ascorbic-acid and Nervous-System-Diseases

It is rare to see a day pass in which we are not told through some popular medium that the population is becoming older. Along with this information comes the "new" revelation that as we enter the next millennium there will be increases in age-associated diseases (e.g., cancer, cardiovascular disease) including the most devastating of these, which involve the nervous system (e.g., Alzheimer's disease [AD] and Parkinson's disease [PD]). It is estimated that within the next 50 years approximately 30% of the population will be aged 65 years or older. Of those between 75 and 84 years of age, 6 million will exhibit some form of AD symptoms, and of those older than 85 years, over 12 million will have some form of dementia associated with AD. What appears more ominous is that many cognitive changes occur even in the absence of specific age-related neurodegenerative diseases. Common components thought to contribute to the manifestation of these disorders and normal age-related declines in brain performance are increased susceptibility to long-term effects of oxidative stress (OS) and inflammatory insults. Unless some means is found to reduce these age-related decrements in neuronal function, health care costs will continue to rise exponentially. Thus, it is extremely important to explore methods to retard or reverse age-related neuronal deficits as well as their subsequent, behavioral manifestations. Fortunately, the growth of knowledge in the biochemistry of cell viability has opened new avenues of research focused at identifying new therapeutic agents that could potentially disrupt the perpetual cycle of events involved in the decrements associated with these detrimental processes. In this regard, a new role in which certain dietary components may play important roles in alleviating certain disorders are beginning to receive increased attention, in particular those involving phytochemicals found in fruits and vegetables.

Topics: Alzheimer Disease; Animals; Ascorbic Acid; Capsicum; Carotenoids; Flavonoids; Fruit; Garlic; Ginkgo biloba; Humans; Nervous System Diseases; Panax; Parkinson Disease; Phenols; Phytotherapy; Plants, Medicinal; Polymers; Polyphenols; Tea; Vitamin E

Topics: Animals; Ascorbic Acid; Biological Transport, Active; Brain; Humans; In Vitro Techniques; Models, Biological; Nervous System; Nervous System Diseases; Nervous System Physiological Phenomena; Synaptic Transmission; Tissue Distribution

Vitamins contain reactive functional groups necessary to their established roles as coenzymes and reducing agents. Their reactive potential may produce injury if vitamin concentration, distribution, or metabolism is altered. However, identification of vitamin toxicity has been difficult. The only well-established human vitamin neurotoxic effects are those due to hypervitaminosis A (pseudotumor cerebri) and pyridoxine (sensory neuropathy). In each case, the neurological effects of vitamin deficiency and vitamin excess are similar. Closely related to the neurological symptoms of hypervitaminosis A are symptoms including headache, pseudotumor cerebri, and embryotoxic effects reported in patients given vitamin A analogs or retinoids. Most tissues contain retinoic acid (RA) and vitamin D receptors, members of a steroid receptor superfamily known to regulate development and gene expression. Vitamin D3 effects on central nervous system (CNS) gene expression are predictable, in addition to the indirect effects owing to its influence on calcium and phosphorus homeostasis. Folates and thiamine cause seizures and excitation when administered in high dosage directly into the brain or cerebrospinal fluid (CSF) of experimental animals but have rarely been reported to cause human neurotoxicity, although fatal reactions to i.v. thiamine are well known. Ascorbic acid influences CNS function after peripheral administration and influences brain cell differentiation and 2-deoxyglucose accumulation by cultured glial cells. Biotin influences gene expression in animals that are not vitamin-deficient and alters astrocyte glucose utilization. The multiple enzymes and binding proteins involved in regeneration of retinal vitamin A illustrate the complexity of vitamin processing in the body. Vitamin A toxicity is also a good general model of vitamin neurotoxicity, because it shows the importance of the ratio of vitamin and vitamin-binding proteins in producing vitamin toxicity and of CNS permeability barriers. Because vitamin A and analogs enter the CNS better than most vitamins, and because retinoids have many effects on enzyme activity and gene expression, Vitamin A neurotoxicity is more likely than that of most, perhaps all other vitamins. Megadose vitamin therapy may cause injury that is confused with disease symptoms. High vitamin intake is more hazardous to peripheral organs than to the nervous system, because CNS vitamin entry is restricted. Vitamin administration into the br

Topics: Abnormalities, Drug-Induced; Animals; Ascorbic Acid; Avitaminosis; Blood-Brain Barrier; Carrier Proteins; Coenzymes; Drug Interactions; Folic Acid; Humans; Injections, Spinal; Liver; Methotrexate; Nervous System Diseases; Oxidation-Reduction; Pseudotumor Cerebri; Pyridoxine; Self Medication; Vitamin A; Vitamins

This monograph on the clinical chemistry of vitamin B12 reviews the literature on daily requirements, methods for measurement, the effects of drugs on vitamin B12 metabolism absorption, pregnancy, clinical conditions associated with vitamin B12 deficiency, errors of metabolism, and reactions to vitamin therapy. Although only very small quantities of vitamin B12 are required to satisfy the daily requirement, a sufficient supply is stored in the liver to meet normal requirements for at least a 3-year period. A number of drugs are known to affect the absorption of vitamin B12, including neomycin, potassium chloride, p-aminosalicylic acid, and colchicine. Significantly reduced serum concentrations of vitamin B12 have been noted in users of oral contraceptives (OCs), although concentrations still remain within the limits of normal. It appears that the vitamin B12 level in OC users reestablishes itself at a different and somewhat lower level. Vitamin B12 binding protein appears to remain unchanged. A vitamin B12 deficiency is unusual in pregnant women who consume a normal, varied diet. On the other hand, lactating women whose diets are low in animal protein and dairy products may have problems providing enough vitamin B12 to meet their own and their infant's needs; supplementary oral vitamins should be considered.

Topics: Absorption; Adult; Alcoholism; Anemia, Pernicious; Ascorbic Acid; Autoantibodies; Biguanides; Biological Transport; Chemical Phenomena; Chemistry; Chlorpromazine; Contraceptives, Oral; Diet; Female; Gastrectomy; Gastritis; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Metabolism, Inborn Errors; Middle Aged; Neoplasms; Nervous System Diseases; Nitrous Oxide; Nutritional Requirements; Pancreatic Diseases; Parasitic Diseases; Pregnancy; Pregnancy Complications; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Na+,K+-ATPase is a crucial protein responsible for maintaining the electrochemical gradients across the cell membrane. The Na+,K+-ATPase is comprised of catalytic α, β, and γ subunits. In adult brains, the α3 subunit, encoded by ATP1A3, is predominantly expressed in neurons, whereas the α2 subunit, encoded by ATP1A2, is expressed in glial cells. In foetal brains, the α2 is expressed in neurons as well. Mutations in α subunits cause a variety of neurologic disorders. Notably, the onset of symptoms in ATP1A2- and ATP1A3-related neurologic disorders is usually triggered by physiological or psychological stressors. To gain insight into the distinct roles of the α2 and α3 subunits in the developing foetal brain, whose developmental dysfunction may be a predisposing factor of neurologic disorders, we compared the phenotypes of mouse foetuses with double homozygous knockout of Atp1a2 and Atp1a3 (α2α3-dKO) to those with single knockout. The brain haemorrhage phenotype of α2α3-dKO was similar to that of homozygous knockout of the gene encoding ascorbic acid (ASC or vitamin C) transporter, SVCT2. The α2α3-dKO brain showed significantly decreased level of ASC compared with the wild-type (WT) and single knockout. We found that the ASC content in the basal ganglia and cerebellum was significantly lower in the adult Atp1a3 heterozygous knockout mouse (α3-HT) than in the WT. Interestingly, we observed a significant decrease in the ASC level in the basal ganglia and cerebellum of α3-HT in the peripartum period, during which mice are under physiological stress. These observations indicate that the α2 and α3 subunits independently contribute to the ASC level in the foetal brain and that the α3 subunit contributes to ASC transport in the adult basal ganglia and cerebellum. We propose that decreases in ASC levels may affect neural network development and are linked to the pathophysiology of ATP1A2- and ATP1A3-related neurologic disorders.

Topics: Animals; Ascorbic Acid; Brain; Disease Models, Animal; Mice; Mice, Knockout; Nerve Net; Nervous System Diseases; Phenotype; Sodium-Potassium-Exchanging ATPase; Vitamins

The aim of this study was to assess the dietary intake of patients with metabolic diseases and nervous system disorders in smoking compared with non-smoking patients. The study included 120 patients with metabolic disorders (ZM) and 100 patients with nervous system disorders (ZUN). Subjects were divided into two groups: smokers and nonsmokers. Data on the pharmacologic treatment and supplementation were obtained during a direct interview with the patient. Dietary intake of the nutrients was assayed on the basis of dietary intake interviews from three preceding days (3 times 24-h recall). BMI was also calculated. It was shown that patients in the ZUN group frequently smoked cigarettes and consumed alcohol. BMI was higher in ZM patients. Smokers in ZM group used more drugs than non-smokers. It was found that smoking patients in ZM group consumed significantly lower amount of sucrose than nonsmokers. Moreover, in the diet of smokers ZUN a significantly lower supply of vitamin C than in nonsmokers was observed. It was shown that smokers consume an excessive amount of fat and sodium and low amount of antioxidant vitamins, calcium, potassium and magnesium.

Topics: Alcohol Drinking; Ascorbic Acid; Body Mass Index; Comorbidity; Dietary Carbohydrates; Dietary Supplements; Eating; Female; Humans; Life Style; Male; Metabolic Diseases; Middle Aged; Nervous System Diseases; Poland; Smoking; Sodium, Dietary

The present study was conducted to investigate whether the conditionally essential amino acid taurine could play any protective role against the potent neurotoxin cadmium (Cd)-induced oxidative impairment in mice brain. Cd administration in the form of CdCl(2 )(at a dose of 4 mg kg(-1) body weight for 3 days, orally) increased the intracellular accumulation of metallic Cd, reactive oxygen species and super oxide radicals. The toxin also augmented the extent of lipid peroxidation, protein carbonylation and the levels of glutathione disulfide. Activities of the antioxidant enzymes and the levels of reduced glutathione as well as total thiols have been significantly decreased due to Cd exposure. In addition, the toxin also caused significant DNA degradation (as evidenced from DNA smearing and diphenylamine reaction). Oral administration of taurine (at a dose of 100 mg kg(-1) body weight for 5 days) was found to be very effective in the prevention of Cd-induced oxidative impairment in the brain tissue of experimental mice. In addition, taurine treatment could also prevent the reduction in the in vivo antioxidant power linearly up to a dose of 100 mg kg(-1) body weight. The preventive role of taurine against Cd-induced cerebral oxidative damage was supported by the observation under scanning electron microscope as well as histological examination of brain segments. To validate the experimental results, a well-known water soluble antioxidant, vitamin C, was used as the positive control in the study. In all, the results suggest that taurine plays a beneficial role against Cd-induced cerebral oxidative stress.

Topics: Animals; Antioxidants; Ascorbic Acid; Body Weight; Brain; Cadmium Chloride; DNA Fragmentation; Dose-Response Relationship, Drug; Glutathione; Lipid Peroxidation; Lipid Peroxides; Male; Malondialdehyde; Mice; Microscopy, Electron, Scanning; Nervous System Diseases; Organ Size; Protein Carbonylation; Reactive Oxygen Species; Sulfhydryl Compounds; Superoxides; Taurine

Free radicals play a crucial role in health and disease and both reactive oxygen species (ROS) and reactive nitrogen species (RNS) have been implicated in CNS effects like excitotoxicity. Theophylline, a re-emerging drug for the treatment of obstructive airway disease, has a narrow therapeutic index which precludes its safe use. The present study evaluated the possible involvement of free radicals in theophylline induced seizures in mice. Aminophylline (100-250 mg/kg) consistently induced seizures and post-ictal mortality, and conventional anticonvulsants and adenosine agonists were ineffective in antagonizing them. Further, phosphodiesterase inhibitors, per se, also did not show any significant seizurogenic potential. Pretreatments with antioxidants, ascorbic acid, alpha-tocopherol and melatonin, all dose dependently reduced seizure incidence and mortality after aminophylline, whereas, antioxidant depletion potentiated such excitotoxicity. Pretreatments with the NO synthase inhibitors, L-NAME and 7-NI blocked aminophylline seizures, whereas, the NO mimetics, L-arginine and glyceryl trinitrate, tended to potentiate this phenomenon. Sub-effective doses of aminophylline (100 mg/kg) also induced seizures when combined with subthreshold intensity of electroshock, and such seizures were similarly antagonized by the antioxidants and NO synthase inhibitors. Biochemical assay of brain homogenates showed that aminophylline seizures were associated with enhancements in brain MDA and NOx (NO metabolites) levels, whereas, SOD activity was reduced, and these changes were attenuated after melatonin and L-NAME pretreatments. The pharmacological and biochemical data are strongly suggestive of the involvement of both ROS and RNS during theophylline-induced seizures.

Topics: alpha-Tocopherol; Aminophylline; Animals; Antioxidants; Arginine; Ascorbic Acid; Dose-Response Relationship, Drug; Female; Free Radicals; Male; Melatonin; Mice; Nervous System Diseases; NG-Nitroarginine Methyl Ester; Nitroglycerin; Phosphodiesterase Inhibitors; Reactive Nitrogen Species; Reactive Oxygen Species; Seizures; Superoxide Dismutase; Theophylline

The objective was to determine the long-term clinical outcome and the effects of treatment of patients with glutathione synthetase (GS) deficiency (n = 28).. The diagnosis was based on demonstration of a marked decrease in GS activity in erythrocytes or cultured fibroblasts in all patients and was supported by finding a decrease in erythrocyte or fibroblast glutathione, presence of 5-oxoprolinuria, or both. The treatment varied but usually included correction of acidosis and supplementation with vitamins C and/or E.. Sixteen patients were severely affected with neurologic symptoms such as seizures and psychomotor retardation; 7 had died at the time of the study. None of the severely affected patients had been treated with both vitamins C and E from the neonatal period. No significant difference was found in GS activity between patients with or without neurologic symptoms or in erythrocyte or fibroblast glutathione levels. Five patients had recurrent bacterial infections.. On the basis of clinical symptoms, patients with GS deficiency can be classified into 3 phenotypes: mild, moderate, and severe. Our results indicate that early supplementation with vitamins C and E may improve the long-term clinical outcome.

Topics: Acidosis; Adult; Anemia, Hemolytic; Ascorbic Acid; Child; Child, Preschool; Erythrocytes; Female; Fibroblasts; Genes, Recessive; Glutathione Synthase; Humans; Infant; Infant, Newborn; Male; Mutation; Nervous System Diseases; Psychomotor Disorders; Time Factors; Vitamin E

Neuronal ceroid-lipofuscinoses (NCL) are a group of neurodegenerative disorders. There is much evidence for a role of peroxidation processes in the pathogenesis of NCL, although this would certainly be indirect. Reduced total antioxidant activity of cerebrospinal fluid (CSF) has been reported in NCL. Since ascorbic acid represents a major antioxidant in CSF, we have now determined this parameter in CSF of two patients with the infantile form of NCL (Santavuori-Haltia disease). However, the ascorbic acid values obtained (103.6 and 181.3 microM) are comparable with control values from the literature as well as with those measured in groups of children with neurologic/psychiatric diseases other than NCL (mean +/- standard deviation: 137.1+/-41.3 microM), with suspected (but excluded) meningitis (124.1+/-34.0 microM) and acute lymphoblastic leukemia (131.7+/-17.0 microM). Our results indicate that CSF ascorbic acid concentrations are not affected by peroxidation processes in infantile NCL, but reveal a sharply decreased ascorbic acid concentration in one of the non-NCL patients, possibly associated with his convulsions and/or his anticonvulsant therapy.

Topics: Ascorbic Acid; Child; Child, Preschool; Developmental Disabilities; Female; Humans; Infant; Male; Mental Disorders; Nervous System Diseases; Neuronal Ceroid-Lipofuscinoses; Reference Values

Possible biochemical events involved in L-2-chloropropionic acid (L-CPA)-induced delayed cerebellar granule cell necrosis following N-methyl-D-aspartate activation were studied in vivo. We examined whether the calcium-sensitive proteolytic enzymes, the calpains, may be activated by L-CPA or whether the generation of excess quantities of cytotoxic free radicals may play a role in the neurotoxicity produced by oral administration of L-CPA (750 mg/kg, pH 7.0). Evidence for free radical-induced cellular damage was examined using biochemical approaches such as examining brains from L-CPA-treated rats for increased lipid peroxidation, DNA damage, or protein oxidation. Second, the ability of antioxidants to provide neuroprotective activity against L-CPA-induced neurotoxicity was examined in vivo. Western blotting using antibodies against spectrin (alpha-fodrin) demonstrated evidence for calpain (EC 3.4.22.17) activation in the cerebellum, but not in the cerebral cortex of L-CPA-treated rats at 36 and 48 hr after L-CPA dosing. In contrast, there was no evidence for oxidative damage to cerebellar proteins or lipids in L-CPA-treated rat brains compared to controls. We also could not find evidence for DNA damage using the TUNEL method for the detection of single- and/ or double-strand breakage in situ in L-CPA-treated brains. We examined whether a number of reported antioxidants may be effective against L-CPA-induced neurotoxicity. The aminosteroids U74389G and U83836E, the free radical scavengers 3-methyl-1-phenylpyrazolin-5-one and N-tert-butylphenylnitrone, and the iron chelator N-ethoxy-2-ethyl-3-hydroxypyridin-4-one were all ineffective in attenuating L-CPA neurotoxicity. We suggest that L-CPA-induced cerebellar necrosis is the result of calpain activation which results in the degradation of cytoskeletal proteins and other proteins necessary for cellular biochemistry. We could find no evidence of oxidative damage to cerebellar proteins, lipids, or DNA as a result of excess amounts of free radicals, and selective antioxidants were unable to provide neuroprotection against L-CPA neurotoxicity, suggesting that oxidative stress does not play a role in the granule cell necrosis.

Topics: Administration, Oral; Animals; Antioxidants; Ascorbic Acid; Aspartic Acid; Blotting, Western; Calpain; Cerebellum; Free Radicals; Glutamic Acid; Hydrocarbons, Chlorinated; Lipid Peroxidation; Male; Necrosis; Nervous System Diseases; Neurons; Oxidative Stress; Propionates; Rats; Spectrin

The free radical levels in the cerebrospinal fluid of 8 patients with neurological diseases and 9 undergoing lumbar anesthesia for surgery were measured. The ascorbate free radical level 10 min after lumbar puncture showed a positive correlation with the hydroxyl radical level. In the patient with mitochondrial encephalomyopathy, the levels of hydroxyl and ascorbate free radicals increased upon discontinuation of treatment and decreased upon its resumption, and the ascorbate free radical levels without therapy fell after lumbar puncture. The free radical levels in the cerebrospinal fluid may reflect the degree of oxidative stress in the central nervous system.

Topics: Aged; Ascorbic Acid; Electron Spin Resonance Spectroscopy; Female; Humans; Hydroxyl Radical; Male; Middle Aged; Mitochondrial Encephalomyopathies; Nervous System Diseases

Before microdialysis (MD) can be introduced into the clinic as an improved method of cerebral monitoring, certain ethical, methodological and clinical factors must be considered. Access to the brain for probe insertion is offered by craniotomy or by routine intracranial pressure (ICP) monitoring and the additional lesion is minimal. Care must be taken that the two devices do not interfere with each other. In contrast to ICP monitoring, MD provides information about multiple aspects of brain metabolism. We can monitor either still intact tissue to prevent additional damage, or injured brain to decide on and control therapies. The parameters used must reflect pathological changes an early stage, and the analysis should be available on-line or immediately after sample collection. The effects off factors such as tube length and flow rate on the behaviour of the chosen parameters (in our case on-line pH, radical scavengers and uric acid) in the MD set-up must be investigated in vitro and in animal models before use in the clinic. The range of non-pathological values of parameters of interest in human brain should be known For this purpose we took measurements during an extracranial-intracranial bypass operation, and were able to compare values with those in a severely damaged brain. The mutual chronology of parameter changes and clinical events must be clear. Future aspects include the use of low-flow methods offering nearly 100% recovery, improved analytical methods, and combination of MD with other monitoring methods to obtain more exact information.

Topics: Animals; Ascorbic Acid; Bicarbonates; Brain; Carbon Dioxide; Craniocerebral Trauma; Critical Care; Cysteine; Feasibility Studies; Glutathione; Humans; Hydrogen-Ion Concentration; Microdialysis; Nervous System Diseases; Rats; Rats, Inbred SHR; Uric Acid

Concentrations of ascorbate (vitamin C) in cerebrospinal fluid (CSF) from human controls (median 163 mumol/l, n = 63) were found to be in the same range as CSF samples from patients (n = 56) with various neurological diseases, but excluding those with blood-CSF barrier dysfunction. The CSF/serum concentration ratio in the former group is non-linear, decreasing with increasing serum concentration. Surprisingly, ascorbate concentration in blood (median 41 mumol/l, n = 119) was decreased significantly in cases of neurological diseases with a blood-CSF barrier dysfunction (median 26 mumol/l, n = 30). In this latter group a linear CSF to serum ratio with a mean of 5.7:1 (with CSF/serum albumin quotients QAlb = 7.8-70.8 x 10(-3), median 10.0 x 10(-3)) was observed, approaching a value > 12.5:1 in the case of complete stop of CSF flow. Serum ascorbate concentrations decreased with decreasing CSF flow rate (1 square root of QAlb), indicating a CSF flow-dependent constant contribution from high intrathecal ascorbate concentration to the varying diet-dependent concentrations in blood. In the control group the biological coefficient of variation for CSF ascorbate concentrations (C.V. = 21.1%) was smaller than for serum concentrations (C.V. = 42.6%), confirming an efficient ascorbate homeostasis in human brain. This was different from uric acid which was used as a reference molecule with an inversed gradient in the same group of control patients. Similar variations in CSF(y) and serum(x) for urate concentrations are observed due to the strong correlation y = 0.1x +/- 10 mumol/l, including 99% of the cases with an urate serum concentration range from 80 mumol/l to 460 mumol/l.

Topics: Ascorbic Acid; Capillary Permeability; Cerebrospinal Fluid; Chromatography, High Pressure Liquid; Humans; Nervous System Diseases; Reproducibility of Results; Uric Acid

A deafferentation syndrome, produced in rats by dorsal root ganglionectomies, is expressed as scratching of partially deafferented limb areas and/or biting of anesthetic limb areas. This self-mutilation may be objective evidence of dysesthesias, thus serving as an experimental model to study chronic dysesthesias and/or pain from deafferentation in man. This study included behavioral observations of the syndrome and the effects of intraventricular apomorphine, a dopamine agonist, on its expression. Thirty-eight female Sprague-Dawley rats underwent unilateral C5-T2 dorsal root ganglionectomies followed immediately by stereotactically guided cannulation of the right lateral ventricle in 20 of the rats. For 2 weeks continuously via an osmotic minipump, 10 rats received apomorphine (5 micrograms/h) and 10 others received L-ascorbate (the vehicle). Rats with ganglionectomies only, as well as those receiving L-ascorbate, demonstrated early onset, more severe and later onset, less severe biting groups (P less than 0.05 Mann-Whitney U). Animals receiving apomorphine exhibited low autotomy scores irrespective of time of bite onset. Among the control groups, but not the experimental animals, the earlier the onset of biting, the more severe was the autotomy. The rats receiving vehicle via the minipump had earlier bite onsets than the rats in the ganglionectomy only group. This may indicate that the presence of the minipump is a stress which can accelerate the onset of biting. Intraventricular apomorphine can affect the deafferentation syndrome in the rat; it seems to decrease the level of autotomy and disrupt the relationship of bite onset with degree of biting.

Topics: Afferent Pathways; Animals; Apomorphine; Ascorbic Acid; Behavior, Animal; Denervation; Female; Forelimb; Hindlimb; Nervous System Diseases; Pain; Rats; Rats, Inbred Strains; Syndrome

A deficiency of hepatic dihydropteridine reductase (DHPR) activity was found in a neurologically impaired infant with mild hyperphenylalaninemia and normal levels of hepatic phenylalanine hydroxylase. DHPR is required for the regeneration of tetrahydrobiopterin, an essential cofactor in aromatic amino acid hydroxylation, a necessary step in the biosynthesis of the neurotransmitters, dopamine and serotonin. Evidence for decreased synthesis of these transmitters in this patient was provided by the finding of reduced levels of homovanillic acid and 5-hydroxyindole acetic acid, metabolites of dopamine and serotonin, respectively, in the cerebrospinal fluid and urine. Treatment with dopamine and serotonin precursors, L-3,4 dihydroxyphenylalanine and 5-hydroxytryptophan, respectively, was associated with improvement in temperament and motor tone and less frequent seizures. However, there was no improvement in gross motor function or language development.

Topics: 5-Hydroxytryptophan; Ascorbic Acid; Consanguinity; Dopamine; Humans; Infant; Levodopa; Liver; Male; NADH, NADPH Oxidoreductases; Nervous System Diseases; Phenylalanine; Phenylalanine Hydroxylase; Phenylketonurias; Serotonin

Rats fed a vitamin E-deficient diet containing 10% "stripped" corn oil had reduced growth rate and elevated platelet count by 12 weeks of age, and a normocytic anemia with elevated reticulocytes by 16 weeks of age. After 5 months, rats became emaciated and developed kyphoscoliosis. Some rats developed skin ulcers and tremors, and mortality was high. Neuromuscular lesions included a chronic necrotizing myopathy and localized axonal dystrophy. There was also a selective activation of lysosomes in the central nervous system microcirculation. Liver ascorbic acid of deficient rats was the same as in those receiving vitamin E. Urinary excretion of p-hydroxyphenylpyruvate after a tyrosine load was also the same in deficient and control rats. It was concluded that neither vitamin C synthesis or utilization was affected the E-deficient rats.

Topics: Age Factors; Anemia; Animals; Ascorbic Acid; Female; Kyphosis; Male; Muscular Diseases; Necrosis; Nervous System Diseases; Rats; Scoliosis; Skin Ulcer; Thrombocytosis; Vitamin E Deficiency

Topics: Adult; Arousal; Arthropathy, Neurogenic; Ascorbic Acid; Behavior; Depression; Humans; Hypochondriasis; Hysteria; Leg; Male; Memory; Middle Aged; MMPI; Motivation; Nervous System Diseases; Physical Fitness; Psychological Tests; Psychomotor Disorders; Scurvy

Topics: Ascorbic Acid; Body Weight; Child, Preschool; Diet Therapy; Humans; Intellectual Disability; Male; Metabolism, Inborn Errors; Nervous System Diseases; Obsessive-Compulsive Disorder; Pedigree; Self Mutilation; Uric Acid

Topics: Ascorbic Acid; Biomedical Research; Drug Therapy; Empirical Research; Nervous System Diseases; Pyridoxine; Research Design

Topics: Ascorbic Acid; Ergocalciferols; Humans; Hypercalcemia; Nervous System Diseases; Urine; Vitamins