1,130 research outputs found
REDUCED FIBRINOLYTIC-ACTIVITY IN GLOMERULI ISOLATED FROM RABBITS INFUSED WITH TUMOR-NECROSIS-FACTOR.
No full textPlatelet aggregation and stimulation of leucocyte procoagulant activity by rickettsial lipopolysaccharides in rabbits and in man.
No full text
Histamine H3 receptors mediate inhibition of noradrenaline release from intestinal sympathetic nerves
No full text1. The present study investigates whether presynaptic histamine receptors regulate noradrenaline release from intestinal sympathetic nerves. The experiments were performed on longitudinal muscle-myenteric plexus preparations of guinea-pig ileum, preincubated with [(3)H]-noradrenaline. 2. In the presence of rauwolscine, electrically-induced [(3)H]-noradrenaline release was inhibited by histamine or R-alpha-methylhistamine, whereas it was unaffected by pyridylethylamine, impromidine, pyrilamine, cimetidine, thioperamide or clobenpropit. The inhibitory effects of histamine or R-alpha-methylhistamine were antagonized by thioperamide or clobenpropit, but not by pyrilamine or cimetidine. In the absence of rauwolscine, none of these drugs modified the release of [(3)H]-noradrenaline. 3. The modulatory action of histamine was attenuated by pertussis toxin and abolished by N-ethylmaleimide. Tetraethylammonium or 4-aminopyridine enhanced the evoked tritium outflow and counteracted the inhibitory effect of histamine. However, the blocking effects of tetraethylammonium and 4-aminopyridine were no longer evident when their enhancing actions were compensated by reduction of Ca(2+) concentration in the superfusion medium. 4. Histamine-induced inhibition of tritium output was enhanced by omega-conotoxin or low Ca(2+) concentration, whereas it was not modified by nifedipine, forskolin, rolipram, phorbol myristate acetate, H7 or lavendustin A. 5. The present results indicate that presynaptic H(3) receptors, located on sympathetic nerve endings, mediate an inhibitory control on intestinal noradrenergic neurotransmission. It is suggested that these receptors are coupled to G(i)/G(o) proteins which modulate the activity of N-type Ca(2+) channels through a direct link, thus reducing the availability of extracellular Ca(2+) at the level of noradrenergic nerve terminals
Low molecular weight heparins prevent thrombin-induced thromboembolism in mice despite low anti-thrombin activity. Evidence that the inhibition of feed-back activation of thrombin generation confers safety advantages over direct thrombin inhibition
No full textActivated human protein C prevents thrombin-induced thromboembolism in mice. Evidence that activated protein C reduces intravascular fibrin accumulation through the inhibition of additional thrombin generation
No full text1077 AMP-Activated Protein Kinase as a Novel Target for the Pharmacological Treatment of Inflammatory Bowel Diseases
No full textAMP-Activated Protein Kinase as a Novel Target for the Pharmacological
Treatment of Inflammatory Bowel Diseases
Luca Antonioli, Matteo Fornai, Rocchina Colucci, Narcisa Ghisu, Marco Tuccori, Oriana
Awwad, Gianfranco Natale, Federica Fulceri, Ilaria Rugani, Emiliano Duranti, Agostino
Virdis, Corrado Blandizzi, Mario Del Tacca
Introduction. Acadesine (ACA), an activator of AMP-activated protein kinase (AMPK), has
been shown to act in a site- and event-specific manner against inflammation, through local
increments of endogenous adenosine levels. However, the effects of ACA on intestinal
inflammation have not been investigated. This study examined the effects of ACA in an
experimental model of colitis and evaluated the underlying anti-inflammatory mechanisms.
Methods. The effects of ACA and dexamethasone (DEX, used as a standard comparator) 2,4-dinitrobenzenesulfonic acid (DNBS, 15 mg/rat), to assess systemic [body and spleen
weight] and tissue inflammatory parameters [macroscopic and microscopic damage, tumour
necrosis factor-α (TNF-α), interleukin-10 (IL-10), superoxide anion production (dihydroethidium
fluorescence) and malondialdehyde (MDA) levels]. Animals received ACA (1, 3,
10 or 30 mg/kg/day), DEX (0.1 mg/kg/day) or vehicle intraperitoneally for 6 days, starting
1 day before DNBS administration. Results. Colitis was associated with a decreased body
weight (-10±5 g vs vehicle; P<0.05) and increased spleen weight (+22±3% vs vehicle;
P<0.05). Microscopic damage score, tissue TNF-α and oxidative stress were also enhanced,
while tissue IL-10 levels were markedly reduced. Treatment with ACA, but not DEX,
improved body weight. Both drugs counteracted the increase in spleen weight and ameliorated
the histological damage (DNBS: 4.8±0.9; ACA 10 mg/kg/day: 3.1±0.7; DEX: 2±0.4; P<0.05
vs DNBS; ANOVA). A reduction of TNF-α and increase in IL-10 tissue levels were also
recorded in rats treated with test drugs. Moreover, ACA or DEX ameliorated colonic oxidative
damage. Data regarding the effects of ACA and DEX on inflammatory parameters are summarized
in table (*P<0.05 vs vehicle; aP<0.05 vs DNBS). Conclusions. The AMPK activator
ACA exerts beneficial effects on bowel inflammation, acting through a rearrangement of
pro-inflammatory/anti-inflammatory cytokine balance and a reduction of oxidative stress.
These findings suggest that the pharmacological modulation of AMPK function could represent
a promising strategy to develop novel classes of drugs effective against intestinal inflammation
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