The relaxant action of hymecromone and lignocaine on induced spasm of the bile duct sphincter.

McFarland, Robert; Corbett, C. R. R.; Taylor, Paul C.; Nash, A. G.

doi:10.1111/j.1365-2125.1984.tb02416.x

Cited by 14 publications

(8 citation statements)

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“…We have chosen to reexamine 4MU and its conjugates, and we have performed rat liver perfusion experiments aimed at identifying the influence of binding and permeation characteristics on the extent of futile cycling between the drug and its metabolites. 4MU (Hymercromone, 7-hydroxy-4-methylcoumarin) is a choleretic agent (16)(17)(18) whose action is attributed mainly to its glucuronide conjugate (4MUG). Besides glucuronidation, 4MU is also known to form a sulfate conjugate (4MUS) in most animal species (19)(20)(21)(22)(23).…”

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confidence: 99%

Futile cycling between 4-methylumbelliferone and its conjugates in perfused rat liver

et al. 1993

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Futile cycling between 4-methylumbelliferone and its sulfate and glucuronide conjugates was examined in the single-pass perfused rat liver preparation. The steady-state hepatic extraction ratio of 4-methylumbelliferone was found to be high (0.97) at a low input concentration of 0.005 mumol/L (tracer), with a net 4-methylumbelliferyl sulfate/4-methylumbelliferyl glucuronide ratio of about 5:1; at 63 mumol/L the steady-state extraction ratio had remained constant despite a shift from net sulfation to net glucuronidation. At higher input 4-methylumbelliferone concentrations, saturation was evidenced by a decreased steady-state extraction ratio and reduced net sulfation and net glucuronidation. Because 4-methylumbelliferyl sulfate and 4-methylumbelliferyl glucuronide deconjugation would result in an intracellular accumulation of 4-methylumbelliferone, the phenomenon was monitored with a shift in tracer [3H]4-methylumbelliferone metabolism from sulfation to glucuronidation with increased intracellular 4-methylumbelliferone concentration. When 4-methylumbelliferyl sulfate (0 to 890 mumol/L) or 4-methylumbelliferyl glucuronide (0 to 460 mumol/L) was delivered simultaneously with tracer [3H]4-methylumbelliferone to the rat liver, notable desulfation of 4-methylumbelliferyl sulfate (18% to 38% rate in) but little deglucuronidation of 4-methylumbelliferyl glucuronide (1.2% to 2.1% rate in) was observed. With 4-methylumbelliferyl sulfate, 4-methylumbelliferone and 4-methylumbelliferyl glucuronide were readily found as metabolites, whereas with 4-methylumbelliferyl glucuronide, levels of the metabolites, 4-methylumbelliferone and 4-methylumbelliferyl sulfate, were much reduced. 4-Methylumbelliferyl sulfate and not 4-methylumbelliferyl glucuronide shifted tracer [3H]4-methylumbelliferone metabolism from [3H]4-methylumbelliferyl sulfate to [3H]4-methylumbelliferyl glucuronide formation in a concentration-dependent fashion. The steady-state extraction ratio for 4-methylumbelliferyl sulfate (0.1 to 0.3) was comparatively higher than that for 4-methylumbelliferyl glucuronide (0.05), and it was found to increase with concentration, an observation explained by the nonlinear protein binding of 4-methylumbelliferyl sulfate. Biliary excretion rates for 4-methylumbelliferone and 4-methylumbelliferyl sulfate were proportional to their input or net formation rates, regardless of whether 4-methylumbelliferone, 4-methylumbelliferyl glucuronide or 4-methylumbelliferyl sulfate was administered. By contrast, the excretion rate of 4-methylumbelliferyl glucuronide when administered was only 1/25 the excretion of 4-methylumbelliferyl glucuronide formed from 4-methylumbelliferone and 4-methylumbelliferyl sulfate. The extent of choleresis paralleled the excretion patterns of preformed and formed 4-methylumbelliferyl glucuronide; bile flow was normal with 4-methylumbelliferyl glucuronide administration and was markedly enhanced with increased 4-methylumbelliferone or 4-methylumbelliferyl sulfate administration. The data suggest the presence of a tr...

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Futile cycling between 4-methylumbelliferone and its conjugates in perfused rat liver

et al. 1993

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“…To evaluate this, we characterized the composition, rheological properties (e.g., viscosity and elasticity properties), and cytokine/chemokine profiles of respiratory secretions from patients under mechanical ventilation due to severe COVID-19, given the importance of these parameters in other respiratory diseases (32,33). As controls for these studies, we have included sputum samples from both healthy individuals and patients with cystic fibrosis (CF) (34), a genetic disease associated with notoriously thick lung secretions (35). These studies provide biochemical, biophysical, and immunological assessment of respiratory secretions in COVID-19.…”

Section: Introductionmentioning

confidence: 99%

Biochemical, biophysical, and immunological characterization of respiratory secretions in severe SARS-CoV-2 infections

et al. 2022

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“…To evaluate this, we characterized the composition, rheological properties (e.g., viscosity and elasticity properties), and cytokine/chemokine profiles of respiratory secretions from patients under mechanical ventilation due to severe COVID-19, given the importance of these parameters in other respiratory diseases (32, 33). As controls for these studies, we have included sputum samples from both healthy individuals and subjects with cystic fibrosis (34), a genetic disease associated with notoriously thick lung secretions (35). These studies provide biochemical, biophysical, and immunological assessment of respiratory secretions in COVID-19.…”

Section: Introductionmentioning

confidence: 99%

Biochemical, Biophysical, and Immunological Characterization of Respiratory Secretions in Severe SARS-CoV-2 (COVID-19) Infections

Kratochvil¹,

Kaber²,

Demirdjian³

et al. 2022

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Thick, viscous respiratory secretions are a major pathogenic feature of COVID-19 disease, but the composition and physical properties of these secretions are poorly understood. We characterized the composition and rheological properties (i.e. resistance to flow) of respiratory secretions collected from intubated COVID-19 patients. We find the percent solids and protein content are greatly elevated in COVID-19 compared to heathy control samples and closely resemble levels seen in cystic fibrosis, a genetic disease known for thick, tenacious respiratory secretions. DNA and hyaluronan (HA) are major components of respiratory secretions in COVID-19 and are likewise abundant in cadaveric lung tissues from these patients. COVID-19 secretions exhibit heterogeneous rheological behaviors with thicker samples showing increased sensitivity to DNase and hyaluronidase treatment. In histologic sections from these same patients, we observe increased accumulation of HA and the hyaladherin versican but reduced tumor necrosis factor–stimulated gene-6 (TSG6) staining, consistent with the inflammatory nature of these secretions. Finally, we observed diminished type I interferon and enhanced inflammatory cytokines in these secretions. Overall, our studies indicate that increases in HA and DNA in COVID-19 respiratory secretion samples correlate with enhanced inflammatory burden and suggest that DNA and HA may be viable therapeutic targets in COVID-19 infection.

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The relaxant action of hymecromone and lignocaine on induced spasm of the bile duct sphincter.

Cited by 14 publications

References 3 publications

Futile cycling between 4-methylumbelliferone and its conjugates in perfused rat liver

Futile cycling between 4-methylumbelliferone and its conjugates in perfused rat liver

Biochemical, biophysical, and immunological characterization of respiratory secretions in severe SARS-CoV-2 infections

Biochemical, Biophysical, and Immunological Characterization of Respiratory Secretions in Severe SARS-CoV-2 (COVID-19) Infections

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