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)

1. Effects of PAF on excitatory neuro-effector transmission in smooth muscle cells of mucosa-free trachea and epithelium-intact bronchiole of the dog were investigated, by isometric tension recording, microelectrode and double sucrose-gap methods. 2. PAF (10(-11)-10(-7) M) dose-dependently enhanced the amplitude of contraction evoked by repetitive field stimulations (10 stimuli at 20 Hz) in both tracheal and bronchiolar tissues. At higher concentrations PAF (> 10(-8) M) increased the amplitude of contraction to a greater extent in the bronchiole than in the trachea. 3. In both muscle tissues, in parallel to the amplitude of contraction, PAF markedly enhanced the amplitude of excitatory junction potentials (e.j.ps) evoked by a single field stimulation in a dose-dependent manner, with no change in the resting membrane potential or input membrane resistance of the smooth muscle cells. PAF (5 x 10(-7) M) enhanced the amplitude of e.j.p. to a greater extent in the bronchiole than in the trachealis. In contrast, lyso-PAF (10(-10)-10(-7) M) showed no effect on e.j.p. amplitude in bronchiolar tissues. At a high concentration (10(-7) M) lyso-PAF slightly enhanced the e.j.p. amplitude in tracheal tissue, however the lyso-PAF induced stimulation of e.j.p. amplitude in the trachea was small compared to that of PAF. 4. PAF (10(-7) M) had no effect on the membrane depolarization induced by acetylcholine (ACh, 10(-9)-10(-5) M) and carbachol (10(-9)-10(-5) M) in tracheal smooth muscle cells. 5. The PAF-antagonists CV3988 (5 x i0-7 M) or WEB2086 (5 x 10-7 M) significantly enhanced the e.j.p. amplitude themselves, PAF (5 x 10-8 M) further enhanced the ej.p. amplitude in the presence of WEB2086 (5 x l0-7 M) but not CV3988 (5 x 10-7 M). In contrast, the new PAF-antagonist, E 6123(5 x l0-8 M), did not affect the ej.p. amplitude itself, and completely inhibited the increase in ej.p. amplitude caused by 5 x 10-8 M PAF. On the other hand, in the presence of the Hi-antagonist,mepyramine, PAF (5 X 10-8 M) further enhanced the ej.p. amplitude.6. The leukotriene synthesis inhibitor AA-861 (10-6 M) or leukotriene antagonist ONO1078 (10-7 M)inhibited the increase in ej.p. amplitude caused by 5 X 10-8 M PAF, respectively.7. In the presence of AA-861 (10-6 M), leukotriene B4 (LTB4, 10-' M) or LTD4 (10-8 M) slightly, and LTC4 (10- M) markedly enhanced the ej.p. amplitude. In contrast, LTE4 (10-8 M) significantly suppressed the e.j.p. amplitude.8. PAF (5 x 10-8 M) attenuated the depression phenomena of ej.ps observed during double stimulus experiments at different time intervals (5-10 s), but had no effect on the summation of ej.ps during repetitive field stimulation at a high frequency (20 Hz) in the trachealis.9. These results indicate that PAF potentiates excitatory neuro-effector transmission mainly through stimulating the release of lipoxygenase products, mainly LTC4 in the dog airway smooth muscle tissues.
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PMID:Effects of PAF on excitatory neuro-effector transmission in dog airways. 133 55

Platelet-activating factor (PAF; 1-alkyl-2-acetyl-glycero-phosphocholine) is a biologically active phospholipid which is synthesized by a variety of blood cells and organ systems. PAF exerts many effects on the cardiovascular system including hypotension, depression of myocardial contractility and coronary constriction. The present study has examined the capacity of the guinea-pig heart to regulate the levels of exogenous PAF in two different models: isolated perfused heart and isolated ventricular myocytes. In the first model, isolated hearts were perfused with labeled PAF (10(-10) M) in a recirculating manner at flow rates of 15 ml/min (normal flow perfusion; NFP) and 2 ml/min (low flow perfusion, LFP). Exogenously provided PAF appeared in the tissue in a time-dependent manner. The rate of extraction of PAF was higher during LFP than during NFP. PAF was metabolized by the heart to two major products, lyso-PAF and 1-alkyl-2-acyl-sn-glycero-3-phosphocholine (1-alkyl-2-acyl-GPC). Lyso-PAF was found primarily in the perfusion buffer while both lyso-PAF and 1-alkyl-2-acyl-GPC were detected in the tissue. No qualitative difference in the metabolic products derived from PAF catabolism was observed between hearts undergoing NFP and LFP. Acetyl hydrolase activity was detected in the perfusion fluid at both flow rates, probably accounting for the formation of lyso-PAF in the perfusate. However, perfusion fluid from LFP contained a higher acetyl hydrolase activity, per micrograms of protein as compared to fluid from NFP. Isolated ventricular myocytes incubated with labeled PAF (3 x 10(-9) M) also converted it to 1-alkyl-2-acyl-GPC. Kinetic experiments suggested that PAF was initially deacetylated to form lyso-PAF and that this intermediate was then rapidly reacylated with a fatty acyl moiety at the sn-2 position. HPLC analysis of the fatty acids inserted at the sn-2 position of 1-alkyl-2-acyl-GPC revealed that the myocytes reacylated lyso-PAF predominantly with arachidonic acid. These data indicate that the guinea-pig heart may regulate PAF levels by at least two mechanisms: (1) it may release acetyl hydrolase into the vascular compartment, particularly under low flow conditions; and (2) the ventricular myocyte has the capacity to take up PAF and catabolize it to inactive products.
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PMID:Metabolism of platelet-activating factor in the guinea-pig heart. 147 12

The effects of insulin-induced hypoglycemia on catecholamine secretion were investigated in patients with various neurological disorders affecting the autonomic nervous system. In control subjects, insulin-induced hypoglycemia resulted in marked increases in plasma epinephrine and norepinephrine levels. Heart rates were increased within 15 minutes after the insulin injection which were associated with slight elevation and depression of systolic and diastolic blood pressure, respectively. In patients with upper level spinal cord lesions (C1-T6) of various etiology, Shy-Drager syndrome and familial amyloidosis, insulin-induced hypoglycemia failed to increase plasma epinephrine and norepinephrine levels and resulted in falls in systolic and/or diastolic blood pressure 15 minutes after the injection. Heart rates were increased at 30-45 minutes after the injection. In patients with lower spinal cord lesions (T10-L1), neurosyphilis or brain stem tumor with orthostatic hypotension, the catecholamine responses were normal and blood pressure did not fall during insulin-induced hypoglycemia. In patients with Parkinson's disease and spinocerebellar degeneration with autonomic symptoms catecholamine responses were not impaired. These findings suggest that any lesion involving the sympathetic efferent systems of baroreflex such as the spinal descending pathway, sympathetic preganglionic neuron and peripheral nervous system causes both impairment of catecholamine secretion and a fall in blood pressure during hypoglycemia, and that lesions in sympatho-afferent system may not affect the secretion of catecholamine and neural control of blood pressure.
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PMID:[Effects of insulin-induced hypoglycemia on catecholamine secretion and blood pressure in neurological disorders affecting autonomic nervous system]. 162 51

We studied RO 15-1788, a new benzodiazepine receptor antagonist, [ethyl 8-fluoro-5, 6-dihydro-5-methyl-6-oxo-4H-imidazo (1, 5a) (1, 4) benzodiazepine-3-carboxylate] to determine its effects in a murine model of hemorrhagic shock. Hemorrhaged rats treated with RO 15-1788 maintained post-reinfusion mean arterial blood pressure (MABP) at significantly higher values compared to rats receiving only the vehicle (final MABP 114 +/- 4 vs 82 +/- 4 mmHg, p less than 0.001). Moreover, RO 15-1788 decreased the release of the lysosomal hydrolase, cathepsin D (p less than 0.02) into the circulation and blunted the plasma accumulation of free amino-nitrogen groups (p less than 0.01). Furthermore, the plasma activity of a myocardial depressant factor (MDF) was significantly lower in RO 15-1788 treated rats subjected to hemorrhagic shock than in those given the vehicle (18 +/- 2 vs 42 +/- 4 U/ml, p less than 0.01). Additionally, in vitro analysis indicated that RO 15-1788 antagonizes PAF induced coronary vasoconstriction and cardiac depression observed in perfused rat hearts, as well as inhibiting PAF induced platelet aggregation in cat platelet rich plasma. Our results suggest that antagonism of PAF actions can contribute significantly to the beneficial effects of RO 15-1788 in hemorrhagic shock.
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PMID:Beneficial actions of RO 15-1788, a benzodiazepine receptor antagonist, in hemorrhagic shock. 311 57

Recent evidence localizing the inflammatory mediator, platelet activating factor, (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) to the membranes of stimulated neutrophils raises the possibility that PAF may, in addition to its activities as a mediator, alter the physical properties of membranes. Accordingly, the effects of PAF and related alkyl ether and acyl analogs on phase transition thermodynamics of dipalmitoylphosphatidylcholine (DPPC) were studied using fluorescence polarization of the fluorescent probe, 1,6-diphenyl-1,3,5-hexatriene (DPH). PAF, its ester analog (1-palmitoyl-2-acetylphosphatidylcholine) and both the corresponding alkyl and acyl lysophospholipid analogs (each at a concentration of 10 mol%) significantly decreased the phase transition temperature and broadened the phase transition of DPPC (P less than 0.05). The relative potency of the lipids in causing this effect was ester-PAF greater than or equal to PAF greater than or equal to lyso-PAF greater than lyso-PC suggesting that the fluidization of the synthetic membranes was attributable to both the 2-position acetyl group and the 1-position alkyl linkage. Furthermore, using various related compounds, increases in chain length and degree of unsaturation in the 2-position were shown to enhance the depression in transition temperature and broadening of the phase transition. Phase transition thermodynamics were also assessed using differential scanning calorimetry. Similar depression in the phase transition temperature was measured for PAF and both the alkyl and acyl lysophospholipids. Broadening of the phase transition for DPPC by the various analogs was assessed by calculation of transition peak width and cooperative unit. Data from fluorescence polarization and differential scanning calorimetry provide similar though not identical results and support the hypothesis that the unique features of PAF may alter membrane physical properties and could ultimately explain some of its biologic actions.
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PMID:Effects of platelet activating factor and related lipids on phase transition of dipalmitoylphosphatidylcholine. 337 Feb 14

In anaphylactic paw edema the reactivity of blood vessels to norepinephrine in the isolated perfused hind legs of rats and mice is reduced. A vasoreactivity depressing factor was postulated and searched for. PAF-acether, histamine and lipoxygenase products were found as being possibly responsible for depression of the vascular reactivity.
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PMID:On the nature of the vasoreactivity depressing factor (VDF) in inflammation and anaphylaxis in the rat and mouse. 644 May 44

Hemodynamic studies were performed in a case of Shy-Drager syndrome with severe orthostatic hypotension. Marked depression of blood pressure was recognized immediately after the tilt-up, wherein decrease in cardiac output was detected (65 leads to 35 ml; stroke volume) during measurements by echocardiography. In association with the depression of blood pressure and decrease in cardiac output, Doppler sonograms showed the overall blood flow reduction in the brain-supplying arteries, suggesting some breakdown of autoregulation of the cerebral blood flow. Medication with indomethacin obviously limited the depression of blood pressure during the standing exercise. The pressor mechanism of indomethacin might be regarded as a result of increased vasoconstrictivity by inhibiting the synthesis of prostaglandins.
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PMID:Hemodynamics in Shy-Drager syndrome and treatment with indomethacin. 666 53

We studied the effects of polymorphonuclear leukocytes (PMNLs) activated by N-formyl-methionyl-leucyl-phenylalanine on the endothelium-dependent relaxation of the rabbit basilar artery (BA). In the presence of activated PMNLs the maximal vessel relaxation to acetylcholine (ACh) and bradykinin (endothelium-dependent dilators) was decreased from 62 +/- 7 and 48 +/- 6% to 23 +/- 9 and 19 +/- 7, respectively, (p < 0.05). The endothelium-independent relaxation to nitroprusside was not affected by PMNLs. When PMNLs were activated in the organ chamber in the presence of a low concentration of platelet-activating factor (PAF, 10(-10) mol/l), the depression of ACh- and bradykinin-induced relaxation increased by 27 +/- 9 and 23 +/- 7%, respectively (p < 0.05), though at this concentration PAF alone did not cause PMNLs to induce endothelial dysfunction. In addition, in the presence of PAF, activated PMNLs inhibited endothelium-dependent relaxation at lower cell concentrations and shorter periods of contact with the endothelium. PMNL effects on the endothelium were correlated with the level of cell exocytosis as tested by accumulation of beta-glucuronidase activity. In the presence of PAF, accumulation of this activity increased from 46 +/- 6 to 79 +/- 8 U/ml (p < 0.05). Examination of BA segments by scanning electron microscopy revealed that, after the treatment with activated PMNLs, the endothelium was morphologically preserved, but in the presence of PAF PMNLs caused more apparent microlesions in the endothelial layer. We conclude that small quantities of PAF potentiate the activation of marginated PMNLs. These cells then become more aggressive towards the endothelium, producing significant depression of the endothelium-dependent relaxation.
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PMID:Leukocyte-induced endothelial dysfunction in the rabbit basilar artery: modulation by platelet-activating factor. 755 83

Comparisons were made between the premenstrual changes reported by nontreatment-seekers (NTS) (n = 32) and those of treatment-seekers (TS) (n = 52). The Premenstrual Assessment Form Luteal Phase and Follicular Phase versions were completed and the Beck Depression Inventory, the Automatic Thoughts Questionnaire and the State-Trait Anxiety Inventory were completed at both the luteal and follicular phases. Prospective daily ratings were made for two treatment cycles on the Daily Ratings Form and TS were screened for a mood-disorder history. Using the commonly cited 30% decrease in dysphoric levels from the pre- to postmenstrual phases as the criterion of prospective confirmation, women with prospectively confirmed dysphoria (PMD +) were not significantly more symptomatic than those without prospective dysphoric confirmation (PMD -). However, TS were more symptomatic than NTS on measures of depression, anxiety and frequency of negative automatic thoughts but not on mood behaviour and physical changes reflected in the PAF scales. No demographic differences were found between TS and NTS. Results did not support the issue of requiring 'confirmation' of self-reports within a help-seeking group or the use of the 30% criterion in particular. Findings further suggest that the 95-item PAF may be inadequate in differentiating TS from others.
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PMID:Correlates of premenstrual dysphoria in help-seeking women. 771 8

The aim of the studies was to evaluate the psychometric properties and construct validity of the Diabetes Health Profile (DHP-1). Content for the DHP-1 was derived following in-depth interviews with 25 insulin dependent and insulin requiring patients, a review of the literature and discussions with health care professionals. Initial analysis of the factor structure of the DHP-1 was carried out on the responses of 239 insulin dependent and insulin requiring patients, with a mean age of 40.85 years (SD = 13.0), resulting in a 43 item three factor solution. The 43 item version of the DHP-1 was completed by 2,239 insulin dependent/requiring patients (mean age = 39.8, SD = 10) years. Fifty-one per cent were men. A forced three factor Principal Factoring Analysis with varimax rotation was carried out. Eleven items were excluded with item factor cross loadings > 0.30 or item factor loadings < 0.30. PAF analysis of the 32 items resulted in a three factor solution accounting for 33% of the total explained variance. The three factors were interpreted as Psychological Distress, Barriers to Activity and Disinhibited Eating. Factor congruence between subsamples were: Psychological distress (0.93), Barriers to Activity (0.93) and Disinhibited Eating (0.99). Coefficients of congruence between men and women were 0.94, 0.92 and 0.99 for Psychological Distress, Barriers to Activity and Disinhibited Eating respectively. Internal consistency of the three factors (Cronbach's alpha) were: Psychological Distress (0.86), Barriers to Activity (0.82), and Disinhibited Eating (0.77). Construct-convergent validity was investigated on a sample of 233 insulin dependent and insulin requiring patients (mean age = 51.46 years). Psychological Distress and Barriers to Activity subscales correlated with the Hospital Depression and Anxiety Scale = 0.50 to 0.62, p < 0.01) and subscales of the SF-36 (range: r = -0.17 to -0.62, p < 0.01). These findings lend support to the construct validity and reliability of the DHP-1 and that it is suitable for further development.
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PMID:The Diabetes Health Profile (DHP): a new instrument for assessing the psychosocial profile of insulin requiring patients--development and psychometric evaluation. 899 93


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