High protein and total lipid concentration are associated with reduced metastability of bile in an early stage of cholesterol gallstone formation

1990 ◽  
Vol 98 (3) ◽  
pp. 739-746 ◽  
Author(s):  
Steven M. Strasberg ◽  
Julius L. Toth ◽  
Steven Gallinger ◽  
P.Robert C. Harvey
1986 ◽  
Vol 251 (5) ◽  
pp. G701-G709 ◽  
Author(s):  
W. W. LaMorte ◽  
J. T. LaMont ◽  
W. Hale ◽  
M. L. Booker ◽  
T. E. Scott ◽  
...  

Mucin hypersecretion from the gallbladder epithelium contributes to cholesterol gallstone formation by accelerating the nucleation of cholesterol-supersaturated bile. Prostaglandins (PGs) and lysophosphatidylcholine (LPC) have both been implicated as potential mediators of mucin hypersecretion, but their roles are unclear. We fed prairie dogs a lithogenic diet (0.34% cholesterol), and after 1, 2, 4, or 6 wk of cholesterol feeding, we measured glycoprotein and LPC concentrations in bile and PG synthesis in gallbladder and liver slices. Hypercholesterolemia and cholesterol supersaturation of bile occurred after 1 wk of cholesterol feeding, but marked crystal formation was delayed until 4 wk, when glycoprotein concentrations became markedly elevated. Glycoprotein hypersecretion was preceded by increased synthesis of PGF2 alpha (P less than 0.002), PGE2 (P less than 0.001), prostacyclin (P less than 0.05), and thromboxane (P = 0.07) in the gallbladder after only 2 wk of cholesterol feeding, but PG synthesis in the liver remained unchanged (P greater than 0.14). LPC concentrations in gallbladder bile also increased at 2 wk (P less than 0.02), but LPC in hepatic bile was unchanged (P = 0.35). In organ culture studies, LPC caused a dose-dependent stimulation of [3H]glycoprotein release from guinea pig gallbladder mucosa that could not be explained solely by LPC's detergent properties. We conclude that gallbladder PG synthesis and LPC production are increased at an early stage of cholesterol gallstone formation in the prairie dog model. These changes probably play a significant role in gallstone pathogenesis, since they mediate hypersecretion of gallbladder mucin and thus favor the nucleation of cholesterol-supersaturated bile.


2009 ◽  
Vol 128 (3) ◽  
pp. 261-268 ◽  
Author(s):  
Ana Lúcia Fernandes Chittó ◽  
Vanessa Schein ◽  
Rodrigo Etges ◽  
Luiz Carlos Kucharski ◽  
Roselis Silveira Martins Da Silva

Author(s):  
Le Quoc Thang ◽  
Nguyen Duc Hanh ◽  
Do Quang Duong

Objective: Exemestane is an anti-breast cancer drug, possesses low water solubility and low permeability. This work aimed at the cause-effect relations and optimization of exemestane-loaded nanostructured lipid carriers (EXE-NLCs) for oral delivery.Methods: Excipient screening was based on exemestane solubilities and the emulsification efficiency of surfactants. A D-optimal design based on three independent variables was applied to evaluate the cause-effect relations and optimise EXE-NLCs formulation. The particle size (PS), polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL) were investigated with respect to three independent variables including liquid lipid to total lipid ratio (X1), surfactant concentration (X2), total lipid concentration (X3).Results: EXE-NLCs were prepared by a hot sonication method employing Labrafac CC and Compritol 888ATO as liquid and solid lipids, respectively, and Cremophor RH40 as a surfactant and Lutrol E-400 as a co-surfactant. All investigated factors: liquid lipid to total lipid ratio, surfactant concentration and total lipid concentration showed significant influences on physicochemical characteristics of EXE-NLCs. The optimal EXE-NLC formulation was composed of liquid lipid to total lipid ratio (X1) of 24 % (w/w), surfactant concentration (X2) of 4 % (w/v) and total lipid concentration (X3) of 4 % (w/v). The PS, PDI, EE and DL of the optimized EXE-NLCs were found to be 41.787 nm; 0.11; 97.605 % and 1.935 %, respectively. The optimized formulation was experimentally examined which demonstrated a good agreement between experimental and predicted values.Conclusion: The cause-effect relations and optimization of EXE-NLCs were investigated and reported for the first time. EXE-NLCs formulation was successfully optimized using D-optimal design and merits further study.


2001 ◽  
Vol 280 (3) ◽  
pp. R843-R853 ◽  
Author(s):  
Frederic Decrock ◽  
René Groscolas ◽  
Ruth J. McCartney ◽  
Brian K. Speake

This study examines the transfer of lipids from the yolk to the embryo of the king penguin, a seabird with a high dietary intake of n–3 fatty acids. The concentrations of total lipid, triacylglycerol (TAG), and phospholipid (PL) in the yolk decreased by ∼80% between days 33 and 55 of development, indicating intensive lipid transfer, whereas the concentration of cholesteryl ester (CE) increased threefold, possibly due to recycling. Total lipid concentration in plasma and liver of the embryo increased by twofold from day 40 to hatching due to the accumulation of CE. Yolk lipids contained high amounts of C20–22 n–3 fatty acids with 22:6(n–3) forming 4 and 10% of the fatty acid mass in TAG and PL, respectively. Both TAG and PL of plasma and liver contained high proportions of 22:6(n–3) (∼15% in plasma and >20% in liver at day 33); liver PL also contained a high proportion of 20:4(n–6) (14%). Thus both 22:6(n–3) and 20:4(n–6), which are, respectively, abundant and deficient in the yolk, undergo biomagnification during transfer to the embryo.


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