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)

Depression of lung endothelial cell metabolic function may be an early and sensitive indicator of lung damage. When such functions are measured in vivo, substrates injected usually must be limited to "trace" doses due to the significant hemodynamic effects of high doses of substrate. Under first-order conditions (i.e., trace doses) the enzyme or transport system rate constant Vmax/Km may be calculated, but independent estimates of each variable (Vmax and Km) are not available. We therefore used multiple indicator-dilution methods and higher substrate concentrations to apply a mathematical model, based on saturable kinetics that yield independent estimates of the apparent kinetic parameters Vmax and Km for pulmonary angiotensin-converting enzyme (ACE). We used the ACE substrate, [3H]benzoyl-phenylalanyl-alanyl-proline ([3H]BPAP) and made these measurements and also estimates of serotonin [5-hydroxytryptamine (5-HT)] removal, before and after acute lung injury induced by intratracheal administration of phorbol myristate acetate (PMA). PMA significantly depressed the percent 5-HT removal (62 +/- 3 to 44 +/- 4%) and BPAP percent metabolism (74 +/- 2 to 66 +/- 2), when trace amounts of either compound were injected as a bolus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pulmonary angiotensin-converting enzyme kinetics after acute lung injury in the rabbit. 284 Dec 74

Single pass extraction of a new iodinated inhibitor of angiotensin-converting enzyme (ACE) was measured by means of indicator-dilution techniques applied to rabbit lungs, perfused in situ at 20 ml/min with Krebs bicarbonate solution containing 3% bovine serum albumin. A bolus containing the inhibitor, N-[1(S)-carboxy-(4-OH-3-125I-phenyl)ethyl]-L-Ala-L-Pro (CPAP), and an intravascular marker, [14C]dextran, was injected and extraction calculated at the peak of the resulting venous outflow-time curve. In 13 of 21 lungs used, a synthetic substrate for ACE, [3H]benzoyl-phenylalanyl-alanyl-proline (BPAP), was added to the bolus and appearance of its hydrolysis product, [3H]benzoyl-Phe, measured in effluent samples. When low amounts (0.15 nmol) of [125I]CPAP were injected, pulmonary extraction (E) of CPAP was 67 +/- 14% (X +/- S.D; n = 21) and metabolism (M) of BPAP was 56 +/- 9% (n = 13). Addition of unlabeled CPAP (3, 34 or 340 nmol) to the Addition of unlabeled CPAP (3, 34 or 340 nmol) to the injected bolus caused dose-dependent reduction of E(CPAP) and M(BPAP) that was no longer evident 10 min after the largest dose of CPAP. Coadministration of the ACE inhibitor, captopril (3, 6, 8 and 28 nmol), also caused dose-dependent, reversible depression of both E(CPAP) and M(BPAP). Accordingly, extraction of CPAP by perfused rabbit lung is saturable. Inasmuch as CPAP inhibits ACE activity (as reflected by BPAP metabolism) and CPAP uptake is inhibited by captopril (which also inhibits BPAP hydrolysis), it appears that a large portion of this saturable process probably reflects binding to vascular ACE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Uptake of N-[1 (S)-carboxy-(4-OH-3-125I-phenyl)ethyl]-L-Ala-L-Pro, an inhibitor of angiotensin-converting enzyme by rabbit lungs in situ. 301 13

Pulmonary angtiotensin-converting enzyme (ACE) is located on the luminal surface of pulmonary microvasculature. Multiple indicator-dilution techniques have been used to measure pulmonary ACE activity in vivo and in isolated lungs. These studies suggest that ACE activity is depressed in several forms of acute lung injury. Depression of ACE activity may reflect impaired substrate delivery to enzyme sites because of flow-related reduction of perfused surface area. To assess the role of altered microvascular flow and surface area in the measurement of ACE activity, we utilized similar techniques to estimate the apparent Km and Vmax of pulmonary ACE in isolated, Krebs-perfused rabbit lungs. Km is an estimate of the affinity of a synthetic ACE substrate, [3H]benzoyl-phenyl-alanyl-alanyl-proline ([3H]BPAP), for ACE and should not be influenced by the rate of substrate delivery to luminal enzyme sites. Conversely, Vmax is an index of the number of ACE sites and should be influenced by perfusion changes that alter the number of perfused sites (recruitment or derecruitment). When isolated lungs were subjected to physiological maneuvers designed to increase or decrease perfused surface area, apparent Vmax increased or decreased respectively. Apparent Km was not altered by these maneuvers. Km and Vmax were independent of changes in perfusion rate when surface area was held constant. Thus these parameters should be useful in evaluating perfusion changes in normal and injured lungs.
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PMID:Effect of flow and surface area on angiotensin-converting enzyme activity in rabbit lungs. 303 60

Preadaptation of adult rats to hypoxia (10% O2 for 5 days) results in tolerance to oxygen-induced lung injury (greater than 95% O2 for 2 days). This study investigated whether hypoxia preadaptation maintained an endothelial cell metabolic function, angiotensin-converting enzyme (ACE) activity, despite exposure to hyperoxia. Lung ACE activity was measured as the capacity of isolated, ventilated, perfused lungs to hydrolyze an ACE substrate, benzoyl-phenylalanyl-alanyl-proline (BPAP), after in vivo hypoxia, hyperoxia, or sequential hypoxia-hyperoxia exposure. The results indicated that (1) hyperoxia decreases BPAP hydrolysis in isolated lungs, (2) hypoxia preadaptation does not affect BPAP hydrolysis (measured at ambient PO2), and (3) hypoxia preadaptation prevents hyperoxia-induced depression of lung ACE activity. These data imply that lung microvascular endothelial cells participate in the development of oxygen tolerance in this model.
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PMID:Hypoxia preadaptation prevents oxygen-induced depression of lung angiotensin-converting enzyme activity. 608 27

The influence of N-acetyl-muramyl-L-alanyl-D-isoglutamine (muramyl dipeptide, MDP) on the plaque-forming cell (PFC) response of mice to sheep red blood cells (SRBC) was studied. The effect of MDP depends on the relative doses of antigen and adjuvant and on the timing of adjuvant addition. For a given concentration of antigen, when SRBC and MDP were simultaneously injected in the i.v. route, MDP led to an enhancement of the response; in contrast, when antigen was injected i.p., a depression of the PFC response was observed. In vitro, the same duality of effect was obtained, for the same spleen cell concentration; addition of MDP led to a stimulation of the response when cultures were set in petri dishes and to an important decrease in the response when cultures were set up in plastic tubes. This inhibitory effect of MDP did not appear when it was added one night after the initiation of the cultures. These contrasting results confirm the adjuvant properties of MDP, but they show that under certain conditions, MDP can stimulate suppressive processes.
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PMID:Opposite effects of the synthetic adjuvant N-acetyl-muramyl-L-alanyl-D-isoglutamine on the immune response in mice depending on experimental conditions. 699 38

Allylamine (AA) and beta-aminopropionitrile (beta APN) are well known vascular toxins with a demonstrated synergistic toxic effect, i.e. given together they cause extensive smooth muscle cell necrosis of the aortic media. In this study, we investigated the possibility that the enzymes involved in the separate toxicity of AA (semicarbazide-sensitive amine oxidase, or SSAO) and beta APN (lysyl oxidase, or LyO), could be the target(s) of their synergistic toxicity. Adult male Sprague-Dawley rats were given AA alone (AA), 100 mg/kg/day, beta APN alone (beta APN), 1 g/kg/day, or both chemicals (AA + beta APN) by gavage for 1, 2, 5 or 10 days. SSAO ahd LYO were assayed in aorta, lung, and bone. SSAO activity in aortas of rats treated with AA + beta APN showed a maximal decrease (40%) at 10 days; more moderate depression of SSAO was seen in lung and bone. LyO changes were most marked in aorta, where activities were consistently and markedly depressed in all rats receiving beta APN (either alone or in combined treatment). Similarly, the lung and bone LyO activity was depressed at all time points in rats receiving beta APN, but to an apparently lesser degree than in aorta. The most striking changes in in vivo enzyme activities were seen in the aorta, the major target organ in this model. No synergistic effect of the two toxins was seen in the depression of LyO enzyme activity, since there was no difference in the degree of enzyme inhibition present between rats given beta APN alone or AA + beta APN, indicating that inhibition of this enzyme is mainly due to the effect of beta APN. We suggest that AA is the primary toxin in this synergistic vasculotoxic effect. It is likely that some effect of beta APN on AA metabolism or detoxification mechanisms results in synergism.
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PMID:Vascular amine oxidase activities during synergistic vasculotoxicity. 790 64

Experimental arthritis and inflammation have been reported to reduce liver cytochrome P-450-dependent mono-oxygenase activities with subsequent impairment of drug metabolism. Interleukin-1 beta (IL-1) is among the proven mediators of both inflammation and P-450 decrease, although some paradoxical effects were sometimes reported in experimental models of arthritis. The aim of the present study was to evaluate the main liver drug-metabolizing isoenzymes during established collagen-induced arthritis in rats, and to investigate whether a systemic IL-1 treatment was able to mimic or sometimes to reverse the influence of the inflammatory process on these enzymes. Arthritis was induced on day 0 by type II collagen and a low dose (0.2 mg) of N-acetylmuramyl-L-alanyl-D-isoglutamine, and human recombinant IL-1 was administered s.c. at the daily dose of 0.02, 0.2 or 2.0 micrograms per arthritic rat, from day 21 to 25 and on day 28. Ethoxyresorufin-O-deethylation was depressed 6-fold in arthritic rat liver microsomes and the highest dosage of IL-1 potentiated this depression. Pentoxyresorufin-O-deethylation decreased by 50% in arthritic rat, a dose-dependent decrease being observed after IL-1 treatment. Progesterone 6 beta-hydroxylation and P-450 IIIA protein increased by 2-fold in both untreated arthritic rat liver microsomes and those treated by the lowest dose of IL-1. The two higher doses decreased this activity, vs. the dose, to reach the naive level. Lauric acid hydroxylation increased 2-fold in arthritic rat and was further potentiated by IL-1. UDP glucuronosyl transferase IA2 activity was increased 2-fold in arthritic rats, with subsequent decrease after 2.0 micrograms of IL-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-1 beta differentially represses drug-metabolizing enzymes in arthritic female rats. 843 2

Cognizant that only 20% of depressed individuals seek treatment, Healthy People 2000 has recommended a goal of increasing this figure to 45%. This flows from a recognition of depression as a serious and costly problem, with women carrying twice the risk of men. Primary care settings are the first contact a depressed woman may make with the health care system. This study piloted a collaborative model in which a Psychiatric Mental Health Advanced Practice Nurse (PMH-APN) was available on site to assist providers to recognize women with depressive symptoms and to provide intervention. Thirty three women were identified by primary care providers and referred for screening to the PMH-APN. Assessment and intervention based on the interpersonal theory of Peplau were accomplished in an average of eight sessions with the PMH-APN. Pre and postintervention descriptive data on the primary outcome (depressive symptoms) and three theoretically congruent mediating variables (performance and social self-esteem and satisfaction with interpersonal relations) were consistent with the expected outcomes of the intervention.
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PMID:Depressive symptom reversal for women in a primary care setting: a pilot study. 979 11

Neurophysiological study of all links of afferent somatosensory systems in neuropathies of different genesis was conducted. Patients with alcoholic (APN) and diabetic (DNP) polyneuropathies have been examined and selected as follows: 19 patients with intensive spontaneous pain syndrome (scoring over 6 on VAS); 20--without pain; 22 patients with allodiny caused by neuropathic pain and 38--without allodiny. Control group included 20 healthy subjects. Symptom complex of pain syndrome encompassed pronounced disorders of cutaneous sensitivity, minus symptoms in deep sensory sphere and high depression level. Neurophisiological appearances of spontaneous pain syndrome in APN and DPN are characterized by generalized mixed damage of peripheral sensible nerves and of 1 beta-afferents of H-reflex arch. Insufficiency of function of pain control system was mainly of deafferent character. Allodiny and spontaneous pain syndrome are reciprocally combined, the former being distinguished by involvement in pathology of 1-[symbol: see text] fibers (motor nerves and efferent links of H-reflex).
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PMID:[Neuropathic pain syndrome: clinico-neurophysiological analysis]. 1462 81

Mobile Decision Support for Advanced Practice Nurses (MODS-APN) is a PDA-based decision support tool designed to assist APNs in the diagnosis and management of smoking cessation, obesity, and depression. It is currently being tested in a randomized, controlled trial (RCT) in a sample of APN students to determine the effect on adherence to clinical practice guideline (CPG) recommendations. Tools such as MODS-APN have the potential to increase CPG adherence, enhance evidence-based practice, promote patient safety, and in the long term improve patient outcomes.
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PMID:Mobile decision support for advanced practice nurses. 1710 12


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