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)

Melatonin (MEL) works in tandem with serotonin (5HT), where an equilibrium exists in perfect health. Under stress or in crisis, it may be that the production of MEL predominates in conjunction with ever increasing production of reactive oxygen species (ROS), may lead to hypoxemia and consequently, to metabolic disruption. The Melatonin Hypothesis could offer an explanation towards certain clinical observation and may support the Catacholamine Hypothesis in the development of depression but it is the role played by carbon monoxide (CO) in inducing hypoxemia which may result in the Cascade Effect that could in turn explain the development of neurodegenerative, neurodevelopmental as well as immune dysfunctional type disorders, prevalent today. CO-induced hypoxemia is an important aspect in any discussion of cell integrity as CO is formed endogenously from the degradation of erythrocytic heme, any hemolytic disturbance or lipid peroxidation, may increase the level in blood. CO, in inducing hypoxemia, causes the generation of large quantities of hydroxyl (-OH) which could damage specific amino acid and disorder protein metabolism that may result in the creation of toxic metabolites. Hydroxyl damage is emerging as the precursor to low-grade inflammation in the presence of C Reactive Protein (CRP) that is currently speculated in the etiology of many known disorders. As disordered protein metabolism may play a crucial role in the formation of the cascade, the hypothesis aims to address the issues of cell viability and the process of cell replication in the event where cell integrity is severely compromised in the face of apoptotic and/or necrotic damage, as the intra-cellular and extra-cellular environments are becoming increasingly hostile. Where -OH damage to specific amino acid in protein may contribute to the Cascade Effect, the hypothesis goes further to explain the importance of the Circardian Cycle and the role of paradoxical sleep, by taking into consideration the need for repair and for regeneration in order to maintain morphology as any cellular event that depends on a redox state is likely to be compromised in an event of hypoxemia. As MEL enters a cell readily because of its high lipid solubility, the role of MEL becomes clear as in its diversity, MEL is a potent oxygen radical scavenger that operates throughout the cell.
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PMID:Role of melatonin in carbon monoxide-induced hypoxemia. 1523 89

Hydroxyl radicals (*OH) are involved in the pathogenesis of ischemia-reperfusion injury and are observed in clinical situations, including acute heart failure, stroke, and myocardial infarction. Acute transient exposure to *OH causes an intracellular Ca(2+) overload and leads to impaired contractility. We investigated whether upregulation of sarcoplasmic reticulum Ca(2+)-ATPase function (SERCA) can attenuate *OH-induced dysfunction. Small, contracting right ventricular papillary muscles from wild-type (WT) SERCA1a-overexpressing (transgenic, TG) and SERCA2a heterogeneous knockout (HET) mice were directly exposed to *OH. This brief 2-min exposure led to a transient elevation of diastolic force (F(dia)) and depression of developed force (F(dev)). In WT mice, F(dia) increased to 485 +/- 49% and F(dev) decreased to 11 +/- 3%. In sharp contrast, in TG mice F(dia) increased only to 241 +/- 17%, whereas F(dev) decreased only to 51 +/- 5% (P < 0.05 vs. WT). In HET mice, F(dia) rose more than WT (to 597 +/- 20%, P < 0.05), whereas F(dev) was reduced in a similar amount. After approximately 45 min after *OH exposure, a new steady state was reached: F(dev) returned to 37 +/- 6% and 32 +/- 6%, whereas F(dia) came back to 238 +/- 28% and 292 +/- 17% in WT and HET mice, respectively. In contrast, the sustained dysfunction was significantly less in TG mice: F(dia) and F(dev) returned to 144 +/- 20% and 67 +/- 6%, respectively. Before exposure to *OH, there is decrease in phospholamban (PLB) phosphorylation at Ser16 (pPLBSer16) and PLB phosphorylation at Thr17 (pPLBThr17) in TG mice and an increase in pPLBSer16 and pPLBThr17 in HET mice versus WT. After exposure to *OH there is decrease in pPLBSer16 in WT, TG, and HET mice but no significant change in the level of pPLBThr17 in any group. The results indicate that SERCA overexpression can reduce the *OH-induced contractile dysfunction in murine myocardium, whereas a reduced SR Ca(2+)-ATPase activity aggravates this injury. Loss of pPLB levels at Ser16 likely amplifies the differences observed in injury response.
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PMID:SERCA overexpression reduces hydroxyl radical injury in murine myocardium. 1679 16

Sugar beet and sugar cane molasses have been shown to be suitable starting materials for producing de-icer preparations. The sucrose in the molasses is hydrolyzed to glucose and fructose by invertase. The reducing sugars are then degraded by NaOH, the alkali being neutralized by the sugar acids produced, resulting in an increase of the ionic strength and consequently depression of the freezing point of the resulting solution. For the preparation of de-icers, the desired freezing point depression to a temperature of less than about -20 degrees C can be achieved by adjusting the amount and concentration of the alkali metal hydroxide used. The resulting products are biodegradable and eliminate the corrosive effects associated with the use of conventional chloride salts. Degradation of invert sugar by NaOH has been achieved without an external heat source. The reaction products showed the same freezing point depression as seen in the degradation products from pure glucose.
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PMID:Alkaline degradation of invert sugar from molasses. 1722 51

Opioids evoke respiratory depression, bradycardia, and reduced respiratory sinus arrhythmia, whereas serotonin (5-HT) agonists stimulate respiration and cardiorespiratory interactions. This study tested whether serotonin agonists can prevent the inhibitory effects of opioids on cardiorespiratory function. Spontaneous and rhythmic inspiratory-related activity and gamma-aminobutyric acid (GABA) neurotransmission to premotor parasympathetic cardioinhibitory neurons in the nucleus ambiguus were recorded simultaneously in an in vitro thick slice preparation. The mu-opioid agonist fentanyl inhibited respiratory frequency. The 5-hydroxytryptamine 1A/7 receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin increased respiratory frequency by itself and also prevented the fentanyl-induced respiratory depression. The 5-hydroxytryptamine 4alpha agonist BIMU-8 did not by itself change inspiratory activity but prevented the mu-opioid-mediated respiratory depression. Both spontaneous and inspiratory-evoked GABAergic neurotransmission to cardiac vagal neurons were inhibited by fentanyl. 8-Hydroxy-2-(di-n-propylamino)tetralin inhibited spontaneous but not inspiratory-evoked GABAergic activity to parasympathetic cardiac neurons. However, 8-hydroxy-2-(di-n-propylamino)tetralin differentially altered the opioid-mediated depression of inspiratory-evoked GABAergic activity but did not change the opioid-induced reduction in spontaneous GABAergic neurotransmission. In contrast, BIMU-8 did not alter GABAergic neurotransmission to cardiac vagal neurons by itself but prevented the fentanyl depression of both spontaneous and inspiratory-elicited GABAergic neurotransmission to cardiac vagal neurons. In the presence of tetrodotoxin, the inhibition of GABAergic inhibitory postsynaptic currents with fentanyl is prevented by coapplication of BIMU-8, indicating that BIMU-8 acts at presynaptic GABAergic terminals to prevent fentanyl-induced depression. These results suggest that activation of 5-hydroxytryptamine receptors, particularly 5-hydroxytryptamine 4alpha agonists, may be a useful therapeutic approach in preventing opioid-evoked cardiorespiratory depression.
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PMID:5-Hydroxytryptamine 1A/7 and 4alpha receptors differentially prevent opioid-induced inhibition of brain stem cardiorespiratory function. 1757 56

Serotonin receptors are present in lymphocytes and might be related to the functionality of these cells in health and in pathology. The serotonergic system is affected in the brain and in peripheral immune cells of depressed patients. The objectives of this work were to evaluate the basal proliferation of lymphocytes, the response to the mitogen concanavalin A, and the role of serotonin 5-HT(1A) receptors. Twenty-nine patients, 19-52 years old, were diagnosed for a major depression episode with the Statistical and Diagnostic Manual-IV of the American Psychiatric Association, approved by ethic committees and gave written consent. The Hamilton depression score was 30.60 +/- 2.65. An apparently healthy group without a family history of psychiatric illness was included. Blood peripheral lymphocytes were isolated by density gradients with Ficoll/Hypaque and differential adhesion to plastic, cultured in 96-well plaques with RPMI-1640 medium with or without 4 mug/ml of concanavalin A. 8-Hydroxy-2-(di-n-propylamino)tetralin (5-40 nM) and WAY-100,478 (0.1-100 microM), agonist and antagonist of 5-HT(1A) receptors, serotonin (12.5-100 nM) or imipramine (0.1-100 microM) were also added. Proliferation was evaluated at 72 h with 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazolium bromide, and the optical density was 570 nm. Basal proliferation was three times higher in depressed patients than in controls, whereas no response to mitogen was obtained, and 5-HT(1A) receptors significantly reacted to the agonist, with increases of about 31-54% at 10, 20 and 40 nM of the specific agonist, indicating initial activation probably in relation to autoimmunity and overreactivity of these receptors in depression. The antagonist reduced proliferation in mitogen-stimulated lymphocytes, 50% in controls and 70% in depressed patients, with a differential concentration dependency; probably, these receptors are more sensitive in depression due to increased 5-HT(1A) receptor transduction. The antagonist also reduced the stimulation produced by the 5-HT(1A) agonist. Imipramine caused biphasic effects according to concentrations, showing a possible dual role for serotonin, although all values were significantly higher in depressed subjects. The described alterations might be of relevance in the pathophysiology of depression.
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PMID:Serotonin, 5-HT1A serotonin receptors and proliferation of lymphocytes in major depression patients. 1770 35

7alpha-Hydroxy-DHEA, 7beta-hydroxy-DHEA and 7beta-hydroxy-EpiA are native metabolites of dehydroepiandrosterone (DHEA) and epiandrosterone (EpiA). Since numerous steroids are reported to interfere with inflammatory and immune processes, our objective was to test the effects of these hydroxysteroids on prostaglandin (PG) production and related enzyme gene expression. Human peripheral blood monocytes were cultured for 4 and 24 h in the presence of each of the steroids (1-100 nM), with and without addition of TNF-alpha (10 ng/mL). Levels of PGE(2), PGD(2) and 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) were measured in the incubation medium, and cell content of cyclooxygenase (COX-2), and PGE and PGD synthases (m-PGES1, H-PGDS, L-PGDS), and peroxisome proliferator activated receptor (PPAR-gamma) was assessed by quantitative RT-PCR and Western blots. Addition of TNF-alpha resulted in elevated PG production and increased COX-2 and m-PGES1 levels. Among the three steroids tested, only 7beta-hydroxy-EpiA decreased COX-2, m-PGES1 and PPAR-gamma expression while markedly decreasing PGE(2) and increasing 15d-PGJ(2) production. These results suggest that 7beta-hydroxy-EpiA is a native trigger of cellular protection through simultaneous activation of 15d-PGJ(2) and depression of PGE(2) synthesis, and that these effects may be mediated by activation of a putative receptor, specific for 7beta-hydroxy-EpiA.
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PMID:7beta-Hydroxy-epiandrosterone-mediated regulation of the prostaglandin synthesis pathway in human peripheral blood monocytes. 1855 3

beta-Hydroxy-beta-methylbutyrate (HMB; 50 microM) has been shown to attenuate the depression in protein synthesis in murine myotubes in response to lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha) with or without interferon-gamma (IFN-gamma), and angiotensin II (ANG II). The mechanism for the depression of protein synthesis by all three agents was the same and was attributed to activation of double-stranded RNA-dependent protein kinase (PKR) with the subsequent phosphorylation of eukaryotic initiation factor 2 (eIF2) on the alpha-subunit as well as increased phosphorylation of the elongation factor (eEF2). Myotubes expressing a catalytically inactive PKR variant, PKRDelta6, showed no depression of protein synthesis in response to either LPS or TNF-alpha, confirming the importance of PKR in this process. There was no effect of any of the agents on phosphorylation of mammalian target of rapamycin (mTOR) or initiation factor 4E-binding protein (4E-BP1), and thus no change in the amount of eIF4E bound to 4E-BP1 or the concentration of the active eIF4E.eIF4G complex. HMB attenuated phosphorylation of eEF2, possibly by increasing phosphorylation of mTOR, and also attenuated phosphorylation of eIF2alpha by preventing activation of PKR. These results suggest that HMB may be effective in attenuating muscle atrophy in a range of catabolic conditions.
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PMID:Attenuation of depression of muscle protein synthesis induced by lipopolysaccharide, tumor necrosis factor, and angiotensin II by beta-hydroxy-beta-methylbutyrate. 1885 27

Macrophagic myofasciitis (MMF) is an emerging condition, characterized by specific muscle lesions assessing long-term persistence of aluminum hydroxide within macrophages at the site of previous immunization. Affected patients mainly complain of arthromyalgias, chronic fatigue, and cognitive difficulties. We designed a comprehensive battery of neuropsychological tests to prospectively delineate MMF-associated cognitive dysfunction (MACD). Compared to control patients with arthritis and chronic pain, MMF patients had pronounced and specific cognitive impairment. MACD mainly affected (i) both visual and verbal memory; (ii) executive functions, including attention, working memory, and planning; and (iii) left ear extinction at dichotic listening test. Cognitive deficits did not correlate with pain, fatigue, depression, or disease duration. Pathophysiological mechanisms underlying MACD remain to be determined. In conclusion, long-term persistence of vaccine-derived aluminum hydroxide within the body assessed by MMF is associated with cognitive dysfunction, not solely due to chronic pain, fatigue and depression.
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PMID:Long-term persistence of vaccine-derived aluminum hydroxide is associated with chronic cognitive dysfunction. 1974 79

Dissolution of fine (-10 microm) and intermediate (+10-53 microm) galena particles was studied in the presence and absence of iron hydroxide colloids at pH 9 with nitrogen and oxygen purging. X-ray photoelectron spectroscopy (XPS) measurements and ethylene diamine-tetra acid (EDTA) extraction of the galena particles after dissolution indicate that galena dissolution is strongly dependent on particle size. Fine galena particles produced a much higher amount of lead hydroxide species per surface area than intermediate galena particles. Gas purging only affected galena dissolution slightly. More iron hydroxide colloids adsorbed on fine particles. Zeta potential measurements indicate that galena dissolution enhances the adsorption of iron hydroxide colloids due to the electrostatic attraction between lead hydroxide products and iron hydroxide colloids at pH 9. This explains the stronger affinity of iron hydroxide colloids to fine galena particles than intermediate galena particles. This study has an important implication in sulfide flotation where iron hydroxide colloids play a dominant role in mineral depression.
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PMID:Dissolution of fine and intermediate sized galena particles and their interactions with iron hydroxide colloids. 2038 Oct 59

The aim of this paper is to better understand oxygen transfer reduction caused by floc suspensions. We demonstrate that the overall floc volume significantly influences oxygen transfer depletion. Submerged fine bubble and coarse bubble diffusers are affected in the same way by this phenomenon. The mixed liquor suspended solids concentration (MLSS concentration) is not an appropriate parameter for describing or relating phenomena that are caused by the overall floc volume in activated sludge (e.g., oxygen transfer depression and sludge sedimentation characteristics). A better correlation is achieved by using the mixed liquor volatile suspended solids concentration (MLVSS concentration). To characterize the effects of the overall floc volume in suspensions whose MLVSS concentration cannot be determined (e.g., inorganic iron hydroxide flocs), a new method-the hydrostatic floc volume (HFV)-that approximates the overall floc volume in floc suspensions is introduced. Application of this method demonstrates that oxygen transfer depression caused by iron hydroxide flocs and activated sludge flocs is similar.
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PMID:Floc volume effects in suspensions and its relevance for wastewater engineering. 2191 54


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