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Bile Salts (bile + salt)
Terms modified by Bile Salts Selected AbstractsEffect of bile salts, lipid, and humic acids on absorption of benzo[a]pyrene by isolated channel catfish (Ictalurus punctatus) intestine segmentsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2001Lynn P. Weber Abstract Dietary absorption of lipophilic contaminants may be a significant route of exposure in aquatic organisms. Bile salts, lipids, and humic acids are important factors that may influence the intestinal absorption of a contaminant such as benzo[a]pyrene (BaP). We hypothesized that bile salts, monoglycerides, and free fatty acids would increase BaP intestinal absorption, while triglycerides, humic acids, and sediment would decrease BaP intestinal absorption. We have established and validated an in vitro model to examine modification of 3H-BaP absorption in everted intestinal segments from channel catfish (Ictalurus punctatus). Uptake of BaP into the everted intestinal segments continued to increase over the times examined in this study (60 min) and apparently occurs passively; thus, fugacity-based models of uptake are supported. Absorption of BaP into intestinal cells was significantly decreased by the addition of monoglycerides and free fatty acids to bile salts in the incubation media. Addition of triglycerides decreased BaP absorption even further. Humic acids may have decreased BaP intestinal absorption, while natural sediment may have increased BaP absorption. The results of this study suggest that all lipids may decrease intestinal uptake of lipophilic contaminants if they remain in unabsorbable excess in the intestinal lumen by retaining BaP in lipid/bile micelles. In contrast, if triglycerides are hydrolyzed into monoglycerides/free fatty acids prior to absorption, lipophilic contaminant uptake will likely be facilitated. Thus, it may be the hydrolytic state of lipids that determines its effects on BaP absorption. Humic acids alone may decrease dietary uptake of BaP, but our results suggest that other components in natural sediment may counteract this effect to cause a slight enhancement of BaP uptake. Further studies are needed to determine the dietary conditions necessary for bio-accumulation to contribute significantly to lipophilic contaminant body burdens in benthivorous fish. Finally, the everted intestinal segment technique has the potential to be used in other species and with different contaminants. [source] Bile salts and cholesterol induce changes in the lipid cell membrane of Lactobacillus reuteriJOURNAL OF APPLIED MICROBIOLOGY, Issue 1 2003M.P. Taranto Abstract Aims: The objective of this study was to evaluate the effect of bile salts and cholesterol in the lipid profile of Lactobacillus reuteri CRL 1098 and to determine the relationship existing between these changes: the in vitro removal of cholesterol and the tolerance of the cells to acid and cold stress. Methods and Results:Lactobacillus reuteri CRL 1098 was grown in the following media: MRS (deMan Rogosa Sharpe; MC, control medium), MB (MC with bile salts), MCH (MC with sterile cholesterol) and MBCH (MC with bile salts and cholesterol). Fatty acids were determined by analytical gas,liquid chromatography, and phospholipids and glycolipids by colorimetric techniques. The cells from different culture media were subjected to cold and acid stress. The MB cultures displayed a decrease in phospholipids and a low ratio of saturated : unsaturated fatty acids. The presence of the unusual C18 : 0,10-OH and C18 : 0,10-oxo fatty acids was the prominent characteristic of the bile salts growing cells. The relative increase in glycolipids and the changes in the fatty acids profiles of the MB cells would be responsible for the cholesterol remotion. The changes induced by bile salts in the lipid profile did not improve the tolerance of L. reuteri CRL 1098 to freezing and acid stress. Conclusions: The changes in lipid profiles reported in this study would play a key role in the response of Lactobacilli to environmental stress. Significance and Impact of the Study: This work provides useful information about the effect of bile salts on the cell membrane of L. reuteri, a probiotic enterolactobacillus. The steady-state response of the cells subjected to bile stress seems to be the appropriate model for evaluating the bacterial behaviour in detergent-containing gastrointestinal tracts, where the bile salts stress would presumably be continuous. [source] Genetic cholestasis, causes and consequences for hepatobiliary transportLIVER INTERNATIONAL, Issue 5 2003Peter L. M. Jansen Abstract: Bile salts take part in an efficient enterohepatic circulation in which most of the secreted bile salts are reclaimed by absorption in the terminal ileum. In the liver, the sodium-dependent taurocholate transporter at the basolateral (sinusoidal) membrane and the bile salt export pump at the canalicular membrane mediate hepatic uptake and hepatobiliary secretion of bile salts. Canalicular secretion is the driving force for the enterohepatic cycling of bile salts and most genetic diseases are caused by defects of canalicular secretion. Impairment of bile flow leads to adaptive changes in the expression of transporter proteins and enzymes of the cytochrome P-450 system involved in the metabolism of cholesterol and bile acids. Bile salts act as ligands for transcription factors. As such, they stimulate or inhibit the transcription of genes encoding transporters and enzymes involved in their own metabolism. Together these changes appear to serve mainly a hepatoprotective function. Progressive familial intrahepatic cholestasis (PFIC) results from mutations in various genes encoding hepatobiliary transport proteins. Mutations in the FIC1 gene cause relapsing or permanent cholestasis. The relapsing type of cholestasis is called benign recurrent intrahepatic cholestasis, the permanent type of cholestasis PFIC type 1. PFIC type 2 results from mutations in the bile salt export pump (BSEP) gene. This is associated with permanent cholestasis since birth. Serum gamma-glutamyltransferase (gamma-GT) activity is low to normal in PFIC types 1 and 2. Bile diversion procedures, causing a decreased bile salt pool, have a beneficial effect in a number of patients with these diseases. However, liver transplantation is often necessary. PFIC type 3 is caused by mutations in the MDR3 gene. MDR3 is a phospholipid translocator in the canalicular membrane. Because of the inability to secrete phospholipids, patients with PFIC type 3 produce bile acid-rich toxic bile that damages the intrahepatic bile ducts. Serum gamma-GT activity is elevated in these patients. Ursodeoxycholic acid therapy is useful for patients with a partial defect. Liver transplantation is a more definitive therapy for these patients. [source] The G protein,coupled receptor G2A: Involvement in hepatic lipid metabolism and gallstone formation in mice,HEPATOLOGY, Issue 4 2008Laura E. Johnson The G2A receptor is a member of the ovarian cancer G protein,coupled receptor 1 family of stress-inducible G protein,coupled receptors. In this study, we examined the hepatobiliary effects of loss of function of G2A in mice fed either a chow or lithogenic diet. G2A-deficient (G2A,/,) mice fed chow had a 25% reduction in biliary phosphatidylcholine content, reduced hepatic gene expression of the phosphatidylcholine transporter adenosine triphosphate,binding cassette B4, and an 8-fold increase in expression of the nuclear receptor liver X receptor (LXR). Despite the increased expression of LXR, transcription of several LXR target genes was reduced. G2A,/, mice fed a lithogenic diet had rapid gallstone formation, an increased cholesterol saturation index, a 2.5-fold increase in farnesoid X receptor expression, a 5-fold increase in LXR expression, and a 90% reduction in cholesterol 7,-hydroxylase expression in comparison with wild-type mice. There were no changes in gallbladder volume. Conclusion: These data demonstrate that the G2A receptor is important for hepatobiliary bile salt, cholesterol, and phospholipid homeostasis and for the pathogenesis of cholesterol gallstone formation. (HEPATOLOGY 2008;48:1138,1148.) [source] Regulation of multidrug resistance 2 P-glycoprotein expression by bile salts in rats and in primary cultures of rat hepatocytesHEPATOLOGY, Issue 2 2000Seema Gupta Biliary phospholipid secretion is tightly coupled to the secretion of free cholesterol and bile salts. The secretion of phospholipids across the canalicular membrane of hepatocytes occurs via the multidrug resistance 2 (mdr2) P-glycoprotein (Pgp). The mechanism underlying the coupling of bile salt and phospholipid secretion has not been elucidated. The aims of this study were to determine the effects of bile acid structure on the expression of mdr2 in vitro and in vivo. Under optimal culture conditions, taurine-conjugated bile acids (50 ,mol/L) increased mdr2 messenger RNA (mRNA) levels in the following order: taurocholate (TCA) (288 ± 36%, P < .005) = taurodeoxycholate (TDCA) (276 ± 36%, P < .025) > taurochenodeoxycholate (TCDCA) (216 ± 34%, P < .025) > tauroursodeoxycholate (TUDCA) (175 ± 28%, P < .05) of control levels. The increase in mdr2 mRNA levels by TCA was both time and concentration dependent. Cholate feeding to rats with intact enterohepatic circulation increased mdr2 transcriptional activity by 4-fold and protein mass by 1.9-fold. Chronic biliary diversion (CBD) decreased mdr2 mRNA levels to 66 ± 9% (P < .025) of sham-operated controls. Intraduodenal infusion of TCA for 48 hours in CBD rats caused a significant increase in mdr2 mRNA levels (224%) as compared with CBD controls. A diet high in cholesterol (4%) decreased mdr2 mRNA levels to 57% ± 2 (P < .001) of pair-fed controls. Squalestatin (1 ,mol/L), an inhibitor of cholesterol biosynthesis, increased mdr2 mRNA levels by 8.8-fold (P < .005) in hepatocyte cultures after 24 hours. In conclusion, in the rat, bile acids up-regulated mdr2 transcriptional activity whereas cholesterol decreased mdr2 mRNA both in vitro and in vivo. [source] Infectious gastroenteritis caused by Vibrio harveyi (V. carchariae) in cultured red drum, Sciaenops ocellatusJOURNAL OF APPLIED ICHTHYOLOGY, Issue 1 2003P.-C. Liu Summary An outbreak of serious mortality among the cultured red drum Sciaenops ocellatus (L.) characterized by a swollen intestine containing transparent yellow fluid (ascites and gastroenteritis) occurred in July 2000 in Taiwan. A motile strain Rd 0700 was isolated from head kidney and/or the intestinal yellow fluid on tryptone soya agar (TSA) supplemented with 2% (w/v) NaCl and/or thiosulfate citrate bile salt (TCBS) sucrose agar plates. Applying biochemical characteristics, this strain was characterized and identified as Vibrio harveyi (V. carchariae). The bacteria could be re-isolated from kidney, liver, and the transparent yellow fluid of swollen intestine of fish after bacterial challenge. The LD50 values of the organism and its extracellular products (ECP) were 2.9×107 colony forming units (CFU) and 3.85 ,g protein g,1 fish body weight, respectively. All moribund/dead fish exhibited gastroenteritis except those killed within 12 h. This is a first report showing that intraperitoneal (i.p.) injection of the ECP from V. carchariae is lethal to red drum and can reproduce gastroenteritis in the fish. [source] Biorelevant dissolution media: Aggregation of amphiphiles and solubility of estradiolJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2006David Ilardia-Arana Abstract Biorelevant dissolution media containing bile salt and lecithin at concentrations appropriate for fed and fasted state are useful when testing oral solid formulations of poorly water-soluble drugs. Dilution of amphiphile solutions affects the aggregation state of the amphiphiles because bile salt is partitioned between the aqueous phase and the aggregates. The aim of the investigation was to study the effect of dilution on the size distribution of aggregates and its effect on the solubilization capacity. Clear buffered solutions of four intestinal amphiphiles (sodium glycocholate, lecithin, monoolein, and oleic acid) and a combination of these were prepared at high bile salt concentration. Micelles in the glycocholate solutions decreased in size when diluted. The addition of insoluble amphiphiles led to bigger micelles with no clear correlation between size of the micelles and amphiphile concentration. Dilution of the two- and four component media caused enlargement of the mixed micelles and formation of vesicles. The solubility of estradiol in the buffer solution was increased with addition of the amphiphiles. A good correlation (R2,=,0.987) was found between estradiol solubility and mass concentration of the amphiphiles. The results demonstrate that, in the case of estradiol, the concentration of amphiphiles rather than the aggregation state determines the solubilization capacity of the medium. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:248,255, 2006 [source] Bile acid sequestrants based on cationic dextran hydrogel microspheres.JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2001Abstract Cationic dextran hydrogel microspheres with pendant quaternary ammonium groups having alkyl substituents (C2,C12) at quaternary nitrogen were synthesized. The in vitro sorption of sodium salts of four bile acids (glycocholic, cholic, taurocholic, and deoxycholic acids) with these hydrogels was studied as a function of substituent alkyl chain length and bile acid hydrophobicity. Sorption experiments were performed in phosphate buffer solutions (pH 7.4) containing one bile salt (individual sorption) or mixtures of several bile salts (competitive sorption). Parameters for individual sorption were calculated taking into consideration the stoichiometric and cooperative binding of bile salts to oppositely charged polymer hydrogels. The results show that the increase in the length of the alkyl chain of the substituent leads to an increase in both ionization constant K0 and overall stability constant of binding K, but decreases the cooperativity parameter u. The competitive sorption studies indicate that the hydrogels display a good affinity for both dihydroxylic and trihydroxylic bile salts. The molar ratio of maximum amounts bound for the two types of bile acid is 2 to 1, which is much lower than those reported for other cationic polymers recommended as bile acid sequestrants. The binding constants for the sorption of bile salts by some dextran hydrogels are 20,30 times higher than those obtained for cholestyramine under similar sorption conditions. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:681,689, 2001 [source] Occurrence of Listonella anguillarum in seed production environments of Japanese flounder Paralichthys olivaceus (Temminck et Schlegel)AQUACULTURE RESEARCH, Issue 9 2005Haruo Sugita Abstract The present study was undertaken to investigate the distribution of Listonella anguillarum in the rearing water, fish and diets (rotifers) of Japanese flounder (Paralichthys olivaceus). A total of 793 isolates were obtained from the seed production environment of Japanese flounder and 175 out of them were identified as L. anguillarum by biochemical characterization, polymerase chain reaction (PCR) detection for VAH1 haemolysin gene and phylogenetic analysis of 16S ribosomal deoxyribonucleic acids (rDNA) sequences. These results strongly suggested that L. anguillarum is rapidly and accurately identified by the combination of incubation on thiosulphate,citrate,bile salt,sucrose agar at 35°C overnight and PCR detection for the VAH1 haemolysin gene. All flounder specimens and all rotifer samples harboured L. anguillarum at high densities of 6.9 × 103,6.3 × 105 colony forming units (CFU) g,1 and 1.5 × 104,2.3 × 106 CFU g,1, respectively, while as low as 5.0 × 100,2.0 × 101 CFU mL,1 of L. aguillarum were detected in only two of 11 seawater samples, even though no vibriosis occurred in larval and juvenile flounder of tanks. This fact strongly suggests that L. anguillarum is an inhabitant in the seed production environments of Japanese flounder. [source] Effect of bile salts, lipid, and humic acids on absorption of benzo[a]pyrene by isolated channel catfish (Ictalurus punctatus) intestine segmentsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2001Lynn P. Weber Abstract Dietary absorption of lipophilic contaminants may be a significant route of exposure in aquatic organisms. Bile salts, lipids, and humic acids are important factors that may influence the intestinal absorption of a contaminant such as benzo[a]pyrene (BaP). We hypothesized that bile salts, monoglycerides, and free fatty acids would increase BaP intestinal absorption, while triglycerides, humic acids, and sediment would decrease BaP intestinal absorption. We have established and validated an in vitro model to examine modification of 3H-BaP absorption in everted intestinal segments from channel catfish (Ictalurus punctatus). Uptake of BaP into the everted intestinal segments continued to increase over the times examined in this study (60 min) and apparently occurs passively; thus, fugacity-based models of uptake are supported. Absorption of BaP into intestinal cells was significantly decreased by the addition of monoglycerides and free fatty acids to bile salts in the incubation media. Addition of triglycerides decreased BaP absorption even further. Humic acids may have decreased BaP intestinal absorption, while natural sediment may have increased BaP absorption. The results of this study suggest that all lipids may decrease intestinal uptake of lipophilic contaminants if they remain in unabsorbable excess in the intestinal lumen by retaining BaP in lipid/bile micelles. In contrast, if triglycerides are hydrolyzed into monoglycerides/free fatty acids prior to absorption, lipophilic contaminant uptake will likely be facilitated. Thus, it may be the hydrolytic state of lipids that determines its effects on BaP absorption. Humic acids alone may decrease dietary uptake of BaP, but our results suggest that other components in natural sediment may counteract this effect to cause a slight enhancement of BaP uptake. Further studies are needed to determine the dietary conditions necessary for bio-accumulation to contribute significantly to lipophilic contaminant body burdens in benthivorous fish. Finally, the everted intestinal segment technique has the potential to be used in other species and with different contaminants. [source] Bicarbonate-rich choleresis induced by secretin in normal rat is taurocholate-dependent and involves AE2 anion exchanger,HEPATOLOGY, Issue 2 2006Jesús M. Banales Canalicular bile is modified along bile ducts through reabsorptive and secretory processes regulated by nerves, bile salts, and hormones such as secretin. Secretin stimulates ductular cystic fibrosis transmembrane conductance regulator (CFTR),dependent Cl, efflux and subsequent biliary HCO3, secretion, possibly via Cl,/HCO3, anion exchange (AE). However, the contribution of secretin to bile regulation in the normal rat, the significance of choleretic bile salts in secretin effects, and the role of Cl,/HCO3, exchange in secretin-stimulated HCO3, secretion all remain unclear. Here, secretin was administered to normal rats with maintained bile acid pool via continuous taurocholate infusion. Bile flow and biliary HCO3, and Cl, excretion were monitored following intrabiliary retrograde fluxes of saline solutions with and without the Cl, channel inhibitor 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) or the Cl,/HCO3, exchange inhibitor 4,4,-diisothiocyanatostilbene-2,2,-disulfonic acid (DIDS). Secretin increased bile flow and biliary excretion of HCO3, and Cl,. Interestingly, secretin effects were not observed in the absence of taurocholate. Whereas secretin effects were all blocked by intrabiliary NPPB, DIDS only inhibited secretin-induced increases in bile flow and HCO3, excretion but not the increased Cl, excretion, revealing a role of biliary Cl,/HCO3, exchange in secretin-induced, bicarbonate-rich choleresis in normal rats. Finally, small hairpin RNA adenoviral constructs were used to demonstrate the involvement of the Na+ -independent anion exchanger 2 (AE2) through gene silencing in normal rat cholangiocytes. AE2 gene silencing caused a marked inhibition of unstimulated and secretin-stimulated Cl,/HCO3, exchange. In conclusion, maintenance of the bile acid pool is crucial for secretin to induce bicarbonate-rich choleresis in the normal rat and that this occurs via a chloride,bicarbonate exchange process consistent with AE2 function. (HEPATOLOGY 2006;43:266,275.) [source] Regulation of multidrug resistance 2 P-glycoprotein expression by bile salts in rats and in primary cultures of rat hepatocytesHEPATOLOGY, Issue 2 2000Seema Gupta Biliary phospholipid secretion is tightly coupled to the secretion of free cholesterol and bile salts. The secretion of phospholipids across the canalicular membrane of hepatocytes occurs via the multidrug resistance 2 (mdr2) P-glycoprotein (Pgp). The mechanism underlying the coupling of bile salt and phospholipid secretion has not been elucidated. The aims of this study were to determine the effects of bile acid structure on the expression of mdr2 in vitro and in vivo. Under optimal culture conditions, taurine-conjugated bile acids (50 ,mol/L) increased mdr2 messenger RNA (mRNA) levels in the following order: taurocholate (TCA) (288 ± 36%, P < .005) = taurodeoxycholate (TDCA) (276 ± 36%, P < .025) > taurochenodeoxycholate (TCDCA) (216 ± 34%, P < .025) > tauroursodeoxycholate (TUDCA) (175 ± 28%, P < .05) of control levels. The increase in mdr2 mRNA levels by TCA was both time and concentration dependent. Cholate feeding to rats with intact enterohepatic circulation increased mdr2 transcriptional activity by 4-fold and protein mass by 1.9-fold. Chronic biliary diversion (CBD) decreased mdr2 mRNA levels to 66 ± 9% (P < .025) of sham-operated controls. Intraduodenal infusion of TCA for 48 hours in CBD rats caused a significant increase in mdr2 mRNA levels (224%) as compared with CBD controls. A diet high in cholesterol (4%) decreased mdr2 mRNA levels to 57% ± 2 (P < .001) of pair-fed controls. Squalestatin (1 ,mol/L), an inhibitor of cholesterol biosynthesis, increased mdr2 mRNA levels by 8.8-fold (P < .005) in hepatocyte cultures after 24 hours. In conclusion, in the rat, bile acids up-regulated mdr2 transcriptional activity whereas cholesterol decreased mdr2 mRNA both in vitro and in vivo. [source] Probiotic characteristics of lactic acid bacteria isolated from kimchiJOURNAL OF APPLIED MICROBIOLOGY, Issue 1 2010J.-H. Chang Abstract Aims:, The present work was aimed at identifying strains of lactic acid bacteria (LAB) from kimchi, with properties suitable for use as starter cultures in yogurt fermentation. Methods and Results:, A total of 2344 LAB strains were obtained from two different sources, one group consisted of commercial LAB strains from kimchi, and the second group consisted of those strains isolated from various types of kimchi. The LAB strains from both groups were screened for resistance to biological barriers (acid and bile salts), and the four most promising strains were selected. Further analysis revealed that KFRI342 of the four selected strains displayed the greatest ability to reduce the growth of the cancer cells, SNU-C4. The in vivo efficacy of strains in quinone reductase induction assay was evaluated, and the extent of DNA strand breakage in individual cells was investigated using the comet assay. Strain KFRI342 was identified as Lactobacillus acidophilus by 16S rRNA sequence analysis, showed protection against tumour initiation and imparted immunostimulation as well as protection against DNA damage. Conclusions:, Strain KFRI342, which showed probiotic characteristics reducing cancer cell growth, could be a suitable starter culture for yogurt fermentation because of its strong acid production and high acid tolerance. Significance and Impact of the Study:, This is the first report to describe a bacterium, isolated from kimchi, Lact. acidophilus KFRI342 which has the probiotic characteristics and the acid tolerance needed for its use as a starter culture in yogurt fermentation. [source] Tolerance to challenges miming gastrointestinal transit by spores and vegetative cells of Bacillus clausiiJOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2006G. Cenci Abstract Aims:, To study Bacillus clausii from a pharmaceutical product (Enterogermina O/C, N/R, SIN, T) and reference strains (B. clausii and Bacillus subtilis) for eco-physiological aspects regarding the gut environment. Methods and Results:, Spores and vegetative cells were challenged in vitro miming the injury of gastrointestinal transit: pH variations, exposure to conjugated and free bile salts, microaerophilic and anaerobic growth. No relevant differences were found studying the growth at pH 8 and 10, whereas at pH 7 the yields obtained for O/C and SIN were higher than those obtained for N/R and T strains. The spores were able to germinate and grow in the presence of conjugated bile salts (up to 1%, w/v) or free bile salts (0·2%) and also exhibited tolerance for the combined acid-bile challenge. As evidenced by lag-time, growth rate and cell yield the tolerance of Enterogermina isolates for conjugated salts was comparable with that of B. clausii type strain (DSM 8716T), and resulted higher than that observed for B. subtilis (ATCC 6051T). All the considered B. clausii strains demonstrated microaerophilic growth, but only some grew anaerobically in a nitrate medium. Conclusions:, The ability of B. clausii spores to germinate after an acid challenge and grow as vegetative cells both in the presence of bile and under limited oxygen availability is consistent with the beneficial health effects evidenced for spore-forming probiotics in recent clinical studies. Significance and Impact of the Study:, The experimental evidence from this study emphasizes some functional properties of B. clausii strains regarding their use as probiotics. [source] Bile salts and cholesterol induce changes in the lipid cell membrane of Lactobacillus reuteriJOURNAL OF APPLIED MICROBIOLOGY, Issue 1 2003M.P. Taranto Abstract Aims: The objective of this study was to evaluate the effect of bile salts and cholesterol in the lipid profile of Lactobacillus reuteri CRL 1098 and to determine the relationship existing between these changes: the in vitro removal of cholesterol and the tolerance of the cells to acid and cold stress. Methods and Results:Lactobacillus reuteri CRL 1098 was grown in the following media: MRS (deMan Rogosa Sharpe; MC, control medium), MB (MC with bile salts), MCH (MC with sterile cholesterol) and MBCH (MC with bile salts and cholesterol). Fatty acids were determined by analytical gas,liquid chromatography, and phospholipids and glycolipids by colorimetric techniques. The cells from different culture media were subjected to cold and acid stress. The MB cultures displayed a decrease in phospholipids and a low ratio of saturated : unsaturated fatty acids. The presence of the unusual C18 : 0,10-OH and C18 : 0,10-oxo fatty acids was the prominent characteristic of the bile salts growing cells. The relative increase in glycolipids and the changes in the fatty acids profiles of the MB cells would be responsible for the cholesterol remotion. The changes induced by bile salts in the lipid profile did not improve the tolerance of L. reuteri CRL 1098 to freezing and acid stress. Conclusions: The changes in lipid profiles reported in this study would play a key role in the response of Lactobacilli to environmental stress. Significance and Impact of the Study: This work provides useful information about the effect of bile salts on the cell membrane of L. reuteri, a probiotic enterolactobacillus. The steady-state response of the cells subjected to bile stress seems to be the appropriate model for evaluating the bacterial behaviour in detergent-containing gastrointestinal tracts, where the bile salts stress would presumably be continuous. [source] Isolation and characterization of a Lactobacillus amylovorus mutant depleted in conjugated bile salt hydrolase activity: relation between activity and bile salt resistanceJOURNAL OF APPLIED MICROBIOLOGY, Issue 4 2000J.P. Grill Growth experiments were conducted on Lactobacillus amylovorus DN-112 053 in batch culture, with or without pH regulation. Conjugated bile salt hydrolase (CBSH) activity was examined as a function of culture growth. The CBSH activity increased during growth but its course depended on bile salts type and culture conditions. A Lact. amylovorus mutant was isolated from the wild-type strain of Lact. amylovorus DN-112 053 after mutagenesis with N-methyl-N,-nitro-N-nitrosoguanidine. An agar plate assay was used to detect mutants without CBSH activity. In resting cell experiments, the strain showed reduced activity. Differences between growth parameters determined for wild-type and mutant strains were not detected. Comparative native gel electrophoresis followed by CBSH activity staining demonstrated the loss of proteins harbouring this activity in the mutant. Four protein bands corresponding to CBSH were observed in the wild-type strain but only one was detected in the mutant. The specific growth rate of the mutant strain was affected more by bile salts than the wild-type strain. Nevertheless, bile was more toxic for the wild-type strain. In viability studies in the presence of nutrients, it was demonstrated that glycodeoxycholic acid exerted a higher toxicity than taurodeoxycholic acid in a pH-dependent manner. No difference was apparent between the two strains. In the absence of nutrients, the wild-type strain died after 2 h whereas no effect was observed for the mutant. The de-energization experiments performed using the ionophores nigericin and valinomycin suggested that the chemical potential of protons (Z,pH) was involved in Lactobacillus bile salt resistance. [source] Relative in vitro efficacy of the phosphate binders lanthanum carbonate and sevelamer hydrochlorideJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2007Valerie Autissier Abstract The high tablet burden and poor compliance associated with phosphate-binding drugs has led to a search for more potent agents. In vitro -binding studies were performed on the recently introduced binder, lanthanum carbonate (LC; Fosrenol®), to compare its phosphate-binding affinity with sevelamer hydrochloride (SH; RenagelÔ). Langmuir equilibrium binding affinities (K1) for LC and SH were established using different phosphorus (5,100 mM) and binder (134,670 mg per 50 mL) concentrations at pH 3,7, with or without salts of bile acids present (30 mM). At all pH levels, LC had a higher binding affinity for phosphate than SH. For LC, K1 was 6.1,±,1.0 mM,1 and was independent of pH. For SH, K1 was pH dependent, being 1.5,±,0.8 mM,1 at pH 5,7 and 0.025,±,0.002 mM,1 at pH 3, that is, >200 times lower than for LC. In the presence of 30 mM bile salts, SH lost 50% of its phosphate, whereas no displacement of phosphate occurred for LC. These findings indicate that LC binds phosphate more effectively than SH across the pH range encountered in the gastrointestinal tract, and has a lower propensity for bound phosphate to be displaced by competing anions in the intestine. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2818,2827, 2007 [source] Bile acid sequestrants based on cationic dextran hydrogel microspheres.JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2001Abstract Cationic dextran hydrogel microspheres with pendant quaternary ammonium groups having alkyl substituents (C2,C12) at quaternary nitrogen were synthesized. The in vitro sorption of sodium salts of four bile acids (glycocholic, cholic, taurocholic, and deoxycholic acids) with these hydrogels was studied as a function of substituent alkyl chain length and bile acid hydrophobicity. Sorption experiments were performed in phosphate buffer solutions (pH 7.4) containing one bile salt (individual sorption) or mixtures of several bile salts (competitive sorption). Parameters for individual sorption were calculated taking into consideration the stoichiometric and cooperative binding of bile salts to oppositely charged polymer hydrogels. The results show that the increase in the length of the alkyl chain of the substituent leads to an increase in both ionization constant K0 and overall stability constant of binding K, but decreases the cooperativity parameter u. The competitive sorption studies indicate that the hydrogels display a good affinity for both dihydroxylic and trihydroxylic bile salts. The molar ratio of maximum amounts bound for the two types of bile acid is 2 to 1, which is much lower than those reported for other cationic polymers recommended as bile acid sequestrants. The binding constants for the sorption of bile salts by some dextran hydrogels are 20,30 times higher than those obtained for cholestyramine under similar sorption conditions. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:681,689, 2001 [source] Skin permeation of retinol in Tween 20-based deformable liposomes: in-vitro evaluation in human skin and keratinocyte modelsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2006Yu-Kyoung Oh To develop a more effective transdermal delivery method for lipophilic functional cosmetic compounds such as retinol, we formulated various deformable liposomes and compared their transdermal delivery efficiency with those of neutral or negatively-charged conventional liposomes. We tested the deformability of liposomes containing edge activators such as bile salts, polyoxyethylene esters and polyoxyethylene ethers. As indicators of deformability, we used the passed volume and phospholipid ratios during extrusion, as well as the deformability index. We found that the type of edge activator significantly affected the extent of deformability, and that Tween 20 provided the highest level of deformability. Accordingly, we used Tween 20 to formulate deformable liposomes containing retinol in the membrane bilayers, and conducted a skin permeation study in Franz diffusion cells, using dermatomed human skin and three-dimensional human keratinocyte layers. As compared with the use of conventional neutral or negatively-charged liposomes, the use of Tween 20-based deformable liposomes significantly increased the skin permeation of retinol. These results suggested that deformable liposomes might be of potential use for the formulation of retinol and other lipophilic functional cosmetic compounds. [source] In-vitro and in-vivo studies of cefpirom using bile salts as absorption enhancersJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2003Yahya Mrestani ABSTRACT Cephalosporins have to be administered by injection because of the poor intestinal absorption of the orally delivered drugs. Because of the obvious drawbacks of drug delivery by injection, the development of alternatives with enhanced oral bioavailability is receiving much attention in pharmaceutical research. Cefpirom (Cp) is a new semi-synthetic amino-2-thiazolyl-methoxyimino cephalosporin that has been substituted in position 3 with a cyclopenteno-pyridinium group in order to create a zwitterionic compound. It exhibits highly hydrophilic properties, as shown from its extremely low partition coefficient, and therefore its lipophilicity was increased using bile salts. The effect of this on the partition coefficients determined in the n-octanol/buffer system was confirmed using an in-vitro transport model with artificial and biological membranes. The pharmacokinetic properties of Cp were investigated in rabbits after intraduodenal administration with and without bile salts. Furthermore, the physiological compatibility of the bile salts was investigated using active D-glucose transport. [source] Phosphatidylcholine Reverses Ethanol-Induced Increase in Transepithelial Endotoxin Permeability and Abolishes Transepithelial Leukocyte ActivationALCOHOLISM, Issue 3 2009Katja Mitzscherling Background:, Chronic alcohol abuse increases both intestinal bacterial overgrowth and intestinal permeability to macromolecules. Intestinal permeability of endotoxin, a component of the outer cell membrane of Gram-negative bacteria, plays a crucial role in the development of alcohol-induced liver disease (ALD). As impaired bile flow leads to endotoxemia and the bile component phosphatidylcholine (PC) is therapeutically active in ALD, we tested the hypothesis that conjugated primary bile salts (CPBS) and PC inhibit ethanol-enhanced transepithelial permeability of endotoxin and the subsequent transepithelial activation of human leukocytes. Methods:, For this purpose, we used a model in which intestinal epithelial cells (Caco-2) were basolaterally cocultivated with mononuclear leukocytes. Cells were challenged apically with endotoxin from Escherichia coli K12 and were incubated with or without the addition of CPBS (1.5 mM), PC (0.38 mM), pooled human bile (2%) in combination with ethanol (0 to 66 mM). Results:, Ethanol decreased integrity of intestinal epithelial cell monolayer and enhanced transepithelial permeability of endotoxin. Both the transepithelial permeability of endotoxin and the transepithelial stimulation of leukocytes were nearly completely abolished after the apical supplementation of PC with CPBS, but not by CPBS alone. Ethanol up to 66 mM was not able to reverse this effect. Conclusions:, A considerable part of the therapeutic and preventive effect of PC supplementation in ALD might result from a reduction of ethanol-enhanced permeability of endotoxin through the intestinal barrier. [source] Optimization of a gastrointestinal model applicable to the evaluation of bioaccessibility in fish feedsJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 7 2009Mariam Hamdan Abstract BACKGROUND: Although several types of in vitro digestibility assays have been applied to nutritional evaluation of feeds for aquatic organisms, all of them are based on the use of closed reactors and do not simulate the gastric phase of the digestion. Our objective was to evaluate the suitability of a gastrointestinal model based on the use of a digestion cell provided by a semi-permeable reaction chamber, which allows continuous removal of digestion products as they are produced. We tested the effects of some factors, like the inclusion of a gastric phase, reaction temperature or bile salts on the hydrolysis of feed proteins by fish enzymes. RESULTS: We found that the most suitable operational conditions to simulate the digestion process must include a short acid pre-digestion as well as the use of bile salts in the reaction mixture. Acid pre-digestion resulted in a significant increase in the liberation of amino acids which represented more than twice that measured when using a single phase. The addition of two bile salts (45 µmol L,1 sodium taurocholate + chenodesoxycolate) resulted in almost a threefold increase in the hydrolysis of feed protein. The use of the described open system also allows the evaluation of carbohydrate hydrolysis as well as determination of residual undigested matter, in a similar manner to that carried out in ruminants with the DAISY system. CONCLUSION: Results suggest the system can be a very suitable model for evaluation of bioaccessibility in fish feeds. Copyright © 2009 Society of Chemical Industry [source] Genetic cholestasis, causes and consequences for hepatobiliary transportLIVER INTERNATIONAL, Issue 5 2003Peter L. M. Jansen Abstract: Bile salts take part in an efficient enterohepatic circulation in which most of the secreted bile salts are reclaimed by absorption in the terminal ileum. In the liver, the sodium-dependent taurocholate transporter at the basolateral (sinusoidal) membrane and the bile salt export pump at the canalicular membrane mediate hepatic uptake and hepatobiliary secretion of bile salts. Canalicular secretion is the driving force for the enterohepatic cycling of bile salts and most genetic diseases are caused by defects of canalicular secretion. Impairment of bile flow leads to adaptive changes in the expression of transporter proteins and enzymes of the cytochrome P-450 system involved in the metabolism of cholesterol and bile acids. Bile salts act as ligands for transcription factors. As such, they stimulate or inhibit the transcription of genes encoding transporters and enzymes involved in their own metabolism. Together these changes appear to serve mainly a hepatoprotective function. Progressive familial intrahepatic cholestasis (PFIC) results from mutations in various genes encoding hepatobiliary transport proteins. Mutations in the FIC1 gene cause relapsing or permanent cholestasis. The relapsing type of cholestasis is called benign recurrent intrahepatic cholestasis, the permanent type of cholestasis PFIC type 1. PFIC type 2 results from mutations in the bile salt export pump (BSEP) gene. This is associated with permanent cholestasis since birth. Serum gamma-glutamyltransferase (gamma-GT) activity is low to normal in PFIC types 1 and 2. Bile diversion procedures, causing a decreased bile salt pool, have a beneficial effect in a number of patients with these diseases. However, liver transplantation is often necessary. PFIC type 3 is caused by mutations in the MDR3 gene. MDR3 is a phospholipid translocator in the canalicular membrane. Because of the inability to secrete phospholipids, patients with PFIC type 3 produce bile acid-rich toxic bile that damages the intrahepatic bile ducts. Serum gamma-GT activity is elevated in these patients. Ursodeoxycholic acid therapy is useful for patients with a partial defect. Liver transplantation is a more definitive therapy for these patients. [source] Role of hepatocytes and bile duct cells in preservation-reperfusion injury of liver graftsLIVER TRANSPLANTATION, Issue 5 2001Marián Kukan In liver transplantation, it is currently hypothesized that nonparenchymal cell damage and/or activation is the major cause of preservation-related graft injury. Because parenchymal cells (hepatocytes) appear morphologically well preserved even after extended cold preservation, their injury after warm reperfusion is ascribed to the consequences of nonparenchymal cell damage and/or activation. However, accumulating evidence over the past decade indicated that the current hypothesis cannot fully explain preservation-related liver graft injury. We review data obtained in animal and human liver transplantation and isolated perfused animal livers, as well as isolated cell models to highlight growing evidence of the importance of hepatocyte disturbances in the pathogenesis of normal and fatty graft injury. Particular attention is given to preservation time-dependent decreases in high-energy adenine nucleotide levels in liver cells, a circumstance that (1) sensitizes hepatocytes to various stimuli and insults, (2) correlates well with graft function after liver transplantation, and (3) may also underlie the preservation time-dependent increase in endothelial cell damage. We also review damage to bile duct cells, which is increasingly being recognized as important in the long-lasting phase of reperfusion injury. The role of hydrophobic bile salts in that context is particularly assessed. Finally, a number of avenues aimed at preserving hepatocyte and bile duct cell integrity are discussed in the context of liver transplantation therapy as a complement to reducing nonparenchymal cell damage and/or activation. [source] Decreased biliary excretion of tributylmethyl ammonium in cholestyramine pretreated rats due to reduced formation of ion-pair complexes with hepatic bile saltsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 9 2007M. K. Choi Abstract The hypothesis that higher molecular weight (MW) quaternary ammoniums (QAs) form lipophilic ion-pair complexes with bile salts in the liver, and are subsequently excreted into bile via a canalicular transporter, P-gp, was re-examined in the present study for its validity. The biliary excretion of tributylmethyl ammonium (TBuMA), a QA with a MW of 200, in bile salt-depleted rats was determined. Depletion was induced by a daily oral administration of a resin, cholestyramine, at a dose of 0.5,g/kg for 2 consecutive weeks, which decreased the concentration of total bile salts in the liver by 38%. When TBuMA was administered intravenously (12,µmol/kg) to these rats, the plasma level, area under the plasma concentration-time curve (AUC), systemic clearance (CL) and volume of distribution (Vss) of the compound remained unchanged, whereas bile flow (23.03 vs 16.94,µl/min, p<0.05) and biliary clearance (CLbile, 12.75 vs 5.34,ml/min/kg, p<0.01) were decreased significantly. These results implied the biliary clearance of TBuMA in rats with bile salt depletion was significantly decreased as a result of decreased ion-pair complexation of TBuMA. The above results are consistent with our hypothesis and the existence of a MW threshold (i.e. 200±50 for rats) for the biliary excretion of QAs. Copyright © 2007 John Wiley & Sons, Ltd. [source] Effects of bosentan, an endothelin receptor antagonist, on bile salt export pump and multidrug resistance,associated protein 2BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2007Yuji Mano Abstract The bile salt export pump (BSEP/Bsep/ABCB11) and multidrug resistance-associated protein 2 (MRP2/Mrp2/ABCC2) are involved in bile acid-dependent and -independent bile secretion, respectively. It has been reported that bosentan, an endothelin receptor antagonist, inhibits Bsep, which may lead to cholestatic liver injury due to the intracellular accumulation of bile salts, while increasing bile salt-independent bile flow. Thus, in this study, the effects of bosentan on BSEP/Bsep and MRP2/Mrp2 were evaluated using membrane vesicles derived from Spodoptera frugiperda (Sf) 9 cells, which express these transporters. The adenosine 5,-triphosphate (ATP)-dependent uptake of 3H-taurocholic acid into membrane vesicles for BSEP/Bsep was inhibited by bosentan, and its IC50 values were 76.8 and 101 µM for BSEP and Bsep, respectively. In contrast, bosentan stimulated the MRP2/Mrp2-mediated ATP-dependent vesicular transport of 3H-estradiol 17,-glucuronide by shifting the sigmoidal dependence of transport rate on substrate concentration to a more hyperbolic one. Collectively, these results suggest that bosentan inhibits BSEP in humans with a similar potency to rats, and that increased bile salt-independent flow in rats by bosentan is at least partly attributable to the activation of Mrp2. Copyright © 2006 John Wiley & Sons, Ltd. [source] Characterisation of Nanohybrids of Porphyrins with Metallic and Semiconducting Carbon Nanotubes by EPR and Optical SpectroscopyCHEMPHYSCHEM, Issue 13 2008Sofie Cambré Abstract Single-walled carbon nanotubes (SWCNTs) are noncovalently functionalised with octaethylporphyrins (OEPs) and the resulting nanohybrids are isolated from the free OEPs. Electron paramagnetic resonance (EPR) spectroscopy of cobalt(II)OEP, adsorbed on the nanotube walls by ,,,-stacking, demonstrates that the CNTs act as electron acceptors. EPR is shown to be very effective in resolving the different interactions for metallic and semiconducting tubes. Moreover, molecular oxygen is shown to bind selectively to nanohybrids with semiconducting tubes. Water solubilisation of the porphyrin/CNT nanohybrids using bile salts, after applying a thorough washing procedure, yields solutions in which at least 99,% of the porphyrins are interacting with the CNTs. Due to this purification, we observe, for the first time, the isolated absorption spectrum of the interacting porphyrins, which is strongly red-shifted compared to the free porphyrin absorption. In addition a quasi-complete quenching of the porphyrin fluorescence is also observed. [source] A review of the potential applications and controversies of non-invasive testing for biomarkers of aspiration in the lung transplant populationCLINICAL TRANSPLANTATION, Issue 3 2010C.S. Davis Davis CS, Gagermeier J, Dilling D, Alex C, Lowery E, Kovacs EJ, Love RB, Fisichella PM. A review of the potential applications and controversies of non-invasive testing for biomarkers of aspiration in the lung transplant population. Clin Transplant 2010: 24: E54,E61. © 2010 John Wiley & Sons A/S. Abstract:, Despite improvements in one-yr survival following lung transplantation, five-yr survival lags significantly behind the transplantation of other solid organs. The contrast in survival persists despite advancements in anti-rejection regimens, suggesting a non-alloimmune mechanism to chronic lung transplant failure. Notably, markers of aspiration have been demonstrated in bronchoalveolar lavage (BAL) fluid concurrent with bronchiolitis obliterans syndrome (BOS). This recent evidence has underscored gastroesophageal reflux (GER) and its associated aspiration risk as a non-alloimmune mechanism of chronic lung transplant failure. Given the suggested safety and efficacy of laparoscopic anti-reflux procedures in the lung transplant population, identifying those at risk for aspiration is of prime importance, especially concerning the potential for long-term improvements in morbidity and mortality. Conventional diagnostic methods for GER and aspiration, such as pH monitoring and detecting pepsin and bile salts in BAL fluid, have gaps in their effectiveness. Therefore, we review the applications and controversies of a non-invasive method of defining reflux injury in the lung transplant population: the detection of biomarkers of aspiration in the exhaled breath condensate. Only by means of assay standardization and directed collaboration may such a non-invasive method be a realization in lung transplantation. [source] | |||||||||||||||||||||||||||||||