UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Buspirone (Buspar) is a azaspirodecanedione anxiolytic agent. Its mechanism of action is extremely complex, but current investigations indicate that its main neuropharmacologic effects are mediated by the 5-HT1A receptors. Other neuroreceptor systems could be involved, as buspirone displays some affinity for DA2 autoreceptors and 5-HT2 receptors. It has been proposed that inhibition of synthesis and release of serotonin result through the combined interactions of neuroreceptors and secondary messenger systems. This action leads to inhibition of the firing rate of 5-HT-containing neurons in the dorsal raphe. From this novel profile, that differs from that of the benzodiazepines, buspirone lacks anticonvulsant and muscle-relaxant properties, and causes only minimal sedation. The drug is rapidly absorbed after oral administration, with a mean bioavailability of 3.9%. After a single oral dose, the mean elimination half-life is 2.1 hours. Buspirone is mainly bound to albumin and alpha 1-acid glycoprotein. It is metabolized to an active metabolite 1-(2-pyrimidinyl) piperazine (1-PP). The mean elimination half-life of 1-PP is 6.1 hours. Buspirone is indicated in the treatment of generalized anxiety disorders. Its efficacy is comparable to the benzodiazepines. Its use in depression and panic disorders requires further investigation. When combined with alcohol or given alone, psychomotor impairment was not detected. Abuse, dependence, and withdrawal symptoms have not been reported. The frequency of adverse effects is low, and the most common effects are headaches, dizziness, nervousness, and lightheadness. Buspirone should be added to drug formularies and could represent a significant addition in psychopharmacology.
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PMID:Buspirone: an update on a unique anxiolytic agent. 304 84

A collaborative study of the humoral and cellular immune status of patients with carcinoma of the Head and Neck (H&N) was conducted at the West Virginia University (WVU) hospital. In addition, blind-coded serum panels were supplied on H&N cancer patients being treated at the National Cancer Institute (NCI). Serum protein analysis of the WVU study groups revealed that at the pretreatment sampling, the alpha-1 acid glycoprotein (AGP), total complement, and IgA levels were significantly elevated. The AGP levels and total complement levels declined to normal levels in the post-treatment period, whereas the IgA levels remained elevated throughout the entire observation period. Levels of serum immune complexes (SIC) were measured in both the WVU and NCI H&N cancer populations using the polyethylene glycol (PEG) precipitation method. In both survey populations all cancer groups had significantly elevated levels of SIC when compared to any of the control populations. The SIC levels never returned to comparative normal values even in cases after successful treatment. A subpopulation of the WVU-H&N cancer study group underwent a short course of intravenous hyperalimentation prior to their treatment regimen. These patients demonstrated a transient decrease in their SIC levels as well as a concomitant increase in their in vitro cell-mediated immune (CMI) correlates. The analysis of in vitro CMI correlates of the WVU study group using both polyclonal mitogens and specific antigens demonstrated a significant depression in these parameters pretreatment and post-treatment. In addition, it was observed that the time course for elevation of selected serum proteins (i.e., IgA and SIC) correlated with concomitant drops in CMI activity. Investigations were also conducted into the effects of immune complex-rich serum fractions upon selected in vitro CMI correlates. Significant blockage of a normal donor leukocyte migration-inhibition assay was demonstrated. Also, a similar inhibition of the ability of normal human lymphocytes to form high affinity rosettes was accomplished with serum from H&N cancer patients.
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PMID:Immune complexes, serum proteins, cell-mediated immunity, and immune regulation in patients with squamous cell carcinoma of the head and neck. 308 60

Plasma fibronectin, an opsonic glycoprotein, is known to modulate the reticuloendothelial phagocytic clearance of nonbacterial and, possibly, bacterial particulates. The decreased plasma fibronectin levels seen after cardiac surgery have been considered to derive mainly from opsonic consumption. In the present study, we demonstrated that the administration of ulinastatin, a human urinary trypsin inhibitor, to patients after cardiac surgery not only inhibited the postoperative depression of plasma fibronectin levels, but also maintained the plasma fibronectin level within the normal range. This effect apparently resulted from the inhibitory activity of ulinastatin on the proteolytic enzymes released after operation. This result suggests that the decreased plasma fibronectin level noted after cardiac surgery may derive mostly from excessive proteolytic enzymes. Our observation also indicates that the prophylactic administration of ulinastatin to patients undergoing major operations will result in a favorably functional reticuloendothelial phagocytic system.
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PMID:Suppressive effect of ulinastatin on plasma fibronectin depression after cardiac surgery. 334 22

Recently detoxified men with alcohol dependence (n = 15) and healthy volunteers (n = 14) were administered oral and intravenous imipramine and desipramine. Alcoholics had significantly greater total body clearance of imipramine (0.93 vs. 0.48 L/hr/kg; P less than 0.05) and desipramine (1.00 vs. 0.62 L/hr/kg; P less than 0.05) than did control subjects. Intrinsic clearance of unbound imipramine was greater in the alcoholic group (19.80 vs. 6.56 L/hr/kg; P less than 0.05), as was the intrinsic clearance of unbound desipramine (14.52 vs. 9.05 L/hr/kg; P less than 0.05). The mean elimination half-life for imipramine was significantly decreased in alcoholics (8.7 vs. 19.9 hours after intravenous infusion and 10.9 vs. 19.6 hours after oral administration; P less than 0.05). The mean elimination half-life for desipramine was decreased in alcoholics after intravenous infusion (16.5 vs. 22.4 hours; P less than 0.05). Unbound fractions of drug in plasma were decreased in the alcoholic group for both imipramine and desipramine after both routes of administration. alpha 1-Acid glycoprotein levels were elevated in the alcoholic group whereas total protein and albumin levels did not differ between groups. These findings suggest that recently detoxified alcoholics may require higher doses of imipramine than do nonalcoholic subjects. Desipramine clearance was affected to a lesser degree than imipramine, suggesting that from a pharmacokinetic standpoint it may be the preferred drug for the treatment of alcoholics with depression. Periodic monitoring of plasma levels may be required for recently abstinent alcoholics treated with antidepressants.
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PMID:Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers. 336 15

6-Methylmercaptopurine ribonucleoside (6-MMPR), an inhibitor of purine nucleotide biosynthesis de novo, was used as a model compound to evaluate the relationship between the levels of intracellular guanosine triphosphate (GTP) and the formation of cellular glycoproteins and their dolichol-oligosaccharide precursors in Sarcoma 180 cells. Previous studies using the purine antimetabolite, 6-thioguanine (6-TG), demonstrated a relationship between the drug-induced decrease in GTP levels and the incorporation of radiolabelled mannose and fucose into cellular glycoproteins; estimation of the importance of these cell-surface alterations to the cytotoxicity produced by this agent was complicated by the incorporation of 6-TG nucleotides into cellular DNA and RNA. In this report, evidence is presented to show that the toxicity of 6-MMPR to Sarcoma 180 cells is associated with the effects of this agent on the intracellular pools of purine nucleotides. GTP functions in part in the activation of the sugar mannose, a step necessary for the biosynthesis of glycoproteins from nucleotide sugar precursors. Thus, 6-MMPR, which blocks the de novo pathway of purine nucleotide biosynthesis, caused a pronounced decrease in the intracellular pools of GTP in Sarcoma 180 cells; this phenomenon was accompanied by a marked reduction in the incorporation of radiolabelled mannose into cellular glycoproteins and their dolichol-linked oligosaccharide precursors. In contrast, the incorporation of glucosamine, a sugar not metabolically activated by GTP, into glycoproteins, and of leucine into protein, were depressed only after prolonged incubation with either 6-MMPR or 6-TG. Adenine restored purine nucleotide pools depleted by 6-MMPR and partially prevented both the reduction in mannose incorporation into glycoprotein and the cytotoxic effects of this antimetabolite. Guanosine partially reversed the effects of 6-MMPR on intracellular GTP pools and mannose incorporation but not the depression of ATP pools produced by this anti-metabolite. However, guanosine did not reverse the cytotoxicity of 6-MMPR but instead enhanced its toxicity. The findings are consistent with the possibility of membrane changes being involved in the cytotoxicity of 6-MMPR, but clearly other factors are involved as well.
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PMID:Inhibition of mannose incorporation into glycoproteins and dolichol-linked intermediates of Sarcoma 180 cells by 6-methylmercaptopurine ribonucleoside. 358 54

The antifreeze glycoproteins (AFGP) of polar fish have the ability to depress the freezing temperature of water approximately 500 times the amount expected based on the number of AFGP molecules in solution; yet AFGP solutions have a purely colligative melting point depression. The difference of solution melting and freezing temperatures is the antifreeze activity of AFGP. One characteristic of AFGP activity that requires further examination is the effect of concentration on antifreeze activity, especially whether the activity saturates at high concentrations or the measured activity increases ad infinitum. This study first surveys the activity of the various antifreeze components from both Pagothenia borchgrevinki and the Arg-containing antifreeze glycoprotein from Eleginus gracilis (EgAF). It was found that all AFGP components examined have a plateau in activity at high concentration, but the actual value of the plateau activity differs between the different length AFGP components and between AFGP and EgAF. While the low molecular weight components of both AFGP and EgAF lose activity at deep supercooling, at high concentration activity is restored. The activity data is then shown to fit a reversible kinetic model of AFGP activity, and the coefficients obtained are used to compare the activity differences between AFGP components and between AFGP and EgAF. The model is also shown to describe the activity of the antifreeze protein of the fish Pseudopleuronectes americanus and the thermal hysteresis protein of the insect, Tenebrio molitor.
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PMID:A kinetic description of antifreeze glycoprotein activity. 370 Mar 96

Low levels of plasma fibronectin (PFN), an adhesive glycoprotein postulated to augment reticuloendothelial function, can predispose animals to a poor clinical outcome following sepsis. In the present study, the PFN levels of adult male rats were measured prior to injection of intraperitoneal Escherichia coli and/or stroma-free hemoglobin (SFH) and subsequently at 4, 24, and 48 hours. Intraperitoneal E coli alone elicited insignificant PFN level depression at four hours, with significantly elevated levels only in the high-dose group at 24 (P less than .05) and 48 hours (P less than .01). Intraperitoneal SFH alone did not alter PFN levels from baseline values; when combined with E coli significant four-hour level depression is noted (P less than .05). Elevation of PFN levels by 24 hours occurs in a dose-dependent fashion, returning to baseline values 48 hours postinoculation. Significant mortality was observed only with high doses of E coli combined with SFH. The PFN levels are elevated 24 to 48 hours following high-dose E coli injection. Stroma-free hemoglobin alone has no effect, but when combined with E coli results in PFN level depression four hours postinoculation, contributing to impairment of systemic host defenses and possibly predisposing to greater mortality.
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PMID:Plasma fibronectin response to Escherichia coli and hemoglobin. 388 48

A previously described defect of in vitro monocyte maturation in patients with squamous-cell carcinoma of the lung (SCC) has been investigated further. The maturation of patients' monocytes in pooled normal human serum was significantly better than in autologous serum. Conversely, the maturation of normal control monocytes was significantly depressed in patients' serum. The defect has been shown to be due to the presence of an inhibitory factor, rather than the lack of a necessary component in the patients' serum. Artificially aggregated gamma-globulin inhibited monocyte maturation in vitro, but the presence of immune complexes in the serum of many patients with SCC did not correlate well with the depression of in vitro maturation of monocytes from the same patient. Similarly, pregnancy-associated alpha 2-glycoprotein, in increased amounts in the serum of patients with SCC, showed no correlation with monocyte maturation. The addition of soluble extracts of tumour, but not of surrounding normal lung tissue significantly inhibited monocyte maturation. The results suggest that the defective monocyte maturation in patients with SCC is at least in part due to serum inhibitory factors, which are likely to be a heterogeneous group.
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PMID:In vitro monocyte maturation in squamous-cell carcinoma of the lung: influence of humoral factors. 617 51

Butyric acid produces multiple effects on mammalian cells in culture, including alterations in morphology, depression of growth rate, increased histone acetylation, and modified production of various proteins and enzymes. The latter effect is exemplified by the induction in HeLa cells of the glycoprotein hormone alpha subunit by millimolar concentrations of the fatty acid. This report demonstrates that increased subunit accumulation in response to sodium butyrate is strikingly dependent on the presence of glucose (or mannose) in the growth medium. In contrast, basal levels of subunit synthesis are only marginally affected when the culture medium is supplemented with one of a variety of hexoses. An increase in the accumulation of HeLa alpha does not occur in medium containing pyruvate as the energy source, and sustained induction requires the simultaneous and continued presence of both glucose and butyrate. The effects of butyrate on HeLa cell morphology and subunit induction can be separated, since the latter is glucose-dependent while the former is not. Failure of butyrate to induce alpha in medium containing pyruvate does not result from restricted subunit secretion, since the levels of intracellular alpha are not increased disproportionately relative to those in the medium. The hexoses which support induction of HeLa alpha (glucose greater than or equal to mannose greater than galactose greater than fructose) are identical to those which have been shown previously to stimulate the glucosylation of lipid-linked oligosaccharides and enhance the synthesis of certain glycoproteins. Labeling of various glycosylation intermediates with [3H]mannose indicates that in glucose medium there is a decrease in the level of radioactivity associated with both dolicholpyrophosphoryl oligosaccharide and cellular glycoproteins and a concomitant increase in the fraction of label recovered in secreted glycoproteins. Butyrate also causes a decrease in [3H]mannose-labeled cellular glycoproteins and an increase in tritiated extracellular glycoproteins, particularly in glucose medium. Likewise, glucose stimulates the incorporation of [3H]glucosamine into immunoprecipitable alpha subunit relative to the bulk of HeLa-secreted glycoproteins, and this is further enhanced by butyrate. However, as demonstrated by lectin chromatography of conditioned media, a nonglycosylated subunit does not accumulate in pyruvate medium, either in the absence or presence of butyrate.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Glucose requirement for induction by sodium butyrate of the glycoprotein hormone alpha subunit in HeLa cells. 620 30

We have characterized a UDP-GlcNAc:Gal beta-3-GalNAc (GlcNAc----GalNAc) beta-6-N-acetylglucosaminyltransferase from rabbit small intestinal epithelium by using freezing point depression glycoprotein as the acceptor. Optimal enzyme activity was obtained at pH 7.0-7.5, at 3 mM MnCl2, and at 0.08% Triton X-100. Ca2+, Mg2+, and Ba2+ also enhanced enzyme activity. The apparent Michaelis constant was 4.80 mM for freezing point depression glycoprotein, 0.59 mM for periodate-treated porcine submaxillary mucin, 0.49 mM for Gal beta 1----3 GalNAc alpha Ph, and 1.03 mM for UDP-GlcNAc. No enzyme activity was observed when asialo ovine submaxillary mucin was used as the acceptor. The 14C-labeled oligosaccharide obtained by alkaline borohydride treatment of the product was shown to be a homogeneous trisaccharide by compositional analysis, Bio-Gel P-4 gel filtration, and high-performance liquid chromatography. The structure of the trisaccharide was identified as Gal beta 1----3-(GlcNAc beta 1----6)GalNAc-H2 by (a) identification of 2,3,4,6-tetramethyl-1,5-diacetylgalactitol and 1,4,5-trimethyl-3,6-diacetyl-2-N-methylacetamidogalactitol by gas-liquid chromatography-mass spectrometry and (b) the complete cleavage of the newly formed glycosidic bond by jack bean beta-hexosaminidase. The structure of the trisaccharide was confirmed by 1H nuclear magnetic resonance (270 MHz) and also by periodate oxidation of the trisaccharide followed by NaBH4 reduction, 4 N HCl hydrolysis, a second NaBH4 reduction, and the identification of threosaminitol on an amino acid analyzer. By acceptor competition studies, the enzyme activity was shown to be a much N-acetylglucosaminyltransferase. We postulate that this glycosyltransferase may play a key role in the regulation of mucin oligosaccharide synthesis.
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PMID:Mucin biosynthesis: characterization of rabbit small intestinal UDP-N-acetylglucosamine:galactose beta-3-N-acetylgalactosaminide (N-acetylglucosamine----N-acetylgalactosamine) beta-6-N-acetylglucosaminyltransferase. 623 49

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