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)

L-Proline and some of its analogs have been shown to prevent spreading depression (SD) in the chick retina at relatively low concentrations and to impair memory processing without provoking toxic or electrophysiological disturbances. Both effects are hypothesized to be caused by inhibition of the effects of glutamate released into the extracellular space. L-Proline, its D-enantiomer, six proline analogs including two homologs (L-azetidine-2-carboxylic acid and DL-pipecolic acid), and five other compounds were examined for their effects on spreading depression and their amnestic and electrophysiological effects. L-Proline, L-baikiain, DL-3,4-dehydroproline, and L-4-hydroxyproline all reduced the incidence of SD in the chick retina and proved to be amnestic. D-Proline, L-pyroglutamic acid, L-azetidine-2-carboxylic acid, DL-pipecolic acid, L-glutamic acid diethylester, L-isoleucine and L-norleucine neither depressed SD nor caused retrograde amnesia. L-Prolyl-L-proline and L-glutamine did not depress SD at low concentrations but had significant amnestic effects. None of the listed compounds induced EEG disturbances. Implications for memory mechanisms are discussed in the light of these results.
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PMID:Amnestic potency of proline analogs correlates with anti-spreading depression potency. 719 Feb 93

Decreases in brain serotonin levels have been implicated in the pathogenesis of human depression. While circulating levels of tryptophan (TRP) might possibly reflect concentration of brain serotonin, a more relevant peripheral measure may be the ratio of plasma TRP to five other neutral amino acids (TRP/5aa ratio). In depressed subjects and normal controls, plasma TRP (free and total), phenylalanine (PHE), tyrosine (TYR), leucine, isoleucine, and valine were measured on three days. When depression was most severe, depressed patients had lower TRP/5aa ratios and total TRP levels and higher PHE and TYR levels. After the patients' conditions improved, these differences disappeared. As Hamilton depression scores improved, the plasma TRP/5aa ratios increased significantly. This finding tends to support the idea that changes in brain serotonin level reflect changes in depression severity.
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PMID:Plasma tryptophan and five other amino acids in depressed and normal subjects. 724 26

The effect of insulin and leucine on amino acid and protein metabolism in muscle is not fully understood. To characterize their separate and combined effects on free amino acids in muscle and plasma, 11 volunteers received an infusion of either leucine (1 g h-1, Group 1) or glucose (20 g h-1, Group 2) for 2 h followed by a combination of the two infusions for an additional 2-h period. In muscle both the leucine infusion and the leucine plus glucose infusion increased the concentration of free leucine significantly, while the sum of the other branched chain amino acids (BCAA), of the aromatic amino acids and of the basic amino acids decreased. Glucose infusion alone decreased the sum of the essential amino acids, the BCAA and the aromatic amino acids. The combination of leucine and glucose augmented the decreases, while the concentrations of glutamate, glutamine and alanine were unaffected. In plasma the leucine infusion doubled the leucine concentration and decreased alanine, valine, methionine, tyrosine, phenylalanine and the sum of the aromatic amino acids. Glucose infusion decreased methionine, serine, isoleucine and the sum of the essential amino acids and of the BCAA. The combination of leucine infusion and hyperinsulinaemia augmented the decreases. The plasma concentrations of the keto acids of valine and isoleucine decreased by the leucine infusion while the concentrations of the keto acid of leucine and isoleucine decreased by glucose infusion. The combination of leucine and glucose had an additive effect. These effects are attributed to a specific effect of leucine on the other two BCAA and a depression of muscle proteolysis by both leucine and insulin, resulting from glucose infusion.
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PMID:The separate and combined effect of leucine and insulin on muscle free amino acids. 782 Sep 76

We investigated the roles of the vagus nerve and the serotonin3 (5-HT3) receptor in mediating the food intake depression associated with amino acid deficiency. The food intake of sham-operated (sham) rats given an isoleucine-imbalanced (IMB) diet was reduced to < 40% of control basal (BAS) diet intake (P = 0.0009), and pretreatment with the 5-HT3 antagonist tropisetron (Trop) increased IMB intake by twofold over the vehicle (VEH)-treated group (P < or = 0.0001), as we have reported before. However, after subdiaphragmatic vagotomy (VAGX), IMB intake was increased to a level intermediate between the sham-VEH and sham-Trop groups, while administration of Trop did not increase IMB intake over VAGX alone. By the end of day 1, the VAGX-Trop group had eaten only 1 g more of IMB than the VAGX-VEH group (NS). We conclude that 1) the vagus is among the physiological systems involved in the anorectic responses to IMB and 2) intact vagal function is necessary for the full effect of 5-HT3 antagonists in alleviating the anorectic responses to IMB.
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PMID:Anorectic responses to dietary amino acid imbalance: effects of vagotomy and tropisetron. 802 48

Cerebral serotonin is synthetized from its blood precursor: tryptophan (TRP), an essential amino acid (6). TRP has been extensively studied since serotonine has been reported to be involved in the pathogenesis of depression (9). In one hand, brain serotonin content depends on regulation by plasma large neutral amino acids (LNAA): leucine, isoleucine, valine, tyrosine and phenylalanine that compete with TRP to cross over the blood brain barrier (7, 13). In the other hand TRP is largely linked with albumin. So, we have studied plasma total TRP, free TRP and the ratio TRP on LNAA as potential cerebral serotonin index. The aim of this study is to observe the blood variations of the biological parameters in fasting and postprandial conditions in 8 depressed women, aged from 57 to 78 years, on a short protein controlled diet: 4 women had TRP poor then rich diet and the others 4 rich then poor. Alimentary proteins modulated diets and each patient was his own control: the results under modulated diet were compared with those under normal diet at the same time. More over, 2 psychotic patients aged 58 and 70 years have been studied at the same time, in each group. Biological datas were compared with clinical evolution.
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PMID:[Plasma tryptophan in a protein controlled diet in depressed patients]. 808 36

The effect of adding cottonseed hulls to casein- and cottonseed-kernel-based diets on the apparent and true ileal digestibility of N and amino acids, and the proportion of this effect accounted for by condensed tannin (CT), were determined using the growing rat. Sixty rats were allocated randomly to ten semipurified diets, containing either casein (four diets) or purified unheated solvent-extracted cottonseed kernel (six diets) as the sole protein source, with Cr2O3 added as an indigestible marker. Two of the casein diets contained no hulls whilst the remaining two diets contained 70 g cottonseed hulls/kg. Two of the cottonseed-kernel-based diets contained no hulls, with two containing 23 g hulls/kg and the remaining two containing 46 g hulls/kg. For each pair of diets, PEG was either included or excluded. The effect of CT was quantified by comparing control rats (-PEG; CT acting) with PEG-supplemented rats (+PEG; CT inactivated) at each level of dietary hulls. The rats were given their respective experimental diets for 14 d. Each rat was given the food ad libitum for 10 min hourly from 08.00 to 18.00 hours. On day 14, samples of digesta were collected at death from the terminal 150 mm of ileum at 7 h from the first meal. Apparent and true ileal digestibilities were calculated for DM, N and the individual amino acids. The principal finding was that the inclusion of hulls depressed the apparent and true ileal digestibilities of N and amino acids, but with the response differing between diets. With the casein-based diet the mean apparent and true ileal amino acid digestibilities were significantly depressed from 0.89 and 0.96 to 0.85 and 0.92 respectively, by the inclusion of 70 g hulls/kg in the diet, and addition of PEG then restored these to 0.89 and 0.95. All of the depression could be explained by the CT content of the hulls. However, with the cottonseed-kernel-based diet the responses fell into three categories. The apparent and true ileal digestibilities of the essential amino acids cystine and methionine were not affected by hull addition, ileal digestibilities of leucine, isoleucine, lysine, threonine and valine were markedly depressed by hull addition with approximately 50% of the depression being explained by CT, whilst the ileal digestibilities of histidine, arginine and phenylalanine were depressed by hull addition but little or none of this effect could be explained by CT. Thus the effect of hulls on protein digestion clearly differed with source of protein. With the cottonseed-kernel-based diet it seems that components of the hulls other than CT also depressed the apparent and true ileal digestibilities of N and amino acids. The identity of these components is unknown.
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PMID:The effect of cottonseed condensed tannins on the ileal digestibility of amino acids in casein and cottonseed kernel. 869 96

The molar ratio of total plasma tryptophan to the sum of other large neutral amino acids (viz., valine, isoleucine, leucine, tyrosine, phenylalanine), thought to reflect brain serotonin formation, was estimated in 69 patients with major depression before and after 1 week of treatment with different serotonin reuptake inhibitors, fluvoxamine (n = 28), fluoxetine (n = 10), citalopram (n = 7), mixed serotonin-noradrenaline reuptake inhibitor amitriptyline (n = 11), clomipramine (n = 8) and the preferentially noradrenaline reuptake inhibitor, nortriptyline (n = 5). A significant difference among 'good', 'intermediate' and 'poor' responders for the percentual variation of tryptophan/large neutral amino acids ratio after 1 week of therapy was found, while pretreatment values of tryptophan/large neutral amino acids ratio, basal Hamilton Depression Rating Scale scores and its percentual variation after 1 week of therapy did not show any significant differences. These results suggest that the percentual variation of tryptophan/large neutral amino acids ratio could be a useful tool in predicting drug response.
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PMID:Predictive value of tryptophan/large neutral amino acids ratio to antidepressant response. 882 15

In an attempt to quantitatively evaluate the destructive effects of free radicals on metabolism, freshly prepared and cryopreserved isolated rat hepatocytes were exposed to and incubated with Fe2+ compounds, reputedly inducing oxygen-derived free radicals (OFR) capable of attacking the lipid structures of cellular membranes. Malondialdehyde (MDA) formation was interpreted as an expression of free radical interaction with polyunsaturated lipids, and in vitro incubations were carried out during the period of constant MDA formation. Protein synthesizing activity was evaluated by incubating control hepatocytes and cells previously exposed to 100 microM of Fe2+, to 100 microM of Fe2+, and 100 microM of desferrioxamine and to 100 microM of desferrioxamine alone with 0.1 microCi of L-[U-14C]isoleucine and in the presence of these compounds. Membrane transport activity was similarly evaluated by following the cellular uptake of alpha-amino-[1-14C]isobutyric acid. Protein-synthesizing activity of freshly prepared and cryopreserved hepatocytes was not affected by Fe2+ treatment, nor by the additions of the iron chelator desferrioxamine. Amino acid transport, however, was inhibited by 100 microM of Fe2+, but was effectively neutralized by the simultaneous addition of 100 microM of desferrioxamine. Cryopreserved hepatocytes equally presented a significantly inhibited amino acid transport activity over the incubation period. The results suggest that the metabolic depression measured in thawed hepatocytes does not result to any large extent from iron-catalysed OFR effects. When OFR production was deliberately induced, the most significant early change was seen in transmembrane amino acid uptake in both fresh and cryopreserved cells.
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PMID:Cryopreservation of isolated rat hepatocytes: effects of iron-mediated oxidative stress of metabolic activity. 913 Mar 86

Serum total tryptophan and the five competing amino acids (CAA), i.e., valine, leucine, tyrosine, phenylalanine, and isoleucine were determined in 35 major depressed subjects of whom 27 with treatment resistant depression (TRD), and 15 normal controls. Twenty-five of the depressed subjects had repeated measurements of the amino acids both before and after antidepressive treatment. The following immune-inflammatory variables were assayed in the above subjects: serum zinc (Zn), total serum protein (TSP), albumin (Alb), transferrin (Tf), iron (Fe), high-density lipoprotein cholesterol (HDL-C), number of peripheral blood leukocytes, and the CD4+/CD8+ T cell (T-helper/T-suppressor) ratio. Serum tryptophan and the tryptophan/CAA ratio were significantly lower in major depressed subjects than in normal controls. The tryptophan/CAA ratio was significantly lower in patients with TRD than in patients without TRD and normal controls. There were no significant alterations in any of the amino acids upon successful therapy. There were significant correlations between serum tryptophan and serum Zn, TSP, Alb, Tf, Fe, and HDL-C (all positive), and number of leukocytes and the CD4+/CD8+ T-cell ratio (all negative). The tryptophan/CAA ratio was significantly and negatively related to the number of leukocytes and the CD4+/CD8+ T-cell ratio. The results suggest that (a) TRD is characterized by lower availability of serum tryptophan; (b) the availability of tryptophan may remain decreased despite clinical recovery; and (c) the lower availability of tryptophan is probably a marker of the immune-inflammatory response during major depression.
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PMID:Serotonin-immune interactions in major depression: lower serum tryptophan as a marker of an immune-inflammatory response. 922 8

Numerous studies suggest that modifications in concentrations of both excitatory and inhibitory amino acids are implicated in the pathophysiology of portal-systemic encephalopathy (PSE), a neuropsychiatric disorder associated with chronic liver disease in humans. In this study, amino acid levels were measured by High Performance Liquid Chromatography (HPLC) in Cerebrospinal Fluid (CSF) of 10 dogs (age range: 3 mo.- 3 yr 4 mo.) exhibiting a congenital portal-systemic shunt, either intra or extra-hepatic, and 8 age-matched control dogs who showed no signs of hepatic or neurologic disorders. Dogs with congenital shunts manifested signs of encephalopathy such as disorientation, head pressing, vocalization, depression, seizures and coma. CSF from dogs with congenital shunts contained significantly increased amounts of glutamate (2 to 3-fold increase, p<0.01), glutamine (6-fold increase, p<0.05) and aromatic amino acids (phenylalanine, tyrosine and tryptophan) compared to CSF of control dogs. Concentrations of GABA and branched chain amino acids (valine, leucine, isoleucine) were within normal limits. Modifications of brain glutamate (an excitatory amino acid) as well as tryptophan (the precursor of serotonin) could contribute to the neurological syndrome characteristic of congenital PSE in dogs.
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PMID:Selective alterations of cerebrospinal fluid amino acids in dogs with congenital portosystemic shunts. 947 3


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