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)

The aetiology of the bone marrow suppression in HIV-infected patients is unknown. We have demonstrated previously that the ability of bone marrow cells, derived from mice made immunodeficient by infection with the retrovirus LP-BM5, to establish long-term stromal cultures is impaired. In this study we determined the ability of bone marrow stromal cells from these immunodeficient mice to produce cytokines important in haemopoiesis. Neither SCF, IL-3, GM-CSF nor TNF alpha were found in conditioned media of long-term bone marrow cultures (LTBMC) of normal or MAIDS mice. We failed to detect mRNA for TNF or IL-1 alpha, by reverse transcription polymerase chain reaction (RT-PCR), in cultures derived from either normal or immunodeficient mice. Steady-state levels of transcripts for IL-6 were equal in cells from normal and MAIDS mice. Steady-state levels of mRNA for TGF beta 1, a known inhibitor of haemopoiesis, were decreased in cultures derived from MAIDS mice at late stages of infection. The mRNA level of the multipotent haemopoietic regulator stem cell factor was also decreased in MAIDS cultures as compared with normals. Transcripts encoding the transmembrane form of the growth factor were almost absent. Addition of soluble GM-CSF and SCF only transiently increased the production of CFUs (BFUE and CFU-G/M) in MAIDS LTBMC. These findings suggest that derangements in cytokine production in stromal cells of immunodeficient mice may contribute to the suppression of haemopoiesis observed in this disease. One mechanism of HIV-induced depression of haemopoiesis may be via alterations of the haemopoietic microenvironment.
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PMID:Impaired cytokine production by bone marrow stromal cells of immunodeficient mice. 766 53

The antianginal effects of YM-16151-4, a combined calcium entry blocking and beta 1-adrenoceptor blocking agent, were evaluated in various experimental angina models and compared with those of nifedipine and propranolol. In anesthetized dogs, YM-16151-4 (0.3 and 1 mg/kg intravenously, i.v.) increased coronary blood flow and reduced myocardial oxygen consumption (MVO2). In isolated dog coronary arteries, YM-16151-4 concentration-dependently inhibited 3,4-diaminopyridine-induced rhythmic contractions with an IC50 value of 91 nM. In anesthetized rats, YM-16151-4 also inhibited the ST-segment depression induced by vasopressin (0.5 U/kg i.v.) with an ED50 value of 29 mg/kg orally, (p.o.). Nifedipine was also effective in these models, but propranolol was not. In addition, YM-16151-4 (0.3 mg/kg i.v.) inhibited the ST-segment elevation in the epicardial ECG induced by coronary artery occlusion in anesthetized dogs. Propranolol (1 mg/kg i.v.) also inhibited this elevation, but nifedipine (0.003 mg/kg i.v.) did not. In anesthetized dogs, furthermore, the prolongation of PQ-interval induced by YM-16151-4 was almost the same as that induced by propranolol. These results demonstrate that YM-16151-4, in contrast to nifedipine and propranolol, is fully effective in these various types of angina models. Thus, YM-16151-4 is expected to prove a valuable antianginal agent in treatment of various types of angina pectoris, with these antianginal effects resulting from the sum of its calcium entry blocking and beta 1-adrenoceptor blocking activities.
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PMID:Antianginal effects of YM-16151-4 in various experimental angina models. 768 38

Microglial cells account for approximately 20% of the total glial population in the central nervous system. They are distributed with no significant local differences in the white and grey matters. In contrast to astrocytes they cover non-overlapping territories. They belong to the mononuclear phagocyte system and form the resident macrophages in the brain tissue, the spinal cord and the retina. Their function in the normal neural parenchyma is unknown. However, in various pathologies they form a most reactive sensor to threats to the nervous system. Within a few hours they exhibit an activation program that we have studied in seven different experimental paradigms, e.g. following nerve section, direct brain trauma, toxic lesion, spreading depression, ischemic lesion, fiber degeneration, autoimmune diseases. Activated microglial cells become immuno-competent and are MHC (major histocompatibility complex) class 1 and class 2 positive. They express the amyloid precursor protein, APP. The complement receptor CR3bi is quickly upregulated. The mitotic activity depends on the colony stimulating factors M-CSF and GM-CSF and the appropriate receptors. Molecules discussed as signals in the activation process of microglia are cytokines such as IL-1, IL-2, IL-6, TGF beta 1. An important role could also be attributed to the unique potassium channel of microglia. Brain macrophages of microglial origin have a strong respiratory burst activity, meaning that they produce oxygen radicals. They also possess Cathepsin B and L and thus are potentially cytotoxic. Taken together, microglia are highly reactive, mobile and multifunctional immune cells of the CNS that can play a universal role in the defence of the neural parenchyma.
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PMID:Microglia, the first line of defence in brain pathologies. 776 26

Quantitative EEG analysis was done on 29 medicated right-handed depressive patients at age over 45 and age and sex matched right-handed 20 normal controls. The patients were all diagnosed as major depression with melancholia by DSM-III-R and were divided into anxiety type (n = 17) and retardation type (n = 12) evaluated with the Hamilton rating scale for depression. Eye closed resting EEGs were recorded on a data recorder from the 16 electrode leads (10-20 system). Artifact rejected 3 minutes EEGs were analyzed by off-line with Fast Fourier Transform from the bilateral frontal (F3, F4), parietal (P3, P4) and occipital (O1, O2) regions. The mean values of absolute amplitude power (microV) and the mean Z scores of inter-, and intrahemispheric coherence were obtained in theta 1 (4.0-6.0 Hz), theta 2 (6.0-8.0 Hz), alpha 1 (8.0-10.5 Hz), alpha 2 (10.5-13.0 Hz), beta 1 (13.0-20.0 Hz), and beta 2 (20.0-40.0 Hz) frequency bands respectively. The main findings were: 1) Beta 1 and beta 2 power were greater in patients with anxiety type depression than in normal controls, and the differences were statistically significant over the parietal and occipital regions in beta 1 and the frontal region in beta 2. The anxiety type was distinguished from the retardation type with the increase of beta 2 power. The retardation type showed higher alpha 1 power over the frontal region and lower alpha 2 power over the occipital region than normal controls. 2) Both types showed greater frontal predominant ratio to the parietal in beta 2 power than did normal controls. The retardation type was distinguished from the anxiety type with the right predominance in beta 1 power over the frontal region. 3) Both groups of patients showed lower frontal interhemispheric coherences than normal controls in each band. In particular, the anxiety type showed significantly lower alpha 2 band and lower beta 1 and beta 2 bands. The parietal interhemispheric coherence was lower in the anxiety type but higher in the retardation type than in normal controls in each band, and this difference was prominent in theta 2 band. 4) The two groups of patients showed higher fronto-parietal intrahemispheric coherences in both hemispheres than the normal controls in each band. Especially, the anxiety type showed higher in theta two and alpha 1 bands.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[EEG power and coherence in presenile and senile depression. Characteristic findings related to differences between anxiety type and retardation type]. 777 54

Beta 3-adrenoceptors is a term used for atypical beta-adrenoceptors which do not fit into either the beta 1- or beta 2-receptor as classified by pharmacological methods. The receptor has been cloned and is thus also genetically defined. Beta 3-adrenoceptors appear to be widely distributed. Until now their importance has been based on studies using agonists with high potency, but yet not selective for beta 3-adrenoceptors. The distribution and functional importance in humans are unclear, and will probably not be clarified before selective antagonists and labelled ligand are developed. Agonists for the beta 3-adrenoceptors may be of clinical value in the treatment of obesity, non-insulin dependent diabetes mellitus, gastrointestinal disorders like irritable colon, inflammatory lung diseases and depression.
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PMID:[Beta 3-receptors: incidence and properties, possible clinical significance]. 784 60

The concept that specific neurons modulate information processing rather than they convey sensory or motor signals seems to be well established. In any representation of the primary pathways responsible for the processing of sensory stimuli or motor outputs, it is notable that noradrenergic, serotonergic or dopaminergic neurons do not appear to be involved. Noradrenergic and serotonergic cells are activated by non specific stimuli coming from all sensory modalities, whereas dopaminergic neurons are activated by stimuli related to motivation, and which have previously taken a significance over the animal's history. Dopaminergic neurons activation therefore depends upon cortical processings which necessitate the participation of noradrenergic and serotonergic neurons. Up to now the clinical efficacy of antidepressants has been correlated with their biochemical property to desensitize cortical beta 1-adrenergic receptors. This does not necessarily mean that this desensitization is essential, but rather that these receptors are extremely sensitive to modifications of noradrenergic transmission and that a reactivation of noradrenergic transmission is central for depression relief. Taking into account data from the literature and results obtained in our laboratory, we propose: 1) that the reactivation of serotonergic neurons is essential to reactivate noradrenergic cells; 2) that the presence of a normal noradrenergic transmission is necessary to obtain a functional subcortical dopaminergic transmission.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Interrelations between neuromediators implicated in depression and antidepressive drugs]. 789 28

The anti-ischemic effect of 5 mg nebivolol o.i.d., a newly developed beta 1-selective adrenoceptor blocking drug with vasodilating properties, was compared with that of atenolol (100 mg o.i.d.) following a treatment period of 6 days. The study was performed in 24 patients with documented coronary artery disease and stable angina pectoris according to a double-blind randomized study, designed using conventional symptom-limited exercise testing. Exercise testing 3 h after the first dose showed a more marked ST-segment reduction by atenolol than by nebivolol (59% vs. 18%). ST-segment depression measured 24 h after administration of the penultimate dose was statistically significantly reduced by nebivolol (from 0.19 +/- 0.07 to 0.13 +/- 0.07 mV; P = 0.0059) but not by atenolol (from 0.17 +/- 0.06 to 0.14 +/- 0.10 mV; P = 0.0703). Approximately 3 h after the last dose, the reduction was comparable (45% and 38% by nebivolol and atenolol, respectively). Exercise duration, exercise time necessary to produce ST-segment depression by 0.1 mV and exercise time to the onset of angina were also prolonged following administration of both drugs. Thus, at steady-state single daily doses of 100 mg atenolol and 5 mg nebivolol were about equieffective when measured at time of maximal effect (i.e. 3 h after drug administration). However, duration of action with respect to the ST-segment depression seems to be slightly longer for nebivolol.
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PMID:Determination of the anti-ischemic activity of nebivolol in comparison with atenolol. 791 Jan 55

To compare the hemodynamic, antiischemic, metabolic, and neurohumoral effects of intravenous esmolol (beta 1 blocking agent) and gallopamil (verapamil-like calcium channel blocker), 14 patients with angiographically proven CAD and reproducible ST segment depression were studied at rest and during exercise under control conditions and after an intravenous bolus injection of esmolol (0.5 mg/kg/1 min, followed by an infusion with 0.2 mg/kg/min) or gallopamil (0.025 mg/kg/3 min). In contrast to gallopamil, esmolol significantly reduced systolic blood pressure (175.7 vs. 160 mm Hg) and heart rate (107.4 vs. 96.9 min-1) during exercise as well as cardiac output (11.57 vs. 9.38 l/min) and significantly enhanced systemic vascular resistance both at rest (1241 vs. 1479 dynes.s.cm-5) and during exercise (805 vs. 947 dynes.s.cm-5). On the other hand, exercise filling pressures and lactate levels (3.66 vs. 3.05 mmol/l) were significantly reduced by gallopamil only. Thus, the significant improvement of exercise tolerance by both esmolol and gallopamil is based on different mechanisms of action: esmolol improves myocardial ischemia by appreciably reducing myocardial oxygen consumption, whereas gallopamil primarily improves oxygen supply and ventricular performance. Plasma catecholamines, atrial natriuretic factor, and aldosterone levels as well as plasma renin activity were identically influenced by esmolol and gallopamil, respectively. A reflex activation of the sympathetic system did not occur.
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PMID:[Anti-ischemia effects of gallopamil and esmolol in an intra-individual comparison in patients with coronary heart disease]. 791 67

Antiischemic effects of beta 1-blocking agents are based on intrinsic negative inotropic and chronotropic properties. Partial beta 1-agonistic activity, although useful in preserving cardiac function, may counteract such antiischemic properties by modulating the intrinsic negative cardiac effects of beta-blockade. To investigate the acute hemodynamic and antiischemic profile of epanolol, a cardioselective beta 1-antagonist and partial agonist, 20 patients with left coronary artery disease underwent two incremental atrial pacing tests, 45 minutes before (APST I) and 15 minutes after (APST II) 4 mg intravenous epanolol, administered over 5 minutes. Additional measurements were carried out at 1, 3, 5, 10, and 15 minutes after epanolol, at basal and fixed heart rates. Epanolol immediately reduced heart rate with a maximum of 10% at 15 minutes and decreased contractility (Vmax) by 7% (both p < .05), whereas cardiac output fell temporarily by 9% (p < .05). Other hemodynamic parameters did not change, except for a significant 11% reduction in myocardial oxygen demand. Despite comparable pacing conditions, both the double product and contractility decreased significantly less during APST II, resulting in a 17% lower myocardial oxygen consumption (p < .05). Myocardial ischemia was markedly reduced, indicated by normalization of lactate metabolism [lactate extraction 16 +/- 7% vs. -7 +/- 8% (APST I)], less ST depression (21%), and modulation of LV end-diastolic pressure postpacing (all p < .05 vs. APST I), whereas angina was absent or less in 14 patients. None of the patients reported an adverse effect. Thus, under resting conditions intravenous epanolol induces moderate, short-lasting negative chronotropic and inotropic effects, but does not alter cardiac pump function or vascular resistance, reflecting its additional beta 1-agonistic properties. Alternatively, during pacing it still reduces ischemia through negative inotropic effects and diminishes myocardial oxygen demand, reflecting its beta 1-antagonistic profile.
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PMID:Acute systemic and antiischemic effects of epanolol in patients with coronary artery disease. 791 33

Previous experiments have described highly specific effects of noradrenergic agonists on synaptic transmission in the dentate gyrus (DG). For example, perfusion of hippocampal slices with the beta-noradrenergic agonist isoproterenol induces a long-lasting potentiation (LLP) of extracellularly recorded responses following stimulation of the medial perforant path (PP), and long-lasting depression (LLD) of responses evoked by stimulation of the lateral PP (Dahl D, Sarvey JM, 1989, Proc Natl Acad Sci USA 86:4776-4780). To examine the possible interactions of LLP, LLD, and long-term potentiation induced by tetanic stimulation (LTP), the authors recorded extracellular field potentials evoked in the DG by stimulation of the lateral or medial perforant path following LTP and LLP or LLD, invoked in different orders. After establishment of LLP or LLD by bath application of isoproterenol, subsequent tetanization of the respective afferents resulted in additional potentiation of the medial PP-evoked response and return of the lateral PP-evoked response to baseline levels. In other slices, application of isoproterenol after establishment of LTP resulted in further potentiation of medial PP-evoked responses but no change in the potentiated response evoked by lateral PP stimulation. Thus the pathway specificity was maintained irrespective of the history of previous potentiation or depression. Experiments using the specific beta 1 antagonist metoprolol further confirmed pathway specificity. Perfusion with 20 microM of metoprolol appeared to reduce LTP evoked by stimulation of the medial but not lateral PP. In a subsequent experiment, metoprolol in the absence of tetanization produced LLD of the medial PP-evoked response and LLP of the lateral PP-evoked response, opposite to the effects of ISO.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pathway specificity of noradrenergic plasticity in the dentate gyrus. 795 92


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