longitudinal descriptive, correlational study currently underway with children 0-19 years who are diagnosed with progressive neurological, metabolic, or chromosomal conditions and their families. The purpose of the study is to determine and document the clinical progression of the condition and the associated bio-psychosocial-spiritual experiences of the parents and siblings age 7-18 years. Approximately 300 families, both newly diagnosed children and those with established conditions, are being recruited in six Canadian cities. Children and their families are being followed for a minimum of 18 months, depending on when they enroll in the study. Family data collection will continue after the child's death if the child dies during the study period. Data collection includes monthly parental assessment of the child's symptoms; an annual functional assessment of the child; and completion of established instruments every 6 months by parents to assess family functioning, marital satisfaction, health status, anxiety, depression, stress, burden, grief, spirituality, and growth, and by siblings to assess coping and health. Impact of participation on parents is assessed after 1 year and at the end of the study. Chart reviews are conducted at enrollment and at the conclusion of the study or at the time of the child's death. Discussion

  1. Simultaneous occurrence of metabolic, hematologic, neurologic and cardiac complications after Roux-en-Y gastric bypass for morbid obesity.

    PubMed

    Kara, Merve; Gundogdu, Yasemin; Karsli, Merve; Ozben, Volkan; Onder, Fatih Oguz; Baca, Bilgi

    2016-10-01

    Roux-en-Y gastric bypass (RYGB) is a commonly performed procedure in the surgical treatment of morbid obesity. Since a major anatomical alteration is made, this procedure may lead to significant postoperative complications, including nutritional deficiencies related to malabsorption. As a consequence of micronutrient deficiencies, secondary metabolic, hematologic and neurologic complications might also develop. Each of these complications is well reported in the literature; however, there are limited data on the simultaneous occurrence of these complications in a single patient. In this report, we aimed to present the diagnosis and management of metabolic, hematologic, neurologic and cardiac complications, which occurred simultaneously in a 57-year-old female patient after undergoing laparoscopic RYGB procedure.

  2. Mammalian aquaglyceroporin function in metabolism.

    PubMed

    Laforenza, Umberto; Bottino, Cinzia; Gastaldi, Giulia

    2016-01-01

    Aquaglyceroporins are integral membrane proteins that are permeable to glycerol as well as water. The movement of glycerol from a tissue/organ to the plasma and vice versa requires the presence of different aquaglyceroporins that can regulate the entrance or the exit of glycerol across the plasma membrane. Actually, different aquaglyceroporins have been discovered in the adipose tissue, small intestine, liver, kidney, heart, skeletal muscle, endocrine pancreas and capillary endothelium, and their differential expression could be related to obesity and the type 2 diabetes. Here we describe the expression and function of different aquaglyceroporins in physiological condition and in obesity and type 2 diabetes, suggesting they are potential therapeutic targets for metabolic disorders. PMID:26456554

  3. The Assessment of Neurological Systems with Functional Imaging

    ERIC Educational Resources Information Center

    Eidelberg, David

    2007-01-01

    In recent years a number of multivariate approaches have been introduced to map neural systems in health and disease. In this review, we focus on spatial covariance methods applied to functional imaging data to identify patterns of regional activity associated with behavior. In the rest state, this form of network analysis can be used to detect…

  4. Clinical assessment of social cognitive function in neurological disorders.

    PubMed

    Henry, Julie D; von Hippel, William; Molenberghs, Pascal; Lee, Teresa; Sachdev, Perminder S

    2016-01-01

    Social cognition broadly refers to the processing of social information in the brain that underlies abilities such as the detection of others' emotions and responding appropriately to these emotions. Social cognitive skills are critical for successful communication and, consequently, mental health and wellbeing. Disturbances of social cognition are early and salient features of many neuropsychiatric, neurodevelopmental and neurodegenerative disorders, and often occur after acute brain injury. Its assessment in the clinic is, therefore, of paramount importance. Indeed, the most recent edition of the American Psychiatric Association's Diagnostic and Statistical Manual for Mental Disorders (DSM-5) introduced social cognition as one of six core components of neurocognitive function, alongside memory and executive control. Failures of social cognition most often present as poor theory of mind, reduced affective empathy, impaired social perception or abnormal social behaviour. Standard neuropsychological assessments lack the precision and sensitivity needed to adequately inform treatment of these failures. In this Review, we present appropriate methods of assessment for each of the four domains, using an example disorder to illustrate the value of these approaches. We discuss the clinical applications of testing for social cognitive function, and finally suggest a five-step algorithm for the evaluation and treatment of impairments, providing quantitative evidence to guide the selection of social cognitive measures in clinical practice.

  5. Clinical assessment of social cognitive function in neurological disorders.

    PubMed

    Henry, Julie D; von Hippel, William; Molenberghs, Pascal; Lee, Teresa; Sachdev, Perminder S

    2016-01-01

    Social cognition broadly refers to the processing of social information in the brain that underlies abilities such as the detection of others' emotions and responding appropriately to these emotions. Social cognitive skills are critical for successful communication and, consequently, mental health and wellbeing. Disturbances of social cognition are early and salient features of many neuropsychiatric, neurodevelopmental and neurodegenerative disorders, and often occur after acute brain injury. Its assessment in the clinic is, therefore, of paramount importance. Indeed, the most recent edition of the American Psychiatric Association's Diagnostic and Statistical Manual for Mental Disorders (DSM-5) introduced social cognition as one of six core components of neurocognitive function, alongside memory and executive control. Failures of social cognition most often present as poor theory of mind, reduced affective empathy, impaired social perception or abnormal social behaviour. Standard neuropsychological assessments lack the precision and sensitivity needed to adequately inform treatment of these failures. In this Review, we present appropriate methods of assessment for each of the four domains, using an example disorder to illustrate the value of these approaches. We discuss the clinical applications of testing for social cognitive function, and finally suggest a five-step algorithm for the evaluation and treatment of impairments, providing quantitative evidence to guide the selection of social cognitive measures in clinical practice. PMID:26670297

  6. EXAMINER executive function battery and neurologic morbidity in pediatric sickle cell disease.

    PubMed

    Schatz, Jeffrey; Stancil, Melita; Katz, Tal; Sanchez, Carmen E

    2014-01-01

    Sickle cell disease (SCD) is blood disorder with a high risk for cerebral vascular morbidities that impact neurocognitive functioning. Specific cognitive abilities are known to be more sensitive to neurologic effects of SCD than IQ scores, yet there is little consensus about which measures to use to assess neurocognitive functioning. We evaluated the ability of the Executive Abilities: Methods and Instruments for Neurobehavioral Evaluation and Research (EXAMINER) Battery to detect neurologic effects in SCD. Thirty-two youth with SCD and sixty demographically-matched comparison youth completed the EXAMINER Battery and selected tests from the Woodcock-Johnson Tests of Cognitive Ability, 3rd edition (WJ-III). Neurologic severity was examined via clinical history for morbidities and midsagittal corpus callosum (CC) area. Results indicated cognitive performance decreased with increasing neurologic morbidity across all cognitive measures; two of four EXAMINER factors were related to CC area. The association with clinical history and midsagittal CC area appeared at least as large for the Examiner Battery scores as for the WJ-III measures. The Examiner Battery showed sensitivity to neurologic history and white matter effects in SCD; this new measure compares favorably to established measures of disease-related neurocognitive effects, but would benefit from further development. PMID:24280593

  7. The concept of technology transfer. [for neurologically handicapped persons with impairment of sensorimotor functions

    NASA Technical Reports Server (NTRS)

    Arnold, L.

    1974-01-01

    Potential benefits from aerospace technology applications are elaborated that will enable the neurologically handicapped to recapture and upgrade some of their motor and sensor functions. Considered are all individuals whose sensorimotor communication systems have been damaged as a result of disease, trauma, or aging.

  8. Nmf9 Encodes a Highly Conserved Protein Important to Neurological Function in Mice and Flies

    PubMed Central

    Zhang, Shuxiao; Ross, Kevin D.; Seidner, Glen A.; Gorman, Michael R.; Poon, Tiffany H.; Wang, Xiaobo; Keithley, Elizabeth M.; Lee, Patricia N.; Martindale, Mark Q.; Joiner, William J.; Hamilton, Bruce A.

    2015-01-01

    Many protein-coding genes identified by genome sequencing remain without functional annotation or biological context. Here we define a novel protein-coding gene, Nmf9, based on a forward genetic screen for neurological function. ENU-induced and genome-edited null mutations in mice produce deficits in vestibular function, fear learning and circadian behavior, which correlated with Nmf9 expression in inner ear, amygdala, and suprachiasmatic nuclei. Homologous genes from unicellular organisms and invertebrate animals predict interactions with small GTPases, but the corresponding domains are absent in mammalian Nmf9. Intriguingly, homozygotes for null mutations in the Drosophila homolog, CG45058, show profound locomotor defects and premature death, while heterozygotes show striking effects on sleep and activity phenotypes. These results link a novel gene orthology group to discrete neurological functions, and show conserved requirement across wide phylogenetic distance and domain level structural changes. PMID:26131556

  9. Cellular metabolism and macrophage functional polarization.

    PubMed

    Zhu, Linnan; Zhao, Qingjie; Yang, Tao; Ding, Wenjun; Zhao, Yong

    2015-01-01

    Macrophages are a functionally heterogeneous cell population that is mainly shaped by a variety of microenvironmental stimuli. Interferon γ (IFN-γ), interleukin-1β (IL-1β), and lipopolysaccharide (LPS) induce a classical activation of macrophages (M1), whereas IL-4 and IL-13 induce an alternative activation program in macrophages (M2). Reprogramming of intracellular metabolisms is required for the proper polarization and functions of activated macrophages. Similar to the Warburg effect observed in tumor cells, M1 macrophages increase glucose consumption and lactate release and decreased oxygen consumption rate. In comparison, M2 macrophages mainly employ oxidative glucose metabolism pathways. In addition, fatty acids, vitamins, and iron metabolisms are also related to macrophage polarization. However, detailed metabolic pathways involved in macrophages have remained elusive. Understanding the bidirectional interactions between cellular metabolism and macrophage functions in physiological and pathological situations and the regulatory pathways involved may offer novel therapies for macrophage-associated diseases.

  10. The use of a battery of tracking tests in the quantitative evaluation of neurological function

    NASA Technical Reports Server (NTRS)

    Repa, B. S.; Albers, J. W.; Potvin, A. R.; Tourtellotte, W. W.

    1972-01-01

    A tracking test battery has been applied in a drug trail designed to compare the efficacy of L-DOPA and amantadine to that of L-DOPA and placebo in the treatment of 28 patients with Parkinson's disease. The drug trial provided an ideal opportunity for objectively evaluating the usefulness of tracking tests in assessing changes in neurologic function. Evaluating changes in patient performance resulting from disease progression and controlled clinical trials is of great importance in establishing effective treatment programs.

  11. Atorvastatin activates autophagy and promotes neurological function recovery after spinal cord injury.

    PubMed

    Gao, Shuang; Zhang, Zhong-Ming; Shen, Zhao-Liang; Gao, Kai; Chang, Liang; Guo, Yue; Li, Zhuo; Wang, Wei; Wang, Ai-Mei

    2016-06-01

    Atorvastatin, a lipid-lowering medication, provides neuroprotective effects, although the precise mechanisms of action remain unclear. Our previous studies confirmed activated autophagy following spinal cord injury, which was conducive to recovery of neurological functions. We hypothesized that atorvastatin could also activate autophagy after spinal cord injury, and subsequently improve recovery of neurological functions. A rat model of spinal cord injury was established based on the Allen method. Atorvastatin (5 mg/kg) was intraperitoneally injected at 1 and 2 days after spinal cord injury. At 7 days post-injury, western blot assay, reverse transcription-polymerase chain reaction, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining results showed increased Beclin-1 and light chain 3B gene and protein expressions in the spinal cord injury + atorvastatin group. Additionally, caspase-9 and caspase-3 expression was decreased, and the number of TUNEL-positive cells was reduced. Compared with the spinal cord injury + saline group, Basso, Beattie, and Bresnahan locomotor rating scale scores significantly increased in the spinal cord injury + atorvastatin group at 14-42 days post-injury. These findings suggest that atorvastatin activated autophagy after spinal cord injury, inhibited apoptosis, and promoted recovery of neurological function. PMID:27482228

  12. Anti-VEGF treatment improves neurological function and augments radiation response in NF2 schwannoma model.

    PubMed

    Gao, Xing; Zhao, Yingchao; Stemmer-Rachamimov, Anat O; Liu, Hao; Huang, Peigen; Chin, ShanMin; Selig, Martin K; Plotkin, Scott R; Jain, Rakesh K; Xu, Lei

    2015-11-24

    Hearing loss is the main limitation of radiation therapy for vestibular schwannoma (VS), and identifying treatment options that minimize hearing loss are urgently needed. Treatment with bevacizumab is associated with tumor control and hearing improvement in neurofibromatosis type 2 (NF2) patients; however, its effect is not durable and its mechanism of action on nerve function is unknown. We modeled the effect anti-VEGF therapy on neurological function in the sciatic nerve model and found that it improves neurological function by alleviating tumor edema, which may further improve results by decreasing muscle atrophy and increasing nerve regeneration. Using a cranial window model, we showed that anti-VEGF treatment may achieve these effects via normalizing the tumor vasculature, improving vessel perfusion, and delivery of oxygenation. It is known that oxygen is a potent radiosensitizer; therefore, we further demonstrated that combining anti-VEGF with radiation therapy can achieve a better tumor control and help lower the radiation dose and, thus, minimize radiation-related neurological toxicity. Our results provide compelling rationale for testing combined therapy in human VS. PMID:26554010

  13. Vasoactive intestinal peptide administration after stroke in rats enhances neurogenesis and improves neurological function.

    PubMed

    Yang, Jie; Shi, Qing-Dong; Yang, Yuan-Bo; Qian, Yi-Hua; Feng, Gai-Feng; Chang, Ling; Zong, Chang-Hong

    2015-11-01

    The aim of this study was to investigate the effects of vasoactive intestinal peptide (VIP) on neurogenesis and neurological function after cerebral ischemia. Rats were intracerebroventricular administered with VIP after a 2h middle cerebral artery occlusion (MCAO) and sacrificed at 7, 14 and 28 days after MCAO. Functional outcome was studied with the modified neurological severity score. The infarct volume was evaluated via histology. Neurogenesis, angiogenesis and the protein expression of vascular endothelial growth factor (VEGF) were measured by immunohistochemistry and Western blotting analysis, respectively. The treatment with VIP significantly reduced the neurological severity score and the infarc volume, and increased the numbers of bromodeoxyuridine (BrdU) immunoreactive cells and doublecortin immunoreactive area in the subventricular zone (SVZ) at 7, 14 and 28 days after ischemia. The cerebral protein levels of VEGF and VEGF expression in the SVZ were also enhanced in VIP-treated rats at 7 days after stroke. VIP treatment obviously increased the number of BrdU positive endothelial cells in the SVZ and density of cerebral microvessels in the ischemic boundary at 28 days after ischemia. Our study suggests that in the ischemic rat brain VIP reduces brain damage and promotes neurogenesis by increasing VEGF. VIP-enhanced neurogenesis is associated with angiogenesis. These changes may contribute to improvement in functional outcome.

  14. Atorvastatin activates autophagy and promotes neurological function recovery after spinal cord injury

    PubMed Central

    Gao, Shuang; Zhang, Zhong-ming; Shen, Zhao-liang; Gao, Kai; Chang, Liang; Guo, Yue; Li, Zhuo; Wang, Wei; Wang, Ai-mei

    2016-01-01

    Atorvastatin, a lipid-lowering medication, provides neuroprotective effects, although the precise mechanisms of action remain unclear. Our previous studies confirmed activated autophagy following spinal cord injury, which was conducive to recovery of neurological functions. We hypothesized that atorvastatin could also activate autophagy after spinal cord injury, and subsequently improve recovery of neurological functions. A rat model of spinal cord injury was established based on the Allen method. Atorvastatin (5 mg/kg) was intraperitoneally injected at 1 and 2 days after spinal cord injury. At 7 days post-injury, western blot assay, reverse transcription-polymerase chain reaction, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining results showed increased Beclin-1 and light chain 3B gene and protein expressions in the spinal cord injury + atorvastatin group. Additionally, caspase-9 and caspase-3 expression was decreased, and the number of TUNEL-positive cells was reduced. Compared with the spinal cord injury + saline group, Basso, Beattie, and Bresnahan locomotor rating scale scores significantly increased in the spinal cord injury + atorvastatin group at 14–42 days post-injury. These findings suggest that atorvastatin activated autophagy after spinal cord injury, inhibited apoptosis, and promoted recovery of neurological function. PMID:27482228

  15. Atorvastatin activates autophagy and promotes neurological function recovery after spinal cord injury.

    PubMed

    Gao, Shuang; Zhang, Zhong-Ming; Shen, Zhao-Liang; Gao, Kai; Chang, Liang; Guo, Yue; Li, Zhuo; Wang, Wei; Wang, Ai-Mei

    2016-06-01

    Atorvastatin, a lipid-lowering medication, provides neuroprotective effects, although the precise mechanisms of action remain unclear. Our previous studies confirmed activated autophagy following spinal cord injury, which was conducive to recovery of neurological functions. We hypothesized that atorvastatin could also activate autophagy after spinal cord injury, and subsequently improve recovery of neurological functions. A rat model of spinal cord injury was established based on the Allen method. Atorvastatin (5 mg/kg) was intraperitoneally injected at 1 and 2 days after spinal cord injury. At 7 days post-injury, western blot assay, reverse transcription-polymerase chain reaction, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining results showed increased Beclin-1 and light chain 3B gene and protein expressions in the spinal cord injury + atorvastatin group. Additionally, caspase-9 and caspase-3 expression was decreased, and the number of TUNEL-positive cells was reduced. Compared with the spinal cord injury + saline group, Basso, Beattie, and Bresnahan locomotor rating scale scores significantly increased in the spinal cord injury + atorvastatin group at 14-42 days post-injury. These findings suggest that atorvastatin activated autophagy after spinal cord injury, inhibited apoptosis, and promoted recovery of neurological function.

  16. Anti-VEGF treatment improves neurological function and augments radiation response in NF2 schwannoma model

    PubMed Central

    Gao, Xing; Zhao, Yingchao; Stemmer-Rachamimov, Anat O.; Liu, Hao; Huang, Peigen; Chin, ShanMin; Selig, Martin K.; Plotkin, Scott R.; Jain, Rakesh K.; Xu, Lei

    2015-01-01

    Hearing loss is the main limitation of radiation therapy for vestibular schwannoma (VS), and identifying treatment options that minimize hearing loss are urgently needed. Treatment with bevacizumab is associated with tumor control and hearing improvement in neurofibromatosis type 2 (NF2) patients; however, its effect is not durable and its mechanism of action on nerve function is unknown. We modeled the effect anti-VEGF therapy on neurological function in the sciatic nerve model and found that it improves neurological function by alleviating tumor edema, which may further improve results by decreasing muscle atrophy and increasing nerve regeneration. Using a cranial window model, we showed that anti-VEGF treatment may achieve these effects via normalizing the tumor vasculature, improving vessel perfusion, and delivery of oxygenation. It is known that oxygen is a potent radiosensitizer; therefore, we further demonstrated that combining anti-VEGF with radiation therapy can achieve a better tumor control and help lower the radiation dose and, thus, minimize radiation-related neurological toxicity. Our results provide compelling rationale for testing combined therapy in human VS. PMID:26554010

  17. Neurologic development of the newborn and young child in relation to maternal thyroid function.

    PubMed

    Smit, B J; Kok, J H; Vulsma, T; Briët, J M; Boer, K; Wiersinga, W M

    2000-03-01

    A prospective observational study was performed in pregnant women with known thyroid disease. We studied the effect of maternal thyroid function in the first half of pregnancy on the neurologic development of the infant in the first 2 y of life. Clinical and thyroid function data were collected from 20 pregnant women with known thyroid disease and their newborn children. Infants were divided into three groups according to their maternal thyroid function within the first half of pregnancy: Group A (n = 7): maternal subclinical hypothyroidism, Group B (n = 6): maternal euthyroidism, and Group C (n = 7): maternal hyperthyroidism or subclinical hyperthyroidism. Neurophysiologic, i.e. motor nerve conduction velocity and somatosensory evoked potentials and neurologic and developmental (Bayley scales) assessments were done. One infant, born to a mother with Graves' disease, developed transient hyperthyroidism. At the age of 6 and 12 mo, the mean mental developmental index (MDI) score was 16 points lower for infants in Group A than for those in Group B (p = 0.03 and 0.02, respectively). At the age of 24 mo, the mean MDI score was 6 points lower, which was not statistically significant. Neurophysiologic and neurologic assessments and the mean Psychomotor Developmental scores did not differ among the three groups. In conclusion, maternal subclinical hypothyroidism in the first half of pregnancy was associated with a lower mean MDI score in their infants during the first year of life.

  18. Cognitive-analytical therapy for a patient with functional neurological symptom disorder-conversion disorder (psychogenic myopia): A case study.

    PubMed

    Nasiri, Hamid; Ebrahimi, Amrollah; Zahed, Arash; Arab, Mostafa; Samouei, Rahele

    2015-05-01

    Functional neurological symptom disorder commonly presents with symptoms and defects of sensory and motor functions. Therefore, it is often mistaken for a medical condition. It is well known that functional neurological symptom disorder more often caused by psychological factors. There are three main approaches namely analytical, cognitive and biological to manage conversion disorder. Any of such approaches can be applied through short-term treatment programs. In this case, study a 12-year-old boy with the diagnosed functional neurological symptom disorder (psychogenic myopia) was put under a cognitive-analytical treatment. The outcome of this treatment modality was proved successful.

  19. Cognitive-analytical therapy for a patient with functional neurological symptom disorder-conversion disorder (psychogenic myopia): A case study

    PubMed Central

    Nasiri, Hamid; Ebrahimi, Amrollah; Zahed, Arash; Arab, Mostafa; Samouei, Rahele

    2015-01-01

    Functional neurological symptom disorder commonly presents with symptoms and defects of sensory and motor functions. Therefore, it is often mistaken for a medical condition. It is well known that functional neurological symptom disorder more often caused by psychological factors. There are three main approaches namely analytical, cognitive and biological to manage conversion disorder. Any of such approaches can be applied through short-term treatment programs. In this case, study a 12-year-old boy with the diagnosed functional neurological symptom disorder (psychogenic myopia) was put under a cognitive-analytical treatment. The outcome of this treatment modality was proved successful. PMID:26487881

  20. Abnormal Brain Iron Metabolism in Irp2 Deficient Mice Is Associated with Mild Neurological and Behavioral Impairments

    PubMed Central

    Zumbrennen-Bullough, Kimberly B.; Becker, Lore; Garrett, Lillian; Hölter, Sabine M.; Calzada-Wack, Julia; Mossbrugger, Ilona; Quintanilla-Fend, Leticia; Racz, Ildiko; Rathkolb, Birgit; Klopstock, Thomas; Wurst, Wolfgang; Zimmer, Andreas; Wolf, Eckhard; Fuchs, Helmut; Gailus-Durner, Valerie; de Angelis, Martin Hrabě; Romney, Steven J.; Leibold, Elizabeth A.

    2014-01-01

    Iron Regulatory Protein 2 (Irp2, Ireb2) is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism. While both mouse models show that loss of Irp2 results in microcytic anemia and altered body iron distribution, discrepant results have drawn into question the role of Irp2 in regulating brain iron metabolism. One model shows that aged Irp2 deficient mice develop adult-onset progressive neurodegeneration that is associated with axonal degeneration and loss of Purkinje cells in the central nervous system. These mice show iron deposition in white matter tracts and oligodendrocyte soma throughout the brain. A contrasting model of global Irp2 deficiency shows no overt or pathological signs of neurodegeneration or brain iron accumulation, and display only mild motor coordination and balance deficits when challenged by specific tests. Explanations for conflicting findings in the severity of the clinical phenotype, brain iron accumulation and neuronal degeneration remain unclear. Here, we describe an additional mouse model of global Irp2 deficiency. Our aged Irp2−/− mice show marked iron deposition in white matter and in oligodendrocytes while iron content is significantly reduced in neurons. Ferritin and transferrin receptor 1 (TfR1, Tfrc), expression are increased and decreased, respectively, in the brain from Irp2−/− mice. These mice show impairments in locomotion, exploration, motor coordination/balance and nociception when assessed by neurological and behavioral tests, but lack overt signs of neurodegenerative disease. Ultrastructural studies of specific brain regions show no evidence of neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron metabolism causing cellular dysfunction that ultimately leads to mild neurological, behavioral and nociceptive impairments. PMID:24896637

  1. Abnormal brain iron metabolism in Irp2 deficient mice is associated with mild neurological and behavioral impairments.

    PubMed

    Zumbrennen-Bullough, Kimberly B; Becker, Lore; Garrett, Lillian; Hölter, Sabine M; Calzada-Wack, Julia; Mossbrugger, Ilona; Quintanilla-Fend, Leticia; Racz, Ildiko; Rathkolb, Birgit; Klopstock, Thomas; Wurst, Wolfgang; Zimmer, Andreas; Wolf, Eckhard; Fuchs, Helmut; Gailus-Durner, Valerie; de Angelis, Martin Hrabě; Romney, Steven J; Leibold, Elizabeth A

    2014-01-01

    Iron Regulatory Protein 2 (Irp2, Ireb2) is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism. While both mouse models show that loss of Irp2 results in microcytic anemia and altered body iron distribution, discrepant results have drawn into question the role of Irp2 in regulating brain iron metabolism. One model shows that aged Irp2 deficient mice develop adult-onset progressive neurodegeneration that is associated with axonal degeneration and loss of Purkinje cells in the central nervous system. These mice show iron deposition in white matter tracts and oligodendrocyte soma throughout the brain. A contrasting model of global Irp2 deficiency shows no overt or pathological signs of neurodegeneration or brain iron accumulation, and display only mild motor coordination and balance deficits when challenged by specific tests. Explanations for conflicting findings in the severity of the clinical phenotype, brain iron accumulation and neuronal degeneration remain unclear. Here, we describe an additional mouse model of global Irp2 deficiency. Our aged Irp2-/- mice show marked iron deposition in white matter and in oligodendrocytes while iron content is significantly reduced in neurons. Ferritin and transferrin receptor 1 (TfR1, Tfrc), expression are increased and decreased, respectively, in the brain from Irp2-/- mice. These mice show impairments in locomotion, exploration, motor coordination/balance and nociception when assessed by neurological and behavioral tests, but lack overt signs of neurodegenerative disease. Ultrastructural studies of specific brain regions show no evidence of neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron metabolism causing cellular dysfunction that ultimately leads to mild neurological, behavioral and nociceptive impairments.

  2. Soft Neurological Signs and Cognitive Function in Obsessive-compulsive Disorder Patients

    PubMed Central

    Dhuri, Chetali Vijay; Parkar, Shubhangi R.

    2016-01-01

    Objective: Modern research on obsessive-compulsive disorder (OCD) indicates that the primary cause of OCD, which was earlier explained only on basis of psychoanalytical theories, is biological. Our study attempts to investigate the neurobiological signs in form of soft neurological signs and cognitive function in OCD. Methods: A cross sectional study was conducted at psychiatric facility of Seth G.S. Medical College and KEM Hospital. Materials and Method: 50 OCD patients and age- and education-matched controls were selected for the study. Established instruments were used to assess the neurological soft signs (NSS) and the cognitive deficits. Results: OCD patients had significant more NSS in tests for motor coordination, sensory integration, complex motor tasks, hard signs, and right/left and spatial orientation. Cognitive deficits in the domains of visuospatial ability, executive function, attention, and working memory were significantly more in OCD patients compared to controls. Conclusion: Our study highlights the role of biological factors in form of soft neurological signs and cognitive dysfunction in the development of the OCD. PMID:27570338

  3. An unusual neurological disorder of copper metabolism clinically resembling Wilson's disease but biochemically a distinct entity.

    PubMed

    Godwin-Austen, R B; Robinson, A; Evans, K; Lascelles, P T

    1978-11-01

    A patient with progressive neurological disease resembling Wilson's disease but in whom Kayser-Fleischer rings were absent, was given 67Cu and 64Cu, orally and intravenously, to measure the rate of absorption of copper using a convolution integral. The data show an abnormal distribution of body copper resulting in low copper concentrations in plasma, urine and liver but with an accumulation in the lower bowel probably due to a defect in mucosal transport. The importance of differentiating this condition from Wilson's disease is stressed.

  4. Sphingosine 1-phosphate in blood: function, metabolism, and fate.

    PubMed

    Thuy, Andreas V; Reimann, Christina-Maria; Hemdan, Nasr Y A; Gräler, Markus H

    2014-01-01

    Sphingosine 1-phosphate (S1P) is a lipid metabolite and a ligand of five G protein-coupled cell surface receptors S1PR1 to S1PR5. These receptors are expressed on various cells and cell types of the immune, cardiovascular, respiratory, hepatic, reproductive, and neurologic systems, and S1P has an impact on many different pathophysiological conditions including autoimmune, cardiovascular, and neurodegenerative diseases, cancer, deafness, osteogenesis, and reproduction. While these diverse signalling properties of S1P have been extensively reviewed, the particular role of S1P in blood is still a matter of debate. Blood contains the highest S1P concentration of all body compartments, and several questions are still not sufficiently answered: Where does it come from and how is it metabolized? Why is the concentration of S1P in blood so high? Are minor changes of the high blood S1P concentrations physiologically relevant? Do blood cells and vascular endothelial cells that are constantly exposed to high blood S1P levels still respond to S1P via S1P receptors? Recent data reveal new insights into the functional role and the metabolic fate of blood-borne S1P. This review aims to summarize our current knowledge regarding the source, secretion, transportation, function, metabolism, and fate of S1P in blood. PMID:24977489

  5. Neurological, Metabolic, and Psychiatric Adverse Events in Children and Adolescents Treated With Aripiprazole.

    PubMed

    Jakobsen, Klaus Damgaard; Bruhn, Christina Hedegaard; Pagsberg, Anne-Katrine; Fink-Jensen, Anders; Nielsen, Jimmi

    2016-10-01

    Aripiprazole is a partial dopamine agonist with only minor neurological and psychiatric adverse effects, making it a potential first-line drug for the treatment of psychiatric disorders. However, the evidence of its use in children and adolescents is rather sparse. The aim of this case study is to discuss adverse drug reaction (ADR) reports concerning aripiprazole-associated neurological and psychiatric events in children and adolescents. The ADR report database at Danish Medicines Agency was searched for all ADRs involving children and adolescents (<18 years) reported by the search term [aripiprazole] AND all spontaneous reports since the introduction of aripiprazole in 2003 until December 31, 2015. Nineteen case reports were included in the study and included both patients with psychotic disorders (PS group) and nonpsychotic disorders (non-PS group). The PS group consisted of 5 patients with schizophrenia and psychoses, not otherwise specified; and the non-PS group consisted of fourteen cases including autism spectrum disorders, attention deficit and hyperactivity disorder, obsessive-compulsive disorder, and Tourette syndrome. The main reported adverse effects in the non-PS group were chronic insomnia, Parkinsonism, behavioral changes psychoses, and weight gain, whereas the adverse effects in the PS group was predominantly anxiety, convulsions, and neuroleptic malignant syndrome. Although aripiprazole is considered safe and well tolerated in children and adolescents, severe adverse events as neuroleptic malignant syndrome, extreme insomnia, and suicidal behavior has been reported to health authorities. Clinicians should pay attention to these possible hazards when prescribing aripiprazole to this vulnerable group of patients. PMID:27504593

  6. Psychologic and neurologic function following treatment for childhood temporal lobe astrocytoma.

    PubMed

    Mulhern, R K; Kovnar, E H; Kun, L E; Crisco, J J; Williams, J M

    1988-01-01

    Seven school-aged children treated for temporal lobe astrocytomas with surgical resection and irradiation were prospectively tested to evaluate their intellectual, academic, personality, and neurologic status after therapy. At their most recent follow-up examination, neuropsychologic functioning was adequate in only two patients. The other five children manifested either intellectual deterioration, learning disability, mental retardation, or psychopathology. These deficits were associated with poor postoperative performance status, inadequate seizure control, tumor recurrence, and younger age at diagnosis. No pattern of intellectual, academic, or personality dysfunction emerged in association with left- versus right-hemisphere tumors.

  7. The use of a tracking test battery in the quantitative evaluation of neurological function

    NASA Technical Reports Server (NTRS)

    Repa, B. S.

    1973-01-01

    A number of tracking tasks that have proven useful to control engineers and psychologists measuring skilled performance have been evaluated for clinical use. Normal subjects as well as patients with previous diagnoses of Parkinson's disease, multiple sclerosis, and cerebral palsy were used in the evaluation. The tests that were studied included step tracking, random tracking, and critical tracking. The results of the present experiments encourage the continued use of tracking tasks as assessment precedures in a clinical environment. They have proven to be reliable, valid, and sensitive measures of neurological function.

  8. Circadian Clock Control of Liver Metabolic Functions.

    PubMed

    Reinke, Hans; Asher, Gad

    2016-03-01

    The circadian clock is an endogenous biological timekeeping system that synchronizes physiology and behavior to day/night cycles. A wide variety of processes throughout the entire gastrointestinal tract and notably the liver appear to be under circadian control. These include various metabolic functions such as nutrient uptake, processing, and detoxification, which align organ function to cycle with nutrient supply and demand. Remarkably, genetic or environmental disruption of the circadian clock can cause metabolic diseases or exacerbate pathological states. In addition, modern lifestyles force more and more people worldwide into asynchrony between the external time and their circadian clock, resulting in a constant state of social jetlag. Recent evidence indicates that interactions between altered energy metabolism and disruptions in the circadian clock create a downward spiral that can lead to diabetes and other metabolic diseases. In this review, we provide an overview of rhythmic processes in the liver and highlight the functions of circadian clock genes under physiological and pathological conditions; we focus on their roles in regulation of hepatic glucose as well as lipid and bile acid metabolism and detoxification and their potential effects on the development of fatty liver and nonalcoholic steatohepatitis.

  9. Neurologic music therapy improves executive function and emotional adjustment in traumatic brain injury rehabilitation.

    PubMed

    Thaut, Michael H; Gardiner, James C; Holmberg, Dawn; Horwitz, Javan; Kent, Luanne; Andrews, Garrett; Donelan, Beth; McIntosh, Gerald R

    2009-07-01

    This study examined the immediate effects of neurologic music therapy (NMT) on cognitive functioning and emotional adjustment with brain-injured persons. Four treatment sessions were held, during which participants were given a pre-test, participated in 30 min of NMT that focused on one aspect of rehabilitation (attention, memory, executive function, or emotional adjustment), which was followed by post-testing. Control participants engaged in a pre-test, 30 min of rest, and then a post-test. Treatment participants showed improvement in executive function and overall emotional adjustment, and lessening of depression, sensation seeking, and anxiety. Control participants improved in emotional adjustment and lessening of hostility, but showed decreases in measures of memory, positive affect, and sensation seeking.

  10. Neurological channelopathies

    PubMed Central

    Graves, T; Hanna, M

    2005-01-01

    Ion channels are membrane-bound proteins that perform key functions in virtually all human cells. Such channels are critically important for the normal function of the excitable tissues of the nervous system, such as muscle and brain. Until relatively recently it was considered that dysfunction of ion channels in the nervous system would be incompatible with life. However, an increasing number of human diseases associated with dysfunctional ion channels are now recognised. Such neurological channelopathies are frequently genetically determined but may also arise through autoimmune mechanisms. In this article clinical, genetic, immunological, and electrophysiological aspects of this expanding group of neurological disorders are reviewed. Clinical situations in which a neurological channelopathy should enter into the differential diagnosis are highlighted. Some practical guidance on how to investigate and treat this complex group of disorders is also included. PMID:15640425

  11. Metabolic hormones in saliva: origins and functions

    PubMed Central

    Zolotukhin, S.

    2012-01-01

    The salivary proteome consists of thousands of proteins, which include, among others, hormonal modulators of energy intake and output. Although the functions of this prominent category of hormones in whole body energy metabolism are well characterized, their functions in the oral cavity, whether as a salivary component, or when expressed in taste cells, are less studied and poorly understood. The respective receptors for the majority of salivary metabolic hormones have been also shown to be expressed in salivary glands, taste cells, or other cells in the oral mucosa. This review provides a comprehensive account of the gastrointestinal hormones, adipokines, and neuropeptides identified in saliva, salivary glands, or lingual epithelium, as well as their respective cognate receptors expressed in the oral cavity. Surprisingly, few functions are assigned to salivary metabolic hormones, and these functions are mostly associated with the modulation of taste perception. Because of the well-characterized correlation between impaired oral nutrient sensing and increased energy intake and body mass index, a conceptually provocative point of view is introduced, whereupon it is argued that targeted changes in the composition of saliva could affect whole body metabolism in response to the activation of cognate receptors expressed locally in the oral mucosa. PMID:22994880

  12. The use of neuropsychological data to detect altered neurological functioning in a child with myelomeningocele.

    PubMed

    Williams, J; Ashcraft, E W

    1993-12-01

    Although children with myelomeningocele often display atypical patterns on psychometric testing, this case study demonstrates the sensitivity of neuropsychological instruments to detect altered neurological functioning in a patient with spina bifida. The subject had a history of myelomeningocele at the lumbosacral level and placement of a ventriculoperitoneal shunt. During a routine neuropsychological evaluation, a 44-point discrepancy between his verbal (verbal IQ = 98) and nonverbal abilities (performance IQ = 54) on the Wechsler Intelligence for Children-Revised was found. In comparison to high average academic achievement, test findings suggested depressed memory skills and extreme slowing in psychomotor speed. A pattern of acute decline in overall cognitive functioning was suggested. Magnetic resonance imaging revealed a left frontoparietal brain mass, which was surgically removed. Follow-up neuropsychological testing 9 months postsurgery indicated an increase in nonverbal intelligence with improved psychomotor speed and information processing. This case study illustrates the importance of obtaining baseline evaluations in this neurologically high-risk population as well as the clinical usefulness of psychometric data in diagnostic workups. PMID:8126234

  13. Effects of underwater sound exposure on neurological function and brain histology.

    PubMed

    Laurer, Helmut L; Ritting, Andrew N; Russ, Andrew B; Bareyre, Florence M; Raghupathi, Ramesh; Saatman, Kathryn E

    2002-07-01

    To evaluate the safety of sonar exposure from a neurological perspective, the vulnerability of the central nervous system to underwater exposure with high-intensity, low-frequency sound (HI-LFS) was experimentally examined. Physiological, behavioral and histological parameters were measured in anesthetized, ventilated rats exposed to brief (5 min), underwater HI-LFS. Exposure to 180 dB sound pressure level (SPL) re 1 microPa at 150 Hz (n = 9) did not alter acute cardiovascular physiology (arterial blood pH, pO(2), pCO(2), heart rate, or mean arterial blood pressure) from that found in controls (n = 11). Rats exposed to either 180 dB SPL re 1 microPa at 150 Hz (n = 12) or 194 dB SPL re 1 microPa at 250 Hz (n = 12) exhibited normal cognitive function at 8 and 9 days after sound exposure. Evaluation of neurological motor function revealed a minor deficit 7 days after 180 dB SPL/150 Hz exposure that resolved by 14 days, and no deficits after 194 dB SPL/250 Hz exposure. No overt histological damage was detected in any group. These data suggest that underwater HI-LFS exposure may cause transient, mild motor dysfunction.

  14. On Functional Module Detection in Metabolic Networks

    PubMed Central

    Koch, Ina; Ackermann, Jörg

    2013-01-01

    Functional modules of metabolic networks are essential for understanding the metabolism of an organism as a whole. With the vast amount of experimental data and the construction of complex and large-scale, often genome-wide, models, the computer-aided identification of functional modules becomes more and more important. Since steady states play a key role in biology, many methods have been developed in that context, for example, elementary flux modes, extreme pathways, transition invariants and place invariants. Metabolic networks can be studied also from the point of view of graph theory, and algorithms for graph decomposition have been applied for the identification of functional modules. A prominent and currently intensively discussed field of methods in graph theory addresses the Q-modularity. In this paper, we recall known concepts of module detection based on the steady-state assumption, focusing on transition-invariants (elementary modes) and their computation as minimal solutions of systems of Diophantine equations. We present the Fourier-Motzkin algorithm in detail. Afterwards, we introduce the Q-modularity as an example for a useful non-steady-state method and its application to metabolic networks. To illustrate and discuss the concepts of invariants and Q-modularity, we apply a part of the central carbon metabolism in potato tubers (Solanum tuberosum) as running example. The intention of the paper is to give a compact presentation of known steady-state concepts from a graph-theoretical viewpoint in the context of network decomposition and reduction and to introduce the application of Q-modularity to metabolic Petri net models. PMID:24958145

  15. On functional module detection in metabolic networks.

    PubMed

    Koch, Ina; Ackermann, Jörg

    2013-08-12

    Functional modules of metabolic networks are essential for understanding the metabolism of an organism as a whole. With the vast amount of experimental data and the construction of complex and large-scale, often genome-wide, models, the computer-aided identification of functional modules becomes more and more important. Since steady states play a key role in biology, many methods have been developed in that context, for example, elementary flux modes, extreme pathways, transition invariants and place invariants. Metabolic networks can be studied also from the point of view of graph theory, and algorithms for graph decomposition have been applied for the identification of functional modules. A prominent and currently intensively discussed field of methods in graph theory addresses the Q-modularity. In this paper, we recall known concepts of module detection based on the steady-state assumption, focusing on transition-invariants (elementary modes) and their computation as minimal solutions of systems of Diophantine equations. We present the Fourier-Motzkin algorithm in detail. Afterwards, we introduce the Q-modularity as an example for a useful non-steady-state method and its application to metabolic networks. To illustrate and discuss the concepts of invariants and Q-modularity, we apply a part of the central carbon metabolism in potato tubers (Solanum tuberosum) as running example. The intention of the paper is to give a compact presentation of known steady-state concepts from a graph-theoretical viewpoint in the context of network decomposition and reduction and to introduce the application of Q-modularity to metabolic Petri net models.

  16. On functional module detection in metabolic networks.

    PubMed

    Koch, Ina; Ackermann, Jörg

    2013-01-01

    Functional modules of metabolic networks are essential for understanding the metabolism of an organism as a whole. With the vast amount of experimental data and the construction of complex and large-scale, often genome-wide, models, the computer-aided identification of functional modules becomes more and more important. Since steady states play a key role in biology, many methods have been developed in that context, for example, elementary flux modes, extreme pathways, transition invariants and place invariants. Metabolic networks can be studied also from the point of view of graph theory, and algorithms for graph decomposition have been applied for the identification of functional modules. A prominent and currently intensively discussed field of methods in graph theory addresses the Q-modularity. In this paper, we recall known concepts of module detection based on the steady-state assumption, focusing on transition-invariants (elementary modes) and their computation as minimal solutions of systems of Diophantine equations. We present the Fourier-Motzkin algorithm in detail. Afterwards, we introduce the Q-modularity as an example for a useful non-steady-state method and its application to metabolic networks. To illustrate and discuss the concepts of invariants and Q-modularity, we apply a part of the central carbon metabolism in potato tubers (Solanum tuberosum) as running example. The intention of the paper is to give a compact presentation of known steady-state concepts from a graph-theoretical viewpoint in the context of network decomposition and reduction and to introduce the application of Q-modularity to metabolic Petri net models. PMID:24958145

  17. Altered white matter metabolism in delayed neurologic sequelae after carbon monoxide poisoning: A proton magnetic resonance spectroscopic study.

    PubMed

    Kuroda, Hiroshi; Fujihara, Kazuo; Mugikura, Shunji; Takahashi, Shoki; Kushimoto, Shigeki; Aoki, Masashi

    2016-01-15

    Proton magnetic resonance spectroscopy ((1)H-MRS) was recently used to examine altered metabolism in the white matter (WM) of patients experiencing carbon monoxide (CO) poisoning; however, only a small number of patients with delayed neurologic sequelae (DNS) were analyzed. We aimed to detect altered metabolism in the WM of patients with DNS using (1)H-MRS; to explore its clinical relevance in the management of patients experiencing CO poisoning. Patients experiencing acute CO poisoning underwent (1)H-MRS and cerebrospinal fluid (CSF) examination within 1week and at 1month after acute poisoning. Metabolites including choline-containing compounds (Cho), creatine (Cr), N-acetylaspartate (NAA), and lactate were measured from the periventricular WM. Myelin basic protein (MBP) concentrations were measured in CSF. Fifty-two patients experiencing acute CO poisoning (15 with DNS, 37 without DNS; median age, 49years; 65% males) underwent (1)H-MRS. Within 1week, NAA/Cr ratios, reflecting neuroaxonal viability, were lower in patients with DNS than in those without DNS (P<0.05). At 1month, when 9 of 15 patients (60%) developed DNS, Cho/Cr ratios were higher, and NAA/Cr and NAA/Cho ratios lower in patients with DNS (P=0.0001, <0.0001, and <0.0001, respectively), indicating increased membrane metabolism and decreased neuroaxonal viability. (1)H-MRS parameter abnormalities correlated with the elevation of MBP in CSF. The presence of a lactate peak was a predictor for a poor long-term outcome. (1)H-MRS within 1week may be useful for predicting DNS development; (1)H-MRS at 1month may be useful for discriminating patients with DNS and predicting long-term outcomes.

  18. Altered white matter metabolism in delayed neurologic sequelae after carbon monoxide poisoning: A proton magnetic resonance spectroscopic study.

    PubMed

    Kuroda, Hiroshi; Fujihara, Kazuo; Mugikura, Shunji; Takahashi, Shoki; Kushimoto, Shigeki; Aoki, Masashi

    2016-01-15

    Proton magnetic resonance spectroscopy ((1)H-MRS) was recently used to examine altered metabolism in the white matter (WM) of patients experiencing carbon monoxide (CO) poisoning; however, only a small number of patients with delayed neurologic sequelae (DNS) were analyzed. We aimed to detect altered metabolism in the WM of patients with DNS using (1)H-MRS; to explore its clinical relevance in the management of patients experiencing CO poisoning. Patients experiencing acute CO poisoning underwent (1)H-MRS and cerebrospinal fluid (CSF) examination within 1week and at 1month after acute poisoning. Metabolites including choline-containing compounds (Cho), creatine (Cr), N-acetylaspartate (NAA), and lactate were measured from the periventricular WM. Myelin basic protein (MBP) concentrations were measured in CSF. Fifty-two patients experiencing acute CO poisoning (15 with DNS, 37 without DNS; median age, 49years; 65% males) underwent (1)H-MRS. Within 1week, NAA/Cr ratios, reflecting neuroaxonal viability, were lower in patients with DNS than in those without DNS (P<0.05). At 1month, when 9 of 15 patients (60%) developed DNS, Cho/Cr ratios were higher, and NAA/Cr and NAA/Cho ratios lower in patients with DNS (P=0.0001, <0.0001, and <0.0001, respectively), indicating increased membrane metabolism and decreased neuroaxonal viability. (1)H-MRS parameter abnormalities correlated with the elevation of MBP in CSF. The presence of a lactate peak was a predictor for a poor long-term outcome. (1)H-MRS within 1week may be useful for predicting DNS development; (1)H-MRS at 1month may be useful for discriminating patients with DNS and predicting long-term outcomes. PMID:26723994

  19. Testosterone replacement in 49,XXXXY syndrome: andrological, metabolic and neurological aspects

    PubMed Central

    Delfino, Michele; Elia, Jlenia; Benedetti, Francesco; Alesi, Laura; Chessa, Luciana; Mazzilli, Fernando

    2015-01-01

    Summary We report the case of a 19-year-old boy, presenting several congenital malformations (facial dysmorphisms, cardiac and musculoskeletal abnormalities), mental retardation, recurrent respiratory infections during growth and delayed puberty. Although previously hospitalised in other medical centres, only psychological support had been recommended for this patient. In our department, genetic, biochemical/hormonal and ultrasound examinations were undertaken. The karyotype was 49,XXXXY, a rare aneuploidy with an incidence of 1/85 000–100 000, characterised by the presence of three extra X chromosomes in phenotypically male subjects. The hormonal/biochemical profile showed hypergonadotropic hypogonadism, insulin resistance and vitamin D deficiency. The patient was then treated with testosterone replacement therapy. After 12 months of treatment, we observed the normalisation of testosterone levels. There was also an increase in pubic hair growth, testicular volume and penis size, weight loss, homeostatic model assessment index reduction and the normalisation of vitamin D values. Moreover, the patient showed greater interaction with the social environment and context. Learning points In cases of plurimalformative syndrome, cognitive impairment, recurrent infections during growth and, primarily, delayed puberty, it is necessary to ascertain as soon as possible whether the patient is suffering from hypogonadism or metabolic disorders due to genetic causes. In our case, the diagnosis of hypogonadism, and then of 49,XXXXY syndrome, was unfortunately made only at the age of 19 years.The testosterone replacement treatment, even though delayed, induced positive effects on: i) development of the reproductive system, ii) regulation of the metabolic profile and iii) interaction with the social environment and context.However, earlier and timely hormonal replacement treatment could probably have improved the quality of life of this subject and his family. PMID:26767114

  20. Effects of youth football on selected clinical measures of neurologic function: a pilot study.

    PubMed

    Munce, Thayne A; Dorman, Jason C; Odney, Tryg O; Thompson, Paul A; Valentine, Verle D; Bergeron, Michael F

    2014-12-01

    We assessed 10 youth football players (13.4 ± 0.7 y) immediately before and after their season to explore the effects of football participation on selected clinical measures of neurologic function. Postseason postural stability in a closed-eye condition was improved compared to preseason (P = .017). Neurocognitive testing with the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) battery revealed that reaction time was significantly faster at postseason (P = .015). There were no significant preseason versus postseason differences in verbal memory (P = .507), visual memory (P = .750), or visual motor speed (P = .087). Oculomotor performance assessed by the King-Devick test was moderately to significantly improved (P = .047-.115). A 12-week season of youth football did not impair the postural stability, neurocognitive function, or oculomotor performance measures of the players evaluated. Though encouraging, continued and more comprehensive investigations of this at-risk population are warranted.

  1. Serine in plants: biosynthesis, metabolism, and functions.

    PubMed

    Ros, Roc; Muñoz-Bertomeu, Jesús; Krueger, Stephan

    2014-09-01

    Serine (Ser) has a fundamental role in metabolism and signaling in living organisms. In plants, the existence of different pathways of Ser biosynthesis has complicated our understanding of this amino acid homeostasis. The photorespiratory glycolate pathway has been considered to be of major importance, whereas the nonphotorespiratory phosphorylated pathway has been relatively neglected. Recent advances indicate that the phosphorylated pathway has an important function in plant metabolism and development. Plants deficient in this pathway display developmental defects in embryos, male gametophytes, and roots. We propose that the phosphorylated pathway is more important than was initially thought because it is the only Ser source for specific cell types involved in developmental events. Here, we discuss its importance as a link between metabolism and development in plants.

  2. Synchrotron-Generated Microbeam Sensorimotor Cortex Transections Induce Seizure Control without Disruption of Neurological Functions

    PubMed Central

    Romanelli, Pantaleo; Fardone, Erminia; Battaglia, Giuseppe; Bräuer-Krisch, Elke; Prezado, Yolanda; Requardt, Herwig; Le Duc, Geraldine; Nemoz, Christian; Anschel, David J.; Spiga, Jenny; Bravin, Alberto

    2013-01-01

    Synchrotron-generated X-ray microplanar beams (microbeams) are characterized by the ability to deliver extremely high doses of radiation to spatially restricted volumes of tissue. Minimal dose spreading outside the beam path provides an exceptional degree of protection from radio-induced damage to the neurons and glia adjacent to the microscopic slices of tissue irradiated. The preservation of cortical architecture following high-dose microbeam irradiation and the ability to induce non-invasively the equivalent of a surgical cut over the cortex is of great interest for the development of novel experimental models in neurobiology and new treatment avenues for a variety of brain disorders. Microbeams (size 100 µm/600 µm, center-to-center distance of 400 µm/1200 µm, peak entrance doses of 360-240 Gy/150-100 Gy) delivered to the sensorimotor cortex of six 2-month-old naïve rats generated histologically evident cortical transections, without modifying motor behavior and weight gain up to 7 months. Microbeam transections of the sensorimotor cortex dramatically reduced convulsive seizure duration in a further group of 12 rats receiving local infusion of kainic acid. No subsequent neurological deficit was associated with the treatment. These data provide a novel tool to study the functions of the cortex and pave the way for the development of new therapeutic strategies for epilepsy and other neurological diseases. PMID:23341950

  3. Functional Neurons Generated from T Cell-Derived Induced Pluripotent Stem Cells for Neurological Disease Modeling

    PubMed Central

    Matsumoto, Takuya; Fujimori, Koki; Andoh-Noda, Tomoko; Ando, Takayuki; Kuzumaki, Naoko; Toyoshima, Manabu; Tada, Hirobumi; Imaizumi, Kent; Ishikawa, Mitsuru; Yamaguchi, Ryo; Isoda, Miho; Zhou, Zhi; Sato, Shigeto; Kobayashi, Tetsuro; Ohtaka, Manami; Nishimura, Ken; Kurosawa, Hiroshi; Yoshikawa, Takeo; Takahashi, Takuya; Nakanishi, Mahito; Ohyama, Manabu; Hattori, Nobutaka; Akamatsu, Wado; Okano, Hideyuki

    2016-01-01

    Summary Modeling of neurological diseases using induced pluripotent stem cells (iPSCs) derived from the somatic cells of patients has provided a means of elucidating pathogenic mechanisms and performing drug screening. T cells are an ideal source of patient-specific iPSCs because they can be easily obtained from samples. Recent studies indicated that iPSCs retain an epigenetic memory relating to their cell of origin that restricts their differentiation potential. The classical method of differentiation via embryoid body formation was not suitable for T cell-derived iPSCs (TiPSCs). We developed a neurosphere-based robust differentiation protocol, which enabled TiPSCs to differentiate into functional neurons, despite differences in global gene expression between TiPSCs and adult human dermal fibroblast-derived iPSCs. Furthermore, neurons derived from TiPSCs generated from a juvenile patient with Parkinson's disease exhibited several Parkinson's disease phenotypes. Therefore, we conclude that TiPSCs are a useful tool for modeling neurological diseases. PMID:26905201

  4. Lipid mediators in the neural cell nucleus: their metabolism, signaling, and association with neurological disorders.

    PubMed

    Farooqui, Akhlaq A

    2009-08-01

    Lipid mediators are important endogenous regulators of neural cell proliferation, differentiation, oxidative stress, inflammation, and apoptosis. They originate from enzymic degradation of glycerophospholipids, sphingolipids, and cholesterol by phospholipases, sphingomyelinases, and cytochrome P450 hydroxylases, respectively. Arachidonic acid-derived lipid mediators are called eicosanoids. Eicosanoids have emerged as key regulators of cell proliferation, differentiation, oxidative stress, and neuroinflammation. Another arachidonic acid-derived lipid mediator is lipoxin. Eicosanoids have proinflammatory effects, whereas lipoxins produce antiinflammatory effects. The crossponding lipid mediators of docosahexaenoic acid metabolism are named docosanoids. They include resolvins, protectins, and neuroprotectins. Docosanoids produce antioxidant, anti-inflammatory, and antiapoptotic effects in the brain tissue. Other glycerophospholipid-derived lipid mediators are platelet-activating factor, lysophosphatidic acid, and endocannabinoids. Degradation of sphingolipids also results in the generation of sphingolipid-derived lipid mediators. Sphingolipid-derived lipid mediators are ceramide, ceramide 1-phosphate, sphingosine, and sphingosine 1-phosphate. They mediate cellular differentiation, cell growth, and apoptosis. Similarly, cholesterol-derived lipid mediators hydroxycholesterol and oxycholesterol produce apoptosis. Most of these mediators originate from the plasma membrane. The nucleus has its own set of enzymes and lipid mediators that originate from the nuclear envelope and matrix. The purpose of this commentary is to describe basic and clinical information on lipid mediators in the nucleus.

  5. Modeling Neurological Disease by Rapid Conversion of Human Urine Cells into Functional Neurons.

    PubMed

    Zhang, Shu-Zhen; Ma, Li-Xiang; Qian, Wen-Jing; Li, Hong-Fu; Wang, Zhong-Feng; Wang, Hong-Xia; Wu, Zhi-Ying

    2016-01-01

    Somatic cells can be directly converted into functional neurons by ectopic expression of defined factors and/or microRNAs. Since the first report of conversion mouse embryonic fibroblasts into functional neurons, the postnatal mouse, and human fibroblasts, astroglia, hepatocytes, and pericyte-derived cells have been converted into functional dopaminergic and motor neurons both in vitro and in vivo. However, it is invasive to get all these materials. In the current study, we provide a noninvasive approach to obtain directly reprogrammed functional neurons by overexpression of the transcription factors Ascl1, Brn2, NeuroD, c-Myc, and Myt1l in human urine cells. These induced neuronal (iN) cells could express multiple neuron-specific proteins and generate action potentials. Moreover, urine cells from Wilson's disease (WD) patient could also be directly converted into neurons. In conclusion, generation of iN cells from nonneural lineages is a feasible and befitting approach for neurological disease modeling. PMID:26770203

  6. Impaired functional default mode network in patients with mild neurological Wilson's disease.

    PubMed

    Han, Yongsheng; Cheng, Hewei; Toledo, Jon B; Wang, Xun; Li, Bo; Han, Yongzhu; Wang, Kai; Fan, Yong

    2016-09-01

    Wilson's disease (WD) is an autosomal recessive metabolic disorder characterized by cognitive, psychiatric and motor signs and symptoms that are associated with structural and pathological brain abnormalities, in addition to liver changes. However, functional brain connectivity pattern of WD patients remains largely unknown. In the present study, we investigated functional brain connectivity pattern of WD patients using resting state functional magnetic resonance imaging. Particularly, we studied default mode network (DMN) using posterior cingulate cortex (PCC) based seed functional connectivity analysis and graph theoretic functional brain network analysis tools, and investigated the relationship between the DMN's functional connectivity pattern of WD patients and their attention functions examined using the attention network test (ANT). Our results demonstrated that WD patients had altered DMN's functional connectivity and lower local and global network efficiency compared with normal controls (NCs). In addition, the functional connectivity between left inferior temporal cortex and right lateral parietal cortex was correlated with altering function, one of the attention functions, across WD and NC subjects. These findings indicated that the DMN's functional connectivity was altered in WD patients, which might be correlated with their attention dysfunction.

  7. Impaired functional default mode network in patients with mild neurological Wilson's disease.

    PubMed

    Han, Yongsheng; Cheng, Hewei; Toledo, Jon B; Wang, Xun; Li, Bo; Han, Yongzhu; Wang, Kai; Fan, Yong

    2016-09-01

    Wilson's disease (WD) is an autosomal recessive metabolic disorder characterized by cognitive, psychiatric and motor signs and symptoms that are associated with structural and pathological brain abnormalities, in addition to liver changes. However, functional brain connectivity pattern of WD patients remains largely unknown. In the present study, we investigated functional brain connectivity pattern of WD patients using resting state functional magnetic resonance imaging. Particularly, we studied default mode network (DMN) using posterior cingulate cortex (PCC) based seed functional connectivity analysis and graph theoretic functional brain network analysis tools, and investigated the relationship between the DMN's functional connectivity pattern of WD patients and their attention functions examined using the attention network test (ANT). Our results demonstrated that WD patients had altered DMN's functional connectivity and lower local and global network efficiency compared with normal controls (NCs). In addition, the functional connectivity between left inferior temporal cortex and right lateral parietal cortex was correlated with altering function, one of the attention functions, across WD and NC subjects. These findings indicated that the DMN's functional connectivity was altered in WD patients, which might be correlated with their attention dysfunction. PMID:27372239

  8. The relationship between subconcussive impacts and concussion history on clinical measures of neurologic function in collegiate football players.

    PubMed

    Gysland, Sonia M; Mihalik, Jason P; Register-Mihalik, Johna K; Trulock, Scott C; Shields, Edgar W; Guskiewicz, Kevin M

    2012-01-01

    Concussions sustained during college and professional football careers have been associated with both acute and chronic neurologic impairment. The contribution of subconcussive impacts to this impairment has not been adequately studied. Therefore, we investigated the relationship between subconcussive impacts and concussion history on clinical measures of neurologic function. Forty-six collegiate football players completed five clinical measures of neurologic function commonly employed in the evaluation of concussion before and after a single season. These tests included the Automated Neuropsychological Assessment Metrics, Sensory Organization Test, Standardized Assessment of Concussion, Balance Error Scoring System, and Graded Symptom Checklist. The Head Impact Telemetry (HIT) System recorded head impact data including the frequency, magnitude, and location of impacts. College football players sustain approximately 1,000 subconcussive impacts to the head over the course of a season, but for the most part, do not demonstrate any clinically meaningful changes from preseason to postseason on measures of neurologic function. Changes in performance were mostly independent of prior concussion history, and the total number, magnitude and location of sustained impacts over one season as observed R(2) values ranged between 0.30 and 0.35. Repetitive subconcussive head impacts over a single season do not appear to result in short-term neurologic impairment, but these relationships should be further investigated for a potential dose-response over a player's career.

  9. Measuring life quality, physical function and psychological well-being in neurological illness.

    PubMed

    O'Doherty, Lorna Jane; Hickey, Anne; Hardiman, Orla

    2010-10-01

    There is little in the literature comparing experiences of patients with disabling and uniformly terminal illness (e.g. amyotrophic lateral sclerosis) and illness characterized by episodic disability and prognostic uncertainty (e.g. multiple sclerosis). This study aimed to compare experiences of disability, quality of life (QoL) and psychological well-being in ALS and MS. One hundred patients with ALS and MS were interviewed at baseline and at six months. Variables measured included function, health related QoL, individualized QoL and psychological distress. Despite the divergent illness experiences of ALS and MS patients, groups did not differ on individualized QoL or mental well-being, and distress was in the normal range. Despite marked deterioration in ALS patients' health, there was no change in mental well-being and QoL. Psychological well-being appeared more important in maintaining QoL (individualized QoL and mental aspects of health related QoL) than physical factors. At the individual level, there was evidence of psychological adaptation to deteriorating function, which underlined the role of specific illness related challenges in determining perceived life quality and emotional well-being. In conclusion, the complex interplay between psychosocial and illness specific factors such as certainty with regard to prognosis has considerable implications for well-being and life quality. Recognizing such factors is essential when designing clinical interventions to promote adjustment and self-management among patients with neurological conditions.

  10. [Metabolic therapy in neurology].

    PubMed

    Zhivolupov, S A; Samartsev, I N; Rashidov, N A; Bodrova, T V; Vorob'eva, M N

    2013-01-01

    We studied the efficacy of rheosorbilact, an original infusion drug based on polyalcohols, in the complex therapy of patients with brain ischemia and diabetic neuropathy. Reosorbilact was used intravenously indrops 200-400 ml in day - 20 days. The primary endpoint of the study was the improvement of quality of life assessed with the SF-36 scale after 1 month of treatment. Patients with brain ischemia underwent neuropsychological tests and ultrasound duplex scanning of the carotid and vertebral arteries. In the group of patients with diabetic neuropathy, we evaluated the intensity of pain syndrome with the NRS, blood glucose level and electroneuromyography parameters of low extremities nerves. Some characteristics of acid-base balance were studied in patients of both groups. The results obtained in the study indicate the significant clinical effect of reosorbilact in patients with brain ischemia and diabetic neuropathy. PMID:23994919

  11. Predictors of Neurological Deficit after Endovascular Treatment of Cerebral Arteriovenous Malformations and Functional Repercussions in Prospective Follow-Up

    PubMed Central

    Jordan, Jose; Llibre, Juan Carlos; Vazquez, Frank

    2014-01-01

    Summary Endovascular therapy is a well-established approach to the treatment of cerebral arteriovenous malformations (AVMs). The objective of this study was to determine the predictive factors of neurological deficit following endovascular procedures. Seventy-one patients with cerebral AVMs who underwent 147 embolization sessions from 2006 to 2011 were followed up prospectively (average 31.1 ± 17.5 months). Functional neurological condition was documented by means of the modified Rankin scale. Factors found to be predictors of neurological deficit were the partial obstruction of drainage veins (OR = 197.6; IC = 2.76 -1416.0; P = 0.015), a positive result in the Propofol test (OR = 50.2; IC = 6.18 - 566.5; P = 0.000), AVM diameter under 3 cm (OR = 21.3; IC: 1.71 − 265.6; P = 0.018), the presence of intranidal aneurysms (OR = 11.2; IC = 1.09 − 114.2; P = 0.042), the absence of post-procedure hypotension (OR = 10.2; IC = 1.35 − 77.7; P = 0.003), deep venous drainage (OR = 7.14; IC = 1.15 − 44.4; P = 0.035), and devascularization in excess of 40% per session (OR = 3.3; IC = 1.11 − 16.8; P = 0.056). Fifty-six patients (78.9%) did not experience changes in their neurological condition after the treatment and 13 patients (18.3%) showed a new neurological deficit related to the treatment; 95.8 % of the patients did not show significant long-term incapacity. Partial obstruction of drainage veins, small AVMs, intranidal aneurysms, faulty hemodynamic control and extensive devascularization were found to be predictors of neurological deficit. A significant number of patients with neurological deficit improved in the long term. PMID:25489896

  12. Neurological function following cerebral ischemia/reperfusion is improved by the Ruyi Zhenbao pill in a rats

    PubMed Central

    WANG, TIAN; DUAN, SIJIN; WANG, HAIPING; SUN, SHAN; HAN, BING; FU, FENGHUA

    2016-01-01

    The present study aimed to investigate the effect and underlying mechanisms of the Ruyi Zhenbao pill on neurological function following cerebral ischemia/reperfusion in rats. Male Sprague-Dawley rats underwent middle cerebral artery occlusion following reperfusion. The rats received intragastrically either sodium carboxymethyl cellulose (control and model groups) or Ruyi Zhenbao pill at doses of 0.2, 0.4 or 0.8 g/kg. Neurological function was assessed by cylinder, adhesive and beam-walking tests after 14-day Ruyi Zhenbao pill treatment. Neurogenesis and angiogenesis were detected using immunofluorescence staining. The expression levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assays. Treatment with 0.4 and 0.8 g/kg Ruyi Zhenbao for 14 days significantly improved neurological function, and increased the number of von Willebrand Factor- and neuronal nuclear antigen-positive cells in the ischemic hemisphere of rats. Ruyi Zhenbao pill treatment also significantly enhanced the expression levels of BDNF, NGF and VEGF in the ischemic hemisphere. The results demonstrated that the Ruyi Zhenbao pill improved neurological function following ischemia in rats. The mechanisms of the Ruyi Zhenbao pill are associated with increasing the expression levels of BDNF, NGF and VEGF, and subsequently promoting neurogenesis and angiogenesis in the ischemic zone. PMID:26893831

  13. Thiamin function, metabolism, uptake, and transport.

    PubMed

    Manzetti, Sergio; Zhang, Jin; van der Spoel, David

    2014-02-11

    Vitamins are crucial components in the diet of animals and many other living organisms. One of these essential nutrients, thiamin, is known to be involved in several cell functions, including energy metabolism and the degradation of sugars and carbon skeletons. Other roles that are connected to this vitamin are neuronal communication, immune system activation, signaling and maintenance processes in cells and tissues, and cell-membrane dynamics. Because of the key functions of thiamin, uptake and transport through the body are crucial. Its uptake route is relatively complex, encompassing a variety of protein families, including the solute carrier anion transporters, the alkaline phosphatase transport system, and the human extraneuronal monoamine transporter family, some of which are multispecific proteins. There are two known structures of protein (subunits) involved in thiamin uptake in prokaryotes. Binding of thiamin to these proteins is strongly guided by electrostatic interactions. The lack of structural information about thiamin binding proteins for higher organisms remains a bottleneck for understanding the uptake process of thiamin in atomic detail. This review includes recent data on thiamin metabolism, related deficiencies and pathologies, and the latest findings on thiamin binding transporters.

  14. Metabolism and functions of copper in brain.

    PubMed

    Scheiber, Ivo F; Mercer, Julian F B; Dringen, Ralf

    2014-05-01

    Copper is an important trace element that is required for essential enzymes. However, due to its redox activity, copper can also lead to the generation of toxic reactive oxygen species. Therefore, cellular uptake, storage as well as export of copper have to be tightly regulated in order to guarantee sufficient copper supply for the synthesis of copper-containing enzymes but also to prevent copper-induced oxidative stress. In brain, copper is of importance for normal development. In addition, both copper deficiency as well as excess of copper can seriously affect brain functions. Therefore, this organ possesses ample mechanisms to regulate its copper metabolism. In brain, astrocytes are considered as important regulators of copper homeostasis. Impairments of homeostatic mechanisms in brain copper metabolism have been associated with neurodegeneration in human disorders such as Menkes disease, Wilson's disease and Alzheimer's disease. This review article will summarize the biological functions of copper in the brain and will describe the current knowledge on the mechanisms involved in copper transport, storage and export of brain cells. The role of copper in diseases that have been connected with disturbances in brain copper homeostasis will also be discussed.

  15. Blood-Brain Barrier Function and Biomarkers of Central Nervous System Injury in Rickettsial Versus Other Neurological Infections in Laos.

    PubMed

    Dittrich, Sabine; Sunyakumthorn, Piyanate; Rattanavong, Sayaphet; Phetsouvanh, Rattanaphone; Panyanivong, Phonepasith; Sengduangphachanh, Amphonsavanh; Phouminh, Phonelavanh; Anantatat, Tippawan; Chanthongthip, Anisone; Lee, Sue J; Dubot-Pérès, Audrey; Day, Nicholas P J; Paris, Daniel H; Newton, Paul N; Turner, Gareth D H

    2015-08-01

    Blood-brain barrier (BBB) function and cerebrospinal fluid (CSF) biomarkers were measured in patients admitted to hospital with severe neurological infections in the Lao People's Democratic Republic (N = 66), including bacterial meningitis (BM; N = 9) or tuberculosis meningitis (TBM; N = 11), Japanese encephalitis virus (JEV; N = 25), and rickettsial infections (N = 21) including murine and scrub typhus patients. The albumin index (AI) and glial fibrillary acidic protein (GFAP) levels were significantly higher in BM and TBM than other diseases but were also raised in individual rickettsial patients. Total tau protein was significantly raised in the CSF of JEV patients. No differences were found between clinical or neurological symptoms, AI, or biomarker levels that allowed distinction between severe neurological involvement by Orientia tsutsugamushi compared with Rickettsia species.

  16. Computerized Functional Reach Test to Measure Balance Stability in Elderly Patients With Neurological Disorders

    PubMed Central

    Scena, Silvio; Steindler, Roberto; Ceci, Moira; Zuccaro, Stefano Maria; Carmeli, Eli

    2016-01-01

    Background The ability to maintain static and dynamic balance is a prerequisite for safe walking and for obtaining functional mobility. For this reason, a reliable and valid means of screening for risk of falls is needed. The functional reach test (FRT) is used in many countries, yet it does not provide some kinematic parameters such as shoulder or pelvic girdles translation. The purpose was to analyze video records measuring of distance, velocity, time length, arm direction and girdles translation while doing FRT. Methods A cross-sectional, descriptive study was conducted where the above variables were correlated to the mini-mental state examination (MMSE) for mental status and the Tinetti balance assessment test, which have been validated, in order to computerize the FRT (cFRT) for elderly patients with neurological disorders. Eighty patients were tested and 54 were eligible to serve as experimental group. The patients underwent the MMSE, the Tinetti test and the FRT. LAB view software was used to record the FRT performances and to process the videos. The control group consisted of 51 healthy subjects who had been previously tested. Results The experimental group was not able to perform the tests as well as the healthy control subjects. The video camera provided valuable kinematic results such as bending down while performing the forward reach test. Conclusions Instead of manual measurement, we proposed to use a cheap with fair resolution web camera to accurately estimate the FRT. The kinematic parameters were correlated with Tinetti and MMSE scores. The performance values established in this study indicate that the cFRT is a reliable and valid assessment, which provides more accurate data than “manual” test about functional reach. PMID:27635176

  17. [Non-invasive brain stimulation in neurology : Transcranial direct current stimulation to enhance cognitive functioning].

    PubMed

    Antonenko, D; Flöel, A

    2016-08-01

    Transcranial direct current stimulation (tDCS) has been successfully used in neuroscientific research to modulate cognitive functions. Recent studies suggested that improvement of behavioral performance is associated with tDCS-induced modulation of neuronal activity and connectivity. Thus, tDCS may also represent a promising tool for reconstitution of cognitive functions in the context of memory decline related to Alzheimer's disease or aphasia following stroke; however, evidence from randomized sham-controlled clinical trials is still scarce. Initial results of tDCS-induced behavioral improvement in patients with Alzheimer's dementia and its precursors indicated that an intense memory training combined with tDCS may be effective. Early interventions in the stage of mild cognitive impairment could be crucial but further evidence is needed to substantiate this. In patients with aphasia following stroke tDCS was applied to the left and right hemispheres, with varying results depending on the severity of the symptoms and polarity of the stimulation. Patients with mild aphasia can benefit from tDCS of the language dominant hemisphere while in patients with severe aphasia tDCS of right hemispheric homologous brain language areas may be particularly relevant. Moreover, recent studies suggested that an intervention in the subacute phase of aphasia could be most promising. In summary, tDCS could provide the exciting possibility to reconstitute cognitive functions in patients with neurological disorders. Future studies have to elucidate whether tDCS can be used in the clinical routine to prevent further cognitive decline in neurodegenerative diseases and whether beneficial effects from experimental studies translate into long-term improvement in activities of daily life. PMID:27167887

  18. Computerized Functional Reach Test to Measure Balance Stability in Elderly Patients With Neurological Disorders

    PubMed Central

    Scena, Silvio; Steindler, Roberto; Ceci, Moira; Zuccaro, Stefano Maria; Carmeli, Eli

    2016-01-01

    Background The ability to maintain static and dynamic balance is a prerequisite for safe walking and for obtaining functional mobility. For this reason, a reliable and valid means of screening for risk of falls is needed. The functional reach test (FRT) is used in many countries, yet it does not provide some kinematic parameters such as shoulder or pelvic girdles translation. The purpose was to analyze video records measuring of distance, velocity, time length, arm direction and girdles translation while doing FRT. Methods A cross-sectional, descriptive study was conducted where the above variables were correlated to the mini-mental state examination (MMSE) for mental status and the Tinetti balance assessment test, which have been validated, in order to computerize the FRT (cFRT) for elderly patients with neurological disorders. Eighty patients were tested and 54 were eligible to serve as experimental group. The patients underwent the MMSE, the Tinetti test and the FRT. LAB view software was used to record the FRT performances and to process the videos. The control group consisted of 51 healthy subjects who had been previously tested. Results The experimental group was not able to perform the tests as well as the healthy control subjects. The video camera provided valuable kinematic results such as bending down while performing the forward reach test. Conclusions Instead of manual measurement, we proposed to use a cheap with fair resolution web camera to accurately estimate the FRT. The kinematic parameters were correlated with Tinetti and MMSE scores. The performance values established in this study indicate that the cFRT is a reliable and valid assessment, which provides more accurate data than “manual” test about functional reach.

  19. Physiological Transgene Regulation and Functional Complementation of a Neurological Disease Gene Deficiency in Neurons

    PubMed Central

    Peruzzi, Pier Paolo; Lawler, Sean E; Senior, Steve L; Dmitrieva, Nina; Edser, Pauline AH; Gianni, Davide; Chiocca, E Antonio; Wade-Martins, Richard

    2009-01-01

    The microtubule-associated protein tau (MAPT) and α-synuclein (SNCA) genes play central roles in neurodegenerative disorders. Mutations in each gene cause familial disease, whereas common genetic variation at both loci contributes to susceptibility to sporadic neurodegenerative disease. Here, we demonstrate exquisite gene regulation of the human MAPT and SNCA transgene loci and functional complementation in neuronal cell cultures and organotypic brain slices using the herpes simplex virus type 1 (HSV-1) amplicon-based infectious bacterial artificial chromosome (iBAC) vector to express complete loci >100 kb. Cell cultures transduced by iBAC vectors carrying a 143 kb MAPT or 135 kb SNCA locus expressed the human loci similar to the endogenous gene. We focused on analysis of the iBAC-MAPT vector carrying the complete MAPT locus. On transduction into neuronal cultures, multiple MAPT transcripts were expressed from iBAC-MAPT under strict developmental and cell type–specific control. In primary neurons from Mapt−/− mice, the iBAC-MAPT vector expressed the human tau protein, as detected by enzyme-linked immunosorbent assay and immunocytochemistry, and restored sensitivity of Mapt−/− neurons to Aβ peptide treatment in dissociated neuronal cultures and in organotypic slice cultures. The faithful retention of gene expression and phenotype complementation by the system provides a novel method to analyze neurological disease genes. PMID:19352323

  20. Estrogen regulation of glucose metabolism and mitochondrial function: therapeutic implications for prevention of Alzheimer's disease.

    PubMed

    Brinton, Roberta Diaz

    2008-01-01

    Estrogen-induced signaling pathways in hippocampal and cortical neurons converge upon the mitochondria to enhance mitochondrial function and to sustain aerobic glycolysis and citric acid cycle-driven oxidative phosphorylation and ATP generation. Data derived from experimental and clinical paradigms investigating estrogen intervention in healthy systems and prior to neurodegenerative insult indicate enhanced neural defense and survival through maintenance of calcium homeostasis, enhanced glycolysis coupled to the citric acid cycle (aerobic glycolysis), sustained and enhanced mitochondrial function, protection against free radical damage, efficient cholesterol trafficking and beta amyloid clearance. The convergence of E(2) mechanisms of action onto mitochondrial is also a potential point of vulnerability when activated in a degenerating neural system and could exacerbate the degenerative processes through increased load on dysregulated calcium homeostasis. The data indicate that as the continuum of neurological health progresses from healthy to unhealthy so too do the benefits of estrogen or hormone therapy. If neurons are healthy at the time of estrogen exposure, their response to estrogen is beneficial for both neuronal survival and neurological function. In contrast, if neurological health is compromised, estrogen exposure over time exacerbates neurological demise. The healthy cell bias of estrogen action hypothesis provides a lens through which to assess the disparities in outcomes across the basic to clinical domains of scientific inquiry and on which to predict future applications of estrogen and hormone therapeutic interventions sustain neurological health and to prevent age-associated neurodegenerative diseases such as Alzheimer's. Overall, E(2) promotes the energetic capacity of brain mitochondria by maximizing aerobic glycolysis (oxidative phosphorylation coupled to pyruvate metabolism). The enhanced aerobic glycolysis in the aging brain would be predicted

  1. The prognostic value of neurologic function in astrocytic spinal cord glioma.

    PubMed Central

    Lee, Hoon K.; Chang, Eric L.; Fuller, Gregory N.; Aldape, Kenneth D.; Atkinson, George J.; Levy, Lawrence B.; McCutcheon, Ian E.; Maor, Moshe H.

    2003-01-01

    To assess the prognostic value of neurologic function (NF) in patients with astrocytic spinal cord glioma, we conducted a retrospective study of 25 patients who were treated at our institution between January 1970 and December 1999. The median age was 40 years, and the median follow-up was 54 months. Nineteen patients had a biopsy, 5 had a subtotal resection, and 1 had a gross total resection. Twenty-two patients received postoperative radiotherapy to a median dose of 45 Gy. NF ratings of 1 and 2 were considered favorable, and 3 and 4 were considered unfavorable, based on a scale of 1 to 4. Dual neuropathologic review confirmed the tumor to be low, intermediate, or high grade, based on the WHO grades I-II, III, or IV, respectively. Actuarial rates of local control (LC), progression-free survival (PFS), and overall survival (OS) were analyzed. Our study results revealed that an improved 5-year OS rate was associated with favorable NF at diagnosis (73% vs. 22% for patients with unfavorable NF; P = 0.04) and favorable NF before radiation therapy (89% vs. 28% for patients with unfavorable NF; P = 0.049). There was a significant difference in OS based on tumor grade ( P < 0.001) and age (risk ratio, 1.04; P = 0.027). PFS and LC were significantly better for young patients and those with lower tumor grade ( P < 0.05). A multivariate analysis of age, NF at diagnosis, and postoperative NF for all patients showed postoperative NF and age to be independent prognostic factors for OS. We conclude that favorable NF may be associated with improved outcome in patients with astrocytic spinal cord glioma. PMID:12816727

  2. Effects of vitamin B-12 supplementation on neurologic and cognitive function in older people: a randomized controlled trial12

    PubMed Central

    Dangour, Alan D; Allen, Elizabeth; Clarke, Robert; Elbourne, Diana; Fletcher, Astrid E; Letley, Louise; Richards, Marcus; Whyte, Ken; Uauy, Ricardo; Mills, Kerry

    2015-01-01

    Background: Moderate vitamin B-12 deficiency is relatively common in older people. However, there is little robust evidence on the effect of vitamin B-12 supplementation on neurologic and cognitive outcomes in later life. Objective: We investigated whether vitamin B-12 supplementation benefits neurologic and cognitive function in moderately vitamin B-12–deficient older people. Design: We conducted a double-blind, randomized, placebo-controlled trial in 7 general practices in South East England, United Kingdom. Study participants were aged ≥75 y and had moderate vitamin B-12 deficiency (serum vitamin B-12 concentrations: 107–210 pmol/L) in the absence of anemia and received 1 mg crystalline vitamin B-12 or a matching placebo as a daily oral tablet for 12 mo. Peripheral motor and sensory nerve conduction, central motor conduction, a clinical neurologic examination, and cognitive function were assessed before and after treatment. Results: A total of 201 participants were enrolled in the trial, and 191 subjects provided outcome data. Compared with baseline, allocation to vitamin B-12 was associated with a 177% increase in serum concentration of vitamin B-12 (641 compared with 231 pmol/L), a 331% increase in serum holotranscobalamin (240 compared with 56 pmol/L), and 17% lower serum homocysteine (14.2 compared with 17.1 μmol/L). In intention-to-treat analysis of covariance models, with adjustment for baseline neurologic function, there was no evidence of an effect of supplementation on the primary outcome of the posterior tibial compound muscle action potential amplitude at 12 mo (mean difference: −0.2 mV; 95% CI: –0.8, 0.3 mV). There was also no evidence of an effect on any secondary peripheral nerve or central motor function outcome, or on cognitive function or clinical examination. Conclusion: Results of the trial do not support the hypothesis that the correction of moderate vitamin B-12 deficiency, in the absence of anemia and of neurologic and cognitive

  3. Neurologic Functional and Quality of Life Outcomes after TBI: Clinic Attendees versus Non-Attendees.

    PubMed

    Patel, Mayur B; Wilson, Laura D; Bregman, Jana A; Leath, Taylor C; Humble, Stephen S; Davidson, Mario A; de Riesthal, Michael R; Guillamondegui, Oscar D

    2015-07-01

    This investigation describes the relationship between TBI patient demographics, quality of life outcome, and functional status outcome among clinic attendees and non-attendees. Of adult TBI survivors with intracranial hemorrhage, 63 attended our TBI clinic and 167 did not attend. All were telephone surveyed using the Extended-Glasgow Outcome Scale (GOSE), the Quality of Life after Brain Injury (QOLIBRI) scale, and a post-discharge therapy questionnaire. To determine risk factors for GOSE and QOLIBRI outcomes, we created multivariable regression models employing covariates of age, injury characteristics, clinic attendance, insurance status, post-discharge rehabilitation, and time from injury. Compared with those with severe TBI, higher GOSE scores were identified in individuals with both mild (odds ratio [OR]=2.0; 95% confidence interval [CI]: 1.1-3.6) and moderate (OR=4.7; 95% CI: 1.6-14.1) TBIs. In addition, survivors with private insurance had higher GOSE scores, compared with those with public insurance (OR=2.0; 95% CI: 1.1-3.6), workers' compensation (OR=8.4; 95% CI: 2.6-26.9), and no insurance (OR=3.1; 95% CI: 1.6-6.2). Compared with those with severe TBI, QOLIBRI scores were 11.7 points (95% CI: 3.7-19.7) higher in survivors with mild TBI and 17.3 points (95% CI: 3.2-31.5) higher in survivors with moderate TBI. In addition, survivors who received post-discharge rehabilitation had higher QOLIBRI scores by 11.4 points (95% CI: 3.7-19.1) than those who did not. Survivors with private insurance had QOLIBRI scores that were 25.5 points higher (95% CI: 11.3-39.7) than those with workers' compensation and 16.8 points higher (95% CI: 7.4-26.2) than those without insurance. Because neurologic injury severity, insurance status, and receipt of rehabilitation or therapy are independent risk factors for functional and quality of life outcomes, future directions will include improving earlier access to post-TBI rehabilitation, social work services, affordable insurance

  4. Factors Associated With Neurological Recovery of Brainstem Function Following Postoperative Conformal Radiation Therapy for Infratentorial Ependymoma

    SciTech Connect

    Merchant, Thomas E.; Chitti, Ramana M.; Li Chenghong; Xiong Xiaoping; Sanford, Robert A.; Khan, Raja B.

    2010-02-01

    Purpose: To identify risk factors associated with incomplete neurological recovery in pediatric patients with infratentorial ependymoma treated with postoperative conformal radiation therapy (CRT). Methods: The study included 68 patients (median age +- standard deviation of 2.6 +- 3.8 years) who were followed for 5 years after receiving CRT (54-59.4 Gy) and were assessed for function of cranial nerves V to VII and IX to XII, motor weakness, and dysmetria. The mean (+- standard deviation) brainstem dose was 5,487 (+-464) cGy. Patients were divided into four groups representing those with normal baseline and follow-up, those with abnormal baseline and full recovery, those with abnormal baseline and partial or no recovery, and those with progressive deficits at 12 (n = 62 patients), 24 (n = 57 patients), and 60 (n = 50 patients) months. Grouping was correlated with clinical and treatment factors. Results: Risk factors (overall risk [OR], p value) associated with incomplete recovery included gender (male vs. female, OR = 3.97, p = 0.036) and gross tumor volume (GTV) (OR/ml = 1.23, p = 0.005) at 12 months, the number of resections (>1 vs. 1; OR = 23.7, p = 0.003) and patient age (OR/year = 0.77, p = 0.029) at 24 months, and cerebrospinal fluid (CSF) shunting (Yes vs. No; OR = 21.9, p = 0.001) and GTV volume (OR/ml = 1.18, p = 0.008) at 60 months. An increase in GTV correlated with an increase in the number of resections (p = 0.001) and CSF shunting (p = 0.035); the number of resections correlated with CSF shunting (p < 0.0001), and male patients were more likely to undergo multiple tumor resections (p = 0.003). Age correlated with brainstem volume (p < 0.0001). There were no differences in outcome based on the absolute or relative volume of the brainstem that received more than 54 Gy. Conclusions: Incomplete recovery of brainstem function after CRT for infratentorial ependymoma is related to surgical morbidity and the volume and the extent of tumor.

  5. Electroacupuncture Treatment Improves Neurological Function Associated with Regulation of Tight Junction Proteins in Rats with Cerebral Ischemia Reperfusion Injury

    PubMed Central

    Zhang, Ya-min; Xu, Hong; Sun, Hua; Chen, Su-hui; Wang, Fu-ming

    2014-01-01

    Strategies to develop effective neuroprotective therapy to reduce brain damage and related behavioral deficits in stroke patients are of great significance. Electroacupuncture (EA), which derives from traditional Chinese medicine, may be effective as a complementary and alternative method for promoting recovery of neurological function and quality of life. Adult Sprague-Dawley rats were randomly divided into 3 groups: (1) sham, (2) middle cerebral artery occlusion (MCAO) model groups of 2 h MCAO followed by 1, 3, 5, or 7 d of reperfusion, and (3) EA groups of 2 h MCAO followed by 1, 3, 5, or 7 d of reperfusion. EA groups received EA therapy by needling at GV20 and left ST36. The results show that EA therapy improved the neurological function and reduced infarct volume, confirmed by modified neurological severity scores and TTC staining. Real-time PCR, immunohistochemistry, and western blot assay verified that EA upregulated the expression of tight junction (TJ) claudin-5, occludin, and zonula occluding-1 from 1 to 7 d after reperfusion. Our findings suggest that EA reduces brain damage and related behavioral deficits via upregulation of the TJ proteins. PMID:25009574

  6. Potential Interactions between the Autonomic Nervous System and Higher Level Functions in Neurological and Neuropsychiatric Conditions

    PubMed Central

    Bassi, Andrea; Bozzali, Marco

    2015-01-01

    The autonomic nervous system (ANS) maintains the internal homeostasis by continuously interacting with other brain structures. Its failure is commonly observed in many neurological and neuropsychiatric disorders, including neurodegenerative and vascular brain diseases, spinal cord injury, and peripheral neuropathies. Despite the different underlying pathophysiological mechanisms, ANS failure associates with various forms of higher level dysfunctions, and may also negatively impact on patients’ clinical outcome. In this review, we will discuss potential relationships between ANS and higher level dysfunctions in a selection of neurological and neuropsychiatric disorders. In particular, we will focus on the effect of a documented fall in blood pressure fulfilling the criteria for orthostatic hypotension and/or autonomic-reflex impairment on cognitive performances. Some evidence supports the hypothesis that cardiovascular autonomic failure may play a negative prognostic role in most neurological disorders. Despite a clear causal relationship between ANS involvement and higher level dysfunctions that is still controversial, this might have implications for neuro-rehabilitation strategies aimed at improving patients’ clinical outcome. PMID:26388831

  7. Neurological soft signs in persons with amnestic mild cognitive impairment and the relationships to neuropsychological functions

    PubMed Central

    2012-01-01

    Background Neurological abnormalities have been reported in people with amnestic mild cognitive impairment (aMCI). The current study aimed to examine the prevalence of neurological soft signs (NSS) in this clinical group and to examine the relationship of NSS to other neuropsychological performances. Methods Twenty-nine people with aMCI and 28 cognitively healthy elderly people were recruited for the present study. The NSS subscales (motor coordination, sensory integration, and disinhibition) of the Cambridge Neurological Inventory and a set of neuropsychological tests were administered to all the participants. Results People with aMCI exhibited significantly more motor coordination signs, disinhibition signs, and total NSS than normal controls. Correlation analysis showed that the motor coordination subscale score and total score of NSS were significantly inversely correlated with the combined Z-score of neuropsychological tests in aMCI group. Conclusions These preliminary findings suggested that people with aMCI demonstrated a higher prevalence of NSS compared to healthy elderly people. Moreover, NSS was found to be inversely correlated with the neuropsychological performances in persons with aMCI. When taken together, these findings suggested that NSS may play a potential important role and serve as a tool to assist in the early detection of aMCI. PMID:22676227

  8. Chapter 38: American neurology.

    PubMed

    Freemon, Frank R

    2010-01-01

    The great formative event in the history of North America, the Civil War of 1861 to 1865, was the stimulus for the development of clinical neurology and the neurosciences. The first neurological research center on the continent was the US Army hospital at Turner's Lane, Philadelphia, PA. Silas Weir Mitchell and his colleagues described causalgia (reflex sympathetic dystrophy), phantom limb sensation, and Horner's syndrome (before Horner). The medical leader of the Northern army was William Hammond. After the conclusion of hostilities, he began a huge clinical practice in New York City. In the United States, clinical neurology began in private practice, unlike Europe, where neurology began in institutions. Hammond's textbook, which first used the term athetosis, was used by a generation of physicians who encountered patients with neurological signs and symptoms. Early in the 20th century, neurological institutions were formed around universities; probably the most famous was the Montreal Neurological Institute founded by Wilder Penfield. The US federal government sponsored extensive research into the function and dysfunction of the nervous system through the Neurological Institute of Neurological Diseases and Blindness, later called the National Institute of Neurological Diseases and Stroke. The government officially classified the final 10 years of the 20th century as the Decade of the Brain and provided an even greater level of research funding. PMID:19892141

  9. Estrogen and mitochondria function in cardiorenal metabolic syndrome.

    PubMed

    Jia, Guanghong; Aroor, Annayya R; Sowers, James R

    2014-01-01

    The cardiorenal metabolic syndrome (CRS) consists of a constellation of cardiac, renal, and metabolic disorders including insulin resistance (IR), obesity, metabolic dyslipidemia, high-blood pressure, and evidence of early cardiac and renal disease. Mitochondria dysfunction often occurs in the CRS, and this dysfunction is promoted by excess reactive oxygen species, genetic factors, IR, aging, and altered mitochondrial biogenesis. Recently, it has been shown that there are important sex-related differences in mitochondria function and metabolic, cardiovascular, and renal components. Sex differences in the CRS have mainly been attributed to the estrogen's effects that are mainly mediated by estrogen receptor (ER) α, ERβ, and G-protein coupled receptor 30. In this review, we discuss the effects of estrogen on the mitochondrial function, insulin metabolic signaling, glucose transport, lipid metabolism, and inflammatory responses from liver, pancreatic β cells, adipocytes, skeletal muscle, and cardiovascular tissue.

  10. Function Over Form: Modeling Groups of Inherited Neurological Conditions in Zebrafish.

    PubMed

    Kozol, Robert A; Abrams, Alexander J; James, David M; Buglo, Elena; Yan, Qing; Dallman, Julia E

    2016-01-01

    Zebrafish are a unique cell to behavior model for studying the basic biology of human inherited neurological conditions. Conserved vertebrate genetics and optical transparency provide in vivo access to the developing nervous system as well as high-throughput approaches for drug screens. Here we review zebrafish modeling for two broad groups of inherited conditions that each share genetic and molecular pathways and overlap phenotypically: neurodevelopmental disorders such as Autism Spectrum Disorders (ASD), Intellectual Disability (ID) and Schizophrenia (SCZ), and neurodegenerative diseases, such as Cerebellar Ataxia (CATX), Hereditary Spastic Paraplegia (HSP) and Charcot-Marie Tooth Disease (CMT). We also conduct a small meta-analysis of zebrafish orthologs of high confidence neurodevelopmental disorder and neurodegenerative disease genes by looking at duplication rates and relative protein sizes. In the past zebrafish genetic models of these neurodevelopmental disorders and neurodegenerative diseases have provided insight into cellular, circuit and behavioral level mechanisms contributing to these conditions. Moving forward, advances in genetic manipulation, live imaging of neuronal activity and automated high-throughput molecular screening promise to help delineate the mechanistic relationships between different types of neurological conditions and accelerate discovery of therapeutic strategies. PMID:27458342

  11. Function Over Form: Modeling Groups of Inherited Neurological Conditions in Zebrafish

    PubMed Central

    Kozol, Robert A.; Abrams, Alexander J.; James, David M.; Buglo, Elena; Yan, Qing; Dallman, Julia E.

    2016-01-01

    Zebrafish are a unique cell to behavior model for studying the basic biology of human inherited neurological conditions. Conserved vertebrate genetics and optical transparency provide in vivo access to the developing nervous system as well as high-throughput approaches for drug screens. Here we review zebrafish modeling for two broad groups of inherited conditions that each share genetic and molecular pathways and overlap phenotypically: neurodevelopmental disorders such as Autism Spectrum Disorders (ASD), Intellectual Disability (ID) and Schizophrenia (SCZ), and neurodegenerative diseases, such as Cerebellar Ataxia (CATX), Hereditary Spastic Paraplegia (HSP) and Charcot-Marie Tooth Disease (CMT). We also conduct a small meta-analysis of zebrafish orthologs of high confidence neurodevelopmental disorder and neurodegenerative disease genes by looking at duplication rates and relative protein sizes. In the past zebrafish genetic models of these neurodevelopmental disorders and neurodegenerative diseases have provided insight into cellular, circuit and behavioral level mechanisms contributing to these conditions. Moving forward, advances in genetic manipulation, live imaging of neuronal activity and automated high-throughput molecular screening promise to help delineate the mechanistic relationships between different types of neurological conditions and accelerate discovery of therapeutic strategies. PMID:27458342

  12. Current neurology

    SciTech Connect

    Appel, S.H. )

    1988-01-01

    The topics covered in this book include: Duchenne muscular dystrophy: DNA diagnosis in practice; Central nervous system magnetic resonance imaging; and Magnetic resonance spectroscopy of neurologic diseases.

  13. 2011 Plant Lipids: Structure, Metabolism, & Function Gordon Research Conference

    SciTech Connect

    Christopher Benning

    2011-02-04

    This is the second Gordon Research Conference on 'Plant Lipids: Structure, Metabolism & Function'. It covers current topics in lipid structure, metabolism and function in eukaryotic photosynthetic organisms including seed plants, algae, mosses and ferns. Work in photosynthetic bacteria is considered as well as it serves the understanding of specific aspects of lipid metabolism in plants. Breakthroughs are discussed in research on plant lipids as diverse as glycerolipids, sphingolipids, lipids of the cell surface, isoprenoids, fatty acids and their derivatives. The program covers nine concepts at the forefront of research under which afore mentioned plant lipid classes are discussed. The goal is to integrate areas such as lipid signaling, basic lipid metabolism, membrane function, lipid analysis, and lipid engineering to achieve a high level of stimulating interaction among diverse researchers with interests in plant lipids. One Emphasis is on the dynamics and regulation of lipid metabolism during plant cell development and in response to environmental factors.

  14. Functional Neurological Symptom Disorder: Mismanagement, Misdiagnosis, Chronic Cough Following Sexual Abuse: A Rare Case Report

    PubMed Central

    BIDAKI, Reza; ZAREPUR, Ehsan; AKRAMI, Maryam; Mohammad, Mohammad

    2016-01-01

    Objective Conversion disorder (CD) is a mental disorder in which patient displays neurological symptoms such as blindness, mutism, paralysis and seizure. It starts when our mind converts our mental stress into a physical symptom. A 15-year-old single white female with chronic cough, which had begun 5 months ago, was brought to our clinic. She had no history of hospitalization. His daily cough was without sputum production or fever, rhinorrhea and stopped during sleep. There was no recent exposure to tobacco smoke or a person with a chronic productive cough. Laboratory tests were normal. She had engaged 4 months ago. Doing sex during engagement is prohibited in her culture but and had anal sex, because of her spouse’s trend. Psychotherapy was done and complete recovery was accomplished. PMID:27247590

  15. Functional Neurological Symptom Disorder: Mismanagement, Misdiagnosis, Chronic Cough Following Sexual Abuse: A Rare Case Report.

    PubMed

    Bidaki, Reza; Zarepur, Ehsan; Akrami, Maryam; Mohammad, Mohammad

    2016-01-01

    Objective Conversion disorder (CD) is a mental disorder in which patient displays neurological symptoms such as blindness, mutism, paralysis and seizure. It starts when our mind converts our mental stress into a physical symptom. A 15-year-old single white female with chronic cough, which had begun 5 months ago, was brought to our clinic. She had no history of hospitalization. His daily cough was without sputum production or fever, rhinorrhea and stopped during sleep. There was no recent exposure to tobacco smoke or a person with a chronic productive cough. Laboratory tests were normal. She had engaged 4 months ago. Doing sex during engagement is prohibited in her culture but and had anal sex, because of her spouse's trend. Psychotherapy was done and complete recovery was accomplished. PMID:27247590

  16. Neurological and neuropsychological functions in adults with a history of developmental arsenic poisoning from contaminated milk powder.

    PubMed

    Yorifuji, Takashi; Kato, Tsuguhiko; Ohta, Hitoshi; Bellinger, David C; Matsuoka, Kenichi; Grandjean, Philippe

    2016-01-01

    During the summer of 1955, mass arsenic poisoning of bottle-fed infants occurred in the western part of Japan due to contaminated milk powder, and more than 100 died; some childhood victims were later found to suffer from neurological sequelae in adolescence. This unique incident enabled us to explore infancy as a critical period of arsenic exposure in regard to developmental neurotoxicity and its possible persistence through adulthood. The purpose of this work is to evaluate the association between developmental arsenic exposure and the neurological outcomes more than 50 years later. We conducted a retrospective cohort study during the period from April 2012 to February 2013 in two hospitals in Okayama Prefecture, Japan. The study sample consisted of 50 individuals: 27 known poisoning victims from Okayama Prefecture, and 23 non-exposed local controls of similar age. In addition to neurological examination, we adapted a battery of neurophysiological and neuropsychological tests to identify the types of brain functions affected by early-life arsenic exposure. While limited abnormalities were found in the neurophysiological tests, neuropsychological deficits were observed. Except for Finger tapping, all test scores in the exposed group--Vocabulary and Block Design from Wechsler Adults Intelligent Scale III, Design memory subtest from Wide Range Assessment of Memory and Learning 2, and Grooved pegboard test--were substantially below those obtained by the unexposed. The exposed group showed average performance at least 1.2 standard deviations below the average for the controls. Exposed participants performed less well than controls, even after exclusion of subjects with recognized disabilities or those with a high level of education. Adults who had suffered arsenic poisoning during infancy revealed neuropsychological dysfunctions, even among those subjects not recognized as having disabilities. Developmental neurotoxicity due to arsenic likely results in permanent

  17. Neurological and neuropsychological functions in adults with a history of developmental arsenic poisoning from contaminated milk powder.

    PubMed

    Yorifuji, Takashi; Kato, Tsuguhiko; Ohta, Hitoshi; Bellinger, David C; Matsuoka, Kenichi; Grandjean, Philippe

    2016-01-01

    During the summer of 1955, mass arsenic poisoning of bottle-fed infants occurred in the western part of Japan due to contaminated milk powder, and more than 100 died; some childhood victims were later found to suffer from neurological sequelae in adolescence. This unique incident enabled us to explore infancy as a critical period of arsenic exposure in regard to developmental neurotoxicity and its possible persistence through adulthood. The purpose of this work is to evaluate the association between developmental arsenic exposure and the neurological outcomes more than 50 years later. We conducted a retrospective cohort study during the period from April 2012 to February 2013 in two hospitals in Okayama Prefecture, Japan. The study sample consisted of 50 individuals: 27 known poisoning victims from Okayama Prefecture, and 23 non-exposed local controls of similar age. In addition to neurological examination, we adapted a battery of neurophysiological and neuropsychological tests to identify the types of brain functions affected by early-life arsenic exposure. While limited abnormalities were found in the neurophysiological tests, neuropsychological deficits were observed. Except for Finger tapping, all test scores in the exposed group--Vocabulary and Block Design from Wechsler Adults Intelligent Scale III, Design memory subtest from Wide Range Assessment of Memory and Learning 2, and Grooved pegboard test--were substantially below those obtained by the unexposed. The exposed group showed average performance at least 1.2 standard deviations below the average for the controls. Exposed participants performed less well than controls, even after exclusion of subjects with recognized disabilities or those with a high level of education. Adults who had suffered arsenic poisoning during infancy revealed neuropsychological dysfunctions, even among those subjects not recognized as having disabilities. Developmental neurotoxicity due to arsenic likely results in permanent

  18. Calcium metabolism and cardiovascular function after spaceflight

    NASA Technical Reports Server (NTRS)

    Hatton, Daniel C.; Yue, Qi; Dierickx, Jacqueline; Roullet, Chantal; Otsuka, Keiichi; Watanabe, Mitsuaki; Coste, Sarah; Roullet, Jean Baptiste; Phanouvang, Thongchan; Orwoll, Eric; Orwoll, Shiela; McCarron, David A.

    2002-01-01

    To determine the influence of dietary calcium on spaceflight-induced alterations in calcium metabolism and blood pressure (BP), 9-wk-old spontaneously hypertensive rats, fed either high- (2%) or low-calcium (0.02%) diets, were flown on an 18-day shuttle flight. On landing, flight animals had increased ionized calcium (P < 0.001), elevated parathyroid hormone levels (P < 0.001), reduced calcitonin levels (P < 0.05), unchanged 1,25(OH)(2)D(3) levels, and elevated skull (P < 0.01) and reduced femur bone mineral density. Basal and thrombin-stimulated platelet free calcium (intracellular calcium concentration) were also reduced (P < 0.05). There was a tendency for indirect systolic BP to be reduced in conscious flight animals (P = 0.057). However, mean arterial pressure was elevated (P < 0.001) after anesthesia. Dietary calcium altered all aspects of calcium metabolism (P < 0.001), as well as BP (P < 0.001), but the only interaction with flight was a relatively greater increase in ionized calcium in flight animals fed low- compared with high-calcium diets (P < 0.05). The results indicate that 1) flight-induced disruptions of calcium metabolism are relatively impervious to dietary calcium in the short term, 2) increased ionized calcium did not normalize low-calcium-induced elevations of BP, and 3) parathyroid hormone was paradoxically increased in the high-calcium-fed flight animals after landing.

  19. The Edinburgh human metabolic network reconstruction and its functional analysis

    PubMed Central

    Ma, Hongwu; Sorokin, Anatoly; Mazein, Alexander; Selkov, Alex; Selkov, Evgeni; Demin, Oleg; Goryanin, Igor

    2007-01-01

    A better understanding of human metabolism and its relationship with diseases is an important task in human systems biology studies. In this paper, we present a high-quality human metabolic network manually reconstructed by integrating genome annotation information from different databases and metabolic reaction information from literature. The network contains nearly 3000 metabolic reactions, which were reorganized into about 70 human-specific metabolic pathways according to their functional relationships. By analysis of the functional connectivity of the metabolites in the network, the bow-tie structure, which was found previously by structure analysis, is reconfirmed. Furthermore, the distribution of the disease related genes in the network suggests that the IN (substrates) subset of the bow-tie structure has more flexibility than other parts. PMID:17882155

  20. Neurological Soft Signs Are Not “Soft” in Brain Structure and Functional Networks: Evidence From ALE Meta-Analysis

    PubMed Central

    Chan, Raymond C. K.

    2014-01-01

    Background: Neurological soft signs (NSS) are associated with schizophrenia and related psychotic disorders. NSS have been conventionally considered as clinical neurological signs without localized brain regions. However, recent brain imaging studies suggest that NSS are partly localizable and may be associated with deficits in specific brain areas. Method: We conducted an activation likelihood estimation meta-analysis to quantitatively review structural and functional imaging studies that evaluated the brain correlates of NSS in patients with schizophrenia and other psychotic disorders. Six structural magnetic resonance imaging (sMRI) and 15 functional magnetic resonance imaging (fMRI) studies were included. Results: The results from meta-analysis of the sMRI studies indicated that NSS were associated with atrophy of the precentral gyrus, the cerebellum, the inferior frontal gyrus, and the thalamus. The results from meta-analysis of the fMRI studies demonstrated that the NSS-related task was significantly associated with altered brain activation in the inferior frontal gyrus, bilateral putamen, the cerebellum, and the superior temporal gyrus. Conclusions: Our findings from both sMRI and fMRI meta-analyses further support the conceptualization of NSS as a manifestation of the “cerebello-thalamo-prefrontal” brain network model of schizophrenia and related psychotic disorders. PMID:23671197

  1. Thiamine in plants: aspects of its metabolism and functions.

    PubMed

    Goyer, Aymeric

    2010-10-01

    Thiamine diphosphate (vitamin B(1)) plays a fundamental role as an enzymatic cofactor in universal metabolic pathways including glycolysis, the pentose phosphate pathway, and the tricarboxylic acid cycle. In addition, thiamine diphosphate has recently been shown to have functions other than as a cofactor in response to abiotic and biotic stress in plants. Recently, several steps of the plant thiamine biosynthetic pathway have been characterized, and a mechanism of feedback regulation of thiamine biosynthesis via riboswitch has been unraveled. This review focuses on these most recent advances made in our understanding of thiamine metabolism and functions in plants. Phenotypes of plant mutants affected in thiamine biosynthesis are described, and genomics, proteomics, and metabolomics data that have increased further our knowledge of plant thiamine metabolic pathways and functions are summarized. Aspects of thiamine metabolism such as catabolism, salvage, and transport in plants are discussed.

  2. Microalgal Metabolic Network Model Refinement through High-Throughput Functional Metabolic Profiling

    PubMed Central

    Chaiboonchoe, Amphun; Dohai, Bushra Saeed; Cai, Hong; Nelson, David R.; Jijakli, Kenan; Salehi-Ashtiani, Kourosh

    2014-01-01

    Metabolic modeling provides the means to define metabolic processes at a systems level; however, genome-scale metabolic models often remain incomplete in their description of metabolic networks and may include reactions that are experimentally unverified. This shortcoming is exacerbated in reconstructed models of newly isolated algal species, as there may be little to no biochemical evidence available for the metabolism of such isolates. The phenotype microarray (PM) technology (Biolog, Hayward, CA, USA) provides an efficient, high-throughput method to functionally define cellular metabolic activities in response to a large array of entry metabolites. The platform can experimentally verify many of the unverified reactions in a network model as well as identify missing or new reactions in the reconstructed metabolic model. The PM technology has been used for metabolic phenotyping of non-photosynthetic bacteria and fungi, but it has not been reported for the phenotyping of microalgae. Here, we introduce the use of PM assays in a systematic way to the study of microalgae, applying it specifically to the green microalgal model species Chlamydomonas reinhardtii. The results obtained in this study validate a number of existing annotated metabolic reactions and identify a number of novel and unexpected metabolites. The obtained information was used to expand and refine the existing COBRA-based C. reinhardtii metabolic network model iRC1080. Over 254 reactions were added to the network, and the effects of these additions on flux distribution within the network are described. The novel reactions include the support of metabolism by a number of d-amino acids, l-dipeptides, and l-tripeptides as nitrogen sources, as well as support of cellular respiration by cysteamine-S-phosphate as a phosphorus source. The protocol developed here can be used as a foundation to functionally profile other microalgae such as known microalgae mutants and novel isolates. PMID:25540776

  3. Effects of estrogen on functional and neurological recovery after spinal cord injury: An experimental study with rats

    PubMed Central

    Letaif, Olavo Biraghi; Cristante, Alexandre Fogaça; de Barros Filho, Tarcísio Eloy Pessoa; Ferreira, Ricardo; dos Santos, Gustavo Bispo; da Rocha, Ivan Dias; Marcon, Raphael Martus

    2015-01-01

    OBJECTIVES: To evaluate the functional and histological effects of estrogen as a neuroprotective agent after a standard experimentally induced spinal cord lesion. METHODS: In this experimental study, 20 male Wistar rats were divided into two groups: one group with rats undergoing spinal cord injury (SCI) at T10 and receiving estrogen therapy with 17-beta estradiol (4mg/kg) immediately following the injury and after the placement of skin sutures and a control group with rats only subjected to SCI. A moderate standard experimentally induced SCI was produced using a computerized device that dropped a weight on the rat's spine from a height of 12.5 mm. Functional recovery was verified with the Basso, Beattie and Bresnahan scale on the 2nd, 7th, 14th, 21st, 28th, 35th and 42nd days after injury and by quantifying the motor-evoked potential on the 42nd day after injury. Histopathological evaluation of the SCI area was performed after euthanasia on the 42nd day. RESULTS: The experimental group showed a significantly greater functional improvement from the 28th to the 42nd day of observation compared to the control group. The experimental group showed statistically significant improvements in the motor-evoked potential compared with the control group. The results of pathological histomorphometry evaluations showed a better neurological recovery in the experimental group, with respect to the proportion and diameter of the quantified nerve fibers. CONCLUSIONS: Estrogen administration provided benefits in neurological and functional motor recovery in rats with SCI beginning at the 28th day after injury. PMID:26598084

  4. Metabolic Determinants of Mitochondrial Function in Oocytes.

    PubMed

    Seidler, Emily A; Moley, Kelle H

    2015-11-01

    Mitochondrial production of cellular energy is essential to oocyte function, zygote development and successful continuation of pregnancy. This review focuses on several key functions of healthy oocyte mitochondria and the effect of pathologic states such as aging, oxidative stress and apoptosis on these functions. The effect of these abnormal conditions is presented in terms of clinical presentations, specifically maternal obesity, diminished ovarian reserve and assisted reproductive technologies.

  5. Fatty acid metabolism in the regulation of T cell function.

    PubMed

    Lochner, Matthias; Berod, Luciana; Sparwasser, Tim

    2015-02-01

    The specific regulation of cellular metabolic processes is of major importance for directing immune cell differentiation and function. We review recent evidence indicating that changes in basic cellular lipid metabolism have critical effects on T cell proliferation and cell fate decisions. While induction of de novo fatty acid (FA) synthesis is essential for activation-induced proliferation and differentiation of effector T cells, FA catabolism via β-oxidation is important for the development of CD8(+) T cell memory as well as for the differentiation of CD4(+) regulatory T cells. We consider the influence of lipid metabolism and metabolic intermediates on the regulation of signaling and transcriptional pathways via post-translational modifications, and discuss how an improved understanding of FA metabolism may reveal strategies for manipulating immune responses towards therapeutic outcomes. PMID:25592731

  6. Dietary supplementation with omega-3 polyunsaturated fatty acids robustly promotes neurovascular restorative dynamics and improves neurological functions after stroke.

    PubMed

    Zhang, Wenting; Wang, Hailian; Zhang, Hui; Leak, Rehana K; Shi, Yejie; Hu, Xiaoming; Gao, Yanqin; Chen, Jun

    2015-10-01

    Stroke is a devastating neurological disease with no satisfactory therapies to preserve long-term neurological function, perhaps due to the sole emphasis on neuronal survival in most preclinical studies. Recent studies have revealed the importance of protecting multiple cell types in the injured brain, such as oligodendrocytes and components of the neurovascular unit, before long-lasting recovery of function can be achieved. For example, revascularization in the ischemic penumbra is critical to provide various neurotrophic factors that enhance the survival and activity of neurons and other progenitor cells, such as oligodendrocyte precursor cells. In the present study, we hypothesized that chronic dietary supplementation with fish oil promotes post-stroke angiogenesis, neurogenesis, and oligodendrogenesis, thereby leading to long-term functional improvements. Mice received dietary supplementation with n-3 PUFA-enriched fish oil for three months before and up to one month after stroke. As expected, dietary n-3 PUFAs significantly increased levels of n-3 PUFAs in the brain and improved long-term behavioral outcomes after cerebral ischemia. n-3 PUFAs also robustly improved revascularization and angiogenesis and boosted the survival of NeuN/BrdU labeled newborn neurons up to 35days after stroke injury. Furthermore, these pro-neurogenic effects were accompanied by robust oligodendrogenesis. Thus, this is the first study to demonstrate that chronic dietary intake of n-3 PUFAs is an effective prophylactic measure not only to protect against ischemic injury for the long term but also to actively promote neurovascular restorative dynamics and brain repair. PMID:25771800

  7. Restricted cooperative games on metabolic networks reveal functionally important reactions.

    PubMed

    Sajitz-Hermstein, Max; Nikoloski, Zoran

    2012-12-01

    Understanding the emerging properties of complex biological systems is in the crux of systems biology studies. Computational methods for elucidating the role of each component in the synergetic interplay can be used to identify targets for genetic and metabolic engineering. In particular, we aim at determining the importance of reactions in a metabolic network with respect to a specific biological function. Therefore, we propose a novel game-theoretic framework which integrates restricted cooperative games with the outcome of flux balance analysis. We define productivity games on metabolic networks and present an analysis of their unrestricted and restricted variants based on the game-theoretic solution concept of the Shapley value. Correspondingly, this concept provides a characterization of the robustness and functional centrality for each enzyme involved in a given metabolic network. Furthermore, the comparison of two different environments - feast and famine - demonstrates the dependence of the results on the imposed flux capacities.

  8. Diverse Activities of Histone Acylations Connect Metabolism to Chromatin Function.

    PubMed

    Dutta, Arnob; Abmayr, Susan M; Workman, Jerry L

    2016-08-18

    Modifications of histones play important roles in balancing transcriptional output. The discovery of acyl marks, besides histone acetylation, has added to the functional diversity of histone modifications. Since all modifications use metabolic intermediates as substrates for chromatin-modifying enzymes, the prevalent landscape of histone modifications in any cell type is a snapshot of its metabolic status. Here, we review some of the current findings of how differential use of histone acylations regulates gene expression as response to metabolic changes and differentiation programs. PMID:27540855

  9. Pathways and functions of gut microbiota metabolism impacting host physiology.

    PubMed

    Krishnan, Smitha; Alden, Nicholas; Lee, Kyongbum

    2015-12-01

    The bacterial populations in the human intestine impact host physiological functions through their metabolic activity. In addition to performing essential catabolic and biotransformation functions, the gut microbiota produces bioactive small molecules that mediate interactions with the host and contribute to the neurohumoral axes connecting the intestine with other parts of the body. This review discusses recent progress in characterizing the metabolic products of the gut microbiota and their biological functions, focusing on studies that investigate the responsible bacterial pathways and cognate host receptors. Several key areas are highlighted for future development: context-based analysis targeting pathways; integration of analytical approaches; metabolic modeling; and synthetic systems for in vivo manipulation of microbiota functions. Prospectively, these developments could further our mechanistic understanding of host-microbiota interactions.

  10. Insulin action in brain regulates systemic metabolism and brain function.

    PubMed

    Kleinridders, André; Ferris, Heather A; Cai, Weikang; Kahn, C Ronald

    2014-07-01

    Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in the brain leads to impairment of neuronal function and synaptogenesis. In addition, insulin signaling modulates phosphorylation of tau protein, an early component in the development of Alzheimer disease. Thus, alterations in insulin action in the brain can contribute to metabolic syndrome, and the development of mood disorders and neurodegenerative diseases.

  11. Metabolic Assessment of Suited Mobility Using Functional Tasks

    NASA Technical Reports Server (NTRS)

    Norcross, J. R.; McFarland, S. M.; Ploutz-Snyder, Robert

    2016-01-01

    Existing methods for evaluating extravehicular activity (EVA) suit mobility have typically focused on isolated joint range of motion or torque, but these techniques have little to do with how well a crewmember functionally performs in an EVA suit. To evaluate suited mobility at the system level through measuring metabolic cost (MC) of functional tasks.

  12. Common Polymorphisms in the Solute Carrier SLC30A10 are Associated With Blood Manganese and Neurological Function

    PubMed Central

    Kippler, Maria; Alhamdow, Ayman; Rahman, Syed Moshfiqur; Smith, Donald R.; Vahter, Marie; Lucchini, Roberto G.; Broberg, Karin

    2016-01-01

    Manganese (Mn) is an essential nutrient in humans, but excessive exposure to Mn may cause neurotoxicity. Despite homeostatic regulation, Mn concentrations in blood vary considerably among individuals. We evaluated if common single-nucleotide polymorphisms (SNPs) in SLC30A10, which likely encodes an Mn transporter, influence blood Mn concentrations and neurological function. We measured blood Mn concentrations by ICP-MS or atomic absorption spectroscopy and genotyped 2 SLC30A10 non-coding SNPs (rs2275707 and rs12064812) by TaqMan PCR in cohorts from Bangladesh (N = 406), the Argentinean Andes (N = 198), and Italy (N = 238). We also measured SLC30A10 expression in whole blood by TaqMan PCR in a sub-group (N = 101) from the Andean cohort, and neurological parameters (sway velocity and finger-tapping speed) in the Italian cohort. The rs2275707 variant allele was associated with increased Mn concentrations in the Andes (8%, P = .027) and Italy (10.6%, P = .012), but not as clear in Bangladesh (3.4%, P = .21; linear regression analysis adjusted for age, gender, and plasma ferritin). This allele was also associated with increased sway velocity (15%, P = .033; adjusted for age and sex) and reduced SLC30A10 expression (−24.6%, P = .029). In contrast, the rs12064812 variant homozygous genotype was associated with reduced Mn concentrations, particularly in the Italian cohort (−18.4%, P = .04), and increased finger-tapping speed (8.7%, P = .025). We show that common SNPs in SLC30A10 are associated with blood Mn concentrations in 3 unrelated cohorts and that their influence may be mediated by altered SLC30A10 expression. Moreover, the SNPs appeared to influence neurological functions independent of blood Mn concentrations, suggesting that SLC30A10 could regulate brain Mn levels. PMID:26628504

  13. Metabolism and epigenetics in the nervous system: Creating cellular fitness and resistance to neuronal death in neurological conditions via modulation of oxygen-, iron-, and 2-oxoglutarate-dependent dioxygenases.

    PubMed

    Karuppagounder, Saravanan S; Kumar, Amit; Shao, Diana S; Zille, Marietta; Bourassa, Megan W; Caulfield, Joseph T; Alim, Ishraq; Ratan, Rajiv R

    2015-12-01

    Modern definitions of epigenetics incorporate models for transient but biologically important changes in gene expression that are unrelated to DNA code but responsive to environmental changes such as injury-induced stress. In this scheme, changes in oxygen levels (hypoxia) and/or metabolic co-factors (iron deficiency or diminished 2-oxoglutarate levels) are transduced into broad genetic programs that return the cell and the organism to a homeostatic set point. Over the past two decades, exciting studies have identified a superfamily of iron-, oxygen-, and 2-oxoglutarate-dependent dioxygenases that sit in the nucleus as modulators of transcription factor stability, co-activator function, histone demethylases, and DNA demethylases. These studies have provided a concrete molecular scheme for how changes in metabolism observed in a host of neurological conditions, including stroke, traumatic brain injury, and Alzheimer's disease, could be transduced into adaptive gene expression to protect the nervous system. We will discuss these enzymes in this short review, focusing primarily on the ten eleven translocation (TET) DNA demethylases, the jumonji (JmJc) histone demethylases, and the oxygen-sensing prolyl hydroxylase domain enzymes (HIF PHDs). This article is part of a Special Issue entitled SI: Neuroprotection. PMID:26232572

  14. Circadian rhythms in myocardial metabolism and function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circadian rhythms in myocardial function and dysfunction are firmly established in both animal models and humans. For example, the incidence of arrhythmias and sudden cardiac death increases when organisms awaken. Such observations have classically been explained by circadian rhythms in neurohumoral...

  15. The role of long non-coding RNAs in neurodevelopment, brain function and neurological disease.

    PubMed

    Roberts, Thomas C; Morris, Kevin V; Wood, Matthew J A

    2014-09-26

    Long non-coding RNAs (lncRNAs) are transcripts with low protein-coding potential that represent a large proportion of the transcriptional output of the cell. Many lncRNAs exhibit features indicative of functionality including tissue-restricted expression, localization to distinct subcellular structures, regulated expression and evolutionary conservation. Some lncRNAs have been shown to associate with chromatin-modifying activities and transcription factors, suggesting that a common mode of action may be to guide protein complexes to target genomic loci. However, the functions (if any) of the vast majority of lncRNA transcripts are currently unknown, and the subject of investigation. Here, we consider the putative role(s) of lncRNAs in neurodevelopment and brain function with an emphasis on the epigenetic regulation of gene expression. Associations of lncRNAs with neurodevelopmental/neuropsychiatric disorders, neurodegeneration and brain cancers are also discussed.

  16. Adult neurology training during child neurology residency.

    PubMed

    Schor, Nina F

    2012-08-21

    As it is currently configured, completion of child neurology residency requires performance of 12 months of training in adult neurology. Exploration of whether or not this duration of training in adult neurology is appropriate for what child neurology is today must take into account the initial reasons for this requirement and the goals of adult neurology training during child neurology residency.

  17. [Basic mechanisms: structure, function and metabolism of plasma lipoproteins].

    PubMed

    Errico, Teresa L; Chen, Xiangyu; Martin Campos, Jesús M; Julve, Josep; Escolà-Gil, Joan Carles; Blanco-Vaca, Francisco

    2013-01-01

    The aim of this work is to present basic information on the lipoprotein physiology. The protein fraction of lipoproteins consists of several apolipoproteins and enzymes whose functions are lipid transport and metabolism. Classification of lipoproteins is based on their density. Chylomicrons, VLDL, IDL, LDL and HDL can be isolated by ultracentrifugation. Both chylomicrons- and VLDL-triglycerides are transported from the intestine and liver, respectively, to the peripheral tissues. The metabolism of VLDL originates IDL and LDL. LDL is the main transporter of cholesterol to extrahepatic tissues. HDL mobilizes cholesterol from peripheral tissues to the liver where it is secreted to bile as free cholesterol or bile salts, a process termed reverse cholesterol transport. Lipoprotein metabolism can be regulated by nuclear receptors that regulate the expression of genes involved in triglyceride and apolipoprotein metabolism. PMID:23769508

  18. [Basic mechanisms: structure, function and metabolism of plasma lipoproteins].

    PubMed

    Errico, Teresa L; Chen, Xiangyu; Martin Campos, Jesús M; Julve, Josep; Escolà-Gil, Joan Carles; Blanco-Vaca, Francisco

    2013-01-01

    The aim of this work is to present basic information on the lipoprotein physiology. The protein fraction of lipoproteins consists of several apolipoproteins and enzymes whose functions are lipid transport and metabolism. Classification of lipoproteins is based on their density. Chylomicrons, VLDL, IDL, LDL and HDL can be isolated by ultracentrifugation. Both chylomicrons- and VLDL-triglycerides are transported from the intestine and liver, respectively, to the peripheral tissues. The metabolism of VLDL originates IDL and LDL. LDL is the main transporter of cholesterol to extrahepatic tissues. HDL mobilizes cholesterol from peripheral tissues to the liver where it is secreted to bile as free cholesterol or bile salts, a process termed reverse cholesterol transport. Lipoprotein metabolism can be regulated by nuclear receptors that regulate the expression of genes involved in triglyceride and apolipoprotein metabolism.

  19. Metabolism Is Central to Tolerogenic Dendritic Cell Function

    PubMed Central

    Sim, Wen Jing; Ahl, Patricia Jennifer; Connolly, John Edward

    2016-01-01

    Immunological tolerance is a fundamental tenant of immune homeostasis and overall health. Self-tolerance is a critical component of the immune system that allows for the recognition of self, resulting in hyporeactivity instead of immunogenicity. Dendritic cells are central to the establishment of dominant immune tolerance through the secretion of immunosuppressive cytokines and regulatory polarization of T cells. Cellular metabolism holds the key to determining DC immunogenic or tolerogenic cell fate. Recent studies have demonstrated that dendritic cell maturation leads to a shift toward a glycolytic metabolic state and preferred use of glucose as a carbon source. In contrast, tolerogenic dendritic cells favor oxidative phosphorylation and fatty acid oxidation. This dichotomous metabolic reprogramming of dendritic cells drives differential cellular function and plays a role in pathologies, such as autoimmune disease. Pharmacological alterations in metabolism have promising therapeutic potential. PMID:26980944

  20. Dose–effect relationships between manganese exposure and neurological, neuropsychological and pulmonary function in confined space bridge welders

    PubMed Central

    Bowler, Rosemarie M; Roels, Harry A; Nakagawa, Sanae; Drezgic, Marija; Diamond, Emily; Park, Robert; Koller, William; Bowler, Russell P; Mergler, Donna; Bouchard, Maryse; Smith, Donald; Gwiazda, Roberto; Doty, Richard L

    2007-01-01

    Background Although adverse neuropsychological and neurological health effects are well known among workers with high manganese (Mn) exposures in mining, ore‐processing and ferroalloy production, the risks among welders with lower exposures are less well understood. Methods Confined space welding in construction of a new span of the San Francisco–Oakland Bay Bridge without adequate protection was studied using a multidisciplinary method to identify the dose–effect relationship between adverse health effects and Mn in air or whole blood. Bridge welders (n = 43) with little or no personal protection equipment and exposed to a welding fume containing Mn, were administered neurological, neuropsychological, neurophysiological and pulmonary tests. Outcome variables were analysed in relation to whole blood Mn (MnB) and a Cumulative Exposure Index (CEI) based on Mn‐air, duration and type of welding. Welders performed a mean of 16.5 months of welding on the bridge, were on average 43.8 years of age and had on average 12.6 years of education. Results The mean time weighted average of Mn‐air ranged from 0.11–0.46 mg/m3 (55% >0.20 mg/m3). MnB >10 µg/l was found in 43% of the workers, but the concentrations of Mn in urine, lead in blood and copper and iron in plasma were normal. Forced expiratory volume at 1s: forced vital capacity ratios (FEV1/FVC) were found to be abnormal in 33.3% of the welders after about 1.5 years of welding at the bridge. Mean scores of bradykinesia and Unified Parkinson Disease Rating Scale exceeded 4 and 6, respectively. Computer assisted tremor analysis system hand tremor and body sway tests, and University of Pennsylvania Smell Identification Test showed impairment in 38.5/61.5, 51.4 and 88% of the welders, respectively. Significant inverse dose–effect relationships with CEI and/or MnB were found for IQ (p⩽0.05), executive function (p⩽0.03), sustaining concentration and sequencing (p⩽0.04), verbal learning (p

  1. Left Brain vs. Right Brain: Findings on Visual Spatial Capacities and the Functional Neurology of Giftedness

    ERIC Educational Resources Information Center

    Kalbfleisch, M. Layne; Gillmarten, Charles

    2013-01-01

    As neuroimaging technologies increase their sensitivity to assess the function of the human brain and results from these studies draw the attention of educators, it becomes paramount to identify misconceptions about what these data illustrate and how these findings might be applied to educational contexts. Some of these "neuromyths" have…

  2. Neurology of Affective Prosody and Its Functional-Anatomic Organization in Right Hemisphere

    ERIC Educational Resources Information Center

    Ross, Elliott D.; Monnot, Marilee

    2008-01-01

    Unlike the aphasic syndromes, the organization of affective prosody in brain has remained controversial because affective-prosodic deficits may occur after left or right brain damage. However, different patterns of deficits are observed following left and right brain damage that suggest affective prosody is a dominant and lateralized function of…

  3. Positron emission tomographic scan investigations of Huntington's disease: cerebral metabolic correlates of cognitive function

    SciTech Connect

    Berent, S.; Giordani, B.; Lehtinen, S.; Markel, D.; Penney, J.B.; Buchtel, H.A.; Starosta-Rubinstein, S.; Hichwa, R.; Young, A.B.

    1988-06-01

    Fifteen drug-free patients with early to mid-stage Huntington's disease (HD) were evaluated with positron emission tomographic (PET) scans of /sup 18/F-2-fluoro-2-deoxy-D-glucose uptake and quantitative measures of neurological function, learning, memory, and general intelligence. In comparison with a group of normal volunteers, the HD patients showed lower metabolism in both caudate (p less than 0.001) and putamen (p less than 0.001) on PET scans. A significant and positive relationship was found between neuropsychological measures of verbal learning and memory and caudate metabolism in the patient group but not in the normal group. Visual-spatial learning did not reflect a similar pattern, but performance intelligence quotient was positively related to both caudate and putamen metabolism in the HD group. Vocabulary level was unrelated to either brain structure. Discussion focuses on these and other observed brain-behavior relationships and on the implications of these findings for general behaviors such as those involved in coping and adaptation.

  4. Phosphatidylserine in the brain: metabolism and function.

    PubMed

    Kim, Hee-Yong; Huang, Bill X; Spector, Arthur A

    2014-10-01

    Phosphatidylserine (PS) is the major anionic phospholipid class particularly enriched in the inner leaflet of the plasma membrane in neural tissues. PS is synthesized from phosphatidylcholine or phosphatidylethanolamine by exchanging the base head group with serine, and this reaction is catalyzed by phosphatidylserine synthase 1 and phosphatidylserine synthase 2 located in the endoplasmic reticulum. Activation of Akt, Raf-1 and protein kinase C signaling, which supports neuronal survival and differentiation, requires interaction of these proteins with PS localized in the cytoplasmic leaflet of the plasma membrane. Furthermore, neurotransmitter release by exocytosis and a number of synaptic receptors and proteins are modulated by PS present in the neuronal membranes. Brain is highly enriched with docosahexaenoic acid (DHA), and brain PS has a high DHA content. By promoting PS synthesis, DHA can uniquely expand the PS pool in neuronal membranes and thereby influence PS-dependent signaling and protein function. Ethanol decreases DHA-promoted PS synthesis and accumulation in neurons, which may contribute to the deleterious effects of ethanol intake. Improvement of some memory functions has been observed in cognitively impaired subjects as a result of PS supplementation, but the mechanism is unclear.

  5. Vitamin D metabolism, sex hormones, and male reproductive function.

    PubMed

    Blomberg Jensen, Martin

    2012-08-01

    The spectrum of vitamin D (VD)-mediated effects has expanded in recent years, and VD is now recognized as a versatile signaling molecule rather than being solely a regulator of bone health and calcium homeostasis. One of the recently identified target areas of VD is male reproductive function. The VD receptor (VDR) and the VD metabolizing enzyme expression studies documented the presence of this system in the testes, mature spermatozoa, and ejaculatory tract, suggesting that both systemic and local VD metabolism may influence male reproductive function. However, it is still debated which cell is the main VD target in the testis and to what extent VD is important for sex hormone production and function of spermatozoa. This review summarizes descriptive studies on testicular VD metabolism and spatial distribution of VDR and the VD metabolizing enzymes in the mammalian testes and discusses mechanistic and association studies conducted in animals and humans. The reviewed evidence suggests some effects of VD on estrogen and testosterone biosynthesis and implicates involvement of both systemic and local VD metabolism in the regulation of male fertility potential.

  6. Contribution of Metabolic Reprogramming to Macrophage Plasticity and Function

    PubMed Central

    El Kasmi, Karim C.; Stenmark, Kurt R.

    2015-01-01

    Macrophages display a spectrum of functional activation phenotypes depending on the composition of the microenvironment they reside in, including type of tissue/organ and character of injurious challenge they are exposed to. Our understanding of how macrophage plasticity is regulated by the local microenvironment is still limited. Here we review and discuss the recent literature regarding the contribution of cellular metabolic pathways to the ability of the macrophage to sense the microenvironment and to alter its function. We propose that distinct alterations in the microenvironment induce a spectrum of inducible and reversible metabolic programs that might form the basis of the inducible and reversible spectrum of functional macrophage activation/polarization phenotypes. We highlight that metabolic pathways in the bidirectional communication between macrophages and stromals cells are an important component of chronic inflammatory conditions. Recent work demonstrates that inflammatory macrophage activation is tightly associated with metabolic reprogramming to aerobic glycolysis, an altered TCA cycle, and reduced mitochondrial respiration. We review cytosolic and mitochondrial mechanisms that promote initiation and maintenance of macrophage activation as they relate to increased aerobic glycolysis and highlight potential pathways through which anti-inflammatory IL-10 could promote macrophage deactivation. Finally, we propose that in addition to their role in energy generation and regulation of apoptosis, mitochondria reprogram their metabolism to also participate regulating macrophage activation and plasticity. PMID:26454572

  7. Metabolism and functions of lipids in myelin.

    PubMed

    Schmitt, Sebastian; Castelvetri, Ludovici Cantuti; Simons, Mikael

    2015-08-01

    Rapid conduction of nerve impulses requires coating of axons by myelin sheaths, which are lipid-rich and multilamellar membrane stacks. The lipid composition of myelin varies significantly from other biological membranes. Studies in mutant mice targeting various lipid biosynthesis pathways have shown that myelinating glia have a remarkable capacity to compensate the lack of individual lipids. However, compensation fails when it comes to maintaining long-term stability of myelin. Here, we summarize how lipids function in myelin biogenesis, axon-glia communication and in supporting long-term maintenance of myelin. We postulate that change in myelin lipid composition might be relevant for our understanding of aging and demyelinating diseases. This article is part of a Special Issue titled Brain Lipids.

  8. The body electric: a long view of electrical therapy for functional neurological disorders.

    PubMed

    McWhirter, Laura; Carson, Alan; Stone, Jon

    2015-04-01

    The use of electricity in medical treatment has always been technology-driven, rather than aetiology-driven; as new techniques have appeared, clinicians have quickly looked to try them in the treatment of all sorts of conditions where existing treatment options are limited. Functional disorders--as identified anachronistically in our analysis--have been key contenders for emerging electrical treatments: with Leyden jars, with galvanic and electromagnetic machines, and more recently with TMS and TENS. Parallels can be drawn with the history of electrical treatments for migraine and headache (Koehler and Boes, 2010). Regardless of the mode of delivery of electricity, stimulating a limb to produce movement has repeatedly been found to aid and assist recovery in functional motor disorders. This may also be true of non-electrical methods: we have found benefits using both therapeutic sedation and explanatory demonstration of a positive Hoover's sign as therapeutic methods of demonstrating normal movement in functionally weak limbs (Stone et al., 2014). Each surge in enthusiasm for new electrical treatments has been followed by questions about the nature of the disorder and validity of the treatment response. Physicians have tended to attribute therapeutic success initially to powerful biological or even metaphysical effects, but with time and experience these explanations have been replaced by views that the treatment works through suggestion and placebo. Discomfort with these conclusions has in the past discouraged ongoing development of electrical treatments, even if the end result for patients has been encouraging. In Edwards's Bayesian model, functional motor and sensory symptoms are hypothesized to arise when 'pathologically precise prior beliefs' mediated by attentional processes cause experience of symptoms via a hierarchy of false inferences (Edwards, 2012). It can be argued that use of TMS or peripheral stimulation to produce movement of a functionally weak

  9. Functional neurology of a brain system: a 3D olfactory bulb model to process natural odorants.

    PubMed

    Migliore, Michele; Cavarretta, Francesco; Hines, Michael L; Shepherd, Gordon M

    2013-01-01

    The network of interactions between mitral and granule cells in the olfactory bulb is a critical step in the processing of odor information underlying the neural basis of smell perception. We are building the first computational model in 3 dimensions of this network in order to analyze the rules for connectivity and function within it. The initial results indicate that this network can be modeled to simulate experimental results on the activation of the olfactory bulb by natural odorants, providing a much more powerful approach for 3D simulation of brain neurons and microcircuits.

  10. Pelizaeus-Merzbacher disease: an X-linked neurologic disorder of myelin metabolism with a novel mutation in the gene encoding proteolipid protein.

    PubMed Central

    Gencic, S; Abuelo, D; Ambler, M; Hudson, L D

    1989-01-01

    The nosology of the inborn errors of myelin metabolism has been stymied by the lack of molecular genetic analysis. Historically, Pelizaeus-Merzbacher disease has encompassed a host of neurologic disorders that present with a deficit of myelin, the membrane elaborated by glial cells that encircles and successively enwraps axons. We describe here a Pelizaeus-Merzbacher pedigree of the classical type, with X-linked inheritance, a typical clinical progression, and a pathologic loss of myelinating cells and myelin in the central nervous system. To discriminate variants of Pelizaeus-Merzbacher disease, a set of oligonucleotide primers was constructed to polymerase-chain-reaction (PCR) amplify and sequence the gene encoding proteolipid protein (PLP), a structural protein that comprises half of the protein of the myelin sheath. The PLP gene in one of two affected males and the carrier mother of this family exhibited a single base difference in the more than 2 kb of the PLP gene sequenced, a C----T transition that would create a serine substitution for proline at the carboxy end of the protein. Our results delineate the clinical features of Pelizaeus-Merzbacher disease, define the possible molecular pathology of this dysmyelinating disorder, and address the molecular classification of inborn errors of myelin metabolism. Patients with the classical form (type I) and the more severely affected, connatal variant of Pelizaeus-Merzbacher disease (type II) would be predicted to display mutation at the PLP locus. The other variants (types III-VI), which have sometimes been categorized as Pelizaeus-Merzbacher disease, may represent mutations in genes encoding other structural myelin proteins or proteins critical to myelination. Images Figure 2 Figure 3 Figure 5 Figure 6 PMID:2773936

  11. Occupational neurology.

    PubMed

    Feldman, R G

    1987-01-01

    The nervous system is vulnerable to the effects of certain chemicals and physical conditions found in the work environment. The activities of an occupational neurologist focus on the evaluation of patients with neurological disorders caused by occupational or environmental conditions. When one is making a differential diagnosis in patients with neurological disorders, the possibility of toxic exposure or encounters with physical factors in the workplace must not be overlooked. Central to an accurate clinical diagnosis is the patient's history. A diagnosis of an occupational or environmental neurological problem requires a careful assessment of the clinical abnormalities and confirmation of these disabilities by objective tests such as nerve conduction velocity, evoked potentials, electroencephalogram, neuropsychological batteries, or nerve biopsy. On the basis of information about hazards in the workplace, safety standards and environmental and biological monitoring can be implemented in the workplace to reduce the risks of undue injury. Clinical manifestations of headache, memory disturbance, and peripheral neuropathy are commonly encountered presentations of the effects of occupational hazards. Physicians in everyday clinical practice must be aware of the signs and symptoms associated with exposure to possible neurotoxins and work methods. Occupational and environmental circumstances must be explored when evaluating patients with neurologic disorders.

  12. [Nineteen cases of school-aged children with degenerative or metabolic neurological disorders initially presenting with learning difficulty and/or behavior disturbance].

    PubMed

    Honzawa, Shiho; Sugai, Kenji; Akaike, Hiroto; Nakayama, Tojo; Fujikawa, Yoshinao; Komaki, Hirofumi; Nakagawa, Eiji; Sasaki, Masayuki

    2012-07-01

    We reported 19 cases of school-aged children. They were initially judged to have learning difficulty or school maladaptation because of attention deficits, hyperactive behaviors or poor school performance, followed by the diagnosis such as degenerative or metabolic neurological diseases. The patients consisted of 4 cases of adrenoleukodystrophy, 5 cases of dentatorubral-pallidoluysian atrophy, 3 cases of Sanfilippo syndrome, 3 cases of subacute sclerosing panencephalitis, and each one case of juvenile Gaucher disease, juvenile Huntington disease, juvenile metachromatic leukodystrophy and Leigh disease. They had markedly poor school performance, and/or abnormal behaviors, followed by seizures, character disorders or psychomotor regression. The diagnostic clues included brain CT scan and/or MRI, peculiar facial appearance and notable family histories. When the children were indicated to have learning difficulty or maladjustment to school life, we should make deliberate differential diagnoses before concluding that they have a learning disorder and/or attention-deficit/hyperactivity disorder. Instead they should be recommended to visit child neurologists, when they present with any problems as aforesaid.

  13. Decreased in vitro mitochondrial function is associated with enhanced brain metabolism, blood flow, and memory in Surf1-deficient mice.

    PubMed

    Lin, Ai-Ling; Pulliam, Daniel A; Deepa, Sathyaseelan S; Halloran, Jonathan J; Hussong, Stacy A; Burbank, Raquel R; Bresnen, Andrew; Liu, Yuhong; Podlutskaya, Natalia; Soundararajan, Anuradha; Muir, Eric; Duong, Timothy Q; Bokov, Alex F; Viscomi, Carlo; Zeviani, Massimo; Richardson, Arlan G; Van Remmen, Holly; Fox, Peter T; Galvan, Veronica

    2013-10-01

    Recent studies have challenged the prevailing view that reduced mitochondrial function and increased oxidative stress are correlated with reduced longevity. Mice carrying a homozygous knockout (KO) of the Surf1 gene showed a significant decrease in mitochondrial electron transport chain Complex IV activity, yet displayed increased lifespan and reduced brain damage after excitotoxic insults. In the present study, we examined brain metabolism, brain hemodynamics, and memory of Surf1 KO mice using in vitro measures of mitochondrial function, in vivo neuroimaging, and behavioral testing. We show that decreased respiration and increased generation of hydrogen peroxide in isolated Surf1 KO brain mitochondria are associated with increased brain glucose metabolism, cerebral blood flow, and lactate levels, and with enhanced memory in Surf1 KO mice. These metabolic and functional changes in Surf1 KO brains were accompanied by higher levels of hypoxia-inducible factor 1 alpha, and by increases in the activated form of cyclic AMP response element-binding factor, which is integral to memory formation. These findings suggest that Surf1 deficiency-induced metabolic alterations may have positive effects on brain function. Exploring the relationship between mitochondrial activity, oxidative stress, and brain function will enhance our understanding of cognitive aging and of age-related neurologic disorders.

  14. RELATIONSHIP BETWEEN INSULIN-RESISTANCE PROCESSING SPEED AND SPECIFIC EXECUTIVE FUNCTION PROFILES IN NEUROLOGICALLY-INTACT OLDER ADULTS

    PubMed Central

    Frazier, Darvis T.; Bettcher, Brianne M.; Dutt, Shubir; Patel, Nihar; Mungas, Dan; Miller, Joshua; Green, Ralph; Kramer, Joel H.

    2016-01-01

    Objective This study investigated the relationship between insulin-resistance and constituent components of executive function in a sample of neurologically-intact older adult subjects using the homeostasis model assessment (HOMA-IR) and latent factors of working memory, cognitive control and processing speed derived from confirmatory factor analysis. Low-density lipoprotein (LDL), mean arterial pressure (MAP), along with body mass index (BMI) and white matter hypointensity (WMH) were used to control for vascular risk factors, adiposity and cerebrovascular injury. Methods The study included 119 elderly subjects recruited from the University of California, San Francisco Memory and Aging Center. Subjects underwent neuropsychological assessment, fasting blood draw and brain magnetic resonance imaging (MRI). Partial correlations and linear regression models were used to examine the HOMA-IR-executive function relationship. Results Pearson correlation adjusting for age showed a significant relationship between HOMA-IR and working memory (rp=−.18, p=.047), a trend with cognitive control (rp=−.17, p=.068), and no relationship with processing speed (rp=.013, p=.892). Linear regression models adjusting for demographic factors (age, education and gender), LDL, MAP, BMI and WMH indicated that HOMA-IR was negatively associated with cognitive control (r=−.256; p=.026) and working memory (r=−.234; p=.054). Conclusions These results suggest a greater level of peripheral insulin-resistance is associated with decreased cognitive control and working memory. After controlling for demographic factors, vascular risk, adiposity and cerebrovascular injury, HOMA-IR remained significantly associated with cognitive control, with working memory showing a trend. These findings substantiate the insulin-resistance-executive function hypothesis and suggest a complex interaction, demonstrated by the differential impact of insulin-resistance on processing speed and specific aspects of

  15. Metabolic Functions of the Lung, Disorders and Associated Pathologies.

    PubMed

    Alvarado, Alcibey; Arce, Isabel

    2016-10-01

    The primary function of the lungs is gas exchange. Approximately 400 million years ago, the Earth's atmosphere gained enough oxygen in the gas phase for the animals that emerged from the sea to breathe air. The first lungs were merely primitive air sacs with a few vessels in the walls that served as accessory organs of gas exchange to supplement the gills. Eons later, as animals grew accustomed to a solely terrestrial life, the lungs became highly compartmentalized to provide the vast air-blood surface necessary for O2 uptake and CO2 elimination, and a respiratory control system was developed to regulate breathing in accordance with metabolic demands and other needs. With the evolution and phylogenetic development, lungs were taking a variety of other specialized functions to maintain homeostasis, which we will call the non-respiratory functions of the lung and that often, and by mistake, are believed to have little or no connection with the replacement gas. In this review, we focus on the metabolic functions of the lung, perhaps the least known, and mainly, in the lipid metabolism and blood-adult lung vascular endothelium interaction. When these functions are altered, respiratory disorders or diseases appear, which are discussed concisely, emphasizing how they impact the most important function of the lungs: external respiration. PMID:27635172

  16. Metabolic Functions of the Lung, Disorders and Associated Pathologies

    PubMed Central

    Alvarado, Alcibey; Arce, Isabel

    2016-01-01

    The primary function of the lungs is gas exchange. Approximately 400 million years ago, the Earth’s atmosphere gained enough oxygen in the gas phase for the animals that emerged from the sea to breathe air. The first lungs were merely primitive air sacs with a few vessels in the walls that served as accessory organs of gas exchange to supplement the gills. Eons later, as animals grew accustomed to a solely terrestrial life, the lungs became highly compartmentalized to provide the vast air-blood surface necessary for O2 uptake and CO2 elimination, and a respiratory control system was developed to regulate breathing in accordance with metabolic demands and other needs. With the evolution and phylogenetic development, lungs were taking a variety of other specialized functions to maintain homeostasis, which we will call the non-respiratory functions of the lung and that often, and by mistake, are believed to have little or no connection with the replacement gas. In this review, we focus on the metabolic functions of the lung, perhaps the least known, and mainly, in the lipid metabolism and blood-adult lung vascular endothelium interaction. When these functions are altered, respiratory disorders or diseases appear, which are discussed concisely, emphasizing how they impact the most important function of the lungs: external respiration.

  17. Metabolic Functions of the Lung, Disorders and Associated Pathologies

    PubMed Central

    Alvarado, Alcibey; Arce, Isabel

    2016-01-01

    The primary function of the lungs is gas exchange. Approximately 400 million years ago, the Earth’s atmosphere gained enough oxygen in the gas phase for the animals that emerged from the sea to breathe air. The first lungs were merely primitive air sacs with a few vessels in the walls that served as accessory organs of gas exchange to supplement the gills. Eons later, as animals grew accustomed to a solely terrestrial life, the lungs became highly compartmentalized to provide the vast air-blood surface necessary for O2 uptake and CO2 elimination, and a respiratory control system was developed to regulate breathing in accordance with metabolic demands and other needs. With the evolution and phylogenetic development, lungs were taking a variety of other specialized functions to maintain homeostasis, which we will call the non-respiratory functions of the lung and that often, and by mistake, are believed to have little or no connection with the replacement gas. In this review, we focus on the metabolic functions of the lung, perhaps the least known, and mainly, in the lipid metabolism and blood-adult lung vascular endothelium interaction. When these functions are altered, respiratory disorders or diseases appear, which are discussed concisely, emphasizing how they impact the most important function of the lungs: external respiration. PMID:27635172

  18. Rare diseases: matching wheelchair users with rare metabolic, neuromuscular or neurological disorders to electric powered indoor/outdoor wheelchairs (EPIOCs)

    PubMed Central

    De Souza, Lorraine H.; Frank, Andrew O.

    2016-01-01

    Abstract Purpose: To describe the clinical features of electric powered indoor/outdoor wheelchair (EPIOC) users with rare diseases (RD) impacting on EPIOC provision and seating. Method: Retrospective review by a consultant in rehabilitation medicine of electronic and case note records of EPIOC recipients with RDs attending a specialist wheelchair service between June 2007 and September 2008. Data were systematically extracted, entered into a database and analysed under three themes; demographic, diagnostic/clinical (including comorbidity and associated clinical features (ACFs) of the illness/disability) and wheelchair factors. Results: Fifty-four (27 male) EPIOC users, mean age 37.3 (SD 18.6, range 11–70) with RDs were identified and reviewed a mean of 64 (range 0–131) months after receiving their wheelchair. Diagnoses included 27 types of RDs including Friedreich’s ataxia, motor neurone disease, osteogenesis imperfecta, arthrogryposis, cerebellar syndromes and others. Nineteen users had between them 36 comorbidities and 30 users had 44 ACFs likely to influence the prescription. Tilt-in-space was provided to 34 (63%) users and specialised seating to 17 (31%). Four users had between them complex control or interfacing issues. Conclusions: The complex and diverse clinical problems of those with RDs present unique challenges to the multiprofessional wheelchair team to maintain successful independent mobility and community living.Implications for RehabilitationPowered mobility is a major therapeutic tool for those with rare diseases enhancing independence, participation, reducing pain and other clinical features.The challenge for rehabilitation professionals is reconciling the physical disabilities with the individual’s need for function and participation whilst allowing for disease progression and/or growth.Powered wheelchair users with rare diseases with a (kypho) scoliosis require a wheelchair system that balances spine stability and movement to maximise

  19. Metabolic functions of FABPs— mechanisms and therapeutic implications

    PubMed Central

    Hotamisligil, Gökhan S.; Bernlohr, David A.

    2015-01-01

    Intracellular and extracellular interactions with proteins enables the functional and mechanistic diversity of lipids. Fatty acid-binding proteins (FABPs) were originally described as intracellular proteins that can affect lipid fluxes, metabolism and signalling within cells. As the functions of this protein family have been further elucidated, it has become evident that they are critical mediators of metabolism and inflammatory processes, both locally and systemically, and therefore are potential therapeutic targets for immunometabolic diseases. In particular, genetic deficiency and small molecule-mediated inhibition of FABP4 (also known as aP2) and FABP5 can potently improve glucose homeostasis and reduce atherosclerosis in mouse models. Further research has shown that in addition to their intracellular roles, some FABPs are found outside the cells, and FABP4 undergoes regulated, vesicular secretion. The circulating form of FABP4 has crucial hormonal functions in systemic metabolism. In this Review we discuss the roles and regulation of both intracellular and extracellular FABP actions, highlighting new insights that might direct drug discovery efforts and opportunities for management of chronic metabolic diseases. PMID:26260145

  20. [Neurological rehabilitation].

    PubMed

    Hömberg, V

    2010-10-01

    This article describes state of the art concepts of neurological rehabilitation in Germany. In parallel to enormous growth of knowledge in the neurosciences also neurological rehabilitation has made significant progress. The increasing use of concepts of evidence based medicine and an early translation of knowledge from the neurosciences into clinical rehabilitation practice contribute to therapeutic advances. It is now widely accepted, that rehabilitation should start early and should be organized in a multidisciplinary professional team. Therapeutic procedures selected should be evidence based and have to be modified to find custom tailored solutions for individual patients. General rules derived from neuroscientific knowledge have been shown to be useful to design new therapeutic techniques. Neuromodulatory stimulation and special pharmacological treatments provide further options for enhancing results of rehabilitation.

  1. [Diagnosis of Alzheimer's disease in Brazil: cognitive and functional evaluation. Recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology].

    PubMed

    Nitrini, Ricardo; Caramelli, Paulo; Bottino, Cássio Machado de Campos; Damasceno, Benito Pereira; Brucki, Sonia Maria Dozzi; Anghinah, Renato

    2005-09-01

    The educational and cultural heterogeneity of the Brazilian population leads to peculiar characteristics regarding the diagnosis of Alzheimer's disease (AD). This consensus had the objective of recommending evidence-based guidelines for the clinical diagnosis of AD in Brazil. Studies on the diagnosis of AD published in Brazil were systematically evaluated in a thorough research of PUBMED and LILACS databases. For global cognitive evaluation, the Mini-Mental State Examination was recommended; for memory evaluation: delayed recall subtest of CERAD or of objects presented as drawings; attention: trail-making or digit-span; language: Boston naming, naming test from ADAS-Cog or NEUROPSI; executive functions: verbal fluency or clock-drawing; conceptualization and abstraction: similarities from CAMDEX or NEUROPSI; construction: drawings from CERAD. For functional evaluation, IQCODE, or Pfeffer Questionnaire or Bayer Scale for Activities of Daily Living was recommended. The panel concluded that the combined use of cognitive and functional evaluation based on interview with informant is recommended. PMID:16172733

  2. [Diagnosis of Alzheimer's disease in Brazil: cognitive and functional evaluation. Recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology].

    PubMed

    Nitrini, Ricardo; Caramelli, Paulo; Bottino, Cássio Machado de Campos; Damasceno, Benito Pereira; Brucki, Sonia Maria Dozzi; Anghinah, Renato

    2005-09-01

    The educational and cultural heterogeneity of the Brazilian population leads to peculiar characteristics regarding the diagnosis of Alzheimer's disease (AD). This consensus had the objective of recommending evidence-based guidelines for the clinical diagnosis of AD in Brazil. Studies on the diagnosis of AD published in Brazil were systematically evaluated in a thorough research of PUBMED and LILACS databases. For global cognitive evaluation, the Mini-Mental State Examination was recommended; for memory evaluation: delayed recall subtest of CERAD or of objects presented as drawings; attention: trail-making or digit-span; language: Boston naming, naming test from ADAS-Cog or NEUROPSI; executive functions: verbal fluency or clock-drawing; conceptualization and abstraction: similarities from CAMDEX or NEUROPSI; construction: drawings from CERAD. For functional evaluation, IQCODE, or Pfeffer Questionnaire or Bayer Scale for Activities of Daily Living was recommended. The panel concluded that the combined use of cognitive and functional evaluation based on interview with informant is recommended.

  3. Insulin Action in Brain Regulates Systemic Metabolism and Brain Function

    PubMed Central

    Kleinridders, André; Ferris, Heather A.; Cai, Weikang

    2014-01-01

    Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in the brain leads to impairment of neuronal function and synaptogenesis. In addition, insulin signaling modulates phosphorylation of tau protein, an early component in the development of Alzheimer disease. Thus, alterations in insulin action in the brain can contribute to metabolic syndrome, and the development of mood disorders and neurodegenerative diseases. PMID:24931034

  4. Type 2 diabetes mellitus and skeletal muscle metabolic function.

    PubMed

    Phielix, Esther; Mensink, Marco

    2008-05-23

    Type 2 diabetic patients are characterized by a decreased fat oxidative capacity and high levels of circulating free fatty acids (FFAs). The latter is known to cause insulin resistance, in particularly in skeletal muscle, by reducing insulin stimulated glucose uptake, most likely via accumulation of lipid inside the muscle cell. A reduced skeletal muscle oxidative capacity can exaggerate this. Furthermore, type 2 diabetes is associated with impaired metabolic flexibility, i.e. an impaired switching from fatty acid to glucose oxidation in response to insulin. Thus, a reduced fat oxidative capacity and metabolic inflexibility are important components of skeletal muscle insulin resistance. The cause of these derangements in skeletal muscle of type 2 diabetic patients remains to be elucidated. An impaired mitochondrial function is a likely candidate. Evidence from both in vivo and ex vivo studies supports the idea that an impaired skeletal muscle mitochondrial function is related to the development of insulin resistance and type 2 diabetes mellitus. A decreased mitochondrial oxidative capacity in skeletal muscle was revealed in diabetic patients, using in vivo 31-Phosphorus Magnetic Resonance Spectroscopy (31P-MRS). However, quantification of mitochondrial function using ex vivo high-resolution respirometry revealed opposite results. Future (human) studies should challenge this concept of impaired mitochondrial function underlying metabolic defects and prove if mitochondria are truly functional impaired in insulin resistance, or low in number, and whether it represents the primary starting point of pathogenesis of insulin resistance, or is just an other feature of the insulin resistant state. PMID:18342897

  5. Wearable accelerometry-based technology capable of assessing functional activities in neurological populations in community settings: a systematic review

    PubMed Central

    2014-01-01

    Background Integrating rehabilitation services through wearable systems has the potential to accurately assess the type, intensity, duration, and quality of movement necessary for procuring key outcome measures. Objectives This review aims to explore wearable accelerometry-based technology (ABT) capable of assessing mobility-related functional activities intended for rehabilitation purposes in community settings for neurological populations. In this review, we focus on the accuracy of ABT-based methods, types of outcome measures, and the implementation of ABT in non-clinical settings for rehabilitation purposes. Data sources Cochrane, PubMed, Web of Knowledge, EMBASE, and IEEE Xplore. The search strategy covered three main areas, namely wearable technology, rehabilitation, and setting. Study selection Potentially relevant studies were categorized as systems either evaluating methods or outcome parameters. Methods Methodological qualities of studies were assessed by two customized checklists, depending on their categorization and rated independently by three blinded reviewers. Results Twelve studies involving ABT met the eligibility criteria, of which three studies were identified as having implemented ABT for rehabilitation purposes in non-clinical settings. From the twelve studies, seven studies achieved high methodological quality scores. These studies were not only capable of assessing the type, quantity, and quality measures of functional activities, but could also distinguish healthy from non-healthy subjects and/or address disease severity levels. Conclusion While many studies support ABT’s potential for telerehabilitation, few actually utilized it to assess mobility-related functional activities outside laboratory settings. To generate more appropriate outcome measures, there is a clear need to translate research findings and novel methods into practice. PMID:24625308

  6. The Cognition Battery of the NIH Toolbox for Assessment of Neurological and Behavioral Function: Validation in an Adult Sample

    PubMed Central

    Weintraub, Sandra; Dikmen, Sureyya S.; Heaton, Robert K.; Tulsky, David S.; Zelazo, Philip David; Slotkin, Jerry; Carlozzi, Noelle E.; Bauer, Patricia J.; Wallner-Allen, Kathleen; Fox, Nathan; Havlik, Richard; Beaumont, Jennifer L.; Mungas, Dan; Manly, Jennifer J.; Moy, Claudia; Conway, Kevin; Edwards, Emmeline; Nowinski, Cindy J.; Gershon, Richard

    2014-01-01

    This paper introduces a special series on validity studies of the Cognition Battery (CB) from the U.S. National Institutes of Health Toolbox for the Assessment of Neurological and Behavioral Function (NIHTB) (R. C. Gershon et al., 2013) in an adult sample. This first paper in the series describes the sample, each of the seven instruments in the NIHTB-CB briefly, and the general approach to data analysis. Data are provided on test-retest reliability and practice effects, and raw scores (mean, standard deviation, range) are presented for each instrument and the gold standard instruments used to measure construct validity. Accompanying papers provide details on each instrument, including information about instrument development, psychometric properties, age and education effects on performance, and convergent and discriminant construct validity. One paper in the series is devoted to a factor analysis of the NIHTB-CB in adults and another describes the psychometric properties of three composite scores derived from the individual measures representing fluid and crystallized abilities and their combination. The NIHTB-CB is designed to provide a brief, comprehensive, common set of measures to allow comparisons among disparate studies and to improve scientific communication. PMID:24959840

  7. Thyroid function and metabolic state in chronic renal failure.

    PubMed

    Spector, D A; Davis, P J; Helderman, J H; Bell, B; Utiger, R D

    1976-12-01

    Thirty-eight patients with chronic renal insufficiency who were in a dialysis program underwent studies of thyroid function and metabolic status. Mean values for serum total and free thyroxine (T4) concentrations and thyroxine-binding globulin capacity were within normal limits. Although mean serum total triiodothyronine (T3) concentration was normal, 43% of the group had low serum T3 and 54% had low serum free T3 concentrations. Serum thyrotrophin (TSH) concentrations were normal in all but four subjects who had very slight elevations. Metabolic status was assessed by various metabolic tests; mean values for each of these tests were normal, and the clinical index scores indicated that all patients were euthyroid. Results of metabolic testing were similar in patients with low and those with normal serum T3 concentrations. Low serum T3 measurements did not accurately reflect metabolic state in patients with chronic renal failure, whereas serum free T4 and TSH concentrations were reliable indicators of thyroid state.

  8. The Tacrolimus Metabolism Rate Influences Renal Function after Kidney Transplantation

    PubMed Central

    Thölking, Gerold; Fortmann, Christian; Koch, Raphael; Gerth, Hans Ulrich; Pabst, Dirk; Pavenstädt, Hermann; Kabar, Iyad; Hüsing, Anna; Wolters, Heiner

    2014-01-01

    The effective calcineurin inhibitor (CNI) tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, as a potent CNI it has nephrotoxic potential leading to impaired renal function in some cases. Therefore, it is of high clinical impact to identify factors which can predict who is endangered to develop CNI toxicity. We hypothesized that the Tac metabolism rate expressed as the blood concentration normalized by the dose (C/D ratio) is such a simple predictor. Therefore, we analyzed the impact of the C/D ratio on kidney function after RTx. Renal function was analyzed 1, 2, 3, 6, 12 and 24 months after RTx in 248 patients with an immunosuppressive regimen including basiliximab, tacrolimus, mycophenolate mofetil and prednisolone. According to keep the approach simple, patients were split into three C/D groups: fast, intermediate and slow metabolizers. Notably, compared with slow metabolizers fast metabolizers of Tac showed significantly lower estimated glomerular filtration rate (eGFR) values at all the time points analyzed. Moreover, fast metabolizers underwent more indication renal biopsies (p = 0.006) which revealed a higher incidence of CNI nephrotoxicity (p = 0.015) and BK nephropathy (p = 0.024) in this group. We herein identified the C/D ratio as an easy calculable risk factor for the development of CNI nephrotoxicity and BK nephropathy after RTx. We propose that the simple C/D ratio should be taken into account early in patient’s risk management strategies. PMID:25340655

  9. The tacrolimus metabolism rate influences renal function after kidney transplantation.

    PubMed

    Thölking, Gerold; Fortmann, Christian; Koch, Raphael; Gerth, Hans Ulrich; Pabst, Dirk; Pavenstädt, Hermann; Kabar, Iyad; Hüsing, Anna; Wolters, Heiner; Reuter, Stefan; Suwelack, Barbara

    2014-01-01

    The effective calcineurin inhibitor (CNI) tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, as a potent CNI it has nephrotoxic potential leading to impaired renal function in some cases. Therefore, it is of high clinical impact to identify factors which can predict who is endangered to develop CNI toxicity. We hypothesized that the Tac metabolism rate expressed as the blood concentration normalized by the dose (C/D ratio) is such a simple predictor. Therefore, we analyzed the impact of the C/D ratio on kidney function after RTx. Renal function was analyzed 1, 2, 3, 6, 12 and 24 months after RTx in 248 patients with an immunosuppressive regimen including basiliximab, tacrolimus, mycophenolate mofetil and prednisolone. According to keep the approach simple, patients were split into three C/D groups: fast, intermediate and slow metabolizers. Notably, compared with slow metabolizers fast metabolizers of Tac showed significantly lower estimated glomerular filtration rate (eGFR) values at all the time points analyzed. Moreover, fast metabolizers underwent more indication renal biopsies (p = 0.006) which revealed a higher incidence of CNI nephrotoxicity (p = 0.015) and BK nephropathy (p = 0.024) in this group. We herein identified the C/D ratio as an easy calculable risk factor for the development of CNI nephrotoxicity and BK nephropathy after RTx. We propose that the simple C/D ratio should be taken into account early in patient's risk management strategies. PMID:25340655

  10. Dependence of Hippocampal Function on ERRγ Regulated Mitochondrial Metabolism

    PubMed Central

    Pei, Liming; Mu, Yangling; Leblanc, Mathias; Alaynick, William; Barish, Grant D.; Pankratz, Matthew; Tseng, Tiffany W.; Kaufman, Samantha; Liddle, Christopher; Yu, Ruth T.; Downes, Michael; Pfaff, Samuel L.; Auwerx, Johan; Gage, Fred H.; Evans, Ronald M.

    2015-01-01

    SUMMARY Neurons utilize mitochondrial oxidative phosphorylation (OxPhos) to generate energy essential for survival, function and behavioral output. Unlike most cells that burn both fat and sugar, neurons only burn sugar. Despite its importance, how neurons meet the increased energy demands of complex behaviors such as learning and memory is poorly understood. Here we show that the estrogen related receptor gamma (ERRγ) orchestrates the expression of a distinct neural gene network promoting mitochondrial oxidative metabolism that reflects the extraordinary neuronal dependence on glucose. ERRγ−/− neurons exhibit decreased metabolic capacity. Impairment of long-term potentiation (LTP) in ERRγ−/− hippocampal slices can be fully rescued by the mitochondrial OxPhos substrate pyruvate, functionally linking the ERRγ knockout metabolic phenotype and memory formation. Consistent with this notion, mice lacking neuronal ERRγ in cerebral cortex and hippocampus exhibit defects in spatial learning and memory. These findings implicate neuronal ERRγ in the metabolic adaptations required for memory formation. PMID:25863252

  11. Bladder function - neurological control

    MedlinePlus Videos and Cool Tools

    ... with urine, sensory nerves send impulses to the brain indicating that the bladder is full. The sensory ... cord to relay this information. In turn, the brain sends impulses back to the bladder instructing the ...

  12. (-)-Epigallocatechin-3-gallate (EGCG) modulates neurological function when intravenously infused in acute and, chronically injured spinal cord of adult rats.

    PubMed

    Renno, Waleed M; Al-Khaledi, Ghanim; Mousa, Alyaa; Karam, Shaima M; Abul, Habib; Asfar, Sami

    2014-02-01

    Spinal cord injury (SCI) causes severe and long lasting motor and sensory deficits, chronic pain, and autonomic dysreflexia. (-)-epigallocatechin-3-gallate (EGCG) has shown to produce neuroprotective effect in a broad range of neurodegenerative disease animal models. This study designed to test the efficacy of intravenous infusion of EGCG for 36 h, in acutely injured rats' spinal cord: within first 4 h post-injury and, in chronically SC injured rats: after one year of injury. Functional outcomes measured using standard BBB scale, The Louisville Swim Scale (LSS) and, pain behavior assessment tests. 72 Female adult rats subjected to moderate thoracic SCI using MASCIS Impactor, blindly randomized as the following: (I) Acute SCI + EGCG (II) Acute SCI + saline. (III) Chronic SCI + EGCG. (IV) Chronic SCI + saline and, sham SCI animals. EGCG i.v. treatment of acute and, chronic SCI animals resulted in significantly better recovery of motor and sensory functions, BBB and LSS (P < 0.005) and (P < 0.05) respectively. Tactile allodynia, mechanical nociception (P < 0.05) significantly improved. Paw withdrawal and, tail flick latencies increase significantly (P < 0.05). Moreover, in the EGCG treated acute SCI animals the percentage of lesion size area significantly reduced (P < 0.0001) and, the number of neurons in the spinal cord increased (P < 0.001). Percent areas of GAP-43 and GFAP immunohistochemistry showed significant (P < 0.05) increase. We conclude that the therapeutic window of opportunity for EGCG to depict neurological recovery in SCI animals, is viable up to one year post SCI when intravenously infused for 36 h. PMID:24071567

  13. (-)-Epigallocatechin-3-gallate (EGCG) modulates neurological function when intravenously infused in acute and, chronically injured spinal cord of adult rats.

    PubMed

    Renno, Waleed M; Al-Khaledi, Ghanim; Mousa, Alyaa; Karam, Shaima M; Abul, Habib; Asfar, Sami

    2014-02-01

    Spinal cord injury (SCI) causes severe and long lasting motor and sensory deficits, chronic pain, and autonomic dysreflexia. (-)-epigallocatechin-3-gallate (EGCG) has shown to produce neuroprotective effect in a broad range of neurodegenerative disease animal models. This study designed to test the efficacy of intravenous infusion of EGCG for 36 h, in acutely injured rats' spinal cord: within first 4 h post-injury and, in chronically SC injured rats: after one year of injury. Functional outcomes measured using standard BBB scale, The Louisville Swim Scale (LSS) and, pain behavior assessment tests. 72 Female adult rats subjected to moderate thoracic SCI using MASCIS Impactor, blindly randomized as the following: (I) Acute SCI + EGCG (II) Acute SCI + saline. (III) Chronic SCI + EGCG. (IV) Chronic SCI + saline and, sham SCI animals. EGCG i.v. treatment of acute and, chronic SCI animals resulted in significantly better recovery of motor and sensory functions, BBB and LSS (P < 0.005) and (P < 0.05) respectively. Tactile allodynia, mechanical nociception (P < 0.05) significantly improved. Paw withdrawal and, tail flick latencies increase significantly (P < 0.05). Moreover, in the EGCG treated acute SCI animals the percentage of lesion size area significantly reduced (P < 0.0001) and, the number of neurons in the spinal cord increased (P < 0.001). Percent areas of GAP-43 and GFAP immunohistochemistry showed significant (P < 0.05) increase. We conclude that the therapeutic window of opportunity for EGCG to depict neurological recovery in SCI animals, is viable up to one year post SCI when intravenously infused for 36 h.

  14. Effects of the neurological wake-up test on clinical examination, intracranial pressure, brain metabolism and brain tissue oxygenation in severely brain-injured patients

    PubMed Central

    2012-01-01

    Introduction Daily interruption of sedation (IS) has been implemented in 30 to 40% of intensive care units worldwide and may improve outcome in medical intensive care patients. Little is known about the benefit of IS in acutely brain-injured patients. Methods This prospective observational study was performed in a neuroscience intensive care unit in a tertiary-care academic center. Twenty consecutive severely brain-injured patients with multimodal neuromonitoring were analyzed for levels of brain lactate, pyruvate and glucose, intracranial pressure (ICP), cerebral perfusion pressure (CPP) and brain tissue oxygen tension (PbtO2) during IS trials. Results Of the 82 trial days, 54 IS-trials were performed as interruption of sedation and analgesics were not considered safe on 28 days (34%). An increase in the FOUR Score (Full Outline of UnResponsiveness score) was observed in 50% of IS-trials by a median of three (two to four) points. Detection of a new neurologic deficit occurred in one trial (2%), and in one-third of IS-trials the trial had to be stopped due to an ICP-crisis (> 20 mmHg), agitation or systemic desaturation. In IS-trials that had to be aborted, a significant increase in ICP and decrease in PbtO2 (P < 0.05), including 67% with critical values of PbtO2 < 20 mmHg, a tendency to brain metabolic distress (P < 0.07) was observed. Conclusions Interruption of sedation revealed new relevant clinical information in only one trial and a large number of trials could not be performed or had to be stopped due to safety issues. Weighing pros and cons of IS-trials in patients with acute brain injury seems important as related side effects may overcome the clinical benefit. PMID:23186037

  15. Magnetic resonance and the human brain: anatomy, function and metabolism.

    PubMed

    Talos, I-F; Mian, A Z; Zou, K H; Hsu, L; Goldberg-Zimring, D; Haker, S; Bhagwat, J G; Mulkern, R V

    2006-05-01

    The introduction and development, over the last three decades, of magnetic resonance (MR) imaging and MR spectroscopy technology for in vivo studies of the human brain represents a truly remarkable achievement, with enormous scientific and clinical ramifications. These effectively non-invasive techniques allow for studies of the anatomy, the function and the metabolism of the living human brain. They have allowed for new understandings of how the healthy brain works and have provided insights into the mechanisms underlying multiple disease processes which affect the brain. Different MR techniques have been developed for studying anatomy, function and metabolism. The primary focus of this review is to describe these different methodologies and to briefly review how they are being employed to more fully appreciate the intricacies associated with the organ, which most distinctly differentiates the human species from the other animal forms on earth.

  16. Magnetic resonance and the human brain: anatomy, function and metabolism.

    PubMed

    Talos, I-F; Mian, A Z; Zou, K H; Hsu, L; Goldberg-Zimring, D; Haker, S; Bhagwat, J G; Mulkern, R V

    2006-05-01

    The introduction and development, over the last three decades, of magnetic resonance (MR) imaging and MR spectroscopy technology for in vivo studies of the human brain represents a truly remarkable achievement, with enormous scientific and clinical ramifications. These effectively non-invasive techniques allow for studies of the anatomy, the function and the metabolism of the living human brain. They have allowed for new understandings of how the healthy brain works and have provided insights into the mechanisms underlying multiple disease processes which affect the brain. Different MR techniques have been developed for studying anatomy, function and metabolism. The primary focus of this review is to describe these different methodologies and to briefly review how they are being employed to more fully appreciate the intricacies associated with the organ, which most distinctly differentiates the human species from the other animal forms on earth. PMID:16568243

  17. A type-II positive allosteric modulator of α7 nAChRs reduces brain injury and improves neurological function after focal cerebral ischemia in rats.

    PubMed

    Sun, Fen; Jin, Kunlin; Uteshev, Victor V

    2013-01-01

    In the absence of clinically-efficacious therapies for ischemic stroke there is a critical need for development of new therapeutic concepts and approaches for prevention of brain injury secondary to cerebral ischemia. This study tests the hypothesis that administration of PNU-120596, a type-II positive allosteric modulator (PAM-II) of α7 nicotinic acetylcholine receptors (nAChRs), as long as 6 hours after the onset of focal cerebral ischemia significantly reduces brain injury and neurological deficits in an animal model of ischemic stroke. Focal cerebral ischemia was induced by a transient (90 min) middle cerebral artery occlusion (MCAO). Animals were then subdivided into two groups and injected intravenously (i.v.) 6 hours post-MCAO with either 1 mg/kg PNU-120596 (treated group) or vehicle only (untreated group). Measurements of cerebral infarct volumes and neurological behavioral tests were performed 24 hrs post-MCAO. PNU-120596 significantly reduced cerebral infarct volume and improved neurological function as evidenced by the results of Bederson, rolling cylinder and ladder rung walking tests. These results forecast a high therapeutic potential for PAMs-II as effective recruiters and activators of endogenous α7 nAChR-dependent cholinergic pathways to reduce brain injury and improve neurological function after cerebral ischemic stroke. PMID:23951360

  18. Epigenetic mechanisms in neurological and neurodegenerative diseases

    PubMed Central

    Landgrave-Gómez, Jorge; Mercado-Gómez, Octavio; Guevara-Guzmán, Rosalinda

    2015-01-01

    The role of epigenetic mechanisms in the function and homeostasis of the central nervous system (CNS) and its regulation in diseases is one of the most interesting processes of contemporary neuroscience. In the last decade, a growing body of literature suggests that long-term changes in gene transcription associated with CNS’s regulation and neurological disorders are mediated via modulation of chromatin structure. “Epigenetics”, introduced for the first time by Waddington in the early 1940s, has been traditionally referred to a variety of mechanisms that allow heritable changes in gene expression even in the absence of DNA mutation. However, new definitions acknowledge that many of these mechanisms used to perpetuate epigenetic traits in dividing cells are used by neurons to control a variety of functions dependent on gene expression. Indeed, in the recent years these mechanisms have shown their importance in the maintenance of a healthy CNS. Moreover, environmental inputs that have shown effects in CNS diseases, such as nutrition, that can modulate the concentration of a variety of metabolites such as acetyl-coenzyme A (acetyl-coA), nicotinamide adenine dinucleotide (NAD+) and beta hydroxybutyrate (β-HB), regulates some of these epigenetic modifications, linking in a precise way environment with gene expression. This manuscript will portray what is currently understood about the role of epigenetic mechanisms in the function and homeostasis of the CNS and their participation in a variety of neurological disorders. We will discuss how the machinery that controls these modifications plays an important role in processes involved in neurological disorders such as neurogenesis and cell growth. Moreover, we will discuss how environmental inputs modulate these modifications producing metabolic and physiological alterations that could exert beneficial effects on neurological diseases. Finally, we will highlight possible future directions in the field of epigenetics

  19. [Vitamin D and neurology].

    PubMed

    Thouvenot, Éric; Camu, William

    2013-10-01

    Vitamin D deficiency is associated with a higher risk of multiple sclerosis and also with a higher relapse rate as well as a higher number of MRI lesions. Elders with vitamin D deficiency have worse cognitive performance. Vitamin D deficiency is a risk factor for developing Alzheimer's disease. Ischemic stroke are more frequent and more severe in patients with low vitamin D levels. Carotid atherosclerosis is more frequent and more severe in patients with vitamin D deficiency. Vitamin D deficiency is associated with a higher risk and worse prognosis of Parkinson's disease. In the different neurological disorders discussed herein, gene polymorphisms that could alter vitamin D metabolism are also associated with a higher incidence or a worse disease prognosis. Despite the links between vitamin D deficiency and the risks of developing neurological disorders, there is, to date, no proof that supplementation could alter the course of these diseases.

  20. Ravel's neurological illness.

    PubMed

    Alonso, R J; Pascuzzi, R M

    1999-01-01

    In the last 10 years of his life, Maurice Ravel (1875-1937) experienced a gradually progressive decline in neurological function. Dr. Alajouanine examined Ravel, noting the presence of aphasia and apraxia with relative preservation of comprehension and memory. The exact diagnosis remains unclear, but the likelihood of a progressive degenerative disorder, such as frontotemporal dementia, is herein discussed. PMID:10718529

  1. Irisin levels in relation to metabolic and liver functions in Egyptian patients with metabolic syndrome.

    PubMed

    Rizk, Fatma H; Elshweikh, Samah A; Abd El-Naby, Amira Y

    2016-04-01

    Irisin is a new myokine that is suspected to influence metabolic syndrome (MetS). However, there is a great controversy with respect to its level in cases of MetS and its correlation with different metabolic parameters. The present study assesses irisin levels in MetS patients and studies its relationship to metabolic and liver functions to evaluate the possible role of the liver in regulation of this level. Sixty subjects were included in this experiment, who were divided into 3 groups: group I (normal control), group II (MetS patients with normal liver enzymes), and group III (MetS with elevated liver enzymes and fatty liver disease). Serum irisin levels showed significant increases in groups II and III compared with group I, and significant increases in group III compared with group II. Also, irisin levels were positively correlated with body mass index, serum triglycerides, homeostatic model assessment of insulin resistance index (HOMA-IR), and liver enzymes. We concluded that serum irisin levels increased in patients with MetS, especially those with elevated liver enzymes, and had a positive correlation with parameters of lipid metabolism and glucose homeostasis with the possibility of hepatic clearance to irisin.

  2. The Spectrum of Neurological Recovery

    PubMed Central

    Mir, Tanveer P.

    2012-01-01

    The equivalence of brain death with death is largely, although not universally accepted. Patients may have suffered insults such as cardiac arrest, vascular catastrophe, poisoning, or head trauma. Early identification of patients at greatest risk of poor neurologic outcome and management in the appropriate critical care setting is the key to maximizing neurological recovery. Recent technological advances and neuroimaging have made it possible to predict neurological reversibility with great accuracy. Significant improvements in therapy such as hypothermia, will improve outcomes in neurological catastrophies, particularly in anoxic-ischemic encephalopathy. The clinical spectrum and diagnostic criteria of minimally conscious and vegetative states is reviewed. The current understanding of the differences in prognosis and prediction of meaningful cognitive and functional recovery in each neurological state is described. Establishing an understanding of the ethical principles that guide medical decisions in clinical practice related to different neurological states is evolving into a new field called neuroethics. PMID:23610514

  3. [Neurological sleep disorders].

    PubMed

    Khatami, Ramin

    2014-11-01

    Neurological sleep disorders are common in the general population and may have a strong impact on quality of life. General practitioners play a key role in recognizing and managing sleep disorders in the general population. They should therefore be familiar with the most important neurological sleep disorders. This review provides a comprehensive overview of the most prevalent and important neurological sleep disorders, including Restless legs syndrome (with and without periodic limb movements in sleep), narcolepsy, NREM- and REM-sleep parasomnias and the complex relationship between sleep and epilepsies. Although narcolepsy is considered as a rare disease, recent discoveries in narcolepsy research provided insight in the function of brain circuitries involved in sleep wake regulation. REM sleep behavioral parasomnia (RBD) is increasingly recognized to represent an early manifestation of neurodegenerative disorders, in particular evolving synucleinopathies. Early diagnosis may thus open new perspectives for developing novel treatment options by targeting neuroprotective substances.

  4. New insights on glucosylated lipids: metabolism and functions.

    PubMed

    Ishibashi, Yohei; Kohyama-Koganeya, Ayako; Hirabayashi, Yoshio

    2013-09-01

    Ceramide, cholesterol, and phosphatidic acid are major basic structures for cell membrane lipids. These lipids are modified with glucose to generate glucosylceramide (GlcCer), cholesterylglucoside (ChlGlc), and phosphatidylglucoside (PtdGlc), respectively. Glucosylation dramatically changes the functional properties of lipids. For instance, ceramide acts as a strong tumor suppressor that causes apoptosis and cell cycle arrest, while GlcCer has an opposite effect, downregulating ceramide activities. All glucosylated lipids are enriched in lipid rafts or microdomains and play fundamental roles in a variety of cellular processes. In this review, we discuss the biological functions and metabolism of these three glucosylated lipids. PMID:23770033

  5. Sialic acid metabolism and sialyltransferases: natural functions and applications

    PubMed Central

    Li, Yanhong

    2012-01-01

    Sialic acids are a family of negatively charged monosaccharides which are commonly presented as the terminal residues in glycans of the glycoconjugates on eukaryotic cell surface or as components of capsular polysaccharides or lipooligosaccharides of some pathogenic bacteria. Due to their important biological and pathological functions, the biosynthesis, activation, transfer, breaking down, and recycle of sialic acids are attracting increasing attention. The understanding of the sialic acid metabolism in eukaryotes and bacteria leads to the development of metabolic engineering approaches for elucidating the important functions of sialic acid in mammalian systems and for large-scale production of sialosides using engineered bacterial cells. As the key enzymes in biosynthesis of sialylated structures, sialyltransferases have been continuously identified from various sources and characterized. Protein crystal structures of seven sialyltransferases have been reported. Wild-type sialyltransferases and their mutants have been applied with or without other sialoside biosynthetic enzymes for producing complex sialic acid-containing oligosaccharides and glycoconjugates. This mini-review focuses on current understanding and applications of sialic acid metabolism and sialyltransferases. PMID:22526796

  6. Functional foods as potential therapeutic options for metabolic syndrome.

    PubMed

    Brown, L; Poudyal, H; Panchal, S K

    2015-11-01

    Obesity as part of metabolic syndrome is a major lifestyle disorder throughout the world. Current drug treatments for obesity produce small and usually unsustainable decreases in body weight with the risk of major adverse effects. Surgery has been the only treatment producing successful long-term weight loss. As a different but complementary approach, lifestyle modification including the use of functional foods could produce a reliable decrease in obesity with decreased comorbidities. Functional foods may include fruits such as berries, vegetables, fibre-enriched grains and beverages such as tea and coffee. Although health improvements continue to be reported for these functional foods in rodent studies, further evidence showing the translation of these results into humans is required. Thus, the concept that these fruits and vegetables will act as functional foods in humans to reduce obesity and thereby improve health remains intuitive and possible rather than proven. PMID:26345360

  7. Functional foods as potential therapeutic options for metabolic syndrome.

    PubMed

    Brown, L; Poudyal, H; Panchal, S K

    2015-11-01

    Obesity as part of metabolic syndrome is a major lifestyle disorder throughout the world. Current drug treatments for obesity produce small and usually unsustainable decreases in body weight with the risk of major adverse effects. Surgery has been the only treatment producing successful long-term weight loss. As a different but complementary approach, lifestyle modification including the use of functional foods could produce a reliable decrease in obesity with decreased comorbidities. Functional foods may include fruits such as berries, vegetables, fibre-enriched grains and beverages such as tea and coffee. Although health improvements continue to be reported for these functional foods in rodent studies, further evidence showing the translation of these results into humans is required. Thus, the concept that these fruits and vegetables will act as functional foods in humans to reduce obesity and thereby improve health remains intuitive and possible rather than proven.

  8. Triacylglycerol Metabolism, Function, and Accumulation in Plant Vegetative Tissues.

    PubMed

    Xu, Changcheng; Shanklin, John

    2016-04-29

    Oils in the form of triacylglycerols are the most abundant energy-dense storage compounds in eukaryotes, and their metabolism plays a key role in cellular energy balance, lipid homeostasis, growth, and maintenance. Plants accumulate oils primarily in seeds and fruits. Plant oils are used for food and feed and, increasingly, as feedstocks for biodiesel and industrial chemicals. Although plant vegetative tissues do not accumulate significant levels of triacylglycerols, they possess a high capacity for their synthesis, storage, and metabolism. The development of plants that accumulate oil in vegetative tissues presents an opportunity for expanded production of triacylglycerols as a renewable and sustainable bioenergy source. Here, we review recent progress in the understanding of triacylglycerol synthesis, turnover, storage, and function in leaves and discuss emerging genetic engineering strategies targeted at enhancing triacylglycerol accumulation in biomass crops. Such plants could potentially be modified to produce oleochemical feedstocks or nutraceuticals. PMID:26845499

  9. Regulation of cardiac metabolism and function by lipogenic factors.

    PubMed

    Bednarski, Tomasz; Pyrkowska, Aleksandra; Opasińska, Agnieszka; Dobrzyń, Paweł

    2016-01-01

    The heart has a limited capacity for lipogenesis and de novo lipid synthesis. However, expression of lipogenic genes in cardiomyocytes is unexpectedly high. Recent studies showed that lipogenic genes are important factors regulating cardiac metabolism and function. Long chain fatty acids are a major source of ATP required for proper heart function, and under aerobic conditions, the heart derives 60-90% of the energy necessary for contractile function from fatty acid oxidation. On the other hand, cardiac lipid over-accumulation (e.g. ceramides, diacylglycerols) leads to heart dysfunction. Downregulation of the lipogenic genes' expression (e.g. sterol regulatory element binding protein 1, stearoyl-CoA desaturase, acetyl-CoA kwacarboxylase) decreased heart steatosis and cardiomyocyte apoptosis, improving systolic and diastolic function of the left ventricle. Lipogenic factors also regulate fatty acids and glucose utilization in the heart, underlining their important role in maintaining energetic homeostasis in pathological states. Fatty acid synthase, the enzyme catalyzing fatty acids de novo synthesis, affects cardiac calcium signaling through regulation of L-type calcium channel activity. Thus, a growing body of evidence suggests that the role of lipogenic genes in cardiomyocytes may be distinct from other tissues. Here, we review recent advances made in understanding the role of lipogenic genes in the control of heart metabolism and its involvement in the pathogenesis of lipotoxic cardiomyopathy. PMID:27333934

  10. Human Neurological Development: Past, Present and Future

    NASA Technical Reports Server (NTRS)

    Pelligra, R. (Editor)

    1978-01-01

    Neurological development is considered as the major human potential. Vision, vestibular function, intelligence, and nutrition are discussed as well as the treatment of neurological disfunctions, coma, and convulsive seizures.

  11. Aging, the metabolic syndrome, and ischemic stroke: redefining the approach for studying the blood-brain barrier in a complex neurological disease.

    PubMed

    Lucke-Wold, Brandon P; Logsdon, Aric F; Turner, Ryan C; Rosen, Charles L; Huber, Jason D

    2014-01-01

    The blood-brain barrier (BBB) has many important functions in maintaining the brain's immune-privileged status. Endothelial cells, astrocytes, and pericytes have important roles in preserving vasculature integrity. As we age, cell senescence can contribute to BBB compromise. The compromised BBB allows an influx of inflammatory cytokines to enter the brain. These cytokines lead to neuronal and glial damage. Ultimately, the functional changes within the brain can cause age-related disease. One of the most prominent age-related diseases is ischemic stroke. Stroke is the largest cause of disability and is third largest cause of mortality in the United States. The biggest risk factors for stroke, besides age, are results of the metabolic syndrome. The metabolic syndrome, if unchecked, quickly advances to outcomes that include diabetes, hypertension, cardiovascular disease, and obesity. The contribution from these comorbidities to BBB compromise is great. Some of the common molecular pathways activated include: endoplasmic reticulum stress, reactive oxygen species formation, and glutamate excitotoxicity. In this chapter, we examine how age-related changes to cells within the central nervous system interact with comorbidities. We then look at how comorbidities lead to increased risk for stroke through BBB disruption. Finally, we discuss key molecular pathways of interest with a focus on therapeutic targets that warrant further investigation.

  12. From Elements to Metabolism: Linking Organismal Stoichiometry to Ecosystem Function

    NASA Astrophysics Data System (ADS)

    Cohen, M. J.; Nifong, R. L.

    2014-12-01

    Metabolism is an integrative metric of ecosystem function and energetics, synthesizing the relative contributions of multiple inputs, processes, and interactions. Stoichiometry is a framework based on elemental ratios for understanding how organisms interact within ecosystems. Linking the two has the potential to yield fresh insight about how ecosystems utilize elements and energy. We sought to quantify the link between the stoichiometry of ecosystem metabolism, specifically the C:N:P ratios of integrated autotrophic assimilation, and the stoichiometric tissue ratios observed in the dominant autotrophs. Using high frequency in situ nutrient sensors we estimated the assimilatory fluxes of C, N, and P in multiple spring-fed rivers of varying autotrophic species composition. We measured autotroph cover in each spring river, collected composite vegetation samples, and evaluated tissue stoichiometry; as expected, we observed large differences in C:N and N:P between algal and vascular plant taxa. We observed associations between measured tissue stoichiometry and elemental ratios at the ecosystem scale, suggesting that aggregated assimilatory fluxes may be useful for partitioning primary production and linking organismal nutrient content to the stoichiometry of ecosystem metabolism.

  13. Linking community size structure and ecosystem functioning using metabolic theory

    PubMed Central

    Yvon-Durocher, Gabriel; Allen, Andrew P.

    2012-01-01

    Understanding how biogeochemical cycles relate to the structure of ecological communities is a central research question in ecology. Here we approach this problem by focusing on body size, which is an easily measured species trait that has a pervasive influence on multiple aspects of community structure and ecosystem functioning. We test the predictions of a model derived from metabolic theory using data on ecosystem metabolism and community size structure. These data were collected as part of an aquatic mesocosm experiment that was designed to simulate future environmental warming. Our analyses demonstrate significant linkages between community size structure and ecosystem functioning, and the effects of warming on these links. Specifically, we show that carbon fluxes were significantly influenced by seasonal variation in temperature, and yielded activation energies remarkably similar to those predicted based on the temperature dependencies of individual-level photosynthesis and respiration. We also show that community size structure significantly influenced fluxes of ecosystem respiration and gross primary production, particularly at the annual time-scale. Assessing size structure and the factors that control it, both empirically and theoretically, therefore promises to aid in understanding links between individual organisms and biogeochemical cycles, and in predicting the responses of key ecosystem functions to future environmental change. PMID:23007088

  14. Sucrose metabolism gene families and their biological functions.

    PubMed

    Jiang, Shu-Ye; Chi, Yun-Hua; Wang, Ji-Zhou; Zhou, Jun-Xia; Cheng, Yan-Song; Zhang, Bao-Lan; Ma, Ali; Vanitha, Jeevanandam; Ramachandran, Srinivasan

    2015-11-30

    Sucrose, as the main product of photosynthesis, plays crucial roles in plant development. Although studies on general metabolism pathway were well documented, less information is available on the genome-wide identification of these genes, their expansion and evolutionary history as well as their biological functions. We focused on four sucrose metabolism related gene families including sucrose synthase, sucrose phosphate synthase, sucrose phosphate phosphatase and UDP-glucose pyrophosphorylase. These gene families exhibited different expansion and evolutionary history as their host genomes experienced differentiated rates of the whole genome duplication, tandem and segmental duplication, or mobile element mediated gene gain and loss. They were evolutionarily conserved under purifying selection among species and expression divergence played important roles for gene survival after expansion. However, we have detected recent positive selection during intra-species divergence. Overexpression of 15 sorghum genes in Arabidopsis revealed their roles in biomass accumulation, flowering time control, seed germination and response to high salinity and sugar stresses. Our studies uncovered the molecular mechanisms of gene expansion and evolution and also provided new insight into the role of positive selection in intra-species divergence. Overexpression data revealed novel biological functions of these genes in flowering time control and seed germination under normal and stress conditions.

  15. Sucrose metabolism gene families and their biological functions

    PubMed Central

    Jiang, Shu-Ye; Chi, Yun-Hua; Wang, Ji-Zhou; Zhou, Jun-Xia; Cheng, Yan-Song; Zhang, Bao-Lan; Ma, Ali; Vanitha, Jeevanandam; Ramachandran, Srinivasan

    2015-01-01

    Sucrose, as the main product of photosynthesis, plays crucial roles in plant development. Although studies on general metabolism pathway were well documented, less information is available on the genome-wide identification of these genes, their expansion and evolutionary history as well as their biological functions. We focused on four sucrose metabolism related gene families including sucrose synthase, sucrose phosphate synthase, sucrose phosphate phosphatase and UDP-glucose pyrophosphorylase. These gene families exhibited different expansion and evolutionary history as their host genomes experienced differentiated rates of the whole genome duplication, tandem and segmental duplication, or mobile element mediated gene gain and loss. They were evolutionarily conserved under purifying selection among species and expression divergence played important roles for gene survival after expansion. However, we have detected recent positive selection during intra-species divergence. Overexpression of 15 sorghum genes in Arabidopsis revealed their roles in biomass accumulation, flowering time control, seed germination and response to high salinity and sugar stresses. Our studies uncovered the molecular mechanisms of gene expansion and evolution and also provided new insight into the role of positive selection in intra-species divergence. Overexpression data revealed novel biological functions of these genes in flowering time control and seed germination under normal and stress conditions. PMID:26616172

  16. Physical, metabolic and developmental functions of the seed coat

    PubMed Central

    Radchuk, Volodymyr; Borisjuk, Ljudmilla

    2014-01-01

    The conventional understanding of the role of the seed coat is that it provides a protective layer for the developing zygote. Recent data show that the picture is more nuanced. The seed coat certainly represents a first line of defense against adverse external factors, but it also acts as channel for transmitting environmental cues to the interior of the seed. The latter function primes the seed to adjust its metabolism in response to changes in its external environment. The purpose of this review is to provide the reader with a comprehensive view of the structure and functionality of the seed coat, and to expose its hidden interaction with both the endosperm and embryo. Any breeding and/or biotechnology intervention seeking to increase seed size or modify seed features will have to consider the implications on this tripartite interaction. PMID:25346737

  17. On the Evolution of New Metabolic Functions in Diploid Organisms

    PubMed Central

    Hall, Barry G.

    1980-01-01

    Evolution of lactose utilization via the ebg system of Escherichia coli requires both structural gene (ebgA) and regulatory gene (ebgR) mutations. Because evolution of new metabolic functions in diploids might be subject to constraints not present in haploid organisms, merodiploid strains carrying a wild-type and an evolved ebgA allele, or a wild-type and an evolved ebgR allele were constructed. I show that heterozygosity at ebgA does not significantly affect the selective advantage of the evolved ebgA allele; whereas heterozygosity at ebgR eliminates the selective advantage of the evolved ebgR allele. It is suggested that, in diploid organisms, evolution of new functions for systems under negative control would be very difficult. PMID:6790336

  18. Artificial cells for replacement of metabolic organ functions.

    PubMed

    Chang, Thomas Ming Swi

    2003-05-01

    Artificial cells are being actively investigated for use in the replacement of cell and organ functions, especially related to metabolic functions. The earliest routine clinical use of artificial cells is in the form of coated activated charcoal for hemoperfusion. Implantation of encapsulated cells are being studied for the treatment of diabetes, liver failure, kidney failure and the use of encapsulated genetically engineered cells for gene therapy. Blood substitutes based on modified hemoglobin are already in Phase III clinical trials in patients with as much as 20 units infused into each patient during trauma surgery. Artificial cells containing enzymes are being developed for clinical trial in hereditary enzyme deficiency diseases and other diseases. Artificial cell is also being investigated for drug delivery and for other uses in biotechnology, chemical engineering and medicine.

  19. Aflatoxicosis alters avian renal function, calcium, and vitamin D metabolism.

    PubMed

    Glahn, R P; Beers, K W; Bottje, W G; Wideman, R F; Huff, W E; Thomas, W

    1991-11-01

    Experiments were designed to determine the effects of aflatoxicosis on avian renal function, calcium (CA), inorganic phosphorous (Pi), and vitamin D metabolism, and to determine if the effects of aflatoxin are reversible upon discontinuation of toxin administration. Three-week-old male broiler chickens (n = 12 per treatment) received aflatoxin (AF; 2 mg/kg po) or an equal volume of corn oil, the AF carrier vehicle, for 10 consecutive days. After 10 d of treatment, half of the birds from each treatment group were anesthetized and prepared for renal function analysis, which included a 2-h phosphate loading period. Ten days after discontinuation of AF treatment, the remaining birds in each treatment group were anesthetized and prepared for renal function analysis. AF decreased plasma 25-hydroxy vitamin D [25(OH)D] and 1,25-dihydroxy vitamin D [1,25(OH)2D] levels after 5 d of treatment. After 10 d of treatment, urine flow rate (V), fractional sodium excretion (FENa), and fractional potassium excretion (FEK) were lower in AF-treated birds. In addition, total plasma Ca tended to be lower (p = .10) and fractional Ca excretion (FECa) tended to be higher (p = .10) in the AF-treated birds. Intravenous phosphate loading produced a sharp increase in urine hydrogen ion concentration ([H+]) in the AF-treated birds. Glomerular filtration rate (GFR) was reduced and plasma osmolality was increased in AF-treated birds 10 d after discontinuation of toxin administration. The results indicate that AF directly or indirectly affects Ca and Pi metabolism in avians. At the present time, the effects may be related to altered vitamin D and parathyroid hormone (PTH) metabolism. Aflatoxicosis may decrease endogenous PTH synthesis and the renal sensitivity to PTH. The AF-related increase in urine [H+] during phosphate loading is probably due to increased Na+/H+ counterport, suggesting that AF stimulates sodium reabsorption. Also, the decrease in GFR exhibited 10 d after toxin removal indicates

  20. The neurology of folic acid deficiency.

    PubMed

    Reynolds, E H

    2014-01-01

    The metabolism of folic acid and the metabolism of vitamin B12 are intimately linked such that deficiency of either vitamin leads to an identical megaloblastic anemia. The neurologic manifestations of folate deficiency overlap with those of vitamin B12 deficiency and include cognitive impairment, dementia, depression, and, less commonly, peripheral neuropathy and subacute combined degeneration of the spinal cord. In both deficiency states there is often dissociation between the neuropsychiatric and the hematologic complications. There is a similar overlap and dissociation between neurologic and hematologic manifestations of inborn errors of folate and vitamin B12 metabolism. Low folate and raised homocysteine levels are risk factors for dementia, including Alzheimer's disease, and depression. Even when folate deficiency is secondary to psychiatric illness due to apathy or poor diet it may eventually aggravate the underlying disorder in a vicious circle effect. Clinical responses to treatment with folates are usually slow over weeks and months, probably due to the efficient blood-brain barrier mechanism for the vitamin, perhaps in turn related to the experimentally demonstrated excitatory properties of folate derivatives. The inappropriate administration of folic acid in the presence of vitamin B12 deficiency may lead to both neurologic and, later, hematologic relapse. Impaired maternal folate intake and status increases the risk of neural tube defects. Periconceptual prophylactic administration of the vitamin reduces, but does not eliminate the risk of neural tube defects even in the absence of folate deficiency. Folates and vitamin B12 have fundamental roles in central nervous system function at all ages, especially in purine, thymidine, neucleotide, and DNA synthesis, genomic and nongenomic methylation and, therefore, in tissue growth, differentiation and repair. There is interest in the potential role of both vitamins in the prevention of disorders of central

  1. Neurological diseases and pain

    PubMed Central

    2012-01-01

    Chronic pain is a frequent component of many neurological disorders, affecting 20–40% of patients for many primary neurological diseases. These diseases result from a wide range of pathophysiologies including traumatic injury to the central nervous system, neurodegeneration and neuroinflammation, and exploring the aetiology of pain in these disorders is an opportunity to achieve new insight into pain processing. Whether pain originates in the central or peripheral nervous system, it frequently becomes centralized through maladaptive responses within the central nervous system that can profoundly alter brain systems and thereby behaviour (e.g. depression). Chronic pain should thus be considered a brain disease in which alterations in neural networks affect multiple aspects of brain function, structure and chemistry. The study and treatment of this disease is greatly complicated by the lack of objective measures for either the symptoms or the underlying mechanisms of chronic pain. In pain associated with neurological disease, it is sometimes difficult to obtain even a subjective evaluation of pain, as is the case for patients in a vegetative state or end-stage Alzheimer's disease. It is critical that neurologists become more involved in chronic pain treatment and research (already significant in the fields of migraine and peripheral neuropathies). To achieve this goal, greater efforts are needed to enhance training for neurologists in pain treatment and promote greater interest in the field. This review describes examples of pain in different neurological diseases including primary neurological pain conditions, discusses the therapeutic potential of brain-targeted therapies and highlights the need for objective measures of pain. PMID:22067541

  2. Muscle metabolic function and free-living physical activity.

    PubMed

    Hunter, Gary R; Larson-Meyer, D Enette; Sirikul, Bovorn; Newcomer, Bradley R

    2006-11-01

    We have previously shown that muscle metabolic function measured during exercise is related to exercise performance and subsequent 1-yr weight gain. Because it is well established that physical activity is important in weight maintenance, we examined muscle function relationships with free-living energy expenditure and physical activity. Subjects were 71 premenopausal black and white women. Muscle metabolism was evaluated by (31)P magnetic resonance spectroscopy during 90-s isometric plantar flexion contractions (45% maximum). Free-living energy expenditure (TEE) was measured using doubly labeled water, activity-related energy expenditure (AEE) was calculated as 0.9 x TEE - sleeping energy expenditure from room calorimetry, and free-living physical activity (ARTE) was calculated by dividing AEE by energy cost of standard physical activities. At the end of exercise, anaerobic glycolytic rate (ANGLY) and muscle concentration of phosphomonoesters (PME) were negatively related to TEE, AEE, and ARTE (P < 0.05). Multiple regression analysis showed that both PME (partial r = -0.29, <0.02) and ANGLY (partial r = -0.24, P < 0.04) were independently related to ARTE. PME, primarily glucose-6-phosphate and fructose-6-phosphate, was significantly related to ratings of perceived exertion (r = 0.21, P < or = 0.05) during a maximal treadmill test. PME was not related to ARTE after inclusion of RPE in the multiple regression model, suggesting that PME may be obtaining its relationship with ARTE through an increased perception of effort during physical activity. In conclusion, physically inactive individuals tend to be more dependent on anaerobic glycolysis during exercise while relying on a glycolytic pathway that may not be functioning optimally. PMID:16825516

  3. Muscle metabolic function and free-living physical activity.

    PubMed

    Hunter, Gary R; Larson-Meyer, D Enette; Sirikul, Bovorn; Newcomer, Bradley R

    2006-11-01

    We have previously shown that muscle metabolic function measured during exercise is related to exercise performance and subsequent 1-yr weight gain. Because it is well established that physical activity is important in weight maintenance, we examined muscle function relationships with free-living energy expenditure and physical activity. Subjects were 71 premenopausal black and white women. Muscle metabolism was evaluated by (31)P magnetic resonance spectroscopy during 90-s isometric plantar flexion contractions (45% maximum). Free-living energy expenditure (TEE) was measured using doubly labeled water, activity-related energy expenditure (AEE) was calculated as 0.9 x TEE - sleeping energy expenditure from room calorimetry, and free-living physical activity (ARTE) was calculated by dividing AEE by energy cost of standard physical activities. At the end of exercise, anaerobic glycolytic rate (ANGLY) and muscle concentration of phosphomonoesters (PME) were negatively related to TEE, AEE, and ARTE (P < 0.05). Multiple regression analysis showed that both PME (partial r = -0.29, <0.02) and ANGLY (partial r = -0.24, P < 0.04) were independently related to ARTE. PME, primarily glucose-6-phosphate and fructose-6-phosphate, was significantly related to ratings of perceived exertion (r = 0.21, P < or = 0.05) during a maximal treadmill test. PME was not related to ARTE after inclusion of RPE in the multiple regression model, suggesting that PME may be obtaining its relationship with ARTE through an increased perception of effort during physical activity. In conclusion, physically inactive individuals tend to be more dependent on anaerobic glycolysis during exercise while relying on a glycolytic pathway that may not be functioning optimally.

  4. Exploring Metabolic Pathways and Regulation through Functional Chemoproteomic and Metabolomic Platforms

    PubMed Central

    Medina-Cleghorn, Daniel; Nomura, Daniel K.

    2014-01-01

    Genome sequencing efforts have revealed a strikingly large number of uncharacterized genes, including poorly or uncharacterized metabolic enzymes, metabolites, and metabolic networks that operate in normal physiology, and also those enzymes and pathways that may be rewired under pathological conditions. Though deciphering the functions of the uncharacterized metabolic genome is a challenging prospect, it also presents an opportunity for identifying novel metabolic nodes that may be important in disease therapy. In this review, we will discuss the chemoproteomic and metabolomic platforms employed in identifying, characterizing, and targeting nodal metabolic pathways important in physiology and disease, describing an integrated workflow for functional mapping of metabolic enzymes. PMID:25237861

  5. Re-visiting the nature and relationships between neurological signs and neurocognitive functions in first-episode schizophrenia: An invariance model across time.

    PubMed

    Chan, Raymond C K; Dai, Shan; Lui, Simon S Y; Ho, Karen K Y; Hung, Karen S Y; Wang, Ya; Geng, Fu-lei; Li, Zhi; Cheung, Eric F C

    2015-07-02

    The present study examined different types of neurological signs in patients with first-episode schizophrenia and their relationships with neurocognitive functions. Both cross-sectional and longitudinal designs were adopted with the use of the abridged Cambridge Neurological Inventory which comprises items capturing motor coordination, sensory integration and disinhibition. A total of 157 patients with first-episode schizophrenia were assessed at baseline and 101 of them were re-assessed at six-month interval. A structural equation model (SEM) with invariance model across time was used for data analysis. The model fitted well with the data at baseline assessment, X^2(21) = 21.78, p = 0.413, NFI = 0.95, NNFI = 1.00, CFI = 1.00, IFI = 1.00, RMSEA = 0.015. Subsequent SEM analysis with invariance model at six-month interval also demonstrated the same stable pattern across time and showed strong measurement invariance and structure invariance across time. Our findings suggest that neurological signs capture more or less the same construct captured by conventional neurocognitive tests in patients with schizophrenia. The measurement and structure of these relationships appear to be stable over time.

  6. Effects of metabolic syndrome on language functions in aging.

    PubMed

    Cahana-Amitay, Dalia; Spiro, Avron; Cohen, Jason A; Oveis, Abigail C; Ojo, Emmanuel A; Sayers, Jesse T; Obler, Loraine K; Albert, Martin L

    2015-02-01

    This study explored effects of the metabolic syndrome (MetS) on language in aging. MetS is a constellation of five vascular and metabolic risk factors associated with the development of chronic diseases and increased risk of mortality, as well as brain and cognitive impairments. We tested 281 English-speaking older adults aged 55-84, free of stroke and dementia. Presence of MetS was based on the harmonized criteria (Alberti et al., 2009). Language performance was assessed by measures of accuracy and reaction time on two tasks of lexical retrieval and two tasks of sentence processing. Regression analyses, adjusted for age, education, gender, diabetes, hypertension, and heart disease, demonstrated that participants with MetS had significantly lower accuracy on measures of lexical retrieval (action naming) and sentence processing (embedded sentences, both subject and object relative clauses). Reaction time was slightly faster on the test of embedded sentences among those with MetS. MetS adversely affects the language performance of older adults, impairing accuracy of both lexical retrieval and sentence processing. This finding reinforces and extends results of earlier research documenting the negative influence of potentially treatable medical conditions (diabetes, hypertension) on language performance in aging. The unanticipated finding that persons with MetS were faster in processing embedded sentences may represent an impairment of timing functions among older individuals with MetS.

  7. Surfactant phosphatidylcholine metabolism and surfactant function in preterm, ventilated lambs

    SciTech Connect

    Jobe, A.H.; Ikegami, M.; Seidner, S.R.; Pettenazzo, A.; Ruffini, L.

    1989-02-01

    Preterm lambs were delivered at 138 days gestational age and ventilated for periods up to 24 h in order to study surfactant metabolism and surfactant function. The surfactant-saturated phosphatidylcholine pool in the alveolar wash was 13 +/- 4 mumol/kg and did not change from 10 min to 24 h after birth. Trace amounts of labeled natural sheep surfactant were mixed with fetal lung fluid at birth. By 24 h, 80% of the label had become lung-tissue-associated, yet there was no loss of label from phosphatidylcholine in the lungs when calculated as the sum of the lung tissue plus alveolar wash. De novo synthesized phosphatidylcholine was labeled with choline given by intravascular injection at 1 h of age. Labeled phosphatidylcholine accumulated in the lung tissue linearly to 24 h, and the labeled phosphatidylcholine moved through lamellar body to alveolar pools. The turnover time for alveolar phosphatidylcholine was estimated to be about 13 h, indicating an active metabolic pool. A less surface-active surfactant fraction recovered as a supernatant after centrifugation of the alveolar washes at 40,000 x g increased from birth to 10 min of ventilation, but no subsequent changes in the distribution of surfactant phosphatidylcholine in surfactant fractions occurred. The results were consistent with recycling pathway(s) that maintained surface-active surfactant pools in preterm ventilated lambs.

  8. Silibinin Regulates Lipid Metabolism and Differentiation in Functional Human Adipocytes

    PubMed Central

    Barbagallo, Ignazio; Vanella, Luca; Cambria, Maria T.; Tibullo, Daniele; Godos, Justyna; Guarnaccia, Laura; Zappalà, Agata; Galvano, Fabio; Li Volti, Giovanni

    2016-01-01

    Silibinin, a natural plant flavonolignan is the main active constituent found in milk thistle (Silybum marianum). It is known to have hepatoprotective, anti-neoplastic effect, and suppresses lipid accumulation in adipocytes. Objective of this study was to investigate the effect of silibinin on adipogenic differentiation and thermogenic capacity of human adipose tissue derived mesenchymal stem cells. Silibinin (10 μM) treatment, either at the beginning or at the end of adipogenic differentiation, resulted in an increase of SIRT-1, PPARα, Pgc-1α, and UCPs gene expression. Moreover, silibinin administration resulted in a decrease of PPARγ, FABP4, FAS, and MEST/PEG1 gene expression during the differentiation, confirming that this compound is able to reduce fatty acid accumulation and adipocyte size. Our data showed that silibinin regulated adipocyte lipid metabolism, inducing thermogenesis and promoting a brown remodeling in adipocyte. Taken together, our findings suggest that silibinin increases UCPs expression by stimulation of SIRT1, PPARα, and Pgc-1α, improved metabolic parameters, decreased lipid mass leading to the formation of functional adipocytes. PMID:26834634

  9. Moonlighting transcriptional activation function of a fungal sulfur metabolism enzyme.

    PubMed

    Levati, Elisabetta; Sartini, Sara; Bolchi, Angelo; Ottonello, Simone; Montanini, Barbara

    2016-01-01

    Moonlighting proteins, including metabolic enzymes acting as transcription factors (TF), are present in a variety of organisms but have not been described in higher fungi so far. In a previous genome-wide analysis of the TF repertoire of the plant-symbiotic fungus Tuber melanosporum, we identified various enzymes, including the sulfur-assimilation enzyme phosphoadenosine-phosphosulfate reductase (PAPS-red), as potential transcriptional activators. A functional analysis performed in the yeast Saccharomyces cerevisiae, now demonstrates that a specific variant of this enzyme, PAPS-red A, localizes to the nucleus and is capable of transcriptional activation. TF moonlighting, which is not present in the other enzyme variant (PAPS-red B) encoded by the T. melanosporum genome, relies on a transplantable C-terminal polypeptide containing an alternating hydrophobic/hydrophilic amino acid motif. A similar moonlighting activity was demonstrated for six additional proteins, suggesting that multitasking is a relatively frequent event. PAPS-red A is sulfur-state-responsive and highly expressed, especially in fruitbodies, and likely acts as a recruiter of transcription components involved in S-metabolism gene network activation. PAPS-red B, instead, is expressed at low levels and localizes to a highly methylated and silenced region of the genome, hinting at an evolutionary mechanism based on gene duplication, followed by epigenetic silencing of this non-moonlighting gene variant. PMID:27121330

  10. Moonlighting transcriptional activation function of a fungal sulfur metabolism enzyme

    PubMed Central

    Levati, Elisabetta; Sartini, Sara; Bolchi, Angelo; Ottonello, Simone; Montanini, Barbara

    2016-01-01

    Moonlighting proteins, including metabolic enzymes acting as transcription factors (TF), are present in a variety of organisms but have not been described in higher fungi so far. In a previous genome-wide analysis of the TF repertoire of the plant-symbiotic fungus Tuber melanosporum, we identified various enzymes, including the sulfur-assimilation enzyme phosphoadenosine-phosphosulfate reductase (PAPS-red), as potential transcriptional activators. A functional analysis performed in the yeast Saccharomyces cerevisiae, now demonstrates that a specific variant of this enzyme, PAPS-red A, localizes to the nucleus and is capable of transcriptional activation. TF moonlighting, which is not present in the other enzyme variant (PAPS-red B) encoded by the T. melanosporum genome, relies on a transplantable C-terminal polypeptide containing an alternating hydrophobic/hydrophilic amino acid motif. A similar moonlighting activity was demonstrated for six additional proteins, suggesting that multitasking is a relatively frequent event. PAPS-red A is sulfur-state-responsive and highly expressed, especially in fruitbodies, and likely acts as a recruiter of transcription components involved in S-metabolism gene network activation. PAPS-red B, instead, is expressed at low levels and localizes to a highly methylated and silenced region of the genome, hinting at an evolutionary mechanism based on gene duplication, followed by epigenetic silencing of this non-moonlighting gene variant. PMID:27121330

  11. Update on Paraneoplastic Neurologic Disorders

    PubMed Central

    Rosenfeld, Myrna R.

    2010-01-01

    When patients with cancer develop neurologic symptoms, common causes include metastasis, infections, coagulopathy, metabolic or nutritional disturbances, and neurotoxicity from treatments. A thorough clinical history, temporal association with cancer therapies, and results of ancillary tests usually reveal one of these mechanisms as the etiology. When no etiology is identified, the diagnosis considered is often that of a paraneoplastic neurologic disorder (PND). With the recognition that PNDs are more frequent than previously thought, the availability of diagnostic tests, and the fact that, for some PNDs, treatment helps, PNDs should no longer be considered diagnostic zebras, and when appropriate should be included in the differential diagnosis early in the evaluation. PMID:20479279

  12. Liver transplantation for hepatic and neurological Wilson's disease.

    PubMed

    Geissler, I; Heinemann, K; Rohm, S; Hauss, J; Lamesch, P

    2003-06-01

    Wilson's disease (WD) is an autosomal-recessive inherited disorder of copper metabolism characterized by excessive deposition of copper throughout the body. If medical treatment fails in cases of fulminant hepatic failure and progressive hepatic dysfunction due to advanced cirrhosis, liver transplantation (OLTx) has been demonstrated to be a valuable treatment option. Between December 1993 and December 2002, 225 OLTxs in 198 patients were performed in our institution. In this consecutive series six patients (three females and three males) were liver grafted for WD. The follow-up ranged from 3 to 7 years. All patients are alive with well-functioning grafts at present. The ceruloplasmin levels increased after transplantation and remained normal. The Kayser-Fleischer ring disappeared in all patients, and urinary copper excretion normalized. The neurological manifestations in the two patients with severe neurological symptoms showed after 2 to 5 years a downward tendency; in one the ataxic movements disappeared completely. The psychiatric disorder in one patient disappeared as well the mild neurological symptoms in the patient with CHILD A cirrhosis. These two patients are fully recovered and returned to work. OLTx should be considered as a treatment option in patients with severe progressive neurological deficits even in cases with stable liver function since liver grafting definitely cures the underlying biochemical defect. In such cases an early decision for liver transplantation is justified because neurological deficits may become irreversible.

  13. Metabolically active functional food ingredients for weight control.

    PubMed

    Kovacs, E M R; Mela, D J

    2006-02-01

    The scale of the obesity epidemic creates a pressing consumer need as well as an enormous business opportunity for successful development and marketing of food products with added benefits for weight control. A number of proposed functional food ingredients have been shown to act post-absorptively to influence substrate utilization or thermogenesis. Characteristics and supporting data on conjugated linoleic acid, diglycerides, medium-chain triglycerides, green tea, ephedrine, caffeine, capsaicin and calcium, are reviewed here, giving examples of how these could act to alter energy expenditure or appetite control. Consideration is also given to other factors, in addition to efficacy, which must be satisfied to get such ingredients into foods. We conclude that, for each of the safe, putatively metabolically active agents, there remain gaps in clinical evidence or knowledge of mechanisms, which need to be addressed in order to specify the dietary conditions and food product compositions where these ingredients could be of most benefit for weight control. PMID:16436103

  14. Maternal blood metal levels and fetal markers of metabolic function

    SciTech Connect

    Ashley-Martin, Jillian; Dodds, Linda; Arbuckle, Tye E.; Ettinger, Adrienne S.; Shapiro, Gabriel D.; Fisher, Mandy; Taback, Shayne; Bouchard, Maryse F.; Monnier, Patricia; Dallaire, Renee; Fraser, William D.

    2015-01-15

    Exposure to metals commonly found in the environment has been hypothesized to be associated with measures of fetal growth but the epidemiological literature is limited. The Maternal–Infant Research on Environmental Chemicals (MIREC) study recruited 2001 women during the first trimester of pregnancy from 10 Canadian sites. Our objective was to assess the association between prenatal exposure to metals (lead, arsenic, cadmium, and mercury) and fetal metabolic function. Average maternal metal concentrations in 1st and 3rd trimester blood samples were used to represent prenatal metals exposure. Leptin and adiponectin were measured in 1363 cord blood samples and served as markers of fetal metabolic function. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between metals and both high (≥90%) and low (≤10%) fetal adiponectin and leptin levels. Leptin levels were significantly higher in female infants compared to males. A significant relationship between maternal blood cadmium and odds of high leptin was observed among males but not females in adjusted models. When adjusting for birth weight z-score, lead was associated with an increased odd of high leptin. No other significant associations were found at the top or bottom 10th percentile in either leptin or adiponectin models. This study supports the proposition that maternal levels of cadmium influence cord blood adipokine levels in a sex-dependent manner. Further investigation is required to confirm these findings and to determine how such findings at birth will translate into childhood anthropometric measures. - Highlights: • We determined relationships between maternal metal levels and cord blood adipokines. • Cord blood leptin levels were higher among female than male infants. • Maternal cadmium was associated with elevated leptin in male, not female infants. • No significant associations were observed between metals and

  15. Glycogen metabolism protects against metabolic insult to preserve carotid body function during glucose deprivation.

    PubMed

    Holmes, Andrew P; Turner, Philip J; Carter, Paul; Leadbeater, Wendy; Ray, Clare J; Hauton, David; Buckler, Keith J; Kumar, Prem

    2014-10-15

    The view that the carotid body (CB) type I cells are direct physiological sensors of hypoglycaemia is challenged by the finding that the basal sensory neuronal outflow from the whole organ is unchanged in response to low glucose. The reason for this difference in viewpoint and how the whole CB maintains its metabolic integrity when exposed to low glucose is unknown. Here we show that, in the intact superfused rat CB, basal sensory neuronal activity was sustained during glucose deprivation for 29.1 ± 1.2 min, before irreversible failure following a brief period of excitation. Graded increases in the basal discharge induced by reducing the superfusate PO2 led to proportional decreases in the time to the pre-failure excitation during glucose deprivation which was dependent on a complete run-down in glycolysis and a fall in cellular energy status. A similar ability to withstand prolonged glucose deprivation was observed in isolated type I cells. Electron micrographs and immunofluorescence staining of rat CB sections revealed the presence of glycogen granules and the glycogen conversion enzymes glycogen synthase I and glycogen phosphorylase BB, dispersed throughout the type I cell cytoplasm. Furthermore, pharmacological attenuation of glycogenolysis and functional depletion of glycogen both significantly reduced the time to glycolytic run-down by ∼33 and 65%, respectively. These findings suggest that type I cell glycogen metabolism allows for the continuation of glycolysis and the maintenance of CB sensory neuronal output in periods of restricted glucose delivery and this may act as a key protective mechanism for the organ during hypoglycaemia. The ability, or otherwise, to preserve energetic status may thus account for variation in the reported capacity of the CB to sense physiological glucose concentrations and may even underlie its function during pathological states associated with augmented CB discharge.

  16. Cytokine Therapies in Neurological Disease.

    PubMed

    Azodi, Shila; Jacobson, Steven

    2016-07-01

    Cytokines are a heterogeneous group of glycoproteins that coordinate physiological functions. Cytokine deregulation is observed in many neurological diseases. This article reviews current research focused on human clinical trials of cytokine and anticytokine therapies in the treatment of several neurological disease including stroke, neuromuscular diseases, neuroinfectious diseases, demyelinating diseases, and neurobehavioral diseases. This research suggests that cytokine therapy applications may play an important role in offering new strategies for disease modulation and treatment. Further, this research provides insights into the causal link between cytokine deregulation and neurological diseases. PMID:27388288

  17. Key sleep neurologic disorders

    PubMed Central

    St. Louis, Erik K.

    2014-01-01

    Summary Sleep disorders are frequent comorbidities in neurologic patients. This review focuses on clinical aspects and prognosis of 3 neurologic sleep disorders: narcolepsy, restless legs syndrome/Willis-Ekbom disease (RLS/WED), and REM sleep behavior disorder (RBD). Narcolepsy causes pervasive, enduring excessive daytime sleepiness, adversely affecting patients' daily functioning. RLS/WED is characterized by an uncomfortable urge to move the legs before sleep, often evolving toward augmentation and resulting in daylong bothersome symptoms. RBD causes potentially injurious dream enactment behaviors that often signify future evolution of overt synucleinopathy neurodegeneration in as many as 81% of patients. Timely recognition, referral for polysomnography, and longitudinal follow-up of narcolepsy, RLS/WED, and RBD patients are imperatives for neurologists in providing quality comprehensive patient care. PMID:24605270

  18. Phosphatidylinositol 3,5-bisphosphate: metabolism and cellular functions.

    PubMed

    Michell, Robert H; Heath, Victoria L; Lemmon, Mark A; Dove, Stephen K

    2006-01-01

    Polyphosphoinositides (PPIn) are low-abundance membrane phospholipids that each bind to a distinctive set of effector proteins and, thereby, regulate a characteristic suite of cellular processes. Major functions of phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P(2)] are in membrane and protein trafficking, and in pH control in the endosome-lysosome axis. Recently identified PtdIns(3,5)P(2) effectors include a family of novel beta-propeller proteins, for which we propose the name PROPPINs [for beta-propeller(s) that binds PPIn], and possibly proteins of the epsin and CHMP (charged multi-vesicular body proteins) families. All eukaryotes, with the exception of some pathogenic protists and microsporidians, possess proteins needed for the formation, metabolism and functions of PtdIns(3,5)P(2). The importance of PtdIns(3,5)P(2) for normal cell function is underscored by recent evidence for its involvement in mammalian cell responses to insulin and for PtdIns(3,5)P(2) dysfunction in the human genetic conditions X-linked myotubular myopathy, Type-4B Charcot-Marie-Tooth disease and fleck corneal dystrophy.

  19. Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection

    PubMed Central

    Hermes, Gretchen; Ajioka, James W; Kelly, Krystyna A; Mui, Ernest; Roberts, Fiona; Kasza, Kristen; Mayr, Thomas; Kirisits, Michael J; Wollmann, Robert; Ferguson, David JP; Roberts, Craig W; Hwang, Jong-Hee; Trendler, Toria; Kennan, Richard P; Suzuki, Yasuhiro; Reardon, Catherine; Hickey, William F; Chen, Lieping; McLeod, Rima

    2008-01-01

    Background Worldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences. Methods To better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5–12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. Histopathology in genetically resistant mice and cytokine and NRAMP knockout mice, effects of inoculation of isolated parasites, and treatment with sulfadiazine or αPD1 ligand were studied. Results Twelve months after infection, a time equivalent to middle to early elderly ages, mice had behavioral and neurological deficits, and brain MRIs showed mild to moderate ventricular dilatation. Lower brain weight correlated with greater magnitude of neurologic abnormalities and inflammation. Full genome microarrays of brains reflected inflammation causing neuronal damage (Gfap), effects on host cell protein processing (ubiquitin ligase), synapse remodeling (Complement 1q), and also increased expression of PD-1L (a ligand that allows persistent LCMV brain infection) and CD 36 (a fatty acid translocase and oxidized LDL receptor that mediates innate immune response to beta amyloid which is associated with pro-inflammation in Alzheimer's disease). Immunostaining detected no inflammation around intra-neuronal cysts, practically no free tachyzoites, and only rare bradyzoites. Nonetheless, there were perivascular, leptomeningeal inflammatory cells, particularly contiguous to the aqueduct of Sylvius and hippocampus

  20. Metabolic regulation of T cell differentiation and function

    PubMed Central

    Park, Benjamin V.; Pan, Fan

    2016-01-01

    Upon encountering pathogens, T cells mount immune responses by proliferating, increasing cellular mass and differentiating. These cellular changes impose significant energetic challenges on T cells. It was believed that TCR and cytokine-mediated signaling are dominant dictators of T cell-mediated immune responses. Recently, it was recognized that T cells utilize metabolic transporters and metabolic sensors that allow them to rapidly respond to nutrient-limiting inflammatory environments. Metabolic sensors allow T cells to find a balance between energy consumption (anabolic metabolism) and production (catabolic metabolism) in order to mount effective immune responses. Also, metabolic regulators interact with cytokine-dependent transcriptional regulators, suggesting a more integrative and advanced model of T cell activation and differentiation. In this review, we will discuss recent discoveries regarding the roles of metabolic regulators in effector and memory T cell development and their interaction with canonical transcription factors. PMID:26277275

  1. Ablation of arginylation in the mouse N-end rule pathway: loss of fat, higher metabolic rate, damaged spermatogenesis, and neurological perturbations.

    PubMed

    Brower, Christopher S; Varshavsky, Alexander

    2009-01-01

    In the N-end rule pathway of protein degradation, the destabilizing activity of N-terminal Asp, Glu or (oxidized) Cys residues requires their conjugation to Arg, which is recognized directly by pathway's ubiquitin ligases. N-terminal arginylation is mediated by the Ate1 arginyltransferase, whose physiological substrates include the Rgs4, Rgs5 and Rgs16 regulators of G proteins. Here, we employed the Cre-lox technique to uncover new physiological functions of N-terminal arginylation in adult mice. We show that postnatal deletion of mouse Ate1 (its unconditional deletion is embryonic lethal) causes a rapid decrease of body weight and results in early death of approximately 15% of Ate1-deficient mice. Despite being hyperphagic, the surviving Ate1-deficient mice contain little visceral fat. They also exhibit an increased metabolic rate, ectopic induction of the Ucp1 uncoupling protein in white fat, and are resistant to diet-induced obesity. In addition, Ate1-deficient mice have enlarged brains, an enhanced startle response, are strikingly hyperkinetic, and are prone to seizures and kyphosis. Ate1-deficient males are also infertile, owing to defects in Ate1(-/-) spermatocytes. The remarkably broad range of specific biological processes that are shown here to be perturbed by the loss of N-terminal arginylation will make possible the dissection of regulatory circuits that involve Ate1 and either its known substrates, such as Rgs4, Rgs5 and Rgs16, or those currently unknown. PMID:19915679

  2. Ablation of Arginylation in the Mouse N-End Rule Pathway: Loss of Fat, Higher Metabolic Rate, Damaged Spermatogenesis, and Neurological Perturbations

    PubMed Central

    Brower, Christopher S.; Varshavsky, Alexander

    2009-01-01

    In the N-end rule pathway of protein degradation, the destabilizing activity of N-terminal Asp, Glu or (oxidized) Cys residues requires their conjugation to Arg, which is recognized directly by pathway's ubiquitin ligases. N-terminal arginylation is mediated by the Ate1 arginyltransferase, whose physiological substrates include the Rgs4, Rgs5 and Rgs16 regulators of G proteins. Here, we employed the Cre-lox technique to uncover new physiological functions of N-terminal arginylation in adult mice. We show that postnatal deletion of mouse Ate1 (its unconditional deletion is embryonic lethal) causes a rapid decrease of body weight and results in early death of ∼15% of Ate1-deficient mice. Despite being hyperphagic, the surviving Ate1-deficient mice contain little visceral fat. They also exhibit an increased metabolic rate, ectopic induction of the Ucp1 uncoupling protein in white fat, and are resistant to diet-induced obesity. In addition, Ate1-deficient mice have enlarged brains, an enhanced startle response, are strikingly hyperkinetic, and are prone to seizures and kyphosis. Ate1-deficient males are also infertile, owing to defects in Ate1−/− spermatocytes. The remarkably broad range of specific biological processes that are shown here to be perturbed by the loss of N-terminal arginylation will make possible the dissection of regulatory circuits that involve Ate1 and either its known substrates, such as Rgs4, Rgs5 and Rgs16, or those currently unknown. PMID:19915679

  3. Association of metabolic syndrome with kidney function and histology in living kidney donors.

    PubMed

    Ohashi, Y; Thomas, G; Nurko, S; Stephany, B; Fatica, R; Chiesa, A; Rule, A D; Srinivas, T; Schold, J D; Navaneethan, S D; Poggio, E D

    2013-09-01

    The selection of living kidney donors is based on a formal evaluation of the state of health. However, this spectrum of health includes subtle metabolic derangements that can cluster as metabolic syndrome. We studied the association of metabolic syndrome with kidney function and histology in 410 donors from 2005 to 2012, of whom 178 donors were systematically followed after donation since 2009. Metabolic syndrome was defined as per the NCEP ATPIII criteria, but using a BMI > 25 kg/m(2) instead of waist circumference. Following donation, donors received counseling on lifestyle modification. Metabolic syndrome was present in 50 (12.2%) donors. Donors with metabolic syndrome were more likely to have chronic histological changes on implant biopsies than donors with no metabolic syndrome (29.0% vs. 9.3%, p < 0.001). This finding was associated with impaired kidney function recovery following donation. At last follow-up, reversal of metabolic syndrome was observed in 57.1% of donors with predonation metabolic syndrome, while only 10.8% of donors developed de novo metabolic syndrome (p < 0.001). In conclusion, metabolic syndrome in donors is associated with chronic histological changes, and nephrectomy in these donors was associated with subsequent protracted recovery of kidney function. Importantly, weight loss led to improvement of most abnormalities that define metabolic syndrome.

  4. Protective effects of Ephedra sinica extract on blood-brain barrier integrity and neurological function correlate with complement C3 reduction after subarachnoid hemorrhage in rats.

    PubMed

    Zuo, Shilun; Li, Wenyan; Li, Qiang; Zhao, Hengli; Tang, Jun; Chen, Qianwei; Liu, Xin; Zhang, John H; Chen, Yujie; Feng, Hua

    2015-11-16

    Early brain injury, which is associated with brain cell death, blood-brain barrier disruption, brain edema, and other pathophysiological events, is thought to be the main target in the prevention of poor outcomes after subarachnoid hemorrhage (SAH). Emerging evidences indicates that complement system, especially complement C3 is detrimental to neurological outcomes of SAH patients. Recently, Ephedra sinica extract was extracted and purified, which exhibits ability to block the activity of the classical and alternative pathways of complement, and improve neurological outcomes after spinal cord injury and ischemic brain injury. However, it is still unclear whether Ephedra sinica extract could attenuate early brain injury after SAH. In the present study, a standard endovascular perforation model was used to produce the experimental SAH in Sprague-Dawley rats. Ephedra sinica extract (15mg/kg) was orally administrated daily and evaluated for effects on modified Garcia score, brain water content, Evans blue extravasation and fluorescence, cortex cell death by TUNEL staining, and the expressions of complement C3/C3b, activated C3, sonic hedgehog, osteopontin and matrix metalloproteinase-9 by western bolt and immunofluorescence staining. We founded that the Ephedra sinica extract alleviated the blood-brain barrier disruption and brain edema, eventually improved neurological functions after SAH in rats. These neuroprotective effects was associated with the inhibition of complement C3, possibly via upregulating sonic hedgehog and osteopontin signal, and reducing the expressions of matrix metalloproteinase-9. Taking together, these observations suggested complement C3 inhibition by the Ephedra sinica extract may be a protective factor against early brain injury after SAH. PMID:26518242

  5. Functional characterization of Yersinia pestis aerobic glycerol metabolism.

    PubMed

    Willias, Stephan P; Chauhan, Sadhana; Motin, Vladimir L

    2014-11-01

    Yersinia pestis biovar Orientalis isolates have lost the capacity to ferment glycerol. Herein we provide experimental validation that a 93 bp in-frame deletion within the glpD gene encoding the glycerol-3-phosphate dehydrogenase present in all biovar Orientalis strains is sufficient to disrupt aerobic glycerol fermentation. Furthermore, the inability to ferment glycerol is often insured by a variety of additional mutations within the glpFKX operon which prevents glycerol internalization and conversion to glycerol-3-phosphate. The physiological impact of functional glpFKX in the presence of dysfunctional glpD was assessed. Results demonstrate no change in growth kinetics at 26 °C and 37 °C. Mutants deficient in glpD displayed decreased intracellular accumulation of glycerol-3-phosphate, a characterized inhibitor of cAMP receptor protein (CRP) activation. Since CRP is rigorously involved in global regulation Y. pestis virulence, we tested a possible influence of a single glpD mutation on virulence. Nonetheless, subcutaneous and intranasal murine challenge was not impacted by glycerol metabolism. As quantified by crystal violet assay, biofilm formation of the glpD-deficient KIM6+ mutant was mildly repressed; whereas, chromosomal restoration of glpD in CO92 resulted in a significant increase in biofilm formation. PMID:25220241

  6. Functional compartmentalization of oxidative and glycolytic metabolism in frog skin

    SciTech Connect

    Skul'skii, I.A.; Lapin, A.V.

    1985-07-01

    One of the basic functions of the epithelial cells of the skin of amphibians is unidirectional transport of Na/sup +/ from the environment into the blood. This transport is carried out in two stages. First, Na/sup +/ is absorbed from the environment by the epithelial cells through their apical membranes. Next, Na/sup +/ is actively drawn into the blood stream with the help of Na-K pumps which are located on the basolateral membranes. Huf, as early as 1957, proposed that ionic homeostasis of Na-transporting epithelial cells may be maintained at the expense of glycolysis, whereas the unidirectional transport of Na/sup +/ requires exclusively energy from oxidative metabolism. At that time, however, little was known about the nature of the Na-K pump and there were no isotopic data on permeability of epithelial cells to Na/sup +/ and K/sup +/. The authors confirm and update Huf's hypothesis in accordance with current knowledge. It was shown that anaerobic conditions (argon atmosphere) and various respiration inhibitors (rotenone, thallium) selectively inhibit unidirectional transport of Na/sup +/, as measured with the help of /sup 22/Na or short-circuit current, without influencing the concentration of sodium and potassium in the cells. The rate of penetration of Na/sup +/ through the apical membrane decrease by at least twice, but, irrespective of a significant flow of Na/sup +/ through the epithelial layer disappears.

  7. Welcome to Neurology: Genetics.

    PubMed

    Pulst, Stefan M

    2015-06-01

    The powers of human genetics and genetic technologies have transformed the complexities of neurology and neuroscience at the basic, translational, and now also the clinical level. We have left an era of black and white views of causative genetic variation and are entering a period of more than 50 shades of grey, fascinated with DNA variants that increase or decrease risk, epigenetic modification, and an unexpectedly large number of variants of unknown or potentially pathogenic significance. Loss-of-function alleles and even complete human gene knockouts for certain genes appear to be compatible with a normal phenotype. PMID:27066541

  8. Neurological theory of hypertension.

    PubMed

    Eggers, A E

    2003-06-01

    Review of the older literature on the relationship between migraine and hypertension, written in the era before either condition could be treated, discloses a high rate of co-morbidity. A neurological theory of essential hypertension is proposed in which the two diseases are brought together into one entity. It is hypothesized that abnormally functioning serotonergic pacemaker cells in the dorsal raphe nucleus, as part of a chronic stress response, inappropriately activate and inhibit parts of the central and autonomic nervous systems, so as to cause the two conditions. This theory builds on a previously published neural theory of migraine.

  9. The neurology of sleep.

    PubMed

    Swick, Todd J

    2005-11-01

    Neurology, by virtue of its study of the brain, is the primary medical science for the elucidation of the anatomy, physiology, pathology and, ultimately, the function of sleep. There has been nothing short of a revolution in the science of sleep over the past 50 years. From the discovery of REM sleep to the identification of Hypocretin/Orexin the basic science and clinical field of sleep medicine has blossomed. This article will explore the anatomy, physiology, biochemistry and, to a limited extent, pathophysiology of the sleep/wake centers of the brain. The field of chronobiology will also be touched upon.

  10. Neurologic Diseases in Special Care Patients.

    PubMed

    Robbins, Miriam R

    2016-07-01

    Neurologic diseases can have a major impact on functional capacity. Patients with neurologic disease require individualized management considerations depending on the extent of impairment and impact on functional capacity. This article reviews 4 of the more common and significant neurologic diseases (Alzheimer disease, cerebrovascular accident/stroke, multiple sclerosis, and Parkinson disease) that are likely to present to a dental office and provides suggestions on the dental management of patients with these conditions.

  11. [Function of pancreas transplants in increased metabolic stress].

    PubMed

    Teuscher, A U; Seaquist, E R; Barrou, Z; Kendall, D M; Robertson, R P

    1995-01-01

    Patients undergoing successful pancreas transplantation have normal glucose levels in the fasting and fed states and normal levels of hemoglobin A1c without use of exogenous inulin or any other medications for diabetes. In some of these patients, these measures have remained stable for more than 10 years. Additionally pancreas transplant recipients recover from short-term hypoglycemia produced by an intravenous pulse of insulin. However, metabolic success has been determined by relatively routine, unsophisticated tests such as oral and intravenous glucose tolerance tests or stimulation with intravenous arginine. These tests may not provide measures of the functional reserve of the pancreas, which is called on during periods of maximal stress. Consequently, we designed studies to ascertain beta and alpha cell performance in recipients of whole pancreas transplants and recipients of a segment of a living related donor. All recipients were recruited from the University of Minnesota Transplant Registry, Minneapolis, Minnesota. Successfully transplanted recipients were subjected to prolonged hyperglycemia to assess insulin secretory reserve using the method of glucose potentiation of arginine induced insulin secretion and to prolonged hypoglycemia to assess glucagon responsiveness and hepatic glucose production using the technique of the hyperinsulinemic hypoglycemic clamp. Our studies show that pancreas transplant recipients have markedly diminished insulin secretory reserve, a defect not evident with conventional tests of beta-cell function. No difference was found between the whole graft and segmental graft recipients. Pancreas transplantation restores the defective glucagon secretory response and enhances hepatic glucose production during prolonged hypoglycemia in subjects with type I diabetes. We conclude that pancreas transplantation does not completely restore beta-cell secretory reserve. This defect might be probably caused in part by cyclosporine and by the

  12. β-cell function is associated with metabolic syndrome in Mexican subjects

    PubMed Central

    Baez-Duarte, Blanca G; Sánchez-Guillén, María Del Carmen; Pérez-Fuentes, Ricardo; Zamora-Ginez, Irma; Leon-Chavez, Bertha Alicia; Revilla-Monsalve, Cristina; Islas-Andrade, Sergio

    2010-01-01

    Aims The clinical diagnosis of metabolic syndrome does not find any parameters to evaluate the insulin sensitivity (IS) or β-cell function. The evaluation of these parameters would detect early risk of developing metabolic syndrome. The aim of this study is to determine the relationship between β-cell function and presence of metabolic syndrome in Mexican subjects. Material and methods This study is part of the Mexican Survey on the Prevention of Diabetes (MexDiab Study) with headquarters in the city of Puebla, Mexico. The study comprised of 444 subjects of both genders, aged between 18 and 60 years and allocated into two study groups: (1) control group of individuals at metabolic balance without metabolic syndrome and (2) group composed of subjects with metabolic syndrome and diagnosed according to the criteria of the Third Report of the National Cholesterol Education Program Expert Panel on Defection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Anthropometric, biochemical, and clinical assessments were carried out. Results Average age of the subjects in the control group (n = 254) was 35.7 ± 11.5 years and 42.0 ± 10.7 years for subjects in the metabolic syndrome group (n = 190). Subjects at metabolic balance without metabolic syndrome showed decreased IS, increased insulin resistance (IR), and altered β-cell function. Individuals with metabolic syndrome showed a high prevalence (P ≤ 0.05) of family history of type 2 diabetes (T2D). This group also showed a significant metabolic imbalance with glucose and insulin levels and lipid profile outside the ranges considered safe to prevent the development of cardiovascular disease and T2D. Conclusion The main finding in this study was the detection of altered β-cell function, decreased IS, an increased IR in subjects at metabolic balance, and the progressive deterioration of β-cell function and IS in subjects with metabolic syndrome as the number of features of metabolic syndrome increases

  13. Neurology and neurologic practice in China.

    PubMed

    Shi, Fu-Dong; Jia, Jian-Ping

    2011-11-29

    In the wake of dramatic economic success during the past 2 decades, the specialized field of neurology has undergone a significant transformation in China. With an increase in life expectancy, the problems of aging and cognition have grown. Lifestyle alterations have been associated with an epidemiologic transition both in the incidence and etiology of stroke. These changes, together with an array of social issues and institution of health care reform, are creating challenges for practicing neurologists throughout China. Notable problems include overcrowded, decrepit facilities, overloaded physician schedules, deteriorating physician-patient relationships, and an insufficient infrastructure to accommodate patients who need specialized neurologic care. Conversely, with the creation of large and sophisticated neurology centers in many cities across the country, tremendous opportunities exist. Developments in neurologic subspecialties enable delivery of high-quality care. Clinical and translational research based on large patient populations as well as highly sophisticated technologies are emerging in many neurologic centers and pharmaceutical companies. Child neurology and neurorehabilitation will be fast-developing subdisciplines. Given China's extensive population, the growth and progress of its neurology complex, and its ever-improving quality control, it is reasonable to anticipate that Chinese neurologists will contribute notably to unraveling the pathogenic factors causing neurologic diseases and to providing new therapeutic solutions. PMID:22123780

  14. Neurology and neurologic practice in China.

    PubMed

    Shi, Fu-Dong; Jia, Jian-Ping

    2011-11-29

    In the wake of dramatic economic success during the past 2 decades, the specialized field of neurology has undergone a significant transformation in China. With an increase in life expectancy, the problems of aging and cognition have grown. Lifestyle alterations have been associated with an epidemiologic transition both in the incidence and etiology of stroke. These changes, together with an array of social issues and institution of health care reform, are creating challenges for practicing neurologists throughout China. Notable problems include overcrowded, decrepit facilities, overloaded physician schedules, deteriorating physician-patient relationships, and an insufficient infrastructure to accommodate patients who need specialized neurologic care. Conversely, with the creation of large and sophisticated neurology centers in many cities across the country, tremendous opportunities exist. Developments in neurologic subspecialties enable delivery of high-quality care. Clinical and translational research based on large patient populations as well as highly sophisticated technologies are emerging in many neurologic centers and pharmaceutical companies. Child neurology and neurorehabilitation will be fast-developing subdisciplines. Given China's extensive population, the growth and progress of its neurology complex, and its ever-improving quality control, it is reasonable to anticipate that Chinese neurologists will contribute notably to unraveling the pathogenic factors causing neurologic diseases and to providing new therapeutic solutions.

  15. Fly model causes neurological rethink

    PubMed Central

    Sadanandappa, Madhumala K

    2013-01-01

    A Drosophila model for a neurological disorder called type 2B Charcot-Marie-Tooth disease reveals that it has its origins in a partial loss of function, rather than a gain of function, which points to the need for a new therapeutic approach. PMID:24336781

  16. Mitochondrial metabolism in hematopoietic stem cells requires functional FOXO3

    PubMed Central

    Rimmelé, Pauline; Liang, Raymond; Bigarella, Carolina L; Kocabas, Fatih; Xie, Jingjing; Serasinghe, Madhavika N; Chipuk, Jerry; Sadek, Hesham; Zhang, Cheng Cheng; Ghaffari, Saghi

    2015-01-01

    Hematopoietic stem cells (HSC) are primarily dormant but have the potential to become highly active on demand to reconstitute blood. This requires a swift metabolic switch from glycolysis to mitochondrial oxidative phosphorylation. Maintenance of low levels of reactive oxygen species (ROS), a by-product of mitochondrial metabolism, is also necessary for sustaining HSC dormancy. Little is known about mechanisms that integrate energy metabolism with hematopoietic stem cell homeostasis. Here, we identify the transcription factor FOXO3 as a new regulator of metabolic adaptation of HSC. ROS are elevated in Foxo3−/− HSC that are defective in their activity. We show that Foxo3−/− HSC are impaired in mitochondrial metabolism independent of ROS levels. These defects are associated with altered expression of mitochondrial/metabolic genes in Foxo3−/− hematopoietic stem and progenitor cells (HSPC). We further show that defects of Foxo3−/− HSC long-term repopulation activity are independent of ROS or mTOR signaling. Our results point to FOXO3 as a potential node that couples mitochondrial metabolism with HSC homeostasis. These findings have critical implications for mechanisms that promote malignant transformation and aging of blood stem and progenitor cells. PMID:26209246

  17. DHA but Not EPA Emulsions Preserve Neurological and Mitochondrial Function after Brain Hypoxia-Ischemia in Neonatal Mice

    PubMed Central

    Sosunov, Sergey A.; Williams, Jill J.; Zirpoli, Hylde; Vlasakov, Iliyan; Deckelbaum, Richard J.; Ten, Vadim S.

    2016-01-01

    Background and Purpose Treatment with triglyceride emulsions of docosahexaenoic acid (tri-DHA) protected neonatal mice against hypoxia-ischemia (HI) brain injury. The mechanism of this neuroprotection remains unclear. We hypothesized that administration of tri-DHA enriches HI-brains with DHA/DHA metabolites. This reduces Ca2+-induced mitochondrial membrane permeabilization and attenuates brain injury. Methods 10-day-old C57BL/6J mice following HI-brain injury received tri-DHA, tri-EPA or vehicle. At 4–5 hours of reperfusion, mitochondrial fatty acid composition and Ca2+ buffering capacity were analyzed. At 24 hours and at 8–9 weeks of recovery, oxidative injury, neurofunctional and neuropathological outcomes were evaluated. In vitro, hyperoxia-induced mitochondrial generation of reactive oxygen species (ROS) and Ca2+ buffering capacity were measured in the presence or absence of DHA or EPA. Results Only post-treatment with tri-DHA reduced oxidative damage and improved short- and long-term neurological outcomes. This was associated with increased content of DHA in brain mitochondria and DHA-derived bioactive metabolites in cerebral tissue. After tri-DHA administration HI mitochondria were resistant to Ca2+-induced membrane permeabilization. In vitro, hyperoxia increased mitochondrial ROS production and reduced Ca2+ buffering capacity; DHA, but not EPA, significantly attenuated these effects of hyperoxia. Conclusions Post-treatment with tri-DHA resulted in significant accumulation of DHA and DHA derived bioactive metabolites in the HI-brain. This was associated with improved mitochondrial tolerance to Ca2+-induced permeabilization, reduced oxidative brain injury and permanent neuroprotection. Interaction of DHA with mitochondria alters ROS release and improves Ca2+ buffering capacity. This may account for neuroprotective action of post-HI administration of tri-DHA. PMID:27513579

  18. Mitochondrial dysfunction is an important cause of neurological deficits in an inflammatory model of multiple sclerosis.

    PubMed

    Sadeghian, Mona; Mastrolia, Vincenzo; Rezaei Haddad, Ali; Mosley, Angelina; Mullali, Gizem; Schiza, Dimitra; Sajic, Marija; Hargreaves, Iain; Heales, Simon; Duchen, Michael R; Smith, Kenneth J

    2016-01-01

    Neuroinflammation can cause major neurological dysfunction, without demyelination, in both multiple sclerosis (MS) and a mouse model of the disease (experimental autoimmune encephalomyelitis; EAE), but the mechanisms remain obscure. Confocal in vivo imaging of the mouse EAE spinal cord reveals that impaired neurological function correlates with the depolarisation of both the axonal mitochondria and the axons themselves. Indeed, the depolarisation parallels the expression of neurological deficit at the onset of disease, and during relapse, improving during remission in conjunction with the deficit. Mitochondrial dysfunction, fragmentation and impaired trafficking were most severe in regions of extravasated perivascular inflammatory cells. The dysfunction at disease onset was accompanied by increased expression of the rate-limiting glycolytic enzyme phosphofructokinase-2 in activated astrocytes, and by selective reduction in spinal mitochondrial complex I activity. The metabolic changes preceded any demyelination or axonal degeneration. We conclude that mitochondrial dysfunction is a major cause of reversible neurological deficits in neuroinflammatory disease, such as MS. PMID:27624721

  19. Mitochondrial dysfunction is an important cause of neurological deficits in an inflammatory model of multiple sclerosis

    PubMed Central

    Sadeghian, Mona; Mastrolia, Vincenzo; Rezaei Haddad, Ali; Mosley, Angelina; Mullali, Gizem; Schiza, Dimitra; Sajic, Marija; Hargreaves, Iain; Heales, Simon; Duchen, Michael R.; Smith, Kenneth J.

    2016-01-01

    Neuroinflammation can cause major neurological dysfunction, without demyelination, in both multiple sclerosis (MS) and a mouse model of the disease (experimental autoimmune encephalomyelitis; EAE), but the mechanisms remain obscure. Confocal in vivo imaging of the mouse EAE spinal cord reveals that impaired neurological function correlates with the depolarisation of both the axonal mitochondria and the axons themselves. Indeed, the depolarisation parallels the expression of neurological deficit at the onset of disease, and during relapse, improving during remission in conjunction with the deficit. Mitochondrial dysfunction, fragmentation and impaired trafficking were most severe in regions of extravasated perivascular inflammatory cells. The dysfunction at disease onset was accompanied by increased expression of the rate-limiting glycolytic enzyme phosphofructokinase-2 in activated astrocytes, and by selective reduction in spinal mitochondrial complex I activity. The metabolic changes preceded any demyelination or axonal degeneration. We conclude that mitochondrial dysfunction is a major cause of reversible neurological deficits in neuroinflammatory disease, such as MS. PMID:27624721

  20. Mesenchymal Stem Cells as Cellular Vectors for Pediatric Neurological Disorders

    PubMed Central

    Phinney, Donald G.; Isakova, Iryna A.

    2014-01-01

    Lysosomal storage diseases are a heterogeneous group of hereditary disorders characterized by a deficiency in lysosomal function. Although these disorders differ in their etiology and phenotype those that affect the nervous system generally manifest as a profound deterioration in neurologic function with age. Over the past several decades implementation of various treatment regimens including bone marrow and cord blood cell transplantation, enzyme replacement, and substrate reduction therapy have proved effective for managing some clinical manifestations of these diseases but their ability to ameliorate neurologic complications remains unclear. Consequently, there exists a need to develop alternative therapies that more effectively target the central nervous system. Recently, direct intracranial transplantation of tissue-specific stem and progenitor cells has been explored as a means to reconstitute metabolic deficiencies in the CNS. In this chapter we discuss the merits of bone marrow-derived mesenchymal stem cells (MSCs) for this purpose. Originally identified as progenitors of connective tissue cell lineages, recent findings have revealed several novel aspects of MSC biology that make them attractive as therapeutic agents in the CNS. We relate these advances in MSC biology to their utility as cellular vectors for treating neurologic sequelae associated with pediatric neurologic disorders. PMID:24858930

  1. Integrative functional genomic analysis unveils the differing dysregulated metabolic processes across hepatocellular carcinoma stages.

    PubMed

    Ramesh, Vignesh; Ganesan, Kumaresan

    2016-08-15

    Hepatocellular carcinoma (HCC) is a highly heterogeneous disease and the development of targeted therapeutics is still at an early stage. The 'omics' based genome-wide profiling comprising the transcriptome, miRNome and proteome are highly useful in identifying the deregulated molecular processes involved in hepatocarcinogenesis. One of the end products and processes of the central dogma being the metabolites and metabolic processes mediate the cellular functions. In recent years, metabolomics based investigations have revealed the major deregulated metabolic processes involved in carcinogenesis. However, the integrative analysis of the holistic metabolic processes with genomics is at an early stage. Since the gene-sets are highly useful in assessing the biological processes and pathways, we made an attempt to infer the deregulated cellular metabolic processes involved in HCC by employing metabolism associated gene-set enrichment analysis. Further, the metabolic process enrichment scores were integrated with the transcriptome profiles of HCC. Integrative analysis shows three distinct metabolic deregulations: i) hepatocyte function related molecular processes involving lipid/fatty acid/bile acid synthesis, ii) inflammatory processes with cytokine, sphingolipid & chondriotin sulphate metabolism and iii) enriched nucleotide metabolic process involving purine/pyrimidine & glucose mediated catabolic process, in hepatocarcinogenesis. The three distinct metabolic processes were found to occur both in tumor and liver cancer cell line profiles. Unsupervised hierarchical clustering of the metabolic processes along with clinical sample information has identified two major clusters based on AFP (alpha-fetoprotein) and metastasis. The study reveals the three major regulatory processes involved in HCC stages. PMID:27107678

  2. Integrative functional genomic analysis unveils the differing dysregulated metabolic processes across hepatocellular carcinoma stages.

    PubMed

    Ramesh, Vignesh; Ganesan, Kumaresan

    2016-08-15

    Hepatocellular carcinoma (HCC) is a highly heterogeneous disease and the development of targeted therapeutics is still at an early stage. The 'omics' based genome-wide profiling comprising the transcriptome, miRNome and proteome are highly useful in identifying the deregulated molecular processes involved in hepatocarcinogenesis. One of the end products and processes of the central dogma being the metabolites and metabolic processes mediate the cellular functions. In recent years, metabolomics based investigations have revealed the major deregulated metabolic processes involved in carcinogenesis. However, the integrative analysis of the holistic metabolic processes with genomics is at an early stage. Since the gene-sets are highly useful in assessing the biological processes and pathways, we made an attempt to infer the deregulated cellular metabolic processes involved in HCC by employing metabolism associated gene-set enrichment analysis. Further, the metabolic process enrichment scores were integrated with the transcriptome profiles of HCC. Integrative analysis shows three distinct metabolic deregulations: i) hepatocyte function related molecular processes involving lipid/fatty acid/bile acid synthesis, ii) inflammatory processes with cytokine, sphingolipid & chondriotin sulphate metabolism and iii) enriched nucleotide metabolic process involving purine/pyrimidine & glucose mediated catabolic process, in hepatocarcinogenesis. The three distinct metabolic processes were found to occur both in tumor and liver cancer cell line profiles. Unsupervised hierarchical clustering of the metabolic processes along with clinical sample information has identified two major clusters based on AFP (alpha-fetoprotein) and metastasis. The study reveals the three major regulatory processes involved in HCC stages.

  3. Dengue: a new challenge for neurology

    PubMed Central

    Puccioni-Sohler, Marzia; Orsini, Marco; Soares, Cristiane N.

    2012-01-01

    Dengue infection is a leading cause of illness and death in tropical and subtropical regions of the world. Forty percent of the world's population currently lives in these areas. The clinical picture resulting from dengue infection can range from relatively minor to catastrophic hemorrhagic fever. Recently, reports have increased of neurological manifestations. Neuropathogenesis seems to be related to direct nervous system viral invasion, autoimmune reaction, metabolic and hemorrhagic disturbance. Neurological manifestations include encephalitis, encephalopathy, meningitis, Guillain-Barré syndrome, myelitis, acute disseminated encephalomyelitis, polyneuropathy, mononeuropathy, and cerebromeningeal hemorrhage. The development of neurological symptoms in patients with positive Immunoglobulin M (IgM) dengue serology suggests a means of diagnosing the neurological complications associated with dengue. Viral antigens, specific IgM antibodies, and the intrathecal synthesis of dengue antibodies have been successfully detected in cerebrospinal fluid. However, despite diagnostic advancements, the treatment of neurological dengue is problematic. The launch of a dengue vaccine is expected to be beneficial. PMID:23355928

  4. Metabolic regulation of stem cell function in tissue homeostasis and organismal ageing.

    PubMed

    Chandel, Navdeep S; Jasper, Heinrich; Ho, Theodore T; Passegué, Emmanuelle

    2016-08-01

    Many tissues and organ systems in metazoans have the intrinsic capacity to regenerate, which is driven and maintained largely by tissue-resident somatic stem cell populations. Ageing is accompanied by a deregulation of stem cell function and a decline in regenerative capacity, often resulting in degenerative diseases. The identification of strategies to maintain stem cell function and regulation is therefore a promising avenue to allay a wide range of age-related diseases. Studies in various organisms have revealed a central role for metabolic pathways in the regulation of stem cell function. Ageing is associated with extensive metabolic changes, and interventions that influence cellular metabolism have long been recognized as robust lifespan-extending measures. In this Review, we discuss recent advances in our understanding of the metabolic control of stem cell function, and how stem cell metabolism relates to homeostasis and ageing. PMID:27428307

  5. The neurological basis of occupation.

    PubMed

    Gutman, Sharon A; Schindler, Victoria P

    2007-01-01

    The purpose of the present paper was to survey the literature about the neurological basis of human activity and its relationship to occupation and health. Activities related to neurological function were organized into three categories: those that activate the brain's reward system; those that promote the relaxation response; and those that preserve cognitive function into old age. The results from the literature review correlating neurological evidence and activities showed that purposeful and meaningful activities could counter the effects of stress-related diseases and reduce the risk for dementia. Specifically, it was found that music, drawing, meditation, reading, arts and crafts, and home repairs, for example, can stimulate the neurogical system and enhance health and well-being, Prospective research studies are needed to examine the effects of purposeful activities on reducing stress and slowing the rate of cognitive decline.

  6. The neurological basis of occupation.

    PubMed

    Gutman, Sharon A; Schindler, Victoria P

    2007-01-01

    The purpose of the present paper was to survey the literature about the neurological basis of human activity and its relationship to occupation and health. Activities related to neurological function were organized into three categories: those that activate the brain's reward system; those that promote the relaxation response; and those that preserve cognitive function into old age. The results from the literature review correlating neurological evidence and activities showed that purposeful and meaningful activities could counter the effects of stress-related diseases and reduce the risk for dementia. Specifically, it was found that music, drawing, meditation, reading, arts and crafts, and home repairs, for example, can stimulate the neurogical system and enhance health and well-being, Prospective research studies are needed to examine the effects of purposeful activities on reducing stress and slowing the rate of cognitive decline. PMID:17623380

  7. Metabolic profiling of Lolium perenne shows functional integration of metabolic responses to diverse subtoxic conditions of chemical stress

    PubMed Central

    Serra, Anne-Antonella; Couée, Ivan; Renault, David; Gouesbet, Gwenola; Sulmon, Cécile

    2015-01-01

    Plant communities are confronted with a great variety of environmental chemical stresses. Characterization of chemical stress in higher plants has often been focused on single or closely related stressors under acute exposure, or restricted to a selective number of molecular targets. In order to understand plant functioning under chemical stress conditions close to environmental pollution conditions, the C3 grass Lolium perenne was subjected to a panel of different chemical stressors (pesticide, pesticide degradation compound, polycyclic aromatic hydrocarbon, and heavy metal) under conditions of seed-level or root-level subtoxic exposure. Physiological and metabolic profiling analysis on roots and shoots revealed that all of these subtoxic chemical stresses resulted in discrete physiological perturbations and complex metabolic shifts. These metabolic shifts involved stressor-specific effects, indicating multilevel mechanisms of action, such as the effects of glyphosate and its degradation product aminomethylphosphonic acid on quinate levels. They also involved major generic effects that linked all of the subtoxic chemical stresses with major modifications of nitrogen metabolism, especially affecting asparagine, and of photorespiration, especially affecting alanine and glycerate. Stress-related physiological effects and metabolic adjustments were shown to be integrated through a complex network of metabolic correlations converging on Asn, Leu, Ser, and glucose-6-phosphate, which could potentially be modulated by differential dynamics and interconversion of soluble sugars (sucrose, trehalose, fructose, and glucose). Underlying metabolic, regulatory, and signalling mechanisms linking these subtoxic chemical stresses with a generic impact on nitrogen metabolism and photorespiration are discussed in relation to carbohydrate and low-energy sensing. PMID:25618145

  8. Neurological soft signs and cognitive functions: Amongst euthymic bipolar I disorder cases, non-affected first degree relatives and healthy controls.

    PubMed

    Sharma, Srikant; Bhatia, Triptish; Mazumdar, Sati; Deshpande, Smita N

    2016-08-01

    Both neurological soft signs (NSS) and cognitive deficits are present among euthymic bipolar patients. NSS could be related to neurocognitive performance, but this is not explored thoroughly. Healthy relatives of patients may also suffer from similar deficits. This study compared NSS and cognitive functions in euthymic Bipolar I Disorder (BPI) cases to their non-affected first degree relatives and healthy controls. We also investigated the association between NSS and cognitive functions in these three groups. NSS were assessed in three groups using Neurological Evaluation Scale-revised (NES-r). Eight cognitive domains were assessed in 31 euthymic BPI cases, their 30 non-affected first degree relatives and 30 healthy controls using Computerized Neurocognitive Battery (CNB). Euthymic BPI patients had significantly more NSS than non-affected first degree relatives on 5/7 tests (p-value ranges from 0.042 to p=0.0001) and healthy controls on all tests (p-value from 0.042 to <0.0001). Non-affected first degree relatives and controls did not have any significant difference. BPI participants performed worse than their non-affected first degree relatives on one neurocognitive domain of CNB (spatial memory accuracy, p=0.03) and healthy controls on four domains (spatial memory accuracy (p=0.04), abstraction and mental flexibility efficiency (p=0.04), spatial memory efficiency (p=0.04), and emotion efficiency (p=0.04). Non-affected relatives and healthy controls were similar on neurocognitive domains. Accuracy and efficiency indices of some specific cognitive domains were negatively associated with AV rating and tap copying NSS ratings. PMID:27520894

  9. Neurological soft signs and cognitive functions: Amongst euthymic bipolar I disorder cases, non-affected first degree relatives and healthy controls

    PubMed Central

    Sharma, Srikant; Bhatia, Triptish; Mazumdar, Sati; Deshpande, Smita N.

    2016-01-01

    Both neurological soft signs (NSS) and cognitive deficits are present among euthymic bipolar patients. NSS could be related to neurocognitive performance, but this is not explored thoroughly. Healthy relatives of patients may also suffer from similar deficits. This study compared NSS and cognitive functions in euthymic Bipolar I Disorder (BPI) cases to their non-affected first degree relatives and healthy controls. We also investigated the association between NSS and cognitive functions in these three groups. NSS were assessed in three groups using Neurological Evaluation Scale-revised (NES-r). Eight cognitive domains were assessed in 31 euthymic BPI cases, their 30 non-affected first degree relatives and 30 healthy controls using Computerized Neurocognitive Battery (CNB). Euthymic BPI patients had significantly more NSS than non-affected first degree relatives on 5/7 tests (p-value ranges from 0.042 to p = 0.0001) and healthy controls on all tests (p-value from 0.042 to <0.0001). Non-affected first degree relatives and controls did not have any significant difference. BPI participants performed worse than their non-affected first degree relatives on one neurocognitive domain of CNB (spatial memory accuracy, p = 0.03) and healthy controls on four domains (spatial memory accuracy (p = 0.04), abstraction and mental flexibility efficiency (p = 0.04), spatial memory efficiency (p = 0.04), and emotion efficiency (p = 0.04). Non-affected relatives and healthy controls were similar on neurocognitive domains. Accuracy and efficiency indices of some specific cognitive domains were negatively associated with AV rating and tap copying NSS ratings. PMID:27520894

  10. Biological functions of histidine-dipeptides and metabolic syndrome.

    PubMed

    Song, Byeng Chun; Joo, Nam-Seok; Aldini, Giancarlo; Yeum, Kyung-Jin

    2014-02-01

    The rapid increase in the prevalence of metabolic syndrome, which is associated with a state of elevated systemic oxidative stress and inflammation, is expected to cause future increases in the prevalence of diabetes and cardiovascular diseases. Oxidation of polyunsaturated fatty acids and sugars produces reactive carbonyl species, which, due to their electrophilic nature, react with the nucleophilic sites of certain amino acids. This leads to formation of protein adducts such as advanced glycoxidation/lipoxidation end products (AGEs/ALEs), resulting in cellular dysfunction. Therefore, an effective reactive carbonyl species and AGEs/ALEs sequestering agent may be able to prevent such cellular dysfunction. There is accumulating evidence that histidine containing dipeptides such as carnosine (β-alanyl-L-histidine) and anserine (β-alanyl-methyl-L-histidine) detoxify cytotoxic reactive carbonyls by forming unreactive adducts and are able to reverse glycated protein. In this review, 1) reaction mechanism of oxidative stress and certain chronic diseases, 2) interrelation between oxidative stress and inflammation, 3) effective reactive carbonyl species and AGEs/ALEs sequestering actions of histidine-dipeptides and their metabolism, 4) effects of carnosinase encoding gene on the effectiveness of histidine-dipeptides, and 5) protective effects of histidine-dipeptides against progression of metabolic syndrome are discussed. Overall, this review highlights the potential beneficial effects of histidine-dipeptides against metabolic syndrome. Randomized controlled human studies may provide essential information regarding whether histidine-dipeptides attenuate metabolic syndrome in humans. PMID:24611099

  11. NEUROLOGICAL ASPECTS OF HUMAN GLYCOSYLATION DISORDERS

    PubMed Central

    Freeze, Hudson H.; Eklund, Erik A.; Ng, Bobby G.; Patterson, Marc C.

    2016-01-01

    This review will present principles of glycosylation, describe the relevant glycosylation pathways and their related disorders, and highlight some of the neurological aspects and issues that continue to challenge researchers. Over 100 rare human genetic disorders that result from deficiencies in the different glycosylation pathways are known today. Most of these disorders impact the central and/or peripheral nervous systems. Patients typically have developmental delay/intellectual disability, hypotonia, seizures, neuropathy, and metabolic abnormalities in multiple organ systems. Between these disorders there is great clinical diversity because all cell types differentially glycosylate proteins and lipids. The patients have hundreds of mis-glycosylated products afflicting a myriad of processes including cell signaling, cell-cell interaction and cell migration. This vast complexity in glycan composition and function, along with limited analytic tools has impeded the identification of key glycosylated molecules that cause pathologies, and to date few critical target proteins have been pinpointed. PMID:25840006

  12. Identification of Functional Differences in Metabolic Networks Using Comparative Genomics and Constraint-Based Models

    PubMed Central

    Hamilton, Joshua J.; Reed, Jennifer L.

    2012-01-01

    Genome-scale network reconstructions are useful tools for understanding cellular metabolism, and comparisons of such reconstructions can provide insight into metabolic differences between organisms. Recent efforts toward comparing genome-scale models have focused primarily on aligning metabolic networks at the reaction level and then looking at differences and similarities in reaction and gene content. However, these reaction comparison approaches are time-consuming and do not identify the effect network differences have on the functional states of the network. We have developed a bilevel mixed-integer programming approach, CONGA, to identify functional differences between metabolic networks by comparing network reconstructions aligned at the gene level. We first identify orthologous genes across two reconstructions and then use CONGA to identify conditions under which differences in gene content give rise to differences in metabolic capabilities. By seeking genes whose deletion in one or both models disproportionately changes flux through a selected reaction (e.g., growth or by-product secretion) in one model over another, we are able to identify structural metabolic network differences enabling unique metabolic capabilities. Using CONGA, we explore functional differences between two metabolic reconstructions of Escherichia coli and identify a set of reactions responsible for chemical production differences between the two models. We also use this approach to aid in the development of a genome-scale model of Synechococcus sp. PCC 7002. Finally, we propose potential antimicrobial targets in Mycobacterium tuberculosis and Staphylococcus aureus based on differences in their metabolic capabilities. Through these examples, we demonstrate that a gene-centric approach to comparing metabolic networks allows for a rapid comparison of metabolic models at a functional level. Using CONGA, we can identify differences in reaction and gene content which give rise to different

  13. The Neurological Examination in Family Practice

    PubMed Central

    Siemens, Peter

    1974-01-01

    The family practitioner has the first opportunity and responsibility of making a diagnosis. Since a large portion of his work is concerned with neurological problems, he should be able to do a complete neurological examination. This examination should include evaluation of the gait, mental function, cranial nerves, motor system and sensory system. With practice, a routine neurological examination can be done rapidly and accurately. PMID:20469138

  14. A Strategy for Functional Interpretation of Metabolomic Time Series Data in Context of Metabolic Network Information

    PubMed Central

    Nägele, Thomas; Fürtauer, Lisa; Nagler, Matthias; Weiszmann, Jakob; Weckwerth, Wolfram

    2016-01-01

    The functional connection of experimental metabolic time series data with biochemical network information is an important, yet complex, issue in systems biology. Frequently, experimental analysis of diurnal, circadian, or developmental dynamics of metabolism results in a comprehensive and multidimensional data matrix comprising information about metabolite concentrations, protein levels, and/or enzyme activities. While, irrespective of the type of organism, the experimental high-throughput analysis of the transcriptome, proteome, and metabolome has become a common part of many systems biological studies, functional data integration in a biochemical and physiological context is still challenging. Here, an approach is presented which addresses the functional connection of experimental time series data with biochemical network information which can be inferred, for example, from a metabolic network reconstruction. Based on a time-continuous and variance-weighted regression analysis of experimental data, metabolic functions, i.e., first-order derivatives of metabolite concentrations, were related to time-dependent changes in other biochemically relevant metabolic functions, i.e., second-order derivatives of metabolite concentrations. This finally revealed time points of perturbed dependencies in metabolic functions indicating a modified biochemical interaction. The approach was validated using previously published experimental data on a diurnal time course of metabolite levels, enzyme activities, and metabolic flux simulations. To support and ease the presented approach of functional time series analysis, a graphical user interface including a test data set and a manual is provided which can be run within the numerical software environment Matlab®. PMID:27014700

  15. A Strategy for Functional Interpretation of Metabolomic Time Series Data in Context of Metabolic Network Information.

    PubMed

    Nägele, Thomas; Fürtauer, Lisa; Nagler, Matthias; Weiszmann, Jakob; Weckwerth, Wolfram

    2016-01-01

    The functional connection of experimental metabolic time series data with biochemical network information is an important, yet complex, issue in systems biology. Frequently, experimental analysis of diurnal, circadian, or developmental dynamics of metabolism results in a comprehensive and multidimensional data matrix comprising information about metabolite concentrations, protein levels, and/or enzyme activities. While, irrespective of the type of organism, the experimental high-throughput analysis of the transcriptome, proteome, and metabolome has become a common part of many systems biological studies, functional data integration in a biochemical and physiological context is still challenging. Here, an approach is presented which addresses the functional connection of experimental time series data with biochemical network information which can be inferred, for example, from a metabolic network reconstruction. Based on a time-continuous and variance-weighted regression analysis of experimental data, metabolic functions, i.e., first-order derivatives of metabolite concentrations, were related to time-dependent changes in other biochemically relevant metabolic functions, i.e., second-order derivatives of metabolite concentrations. This finally revealed time points of perturbed dependencies in metabolic functions indicating a modified biochemical interaction. The approach was validated using previously published experimental data on a diurnal time course of metabolite levels, enzyme activities, and metabolic flux simulations. To support and ease the presented approach of functional time series analysis, a graphical user interface including a test data set and a manual is provided which can be run within the numerical software environment Matlab®.

  16. Medical marijuana in neurology.

    PubMed

    Benbadis, Selim R; Sanchez-Ramos, Juan; Bozorg, Ali; Giarratano, Melissa; Kalidas, Kavita; Katzin, Lara; Robertson, Derrick; Vu, Tuan; Smith, Amanda; Zesiewicz, Theresa

    2014-12-01

    Constituents of the Cannabis plant, cannabinoids, may be of therapeutic value in neurologic diseases. The most abundant cannabinoids are Δ(9)-tetrahydrocannabinol, which possesses psychoactive properties, and cannabidiol, which has no intrinsic psychoactive effects, but exhibits neuroprotective properties in preclinical studies. A small number of high-quality clinical trials support the safety and efficacy of cannabinoids for treatment of spasticity of multiple sclerosis, pain refractory to opioids, glaucoma, nausea and vomiting. Lower level clinical evidence indicates that cannabinoids may be useful for dystonia, tics, tremors, epilepsy, migraine and weight loss. Data are also limited in regards to adverse events and safety. Common nonspecific adverse events are similar to those of other CNS 'depressants' and include weakness, mood changes and dizziness. Cannabinoids can have cardiovascular adverse events and, when smoked chronically, may affect pulmonary function. Fatalities are rare even with recreational use. There is a concern about psychological dependence, but physical dependence is less well documented. Cannabis preparations may presently offer an option for compassionate use in severe neurologic diseases, but at this point, only when standard-of-care therapy is ineffective. As more high-quality clinical data are gathered, the therapeutic application of cannabinoids will likely expand.

  17. Medical marijuana in neurology.

    PubMed

    Benbadis, Selim R; Sanchez-Ramos, Juan; Bozorg, Ali; Giarratano, Melissa; Kalidas, Kavita; Katzin, Lara; Robertson, Derrick; Vu, Tuan; Smith, Amanda; Zesiewicz, Theresa

    2014-12-01

    Constituents of the Cannabis plant, cannabinoids, may be of therapeutic value in neurologic diseases. The most abundant cannabinoids are Δ(9)-tetrahydrocannabinol, which possesses psychoactive properties, and cannabidiol, which has no intrinsic psychoactive effects, but exhibits neuroprotective properties in preclinical studies. A small number of high-quality clinical trials support the safety and efficacy of cannabinoids for treatment of spasticity of multiple sclerosis, pain refractory to opioids, glaucoma, nausea and vomiting. Lower level clinical evidence indicates that cannabinoids may be useful for dystonia, tics, tremors, epilepsy, migraine and weight loss. Data are also limited in regards to adverse events and safety. Common nonspecific adverse events are similar to those of other CNS 'depressants' and include weakness, mood changes and dizziness. Cannabinoids can have cardiovascular adverse events and, when smoked chronically, may affect pulmonary function. Fatalities are rare even with recreational use. There is a concern about psychological dependence, but physical dependence is less well documented. Cannabis preparations may presently offer an option for compassionate use in severe neurologic diseases, but at this point, only when standard-of-care therapy is ineffective. As more high-quality clinical data are gathered, the therapeutic application of cannabinoids will likely expand. PMID:25427150

  18. Selection for increased mass-independent maximal metabolic rate suppresses innate but not adaptive immune function

    PubMed Central

    Downs, Cynthia J.; Brown, Jessi L.; Wone, Bernard; Donovan, Edward R.; Hunter, Kenneth; Hayes, Jack P.

    2013-01-01

    Both appropriate metabolic rates and sufficient immune function are essential for survival. Consequently, eco-immunologists have hypothesized that animals may experience trade-offs between metabolic rates and immune function. Previous work has focused on how basal metabolic rate (BMR) may trade-off with immune function, but maximal metabolic rate (MMR), the upper limit to aerobic activity, might also trade-off with immune function. We used mice artificially selected for high mass-independent MMR to test for trade-offs with immune function. We assessed (i) innate immune function by quantifying cytokine production in response to injection with lipopolysaccharide and (ii) adaptive immune function by measuring antibody production in response to injection with keyhole limpet haemocyanin. Selection for high mass-independent MMR suppressed innate immune function, but not adaptive immune function. However, analyses at the individual level also indicate a negative correlation between MMR and adaptive immune function. By contrast BMR did not affect immune function. Evolutionarily, natural selection may favour increasing MMR to enhance aerobic performance and endurance, but the benefits of high MMR may be offset by impaired immune function. This result could be important in understanding the selective factors acting on the evolution of metabolic rates. PMID:23303541

  19. Estrogen-Related Receptor α (ERRα) and ERRγ Are Essential Coordinators of Cardiac Metabolism and Function

    PubMed Central

    Wang, Ting; McDonald, Caitlin; Petrenko, Nataliya B.; Leblanc, Mathias; Wang, Tao; Giguere, Vincent; Evans, Ronald M.; Patel, Vickas V.

    2015-01-01

    Almost all cellular functions are powered by a continuous energy supply derived from cellular metabolism. However, it is little understood how cellular energy production is coordinated with diverse energy-consuming cellular functions. Here, using the cardiac muscle system, we demonstrate that nuclear receptors estrogen-related receptor α (ERRα) and ERRγ are essential transcriptional coordinators of cardiac energy production and consumption. On the one hand, ERRα and ERRγ together are vital for intact cardiomyocyte metabolism by directly controlling expression of genes important for mitochondrial functions and dynamics. On the other hand, ERRα and ERRγ influence major cardiomyocyte energy consumption functions through direct transcriptional regulation of key contraction, calcium homeostasis, and conduction genes. Mice lacking both ERRα and cardiac ERRγ develop severe bradycardia, lethal cardiomyopathy, and heart failure featuring metabolic, contractile, and conduction dysfunctions. These results illustrate that the ERR transcriptional pathway is essential to couple cellular energy metabolism with energy consumption processes in order to maintain normal cardiac function. PMID:25624346

  20. [Specific features of neurological complications developing in patients with type 2 diabetes mellitus and metabolic syndrome: possibility for correction and prevention].

    PubMed

    Shishkova, V N

    2015-01-01

    The prevalence of type 2 diabetes mellitus (DM) and preceding metabolic disturbances has reached epidemic proportions. Oxidative stress plays a significant role in the development of micro- and macrovascular complications in patients with DM. The accumulation of free radicals is responsible for the development of systemic and vascular inflammation, endothelial dysfunction, and hypercoagulable and ischemic states. Since vascular and nervous system damages do not level off even under adequate glycemic control, there is a need for complex pathogenetic treatment strategies. Antioxidant therapy using mexidol is one of the compulsory components of combination therapy for complications of DM.

  1. Metabolism

    MedlinePlus

    Metabolism refers to all the physical and chemical processes in the body that convert or use energy, ... Tortora GJ, Derrickson BH. Metabolism. In: Tortora GJ, Derrickson BH. Principles of Anatomy and Physiology . 14th ed. Hoboken, NJ: John H Wiley and Sons; 2013: ...

  2. Detecting Functional Groups of Arabidopsis Mutants by Metabolic Profiling and Evaluation of Pleiotropic Responses

    PubMed Central

    Hofmann, Jörg; Börnke, Frederik; Schmiedl, Alfred; Kleine, Tatjana; Sonnewald, Uwe

    2011-01-01

    Metabolic profiles and fingerprints of Arabidopsis thaliana plants with various defects in plastidic sugar metabolism or photosynthesis were analyzed to elucidate if the genetic mutations can be traced by comparing their metabolic status. Using a platform of chromatographic and spectrometric tools data from untargeted full MS scans as well as from selected metabolites including major carbohydrates, phosphorylated intermediates, carboxylates, free amino acids, major antioxidants, and plastidic pigments were evaluated. Our key observations are that by multivariate statistical analysis each mutant can be separated by a unique metabolic signature. Closely related mutants come close. Thus metabolic profiles of sugar mutants are different but more similar than those of photosynthesis mutants. All mutants show pleiotropic responses mirrored in their metabolic status. These pleiotropic responses are typical and can be used for separating and grouping of the mutants. Our findings show that metabolite fingerprints can be taken to classify mutants and hence may be used to sort genes into functional groups. PMID:22639613

  3. Small RNA functions in carbon metabolism and virulence of enteric pathogens

    PubMed Central

    Papenfort, Kai; Vogel, Jörg

    2014-01-01

    Enteric pathogens often cycle between virulent and saprophytic lifestyles. To endure these frequent changes in nutrient availability and composition bacteria possess an arsenal of regulatory and metabolic genes allowing rapid adaptation and high flexibility. While numerous proteins have been characterized with regard to metabolic control in pathogenic bacteria, small non-coding RNAs have emerged as additional regulators of metabolism. Recent advances in sequencing technology have vastly increased the number of candidate regulatory RNAs and several of them have been found to act at the interface of bacterial metabolism and virulence factor expression. Importantly, studying these riboregulators has not only provided insight into their metabolic control functions but also revealed new mechanisms of post-transcriptional gene control. This review will focus on the recent advances in this area of host-microbe interaction and discuss how regulatory small RNAs may help coordinate metabolism and virulence of enteric pathogens. PMID:25077072

  4. Microvesicles from brain-extract—treated mesenchymal stem cells improve neurological functions in a rat model of ischemic stroke

    PubMed Central

    Lee, Ji Yong; Kim, Eiru; Choi, Seong-Mi; Kim, Dong-Wook; Kim, Kwang Pyo; Lee, Insuk; Kim, Han-Soo

    2016-01-01

    Transplantation of mesenchymal stem cells (MSCs) was reported to improve functional outcomes in a rat model of ischemic stroke, and subsequent studies suggest that MSC-derived microvesicles (MVs) can replace the beneficial effects of MSCs. Here, we evaluated three different MSC-derived MVs, including MVs from untreated MSCs (MSC-MVs), MVs from MSCs treated with normal rat brain extract (NBE-MSC-MVs), and MVs from MSCs treated with stroke-injured rat brain extract (SBE-MSC-MVs), and tested their effects on ischemic brain injury induced by permanent middle cerebral artery occlusion (pMCAO) in rats. NBE-MSC-MVs and SBE-MSC-MVs had significantly greater efficacy than MSC-MVs for ameliorating ischemic brain injury with improved functional recovery. We found similar profiles of key signalling proteins in NBE-MSC-MVs and SBE-MSC-MVs, which account for their similar therapeutic efficacies. Immunohistochemical analyses suggest that brain-extract—treated MSC-MVs reduce inflammation, enhance angiogenesis, and increase endogenous neurogenesis in the rat brain. We performed mass spectrometry proteomic analyses and found that the total proteomes of brain-extract—treated MSC-MVs are highly enriched for known vesicular proteins. Notably, MSC-MV proteins upregulated by brain extracts tend to be modular for tissue repair pathways. We suggest that MSC-MV proteins stimulated by the brain microenvironment are paracrine effectors that enhance MSC therapy for stroke injury. PMID:27609711

  5. Microvesicles from brain-extract-treated mesenchymal stem cells improve neurological functions in a rat model of ischemic stroke.

    PubMed

    Lee, Ji Yong; Kim, Eiru; Choi, Seong-Mi; Kim, Dong-Wook; Kim, Kwang Pyo; Lee, Insuk; Kim, Han-Soo

    2016-01-01

    Transplantation of mesenchymal stem cells (MSCs) was reported to improve functional outcomes in a rat model of ischemic stroke, and subsequent studies suggest that MSC-derived microvesicles (MVs) can replace the beneficial effects of MSCs. Here, we evaluated three different MSC-derived MVs, including MVs from untreated MSCs (MSC-MVs), MVs from MSCs treated with normal rat brain extract (NBE-MSC-MVs), and MVs from MSCs treated with stroke-injured rat brain extract (SBE-MSC-MVs), and tested their effects on ischemic brain injury induced by permanent middle cerebral artery occlusion (pMCAO) in rats. NBE-MSC-MVs and SBE-MSC-MVs had significantly greater efficacy than MSC-MVs for ameliorating ischemic brain injury with improved functional recovery. We found similar profiles of key signalling proteins in NBE-MSC-MVs and SBE-MSC-MVs, which account for their similar therapeutic efficacies. Immunohistochemical analyses suggest that brain-extract-treated MSC-MVs reduce inflammation, enhance angiogenesis, and increase endogenous neurogenesis in the rat brain. We performed mass spectrometry proteomic analyses and found that the total proteomes of brain-extract-treated MSC-MVs are highly enriched for known vesicular proteins. Notably, MSC-MV proteins upregulated by brain extracts tend to be modular for tissue repair pathways. We suggest that MSC-MV proteins stimulated by the brain microenvironment are paracrine effectors that enhance MSC therapy for stroke injury. PMID:27609711

  6. Mice with mutations of Dock7 have generalized hypopigmentation and white-spotting but show normal neurological function.

    PubMed

    Blasius, Amanda L; Brandl, Katharina; Crozat, Karine; Xia, Yu; Khovananth, Kevin; Krebs, Philippe; Smart, Nora G; Zampolli, Antonella; Ruggeri, Zaverio M; Beutler, Bruce A

    2009-02-24

    The classical recessive coat color mutation misty (m) arose spontaneously on the DBA/J background and causes generalized hypopigmentation and localized white-spotting in mice, with a lack of pigment on the belly, tail tip, and paws. Here we describe moonlight (mnlt), a second hypopigmentation and white-spotting mutation identified on the C57BL/6J background, which yields a phenotypic copy of m/m coat color traits. We demonstrate that the 2 mutations are allelic. m/m and mnlt/mnlt phenotypes both result from mutations that truncate the dedicator of cytokinesis 7 protein (DOCK7), a widely expressed Rho family guanine nucleotide exchange factor. Although Dock7 is transcribed at high levels in the developing brain and has been implicated in both axon development and myelination by in vitro studies, we find no requirement for DOCK7 in neurobehavioral function in vivo. However, DOCK7 has non-redundant role(s) related to the distribution and function of dermal and follicular melanocytes. PMID:19202056

  7. Microvesicles from brain-extract-treated mesenchymal stem cells improve neurological functions in a rat model of ischemic stroke.

    PubMed

    Lee, Ji Yong; Kim, Eiru; Choi, Seong-Mi; Kim, Dong-Wook; Kim, Kwang Pyo; Lee, Insuk; Kim, Han-Soo

    2016-09-09

    Transplantation of mesenchymal stem cells (MSCs) was reported to improve functional outcomes in a rat model of ischemic stroke, and subsequent studies suggest that MSC-derived microvesicles (MVs) can replace the beneficial effects of MSCs. Here, we evaluated three different MSC-derived MVs, including MVs from untreated MSCs (MSC-MVs), MVs from MSCs treated with normal rat brain extract (NBE-MSC-MVs), and MVs from MSCs treated with stroke-injured rat brain extract (SBE-MSC-MVs), and tested their effects on ischemic brain injury induced by permanent middle cerebral artery occlusion (pMCAO) in rats. NBE-MSC-MVs and SBE-MSC-MVs had significantly greater efficacy than MSC-MVs for ameliorating ischemic brain injury with improved functional recovery. We found similar profiles of key signalling proteins in NBE-MSC-MVs and SBE-MSC-MVs, which account for their similar therapeutic efficacies. Immunohistochemical analyses suggest that brain-extract-treated MSC-MVs reduce inflammation, enhance angiogenesis, and increase endogenous neurogenesis in the rat brain. We performed mass spectrometry proteomic analyses and found that the total proteomes of brain-extract-treated MSC-MVs are highly enriched for known vesicular proteins. Notably, MSC-MV proteins upregulated by brain extracts tend to be modular for tissue repair pathways. We suggest that MSC-MV proteins stimulated by the brain microenvironment are paracrine effectors that enhance MSC therapy for stroke injury.

  8. The human NAD metabolome: Functions, metabolism and compartmentalization

    PubMed Central

    Nikiforov, Andrey; Kulikova, Veronika; Ziegler, Mathias

    2015-01-01

    Abstract The metabolism of NAD has emerged as a key regulator of cellular and organismal homeostasis. Being a major component of both bioenergetic and signaling pathways, the molecule is ideally suited to regulate metabolism and major cellular events. In humans, NAD is synthesized from vitamin B3 precursors, most prominently from nicotinamide, which is the degradation product of all NAD-dependent signaling reactions. The scope of NAD-mediated regulatory processes is wide including enzyme regulation, control of gene expression and health span, DNA repair, cell cycle regulation and calcium signaling. In these processes, nicotinamide is cleaved from NAD+ and the remaining ADP-ribosyl moiety used to modify proteins (deacetylation by sirtuins or ADP-ribosylation) or to generate calcium-mobilizing agents such as cyclic ADP-ribose. This review will also emphasize the role of the intermediates in the NAD metabolome, their intra- and extra-cellular conversions and potential contributions to subcellular compartmentalization of NAD pools. PMID:25837229

  9. The brown fat secretome: metabolic functions beyond thermogenesis

    PubMed Central

    Wang, Guo-Xiao; Zhao, Xu-Yun; Lin, Jiandie D.

    2015-01-01

    Brown fat is highly active in fuel oxidation and dissipates chemical energy through uncoupling protein 1 (UCP1)-mediated heat production. Activation of brown fat leads to increased energy expenditure, reduced adiposity, and lower plasma glucose and lipid levels, thus contributing to better homeostasis. Uncoupled respiration and thermogenesis have been considered to be responsible for the metabolic benefits of brown adipose tissue. Recent studies have demonstrated that brown adipocytes also secrete factors that act locally and systemically to influence fuel and energy metabolism. This review discusses the evidence supporting a thermogenesis-independent role of brown fat, particularly through its release of secreted factors, and their implications in physiology and therapeutic development. PMID:25843910

  10. Increasing pharmacological knowledge about human neurological and psychiatric disorders through functional neuroimaging and its application in drug discovery.

    PubMed

    Nathan, Pradeep J; Phan, K Luan; Harmer, Catherine J; Mehta, Mitul A; Bullmore, Edward T

    2014-02-01

    Functional imaging methods such as fMRI have been widely used to gain greater understanding of brain circuitry abnormalities in CNS disorders and their underlying neurochemical basis. Findings suggest that: (1) drugs with known clinical efficacy have consistent effects on disease relevant brain circuitry, (2) brain activation changes at baseline or early drug effects on brain activity can predict long-term efficacy; and (3) fMRI together with pharmacological challenges could serve as experimental models of disease phenotypes and be used for screening novel drugs. Together, these observations suggest that drug related modulation of disease relevant brain circuitry may serve as a promising biomarker/method for use in drug discovery to demonstrate target engagement, differential efficacy, dose-response relationships, and prediction of clinically relevant changes.

  11. Ketogenic diets, mitochondria, and neurological diseases

    PubMed Central

    Gano, Lindsey B.; Patel, Manisha; Rho, Jong M.

    2014-01-01

    The ketogenic diet (KD) is a broad-spectrum therapy for medically intractable epilepsy and is receiving growing attention as a potential treatment for neurological disorders arising in part from bioenergetic dysregulation. The high-fat/low-carbohydrate “classic KD”, as well as dietary variations such as the medium-chain triglyceride diet, the modified Atkins diet, the low-glycemic index treatment, and caloric restriction, enhance cellular metabolic and mitochondrial function. Hence, the broad neuroprotective properties of such therapies may stem from improved cellular metabolism. Data from clinical and preclinical studies indicate that these diets restrict glycolysis and increase fatty acid oxidation, actions which result in ketosis, replenishment of the TCA cycle (i.e., anaplerosis), restoration of neurotransmitter and ion channel function, and enhanced mitochondrial respiration. Further, there is mounting evidence that the KD and its variants can impact key signaling pathways that evolved to sense the energetic state of the cell, and that help maintain cellular homeostasis. These pathways, which include PPARs, AMP-activated kinase, mammalian target of rapamycin, and the sirtuins, have all been recently implicated in the neuroprotective effects of the KD. Further research in this area may lead to future therapeutic strategies aimed at mimicking the pleiotropic neuroprotective effects of the KD. PMID:24847102

  12. Ornithine and Homocitrulline Impair Mitochondrial Function, Decrease Antioxidant Defenses and Induce Cell Death in Menadione-Stressed Rat Cortical Astrocytes: Potential Mechanisms of Neurological Dysfunction in HHH Syndrome.

    PubMed

    Zanatta, Ângela; Rodrigues, Marília Danyelle Nunes; Amaral, Alexandre Umpierrez; Souza, Débora Guerini; Quincozes-Santos, André; Wajner, Moacir

    2016-09-01

    Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is caused by deficiency of ornithine translocase leading to predominant tissue accumulation and high urinary excretion of ornithine (Orn), homocitrulline (Hcit) and ammonia. Although affected patients commonly present neurological dysfunction manifested by cognitive deficit, spastic paraplegia, pyramidal and extrapyramidal signs, stroke-like episodes, hypotonia and ataxia, its pathogenesis is still poorly known. Although astrocytes are necessary for neuronal protection. Therefore, in the present study we investigated the effects of Orn and Hcit on cell viability (propidium iodide incorporation), mitochondrial function (thiazolyl blue tetrazolium bromide-MTT-reduction and mitochondrial membrane potential-ΔΨm), antioxidant defenses (GSH) and pro-inflammatory response (NFkB, IL-1β, IL-6 and TNF-α) in unstimulated and menadione-stressed cortical astrocytes that were previously shown to be susceptible to damage by neurotoxins. We first observed that Orn decreased MTT reduction, whereas both amino acids decreased GSH levels, without altering cell viability and the pro-inflammatory factors in unstimulated astrocytes. Furthermore, Orn and Hcit decreased cell viability and ΔΨm in menadione-treated astrocytes. The present data indicate that the major compounds accumulating in HHH syndrome impair mitochondrial function and reduce cell viability and the antioxidant defenses in cultured astrocytes especially when stressed by menadione. It is presumed that these mechanisms may be involved in the neuropathology of this disease. PMID:27161368

  13. Ornithine and Homocitrulline Impair Mitochondrial Function, Decrease Antioxidant Defenses and Induce Cell Death in Menadione-Stressed Rat Cortical Astrocytes: Potential Mechanisms of Neurological Dysfunction in HHH Syndrome.

    PubMed

    Zanatta, Ângela; Rodrigues, Marília Danyelle Nunes; Amaral, Alexandre Umpierrez; Souza, Débora Guerini; Quincozes-Santos, André; Wajner, Moacir

    2016-09-01

    Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is caused by deficiency of ornithine translocase leading to predominant tissue accumulation and high urinary excretion of ornithine (Orn), homocitrulline (Hcit) and ammonia. Although affected patients commonly present neurological dysfunction manifested by cognitive deficit, spastic paraplegia, pyramidal and extrapyramidal signs, stroke-like episodes, hypotonia and ataxia, its pathogenesis is still poorly known. Although astrocytes are necessary for neuronal protection. Therefore, in the present study we investigated the effects of Orn and Hcit on cell viability (propidium iodide incorporation), mitochondrial function (thiazolyl blue tetrazolium bromide-MTT-reduction and mitochondrial membrane potential-ΔΨm), antioxidant defenses (GSH) and pro-inflammatory response (NFkB, IL-1β, IL-6 and TNF-α) in unstimulated and menadione-stressed cortical astrocytes that were previously shown to be susceptible to damage by neurotoxins. We first observed that Orn decreased MTT reduction, whereas both amino acids decreased GSH levels, without altering cell viability and the pro-inflammatory factors in unstimulated astrocytes. Furthermore, Orn and Hcit decreased cell viability and ΔΨm in menadione-treated astrocytes. The present data indicate that the major compounds accumulating in HHH syndrome impair mitochondrial function and reduce cell viability and the antioxidant defenses in cultured astrocytes especially when stressed by menadione. It is presumed that these mechanisms may be involved in the neuropathology of this disease.

  14. [Sleep and neurological diseases].

    PubMed

    Mayer, G

    2016-06-01

    Knowledge of the physiology of sleep-wake regulation can contribute to an understanding of the pathophysiology and symptoms of neurological diseases and is helpful for initiating specific therapies for sleep-wake cycle stabilization. Based on historically important observations on the close relationship between sleep and neurological diseases, new insights and developments in selected neurological entities are presented in this review article. PMID:27167889

  15. Genetic disorders of thyroid metabolism and brain development

    PubMed Central

    Kurian, Manju A; Jungbluth, Heinz

    2014-01-01

    Normal thyroid metabolism is essential for human development, including the formation and functioning of the central and peripheral nervous system. Disorders of thyroid metabolism are increasingly recognized within the spectrum of paediatric neurological disorders. Both hypothyroid and hyperthyroid disease states (resulting from genetic and acquired aetiologies) can lead to characteristic neurological syndromes, with cognitive delay, extrapyramidal movement disorders, neuropsychiatric symptoms, and neuromuscular manifestations. In this review, the neurological manifestations of genetic disorders of thyroid metabolism are outlined, with particular focus on Allan-Herndon-Dudley syndrome and benign hereditary chorea. We report in detail the clinical features, major neurological and neuropsychiatric manifestations, molecular genetic findings, disease mechanisms, and therapeutic strategies for these emerging genetic ‘brain-thyroid’ disorders. PMID:24665922

  16. A comparative study of the effects of asan, pranayama and asan-pranayama training on neurological and neuromuscular functions of Pondicherry police trainees

    PubMed Central

    Trakroo, Madanmohan; Bhavanani, Ananda Balayogi; Pal, Gopal Krushna; Udupa, Kaviraja; Krishnamurthy, N

    2013-01-01

    Background: Though neurological benefits of yoga training have been reported, lacunae still exists in understanding neurophysiological effects of such training. Hence, the present study was conducted to find the effect of yogasanas and pranayams on neurological and neuromuscular functions in healthy human volunteers and also determined differential effects of training in asan, pranayama and their combination. Materials and Methods: Eighty male trainees from Pondicherry Police Training School were randomly divided into asan, pranayama, and asan-pranayama groups who received a training of 4 days a week for 6 months and a control group. Electroencephalogram (EEG), nerve conduction (NC), electromyogram (EMG), visual evoked potentials (VEP), and auditory reaction time (ART) were recorded before and after the study period. NC, EMG, and VEP data were obtained from 28 subjects; EEG data from 48 subjects; and RT from 67 subjects. Intergroup differences were assessed by AVOVA/Kruskal–Wallis and intragroup differences by Student's t-test. Results and Discussion: Police trainees showed beneficial effects of yoga training, although they were undergoing intensive police training and the yoga training was relatively less intense. Alpha, theta, and total power of EEG increased as a result of asan training. A shortening of visual reaction time and a decrease in red-green discriminatory reaction time signifies an improved and faster processing of visual input. They also showed a decrease in resting EMG voltage, signifying better muscular relaxation following pranayama training. Beta, theta and total power of EEG increased. ART and red-green discriminatory reaction times decreased in the trainees, signifying a more alert state as well as improved central neural processing. A combination of asan and pranayama training for 6 months produced an improvement in motor and sensory nerve conduction. Total power of EEG, alpha and theta power as well as delta % increased, while reaction time

  17. APE1/Ref-1 facilitates recovery of gray and white matter and neurological function after mild stroke injury.

    PubMed

    Stetler, R Anne; Gao, Yanqin; Leak, Rehana K; Weng, Zhongfang; Shi, Yejie; Zhang, Lili; Pu, Hongjian; Zhang, Feng; Hu, Xiaoming; Hassan, Sulaiman; Ferguson, Carolyn; Homanics, Gregg E; Cao, Guodong; Bennett, Michael V L; Chen, Jun

    2016-06-21

    A major hallmark of oxidative DNA damage after stroke is the induction of apurinic/apyrimidinic (AP) sites and strand breaks. To mitigate cell loss after oxidative DNA damage, ischemic cells rapidly engage the base excision-repair proteins, such as the AP site-repairing enzyme AP endonuclease-1 (APE1), also named redox effector factor-1 (Ref-1). Although forced overexpression of APE1 is known to protect against oxidative stress-induced neurodegeneration, there is no concrete evidence demonstrating a role for endogenous APE1 in the long-term recovery of gray and white matter following ischemic injury. To address this gap, we generated, to our knowledge, the first APE1 conditional knockout (cKO) mouse line under control of tamoxifen-dependent Cre recombinase. Using a well-established model of transient focal cerebral ischemia (tFCI), we show that induced deletion of APE1 dramatically enlarged infarct volume and impaired the recovery of sensorimotor and cognitive deficits. APE1 cKO markedly increased postischemic neuronal and oligodendrocyte degeneration, demonstrating that endogenous APE1 preserves both gray and white matter after tFCI. Because white matter repair is instrumental in behavioral recovery after stroke, we also examined the impact of APE1 cKO on demyelination and axonal conduction and discovered that APE1 cKO aggravated myelin loss and impaired neuronal communication following tFCI. Furthermore, APE1 cKO increased AP sites and activated the prodeath signaling proteins, PUMA and PARP1, after tFCI in topographically distinct manners. Our findings provide evidence that endogenous APE1 protects against ischemic infarction in both gray and white matter and facilitates the functional recovery of the central nervous system after mild stroke injury.

  18. APE1/Ref-1 facilitates recovery of gray and white matter and neurological function after mild stroke injury

    PubMed Central

    Stetler, R. Anne; Gao, Yanqin; Leak, Rehana K.; Weng, Zhongfang; Zhang, Lili; Pu, Hongjian; Zhang, Feng; Hu, Xiaoming; Hassan, Sulaiman; Ferguson, Carolyn; Homanics, Gregg E.; Cao, Guodong; Bennett, Michael V. L.; Chen, Jun

    2016-01-01

    A major hallmark of oxidative DNA damage after stroke is the induction of apurinic/apyrimidinic (AP) sites and strand breaks. To mitigate cell loss after oxidative DNA damage, ischemic cells rapidly engage the base excision-repair proteins, such as the AP site-repairing enzyme AP endonuclease-1 (APE1), also named redox effector factor-1 (Ref-1). Although forced overexpression of APE1 is known to protect against oxidative stress-induced neurodegeneration, there is no concrete evidence demonstrating a role for endogenous APE1 in the long-term recovery of gray and white matter following ischemic injury. To address this gap, we generated, to our knowledge, the first APE1 conditional knockout (cKO) mouse line under control of tamoxifen-dependent Cre recombinase. Using a well-established model of transient focal cerebral ischemia (tFCI), we show that induced deletion of APE1 dramatically enlarged infarct volume and impaired the recovery of sensorimotor and cognitive deficits. APE1 cKO markedly increased postischemic neuronal and oligodendrocyte degeneration, demonstrating that endogenous APE1 preserves both gray and white matter after tFCI. Because white matter repair is instrumental in behavioral recovery after stroke, we also examined the impact of APE1 cKO on demyelination and axonal conduction and discovered that APE1 cKO aggravated myelin loss and impaired neuronal communication following tFCI. Furthermore, APE1 cKO increased AP sites and activated the prodeath signaling proteins, PUMA and PARP1, after tFCI in topographically distinct manners. Our findings provide evidence that endogenous APE1 protects against ischemic infarction in both gray and white matter and facilitates the functional recovery of the central nervous system after mild stroke injury. PMID:27274063

  19. APE1/Ref-1 facilitates recovery of gray and white matter and neurological function after mild stroke injury.

    PubMed

    Stetler, R Anne; Gao, Yanqin; Leak, Rehana K; Weng, Zhongfang; Shi, Yejie; Zhang, Lili; Pu, Hongjian; Zhang, Feng; Hu, Xiaoming; Hassan, Sulaiman; Ferguson, Carolyn; Homanics, Gregg E; Cao, Guodong; Bennett, Michael V L; Chen, Jun

    2016-06-21

    A major hallmark of oxidative DNA damage after stroke is the induction of apurinic/apyrimidinic (AP) sites and strand breaks. To mitigate cell loss after oxidative DNA damage, ischemic cells rapidly engage the base excision-repair proteins, such as the AP site-repairing enzyme AP endonuclease-1 (APE1), also named redox effector factor-1 (Ref-1). Although forced overexpression of APE1 is known to protect against oxidative stress-induced neurodegeneration, there is no concrete evidence demonstrating a role for endogenous APE1 in the long-term recovery of gray and white matter following ischemic injury. To address this gap, we generated, to our knowledge, the first APE1 conditional knockout (cKO) mouse line under control of tamoxifen-dependent Cre recombinase. Using a well-established model of transient focal cerebral ischemia (tFCI), we show that induced deletion of APE1 dramatically enlarged infarct volume and impaired the recovery of sensorimotor and cognitive deficits. APE1 cKO markedly increased postischemic neuronal and oligodendrocyte degeneration, demonstrating that endogenous APE1 preserves both gray and white matter after tFCI. Because white matter repair is instrumental in behavioral recovery after stroke, we also examined the impact of APE1 cKO on demyelination and axonal conduction and discovered that APE1 cKO aggravated myelin loss and impaired neuronal communication following tFCI. Furthermore, APE1 cKO increased AP sites and activated the prodeath signaling proteins, PUMA and PARP1, after tFCI in topographically distinct manners. Our findings provide evidence that endogenous APE1 protects against ischemic infarction in both gray and white matter and facilitates the functional recovery of the central nervous system after mild stroke injury. PMID:27274063

  20. Happiness and neurological diseases.

    PubMed

    Barak, Yoram; Achiron, Anat

    2009-04-01

    Happiness is an emotional state reflecting positive feelings and satisfaction with life, which, as an outcome in disease states or as an end point in clinical trials, is a neglected concept in most therapeutic areas. In neurological disease, happiness is important as it can be diminished either as a direct result of damage to neuronal tissue or as a reaction to a poor prognosis. The monitoring and maintenance of happiness and wellbeing have historically been considered to be peripheral to medicine. However, as happiness interacts with the patient's physical health, it is an important parameter to assess alongside all aspects of any given disease. Happiness provides a reliable overview of the patient's general status over and above standard parameters for quality of life, and is more wide-ranging than the narrow measures of disease activity or treatment efficacy that are the focus of most clinical trials. In many studies, happiness has been associated with health and success in most areas of life, including performance at work, sporting achievement and social functioning. For approximately a decade, previously studied aspects of psychology have been grouped under the label of positive psychology (PoP). Principles of this discipline are now being used to guide some treatments in neurological and psychiatric diseases. PoP aims to define patient wellbeing in scientific terms and to increase understanding of happiness, meaning in life, resilience and character strengths, as well as to determine how this knowledge can be applied clinically to promote health. Some evidence has emerged recently suggesting that improvements in patient status can result from interventions to improve the patient's level of happiness in diseases, including epilepsy, Huntington's disease, multiple sclerosis, Parkinson's disease and stroke. Several effective approaches to increase happiness employ activities to engage and stimulate patients who might otherwise be unoccupied and isolated. In

  1. High density lipoprotein and metabolic disease: Potential benefits of restoring its functional properties

    PubMed Central

    Klancic, Teja; Woodward, Lavinia; Hofmann, Susanna M.; Fisher, Edward A.

    2016-01-01

    Background High density lipoproteins (HDLs) are thought to be atheroprotective and to reduce the risk of cardiovascular disease (CVD). Besides their antioxidant, antithrombotic, anti-inflammatory, anti-apoptotic properties in the vasculature, HDLs also improve glucose metabolism in skeletal muscle. Scope of the review Herein, we review the functional role of HDLs to improve metabolic disorders, especially those involving insulin resistance and to induce regression of CVD with a particular focus on current pharmacological treatment options as well as lifestyle interventions, particularly exercise. Major conclusions Functional properties of HDLs continue to be considered important mediators to reverse metabolic dysfunction and to regress atherosclerotic cardiovascular disease. Lifestyle changes are often recommended to reduce the risk of CVD, with exercise being one of the most important of these. Understanding how exercise improves HDL function will likely lead to new approaches to battle the expanding burden of obesity and the metabolic syndrome. PMID:27110484

  2. Preserved pontine glucose metabolism in Alzheimer disease: A reference region for functional brain image (PET) analysis

    SciTech Connect

    Minoshima, Satoshi; Frey, K.A.; Foster, N.L.; Kuhl, D.W.

    1995-07-01

    Our goal was to examine regional preservation of energy metabolism in Alzheimer disease (AD) and to evaluate effects of PET data normalization to reference regions. Regional metabolic rates in the pons, thalamus, putamen, sensorimotor cortex, visual cortex, and cerebellum (reference regions) were determined stereotaxically and examined in 37 patients with probable AD and 22 normal controls based on quantitative {sup 18}FDG-PET measurements. Following normalization of metabolic rates of the parietotemporal association cortex and whole brain to each reference region, distinctions of the two groups were assessed. The pons showed the best preservation of glucose metabolism in AD. Other reference regions showed relatively preserved metabolism compared with the parietotemporal association cortex and whole brain, but had significant metabolic reduction. Data normalization to the pons not only enhanced statistical significance of metabolic reduction in the parietotemporal association cortex, but also preserved the presence of global cerebral metabolic reduction indicated in analysis of the quantitative data. Energy metabolism in the pons in probable AD is well preserved. The pons is a reliable reference for data normalization and will enhance diagnostic accuracy and efficiency of quantitative and nonquantitative functional brain imaging. 39 refs., 2 figs., 3 tabs.

  3. Role of mitochondrial function in cell death and body metabolism.

    PubMed

    Lee, Myung-Shik

    2016-01-01

    Mitochondria are the key players in apoptosis and necrosis. Mitochondrial DNA (mtDNA)-depleted r0 cells were resistant to diverse apoptosis inducers such as TNF-alpha, TNFSF10, staurosporine and p53. Apoptosis resistance was accompanied by the absence of mitochondrial potential loss or cytochrome c translocation. r0 cells were also resistant to necrosis induced by reactive oxygen species (ROS) donors due to upregulation of antioxidant enzymes such as manganese superoxide dismutase. Mitochondria also has a close relationship with autophagy that plays a critical role in the turnover of senescent organelles or dysfunctional proteins and may be included in 'cell death' category. It was demonstrated that autophagy deficiency in insulin target tissues such as skeletal muscle induces mitochondrial stress response, which leads to the induction of FGF21 as a 'mitokine' and affects the whole body metabolism. These results show that mitochondria are not simply the power plants of cells generating ATP, but are closely related to several types of cell death and autophagy. Mitochondria affect various pathophysiological events related to diverse disorders such as cancer, metabolic disorders and aging. PMID:27100503

  4. Commodity specific rates of temporal discounting: does metabolic function underlie differences in rates of discounting?

    PubMed

    Charlton, Shawn R; Fantino, Edmund

    2008-03-01

    Discounting rates vary as a function of commodity type. Previous studies suggest five potential characteristics of the commodity that could explain these differences: type of reinforcer (primary or secondary), if the commodity is perishable, if the commodity is satiable, if the commodity can be directly consumed, and immediacy of consumption. This paper suggests that these characteristics may best be viewed as related to a more fundamental characteristic: metabolic processing. In order to explore the possibility that metabolic processing underlies changes in discount rates, the difference in discounting between food, money, music CDs, DVDs, and books are compared. Music CDs, DVDs, and books share many characteristics in common with food, including gaining value through a physiological process, but are not directly metabolized. Results are consistent with previous findings of commodity specific discount rates and show that metabolic function plays a role in determining discount rates with those commodities that are metabolized being discounted at a higher rate. These results are interpreted as evidence that the discount rate for different commodities lies along a continuum with those that serve an exchange function rather than a direct function (money) anchoring the low end and those that serve a direct metabolic function capping the high end (food, alcohol, drugs). PMID:17919848

  5. Clinical neurology and executive dysfunction.

    PubMed

    Filley, C M

    2000-01-01

    Executive function is a uniquely human ability that permits an individual to plan, carry out, and monitor a sequence of actions that is intended to accomplish a goal. This crucial neurobehavioral capacity depends on the integrity of the frontal lobes, most importantly the dorsolateral prefrontal cortices and their connections. Executive dysfunction is associated with a wide range of neurologic disorders that affect these regions. In this paper, executive dysfunction is considered from the perspective of behavioral neurology, and the lesion method is employed to illustrate this impairment in a diverse group of disorders. Frontal system damage leading to disturbed executive function is common and clinically significant. Recognition of this syndrome is critical for ensuring the correct diagnosis, accurate prognosis, and appropriate treatment of affected patients. Executive dysfunction also represents an intriguing aspect of brain-behavior relationships and offers important insights into one of the highest cerebral functions. PMID:10879543

  6. Extra-cell cycle regulatory functions of cyclin-dependent kinases (CDK) and CDK inhibitor proteins contribute to brain development and neurological disorders

    PubMed Central

    Kawauchi, Takeshi; Shikanai, Mima; Kosodo, Yoichi

    2013-01-01

    In developing brains, neural progenitors exhibit cell cycle-dependent nuclear movement within the ventricular zone [interkinetic nuclear migration (INM)] and actively proliferate to produce daughter progenitors and/or neurons, whereas newly generated neurons exit from the cell cycle and begin pial surface-directed migration and maturation. Dysregulation of the balance between the proliferation and the cell cycle exit in neural progenitors is one of the major causes of microcephaly (small brain). Recent studies indicate that cell cycle machinery influences not only the proliferation but also INM in neural progenitors. Furthermore, several cell cycle-related proteins, including p27kip1, p57kip2, Cdk5, and Rb, regulate the migration of neurons in the postmitotic state, suggesting that the growth arrest confers dual functions on cell cycle regulators. Consistently, several types of microcephaly occur in conjunction with neuronal migration disorders, such as periventricular heterotopia and lissencephaly. However, cell cycle re-entry by disturbance of growth arrest in mature neurons is thought to trigger neuronal cell death in Alzheimer's disease. In this review, we introduce the cell cycle protein-mediated regulation of two types of nuclear movement, INM and neuronal migration, during cerebral cortical development, and discuss the roles of growth arrest in cortical development and neurological disorders. PMID:23294285

  7. The Neurologic Manifestations of Mitochondrial Disease

    ERIC Educational Resources Information Center

    Parikh, Sumit

    2010-01-01

    The nervous system contains some of the body's most metabolically demanding cells that are highly dependent on ATP produced via mitochondrial oxidative phosphorylation. Thus, the neurological system is consistently involved in patients with mitochondrial disease. Symptoms differ depending on the part of the nervous system affected. Although almost…

  8. The neurology in Shakespeare.

    PubMed

    Fogan, L

    1989-08-01

    William Shakespeare's 37 plays and poetry contain many references of interest for almost all of the medical specialties. To support that the Bard could be considered a Renaissance neurologist, the following important neurological phenomena have been selected from his repertoire for discussion: tremors, paralysis and stroke, sleep disturbances, epilepsy, dementia, encephalopathies, and the neurology of syphilis. PMID:2667505

  9. Microbial community assembly and metabolic function during mammalian corpse decomposition

    USGS Publications Warehouse

    Metcalf, Jessica L; Xu, Zhenjiang Zech; Weiss, Sophie; Lax, Simon; Van Treuren, Will; Hyde, Embriette R.; Song, Se Jin; Amir, Amnon; Larsen, Peter; Sangwan, Naseer; Haarmann, Daniel; Humphrey, Greg C; Ackermann, Gail; Thompson, Luke R; Lauber, Christian; Bibat, Alexander; Nicholas, Catherine; Gebert, Matthew J; Petrosino, Joseph F; Reed, Sasha C.; Gilbert, Jack A; Lynne, Aaron M; Bucheli, Sibyl R; Carter, David O; Knight, Rob

    2016-01-01

    Vertebrate corpse decomposition provides an important stage in nutrient cycling in most terrestrial habitats, yet microbially mediated processes are poorly understood. Here we combine deep microbial community characterization, community-level metabolic reconstruction, and soil biogeochemical assessment to understand the principles governing microbial community assembly during decomposition of mouse and human corpses on different soil substrates. We find a suite of bacterial and fungal groups that contribute to nitrogen cycling and a reproducible network of decomposers that emerge on predictable time scales. Our results show that this decomposer community is derived primarily from bulk soil, but key decomposers are ubiquitous in low abundance. Soil type was not a dominant factor driving community development, and the process of decomposition is sufficiently reproducible to offer new opportunities for forensic investigations.

  10. Microbial community assembly and metabolic function during mammalian corpse decomposition.

    PubMed

    Metcalf, Jessica L; Xu, Zhenjiang Zech; Weiss, Sophie; Lax, Simon; Van Treuren, Will; Hyde, Embriette R; Song, Se Jin; Amir, Amnon; Larsen, Peter; Sangwan, Naseer; Haarmann, Daniel; Humphrey, Greg C; Ackermann, Gail; Thompson, Luke R; Lauber, Christian; Bibat, Alexander; Nicholas, Catherine; Gebert, Matthew J; Petrosino, Joseph F; Reed, Sasha C; Gilbert, Jack A; Lynne, Aaron M; Bucheli, Sibyl R; Carter, David O; Knight, Rob

    2016-01-01

    Vertebrate corpse decomposition provides an important stage in nutrient cycling in most terrestrial habitats, yet microbially mediated processes are poorly understood. Here we combine deep microbial community characterization, community-level metabolic reconstruction, and soil biogeochemical assessment to understand the principles governing microbial community assembly during decomposition of mouse and human corpses on different soil substrates. We find a suite of bacterial and fungal groups that contribute to nitrogen cycling and a reproducible network of decomposers that emerge on predictable time scales. Our results show that this decomposer community is derived primarily from bulk soil, but key decomposers are ubiquitous in low abundance. Soil type was not a dominant factor driving community development, and the process of decomposition is sufficiently reproducible to offer new opportunities for forensic investigations.

  11. Microbial community assembly and metabolic function during mammalian corpse decomposition.

    PubMed

    Metcalf, Jessica L; Xu, Zhenjiang Zech; Weiss, Sophie; Lax, Simon; Van Treuren, Will; Hyde, Embriette R; Song, Se Jin; Amir, Amnon; Larsen, Peter; Sangwan, Naseer; Haarmann, Daniel; Humphrey, Greg C; Ackermann, Gail; Thompson, Luke R; Lauber, Christian; Bibat, Alexander; Nicholas, Catherine; Gebert, Matthew J; Petrosino, Joseph F; Reed, Sasha C; Gilbert, Jack A; Lynne, Aaron M; Bucheli, Sibyl R; Carter, David O; Knight, Rob

    2016-01-01

    Vertebrate corpse decomposition provides an important stage in nutrient cycling in most terrestrial habitats, yet microbially mediated processes are poorly understood. Here we combine deep microbial community characterization, community-level metabolic reconstruction, and soil biogeochemical assessment to understand the principles governing microbial community assembly during decomposition of mouse and human corpses on different soil substrates. We find a suite of bacterial and fungal groups that contribute to nitrogen cycling and a reproducible network of decomposers that emerge on predictable time scales. Our results show that this decomposer community is derived primarily from bulk soil, but key decomposers are ubiquitous in low abundance. Soil type was not a dominant factor driving community development, and the process of decomposition is sufficiently reproducible to offer new opportunities for forensic investigations. PMID:26657285

  12. Diabetes, insulin-mediated glucose metabolism and Sertoli/blood-testis barrier function

    PubMed Central

    Alves, Marco G.; Martins, Ana D.; Cavaco, José E.; Socorro, Sílvia; Oliveira, Pedro F.

    2013-01-01

    Blood testis barrier (BTB) is one of the tightest blood-barriers controlling the entry of substances into the intratubular fluid. Diabetes Mellitus (DM) is an epidemic metabolic disease concurrent with falling fertility rates, which provokes severe detrimental BTB alterations. It induces testicular alterations, disrupting the metabolic cooperation between the cellular constituents of BTB, with dramatic consequences on sperm quality and fertility. As Sertoli cells are involved in the regulation of spermatogenesis, providing nutritional support for germ cells, any metabolic alteration in these cells derived from DM may be responsible for spermatogenesis disruption, playing a crucial role in fertility/subfertility associated with this pathology. These cells have a glucose sensing machinery that reacts to hormonal fluctuations and several mechanisms to counteract hyper/hypoglycemic events. The role of DM on Sertoli/BTB glucose metabolism dynamics and the metabolic molecular mechanisms through which DM and insulin deregulation alter its functioning, affecting male reproductive potential will be discussed. PMID:24665384

  13. Neurologic presentations of AIDS.

    PubMed

    Singer, Elyse J; Valdes-Sueiras, Miguel; Commins, Deborah; Levine, Andrew

    2010-02-01

    The human immunodeficiency virus (HIV), the cause of AIDS, has infected an estimated 33 million individuals worldwide. HIV is associated with immunodeficiency, neoplasia, and neurologic disease. The continuing evolution of the HIV epidemic has spurred an intense interest in a hitherto neglected area of medicine, neuroinfectious diseases and their consequences. This work has broad applications for the study of central nervous system (CNS) tumors, dementias, neuropathies, and CNS disease in other immunosuppressed individuals. HIV is neuroinvasive (can enter the CNS), neurotrophic (can live in neural tissues), and neurovirulent (causes disease of the nervous system). This article reviews the HIV-associated neurologic syndromes, which can be classified as primary HIV neurologic disease (in which HIV is both necessary and sufficient to cause the illness), secondary or opportunistic neurologic disease (in which HIV interacts with other pathogens, resulting in opportunistic infections and tumors), and treatment-related neurologic disease (such as immune reconstitution inflammatory syndrome). PMID:19932385

  14. Neurology issues in schizophrenia.

    PubMed

    Hüfner, Katharina; Frajo-Apor, Beatrice; Hofer, Alex

    2015-05-01

    Schizophrenia ranks among the leading causes of disability worldwide. The presence of neurological signs co-occurring with the psychiatric symptoms is indicative of an organic brain pathology. In the present article, we review the current literature on neurology issues in schizophrenia. Firstly, common neurological signs found in patients with schizophrenia (neurological soft signs and smell abnormalities) and their association with imaging findings are reviewed. Secondly, the significant association of schizophrenia with epilepsy and stroke is described as well as the absent association with other organic brain diseases such as multiple sclerosis. Thirdly, we discuss the potential role of NMDA receptor antibodies in schizophrenia. Fourthly, neurological side effects of antipsychotic drugs and their treatment are reviewed; and lastly, we discuss neurocognitive deficits in patients with schizophrenia and their treatment. The focus of the review remains on articles with relevance to the clinician. PMID:25773225

  15. Neurology and orthopaedics

    PubMed Central

    Houlden, Henry; Charlton, Paul; Singh, Dishan

    2007-01-01

    Neurology encompasses all aspects of medicine and surgery, but is closer to orthopaedic surgery than many other specialities. Both neurological deficits and bone disorders lead to locomotor system abnormalities, joint complications and limb problems. The main neurological conditions that require the attention of an orthopaedic surgeon are disorders that affect the lower motor neurones. The most common disorders in this group include neuromuscular disorders and traumatic peripheral nerve lesions. Upper motor neurone disorders such as cerebral palsy and stroke are also frequently seen and discussed, as are chronic conditions such as poliomyelitis. The management of these neurological problems is often coordinated in the neurology clinic, and this group, probably more than any other, requires a multidisciplinary team approach. PMID:17308288

  16. Psychosocial and metabolic function by smoking status in individuals with binge eating disorder and obesity.

    PubMed

    Udo, Tomoko; White, Marney A; Barnes, Rachel D; Ivezaj, Valentina; Morgan, Peter; Masheb, Robin M; Grilo, Carlos M

    2016-02-01

    Individuals with binge eating disorder (BED) report smoking to control appetite and weight. Smoking in BED is associated with increased risk for comorbid psychiatric disorders, but its impact on psychosocial functioning and metabolic function has not been evaluated. Participants were 429 treatment-seeking adults (72.4% women; mean age 46.2±11.0years old) with BED comorbid with obesity. Participants were categorized into current smokers (n=66), former smokers (n=145), and never smokers (n=218). Smoking status was unrelated to most historical eating/weight variables and to current eating disorder psychopathology. Smoking status was associated with psychiatric, psychosocial, and metabolic functioning. Compared with never smokers, current smokers were more likely to meet lifetime diagnostic criteria for alcohol (OR=5.51 [95% CI=2.46-12.33]) and substance use disorders (OR=7.05 [95% CI=3.37-14.72]), poorer current physical quality of life, and increased risk for metabolic syndrome (OR=1.80 [95% CI=0.97-3.35]) and related metabolic risks (reduced HDL, elevated total cholesterol). On the other hand, the odds of meeting criteria for lifetime psychiatric comorbidity or metabolic abnormalities were not significantly greater in former smokers, relative to never smokers. Our findings suggest the importance of promoting smoking cessation in treatment-seeking patients with BED and obesity for its potential long-term implications for psychiatric and metabolic functioning.

  17. mTORC1-dependent metabolic reprogramming is a prerequisite for Natural Killer cell effector function

    PubMed Central

    Donnelly, Raymond P.; Loftus, Róisín M.; Keating, Sinéad E.; Liou, Kevin T.; Biron, Christine A.; Gardiner, Clair M.; Finlay, David K.

    2014-01-01

    The mammalian target of rapamcyin complex 1 (mTORC1) is a key regulator of cellular metabolism and also has fundamental roles in controlling immune responses. Emerging evidence suggests that these two functions of mTORC1 are integrally linked. However, little is known regarding mTORC1 function in controlling the metabolism and function of natural killer (NK) cells, lymphocytes that play key roles in anti-viral and anti-tumour immunity. This study investigated the hypothesis that mTORC1-controlled metabolism underpins normal NK cell pro-inflammatory function. We demonstrate that mTORC1 is robustly stimulated in NK cells activated in vivo and in vitro. This mTORC1 activity is required for the production of the key NK cell effector molecules IFNγ, important in delivering antimicrobial and immunoregulatory functions, and granzyme B, a critical component of NK cell cytotoxic granules. The data reveal that NK cells undergo dramatic metabolic reprogramming upon activation, up-regulating rates of glucose uptake and glycolysis, and that mTORC1 activity is essential for attaining this elevated glycolytic state. Directly limiting the rate of glycolysis is sufficient to inhibit IFNγ production and granzyme B expression. This study provides the highly novel insight that mTORC1-mediated metabolic reprogramming of NK cells is a prerequisite for the acquisition of normal effector functions. PMID:25261477

  18. Chronic Alcohol Ingestion in Rats Alters Lung Metabolism, Promotes Lipid Accumulation, and Impairs Alveolar Macrophage Functions

    PubMed Central

    Romero, Freddy; Shah, Dilip; Duong, Michelle; Stafstrom, William; Hoek, Jan B.; Kallen, Caleb B.; Lang, Charles H.

    2014-01-01

    Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. Although alcoholism has been shown to alter hepatic metabolism, leading to lipid accumulation, hepatitis, and, eventually, cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II cells and alveolar macrophages (AMs) in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids (FAs). Furthermore, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triglycerides and free FAs within distal airspaces, AMs, and, to a lesser extent, alveolar epithelial type II cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in FAs alter AM phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and

  19. Effect of Meditation on Endothelial Function in Black Americans with Metabolic Syndrome: A Randomized Trial

    PubMed Central

    Vaccarino, Viola; Kondwani, Kofi A.; Kelley, Mary E.; Murrah, Nancy V.; Boyd, Linda; Ahmed, Yusuf; Meng, Yuan X.; Gibbons, Gary H.; Hooper, W. Craig; De Staercke, Christine; Quyyumi, Arshed A.

    2013-01-01

    Objectives Psychological stress may play a role in metabolic syndrome. A consequence of metabolic syndrome is endothelial dysfunction, which is also influenced by psychological stress. We sought to compare the effect of consciously resting meditation (CRM), a sound (mantra)-based meditation, with a control intervention of health education (HE) on endothelial function in the setting of metabolic syndrome. Methods Sixty-eight black Americans with metabolic system risk factors (age 30 to 65 years) were randomized to either CRM (N=33), or to HE (N=35); interventions were matched for frequency and duration of sessions and lasted 12 months. Endothelial function was assessed by brachial artery flow-mediated dilation (FMD%) at baseline, 6 and 12 months. Arterial elasticity, metabolic risk factors, psychosocial and behavioral variables were secondary endpoints. Results Although FMD % improved in the CRM group over 12 months, this increase was not significantly higher than in the HE group (p=0.51 for the interaction between group and time). Non-endothelium dependent dilation and arterial elasticity did not change in either group. Most metabolic syndrome risk factors showed beneficial trends in the CRM group only. A risk factor score counting the number of metabolic syndrome components decreased in the CRM group but not in the control HE group (p=0.049 for the interaction between treatment group and time). Conclusions Among black Americans with metabolic syndrome risk factors, CRM, a sound-based meditation, did not improve endothelial function significantly more than a control intervention of health education. CRM resulted in favorable trends in metabolic syndrome risk factors which were examined as secondary outcomes. PMID:23788695

  20. [Neurological interpretation of dreams] .

    PubMed

    Pareja, J A; Gil-Nagel, A

    2000-10-01

    Cerebral cortical activity is constant throughout the entire human life, but substantially changes during the different phases of the sleep-wake cycle (wakefulness, non-REM sleep and REM sleep), as well as in relation to available information. In particular, perception of the environment is closely linked to the wake-state, while during sleep perception turns to the internal domain or endogenous cerebral activity. External and internal information are mutually exclusive. During wakefulness a neuronal mechanism allows attention to focus on the environment whereas endogenous cortical activity is ignored. The opposite process is provided during sleep. The function external attention-internal attention is coupled with the two modes of brain function during wakefulness and during sleep, providing two possible cortical status: thinking and dreaming. Several neurological processes may influence the declaration of the three states of being or may modify their orderly oscillation through the sleep-wake cycle. In addition, endogenous information and its perception (dreams) may be modified. Disturbances of dreaming may configurate in different general clinical scenarios: lack of dreaming, excess of dreaming (epic dreaming), paroxysmal dreaming (epileptic), nightmares, violent dreaming, daytime-dreaming (hallucinations), and lucid dreaming. Sensorial deprivation, as well as the emergence of internal perception may be the underlying mechanism of hallucinations. The probable isomorphism between hallucinations and dreaming is postulated, analyzed and discussed. PMID:11143502

  1. [Neurological interpretation of dreams] .

    PubMed

    Pareja, J A; Gil-Nagel, A

    2000-10-01

    Cerebral cortical activity is constant throughout the entire human life, but substantially changes during the different phases of the sleep-wake cycle (wakefulness, non-REM sleep and REM sleep), as well as in relation to available information. In particular, perception of the environment is closely linked to the wake-state, while during sleep perception turns to the internal domain or endogenous cerebral activity. External and internal information are mutually exclusive. During wakefulness a neuronal mechanism allows attention to focus on the environment whereas endogenous cortical activity is ignored. The opposite process is provided during sleep. The function external attention-internal attention is coupled with the two modes of brain function during wakefulness and during sleep, providing two possible cortical status: thinking and dreaming. Several neurological processes may influence the declaration of the three states of being or may modify their orderly oscillation through the sleep-wake cycle. In addition, endogenous information and its perception (dreams) may be modified. Disturbances of dreaming may configurate in different general clinical scenarios: lack of dreaming, excess of dreaming (epic dreaming), paroxysmal dreaming (epileptic), nightmares, violent dreaming, daytime-dreaming (hallucinations), and lucid dreaming. Sensorial deprivation, as well as the emergence of internal perception may be the underlying mechanism of hallucinations. The probable isomorphism between hallucinations and dreaming is postulated, analyzed and discussed.

  2. A worm of one's own: how helminths modulate host adipose tissue function and metabolism.

    PubMed

    Guigas, Bruno; Molofsky, Ari B

    2015-09-01

    Parasitic helminths have coexisted with human beings throughout time. Success in eradicating helminths has limited helminth-induced morbidity and mortality but is also correlated with increasing rates of 'western' diseases, including metabolic syndrome and type 2 diabetes. Recent studies in mice describe how type 2 immune cells, traditionally associated with helminth infection, maintain adipose tissue homeostasis and promote adipose tissue beiging, protecting against obesity and metabolic dysfunction. Here, we review these studies and discuss how helminths and helminth-derived molecules may modulate these physiologic pathways to improve metabolic functions in specific tissues, such as adipose and liver, as well as at the whole-organism level.

  3. Angiogenesis and vascular functions in modulation of obesity, adipose metabolism, and insulin sensitivity.

    PubMed

    Cao, Yihai

    2013-10-01

    White and brown adipose tissues are hypervascularized and the adipose vasculature displays phenotypic and functional plasticity to coordinate with metabolic demands of adipocytes. Blood vessels not only supply nutrients and oxygen to nourish adipocytes, they also serve as a cellular reservoir to provide adipose precursor and stem cells that control adipose tissue mass and function. Multiple signaling molecules modulate the complex interplay between the vascular system and the adipocytes. Understanding fundamental mechanisms by which angiogenesis and vasculatures modulate adipocyte functions may provide new therapeutic options for treatment of obesity and metabolic disorders by targeting the adipose vasculature.

  4. Metabolic changes assessed by MRS accurately reflect brain function during drug-induced epilepsy in mice in contrast to fMRI-based hemodynamic readouts.

    PubMed

    Seuwen, Aline; Schroeter, Aileen; Grandjean, Joanes; Rudin, Markus

    2015-10-15

    Functional proton magnetic resonance spectroscopy (1H-MRS) enables the non-invasive assessment of neural activity by measuring signals arising from endogenous metabolites in a time resolved manner. Proof-of-principle of this approach has been demonstrated in humans and rats; yet functional 1H-MRS has not been applied in mice so far, although it would be of considerable interest given the many genetically engineered models of neurological disorders established in this species only. Mouse 1H-MRS is challenging as the high demands on spatial resolution typically result in long data acquisition times not commensurable with functional studies. Here, we propose an approach based on spectroscopic imaging in combination with the acquisition of the free induction decay to maximize signal intensity. Highly resolved metabolite maps have been recorded from mouse brain with 12 min temporal resolution. This enabled monitoring of metabolic changes following the administration of bicuculline, a GABA-A receptor antagonist. Changes in levels of metabolites involved in energy metabolism (lactate and phosphocreatine) and neurotransmitters (glutamate) were investigated in a region-dependent manner and shown to scale with the bicuculline dose. GABAergic inhibition induced spectral changes characteristic for increased neurotransmitter turnover and oxidative stress. In contrast to metabolic readouts, BOLD and CBV fMRI responses did not scale with the bicuculline dose indicative of the failure of neurovascular coupling. Nevertheless fMRI measurements supported the notion of increased oxidative stress revealed by functional MRS. Hence, the combined analysis of metabolic and hemodynamic changes in response to stimulation provides complementary insight into processes associated with neural activity.

  5. Metabolic changes assessed by MRS accurately reflect brain function during drug-induced epilepsy in mice in contrast to fMRI-based hemodynamic readouts.

    PubMed

    Seuwen, Aline; Schroeter, Aileen; Grandjean, Joanes; Rudin, Markus

    2015-10-15

    Functional proton magnetic resonance spectroscopy (1H-MRS) enables the non-invasive assessment of neural activity by measuring signals arising from endogenous metabolites in a time resolved manner. Proof-of-principle of this approach has been demonstrated in humans and rats; yet functional 1H-MRS has not been applied in mice so far, although it would be of considerable interest given the many genetically engineered models of neurological disorders established in this species only. Mouse 1H-MRS is challenging as the high demands on spatial resolution typically result in long data acquisition times not commensurable with functional studies. Here, we propose an approach based on spectroscopic imaging in combination with the acquisition of the free induction decay to maximize signal intensity. Highly resolved metabolite maps have been recorded from mouse brain with 12 min temporal resolution. This enabled monitoring of metabolic changes following the administration of bicuculline, a GABA-A receptor antagonist. Changes in levels of metabolites involved in energy metabolism (lactate and phosphocreatine) and neurotransmitters (glutamate) were investigated in a region-dependent manner and shown to scale with the bicuculline dose. GABAergic inhibition induced spectral changes characteristic for increased neurotransmitter turnover and oxidative stress. In contrast to metabolic readouts, BOLD and CBV fMRI responses did not scale with the bicuculline dose indicative of the failure of neurovascular coupling. Nevertheless fMRI measurements supported the notion of increased oxidative stress revealed by functional MRS. Hence, the combined analysis of metabolic and hemodynamic changes in response to stimulation provides complementary insight into processes associated with neural activity. PMID:26166624

  6. Molecular changes in hepatic metabolism and transport in cirrhosis and their functional importance

    PubMed Central

    Dietrich, Christoph G; Götze, Oliver; Geier, Andreas

    2016-01-01

    Liver cirrhosis is the common endpoint of many hepatic diseases and represents a relevant risk for liver failure and hepatocellular carcinoma. The progress of liver fibrosis and cirrhosis is accompanied by deteriorating liver function. This review summarizes the regulatory and functional changes in phase I and phase II metabolic enzymes as well as transport proteins and provides an overview regarding lipid and glucose metabolism in cirrhotic patients. Interestingly, phase I enzymes are generally downregulated transcriptionally, while phase II enzymes are mostly preserved transcriptionally but are reduced in their function. Transport proteins are regulated in a specific way that resembles the molecular changes observed in obstructive cholestasis. Lipid and glucose metabolism are characterized by insulin resistance and catabolism, leading to the disturbance of energy expenditure and wasting. Possible non-invasive tests, especially breath tests, for components of liver metabolism are discussed. The heterogeneity and complexity of changes in hepatic metabolism complicate the assessment of liver function in individual patients. Additionally, studies in humans are rare, and species differences preclude the transferability of data from rodents to humans. In clinical practice, some established global scores or criteria form the basis for the functional evaluation of patients with liver cirrhosis, but difficult treatment decisions such as selection for transplantation or resection require further research regarding the application of existing non-invasive tests and the development of more specific tests. PMID:26755861

  7. Physiological Interactions of Nanoparticles in Energy Metabolism, Immune Function and Their Biosafety: A Review.

    PubMed

    Gomes, Antony; Sengupta, Jayeeta; Datta, Poulami; Ghosh, Sourav; Gomes, Aparna

    2016-01-01

    Nanoparticles owing to their unique physico-chemical properties have found its application in various biological processes, including metabolic pathways taking place within the body. This review tried to focus the involvement of nanoparticles in metabolic pathways and its influence in the energy metabolism, a fundamental criteria for the survival and physiological activity of living beings. The human body utilizes energy derived from food resources through a series of biochemical reactions involving several enzymes, co-factors (metals, non-metals, vitamins etc.) through the metabolic pathways (glycolysis, tri carboxylic acid cycle, oxidative phosphorylation, electron transport chain, etc.) in cellular system. Energy metabolism is also involved in the immune networking of the body for self defence and against pathophysiology. The immune system comprises of different cells and tissues, bioactive molecules for self defence and to fight against diseases. In the recent times, it has been reported through in vivo and in vitro studies that nanoparticles have direct influence on body's immune functions, and can modulate immunity by either suppressing or enhancing it. A comprehensive overview of nanoparticles and its involvement in immune function of the body in normal and pathophysiological conditions has been discussed. Considering these perspectives on nanoparticle interaction another important area which has been highlighted is the biosafety issues which are necessary before therapeutic applications. It is expected that development of physiologically compatible nanoparticles controlling energy metabolic processes, immune functions may show new dimension in the pathophysiology linked with energy and immunity.

  8. Physiological Interactions of Nanoparticles in Energy Metabolism, Immune Function and Their Biosafety: A Review.

    PubMed

    Gomes, Antony; Sengupta, Jayeeta; Datta, Poulami; Ghosh, Sourav; Gomes, Aparna

    2016-01-01

    Nanoparticles owing to their unique physico-chemical properties have found its application in various biological processes, including metabolic pathways taking place within the body. This review tried to focus the involvement of nanoparticles in metabolic pathways and its influence in the energy metabolism, a fundamental criteria for the survival and physiological activity of living beings. The human body utilizes energy derived from food resources through a series of biochemical reactions involving several enzymes, co-factors (metals, non-metals, vitamins etc.) through the metabolic pathways (glycolysis, tri carboxylic acid cycle, oxidative phosphorylation, electron transport chain, etc.) in cellular system. Energy metabolism is also involved in the immune networking of the body for self defence and against pathophysiology. The immune system comprises of different cells and tissues, bioactive molecules for self defence and to fight against diseases. In the recent times, it has been reported through in vivo and in vitro studies that nanoparticles have direct influence on body's immune functions, and can modulate immunity by either suppressing or enhancing it. A comprehensive overview of nanoparticles and its involvement in immune function of the body in normal and pathophysiological conditions has been discussed. Considering these perspectives on nanoparticle interaction another important area which has been highlighted is the biosafety issues which are necessary before therapeutic applications. It is expected that development of physiologically compatible nanoparticles controlling energy metabolic processes, immune functions may show new dimension in the pathophysiology linked with energy and immunity. PMID:27398436

  9. The effect of ozone inhalation on metabolic functioning of vascular endothelium and on ventilatory function

    SciTech Connect

    Gross, K.B.; White, H.J.; Sargent, N.E. )

    1991-06-15

    The primary purpose of this research was to determine the effect of ozone inhalation on pulmonary vascular endothelium. Male Fischer-344 rats were exposed to 0.5 or 0.7 ppm ozone, 20 hr/day for 7 days. Lungs were excised and perfused with Krebs medium containing (14C)serotonin or (14C)hippurylhistidylleucine (HHL). When compared to controls, the animals exposed to the lower ozone concentration showed no statistically significant changes in serotonin removal. In contrast, the higher ozone concentration resulted in a 32% decrease (p less than 0.0001) in serotonin removal, but had no effect on HHL. Rats similarly exposed to 0.7 ppm ozone but allowed to recover for 14 days in clean air showed no decrease in serotonin removal compared to their controls. Animals exposed sequentially to 0.5 ppm ozone for 7 days and then to 0.7 ppm for 7 days showed no alteration in serotonin metabolism, suggesting the development of tolerance initiated by the lower dose. After 7 days exposure to 0.7 ppm ozone, lung ventilatory function measurements revealed small though significant decreases in several parameters. Electron microscopic evaluation of lung capillary endothelium from animals exposed to the 0.7 ppm ozone showed no changes. Positive control animals exposed to greater than 95% oxygen, 20 hr/day for 2 days showed a 23% decrease in serotonin removal (p less than 0.03) and a 12% decrease in HHL removal (p less than 0.017). These studies indicate that inhalation of ozone can induce functional alterations in the lung endothelium, and that this effect occurs at a dosage of ozone that produces minimal ventilatory changes and no observable endothelial ultrastructural changes.

  10. Neurologic complications of vaccinations.

    PubMed

    Miravalle, Augusto A; Schreiner, Teri

    2014-01-01

    This chapter reviews the most common neurologic disorders associated with common vaccines, evaluates the data linking the disorder with the vaccine, and discusses the potential mechanism of disease. A literature search was conducted in PubMed using a combination of the following terms: vaccines, vaccination, immunization, and neurologic complications. Data were also gathered from publications of the American Academy of Pediatrics Committee on Infectious Diseases, the World Health Organization, the US Centers for Disease Control and Prevention, and the Vaccine Adverse Event Reporting System. Neurologic complications of vaccination are rare. Many associations have been asserted without objective data to support a causal relationship. Rarely, patients with a neurologic complication will have a poor outcome. However, most patients recover fully from the neurologic complication. Vaccinations have altered the landscape of infectious disease. However, perception of risk associated with vaccinations has limited the success of disease eradication measures. Neurologic complications can be severe, and can provoke fear in potential vaccines. Evaluating whether there is causal link between neurologic disorders and vaccinations, not just temporal association, is critical to addressing public misperception of risk of vaccination. Among the vaccines available today, the cost-benefit analysis of vaccinations and complications strongly argues in favor of vaccination.

  11. Emergence of Complexity in Protein Functions and Metabolic Networks

    NASA Technical Reports Server (NTRS)

    Pohorille, Andzej

    2009-01-01

    In modern organisms proteins perform a majority of cellular functions, such as chemical catalysis, energy transduction and transport of material across cell walls. Although great strides have been made towards understanding protein evolution, a meaningful extrapolation from contemporary proteins to their earliest ancestors is virtually impossible. In an alternative approach, the origin of water-soluble proteins was probed through the synthesis of very large libraries of random amino acid sequences and subsequently subjecting them to in vitro evolution. In combination with computer modeling and simulations, these experiments allow us to address a number of fundamental questions about the origins of proteins. Can functionality emerge from random sequences of proteins? How did the initial repertoire of functional proteins diversify to facilitate new functions? Did this diversification proceed primarily through drawing novel functionalities from random sequences or through evolution of already existing proto-enzymes? Did protein evolution start from a pool of proteins defined by a frozen accident and other collections of proteins could start a different evolutionary pathway? Although we do not have definitive answers to these questions, important clues have been uncovered. Considerable progress has been also achieved in understanding the origins of membrane proteins. We will address this issue in the example of ion channels - proteins that mediate transport of ions across cell walls. Remarkably, despite overall complexity of these proteins in contemporary cells, their structural motifs are quite simple, with -helices being most common. By combining results of experimental and computer simulation studies on synthetic models and simple, natural channels, I will show that, even though architectures of membrane proteins are not nearly as diverse as those of water-soluble proteins, they are sufficiently flexible to adapt readily to the functional demands arising during

  12. Genome-wide functional annotation and structural verification of metabolic ORFeome of Chlamydomonas reinhardtii

    PubMed Central

    2011-01-01

    Background Recent advances in the field of metabolic engineering have been expedited by the availability of genome sequences and metabolic modelling approaches. The complete sequencing of the C. reinhardtii genome has made this unicellular alga a good candidate for metabolic engineering studies; however, the annotation of the relevant genes has not been validated and the much-needed metabolic ORFeome is currently unavailable. We describe our efforts on the functional annotation of the ORF models released by the Joint Genome Institute (JGI), prediction of their subcellular localizations, and experimental verification of their structural annotation at the genome scale. Results We assigned enzymatic functions to the translated JGI ORF models of C. reinhardtii by reciprocal BLAST searches of the putative proteome against the UniProt and AraCyc enzyme databases. The best match for each translated ORF was identified and the EC numbers were transferred onto the ORF models. Enzymatic functional assignment was extended to the paralogs of the ORFs by clustering ORFs using BLASTCLUST. In total, we assigned 911 enzymatic functions, including 886 EC numbers, to 1,427 transcripts. We further annotated the enzymatic ORFs by prediction of their subcellular localization. The majority of the ORFs are predicted to be compartmentalized in the cytosol and chloroplast. We verified the structure of the metabolism-related ORF models by reverse transcription-PCR of the functionally annotated ORFs. Following amplification and cloning, we carried out 454FLX and Sanger sequencing of the ORFs. Based on alignment of the 454FLX reads to the ORF predicted sequences, we obtained more than 90% coverage for more than 80% of the ORFs. In total, 1,087 ORF models were verified by 454 and Sanger sequencing methods. We obtained expression evidence for 98% of the metabolic ORFs in the algal cells grown under constant light in the presence of acetate. Conclusions We functionally annotated approximately 1

  13. Neurology and international organizations.

    PubMed

    Mateen, Farrah J

    2013-07-23

    A growing number of international stakeholders are engaged with neurologic diseases. This article provides a brief overview of important international stakeholders in the practice of neurology, including global disease-specific programs, United Nations agencies, governmental agencies with international influence, nongovernmental organizations, international professional organizations, large private donors, private-public partnerships, commercial interests, armed forces, and universities and colleges. The continued engagement of neurologists is essential for the growing number of international organizations that can and should incorporate neurologic disease into their global agendas.

  14. William Shakespeare's neurology.

    PubMed

    Paciaroni, Maurizio; Bogousslavsky, Julien

    2013-01-01

    Many of Shakespeare's plays contain characters who appear to be afflicted by neurological or psychiatric disorders. Shakespeare, in his descriptive analysis of his protagonists, was contributing to the understanding of these disorders. In fact, Charcot frequently used Shakespearean references in his neurological teaching sessions, stressing how acute objective insight is essential to achieving expert clinical diagnosis. Charcot found in Shakespeare the same rigorous observational techniques for which he himself became famous. This chapter describes many of Shakespearean characters suffering from varied neurological disorders, including Parkinsonism, epilepsy, sleeping disturbances, dementia, headache, prion disease, and paralyses. PMID:24290473

  15. Apolipoproteins in the brain: implications for neurological and psychiatric disorders

    PubMed Central

    Elliott, David A; Weickert, Cyndi Shannon; Garner, Brett

    2011-01-01

    The brain is the most lipid-rich organ in the body and, owing to the impermeable nature of the blood–brain barrier, lipid and lipoprotein metabolism within this organ is distinct from the rest of the body. Apolipoproteins play a well-established role in the transport and metabolism of lipids within the CNS; however, evidence is emerging that they also fulfill a number of functions that extend beyond lipid transport and are critical for healthy brain function. The importance of apolipoproteins in brain physiology is highlighted by genetic studies, where apolipoprotein gene polymorphisms have been identified as risk factors for several neurological diseases. Furthermore, the expression of brain apolipoproteins is significantly altered in several brain disorders. The purpose of this article is to provide an up-to-date assessment of the major apolipoproteins found in the brain (ApoE, ApoJ, ApoD and ApoA-I), covering their proposed roles and the factors influencing their level of expression. Particular emphasis is placed on associations with neurological and psychiatric disorders. PMID:21423873

  16. Pentosan polysulfate treatment ameliorates motor function with increased serum soluble vascular cell adhesion molecule-1 in HTLV-1-associated neurologic disease.

    PubMed

    Nakamura, Tatsufumi; Satoh, Katsuya; Fukuda, Taku; Kinoshita, Ikuo; Nishiura, Yoshihiro; Nagasato, Kunihiko; Yamauchi, Atsushi; Kataoka, Yasufumi; Nakamura, Tadahiro; Sasaki, Hitoshi; Kumagai, Kenji; Niwa, Masami; Noguchi, Mitsuru; Nakamura, Hideki; Nishida, Noriyuki; Kawakami, Atsushi

    2014-06-01

    The main therapeutic strategy against human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) characterized by lower extremity motor dysfunction is immunomodulatory treatment, with drugs such as corticosteroid hormone and interferon-α, at present. However, there are many issues in long-term treatment with these drugs, such as insufficient effects and various side effects. We now urgently need to develop other therapeutic strategies. The heparinoid, pentosan polysulfate sodium (PPS), has been safely used in Europe for the past 50 years as a thrombosis prophylaxis and for the treatment of phlebitis. We conducted a clinical trial to test the effect of subcutaneous administration of PPS in 12 patients with HAM/TSP in an open-labeled design. There was a marked improvement in lower extremity motor function, based on reduced spasticity, such as a reduced time required for walking 10 m and descending a flight of stairs. There were no significant changes in HTLV-I proviral copy numbers in peripheral blood contrary to the inhibitory effect of PPS in vitro for intercellular spread of HTLV-I. However, serum soluble vascular cell adhesion molecule (sVCAM)-1 was significantly increased without significant changes of serum level of chemokines (CXCL10 and CCL2). There was a positive correlation between increased sVCAM-1and reduced time required for walking 10 m. PPS might induce neurological improvement by inhibition of chronic inflammation in the spinal cord, through blocking the adhesion cascade by increasing serum sVCAM-1, in addition to rheological improvement of the microcirculation. PPS has the potential to be a new therapeutic tool for HAM/TSP.

  17. Functional genomics and SNP analysis of human genes encoding proline metabolic enzymes

    PubMed Central

    Williams, D. Bart; Zhaorigetu, Siqin; Khalil, Shadi; Wan, Guanghua; Valle, David

    2009-01-01

    Proline metabolism in mammals involves two other amino acids, glutamate and ornithine, and five enzymatic activities, Δ1-pyrroline-5-carboxylate (P5C) reductase (P5CR), proline oxidase, P5C dehydrogenase, P5C synthase and ornithine-δ-aminotransferase (OAT). With the exception of OAT, which catalyzes a reversible reaction, the other 4 enzymes are unidirectional, suggesting that proline metabolism is purpose-driven, tightly regulated, and compartmentalized. In addition, this tri-amino-acid system also links with three other pivotal metabolic systems, namely the TCA cycle, urea cycle, and pentose phosphate pathway. Abnormalities in proline metabolism are relevant in several diseases: six monogenic inborn errors involving metabolism and/or transport of proline and its immediate metabolites have been described. Recent advances in the Human Genome Project, in silico database mining techniques, and research in dissecting the molecular basis of proline metabolism prompted us to utilize functional genomic approaches to analyze human genes which encode proline metabolic enzymes in the context of gene structure, regulation of gene expression, mRNA variants, protein isoforms, and single nucleotide polymorphisms. PMID:18506409

  18. [Child neurology and rehabilitation].

    PubMed

    Kumagai, K

    2000-05-01

    The history of child neurology and the changing pattern of research methods in this field are reviewed with special reference to holoprosencephaly and recent technical advances in sleep research. This is followed by a discussion on the relationship between child neurology and rehabilitation. The majority of child neurologic disorders are developmental disabilities, but acquired child neurological diseases also show chronic progressive course in many cases. Therefore, child neurologist should understand the basis of rehabilitation approach and appreciate the three classes of disabilities; subsequently, a plan needs to be incorporating medical treatment and a program of rehabilitation for the disabled children. It is important that the role of the various rehabilitation specialists (rehabilitation doctor, physiotherapist, occupational therapist, and others) are understood in relation to the work of pediatric neurologist. Finally, a brief discussion is presented on the rehabilitation approach of patients with hypoxic encephalopathy and the information of welfare equipment.

  19. Haematology and neurology

    PubMed Central

    Austin, Steven; Cohen, Hannah; Losseff, Nick

    2007-01-01

    This review aims to update the reader on advances in the understanding of haematological conditions that may arise in neurological practice. Thrombophilia, antiphospholipid antibody syndrome, thrombotic thrombocytopenic purpura, sickle cell and clonal disorders associated with neuropathy are discussed. PMID:17369588

  20. Neurological Sequelae of Lupus

    MedlinePlus

    ... Page Synonym(s): Lupus - Neurological Sequelae, Systemic Lupus Erythematosus Table of Contents (click to jump to sections) What ... health problems and have a normal lifespan with periodic doctor visits and treatments with various drugs. What ...

  1. Translating the basic knowledge of mitochondrial functions to metabolic therapy: role of L-carnitine.

    PubMed

    Marcovina, Santica M; Sirtori, Cesare; Peracino, Andrea; Gheorghiade, Mihai; Borum, Peggy; Remuzzi, Giuseppe; Ardehali, Hossein

    2013-02-01

    Mitochondria play important roles in human physiological processes, and therefore, their dysfunction can lead to a constellation of metabolic and nonmetabolic abnormalities such as a defect in mitochondrial gene expression, imbalance in fuel and energy homeostasis, impairment in oxidative phosphorylation, enhancement of insulin resistance, and abnormalities in fatty acid metabolism. As a consequence, mitochondrial dysfunction contributes to the pathophysiology of insulin resistance, obesity, diabetes, vascular disease, and chronic heart failure. The increased knowledge on mitochondria and their role in cellular metabolism is providing new evidence that these disorders may benefit from mitochondrial-targeted therapies. We review the current knowledge of the contribution of mitochondrial dysfunction to chronic diseases, the outcomes of experimental studies on mitochondrial-targeted therapies, and explore the potential of metabolic modulators in the treatment of selected chronic conditions. As an example of such modulators, we evaluate the efficacy of the administration of L-carnitine and its analogues acetyl and propionyl L-carnitine in several chronic diseases. L-carnitine is intrinsically involved in mitochondrial metabolism and function as it plays a key role in fatty acid oxidation and energy metabolism. In addition to the transportation of free fatty acids across the inner mitochondrial membrane, L-carnitine modulates their oxidation rate and is involved in the regulation of vital cellular functions such as apoptosis. Thus, L-carnitine and its derivatives show promise in the treatment of chronic conditions and diseases associated with mitochondrial dysfunction but further translational studies are needed to fully explore their potential. PMID:23138103

  2. Apotemnophilia: a neurological disorder.

    PubMed

    Brang, David; McGeoch, Paul D; Ramachandran, Vilayanur S

    2008-08-27

    Apotemnophilia, a disorder that blurs the distinction between neurology and psychiatry, is characterized by the intense and longstanding desire for amputation of a specific limb. Here we present evidence from two individuals suggestive that this condition, long thought to be entirely psychological in origin, actually has a neurological basis. We found heightened skin conductance response to pinprick below the desired line of amputation. We propose apotemnophilia arises from congenital dysfunction of the right superior parietal lobule and its connection with the insula.

  3. Altered mitochondrial function and metabolic inflexibility associated with loss of caveolin-1.

    PubMed

    Asterholm, Ingrid Wernstedt; Mundy, Dorothy I; Weng, Jian; Anderson, Richard G W; Scherer, Philipp E

    2012-02-01

    Caveolin-1 is a major structural component of raft structures within the plasma membrane and has been implicated as a regulator of cellular signal transduction with prominent expression in adipocytes. Here, we embarked on a comprehensive characterization of the metabolic pathways dysregulated in caveolin-1 null mice. We found that these mice display decreased circulating levels of total and high molecular weight adiponectin and a reduced ability to change substrate use in response to feeding/fasting conditions. Caveolin-1 null mice are extremely lean but retain muscle mass despite lipodystrophy and massive metabolic dysfunction. Hepatic gluconeogenesis is chronically elevated, while hepatic steatosis is reduced. Our data suggest that the complex phenotype of the caveolin-1 null mouse is caused by altered metabolic and mitochondrial function in adipose tissue with a subsequent compensatory response driven mostly by the liver. This mouse model highlights the central contributions of adipose tissue for system-wide preservation of metabolic flexibility. PMID:22326219

  4. Altered Mitochondrial Function and Metabolic Inflexibility Associated with Loss of Caveolin-1

    PubMed Central

    Asterholm, Ingrid Wernstedt; Mundy, Dorothy I.; Weng, Jian; Anderson, Richard G. W.; Scherer, Philipp E.

    2012-01-01

    Caveolin-1 is a major structural component of raft structures within the plasma membrane and has been implicated as a regulator of cellular signal transduction with prominent expression in adipocytes. Here, we embarked on a comprehensive characterization of the metabolic pathways dysregulated in caveolin-1 null mice. We found that these mice display decreased circulating levels of total and high molecular weight adiponectin and a reduced ability to change substrate use in response to feeding/fasting conditions. Caveolin-1 null mice are extremely lean, but retain muscle mass despite lipodystrophy and massive metabolic dysfunction. Hepatic gluconeogenesis is chronically elevated, while hepatic steatosis is reduced. Our data suggest that the complex phenotype of the caveolin-1 null mouse is caused by altered metabolic and mitochondrial function in adipose tissue with a subsequent compensatory response driven mostly by the liver. This mouse model highlights the central contributions of adipose tissue for system-wide preservation of metabolic flexibility. PMID:22326219

  5. Retinoic Acid-Related Orphan Receptors (RORs): Regulatory Functions in Immunity, Development, Circadian Rhythm, and Metabolism

    PubMed Central

    Cook, Donald N.; Kang, Hong Soon; Jetten, Anton M.

    2015-01-01

    In this overview, we provide an update on recent progress made in understanding the mechanisms of action, physiological functions, and roles in disease of retinoic acid related orphan receptors (RORs). We are particularly focusing on their roles in the regulation of adaptive and innate immunity, brain function, retinal development, cancer, glucose and lipid metabolism, circadian rhythm, metabolic and inflammatory diseases and neuropsychiatric disorders. We also summarize the current status of ROR agonists and inverse agonists, including their regulation of ROR activity and their therapeutic potential for management of various diseases in which RORs have been implicated. PMID:26878025

  6. Wikipedia and neurological disorders.

    PubMed

    Brigo, Francesco; Igwe, Stanley C; Nardone, Raffaele; Lochner, Piergiorgio; Tezzon, Frediano; Otte, Willem M

    2015-07-01

    Our aim was to evaluate Wikipedia page visits in relation to the most common neurological disorders by determining which factors are related to peaks in Wikipedia searches for these conditions. Millions of people worldwide use the internet daily as a source of health information. Wikipedia is a popular free online encyclopedia used by patients and physicians to search for health-related information. The following Wikipedia articles were considered: Alzheimer's disease; Amyotrophic lateral sclerosis; Dementia; Epilepsy; Epileptic seizure; Migraine; Multiple sclerosis; Parkinson's disease; Stroke; Traumatic brain injury. We analyzed information regarding the total article views for 90 days and the rank of these articles among all those available in Wikipedia. We determined the highest search volume peaks to identify possible relation with online news headlines. No relation between incidence or prevalence of neurological disorders and the search volume for the related articles was found. Seven out of 10 neurological conditions showed relations in search volume peaks and news headlines. Six out of these seven peaks were related to news about famous people suffering from neurological disorders, especially those from showbusiness. Identification of discrepancies between disease burden and health seeking behavior on Wikipedia is useful in the planning of public health campaigns. Celebrities who publicly announce their neurological diagnosis might effectively promote awareness programs, increase public knowledge and reduce stigma related to diagnoses of neurological disorders.

  7. Neurology in Asia.

    PubMed

    Tan, Chong-Tin

    2015-02-10

    Asia is important as it accounts for more than half of the world population. The majority of Asian countries fall into the middle income category. As for cultural traditions, Asia is highly varied, with many languages spoken. The pattern of neurologic diseases in Asia is largely similar to the West, with some disease features being specific to Asia. Whereas Asia constitutes 60% of the world's population, it contains only 20% of the world's neurologists. This disparity is particularly evident in South and South East Asia. As for neurologic care, it is highly variable depending on whether it is an urban or rural setting, the level of economic development, and the system of health care financing. To help remedy the shortage of neurologists, most counties with larger populations have established training programs in neurology. These programs are diverse, with many areas of concern. There are regional organizations serving as a vehicle for networking in neurology and various subspecialties, as well as an official journal (Neurology Asia). The Asian Epilepsy Academy, with its emphasis on workshops in various locations, EEG certification examination, and fellowships, may provide a template of effective regional networking for improving neurology care in the region.

  8. Brain glycogen—new perspectives on its metabolic function and regulation at the subcellular level

    PubMed Central

    Obel, Linea F.; Müller, Margit S.; Walls, Anne B.; Sickmann, Helle M.; Bak, Lasse K.; Waagepetersen, Helle S.; Schousboe, Arne

    2012-01-01

    Glycogen is a complex glucose polymer found in a variety of tissues, including brain, where it is localized primarily in astrocytes. The small quantity found in brain compared to e.g., liver has led to the understanding that brain glycogen is merely used during hypoglycemia or ischemia. In this review evidence is brought forward highlighting what has been an emerging understanding in brain energy metabolism: that glycogen is more than just a convenient way to store energy for use in emergencies—it is a highly dynamic molecule with versatile implications in brain function, i.e., synaptic activity and memory formation. In line with the great spatiotemporal complexity of the brain and thereof derived focus on the basis for ensuring the availability of the right amount of energy at the right time and place, we here encourage a closer look into the molecular and subcellular mechanisms underlying glycogen metabolism. Based on (1) the compartmentation of the interconnected second messenger pathways controlling glycogen metabolism (calcium and cAMP), (2) alterations in the subcellular location of glycogen-associated enzymes and proteins induced by the metabolic status and (3) a sequential component in the intermolecular mechanisms of glycogen metabolism, we suggest that glycogen metabolism in astrocytes is compartmentalized at the subcellular level. As a consequence, the meaning and importance of conventional terms used to describe glycogen metabolism (e.g., turnover) is challenged. Overall, this review represents an overview of contemporary knowledge about brain glycogen and its metabolism and function. However, it also has a sharp focus on what we do not know, which is perhaps even more important for the future quest of uncovering the roles of glycogen in brain physiology and pathology. PMID:22403540

  9. Brain glycogen-new perspectives on its metabolic function and regulation at the subcellular level.

    PubMed

    Obel, Linea F; Müller, Margit S; Walls, Anne B; Sickmann, Helle M; Bak, Lasse K; Waagepetersen, Helle S; Schousboe, Arne

    2012-01-01

    Glycogen is a complex glucose polymer found in a variety of tissues, including brain, where it is localized primarily in astrocytes. The small quantity found in brain compared to e.g., liver has led to the understanding that brain glycogen is merely used during hypoglycemia or ischemia. In this review evidence is brought forward highlighting what has been an emerging understanding in brain energy metabolism: that glycogen is more than just a convenient way to store energy for use in emergencies-it is a highly dynamic molecule with versatile implications in brain function, i.e., synaptic activity and memory formation. In line with the great spatiotemporal complexity of the brain and thereof derived focus on the basis for ensuring the availability of the right amount of energy at the right time and place, we here encourage a closer look into the molecular and subcellular mechanisms underlying glycogen metabolism. Based on (1) the compartmentation of the interconnected second messenger pathways controlling glycogen metabolism (calcium and cAMP), (2) alterations in the subcellular location of glycogen-associated enzymes and proteins induced by the metabolic status and (3) a sequential component in the intermolecular mechanisms of glycogen metabolism, we suggest that glycogen metabolism in astrocytes is compartmentalized at the subcellular level. As a consequence, the meaning and importance of conventional terms used to describe glycogen metabolism (e.g., turnover) is challenged. Overall, this review represents an overview of contemporary knowledge about brain glycogen and its metabolism and function. However, it also has a sharp focus on what we do not know, which is perhaps even more important for the future quest of uncovering the roles of glycogen in brain physiology and pathology.

  10. Social networks and neurological illness.

    PubMed

    Dhand, Amar; Luke, Douglas A; Lang, Catherine E; Lee, Jin-Moo

    2016-10-01

    Every patient is embedded in a social network of interpersonal connections that influence health outcomes. Neurologists routinely need to engage with a patient's family and friends due to the nature of the illness and its social sequelae. Social isolation is a potent determinant of poor health and neurobiological changes, and its effects can be comparable to those of traditional risk factors. It would seem reasonable, therefore, to map and follow the personal networks of neurology patients. This approach reveals influential people, their habits, and linkage patterns that could facilitate or limit health behaviours. Personal network information can be particularly valuable to enhance risk factor management, medication adherence, and functional recovery. Here, we propose an agenda for research and clinical practice that includes mapping the networks of patients with diverse neurological disorders, evaluating the impact of the networks on patient outcomes, and testing network interventions. PMID:27615420

  11. Absorption, metabolism, and functions of β-cryptoxanthin.

    PubMed

    Burri, Betty J; La Frano, Michael R; Zhu, Chenghao

    2016-02-01

    β-Cryptoxanthin, a carotenoid found in fruits and vegetables such as tangerines, red peppers, and pumpkin, has several functions important for human health. Most evidence from observational, in vitro, animal model, and human studies suggests that β-cryptoxanthin has relatively high bioavailability from its common food sources, to the extent that some β-cryptoxanthin-rich foods might be equivalent to β-carotene-rich foods as sources of retinol. β-Cryptoxanthin is an antioxidant in vitro and appears to be associated with decreased risk of some cancers and degenerative diseases. In addition, many in vitro, animal model, and human studies suggest that β-cryptoxanthin-rich foods may have an anabolic effect on bone and, thus, may help delay osteoporosis. PMID:26747887

  12. Intrinsic and Tumor Microenvironment-Induced Metabolism Adaptations of T Cells and Impact on Their Differentiation and Function.

    PubMed

    Kouidhi, Soumaya; Noman, Muhammad Zaeem; Kieda, Claudine; Elgaaied, Amel Benammar; Chouaib, Salem

    2016-01-01

    It is well recognized that the immune system and metabolism are highly integrated. In this context, multilevel interactions between metabolic system and T lymphocyte signaling and fate exist. This review will discuss different potential cell metabolism pathways involved in shaping T lymphocyte function and differentiation. We will also provide a general framework for understanding how tumor microenvironmental metabolism, associated with hypoxic stress, interferes with T-cell priming and expansion. How T-cell metabolism drives T-cell-mediated immunity and how the manipulation of metabolic programing for therapeutic purposes will be also discussed. PMID:27066006

  13. Dietary Proteins as Determinants of Metabolic and Physiologic Functions of the Gastrointestinal Tract

    PubMed Central

    Jahan-Mihan, Alireza; Luhovyy, Bohdan L.; Khoury, Dalia El; Anderson, G. Harvey

    2011-01-01

    Dietary proteins elicit a wide range of nutritional and biological functions. Beyond their nutritional role as the source of amino acids for protein synthesis, they are instrumental in the regulation of food intake, glucose and lipid metabolism, blood pressure, bone metabolism and immune function. The interaction of dietary proteins and their products of digestion with the regulatory functions of the gastrointestinal (GI) tract plays a dominant role in determining the physiological properties of proteins. The site of interaction is widespread, from the oral cavity to the colon. The characteristics of proteins that influence their interaction with the GI tract in a source-dependent manner include their physico-chemical properties, their amino acid composition and sequence, their bioactive peptides, their digestion kinetics and also the non-protein bioactive components conjugated with them. Within the GI tract, these products affect several regulatory functions by interacting with receptors releasing hormones, affecting stomach emptying and GI transport and absorption, transmitting neural signals to the brain, and modifying the microflora. This review discusses the interaction of dietary proteins during digestion and absorption with the physiological and metabolic functions of the GI tract, and illustrates the importance of this interaction in the regulation of amino acid, glucose, lipid metabolism, and food intake. PMID:22254112

  14. Clinical neurologic indices of toxicity in animals.

    PubMed Central

    O'Donoghue, J L

    1996-01-01

    The fundamental structures and functions of the nervous systems of animals and humans are conserved in many ways across species. These similarities provide a basis for developing common neurologic examinations for a number of species of animals and also provide a basis for developing risk assessments across species for neurologic end points. The neurologic examination requires no expensive equipment and can be conducted in the field or wherever impaired animals are identified. The proper conduct of neurologic examinations in animals assumes that the examiner has a fundamental understanding of the normal structure and function of the nervous system as well as knowledge about the spontaneous disease background of the species being studied. PMID:9182039

  15. Neurofilament dynamics and involvement in neurological disorders.

    PubMed

    Gentil, Benoit J; Tibshirani, Michael; Durham, Heather D

    2015-06-01

    Neurons are extremely polarised cells in which the cytoskeleton, composed of microtubules, microfilaments and neurofilaments, plays a crucial role in maintaining structure and function. Neurofilaments, the 10-nm intermediate filaments of neurons, provide structure and mechanoresistance but also provide a scaffolding for the organization of the nucleus and organelles such as mitochondria and ER. Disruption of neurofilament organization and expression or metabolism of neurofilament proteins is characteristic of certain neurological syndromes including Amyotrophic Lateral Sclerosis, Charcot-Marie-Tooth sensorimotor neuropathies and Giant Axonal Neuropathy. Microfluorometric live imaging techniques have been instrumental in revealing the dynamics of neurofilament assembly and transport and their functions in organizing intracellular organelle networks. The insolubility of neurofilament proteins has limited identifying interactors by conventional biochemical techniques but yeast two-hybrid experiments have revealed new roles for oligomeric, nonfilamentous structures including vesicular trafficking. Although having long half-lives, new evidence points to degradation of subunits by the ubiquitin-proteasome system as a mechanism of normal turnover. Although certain E3-ligases ubiquitinating neurofilament proteins have been identified, the overall process of neurofilament degradation is not well understood. We review these mechanisms of neurofilament homeostasis and abnormalities in motor neuron and peripheral nerve disorders. Much remains to discover about the disruption of processes that leads to their pathological aggregation and accumulation and the relevance to pathogenesis. Understanding these mechanisms is crucial for identifying novel therapeutic strategies.

  16. Divergent Expression and Metabolic Functions of Human Glucuronosyltransferases through Alternative Splicing.

    PubMed

    Rouleau, Michèle; Tourancheau, Alan; Girard-Bock, Camille; Villeneuve, Lyne; Vaucher, Jonathan; Duperré, Anne-Marie; Audet-Delage, Yannick; Gilbert, Isabelle; Popa, Ion; Droit, Arnaud; Guillemette, Chantal

    2016-09-27

    Maintenance of cellular homeostasis and xenobiotic detoxification is mediated by 19 human UDP-glucuronosyltransferase enzymes (UGTs) encoded by ten genes that comprise the glucuronidation pathway. Deep RNA sequencing of major metabolic organs exposes a substantial expansion of the UGT transcriptome by alternative splicing, with variants representing 20% to 60% of canonical transcript expression. Nearly a fifth of expressed variants comprise in-frame sequences that may create distinct structural and functional features. Follow-up cell-based assays reveal biological functions for these alternative UGT proteins. Some isoforms were found to inhibit or induce inactivation of drugs and steroids in addition to perturbing global cell metabolism (energy, amino acids, nucleotides), cell adhesion, and proliferation. This work highlights the biological relevance of alternative UGT expression, which we propose increases protein diversity through the evolution of metabolic regulators from specific enzymes. PMID:27681425

  17. The essential functions of endoplasmic reticulum chaperones in hepatic lipid metabolism.

    PubMed

    Zhang, LiChun; Wang, Hong-Hui

    2016-07-01

    The endoplasmic reticulum (ER) is an essential organelle for protein and lipid synthesis in hepatocytes. ER homeostasis is vital to maintain normal hepatocyte physiology. Perturbed ER functions causes ER stress associated with accumulation of unfolded protein in the ER that activates a series of adaptive signalling pathways, termed unfolded protein response (UPR). The UPR regulates ER chaperone levels to preserve ER protein-folding environment to protect the cell from ER stress. Recent findings reveal an array of ER chaperones that alter the protein-folding environment in the ER of hepatocytes and contribute to dysregulation of hepatocyte lipid metabolism and liver disease. In this review, we will discuss the specific functions of these chaperones in regulation of lipid metabolism, especially de novo lipogenesis and lipid transport and demonstrate their homeostatic role not only for ER-protein synthesis but also for lipid metabolism in hepatocyte. PMID:27133206

  18. Divergent Expression and Metabolic Functions of Human Glucuronosyltransferases through Alternative Splicing.

    PubMed

    Rouleau, Michèle; Tourancheau, Alan; Girard-Bock, Camille; Villeneuve, Lyne; Vaucher, Jonathan; Duperré, Anne-Marie; Audet-Delage, Yannick; Gilbert, Isabelle; Popa, Ion; Droit, Arnaud; Guillemette, Chantal

    2016-09-27

    Maintenance of cellular homeostasis and xenobiotic detoxification is mediated by 19 human UDP-glucuronosyltransferase enzymes (UGTs) encoded by ten genes that comprise the glucuronidation pathway. Deep RNA sequencing of major metabolic organs exposes a substantial expansion of the UGT transcriptome by alternative splicing, with variants representing 20% to 60% of canonical transcript expression. Nearly a fifth of expressed variants comprise in-frame sequences that may create distinct structural and functional features. Follow-up cell-based assays reveal biological functions for these alternative UGT proteins. Some isoforms were found to inhibit or induce inactivation of drugs and steroids in addition to perturbing global cell metabolism (energy, amino acids, nucleotides), cell adhesion, and proliferation. This work highlights the biological relevance of alternative UGT expression, which we propose increases protein diversity through the evolution of metabolic regulators from specific enzymes.

  19. MIRAGE: a functional genomics-based approach for metabolic network model reconstruction and its application to cyanobacteria networks.

    PubMed

    Vitkin, Edward; Shlomi, Tomer

    2012-01-01

    Genome-scale metabolic network reconstructions are considered a key step in quantifying the genotype-phenotype relationship. We present a novel gap-filling approach, MetabolIc Reconstruction via functionAl GEnomics (MIRAGE), which identifies missing network reactions by integrating metabolic flux analysis and functional genomics data. MIRAGE's performance is demonstrated on the reconstruction of metabolic network models of E. coli and Synechocystis sp. and validated via existing networks for these species. Then, it is applied to reconstruct genome-scale metabolic network models for 36 sequenced cyanobacteria amenable for constraint-based modeling analysis and specifically for metabolic engineering. The reconstructed network models are supplied via standard SBML files. PMID:23194418

  20. Towards stable kinetics of large metabolic networks: Nonequilibrium potential function approach.

    PubMed

    Chen, Yong-Cong; Yuan, Ruo-Shi; Ao, Ping; Xu, Min-Juan; Zhu, Xiao-Mei

    2016-06-01

    While the biochemistry of metabolism in many organisms is well studied, details of the metabolic dynamics are not fully explored yet. Acquiring adequate in vivo kinetic parameters experimentally has always been an obstacle. Unless the parameters of a vast number of enzyme-catalyzed reactions happened to fall into very special ranges, a kinetic model for a large metabolic network would fail to reach a steady state. In this work we show that a stable metabolic network can be systematically established via a biologically motivated regulatory process. The regulation is constructed in terms of a potential landscape description of stochastic and nongradient systems. The constructed process draws enzymatic parameters towards stable metabolism by reducing the change in the Lyapunov function tied to the stochastic fluctuations. Biologically it can be viewed as interplay between the flux balance and the spread of workloads on the network. Our approach allows further constraints such as thermodynamics and optimal efficiency. We choose the central metabolism of Methylobacterium extorquens AM1 as a case study to demonstrate the effectiveness of the approach. Growth efficiency on carbon conversion rate versus cell viability and futile cycles is investigated in depth. PMID:27415300

  1. Direct visualization of functional heterogeneity in hepatobiliary metabolism using 6-CFDA as model compound

    PubMed Central

    Lin, Chih-Ju; Li, Feng-Chieh; Lee, Yu-Yang; Tseng, Te-Yu; Chen, Wei-Liang; Hovhannisyan, Vladimir; Kang, Ning; Horton, Nicholas G.; Chiang, Shu-Jen; Xu, Chris; Lee, Hsuan-Shu; Dong, Chen-Yuan

    2016-01-01

    Hepatobiliary metabolism is one of the major functions of the liver. However, little is known of the relationship between the physiological location of the hepatocytes and their metabolic potential. By the combination of time-lapse multiphoton microscopy and first order kinetic constant image analysis, the hepatocellular metabolic rate of the model compound 6-carboxyfluorescein diacetate (6-CFDA) is quantified at the single cell level. We found that the mouse liver can be divided into three zones, each with distinct metabolic rate constants. The sinusoidal uptake coefficients k1 of Zones 1, 2, and 3 are respectively 0.239 ± 0.077, 0.295 ± 0.087, and 0.338 ± 0.133 min−1, the apical excreting coefficients k2 of Zones 1, 2, and 3 are 0.0117 ± 0.0052, 0.0175 ± 0.0052, and 0.0332 ± 0.0195 min−1, respectively. Our results show not only the existence of heterogeneities in hepatobiliary metabolism, but they also show that Zone 3 is the main area of metabolism. PMID:27699121

  2. Direct visualization of functional heterogeneity in hepatobiliary metabolism using 6-CFDA as model compound

    PubMed Central

    Lin, Chih-Ju; Li, Feng-Chieh; Lee, Yu-Yang; Tseng, Te-Yu; Chen, Wei-Liang; Hovhannisyan, Vladimir; Kang, Ning; Horton, Nicholas G.; Chiang, Shu-Jen; Xu, Chris; Lee, Hsuan-Shu; Dong, Chen-Yuan

    2016-01-01

    Hepatobiliary metabolism is one of the major functions of the liver. However, little is known of the relationship between the physiological location of the hepatocytes and their metabolic potential. By the combination of time-lapse multiphoton microscopy and first order kinetic constant image analysis, the hepatocellular metabolic rate of the model compound 6-carboxyfluorescein diacetate (6-CFDA) is quantified at the single cell level. We found that the mouse liver can be divided into three zones, each with distinct metabolic rate constants. The sinusoidal uptake coefficients k1 of Zones 1, 2, and 3 are respectively 0.239 ± 0.077, 0.295 ± 0.087, and 0.338 ± 0.133 min−1, the apical excreting coefficients k2 of Zones 1, 2, and 3 are 0.0117 ± 0.0052, 0.0175 ± 0.0052, and 0.0332 ± 0.0195 min−1, respectively. Our results show not only the existence of heterogeneities in hepatobiliary metabolism, but they also show that Zone 3 is the main area of metabolism.

  3. Towards stable kinetics of large metabolic networks: Nonequilibrium potential function approach

    NASA Astrophysics Data System (ADS)

    Chen, Yong-Cong; Yuan, Ruo-Shi; Ao, Ping; Xu, Min-Juan; Zhu, Xiao-Mei

    2016-06-01

    While the biochemistry of metabolism in many organisms is well studied, details of the metabolic dynamics are not fully explored yet. Acquiring adequate in vivo kinetic parameters experimentally has always been an obstacle. Unless the parameters of a vast number of enzyme-catalyzed reactions happened to fall into very special ranges, a kinetic model for a large metabolic network would fail to reach a steady state. In this work we show that a stable metabolic network can be systematically established via a biologically motivated regulatory process. The regulation is constructed in terms of a potential landscape description of stochastic and nongradient systems. The constructed process draws enzymatic parameters towards stable metabolism by reducing the change in the Lyapunov function tied to the stochastic fluctuations. Biologically it can be viewed as interplay between the flux balance and the spread of workloads on the network. Our approach allows further constraints such as thermodynamics and optimal efficiency. We choose the central metabolism of Methylobacterium extorquens AM1 as a case study to demonstrate the effectiveness of the approach. Growth efficiency on carbon conversion rate versus cell viability and futile cycles is investigated in depth.

  4. Genomic islands link secondary metabolism to functional adaptation in marine Actinobacteria.

    PubMed

    Penn, Kevin; Jenkins, Caroline; Nett, Markus; Udwary, Daniel W; Gontang, Erin A; McGlinchey, Ryan P; Foster, Brian; Lapidus, Alla; Podell, Sheila; Allen, Eric E; Moore, Bradley S; Jensen, Paul R

    2009-10-01

    Genomic islands have been shown to harbor functional traits that differentiate ecologically distinct populations of environmental bacteria. A comparative analysis of the complete genome sequences of the marine Actinobacteria Salinispora tropica and Salinispora arenicola reveals that 75% of the species-specific genes are located in 21 genomic islands. These islands are enriched in genes associated with secondary metabolite biosynthesis providing evidence that secondary metabolism is linked to functional adaptation. Secondary metabolism accounts for 8.8% and 10.9% of the genes in the S. tropica and S. arenicola genomes, respectively, and represents the major functional category of annotated genes that differentiates the two species. Genomic islands harbor all 25 of the species-specific biosynthetic pathways, the majority of which occur in S. arenicola and may contribute to the cosmopolitan distribution of this species. Genome evolution is dominated by gene duplication and acquisition, which in the case of secondary metabolism provide immediate opportunities for the production of new bioactive products. Evidence that secondary metabolic pathways are exchanged horizontally, coupled with earlier evidence for fixation among globally distributed populations, supports a functional role and suggests that the acquisition of natural product biosynthetic gene clusters represents a previously unrecognized force driving bacterial diversification. Species-specific differences observed in clustered regularly interspaced short palindromic repeat sequences suggest that S. arenicola may possess a higher level of phage immunity, whereas a highly duplicated family of polymorphic membrane proteins provides evidence for a new mechanism of marine adaptation in Gram-positive bacteria.

  5. Metabolic status, gonadotropin secretion, and ovarian function during acute nutrient restriction of beef heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of acute nutritional restriction on metabolic status, gonadotropin secretion, and ovarian function of heifers was determined in 2 experiments. In Exp. 1, 14-mo-old heifers were fed a diet supplying 1.2 × maintenance energy requirements (1.2M). After 10 d, heifers were fed 1.2M or were res...

  6. Hydrodynamics-Based Functional Forms of Activity Metabolism: A Case for the Power-Law Polynomial Function in Animal Swimming Energetics

    PubMed Central

    Papadopoulos, Anthony

    2009-01-01

    The first-degree power-law polynomial function is frequently used to describe activity metabolism for steady swimming animals. This function has been used in hydrodynamics-based metabolic studies to evaluate important parameters of energetic costs, such as the standard metabolic rate and the drag power indices. In theory, however, the power-law polynomial function of any degree greater than one can be used to describe activity metabolism for steady swimming animals. In fact, activity metabolism has been described by the conventional exponential function and the cubic polynomial function, although only the power-law polynomial function models drag power since it conforms to hydrodynamic laws. Consequently, the first-degree power-law polynomial function yields incorrect parameter values of energetic costs if activity metabolism is governed by the power-law polynomial function of any degree greater than one. This issue is important in bioenergetics because correct comparisons of energetic costs among different steady swimming animals cannot be made unless the degree of the power-law polynomial function derives from activity metabolism. In other words, a hydrodynamics-based functional form of activity metabolism is a power-law polynomial function of any degree greater than or equal to one. Therefore, the degree of the power-law polynomial function should be treated as a parameter, not as a constant. This new treatment not only conforms to hydrodynamic laws, but also ensures correct comparisons of energetic costs among different steady swimming animals. Furthermore, the exponential power-law function, which is a new hydrodynamics-based functional form of activity metabolism, is a special case of the power-law polynomial function. Hence, the link between the hydrodynamics of steady swimming and the exponential-based metabolic model is defined. PMID:19333397

  7. Neurological Complications of Transplantation

    PubMed Central

    Pruitt, Amy A.; Graus, Francesc; Rosenfeld, Myrna R.

    2013-01-01

    Hematopoietic cell transplantation (HCT) is the preferred treatment for an expanding range of neoplastic and nonmalignant conditions. Increasing numbers of solid organ transplantations (SOTs) add an additional population of immunosuppressed patients with multiple potential neurological problems. While the spectrum of neurological complications varies with conditioning procedure and hematopoietic cell or solid organ source, major neurological complications occur with all transplantation procedures. This 2 part review emphasizes a practical consultative approach to central and peripheral nervous system problems related to HCT or SOT with clinical and neuroimaging examples from the authors’ institutional experience with the following conditions: the diversity of manifestations of common infections such as varicella zoster virus, Aspergillus, and progressive multifocal leukoencephalopathy (PML), drug therapy-related complications, stroke mechanisms, the spectrum of graft versus host disease (GVHD), and neurologically important syndromes of immune reconstitution inflammatory syndrome (IRIS), posterior reversible encephalopathy syndrome (PRES), and posttransplantation lymphoproliferative disorder (PTLD). These complications preferentially occur at specific intervals after HCT and SOT, and neurological consultants must recognize an extensive spectrum of syndromes in order to effect timely diagnosis and expedite appropriate treatment. PMID:23983885

  8. Neurology and Don Quixote.

    PubMed

    Palma, Jose-Alberto; Palma, Fermin

    2012-01-01

    Don Quixote de la Mancha, which is considered one of the most important and influential works of Western modern prose, contains many references of interest for almost all of the medical specialties. In this regard, numerous references to neurology can be found in Cervantes' immortal work. In this study, we aimed to read Don Quixote from a neurologist's point of view, describing the neurological phenomena scattered throughout the novel, including tremors, sleep disturbances, neuropsychiatric symptoms, dementia, epilepsy, paralysis, stroke, syncope, traumatic head injury, and headache; we relate these symptoms with depictions of those conditions in the medical literature of the time. We also review Cervantes' sources of neurological information, including the works by renowned Spanish authors such as Juan Huarte de San Juan, Dionisio Daza Chacón and Juan Valverde de Amusco, and we hypothesize that Don Quixote's disorder was actually a neurological condition. Although Cervantes wrote it four centuries ago, Don Quixote contains plenty of references to neurology, and many of the ideas and concepts reflected in it are still of interest. PMID:23006630

  9. Ongoing resolution of duplicate gene functions shapes the diversification of a metabolic network

    PubMed Central

    Kuang, Meihua Christina; Hutchins, Paul D; Russell, Jason D; Coon, Joshua J; Hittinger, Chris Todd

    2016-01-01

    The evolutionary mechanisms leading to duplicate gene retention are well understood, but the long-term impacts of paralog differentiation on the regulation of metabolism remain underappreciated. Here we experimentally dissect the functions of two pairs of ancient paralogs of the GALactose sugar utilization network in two yeast species. We show that the Saccharomyces uvarum network is more active, even as over-induction is prevented by a second co-repressor that the model yeast Saccharomyces cerevisiae lacks. Surprisingly, removal of this repression system leads to a strong growth arrest, likely due to overly rapid galactose catabolism and metabolic overload. Alternative sugars, such as fructose, circumvent metabolic control systems and exacerbate this phenotype. We further show that S. cerevisiae experiences homologous metabolic constraints that are subtler due to how the paralogs have diversified. These results show how the functional differentiation of paralogs continues to shape regulatory network architectures and metabolic strategies long after initial preservation. DOI: http://dx.doi.org/10.7554/eLife.19027.001 PMID:27690225

  10. Integrating gene and protein expression data with genome-scale metabolic networks to infer functional pathways

    PubMed Central

    2013-01-01

    Background The study of cellular metabolism in the context of high-throughput -omics data has allowed us to decipher novel mechanisms of importance in biotechnology and health. To continue with this progress, it is essential to efficiently integrate experimental data into metabolic modeling. Results We present here an in-silico framework to infer relevant metabolic pathways for a particular phenotype under study based on its gene/protein expression data. This framework is based on the Carbon Flux Path (CFP) approach, a mixed-integer linear program that expands classical path finding techniques by considering additional biophysical constraints. In particular, the objective function of the CFP approach is amended to account for gene/protein expression data and influence obtained paths. This approach is termed integrative Carbon Flux Path (iCFP). We show that gene/protein expression data also influences the stoichiometric balancing of CFPs, which provides a more accurate picture of active metabolic pathways. This is illustrated in both a theoretical and real scenario. Finally, we apply this approach to find novel pathways relevant in the regulation of acetate overflow metabolism in Escherichia coli. As a result, several targets which could be relevant for better understanding of the phenomenon leading to impaired acetate overflow are proposed. Conclusions A novel mathematical framework that determines functional pathways based on gene/protein expression data is presented and validated. We show that our approach is able to provide new insights into complex biological scenarios such as acetate overflow in Escherichia coli. PMID:24314206

  11. Proteomic analysis uncovers a metabolic phenotype in C. elegans after nhr-40 reduction of function

    SciTech Connect

    Pohludka, Michal; Simeckova, Katerina; Vohanka, Jaroslav; Yilma, Petr; Novak, Petr; Krause, Michael W.; Kostrouchova, Marta; Kostrouch, Zdenek

    2008-09-12

    Caenorhabditis elegans has an unexpectedly large number (284) of genes encoding nuclear hormone receptors, most of which are nematode-specific and are of unknown function. We have exploited comparative two-dimensional chromatography of synchronized cultures of wild type C. elegans larvae and a mutant in nhr-40 to determine if proteomic approaches will provide additional insight into gene function. Chromatofocusing, followed by reversed-phase chromatography and mass spectrometry, identified altered chromatographic patterns for a set of proteins, many of which function in muscle and metabolism. Prompted by the proteomic analysis, we find that the penetrance of the developmental phenotypes in the mutant is enhanced at low temperatures and by food restriction. The combination of our phenotypic and proteomic analysis strongly suggests that NHR-40 provides a link between metabolism and muscle development. Our results highlight the utility of comparative two-dimensional chromatography to provide a relatively rapid method to gain insight into gene function.

  12. White matter injury and microglia/macrophage polarization are strongly linked with age-related long-term deficits in neurological function after stroke.

    PubMed

    Suenaga, Jun; Hu, Xiaoming; Pu, Hongjian; Shi, Yejie; Hassan, Sulaiman Habib; Xu, Mingyue; Leak, Rehana K; Stetler, R Anne; Gao, Yanqin; Chen, Jun

    2015-10-01

    , aged mice exhibited significantly reduced M2 polarization compared to young adults. Remarkably, we discovered a strong positive correlation between favorable neurological outcomes after dMCAO and MBP levels or the number of M2 microglia/macrophages. In conclusion, our studies suggest that the distal MCAO stroke model consistently results in ischemic brain injury with long-term behavioral deficits, and is therefore suitable for the evaluation of long-term stroke outcomes. Furthermore, aged mice exhibit deterioration of functional outcomes after stroke and this deterioration is linked to white matter damage and reductions in M2 microglia/macrophage polarization.

  13. White matter injury and microglia/macrophage polarization are strongly linked with age-related long-term deficits in neurological function after stroke

    PubMed Central

    Suenaga, Jun; Hu, Xiaoming; Pu, Hongjian; Shi, Yejie; Hassan, Sulaiman Habib; Xu, Mingyue; Leak, Rehana K.; Stetler, R. Anne; Gao, Yanqin; Chen, Jun

    2015-01-01

    , aged mice exhibited significantly reduced M2 polarization compared to young adults. Remarkably, we discovered a strong positive correlation between favorable neurological outcomes after dMCAO and MBP levels or the number of M2 microglia/macrophages. In conclusion, our studies suggest that the distal MCAO stroke model consistently results in ischemic brain injury with long-term behavioral deficits, and is therefore suitable for the evaluation of long-term stroke outcomes. Furthermore, aged mice exhibit deterioration of functional outcomes after stroke and this deterioration is linked to white matter damage and reductions in M2 microglia/macrophage polarization. PMID:25836044

  14. [Biopterin and child neurologic disease].

    PubMed

    Shintaku, Haruo

    2009-01-01

    Tetrahydrobiopterin (BH4) deficiencies are disorders affecting phenylalanine metabolism in the liver and neurotransmitter biosynthesis in the brain. BH4 is the essential cofactor in the enzymatic hydroxylation of 3 aromatic amino acids (phenylalanine, tyrosine, and tryptophan). BH4 is synthesized from guanosine triphosphate (GTP), catalyzed by GTP cyclohydrolase I (GTPCH), 6-pyruvoyl-tetrahydropterin synthase, and sepiapterin reductase (SR), and in aromatic amino acids, the hydoxylating system is regenerated by pterin-4a-carbinolamine dehydrolase and dihydropteridine reductase (DHPR). BH4 deficiency has been diagnosed in patients with hyperphenylalaninemia (HPA) by neonatal mass-screening based on BH4 oral-loading tests, analysis of urinary or serum pteridines, and measurement of DHPR activity in blood using a Guthrie card. BH4 deficiency without treatment causes combined symptoms of HPA and neurotransmitter (dopamine, norepinephrine, epinephrine, and serotonin) deficiency, such as red hair, psychomotor retardation, and progressive neurological deterioration. However, autosomal dominant GTPCH deficiency and autosomal recessive SR deficiency leads to BH4 and neurotransmitter deficiency without HPA and may not be detected by neonatal screening for phenylketonuria. The former is Segawa's disease, which is characterized by dopa-responsive dystonia with marked diurnal fluctuation and is caused by a defect of GTPCH, and the latter is SR deficiency, which is characterized by progressive psychomotor retardation, dystonia, and severe dopamine and serotonin deficiencies. Biochemical diagnosis is performed by the measurement of neopterin and biopterin levels, since both are low in Segawa disease, and the biopterin level is high in SR deficiency in cerebrospinal fluid. We must consider metabolic disorders of biopterin in child neurologic diseases with dystonia.

  15. Genetic neurological channelopathies: molecular genetics and clinical phenotypes

    PubMed Central

    Spillane, J; Kullmann, D M; Hanna, M G

    2016-01-01

    Evidence accumulated over recent years has shown that genetic neurological channelopathies can cause many different neurological diseases. Presentations relating to the brain, spinal cord, peripheral nerve or muscle mean that channelopathies can impact on almost any area of neurological practice. Typically, neurological channelopathies are inherited in an autosomal dominant fashion and cause paroxysmal disturbances of neurological function, although the impairment of function can become fixed with time. These disorders are individually rare, but an accurate diagnosis is important as it has genetic counselling and often treatment implications. Furthermore, the study of less common ion channel mutation-related diseases has increased our understanding of pathomechanisms that is relevant to common neurological diseases such as migraine and epilepsy. Here, we review the molecular genetic and clinical features of inherited neurological channelopathies. PMID:26558925

  16. Neurological complications of transplantation.

    PubMed

    Pustavoitau, Aliaksei; Bhardwaj, Anish; Stevens, Robert

    2011-01-01

    Recipients of solid organ or hematopoietic cell transplants are at risk of life-threatening neurological disorders including encephalopathy, seizures, infections and tumors of the central nervous system, stroke, central pontine myelinolysis, and neuromuscular disorders-often requiring admission to, or occurring in, the intensive care unit (ICU). Many of these complications are linked directly or indirectly to immunosuppressive therapy. However, neurological disorders may also result from graft versus host disease, or be an expression of the underlying disease which prompted transplantation, as well as injury induced during radiation, chemotherapy, surgery, and ICU stay. In rare cases, neuroinfectious pathogens may be transmitted with the transplanted tissue or organ. Diagnosis may be a challenge because clinical symptoms and findings on neuroimaging lack specificity, and a biological specimen or tissue diagnosis is often needed for definitive diagnosis. Management is centered on preventing further neurological injury, etiology-targeted therapy, and balancing the benefits and toxicities of specific immunosuppressive agents. PMID:21764765

  17. Genomics in Neurological Disorders

    PubMed Central

    Han, Guangchun; Sun, Jiya; Wang, Jiajia; Bai, Zhouxian; Song, Fuhai; Lei, Hongxing

    2014-01-01

    Neurological disorders comprise a variety of complex diseases in the central nervous system, which can be roughly classified as neurodegenerative diseases and psychiatric disorders. The basic and translational research of neurological disorders has been hindered by the difficulty in accessing the pathological center (i.e., the brain) in live patients. The rapid advancement of sequencing and array technologies has made it possible to investigate the disease mechanism and biomarkers from a systems perspective. In this review, recent progresses in the discovery of novel risk genes, treatment targets and peripheral biomarkers employing genomic technologies will be discussed. Our major focus will be on two of the most heavily investigated neurological disorders, namely Alzheimer’s disease and autism spectrum disorder. PMID:25108264

  18. Genetic Analysis in Neurology

    PubMed Central

    Pittman, Alan; Hardy, John

    2014-01-01

    In recent years, neurogenetics research had made some remarkable advances owing to the advent of genotyping arrays and next-generation sequencing. These improvements to the technology have allowed us to determine the whole-genome structure and its variation and to examine its effect on phenotype in an unprecedented manner. The identification of rare disease-causing mutations has led to the identification of new biochemical pathways and has facilitated a greater understanding of the etiology of many neurological diseases. Furthermore, genome-wide association studies have provided information on how common genetic variability impacts on the risk for the development of various complex neurological diseases. Herein, we review how these technological advances have changed the approaches being used to study the genetic basis of neurological disease and how the research findings will be translated into clinical utility. PMID:23571731

  19. Brain imaging and brain function

    SciTech Connect

    Sokoloff, L.

    1985-01-01

    This book is a survey of the applications of imaging studies of regional cerebral blood flow and metabolism to the investigation of neurological and psychiatric disorders. Contributors review imaging techniques and strategies for measuring regional cerebral blood flow and metabolism, for mapping functional neural systems, and for imaging normal brain functions. They then examine the applications of brain imaging techniques to the study of such neurological and psychiatric disorders as: cerebral ischemia; convulsive disorders; cerebral tumors; Huntington's disease; Alzheimer's disease; depression and other mood disorders. A state-of-the-art report on magnetic resonance imaging of the brain and central nervous system rounds out the book's coverage.

  20. Paraneoplastic neurological syndromes

    PubMed Central

    Leypoldt, F; Wandinger, K-P

    2014-01-01

    Paraneoplastic neurological syndromes are immune-mediated erroneous attacks on the central or peripheral nervous systems, or both, directed originally against the tumour itself. They have been known for more than 40 years, but recently the discovery of new subgroups of paraneoplastic encephalitis syndromes with a remarkably good response to immune therapy has ignited new clinical and scientific interest. Knowledge of these subgroups and their associated autoantibodies is important in therapeutic decision-making. However, the abundance of new autoantibodies and syndromes can be confusing. This review paper summarizes current knowledge and new developments in the field of paraneoplastic neurological syndromes, their classification, pathophysiology and treatment. PMID:23937626

  1. Neurologic effects of alcoholism.

    PubMed Central

    Diamond, I; Messing, R O

    1994-01-01

    Alcoholism, a worldwide disorder, is the cause of a variety of neurologic disorders. In this article we discuss the cellular pathophysiology of ethanol addition and abuse as well as evidence supporting and refuting the role of inheritance in alcoholism. A genetic marker for alcoholism has not been identified, but neurophysiologic studies may be promising. Some neurologic disorders related to longterm alcoholism are due predominantly to inadequate nutrition (the thiamine deficiency that causes Wernicke's encephalopathy), but others appear to involve the neurotoxicity of ethanol on brain (alcohol withdrawal syndrome and dementia) and peripheral nerves (alcoholic neuropathy and myopathy). Images PMID:7975567

  2. 2009 Plant Lipids: Structure, Metabolism & Function Gordon Research Conference - February 1- 6 ,2009

    SciTech Connect

    Kent D. Chapman

    2009-02-06

    The Gordon Research Conference on 'Plant Lipids: Structure, Metabolism and Function' has been instituted to accelerate research productivity in the field of plant lipids. This conference will facilitate wide dissemination of research breakthroughs, support recruitment of young scientists to the field of plant lipid metabolism and encourage broad participation of the plant lipid community in guiding future directions for research in plant lipids. This conference will build upon the strengths of the successful, previous biannual meetings of the National Plant Lipid Cooperative (www.plantlipids.org) that began in 1993, but will reflect a broader scope of topics to include the biochemistry, cell biology, metabolic regulation, and signaling functions of plant acyl lipids. Most importantly, this conference also will serve as a physical focal point for the interaction of the plant lipid research community. Applications to attend this conference will be open to all researchers interested in plant lipids and will provide a venue for the presentation of the latest research results, networking opportunities for young scientists, and a forum for the development and exchange of useful lipid resources and new ideas. By bringing together senior- and junior-level scientists involved in plant lipid metabolism, a broad range of insights will be shared and the community of plant lipid researchers will function more as a network of vested partners. This is important for the vitality of the research community and for the perceived value that will encourage conference attendance into the future.

  3. Fatty Aldehyde and Fatty Alcohol Metabolism: Review and Importance for Epidermal Structure and Function

    PubMed Central

    Rizzo, William B.

    2014-01-01

    Normal fatty aldehyde and alcohol metabolism is essential for epidermal differentiation and function. Long-chain aldehydes are produced by catabolism of several lipids including fatty alcohols, sphingolipids, ether glycerolipids, isoprenoid alcohols and certain aliphatic lipids that undergo α- or ω-oxidation. The fatty aldehyde generated by these pathways is chiefly metabolized to fatty acid by fatty aldehyde dehydrogenase (FALDH, alternately known as ALDH3A2), which also functions to oxidize fatty alcohols as a component of the fatty alcohol:NAD oxidoreductase (FAO) enzyme complex. Genetic deficiency of FALDH/FAO in patients with Sjögren-Larsson syndrome (SLS) results in accumulation of fatty aldehydes, fatty alcohols and related lipids (ether glycerolipids, wax esters) in cultured keratinocytes. These biochemical changes are associated with abnormalities in formation of lamellar bodies in the stratum granulosum and impaired delivery of their precursor membranes to the stratum corneum (SC). The defective extracellular SC membranes are responsible for a leaky epidermal water barrier and ichthyosis. Although lamellar bodies appear to be the pathogenic target for abnormal fatty aldehyde/alcohol metabolism in SLS, the precise biochemical mechanisms are yet to be elucidated. Nevertheless, studies in SLS highlight the critical importance of FALDH and normal fatty aldehyde/alcohol metabolism for epidermal function. PMID:24036493

  4. A coherent neurobiological framework for functional neuroimaging provided by a model integrating compartmentalized energy metabolism.

    PubMed

    Aubert, Agnès; Pellerin, Luc; Magistretti, Pierre J; Costalat, Robert

    2007-03-01

    Functional neuroimaging has undergone spectacular developments in recent years. Paradoxically, its neurobiological bases have remained elusive, resulting in an intense debate around the cellular mechanisms taking place upon activation that could contribute to the signals measured. Taking advantage of a modeling approach, we propose here a coherent neurobiological framework that not only explains several in vitro and in vivo observations but also provides a physiological basis to interpret imaging signals. First, based on a model of compartmentalized energy metabolism, we show that complex kinetics of NADH changes observed in vitro can be accounted for by distinct metabolic responses in two cell populations reminiscent of neurons and astrocytes. Second, extended application of the model to an in vivo situation allowed us to reproduce the evolution of intraparenchymal oxygen levels upon activation as measured experimentally without substantially altering the initial parameter values. Finally, applying the same model to functional neuroimaging in humans, we were able to determine that the early negative component of the blood oxygenation level-dependent response recorded with functional MRI, known as the initial dip, critically depends on the oxidative response of neurons, whereas the late aspects of the signal correspond to a combination of responses from cell types with two distinct metabolic profiles that could be neurons and astrocytes. In summary, our results, obtained with such a modeling approach, support the concept that both neuronal and glial metabolic responses form essential components of neuroimaging signals. PMID:17360498

  5. The Changes of Energy Interactions between Nucleus Function and Mitochondria Functions Causing Transmutation of Chronic Inflammation into Cancer Metabolism.

    PubMed

    Ponizovskiy, Michail R

    2016-01-01

    Interactions between nucleus and mitochondria functions induce the mechanism of maintenance stability of cellular internal energy according to the first law of thermodynamics in able-bodied cells and changes the mechanisms of maintenance stability of cellular internal energy creating a transition stationary state of ablebodied cells into quasi-stationary pathologic states of acute inflammation transiting then into chronic inflammation and then transmuting into cancer metabolism. The mechanisms' influences of intruding etiologic pathologic agents (microbe, virus, etc.) lead to these changes of energy interactions between nucleus and mitochondria functions causing general acute inflammation, then passing into local chronic inflammation, and reversing into cancer metabolism transmutation. Interactions between biochemical processes and biophysical processes of cellular capacitors' operations create a supplementary mechanism of maintenance stability of cellular internal energy in the norm and in pathology. Discussion of some scientific works eliminates doubts of the authors of these works. PMID:27480780

  6. Overexpressing superoxide dismutase 2 induces a supernormal cardiac function by enhancing redox-dependent mitochondrial function and metabolic dilation.

    PubMed

    Kang, Patrick T; Chen, Chwen-Lih; Ohanyan, Vahagn; Luther, Daniel J; Meszaros, J Gary; Chilian, William M; Chen, Yeong-Renn

    2015-11-01

    During heightened cardiac work, O2 consumption by the heart benefits energy production via mitochondria. However, some electrons leak from the respiratory chain and yield superoxide, which is rapidly metabolized into H2O2 by SOD2. To understand the systemic effects of the metabolic dilator, H2O2, we studied mice with cardiac-specific SOD2 overexpression (SOD2-tg), which increases the H2O2 produced by cardiac mitochondria. Contrast echocardiography was employed to evaluate cardiac function, indicating that SOD2-tg had a significantly greater ejection fraction and a lower mean arterial pressure (MAP) that was partially normalized by intravenous injection of catalase. Norepinephrine-mediated myocardial blood flow (MBF) was significantly enhanced in SOD2-tg mice. Coupling of MBF to the double product (Heart Rate×MAP) was increased in SOD2-tg mice, indicating that the metabolic dilator, "spilled" over, inducing systemic vasodilation. The hypothesis that SOD2 overexpression effectively enhances mitochondrial function was further evaluated. Mitochondria of SOD2-tg mice had a decreased state 3 oxygen consumption rate, but maintained the same ATP production flux under the basal and L-NAME treatment conditions, indicating a higher bioenergetic efficiency. SOD2-tg mitochondria produced less superoxide, and had lower redox activity in converting cyclic hydroxylamine to stable nitroxide, and a lower GSSG concentration. EPR analysis of the isolated mitochondria showed a significant decrease in semiquinones at the SOD2-tg Qi site. These results support a more reductive physiological setting in the SOD2-tg murine heart. Cardiac mitochondria exhibited no significant differences in the respiratory control index between WT and SOD2-tg. We conclude that SOD2 overexpression in myocytes enhances mitochondrial function and metabolic vasodilation, leading to a phenotype of supernormal cardiac function.

  7. mTOR, metabolism, and the regulation of T-cell differentiation and function

    PubMed Central

    Waickman, Adam T; Powell, Jonathan D.

    2012-01-01

    Summary Upon antigen recognition, naive T cells undergo rapid expansion and activation. The energy requirements for this expansion are formidable, and T-cell activation is accompanied by dramatic changes in cellular metabolism. Furthermore, the outcome of antigen engagement is guided by multiple cues derived from the immune microenvironment. Mammalian target of rapamycin (mTOR) is emerging as a central integrator of these signals playing a critical role in driving T-cell differentiation and function. Indeed, multiple metabolic programs are controlled by mTOR signaling. In this review, we discuss the role of mTOR in regulating metabolism and how these pathways intersect with the ability of mTOR to integrate cues that guide the outcome of T-cell receptor engagement. PMID:22889214

  8. Metabolomic strategies for the identification of new enzyme functions and metabolic pathways

    PubMed Central

    Prosser, Gareth A; Larrouy-Maumus, Gerald; de Carvalho, Luiz Pedro S

    2014-01-01

    Recent technological advances in accurate mass spectrometry and data analysis have revolutionized metabolomics experimentation. Activity-based and global metabolomic profiling methods allow simultaneous and rapid screening of hundreds of metabolites from a variety of chemical classes, making them useful tools for the discovery of novel enzymatic activities and metabolic pathways. By using the metabolome of the relevant organism or close species, these methods capitalize on biological relevance, avoiding the assignment of artificial and non-physiological functions. This review discusses state-of-the-art metabolomic approaches and highlights recent examples of their use for enzyme annotation, discovery of new metabolic pathways, and gene assignment of orphan metabolic activities across diverse biological sources. PMID:24829223

  9. Mitochondrial function, zinc, and intermediary metabolism relationships in normal prostate and prostate cancer.

    PubMed

    Costello, L C; Franklin, R B; Feng, Pei

    2005-06-01

    Human prostate secretory epithelial cells have the uniquely specialized function of accumulating and secreting extremely high levels of citrate. This is achieved by their ability to accumulate high cellular levels of zinc that inhibit citrate oxidation. This process of net citrate production requires unique metabolic/bioenergetic mitochondrial relationships. In prostate cancer, the malignant cells undergo a metabolic transformation from zinc-accumulating citrate-producing sane cells to citrate-oxidizing malignant cells that lost the ability to accumulate zinc. This review describes the metabolic/bioenergetic, zinc and mitochondrial relationships involved in normal and malignant prostate. Hopefully, this report will generate much needed interest and research in this neglected, but critically important, area of investigation. PMID:16050980

  10. Metabolomic strategies for the identification of new enzyme functions and metabolic pathways.

    PubMed

    Prosser, Gareth A; Larrouy-Maumus, Gerald; de Carvalho, Luiz Pedro S

    2014-06-01

    Recent technological advances in accurate mass spectrometry and data analysis have revolutionized metabolomics experimentation. Activity-based and global metabolomic profiling methods allow simultaneous and rapid screening of hundreds of metabolites from a variety of chemical classes, making them useful tools for the discovery of novel enzymatic activities and metabolic pathways. By using the metabolome of the relevant organism or close species, these methods capitalize on biological relevance, avoiding the assignment of artificial and non-physiological functions. This review discusses state-of-the-art metabolomic approaches and highlights recent examples of their use for enzyme annotation, discovery of new metabolic pathways, and gene assignment of orphan metabolic activities across diverse biological sources.

  11. Autophagy enforces functional integrity of regulatory T cells by coupling environmental cues and metabolic homeostasis

    PubMed Central

    Wei, Jun; Long, Lingyun; Yang, Kai; Guy, Cliff; Shrestha, Sharad; Chen, Zuojia; Wu, Chuan; Vogel, Peter; Neale, Geoffrey; Green, Douglas R; Chi, Hongbo

    2015-01-01

    Regulatory T (Treg) cells respond to immune and inflammatory signals to mediate immunosuppression, but how functional integrity of Treg cells is maintained under activating environments remains elusive. Here we found that autophagy was active in Treg cells and supported their lineage stability and survival fitness. Treg cell-specific deletion of the essential autophagy gene Atg7 or Atg5 led to loss of Treg cells, increased tumor resistance, and development of inflammatory disorders. Atg7-deficient Treg cells had increased apoptosis and readily lost Foxp3 expression, especially after activation. Mechanistically, autophagy deficiency upregulated mTORC1 and c-Myc function and glycolytic metabolism that contributed to defective Treg function. Therefore, autophagy couples environmental signals and metabolic homeostasis to protect lineage and survival integrity of Treg cells in activating contexts. PMID:26808230

  12. Liver transplantation in neurological Wilson's Disease: is there indication? A case report.

    PubMed

    Mocchegiani, F; Gemini, S; Vincenzi, P; Montalti, R; Vecchi, A; Nicolini, D; Federici, A; Coletta, M; Pansini, M; Lanari, J; Svegliati Baroni, G; Risaliti, A; Vivarelli, M

    2014-09-01

    Wilson's disease (WD) is an autosomal recessive disorder characterized by copper overload. In this disease, inadequate hepatic excretion leads to copper accumulation in the liver, brain, kidney, and cornea. Severe neurological symptoms can develop in patients with WD, often in the absence of relevant liver damage: it is unclear whether liver transplantation (LT) could reverse neurological symptoms, and at present LT is not recommended in this setting. We report a case of regression of neurological symptoms in a patient affected by WD with prevalent neurological involvement. A 19-year-old man with disabling neuropsychiatric symptoms from WD that included frontal ataxia, akinesia, dystonia, tremors, and behavioral disorders in the presence of preserved liver function (Model for End-Stage Liver Disease score=7; Child-Turcotte-Pugh score=A5) underwent LT in November 2009. At the time of LT, encephalic magnetic resonance imaging (MRI) indicated diffuse neurodegenerative alterations involving subtentorial and supratentorial structures; bilateral Kayser-Fleischer ring was present. Four years after LT, laboratory tests show normalized copper metabolism and excellent liver function test results. Encephalic MRI shows a substantial improvement of already-known signal alterations at nuclei thalamus and putamen, mesencephalon, and pons. Kayser-Fleischer ring disappeared from the right eye, but a little remnant is still visible in the left eye. At neurological examination, all of the previous symptoms and signs are no longer present and behavioral disorders are no longer present; psychosocial functions are completely restored. The present case provides some evidence that LT may be a valid therapeutic option for WD patients with marked neurological impairment, particularly in those no longer responsive to chelation therapy.

  13. Bridging Between Proline Structure, Functions, Metabolism, and Involvement in Organism Physiology.

    PubMed

    Saibi, Walid; Feki, Kaouthar; Yacoubi, Ines; Brini, Faiçal

    2015-08-01

    Much is now known about proline multifunctionality and metabolism; some aspects of its biological functions are still unclear. Here, we discuss some cases in the proline, structure, definition, metabolism, compartmentalization, accumulation, plausible functions and also its implication in homeostasis and organism physiology. Indeed, we report the role of proline in cellular homeostasis, including redox balance and energy status and their implication as biocatalyst for aldolase activity. Proline can act as a signaling molecule to modulate mitochondrial functions, influence cell proliferation or cell death, and trigger specific gene expression, which can be essential for plant recovery from stresses. Although, the regulation and the function of proline accumulation, during abiotic stresses, are not yet completely understood. The engineering of proline metabolism could lead to new opportunities to improve plant tolerance against environmental stresses. This atypical amino acid has a potential role in the toxicity during growth of some microorganism, vegetal, and mammalian species. Furthermore, we note that the purpose through the work is to provide a rich, concise, and mostly cohesive source on proline, considered as a platform and an anchor between several disciplines and biological functions.

  14. Proposed physiologic functions of boron in plants pertinent to animal and human metabolism.

    PubMed Central

    Blevins, D G; Lukaszewski, K M

    1994-01-01

    Boron has been recognized since 1923 as an essential micronutrient element for higher plants. Over the years, many roles for boron in plants have been proposed, including functions in sugar transport, cell wall synthesis and lignification, cell wall structure, carbohydrate metabolism, RNA metabolism, respiration, indole acetic acid metabolism, phenol metabolism and membrane transport. However, the mechanism of boron involvement in each case remains unclear. Recent work has focused on two major plant-cell components: cell walls and membranes. In both, boron could play a structural role by bridging hydroxyl groups. In membranes, it could also be involved in ion transport and redox reactions by stimulating enzymes like nicotinamide adenine dinucleotide and reduced (NADH) oxidase. There is a very narrow window between the levels of boron required by and toxic to plants. The mechanisms of boron toxicity are also unknown. In nitrogen-fixing leguminous plants, foliarly applied boron causes up to a 1000% increase in the concentration of allantoic acid in leaves. In vitro studies show that boron inhibits the manganese-dependent allantoate amidohydrolase, and foliar application of manganese prior to application of boron eliminates allantoic acid accumulation in leaves. Interaction between borate and divalent cations like manganese may alter metabolic pathways, which could explain why higher concentrations of boron can be toxic to plants. PMID:7889877

  15. The function of the aerenchyma in arborescent lycopsids: evidence of an unfamiliar metabolic strategy.

    PubMed

    Green, W A

    2010-08-01

    Most species of the modern family Isoëtaceae (Quillworts) some other modern hydrophytes, use a metabolic pathway for carbon fixation that involves uptake of sedimentary carbon and enrichment of CO(2) in internal gas spaces as a carbon-concentrating mechanism. This metabolism, which is related to 'aquatic CAM', is characterized by morphological, physiological and biochemical adaptations for decreasing photorespirative loss, aerating roots and maintaining high growth rates in anoxic, oligotrophic, stressed environments. Some of the closest relatives of the Isoëtaceae were the 'arborescent lycopsids', which were among the dominant taxa in the coal swamps found in lowland ecosystems during the Carboniferous and Permian periods (approx. 300 Ma). Morphological, ecological and geochemical evidence supports the hypothesis that the arborescent lycopsids had an unusual metabolism similar to that of modern Isoëtaceae and processed a biogeochemically significant proportion of organically fixed carbon over a period of about 100 million years in the late Palaeozoic. The temporal coincidence between the dominance of plants with this metabolism and an anomalous global atmosphere (high O(2); low CO(2)) supports the idea that biosphere feedbacks are important in regulating global climatic homeostasis. The potential influence of this metabolism on the global carbon cycle and its specific adaptive function suggest that it should perhaps be considered a fourth major photosynthetic pathway.

  16. Discrete Functions of Nuclear Receptor Rev-erbα Couple Metabolism to the Clock

    PubMed Central

    Zhang, Yuxiang; Fang, Bin; Emmett, Matthew J.; Damle, Manashree; Sun, Zheng; Feng, Dan; Armour, Sean M.; Remsberg, Jarrett R.; Jager, Jennifer; Soccio, Raymond E.; Steger, David J.; Lazar, Mitchell A.

    2015-01-01

    SUMMARY Circadian and metabolic physiology are intricately intertwined, as illustrated by Rev-erbα, a transcription factor (TF) that functions both as a core repressive component of the cell autonomous clock and as a regulator of metabolic genes. Here we show that Rev-erbα modulates the clock and metabolism by different genomic mechanisms. Clock control requires Rev-erbα to bind directly to the genome at its cognate sites, where it competes with activating ROR TFs. By contrast, Rev-erbα regulates metabolic genes primarily by recruiting the HDAC3 corepressor to sites to which it is tethered by cell type-specific transcription factors. Thus, direct competition between Rev-erbα and ROR TFs provides a universal mechanism for self-sustained control of molecular clock across all tissues, whereas Rev-erbα utilizes lineage-determining factors to convey a tissue-specific epigenomic rhythm that regulates metabolism tailored to the specific need of that tissue. PMID:26044300

  17. PPARs, Cardiovascular Metabolism, and Function: Near- or Far-from-Equilibrium Pathways

    PubMed Central

    Lecarpentier, Yves; Claes, Victor; Hébert, Jean-Louis

    2010-01-01

    Peroxisome proliferator-activated receptors (PPAR α, β/δ and γ) play a key role in metabolic regulatory processes and gene regulation of cellular metabolism, particularly in the cardiovascular system. Moreover, PPARs have various extra metabolic roles, in circadian rhythms, inflammation and oxidative stress. In this review, we focus mainly on the effects of PPARs on some thermodynamic processes, which can behave either near equilibrium, or far-from-equilibrium. New functions of PPARs are reported in the arrhythmogenic right ventricular cardiomyopathy, a human genetic heart disease. It is now possible to link the genetic desmosomal abnormalitiy to the presence of fat in the right ventricle, partly due to an overexpression of PPARγ. Moreover, PPARs are directly or indirectly involved in cellular oscillatory processes such as the Wnt-b-catenin pathway, circadian rhythms of arterial blood pressure and cardiac frequency and glycolysis metabolic pathway. Dysfunction of clock genes and PPARγ may lead to hyperphagia, obesity, metabolic syndrome, myocardial infarction and sudden cardiac death, In pathological conditions, regulatory processes of the cardiovascular system may bifurcate towards new states, such as those encountered in hypertension, type 2 diabetes, and heart failure. Numerous of these oscillatory mechanisms, organized in time and space, behave far from equilibrium and are “dissipative structures”. PMID:20706650

  18. Functional Metabolic Map of Faecalibacterium prausnitzii, a Beneficial Human Gut Microbe

    PubMed Central

    Heinken, Almut; Khan, M. Tanweer; Paglia, Giuseppe; Rodionov, Dmitry A.; Harmsen, Hermie J. M.

    2014-01-01

    The human gut microbiota plays a central role in human well-being and disease. In this study, we present an integrated, iterative approach of computational modeling, in vitro experiments, metabolomics, and genomic analysis to accelerate the identification of metabolic capabilities for poorly characterized (anaerobic) microorganisms. We demonstrate this approach for the beneficial human gut microbe Faecalibacterium prausnitzii strain A2-165. We generated an automated draft reconstruction, which we curated against the limited biochemical data. This reconstruction modeling was used to develop in silico and in vitro a chemically defined medium (CDM), which was validated experimentally. Subsequent metabolomic analysis of the spent medium for growth on CDM was performed. We refined our metabolic reconstruction according to in vitro observed metabolite consumption and secretion and propose improvements to the current genome annotation of F. prausnitzii A2-165. We then used the reconstruction to systematically characterize its metabolic properties. Novel carbon source utilization capabilities and inabilities were predicted based on metabolic modeling and validated experimentally. This study resulted in a functional metabolic map of F. prausnitzii, which is available for further applications. The presented workflow can be readily extended to other poorly characterized and uncharacterized organisms to yield novel biochemical insights about the target organism. PMID:25002542

  19. The function of the aerenchyma in arborescent lycopsids: evidence of an unfamiliar metabolic strategy.

    PubMed

    Green, W A

    2010-08-01

    Most species of the modern family Isoëtaceae (Quillworts) some other modern hydrophytes, use a metabolic pathway for carbon fixation that involves uptake of sedimentary carbon and enrichment of CO(2) in internal gas spaces as a carbon-concentrating mechanism. This metabolism, which is related to 'aquatic CAM', is characterized by morphological, physiological and biochemical adaptations for decreasing photorespirative loss, aerating roots and maintaining high growth rates in anoxic, oligotrophic, stressed environments. Some of the closest relatives of the Isoëtaceae were the 'arborescent lycopsids', which were among the dominant taxa in the coal swamps found in lowland ecosystems during the Carboniferous and Permian periods (approx. 300 Ma). Morphological, ecological and geochemical evidence supports the hypothesis that the arborescent lycopsids had an unusual metabolism similar to that of modern Isoëtaceae and processed a biogeochemically significant proportion of organically fixed carbon over a period of about 100 million years in the late Palaeozoic. The temporal coincidence between the dominance of plants with this metabolism and an anomalous global atmosphere (high O(2); low CO(2)) supports the idea that biosphere feedbacks are important in regulating global climatic homeostasis. The potential influence of this metabolism on the global carbon cycle and its specific adaptive function suggest that it should perhaps be considered a fourth major photosynthetic pathway. PMID:20356894

  20. Functional metabolic map of Faecalibacterium prausnitzii, a beneficial human gut microbe.

    PubMed

    Heinken, Almut; Khan, M Tanweer; Paglia, Giuseppe; Rodionov, Dmitry A; Harmsen, Hermie J M; Thiele, Ines

    2014-09-01

    The human gut microbiota plays a central role in human well-being and disease. In this study, we present an integrated, iterative approach of computational modeling, in vitro experiments, metabolomics, and genomic analysis to accelerate the identification of metabolic capabilities for poorly characterized (anaerobic) microorganisms. We demonstrate this approach for the beneficial human gut microbe Faecalibacterium prausnitzii strain A2-165. We generated an automated draft reconstruction, which we curated against the limited biochemical data. This reconstruction modeling was used to develop in silico and in vitro a chemically defined medium (CDM), which was validated experimentally. Subsequent metabolomic analysis of the spent medium for growth on CDM was performed. We refined our metabolic reconstruction according to in vitro observed metabolite consumption and secretion and propose improvements to the current genome annotation of F. prausnitzii A2-165. We then used the reconstruction to systematically characterize its metabolic properties. Novel carbon source utilization capabilities and inabilities were predicted based on metabolic modeling and validated experimentally. This study resulted in a functional metabolic map of F. prausnitzii, which is available for further applications. The presented workflow can be readily extended to other poorly characterized and uncharacterized organisms to yield novel biochemical insights about the target organism.

  1. Infant neurologic assessment.

    PubMed

    Hobdell, E

    2001-08-01

    Infant neurologic assessment reflects the ongoing maturation of the central nervous system. Traditional approaches to assessment cannot be used. Key factors are accurate observation and flexibility in obtaining the data. A case example using a 4-month-old infant illustrates specific approaches to assessment. PMID:11497071

  2. Self-healing of optical functions by molecular metabolism in a swollen elastomer

    NASA Astrophysics Data System (ADS)

    Saito, Mitsunori; Nishimura, Tatsuya; Sakiyama, Kohei; Inagaki, Sota

    2012-12-01

    Optical functions of organic dyes, e.g., fluorescence or photochromism, tend to degrade by light irradiation, which causes a short lifetime of photonic devices. Self-healing of optical functions is attainable by metabolizing bleached molecules with nonirradiated ones. A polydimethylsiloxane elastomer provides a useful matrix for dye molecules, since its flexible structure with nano-sized intermolecular spaces allows dye diffusion from a reservoir to an operation region. Swelling the elastomer with a suitable solvent promotes both dissolution and diffusion of dye molecules. This self-healing function was demonstrated by an experiment in which a photochromic elastomer exhibited improved durability against a repeated coloring-decoloring process.

  3. [Certification for specialists on neurology by Japanese Society of Neurology].

    PubMed

    Suzuki, Norihiro

    2009-11-01

    In accordance with recent ever increasing numbers in elder population in Japan, number of patients of age-related neurological diseases such as stroke, dementia and neurodegenerative diseases, etc., also remarkably increasing. Naturally, social needs for medical intervention in neurological fields inevitably become indispensable. The role of the neurologists, especially specialists of neurology, must be substantially important in the near future. The Japanese Society of Neurology has already launched the system for quality-certified specialists for neurology in 1970's. The aim of the system to educate and certify specialists for neurology has been announced as follows; the specialist of neurology must widely experienced and practiced in clinical fields, and must properly diagnose and judge the neurological illness even they are so complicate and difficult to manage (Rinsho Shinkeigaku (Clinical Neurology) 38 (6): 593-619, 1998). However, in future, the specialists for neurology must cultivate and keep the minds of "Professionalism" of physicians as well as their skills for clinical neurology. The Professionalism consists of altruism, accountability, excellence, duty, honor and integrity, respect and a personal commitment to life-long learning (ABIM: American Board of Internal Medicine, Project Professionalism, 1990-). The specialists of neurology with recent privilege in clinical insurance system for their special ability and techniques for neurological examination, should not only share their clinical specialty but also provide their opinion based upon Professionalism to all over the world. PMID:20030199

  4. Leptin's metabolic and immune functions can be uncoupled at the ligand/receptor interaction level.

    PubMed

    Zabeau, Lennart; Jensen, Cathy J; Seeuws, Sylvie; Venken, Koen; Verhee, Annick; Catteeuw, Dominiek; van Loo, Geert; Chen, Hui; Walder, Ken; Hollis, Jacob; Foote, Simon; Morris, Margaret J; Van der Heyden, José; Peelman, Frank; Oldfield, Brian J; Rubio, Justin P; Elewaut, Dirk; Tavernier, Jan

    2015-02-01

    The adipocyte-derived cytokine leptin acts as a metabolic switch, connecting the body's metabolism to high-energy consuming processes such as reproduction and immune responses. We here provide genetic and biochemical evidence that the metabolic and immune functions of leptin can be uncoupled at the receptor level. First, homozygous mutant fatt/fatt mice carry a spontaneous splice mutation causing deletion of the leptin receptor (LR) immunoglobulin-like domain (IGD) in all LR isoforms. These mice are hyperphagic and morbidly obese, but display only minimal changes in size and cellularity of the thymus, and cellular immune responses are unaffected. These animals also displayed liver damage in response to concavalin A comparable to wild-type and heterozygous littermates. Second, treatment of healthy mice with a neutralizing nanobody targeting IGD induced weight gain and hyperinsulinaemia, but completely failed to block development of experimentally induced autoimmune diseases. These data indicate that leptin receptor deficiency or antagonism profoundly affects metabolism, with little concomitant effects on immune functions. PMID:25098352

  5. Functional consequences of perturbing polyamine metabolism in the malaria parasite, Plasmodium falciparum.

    PubMed

    Clark, K; Niemand, J; Reeksting, S; Smit, S; van Brummelen, A C; Williams, M; Louw, A I; Birkholtz, L

    2010-02-01

    Inhibition of polyamine biosynthesis and/or the perturbation of polyamine functionality have been exploited with success against parasitic diseases such as Trypanosoma infections. However, when the classical polyamine biosynthesis inhibitor, alpha-difluoromethylornithine, is used against the human malaria parasite, Plasmodium falciparum, it results in only a cytostatic growth arrest. Polyamine metabolism in this parasite has unique properties not shared by any other organism. These include the bifunctional arrangement of the catalytic decarboxylases and an apparent absence of the typical polyamine interconversion pathways implying different mechanisms for the regulation of polyamine homeostasis that includes the uptake of exogenous polyamines at least in vitro. These properties make polyamine metabolism an enticing drug target in P. falciparum provided that the physiological and functional consequences of polyamine metabolism perturbation are understood. This review highlights our current understanding of the biological consequences of inhibition of the biosynthetic enzymes in the polyamine pathway in P. falciparum as revealed by several global analytical approaches. Ultimately, the evidence suggests that polyamine metabolism in P. falciparum is a validated drug target worth exploiting. PMID:19997948

  6. Microbial structures, functions, and metabolic pathways in wastewater treatment bioreactors revealed using high-throughput sequencing.

    PubMed

    Ye, Lin; Zhang, Tong; Wang, Taitao; Fang, Zhiwei

    2012-12-18

    The objective of this study was to explore microbial community structures, functional profiles, and metabolic pathways in a lab-scale and a full-scale wastewater treatment bioreactors. In order to do this, over 12 gigabases of metagenomic sequence data and 600,000 paired-end sequences of bacterial 16S rRNA gene were generated with the Illumina HiSeq 2000 platform, using DNA extracted from activated sludge in the two bioreactors. Three kinds of sequences (16S rRNA gene amplicons, 16S rRNA gene sequences obtained from metagenomic sequencing, and predicted proteins) were used to conduct taxonomic assignments. Specially, relative abundances of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) were analyzed. Compared with quantitative real-time PCR (qPCR), metagenomic sequencing was demonstrated to be a better approach to quantify AOA and AOB in activated sludge samples. It was found that AOB were more abundant than AOA in both reactors. Furthermore, the analysis of the metabolic profiles indicated that the overall patterns of metabolic pathways in the two reactors were quite similar (73.3% of functions shared). However, for some pathways (such as carbohydrate metabolism and membrane transport), the two reactors differed in the number of pathway-specific genes.

  7. Microbial structures, functions, and metabolic pathways in wastewater treatment bioreactors revealed using high-throughput sequencing.

    PubMed

    Ye, Lin; Zhang, Tong; Wang, Taitao; Fang, Zhiwei

    2012-12-18

    The objective of this study was to explore microbial community structures, functional profiles, and metabolic pathways in a lab-scale and a full-scale wastewater treatment bioreactors. In order to do this, over 12 gigabases of metagenomic sequence data and 600,000 paired-end sequences of bacterial 16S rRNA gene were generated with the Illumina HiSeq 2000 platform, using DNA extracted from activated sludge in the two bioreactors. Three kinds of sequences (16S rRNA gene amplicons, 16S rRNA gene sequences obtained from metagenomic sequencing, and predicted proteins) were used to conduct taxonomic assignments. Specially, relative abundances of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) were analyzed. Compared with quantitative real-time PCR (qPCR), metagenomic sequencing was demonstrated to be a better approach to quantify AOA and AOB in activated sludge samples. It was found that AOB were more abundant than AOA in both reactors. Furthermore, the analysis of the metabolic profiles indicated that the overall patterns of metabolic pathways in the two reactors were quite similar (73.3% of functions shared). However, for some pathways (such as carbohydrate metabolism and membrane transport), the two reactors differed in the number of pathway-specific genes. PMID:23151157

  8. Respiratory, metabolic and cardiac functions are altered by disinhibition of subregions of the medial prefrontal cortex

    PubMed Central

    Hassan, Sarah F; Cornish, Jennifer L; Goodchild, Ann K

    2013-01-01

    The prefrontal cortex (PFC) is referred to as the visceral motor cortex; however, little is known about whether this region influences respiratory or metabolic outflows. The aim of this study was to describe simultaneous changes in respiratory, metabolic and cardiovascular functions evoked by disinhibition of the medial PFC (mPFC) and adjacent lateral septal nucleus (LSN). In urethane-anaesthetized rats, bicuculline methiodide was microinjected (2 mm; GABA-A receptor antagonist) into 90 sites in the mPFC at 0.72–4.00 mm from bregma. Phrenic nerve amplitude and frequency, arterial pressure, heart rate, splanchnic and lumbar sympathetic nerve activities (SNA), expired CO2, and core and brown adipose tissue temperatures were measured. Novel findings included disturbances to respiratory rhythm evoked from all subregions of the mPFC. Injections into the cingulate cortex evoked reductions in central respiratory function exclusively, whereas in ventral sites, particularly the infralimbic region, increases in respiratory drive and frequency, and metabolic and cardiac outflows were evoked. Disinhibition of sites in surrounding regions revealed that the LSN could evoke cardiovascular changes accompanied by distinct oscillations in SNA, as well as increases in respiratory amplitude. We show that activation of neurons within the mPFC and LSN influence respiratory, metabolic and cardiac outflows in a site-dependent manner. This study has implications with respect to the altered PFC neuronal activity seen in stress-related and mental health disorders, and suggests how basic physiological systems may be affected. PMID:24042503

  9. Relationships between brain metabolism decrease in normal aging and changes in structural and functional connectivity.

    PubMed

    Chételat, Gaël; Landeau, Brigitte; Salmon, Eric; Yakushev, Igor; Bahri, Mohamed Ali; Mézenge, Florence; Perrotin, Audrey; Bastin, Christine; Manrique, Alain; Scheurich, Armin; Scheckenberger, Mathias; Desgranges, Béatrice; Eustache, Francis; Fellgiebel, Andreas

    2013-08-01

    Normal aging is characterized by brain glucose metabolism decline predominantly in the prefrontal cortex. The goal of the present study was to assess whether this change was associated with age-related alteration of white matter (WM) structural integrity and/or functional connectivity. FDG-PET data from 40 young and 57 elderly healthy participants from two research centers (n=49/48 in Center 1/2) were analyzed. WM volume from T1-weighted MRI (Center 1), fractional anisotropy from diffusion-tensor imaging (Center 2), and resting-state fMRI data (Center 1) were also obtained. Group comparisons were performed within each imaging modality. Then, positive correlations were assessed, within the elderly, between metabolism in the most affected region and the other neuroimaging modalities. Metabolism decline in the elderly predominated in the left inferior frontal junction (LIFJ). LIFJ hypometabolism was significantly associated with macrostructural and microstructural WM disturbances in long association fronto-temporo-occipital fibers, while no relationship was found with functional connectivity. The findings offer new perspectives to understand normal aging processes and open avenues for future studies to explore causality between age-related metabolism and connectivity changes. PMID:23518010

  10. The effect of metal oxide nanoparticles on functional bacteria and metabolic profiles in agricultural soil.

    PubMed

    Chai, Hankui; Yao, Jun; Sun, Jingjing; Zhang, Chi; Liu, Wenjuan; Zhu, Mijia; Ceccanti, Brunello

    2015-04-01

    A significant knowledge gap in nanotechnology is the absence of standardized protocols for examining the effect of engineered nanoparticles on soil microorganisms. In this study, agricultural soil was exposed to ZnO, SiO2, TiO2 and CeO2 nanoparticles at 1 mg g(-1). The toxicity effect was evaluated by thermal metabolism, the abundance of functional bacteria and enzymatic activity. ZnO and CeO2 nanoparticles were observed to hinder thermogenic metabolism, reduce numbers of soil Azotobacter, P-solubilizing and K-solubilizing bacteria and inhibit enzymatic activities. TiO2 nanoparticles reduced the abundance of functional bacteria and enzymatic activity. SiO2 nanoparticles slightly boosted the soil microbial activity. Pearson's correlation analysis showed that thermodynamic parameters had a strong correlation with abundance of functional bacteria and enzymatic activity. These findings demonstrated that the combined approach of monitoring thermal metabolism, functional bacteria and enzymatic activity is feasible for testing the ecotoxicity of nanoparticles on agricultural soil.

  11. Astrocytes: The missing link in neurological disease?

    PubMed Central

    Lin, Chia-Ching John; Deneen, Benjamin

    2013-01-01

    The central nervous system (CNS) is comprised of numerous cell types that work in concert to facilitate proper function and homeostasis. Disruption of these carefully orchestrated networks results in neuronal dysfunction, manifesting itself in a variety of neurological disorders. While neuronal dysregulation is causative of symptoms manifest in the clinic, the etiology of these disorders is often more complex than simply a loss of neurons or intrinsic dysregulation of their function. In the adult brain, astrocytes comprise the most abundant cell type and play key roles in CNS physiology, therefore it stands to reason that dysregulation of normal astrocyte function contributes to the etiology and progression of varied neurological disorders. We review here some neurological disorders associated with an astrocyte factor and discuss how the related astrocyte dysfunction contributes to the etiology and/or progression of these disorders. PMID:24365571

  12. Diet and Gut Microbial Function in Metabolic and Cardiovascular Disease Risk.

    PubMed

    Meyer, Katie A; Bennett, Brian J

    2016-10-01

    Over the past decade, the gut microbiome has emerged as a novel and largely unexplored source of variability for metabolic and cardiovascular disease risk, including diabetes. Animal and human studies support several possible pathways through which the gut microbiome may impact health, including the production of health-related metabolites from dietary sources. Diet is considered important to shaping the gut microbiota; in addition, gut microbiota influence the metabolism of many dietary components. In the present paper, we address the distinction between compositional and functional analysis of the gut microbiota. We focus on literature that highlights the value of moving beyond surveys of microbial composition to measuring gut microbial functioning to delineate mechanisms related to the interplay between diet and gut microbiota in cardiometabolic health. PMID:27541295

  13. Dynamics of Panax ginseng Rhizospheric Soil Microbial Community and Their Metabolic Function

    PubMed Central

    Li, Yong; Ying, YiXin; Ding, WanLong

    2014-01-01

    The bacterial communities of 1- to 6-year ginseng rhizosphere soils were characterized by culture-independent approaches, random amplified polymorphic DNA (RAPD), and amplified ribosomal DNA restriction analysis (ARDRA). Culture-dependent method (Biolog) was used to investigate the metabolic function variance of microbe living in rhizosphere soil. Results showed that significant genetic and metabolic function variance were detected among soils, and, with the increasing of cultivating years, genetic diversity of bacterial communities in ginseng rhizosphere soil tended to be decreased. Also we found that Verrucomicrobia, Acidobacteria, and Proteobacteria were the dominants in rhizosphere soils, but, with the increasing of cultivating years, plant disease prevention or plant growth promoting bacteria, such as Pseudomonas, Burkholderia, and Bacillus, tended to be rare. PMID:25214872

  14. Dynamics of Panax ginseng Rhizospheric Soil Microbial Community and Their Metabolic Function.

    PubMed

    Li, Yong; Ying, YiXin; Ding, WanLong

    2014-01-01

    The bacterial communities of 1- to 6-year ginseng rhizosphere soils were characterized by culture-independent approaches, random amplified polymorphic DNA (RAPD), and amplified ribosomal DNA restriction analysis (ARDRA). Culture-dependent method (Biolog) was used to investigate the metabolic function variance of microbe living in rhizosphere soil. Results showed that significant genetic and metabolic function variance were detected among soils, and, with the increasing of cultivating years, genetic diversity of bacterial communities in ginseng rhizosphere soil tended to be decreased. Also we found that Verrucomicrobia, Acidobacteria, and Proteobacteria were the dominants in rhizosphere soils, but, with the increasing of cultivating years, plant disease prevention or plant growth promoting bacteria, such as Pseudomonas, Burkholderia, and Bacillus, tended to be rare.

  15. Metabolic activity and functional diversity changes in sediment prokaryotic communities organically enriched with mussel biodeposits.

    PubMed

    Pollet, Thomas; Cloutier, Olivier; Nozais, Christian; McKindsey, Christopher W; Archambault, Philippe

    2015-01-01

    This experimental microcosm study reports the influence of organic enrichments by mussel biodeposits on the metabolic activity and functional diversity of benthic prokaryotic communities. The different biodeposit enrichment regimes created, which mimicked the quantity of faeces and pseudo-faeces potentially deposited below mussel farms, show a clear stimulatory effect of this organic enrichment on prokaryotic metabolic activity. This effect was detected once a certain level of biodeposition was attained with a tipping point estimated between 3.25 and 10 g day-1 m-2. Prokaryotic communities recovered their initial metabolic activity by 11 days after the cessation of biodeposit additions. However, their functional diversity remained greater than prior to the disturbance suggesting that mussel biodeposit enrichment may disturb the functioning and perhaps the role of prokaryotic communities in benthic ecosystems. This manipulative approach provided new information on the influence of mussel biodeposition on benthic prokaryotic communities and dose-response relationships and may support the development of carrying capacity models for bivalve culture.

  16. Functional Analysis of Free Fatty Acid Receptor GPR120 in Human Eosinophils: Implications in Metabolic Homeostasis

    PubMed Central

    Konno, Yasunori; Ueki, Shigeharu; Takeda, Masahide; Kobayashi, Yoshiki; Tamaki, Mami; Moritoki, Yuki; Oyamada, Hajime; Itoga, Masamichi; Kayaba, Hiroyuki; Omokawa, Ayumi; Hirokawa, Makoto

    2015-01-01

    Recent evidence has shown that eosinophils play an important role in metabolic homeostasis through Th2 cytokine production. GPR120 (FFA4) is a G protein-coupled receptor (GPCR) for long-chain fatty acids that functions as a regulator of physiological energy metabolism. In the present study, we aimed to investigate whether human eosinophils express GPR120 and, if present, whether it possesses a functional capacity on eosinophils. Eosinophils isolated from peripheral venous blood expressed GPR120 at both the mRNA and protein levels. Stimulation with a synthetic GPR120 agonist, GW9508, induced rapid down-regulation of cell surface expression of GPR120, suggesting ligand-dependent receptor internalization. Although GPR120 activation did not induce eosinophil chemotactic response and degranulation, we found that GW9508 inhibited eosinophil spontaneous apoptosis and Fas receptor expression. The anti-apoptotic effect was attenuated by phosphoinositide 3-kinase (PI3K) inhibitors and was associated with inhibition of caspase-3 activity. Eosinophil response investigated using ELISpot assay indicated that stimulation with a GPR120 agonist induced IL-4 secretion. These findings demonstrate the novel functional properties of fatty acid sensor GPR120 on human eosinophils and indicate the previously unrecognized link between nutrient metabolism and the immune system. PMID:25790291

  17. Metabolic Activity and Functional Diversity Changes in Sediment Prokaryotic Communities Organically Enriched with Mussel Biodeposits

    PubMed Central

    Pollet, Thomas; Cloutier, Olivier; Nozais, Christian; McKindsey, Christopher W.; Archambault, Philippe

    2015-01-01

    This experimental microcosm study reports the influence of organic enrichments by mussel biodeposits on the metabolic activity and functional diversity of benthic prokaryotic communities. The different biodeposit enrichment regimes created, which mimicked the quantity of faeces and pseudo-faeces potentially deposited below mussel farms, show a clear stimulatory effect of this organic enrichment on prokaryotic metabolic activity. This effect was detected once a certain level of biodeposition was attained with a tipping point estimated between 3.25 and 10 g day-1 m-2. Prokaryotic communities recovered their initial metabolic activity by 11 days after the cessation of biodeposit additions. However, their functional diversity remained greater than prior to the disturbance suggesting that mussel biodeposit enrichment may disturb the functioning and perhaps the role of prokaryotic communities in benthic ecosystems. This manipulative approach provided new information on the influence of mussel biodeposition on benthic prokaryotic communities and dose-response relationships and may support the development of carrying capacity models for bivalve culture. PMID:25923715

  18. Air Pollution Exposure During Pregnancy and Fetal Markers of Metabolic function: The MIREC Study.

    PubMed

    Lavigne, Eric; Ashley-Martin, Jillian; Dodds, Linda; Arbuckle, Tye E; Hystad, Perry; Johnson, Markey; Crouse, Dan L; Ettinger, Adrienne S; Shapiro, Gabriel D; Fisher, Mandy; Morisset, Anne-Sophie; Taback, Shayne; Bouchard, Maryse F; Sun, Liu; Monnier, Patricia; Dallaire, Renée; Fraser, William D

    2016-05-01

    Previous evidence suggests that exposure to outdoor air pollution during pregnancy could alter fetal metabolic function, which could increase the risk of obesity in childhood. However, to our knowledge, no epidemiologic study has investigated the association between prenatal exposure to air pollution and indicators of fetal metabolic function. We investigated the association between maternal exposure to nitrogen dioxide and fine particulate matter (aerodynamic diameter ≤2.5 µm) and umbilical cord blood leptin and adiponectin levels with mixed-effects linear regression models among 1,257 mother-infant pairs from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, conducted in Canada (2008-2011). We observed that an interquartile-range increase in average exposure to fine particulate matter (3.2 µg/m(3)) during pregnancy was associated with an 11% (95% confidence interval: 4, 17) increase in adiponectin levels. We also observed 13% (95% confidence interval: 6, 20) higher adiponectin levels per interquartile-range increase in average exposure to nitrogen dioxide (13.6 parts per billion) during pregnancy. Significant associations were seen between air pollution markers and cord blood leptin levels in models that adjusted for birth weight z score but not in models that did not adjust for birth weight z score. The roles of prenatal exposure to air pollution and fetal metabolic function in the potential development of childhood obesity should be further explored.

  19. Diurnal Changes in Mitochondrial Function Reveal Daily Optimization of Light and Dark Respiratory Metabolism in Arabidopsis*

    PubMed Central

    Lee, Chun Pong; Eubel, Holger; Millar, A. Harvey

    2010-01-01

    Biomass production by plants is often negatively correlated with respiratory rate, but the value of this rate changes dramatically during diurnal cycles, and hence, biomass is the cumulative result of complex environment-dependent metabolic processes. Mitochondria in photosynthetic plant tissues undertake substantially different metabolic roles during light and dark periods that are dictated by substrate availability and the functional capacity of mitochondria defined by their protein composition. We surveyed the heterogeneity of the mitochondrial proteome and its function during a typical night and day cycle in Arabidopsis shoots. This used a staged, quantitative analysis of the proteome across 10 time points covering 24 h of the life of 3-week-old Arabidopsis shoots grown under 12-h dark and 12-h light conditions. Detailed analysis of enzyme capacities and substrate-dependent respiratory processes of isolated mitochondria were also undertaken during the same time course. Together these data reveal a range of dynamic changes in mitochondrial capacity and uncover day- and night-enhanced protein components. Clear diurnal changes were evident in mitochondrial capacities to drive the TCA cycle and to undertake functions associated with nitrogen and sulfur metabolism, redox poise, and mitochondrial antioxidant defense. These data quantify the nature and nuances of a daily rhythm in Arabidopsis mitochondrial respiratory capacity. PMID:20601493

  20. Metabolism and Ovarian Function in PCOS Women: A Therapeutic Approach with Inositols.

    PubMed

    Laganà, Antonio Simone; Rossetti, Paola; Buscema, Massimo; La Vignera, Sandro; Condorelli, Rosita Angela; Gullo, Giuseppe; Granese, Roberta; Triolo, Onofrio

    2016-01-01

    Polycystic ovary syndrome (PCOS) is characterized by chronical anovulation and hyperandrogenism which may be present in a different degree of severity. Insulin-resistance and hyperinsulinemia are the main physiopathological basis of this syndrome and the failure of inositol-mediated signaling may concur to them. Myo (MI) and D-chiro-inositol (DCI), the most studied inositol isoforms, are classified as insulin sensitizers. In form of glycans, DCI-phosphoglycan and MI-phosphoglycan control key enzymes were involved in glucose and lipid metabolism. In form of phosphoinositides, they play an important role as second messengers in several cellular biological functions. Considering the key role played by insulin-resistance and androgen excess in PCOS patients, the insulin-sensitizing effects of both MI and DCI were tested in order to ameliorate symptoms and signs of this syndrome, including the possibility to restore patients' fertility. Accumulating evidence suggests that both isoforms of inositol are effective in improving ovarian function and metabolism in patients with PCOS, although MI showed the most marked effect on the metabolic profile, whereas DCI reduced hyperandrogenism better. The purpose of this review is to provide an update on inositol signaling and correlate data on biological functions of these multifaceted molecules, in view of a rational use for the therapy in women with PCOS. PMID:27579037

  1. Metabolism and Ovarian Function in PCOS Women: A Therapeutic Approach with Inositols

    PubMed Central

    Rossetti, Paola; Buscema, Massimo; Condorelli, Rosita Angela; Gullo, Giuseppe; Triolo, Onofrio

    2016-01-01

    Polycystic ovary syndrome (PCOS) is characterized by chronical anovulation and hyperandrogenism which may be present in a different degree of severity. Insulin-resistance and hyperinsulinemia are the main physiopathological basis of this syndrome and the failure of inositol-mediated signaling may concur to them. Myo (MI) and D-chiro-inositol (DCI), the most studied inositol isoforms, are classified as insulin sensitizers. In form of glycans, DCI-phosphoglycan and MI-phosphoglycan control key enzymes were involved in glucose and lipid metabolism. In form of phosphoinositides, they play an important role as second messengers in several cellular biological functions. Considering the key role played by insulin-resistance and androgen excess in PCOS patients, the insulin-sensitizing effects of both MI and DCI were tested in order to ameliorate symptoms and signs of this syndrome, including the possibility to restore patients' fertility. Accumulating evidence suggests that both isoforms of inositol are effective in improving ovarian function and metabolism in patients with PCOS, although MI showed the most marked effect on the metabolic profile, whereas DCI reduced hyperandrogenism better. The purpose of this review is to provide an update on inositol signaling and correlate data on biological functions of these multifaceted molecules, in view of a rational use for the therapy in women with PCOS. PMID:27579037

  2. Large-scale functional analysis of the roles of phosphorylation in yeast metabolic pathways.

    PubMed

    Schulz, Juliane Caroline; Zampieri, Mattia; Wanka, Stefanie; von Mering, Christian; Sauer, Uwe

    2014-11-25

    Protein phosphorylation is a widespread posttranslational modification that regulates almost all cellular functions. To investigate the large number of phosphorylation events with unknown functions, we monitored the concentrations of several hundred intracellular metabolites in Saccharomyces cerevisiae yeast strains with deletions of 118 kinases or phosphatases. Whereas most deletion strains had no detectable difference in growth compared to wild-type yeast, two-thirds of deletion strains had alterations in metabolic profiles. For about half of the kinases and phosphatases encoded by the deleted genes, we inferred specific regulatory roles on the basis of knowledge about the affected metabolic pathways. We demonstrated that the phosphatase Ppq1 was required for metal homeostasis. Combining metabolomic data with published phosphoproteomic data in a stoichiometric model enabled us to predict functions for phosphorylation in the regulation of 47 enzymes. Overall, we provided insights and testable predictions covering greater than twice the number of known phosphorylated enzymes in yeast, suggesting extensive phosphorylation-dependent regulation of yeast metabolism.

  3. Neurological crisis mimicking acute pancreatitis in tyrosinemia type I.

    PubMed

    Kalkanoğlu, H S; Coşkun, T

    1999-01-01

    Hereditary tyrosinemia results from an inborn error in the final step of tyrosine metabolism. Neurological manifestations have been reported in nearly half of patients during illness to have characteristics of altered consciousness, weakness, anorexia, vomiting, and pain in the extremities and abdomen. His physical findings and laboratory results pointed out acute pancreatitis. There have been some reports of acute and chronic pancreatitis in patients with metabolic diseases; however, this is the first case with tyrosinemia type I who exhibited clinical and biochemical findings of acute pancreatitis during neurological crisis. The presented case suggests the possibility that the pancreas is affected in neurological crisis. The determination of amylase concentration both in serum and urine samples of further cases will clarity the association between pancreatitis and neurological crisis. PMID:10770119

  4. The functional gene composition and metabolic potential of coral-associated microbial communities

    PubMed Central

    Zhang, Yanying; Ling, Juan; Yang, Qingsong; Wen, Chongqing; Yan, Qingyun; Sun, Hongyan; Van Nostrand, Joy D.; Shi, Zhou; Zhou, Jizhong; Dong, Junde

    2015-01-01

    The phylogenetic diversity of coral-associated microbes has been extensively examined, but some contention remains regarding whether coral-associated microbial communities are species-specific or site-specific. It is suggested that corals may associate with microbes in terms of function, although little is known about the differences in coral-associated microbial functional gene composition and metabolic potential among coral species. Here, 16S rRNA Illumina sequencing and functional gene array (GeoChip 5.0) were used to assess coral-associated microbial communities. Our results indicate that both host species and environmental variables significantly correlate with shifts in the microbial community structure and functional potential. Functional genes related to key biogeochemical cycles including carbon, nitrogen, sulfur and phosphorus cycling, metal homeostasis, organic remediation, antibiotic resistance and secondary metabolism were shown to significantly vary between and among the four study corals (Galaxea astreata, Porites lutea, Porites andrewsi and Pavona decussata). Genes specific for anammox were also detected for the first time in the coral holobiont and positively correlated with ammonium. This study reveals that variability in the functional potential of coral-associated microbial communities is largely driven by changes in environmental factors and further demonstrates the importance of linking environmental parameters with genomic data in complex environmental systems. PMID:26536917

  5. The Circadian Clock Maintains Cardiac Function by Regulating Mitochondrial Metabolism in Mice

    PubMed Central

    Kohsaka, Akira; Das, Partha; Hashimoto, Izumi; Nakao, Tomomi; Deguchi, Yoko; Gouraud, Sabine S.; Waki, Hidefumi; Muragaki, Yasuteru; Maeda, Masanobu

    2014-01-01

    Cardiac function is highly dependent on oxidative energy, which is produced by mitochondrial respiration. Defects in mitochondrial function are associated with both structural and functional abnormalities in the heart. Here, we show that heart-specific ablation of the circadian clock gene Bmal1 results in cardiac mitochondrial defects that include morphological changes and functional abnormalities, such as reduced enzymatic activities within the respiratory complex. Mice without cardiac Bmal1 function show a significant decrease in the expression of genes associated with the fatty acid oxidative pathway, the tricarboxylic acid cycle, and the mitochondrial respiratory chain in the heart and develop severe progressive heart failure with age. Importantly, similar changes in gene expression related to mitochondrial oxidative metabolism are also observed in C57BL/6J mice subjected to chronic reversal of the light-dark cycle; thus, they show disrupted circadian rhythmicity. These findings indicate that the circadian clock system plays an important role in regulating mitochondrial metabolism and thereby maintains cardiac function. PMID:25389966

  6. The functional gene composition and metabolic potential of coral-associated microbial communities.

    PubMed

    Zhang, Yanying; Ling, Juan; Yang, Qingsong; Wen, Chongqing; Yan, Qingyun; Sun, Hongyan; Van Nostrand, Joy D; Shi, Zhou; Zhou, Jizhong; Dong, Junde

    2015-01-01

    The phylogenetic diversity of coral-associated microbes has been extensively examined, but some contention remains regarding whether coral-associated microbial communities are species-specific or site-specific. It is suggested that corals may associate with microbes in terms of function, although little is known about the differences in coral-associated microbial functional gene composition and metabolic potential among coral species. Here, 16S rRNA Illumina sequencing and functional gene array (GeoChip 5.0) were used to assess coral-associated microbial communities. Our results indicate that both host species and environmental variables significantly correlate with shifts in the microbial community structure and functional potential. Functional genes related to key biogeochemical cycles including carbon, nitrogen, sulfur and phosphorus cycling, metal homeostasis, organic remediation, antibiotic resistance and secondary metabolism were shown to significantly vary between and among the four study corals (Galaxea astreata, Porites lutea, Porites andrewsi and Pavona decussata). Genes specific for anammox were also detected for the first time in the coral holobiont and positively correlated with ammonium. This study reveals that variability in the functional potential of coral-associated microbial communities is largely driven by changes in environmental factors and further demonstrates the importance of linking environmental parameters with genomic data in complex environmental systems.

  7. Neurology goes global

    PubMed Central

    Mateen, Farrah J.

    2014-01-01

    Summary In recent years, the need for additional neurologists and neurologic expertise in many low- and middle-income countries (LMIC) has become more apparent. Many organizations are committed to this unmet need, but the scope of the problem remains mostly underappreciated. Neurologists may be skeptical about their value in resource-limited settings, yet we are critically needed and can have a marked effect. International experiences, however, must be carried out in ethical, informed, and sustainable ways in tandem with local health care providers when possible. We present a brief overview of critical issues in global neurology, the importance of focusing on benefits to the LMIC, and options for volunteer opportunities in clinical service, education, research, and disaster relief. Finally, we offer practical pointers and resources for planning these experiences. PMID:25110621

  8. Insomnia in neurological diseases.

    PubMed

    Provini, Federica; Lombardi, Carolina; Lugaresi, Elio

    2005-03-01

    Insomnia is the most common sleep complaint. Insomnia is not a disease itself but mostly a clinical sign of an underlying disease. Degenerative and vascular diseases involving the central nervous system (CNS) may impair sleep either as a result of the brain lesion or because of illness-related discomfort (motor immobility, social and familial impairment, depression, drugs). Some neurological conditions characterized by movement disorders that start or persist during sleep hinder sleep onset and/or sleep continuity, causing a poor sleep complaint. CNS lesions and/or dysfunction in three specific neurological conditions (fatal familial insomnia, Morvan's chorea, and delirium tremens) impair the basic mechanisms of sleep generation inducing a syndrome in which the inability to sleep is consistently associated with motor and sympathergic overactivation. Agrypnia excitata is the term that aptly defines this generalized overactivation syndrome.

  9. Simulation in neurology.

    PubMed

    Micieli, Giuseppe; Cavallini, Anna; Santalucia, Paola; Gensini, Gianfranco

    2015-10-01

    Simulation is a frontier for disseminating knowledge in almost all the fields of medicine and it is attracting growing interest because it offers a means of developing new teaching and training models, as well as of verifying what has been learned in a critical setting that simulates clinical practice. The role of simulation in neurology, until now limited by the obvious physical limitations of the dummies used to train students and learners, is now increasing since, today, it allows anamnestic data to be related to the instrumental evidence necessary for diagnosis and therapeutic decision-making, i.e., to the findings of neurophysiological investigations (EEG, carotid and vertebral echography and transcranial Doppler, for example) and neuroradiological investigations (CT, MRI imaging), as well as vital parameter monitoring (ECG, saturimetry, blood pressure, respiratory frequency, etc.). Simulation, by providing learners with opportunities to discuss, with experts, different profiles of biological parameters (both during the simulation itself and in the subsequent debriefing session), is becoming an increasingly important tool for training those involved in evaluation of critical neurological patients (stroke, Guillan Barrè syndrome, myasthenia, status epilepticus, headache, vertigo, confusional status, etc.) and complex cases. In this SIMMED (Italian Society for Simulation in Medicine) position paper, the applications (present and, possibly, future) of simulation in neurology are reported.

  10. [Neurological Disorders and Pregnancy].

    PubMed

    Berlit, P

    2016-02-01

    Neurological disorders caused by pregnancy and puerperium include the posterior reversible encephalopathy syndrome, the amniotic fluid embolism syndrome (AFES), the postpartum angiopathy due to reversible vasoconstriction syndrome, and the Sheehan syndrome. Hypertension and proteinuria are the hallmarks of preeclampsia, seizures define eclampsia. Hemolysis, elevated liver enzymes and low platelets constitute the HELLP syndrome. Vision disturbances including cortical blindness occur in the posterior reversible encephalopathy syndrome (PRES). The Sheehan syndrome presents with panhypopituitarism post partum due to apoplexia of the pituitary gland in severe peripartal blood loss leading to longstanding hypotension. Some neurological disorders occur during pregnancy and puerperium with an increased frequency. These include stroke, sinus thrombosis, the restless legs syndrome and peripheral nerve syndromes, especially the carpal tunnel syndrome. Chronic neurologic diseases need an interdisciplinary approach during pregnancy. Some anticonvulsants double the risk of birth defects. The highest risk exists for valproic acid, the lowest for lamotrigine and levetiracetam. For MS interval treatment, glatiramer acetate and interferones seem to be safe during pregnancy. All other drugs should be avoided. PMID:26953551

  11. Metabolic functions of Pseudomonas fluorescens strains from Populus deltoides depend on rhizosphere or endosphere isolation compartment

    PubMed Central

    Timm, Collin M.; Campbell, Alisha G.; Utturkar, Sagar M.; Jun, Se-Ran; Parales, Rebecca E.; Tan, Watumesa A.; Robeson, Michael S.; Lu, Tse-Yuan S.; Jawdy, Sara; Brown, Steven D.; Ussery, David W.; Schadt, Christopher W.; Tuskan, Gerald A.; Doktycz, Mitchel J.; Weston, David J.; Pelletier, Dale A.

    2015-01-01

    The bacterial microbiota of plants is diverse, with 1000s of operational taxonomic units (OTUs) associated with any individual plant. In this work, we used phenotypic analysis, comparative genomics, and metabolic models to investigate the differences between 19 sequenced Pseudomonas fluorescens strains. These isolates represent a single OTU and were collected from the rhizosphere and endosphere of Populus deltoides. While no traits were exclusive to either endosphere or rhizosphere P. fluorescens isolates, multiple pathways relevant for plant-bacterial interactions are enriched in endosphere isolate genomes. Further, growth phenotypes such as phosphate solubilization, protease activity, denitrification and root growth promotion are biased toward endosphere isolates. Endosphere isolates have significantly more metabolic pathways for plant signaling compounds and an increased metabolic range that includes utilization of energy rich nucleotides and sugars, consistent with endosphere colonization. Rhizosphere P. fluorescens have fewer pathways representative of plant-bacterial interactions but show metabolic bias toward chemical substrates often found in root exudates. This work reveals the diverse functions that may contribute to colonization of the endosphere by bacteria and are enriched among closely related isolates. PMID:26528266

  12. Calorie Restriction Prevents Metabolic Aging Caused by Abnormal SIRT1 Function in Adipose Tissues.

    PubMed

    Xu, Cheng; Cai, Yu; Fan, Pengcheng; Bai, Bo; Chen, Jie; Deng, Han-Bing; Che, Chi-Ming; Xu, Aimin; Vanhoutte, Paul M; Wang, Yu

    2015-05-01

    Adipose tissue is a pivotal organ determining longevity, due largely to its role in maintaining whole-body energy homeostasis and insulin sensitivity. SIRT1 is a NAD-dependent protein deacetylase possessing antiaging activities in a wide range of organisms. The current study demonstrates that mice with adipose tissue-selective overexpression of hSIRT1(H363Y), a dominant-negative mutant that disrupts endogenous SIRT1 activity, show accelerated development of metabolic aging. These mice, referred to as Adipo-H363Y, exhibit hyperglycemia, dyslipidemia, ectopic lipid deposition, insulin resistance, and glucose intolerance at a much younger age than their wild-type littermates. The metabolic defects of Adipo-H363Y are associated with abnormal epigenetic modifications and chromatin remodeling in their adipose tissues, as a result of excess accumulation of biotin, which inhibits endogenous SIRT1 activity, leading to increased inflammation, cellularity, and collagen deposition. The enzyme acetyl-CoA carboxylase 2 plays an important role in biotin accumulation within adipose tissues of Adipo-H363Y. Calorie restriction prevents biotin accumulation, abolishes abnormal histone biotinylation, and completely restores the metabolic and adipose functions of Adipo-H363Y. The effects are mimicked by short-term restriction of biotin intake, an approach potentially translatable to humans for maintaining the epigenetic and chromatin remodeling capacity of adipose tissues and preventing aging-associated metabolic disorders.

  13. Metabolic functions of Pseudomonas fluorescens strains from Populus deltoides depend on rhizosphere or endosphere isolation compartment

    SciTech Connect

    Timm, Collin M.; Campbell, Alicia G.; Utturkar, Sagar M.; Jun, Se Ran; Parales, Rebecca E.; Tan, Mesa; Robeson, Michael S.; Lu, Tse-Yuan S.; Jawdy, Sara; Schadt, Christopher Warren; Doktycz, Mitchel John; Weston, David; Pelletier, Dale A.

    2015-10-14

    The bacterial microbiota of plants is diverse, with ~1000s of operational taxonomic units (OTUs) associated with any individual plant. In this work we investigate how 19 sequenced Pseudomonas fluorescens strains representing a single OTU isolated from Populus deltoides rhizosphere and endosphere differ using phenotypic analysis, comparative genomics, and metabolic models. While no traits were exclusive to either endosphere or rhizosphere P. fluorescens isolates, multiple pathways relevant for bacterial-plant interactions are enriched in endosphere isolate genomes and growth phenotypes such as phosphate solubilization, protease activity, denitrification and root growth promotion are biased towards endosphere isolates. Endosphere isolates have more metabolic pathways for plant signaling compounds and an increased metabolic range that includes utilization of energy rich nucleotides and sugars, consistent with endosphere colonization. Rhizosphere P. fluorescens have fewer pathways important for bacterial-plant interactions but show metabolic bias towards chemical substrates often found in root exudates. This work reveals the diverse functions that may contribute to colonization of the endosphere by bacteria that are enriched in event he most closely related isolates.

  14. Metabolic functions of Pseudomonas fluorescens strains from Populus deltoides depend on rhizosphere or endosphere isolation compartment

    DOE PAGES

    Timm, Collin M.; Campbell, Alicia G.; Utturkar, Sagar M.; Jun, Se Ran; Parales, Rebecca E.; Tan, Mesa; Robeson, Michael S.; Lu, Tse-Yuan S.; Jawdy, Sara; Schadt, Christopher Warren; et al

    2015-10-14

    The bacterial microbiota of plants is diverse, with ~1000s of operational taxonomic units (OTUs) associated with any individual plant. In this work we investigate how 19 sequenced Pseudomonas fluorescens strains representing a single OTU isolated from Populus deltoides rhizosphere and endosphere differ using phenotypic analysis, comparative genomics, and metabolic models. While no traits were exclusive to either endosphere or rhizosphere P. fluorescens isolates, multiple pathways relevant for bacterial-plant interactions are enriched in endosphere isolate genomes and growth phenotypes such as phosphate solubilization, protease activity, denitrification and root growth promotion are biased towards endosphere isolates. Endosphere isolates have more metabolic pathwaysmore » for plant signaling compounds and an increased metabolic range that includes utilization of energy rich nucleotides and sugars, consistent with endosphere colonization. Rhizosphere P. fluorescens have fewer pathways important for bacterial-plant interactions but show metabolic bias towards chemical substrates often found in root exudates. This work reveals the diverse functions that may contribute to colonization of the endosphere by bacteria that are enriched in event he most closely related isolates.« less

  15. Metabolic functions of Pseudomonas fluorescens strains from Populus deltoides depend on rhizosphere or endosphere isolation compartment.

    PubMed

    Timm, Collin M; Campbell, Alisha G; Utturkar, Sagar M; Jun, Se-Ran; Parales, Rebecca E; Tan, Watumesa A; Robeson, Michael S; Lu, Tse-Yuan S; Jawdy, Sara; Brown, Steven D; Ussery, David W; Schadt, Christopher W; Tuskan, Gerald A; Doktycz, Mitchel J; Weston, David J; Pelletier, Dale A

    2015-01-01

    The bacterial microbiota of plants is diverse, with 1000s of operational taxonomic units (OTUs) associated with any individual plant. In this work, we used phenotypic analysis, comparative genomics, and metabolic models to investigate the differences between 19 sequenced Pseudomonas fluorescens strains. These isolates represent a single OTU and were collected from the rhizosphere and endosphere of Populus deltoides. While no traits were exclusive to either endosphere or rhizosphere P. fluorescens isolates, multiple pathways relevant for plant-bacterial interactions are enriched in endosphere isolate genomes. Further, growth phenotypes such as phosphate solubilization, protease activity, denitrification and root growth promotion are biased toward endosphere isolates. Endosphere isolates have significantly more metabolic pathways for plant signaling compounds and an increased metabolic range that includes utilization of energy rich nucleotides and sugars, consistent with endosphere colonization. Rhizosphere P. fluorescens have fewer pathways representative of plant-bacterial interactions but show metabolic bias toward chemical substrates often found in root exudates. This work reveals the diverse functions that may contribute to colonization of the endosphere by bacteria and are enriched among closely related isolates. PMID:26528266

  16. Development of an Objective Space Suit Mobility Performance Metric Using Metabolic Cost and Functional Tasks

    NASA Technical Reports Server (NTRS)

    McFarland, Shane M.; Norcross, Jason

    2016-01-01

    Existing methods for evaluating EVA suit performance and mobility have historically concentrated on isolated joint range of motion and torque. However, these techniques do little to evaluate how well a suited crewmember can actually perform during an EVA. An alternative method of characterizing suited mobility through measurement of metabolic cost to the wearer has been evaluated at Johnson Space Center over the past several years. The most recent study involved six test subjects completing multiple trials of various functional tasks in each of three different space suits; the results indicated it was often possible to discern between different suit designs on the basis of metabolic cost alone. However, other variables may have an effect on real-world suited performance; namely, completion time of the task, the gravity field in which the task is completed, etc. While previous results have analyzed completion time, metabolic cost, and metabolic cost normalized to system mass individually, it is desirable to develop a single metric comprising these (and potentially other) performance metrics. This paper outlines the background upon which this single-score metric is determined to be feasible, and initial efforts to develop such a metric. Forward work includes variable coefficient determination and verification of the metric through repeated testing.

  17. Neurology of the pituitary.

    PubMed

    Samarasinghe, Shanika; Emanuele, Mary Ann; Mazhari, Alaleh

    2014-01-01

    The anterior pituitary hormones are essential for reproduction, growth, metabolic homeostasis, stress response, and adaptation to changes in the external environment. Each pituitary hormone is secreted in a distinctive pulsatile manner reflecting its regulation by the central nervous system through a complex interaction between hypothalamic neuroendocrine pathways, feedback effects from peripheral target gland hormones, and intrapituitary mechanisms. While the most common cause of a pituitary mass is an adenoma, the differential diagnosis is broad and includes pituitary hyperplasia, lymphocytic hypophysitis, craniopharyngioma among others. Patients with pituitary adenomas can be asymptomatic or present with symptoms due to mass effect, pituitary hormone dysfunction, or both. Prolactinomas represent 40% of pituitary adenomas, the majority of which are microadenomas. Hyperfunction of growth hormone and ACTH are far less common, while TSH-producing tumors are exceedingly rare. Hypopituitarism in patients with pituitary adenomas can be partial or complete. The clinical picture will depend on the type, degree, and rapidity of onset of pituitary hormone deficiency. An MRI specifically focused on the sellar region is the imaging modality of choice to detect pituitary pathology. Management of pituitary tumors ranges from observation of nonfunctioning microadenomas through medical, surgical, and radiotherapeutic approaches dependent on tumor type, function, size, and invasiveness.

  18. Beneficial effects of herbs, spices and medicinal plants on the metabolic syndrome, brain and cognitive function.

    PubMed

    Panickar, Kiran S

    2013-03-01

    Herbs and spices have been used since ancient times to not only improve the flavor of edible food but also to prevent and treat chronic health maladies. While the scientific evidence for the use of such common herbs and medicinal plants then had been scarce or lacking, the beneficial effects observed from such use were generally encouraging. It is, therefore, not surprising that the tradition of using such herbs, perhaps even after the advent of modern medicine, has continued. More recently, due to an increased interest in understanding the nutritional effects of herbs/spices more comprehensively, several studies have examined the cellular and molecular modes of action of the active chemical components in herbs and their biological properties. Beneficial actions of herbs/spices include anti-inflammatory, antioxidant, anti-hypertensive, gluco-regulatory, and anti-thrombotic effects. One major component of herbs and spices is the polyphenols. Some of the aforementioned properties are attributed to the polyphenols and they are associated with attenuating the metabolic syndrome. Detrimental changes associated with the metabolic syndrome over time affect brain and cognitive function. Metabolic syndrome and type-2 diabetes are also risk factors for Alzheimer's disease and stroke. In addition, the neuroprotective effects of herbs and spices have been demonstrated and, whether directly or indirectly, such beneficial effects may also contribute to an improvement in cognitive function. This review evaluates the current evidence available for herbs/spices in potentially improving the metabolic syndrome, as well as their neuroprotective effects on the brain, and cognitive function in animal and human studies.

  19. Improvement of erectile function by Korean red ginseng (Panax ginseng) in a male rat model of metabolic syndrome

    PubMed Central

    Kim, Sung-Dae; Kim, Young-Joo; Huh, Jung-Sik; Kim, Sae-Woong; Sohn, Dong-Wan

    2013-01-01

    The seriousness of metabolic syndrome is not due to the disease itself but its promotion of other diseases, such as erectile dysfunction and cardiovascular and cerebrovascular diseases. We investigated the effects of Korean red ginseng (KRG, Panax ginseng) extract on erectile function in a rat model of metabolic syndrome. We divided the rats into three groups: control, metabolic syndrome+normal saline (N/S) and metabolic syndrome+KRG. To determine the occurrence of metabolic syndrome in all groups, body weight and various biochemical parameters (e.g., blood glucose, insulin, cholesterol) were measured, and the intra-abdominal glucose tolerance test was performed. To investigate penile erection, the peak intracavernosal pressure (ICP), mean arterial pressure (MAP) and Masson's trichrome stain were evaluated. Erectile function was also investigated by measuring the cyclic guanosine monophosphate (cGMP) levels of the corpus cavernosum. We found that the various biochemical parameters and body weight were similar in the metabolic syndrome+KRG group and the control group, although the values were slightly higher. The peak ICP/MAP ratio of the metabolic syndrome+N/S group was markedly decreased compared to the other groups. The cGMP level of the corpus cavernosum in the metabolic syndrome+N/S group was significantly lower than that of the other groups. As demonstrated in this model of metabolic syndrome with erectile dysfunction, KRG may improve erectile function. PMID:23377529

  20. C1 metabolism and the Calvin cycle function simultaneously and independently during HCHO metabolism and detoxification in Arabidopsis thaliana treated with HCHO solutions.

    PubMed

    Song, Zhong-Bang; Xiao, Su-Qin; You, Lan; Wang, Sha-Sha; Tan, Hao; Li, Kun-Zhi; Chen, Li-Mei

    2013-08-01

    Formaldehyde (HCHO) is suggested to be detoxified through one-carbon (C1) metabolism or assimilated by the Calvin cycle in plants. To further understand the function of the Calvin cycle and C1 metabolism in HCHO metabolism in plants, HCHO elimination and metabolism by Arabidopsis thaliana in HCHO solutions was investigated in this study. Results verified that Arabidopsis could completely eliminate aqueous HCHO from the HCHO solutions. Carbon-13 nuclear magnetic resonance ((13)C-NMR) analysis showed that H(13)CHO absorbed by Arabidopsis was first oxidized to H(13)COOH. Subsequently, a clear increase in [U-(13)C]Gluc peaks accompanied by a strong enhancement in peaks of [2-(13)C]Ser and [3-(13)C]Ser appeared in Arabidopsis. Pretreatment with cyclosporin A or L-carnitine, which might inhibit the transport of (13)C-enriched compounds into chloroplasts and mitochondria, caused a remarkable decline in yields of both [U-(13)C]Gluc and [3-(13)C]Ser in H(13)CHO-treated Arabidopsis. These results suggested that both the Calvin cycle and the C1 metabolism functioned simultaneously during HCHO detoxification. Moreover, both functioned more quickly under high H(13)CHO stress than low H(13)CHO stress. When a photorespiration mutant was treated in 6 mm H(13)CHO solution, formation of [U-(13)C]Gluc and [2-(13)C]Ser was completely inhibited, but generation of [3-(13)C]Ser was not significantly affected. This evidence suggested that the Calvin cycle and C1 metabolism functioned independently in Arabidopsis during HCHO metabolism.

  1. Mitochondria in Neuroplasticity and Neurological Disorders

    PubMed Central

    Mattson, Mark P.; Gleichmann, Marc; Cheng, Aiwu

    2009-01-01

    Mitochondrial electron transport generates the ATP that is essential for the excitability and survival of neurons, and the protein phosphorylation reactions that mediate synaptic signaling and related long-term changes in neuronal structure and function. Mitochondria are highly dynamic organelles that divide, fuse and move purposefully within axons and dendrites. An Major functions of mitochondria in neurons include the regulation of Ca2+ and redox signaling, developmental and synaptic plasticity, and the arbitration of cell survival and death. The importance of mitochondria in neurons is evident in the neurological phenotypes in rare diseases caused by mutations in mitochondrial genes. Mitochondria-mediated oxidative stress, perturbed Ca2+ homeostasis and apoptosis may also contribute to the pathogenesis of prominent neurological diseases including Alzheimer’s, Parkinson’s and Huntington’s diseases, stroke, ALS and psychiatric disorders. Advances in understanding the molecular and cell biology of mitochondria are leading to novel approaches for the prevention and treatment of neurological disorders. PMID:19081372

  2. Liver disease alters high-density lipoprotein composition, metabolism and function.

    PubMed

    Trieb, Markus; Horvath, Angela; Birner-Gruenberger, Ruth; Spindelboeck, Walter; Stadlbauer, Vanessa; Taschler, Ulrike; Curcic, Sanja; Stauber, Rudolf E; Holzer, Michael; Pasterk, Lisa; Heinemann, Akos; Marsche, Gunther

    2016-07-01

    High-density lipoproteins (HDL) are important endogenous inhibitors of inflammatory responses. Functional impairment of HDL might contribute to the excess mortality experienced by patients with liver disease, but the effect of cirrhosis on HDL metabolism and function remain elusive. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function using apolipoprotein (apo) B-depleted sera from patients with compensated cirrhosis, patients with acutely decompensated cirrhosis and healthy controls. We observed that sera of cirrhotic patients showed reduced levels of HDL-cholesterol and profoundly suppressed activities of several enzymes involved in HDL maturation and metabolism. Native gel electrophoresis analyses revealed that cirrhotic serum HDL shifts towards the larger HDL2 subclass. Proteomic assessment of isolated HDL identified several proteins, including apoA-I, apoC-III, apoE, paraoxonase 1 and acute phase serum amyloid A to be significantly altered in cirrhotic patients. With regard to function, these alterations in levels, composition and structure of HDL were strongly associated with metrics of function of apoB-depleted sera, including cholesterol efflux capability, paraoxonase activity, the ability to inhibit monocyte production of cytokines and endothelial regenerative activities. Of particular interest, cholesterol efflux capacity appeared to be strongly associated with liver disease mortality. Our findings may be clinically relevant and improve our ability to monitor cirrhotic patients at high risk. PMID:27106140

  3. Liver disease alters high-density lipoprotein composition, metabolism and function.

    PubMed

    Trieb, Markus; Horvath, Angela; Birner-Gruenberger, Ruth; Spindelboeck, Walter; Stadlbauer, Vanessa; Taschler, Ulrike; Curcic, Sanja; Stauber, Rudolf E; Holzer, Michael; Pasterk, Lisa; Heinemann, Akos; Marsche, Gunther

    2016-07-01

    High-density lipoproteins (HDL) are important endogenous inhibitors of inflammatory responses. Functional impairment of HDL might contribute to the excess mortality experienced by patients with liver disease, but the effect of cirrhosis on HDL metabolism and function remain elusive. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function using apolipoprotein (apo) B-depleted sera from patients with compensated cirrhosis, patients with acutely decompensated cirrhosis and healthy controls. We observed that sera of cirrhotic patients showed reduced levels of HDL-cholesterol and profoundly suppressed activities of several enzymes involved in HDL maturation and metabolism. Native gel electrophoresis analyses revealed that cirrhotic serum HDL shifts towards the larger HDL2 subclass. Proteomic assessment of isolated HDL identified several proteins, including apoA-I, apoC-III, apoE, paraoxonase 1 and acute phase serum amyloid A to be significantly altered in cirrhotic patients. With regard to function, these alterations in levels, composition and structure of HDL were strongly associated with metrics of function of apoB-depleted sera, including cholesterol efflux capability, paraoxonase activity, the ability to inhibit monocyte production of cytokines and endothelial regenerative activities. Of particular interest, cholesterol efflux capacity appeared to be strongly associated with liver disease mortality. Our findings may be clinically relevant and improve our ability to monitor cirrhotic patients at high risk.

  4. Neurological complications of infantile osteopetrosis.

    PubMed

    Lehman, R A; Reeves, J D; Wilson, W B; Wesenberg, R L

    1977-11-01

    Seven cases of infantile osteopetrosis are presented. Five of these were available for detailed clinical examination and 2 for retrospective review, including autopsy slides. Neurological deficits in these patients are reviewed. Involvement of the central nervous system parenchyma was suggested by observations of delayed development, ocular abnormalities, and reflex changes as well as radiographic and autopsy findings. Cerebral atrophy was present in several of our patients as well as some reported in the literature and may account for the ventricular enlargement found in many of these patients. Though hydrocephalus may be present, it is unclear that this is frequent or that it can occur without antecedent intracranial hemorrhage. The large head size is not accounted for by calvarial thickening or by hydrocephalus. Despite our patients' small stature, pituitary function appeared to be normal. Surgical decompression may stabilize cranial nerve function, particularly when the optic nerves are involved. PMID:617576

  5. [Post-ischemia neurologic recovery].

    PubMed

    Guiraud-Chaumeil, Bernard; Pariente, Jérémie; Albucher, Jean-François; Loubinoux, Isabelle; Chollet, François

    2002-01-01

    Stroke is one of the most common affliction of patients with neurological symptoms. Rehabilitation of stroke patients is a difficult task. Our knowledge on rehabilitation has recently improved with the emergence of data from new neuroimaging techniques. A prospective, double blind, cross over, placebo, controlled study on 8 patients with pure motor hemiparesia, is conducted to determine the influence of a single dose of fluoxetine on motor performance and cerebral activation of patients recovering from stroke. Each patient undergoes two functional magnetic resonance imaging (fMRI) examinations, one under fluoxetine and one under placebo. A single dose of fluoxetine is enough to modulate cerebral sensori-motor activation and significantly improves motor skills of the affected side. Further studies are required to investigate the effect of chronic administration of fluoxetine on motor function. PMID:12587340

  6. Plasticity of muscle function in a thermoregulating ectotherm (Crocodylus porosus): biomechanics and metabolism.

    PubMed

    Seebacher, Frank; James, Rob S

    2008-03-01

    Thermoregulation and thermal sensitivity of performance are thought to have coevolved so that performance is optimized within the selected body temperature range. However, locomotor performance in thermoregulating crocodiles (Crocodylus porosus) is plastic and maxima shift to different selected body temperatures in different thermal environments. Here we test the hypothesis that muscle metabolic and biomechanical parameters are optimized at the body temperatures selected in different thermal environments. Hence, we related indices of anaerobic (lactate dehydrogenase) and aerobic (cytochrome c oxidase) metabolic capacities and myofibrillar ATPase activity to the biomechanics of isometric and work loop caudofemoralis muscle function. Maximal isometric stress (force per muscle cross-sectional area) did not change with thermal acclimation, but muscle work loop power output increased with cold acclimation as a result of shorter activation and relaxation times. The thermal sensitivity of myofibrillar ATPase activity decreased with cold acclimation in caudofemoralis muscle. Neither aerobic nor anaerobic metabolic capacities were directly linked to changes in muscle performance during thermal acclimation, although there was a negative relationship between anaerobic capacity and isometric twitch stress in cold-acclimated animals. We conclude that by combining thermoregulation with plasticity in biomechanical function, crocodiles maximize performance in environments with highly variable thermal properties.

  7. Expression and functional studies of genes involved in transport and metabolism of glycerol in Pachysolen tannophilus

    PubMed Central

    2013-01-01

    Background Pachysolen tannophilus is a non-conventional yeast, which can metabolize many of the carbon sources found in low cost feedstocks including glycerol and xylose. The xylose utilisation pathways have been extensively studied in this organism. However, the mechanism behind glycerol metabolism is poorly understood. Using the recently published genome sequence of P. tannophilus CBS4044, we searched for genes with functions in glycerol transport and metabolism by performing a BLAST search using the sequences of the relevant genes from Saccharomyces cerevisiae as queries. Results Quantitative real-time PCR was performed to unveil the expression patterns of these genes during growth of P. tannophilus on glycerol and glucose as sole carbon sources. The genes predicted to be involved in glycerol transport in P. tannophilus were expressed in S. cerevisiae to validate their function. The S. cerevisiae strains transformed with heterologous genes showed improved growth and glycerol consumption rates with glycerol as the sole carbon source. Conclusions P. tannophilus has characteristics relevant for a microbial cell factory to be applied in a biorefinery setting, i.e. its ability to utilise the carbon sources such as xylose and glycerol. However, the strain is not currently amenable to genetic modification and transformation. Heterologous expression of the glycerol transporters from P. tannophilus, which has a relatively high growth rate on glycerol, could be used as an approach for improving the efficiency of glycerol assimilation in other well characterized and applied cell factories such as S. cerevisiae. PMID:23514356

  8. Adipocyte Versus Somatotrope Leptin: Regulation of Metabolic Functions in the Mouse.

    PubMed

    Odle, Angela Katherine; Allensworth-James, Melody; Haney, Anessa; Akhter, Noor; Syed, Mohsin; Childs, Gwen V

    2016-04-01

    Leptin regulates food intake and energy expenditure (EE) and is produced in adipocytes, the pituitary, and several other tissues. Animals that are leptin or leptin receptor deficient have major metabolic complications, including obesity. This study tests the hypothesis that the pituitary somatotrope may contribute a source of leptin that maintains some of these metabolic functions. We created 2 different tissue-specific leptin knockout animals: a Somatotrope-Lep-null model and an Adipocyte-Lep-null model. Metabolic analysis of both models, along with a global deletion model, was performed. The Somatotrope-Lep-null animals had fewer somatotropes, and females had a 76% decrease in serum prolactin. During the dark (feeding) phase, females had a 35% increase in ambulation coupled with a 4% increase in EE. Mutants showed no change in food intake or weight gain and EE was unchanged in males. During the light (sleep) phase, Somatotrope-Lep-null mutant males had lower EE and females continued to have higher EE. The respiratory quotients (RQs) of mutants and littermate controls were decreased in males and increased in females; all were within the range that indicates predominant carbohydrate burning. The massively obese Adipocyte-Lep-null animals, however, had significant increases in food intake, sleep, and increased EE, with decreased activity. Changes in RQ were sexually dimorphic, with female mutants having higher RQ and males having decreased RQ. We conclude that both adipocyte and somatotrope leptin contribute to the metabolic homeostasis of the mouse, and that extraadipocyte sources of leptin cannot overcome the major metabolic challenges seen in these animals.

  9. Apolipoprotein D in Lipid Metabolism and Its Functional Implication in Atherosclerosis and Aging

    PubMed Central

    Perdomo, German; Dong, H. Henry

    2009-01-01

    Dyslipidemia is characterized by increased triglyceride and low-density lipoprotein (LDL) levels, and decreased high-density lipoprotein (HDL) levels. Such an atherogenic lipid profile often predisposes an at risk individual to coronary artery disease with incompletely understood mechanisms. Apolipoprotein D (apoD) is an atypical apolipoprotein. Unlike canonical apolipoproteins that are produced mainly in liver and intestine, apoD is expressed widely in mammalian tissues. ApoD does not share significant degrees of homology in amino acid sequence with other apolipoproteins. Instead, apoD is structurally similar to lipocalins, a diverse family of lipid-binding proteins that are responsible for transporting lipids and other small hydrophobic molecules for metabolism. Plasma ApoD is present mainly in HDL and to a lesser extent in low density lipoproteins (LDL) and very low-density lipoproteins (VLDL). Genetic variants of apoD are associated with abnormal lipid metabolism and increased risk of developing metabolic syndrome. Increased apoD deposition is detectable in atherosclerotic lesions of humans with established cardiovascular disease as well as mice with premature atherosclerosis. Moreover, apoD is associated with anti-oxidation and anti-stress activities, contributing to lifespan expansion in fruit flies. Elderly subjects and patients with Alzheimer exhibit markedly elevated apoD production in the brain. Thus, apoD is emerged as a significant player in lipid metabolism and aging. Here we focus our review on recent advances toward our understanding of apoD in lipid metabolism and address whether apoD dysregulation contributes to the pathogenesis of dyslipidemia and atherosclerosis. We will also discuss the functional implication of apoD in aging. PMID:19946382

  10. Glucosinolate metabolism, functionality and breeding for the improvement of Brassicaceae vegetables.

    PubMed

    Ishida, Masahiko; Hara, Masakazu; Fukino, Nobuko; Kakizaki, Tomohiro; Morimitsu, Yasujiro

    2014-05-01

    Unique secondary metabolites, glucosinolates (S-glucopyranosyl thiohydroximates), are naturally occurring S-linked glucosides found mainly in Brassicaceae plants. They are enzymatically hydrolyzed to produce sulfate ions, D-glucose, and characteristic degradation products such as isothiocyanates. The functions of glucosinolates in the plants remain unclear, but isothiocyanates possessing a pungent or irritating taste and odor might be associated with plant defense from microbes. Isothiocyanates have been studied extensively in experimental in vitro and in vivo carcinogenesis models for their cancer chemopreventive properties. The beneficial isothiocyanates, glucosinolates that are functional for supporting human health, have received attention from many scientists studying plant breeding, plant physiology, plant genetics, and food functionality. This review presents a summary of recent topics related with glucosinolates in the Brassica family, along with a summary of the chemicals, metabolism, and genes of glucosinolates in Brassicaceae. The bioavailabilities of isothiocyanates from certain functional glucosinolates and the importance of breeding will be described with emphasis on glucosinolates.

  11. Glucosinolate metabolism, functionality and breeding for the improvement of Brassicaceae vegetables

    PubMed Central

    Ishida, Masahiko; Hara, Masakazu; Fukino, Nobuko; Kakizaki, Tomohiro; Morimitsu, Yasujiro

    2014-01-01

    Unique secondary metabolites, glucosinolates (S-glucopyranosyl thiohydroximates), are naturally occurring S-linked glucosides found mainly in Brassicaceae plants. They are enzymatically hydrolyzed to produce sulfate ions, D-glucose, and characteristic degradation products such as isothiocyanates. The functions of glucosinolates in the plants remain unclear, but isothiocyanates possessing a pungent or irritating taste and odor might be associated with plant defense from microbes. Isothiocyanates have been studied extensively in experimental in vitro and in vivo carcinogenesis models for their cancer chemopreventive properties. The beneficial isothiocyanates, glucosinolates that are functional for supporting human health, have received attention from many scientists studying plant breeding, plant physiology, plant genetics, and food functionality. This review presents a summary of recent topics related with glucosinolates in the Brassica family, along with a summary of the chemicals, metabolism, and genes of glucosinolates in Brassicaceae. The bioavailabilities of isothiocyanates from certain functional glucosinolates and the importance of breeding will be described with emphasis on glucosinolates. PMID:24987290

  12. Glucosinolate metabolism, functionality and breeding for the improvement of Brassicaceae vegetables.

    PubMed

    Ishida, Masahiko; Hara, Masakazu; Fukino, Nobuko; Kakizaki, Tomohiro; Morimitsu, Yasujiro

    2014-05-01

    Unique secondary metabolites, glucosinolates (S-glucopyranosyl thiohydroximates), are naturally occurring S-linked glucosides found mainly in Brassicaceae plants. They are enzymatically hydrolyzed to produce sulfate ions, D-glucose, and characteristic degradation products such as isothiocyanates. The functions of glucosinolates in the plants remain unclear, but isothiocyanates possessing a pungent or irritating taste and odor might be associated with plant defense from microbes. Isothiocyanates have been studied extensively in experimental in vitro and in vivo carcinogenesis models for their cancer chemopreventive properties. The beneficial isothiocyanates, glucosinolates that are functional for supporting human health, have received attention from many scientists studying plant breeding, plant physiology, plant genetics, and food functionality. This review presents a summary of recent topics related with glucosinolates in the Brassica family, along with a summary of the chemicals, metabolism, and genes of glucosinolates in Brassicaceae. The bioavailabilities of isothiocyanates from certain functional glucosinolates and the importance of breeding will be described with emphasis on glucosinolates. PMID:24987290

  13. Vascular endothelial growth factors: multitasking functionality in metabolism, health and disease.

    PubMed

    Smith, Gina A; Fearnley, Gareth W; Harrison, Michael A; Tomlinson, Darren C; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan

    2015-07-01

    Vascular endothelial growth factors (VEGFs) bind to VEGF receptor tyrosine kinases (VEGFRs). The VEGF and VEGFR gene products regulate diverse regulatory pathways in mammalian development, health and disease. The interaction between a particular VEGF and its cognate VEGFR activates multiple signal transduction pathways which regulate different cellular responses including metabolism, gene expression, proliferation, migration, and survival. The family of VEGF isoforms regulate vascular physiology and promote tissue homeostasis. VEGF dysfunction is implicated in major chronic disease states including atherosclerosis, diabetes, and cancer. More recent studies implicate a strong link between response to VEGF and regulation of vascular metabolism. Understanding how this family of multitasking cytokines regulates cell and animal function has implications for treating many different diseases.

  14. D-Lactate production as a function of glucose metabolism in Saccharomyces cerevisiae.

    PubMed

    Stewart, Benjamin J; Navid, Ali; Kulp, Kristen S; Knaack, Jennifer L S; Bench, Graham

    2013-02-01

    Methylglyoxal, a reactive, toxic dicarbonyl, is generated by the spontaneous degradation of glycolytic intermediates. Methylglyoxal can form covalent adducts with cellular macromolecules, potentially disrupting cellular function. We performed experiments using the model organism Saccharomyces cerevisiae, grown in media containing low, moderate and high glucose concentrations, to determine the relationship between glucose consumption and methylglyoxal metabolism. Normal growth experiments and glutathione depletion experiments showed that metabolism of methylglyoxal by log-phase yeast cultured aerobically occurred primarily through the glyoxalase pathway. Growth in high-glucose media resulted in increased generation of the methylglyoxal metabolite D-lactate and overall lower efficiency of glucose utilization as measured by growth rates. Cells grown in high-glucose media maintained higher glucose uptake flux than cells grown in moderate-glucose or low-glucose media. Computational modelling showed that increased glucose consumption may impair catabolism of triose phosphates as a result of an altered NAD⁺:NADH ratio.

  15. D-Lactate Production as a Function of Glucose Metabolism in Saccharomyces cerevisiae

    PubMed Central

    Stewart, Benjamin J.; Navid, Ali; Kulp, Kristen S.; Knaack, Jennifer L. S.; Bench, Graham

    2013-01-01

    Methylglyoxal, a reactive, toxic dicarbonyl, is generated by the spontaneous degradation of glycolytic intermediates. Methylglyoxal can form covalent adducts with cellular macromolecules, potentially disrupting cellular function. We performed experiments using the model organism Saccharomyces cerevisiae grown in media containing low, moderate, and high glucose concentrations to determine the relationship between glucose consumption and methylglyoxal metabolism. Normal growth experiments and glutathione depletion experiments showed that metabolism of methylglyoxal by log-phase yeast cultured aerobically occurred primarily through the glyoxalase pathway. Growth in high-glucose media resulted in increased generation of the methylglyoxal metabolite D-lactate and overall lower efficiency of glucose utilization as measured by growth rates. Cells grown in high-glucose media maintained higher glucose uptake flux than cells grown in moderate-glucose or low-glucose media. Computational modeling showed that increased glucose consumption may impair catabolism of triose phosphates as a result of an altered NAD+/NADH ratio. PMID:23361949

  16. Mitochondrial Functional Impairment in Response to Environmental Toxins in the Cardiorenal Metabolic Syndrome

    PubMed Central

    Jia, Guanghong; Aroor, Annayya R.; Martinez-Lemus, Luis A.; Sowers, James R.

    2015-01-01

    Environmental toxins can promote cardiovascular, metabolic and renal abnormalities, which characterize the cardiorenal metabolic syndrome (CRS). Heavy metals, such as mercury and arsenic, represent two of the most toxic pollutants. Exposure to these toxins is increasing due to increased industrialization throughout much of the world. Studies conducted to understand the impact of environmental toxins have shown a major impact on mitochondrial structure and function. The maladaptive adaptive stress products caused by these toxins, including aggregated proteins, damaged organelles, and intracellular pathogens, can be removed through autophagy, which is also known as mitophagy in mitochondria. Although the underlying mechanisms involved in the regulation of mitophagy in response to pollution are not well understood, accumulating evidence supports a role for maladaptive mitochondrial responses to environmental pollution in the pathogenesis of the CRS. In this review, we discuss ongoing research, which explores the mechanisms by which these toxins promote abnormalities in mitophagy and associated mitochondrial dysfunction and the CRS. PMID:25559775

  17. Vascular endothelial growth factors: multitasking functionality in metabolism, health and disease.

    PubMed

    Smith, Gina A; Fearnley, Gareth W; Harrison, Michael A; Tomlinson, Darren C; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan

    2015-07-01

    Vascular endothelial growth factors (VEGFs) bind to VEGF receptor tyrosine kinases (VEGFRs). The VEGF and VEGFR gene products regulate diverse regulatory pathways in mammalian development, health and disease. The interaction between a particular VEGF and its cognate VEGFR activates multiple signal transduction pathways which regulate different cellular responses including metabolism, gene expression, proliferation, migration, and survival. The family of VEGF isoforms regulate vascular physiology and promote tissue homeostasis. VEGF dysfunction is implicated in major chronic disease states including atherosclerosis, diabetes, and cancer. More recent studies implicate a strong link between response to VEGF and regulation of vascular metabolism. Understanding how this family of multitasking cytokines regulates cell and animal function has implications for treating many different diseases. PMID:25868665

  18. Metabolic rate of carrying added mass: a function of walking speed, carried mass and mass location.

    PubMed

    Schertzer, Eliran; Riemer, Raziel

    2014-11-01

    The effort of carrying additional mass at different body locations is important in ergonomics and in designing wearable robotics. We investigate the metabolic rate of carrying a load as a function of its mass, its location on the body and the subject's walking speed. Novel metabolic rate prediction equations for walking while carrying loads at the ankle, knees and back were developed based on experiments where subjects walked on a treadmill at 4, 5 or 6km/h bearing different amounts of added mass (up to 2kg per leg and 22kg for back). Compared to previously reported equations, ours are 7-69% more accurate. Results also show that relative cost for carrying a mass at a distal versus a proximal location changes with speed and mass. Contrary to mass carried on the back, mass attached to the leg cannot be modeled as an increase in body mass. PMID:24793822

  19. Neurological complication of dengue infection.

    PubMed

    Murthy, J M K

    2010-01-01

    Dengue infection is endemic in more than 100 countries, mostly in the developing world. Recent observations indicate that the clinical profile of dengue is changing, and that neurological manifestations are being reported more frequently. The exact incidence of various neurological complications is uncertain. The pathogenesis of neurological manifestations is multiple and includes: neurotrophic effect of the dengue virus, related to the systemic effects of dengue infection, and immune mediated. In countries endemic to dengue, it will be prudent to investigate for dengue infection in patients with fever and acute neurological manifestations. There is need for understanding of the pathogenesis of various neurological manifestations.

  20. Neurology and psychiatry in Babylon.

    PubMed

    Reynolds, Edward H; Wilson, James V Kinnier

    2014-09-01

    We here review Babylonian descriptions of neurological and psychiatric disorders, including epilepsy, stroke, psychoses, obsessive compulsive disorder, phobias, psychopathic behaviour, depression and anxiety. Most of these accounts date from the first Babylonian dynasty of the first half of the second millennium BC, within a millennium and a half of the origin of writing. The Babylonians were remarkably acute and objective observers of medical disorders and human behaviour. Their detailed descriptions are surprisingly similar to modern 19th and 20th century AD textbook accounts, with the exception of subjective thoughts and feelings which are more modern fields of enquiry. They had no knowledge of brain or psychological function. Some neuropsychiatric disorders, e.g. stroke or facial palsy, had a physical basis requiring the attention of a physician or asû, using a plant and mineral based pharmacology; some disorders such as epilepsy, psychoses, depression and anxiety were regarded as supernatural due to evil demons or spirits, or the anger of personal gods, and thus required the intervention of the priest or ašipu; other disorders such as obsessive compulsive disorder and psychopathic behaviour were regarded as a mystery. The Babylonians were the first to describe the clinical foundations of neurology and psychiatry. We discuss these accounts in relation to subsequent and more modern clinical descriptions.

  1. Neurologic complications after liver transplantation

    PubMed Central

    Živković, Saša A

    2013-01-01

    Neurologic complications are relatively common after solid organ transplantation and affect 15%-30% of liver transplant recipients. Etiology is often related to immunosuppressant neurotoxicity and opportunistic infections. Most common complications include seizures and encephalopathy, and occurrence of central pontine myelinolysis is relatively specific for liver transplant recipients. Delayed allograft function may precipitate hepatic encephalopathy and neurotoxicity of calcineurin inhibitors typically manifests with tremor, headaches and encephalopathy. Reduction of neurotoxic immunosuppressants or conversion to an alternative medication usually result in clinical improvement. Standard preventive and diagnostic protocols have helped to reduce the prevalence of opportunistic central nervous system (CNS) infections, but viral and fungal CNS infections still affect 1% of liver transplant recipients, and the morbidity and mortality in the affected patients remain fairly high. Critical illness myopathy may also affect up to 7% of liver transplant recipients. Liver insufficiency is also associated with various neurologic disorders which may improve or resolve after successful liver transplantation. Accurate diagnosis and timely intervention are essential to improve outcomes, while advances in clinical management and extended post-transplant survival are increasingly shifting the focus to chronic post-transplant complications which are often encountered in a community hospital and an outpatient setting. PMID:24023979

  2. Neurology and psychiatry in Babylon.

    PubMed

    Reynolds, Edward H; Wilson, James V Kinnier

    2014-09-01

    We here review Babylonian descriptions of neurological and psychiatric disorders, including epilepsy, stroke, psychoses, obsessive compulsive disorder, phobias, psychopathic behaviour, depression and anxiety. Most of these accounts date from the first Babylonian dynasty of the first half of the second millennium BC, within a millennium and a half of the origin of writing. The Babylonians were remarkably acute and objective observers of medical disorders and human behaviour. Their detailed descriptions are surprisingly similar to modern 19th and 20th century AD textbook accounts, with the exception of subjective thoughts and feelings which are more modern fields of enquiry. They had no knowledge of brain or psychological function. Some neuropsychiatric disorders, e.g. stroke or facial palsy, had a physical basis requiring the attention of a physician or asû, using a plant and mineral based pharmacology; some disorders such as epilepsy, psychoses, depression and anxiety were regarded as supernatural due to evil demons or spirits, or the anger of personal gods, and thus required the intervention of the priest or ašipu; other disorders such as obsessive compulsive disorder and psychopathic behaviour were regarded as a mystery. The Babylonians were the first to describe the clinical foundations of neurology and psychiatry. We discuss these accounts in relation to subsequent and more modern clinical descriptions. PMID:25037816

  3. Moderate exercise increases the metabolism and immune function of lymphocytes in rats.

    PubMed

    Navarro, Francisco; Bacurau, Aline Villa Nova; Pereira, Guilherme Borges; Araújo, Ronaldo Carvalho; Almeida, Sandro Soares; Moraes, Milton Rocha; Uchida, Marco Carlos; Costa Rosa, Luis Fernando Bicudo Pereira; Navalta, James; Prestes, Jonato; Bacurau, Reury Frank Pereira

    2013-05-01

    Exercise modulates both glucose and glutamine metabolism which influences lymphocyte function. We investigated the influence of chronic moderate exercise on glucose and glutamine metabolism in lymphocytes, the associated influence on proliferation, and cytokine and immunoglobulin production. Male Wistar rats (8 weeks old) were placed in an exercise training group (N = 15, 1 h day(-1) at 60 % VO₂max, 5 days week(-1)) for 8 weeks of exercise, or a sedentary control group. Twenty-four hours following the final training session, lymphocytes were separated, and the incorporation of [U-14C]-glucose, [U-14C]-glutamine, and [2-14C]-thymidine from the supernatant was measured. The activity of glucose-6-phosphate dehydrogenase, hexokinase, and glutaminase was measured. Lymphocytes were stimulated with ConA and LPS and incubated with the Mycobacterium bovis bacille Calmette-Guerin (BCG) vaccine and plasma IgG and IgE were measured. Glutamine metabolism increased in both T and B lymphocytes in the trained group. In the trained group, proliferative capacity increased T lymphocytes under ConA stimulation, and increased B lymphocytes with LPS. There was a significant increase in IL-2 production and decrease in IL-4 in the trained group compared with sedentary controls. IL-2R and TNFR increased in trained rats while IL-4R decreased and were more pronounced in T lymphocytes compared with B lymphocytes. In both lymphocyte subsets, exercise training significantly increased the expression of CD54+ and CD30+ cell markers. Exercise training increased plasma IgG compared with the sedentary group. In conclusion, moderate exercise training improves immune function and metabolism in T and B lymphocytes, reflecting an increased ability to respond to immune challenges. PMID:23212119

  4. Systematic analysis of the regulatory functions of microRNAs in chicken hepatic lipid metabolism

    PubMed Central

    Li, Hong; Ma, Zheng; Jia, Lijuan; Li, Yanmin; Xu, Chunlin; Wang, Taian; Han, Ruili; Jiang, Ruirui; Li, Zhuanjian; Sun, Guirong; Kang, Xiangtao; Liu, Xiaojun

    2016-01-01

    Laying performance is an important economic trait in hens, and this physiological process is largely influenced by the liver function. The livers of hens at 20- and 30-week-old stages were investigated using the next generation sequencing to identify the differences of microRNA expression profiles. Compared with the 20-week-old hens, 67 down- and 13 up-regulated microRNAs were verified to be significant differentially expressed (false discovery rate, FDR ≤ 0.05) (SDE) in the 30-week-old. We also identified 13 down- and 6 up-regulated novel differentially expressed (DE) microRNAs. miR-22-3p and miR-146b-5p, which exhibit critical roles in mammalian lipid metabolism, showed the most abundant expression and the highest fold-change, respectively. A total of 648 potential target genes of the SDE microRNAs were identified through an integrated analysis of microRNAs and the DE genes obtained in previous RNA-sequencing, including FADS1, FADS2, ELOVL6 and ACSL5, which are critical lipid metabolism-related regulators. Bioinformatic analyses revealed that target genes were mainly enriched in lipid-related metabolism processes. This work provides the first study of the expression patterns of hepatic microRNAs between 20- and 30-week old hens. The findings may serve as a fundamental resource for understanding the detailed functions of microRNAs in the molecular regulatory systems of lipid metabolism. PMID:27535581

  5. Glucose ameliorates the metabolic profile and mitochondrial function of platelet concentrates during storage in autologous plasma

    PubMed Central

    Amorini, Angela M.; Tuttobene, Michele; Tomasello, Flora M.; Biazzo, Filomena; Gullotta, Stefano; De Pinto, Vito; Lazzarino, Giuseppe; Tavazzi, Barbara

    2013-01-01

    Background It is essential that the quality of platelet metabolism and function remains high during storage in order to ensure the clinical effectiveness of a platelet transfusion. New storage conditions and additives are constantly evaluated in order to achieve this. Using glucose as a substrate is controversial because of its potential connection with increased lactate production and decreased pH, both parameters triggering the platelet lesion during storage. Materials and methods In this study, we analysed the morphological status and metabolic profile of platelets stored for various periods in autologous plasma enriched with increasing glucose concentrations (13.75, 27.5 and 55 mM). After 0, 2, 4, 6 and 8 days, high energy phosphates (ATP, GTP, ADP, AMP), oxypurines (hypoxanthine, xanthine, uric acid), lactate, pH, mitochondrial function, cell lysis and morphology, were evaluated. Results The data showed a significant dose-dependent improvement of the different parameters in platelets stored with increasing glucose, compared to what detected in controls. Interestingly, this phenomenon was more marked at the highest level of glucose tested and in the period of time generally used for platelet transfusion (0–6 days). Conclusion These results indicate that the addition of glucose during platelet storage ameliorates, in a dose-dependent manner, the biochemical parameters related to energy metabolism and mitochondrial function. Since there was no correspondence between glucose addition, lactate increase and pH decrease in our experiments, it is conceivable that platelet derangement during storage is not directly caused by glucose through an increase of anaerobic glycolysis, but rather to a loss of mitochondrial functions caused by reduced substrate availability. PMID:22682337

  6. Neurologic injury in snowmobiling

    PubMed Central

    Plog, Benjamin A.; Pierre, Clifford A.; Srinivasan, Vasisht; Srinivasan, Kaushik; Petraglia, Anthony L.; Huang, Jason H.

    2014-01-01

    Background: Snowmobiles are increasingly popular recreational, all-terrain utility vehicles that require skill and physical strength to operate given their inherent maneuverability, acceleration, and top speed capabilities. These same characteristics increase the risk of injury with the operation of these vehicles, particularly neurological injury. We characterize our series of 107 patients involved in snowmobiling accidents. Methods: From January 2004 to January 2012, all snowmobiling-related injuries referred to our regional trauma center were reviewed. Information had been recorded in the hospital's trauma registry and medical records were retrospectively reviewed for data pertaining to the injuries, with particular emphasis on neurological injuries and any associated details. Results: A total of 107 patients were identified. Ninety percent of injured riders were male. The mean age was 34.4 years (range 10-70), with 7% younger than age 16. The mean Injury Severity Score was 12.0 ± 0.69 (range 1-34). Although not documented in all patients, alcohol use was found in 7.5% of the patients and drug use found in one patient. Documentation of helmet use was available for only 31 of the patients; of which 13% were not helmeted. Causes included being thrown, flipped, or roll-over (33%), striking a stationary object (27%), being struck by a snowmobile (9%), striking another snowmobile (5.5%) or a car, train, or truck (5.5%), being injured by the machine itself (9%), other (2%) or unspecified (18%). Head injuries occurred in 35% patients, including concussion, subarachnoid hemorrhage, subdural hematoma, contusion, and facial/skull fracture. Spinal fractures occurred in 21% of the patients. Fractures to the thoracic spine were the most common (50%), followed by the cervical (41%) and lumbar (36%) spine. There were also three brachial plexus injuries, one tibial nerve injury, and one internal carotid artery dissection. Average length of stay was 4.98 ± 0.56 days

  7. The functional neuroanatomy of Tourette's syndrome: an FDG PET study III: functional coupling of regional cerebral metabolic rates.

    PubMed

    Jeffries, K J; Schooler, C; Schoenbach, C; Herscovitch, P; Chase, T N; Braun, A R

    2002-07-01

    Functional coupling of regional cerebral metabolic rates for glucose measured with [18F]-Fluoro-2-deoxy-D-glucose PET was compared in 18 drug-free patients with Tourette's Syndrome (TS) and 16 age- and sex-matched control subjects. Pearson product-moment correlation matrices containing correlations between metabolic rates in regions sampled throughout the brain were generated independently for TS patients and controls and compared. Significant differences between Z-transformed correlation coefficients were used to identify group differences, and revealed that the connectivity of the ventral striatum was most severely affected in TS. Changes in the coupling of other brain areas-primary motor areas, somatosensory association areas, and insula-also appeared to differentiate TS patients and controls. Evaluation of interrelationships between cortico-striato-thalamo-cortical circuits revealed the existence of functional connections between the motor and lateral orbitofrontal circuits in both groups, however, a reversal in the pattern of these interactions differentiated TS patients and controls. In controls, activity in these circuits appeared to be negatively correlated-i.e. increased activity in one is associated with relative inactivity the other. In TS patients, on the other hand, activity in the motor and lateral orbitofrontal circuits appears to be positively coupled. These results lend further credence to the hypothesis that altered limbic-motor interactions represent a pathophysiological hallmark of this disease.

  8. Butyrate alleviates metabolic impairments and protects pancreatic β cell function in pregnant mice with obesity.

    PubMed

    Li, Hua-Ping; Chen, Xuan; Li, Ming-Qing

    2013-01-01

    The relative or absolute deficiency of pancreatic β-cell mass function underlies the pathogenesis of diabetes. It is necessary to alleviate the metabolic stress and reduce the demand for insulin to decrease the effects of mutations affecting β-cell expansion. Butyrate is a natural nutrient existed in food and can also be produced physiologically through the intestinal fermentation of fiber. Pregnancy and obesity model would be helpful for understanding how β-cell adapt to insulin resistance and how butyrate alleviate the metabolic impairment and protect pancreatic β cell function in pregnant mice with obesity. C57BL/6J female mice were divided into three groups and fed with high fat food (HF group, 40% energy from fat), high fat with sodium butyrate food (HSF group, 95% HF with 5% butyrate), or control food (CF group, 14% energy from fat), respectively. The feeding would last for 14 weeks before mating and throughout the gestation period. A subset of dams were sacrificed at gestational day (GD) 14.5 to evaluate the changes of metabolism and β-cell function, mass, proliferation and apoptosis, inflammatory reaction of islet from different diet. Pancreases were double immuno-labeled to assess the islet morphology, insulin expression, expression of proliferation gene PCNA and anti-apoptosis gene bcl-2. Moreover, we detected the expression of NF-κB, phosphorylated NF-κB (pNF-κB) to evaluate the islet inflammatory response with immunohistochemistry. Mice fed with HSF showed obviously changes including the decreased values of weight gain, glucose, insulin, triglyceride and total cholesterol level of blood compared with high fat diet group, and the reduced circulating maternal pro-inflammation factors at GD14.5. Mice fed with HF displayed β-cell hyperplasia with a greater β-cell size and β-cell area in pancreas. Furthermore, the higher ratio of apoptosis and inflammatory response were found in HF group compared with HSF and CF group, while the proliferation

  9. Intraspecific variation in flight metabolic rate in the bumblebee Bombus impatiens: repeatability and functional determinants in workers and drones.

    PubMed

    Darveau, Charles-A; Billardon, Fannie; Bélanger, Kasandra

    2014-02-15

    The evolution of flight energetics requires that phenotypes be variable, repeatable and heritable. We studied intraspecific variation in flight energetics in order to assess the repeatability of flight metabolic rate and wingbeat frequency, as well as the functional basis of phenotypic variation in workers and drones of the bumblebee species Bombus impatiens. We showed that flight metabolic rate and wingbeat frequency were highly repeatable in workers, even when controlling for body mass variation using residual analysis. We did not detect significant repeatability in drones, but a smaller range of variation might have prevented us from finding significant values in our sample. Based on our results and previous findings, we associated the high repeatability of flight phenotypes in workers to the functional links between body mass, thorax mass, wing size, wingbeat frequency and metabolic rate. Moreover, differences between workers and drones were as predicted from these functional associations, where drones had larger wings for their size, lower wingbeat frequency and lower flight metabolic rate. We also investigated thoracic muscle metabolic phenotypes by measuring the activity of carbohydrate metabolism enzymes, and we found positive correlations between mass-independent metabolic rate and the activity of all enzymes measured, but in workers only. When comparing workers and drones that differ in flight metabolic rate, only the activity of the enzymes hexokinase and trehalase showed the predicted differences. Overall, our study indicates that there should be correlated evolution among physiological phenotypes at multiple levels of organization and morphological traits associated with flight.

  10. Intraspecific variation in flight metabolic rate in the bumblebee Bombus impatiens: repeatability and functional determinants in workers and drones.

    PubMed

    Darveau, Charles-A; Billardon, Fannie; Bélanger, Kasandra

    2014-02-15

    The evolution of flight energetics requires that phenotypes be variable, repeatable and heritable. We studied intraspecific variation in flight energetics in order to assess the repeatability of flight metabolic rate and wingbeat frequency, as well as the functional basis of phenotypic variation in workers and drones of the bumblebee species Bombus impatiens. We showed that flight metabolic rate and wingbeat frequency were highly repeatable in workers, even when controlling for body mass variation using residual analysis. We did not detect significant repeatability in drones, but a smaller range of variation might have prevented us from finding significant values in our sample. Based on our results and previous findings, we associated the high repeatability of flight phenotypes in workers to the functional links between body mass, thorax mass, wing size, wingbeat frequency and metabolic rate. Moreover, differences between workers and drones were as predicted from these functional associations, where drones had larger wings for their size, lower wingbeat frequency and lower flight metabolic rate. We also investigated thoracic muscle metabolic phenotypes by measuring the activity of carbohydrate metabolism enzymes, and we found positive correlations between mass-independent metabolic rate and the activity of all enzymes measured, but in workers only. When comparing workers and drones that differ in flight metabolic rate, only the activity of the enzymes hexokinase and trehalase showed the predicted differences. Overall, our study indicates that there should be correlated evolution among physiological phenotypes at multiple levels of organization and morphological traits associated with flight. PMID:24198266

  11. Sequence- and Structure-Based Functional Annotation and Assessment of Metabolic Transporters in Aspergillus oryzae: A Representative Case Study

    PubMed Central

    Raethong, Nachon; Wong-ekkabut, Jirasak; Laoteng, Kobkul; Vongsangnak, Wanwipa

    2016-01-01

    Aspergillus oryzae is widely used for the industrial production of enzymes. In A. oryzae metabolism, transporters appear to play crucial roles in controlling the flux of molecules for energy generation, nutrients delivery, and waste elimination in the cell. While the A. oryzae genome sequence is available, transporter annotation remains limited and thus the connectivity of metabolic networks is incomplete. In this study, we developed a metabolic annotation strategy to understand the relationship between the sequence, structure, and function for annotation of A. oryzae metabolic transporters. Sequence-based analysis with manual curation showed that 58 genes of 12,096 total genes in the A. oryzae genome encoded metabolic transporters. Under consensus integrative databases, 55 unambiguous metabolic transporter genes were distributed into channels and pores (7 genes), electrochemical potential-driven transporters (33 genes), and primary active transporters (15 genes). To reveal the transporter functional role, a combination of homology modeling and molecular dynamics simulation was implemented to assess the relationship between sequence to structure and structure to function. As in the energy metabolism of A. oryzae, the H+-ATPase encoded by the AO090005000842 gene was selected as a representative case study of multilevel linkage annotation. Our developed strategy can be used for enhancing metabolic network reconstruction. PMID:27274991

  12. Estrogen receptor alpha activation enhances mitochondrial function and systemic metabolism in high-fat-fed ovariectomized mice.

    PubMed

    Hamilton, Dale J; Minze, Laurie J; Kumar, Tanvi; Cao, Tram N; Lyon, Christopher J; Geiger, Paige C; Hsueh, Willa A; Gupte, Anisha A

    2016-09-01

    Estrogen impacts insulin action and cardiac metabolism, and menopause dramatically increases cardiometabolic risk in women. However, the mechanism(s) of cardiometabolic protection by estrogen remain incompletely understood. Here, we tested the effects of selective activation of E2 receptor alpha (ERα) on systemic metabolism, insulin action, and cardiac mitochondrial function in a mouse model of metabolic dysfunction (ovariectomy [OVX], insulin resistance, hyperlipidemia, and advanced age). Middle-aged (12-month-old) female low-density lipoprotein receptor (Ldlr)(-/-) mice were subjected to OVX or sham surgery and fed "western" high-fat diet (WHFD) for 3 months. Selective ERα activation with 4,4',4″-(4-Propyl-[1H]-pyrazole-1,3,5-triyl) (PPT), prevented weight gain, improved insulin action, and reduced visceral fat accumulation in WHFD-fed OVX mice. PPT treatment also elevated systemic metabolism, increasing oxygen consumption and core body temperature, induced expression of several metabolic genes such as peroxisome proliferator-activated receptor gamma, coactivator 1 alpha, and nuclear respiratory factor 1 in heart, liver, skeletal muscle, and adipose tissue, and increased cardiac mitochondrial function. Taken together, selective activation of ERα with PPT enhances metabolic effects including insulin resistance, whole body energy metabolism, and mitochondrial function in OVX mice with metabolic syndrome. PMID:27582063

  13. Recognition and treatment of neurologic Wilson's disease.

    PubMed

    Lorincz, Matthew T

    2012-11-01

    As Wilson's disease is both preventable and treatable, the diagnosis must not be missed. Despite this, it is usually misdiagnosed. Misdiagnosis and delay in treatment are clinically relevant because if left untreated, Wilson's disease progresses to hepatic failure or severe neurologic disability, and death. Those adequately treated have a normal life span. Wilson's disease is an autosomal recessive disease caused by mutations in the ATP7B gene. Mutations in ATP7B result in abnormal copper metabolism and subsequent toxic accumulation of copper. The clinical manifestations of neurologic Wilson's disease include variable combinations of dysarthria, dystonia, tremor, parkinsonism, ataxia, and choreoathetosis. Once the possibility of Wilson's disease is considered, diagnosis is straight forward. Currently available treatments, including zinc acetate and trientine, are generally well tolerated and effective.

  14. Protective effects of ginseng on neurological disorders

    PubMed Central

    Ong, Wei-Yi; Farooqui, Tahira; Koh, Hwee-Ling; Farooqui, Akhlaq A.; Ling, Eng-Ang

    2015-01-01

    Ginseng (Order: Apiales, Family: Araliaceae, Genus: Panax) has been used as a traditional herbal medicine for over 2000 years, and is recorded to have antianxiety, antidepressant and cognition enhancing properties. The protective effects of ginseng on neurological disorders are discussed in this review. Ginseng species and ginsenosides, and their intestinal metabolism and bioavailability are briefly introduced. This is followed by molecular mechanisms of effects of ginseng on the brain, including glutamatergic transmission, monoamine transmission, estrogen signaling, nitric oxide (NO) production, the Keap1/Nrf2 adaptive cellular stress pathway, neuronal survival, apoptosis, neural stem cells and neuroregeneration, microglia, astrocytes, oligodendrocytes and cerebral microvessels. The molecular mechanisms of the neuroprotective effects of ginseng in Alzheimer’s disease (AD) including β-amyloid (Aβ) formation, tau hyperphosphorylation and oxidative stress, major depression, stroke, Parkinson’s disease and multiple sclerosis are presented. It is hoped that this discussion will stimulate more studies on the use of ginseng in neurological disorders. PMID:26236231

  15. Prenatal Antecedents of Newborn Neurological Maturation

    ERIC Educational Resources Information Center

    DiPietro, Janet A.; Kivlighan, Katie T.; Costigan, Kathleen A.; Rubin, Suzanne E.; Shiffler, Dorothy E.; Henderson, Janice L.; Pillion, Joseph P.

    2010-01-01

    Fetal neurobehavioral development was modeled longitudinally using data collected at weekly intervals from 24 to 38 weeks gestation in a sample of 112 healthy pregnancies. Predictive associations between 3 measures of fetal neurobehavioral functioning and their developmental trajectories to neurological maturation in the first weeks after birth…

  16. Beclin 2 Functions in Autophagy, Degradation of G Protein-Coupled Receptors, and Metabolism

    PubMed Central

    He, Congcong; Wei, Yongjie; Sun, Kai; Li, Binghua; Dong, Xiaonan; Zou, Zhongju; Liu, Yang; Kinch, Lisa N.; Khan, Shaheen; Sinha, Sangita; Xavier, Ramnik J.; Grishin, Nick V.; Xiao, Guanghua; Eskelinen, Eeva-Liisa; Scherer, Philipp E.; Whistler, Jennifer L.; Levine, Beth

    2013-01-01

    Summary The molecular mechanism of autophagy and its relationship to other lysosomal degradation pathways remain incompletely understood. Here, we identified a previously uncharacterized mammalian-specific protein, Beclin 2, which like Beclin 1, functions in autophagy and interacts with class III PI3K complex components and Bcl-2. However, Beclin 2, but not Beclin 1, functions in an additional lysosomal degradation pathway. Beclin 2 is required for ligand-induced endolysosomal degradation of several G protein-coupled receptors (GPCRs) through its interaction with GASP1. Beclin 2 homozygous knockout mice have decreased embryonic viability, and heterozygous knockout mice have defective autophagy, increased levels of brain cannabinoid 1 receptor, elevated food intake, and obesity and insulin resistance. Our findings identify Beclin 2 as a novel converging regulator of autophagy and GPCR turnover, and highlight the functional and mechanistic diversity of Beclin family members in autophagy, endolysosomal trafficking and metabolism. PMID:23954414

  17. Thermography in Neurologic Practice

    PubMed Central

    Neves, Eduardo Borba; Vilaça-Alves, José; Rosa, Claudio; Reis, Victor Machado

    2015-01-01

    One kind of medical images that has been developed in the last decades is thermal images. These images are assessed by infrared cameras and have shown an exponential development in recent years. In this sense, the aim of this study was to describe possibilities of thermography usage in the neurologic practice. It was performed a systematic review in Web of Knowledge (Thompson Reuters), set in all databases which used two combination of keywords as “topic”: “thermography” and “neurology”; and “thermography” and “neurologic”. The chronological period was defined from 2000 to 2014 (the least 15 years). Among the studies included in this review, only seven were with experimental design. It is few to bring thermography as a daily tool in clinical practice. However, these studies have suggested good results. The studies of review and an analyzed patent showed that the authors consider the thermography as a diagnostic tool and they recommend its usage. It can be concluded that thermography is already used as a diagnostic and monitoring tool of patients with neuropathies, particularly in complex regional pain syndrome, and stroke. And yet, this tool has great potential for future research about its application in diagnosis of other diseases of neurological origin. PMID:26191090

  18. Neurology and diving.

    PubMed

    Massey, E Wayne; Moon, Richard E

    2014-01-01

    Diving exposes a person to the combined effects of increased ambient pressure and immersion. The reduction in pressure when surfacing can precipitate decompression sickness (DCS), caused by bubble formation within tissues due to inert gas supersaturation. Arterial gas embolism (AGE) can also occur due to pulmonary barotrauma as a result of breath holding during ascent or gas trapping due to disease, causing lung hyperexpansion, rupture and direct entry of alveolar gas into the blood. Bubble disease due to either DCS or AGE is collectively known as decompression illness. Tissue and intravascular bubbles can induce a cascade of events resulting in CNS injury. Manifestations of decompression illness can vary in severity, from mild (paresthesias, joint pains, fatigue) to severe (vertigo, hearing loss, paraplegia, quadriplegia). Particularly as these conditions are uncommon, early recognition is essential to provide appropriate management, consisting of first aid oxygen, targeted fluid resuscitation and hyperbaric oxygen, which is the definitive treatment. Less common neurologic conditions that do not require hyperbaric oxygen include rupture of a labyrinthine window due to inadequate equalization of middle ear pressure during descent, which can precipitate vertigo and hearing loss. Sinus and middle ear overpressurization during ascent can compress the trigeminal and facial nerves respectively, causing temporary facial hypesthesia and lower motor neuron facial weakness. Some conditions preclude safe diving, such as seizure disorders, since a convulsion underwater is likely to be fatal. Preventive measures to reduce neurologic complications of diving include exclusion of individuals with specific medical conditions and safe diving procedures, particularly related to descent and ascent.

  19. Correlating Structure and Function of Drug-Metabolizing Enzymes: Progress and Ongoing Challenges

    PubMed Central

    Johnson, Eric F.; Connick, J. Patrick; Reed, James R.; Backes, Wayne L.; Desai, Manoj C.; Xu, Lianhong; Estrada, D. Fernando; Laurence, Jennifer S.

    2014-01-01

    This report summarizes a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics at Experimental Biology held April 20-24 in Boston, MA. Presentations discussed the status of cytochrome P450 (P450) knowledge, emphasizing advances and challenges in relating structure with function and in applying this information to drug design. First, at least one structure of most major human drug-metabolizing P450 enzymes is known. However, the flexibility of these active sites can limit the predictive value of one structure for other ligands. A second limitation is our coarse-grain understanding of P450 interactions with membranes, other P450 enzymes, NADPH–cytochrome P450 reductase, and cytochrome b5. Recent work has examined differential P450 interactions with reductase in mixed P450 systems and P450:P450 complexes in reconstituted systems and cells, suggesting another level of functional control. In addition, protein nuclear magnetic resonance is a new approach to probe these protein/protein interactions, identifying interacting b5 and P450 surfaces, showing that b5 and reductase binding are mutually exclusive, and demonstrating ligand modulation of CYP17A1/b5 interactions. One desired outcome is the application of such information to control drug metabolism and/or design selective P450 inhibitors. A final presentation highlighted development of a CYP3A4 inhibitor that slows clearance of human immunodeficiency virus drugs otherwise rapidly metabolized by CYP3A4. Although understanding P450 structure/function relationships is an ongoing challenge, translational advances will benefit from continued integration of existing and new biophysical approaches. PMID:24130370

  20. Dichloroacetate selectively improves cardiac function and metabolism in female and male rainbow trout.

    PubMed

    Battiprolu, Pavan K; Rodnick, Kenneth J

    2014-11-15

    Cardiac tissue from female rainbow trout demonstrates a sex-specific preference for exogenous glucose and glycolysis, impaired Ca(2+) handling, and a greater tolerance for hypoxia and reoxygenation than cardiac tissue from male rainbow trout. We tested the hypothesis that dichloroacetate (DCA), an activator of pyruvate dehydrogenase, enhances cardiac energy metabolism and Ca(2+) handling in female preparations and provide cardioprotection for hypoxic male tissue. Ventricle strips from sexually immature fish with very low (male) and nondetectable (female) plasma sex steroids were electrically paced in oxygenated or hypoxic Ringer solution with or without 1 mM DCA. In the presence of 5 mM glucose, aerobic tissue from male trout could be paced at a higher frequency (1.79 vs. 1.36 Hz) with lower resting tension and less contractile dysfunction than female tissue. At 0.5 Hz, DCA selectively reduced resting tension below baseline values and lactate efflux by 75% in aerobic female ventricle strips. DCA improved the functional recovery of developed twitch force, reduced lactate efflux by 50%, and doubled citrate in male preparations after hypoxia-reoxygenation. Independent of female sex steroids, reduced myocardial pyruvate dehydrogenase activity and impaired carbohydrate oxidation might explain the higher lactate efflux, compromised function of the sarcoplasmic reticulum, and reduced mechanical performance of aerobic female tissue. Elevated oxidative metabolism and reduced glycolysis might also underlie the beneficial effects of DCA on the mechanical recovery of male cardiac tissue after hypoxia-reoxygenation. These results support the use of rainbow trout as an experimental model of sex differences of cardiovascular energetics and function, with the potential for modifying metabolic phenotypes and cardioprotection independent of sex steroids. PMID:25217653

  1. Correlating structure and function of drug-metabolizing enzymes: progress and ongoing challenges.

    PubMed

    Johnson, Eric F; Connick, J Patrick; Reed, James R; Backes, Wayne L; Desai, Manoj C; Xu, Lianhong; Estrada, D Fernando; Laurence, Jennifer S; Scott, Emily E

    2014-01-01

    This report summarizes a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics at Experimental Biology held April 20-24 in Boston, MA. Presentations discussed the status of cytochrome P450 (P450) knowledge, emphasizing advances and challenges in relating structure with function and in applying this information to drug design. First, at least one structure of most major human drug-metabolizing P450 enzymes is known. However, the flexibility of these active sites can limit the predictive value of one structure for other ligands. A second limitation is our coarse-grain understanding of P450 interactions with membranes, other P450 enzymes, NADPH-cytochrome P450 reductase, and cytochrome b5. Recent work has examined differential P450 interactions with reductase in mixed P450 systems and P450:P450 complexes in reconstituted systems and cells, suggesting another level of functional control. In addition, protein nuclear magnetic resonance is a new approach to probe these protein/protein interactions, identifying interacting b5 and P450 surfaces, showing that b5 and reductase binding are mutually exclusive, and demonstrating ligand modulation of CYP17A1/b5 interactions. One desired outcome is the application of such information to control drug metabolism and/or design selective P450 inhibitors. A final presentation highlighted development of a CYP3A4 inhibitor that slows clearance of human immunodeficiency virus drugs otherwise rapidly metabolized by CYP3A4. Although understanding P450 structure/function relationships is an ongoing challenge, translational advances will benefit from continued integration of existing and new biophysical approaches.

  2. Catalytic function of the mycobacterial binuclear iron monooxygenase in acetone metabolism.

    PubMed

    Furuya, Toshiki; Nakao, Tomomi; Kino, Kuniki

    2015-10-01

    Mycobacteria such as Mycobacterium smegmatis strain mc(2)155 and Mycobacterium goodii strain 12523 are able to grow on acetone and use it as a source of carbon and energy. We previously demonstrated by gene deletion analysis that the mimABCD gene cluster, which encodes a binuclear iron monooxygenase, plays an essential role in acetone metabolism in these mycobacteria. In the present study, we determined the catalytic function of MimABCD in acetone metabolism. Whole-cell assays were performed using Escherichia coli cells expressing the MimABCD complex. When the recombinant E. coli cells were incubated with acetone, a product was detected by gas chromatography (GC) analysis. Based on the retention time and the gas chromatography-mass spectrometry (GC-MS) spectrum, the reaction product was identified as acetol (hydroxyacetone). The recombinant E. coli cells produced 1.02 mM of acetol from acetone within 24 h. Furthermore, we demonstrated that MimABCD also was able to convert methylethylketone (2-butanone) to 1-hydroxy-2-butanone. Although it has long been known that microorganisms such as mycobacteria metabolize acetone via acetol, this study provides the first biochemical evidence for the existence of a microbial enzyme that catalyses the conversion of acetone to acetol.

  3. Metabolic Plasticity in Cancer Cells: Reconnecting Mitochondrial Function to Cancer Control

    PubMed Central

    Ramanujan, V. Krishnan

    2015-01-01

    Anomalous increase in glycolytic activity defines one of the key metabolic alterations in cancer cells. A realization of this feature has led to critical advancements in cancer detection techniques such as positron emission tomography (PET) as well as a number of therapeutic avenues targeting the key glycolytic steps within a cancer cell. A normal healthy cell’s survival relies on a sensitive balance between the primordial glycolysis and a more regulated mitochondrial bioenergetics. The salient difference between these two bioenergetics pathways is that oxygen availability is an obligatory requirement for mitochondrial pathway while glycolysis can function without oxygen. Early observations that some cancer cells up-regulate glycolytic activity even in the presence of oxygen (aerobic glycolysis) led to a hypothesis that such an altered cancer cell metabolism stems from inherent mitochondrial dysfunction. While a general validity of this hypothesis is still being debated, a number of recent research efforts have yielded clarity on the physiological origins of this aerobic glycolysis phenotype in cancer cells. Building on these recent studies, we present a generalized scheme of cancer cell metabolism and propose a novel hypothesis that might rationalize new avenues of cancer intervention. PMID:26457230

  4. Peroxisomes are required for lipid metabolism and muscle function in Drosophila melanogaster.

    PubMed

    Faust, Joseph E; Manisundaram, Arvind; Ivanova, Pavlina T; Milne, Stephen B; Summerville, James B; Brown, H Alex; Wangler, Michael; Stern, Michael; McNew, James A

    2014-01-01

    Peroxisomes are ubiquitous organelles that perform lipid and reactive oxygen species metabolism. Defects in peroxisome biogenesis cause peroxisome biogenesis disorders (PBDs). The most severe PBD, Zellweger syndrome, is characterized in part by neuronal dysfunction, craniofacial malformations, and low muscle tone (hypotonia). These devastating diseases lack effective therapies and the development of animal models may reveal new drug targets. We have generated Drosophila mutants with impaired peroxisome biogenesis by disrupting the early peroxin gene pex3, which participates in budding of pre-peroxisomes from the ER and peroxisomal membrane protein localization. pex3 deletion mutants lack detectible peroxisomes and die before or during pupariation. At earlier stages of development, larvae lacking Pex3 display reduced size and impaired lipid metabolism. Selective loss of peroxisomes in muscles impairs muscle function and results in flightless animals. Although, hypotonia in PBD patients is thought to be a secondary effect of neuronal dysfunction, our results suggest that peroxisome loss directly affects muscle physiology, possibly by disrupting energy metabolism. Understanding the role of peroxisomes in Drosophila physiology, specifically in muscle cells may reveal novel aspects of PBD etiology.

  5. Antioxidant Drug Tempol Promotes Functional Metabolic Changes in the Gut Microbiota.

    PubMed

    Cai, Jingwei; Zhang, Limin; Jones, Richard A; Correll, Jared B; Hatzakis, Emmanuel; Smith, Philip B; Gonzalez, Frank J; Patterson, Andrew D

    2016-02-01

    Recent studies have identified the important role of the gut microbiota in the pathogenesis and progression of obesity and related metabolic disorders. The antioxidant tempol was shown to prevent or reduce weight gain and modulate the gut microbiota community in mice; however, the mechanism by which tempol modulates weight gain/loss with respect to the host and gut microbiota has not been clearly established. Here we show that tempol (0, 1, 10, and 50 mg/kg p.o. for 5 days) decreased cecal bacterial fermentation and increased fecal energy excretion in a dose-dependent manner. Liver (1)H NMR-based metabolomics identified a dose-dependent decrease in glycogen and glucose, enhanced glucogenic and ketogenic activity (tyrosine and phenylalanine), and increased activation of the glycolysis pathway. Serum (1)H NMR-based metabolomics indicated that tempol promotes enhanced glucose catabolism. Hepatic gene expression was significantly altered as demonstrated by an increase in Pepck and G6pase and a decrease in Hnf4a, ChREBP, Fabp1, and Cd36 mRNAs. No significant change in the liver and serum metabolomic profiles was observed in germ-free mice, thus establishing a significant role for the gut microbiota in mediating the beneficial metabolic effects of tempol. These results demonstrate that tempol modulates the gut microbial community and its function, resulting in reduced host energy availability and a significant shift in liver metabolism toward a more catabolic state. PMID:26696396

  6. Tributyltin chloride leads to adiposity and impairs metabolic functions in the rat liver and pancreas.

    PubMed

    Bertuloso, Bruno D; Podratz, Priscila L; Merlo, Eduardo; de Araújo, Julia F P; Lima, Leandro C F; de Miguel, Emilio C; de Souza, Leticia N; Gava, Agata L; de Oliveira, Miriane; Miranda-Alves, Leandro; Carneiro, Maria T W D; Nogueira, Celia R; Graceli, Jones B

    2015-05-19

    Tributyltin chloride (TBT) is an environmental contaminant used in antifouling paints of boats. Endocrine disruptor effects of TBT are well established in animal models. However, the adverse effects on metabolism are less well understood. The toxicity of TBT in the white adipose tissue (WAT), liver and pancreas of female rats were assessed. Animals were divided into control and TBT (0.1 μg/kg/day) groups. TBT induced an increase in the body weight of the rats by the 15th day of oral exposure. The weight gain was associated with high parametrial (PR) and retroperitoneal (RP) WAT weights. TBT-treatment increased the adiposity, inflammation and expression of ERα and PPARγ proteins in both RP and PR WAT. In 3T3-L1 cells, estrogen treatment reduced lipid droplets accumulation, however increased the ERα protein expression. In contrast, TBT-treatment increased the lipid accumulation and reduced the ERα expression. WAT metabolic changes led to hepatic inflammation, lipid accumulation, increase of PPARγ and reduction of ERα protein expression. Accordingly, there were increases in the glucose tolerance and insulin sensitivity tests with increases in the number of pancreatic islets and insulin levels. These findings suggest that TBT leads to adiposity in WAT specifically, impairing the metabolic functions of the liver and pancreas.

  7. The Effect of Marine Derived n-3 Fatty Acids on Adipose Tissue Metabolism and Function

    PubMed Central

    Todorčević, Marijana; Hodson, Leanne

    2015-01-01

    Adipose tissue function is key determinant of metabolic health, with specific nutrients being suggested to play a role in tissue metabolism. One such group of nutrients are the n-3 fatty acids, specifically eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3). Results from studies where human, animal and cellular models have been utilised to investigate the effects of EPA and/or DHA on white adipose tissue/adipocytes suggest anti-obesity and anti-inflammatory effects. We review here evidence for these effects, specifically focusing on studies that provide some insight into metabolic pathways or processes. Of note, limited work has been undertaken investigating the effects of EPA and DHA on white adipose tissue in humans whilst more work has been undertaken using animal and cellular models. Taken together it would appear that EPA and DHA have a positive effect on lowering lipogenesis, increasing lipolysis and decreasing inflammation, all of which would be beneficial for adipose tissue biology. What remains to be elucidated is the duration and dose required to see a favourable effect of EPA and DHA in vivo in humans, across a range of adiposity. PMID:26729182

  8. Homeostatic functions of the p53 tumor suppressor: regulation of energy metabolism and antioxidant defense

    PubMed Central

    Olovnikov, Ivan A.; Kravchenko, Julia E.; Chumakov, Peter M.

    2008-01-01

    The p53 tumor suppressor plays pivotal role in the organism by supervising strict compliance of individual cells to needs of the whole organisms. It has been widely accepted that p53 acts in response to stresses and abnormalities in cell physiology by mobilizing the repair processes or by removing the diseased cells through initiating the cell death programs. Recent studies, however, indicate that even under normal physiological conditions certain activities of p53 participate in homeostatic regulation of metabolic processes and that these activities are important for prevention of cancer. These novel functions of p53 help to align metabolic processes with the proliferation and energy status, to maintain optimal mode of glucose metabolism and to boost the energy efficient mitochondrial respiration in response to ATP deficiency. Additional activities of p53 in non-stressed cells tune up the antioxidant defense mechanisms reducing the probability of mutations caused by DNA oxidation under conditions of daily stresses. The deficiency in the p53-mediated regulation of glycolysis and mitochondrial respiration greatly accounts for the deficient respiration of the predominance of aerobic glycolysis in cancer cells (the Warburg effect), while the deficiency in the p53-modulated antioxidant defense mechanisms contributes to mutagenesis and additionally boosts the carcinogenesis process. PMID:19101635

  9. Enhancing enzyme stability and metabolic functional ability of β-galactosidase through functionalized polymer nanofiber immobilization.

    PubMed

    Misson, Mailin; Jin, Bo; Chen, Binghui; Zhang, Hu

    2015-10-01

    A functionalized polystyrene nanofiber (PSNF) immobilized β-galactosidase assembly (PSNF-Gal) was synthesized as a nanobiocatalyst aiming to enhance the biocatalyst stability and functional ability. The PSNF fabricated by electrospinning was functionalized through a chemical oxidation method for enzyme binding. The bioengineering performance of the enzyme carriers was further evaluated for bioconversion of lactose to galacto-oligosaccharides (GOS). The modified PSNF-Gal demonstrated distinguished performances to preserve the same activity as the free β-galactosidase at the optimum pH of 7.0, and to enhance the enzyme stability of PSNF-Gal in an alkaline condition up to pH 10. The PSNF assembly demonstrated improved thermal stability from 37 to 60 °C. The nanobiocatalyst was able to retain 30 % of its initial activity after ninth operation cycles comparing to four cycles with the unmodified counterpart. In contrast with free β-galactosidase, the modified PSNF-Gal enhanced the GOS yield from 14 to 28 %. These findings show the chemically modified PSNF-based nanobiocatalyst may be pertinent for various enzyme-catalysed bioprocessing applications.

  10. Mitochondrial (Dys)function in Adipocyte (De)differentiation and Systemic Metabolic Alterations

    PubMed Central

    De Pauw, Aurélia; Tejerina, Silvia; Raes, Martine; Keijer, Jaap; Arnould, Thierry

    2009-01-01

    In mammals, adipose tissue, composed of BAT and WAT, collaborates in energy partitioning and performs metabolic regulatory functions. It is the most flexible tissue in the body, because it is remodeled in size and shape by modifications in adipocyte cell size and/or number, depending on developmental status and energy fluxes. Although numerous reviews have focused on the differentiation program of both brown and white adipocytes as well as on the pathophysiological role of white adipose tissues, the importance of mitochondrial activity in the differentiation or the dedifferentiation programs of adipose cells and in systemic metabolic alterations has not been extensively reviewed previously. Here, we address the crucial role of mitochondrial functions during adipogenesis and in mature adipocytes and discuss the cellular responses of white adipocytes to mitochondrial activity impairment. In addition, we discuss the increase in scientific knowledge regarding mitochondrial functions in the last 10 years and the recent suspicion of mitochondrial dysfunction in several 21st century epidemics (ie, obesity and diabetes), as well as in lipodystrophy found in HIV-treated patients, which can contribute to the development of new therapeutic strategies targeting adipocyte mitochondria. PMID:19700756

  11. Effects of melatonin on water metabolism and renal function in male Syrian hamsters (Mesocricetus auratus).

    PubMed

    Richardson, B A; Studier, E H; Stallone, J N; Kennedy, C M

    1992-09-01

    The pineal indoleamine, melatonin, has been shown to influence many physiological systems within the mammalian body. Few studies, however, have examined the influence of melatonin on renal function. This study investigated the effects of melatonin on water metabolism and renal function. Young adult male Syrian hamsters were maintained on a long photoperiod (LD 14:10) in metabolic cages. The animals received daily (1700) injections of either control vehicle or 25 micrograms of melatonin for 85 consecutive days. Melatonin administration resulted in significant increases in water consumption and urine production. Water budgets were also significantly influenced by melatonin, as were urinary osmolality, urinary sodium, and potassium concentrations, but urinary calcium concentrations were essentially unaltered. When excretion rates for sodium, potassium, and calcium were calculated, no differences were observed between the vehicle control and melatonin-treated groups. Injections of melatonin also significantly decreased plasma antidiuretic hormone (ADH). These results demonstrate that afternoon injections of melatonin can alter renal function, which may involve direct (i.e., on ADH secretion and/or thirst mechanisms) or indirect (i.e., behavioral) effects. PMID:1453309

  12. Functional and metabolic disorders in celiac disease: new implications for nutritional treatment.

    PubMed

    Farnetti, Sara; Zocco, Maria Assunta; Garcovich, Matteo; Gasbarrini, Antonio; Capristo, Esmeralda

    2014-11-01

    Celiac disease (CD) is a chronic disease causing the inflammation of the proximal small intestine, in genetically predisposed individuals. This is triggered by the consumption of the gluten protein and the side effects of the disease are mitigated by a lifelong gluten-free diet (GFD) treatment. The predominant consequence of CD is malnutrition due to malabsorption (with diarrhea, weight loss, nutritional deficiencies, and altered blood parameters), especially in patients who do not show strict adherence to GFD treatment. Recent evidence shows that, despite a lifelong GFD, some functional disorders persist, such as compromised gallbladder function and motility, exocrine pancreatic insufficiency, increased gut permeability, small-intestinal bowel overgrowth, nonalcoholic fatty liver disease (NAFLD), lactose intolerance, and milk allergy. These abnormalities may predispose to the occurrence of overweight and obesity even in CD patients. This review focuses on the principal functional and metabolic disorders in both treated and untreated CD, ranging from alterations of the gastrointestinal system to impaired glucose and lipid metabolism and insulin secretion with the aim of providing new implications beyond a GFD, for an ad hoc nutrition treatment in these patients.

  13. The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity

    PubMed Central

    Heimbucher, Thomas; Liu, Zheng; Bossard, Carine; McCloskey, Richard; Carrano, Andrea C.; Riedel, Christian G.; Tanasa, Bogdan; Klammt, Christian; Fonslow, Bryan R.; Riera, Celine E.; Lillemeier, Bjorn F.; Kemphues, Kenneth; Yates, John R.; O'Shea, Clodagh; Hunter, Tony; Dillin, Andrew

    2015-01-01

    SUMMARY One of the major determinants of aging in organisms ranging from worms to man are FOXO family transcription factors, which are downstream effectors of Insulin/IGF-1 signaling (IIS). The molecular mechanisms that actively promote DAF16/FOXO stability and function are unknown. Here we identify the deubiquitylating enzyme MATH-33 as an essential DAF-16 regulator in IIS, which stabilizes active DAF-16 protein levels and, as a consequence, influences DAF-16 functions, such as metabolism, stress response and longevity in C. elegans. MATH-33 associates with DAF-16 in cellulo and in vitro. MATH-33 functions as a deubiquitylase by actively removing ubiquitin moieties from DAF-16, thus counteracting the action of the RLE-1 E3-ubiquitin ligase. Our findings support a model in which MATH-33 promotes DAF-16 stability in response to decreased IIS by directly modulating its ubiquitylation state, suggesting that regulated oscillations in the stability of DAF-16 protein play an integral role in controlling processes such as metabolism and longevity. PMID:26154057

  14. Microbial community proteomics for characterizing the range of metabolic functions and activities of human gut microbiota

    DOE PAGES

    Xiong, Weili; Abraham, Paul E.; Li, Zhou; Pan, Chongle; Robert L. Hettich

    2015-01-01

    We found that the human gastrointestinal (GI) tract is a complex, dynamic ecosystem that consists of a carefully tuned balance of human host and microbiota membership. The microbiome component is not insignificant, but rather provides important functions that are absolutely critical to many aspects of human health, including nutrient transformation and absorption, drug metabolism, pathogen defense, and immune system development. Microbial community proteomics (sometimes referred to as metaproteomics) provides a powerful approach to measure the range and details of human gut microbiota functions and metabolic activities, revealing information about microbiome development and stability especially with regard to human health vs.more » disease states. In most cases, both microbial and human proteins are extracted from fecal samples and then measured by the high performance MS-based proteomics technology. We review the field of human gut microbiome community proteomics, with a focus on the experimental and informatics considerations involved in characterizing systems that range from low complexity defined model gut microbiota in gnotobiotic mice, to the simple gut microbiota in the GI tract of newborn infants, and finally to the complex gut microbiota in adults. Moreover, the current state-of-the-art in experimental and bioinformatics capabilities for community proteomics enable a detailed measurement of the gut microbiota, yielding valuable insights into the broad functional profiles of even complex microbiota. Future developments are likely to expand into improved analysis throughput and coverage depth, as well as post-translational modification characterizations.« less

  15. Microbial community proteomics for characterizing the range of metabolic functions and activities of human gut microbiota

    SciTech Connect

    Xiong, Weili; Abraham, Paul E.; Li, Zhou; Pan, Chongle; Robert L. Hettich

    2015-01-01

    We found that the human gastrointestinal (GI) tract is a complex, dynamic ecosystem that consists of a carefully tuned balance of human host and microbiota membership. The microbiome component is not insignificant, but rather provides important functions that are absolutely critical to many aspects of human health, including nutrient transformation and absorption, drug metabolism, pathogen defense, and immune system development. Microbial community proteomics (sometimes referred to as metaproteomics) provides a powerful approach to measure the range and details of human gut microbiota functions and metabolic activities, revealing information about microbiome development and stability especially with regard to human health vs. disease states. In most cases, both microbial and human proteins are extracted from fecal samples and then measured by the high performance MS-based proteomics technology. We review the field of human gut microbiome community proteomics, with a focus on the experimental and informatics considerations involved in characterizing systems that range from low complexity defined model gut microbiota in gnotobiotic mice, to the simple gut microbiota in the GI tract of newborn infants, and finally to the complex gut microbiota in adults. Moreover, the current state-of-the-art in experimental and bioinformatics capabilities for community proteomics enable a detailed measurement of the gut microbiota, yielding valuable insights into the broad functional profiles of even complex microbiota. Future developments are likely to expand into improved analysis throughput and coverage depth, as well as post-translational modification characterizations.

  16. [Adipose tissue secretory function: implication in metabolic and cardiovascular complications of obesity].

    PubMed

    Guerre-Millo, Michèle

    2006-01-01

    The adipose tissue exerts a double function that is crucial for energy homeostasis. On the one hand, it is the only organ suited to stock triglycerides in highly specialized cells, the adipocytes. On the other hand, the adipose tissue produces biologically active molecules, collectively named "adipokines", which have been implicated in energy balance and glucose and lipid metabolism. Both adipocytes and cells of the stromal fraction participate in this function of secretion. The adipokines acts locally, in an autocrine or paracrine manner, and distantly (endocrine), on various targets, including muscles, the liver and the hypothalamus. Some adipokines, as TNFalpha and IL6, promote insulin resistance and inflammation, whereas others, as leptin and adiponectin, are required for energy and glucose homeostasis. In obesity, adipose cell hypertrophy and the recruitment of macrophages alter the secretory function and induce an inflammatory profile in the adipose tissue. Analyses of gene expression suggest that hypoxia is one of the factors favoring the attraction of the macrophages. The local and systemic consequences of interactions between macrophages and adipocytes are currently actively studied, to understand their potential implication in the metabolic and cardiovascular complications associated with obesity.

  17. Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism

    PubMed Central

    Krueger, Sharon K.; Williams, David E.

    2005-01-01

    Flavin-containing monooxygenase (FMO) oxygenates drugs and xenobiotics containing a “soft-nucleophile”, usually nitrogen or sulfur. FMO, like cytochrome P450 (CYP), is a monooxygenase, utilizing the reducing equivalents of NADPH to reduce 1 atom of molecular oxygen to water, while the other atom is used to oxidize the substrate. FMO and CYP also exhibit similar tissue and cellular location, molecular weight, substrate specificity, and exist as multiple enzymes under developmental control. The human FMO functional gene family is much smaller (5 families each with a single member) than CYP. FMO does not require a reductase to transfer electrons from NADPH and the catalytic cycle of the 2 monooxygenases is strikingly different. Another distinction is the lack of induction of FMOs by xenobiotics. In general, CYP is the major contributor to oxidative xenobiotic metabolism. However, FMO activity may be of significance in a number of cases and should not be overlooked. FMO and CYP have overlapping substrate specificities, but often yield distinct metabolites with potentially significant toxicological/pharmacological consequences. The physiological function(s) of FMO are poorly understood. Three of the 5 expressed human FMO genes, FMO1, FMO2 and FMO3, exhibit genetic polymorphisms. The most studied of these is FMO3 (adult human liver) in which mutant alleles contribute to the disease known as trimethylaminuria. The consequences of these FMO genetic polymorphisms in drug metabolism and human health are areas of research requiring further exploration. PMID:15922018

  18. Functional and metabolic disorders in celiac disease: new implications for nutritional treatment.

    PubMed

    Farnetti, Sara; Zocco, Maria Assunta; Garcovich, Matteo; Gasbarrini, Antonio; Capristo, Esmeralda

    2014-11-01

    Celiac disease (CD) is a chronic disease causing the inflammation of the proximal small intestine, in genetically predisposed individuals. This is triggered by the consumption of the gluten protein and the side effects of the disease are mitigated by a lifelong gluten-free diet (GFD) treatment. The predominant consequence of CD is malnutrition due to malabsorption (with diarrhea, weight loss, nutritional deficiencies, and altered blood parameters), especially in patients who do not show strict adherence to GFD treatment. Recent evidence shows that, despite a lifelong GFD, some functional disorders persist, such as compromised gallbladder function and motility, exocrine pancreatic insufficiency, increased gut permeability, small-intestinal bowel overgrowth, nonalcoholic fatty liver disease (NAFLD), lactose intolerance, and milk allergy. These abnormalities may predispose to the occurrence of overweight and obesity even in CD patients. This review focuses on the principal functional and metabolic disorders in both treated and untreated CD, ranging from alterations of the gastrointestinal system to impaired glucose and lipid metabolism and insulin secretion with the aim of providing new implications beyond a GFD, for an ad hoc nutrition treatment in these patients. PMID:25072743

  19. Effects of melatonin on water metabolism and renal function in male Syrian hamsters (Mesocricetus auratus).

    PubMed

    Richardson, B A; Studier, E H; Stallone, J N; Kennedy, C M

    1992-09-01

    The pineal indoleamine, melatonin, has been shown to influence many physiological systems within the mammalian body. Few studies, however, have examined the influence of melatonin on renal function. This study investigated the effects of melatonin on water metabolism and renal function. Young adult male Syrian hamsters were maintained on a long photoperiod (LD 14:10) in metabolic cages. The animals received daily (1700) injections of either control vehicle or 25 micrograms of melatonin for 85 consecutive days. Melatonin administration resulted in significant increases in water consumption and urine production. Water budgets were also significantly influenced by melatonin, as were urinary osmolality, urinary sodium, and potassium concentrations, but urinary calcium concentrations were essentially unaltered. When excretion rates for sodium, potassium, and calcium were calculated, no differences were observed between the vehicle control and melatonin-treated groups. Injections of melatonin also significantly decreased plasma antidiuretic hormone (ADH). These results demonstrate that afternoon injections of melatonin can alter renal function, which may involve direct (i.e., on ADH secretion and/or thirst mechanisms) or indirect (i.e., behavioral) effects.

  20. The SOS Pilot Study: A RCT of Routine Oxygen Supplementation Early after Acute Stroke—Effect on Recovery of Neurological Function at One Week

    PubMed Central

    Roffe, Christine; Ali, Khalid; Warusevitane, Anushka; Sills, Sheila; Pountain, Sarah; Allen, Martin; Hodsoll, John; Lally, Frank; Jones, Peter; Crome, Peter

    2011-01-01

    Mild hypoxia is common after stroke and associated with poor long-term outcome. Oxygen supplementation could prevent hypoxia and improve recovery. A previous study of routine oxygen supplementation showed no significant benefit at 7 and 12 months. This pilot study reports the effects of routine oxygen supplementation for 72 hours on oxygen saturation and neurological outcomes at 1 week after a stroke. Methods Patients with a clinical diagnosis of acute stroke were recruited within 24 h of hospital admission between October 2004 and April 2008. Participants were randomized to oxygen via nasal cannulae (72 h) or control (room air, oxygen given only if clinically indicated). Clinical outcomes were assessed by research team members at 1 week. Baseline data for oxygen (n = 148) and control (n = 141) did not differ between groups. Results The median (interquartile range) National Institutes of Health Stroke Scale (NIHSS) score for the groups at baseline was 6 (7) and 5 (7) respectively. The median Nocturnal Oxygen Saturation during treatment was 1.4% (0.3) higher in the oxygen than in the control group (p<0.001) during the intervention. At 1 week, the median NIHSS score had reduced by 2 (3) in the oxygen and by 1 (2) in the control group. 31% of participants in the oxygen group and 14% in the control group had an improvement of ≥4 NIHSS points at 1 week doubling the odds of improvement in the oxygen group (OR: 2.9). Conclusion Our data show that routine oxygen supplementation started within 24 hours of hospital admission with acute stroke led to a small, but statistically significant, improvement in neurological recovery at 1 week. However, the difference in NIHSS improvement may be due to baseline imbalance in stroke severity between the two groups and needs to be confirmed in a larger study and linked to longer-term clinical outcome. Trial Registration Controlled-Trials.com ISRCTN12362720; European Clinical Trials Database 2004-001866-41 PMID:21625533

  1. mTORC1 couples immune signals and metabolic programming to establish Treg cell function

    PubMed Central

    Zeng, Hu; Yang, Kai; Cloer, Caryn; Neale, Geoffrey; Vogel, Peter; Chi, Hongbo

    2013-01-01

    The mechanistic target of rapamycin (mTOR) pathway integrates diverse environmental inputs, including immune signals and metabolic cues, to direct T cell fate decisions1. Activation of mTOR, comprised of mTORC1 and mTORC2 complexes, delivers an obligatory signal for proper activation and differentiation of effector CD4+ T cells2,3, whereas in the regulatory T cell (Treg) compartment, the Akt-mTOR axis is widely acknowledged as a crucial negative regulator of Treg de novo differentiation4–8 and population expansion9. However, whether mTOR signaling affects the homeostasis and function of Tregs remains largely unexplored. Here we show that mTORC1 signaling is a pivotal positive determinant of Treg function. Tregs have elevated steady-state mTORC1 activity compared to naïve T cells. Signals via T cell receptor (TCR) and IL-2 provide major inputs for mTORC1 activation, which in turn programs suppressive function of Tregs. Disruption of mTORC1 through Treg-specific deletion of the essential component Raptor leads to a profound loss of Treg suppressive activity in vivo and development of a fatal early-onset inflammatory disorder. Mechanistically, Raptor/mTORC1 signaling in Tregs promotes cholesterol/lipid metabolism, with the mevalonate pathway particularly important for coordinating Treg proliferation and upregulation of suppressive molecules CTLA-4 and ICOS to establish Treg functional competency. In contrast, mTORC1 does not directly impact the expression of Foxp3 or anti- and pro-inflammatory cytokines in Tregs, suggesting a non-conventional mechanism for Treg functional regulation. Lastly, we provide evidence that mTORC1 maintains Treg function partly through inhibiting the mTORC2 pathway. Our results demonstrate that mTORC1 acts as a fundamental ‘rheostat’ in Tregs to link immunological signals from TCR and IL-2 to lipogenic pathways and functional fitness, and highlight a central role of metabolic programming of Treg suppressive activity in immune

  2. Vacuole membrane contact sites and domains: emerging hubs to coordinate organelle function with cellular metabolism.

    PubMed

    Malia, Pedro Carpio; Ungermann, Christian

    2016-04-15

    Eukaryotic cells rely on a set of membrane-enclosed organelles to perform highly efficient reactions in an optimized environment. Trafficking of molecules via vesicular carriers and membrane contact sites (MCS) allow the coordination between these compartments, though the precise mechanisms are still enigmatic. Among the cellular organelles, the lysosome/vacuole stands out as a central hub, where multiple pathways merge. Importantly, the delivered material is degraded and the monomers are recycled for further usage, which explains its wide variety of roles in controlling cellular metabolism. We will highlight recent advances in the field by focusing on the yeast vacuole as a model system to understand lysosomal function in general.

  3. Fellowship programs in behavioral neurology.

    PubMed

    Green, R C; Benjamin, S; Cummings, J L

    1995-03-01

    We sent a behavioral neurology fellowship questionnaire to each of the training directors of 160 neurology residency programs throughout the world, seeking information about programs offering advanced training in behavioral neurology (or similar fellowships in cognitive neurology, neurobehavior, or cognitive neuroscience). Response rate was 100%. Thirty-four respondents reported active fellowship programs in behavioral neurology, and 28 additional respondents indicated that a behavioral neurology fellowship was planned. Nine of the 34 programs (26.5%) defined themselves as exclusively or predominantly concerned with dementia and age-related neurobehavioral disorders. Directors of the 34 active fellowship programs estimated that their combined programs had graduated 199 fellows and were currently training fifty. Most fellowships concentrated on outpatient clinical training, with teaching required by 78.1% and research required by 81.8%. Specialty certification for behavioral neurology was favored by over 75% of behavioral neurology fellowship training directors but by only 30% of training directors in residency programs without behavioral neurology fellowships. Behavioral neurology training programs have grown dramatically in response to an increased recognition of the academic interest in and the clinical needs for these services. PMID:7898686

  4. Correlation of Normal Diastolic Cardiac Function With VO in the Metabolic Syndrome.

    PubMed

    Chockalingam, Anand; Linden, Melissa A; Dellsperger, Kevin C; Thomas, Tom R

    2009-01-01

    Morbid obesity and diabetes cause diastolic dysfunction that can be detected by Doppler echocardiography. Patients with the metabolic syndrome could demonstrate early diastolic dysfunction that may influence effort tolerance. A total of 32 patients (17 men) who fulfilled >/=2 of the 5 metabolic syndrome criteria were studied. The average age of patients was 37+/-2 years. All patients were overweight/obese (mean body mass index of 34.4+/-0.7 kg/m(2)), 15 had blood pressure >130/85 mm Hg, 19 had elevated triglyceride levels (>150 mg/dL), and 17 had low high-density lipoprotein cholesterol levels (men <40 mg/dL, women <50 mg/dL). Maximal exercise was performed using Bruce treadmill protocol with standard stress echocardiography and tissue Doppler. Maximal oxygen consumption (VO(2max)) was measured using indirect calorimetry. Left ventricular filling pressure was indirectly derived from dividing pulse Doppler early mitral inflow velocity (E) by tissue Doppler early diastolic mitral annular motion (E') or E/E'. The group's average treadmill time was 8.06+/-0.28 minutes, VO(2max) was 28.6+/-1.1 mL/kg/min, and 8.2+/-0.3 metabolic equivalents. None had evidence of myocardial ischemia or systolic or diastolic dysfunction with exercise. Mean "resting" E/E' and "post-exercise" E/E' were 7.01+/-0.04 and 7.41+/-0.41, respectively. There was no significant correlation between resting E/E' and VO(2max) (r=-0.266; P=.14). The post-exercise E/E' significantly correlated with VO(2max) (r=-0.483; P=.005) and metabolic equivalents (r=-0.487; P=.005). Diastolic function is preserved in early metabolic syndrome. Even in the normal diastolic function range, exercise E/E' is inversely related to VO(2max). Further longitudinal studies are needed to determine whether they develop diastolic dysfunction and related heart failure.

  5. Morning and Evening Blue-Enriched Light Exposure Alters Metabolic Function in Normal Weight Adults

    PubMed Central

    Cheung, Ivy N.; Zee, Phyllis C.; Shalman, Dov; Malkani, Roneil G.; Kang, Joseph; Reid, Kathryn J.

    2016-01-01

    Increasing evidence points to associations between light-dark exposure patterns, feeding behavior, and metabolism. This study aimed to determine the acute effects of 3 hours of morning versus evening blue-enriched light exposure compared to dim light on hunger, metabolic function, and physiological arousal. Nineteen healthy adults completed this 4-day inpatient protocol under dim light conditions (<20lux). Participants were randomized to 3 hours of blue-enriched light exposure on Day 3 starting either 0.5 hours after wake (n = 9; morning group) or 10.5 hours after wake (n = 10; evening group). All participants remained in dim light on Day 2 to serve as their baseline. Subjective hunger and sleepiness scales were collected hourly. Blood was sampled at 30-minute intervals for 4 hours in association with the light exposure period for glucose, insulin, cortisol, leptin, and ghrelin. Homeostatic model assessment of insulin resistance (HOMA-IR) and area under the curve (AUC) for insulin, glucose, HOMA-IR and cortisol were calculated. Compar