Nonalcoholic Fatty Liver (NAFL): Overview

Caldwell, Stephen H.; Al‐Osaimi, Abdullah; Chang, Charissa; Davis, Christine A.; Hespenheide, Elizabeth E; Krugner‐Higby, Lisa; Hylton, Anita Impaglizzo; Iezzoni, Julia C.; Le, Tri H.; Nakamoto, Robert K.; Redick, Jan A.; Peterson, Theresa C.

doi:10.1007/4-431-27172-4_1

Cited by 3 publications

(2 citation statements)

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“…Parenteral administration of therapeutic doses of quinidine and quinine caused forearm vasodilatation and decreased mean arterial blood pressure Bateman & Dyson, 1986;Nappi & Mason, 1990;Mariano et al, 1992). It has been known for over 60 years that quinine and quinidine can attenuate vasoconstrictor responses to sympathetic nerve stimulation and regional noradrenaline (NA) infusion, effects consistent with their postjunctional a-adrenoceptor antagonistic properties (Nelson, 1928;Hiatt, 1950;Schmid et al, 1974;Mecca et al, 1980;Caldwell et al, 1983). In rat cardiac membranes, human platelets and rat kidney, quinidine is a competitive antagonist at oel-and a2-receptors, but it is substantially more potent in antagonizing aj-than X2-adrenoceptors (Motulsky et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

Stereoselective effects of the enantiomers, quinidine and quinine, on depolarization‐ and agonist‐mediated responses in rat isolated aorta

Pozo

Pérez‐Vizcaíno

Villamor

et al. 1996

British J Pharmacology

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1. The effects of the two enantiomers, quinidine and quinine, were studied on depolarization- and agonist-induced isometric contractions in rat isolated thoracic aortic rings. 2. Quinidine or quinine (10(-6)M-3 x 10(-4)M) produced a concentration-dependent relaxation of 80 mM KCl-contracted rings, the pD2 values being 4.89 and 4.23, respectively. Thus, quinidine was about 4-5 times more potent than quinine. 3. The voltage-dependence of quinidine- and quinine-induced inhibition was studied in rings that had been incubated in 5 or 40 mM KCl Ca(2+)-free solution and then contracted by changing the bath solution to 100 mM KCl and 2 mM Ca2+. The inhibitory effects of quinidine were significantly enhanced when the rings were preincubated in 40 mM KCl (depolarizing conditions), when compared to normally polarized rings. In contrast, the effects of quinine were similar in 5 or 40 mM KCl solution. 4. The antagonism of noradrenaline (NA)-induced contractions by low concentrations of quinidine (< 10(-4)M) and quinine (< 3 x 10(-4)M) was competitive, as demonstrated by the concentration-dependent parallel rightward shift of the NA concentration-response curves (pA2 values 6.20 and 5.68, respectively, P < 0.05). 5. At low concentrations (< or = 3 x 10(-5)M), quinidine and quinine did not shift the concentration-response curve to 5-hydroxytryptamine (5-HT) or endothelin-1, whereas at higher concentrations they produced a downward shift of these curves. Quinidine and quinine (> 10(-4)M) inhibited to a similar extent both the phasic (induced in Ca(2+)-free media) and tonic responses (after restoring extracellular Ca2+) induced by 5-HT. 6. In conclusion, quinidine and quinine produced a stereoselective inhibition of depolarization and NA-induced contractions, quinidine being more potent than quinine. The inhibition of KCl-induced contractions could be attributed to inhibition of Ca2+ entry. Both drugs also behaved as competitive antagonists of alpha 1D-adrenoceptors. At high concentrations, quinidine and quinine also decreased the contractions induced by endothelin-1 and 5-HT in a non-stereoselective manner.

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Section: Introductionmentioning

confidence: 99%

Stereoselective effects of the enantiomers, quinidine and quinine, on depolarization‐ and agonist‐mediated responses in rat isolated aorta

Pozo

Pérez‐Vizcaíno

Villamor

et al. 1996

British J Pharmacology

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“…We were the first to reported on the role for platelet derived growth factor (PDGF) in experimental models of hepatic fibrosis [8,9] and we showed that PTX blocked fibrosis via an effect on PDGF and that this occurred by blocking phosphorylation of c-jun on serine 73 [10]. We began investigations of non alcoholic steatohepatitis (NASH) mediated fibrosis [11,12] and reported that ribavirin but not interferon inhibited fibrosis also associated with HCV and that this effect was mediated by the block of phosphorylation of c-jun on ser 73 and resulted in decreased synthesis of collagen and hepatic stellate cell (HSC) proliferation [13]. We reported that PTX decreased NASH sera-stimulated FSI (our patented diagnostic test for fibrosis using HSCs as the target cell) and c-Jun phosphorylation as assessed by 3 H-thymidine incorporation and Western analysis respectively, such that NASH patient sera stimulated HSC proliferation and increased phosphorylated c-Jun in HSCs and that PTX significantly decreased NASH patient sera stimulated HSC proliferation and decreased NASH sera-stimulated phosphorylated c-Jun in HSCs [14].…”

mentioning

confidence: 99%