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)

We have tested the hypothesis that the cortex may play a role in the development of fever. Male Sprague-Dawley rats equipped with AM transmitters for telemetric measurement of body temperature were given intracerebroventricular prostaglandin E1 (PGE1), corticotropin-releasing hormone (CRH), or intravenous E. coli endotoxin. Application of cotton pellets soaked with 3.3 M KCl to the frontal cortex (to induce spreading depression) significantly reduced fevers to PGE1 and endotoxin when compared with fever magnitude with 0.9% NaCl application to the cortex. Neither CRH-induced hyperthermia nor normal body temperatures were altered by the spreading depression. Our results reveal a novel action of spreading depression on thermoregulatory function and indicate cortical involvement in the development of fever.
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PMID:Cortical spreading depression blocks prostaglandin E1 and endotoxin fever in rats. 844 3

Exposure to hypoxia (10% O2 for 5 to 7 days) results in increased survival and decreased pulmonary toxicity of adult rats subsequently exposed to hyperoxia (> 97% O2). These experiments tested whether hypoxia preexposure minimized the decrease in lung metabolism of prostaglandin E1 (PGE1), a vasoactive and antiinflammatory prostaglandin, caused by hyperoxia. Transpulmonary PGE1 clearance was measured as fractional metabolism of PGE1 (2 microM to 30 microM) infused during a 45-second period in an isolated, buffer-perfused rat lung preparation after exposure of rats to one of the following conditions: (1) hyperoxia (> 97% O2 for 48 hours), (2) hypoxia (10% O2 for 120 hours), or (3) hypoxia followed by hyperoxia. Hyperoxia exposure decreased both lung PGE1 metabolism and lung prostaglandin dehydrogenase activity (PGDH). Hypoxia also decreased lung PGE1 metabolism but, in contrast, increased lung PGDH activity. Hypoxia preexposure did not prevent the depression of PGE1 metabolism or PGDH activity caused by hyperoxia, which indicates that survival in hyperoxia did not depend on lung PGE1 metabolism. Hypoxia itself impaired transpulmonary metabolism of PGE1 despite increasing PGDH activity, which suggests possible interference with substrate delivery.
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PMID:Effects of hypoxia and hyperoxia on lung prostaglandin E1 metabolism. 907 31

We investigated the effects of low-dose prostaglandin E1 (PGE1) on intra- and post-operative renal function in 109 adult patients undergoing upper abdominal surgery. Anesthesia was maintained with a combination of thoracic epidural combined with inhalational anesthesia. Sixty-seven patients received PGE1 at a rate of 0.2 microgram.kg-1.min-1 throughout surgery. Forty-two patients, who did not receive PGE1, served as control. Pre- and post-operative renal function was evaluated with serum levels of BUN and creatinine (Cr), while intra-operative renal function was evaluated mainly with urine output and urine flow rate during anesthesia. Urinary Na excretion and creatinine clearance (Ccr) were determined during surgery in limited cases. Urine output and urine flow rate during anesthesia were greater in PGE1 group than in control group, whereas infusion volumes and infusion rates were not different between the groups. In PGE1 group, urine flow rate was greater during surgery than before surgery, while in control group, it was unchanged. Na excretion during anesthesia was also greater in PGE1 group than in control group. In control group, Na excretion and Ccr were smaller during surgery than before surgery, while in PGE1 group, they were unchanged. Postoperative serum BUN and creatinine levels were not different between the groups. Decreased Na excretion and decreased Ccr in control group indicated that renal function was depressed during surgery, whereas unchanged Ccr, unchanged Na excretion and increased urine flow rate in PGE1 group indicated that renal function was well-maintained during surgery with PGE1. Low-dose PGE1 thus prevented depression of renal function during surgical anesthesia.
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PMID:[The effect of low-dose prostaglandin E1 on intra- and post-operative renal function]. 912 16

1. Membrane potential (Vm) and resistance (Rm) of ventral respiratory group (VRG) neurons were measured in the isolated brainstem-spinal cord from newborn rats during bath application of the opioid receptor agonists fentanyl or [D-Ala2, D-Leu5]-enkephalin (Ala-Leu-Enk) and of the prostaglandin E1 (PGE1). 2. PGE1 (0.1-3 microM) and fentanyl or Ala-Leu-Enk (1-50 microM) produced depression and, at higher doses, block of inspiratory nerve activity and respiration-related postsynaptic potentials. This apnoea was associated with hyperpolarization and Rm fall in 25% of thirty-two VRG neurons tested, whereas resting Vm and Rm were not changed in the other cells. 3. The selective mu- and delta-receptor blockers naloxonazine (10-20 microM) and naltrindole (50-100 microM) antagonized the effects of 5 microM fentanyl and 50 microM Ala-Leu-Enk, respectively. 4. Opioid- and PGE1-evoked respiratory depression was reversed upon elevation of endogenous cAMP levels by stimulating adenylyl cyclase with 100 microM forskolin, activating dopamine D1 receptors with 50-100 microM 6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2, 3,4,5-tetrahydro-1H-3-benzazepine (6-chloro-APB) or preventing cAMP breakdown with 50-100 microM isobutylmethylxanthine. 5. The results indicate that opioid- or prostaglandin-induced respiratory depression is due to a fall in cAMP levels in cells responsible for generation of rhythm or providing a tonic drive to the respiratory network. 6. We suggest that elevation of cAMP levels is an effective antidote in neonates against such forms of respiratory depression.
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PMID:cAMP-dependent reversal of opioid- and prostaglandin-mediated depression of the isolated respiratory network in newborn rats. 935 Jun 24

In view of the large number of cancer patients treated with FANS and/or corticosteroids for long periods of time. Authors discuss how the use of antisecretory drugs for gastroprotection has become common practice in spite of the lack of clear scientific evidence. The paper analyses the principal mechanisms of gastrotoxicity of FANS, essentially associated with the inhibition of prostaglandins and consequent reduction of the secretion of mucous and bicarbonate. It also discusses the numerous controlled trials evaluating the efficacy of ranitidine for gastroprotection versus placebo and versus the analogous synthetic substance, misoprostole, derived from prostaglandin E1. This analysis shows that misoprostole provides significant protection against both gastric and duodenal ulcers, whilst the antisecretory drug protects only against localised duodenal ulcer. The conclusion is that optimum protection against FANS is provided by misoprostole. In any case more than 30% of patients are destined to develop ulcerous or minor lesions for which treatment with antisecretory drugs is correct. After analysis of the available literature on the gastrotoxicity of corticosteroids, it is clear that this risk is real only for a small sub-population of patients (treated in dual therapy with FANS, for long periods, with high doses or in presence of ulcer anamnesis). It is not known in these cases whether prophylactic treatment is suitable, nor which would be the best prophylactic treatment. In other cases the problem does not arise since the number of patients developing ulcers is similar with corticosteroids treatment or with placebo. Some further interesting features of ranitidine compared to cimetidine (its better pharmacological profile due to the lack of side effects, lack of medullary depression, lack of interference with the immunological system, lack of antiandrogen effects) are also discussed. Particularly interesting is the lack of interference with cyclophosphamide metabolism, such interference having shown for cimetidine. Studies involving ranitidine treatment in association with interleukin-2 for renal carcinoma and metastatic melanoma are also of interest although no statistically significant results are available as yet.
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PMID:[Gastroprotection in cancer patients: rational approach, pharmacologic role of antisecretory agents and eventual ulterior prospectives in oncology]. 961 79

The change in blood flow after anastomosis and the effects on the anastomosed artery of different classes of vasodilators such as lidocaine and chlorpromazine given topically (n = 10 in each group), and prostaglandin E1 (PGE1)(n = 12) and diltiazem hydrochloride (n = 10) given systemically, were investigated in the femoral arteries of rats. The blood flow after anastomosis decreased by 45%-60% compared with that before the anastomosis. Lidocaine showed almost the same pattern of blood flow as chlorpromazine. The former dilated the diameter of the vessel less than the latter, and the depression of the heart rate was less with lidocaine than in chlorpromazine. PGE1 had a longer and stronger vasodilatative action than diltiazem, and resulted in a remarkable increase in blood flow. Clinically, the topical application of chlorpromazine or lidocaine is recommended during an operation, and PGE1 should be given systemically after an operation to obtain adequate blood flow.
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PMID:The blood flow patterns of microsurgical procedures in rats with topical and systemic vasodilators. 978 27

We hypothesized that depression of liver function by norepinephrine can be improved by prostaglandin E1. Isolated perfused rat liver was selected as an experimental model, since the flow rate can be regulated in it. Twenty-one rats were randomly allocated to three groups: control, norepinephrine, and norepinephrine and prostaglandin E1 groups. The liver was perfused in a recirculating system at a constant flow rate of 20 ml/min. After administration of two milligrams of lidocaine in each group, lidocaine and monoethylglycinexylidide concentrations in the recirculating system were measured. Lidocaine pharmacokinetics were analyzed using the SAAM II program, including metabolic rate from lidocaine to monoethylglycinexylidide using time-concentration curves. Norepinephrine significantly increased perfusion pressure and the area under the time-concentration curve for lidocaine. Norepinephrine decreased the clearance and the elimination rate constant of lidocaine compared with those in the control group. Although administration of prostaglandin E1 after infusion of norepinephrine did not significantly change perfusion pressure, it significantly (p < 0.05) improved metabolic rate, clearance and the elimination rate constant of lidocaine in the isolated rat liver model.
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PMID:The effects of norepinephrine and prostaglandin E1 on pharmacokinetics of lidocaine in isolated perfused rat liver. 1132 17

Pulmonary artery hypoplasia, either congenital or acquired, is a rare abnormality seen in adults. We reported the first case of adult, isolated, left pulmonary artery hypoplasia, with exertional angina and prominent ST depression in exercise stress test, that seemed to be caused by exertional hypoxemia. Several vasodilators, including nitroglycerin, prostaglandin E1, and nifedipine, were administered individually, each with subsequent hemodynamic monitoring, pulse oximetric monitoring, and exercise test. Vasodilator administrations reduced pulmonary vascular resistance (baseline, 599; vasodilators, 306, 211, and 284 dyne x sec x m2/cm5, respectively) and attenuated ST depression (by 52, 72, and 27%, respectively) but without an immediate benefit on exercise tolerance. All vasodilators except nifedipine ameliorated exertional hypoxemia (expressed by arterial oxygen saturation during peak exercise, baseline, 69%; vasodilators, 85, 78, and 65%, respectively). Additional oxygen supply after nitroglycerin administration further benefited exertional hypoxemia (arterial oxygen saturation, 96%) and exercise ST depression (attenuated by 82%).
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PMID:Adult isolated hypoplasia of left pulmonary artery with exertional angina and abnormal exercise stress test: a case report and treatment implication. 1152 25

In the present study, we examined the effect of prostaglandin (PG) E2 on interleukin (IL) -12 production in monocytes stimulated with a combination of lipopolysaccharide (LPS) from Actinobacillus actinomycetemcomitans and interferon-gamma (A. actinomycetemcomitans-LPS/IFN-gamma). Indomethacin, a cyclooxygenase inhibitor, enhanced IL-12 production, but inhibited PGE2 generation in A. actinomycetemcomitans-LPS/IFN-gamma-stimulated monocytes. Exogenous PGE2 inhibited IL-12 release in the cells. EP2, EP3 and EP4 receptor mRNA expression was detected in monocytes by reverse transcription-polymerase chain reaction. 11-deoxy-PGE1 (an EP2/EP4 agonist) inhibited IL-12 production in A. actinomycetemcomitans-LPS/IFN-gamma-challenged monocytes, whereas butaprost (an EP2 agonist) or ONO-AP-324 (an EP3 agonist) had no effect on IL-12 production. Dibutyryl cAMP, a cAMP analogue, and forskolin, an adenylate cyclase activator, mimicked depression of IL-12 production by PGE2. From these results, we suggest that PGE2 inhibits IL-12 production via EP4 receptors by cAMP-dependent pathways in A. actinomycetemcomitans-LPS/IFN-gamma-challenged monocytes.
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PMID:Prostaglandin E2 downregulates interleukin-12 production through EP4 receptors in human monocytes stimulated with lipopolysaccharide from Actinobacillus actinomycetemcomitans and interferon-gamma. 1275 65

Prostanoids can suppress vascular smooth muscle cell (VSMC) proliferation, but the mechanism through which this is mediated has not been identified. In this study, we show rat aortic VSMCs to express the EP1, EP2, EP3, EP4, and IP receptors. The EP4 receptor-specific agonist, 11-deoxy-PGE1, induced a time-dependent phosphorylation of protein kinase C and extracellular signal-regulated kinase (ERK) 1/2 in serum-depleted (0.1%) VSMCs, whereas the EP2 receptor agonist, butaprost, was without effect. PGI2 or iloprost at the IP receptor inhibited basal ERK phosphorylation with IC50 values of 10 nmol/L. Iloprost also attenuated the sustained activation of ERK induced by endothelin-1 or basic fibroblast growth factor (bFGF). Endothelin-1 or bFGF significantly increased the number of VSMCs counted 24 hours later compared with basal, and both responses were blocked by the MEK inhibitor, U0126, or iloprost. Under basal conditions, U0126 or iloprost reduced the number of viable cells and increased caspase-3 activity, which could be reversed by coapplication with endothelin-1, bFGF, or the adenylate cyclase inhibitor, SQ22536. Endothelin-1, bFGF, or SQ22536 prevented the depression to below basal levels of ERK phosphorylation induced by iloprost. Forskolin activated caspase-3 and attenuated basal ERK phosphorylation, which were prevented by SQ22536, endothelin-1, or bFGF. These data suggest that iloprost induces apoptosis via a cAMP-mediated suppression of ERK activity. In turn, this apoptotic response can be blocked by a mitogenic stimulus that re-establishes ERK activity back to basal levels, but at the expense of any concomitant proliferative activity. However, ERK stimulation by a selective EP4 receptor agonist, suggests that prostanoids may have diverse and complex roles in VSMC physiology.
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PMID:Prostacyclin induces apoptosis of vascular smooth muscle cells by a cAMP-mediated inhibition of extracellular signal-regulated kinase activity and can counteract the mitogenic activity of endothelin-1 or basic fibroblast growth factor. 1496 6


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