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)

To elucidate cellular mechanisms of myocardial depression in Pseudomonas sepsis the effects of sublethal concentrations of P. aeruginosa exotoxin A--a main virulence factor--were studied in cultured neonatal rat cardiomyocytes. It is known that this toxin exerts its pathogenic effect by inhibition of protein synthesis via ADP-ribosylation and thereby inactivation of elongation factor 2 (EF-2). Within 48 72 h, half maximal inhibition of protein synthesis occurs at 4-10 ng/ml. The toxin prevents the beta-adrenoceptor(AR)-mediated myosin heavy chain isozyme shift (V3/V1), while the T3-induced myosin shift is not suppressed. While beta 1-AR-downregulation by excess of norepinephrine (NE) is not affected, protein synthesis-dependent receptor upregulation in the recover period after removal of NE is completely suppressed by P. aeruginosa exotoxin A. Thus, a non-lethal, partial inhibition of global cellular protein synthesis by P. aeruginosa exotoxin A: (1) completely prevents beta 1-AR-mediated myosin isozyme shift and beta-AR upregulation: (2) sustains the cardiomyocytes in a catecholamine-refractory contractile state in the recovery period after catecholamine desensitization: (3) suggests cellular mechanisms by which P. aeruginosa exotoxin A might impair heart function in Pseudomonas sepsis: and (4) may help reveal the possible influence of endogenous inhibitors of EF-2.
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PMID:Partial inhibition of protein synthesis by Pseudomonas exotoxin A deranges catecholamine sensitivity of cultured rat heart myocytes. 914 Aug 36

Individuals who report illness (e.g. nausea, headache) from common chemical odors tend to report CNS symptoms suggestive of olfactory-limbic system involvement. This study compared the resting quantitative electroencephalographic (qEEG) patterns of young adult college students reporting subjectively elevated chemical odor intolerance ratings (HICI) with those of controls reporting little or no odor intolerance (LOCI). Each group was subdivided into those with higher (HIDEP) vs. lower (LODEP) ratings of concomitant depression. Nineteen channels of EEG were recorded during a single session over four separate rest periods, respectively, following baseline, cognitive, chemical exposure and olfactory identification tests. Each recording involved two 30-s, eyes-closed, filtered room air breathing conditions: (1) nose inhalation followed by mouth exhalation and (2) mouth inhalation followed by mouth exhalation. HICI showed significantly less beta 1 (beta 1) over the temporal-central region during nose than during mouth inhalation. Over some temporal and central leads, task, DEP and CI interacted to influence beta 1 as well. For theta (theta), CI differences emerged during nose inhalation after the cognitive task at Cz, after chemical exposures at C3, Cz and C4 and after the olfactory ID task at C4. CI differences emerged during mouth breathing after the olfactory ID task at Cz, C4 and T4. The T5-T6 coronal array showed significant CI differences after chemical exposures during nose breathing and during mouth breathing after the cognitive and olfactory ID tasks. The theta findings in the HICI may be related to reports of disturbed attention in CI.
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PMID:Quantitative EEG patterns during nose versus mouth inhalation of filtered room air in young adults with and without self-reported chemical odor intolerances. 950 9

Third-generation beta-blocking agents developed for the hypertension market are proving useful in the treatment of chronic heart failure (HF). These compounds share the ancillary property of vasodilation, which improves acute tolerability by unloading the failing left ventricle at a time when beta-adrenergic withdrawal produces myocardial depression. In the case of carvedilol and bucindolol, this allows for the administration of nonselective beta blockade. Because of blockade of both beta 1 and beta 2 adrenergic receptors as well as other properties, these compounds possess a more comprehensive antiadrenergic profile than second-generation, beta 1-selective compounds. For this and potentially other reasons, third-generation beta-blocking agents have theoretical efficacy advantages that have yet to be demonstrated in large-scale trials. Ongoing trials with either second- or third-generation compounds and one trial directly comparing a compound from each class will provide the answer as to whether third-generation compounds have an advantage in the treatment of chronic HF.
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PMID:The role of third-generation beta-blocking agents in chronic heart failure. 985 89

Lentinan is a beta 1-->3 glucan isolated from Lentinus edodes (Shiitake mushroom) which has immune modulating properties. We have conducted two phase I/II placebo-controlled trials on a total of 98 patients. In one study at the San Francisco General Hospital (SFGH), ten patients each were administered 2, 5, or 10 mg of lentinan or placebo i.v. once a week for eight weeks. In the second study at the Community Research Initiative in New York (CRI), two groups of 20 patients each were administered 1 or 5 mg of lentinan i.v. twice a week for 12 weeks, and ten patients were administered placebo (vehicle containing mannitol plus dextran 40) i.v. twice a week. Entry criteria were an HIV positive test, CD4 levels of 200-500 cells, age 18-60 years, and without current opportunistic infections. This study confirms, in Caucasian subjects also, the good tolerability of lentinan observed in Japanese cancer patients. Side effects were mainly mild, especially when infusion was carried out over a 30-minute period. In the SFGH study, where administration was over a ten minute period, there were nine side effects severe enough to be reported to the FDA (one case each of anaphylactoid reaction, back pain, leg pain, depression, rigor, fever, chills, granulocytopenia and elevated liver enzymes) and there were four patients who discontinued therapy because of side effects. In the CRI study, where infusion was over a 30-minute period, there were no side effects reportable to the FDA and there were four dropouts due to side effects or personal preference. Most side effects resolved promptly after the discontinuation of medication, and all of them were relieved within 24 hours. Patients in the study have shown a trend toward increases in CD4 cells and in some patients neutrophil activity. Because of the small numbers, these values do not have statistical significance. Inasmuch as no side effects such as anemia, leukopenia, pancreatitis or neuropathy were seen, and in view of the positive effects of lentinan on certain surrogate markers (recognizing that these were small studies), we recommended a long-term clinical trial of lentinan in combination with didanosine (ddI) or zidovudine in HIV positive patients. Most patients in these trials did not have measurable p24 levels. In the CRI trials of ten patients with elevated p24 levels, eight on lentinan and two on placebo had decreased p24 levels. Of these decreases, those with lentinan and one with placebo were marked. These results were provocative and needed confirmation. Subsequent to this study, a trial of lentinan in combination with didanosine (ddI) showed a mean increase of 142 CD4 cells/mm3 over a twelve month period, in contrast to a decrease in CD4 cells in patients on ddI alone (Gordon et al. 1995).
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PMID:A placebo-controlled trial of the immune modulator, lentinan, in HIV-positive patients: a phase I/II trial. 1050 66

The influence of new nootrope and adaptogen preparations representing dry extracts from Scutellaria baicalensis (Georgi), Bergenia crassifolia (Fritsch), and velvet antlers of Siberian deer (Cervus elaphus sibiricus) on the bioelectric activity (cortex Fourier spectral EEG power) under conflict situation and conditioned reflex development was studied in rats. In both tests, the drugs produced similar changes in the EEG activity: (i) increase in the partial contribution of delta-activity and general spectral power, (ii) depression in the alpha and beta 1-rhythm power, (iii) depression of theta-activity in some cases. The EEG activity changes depended on the initial state and were closely connected with the behavior of the test animals. The drug administration led to normalization of the alpha and beta 1 activity correlated with the improved behavioral characteristics. At the same time, the delta activity was virtually not affected and lost the correlation with behavior.
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PMID:[Effect of natural nootropic and adaptogen preparations on the cortex bioelectrical activity in rats]. 1202 93

Hippocampal long-term potentiation (LTP) is a form of synaptic plasticity used as a cellular model of memory. Beta amyloid (A beta) is involved in Alzheimer's disease (AD), a neurode-generative disorder leading to cognitive deficits. Nicotine is also claimed to act as a cognitive enhancer. A beta is known to bind with high affinity to the alpha 7-nicotinic acetylcholine receptor (nAChR). Here we have investigated the effect of intracerebroventricular (i.c.v.) injection of the endogenous peptide A beta 1-40 on LTP in area CA1 of urethananesthetized rats. We also examined the effect of A beta 12-28 (i.c.v.), which binds with high affinity to the alpha 7-nAChR and the specific alpha 7-nAChR antagonist methyllycaconitine (MLA) on LTP. We found that A beta 12-28 had no effect on LTP, whereas MLA depressed significantly LTP, suggesting that activation of the alpha 7-nAChR is a requirement for LTP. Within the in vivo environment, where other factors may compete with A beta 12-28 for binding to alpha 7-nAChR, it does not appear to modulate LTP. To determine if the depressive action of A beta 1-40 on LTP could be modulated by nicotine, these agents were also co-applied. Injection of 1 or 10 nmol A beta 1-40 caused a significant depression of LTP, whereas nicotine alone (3 mg/kg) had no effect on LTP. Co-injection of nicotine with A beta 1-40 1 h prior to LTP induction caused a further significant depression of LTP compared with A beta 1-40 alone. These results demonstrate that nicotine enhances the deficit in LTP produced by A beta 1-40. This then suggests that nicotine may exacerbate the depressive actions of A beta on synaptic plasticity in AD.
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PMID:Nicotine enhances the depressive actions of A beta 1-40 on long-term potentiation in the rat hippocampal CA1 region in vivo. 1261 41

Endogenous catecholamines released during myocardial ischemia have been considered both to aggravate cell injury and exacerbate arrhythmias and to exert a protective action on the post-ischemic contractile function. The present work was addressed to look for evidence to explain this controversy. The effects of cardiac catecholamine depletion and of alpha- and beta-adrenoceptor (AR) blockade on the post-ischemic contractile dysfunction, as well as its possible relationship with cardiac oxidative stress, were studied in isolated and perfused rat hearts submitted to 20 min of ischemia and 30 min of reperfusion (stunning). Catecholamine depletion improves the contractile recovery in the stunned heart. This mechanical effect was associated with decreased levels of lipid peroxidation. A similar enhancement of the contractile function during reperfusion was detected after the simultaneous blockade of alpha 1- and beta-ARs with prazosin plus propranolol. To ascertain which specific AR pathway was involved in the effects of catecholamines on the stunned heart, selective AR blockers, prazosin (alpha 1-blocker), atenolol (beta 1-blocker), ICI 118,551 (beta 2-blocker) and selective inhibitors of Gi-PI3K pathway (pertussis toxin and wortmannin) were alternatively combined. The results indicate that catecholamines released during ischemia exert a dual action on the contractile behavior of the stunned heart: a deleterious effect, related to the activation of the beta 2-AR-Gi-PI3K-pathway, which was counteracted by a beneficial effect, triggered by the stimulation of alpha 1-AR. Neither the depression nor the enhancement of the post-ischemic contractile recovery were related with the increase in ROS formation induced by endogenous catecholamines.
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PMID:beta 2-Adrenergic stimulation is involved in the contractile dysfunction of the stunned heart. 1657 88

Complex regional pain syndromes (CRPS) are characterized by persistent and severe pain after trauma or surgery. Neuro-immune alterations are assumed to play a pathophysiological role. Here we set out to investigate whether patients with CRPS have altered systemic pro- and anti-inflammatory cytokine profiles compared to controls on mRNA and protein level. We studied blood cytokine mRNA and protein levels of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF), interleukin-2 (IL-2) and IL-8 and the anti-inflammatory cytokines IL-4, IL-10, and transforming growth factor-beta1 (TGF beta 1) in 40 prospectively recruited patients with CRPS I, two patients with CRPS II, and 34 controls. Quantitative real-time PCR and enzyme linked immunosorbent assay were used. Additionally, the patients underwent quantitative sensory testing and were assessed with the McGill pain questionnaire and the Hospital anxiety and depression scale. Patients with CRPS had higher blood TNF and IL-2 mRNA levels (p=0.005; p=0.04) and lower IL-8 mRNA levels (p<0.001) than controls. The mRNA for the anti-inflammatory cytokines IL-4 and IL-10 was reduced in the patient group (p=0.004; p=0.006), whereas TGF beta 1 mRNA levels did not differ between groups. These results were paralleled by serum protein levels, except for TGF beta 1, which was reduced in patients with CRPS, and for IL-8, which gave similar protein values in both groups. Sensory testing showed a predominant loss of small fiber-related modalities in the patient group. The shift towards a pro-inflammatory cytokine profile in patients with CRPS suggests a potential pathogenic role in the generation of pain.
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PMID:Differential expression patterns of cytokines in complex regional pain syndrome. 1789 83

In chronic experiments on rabbits, myoelectric activity (contractile activity index) in proximal and distal part of the jejunum and proximal part of the ileum was studied under psychogenic stress caused by rigid fastening of the rabbit to table in supine position. Inhibition of contractile activity in the proximal and distal parts of thejejunum in the 1st phase of the stressor response manifested on the background of blockade of presynaptic alpha 2-adrenoceptor with yohimbin, nonselective blockade of alpha-adrenoceptor with dihydroergotoxin, or blockade of beta 1/beta 2-adrenoceptor with propranolol. Conclusion is made that the stressor inhibition of contractile activity in the proximal and distal parts of the jejunum was not "adrenergic cholinergic" or "adrenergic" in origin. The contractile activity inhibition of the jejunum was actualized with the contribution of "nonadrenergic noncholinergic" inhibitory mechanism and mediated via nonadrenergic inhibitory neurons of the enteric nervous system. Depression of the contractile activity in the proximal part of ileum being preserved after blockade of presynaptic "alpha 2-adrenoceptor" or blockade of beta 1/beta 2-adrenoceptor, was not "adrenergic cholinergic" or "beta-adrenergic". Nonselective blockade of alpha-adrenoceptor resulted in diminished stressor inhibition of the contractile activity in the proximal part of ileum. The data obtained suggest that the stressor inhibition of the contractile activity in the proximal part of ileum was caused by "nonadrenergic noncholinergic" inhibitory mechanism with participation of the "alpha-adrenergic" inhibition. The "nonadrenergic noncholinergic" inhibition of the contractile activity in the jejunum and ileum might result from activation of enteric inhibitory neurons with a stressor factor of hormonal nature.
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PMID:[Mechanism of inhibition of the contractile activity in the jejunum and ileum under psychogenic stress in rabbits]. 1963 88

Tinnitus is the continuous perception of an internal auditory stimulus. This permanent sound often affects a person's emotional state inducing distress and depressive feelings changes in 6-25% of the affected population. Distress and depression are two distinct emotional states. Whereas distress describes a transient aversive state, interfering with a person's ability to adequately adapt to stressors, depressive feelings should rather be considered as a more constant emotional state. Based on previous observations in chronic pain, posttraumatic stress disorder and depression, we assume that both states are related to separate neural circuits. We used the Dutch version of the Tinnitus Questionnaire to assess the global index of distress together with the Beck Depression Inventory to evaluate the depressive symptoms accompanying tinnitus. Furthermore sLORETA analysis was performed to correlate current density distribution with distress and depression scores, revealing a lateralization effect of depression versus distress. Distress is mainly correlated with alpha 2, beta 1 and beta 2 activity of the right frontopolar cortex and orbitofrontal cortex in combination with beta 2 activation of the anterior cingulate cortex. In contrast, the more permanent depressive alterations induced by tinnitus are associated with activity of alpha 2 activity in the left frontopolar and orbitofrontal cortex. These specific neural circuits are embedded in a greater neural network, with the parahippocampal region functioning as a crucial linkage between both tinnitus related pathways.
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PMID:Disentangling depression and distress networks in the tinnitus brain. 2280 88


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