Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Theophylline overdosage can cause life-threatening symptoms, that include seizures and cardiac arrhythmias, and can be fatal. Neither the onset of toxicity nor the severity of symptoms is well predicted by serum theophylline concentrations. Since depressed vitamin B6 plasma levels can occur in patients receiving theophylline, we explored a B6-theophylline interaction in a rabbit model. Administration of theophylline preparations intraperitoneally (aminophylline) or orally (sustained release anhydrous theophylline) resulted in a 47% depression of plasma pyridoxal 5'-phosphate (PLP) levels. The 87% increase in PLP with pyridoxine administration was only 18% when aminophylline was also given. The mechanism of the theophylline-B6 interaction is obscure. Ethylenediamine in some theophylline preparations binds directly to PLP, potentially increasing the less direct theophylline effect. Pyridoxine supplementation resulted in higher average PLP levels but did not prevent death in animals with profoundly low PLP levels. If these data apply to humans, B6 deficiency may contribute to chronic theophylline toxicity; however, pyridoxine administration in the dosage used may not prevent toxicity. Larger doses may prove beneficial after further investigation.
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PMID:Depression of vitamin B6 levels due to theophylline. 236 33

In experiments on cats it was shown that nicotinamide injected intravenously in a dose of 300 to 500 mg per kg body weight depressed singular epileptic foci and groups of foci with synchronized activity induced in the animals' brain cortex by application of strychnine (0.1 ml of 3% solution). The vitamin was also effective, though to a lesser degree, in depressing foci induced by application of penicillin (2% solution). Pyridoxal-5-phosphate (Pyr-5-Ph) injected intravenously in a dose of 10 mg/kg depressed singular foci and groups of foci with synchronized activity induced by application of 2% solution of penicillin, but was less effective in depressing strychnine-induced foci. Combined application of both drugs even in lower doses (nicotinamide, 200 mg/kg; Pyr-5-Ph, 5 mg/kg) resulted in depression of groups of epileptic foci induced by combined application of strychnine and penicillin. Mechanisms of the effects discovered are discussed. A question on possible use of combined nicotinamide and pyridoxal-5-phosphate in the treatment of epilepsy is raised.
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PMID:[Use of nicotinamide and pyridoxal-5-phosphate to treat experimental epilepsy]. 645 75

Discussion focused on the use of hormone therapy for treating tension and depression experienced by women at various times during their life cycle. Teenagers frequently experience mood changes and discomfort during the early menstrual years. Most of these problems gradually disappear without treatment. In cases of severe dysmenorrhea, conventional estrogen and progestogen pills can be administered. Many women experience tension or depression during pregnancy. These feelings are usually induced by ambivalent feelings toward the pregnancy, concern about the pregnancy outcome, or fear of labor. Reassurance is the only therapy needed by most of these women. Neurotic puerperal reactions are rare but when they occur they are usually mild and disappear quickly. Prostaglandins are sometimes used to treat puerperal psychosis but prompt psychiatric care is probably more effective. About 10% of all females suffer from premenstrual syndrome. Dydrogesterone is effective in treating about 70% of these cases. Pyridoxine relieves symptoms in about 50% of these patients. Many women experience postmenopausal depression. Depression at that time can be induced by physiological changes; however, women during that stage of life may also be suffering from externally induced depression. If the depression has a physiological basis, estrogen replacement therapy is usually helpful. About 6% of the women who use oral contraceptives experience depression. These symptoms are sometimes relieved by administering pyridoxine or by taking a weak progestogen during the last week of pill taking.
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PMID:Tension and depression in women--the place of hormone therapy. 719 99

Pyridoxine (PN) was intraperitoneally given at 250 and 500 mg/kg to male rats for 2, 4, or 6 weeks, and its effects on male fertility evaluated in terms of the optimal treatment period and detection parameters. Animals of all PN groups showed depression of body weight gains from week I of treatment onwards, significant at all but the 250 mg/kg 2 week administration I week time point. After 2 weeks treatment, the testes demonstrated only very slight histopathological changes. The 4- and 6-week treatments caused decreased spermatozoal motility and some histopathological changes in the testes including degeneration of germinal epithelial cells with both doses and also decreases in the fertility index and mean velocity of sperm, reduction in the testes and epididymides weights, and changes in testicular proteins. In the animals undergoing a 4-week recovery period following 4 or 6 weeks exposure, changes disappeared with the 250 mg/kg dose, but still remained with 500 mg/kg. From these findings, it is concluded that a treatment period of 4 weeks is sufficient for evaluation of drug effects on male fertility and that histopathology can detect the slightest toxic effects on the testis.
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PMID:Effects of pyridoxine on male fertility. 866 59

Pyridoxine nutritional status has a significant and selective modulatory impact on central production of both serotonin and GABA - neurotransmitters which control depression, pain perception, and anxiety - owing to the fact that the decarboxylases which produce these neurotransmitters have a relatively low affinity for pyridoxal phosphate (PLP). Pyridoxine deficiency leads to increased sympathetic outflow and hypertension in rodents, possibly reflecting decreased central production of these neurotransmitters; conversely, supplemental pyridoxine lowers blood pressure in many animal models of hypertension, and there is preliminary evidence for antihypertensive activity in humans as well. Additionally, physiological levels of PLP interact with glucocorticoid receptors to down-regulate their activity. Thus, high-dose pyridoxine, by amplifying tissue levels of PLP, may be expected to have a favorable impact on certain dysphoric mental states, while diminishing sympathetic output and acting peripherally to blunt the physiological impact of corticosteroids. In light of growing evidence that chronic dysphoria, particularly when accompanied by hopelessness or cynicism, has a major negative impact on morbidity and mortality from a wide range of disorders, high intakes of pyridoxine may have the potential to improve prognosis in many individuals. With respect to cardiovascular health, reduction of homocysteine levels should contribute to this benefit. These predictions are consistent with recent epidemiology correlating plasma PLP levels with risk for vascular events and overall survival.
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PMID:High-dose pyridoxine as an 'anti-stress' strategy. 1085 91

In the 1st part of this study, monosynaptic excitatory postsynaptic potentials (EPSPs) in layer V of the rat prefrontal cortex (PFC) were evoked by electrical stimulation of layer I. Recordings with intracellular sharp, microelectrodes showed a concentration-dependent inhibition of the EPSP by adenosine 5'-O-(2-thiodiphosphate) (ADP-beta-S). Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), when given alone depressed the EPSP and in addition antagonized the effect of ADP-beta-S. Exclusion of the N-methyl-D-aspartate (NMDA) component of the EPSP by D(.)-amino-5-phosphonopentanoic acid (AP-5) abolished the ADP-beta-S-induced depression. The pressure-application of both NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) caused reproducible depolarizations. ADP-beta-S inhibited the effect of NMDA, but did not alter that of AMPA. PPADS was also under these conditions antagonistic with ADP-beta-S. In the 2nd part of the study, NMDA-induced currents were measured by whole-cell patch-clamp pipettes. ADP-beta-S caused a concentration-dependent inhibition of the responses to NMDA. PPADS alone did not alter the NMDA-currents but again antagonized the action of ADP-beta-S; 2'-deoxy-N(6)-methyladenosine-3',5'-diphosphate (MRS 2179) also abolished the NMDA effect. The ADP-beta-S-induced inhibition persisted in the presence of tetrodotoxin (TTX) or guanosine 5'-O-(3-thiodiphosphate) (GDP-beta-S) applied to the external medium and the pipette solution, respectively. The 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) moderately decreased the ADP-beta-S effect. The inhibitory function of ADP-beta-S on EPSPs and the interaction with PPADS was observed also in layer V pyramidal neurons of the parietal somatosensory cortex. In conclusion, metabotropic P2Y(1) receptors appear to exert a new modulatory influence on fast excitatory amino acid transmission in the cerebral cortex.
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PMID:P2Y(1) receptor activation inhibits NMDA receptor-channels in layer V pyramidal neurons of the rat prefrontal and parietal cortex. 1242 96

The increasing number of older people is characteristic for most industrialised nations and implicates the known psychosocial and economic consequences. Therefore, an optimal nutrient supply that promotes continuing mental and physical well-being is particularly important. In this respect, vitamin B(12) and folic acid play a major role, since deficiency of both vitamins is associated with the pathogenesis of different diseases such as declining neurocognitive function and atherosclerotic lesions. Vitamin B(12) and folic acid act as coenzymes and show a close molecular interaction on the basis of the homocysteine metabolism. In addition to the serum concentrations of the vitamins, the metabolites homocysteine and methylmalonic acid are sensitive markers of cobalamin and folate status. Depending on the used marker, 3-60% of the elderly are classified as vitamin B(12) deficient and about 29% as folate deficient. Predominantly, this high prevalence of poor cobalamin status is caused by the increasing prevalence of atrophic gastritis type B, which occurs with a frequency of approximately 20-50% in elderly subjects. Atrophic gastritis results in declining gastric acid and pepsinogen secretion, and hence decreasing intestinal digestion and absorption of both B vitamins. This is the reason why an insufficient vitamin B(12) status in the elderly is rarely due to low dietary intake. In contrast, folic acid intake among elderly subjects is generally well below the recommended dietary reference values. Even moderately increased homocysteine levels or poor folate and vitamin B(12) status are associated with vascular disease and neurocognitive disorders. Results of a meta-analysis of prospective studies revealed that a 25% lower homocysteine level (about 3 micromol/L) was associated with an 11% lower ischemic heart disease risk and 19% lower stroke risk. It is still discussed, whether hyperhomocysteinemia is causally related to vascular disease or whether it is a consequence of atherosclerosis. Estimated risk reduction is based on cohort studies, not on clinical trials. Homocysteine initiates different proatherogenetic mechanisms such as the formation of reactive oxygen species and an enhanced fibrin synthesis. Supplementation of folic acid (0.5-5 mg/d) reduces the homocysteine concentration by 25%. Additional vitamin B(12) (0.5 mg/d) induces further reduction by 7%. In secondary prevention, supplementation already led to clinical improvements (reduction of restenosis rate and plaques). Depression, dementia, and mental impairment are often associated with folate and vitamin B(12) deficiency. The biochemical reason of this finding may be the importance of folic acid and vitamin B(12) for the transmethylation of neuroactive substances (myelin, neurotransmitters) which is impaired in vitamin deficiency ("hypomethylation hypothesis"). In recent years, there is increasing evidence for a role of folic acid in cancer prevention. As a molecular mechanism of a preventive effect of folic acid the hypomethylation of certain DNA sections in folate deficiency has been suggested. Since folate and vitamin B(12) intake and status are mostly insufficient in elderly subjects, a supplementation can generally be recommended.
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PMID:[Age-associated changes in the metabolism of vitamin B(12) and folic acid: prevalence, aetiopathogenesis and pathophysiological consequences]. 1510 81

Vitamin B(12) deficiency is a common problem in elderly subjects. If a serum cobalamin level of about 150 pmol/L (200 pg/mL) is considered normal, 10-15% of the elderly are deficient. Today, however, a threshold of 220-258 pmol/L (300-350 pg/mL) is recognized as desirable in the elderly, or else sensitive markers like the blood concentration of homocysteine or methylmalonic acid (MMA) are used. Then the prevalence of cobalamin deficiency rises to up to 43%. In the elderly, this high prevalence of poor cobalamin status is predominantly caused by atrophic gastritis type B. Atrophic gastritis results in declining gastric acid and pepsinogen secretion, and hence decreasing intestinal absorption of the cobalamin protein complexes from food. About 20-50% of the elderly are affected. Furthermore, the reduced acid secretion leads to an alkalinization of the small intestine, which may result in bacterial overgrowth and thus to a further decrease of the bioavailability of the vitamin. In addition, some drugs such as proton pump inhibitors or H2 receptor antagonists inhibit the intestinal absorption of vitamin B(12). An already moderately reduced vitamin B(12) level is associated with vascular disease and neurocognitive disorders such as depression and impaired cognitive performance. Furthermore, a poor vitamin B(12) status is assumed to be involved in the development and progression of dementia (e.g., Alzheimer's dementia). This is especially observable if the folic acid status is reduced as well. Due to the insecure supply, the cobalamin status of elderly persons (>/=60 years) should be regularly controlled and a general supplementation with vitamin B(12) (>50 microg/day) should be considered.
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PMID:Cobalamin: a critical vitamin in the elderly. 1553 65

Vitamin B(12) deficiency is common in older adults, and may be associated with cognitive impairment and depression. The main purpose of this study is to explore clinical effectiveness of regular vitamin B(12) supplementation on cognitive function and depressive symptoms among oldest old men living in a Taiwanese veterans care home. All residents of Banchiao Veterans Care Home were invited for study. Status of regular vitamin B(12) supplementation was determined. Cognitive function and depressive symptoms were evaluated by mini-mental state examination (MMSE) and geriatric depression scale (GDS). Subjects with renal insufficiency or established diagnosis of vitamin B(12) deficiency were excluded. Comparisons of demographic data, MMSE, GDS, and serum vitamin B(12) between subjects with and without regular supplementation were done. In total, 419 residents (mean age=80.8+/-5.5 years, all males) were enrolled. The mean serum level of vitamin B(12) was 1294.1+/-189.1 pg/ml (range: 50-30,000 pg/ml). Forty-five subjects (10.7%) reported regular vitamin B(12) supplementation, and their mean serum levels of vitamin B(12) were significantly higher than the non-supplementation subjects (8057.4+/-1408.3 pg/ml vs. 480.4+/-14.5 pg/ml, p<0.001). The mean MMSE (26.7+/-4.6 vs. 26.7+/-3.7, p=0.965), GDS (1.8+/-1.7 vs. 1.9+/-2.3, p=0.595), prevalence of cognitive impairment (13.6% vs. 19.3%, p=0.420) and depressive symptoms (4.5% vs. 8.4%, p=0.375) were similar between subjects with and without regular vitamin B(12) supplementation. In conclusion, regular vitamin B(12) supplementation and high serum level of vitamin B(12) are not associated with better cognitive function or depressive symptoms among asymptomatic oldest old men in a Taiwanese veterans care home.
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PMID:Regular vitamin B12 supplementation among older Chinese men in a veterans care home in Taiwan. 1877 74

Pyridoxal phosphate and pyridoxamine phosphate, the catalytically active forms of vitamin B(6), influence brain function by participating at stages in metabolism of proteins, lipids, carbohydrates, other coenzymes and hormones. Vitamin B(6) participates in the metabolism of amino acids in the form of decarboxylation, transamination, deamination, racemization and desulfhydration reactions. The crucial roles that these coenzymes play in the maintenance of functional integrity of the brain become evident when one realizes that some compounds implicated as neurotransmitters are synthesized and/or metabolized by the aid of the vitamin B(6)-dependent enzymatic reactions. These include dopamine, norepinephrine and serotonin, tyramine, tryptamine, taurine, histamine, gamma aminobutyric acid, and even acetylcholine indirectly. In recent years, the above-mentioned biogenic amines have become of considerable interest to neurobiologists who are investigating the etiology and the pathological manifestations of many disorders of the central nervous system such as Parkinsonism, Huntington's chorea, minimal brain disfunction, schizophrenia, depression, sleep disorders and seizure disorders. Vitamin B(6) deficiency in these cases is characterized by anemia, growth retardation and alteration in neuronal function, including neuropathies, hyperirritability, hyperexcitability and convulsions. The importance of vitamin B(6) in the study of brain function assumes still greater significance when one considers the effects of nutritional deficiencies on growth and development of the brain and mental processes and in the involvement of vitamin B(6) in some inborn errors of metabolism which result in mental retardation. Vitamin B(6) deficiency results in a lowered concentration of Coenzyme A in blood, in reduced absorption and storage of vitamin B(12), and in increased excretion of vitamin C. Furthermore, vitamin B(6) acts synergistically with vitamin E to control metabolism of unsaturated fats, with vitamin C in tyrosine metabolism and with niacin in its action and participates in niacin synthesis. In addition, vitamin B(6) deficiency results in insufficiency of insulin and in alteration of the functions of adrenal and pituitary glands, since it is involved in the synthesis of growth hormone, follicle-stimulating hormone, luteinizing hormone, aldosterone, glucagon, cortisol, estradiol, testosterone and epinephrine. It is hoped that by understanding the factors that regulate the synthesis, binding, storage and degradation of pyridoxal phosphate in the brain, a better insight into the role of vitamin B(6) in neurobiology may be gained.
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PMID:Regulation and function of pyridoxal phosphate in CNS. 1964 63


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