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Query: UMLS:C0009443 (cold)
 92,137 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Addition of the 3-series fatty acid precursor (icosapentaenoic acid, IPA), its endoperoxide [prostaglandin (PG)H(3)], or thromboxane A(3) to human platelet-rich plasma (PRP) does not result in aggregation of the platelets. In fact, preincubation of human PRP with exogenous PGH(3) actually inhibited aggregation by increasing platelet cyclic AMP concentrations. PGH(3) undergoes rapid spontaneous degradation to PGD(3) in human PRP. The PGD(3) so formed is adequate to account for the increase of platelet cAMP and inhibition of aggregation. Furthermore, addition of PGD-specific antisera to human PRP blocked the platelet inhibitory activity of exogenous PGH(3). PGD(3) has considerable potential as a circulating antithrombotic agent. Pretreatment of human PRP with the adenylate cyclase inhibitor 2',5'-dideoxyadenosine blocked the increase of platelet cyclic AMP and the inhibition of aggregation normally produced by PGI(2), PGE(1), PGD(2), PGH(3), and PGD(3). Furthermore, the dideoxyadenosine unmasked a direct but moderate reversible aggregatory effect in response to the subsequent addition of PGH(3). Similarly, the dideoxyadenosine markedly enhanced the aggregation produced by exogenous PGH(2). IPA is readily incorporated into tissue lipids but proved to be a poor substrate for kidney, blood vessel, or heart cyclooxygenase. IPA was previously shown to be a poor substrate for platelet cyclooxygenase. IPA is readily deacylated from the renal phospholipid pool in response to bradykinin, a substance that also stimulates the release of arachidonic acid. A diet that relies primarily on cold-water fish, as in the case of the Greenland Eskimos, lowers endogenous arachidonic acid and markedly increases the IPA content of tissue lipids. Thus, because IPA has the potential to act as an antagonist with arachidonic acid for platelet cyclooxygenase and lipoxygenase, the simultaneous release of IPA could suppress any residual arachidonic acid conversion to its aggregatory metabolites.
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PMID:Triene prostaglandins: prostaglandin D3 and icosapentaenoic acid as potential antithrombotic substances. 23 Apr 92

Thrombin, a peptide with native protease activity, caused a rapid (less than 1 min) increase in glycogenolysis of about 30%, assessed from rates of production of glucose+lactate+pyruvate, and in oxygen uptake in perfused rat liver. These increases were followed by a rapid return to basal values within 5 min. The effect of thrombin on glycogenolysis was dose-dependent and was maximal at perfusate concentrations around 1 U/ml. Interestingly, the effect of thrombin on glycogenolysis could be elicited only once in any given liver. The activation of glycogenolysis by thrombin was diminished nearly 50% by prior infusion of the protease inhibitor, diisopropyl fluorophosphate (10 microM), and over 90% when thrombin was treated with diisopropyl fluorophosphate prior to infusion. The stimulation of glycogenolysis by thrombin could be detected in isolated hepatocytes or in livers stored for 24 h in cold Euro-Collins solution, a treatment which destroys endothelial cells. Further, thrombin stimulated production of prostaglandin D2 from arachidonic acid in cultured hepatic endothelial but not Kupffer cells. The effect of thrombin on carbohydrate output was also blocked by a phospholipase A2 inhibitor (quinacrine, 50 microM) and by an inhibitor of the cyclooxygenase (indomethacin, 20 microM), suggesting the involvement of cyclooxygenase in the mechanism of action of thrombin. In support of this idea, the transient kinetics of stimulation of glycogenolysis by thrombin and arachidonic acid was nearly identical to release of thromboxane B2 (80-420 pg/ml) and prostaglandin D2 (300-900 pg/ml) from the perfused liver. Further, a second addition of thrombin failed to increase thromboxane and prostaglandin D2 release as well as carbohydrate production, supporting a causal link between these phenomena. Taken together, these data support the hypothesis that thrombin interacts with receptors in the liver, possibly on endothelial cells, leading to activation of phospholipase A2 and subsequent transient production of prostaglandins and thromboxanes. These mediators subsequently interact with receptors on parenchymal cells, leading to a transient stimulation of glycogenolysis.
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PMID:Transient activation of hepatic glycogenolysis by thrombin in perfused rat livers. 139 79

We recently reported that human recombinant interleukin-6 (hrIL-6) microinjected into the preoptic area (POA) of guinea pigs induced fever at high doses, suggesting that IL-6 may be another endogenous pyrogen. This study was undertaken to determine whether hrIL-6 affects the single-unit activity of thermosensitive and thermally insensitive neurons in hypothalamic tissue slices and whether indomethacin (Indo) or naloxone (Nal), a cyclooxygenase inhibitor and a mu-opioid receptor antagonist, respectively, influences the effects of hrIL-6 on those neurons. hrIL-6 (2 x 10(3)-8 x 10(3) U/ml) depressed the activity in 50 (83%) of 60 warm-sensitive (W) neurons and excited all 4 cold-sensitive (C) neurons found. It had no effect, however, on 14 (48%) of 29 thermally insensitive (I) neurons, albeit 7 and 8 I neurons decreased and increased their firing rates, respectively. Indo (0.05-1 mg/ml) blocked the effect of hrIL-6 on 22 of 24 W neurons and 2 C neurons tested. Nal(0.1-1 mg/ml) blocked or reduced the effect of hrIL-6 on 21 of 25 W neurons and 1 C neuron recorded. These drugs induced no neuronal response per se. Nal at 2-5 mg/ml, which increased the activity of four W neurons by itself, reversed their depressed response to hrIL-6. These results support the possibility that IL-6-induced fevers may be mediated through an effect on thermosensitive neurons in the POA and that opioids and prostaglandin E may both be involved in this process.
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PMID:Hypothalamic neuronal responses to interleukin-6 in tissue slices: effects of indomethacin and naloxone. 150 50

The body wall of the pulmonate land slug Ariolimax columbianus secretes mucus packaged in granules bounded by two closely adjacent membranes. Newly secreted granules rupture in the presence of ATP (approximately 1 microM). This response is apparently mediated by an ATP receptor and is lost by granules held in osmotically balanced saline solutions with relatively low [K+] or [Cl-], but is retained for long periods in solutions with high [K+] and [Cl-]. Rupture by ATP is blocked by indomethacin, furosemide, nigericin, or verapamil, implicating in the ATP-rupturing process a cyclooxygenase product of arachidonic acid as well as activation of K(+)-Cl- transport and efflux of Ca2+ through activated channels according to a proposed electrical potential (proton) gradient. Mechanical stress, exposure to cold (e.g., 1 h at 0 degree C), and pertussis toxin also cause rupture that is blocked by the pharmacological agents that block ATP action. The results suggest that a single basic mechanism causes rupture of the granules, releasing mucins that form the mucous layer protecting the body wall.
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PMID:Triggering by ATP of product release by mucous granules of the land slug Ariolimax columbianus. 155 Feb 14

Previous studies have demonstrated a marked release of prostanoids from hepatic tissue after liver grafting. In addition, eicosanoid synthesis was shown to be regulated at the level of key enzymes. The present study addressed changes of the local availability of these enzymes during and after porcine orthotopic liver transplantation. We determined kinetic parameters of cyclooxygenase (CO), the initial enzyme of prostaglandin synthesis, of prostacyclin and thromboxane synthase (PCS, TXS), two more peripheral enzymes, in microsomal preparations of hepatic and gluteal muscle biopsies, and the activity of 5-lipoxygenase (5-LO), the key enzyme of leukotriene synthesis. Maximal velocity (Vmax) of CO and PCS showed a 4-fold increase both in liver and gluteal muscle tissue 1 hr after reperfusion of the grafted liver and a more than 20-fold increase after 24 hr (P less than 0.001), whereas apparent affinities (Km) remained unchanged. In contrast, Vmax of TXS and the activity of 5-LO disclosed a striking increase only within the hepatic graft (P less than 0.001). No changes of enzymatic activity could be observed during donor operation, cold storage, and 5 min after reperfusion. Results were independent of the duration of preservation (3 hr and 20 hr with Euro-Collins) and the addition of Iloprost, a prostacyclin-analogue. These results suggest that after liver grafting, abnormalities at the level of local enzyme expression in hepatic and extrahepatic tissues might contribute to preservation damage and systemic injury of the host.
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PMID:Rapid increase in the activity of enzymes of eicosanoid synthesis in hepatic and extrahepatic tissues after experimental liver transplantation. 190 22

Leukotrienes accumulate in brain tissue after cerebral ischemia and in brain tumors. Thus, their release might contribute to the blood-brain barrier damage observed under these conditions and, hence, brain edema. The effect of these substances on the permeability of pial vessels and whether inhibition of LT synthesis reduces cold injury brain edema were studied. The pial vasculature of cats was studied by fluorescence microscopy. The cortex was superfused with LTC4, LTD4, or LTE4 via a cranial window. Na(+)-fluorescein was intravenously administered as blood-brain barrier indicator. LT concentrations up to 2 microM did not induce any leakage of the blood-brain barrier indicator into the parenchyma. However, all LTs tested constricted pial arteries and veins. Brain edema formation was studied in rabbits with cold injury. BW755C, an inhibitor of cyclooxygenase and lipoxygenase preventing formation of LTs, was given before and after trauma. Control animals received saline only. BW755C was ineffective in attenuating cold injury edema. Hemispheric swelling in control animals was 7.8 +/- 1.1%, and 7.7 +/- 0.4% in animals with treatment. LTs, even when administered to the brain in concentrations exceeding levels occurring under pathological conditions, did not induce barrier damage, nor did inhibition of LT synthesis attenuate formation of vasogenic edema. The results provide further evidence against LTs as mediator compounds of this process.
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PMID:Role of leukotrienes as mediator compounds in brain edema. 211 15

Transcranial cold injury in rats and guinea pigs induced cerebral extravasation of albumin labeled with Evans blue dye or 125I, respective indicators of the area and amount of blood-brain barrier (BBB) disruption. Radioimmunoassay of brain extracts showed that cold injury induced leukotriene (LT)C4 in rat and guinea pig brains 15 min after injury. In guinea pigs, the LT synthesis inhibitor phenidone (30 mg/kg, i.p.) completely blocked cold-induced LTC4 in brain. Phenidone (30 and 100 mg/kg) also inhibited cerebral tissue accumulation of 125I-albumin and dye in rats and guinea pigs. Phenidone is reported to show antioxidant properties and selective lipoxygenase inhibition of arachidonic acid metabolism compared to cyclooxygenase inhibitors, meclofenamate sodium, and other nonsteroidal anti-inflammatory agents. Since several oxygen and hydroxyl radical scavengers and the cyclooxygenase inhibitor, meclofenamate sodium, did not inhibit protein extravasation, the findings support a role for LT as a mediator of cold-induced changes in BBB permeability in rats and guinea pigs and suggest that the inhibitory effects of phenidone on BBB permeability may be due to inhibition of LT production.
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PMID:Cold injury, blood-brain barrier changes, and leukotriene synthesis: inhibition by phenidone. 212 46

The abstract BW755C is a novel non-steroidal anti-inflammatory agent. It inhibits synthesis of prostaglandins and leukotrienes by inhibition in the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism. Cold injury induced vasogenic oedema was produced in 18 cats. The animals were sacrificed at six and twenty-four hours. One group was treated with BW755C. Seventeen white rabbits bearing an experimental brain tumour VX-2 carcinoma were treated for five consecutive days from the eight day after tumour injection to the thirteenth day. Untreated tumour bearing rabbits were used as control. Brain water content was measured by specific gravity method. BW755C did not reduce the water content following cold injury. There was no effect upon peritumoural oedema. The use of this novel blocking agent with diffuse effects in the arachidonic cascade was not beneficial for the reduction or prevention of brain oedema.
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PMID:Effects of the arachidonate lipoxygenase inhibitor BW755C on traumatic and peritumoural brain oedema. 212 85

Arachidonic acid (AA) metabolism is implicated as an intracellular and/or intercellular second messenger system for the transmission of cytokine-initiated signals that affect neutrophils and mediate systemic toxicity. The purpose of the present study is to ascertain if cytokines that are known to affect neutrophil function in vivo and in vitro directly stimulate neutrophil AA metabolism in vitro. The recombinant human cytokines multi-colony stimulating factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 1, tumor necrosis factor (TNF), and interleukin 6 and the calcium ionophore A23187 were incubated with purified 14C-AA radiolabeled human peripheral blood neutrophils and the effects were assayed by one- and two-dimensional thin layer lipid chromatography. None of the cytokines appeared to induce the release of cell-incorporated AA or to increase the level of radiolabeled phosphatidic acid. TNF induces severe systemic toxicity that is inhibited by cyclooxygenase inhibitors, which suggests a role for AA metabolites in the pathophysiologic effects of TNF; we have confirmed that TNF and endotoxin act synergistically to induce indomethacin-inhibitable fatal shock in rats. However, when in 3H-AA radiolabeled human neutrophils were incubated with TNF in kinetic, cold-chase, and TNF preincubation experiments, TNF was not found to increase AA metabolism, although changes in the intracellular neutral lipid content were noted. GM-CSF, which has been reported by previous investigators to directly induce the release of AA, did not release neutrophil-associated 3H-AA. In conclusion, the direct release of AA from membrane-associated phospholipids does not appear to be a major second messenger pathway for cytokine-initiated activation of neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokine- and calcium ionophore A23187-mediated arachidonic acid metabolism in neutrophils. 212 4

Selective dopamine (DA) DA1 and DA2 receptor agonists and antagonists were examined for their effects on cold-stress gastric lesions, 100% ethanol gastric lesions and basal gastric acid secretion. The selective DA1 agonist SKF 38393 [R-(+)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol.HCl] attenuated cold-stress and ethanol lesions and blocked basal acid output. The protective effects of SKF 38393 were reversed by the cyclooxygenase inhibitors indomethacin, sodium meclofenamate, by the peripherally selective DA receptor antagonist domperidone and by the tissue sulfhydryl blocker, N-ethylmaleimide. The DA1 antagonist, SCH 23390, worsened lesion formation and augmented gastric acid secretion. N-0437 [S-(-)-2-N-propyl-N-2-thienylethylamino)-5-hydroxytetralin], a DA2 agonist, was less potent than SKF 38393 at reducing experimental gastric lesion formation, but slightly more potent at attenuating gastric secretion. The DA2 antagonist, eticlopride, was inactive in all models. Based upon these in vivo data, we suggest that: 1) the gut DA receptor may be of the DA1 subtype and 2) that activation of gut DA1 receptors produces gastroprotection by several mechanisms, at least one of which is by reducing gastric acid output.
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PMID:Activity of selective dopamine DA1 and DA2 agonists and antagonists on experimental gastric lesions and gastric acid secretion. 253 Mar 41


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