Search

The association of unconjugated bilirubin (UCB) with amorphous calcium phosphate was studied in vitro. To this end UCB, solubilized in different micellar bile salt solutions, was incubated with freshly prepared calcium phosphate precipitate. It was demonstrated that amorphous calcium phosphate (ACP) rapidly binds and precipitates UCB in a dose-dependent way. The results indicate that binding of UCB to ACP is specific: binding to barium phosphate was negligible and addition of low amounts of Mg2+ before formation of the calcium phosphate precipitate (Ca:Mg = 5:1) inhibited binding by 80%. Free Ca2+ stimulated binding, whereas free phosphate ions inhibited binding of UCB in taurocholate solutions and to a lesser extent in glycocholate solutions. The apparent affinity of UCB for amorphous calcium phosphate was different in the various bile salt solutions. Binding of UCB decreased at pH > 8.5 in taurocholate solutions, but not in glycocholate solutions where binding of UCB was constant from pH 7.5-10.5. We propose a model in which UCB directly binds to amorphous calcium phosphate in the presence of bile salts that weakly interact with ACP, like taurocholate. In the presence of bile salts that strongly interact with ACP, such as glycochenodeoxycholate, binding of UCB may also occur via the bile salt. In conditions of unconjugated hyperbilirubinemia, such as the Crigler-Najjar syndrome, neonatal jaundice, and in the Gunn rat, considerable amounts of UCB diffuse across the intestinal mucosa. Binding of UCB to calcium phosphate in the intestine may stimulate its excretion and thereby constitute a relevant mechanism of excretion.

The association of unconjugated bilirubin (UCB) with amorphous calcium phosphate was studied in vitro. To this end UCB, solubilized in different micellar bile salt solutions, was incubated with freshly prepared calcium phosphate precipitate. It was demonstrated that amorphous calcium phosphate (ACP) rapidly binds and precipitates UCB in a dose-dependent way. The results indicate that binding of UCB to ACP is specific: binding to barium phosphate was negligible and addition of low amounts of Mg2+ before formation of the calcium phosphate precipitate (Ca:Mg = 5:1) inhibited binding by 80%. Free Ca2+ stimulated binding, whereas free phosphate ions inhibited binding of UCB in taurocholate solutions and to a lesser extent in glycocholate solutions. The apparent affinity of UCB for amorphous calcium phosphate was different in the various bile salt solutions. Binding of UCB decreased at pH > 8.5 in taurocholate solutions, but not in glycocholate solutions where binding of UCB was constant from pH 7.5-10.5. We propose a model in which UCB directly binds to amorphous calcium phosphate in the presence of bile salts that weakly interact with ACP, like taurocholate. In the presence of bile salts that strongly interact with ACP, such as glycochenodeoxycholate, binding of UCB may also occur via the bile salt. In conditions of unconjugated hyperbilirubinemia, such as the Crigler-Najjar syndrome, neonatal jaundice, and in the Gunn rat, considerable amounts of UCB diffuse across the intestinal mucosa. Binding of UCB to calcium phosphate in the intestine may stimulate its excretion and thereby constitute a relevant mechanism of excretion.

Nutritional factors are important determinants of colorectal cancer risk. Diets high in fat and/or low in fibre are especially recognised to increase risk. Dietary calcium and vitamin D have been suggested to be protective against colorectal cancer. With respect to calcium, its possible effect is thought to be mediated at least in part through intraluminal precipitation of hydrophobic, cytotoxic substances, in particular fatty and bile acids, which can promote colorectal cancer development. Data from studies in vitro and in animals support a protective effect of calcium, but studies in humans, both epidemiological and interventional, have given inconclusive results. With respect to vitamin D, data from only a small number of studies are available. Results suggest a protective effect by inhibition of cell proliferation, mediated through specific receptors. It is concluded that there are currently insufficient reasons to supplement subjects at increased colon cancer risk with calcium or vitamin D, especially when dietary intake of these substances is in agreement with general guidelines.

Nutritional factors are important determinants of colorectal cancer risk. Diets high in fat and/or low in fibre are especially recognised to increase risk. Dietary calcium and vitamin D have been suggested to be protective against colorectal cancer. With respect to calcium, its possible effect is thought to be mediated at least in part through intraluminal precipitation of hydrophobic, cytotoxic substances, in particular fatty and bile acids, which can promote colorectal cancer development. Data from studies in vitro and in animals support a protective effect of calcium, but studies in humans, both epidemiological and interventional, have given inconclusive results. With respect to vitamin D, data from only a small number of studies are available. Results suggest a protective effect by inhibition of cell proliferation, mediated through specific receptors. It is concluded that there are currently insufficient reasons to supplement subjects at increased colon cancer risk with calcium or vitamin D, especially when dietary intake of these substances is in agreement with general guidelines.

Diet is a major determinant of colon cancer risk. Calcium may protect against colon cancer, presumably by binding cytotoxic bile acids and fatty acids. Numerous studies support this proposition. In subjects at risk for colon cancer oral calcium supplementation has been shown to reduce rectal epithelial proliferation rate, thereby supposedly decreasing cancer risk. In contrast to the original hypothesis that phosphate counteracts the effect of calcium, evidence has now been provided that phosphate is crucial for the intraluminal binding of bile acids in complexes of calcium, phosphate, and bile acids. Supplemental calcium has been shown to reduce the cytotoxic potential of fecal water, which is probably attributable to the profound effect of calcium on bile acid and fatty acid metabolism. However, some reservation with regard to the protective ability of calcium seems to be warranted as we found that oral calcium supplementation caused an increase in epithelial proliferation rate in the sigmoid of patients with adenomatous polyps. Further controlled studies evaluating the effects of calcium on the epithelium of different parts of the colon should now be performed.

Diet is a major determinant of colon cancer risk. Calcium may protect against colon cancer, presumably by binding cytotoxic bile acids and fatty acids. Numerous studies support this proposition. In subjects at risk for colon cancer oral calcium supplementation has been shown to reduce rectal epithelial proliferation rate, thereby supposedly decreasing cancer risk. In contrast to the original hypothesis that phosphate counteracts the effect of calcium, evidence has now been provided that phosphate is crucial for the intraluminal binding of bile acids in complexes of calcium, phosphate, and bile acids. Supplemental calcium has been shown to reduce the cytotoxic potential of fecal water, which is probably attributable to the profound effect of calcium on bile acid and fatty acid metabolism. However, some reservation with regard to the protective ability of calcium seems to be warranted as we found that oral calcium supplementation caused an increase in epithelial proliferation rate in the sigmoid of patients with adenomatous polyps. Further controlled studies evaluating the effects of calcium on the epithelium of different parts of the colon should now be performed.

Diet is a major determinant of colon cancer risk. Calcium may protect against colon cancer, presumably by binding cytotoxic bile acids and fatty acids. Numerous studies support this proposition. In subjects at risk for colon cancer oral calcium supplementation has been shown to reduce rectal epithelial proliferation rate, thereby supposedly decreasing cancer risk. In contrast to the original hypothesis that phosphate counteracts the effect of calcium, evidence has now been provided that phosphate is crucial for the intraluminal binding of bile acids in complexes of calcium, phosphate, and bile acids. Supplemental calcium has been shown to reduce the cytotoxic potential of fecal water, which is probably attributable to the profound effect of calcium on bile acid and fatty acid metabolism. However, some reservation with regard to the protective ability of calcium seems to be warranted as we found that oral calcium supplementation caused an increase in epithelial proliferation rate in the sigmoid of patients with adenomatous polyps. Further controlled studies evaluating the effects of calcium on the epithelium of different parts of the colon should now be performed.

The association of unconjugated bilirubin (UCB) with amorphous calcium phosphate was studied in vitro. To this end UCB, solubilized in different micellar bile salt solutions, was incubated with freshly prepared calcium phosphate precipitate. It was demonstrated that amorphous calcium phosphate (ACP) rapidly binds and precipitates UCB in a dose-dependent way. The results indicate that binding of UCB to ACP is specific: binding to barium phosphate was negligible and addition of low amounts of Mg2+ before formation of the calcium phosphate precipitate (Ca:Mg = 5:1) inhibited binding by 80%. Free Ca2+ stimulated binding, whereas free phosphate ions inhibited binding of UCB in taurocholate solutions and to a lesser extent in glycocholate solutions. The apparent affinity of UCB for amorphous calcium phosphate was different in the various bile salt solutions. Binding of UCB decreased at pH > 8.5 in taurocholate solutions, but not in glycocholate solutions where binding of UCB was constant from pH 7.5-10.5. We propose a model in which UCB directly binds to amorphous calcium phosphate in the presence of bile salts that weakly interact with ACP, like taurocholate. In the presence of bile salts that strongly interact with ACP, such as glycochenodeoxycholate, binding of UCB may also occur via the bile salt. In conditions of unconjugated hyperbilirubinemia, such as the Crigler-Najjar syndrome, neonatal jaundice, and in the Gunn rat, considerable amounts of UCB diffuse across the intestinal mucosa. Binding of UCB to calcium phosphate in the intestine may stimulate its excretion and thereby constitute a relevant mechanism of excretion.

Nutritional factors are important determinants of colorectal cancer risk. Diets high in fat and/or low in fibre are especially recognised to increase risk. Dietary calcium and vitamin D have been suggested to be protective against colorectal cancer. With respect to calcium, its possible effect is thought to be mediated at least in part through intraluminal precipitation of hydrophobic, cytotoxic substances, in particular fatty and bile acids, which can promote colorectal cancer development. Data from studies in vitro and in animals support a protective effect of calcium, but studies in humans, both epidemiological and interventional, have given inconclusive results. With respect to vitamin D, data from only a small number of studies are available. Results suggest a protective effect by inhibition of cell proliferation, mediated through specific receptors. It is concluded that there are currently insufficient reasons to supplement subjects at increased colon cancer risk with calcium or vitamin D, especially when dietary intake of these substances is in agreement with general guidelines.