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)

This investigation tested the hypothesis that depressed patients have abnormal diurnal variation of natural killer (NK) cell measures. The diurnal variation of levels of Leu-11 NK cells and NK cytotoxic activity was significantly less in 24 patients with major depression than in 24 normal comparison subjects. These findings provide evidence that aspects of immune, as well as neural and endocrine, chronobiology are abnormal in depression.
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PMID:Abnormal diurnal variation in circulating natural killer cell phenotypes and cytotoxic activity in major depression. 153 92

The effects of major depression on peripheral blood natural killer cell phenotypes and natural killer cell activity were studied by comparing depressed and normal control subjects. Depressed subjects exhibited (1) significant reductions in Leu-11 (CD16) natural killer effector cells and natural killer cell activity and (2) a dissociation of the normal positive correlation between the percentage of Leu-11 cells and natural killer cell activity. These findings suggest that alterations in the availability and the killing capacity of circulating Leu-11 natural killer cells appear to be responsible for depression-related reductions in natural killer cell activity. Moreover, men with major depression showed marked reductions in Leu-11 cells, natural killer cell activity, and Leu-7 (HNK-1) lymphocytes compared with normal control men. By contrast, depressed women did not differ significantly from normal control women on any of these three immune function measures. Severity of depression as assessed by Hamilton Rating Scale for Depression scores was not associated with natural killer cell activity or Leu-7 lymphocyte levels in either men or women with major depression. Hamilton Rating Scale for Depression severity ratings were, however, strongly inversely correlated with Leu-11 lymphocyte counts among men, but not women, with major depression. These data begin to elucidate the immunological mechanisms by which natural killer cell activity is altered in depression and suggest that some measures of immunity may be differentially affected in male and female subjects with the syndrome of major depression.
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PMID:Circulating natural killer cell phenotypes in men and women with major depression. Relation to cytotoxic activity and severity of depression. 153 2

This study examined psychologic distress and immune function in patients with chronic-progressive multiple sclerosis participating in a placebo-control trial of cyclosporine. Immune measures included percentages and absolute numbers of CD2+, CD4+, CD8+, Leu-11-b+, HLA-DR (IA+), and transferrin-receptor-positive cells, which were evaluated by immunofluorescence using monoclonal antibodies. Distress was measured with self-report scales. The Expanded Disability Status Scale assessed neurologic disability. Subjects were followed up for 2 years, and their high-depressed and low-depressed times were compared. Times of greater depression were associated with lower CD8+ cell numbers and CD8+%, and a higher CD4/CD8 ratio. CD4+ cell numbers and percent were also higher when subjects were depressed, but only in the placebo group. There were no differences in Expanded Disability Status Scale when subjects were more depressed. Evaluation of a single subject revealed that Ia+ and transferrin-receptor-positive lymphocytes increased 3 months before distress increased. It was concluded that distress is associated with immune dysregulation in multiple sclerosis, although the mechanisms of this association have yet to be delineated.
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PMID:A prospective study of depression and immune dysregulation in multiple sclerosis. 153 25

The possible role of amino acid availability and a functional hypothalamic-pituitary-adrenal axis in the mood disturbances often reported in postpartum women and in users of the oral contraceptive was examined by measuring amino acids and doing a dexamethasone suppression test. Plasma cortisol, tryptophan, tyrosine, their competing amino acids in brain uptake (CAA), and the effect of 1mg dexamethasone were determined in 10 women taking oral contraceptives, 31 women 3 days postpartum, and 9 controls. The pill contained 30 mcg ethinyl estradiol and .075 mg gestodene (2 women), and 30 mg ethinyl estradiol and .15 mg desogestrel (8 women). The subject also took self-rating mood scales: Zung Depression, Zung Anxiety, Beck Depression and State Anxiety Inventory. Cortisol was significantly higher in postpartum women and pill users than in normal controls. Tryptophan, valine, isoleucine and leucine were lower in postpartum women. Tyrosine and tyrosine CAA were lower in postpartum women and pill users. 80% of the postpartum group had negative dexamethasone suppression tests, i.e., cortisol 5 mcg/dl 24 hours after 1 mg dexamethasone. After dexamethasone valine was significantly higher and tryptophan/CAA and tyrosine/CAA ratios were lower, as a result of slightly lower tryptophan and tyrosine and slightly higher CAAs. Furthermore, effects on the amino acid ratios were only evident in women exhibiting dexamethasone suppression. There was a significant negative correlation between depression and anxiety scores and the tryptophan/CAA ratio. The results indicated first that the dexamethasone suppression test is an invalid marker for major depression, and also that availability of the amino acid precursors of brain neurotransmitters may affect mood in the puerperium.
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PMID:Disturbances in dexamethasone suppression test and lower availability of L-tryptophan and tyrosine in early puerperium and in women under contraceptive therapy. 156 Apr 30

The effects on C fiber evoked activity in lumbar dorsal horn convergent neurones of i.v. morphine alone, of Tyr-D-Thr-Gly-Phe-Leu-Thr (DTLET) alone or of either of these drugs in association with 5-deoxyadenosylcobalamine (dibencozide) were investigated in anesthetized rats. Both morphine and DTLET depressed the neuronal responses in a dose-related fashion, with the former requiring lower doses. Although dibencozide alone was devoid of any effect, it significantly enhanced the depressive effects of all doses of morphine tested and of the lower two doses of DTLET. It is concluded that dibencozide enhances the spinal depression of nociceptive information elicited by mu and delta opioid agonists. This drug could provide a useful tool for the study of interactions between opioids and opioids receptors. It is also suggested that dibencozide could be useful in clinical practice for reducing the dosage of opioids.
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PMID:Depressive effects of mu and delta opioid receptor agonists on activities of dorsal horn neurones are enhanced by dibencozide. 164 26

A biochemical basis for the development of tolerance to morphine has yet to be defined. Although a number of models have been proposed, none can account for complete tolerance to this drug. Previous studies in our laboratory indicated that the development of complete tolerance to certain morphine-induced behaviors (antinociception, catalepsy and respiratory depression) is associated with changes in the activity of some form(s) of phosphodiesterase with cyclic GMP as substrate (cGMP-PDE) activity in the brain areas that mediate these behaviors (periaqueductal gray, striatum and medulla). In the present study, experiments were performed in which Cyclo(Leu-Gly), a dipeptide that inhibits the development of tolerance to morphine, was administered daily (2 mg/kg) to morphine-naive rats, coadministered with morphine or coadministered with morphine to morphine-tolerant rats and the cGMP-PDE activity was measured. The development of tolerance to the effects was inhibited or reversed by administration of cyclo(Leu-Gly) and there were corresponding changes in cGMP-PDE activity in various brain regions. Differences in cGMP hydrolysis between brain regions from morphine-tolerant animals, tolerance-inhibited animals and tolerance-reversed animals strengthens the evidence for direct involvement of cGMP-PDE(s) in tolerance phenomena.
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PMID:Effect of cyclo(Leu-Gly) on cyclic GMP-phosphodiesterase activity changes associated with development of tolerance to morphine-induced antinociception, catalepsy, respiratory depression and mydriasis. 165 44

Some children with coeliac disease show behavioural disorders such as depression and other signs which have been correlated with reduced central monoamine metabolism. We have therefore investigated the brain availability of the monoamine precursors tryptophan and tyrosine in 15 untreated children with coeliac disease and 12 treated children with coeliac disease as well as in 12 control children. Significantly decreased plasma concentrations of tryptophan were found in untreated children (mean (SD) 13 (4) mumols/l, p less than 0.001) compared with treated children (31 (13) mumols/l), and in both groups of coeliac children when compared with control children (81 (22) mumols/l). A significantly lower ratio of plasma tryptophan to large neutral amino acids (tyrosine, valine, isoleucine, leucine, and phenylalanine) was also observed, which could indicate impaired brain availability of tryptophan in coeliac children and was more pronounced in untreated children. The impaired availability of tryptophan could produce decreased central serotonin synthesis and in turn behaviour disorders in children with coeliac disease.
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PMID:Plasma precursor amino acids of central nervous system monoamines in children with coeliac disease. 177 52

The primary mechanism of cyanide (CN) intoxication is the inhibition of metabolism in the central nervous system. We determined the effects of CN on several biochemical processes in neuroblastoma x glioma hybrid NG108-15 cells, which possess numerous neuronal properties. These cells were not sensitive to a high concentration (1 mM) of NaCN, but became sensitive in the presence of the anaerobic glycolysis inhibitors sodium iodoacetate (IA) and 2-deoxyglucose (2-DG):cellular metabolic processes (e.g., DNA, RNA and protein synthesis) decreased to about 40% of control due to treatment with 0.5 mM NaCN + 0.05 mM IA and 0.1 mM NaCN + 20 mM 2-DG. ATP in cells exposed to 0.01 or 0.1 mM NaCN + 20 mM 2-DG was reduced 75% and 100% respectively within one min. Pretreatment of cells with the CN antidote cobalt (II) chloride (CoCl2) (0.06-0.18 mM) for 5 min prevented the depression of both [3H]leucine incorporation and ATP synthesis due to 1 mM NaCN + 20 mM 2-DG in a concentration-dependent manner. A proposed CN antidote alpha-ketoglutaric acid (disodium salt) also prevented the depression of cellular metabolism due to NaCN plus 2-DG. These results indicate that blocking anaerobic glycolysis makes NG108-15 cells sensitive to a low concentration of CN. Thus NG108-15 cells should be useful to study the mechanisms of neurotoxicity of CN and to test antidotes.
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PMID:Cyanide sensitive and insensitive bioenergetics in a clonal neuroblastoma x glioma hybrid cell line. 179 58

1. It has been established that chronic hyperammonaemia, whether caused by portacaval shunting or other means, leads to a variety of metabolic changes, including a depression in the cerebral metabolic rate of glucose (CMRGlc) increased permeability of the blood-brain barrier to neutral amino acids, and an increase in the brain content of aromatic amino acids. The preceding paper [Jessy, DeJoseph & Hawkins (1991) Biochem. J. 277, 693-696] showed that the depression in CMRGlc caused by hyperammonaemia correlated more closely with glutamine, a metabolite of ammonia, than with ammonia itself. This suggested that ammonia (NH3 and NH4+) was without effect. The present experiments address the question whether ammonia, in the absence of net glutamine synthesis, induces any of the metabolic symptoms of cerebral dysfunction associated with hyperammonaemia. 2. Small doses of methionine sulphoximine, an inhibitor of glutamine synthetase, were used to raise the plasma ammonia levels of normal rats without increasing the brain glutamine content. These hyperammonaemic rats, with plasma and brain ammonia levels equivalent to those known to depress brain function, behaved normally over 48 h. There was no depression of cerebral energy metabolism (i.e. the rate of glucose consumption). Contents of key intermediary metabolites and high-energy phosphates were normal. Neutral amino acid transport (tryptophan and leucine) and the brain contents of aromatic amino acids were unchanged. 3. The data suggest that ammonia is without effect at concentrations less than 1 mumol/ml if it is not converted into glutamine. The deleterious effect of chronic hyperammonaemia seems to begin with the synthesis of glutamine.
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PMID:Hyperammonaemia does not impair brain function in the absence of net glutamine synthesis. 187 6

The main adverse reaction to the immunosuppressive drug cyclosporine is dose-dependent renal dysfunction. Although renal vasoconstriction without major tubular dysfunction is usually noted, recent studies have demonstrated an inhibition of renal cortical microsomal protein synthesis. Sprague-Dawley rats and appropriate pair-fed controls were given cyclosporine orally in doses of 5, 10, 25, and 50 mg/kg/day for periods up to 10 days. A dose-dependent decline in glomerular filtration rate and effective renal plasma flow was maximal by day 3 and did not worsen despite continued dosing. Microsomal protein synthesis as measured by [3H]leucine incorporation was also depressed in a dose-dependent fashion; however, inhibition did not reach the nadir until day 4, 1 day after renal dysfunction was established. When cyclosporine was discontinued, microsomal protein synthesis was normalized by 4 days after drug withdrawal; in contrast, the return of glomerular filtration rate and effective renal plasma flow to normal required 8 days after drug discontinuation. Tubular function as measured by fractional excretion of lithium, enzymuria, and urinary osmolality was well maintained despite the depression of renal hemodynamics. There was no evidence of tubular necrosis by light or electron microscopy. Although cyclosporine produces reductions in renal microsomal protein synthesis, measured by "run-off" translation assays, these effects appear unlikely to be the direct cause of acute renal dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclosporine-induced renal dysfunction: correlations between cellular events and whole kidney function. 193 33


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