UMLS:C0011570 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although studies indicate that simple hemorrhage induces profound depression of cell-mediated immunity and enhances the host's susceptibility to sepsis, the mechanism for this remains unknown. Since the Kupffer cells (KC) are positioned to have constant exposure to various immunomodulators and antigens released during hypotension, we have examined whether antigen presentation by KC, a critical component in eliciting an antigen specific immune response or those processes associated with it, are depressed following hemorrhage. C3H/HeN mice were bled to and maintained at a mean BP of 35 mmHg for 60 min, and then resuscitated with their own blood and adequate fluids. The mice were killed at varying periods of time after hemorrhage to obtain KC from the liver, and assessed for their capacity to present antigen to a sensitized clone Th/cell line (D10.G4.1). Hemorrhaged mice exhibited a marked decrease in antigen presenting capacity beginning as little as 2 h and lasting up to 3-5 days post-hemorrhage. The ability of KC to express mouse interleukin 1 (mIL-1) showed a significant decline at 2 h following hemorrhage, but this effect was not apparent at 24 h post-hemorrhage. In contrast, KC capacity to produce IL-1, IL-6 and tumour necrosis factor (TNF) (cytokines which can co-stimulate T cell antigen presentation) was markedly enhanced during the first 24 h following hemorrhage. A marked decrease was observed in both the mean of the average fluorescence per KC and the percent of Ia antigen-positive KC which persisted for at least 3 days after hemorrhage. The ability of ibuprofen (a cyclooxygenase blocker) to partially restore the antigen presenting capacity of KC from hemorrhaged mice in vitro indicates that prostaglandins are involved in this dysfunction. Thus, the depression of KC antigen presentation, as well as the enhanced capacity of these cells to release inflammatory mediators (TNF, IL-1, IL-6 and prostanoids) which may produce cell and organ dysfunction, could contribute to the host's enhanced susceptibility to sepsis following hemorrhage.
...
PMID:Differential effects of hemorrhage on Kupffer cells: decreased antigen presentation despite increased inflammatory cytokine (IL-1, IL-6 and TNF) release. 131 64

Thermal injury in rats leads to an impairment of polymorphonuclear leukocyte (PMN) functions, particularly oxidative metabolism and phosphoinositide turnover. As prostaglandin E2, which has immunosuppressive properties, is released in high levels after burn trauma, we investigated the in vitro and in vivo effects of a nonsteroidal antiinflammatory drug, niflumic acid, on oxidative and phosphoinositide metabolism in PMNs from healthy and burned rats. Given the role of fluoride ions on PMN, the influence of niflumic acid was compared with that of sodium fluoride (NaF) at equivalent doses of F-. In vitro, niflumic acid and sodium fluoride had no effect on oxidative metabolism in stimulated by formyl methionyl-leucyl-phenylalanine (FMLP) or opsonized zymosan (OZ) or nonstimulated PMNs from healthy and burned rats. Niflumic acid slightly increased the production of inositol phosphate by nonstimulated PMNs from healthy and burned rats. Niflumic acid and NaF partly restored the stimulating effect of FMLP on inositol phosphate production by PMNs from burned rats. In vivo treatment with niflumic acid and NaF increased the oxidative metabolism of PMNs from burned rats but not healthy rats. Niflumic acid, more than NaF, restored the activity of both stimulants on phosphoinositide metabolism in PMNs from burned rats. In conclusion, at non-antiinflammatory doses, while inhibiting cyclooxygenase activity, niflumic acid exerts a complex effect on the burn-induced depression of PMN functions. The fluoride anion induces similar but generally weaker effects and seems to be involved in the restoring effects of niflumic acid on PMN functions in burned rats.
...
PMID:Effects of niflumic acid on polyphosphoinositide and oxidative metabolism in polymorphonuclear leukocytes from healthy and thermally injured rats. 133 50

This study examines the action of three putative functional bradykinin (BK) antagonists isolated from Mandevilla velutina on BK and other agonist-induced contraction or relaxation responses in intact or in epithelium-denuded strips of tracheal muscle from guinea pigs. Compound MV 8612 (8 and 16 microM) and MV 8610 (12 and 24 microM) caused a graded rightward displacement of BK dose-response curves in the isolated guinea pig trachea (dose ratio 2- to 4-fold). Compound MV 8608 (28 microM) had a small effect on BK contractile responses. At high concentrations, compound MV 8612 (24 microM) caused a slight but significant depression of the BK-induced maximal responses. These pharmacological actions appear to be quite selective towards BK, since within the same concentration range these compounds failed to interfere with the sensitivities to prostaglandin F2 alpha, carbachol and histamine. However, these compounds significantly enhanced maximal responses to the latter two agonists, an action that was not influenced by indomethacin. In addition, MV 8612 and MV 8608 (16 and 56 microM) significantly potentiated BK-mediated epithelium-dependent relaxation responses in preparations precontracted with carbachol. These compounds also significantly potentiated isoprenaline but not theophylline-relaxant responses, an action that seems to occur independently of the generation of cyclooxygenase products of arachidonic acid pathway. These results further extend our previous studies and indicate that some of the M. velutina compounds exert a weak though selective antagonistic action against BK-induced contractile responses of the isolated epithelium-denuded guinea pig tracheal smooth muscle and potentiate BK-induced relaxations in tissues with intact epithelium precontracted with carbachol.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Effect of compounds from Mandevilla velutina on bradykinin-mediated contractile and relaxant responses of the isolated guinea pig trachea. 138 76

Septic multi-organ failure represents a common cause for operative mortality following open-heart surgery. One major reason might be the depression of cell-mediated immunity. The purpose of this prospective randomized trial was to quantify and specify the effects of open-heart surgery on cell-mediated immune mechanisms. In addition, the immunorestorative potential of a combined immunomodulatory therapy with the cyclooxygenase inhibitor indomethacin and the thymomimetic substance Thymopentin versus single drug administration of indomethacin was investigated. Twenty patients were given indomethacin for the first 5 postoperative days (group A). Another 20 patients also received Thymopentin perioperatively and on the second and fourth postoperative days (group B), while 20 patients underwent conventional therapy (group C). Cell-mediated immune response was quantified in vitro by measuring CD3+ T-lymphocytes and their subsets, CD4+ T-helper and CD8+ T-suppressor cells. Lymphocyte responsiveness to a specific (Antigen-Cocktail) and non-specific mitogen (phytohemagglutinin) provided information about the quality of cell-mediated immune response. On the first postoperative day CD3+ T-lymphocyte counts and Antigen-Cocktail-induced lymphocyte proliferation decreased significantly in all groups. The number of CD4+ T-Helper cells fell significantly only in groups A and C, while the decrease in group B was not statistically significant; the same applied to phytohemagglutinin-induced lymphocyte response. The CD4+/CD8+ ratio was significantly depressed only in group C, decreased slightly in group A and did not change as compared to baseline values in group B. All investigated parameters remained significantly depressed until the seventh postoperative day in group C.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Changes in lymphocyte subsets and mitogen responsiveness following open-heart surgery and possible therapeutic approaches. 138 13

Vasopressor response and release of eicosanoids following intravenous injection of arachidonic acid (AA) were examined in normotensive rats. AA administration caused a rapid initial fall of arterial pressure followed by a brief rise and a subsequent prolonged fall in anesthetized rats. Immediately after AA injection the blood levels of TXB2 and 6-keto-PGF1 alpha, the stable metabolites of TXA2 and prostacyclin, rose, from 1.52 +/- 0.23 ng/ml to 176.4 +/- 42.6 ng/ml and from 4.05 +/- 0.67 ng/ml to 171.4 +/- 31.2 ng/ml, respectively. Blood pressure behaviour and eicosanoid blood level were influenced by different inhibitors and antagonists of vasoactive mediators. The cyclooxygenase inhibitor acetylsalicylic acid completely eliminated the second blood pressure depression after AA injection and simultaneously diminished TXB2 and 6-keto-PGF1 alpha formation in murine blood, whereas the TXA2 receptor antagonist BM 13.177 prevented the return of the blood pressure to preinjection level after the initial brief fall in arterial pressure. Although the TXA2 synthase inhibitor HOE 944 markedly inhibited TXB2 formation, no influence on AA-induced blood pressure changes could be registered. The receptor antagonist of platelet activating factor BN 52021 and the serotonin and histamine receptor antagonist cyproheptadine also reduced TXB2 amounts, in murine blood without any effects on blood pressure behaviour.
...
PMID:Relevance of vasoactive mediators for the blood pressure effects of intravenous arachidonic acid injection in rats. 150 52

The effects of arachidonic acid (AA) and other long-chain fatty acids on voltage-dependent Ca channel current (ICa) were investigated, with the whole cell patch clamp method, in longitudinal smooth muscle cells of rabbit ileum. 10-30 microM AA caused a gradual depression of ICa. The inhibitory effect of AA was not prevented by indomethacin (10 microM) (an inhibitor of cyclooxygenase) or nordihydroguaiaretic acid (10 microM) (an inhibitor of lipoxygenase). 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine (H7; 25-50 microM) or staurosporine (2 microM) (inhibitors of protein kinase C) did not block the AA-induced inhibition of ICa, and application of phorbol ester (a protein kinase C activator) (phorbol-12,13-dibutyrate, 0.2 microM) did not mimic the AA action. Some other cis-unsaturated fatty acids (palmitoleic, linoleic, and oleic acids) were also found to depress ICa, while a trans-unsaturated fatty acid (linolelaidic acid) and saturated fatty acids (capric, lauric, myristic, and palmitic acids) had no inhibitory effects on ICa. Myristic acid consistently increased the amplitude of ICa at negative membrane potentials. The present results suggest the possible role of AA, and perhaps other fatty acids, in the physiological and/or pathological modulation of ICa in smooth muscle.
...
PMID:Modulation of voltage-dependent Ca channel current by arachidonic acid and other long-chain fatty acids in rabbit intestinal smooth muscle. 151 58

Endothelial cells modulate the function of their underlying smooth muscle. Thus, altered endothelial behavior could be important in the pathogenesis of vascular and lymphatic diseases, including human and animal filariasis. Endothelium-dependent relaxation is depressed in both in vivo canine femoral artery of dogs infected with Dirofilaria immitis and in vitro rat aorta exposed to adult D. immitis. The experiments reported here were designed to determine if filarial cyclooxygenase products could depress endothelium-dependent relaxation in vitro. Pretreatment of the parasites, but not the vascular ring, with either indomethacin or aspirin, prevented filarial-induced depression of relaxation. Analysis of heartworm-conditioned medium by gas chromatography--mass spectrometry revealed two peaks in the biologically active medium that were not present in the control. One peak had a retention time and chromatographic profile characteristic of derivatized PGD2 standard, and the other was not identified. Incubation of the vascular ring with PGD2 mimicked filarial-induced depression of endothelium-dependent relaxation at low, but not high, concentrations of acetylcholine. Thus, filarial PGD2 may be involved in altered endothelium-dependent relaxation seen in heartworm-infected dogs.
...
PMID:Dirofilaria immitis: do filarial cyclooxygenase products depress endothelium-dependent relaxation in the in vitro rat aorta? 151 64

This investigation focuses on the changes in the concentrations of cyclooxygenase (CO) products present within the crevicular fluid in naturally-progressing periodontitis in the beagle and the effects of various non-steroidal anti-inflammatory drugs (NSAIDs) on these metabolite levels and disease progression. Six groups of 5-6 beagles with periodontitis were followed for 6 months to determine the pretreatment rate of radiographic bone loss. At baseline, groups of animals were placed on soft chow to promote disease progression. Groups were treated with either placebo, three different formulations of systemic ibuprofen, systemic naproxen or topical flurbiprofen. During the 6-month treatment phase, crevicular fluid (CF) samples and radiographs were taken at regular intervals. Radioimmunoassay of CF samples from untreated animals demonstrated a steady increase in prostaglandin E2 (PGE2) over baseline values. At 1 month, CF-PGE2 levels increased 2-fold over baseline and, by 6 months, had reached a 5- to 6-fold elevation. Crevicular fluid thromboxane B2 (CF-TxB2) levels rapidly reached a 4- to 5-fold peak over baseline at 1 month and subsequently dropped to a 2-fold elevation for the remainder of the study. The rate of bone loss (BLOSS) in untreated animals increased 38% during the 6-month period, as compared to baseline pretreatment BLOSS rates. Overall, there was a significant depression in the CF levels of both PGE2 and TxB2 in all NSAID-treated groups. All NSAID treatments significantly retarded BLOSS, ranging from 21.0-36.9% of the control BLOSS rate. Furthermore, CO activation represents a major regulatory step in bone destruction and may thereby serve as an important site for pharmacological modulation.
...
PMID:Effects of NSAIDs on beagle crevicular cyclooxygenase metabolites and periodontal bone loss. 160 34

Using helical strips of the bovine middle cerebral arteries, changes in vascular tension were measured during isometric contractions induced by endothelin. 1) Both Ca(++)-free media and Ca(++)-antagonists depressed the endothelin-induced contractions only by 40% of the control, suggesting the involvement of both Ca(++)-entry from outside the muscle cell and intracellular Ca(++)-release from the sarcoplasmic reticulum. 2) Endothelin-induced contractions were significantly depressed by 1 microgram/ml tetrodotoxin (TTX). Relative size of depression by TTX was practically the same as that observed in Na(+)-free media without TTX. These results indicated a partial involvement of Na(+)-entry through TTX-sensitive Na(+)-channels. 3) Endothelin-induced contractions were effectively depressed by NCDC, an inhibitor of phospholipase C, suggesting the involvement of PI-turnover in the contraction. 4) Protein kinase inhibitors such as H-7 and H-8 effectively depressed endothelin-induced contractions. This result suggested the phosphorylation of a certain protein by protein kinase C as a cause of long lasting contractions. 5) A phospholipase A2 (PL A2) inhibitor, quinacrine, significantly depressed the endothelin-induced contractions, suggesting a possible involvement of PL A2. However, neither the cyclooxygenase inhibitor nor the lipoxygenase inhibitor depressed endothelin-induced contractions.
...
PMID:[A pharmacological study on the mechanism of the endothelin-induced contraction of the bovine cerebral artery]. 164 17

Adherence to extracellular matrix proteins modulates the functional and secretory activities of mononuclear phagocytes, although the mechanisms regulating these adherence-dependent changes are poorly understood. In this study, the ability of rat inflammatory peritoneal macrophages (PM) to adhere to an endothelial cell-derived extracellular matrix or a denatured collagen/fibronectin-coated surface and perform antibody dependent cell cytotoxicity (ADCC) and secrete reactive oxygen intermediates was compared with PM adherent to tissue culture plastic. Prostaglandin E2 (PGE2) and thromboxane B2 (TxB2), two major cyclooxygenase products released by inflammatory macrophages, were also measured by PM adherent to the protein coated surfaces. Rat exudate PM were equally adherent to tissue culture plastic or wells coated with either endothelial cell derived matrix or denatured collagen (gelatin)/fibronectin. PM adherent to a denatured collagen/fibronectin-coated wells demonstrated significantly less cytolytic activity (15 +/- 2% lysis) when compared with either tissue culture plastic adherent PM (43 +/- 7% lysis) or PM adherent to extracellular matrix (59 +/- 11% lysis). PM adherent to extracellular matrix released twofold more TxB2 than plastic adherent PM, while PM adherent to denatured collagen/fibronectin released 40% more PGE2 than cells adherent to tissue culture plastic or 80% more PGE2 than PM adherent to the extracellular matrix. PM adherent to denatured collagen/fibronectin release less superoxide anion (27 +/- .9 nmoles/10(6) PM) than PM adherent to either tissue culture plastic (43 +/- 1 nmoles/10(6) PM) or the extracellular matrix (60 +/- 0.5 nmoles/10(6) PM). Furthermore, incubation of plastic adherent PM with exogenous PGE2 reduced superoxide production in a dose-dependent manner. These results demonstrate that the inhibition of ADCC and secretion of reactive oxygen intermediates by PM adherent to a denatured collagen/fibronectin surface correlated with an increased release of the immunosuppressive prostanoid PGE2. Furthermore, the addition of exogenous PGE2 to plastic adherent PM reproduced the depression in ADCC and superoxide anion production observed by PM adherent to a denatured collagen/fibronectin surface. These studies suggest that the increased production and release of PGE2 by inflammatory macrophages adherent to a denatured collagen surface may act to suppress cytotoxic mechanisms and thereby constitutes part of an autocrine feedback mechanism regulating macrophage function during wound injury.
...
PMID:Surface contact modulation of inflammatory macrophage antibody dependent cytotoxicity and prostanoid release. 166 Aug 99

1 2 3 4 5 6 7 8 9 10 Next >>