Cathedrals, Monasteries, and Churches

Robinson, David M.; Spurgeon, Jack; Thomas, H Lucy; McLees, David; Knight, Jeremy

doi:10.1080/00665983.1993.11785943

Cited by 1 publication

(2 citation statements)

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“…Patel, V. et al (1996 This meeting. In previous studies we have shown that in both vascular and airways smooth muscle cell types, PDGF stimulates a sustained activation of MAP kinase and this may be obligatory for the initiation of DNA synthesis by PDGF (Malarkey et al, 1995;Malarkey et al, 1996). To test this hypothesis we have utilised the 17-mer antisense phosphorothioate modified deoxyoligonucleotides (ODN) directed against both the 42 and 44 kDa forms of MAP kinase (Sale et al, 1995) and determined the effect upon MAP kinase expression and function in vascular smooth muscle cells.…”

Section: Dissociation Of [35s]mentioning

confidence: 97%

“…A major cell signalling pathway stimulated by both growth factors and G-protein receptor coupled agonists involves the activation of the mitogen-activated protein (MAP) kinases (Malarkey et al, 1995). This enzyme family is believed to play a crucial role in the initiation of DNA synthesis in smooth muscle cells (Robinson et al, 1996). Recently, PD098059 an inhibitor of the activation of the immediate upstream activator of MAP kinase, MAP kinase kinase (MEK) has been developed (Dudley et al, 1995;Alessi et al, 1995).…”

Section: Dissociation Of [35s]mentioning

confidence: 99%

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1996

British J Pharmacology

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The cell wall components of Staphylococcus aureus, lipoteichoic acid (LTA) and peptidoglycan (PepG), synergise to induce nitric oxide synthase (iNOS) and to cause multiple organ dysfunction syndrome (MODS) and circulatory failure in the rat (De Kimpe et al, 1995). Pretreatment of rats with aminoguanidine (AMG) prevents circulatory failure, MODS (except renal failure) and the expression of iNOS protein caused by LTA+PepG (Kengatharan et al, 1996). Here, we investigate whether prevention of iNOS expression (with dexamethasone) or inhibition of iNOS activity (with AMG) protects against MODS and circulatory failure elicited by LTA+PepG. Male Wistar rats (250-350g) were anaesthetised with thiopentobarbitone sodium (120mgkg-', i.p.). The trachea was cannulated to facilitate respiration, the carotid artery for measuring mean arterial blood pressure (MAP), heart rate and arterial oxygen tension (PaO2), and the jugular vein for administration of compounds. Dexamethasone (DEX, 3mgkg-', i.p.) was given 120 min before injection of LTA (3mgkg-', bolus) plus PepG (lOmgkg-', injected over 3045 min), whereas the iNOS-selective inhibitor AMG (5mgkg' i.v. bolus plus 1Omgkg-'h-' infusion) was given 120min after PepG+LTA. The pressor response to noradrenaline (NA, lIggkg-') was assessed prior to and every 60 min after the injection of LTA+PepG. At 90 min, plasma levels of TNFa were measured using an ELISA kit and, at 360 min, plasma samples were taken for the determination of biochemical markers of organ injury and nitrite+nitrate (total plasma nitrite). At 360 min, the rats were killed and various tissues were removed to determine iNOS activity in homogenates via the conversion of [3H]L-arginine to [3H]Lcitrulline, and for Western blot analysis. Treatment with DEX or AMG attenuated (i) the hypotension and the vascular hyporeactivity to NA, (ii) the fall in PaO2, (iii) the increase in plasma levels of alanine aminotransferase (ALT), (iv) the increase in iNOS activity, and (v) the rise in total plasma nitrite induced by LTA+PepG (Table 1). The expression of iNOS protein and the increases in urea or creatinine were attenuated by DEX, but not by AMG. Furthermore, DEX reduced the increase in TNFa levels induced by. PepG+LTA (TNFa, 39t4 ngml-for PepG+LTA vs 10t2 ngml-' with DEX treatment, n=6-8, p<0.05). Thus, enhanced formation of NO due to expression of iNOS contributes importantly to circulatory failure, respiratory failure and liver injury caused by LTA+PepG in anaesthetised rats.

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Section: Dissociation Of [35s]mentioning

confidence: 97%