On the solubility of calcium deoxycholate: kinetics of precipitation and the effect of conjugated bile salts and lecithin

Lichtenberg, Dov; Younis, Nadia; Bor, A.; Kushnir, Tamar; Shefi, M; Almog, Shlomo; Nir, Shlomo

doi:10.1016/0009-3084(88)90042-4

Cited by 9 publications

(2 citation statements)

References 20 publications

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“…Of note, the treatment concentrations we used in this experiment were increased from those used in prior assays in order to achieve reliable precipitation and solubilization dynamics of deoxycholate, yet these concentrations are still well within the physiologically relevant range. This mechanism is in agreement with previous biochemical analyses of deoxycholate, which have demonstrated that precipitation dynamics are influenced by pH, micelle formation, and calcium concentration (37,46). These reports also implicated mixed micelle formation in the maintenance of deoxycholate solubility in the upper intestinal tract and suggested that heterogeneous micelle formation is not specific to deoxycholate and cholate mixtures only, but instead they showed that other bile acids also contribute to deoxycholate solubility by forming mixed micelle complexes.…”

Section: Resultssupporting

confidence: 92%

Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD

et al. 2016

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bSalmonella spp. are carried by and can acutely infect agricultural animals and humans. After ingestion, salmonellae traverse the upper digestive tract and initiate tissue invasion of the distal ileum, a virulence process carried out by the type III secretion system encoded within Salmonella pathogenicity island 1 (SPI-1). Salmonellae coordinate SPI-1 expression with anatomical location via environmental cues, one of which is bile, a complex digestive fluid that causes potent repression of SPI-1 genes. The individual components of bile responsible for SPI-1 repression have not been previously characterized, nor have the bacterial signaling processes that modulate their effects been determined. Here, we characterize the mechanism by which bile represses SPI-1 expression. Individual bile acids exhibit repressive activity on SPI-1-regulated genes that requires neither passive diffusion nor OmpF-mediated entry. By using genetic methods, the effects of bile and bile acids were shown to require the invasion gene transcriptional activator hilD and to function independently of known upstream signaling pathways. Protein analysis techniques showed that SPI-1 repression by bile acids is mediated by posttranslational destabilization of HilD. Finally, we found that bile acids function synergistically to achieve the overall repressive activity of bile. These studies demonstrate a common mechanism by which diverse environmental cues (e.g., certain short-chain fatty acids and bile acids) inhibit SPI-1 expression. These data provide information relevant to Salmonella pathogenesis during acute infection in the intestine and during chronic infection of the gallbladder and inform the basis for development of therapeutics to inhibit invasion as a means of repressing Salmonella pathogenicity.

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Section: Resultssupporting

confidence: 92%

Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD

et al. 2016

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“…All excipients studied have been categorized as generally regarded as safe (GRAS) by the US FDA, and many are currently used in FDA approved drug products (Strickley, 2004). NaDC selection was based on numerous studies on the solubilization and permeation enhancing behavior of bile salts (D’Archivio, et al, 1997; Gu et al, 1992; Lichtenberg et al, 1988; Reis et al, 2004) inclusive of retinoid solubilization (Li et al, 1996; Mohapatra and Mishra, 2011). The aqueous solubility of 4HPR at 37 ˚C in the presence of excipients is shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

In vivo controlled release of fenretinide from long-acting release depots for chemoprevention of oral squamous cell carcinoma recurrence

Nieto

Pei

Wang

et al. 2018

International Journal of Pharmaceutics

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Local, long-acting release fenretinide (4HPR) millicylindrical implants were prepared and evaluated for their release kinetics in vivo and their ability to suppress oral cancer tumor explant growth. Poly(lactic-co-glycolic acid)(PLGA) implants were prepared as a function of drug loading and the presence of various excipients (pore-formers, solubilizers, crystallization inhibitors) to enhance release of the insoluble 4HPR. Release kinetics and bioerosion of PLGA were monitored both in vitro in a PBS/Tween 80 buffer and in vivo by recovery of the drug remaining at the injection site. 4HPR was released from PLGA implants much slower in vivo than in the drug solubilizing media in vitro, with a 3-week lag phase and continuous release of >2 months, but showed some release enhancement by addition of solubilizers. Water-soluble PVA/sucrose implants for release of 4HPR served to determine if drug dissolution provided suitable controlled release without the PLGA, and this formulation showed continuous drug release over 6 weeks in vivo. Placement of PLGA-4HPR implants adjacent to oral cancer tumor murine xenografts showed inhibition of tumor growth relative to sham implants, indicating the potential for the local 4HPR delivery approach to be useful for oral cancer chemoprevention.

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The use of C6-NBD-PC for assaying phospholipase A2-activity: Scope and limitations

Meyuhas

Yedgar

Rotenberg

et al. 1992

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metaboli

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On the solubility of calcium deoxycholate: kinetics of precipitation and the effect of conjugated bile salts and lecithin

Cited by 9 publications

References 20 publications

Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD

Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD

In vivo controlled release of fenretinide from long-acting release depots for chemoprevention of oral squamous cell carcinoma recurrence

The use of C6-NBD-PC for assaying phospholipase A2-activity: Scope and limitations

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