Effect of anions or foods on absolute bioavailability of calcium from calcium salts in mice by pharmacokinetics

PubMed Central

Ueda, Yukari; Taira, Zenei

2013-01-01

We studied the absolute bioavailability of calcium from calcium L-lactate in mice using pharmacokinetics, and reviewed the absolute bioavailability of calcium from three other calcium salts in mice previously studied: calcium chloride, calcium acetate, and calcium ascorbate. The results showed that calcium metabolism is linear between intravenous administration of 15 mg/kg and 30 mg/kg, and is not affected by anions. Results after oral calcium administration of 150 mg/kg showed that the intestinal absorption process was significantly different among the four calcium salts. The rank of absolute bioavailability of calcium was calcium ascorbate > calcium L-lactate ≥ calcium acetate > calcium chloride. The mean residence time (MRTab) of calcium from calcium ascorbate (32.2 minutes) in the intestinal tract was much longer than that from calcium L-lactate (9.5 minutes), calcium acetate (15.0 minutes) and calcium chloride (13.6 minutes). Furthermore, the foods di-D-fructo-furanose-1,2′:2,3′-dianhydride, sudachi (Citrus sudachi) juice, and moromi-su (a Japanese vinegar) increased the absolute bioavailability of calcium from calcium chloride by 2.46-fold, 2.86-fold, and 1.23-fold, respectively, and prolonged MRTab by 48.5 minutes, 43.1 minutes, and 44.9 minutes, respectively. In conclusion, the prolonged MRTab of calcium in the intestinal tract by anion or food might cause the increased absorbability of calcium. PMID:27186137

Evidence that low plasma 1,25-dihydroxyvitamin D causes intestinal malabsorption of calcium and phosphate in juvenile X-linked hypophosphatemic mice.

PubMed

Meyer, R A; Meyer, M H; Gray, R W; Bruns, M E

1987-02-01

X-linked hypophosphatemic (Hyp) mice are a model for human sex-linked vitamin D-resistant rickets. We have reported intestinal malabsorption of calcium in young Hyp mice, and in this report we have explored the mechanism for it. To test for resistance of the intestine to 1,25(OH)2 vitamin D3, this hormone was continually infused via osmotic minipumps into 4-week-old normal and Hyp mice at 0, 17, 50 or 150 ng/kg/day. After 3 days, 45Ca and inorganic 32P were administered by gavage, and the mice were sacrificed on the fifth day. The Hyp mice showed responses to the hormone equivalent to the normal mice in terms of increased intestinal absorption of both 45Ca and 32P, increased plasma isotope levels, increased femoral isotope content, and increased duodenal and renal 9 kD vitamin D-dependent calcium-binding protein (calbindin-D9K; CaBP). Plasma 1,25(OH)2D was measured in these mice. There were significant correlations of plasma 1,25(OH)2D to the intestinal absorption of 45Ca and 32P and to duodenal and renal CaBP. Plasma 1,25(OH)2D was also measured in stock normal and Hyp mice and was found to be lower in 4-week-old Hyp mice than in 4-week-old normal mice (113 +/- 10 pM (n = 18) vs. 67 +/- 10 (n = 20), normal vs. Hyp, p less than .01), but unchanged at 13 weeks of age (77 +/- 13 (n = 13) vs. 70 +/- 15 (n = 15), NS). This observed difference in plasma 1,25(OH)2D between normal and Hyp mice at 4 weeks of age was sufficient to explain the observed normal-to-Hyp differences in intestinal absorption of 45Ca and duodenal and renal CaBP. It also explained 72 +/- 18% of the observed difference in 32P absorption. We conclude that Hyp mouse intestine is not resistant to 1,25(OH)2D and that the lower plasma 1,25(OH)2D of 4-week-old Hyp mice causes intestinal malabsorption of calcium and phosphate.

Increased intracellular calcium level and impaired nutrient absorption are important pathogenicity traits in the chicken intestinal epithelium during Campylobacter jejuni colonization.

PubMed

Awad, Wageha A; Smorodchenko, Alina; Hess, Claudia; Aschenbach, Jörg R; Molnár, Andor; Dublecz, Károly; Khayal, Basel; Pohl, Elena E; Hess, Michael

2015-08-01

Although a high number of chickens carry Campylobacter jejuni, the mechanistic action of colonization in the intestine is still poorly understood. The current study was therefore designed to investigate the effects of C. jejuni on glucose uptake, amino acids availability in digesta, and intracellular calcium [Ca(2+)]i signaling in the intestines of broiler chickens. For this, we compared: control birds (n = 60) and C. jejuni-infected birds (n = 60; infected orally with 1 × 10(8) CFU of C. jejuni NCTC 12744 at 14 days of age). Our results showed that glucose uptake was reduced due to C. jejuni infection in isolated jejunal, but not in cecal mucosa at 14 days postinfection (dpi). The decrease in intestinal glucose absorption coincided with a decrease in body weight gain during the 2-week post-infectious period. A reduction in the amount of the amino acids (serine, proline, valine, leucine, phenylalanine, arginine, histidine, and lysine) in ileal digesta of the infected birds at 2 and/or 7 dpi was found, indicating that Campylobacter utilizes amino acids as a carbon source for their multiplication. Applying the cell-permeable Ca(2+) indicator Fluo-4 and two-photon microscopy, we revealed that [Ca(2+)]i was increased in the jejunal and cecal mucosa of infected birds. The muscarinic agonist carbachol induced an increase in [Ca(2+)]i in jejunum and cecum mucosa of control chickens, a response absent in the mucosa of infected chickens, demonstrating that the modulation of [Ca(2+)]i by Campylobacter might be involved in facilitating the necessary cytoskeletal rearrangements that occur during the bacterial invasion of epithelial cells. In conclusion, this study demonstrates the multifaceted interactions of C. jejuni with the gastrointestinal mucosa of broiler chickens. For the first time, it could be shown that a Campylobacter infection could interfere with intracellular Ca(2+) signaling and nutrient absorption in the small intestine with consequences on

Calcium glycerophosphate preserves transepithelial integrity in the Caco-2 model of intestinal transport.

PubMed

Datta, Palika; Weis, Margaret T

2015-08-14

To assess the direct effects of ischemia on intestinal epithelial integrity. Furthermore, clinical efforts at mitigating the effect of hypoperfusion on gut permeability have focused on restoring gut vascular function. We report that, in the Caco-2 cell model of transepithelial transport, calcium glycerophosphate (CGP), an inhibitor of intestinal alkaline phosphatase F3, has a significant effect to preserve transepithelial electrical resistance (TEER) and to attenuate increases in mannitol flux rates during hypoxia or cytokine stimulation. The effect was observable even at concentrations as low as 1 μmol/L. As celiac disease is also marked by a loss of gut epithelial integrity, the effect of CGP to attenuate the effect of the α-gliadin peptide 31-55 was also examined. In this instance, CGP exerted little effect of preservation of TEER, but significantly attenuated peptide induced increase in mannitol flux. It appears that CGP treatment might synergize with other therapies to preserve gut epithelial integrity.

Calcium glycerophosphate preserves transepithelial integrity in the Caco-2 model of intestinal transport

PubMed Central

Datta, Palika; Weis, Margaret T

2015-01-01

AIM: To assess the direct effects of ischemia on intestinal epithelial integrity. Furthermore, clinical efforts at mitigating the effect of hypoperfusion on gut permeability have focused on restoring gut vascular function. METHODS: We report that, in the Caco-2 cell model of transepithelial transport, calcium glycerophosphate (CGP), an inhibitor of intestinal alkaline phosphatase F3, has a significant effect to preserve transepithelial electrical resistance (TEER) and to attenuate increases in mannitol flux rates during hypoxia or cytokine stimulation. RESULTS: The effect was observable even at concentrations as low as 1 μmol/L. As celiac disease is also marked by a loss of gut epithelial integrity, the effect of CGP to attenuate the effect of the α-gliadin peptide 31-55 was also examined. In this instance, CGP exerted little effect of preservation of TEER, but significantly attenuated peptide induced increase in mannitol flux. CONCLUSION: It appears that CGP treatment might synergize with other therapies to preserve gut epithelial integrity. PMID:26290632

Investigation of the effects of vitamin D and calcium on intestinal motility: In vitro tests and implications for clinical treatment.

PubMed

Giraldi, Guglielmo; Fioravanti, Angelo; De Luca d'Alessandro, Eugenia; Palmery, Maura; Martinoli, Lucia

2015-09-01

The presence of vitamin D receptors in small intestine muscle cells may lead one to think that vitamin D may act locally, influencing intracellular calcium concentration and contributing to the contraction-relaxation regulation of the intestinal smooth muscle cells. This study investigates the potential effects of vitamin D and calcium on intestinal motility using an in vitro test. Different calcium concentrations added to the tissue not pre-treated with 1,25-dihydroxycholecalciferol [1α,25(OH)2D3] produced no response at low doses (1.25 × 10-3 and 2.0 × 10-3 mol L-1) and only a very weak response at higher concentration (3.0 × 10-3 mol L-1). The addition of 1α,25(OH)2D3 (1.44 × 10-10 mol L-1) had no effect on isolated ileum motility. When calcium (3.0 × 10-3 mol L-1) was added after at least 3 hours, it evoked evident and persistent contractions for 60-90 minutes. The contractions were at about 40 % of the peak produced by acetylcholine. Thus, simultaneous intake of vitamin D and calcium might be a useful co-adjuvant in intestinal atony therapy aimed to stimulate normal gut motility in humans. These findings imply that supplemental vitamin D may be important in all cases where calcium has to be prescribed.

Deletion of the Intestinal Plasma Membrane Calcium Pump, Isoform 1, Atp2b1, in Mice is Associated with Decreased Bone Mineral Density and Impaired Responsiveness to 1, 25-Dihydroxyvitamin D3

PubMed Central

Ryan, Zachary C.; Craig, Theodore A.; Filoteo, Adelaida G.; Westendorf, Jennifer J.; Cartwright, Elizabeth J.; Neyses, Ludwig; Strehler, Emanuel E.; Kumar, Rajiv

2016-01-01

The physiological importance of the intestinal plasma membrane calcium pump, isoform 1, (Pmca1, Atp2b1), in calcium absorption and homeostasis has not been previously demonstrated in vivo. Since global germ-line deletion of the Pmca1 in mice is associated with embryonic lethality, we selectively deleted the Pmca1 in intestinal absorptive cells. Mice with loxP sites flanking exon 2 of the Pmca1 gene (Pmca1fl/fl) were crossed with mice expressing Cre recombinase in the intestine under control of the villin promoter to give mice in which the Pmca1 had been deleted in the intestine (Pmca1EKO mice). Pmca1EKO mice were born at a reduced frequency and were small at the time of birth when compared to wild-type (Wt) litter mates. At two months of age, Pmca1EKO mice fed a 0.81% calcium, 0.34% phosphorus, normal vitamin D diet had reduced whole body bone mineral density (P <0.037), and reduced femoral bone mineral density (P <0.015). There was a trend towards lower serum calcium and higher serum parathyroid hormone (PTH) and 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) concentrations in Pmca1EKO mice compared to Wt mice but the changes were not statistically significant. The urinary phosphorus/creatinine ratio was increased in Pmca1EKO mice (P <0.004). Following the administration of 200 ng of 1α,25(OH)2D3 intraperitoneally to Wt mice, active intestinal calcium transport increased ∼2-fold, whereas Pmca1EKO mice administered an equal amount of 1α,25(OH)2D3 failed to show an increase in active calcium transport. Deletion of the Pmca1 in the intestine is associated with reduced growth and bone mineralization, and a failure to up-regulate calcium absorption in response to 1α,25(OH)2D3. PMID:26392310

Dietary protein, calcium metabolism, and skeletal homeostasis revisited.

PubMed

Kerstetter, Jane E; O'Brien, Kimberly O; Insogna, Karl L

2003-09-01

High dietary protein intakes are known to increase urinary calcium excretion and, if maintained, will result in sustained hypercalciuria. To date, the majority of calcium balance studies in humans have not detected an effect of dietary protein on intestinal calcium absorption or serum parathyroid hormone. Therefore, it is commonly concluded that the source of the excess urinary calcium is increased bone resorption. Recent studies from our laboratory indicate that alterations in dietary protein can, in fact, profoundly affect intestinal calcium absorption. In short-term dietary trials in healthy adults, we fixed calcium intake at 20 mmol/d while dietary protein was increased from 0.7 to 2.1 g/kg. Increasing dietary protein induced hypercalciuria in 20 women [from 3.4 +/- 0.3 ( +/- SE) during the low-protein to 5.4 +/- 0.4 mmol/d during the high-protein diet]. The increased dietary protein was accompanied by a significant increase in intestinal calcium absorption from 18.4 +/- 1.3% to 26.3 +/- 1.5% (as determined by dual stable isotopic methodology). Dietary protein intakes at and below 0.8 g/kg were associated with a probable reduction in intestinal calcium absorption sufficient to cause secondary hyperparathyroidism. The long-term consequences of these low-protein diet-induced changes in mineral metabolism are not known, but the diet could be detrimental to skeletal health. Of concern are several recent epidemiologic studies that demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low-protein diets. Studies are needed to determine whether low protein intakes directly affect rates of bone resorption, bone formation, or both.

Identification and quantitive analysis of calcium phosphate microparticles in intestinal tissue by nuclear microscopy

NASA Astrophysics Data System (ADS)

Gomez-Morilla, Inmaculada; Thoree, Vinay; Powell, Jonathan J.; Kirkby, Karen J.; Grime, Geoffrey W.

2006-08-01

Microscopic particles (0.5-2 μm diameter), rich in calcium and phosphorus, are found in the lumen of the mid-distal gut of all mammals investigated, including humans, and these may play a role in immuno-surveillance and immune regulation of antigens from food and symbiotic bacteria that are contained in the gut. Whether these particles can cross in to tissue of the intestinal mucosa is unclear. If so, characterising their morphology and chemical composition is an important task in elucidating their function. The analysis of calcium phosphate in biological tissues has been approached in several ways including optical microscopy, scanning electron microscopy and, most recently in this work, with nuclear microscopy. In this paper, we describe the use of microPIXE and microRBS to locate these particles and to determine, accurately, the ratio of phosphorus to calcium using the information on sample thickness obtained from RBS to allow the PIXE ratios to be corrected. A commercial sample of hydroxy apatite was used to demonstrate accuracy and precision of the technique. Then, in a pilot study on intestinal tissue of mice, we demonstrated the presence of calcium phosphate microparticles, consistent with confocal microscopy observations, and we identified the average molar P:Ca molar ratio as 1.0. Further work will confirm the exact chemical speciation of these particles and will examine the influence of differing calcium containing diets on the formation of these microparticles.

Simple test of intestinal calcium absorption measured by stable strontium.

PubMed Central

Milsom, S; Ibbertson, K; Hannan, S; Shaw, D; Pybus, J

1987-01-01

A clinical test of intestinal calcium absorption has been developed using non-radioactive stable strontium as a calcium tracer. In nine elderly subjects there was a close correlation between the fractional absorption of strontium and radioactive calcium (45Ca) during a five hour period after the simultaneous oral administration of the two tracers. Comparable precision was achieved with each tracer in six subjects in whom the test was repeated after two weeks. The effect of food on strontium absorption was examined in a further 33 normal subjects (age 21-60 years), and the administration of the strontium with a standard breakfast was shown to reduce the variance at individual time points. A simplified test in which serum strontium concentration was measured four hours after the oral dose given with a standard breakfast was adopted as the routine procedure. The normal range (mean (2 SD], established over 97 tests in 53 patients, was 7.0-18.0% of the dose in the extracellular fluid. A further 30 patients with possible disorders of calcium absorption (10 with primary hyperparathyroidism and 20 with coeliac disease) were studied by this standard test. In both groups of patients the mean four hour strontium values were significantly different from normal. This standard strontium absorption test allows assessment of calcium absorption with sufficient sensitivity and precision to have a wide application in clinical practice. PMID:3115389

1,25-Dihydroxyvitamin D3 Controls a Cohort of Vitamin D Receptor Target Genes in the Proximal Intestine That Is Enriched for Calcium-regulating Components*

PubMed Central

Lee, Seong Min; Riley, Erin M.; Meyer, Mark B.; Benkusky, Nancy A.; Plum, Lori A.; DeLuca, Hector F.; Pike, J. Wesley

2015-01-01

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) plays an integral role in calcium homeostasis in higher organisms through its actions in the intestine, kidney, and skeleton. Interestingly, although several intestinal genes are known to play a contributory role in calcium homeostasis, the entire caste of key components remains to be identified. To examine this issue, Cyp27b1 null mice on either a normal or a high calcium/phosphate-containing rescue diet were treated with vehicle or 1,25(OH)2D3 and evaluated 6 h later. RNA samples from the duodena were then subjected to RNA sequence analysis, and the data were analyzed bioinformatically. 1,25(OH)2D3 altered expression of large collections of genes in animals under either dietary condition. 45 genes were found common to both 1,25(OH)2D3-treated groups and were composed of genes previously linked to intestinal calcium uptake, including S100g, Trpv6, Atp2b1, and Cldn2 as well as others. An additional distinct network of 56 genes was regulated exclusively by diet. We then conducted a ChIP sequence analysis of binding sites for the vitamin D receptor (VDR) across the proximal intestine in vitamin D-sufficient normal mice treated with vehicle or 1,25(OH)2D3. The residual VDR cistrome was composed of 4617 sites, which was increased almost 4-fold following hormone treatment. Interestingly, the majority of the genes regulated by 1,25(OH)2D3 in each diet group as well as those found in common in both groups contained frequent VDR sites that likely regulated their expression. This study revealed a global network of genes in the intestine that both represent direct targets of vitamin D action in mice and are involved in calcium absorption. PMID:26041780

Effect of cortisone treatment on the active transport of calcium by the small intestine.

PubMed

Kimberg, D V; Baerg, R D; Gershon, E; Graudusius, R T

1971-06-01

It is generally recognized that glucocorticoid administration may diminish calcium absorption in vivo as well as the active transport of calcium by the intestine in vitro. Recent studies by others have emphasized the possibility of an alteration in the metabolism of vitamin D to 25-hydroxycholecalciferol in accounting for the steroid effects on calcium absorption. The results obtained in the present studies fail to support this hypothesis. The present studies confirm that the administration of cortisone or other glucocorticoids to the rat interferes with the active transport of calcium by duodenal gut sacs in vitro. This abnormality is not due to an alteration in the permeability of the intestine to calcium, and it cannot be corrected by the administration of either massive doses of vitamin D(2) or modest doses of 25-hydroxycholecalciferol. Experiments concerned with the effects of cortisone on the level of the vitamin D-dependent duodenal calcium-binding protein, the amount of bioassayable vitamin D activity in the mucosa, and the distribution and metabolism of (3)H-vitamin D(3), did not provide evidence in favor of a harmone-related defect in either the localization of vitamin D or its metabolism to 25-hydroxycholecalciferol. Alterations in the transport of iron and D-galactose, not dependent on vitamin D, suggest that cortisone treatment may be responsible for more than a simple antagonism to the effects of vitamin D. The results of the present studies indicate that cortisone administration affects the cellular mechanisms mediating calcium transport in a manner that is opposite to the effects of vitamin D, but seems to be independent of any direct interaction with the parent vitamin or its metabolites. If a disorder in vitamin D metabolism is at all involved, it is at a step subsequent to 25-hydroxylation.

Intra-Amniotic Administration (Gallus gallus) of Cicer arietinum and Lens culinaris Prebiotics Extracts and Duck Egg White Peptides Affects Calcium Status and Intestinal Functionality

PubMed Central

Hou, Tao; Glahn, Raymond P.; Tako, Elad

2017-01-01

Calcium (Ca) is one of the most abundant inorganic elements in the human body and has many important physiological roles. Prebiotics and bioactive peptides are two important substances used to promote calcium uptake. However, the difference in mechanisms of the calcium uptake from these two supplements is not clear. By using the Gallus gallus model and the intra-amniotic administration procedure, the aim of this study was to investigate whether Ca status, intestinal functionality, and health-promoting bacterial populations were affected by prebiotics extracted from chickpea and lentil, and duck egg white peptides (DPs). Eleven groups (non-injected; 18 MΩ H2O; 4 mmol/L CaCl2; 50 mg/mL chickpea + 4 mmol/L CaCl2; 50 mg/mL lentil + 4 mmol/L CaCl2; 40 mg/mL DPs + 4 mmol/L CaCl2; 5 mg/mL Val-Ser-Glu-Glu (VSEE) + 4 mmol/L CaCl2; 50 mg/mL chickpea; 50 mg/mL lentil; 40 mg/mL DPs; 5 mg/mL VSEE) were utilized. Upon hatch, blood, cecum, small intestine, liver and bone were collected for assessment of serum bone alkaline phosphate level (BALP), the relative abundance of intestinal microflora, expression of Ca-related genes, brush border membrane (BBM) functional genes, and liver and bone mineral levels, respectively. The BALP level increased in the presence of lentil, DPs and VSEE (p < 0.05). The relative abundance of probiotics increased significantly (p < 0.05) by VSEE + Ca and chickpea. The expression of CalbindinD9k (Ca transporter) increased (p < 0.05) in Ca, chickpea + Ca and lentil + Ca groups. In addition, the brush border membrane functionality genes expressions increased (p < 0.05) by the chickpea or lentil extracts. Prebiotics and DPs beneficially affected the intestinal microflora and duodenal villus surface area. This research expands the understanding of the prebiotics’ properties of chickpea and lentil extracts, and peptides’ effects on calcium metabolism and gut health. PMID:28754012

Intra-Amniotic Administration (Gallus gallus) of Cicer arietinum and Lens culinaris Prebiotics Extracts and Duck Egg White Peptides Affects Calcium Status and Intestinal Functionality.

PubMed

Hou, Tao; Kolba, Nikolai; Glahn, Raymond P; Tako, Elad

2017-07-21

Calcium (Ca) is one of the most abundant inorganic elements in the human body and has many important physiological roles. Prebiotics and bioactive peptides are two important substances used to promote calcium uptake. However, the difference in mechanisms of the calcium uptake from these two supplements is not clear. By using the Gallus gallus model and the intra-amniotic administration procedure, the aim of this study was to investigate whether Ca status, intestinal functionality, and health-promoting bacterial populations were affected by prebiotics extracted from chickpea and lentil, and duck egg white peptides (DPs). Eleven groups (non-injected; 18 MΩ H₂O; 4 mmol/L CaCl₂; 50 mg/mL chickpea + 4 mmol/L CaCl₂; 50 mg/mL lentil + 4 mmol/L CaCl₂; 40 mg/mL DPs + 4 mmol/L CaCl₂; 5 mg/mL Val-Ser-Glu-Glu (VSEE) + 4 mmol/L CaCl₂; 50 mg/mL chickpea; 50 mg/mL lentil; 40 mg/mL DPs; 5 mg/mL VSEE) were utilized. Upon hatch, blood, cecum, small intestine, liver and bone were collected for assessment of serum bone alkaline phosphate level (BALP), the relative abundance of intestinal microflora, expression of Ca-related genes, brush border membrane (BBM) functional genes, and liver and bone mineral levels, respectively. The BALP level increased in the presence of lentil, DPs and VSEE ( p < 0.05). The relative abundance of probiotics increased significantly ( p < 0.05) by VSEE + Ca and chickpea. The expression of CalbindinD9k (Ca transporter) increased ( p < 0.05) in Ca, chickpea + Ca and lentil + Ca groups. In addition, the brush border membrane functionality genes expressions increased ( p < 0.05) by the chickpea or lentil extracts. Prebiotics and DPs beneficially affected the intestinal microflora and duodenal villus surface area. This research expands the understanding of the prebiotics' properties of chickpea and lentil extracts, and peptides' effects on calcium metabolism and gut health.

1,25-Dihydroxyvitamin D3 Controls a Cohort of Vitamin D Receptor Target Genes in the Proximal Intestine That Is Enriched for Calcium-regulating Components.

PubMed

Lee, Seong Min; Riley, Erin M; Meyer, Mark B; Benkusky, Nancy A; Plum, Lori A; DeLuca, Hector F; Pike, J Wesley

2015-07-17

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) plays an integral role in calcium homeostasis in higher organisms through its actions in the intestine, kidney, and skeleton. Interestingly, although several intestinal genes are known to play a contributory role in calcium homeostasis, the entire caste of key components remains to be identified. To examine this issue, Cyp27b1 null mice on either a normal or a high calcium/phosphate-containing rescue diet were treated with vehicle or 1,25(OH)2D3 and evaluated 6 h later. RNA samples from the duodena were then subjected to RNA sequence analysis, and the data were analyzed bioinformatically. 1,25(OH)2D3 altered expression of large collections of genes in animals under either dietary condition. 45 genes were found common to both 1,25(OH)2D3-treated groups and were composed of genes previously linked to intestinal calcium uptake, including S100g, Trpv6, Atp2b1, and Cldn2 as well as others. An additional distinct network of 56 genes was regulated exclusively by diet. We then conducted a ChIP sequence analysis of binding sites for the vitamin D receptor (VDR) across the proximal intestine in vitamin D-sufficient normal mice treated with vehicle or 1,25(OH)2D3. The residual VDR cistrome was composed of 4617 sites, which was increased almost 4-fold following hormone treatment. Interestingly, the majority of the genes regulated by 1,25(OH)2D3 in each diet group as well as those found in common in both groups contained frequent VDR sites that likely regulated their expression. This study revealed a global network of genes in the intestine that both represent direct targets of vitamin D action in mice and are involved in calcium absorption. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Derangement of calcium metabolism in diabetes mellitus: negative outcome from the synergy between impaired bone turnover and intestinal calcium absorption.

PubMed

Wongdee, Kannikar; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

2017-01-01

Both types 1 and 2 diabetes mellitus (T1DM and T2DM) are associated with profound deterioration of calcium and bone metabolism, partly from impaired intestinal calcium absorption, leading to a reduction in calcium uptake into the body. T1DM is associated with low bone mineral density (BMD) and osteoporosis, whereas the skeletal changes in T2DM are variable, ranging from normal to increased and to decreased BMD. However, both types of DM eventually compromise bone quality through production of advanced glycation end products and misalignment of collagen fibrils (so-called matrix failure), thereby culminating in a reduction of bone strength. The underlying cellular mechanisms (cellular failure) are related to suppression of osteoblast-induced bone formation and bone calcium accretion, as well as to enhancement of osteoclast-induced bone resorption. Several other T2DM-related pathophysiological changes, e.g., osteoblast insulin resistance, impaired productions of osteogenic growth factors (particularly insulin-like growth factor 1 and bone morphogenetic proteins), overproduction of pro-inflammatory cytokines, hyperglycemia, and dyslipidemia, also aggravate diabetic osteopathy. In the kidney, DM and the resultant hyperglycemia lead to calciuresis and hypercalciuria in both humans and rodents. Furthermore, DM causes deranged functions of endocrine factors related to mineral metabolism, e.g., parathyroid hormone, 1,25-dihydroxyvitamin D 3 , and fibroblast growth factor-23. Despite the wealth of information regarding impaired bone remodeling in DM, the long-lasting effects of DM on calcium metabolism in young growing individuals, pregnant women, and neonates born to women with gestational DM have received scant attention, and their underlying mechanisms are almost unknown and worth exploring.

Intestinal absorption of calcium from calcium ascorbate in rats.

PubMed

Tsugawa, N; Yamabe, T; Takeuchi, A; Kamao, M; Nakagawa, K; Nishijima, K; Okano, T

1999-01-01

The intestinal absorption of calcium (Ca) from Ca ascorbate (Ca-AsA) was investigated in normal rats. Each animal was perorally administered either 5mg (low dose) or 10mg (high dose) of Ca in 1ml of distilled water as Ca-AsA, Ca carbonate (CaCO3), or Ca chloride (CaCl2), which were intrinsically labeled with 45Ca using 45CaCl2. The amount of radioactivity in plasma was measured periodically up to 34h after dosing, and pharmacokinetic parameters were calculated from the radioactivity in plasma. The time taken to reach the maximum 45Ca level (Tmax) did not differ among the three groups. The area under the plasma 45Ca level/time curve (AUCinfinity) value for the Ca-AsA group was significantly higher than those for the CaCO3 and the CaCl2 groups. The radioactivity at Tmax (Cmax) for the Ca-AsA group was significantly higher than those for the CaCO3 and the CaCl2 groups for the low dose, and comparable with or significantly higher than those for the CaCl2 and CaCO3 groups for the high dose. Similar results were observed for whole-body 45Ca retention. Radioactivity in the femur 34h after dosing was the highest in the Ca-AsA group and the lowest in the CaCO3 group. The rank order of solubility in water, the first fluid (pH 1.2, JP-1) of JPXIII disintegration medium, acetate buffer solution (pH 4.0), triethanolamine-malate buffer solution (pH 7.0) and ammonium chloride buffer solution (pH 10.0) at 37 degrees C was CaCl2 > Ca-AsA > CaCO3. In contrast, the rank order of the solubility in the second fluid (pH 6.8, JP-2) of JPXIII disintegration medium at 37 degrees C was Ca-AsA > CaCl2 > CaCO3. These results indicate that the absorbability of Ca from Ca-AsA is almost comparable with, or higher than, that from CaCl2 and significantly higher than that from CaCO3 because of its high degree of solubility in the intestine. Therefore, Ca-AsA would be useful as a Ca supplement with relatively high absorption from intestine.

[Strontium and calcium metabolism. Interaction of strontium and vitamin D].

PubMed

Rousselet, F; El Solh, N; Maurat, J P; Gruson, M; Girard, M L

1975-01-01

Oral administration of strontium to calcium wellfed rats blocks the intestinal absorption of calcium. When high doses of vitamine D are given over long period, the inhibition of calcium intestinal absorption disapears. Under these conditions the absorption of strontium is increased. It is suggested that there is only one absorption mechanism for these two cations. An overdose of the vitamine D increases the renal elimination of strontium but under these conditions the plasma concentration of the strontium is unchanged. Vitamine D brings about the some action on the bone fixation of the strontium as it does on the bone fixation of calcium. The bone fixation is increased with low dosages. The bone fixation is decreased with high dosages.

The effect of calcium on non-heme iron uptake, efflux, and transport in intestinal-like epithelial cells (Caco-2 cells).

PubMed

Gaitán, Diego Alejandro; Flores, Sebastian; Pizarro, Fernando; Olivares, Manuel; Suazo, Miriam; Arredondo, Miguel

2012-03-01

It has been suggested that calcium inhibits the absorption of dietary iron by directly affecting enterocytes. However, it is not clear if this effect is due to a decreased uptake of iron or its efflux from enterocytes. We studied the effect of calcium on the uptake, efflux, and net absorption of non-heme iron using the intestinal-like epithelial cell line Caco-2 as an in vitro model. Caco-2 cells were incubated for 60 min in a buffer supplemented with non-heme iron (as sulfate) and calcium to achieve calcium to iron molar ratios ranging from 50:1 to 1,000:1. The uptake, efflux, and net absorption of non-heme iron were calculated by following a radioisotope tracer of (55)Fe that had been added to the buffer. Administration of calcium and iron at molar ratios between 500 and 1,000:1 increased the uptake of non-heme iron and decreased efflux. Calcium did not have an effect on the net absorption of non-heme iron. At typical supplementary doses for calcium and non-heme iron, calcium may not have an effect on the absorption of non-heme iron. The effect of higher calcium to iron molar ratios on the efflux of non-heme iron may be large enough to explain results from human studies.

Calcium deprivation increases the palatability of calcium solutions in rats.

PubMed

McCaughey, Stuart A; Forestell, Catherine A; Tordoff, Michael G

2005-02-15

Calcium-deprived rats have elevated intakes of CaCl2, other calcium salts, and some non-calcium compounds. We used taste reactivity to examine the effects of calcium deprivation on the palatability of CaCl2 and other solutions. Nine male Sprague-Dawley rats were calcium-deprived by maintenance on a low-calcium diet, and eight replete rats were used as controls. All rats were videotaped during intraoral infusion of the following solutions: 30 and 300 mM CaCl2, 30 mM calcium lactate, 100 and 600 mM NaCl, 30 mM MgCl2, 1 mM quinine.HCl, 2.5 mM sodium saccharin, and deionized water. We counted individual orofacial and somatic movements elicited by the infusions and used them to calculate total ingestive and aversive scores. Relative to controls, calcium-deprived rats gave a significantly larger number of tongue protrusions and had higher total ingestive scores for CaCl2, calcium lactate, NaCl, and MgCl2. Our results suggest that CaCl2, calcium lactate, NaCl, and MgCl2 taste more palatable to rats when they are calcium-deprived than replete, and this may be responsible for the increased intake of these solutions following calcium deprivation.

The Extracellular Calcium-Sensing Receptor in the Intestine: Evidence for Regulation of Colonic Absorption, Secretion, Motility, and Immunity.

PubMed

Tang, Lieqi; Cheng, Catherine Y; Sun, Xiangrong; Pedicone, Alexandra J; Mohamadzadeh, Mansour; Cheng, Sam X

2016-01-01

Different from other epithelia, the intestinal epithelium has the complex task of providing a barrier impeding the entry of toxins, food antigens, and microbes, while at the same time allowing for the transfer of nutrients, electrolytes, water, and microbial metabolites. These molecules/organisms are transported either transcellularly, crossing the apical and basolateral membranes of enterocytes, or paracellularly, passing through the space between enterocytes. Accordingly, the intestinal epithelium can affect energy metabolism, fluid balance, as well as immune response and tolerance. To help accomplish these complex tasks, the intestinal epithelium has evolved many sensing receptor mechanisms. Yet, their roles and functions are only now beginning to be elucidated. This article explores one such sensing receptor mechanism, carried out by the extracellular calcium-sensing receptor (CaSR). In addition to its established function as a nutrient sensor, coordinating food digestion, nutrient absorption, and regulating energy metabolism, we present evidence for the emerging role of CaSR in the control of intestinal fluid homeostasis and immune balance. An additional role in the modulation of the enteric nerve activity and motility is also discussed. Clearly, CaSR has profound effects on many aspects of intestinal function. Nevertheless, more work is needed to fully understand all functions of CaSR in the intestine, including detailed mechanisms of action and specific pathways involved. Considering the essential roles CaSR plays in gastrointestinal physiology and immunology, research may lead to a translational opportunity for the development of novel therapies that are based on CaSR's unique property of using simple nutrients such as calcium, polyamines, and certain amino acids/oligopeptides as activators. It is possible that, through targeting of intestinal CaSR with a combination of specific nutrients, oral solutions that are both inexpensive and practical may be

The Extracellular Calcium-Sensing Receptor in the Intestine: Evidence for Regulation of Colonic Absorption, Secretion, Motility, and Immunity

PubMed Central

Tang, Lieqi; Cheng, Catherine Y.; Sun, Xiangrong; Pedicone, Alexandra J.; Mohamadzadeh, Mansour; Cheng, Sam X.

2016-01-01

Different from other epithelia, the intestinal epithelium has the complex task of providing a barrier impeding the entry of toxins, food antigens, and microbes, while at the same time allowing for the transfer of nutrients, electrolytes, water, and microbial metabolites. These molecules/organisms are transported either transcellularly, crossing the apical and basolateral membranes of enterocytes, or paracellularly, passing through the space between enterocytes. Accordingly, the intestinal epithelium can affect energy metabolism, fluid balance, as well as immune response and tolerance. To help accomplish these complex tasks, the intestinal epithelium has evolved many sensing receptor mechanisms. Yet, their roles and functions are only now beginning to be elucidated. This article explores one such sensing receptor mechanism, carried out by the extracellular calcium-sensing receptor (CaSR). In addition to its established function as a nutrient sensor, coordinating food digestion, nutrient absorption, and regulating energy metabolism, we present evidence for the emerging role of CaSR in the control of intestinal fluid homeostasis and immune balance. An additional role in the modulation of the enteric nerve activity and motility is also discussed. Clearly, CaSR has profound effects on many aspects of intestinal function. Nevertheless, more work is needed to fully understand all functions of CaSR in the intestine, including detailed mechanisms of action and specific pathways involved. Considering the essential roles CaSR plays in gastrointestinal physiology and immunology, research may lead to a translational opportunity for the development of novel therapies that are based on CaSR's unique property of using simple nutrients such as calcium, polyamines, and certain amino acids/oligopeptides as activators. It is possible that, through targeting of intestinal CaSR with a combination of specific nutrients, oral solutions that are both inexpensive and practical may be

Dietary calcium and cholecalciferol modulate cyclin D1 expression, apoptosis, and tumorigenesis in intestine of adenomatous polyposis coli1638N/+ mice.

PubMed

Yang, Kan; Lamprecht, Sergio A; Shinozaki, Hiroharu; Fan, Kunhua; Yang, Wancai; Newmark, Harold L; Kopelovich, Levy; Edelmann, Winfried; Jin, Bo; Gravaghi, Claudia; Augenlicht, Leonard; Kucherlapati, Raju; Lipkin, Martin

2008-09-01

Both epidemiological and experimental findings have indicated that components of Western diets influence colonic tumorigenesis. Among dietary constituents, calcium and cholecalciferol have emerged as promising chemopreventive agents. We have demonstrated that a Western-style diet (WD) with low levels of calcium and cholecalciferol and high levels of (n-6) PUFA, increased the incidence of neoplasia in mouse intestine compared with a standard AIN-76A diet; models included wild-type mice and mice with targeted mutations. In the present study, adenomatous polyposis coli (Apc)(1638N/+) mice carrying a heterozygous Apc mutation were fed either an AIN-76A diet, a WD, or a WD supplemented with calcium and cholecalciferol (WD/Ca/VitD3). Diets were fed for 24 wk and effects on cellular and molecular events were assessed by performing immunohistochemistry in colonic epithelium along the crypt-to-surface continuum. Feeding WD to Apc(1638N/+) mice not only enhanced cyclin D1 expression in colonic epithelium compared with AIN-76A treatment as previously reported but also significantly increased the expression of the antiapoptotic protein B-cell lymphoma 2 (Bcl-2) concomitantly with a decrease in the proapoptotic Bcl2-associated X protein and the number of apoptotic epithelial cells. WD treatment enhanced mutant Apc-driven small intestinal carcinogenesis and also resulted in the formation of a small number of colonic adenomas (0.16 +/- 0.09; P < 0.05). By contrast, the WD/Ca/VitD3 diet reversed WD-induced growth, promoting changes in colonic epithelium. Importantly, Apc(1638N/+) mice fed the WD/Ca/VitD3 diet did not develop colonic tumors, further indicating that dietary calcium and cholecalciferol have a key role in the chemoprevention of colorectal neoplasia in this mouse model of human colon cancer.

New approaches to increase intestinal length: Methods used for intestinal regeneration and bioengineering

PubMed Central

Shirafkan, Ali; Montalbano, Mauro; McGuire, Joshua; Rastellini, Cristiana; Cicalese, Luca

2016-01-01

Inadequate absorptive surface area poses a great challenge to the patients suffering a variety of intestinal diseases causing short bowel syndrome. To date, these patients are managed with total parenteral nutrition or intestinal transplantation. However, these carry significant morbidity and mortality. Currently, by emergence of tissue engineering, anticipations to utilize an alternative method to increase the intestinal absorptive surface area are increasing. In this paper, we will review the improvements made over time in attempting elongating the intestine with surgical techniques as well as using intestinal bioengineering. Performing sequential intestinal lengthening was the preliminary method applied in humans. However, these methods did not reach widespread use and has limited outcome. Subsequent experimental methods were developed utilizing scaffolds to regenerate intestinal tissue and organoids unit from the intestinal epithelium. Stem cells also have been studied and applied in all types of tissue engineering. Biomaterials were utilized as a structural support for naive cells to produce bio-engineered tissue that can achieve a near-normal anatomical structure. A promising novel approach is the elongation of the intestine with an acellular biologic scaffold to generate a neo-formed intestinal tissue that showed, for the first time, evidence of absorption in vivo. In the large intestine, studies are more focused on regeneration and engineering of sphincters and will be briefly reviewed. From the review of the existing literature, it can be concluded that significant progress has been achieved in these experimental methods but that these now need to be fully translated into a pre-clinical and clinical experimentation to become a future viable therapeutic option. PMID:27011901

Prolonged exposure to 1,25(OH)2D3 and high ionized calcium induces FGF-23 production in intestinal epithelium-like Caco-2 monolayer: A local negative feedback for preventing excessive calcium transport.

PubMed

Rodrat, Mayuree; Wongdee, Kannikar; Panupinthu, Nattapon; Thongbunchoo, Jirawan; Teerapornpuntakit, Jarinthorn; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

2018-02-15

Overdose of oral calcium supplement and excessive intestinal calcium absorption can contribute pathophysiological conditions, e.g., nephrolithiasis, vascular calcification, dementia, and cardiovascular accident. Since our previous investigation has indicated that fibroblast growth factor (FGF)-23 could abolish the 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]-enhanced calcium absorption, we further hypothesized that FGF-23 produced locally in the enterocytes might be part of a local negative feedback loop to regulate calcium absorption. Herein, 1,25(OH) 2 D 3 was found to enhance the transcellular calcium transport across the epithelium-like Caco-2 monolayer, and this stimulatory effect was diminished by preceding prolonged exposure to high-dose 1,25(OH) 2 D 3 or high concentration of apical ionized calcium. Pretreatment with a neutralizing antibody for FGF-23 prevented this negative feedback regulation of calcium hyperabsorption induced by 1,25(OH) 2 D 3 . FGF-23 exposure completely abolished the 1,25(OH) 2 D 3 -enhanced calcium transport. Western blot analysis revealed that FGF-23 expression was upregulated in a dose-dependent manner by 1,25(OH) 2 D 3 or apical calcium exposure. Finally, calcium-sensing receptor (CaSR) inhibitors were found to prevent the apical calcium-induced suppression of calcium transport. In conclusion, prolonged exposure to high apical calcium and calcium hyperabsorption were sensed by CaSR, which, in turn, increased FGF-23 expression to suppress calcium transport. This local negative feedback loop can help prevent unnecessary calcium uptake and its detrimental consequences. Copyright © 2018 Elsevier Inc. All rights reserved.

The effect of essential fatty acid deficiency on the stimulation of intestinal calcium transport by 1,25-dihydroxyvitamin D3.

PubMed

Kreutter, D; Matsumoto, T; Peckham, R; Zawalich, K; Wen, W H; Zolock, D T; Rasmussen, H

1983-04-25

The effect of altering the lipid composition of the brush-border membrane on the ability of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) to stimulate calcium transport across the intestinal mucosa was examined by raising chicks on a vitamin D, essential fatty acid-deficient diet (-DEFAD) and measuring calcium absorption from duodenal sacs in situ and calcium uptake into brush-border membrane vesicles in vitro. Administration of 1,25-(OH)2D3 to -DEFAD and to -D control chicks led to the same increase in calcium transport in situ, whereas calcium transport in isolated brush-border membrane vesicles was not stimulated in the EFAD group, but responded normally in the control group. When the incubation temperature was increased to 34 degrees C, brush-border membrane vesicles from 1,25-(OH)2D3-treated essential fatty acid-deficient (+DE-FAD) chicks accumulated calcium at a faster rate than did vesicles from -DEFAD chicks. There was a marked decrease in the linoleic acid content and an increase in the oleic acid content of both the total lipid extract of the brush-border membrane as well as the phosphatidylcholine and phosphatidylethanolamine fractions, which could explain the temperature sensitivity of the in vitro system. When the diet of the EFAD chicks was supplemented with linoleic acid, the rate of calcium uptake into subsequently isolated vesicles from +DE-FAD chicks correlated with the amount of linoleic acid in the brush-border membranes. These results support the concept that the action of 1,25-(OH)2D3 on membrane lipid turnover and structure plays a critically important role in the 1,25-(OH)2D3-mediated cellular transport responses.

Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D–induced inhibition of bone mineralization

PubMed Central

Lieben, Liesbet; Masuyama, Ritsuko; Torrekens, Sophie; Van Looveren, Riet; Schrooten, Jan; Baatsen, Pieter; Lafage-Proust, Marie-Hélène; Dresselaers, Tom; Feng, Jian Q.; Bonewald, Lynda F.; Meyer, Mark B.; Pike, J. Wesley; Bouillon, Roger; Carmeliet, Geert

2012-01-01

Serum calcium levels are tightly controlled by an integrated hormone-controlled system that involves active vitamin D [1,25(OH)2D], which can elicit calcium mobilization from bone when intestinal calcium absorption is decreased. The skeletal adaptations, however, are still poorly characterized. To gain insight into these issues, we analyzed the consequences of specific vitamin D receptor (Vdr) inactivation in the intestine and in mature osteoblasts on calcium and bone homeostasis. We report here that decreased intestinal calcium absorption in intestine-specific Vdr knockout mice resulted in severely reduced skeletal calcium levels so as to ensure normal levels of calcium in the serum. Furthermore, increased 1,25(OH)2D levels not only stimulated bone turnover, leading to osteopenia, but also suppressed bone matrix mineralization. This resulted in extensive hyperosteoidosis, also surrounding the osteocytes, and hypomineralization of the entire bone cortex, which may have contributed to the increase in bone fractures. Mechanistically, osteoblastic VDR signaling suppressed calcium incorporation in bone by directly stimulating the transcription of genes encoding mineralization inhibitors. Ablation of skeletal Vdr signaling precluded this calcium transfer from bone to serum, leading to better preservation of bone mass and mineralization. These findings indicate that in mice, maintaining normocalcemia has priority over skeletal integrity, and that to minimize skeletal calcium storage, 1,25(OH)2D not only increases calcium release from bone, but also inhibits calcium incorporation in bone. PMID:22523068

Transgenic plants with increased calcium stores

NASA Technical Reports Server (NTRS)

Robertson, Dominique (Inventor); Wyatt, Sarah (Inventor); Tsou, Pei-Lan (Inventor); Boss, Wendy (Inventor)

2004-01-01

The present invention provides transgenic plants over-expressing a transgene encoding a calcium-binding protein or peptide (CaBP). Preferably, the CaBP is a calcium storage protein and over-expression thereof does not have undue adverse effects on calcium homeostasis or biochemical pathways that are regulated by calcium. In preferred embodiments, the CaBP is calreticulin (CRT) or calsequestrin. In more preferred embodiments, the CaBP is the C-domain of CRT, a fragment of the C-domain, or multimers of the foregoing. In other preferred embodiments, the CaBP is localized to the endoplasmic reticulum by operatively associating the transgene encoding the CaBP with an endoplasmic reticulum localization peptide. Alternatively, the CaBP is targeted to any other sub-cellular compartment that permits the calcium to be stored in a form that is biologically available to the plant. Also provided are methods of producing plants with desirable phenotypic traits by transformation of the plant with a transgene encoding a CaBP. Such phenotypic traits include increased calcium storage, enhanced resistance to calcium-limiting conditions, enhanced growth and viability, increased disease and stress resistance, enhanced flower and fruit production, reduced senescence, and a decreased need for fertilizer production. Further provided are plants with enhanced nutritional value as human food or animal feed.

Small-molecule activators of TMEM16A, a calcium-activated chloride channel, stimulate epithelial chloride secretion and intestinal contraction

PubMed Central

Namkung, Wan; Yao, Zhen; Finkbeiner, Walter E.; Verkman, A. S.

2011-01-01

TMEM16A (ANO1) is a calcium-activated chloride channel (CaCC) expressed in secretory epithelia, smooth muscle, and other tissues. Cell-based functional screening of ∼110,000 compounds revealed compounds that activated TMEM16A CaCC conductance without increasing cytoplasmic Ca2+. By patch-clamp, N-aroylaminothiazole “activators” (Eact) strongly increased Cl− current at 0 Ca2+, whereas tetrazolylbenzamide “potentiators” (Fact) were not active at 0 Ca2+ but reduced the EC50 for Ca2+-dependent TMEM16A activation. Of 682 analogs tested, the most potent activator (Eact) and potentiator (Fact) produced large and more sustained CaCC Cl− currents than general agonists of Ca2+ signaling, with EC50 3–6 μM and Cl− conductance comparable to that induced transiently by Ca2+-elevating purinergic agonists. Analogs of activators were identified that fully inhibited TMEM16A Cl− conductance, providing further evidence for direct TMEM16A binding. The TMEM16A activators increased CaCC conductance in human salivary and airway submucosal gland epithelial cells, and IL-4 treated bronchial cells, and stimulated submucosal gland secretion in human bronchi and smooth muscle contraction in mouse intestine. Small-molecule, TMEM16A-targeted activators may be useful for drug therapy of cystic fibrosis, dry mouth, and gastrointestinal hypomotility disorders, and for pharmacological dissection of TMEM16A function.—Namkung, W., Yao, Z., Finkbeiner, W. E., Verkman, A. S. Small-molecule activators of TMEM16A, a calcium-activated chloride channel, stimulate epithelial chloride secretion and intestinal contraction. PMID:21836025

Characterization of sea cucumber (stichopus japonicus) ovum hydrolysates: calcium chelation, solubility and absorption into intestinal epithelial cells.

PubMed

Sun, Na; Cui, Pengbo; Lin, Songyi; Yu, Cuiping; Tang, Yue; Wei, Ye; Xiong, Youling; Wu, Haitao

2017-10-01

Sea cucumber (Stichopus japonicus) ovum hydrolysates (SCOHs) chelated with calcium were produced to investigate the characteristics of calcium binding and solubility, as well as to study any effects on calcium absorption by human intestinal epithelial cells. The results of the present study show that the calcium-binding capacity of SCOHs depended greatly on the type of proteases. The maximum level of Ca binding (0.38 mmol L -1 ) occurred when trypsin was used, with a peptide yield of 85.7%. Investigation of the possible chelating modes between SCOHs and calcium ions indicated that calcium ions bound to SCOHs primarily via interactions with carboxyl oxygen and amino nitrogen atoms of Glu and Asp and also that the phosphoserine residues might be also responsible for SCOH-calcium chelation. Moreover, SCOH-calcium complexes maintained the solubility of calcium under simulated gastrointestinal digestion, regardless of the presence of dietary components such as oxalate. Furthermore, SCOH-Ca led to higher peak intracellular [Ca 2+ ] i in both Caco-2 cells (338.3 nmol L -1 versus 269.6 nmol L -1 ) and HT-29 cells (373.9 nmol L -1 versus 271.7 nmol L -1 ) than casein phosphopeptide-Ca. Carboxyl oxygen and amino nitrogen atoms in the SCOHs could bind calcium ions, forming SCOH-calcium complexes. These complexes improved calcium solubility under simulated gastrointestinal digestion and also promoted calcium absorption in Caco-2 and HT-29 cells. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Calcium bioavailability and kinetics of calcium ascorbate and calcium acetate in rats.

PubMed

Cai, Jianwei; Zhang, Qinmin; Wastney, Meryl E; Weaver, Connie M

2004-01-01

The objective was to investigate the bioavailability and mechanism of calcium absorption of calcium ascorbate (ASC) and calcium acetate (AC). A series of studies was performed in adult Sprague-Dawley male rats. In the first study, each group of rats (n = 10/group) was assigned to one of the five test meals labeled with (45)Ca: (i) 25 mg calcium as heated ASC or (ii) unheated ASC, (iii) 25 mg calcium as unheated AC, (iv) 3.6 mg Ca as unheated ASC, or (v) unheated AC. Femur uptake indicated better calcium bioavailability from ASC than AC at both calcium loads. A 5-min heat treatment partly reduced bioavailability of ASC. Kinetic studies were performed to further investigate the mechanism of superior calcium bioavailability from ASC. Two groups of rats (n = 10/group) received oral doses of 25 mg Ca as ASC or AC. Each dose contained 20 micro Ci (45)Ca. Two additional groups of rats (n = 10/group) received an intravenous injection (iv) of 10 micro Ci (45)Ca after receiving an unlabeled oral dose of 25 mg calcium as ASC or AC. Sequential blood samples were collected over 48 hrs. Urine and fecal samples were collected every 12 hrs for 48 hrs and were analyzed for total calcium and (45)Ca content. Total calcium and (45)Ca from serum, urine, and feces were fitted by a compartment kinetics model with saturable and nonsaturable absorption pathways by WinSAAM (Windows-based Simulation Analysis and Modeling). The difference in calcium bioavailability between the two salts was due to differences in saturable rather than passive intestinal absorption and not to endogenous secretion or calcium deposition rate. The higher bioavailability of calcium ascorbate was due to a longer transit time in the small intestine compared with ASC.

An evaluation of in vitro intestinal absorption of iron, calcium and potassium in chickens receiving gold nanoparticles.

PubMed

Sembratowicz, I; Ognik, K; Stępniowska, A

2016-08-01

This study evaluated the effect of oral administration of colloidal gold nanoparticles on accumulation of gold in the small intestine and intestinal absorption of iron, calcium and potassium under in vitro conditions. The gold nanoparticles are non-ionic, nanocrystalline, chemically pure particles 5 nm in size, produced in a physical process. In total, 126 one day-old Ross 308 chicks were assigned to 7 experimental groups of 18 birds each (3 replications of 6 individuals each). The control group (G-C) did not receive gold nanoparticles. Groups: Au-5(7), Au-10(7) and Au-15(7) received gold nanoparticles in their drinking water in the amounts of 5 mg l(-1) for group Au-5(7), 10 mg l(-1) for group Au-10(7) and 15 mg l(-1) for group Au-15(7) in 8-14, 22-28 and 36-42 d of life. The birds in groups Au-5(3), Au-10(3) and Au-15(3) received gold nanoparticles in the same amounts, but only in 8-10, 22-24 and 36-38 d of life. The study revealed that nanogold supplied via ingestion leads to dose- and time-dependent accumulation of gold in the intestinal walls. Nanogold present in the jejunum has a negative impact on the absorption of calcium, iron and potassium under in vitro conditions.

Effect of Potassium Citrate on Calcium Phosphate Stones in a Model of Hypercalciuria

PubMed Central

Asplin, John R.; Frick, Kevin K.; Granja, Ignacio; Culbertson, Christopher D.; Ng, Adeline; Grynpas, Marc D.; Bushinsky, David A.

2015-01-01

Potassium citrate is prescribed to decrease stone recurrence in patients with calcium nephrolithiasis. Citrate binds intestinal and urine calcium and increases urine pH. Citrate, metabolized to bicarbonate, should decrease calcium excretion by reducing bone resorption and increasing renal calcium reabsorption. However, citrate binding to intestinal calcium may increase absorption and renal excretion of both phosphate and oxalate. Thus, the effect of potassium citrate on urine calcium oxalate and calcium phosphate supersaturation and stone formation is complex and difficult to predict. To study the effects of potassium citrate on urine supersaturation and stone formation, we utilized 95th-generation inbred genetic hypercalciuric stone-forming rats. Rats were fed a fixed amount of a normal calcium (1.2%) diet supplemented with potassium citrate or potassium chloride (each 4 mmol/d) for 18 weeks. Urine was collected at 6, 12, and 18 weeks. At 18 weeks, stone formation was visualized by radiography. Urine citrate, phosphate, oxalate, and pH levels were higher and urine calcium level was lower in rats fed potassium citrate. Furthermore, calcium oxalate and calcium phosphate supersaturation were higher with potassium citrate; however, uric acid supersaturation was lower. Both groups had similar numbers of exclusively calcium phosphate stones. Thus, potassium citrate effectively raises urine citrate levels and lowers urine calcium levels; however, the increases in urine pH, oxalate, and phosphate levels lead to increased calcium oxalate and calcium phosphate supersaturation. Potassium citrate induces complex changes in urine chemistries and resultant supersaturation, which may not be beneficial in preventing calcium phosphate stone formation. PMID:25855777

Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiological stress.

PubMed

Karl, J Philip; Margolis, Lee M; Madslien, Elisabeth H; Murphy, Nancy E; Castellani, John W; Gundersen, Yngvar; Hoke, Allison V; Levangie, Michael W; Kumar, Raina; Chakraborty, Nabarun; Gautam, Aarti; Hammamieh, Rasha; Martini, Svein; Montain, Scott J; Pasiakos, Stefan M

2017-06-01

The magnitude, temporal dynamics, and physiological effects of intestinal microbiome responses to physiological stress are poorly characterized. This study used a systems biology approach and a multiple-stressor military training environment to determine the effects of physiological stress on intestinal microbiota composition and metabolic activity, as well as intestinal permeability (IP). Soldiers ( n = 73) were provided three rations per day with or without protein- or carbohydrate-based supplements during a 4-day cross-country ski-march (STRESS). IP was measured before and during STRESS. Blood and stool samples were collected before and after STRESS to measure inflammation, stool microbiota, and stool and plasma global metabolite profiles. IP increased 62 ± 57% (mean ± SD, P < 0.001) during STRESS independent of diet group and was associated with increased inflammation. Intestinal microbiota responses were characterized by increased α-diversity and changes in the relative abundance of >50% of identified genera, including increased abundance of less dominant taxa at the expense of more dominant taxa such as Bacteroides Changes in intestinal microbiota composition were linked to 23% of metabolites that were significantly altered in stool after STRESS. Together, pre-STRESS Actinobacteria relative abundance and changes in serum IL-6 and stool cysteine concentrations accounted for 84% of the variability in the change in IP. Findings demonstrate that a multiple-stressor military training environment induced increases in IP that were associated with alterations in markers of inflammation and with intestinal microbiota composition and metabolism. Associations between IP, the pre-STRESS microbiota, and microbiota metabolites suggest that targeting the intestinal microbiota could provide novel strategies for preserving IP during physiological stress. NEW & NOTEWORTHY Military training, a unique model for studying temporal dynamics of intestinal barrier and intestinal

Bone Markers, Calcium Metabolism, and Calcium Kinetics During Extended-Duration Space Flight on the Mir Space Station

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Wastney, Meryl E.; O'Brien, Kimberly O.; Morukov, Boris V.; Larina, Irina M.; Abrams, Steven A.; Davis-Street, Janis E.; Oganov, Victor; Shackelford, Linda C.

2005-01-01

true intestinal calcium absorption was significantly lower during flight compared with preflight values (233 +/- 87 versus 460 +/- 47 mg/day; p < 0.01). Weightlessness had a detrimental effect on the balance in bone turnover such that the daily difference in calcium retention during flight compared with preflight values approached 300 mg/day (-234 +/- 102 versus 63 +/- 75 mg/day; p < 0.01). CONCLUSIONS: These bone marker and calcium kinetic studies indicated that the bone loss that occurs during space flight is a consequence of increased bone resorption and decreased intestinal calcium absorption.

Increase of calcium and reduction of lactose concentration in milk by treatment with kefir grains and eggshell.

PubMed

Fina, Brenda L; Brun, Lucas R; Rigalli, Alfredo

2016-01-01

Dairy products are the main source of calcium (Ca), but the loss of the consumption habit contributes to low consumption in adulthood, which leads to osteoporosis and increased fracture risk. Domestic use of kefir is straightforward and the eggshell is a natural discarded source of Ca. This paper proposes the development of an enriched Ca reduced lactose milk using eggshell and kefir. During the in vitro preparation, the pH, Ca and lactose contents were measured. Ca intestinal absorption of untreated milk and milk with kefir was compared. Finally, human volunteers consumed this dairy product and 24-h urine Ca was measured. Results showed that the beverage has lower lactose and higher Ca than untreated milk and milk with kefir. Intestinal Ca absorption was not different between both milks and an increase in urinary Ca excretion was observed in humans. This study provides a methodology to prepare at home a dairy product that could contribute to improve the Ca intake in adults.

Direct stimulation of the transcellular and paracellular calcium transport in the rat cecum by prolactin.

PubMed

Kraidith, Kamonshanok; Jantarajit, Walailuk; Teerapornpuntakit, Jarinthorn; Nakkrasae, La-iad; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

2009-09-01

Prolactin (PRL) is reported to stimulate calcium absorption in the rat's small intestine. However, little is known regarding its effects on the cecum, a part of the large intestine with the highest rate of intestinal calcium transport. We demonstrated herein by quantitative real-time polymerase chain reaction and Western blot analysis that the cecum could be a target organ of PRL since cecal epithelial cells strongly expressed PRL receptors. In Ussing chamber experiments, PRL enhanced the transcellular cecal calcium absorption in a biphasic dose-response manner. PRL also increased the paracellular calcium permeability and passive calcium transport in the cecum, which could be explained by the PRL-induced decrease in transepithelial resistance and increase in cation selectivity of the cecal epithelium. PRL actions in the cecum were abolished by inhibitors of phosphoinositide 3-kinase (PI3K), protein kinase C (PKC), and RhoA-associated coiled-coil forming kinase (ROCK), but not inhibitors of gene transcription and protein biosynthesis. In conclusion, PRL directly enhanced the transcellular and paracellular calcium transport in the rat cecum through the nongenomic signaling pathways involving PI3K, PKC, and ROCK.

Administration of Inulin-Supplemented Gluten-Free Diet Modified Calcium Absorption and Caecal Microbiota in Rats in a Calcium-Dependent Manner.

PubMed

Krupa-Kozak, Urszula; Markiewicz, Lidia H; Lamparski, Grzegorz; Juśkiewicz, Jerzy

2017-07-06

In coeliac disease (CD), the risk of adverse calcium balance and reduced bone density is induced mainly by the disease, but also by a gluten-free diet (GFD), the only accepted CD therapy. Prebiotics through the beneficial impact on intestinal microbiota may stimulate calcium (Ca) absorption. In the present study, we hypothesised that the dietary inulin in GFD would influence positively the intestinal microbiota, and by that will stimulate the absorption of calcium (Ca), especially in the conditions of Ca malnutrition. In a six-weeks nutritional experiment on growing a significant ( p < 0.05) luminal acidification, decrease in ammonia concentration and stimulation of short chain fatty acids formation indicated inulin-mediated beneficial effects on the caecal microbiota. However, the effect of inulin on characteristics of intestinal microbiota and mineral utilization depended on the dietary Ca intake from GFDs. Inulin stimulated bifidobacteria, in particular B. animalis species, only if a recommended amount of Ca was provided. Most benefits to mineral utilization from inulin consumption were seen in rats fed Ca-restricted GFD where it increased the relative Ca absorption. Administration of inulin to a GFDs could be a promising dietary strategy for beneficial modulation of intestinal ecosystem and by that for the improvement the Ca absorption.

Significance of Ca-soap formation for calcium absorption in the rat.

PubMed Central

Gacs, G; Barltrop, D

1977-01-01

The significance of calcium soap formation in the inhibition of calcium absorption has been studied in rats. 47Ca labelled soaps of fatty acids were introduced into the duodenum and the absorption of calcium measured after four hours in a whole body counter. The absorption of calcium was inversely correlated with the chain length of the fatty acid varying from 1% for Ca-stearate to 60% for Ca-hexanoate. Increasing the degree of unsaturation of the fatty acid was accompanied by increased calcium absorption. The availability of calcium for absorption from the soaps was correlated with their solubility in 1% aqueous Na-tauroglycocholate. The percentages of calcium as soap in the small intestine and the faeces after intragastric administration of calcium and fats were similar, which suggests that the faecal content of calcium soaps is an index of intestinal soap formation. Soap formation was negligible when CaCl2 was given with tristearate, triolaeate, or tridecanoate and no depression of calcium absorption was observed. Calcium absorption was markedly impaired by the addition of phosphates at a Ca/P ratio of 1:1 irrespective of the presence of neutral fats. Stearic acid resulted in significant soap formation and reduced calcium absorption. The degree of Ca-soap formation and the inhibition of calcium absorption were well correlated. The results suggest that, although calcium soap formation may markedly depress calcium absorption in the rat, no significant soap formation takes place when fats are given in the form of triglycerides. PMID:838405

Disruption of Calcium Homeostasis During Exercise as a Mediator of Bone Metabolism

DTIC Science & Technology

2015-10-01

Meeting of the American College of Sports Medicine (Appendix A). 15. SUBJECT TERMS calcium homeostasis, exercise, bone resorption, parathyroid hormone ... hormone (PTH). PTH can defend serum Ca by reducing urinary Ca excretion, increasing intestinal Ca absorption, and increasing mobilization of skeletal Ca...certain conditions. It is our contention that disruptions in calcium homeostasis during exercise lead to increases in parathyroid hormone (PTH) and

Oral Administration of Probiotics Increases Paneth Cells and Intestinal Antimicrobial Activity.

PubMed

Cazorla, Silvia I; Maldonado-Galdeano, Carolina; Weill, Ricardo; De Paula, Juan; Perdigón, Gabriela D V

2018-01-01

The huge amount of intestinal bacteria represents a continuing threat to the intestinal barrier. To meet this challenge, gut epithelial cells produce antimicrobial peptides (AMP) that act at the forefront of innate immunity. We explore whether this antimicrobial activity and Paneth cells, the main intestinal cell responsible of AMP production, are influenced by probiotics administration, to avoid the imbalance of intestinal microbiota and preserve intestinal barrier. Administration of Lactobacillus casei CRL 431 (Lc 431) and L. paracasei CNCM I-1518 (Lp 1518) to 42 days old mice, increases the number of Paneth cells on small intestine, and the antimicrobial activity against the pathogens Staphylococcus aureus and Salmonella Typhimurium in the intestinal fluids. Specifically, strong damage of the bacterial cell with leakage of cytoplasmic content, and cellular fragmentation were observed in S. Typhimurium and S. aureus . Even more important, probiotics increase the antimicrobial activity of the intestinal fluids at the different ages, from weaning (21 days old) to old age (180 days old). Intestinal antimicrobial activity stimulated by oral probiotics, do not influence significantly the composition of total anaerobic bacteria, lactobacilli and enterobacteria in the large intestine, at any age analyzed. This result, together with the antimicrobial activity observed against the same probiotic bacteria; endorse the regular consumption of probiotics without adverse effect on the intestinal homeostasis in healthy individuals. We demonstrate that oral probiotics increase intestinal antimicrobial activity and Paneth cells in order to strengthen epithelial barrier against pathogens. This effect would be another important mechanism by which probiotics protect the host mainly against infectious diseases.

Modulation of bicarbonate secretion in rabbit duodenum: the role of calcium.

PubMed

Hogan, D L; Yao, B; Isenberg, J I

1998-01-01

Surface epithelial bicarbonate secretion protects the proximal duodenum from acid peptic injury. Cyclic adenosine monophosphate and calcium serve as intracellular mediators of intestinal transport. Experiments were performed to examine whether calcium participates in duodenal bicarbonate transport. Stripped duodenal mucosa from rabbits was studied in Ussing chambers. HCO3- transport was stimulated by the calcium ionophore A23187, carbachol, vasoactive intestinal peptide, prostaglandin E2, dibutyryl-cyclic adenosine monophosphate, and electrical field stimulation. A23187 stimulated HCO3- secretion and Isc; tetrodotoxin failed to inhibit this effect. The calcium-channel blocker verapamil abolished HCO3- secretion stimulated by carbachol, vasoactive intestinal peptide, and electrical field stimulation, but failed to alter basal, prostaglandin E2- or dibutyryl-cyclic adenosine monophosphate-stimulated HCO3- secretion. Therefore, calcium is likely required during stimulation of duodenal epithelial HCO3- transport by carbachol, vasoactive intestinal peptide, and electrical field stimulation. Prostaglandin E2 and dibutyryl-cyclic adenosine monophosphate appear to activate duodenal HCO3- secretion by a calcium-independent pathway(s).

Bioaccessibility of four calcium sources in different whey-based dairy matrices assessed by in vitro digestion.

PubMed

Lorieau, Lucie; Le Roux, Linda; Gaucheron, Frédéric; Ligneul, Amandine; Hazart, Etienne; Dupont, Didier; Floury, Juliane

2018-04-15

Numerous calcium sources are available to enrich food, but their behavior during digestion is still unknown. This study focused on the influence of the gastro-intestinal pH, the food structure and the calcium source on the bioaccessibility of the nutrient. Four calcium sources were studied: calcium carbonate, calcium citrate malate, calcium phosphate and calcium bisglycinate. These were added to dairy matrices, containing cream and whey proteins, of different forms (liquid or gel). The kinetics of solubility and ionic calcium concentration during in vitro digestion were studied, as function of gastro-intestinal pH. All calcium sources were almost fully soluble in the gastric compartment, and then became insoluble in the intestinal phase. The level of calcium insolubilisation in the intestinal phase was not significantly influenced by the matrix structure (liquid or gel), but was more dependent on the calcium source, this effect leading to different final calcium bioaccessibility from 36% to 20%. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effect of variable calcium and very low calcium diets on human calcium metabolism. Ph.D. Thesis. Final Report

NASA Technical Reports Server (NTRS)

Chu, J.

1971-01-01

The effects of a very low calcium diet, with variable high and low protein intake, on the dynamics of calcium metabolism and the mechanism of calciuretics, are examined. The experiment, using male subjects, was designed to study the role of intestinal calcium absorption on urinary calcium excretion, and the rate of production of endogeneously secreted calcium in the gastrointestinal tract. The study showed an average of 70% fractional absorption rate during very low calcium intake, and that a decrease in renal tubular reabsorption of calcium is responsible for calciuretic effects of high protein intake. The study also indicates that there is a tendency to develop osteoporosis after long periods of low calcium intake, especially with a concurrent high protein intake.

Calcium homeostasis and vitamin D metabolism and expression in strongly calcifying laying birds.

PubMed

Bar, Arie

2008-12-01

Egg laying and shell calcification impose severe extra demands on ionic calcium (Ca2+) homeostasis; especially in birds characterized by their long clutches (series of eggs laid sequentially before a "pause day"). These demands induce vitamin D metabolism and expression. The metabolism of vitamin D is also altered indirectly, by other processes associated with increased demands for calcium, such as growth, bone formation and egg production. A series of intestinal, renal or bone proteins are consequently expressed in the target organs via mechanisms involving a vitamin D receptor. Some of these proteins (carbonic anhydrase, calbindin and calcium-ATPase) are also found in the uterus (eggshell gland) or are believed to be involved in calcium transport in the intestine or kidney (calcium channels). The present review deals with vitamin D metabolism and the expression of the above-mentioned proteins in birds, with special attention to the strongly calcifying laying bird.

Loss of Cystic Fibrosis Transmembrane Regulator Impairs Intestinal Oxalate Secretion.

PubMed

Knauf, Felix; Thomson, Robert B; Heneghan, John F; Jiang, Zhirong; Adebamiro, Adedotun; Thomson, Claire L; Barone, Christina; Asplin, John R; Egan, Marie E; Alper, Seth L; Aronson, Peter S

2017-01-01

Patients with cystic fibrosis have an increased incidence of hyperoxaluria and calcium oxalate nephrolithiasis. Net intestinal absorption of dietary oxalate results from passive paracellular oxalate absorption as modified by oxalate back secretion mediated by the SLC26A6 oxalate transporter. We used mice deficient in the cystic fibrosis transmembrane conductance regulator gene (Cftr) to test the hypothesis that SLC26A6-mediated oxalate secretion is defective in cystic fibrosis. We mounted isolated intestinal tissue from C57BL/6 (wild-type) and Cftr -/- mice in Ussing chambers and measured transcellular secretion of [ 14 C]oxalate. Intestinal tissue isolated from Cftr -/- mice exhibited significantly less transcellular oxalate secretion than intestinal tissue of wild-type mice. However, glucose absorption, another representative intestinal transport process, did not differ in Cftr -/- tissue. Compared with wild-type mice, Cftr -/- mice showed reduced expression of SLC26A6 in duodenum by immunofluorescence and Western blot analysis. Furthermore, coexpression of CFTR stimulated SLC26A6-mediated Cl - -oxalate exchange in Xenopus oocytes. In association with the profound defect in intestinal oxalate secretion, Cftr -/- mice had serum and urine oxalate levels 2.5-fold greater than those of wild-type mice. We conclude that defective intestinal oxalate secretion mediated by SLC26A6 may contribute to the hyperoxaluria observed in this mouse model of cystic fibrosis. Future studies are needed to address whether similar mechanisms contribute to the increased risk for calcium oxalate stone formation observed in patients with cystic fibrosis. Copyright © 2016 by the American Society of Nephrology.

The salutary effect of dietary calcium on bone mass in a rat model of simulated weightlessness

NASA Technical Reports Server (NTRS)

Bikle, D. D.; Globus, R.; Halloran, B. P.; Morey-Holton, E.

1985-01-01

Whether supplementation of dietary calcium reduces the differences in bone mass of unweighed limbs and normally weighted limbs, and whether parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25(OH)2D) respond differently to dietary calcium in unweighted animals in comparison with pair-fed controls was studied. The hind limbs of rats were unweighted by a tail suspension method and diets containing 0.1% to 2.4% calcium. After 2 weeks serum calcium, phosphorus, PTH and 1,25(OH)2D intestinal calcium transport were determined and bone mass, ash weight, and calcium in the tibia, L-1 vertebra, and humerus were measured. No significant differences in body weights were observed among the various groups. Suspended rats maintained constant levels of serum calcium and phosphate over the wide range of dietary calcium. Serum PTH and 1,25(OH)2D and intestinal calcium transport fell as dietary calcium was increased. Bone calcium in the tibia and vertebra from suspended rats remained less than that from pair-fed control. It is suggested that although no striking difference between suspended and control animals was observed in response to dieteary calcium, increasing dietary calcium may reduce the negative impact of unloading on the calcium content of the unweighted bones. The salutary effect of high dietary calcium appears to be due to inhibition of bone resorption rather than to stimulation of bone formation.

Extracellular calcium- and magnesium-mediated regulation of passive calcium transport across Caco-2 monolayers.

PubMed

Davies, Sarah L; Gibbons, Claire E; Steward, Martin C; Ward, Donald T

2008-10-01

The calcium-sensing receptor (CaR) is expressed on intestinal epithelial serosal membrane and in Caco-2 cells. In renal epithelium, CaR expressed on the basolateral membrane acts to limit excess tubular Ca2+ reabsorption. Therefore, here we investigated whether extracellular calcium (Ca(o)2+) can regulate active or passive 45Ca2+ transport across differentiated Caco-2 monolayers via CaR-dependent or CaR-independent mechanisms. Raising the Ca(o)2+ concentration from 0.8 to 1.6 mM increased transepithelial electrical resistance (TER) and decreased passive Ca2+ permeability but failed to alter active Ca2+ transport. The Ca(o)2+ effect on TER was rapid, sustained and concentration-dependent. Increasing basolateral Mg2+ concentration increased TER and inhibited both passive and active Ca2+ transport, whereas spermine and the CaR-selective calcimimetic NPS R-467 were without effect. We conclude that small increases in divalent cation concentration elicit CaR-independent increases in TER and inhibit passive Ca2+ transport across Caco-2 monolayers, most probably through a direct effect on tight junction permeability. Whilst it is known that the complete removal of Ca(o)2+ lowers TER, here we show that Ca(o)2+ addition actually increases TER in a concentration-dependent manner. Therefore, such Ca(o)2+-sensitivity could modulate intestinal solute transport including the limiting of excess Ca2+ absorption.

HIV induces production of IL-18 from intestinal epithelial cells that increases intestinal permeability and microbial translocation

PubMed Central

Allam, Ossama; Samarani, Suzanne; Mehraj, Vikram; Jenabian, Mohammad-Ali; Tremblay, Cecile; Routy, Jean-Pierre; Amre, Devendra

2018-01-01

Interleukin-18 (IL-18) is a pleiotropic cytokine of the IL-1 family with multiple context dependent functions. We and others have shown that HIV infection is accompanied by increased circulating levels of IL-18 along with decreased levels of its antagonist, Interleukin-18 Binding Protein (IL-18BP). The infection is also accompanied by intestinal inflammation and decreased intestinal integrity as measured by intestinal permeability, regeneration and repair. However, little is known concerning the relation between high level of IL-18 associated with the viral infection and intestinal permeability. Here we demonstrate that HIV treatment increases production of IL-18 and decreases that of IL-18BP production in human intestinal epithelial cell (IEC) lines. IL-18 causes apoptosis of the IEC by activating caspase-1 and caspase-3. It induces epithelial barrier hyperpermeability by decreasing and disrupting both tight and adherens junction proteins, occludin, claudin 2 and beta-catenin. Disorganization of F-actin was also observed in the IEC that were exposed to the cytokine. Moreover IL-18 decreases transepithelial electrical resistance (TEER) in Caco-2 and increases permeability in HT29 monolayers. The cells’ treatment with IL-18 causes an increase in the expression of phosphorylated myosin II regulatory light-chain (p-MLC) and myosin light-chain kinase (MLCK), and a decrease in phosphorylated Signal Transducer and Activator of Transcription (p-STAT)-5. This increase in p-MLC is suppressed by a Rho-kinase (ROCK)-specific inhibitor. Interestingly, the levels of the cytokine correlate with those of LPS in the circulation in three different categories of HIV infected patients (HAART-naïve and HAART-treated HIV-infected individuals, and Elite controls) as well as in healthy controls. Collectively, these results suggest that the HIV-induced IL-18 plays a role in increased intestinal permeability and microbial translocation observed in HIV-infected individuals. PMID:29601578

Klotho Prevents Renal Calcium Loss

PubMed Central

Alexander, R. Todd; Woudenberg-Vrenken, Titia E.; Buurman, Jan; Dijkman, Henry; van der Eerden, Bram C. J.; van Leeuwen, Johannes P.T.M.; Bindels, René J.

2009-01-01

Disturbed calcium (Ca2+) homeostasis, which is implicit to the aging phenotype of klotho-deficient mice, has been attributed to altered vitamin D metabolism, but alternative possibilities exist. We hypothesized that failed tubular Ca2+ absorption is primary, which causes increased urinary Ca2+ excretion, leading to elevated 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and its sequelae. Here, we assessed intestinal Ca2+ absorption, bone densitometry, renal Ca2+ excretion, and renal morphology via energy-dispersive x-ray microanalysis in wild-type and klotho−/− mice. We observed elevated serum Ca2+ and fractional excretion of Ca2+ (FECa) in klotho−/− mice. Klotho−/− mice also showed intestinal Ca2+ hyperabsorption, osteopenia, and renal precipitation of calcium-phosphate. Duodenal mRNA levels of transient receptor potential vanilloid 6 (TRPV6) and calbindin-D9K increased. In the kidney, klotho−/− mice exhibited increased expression of TRPV5 and decreased expression of the sodium/calcium exchanger (NCX1) and calbindin-D28K, implying a failure to absorb Ca2+ through the distal convoluted tubule/connecting tubule (DCT/CNT) via TRPV5. Gene and protein expression of the vitamin D receptor (VDR), 25-hydroxyvitamin D-1-α-hydroxylase (1αOHase), and calbindin-D9K excluded renal vitamin D resistance. By modulating the diet, we showed that the renal Ca2+ wasting was not secondary to hypercalcemia and/or hypervitaminosis D. In summary, these findings illustrate a primary defect in tubular Ca2+ handling that contributes to the precipitation of calcium-phosphate in DCT/CNT. This highlights the importance of klotho to the prevention of renal Ca2+ loss, secondary hypervitaminosis D, osteopenia, and nephrocalcinosis. PMID:19713312

Nivalenol induces oxidative stress and increases deoxynivalenol pro-oxidant effect in intestinal epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Del Regno, Marisanta; Adesso, Simona; Popolo, Ada

Mycotoxins are secondary fungal metabolites often found as contaminants in almost all agricultural commodities worldwide, and the consumption of food or feed contaminated by mycotoxins represents a major risk for human and animal health. Reactive oxygen species are normal products of cellular metabolism. However, disproportionate generation of reactive oxygen species poses a serious problem to bodily homeostasis and causes oxidative tissue damage. In this study we analyzed the effect of two trichothecenes mycotoxins: nivalenol and deoxynivalenol, alone and in combination, on oxidative stress in the non-tumorigenic intestinal epithelial cell line IEC-6. Our results indicate the pro-oxidant nivalenol effect in IEC-6,more » the stronger pro-oxidant effect of nivalenol when compared to deoxynivalenol and, interestingly, that nivalenol increases deoxynivalenol pro-oxidative effects. Mechanistic studies indicate that the observed effects were mediated by NADPH oxidase, calcium homeostasis alteration, NF-kB and Nrf2 pathways activation and by iNOS and nitrotyrosine formation. The toxicological interaction by nivalenol and deoxynivalenol reported in this study in IEC-6, points out the importance of the toxic effect of these mycotoxins, mostly in combination, further highlighting the risk assessment process of these toxins that are of growing concern. - Highlights: • Nivalenol induces oxidative stress in intestinal epithelial cells (IECs). • Nivalenol increases deoxynivalenol pro-oxidant effects in IECs. • Nivalenol and deoxynivalenol trigger antioxidant response IECs. • These results indicate the importance of mycotoxins co-contamination.« less

Calcium metabolism in health and disease.

PubMed

Peacock, Munro

2010-01-01

This brief review focuses on calcium balance and homeostasis and their relationship to dietary calcium intake and calcium supplementation in healthy subjects and patients with chronic kidney disease and mineral bone disorders (CKD-MBD). Calcium balance refers to the state of the calcium body stores, primarily in bone, which are largely a function of dietary intake, intestinal absorption, renal excretion, and bone remodeling. Bone calcium balance can be positive, neutral, or negative, depending on a number of factors, including growth, aging, and acquired or inherited disorders. Calcium homeostasis refers to the hormonal regulation of serum ionized calcium by parathyroid hormone, 1,25-dihydroxyvitamin D, and serum ionized calcium itself, which together regulate calcium transport at the gut, kidney, and bone. Hypercalcemia and hypocalcemia indicate serious disruption of calcium homeostasis but do not reflect calcium balance on their own. Calcium balance studies have determined the dietary and supplemental calcium requirements needed to optimize bone mass in healthy subjects. However, similar studies are needed in CKD-MBD, which disrupts both calcium balance and homeostasis, because these data in healthy subjects may not be generalizable to this patient group. Importantly, increasing evidence suggests that calcium supplementation may enhance soft tissue calcification and cardiovascular disease in CKD-MBD. Further research is needed to elucidate the risks and mechanisms of soft tissue calcification with calcium supplementation in both healthy subjects and CKD-MBD patients.

The effect of administration of copper nanoparticles to chickens in drinking water on estimated intestinal absorption of iron, zinc, and calcium.

PubMed

Ognik, Katarzyna; Stępniowska, Anna; Cholewińska, Ewelina; Kozłowski, Krzysztof

2016-09-01

Copper nanoparticles used as a dietary supplement for poultry could affect the absorption of mineral elements. Hence the aim of the study was to determine the effect of administration of copper nanoparticles to chickens in drinking water on intestinal absorption of iron, zinc, and calcium. The experiment was carried out on 126 chicks assigned to seven experimental groups of 18 birds each (3 replications of 6 individuals each). The control group (G-C) did not receive copper nanoparticles. Groups: Cu-5(7), Cu-10(7), and Cu-15(7) received gold nanoparticles in their drinking water in the amounts of 5 mg/L for group Cu-5(7), 10 mg/L for group Cu-10(7), and 15 mg/L for group Cu-15(7) during 8 to 14, 22 to 28, and 36 of 42 days of the life of the chicks. The birds in groups Cu-5(3), Cu-10(3), and Cu-15(3) received copper nanoparticles in the same amounts, but only during 8 to 10, 22 to 24, and 36 to 38 days of life. Blood for analysis was collected from the wing vein of all chicks at the age of 42 days. After the rearing period (day 42), six birds from each experimental group with body weight similar to the group average were slaughtered. The carcasses were dissected and samples of the jejunum were collected for analysis of absorption of selected minerals. Mineral absorption was tested using the in vitro gastrointestinal sac technique. Oral administration of copper nanoparticles to chickens in the amount of 5, 10, and 15 mg/L led to accumulation of this element in the intestinal walls. The highest level of copper nanoparticles applied increased Cu content in the blood plasma of the birds. The in vitro study suggests that copper accumulated in the intestines reduces absorption of calcium and zinc, but does not affect iron absorption. © 2016 Poultry Science Association Inc.

Measurement of Intracellular Ionized Calcium in a Free-living Soil Nematode, Caenorhabditis elegans.

PubMed

Kawaii, S; Yoshizawa, Y; Mizutani, J

1993-01-01

A calcium chelating fluorescence indicator, fura-2, was used to measure intracellular ionized calcium in Caenorhabditis elegans. The indicator loading process was harmless to the nematode, and completed within 2-3 h. Fura-2 was loaded mainly at its intestinal tract. The effects of DOPA on locomotion and the level of intracellular calcium were investigated and measured by using a microfluorometer. The addition of DOPA temporarily increased [Ca(2+)]i for several minutes.

Reduced intestinal brain-derived neurotrophic factor increases vagal sensory innervation of the intestine and enhances satiation.

PubMed

Biddinger, Jessica E; Fox, Edward A

2014-07-30

Brain-derived neurotrophic factor (BDNF) is produced by developing and mature gastrointestinal (GI) tissues that are heavily innervated by autonomic neurons and may therefore control their development or function. To begin investigating this hypothesis, we compared the morphology, distribution, and density of intraganglionic laminar endings (IGLEs), the predominant vagal GI afferent, in mice with reduced intestinal BDNF (INT-BDNF(-/-)) and controls. Contrary to expectations of reduced development, IGLE density and longitudinal axon bundle number in the intestine of INT-BDNF(-/-) mice were increased, but stomach IGLEs were normal. INT-BDNF(-/-) mice also exhibited increased vagal sensory neuron numbers, suggesting that their survival was enhanced. To determine whether increased intestinal IGLE density or other changes to gut innervation in INT-BDNF(-/-) mice altered feeding behavior, meal pattern and microstructural analyses were performed. INT-BDNF(-/-) mice ate meals of much shorter duration than controls, resulting in reduced meal size. Increased suppression of feeding in INT-BDNF(-/-) mice during the late phase of a scheduled meal suggested that increased satiation signaling contributed to reduced meal duration and size. Furthermore, INT-BDNF(-/-) mice demonstrated increases in total daily intermeal interval and satiety ratio, suggesting that satiety signaling was augmented. Compensatory responses maintained normal daily food intake and body weight in INT-BDNF(-/-) mice. These findings suggest a target organ-derived neurotrophin suppresses development of that organ's sensory innervation and sensory neuron survival and demonstrate a role for BDNF produced by peripheral tissues in short-term controls of feeding, likely through its regulation of development or function of gut innervation, possibly including augmented intestinal IGLE innervation. Copyright © 2014 the authors 0270-6474/14/3410379-15$15.00/0.

An endogenous nanomineral chaperones luminal antigen and peptidoglycan to intestinal immune cells

NASA Astrophysics Data System (ADS)

Powell, Jonathan J.; Thomas-McKay, Emma; Thoree, Vinay; Robertson, Jack; Hewitt, Rachel E.; Skepper, Jeremy N.; Brown, Andy; Hernandez-Garrido, Juan Carlos; Midgley, Paul A.; Gomez-Morilla, Inmaculada; Grime, Geoffrey W.; Kirkby, Karen J.; Mabbott, Neil A.; Donaldson, David S.; Williams, Ifor R.; Rios, Daniel; Girardin, Stephen E.; Haas, Carolin T.; Bruggraber, Sylvaine F. A.; Laman, Jon D.; Tanriver, Yakup; Lombardi, Giovanna; Lechler, Robert; Thompson, Richard P. H.; Pele, Laetitia C.

2015-05-01

In humans and other mammals it is known that calcium and phosphate ions are secreted from the distal small intestine into the lumen. However, why this secretion occurs is unclear. Here, we show that the process leads to the formation of amorphous magnesium-substituted calcium phosphate nanoparticles that trap soluble macromolecules, such as bacterial peptidoglycan and orally fed protein antigens, in the lumen and transport them to immune cells of the intestinal tissue. The macromolecule-containing nanoparticles utilize epithelial M cells to enter Peyer's patches, small areas of the intestine concentrated with particle-scavenging immune cells. In wild-type mice, intestinal immune cells containing these naturally formed nanoparticles expressed the immune tolerance-associated molecule ‘programmed death-ligand 1’, whereas in NOD1/2 double knockout mice, which cannot recognize peptidoglycan, programmed death-ligand 1 was undetected. Our results explain a role for constitutively formed calcium phosphate nanoparticles in the gut lumen and show how this helps to shape intestinal immune homeostasis.

Calcium metabolism in birds.

PubMed

de Matos, Ricardo

2008-01-01

Calcium is one of the most important plasma constituents in mammals and birds. It provides structural strength and support (bones and eggshell) and plays vital roles in many of the biochemical reactions in the body. The control of calcium metabolism in birds is highly efficient and closely regulated in a number of tissues, primarily parathyroid gland, intestine, kidney, and bone. The hormones with the greatest involvement in calcium regulation in birds are parathyroid hormone, 1,25-dihydroxyvitamin D(3) (calcitriol), and estrogen, with calcitonin playing a minor and uncertain role. The special characteristics of calcium metabolism in birds, mainly associated with egg production, are discussed, along with common clinical disorders secondary to derangements in calcium homeostasis.

Supplemental Oxygen and Carbon Dioxide Each Increase Subcutaneous and Intestinal Intramural Oxygenation

PubMed Central

Ratnaraj, Jebadurai; Kabon, Barbara; Talcott, Michael R.; Sessler, Daniel I.

2005-01-01

Oxidative killing by neutrophils, a primary defense against surgical pathogens, is directly related to tissue oxygenation. We tested the hypothesis that supplemental inspired oxygen or mild hypercapnia (end-tidal PCO2 of 50 mmHg) improves intestinal oxygenation. Pigs (25±2.5 kg) were used in two studies in random order: 1) Oxygen Study — 30% vs. 100% inspired oxygen concentration at an end-tidal PCO2 of 40 mmHg, and 2) Carbon Dioxide Study — end-tidal PCO2 of 30 mmHg vs. 50 mmHg with 30% oxygen. Within each study, treatment order was randomized. Treatments were maintained for 1.5 hours; measurements were averaged over the final hour. A tonometer inserted in the subcutaneous tissue of the left upper foreleg measured subcutaneous oxygen tension. Tonometers inserted into the intestinal wall measured intestinal intramural oxygen tension from the small and large intestines. 100% oxygen administration doubled subcutaneous oxygen partial pressure (PO2) (57±10 to 107±48 mmHg, P=0.006) and large intestine intramural PO2 (53±14 to 118±72 mmHg, P=0.014); intramural PO2increased 40% in the small intestine (37±10 to 52±25 mmHg, P=0.004). An end-tidal PCO2 of 50 mmHg increased large intestinal PO2 approximately 16% (49±10 to 57±12 mmHg, P=0.039), while intramural PO2 increased by 45% in the small intestine (31±12 to 44±16 mmHg, P=0.002). Supplemental oxygen and mild hypercapnia each increased subcutaneous and intramural tissue PO2, with supplemental oxygen being most effective. PMID:15281531

[Aging and homeostasis. Management of disorders in bone and calcium metabolism associated with ageing.

PubMed

Takeuchi, Yasuhiro

Disorders in bone and calcium metabolism associated with aging are based on secondary hyperparathyroidism due to impaired intestinal calcium absorption caused by insufficient vitamin D actions and augmented bone resorption due to sex hormone deficiency. Both of them are involved in the development of osteoporosis that increases risk of fractures. Therefore, the most important thing for management of disorders in bone and calcium metabolism associated with aging is to prevent fractures with appropriate drugs for osteoporosis.

Biogenic Fish-gut Calcium Carbonate is a Stable Amorphous Phase in the Gilt-head Seabream, Sparus aurata

PubMed Central

Foran, Elizabeth; Weiner, Steve; Fine, Maoz

2013-01-01

The main source of calcium carbonate (CaCO3) in the ocean comes from the shells of calcifying planktonic organisms, but substantial amounts of CaCO3 are also produced in fish intestines. The precipitation of CaCO3 assists fish in intestinal water absorption and aids in whole body Ca2+ homeostasis. Here we report that the product formed in the intestinal lumen of the gilt-head seabream, Sparus aurata, is an amorphous calcium carbonate (ACC) phase. With FTIR spectroscopy and SEM imaging, our study shows that the fish-derived carbonates from S. aurata are maintained as a stable amorphous phase throughout the intestinal tract. Moreover, intestinal deposits contained up to 54 mol% Mg2+, the highest concentration yet reported in biogenic ACC. Mg is most likely responsible for stabilizing this inherently unstable mineral. The fish carbonates also displayed initial rapid dissolution when exposed to seawater, exhibiting a significant increase in carbonate concentration. PMID:23609008

The role of calcium in osteoporosis.

PubMed

Arnaud, C D; Sanchez, S D

1990-01-01

Calcium requirements may vary throughout the lifespan. During the growth years and up to age 25-30, it is important to maximize dietary intake of calcium to maintain positive calcium balance and achieve peak bone mass, thereby possibly decreasing the risk of fracture when bone is subsequently lost. The RDA for age 10-25 is 1200 mg/day. Calcium intake need not be greater than 800 mg/day during the relatively short period of time between the end of bone building and the onset of bone loss (30 to 40 years old). Starting at age 40-45, both men and women lose bone slowly, but women lose bone more rapidly around the menopause and for about 10 years after. Intestinal calcium absorption and the ability to adapt to low calcium diets are impaired in many postmenopausal women and elderly persons owing to a suspected functional or absolute decrease in the ability of the kidney to produce 1,25(OH)2D3. The bones then become more and more a source of calcium to maintain critical extracellular fluid calcium levels. Available evidence suggests that the impairments of intestinal calcium absorption observed during the menopause and aging can be overcome only by inordinately large calcium intakes (1500 to 2500 mg/day). Since this amount is difficult to derive from the diet, can cause constipation, and may not prevent trabecular bone loss, it should not be used as a substitute for sex hormone replacement. Women taking estrogen replacement should be provided the RDA for calcium of 800 mg/day at a minimum. Those who cannot or will not take estrogen should be asked to ingest at least 1000 to 1500 mg/day of calcium to delay cortical bone loss and prevent secondary hyperparathyroidism. It should be emphasized that up to 2000 mg/day of calcium is safe in teenaged children and adults. Excessive dietary intake of protein and fiber may induce significant negative calcium balance and thus increase dietary calcium requirements. It is also possible that excessive intakes of phosphate could have a

Calcium absorption is not increased by caseinophosphopeptides.

PubMed

Teucher, Birgit; Majsak-Newman, Gosia; Dainty, Jack R; McDonagh, David; FitzGerald, Richard J; Fairweather-Tait, Susan J

2006-07-01

One of the suggested health benefits of caseinophosphopeptides (CPPs) is their ability to enhance calcium absorption. This possibility is based on the assumption that they resist proteolysis in the upper gastrointestinal tract and maintain calcium in a soluble form at alkaline pH in the distal ileum. The effects of CPP-enriched preparations (containing candidate functional food ingredients) on calcium absorption from a calcium lactate drink were tested. A randomized crossover trial was undertaken in 15 adults in whom we measured the absorption of calcium from a calcium lactate drink (drink A: 400 mg Ca as lactate) and 2 preparations enriched with forms of CPP (1.7 g each; drinks B and C). Both drinks B and C contained 400 mg Ca as calcium lactate plus approximately 100 mg CPP-derived calcium). Each volunteer received the 3 drinks in random order. Absorption was measured by the dual-label calcium stable-isotope technique. The quantity of calcium absorbed was significantly lower from drink A (103 mg) than from drink B (117 mg; P = 0.012) or drink C (121 mg; P = 0.002), which indicated a positive effect of the CPPs. However, because the CPP preparations contributed additional calcium besides that found in the calcium lactate (drink A), fractional absorption of calcium from drink B (23%) was slightly but significantly (P = 0.015) lower than that from drink A (26%). The differences in calcium absorption are unlikely to have any biological significance. CPPs are unsuitable as candidate ingredients for functional foods that are designed to deliver improved calcium nutrition.

An Endogenous Nanomineral Chaperones Luminal Antigen and Peptidoglycan to Intestinal Immune Cells

PubMed Central

Powell, Jonathan J; Thomas-McKay, Emma; Thoree, Vinay; Robertson, Jack; Hewitt, Rachel E; Skepper, Jeremy N; Brown, Andy; Hernandez-Garrido, Juan Carlos; Midgley, Paul A; Gomez-Morilla, Inmaculada; Grime, Geoffrey W; Kirkby, Karen J; Mabbott, Neil A; Donaldson, David S; Williams, Ifor R; Rios, Daniel; Girardin, Stephen E; Haas, Carolin T; Bruggraber, Sylvaine FA; Laman, Jon D; Tanriver, Yakup; Lombardi, Giovanna; Lechler, Robert; Thompson, Richard P H; Pele, Laetitia C

2015-01-01

In humans and other mammals, it is known that calcium and phosphate ions are secreted from the distal small intestine into the lumen. However, why this secretion occurs is unclear. Here, we show that the process leads to the formation of amorphous magnesium-substituted calcium phosphate nanoparticles that trap soluble macromolecules, such as bacterial peptidoglycan and orally-fed protein antigens, in the lumen and transport them to immune cells of the intestinal tissue. The macromolecule-containing nanoparticles utilize epithelial M cells to enter Peyer’s patches - small areas of the intestine concentrated with particle-scavenging immune cells. In wild type mice, intestinal immune cells containing these naturally-formed nanoparticles expressed the immune tolerance-associated molecule ‘programmed death-ligand 1 (PD-L1)’, whereas in NOD1/2 double knock-out mice, which cannot recognize peptidoglycan, PD-L1 was undetected. Our results explain a role for constitutively formed calcium phosphate nanoparticles in the gut lumen and how this helps to shape intestinal immune homeostasis. PMID:25751305

Calcium Kinetics During Space Flight

NASA Technical Reports Server (NTRS)

Smith, Scott M.; OBrien, K. O.; Abrams, S. A.; Wastney, M. E.

2005-01-01

Bone loss during space flight is one of the most critical challenges to astronaut health on space exploration missions. Defining the time course and mechanism of these changes will aid in developing means to counteract bone loss during space flight, and will have relevance for other clinical situations that impair weight-bearing activity. Bone health is a product of the balance between bone formation and bone resorption. Early space research could not clearly identify which of these was the main process altered in bone loss, but identification of the collagen crosslinks in the 1990s made possible a clear understanding that the impact of space flight was greater on bone resorption, with bone formation being unchanged or only slightly decreased. Calcium kinetics data showed that bone resorption was greater during flight than before flight (668 plus or minus 130 vs. 427 plus or minus 153 mg/d, p less than 0.001), and clearly documented that true intestinal calcium absorption was lower during flight than before flight (233 plus or minus 87 vs. 460 plus or minus 47 mg/d, p less than 0.01). Weightlessness had a detrimental effect on the balance in bone turnover: the difference between daily calcium balance during flight (-234 plus or minus 102 mg/d) and calcium balance before flight (63 plus or minus 75 mg/d) approached 300 mg/d (p less than 0.01). These data demonstrate that the bone loss that occurs during space flight is a consequence of increased bone resorption and decreased intestinal calcium absorption. Examining the changes in bone and calcium homeostasis in the initial days and weeks of space flight, as well as at later times on missions longer than 6 months, is critical to understanding the nature of bone adaptation to weightlessness. To increase knowledge of these changes, we studied bone adaptation to space flight on the 16-day Space Shuttle Columbia (STS-107) mission. When the brave and talented crew of Columbia were lost during reentry on the tragic morning

Effect of animal and vegetable protein intake on oxalate excretion in idiopathic calcium stone disease.

PubMed

Marangella, M; Bianco, O; Martini, C; Petrarulo, M; Vitale, C; Linari, F

1989-04-01

Oxalate excretion was measured in healthy subjects and idiopathic calcium stone-formers on dietary regimens which differed in the type and amount of protein allowed; 24-h urine collections were obtained from 41 practising vegetarians and 40 normal persons on a free, mixed, "mediterranean" diet. Twenty idiopathic calcium stone-formers were also studied while on two low calcium, low oxalate diets which differed in that animal protein was high in one and restricted in the other. Vegetarians had higher urinary oxalate levels than controls and although the calcium levels were markedly lower, urinary saturation with calcium/oxalate was significantly higher. This mild hypercalciuria was interpreted as being secondary to both a higher intake and increased fractional intestinal absorption of oxalate. Changing calcium stone-formers from a high to a low animal protein intake produced a significant decrease in calcium excretion but there was no variation in urinary oxalate. As a result, the decrease in calcium oxalate saturation was only marginal and not significant. It was concluded that dietary animal protein has a minimal effect on oxalate excretion. Mild hyperoxaluria of idiopathic calcium stone disease is likely to be intestinal in origin. Calcium stone-formers should be advised to avoid an excess of animal protein but the risks of a vegetable-rich diet should also be borne in mind.

Chronic binge alcohol administration increases intestinal T cell proliferation and turnover in rhesus macaques

PubMed Central

Veazey, Ronald S.; Amedee, Angela; Wang, Xiaolei; Kaack, M. Bernice; Porretta, Constance; Dufour, Jason; Welsh, David; Happel, Kyle; Pahar, Bapi; Molina, Patricia E.; Nelson, Steve; Bagby, Gregory J.

2015-01-01

Background Alcohol use results in changes in intestinal epithelial cell turnover and microbial translocation, yet less in known about the consequences on intestinal lymphocytes in the gut. Here we compared T cell subsets in the intestine of macaques before and after 3 months of chronic alcohol administration to examine the effects of alcohol on intestinal T cell subsets. Methods Rhesus macaques received either alcohol or isocaloric sucrose as a control treatment daily over a 3 month period via indwelling gastric catheters. Intestinal lymphocytes subsets were identified in biopsy samples by flow cytometry. Twenty-four hours prior to sampling, animals were inoculated with BrdU to assess lymphocyte proliferation. Immunohistochemistry was performed on tissue samples to quantitate CD3+ cells. Results Animals receiving alcohol had increased rates of intestinal T cell turnover of both CD4+ and CD8+ T cells as reflected by increased BrdU incorporation. However, absolute numbers of T cells were decreased in intestinal tissues as evidenced by immunohistochemistry for total CD3 expression per mm2 intestinal lamina propria in tissue sections. Combining immunohistochemistry and flow cytometry data showed that the absolute numbers of CD8+ T cells were significantly decreased, whereas total of CD4+ T cells were minimally decreased. Conclusions Collectively, these data indicate alcohol exposure to the small intestine results in marked loss of CD3+ T cells, accompanied by marked increases in CD4+ and CD8+ T cell proliferation and turnover, which we speculate is an attempt to maintain stable numbers of T cells in tissues. This suggests alcohol results in accelerated T cell turnover in the gut, which may contribute to premature T cell senescence. Further these data indicate that chronic alcohol administration results in increased levels of HIV target cells (proliferating CD4+ T cells) that may support higher levels of HIV replication in intestinal tissues. PMID:26146859

The Role of Calcium in Osteoporosis

NASA Technical Reports Server (NTRS)

Arnaud, C. D.; Sanchez, S. D.

1991-01-01

Calcium requirements may vary throughout the lifespan. During the growth years and up to age 25 to 30, it is important to maximize dietary intake of calcium to maintain positive calcium balance and achieve peak bone mass, thereby possibly decreasing the risk of fracture when bone is subsequently lost. Calcium intake need not be greater than 800 mg/day during the relatively short period of time between the end of bone building and the onset of bone loss (30 to 40 years). Starting at age 40 to 50, both men and women lose bone slowly, but women lose bone more rapidly around the menopause and for about 10 years after. Intestinal calcium absorption and the ability to adapt to low calcium diets are impaired in many postmenopausal women and elderly persons owing to a suspected functional or absolute decrease in the ability of the kidney to produce 1,25(OH)2D2. The bones then become more and more a source of calcium to maintain critical extracellular fluid calcium levels. Excessive dietary intake of protein and fiber may induce significant negative calcium balance and thus increase dietary calcium requirements. Generally, the strongest risk factors for osteoporosis are uncontrollable (e.g., sex, age, and race) or less controllable (e.g., disease and medications). However, several factors such as diet, physical activity, cigarette smoking, and alcohol use are lifestyle related and can be modified to help reduce the risk of osteoporosis.

Aqueous solubility of calcium L-lactate, calcium D-gluconate, and calcium D-lactobionate: importance of complex formation for solubility increase by hydroxycarboxylate mixtures.

PubMed

Vavrusova, Martina; Munk, Merete Bøgelund; Skibsted, Leif H

2013-08-28

Among the calcium hydroxycarboxylates important for cheese quality, D-lactobionate [Ksp = (7.0 ± 0.3) × 10(-3) mol(3) L(-3)] and L-lactate [Ksp = (5.8 ± 0.2) × 10(-3) mol(3) L(-3)] were found more soluble than D-gluconate [Ksp = (7.1 ± 0.2) × 10(-4) mol(3) L(-3)], as indicated by the solubility products determined electrochemically for aqueous 1.0 M NaCl at 25.0 °C. Still, solubility of calcium L-lactate increases by 45% in the presence of 0.50 M sodium D-gluconate and by 37% in the presence of 0.50 M sodium D-lactobionate, while solubility of calcium D-gluconate increases by 66 and 85% in the presence of 0.50 M sodium L-lactate and 0.50 M sodium D-lactobionate, respectively, as determined by complexometric titration. Sodium L-lactate and sodium D-gluconate have only little influence on solubility of calcium D-lactobionate. The increased solubility is described quantitatively by calcium binding to D-gluconate (K1 = 14 ± 3 mol(-1) L) in 1.0 M NaCl at 25 °C, D-lactobionate (K1 = 11 ± 2 mol(-1) L), and L-lactate (K1 = 8 ± 2 mol(-1) L), as indicated by the association constants determined electrochemically. In mixed hydroxycarboxylate solutions, calcium binding is quantitatively described by the geometric mean of the individual association constants for both aqueous 1.0 and 0.20 M NaCl, indicating a 1:1 stoichiometry for complex formation.

Increasing serotonin concentrations alter calcium and energy metabolism in dairy cows.

PubMed

Laporta, Jimena; Moore, Spencer A E; Weaver, Samantha R; Cronick, Callyssa M; Olsen, Megan; Prichard, Austin P; Schnell, Brian P; Crenshaw, Thomas D; Peñagaricano, Francisco; Bruckmaier, Rupert M; Hernandez, Laura L

2015-07-01

A 4×4 Latin square design in which varied doses (0, 0.5, 1.0, and 1.5 mg/kg) of 5-hydroxy-l-tryptophan (5-HTP, a serotonin precursor) were intravenously infused into late-lactation, non-pregnant Holstein dairy cows was used to determine the effects of serotonin on calcium and energy metabolism. Infusion periods lasted 4 days, with a 5-day washout between periods. Cows were infused at a constant rate for 1 h each day. Blood was collected pre- and 5, 10, 30, 60, 90, and 120 min post-infusion, urine was collected pre- and post-infusion, and milk was collected daily. All of the 5-HTP doses increased systemic serotonin as compared to the 0 mg/kg dose, and the 1.0 and 1.5 mg/kg doses increased circulating glucose and non-esterified fatty acids (NEFA) and decreased beta-hydroxybutyrate (βHBA) concentrations. Treatment of cows with either 1.0 or 1.5 mg/kg 5-HTP doses decreased urine calcium elimination, and the 1.5 mg/kg dose increased milk calcium concentrations. No differences were detected in the heart rates, respiration rates, or body temperatures of the cows; however, manure scores and defecation frequency were affected. Indeed, cows that received 5-HTP defecated more, and the consistency of their manure was softer. Treatment of late-lactation dairy cows with 5-HTP improved energy metabolism, decreased loss of calcium into urine, and increased calcium secretion into milk. Further research should target the effects of increasing serotonin during the transition period to determine any benefits for post-parturient calcium and glucose metabolism. © 2015 Society for Endocrinology.

Ursodeoxycholic and deoxycholic acids: A good and a bad bile acid for intestinal calcium absorption.

PubMed

Rodríguez, Valeria; Rivoira, María; Marchionatti, Ana; Pérez, Adriana; Tolosa de Talamoni, Nori

2013-12-01

The aim of this study was to investigate the effect of ursodeoxycholic acid (UDCA) on intestinal Ca(2+) absorption and to find out whether the inhibition of this process caused by NaDOC could be prevented by UDCA. Chicks were employed and divided into four groups: (a) controls, (b) treated with 10mM NaDOC, (c) treated with 60 μg UDCA/100g of b.w., and (d) treated with 10mM NaDOC and 60 μg UDCA/100g of b.w. UDCA enhanced intestinal Ca(2+) absorption, which was time and dose-dependent. UDCA avoided the inhibition of intestinal Ca(2+) absorption caused by NaDOC. Both bile acids altered protein and gene expression of molecules involved in the transcellular pathway of intestinal Ca(2+) absorption, but in the opposite way. UDCA aborted the oxidative stress produced by NaDOC in the intestine. UDCA and UDCA plus NaDOC increased vitamin D receptor protein expression. In conclusion, UDCA is a beneficial bile acid for intestinal Ca(2+) absorption. Contrarily, NaDOC inhibits the intestinal cation absorption through triggering oxidative stress. The use of UDCA in patients with cholestasis would be benefited because of the protective effect on the intestinal Ca(2+) absorption, avoiding the inhibition caused by hydrophobic bile acids and neutralizing the oxidative stress. Copyright © 2013 Elsevier Inc. All rights reserved.

Expression of the high capacity calcium-binding domain of calreticulin increases bioavailable calcium stores in plants

NASA Technical Reports Server (NTRS)

Wyatt, Sarah E.; Tsou, Pei-Lan; Robertson, Dominique; Brown, C. S. (Principal Investigator)

2002-01-01

Modulation of cytosolic calcium levels in both plants and animals is achieved by a system of Ca2+-transport and storage pathways that include Ca2+ buffering proteins in the lumen of intracellular compartments. To date, most research has focused on the role of transporters in regulating cytosolic calcium. We used a reverse genetics approach to modulate calcium stores in the lumen of the endoplasmic reticulum. Our goals were two-fold: to use the low affinity, high capacity Ca2+ binding characteristics of the C-domain of calreticulin to selectively increase Ca2+ storage in the endoplasmic reticulum, and to determine if those alterations affected plant physiological responses to stress. The C-domain of calreticulin is a highly acidic region that binds 20-50 moles of Ca2+ per mole of protein and has been shown to be the major site of Ca2+ storage within the endoplasmic reticulum of plant cells. A 377-bp fragment encoding the C-domain and ER retention signal from the maize calreticulin gene was fused to a gene for the green fluorescent protein and expressed in Arabidopsis under the control of a heat shock promoter. Following induction on normal medium, the C-domain transformants showed delayed loss of chlorophyll after transfer to calcium depleted medium when compared to seedlings transformed with green fluorescent protein alone. Total calcium measurements showed a 9-35% increase for induced C-domain transformants compared to controls. The data suggest that ectopic expression of the calreticulin C-domain increases Ca2+ stores, and that this Ca2+ reserve can be used by the plant in times of stress.

Chronic Binge Alcohol Administration Increases Intestinal T-Cell Proliferation and Turnover in Rhesus Macaques.

PubMed

Veazey, Ronald S; Amedee, Angela; Wang, Xiaolei; Bernice Kaack, M; Porretta, Constance; Dufour, Jason; Welsh, David; Happel, Kyle; Pahar, Bapi; Molina, Patricia E; Nelson, Steve; Bagby, Gregory J

2015-08-01

Alcohol use results in changes in intestinal epithelial cell turnover and microbial translocation, yet less is known about the consequences on intestinal lymphocytes in the gut. Here, we compared T-cell subsets in the intestine of macaques before and after 3 months of chronic alcohol administration to examine the effects of alcohol on intestinal T-cell subsets. Rhesus macaques received either alcohol or isocaloric sucrose as a control treatment daily over a 3-month period via indwelling gastric catheters. Intestinal lymphocyte subsets were identified in biopsy samples by flow cytometry. Twenty-four hours prior to sampling, animals were inoculated with bromo-deoxyuridine (BrdU) to assess lymphocyte proliferation. Immunohistochemistry was performed on tissue samples to quantitate CD3+ cells. Animals receiving alcohol had increased rates of intestinal T-cell turnover of both CD4+ and CD8+ T cells as reflected by increased BrdU incorporation. However, absolute numbers of T cells were decreased in intestinal tissues as evidenced by immunohistochemistry for total CD3 expression per mm(2) intestinal lamina propria in tissue sections. Combining immunohistochemistry and flow cytometry data showed that the absolute numbers of CD8+ T cells were significantly decreased, whereas absolute numbers of total CD4+ T cells were minimally decreased. Collectively, these data indicate that alcohol exposure to the small intestine results in marked loss of CD3+ T cells, accompanied by marked increases in CD4+ and CD8+ T-cell proliferation and turnover, which we speculate is an attempt to maintain stable numbers of T cells in tissues. This suggests that alcohol results in accelerated T-cell turnover in the gut, which may contribute to premature T-cell senescence. Further, these data indicate that chronic alcohol administration results in increased levels of HIV target cells (proliferating CD4+ T cells) that may support higher levels of HIV replication in intestinal tissues. Copyright �

Molecular Mechanisms for Regulation of Intestinal Calcium Absorption by Vitamin D and Other Factors

PubMed Central

Fleet, James C.; Schoch, Ryan D.

2011-01-01

Optimal intestinal calcium (Ca) absorption is necessary for the protection of bone and the prevention of osteoporosis. Ca absorption can be represented as the sum of a saturable pathway and a non-saturable pathway that is primarily dependent upon luminal Ca concentration. While models have been proposed to describe these transport components, significant gaps still exist in our understanding of these processes. Habitual low intake of Ca up-regulates the saturable transport pathway, a process mediated by increased renal production of 1,25 dihydroxyvitamin D (1,25(OH)2 D). Consistent with this, low vitamin D status as well as deletion/mutation of the vitamin D receptor (VDR) or 25 hydroxyvitamin D-1α hydroxylase (CYP27B1) genes limit Ca absorption by reducing the saturable pathway. There is some evidence that non-saturable Ca absorption in the ileum is also regulated by vitamin D status, but the mechanism is unclear. Treatment with a number of hormones can regulate Ca absorption in vivo [e.g. parathyroid hormone (PTH), thyroid hormone, growth hormone (GH)/insulin-like growth factor I (IGF-1), estrogen, testosterone]. However, some of these actions are indirect (i.e. mediated through the regulation of vitamin D metabolism or signaling), whereas only a few (e.g. estrogen, IGF-1) have been shown to persist in the absence of vitamin D signaling. PMID:21182397

A plant Kunitz-type inhibitor mimics bradykinin-induced cytosolic calcium increase and intestinal smooth muscle contraction.

PubMed

Andrade, Sheila Siqueira; Smaili, Soraya Soubhi; Monteforte, Priscila Totarelli; Miranda, Antônio; Kouyoumdjian, Maria; Sampaio, Misako Uemura; Lopes, Guiomar Silva; Oliva, Maria Luiza V

2012-09-01

BbKI is a kallikrein inhibitor with a reactive site sequence similar to that of kinins, the vasoactive peptides inserted in kininogen moieties. This structural similarity probably contributes to the strong interaction with plasma kallikrein, the enzyme that releases, from high-molecular weight kininogen (HMWK), the proinflammatory peptide bradykinin, which acts on B(2) receptors (B(2)R). BbKI was examined on smooth muscle contraction and Ca(2+) mobilization, in which the kallikrein-kinin system is involved. Contrary to expectations, BbKI (1.8 μm) increased [Ca(2+)](c) and contraction, as observed with BK (2.0 μm). Not blocked by B(1) receptors (B(1)R), the BbKI agonistic effect was blocked by the B(2)R antagonist, HOE-140 (6 μm), and the involvement of B(2)R was confirmed in B(2)R-knockout mice intestine. The same tissue response was obtained using a synthetic peptide derived from the BbKI reactive site structure, more resistant than BK to angiotensin I-converting enzyme (ACE) hydrolysis. Depending on the concentration, BbKI has a dual effect. At a low concentration, BbKI acts as a potent kallikrein inhibitor; however, due to the similarity to BK, in high concentrations, BbKI greatly increases Ca(2+) release from internal storages, as a consequence of its interaction with B(2)R. Therefore, the antagonistic and agonistic effects of BbKI may be considered in conditions of B(2)R involvement.

Amyotrophic lateral sclerosis immunoglobulins increase intracellular calcium in a motoneuron cell line.

PubMed

Colom, L V; Alexianu, M E; Mosier, D R; Smith, R G; Appel, S H

1997-08-01

A hybrid motoneuron cell line (VSC4.1) was used as a model system to study the relationship between alterations in intracellular calcium and subsequent cell death induced by immunoglobulin fractions purified from sera of patients with ALS. Using fluo-3 fluorescence imaging, immunoglobulins from 8 of 10 patients with ALS were found to induce transient increases in intracellular calcium ([Ca2+]i) in differentiated VSC4.1 cells. These transient [Ca2+]i increases required extracellular calcium entry through voltage-gated calcium channels sensitive to synthetic FTX and to high concentrations (>1 microM) of omega-agatoxin IVa. The incidence of transient [Ca2+]i increases induced by ALS immunoglobulins correlated with the extent of cytotoxicity induced by the same ALS immunoglobulins in parallel cultures of VSC4.1 cells. Furthermore, manipulations which blocked transient [Ca2+]i increases (addition of synthetic FTX or omega-agatoxin IVa) also inhibited the cytotoxic effects of ALS immunoglobulins. No transient calcium increases were observed in VSC4.1 cells following addition of immunoglobulins from 7 neurologic disease control patients. However, transient [Ca2+]i increases were observed following addition of immunoglobulins from 4 of 5 patients with myasthenia gravis (MG). The [Ca2+]i changes induced by MG immunoglobulins were not blocked by s-FTX, suggesting that they result from a different mechanism than those induced by ALS immunoglobulins. These results suggest that immunoglobulins from patients with ALS can induce transient increases in intracellular calcium in a motoneuron cell line, which may represent early events in the cascade of processes leading to injury and death of susceptible cells.

Mesenchymal stem cells increase antioxidant capacity in intestinal ischemia/reperfusion damage.

PubMed

Inan, M; Bakar, E; Cerkezkayabekir, A; Sanal, F; Ulucam, E; Subaşı, C; Karaöz, E

2017-07-01

Mesenchymal stem cells (MSCs) may have beneficial effects in reversing intestinal damage resulting from circulatory disorders. The hypothesis of this study is that MSCs increase antioxidant capacity of small bowel tissue following intestinal ischemia reperfusion (I/R) damage. A total of 100 rats were used for the control group and three experimental groups, as follows: the sham control, local MSC, and systemic MSC groups. Each group consisted of 10 animals on days 1, 4, and 7 of the experiment. Ischemia was established by clamping the superior mesenteric artery (SMA) for 45min; following this, reperfusion was carried out for 1, 4, and 7days in all groups. In the local and systemic groups, MSCs were administered intravenously and locally just after the ischemia, and they were investigated after 1, 4, and 7days. The superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (Gpx) activities, as well as malondialdehyde (MDA) and total protein levels, were measured. Histopathological analysis was performed using light and electron microscopy. The indicators of proliferation from the effects of anti- and pro-inflammatory cytokines were evaluated using immunohistochemistry. MDA was increased (P<0.05) in the sham control group and decreased (P<0.05) in the MSC groups. SOD, CAT, and Gpx were decreased in the local MSC group (P<0.05). The highest level of amelioration was observed on day 7 in the local MSC group via light and electron microscopy. It was found that the MSCs arrived at the damaged intestinal wall in the MSC groups immediately after injection. Pro-inflammatory cytokines interleukin-1β (IL1β), transforming growth factor-β1 (TGFβ1), tumor necrosis factor-α (TNFα), IL6, MIP2, and MPO decreased (P<0.05), while anti-inflammatory cytokines EP3 and IL1ra increased (p<0.05) in the local and systemic MSC groups. In addition, proliferation indicators, such as PCNA and KI67, increased (P<0.05) in the local and systemic MSC groups. Parallel to our

Calcium Imaging of Nerve-Mast Cell Signaling in the Human Intestine

PubMed Central

Buhner, Sabine; Barki, Natasja; Greiter, Wolfgang; Giesbertz, Pieter; Demir, Ihsan E.; Ceyhan, Güralp O.; Zeller, Florian; Daniel, Hannelore; Schemann, Michael

2017-01-01

Introduction: It is suggested that an altered microenvironment in the gut wall alters communication along a mast cell nerve axis. We aimed to record for the first time signaling between mast cells and neurons in intact human submucous preparations. Methods: We used the Ca2+ sensitive dye Fluo-4 AM to simultaneously image changes in intracellular calcium [Ca+2]i (%ΔF/F) in neurons and mast cells. Data are presented as median with interquartile ranges (25/75%). Results: We recorded nerve responses in 29 samples upon selective activation of 223 mast cells by IgE receptor cross linking with the antibody mAb22E7. Mast cells responded to mAb22E7 with a median [Ca+2]i increase of 20% (11/39) peaking 90 s (64/144) after the application. Only very few neurons responded and the median percentage of responding neuronal area was 0% (0/5.9). Mast cell activation remained in the presence of the fast sodium channel blocker tetrodotoxin. Specific neuronal activation by transmural electrical field stimulation (EFS) in 34 samples evoked instantaneously [Ca+2]i signals in submucous neurons. This was followed by a [Ca+2]i peak response of 8%ΔF/F (4/15) in 33% of 168 mast cells in the field of view. The mast cell response was abolished by the nerve blocker tetrododoxin, reduced by the Calcitonin Gene-Related Peptide receptor 1 antagonist BIBN-4096 and the Vasoactive Intestinal Peptide receptor antagonist PG97-269, but not by blockade of the neurokinin receptors 1–3. Conclusion: The findings revealed bidirectional signaling between mast cells and submucous neurons in human gut. In our macroscopically normal preparations a nerve to mast cell signaling was very prominent whereas a mast cell to nerve signaling was rather rare. PMID:29238306

Increased serum serotonin improves parturient calcium homeostasis in dairy cows.

PubMed

Hernández-Castellano, Lorenzo E; Hernandez, Laura L; Weaver, Samantha; Bruckmaier, Rupert M

2017-02-01

Hypocalcemia in dairy cows is caused by the sudden increase in calcium demand by the mammary gland for milk production at the onset of lactation. Serotonin (5-HT) is a key factor for calcium homeostasis, modulating calcium concentration in blood. Therefore, it is hypothesized that administration of 5-hydroxy-l-tryptophan (5-HTP), a 5-HT precursor, can increase 5-HT concentrations in blood and, in turn, induce an increase in blood calcium concentration. In this study, 20 Holstein dairy cows were randomly assigned to 2 experimental groups. Both groups received a daily i.v. infusion of 1 L of either 0.9% NaCl (C group; n = 10) or 0.9% NaCl containing 1 mg of 5-HTP/kg of BW (5-HTP group, n = 10). Infusions started d 10 before the estimated parturition and ceased the day of parturition, resulting in at least 4 d of infusion (8.37 ± 0.74 d of infusion). Until parturition, blood samples were collected every morning before the infusions, after parturition samples were taken daily until d 7, and a final sample was collected on d 30. Milk yield was recorded during this period. No differences between groups were observed for blood glucose, magnesium, and β-hydroxybutyrate. Cows receiving the 5-HTP infusion showed an increase in fatty acid concentrations from d -3 to -1 before parturition. Serum 5-HT concentrations were increased at d -4 related to parturition until d 5 postpartum in the 5-HTP group compared with the C group. In addition, cows from the 5-HTP group had increased 5-HT concentrations in colostrum, but not in mature milk, on d 7 postpartum. Serum calcium concentrations decreased in both groups around parturition; however, calcium remained higher in the 5-HTP group than in controls, with a significant difference between groups on d 1 (1.62 ± 0.08 vs. 1.93 ± 0.09 mmol/L in control and 5-HTP groups, respectively) and d 2 (1.83 ± 0.06 vs. 2.07 ± 0.07 mmol/L in control and 5-HTP groups, respectively). Additionally, colostrum yield (first milking) was lower in the

Mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression☆

PubMed Central

Gómez-Sánchez, Rubén; Gegg, Matthew E.; Bravo-San Pedro, José M.; Niso-Santano, Mireia; Alvarez-Erviti, Lydia; Pizarro-Estrella, Elisa; Gutiérrez-Martín, Yolanda; Alvarez-Barrientos, Alberto; Fuentes, José M.; González-Polo, Rosa Ana; Schapira, Anthony H.V.

2014-01-01

Mutations of the PTEN-induced kinase 1 (PINK1) gene are a cause of autosomal recessive Parkinson's disease (PD). This gene encodes a mitochondrial serine/threonine kinase, which is partly localized to mitochondria, and has been shown to play a role in protecting neuronal cells from oxidative stress and cell death, perhaps related to its role in mitochondrial dynamics and mitophagy. In this study, we report that increased mitochondrial PINK1 levels observed in human neuroblastoma SH-SY5Y cells after carbonyl cyanide m-chlorophelyhydrazone (CCCP) treatment were due to de novo protein synthesis, and not just increased stabilization of full length PINK1 (FL-PINK1). PINK1 mRNA levels were significantly increased by 4-fold after 24 h. FL-PINK1 protein levels at this time point were significantly higher than vehicle-treated, or cells treated with CCCP for 3 h, despite mitochondrial content being decreased by 29%. We have also shown that CCCP dissipated the mitochondrial membrane potential (Δψm) and induced entry of extracellular calcium through L/N-type calcium channels. The calcium chelating agent BAPTA-AM impaired the CCCP-induced PINK1 mRNA and protein expression. Furthermore, CCCP treatment activated the transcription factor c-Fos in a calcium-dependent manner. These data indicate that PINK1 expression is significantly increased upon CCCP-induced mitophagy in a calcium-dependent manner. This increase in expression continues after peak Parkin mitochondrial translocation, suggesting a role for PINK1 in mitophagy that is downstream of ubiquitination of mitochondrial substrates. This sensitivity to intracellular calcium levels supports the hypothesis that PINK1 may also play a role in cellular calcium homeostasis and neuroprotection. PMID:24184327

The extent of intestinal failure-associated liver disease in patients referred for intestinal rehabilitation is associated with increased mortality: an analysis of the pediatric intestinal failure consortium database.

PubMed

Javid, Patrick J; Oron, Assaf P; Duggan, Christopher; Squires, Robert H; Horslen, Simon P

2017-09-05

The advent of regional multidisciplinary intestinal rehabilitation programs has been associated with improved survival in pediatric intestinal failure. Yet, the optimal timing of referral for intestinal rehabilitation remains unknown. We hypothesized that the degree of intestinal failure-associated liver disease (IFALD) at initiation of intestinal rehabilitation would be associated with overall outcome. The multicenter, retrospective Pediatric Intestinal Failure Consortium (PIFCon) database was used to identify all subjects with baseline bilirubin data. Conjugated bilirubin (CBili) was used as a marker for IFALD, and we stratified baseline bilirubin values as CBili<2 mg/dL, CBili 2-4 mg/dL, and CBili>4 mg/dL. The association between baseline CBili and mortality was examined using Cox proportional hazards regression. Of 272 subjects in the database, 191 (70%) children had baseline bilirubin data collected. 38% and 28% of patients had CBili >4 mg/dL and CBili <2 mg/dL, respectively, at baseline. All-cause mortality was 23%. On univariate analysis, mortality was associated with CBili 2-4 mg/dL, CBili >4 mg/dL, prematurity, race, and small bowel atresia. On regression analysis controlling for age, prematurity, and diagnosis, the risk of mortality was increased by 3-fold for baseline CBili 2-4 mg/dL (HR 3.25 [1.07-9.92], p=0.04) and 4-fold for baseline CBili >4 mg/dL (HR 4.24 [1.51-11.92], p=0.006). On secondary analysis, CBili >4 mg/dL at baseline was associated with a lower chance of attaining enteral autonomy. In children with intestinal failure treated at intestinal rehabilitation programs, more advanced IFALD at referral is associated with increased mortality and decreased prospect of attaining enteral autonomy. Early referral of children with intestinal failure to intestinal rehabilitation programs should be strongly encouraged. Treatment Study, Level III. Copyright © 2017 Elsevier Inc. All rights reserved.

Thapsigargin defines the roles of cellular calcium in secretagogue-stimulated enzyme secretion from pancreatic acini.

PubMed

Metz, D C; Patto, R J; Mrozinski, J E; Jensen, R T; Turner, R J; Gardner, J D

1992-10-15

In the present study we used thapsigargin (TG), an inhibitor of microsomal calcium ATPase, to evaluate the roles of free cytoplasmic calcium and intracellular stored calcium in secretagogue-stimulated enzyme secretion from rat pancreatic acini. Using microspectrofluorimetry of fura-2-loaded pancreatic acini, we found that TG caused a sustained increase in free cytoplasmic calcium by mobilizing calcium from inositol 1,4,5-trisphosphate-sensitive intracellular stores and by increasing influx of extracellular calcium. TG also caused a small increase in basal amylase secretion, inhibited the stimulation of amylase secretion caused by secretagogues that increase inositol 1,4,5-trisphosphate, and potentiated the stimulation of amylase secretion caused by 12-O-tetradecanoylphorbol-13-acetate or secretagogues that increase cyclic adenosine 3',5'-monophosphate. Bombesin, which like TG increased free cytoplasmic calcium, also potentiated the stimulation of amylase secretion caused by secretagogues that increase cyclic adenosine 3',5'-monophosphate, but did not inhibit the stimulation of amylase secretion caused by secretagogues that increase inositol 1,4,5-trisphosphate. Finally, TG inhibited the sustained phase of cholecystokinin-stimulated amylase secretion and potentiated the time course of vasoactive intestinal peptide-stimulated amylase secretion. The present findings indicate that stimulation of amylase secretion by secretagogues that increase inositol 1,4,5-trisphosphate does not depend on increased free cytoplasmic calcium per se. In contrast, TG-induced potentiation of the stimulation of secretagogues that increase cellular cyclic adenosine 3',5'-monophosphate appears to result from increased free cytoplasmic calcium per se.

Na+/H+ exchanger 3 inhibitor diminishes the amino-acid-enhanced transepithelial calcium transport across the rat duodenum.

PubMed

Thammayon, Nithipak; Wongdee, Kannikar; Lertsuwan, Kornkamon; Suntornsaratoon, Panan; Thongbunchoo, Jirawan; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

2017-04-01

Na + /H + exchanger (NHE)-3 is important for intestinal absorption of nutrients and minerals, including calcium. The previous investigations have shown that the intestinal calcium absorption is also dependent on luminal nutrients, but whether aliphatic amino acids and glucose, which are abundant in the luminal fluid during a meal, similarly enhance calcium transport remains elusive. Herein, we used the in vitro Ussing chamber technique to determine epithelial electrical parameters, i.e., potential difference (PD), short-circuit current (Isc), and transepithelial resistance, as well as 45 Ca flux in the rat duodenum directly exposed on the mucosal side to glucose or various amino acids. We found that mucosal glucose exposure led to the enhanced calcium transport, PD, and Isc, all of which were insensitive to NHE3 inhibitor (100 nM tenapanor). In the absence of mucosal glucose, several amino acids (12 mM in the mucosal side), i.e., alanine, isoleucine, leucine, proline, and hydroxyproline, markedly increased the duodenal calcium transport. An inhibitor for NHE3 exposure on the mucosal side completely abolished proline- and leucine-enhanced calcium transport, but not transepithelial transport of both amino acids themselves. In conclusion, glucose and certain amino acids in the mucosal side were potent stimulators of the duodenal calcium absorption, but only amino-acid-enhanced calcium transport was NHE3-dependent.

Increased oral AUC of baicalin in streptozotocin-induced diabetic rats due to the increased activity of intestinal beta-glucuronidase.

PubMed

Liu, Li; Deng, Yuan-Xiong; Liang, Yan; Pang, Xiao-Yan; Liu, Xiao-Dong; Liu, Yao-Wu; Yang, Jian-Song; Xie, Lin; Wang, Guang-Ji

2010-01-01

The purpose of the study was to investigate the pharmacokinetics of baicalin, a major bioactive component of Scutellariae radix, in diabetic conditions. The 4-week diabetic rats were induced by intraperitoneal administration of streptozotocin. Plasma concentrations of baicalin were measured following oral (200 mg/kg) or intravenous (12 mg/kg) administration. Everted intestinal transport, intestinal mucosal metabolism of baicalin and intestinal beta-glucuronidase activity were also investigated. It was found that the diabetic condition significantly increased the exposure of baicalin following oral doses (AUC 100.77 +/- 4.16 microg x h/mL in diabetic rats vs. 48.48 +/- 7.94 microg x h/mL in normal rats). In contrast, the diabetic condition significantly decreased the exposure of baicalin following intravenous doses (AUC 11.20 +/- 2.28 microg x h/mL in diabetic rats vs. 18.02 +/- 3.45 microg x h/mL in normal rats). We also found lower apparent permeability coefficients of baicalin in the ileum of diabetic rats (8.43 x 10 (-6) +/- 2.40 x 10 (-6) cm/s in diabetic rats vs. 5.21 x 10 (-5) +/- 1.55 x 10 (-5) cm/s in normal rats). Further studies showed that the diabetic condition enhanced the hydrolysis of baicalin to baicalein in intestinal mucosal, accompanied by an increase of beta-glucuronidase activity. All these results suggested that the higher oral exposure of baicalin in diabetic rats did not result from the decreased hepatic metabolism or increased intestinal absorption of baicalin. The enhancement of intestinal beta-glucuronidase activity may partly account for the higher exposure of baicalin in diabetic rats after oral administration. Copyright Georg Thieme Verlag KG Stuttgart . New York.

Effect of prostaglandin on indomethacin-induced increased intestinal permeability in man.

PubMed

Bjarnason, I; Smethurst, P; Clark, P; Menzies, I; Levi, J; Peters, T

1989-01-01

This study examines whether NSAID induced disruption of small intestinal integrity is preventable by concomitant prostaglandin administration, and whether prostaglandins themselves interfere with intestinal permeability and absorption. Twelve subjects underwent testing following treatment as indicated: baseline, no treatment rioprostil, 300 micrograms, at -9 and -1 h indomethacin, 75 mg and 50 mg, at -9 and -1 h respectively rioprostil plus indomethacin, regimen as above. At 0800 h (0 h) subjects drink a solution containing 51CrEDTA 100 microCi, L-rhamnose 0.5 g, D-xylose 0.5 g and 3-O-methyl-glucose 0.2 g; this is followed by a 5-h urine collection. The amount of test substance in the urine reflects non-mediated intercellular and transcellular permeability, and passive and active carrier mediated transport systems, respectively. Permeation of L-rhamnose, D-xylose and 3-O-methyl-glucose is unaffected by rioprostil and/or indomethacin. Indomethacin significantly increases intestinal permeability to 51CrEDTA; coadministration of rioprostil, however, significantly decreases this detrimental effect of indomethacin. These findings suggest that prostaglandins are essential for maintaining small intestinal integrity in man and lend further support to the suggestion that NSAIDs damage the small intestine by reducing mucosal prostaglandin synthesis.

Chlorogenic Acid Decreases Intestinal Permeability and Increases Expression of Intestinal Tight Junction Proteins in Weaned Rats Challenged with LPS

PubMed Central

Ruan, Zheng; Liu, Shiqiang; Zhou, Yan; Mi, Shumei; Liu, Gang; Wu, Xin; Yao, Kang; Assaad, Houssein; Deng, Zeyuan; Hou, Yongqing; Wu, Guoyao; Yin, Yulong

2014-01-01

Chlorogenic acid, a natural phenolic acid present in fruits and plants, provides beneficial effects for human health. The objectives of this study were to investigate whether chlorogenic acid (CHA) could improve the intestinal barrier integrity for weaned rats with lipopolysaccharide (LPS) challenge. Thirty-two weaned male Sprague Dawley rats (21±1 d of age; 62.26±2.73 g) were selected and randomly allotted to four treatments, including weaned rat control, LPS-challenged and chlorogenic acid (CHA) supplemented group (orally 20 mg/kg and 50 mg/kg body). Dietary supplementation with CHA decreased (P<0.05) the concentrations of urea and albumin in the serum, compared to the LPS-challenged group. The levels of IFN-γ and TNF-α were lower (P<0.05) in the jejunal and colon of weaned rats receiving CHA supplementation, in comparison with the control group. CHA supplementation increased (P<0.05) villus height and the ratio of villus height to crypt depth in the jejunal and ileal mucosae under condictions of LPS challenge. CHA supplementation decreased (P<0.05) intestinal permeability, which was indicated by the ratio of lactulose to mannitol and serum DAO activity, when compared to weaned rats with LPS challenge. Immunohistochemical analysis of tight junction proteins revealed that ZO-1 and occludin protein abundances in the jejunum and colon were increased (P<0.05) by CHA supplementation. Additionally, results of immunoblot analysis revealed that the amount of occludin in the colon was also increased (P<0.05) in CHA-supplemented rats. In conclusion, CHA decreases intestinal permeability and increases intestinal expression of tight junction proteins in weaned rats challenged with LPS. PMID:24887396

Concentrations of cadmium and selected essential elements in malignant large intestine tissue

PubMed Central

Dziki, Adam; Kilanowicz, Anna; Sapota, Andrzej; Duda-Szymańska, Joanna; Daragó, Adam

2015-01-01

Introduction Colorectal cancer is one of the most common cancers worldwide. Incidence rates of large intestine cancer indicate a role of environmental and occupational factors. The role of essential elements and their interaction with toxic metals can contribute to the explanation of a complex mechanism by which large intestine cancer develops. Bearing this in mind, determining the levels of essential and toxic elements in tissues (organs), as well as in body fluids, seems to shed light on their role in the mode of action in malignant disease. Aim Determination of the levels of cadmium, zinc, copper, selenium, calcium, magnesium, and iron in large intestine malignant tissue. Material and methods Two intraoperative intestine sections were investigated: one from the malignant tissue and the other one from the normal tissue, collected from each person with diagnosed large intestine cancer. Cadmium, zinc, copper, calcium, magnesium, and iron levels were determined with atomic absorption spectrometry, and selenium levels by spectrofluorimetric method. Results The levels of copper, selenium, and magnesium were higher in the malignant than in normal tissues. In addition, the zinc/copper and calcium/magnesium relationship was altered in malignant tissue, where correlations were lower compared to non-malignant tissue. Conclusions The results seems to demonstrate disturbed homeostasis of some essential elements. However, it is hard to confirm their involvement in the aetiology of colorectal cancer. PMID:27110307

Impact of Increasing Dietary Calcium Levels on Calcium Excretion and Vitamin D Metabolites in the Blood of Healthy Adult Cats.

PubMed

Paßlack, Nadine; Schmiedchen, Bettina; Raila, Jens; Schweigert, Florian J; Stumpff, Friederike; Kohn, Barbara; Neumann, Konrad; Zentek, Jürgen

2016-01-01

Dietary calcium (Ca) concentrations might affect regulatory pathways within the Ca and vitamin D metabolism and consequently excretory mechanisms. Considering large variations in Ca concentrations of feline diets, the physiological impact on Ca homeostasis has not been evaluated to date. In the present study, diets with increasing concentrations of dicalcium phosphate were offered to ten healthy adult cats (Ca/phosphorus (P): 6.23/6.02, 7.77/7.56, 15.0/12.7, 19.0/17.3, 22.2/19.9, 24.3/21.6 g/kg dry matter). Each feeding period was divided into a 10-day adaptation and an 8-day sampling period in order to collect urine and faeces. On the last day of each feeding period, blood samples were taken. Urinary Ca concentrations remained unaffected, but faecal Ca concentrations increased (P < 0.001) with increasing dietary Ca levels. No effect on whole and intact parathyroid hormone levels, fibroblast growth factor 23 and calcitriol concentrations in the blood of the cats were observed. However, the calcitriol precursors 25(OH)D2 and 25(OH)D3, which are considered the most useful indicators for the vitamin D status, decreased with higher dietary Ca levels (P = 0.013 and P = 0.033). Increasing dietary levels of dicalcium phosphate revealed an acidifying effect on urinary fasting pH (6.02) and postprandial pH (6.01) (P < 0.001), possibly mediated by an increase of urinary phosphorus (P) concentrations (P < 0.001). In conclusion, calcitriol precursors were linearly affected by increasing dietary Ca concentrations. The increase in faecal Ca excretion indicates that Ca homeostasis of cats is mainly regulated in the intestine and not by the kidneys. Long-term studies should investigate the physiological relevance of the acidifying effect observed when feeding diets high in Ca and P.

Antioxidant and antiapoptotic properties of melatonin restore intestinal calcium absorption altered by menadione.

PubMed

Carpentieri, A; Marchionatti, A; Areco, V; Perez, A; Centeno, V; Tolosa de Talamoni, N

2014-02-01

The intestinal Ca²⁺ absorption is inhibited by menadione (MEN) through oxidative stress and apoptosis. The aim of this study was to elucidate whether the antioxidant and antiapoptotic properties of melatonin (MEL) could protect the gut against the oxidant MEN. For this purpose, 4-week-old chicks were divided into four groups: (1) controls, (2) treated i.p. with MEN (2.5 μmol/kg of b.w.), (3) treated i.p. with MEL (10 mg/kg of b.w.), and (4) treated with 10 mg MEL/kg of b.w after 2.5 μmol MEN/kg of b.w. Oxidative stress was assessed by determination of glutathione (GSH) and protein carbonyl contents as well as antioxidant enzyme activities. Apoptosis was assayed by the TUNEL technique, protein expression, and activity of caspase 3. The data show that MEL restores the intestinal Ca²⁺ absorption altered by MEN. In addition, MEL reversed the effects caused by MEN such as decrease in GSH levels, increase in the carbonyl content, alteration in mitochondrial membrane permeability, and enhancement of superoxide dismutase and catalase activities. Apoptosis triggered by MEN in the intestinal cells was arrested by MEL, as indicated by normalization of the mitochondrial membrane permeability, caspase 3 activity, and DNA fragmentation. In conclusion, MEL reverses the inhibition of intestinal Ca²⁺ absorption produced by MEN counteracting oxidative stress and apoptosis. These findings suggest that MEL could be a potential drug of choice for the reversal of impaired intestinal Ca²⁺ absorption in certain gut disorders that occur with oxidative stress and apoptosis.

Calcium fertilization increases the concentration of calcium in sapwood and calcium oxalate in foliage of red spruce

Treesearch

Kevin T. Smith; Walter C. Shortle; Jon H. Connolly; Rakesh Minocha; Jody Jellison

2009-01-01

Calcium cycling plays a key role in the health and productivity of red spruce forests in the northeastern US. A portion of the flowpath of calcium within forests includes translocation as Ca2+ in sapwood and accumulation as crystals of calcium oxalate in foliage. Concentrations of Ca in these tree tissues have been used as markers of...

Calcium modulation of the effects of serotonin, carbachol, and histamine on rabbit ileal ion transport.

PubMed Central

Chough, S. P.; Goldenring, J. R.; Hurst, R. D.; Ballantyne, G. H.; Modlin, I. M.

1993-01-01

In mammalian intestine, a number of secretagogues have been shown to work through either cyclic nucleotide or calcium mediated pathways to elicit ion secretion. Because excessive intestinal electrolyte and fluid secretion is central to the pathogenesis of a variety of diarrheal disorders, understanding of these processes is essential to the development of future clinical treatments. In the current study, the effects of serotonin (5HT), histamine, and carbachol on intestinal ion transport were examined in in vitro preparations of rabbit ileum. All three agonists induced a rapid and transient increase short-circuit current (delta Isc) across ileal mucosa. Inhibition of the delta Isc response of all three agents in chloride-free solution or in the presence of bumetanide confirmed that chloride is the main electrolyte involved in electrogenic ion secretion. Pretreatment of tissue with tetrodotoxin or atropine did not effect secretagogue-mediated electrolyte secretion. While tachyphylaxis of delta Isc response was shown to develop after repeated exposure of a secretagogue to tissue, delta Isc responses after sequential addition of different agonists indicate that cross-tachyphylaxis between agents did not occur. Serotonin, histamine, and carbachol have previously been reported to mediate electrolyte secretion through calcium-dependent pathways. To access the role of extracellular calcium in regulating ion secretion, the effect of verapamil on each agent was tested; verapamil decreased 5HT-induced delta Isc by 65.2% and histamine response by 33.5%, but had no effect on carbachol-elicited chloride secretion. An additive secretory effect was found upon simultaneous exposure of 5HT and carbachol to the system; no other combination of agents produced a significant additive effect. Findings from this study support previous work which has suggested that multiple calcium pathways may be involved in mediating chloride secretion in mammalian intestine. PMID:7716972

The role of calcium intake in preventing bone fragility, hypertension, and certain cancers.

PubMed

Barger-Lux, M J; Heaney, R P

1994-08-01

This paper examines the evidence that connects calcium intake and vitamin D status to bone fragility, hypertension, colon cancer, and breast cancer. Human calcium physiology, with an intestinal absorptive barrier and inefficient conservation, reflects the abundance of calcium in the primordial human food supply. The calcium intake of stone-age adults is estimated at 50 to 75 mmol/d, three to five times the median calcium intake of present-day U.S. adults. Long-term calcium restriction and/or insufficient vitamin D may promote the development of bone fragility, high blood pressure, colon cancer, and breast cancer in susceptible individuals. Conversely, improvement in calcium intake and/or in vitamin D status may help to prevent these serious health problems. At least 12 intervention studies have established the skeletal benefit of increased calcium intake among women in the late postmenopause. Other reports suggest that adequate calcium may protect against salt-sensitive and pregnancy-associated hypertension. High intakes of both dietary calcium and vitamin D are associated with reduced development of precancerous changes in colonic mucosa. Preliminary findings also suggest that vitamin D has a protective effect against breast cancer.

Analysis and effects of cytosolic free calcium increases in response to elicitors in Nicotiana plumbaginifolia cells.

PubMed

Lecourieux, David; Mazars, Christian; Pauly, Nicolas; Ranjeva, Raoul; Pugin, Alain

2002-10-01

Cell suspensions obtained from Nicotiana plumbaginifolia plants stably expressing the apoaequorin gene were used to analyze changes in cytosolic free calcium concentrations ([Ca(2+)](cyt)) in response to elicitors of plant defenses, particularly cryptogein and oligogalacturonides. The calcium signatures differ in lag time, peak time, intensity, and duration. The intensities of both signatures depend on elicitor concentration and extracellular calcium concentration. Cryptogein signature is characterized by a long-sustained [Ca(2+)](cyt) increase that should be responsible for sustained mitogen-activated protein kinase activation, microtubule depolymerization, defense gene activation, and cell death. The [Ca(2+)](cyt) increase in elicitor-treated cells first results from a calcium influx, which in turns leads to calcium release from internal stores and additional Ca(2+) influx. H(2)O(2) resulting from the calcium-dependent activation of the NADPH oxidase also participates in [Ca(2+)](cyt) increase and may activate calcium channels from the plasma membrane. Competition assays with different elicitins demonstrate that [Ca(2+)](cyt) increase is mediated by cryptogein-receptor interaction.

Analysis and Effects of Cytosolic Free Calcium Increases in Response to Elicitors in Nicotiana plumbaginifolia Cells

PubMed Central

Lecourieux, David; Mazars, Christian; Pauly, Nicolas; Ranjeva, Raoul; Pugin, Alain

2002-01-01

Cell suspensions obtained from Nicotiana plumbaginifolia plants stably expressing the apoaequorin gene were used to analyze changes in cytosolic free calcium concentrations ([Ca2+]cyt) in response to elicitors of plant defenses, particularly cryptogein and oligogalacturonides. The calcium signatures differ in lag time, peak time, intensity, and duration. The intensities of both signatures depend on elicitor concentration and extracellular calcium concentration. Cryptogein signature is characterized by a long-sustained [Ca2+]cyt increase that should be responsible for sustained mitogen-activated protein kinase activation, microtubule depolymerization, defense gene activation, and cell death. The [Ca2+]cyt increase in elicitor-treated cells first results from a calcium influx, which in turns leads to calcium release from internal stores and additional Ca2+ influx. H2O2 resulting from the calcium-dependent activation of the NADPH oxidase also participates in [Ca2+]cyt increase and may activate calcium channels from the plasma membrane. Competition assays with different elicitins demonstrate that [Ca2+]cyt increase is mediated by cryptogein–receptor interaction. PMID:12368509

Effect of hydrocortisone on total body calcium in rats. [/sup 47/Ca and /sup 85/Sr tracer techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yasumura, S.; Ellis, K.J.; Cohn, S.H.

Administration of 5 mg. of hydrocortisone acetate to rats every other day for 2 weeks resulted in growth retardation and weight loss as indicated by body weights of experimental animals, which averaged 33 percent lower than those of the controls, and a significant decrease in the length of the tibiae and femurs (p less than 0.01 for treated vs controls). However, despite the smaller size of the treated animals, the values for total body calcium (TBCa) and the calcium in the tibia and femur did not differ significantly from control values. Thus, there was more calcium per unit length ofmore » bone, resulting in an increase in the skeletal density of treated rats. This finding was confirmed by x-ray examination of these bones. The net intestinal absorption of calcium (rate of initial entry) calculated from plasma levels following an oral and intravenous dose of /sup 47/Ca and /sup 85/Sr, respectively, was not significantly different in hydrocortisone-treated rats compared to controls. This would indicate that the rate of intestinal absorption of calcium is unimpaired despite the administration of massive doses of corticosteroids. When the animals were placed on a calcium-deficient diet, both TBCa and tibia and femur calcium levels were decreased. Subsequent administration of hydrocortisone did not alter the calcium values. The results of this study are compatible with the hypothesis that hydrocortisone promotes weight loss, retards growth, but inhibits the rate of bone resorption.« less

Calcium supplementation modulates gut microbiota in a prebiotic manner in dietary obese mice.

PubMed

Chaplin, Alice; Parra, Pilar; Laraichi, Sarah; Serra, Francisca; Palou, Andreu

2016-02-01

Dietary calcium has been inversely associated with body fat and energy balance. The main scope of this study has been to assess the potential contribution of gut microbiota on energy regulation mediated by calcium. Gut microbiota in C57BL/6J mice receiving calcium supplementation under a high-fat (HF) diet were analysed by PCR and their relationships with host metabolic parameters were determined. Calcium conferred a prebiotic-like effect on gut microbiota, and animals presented lower plasmatic endotoxin levels, increased expression of angiopoietin-like 4 in intestine and lower hepatic lipid content, although increased expression of stress markers in adipose tissue and of inflammation in liver was also found. To determine whether slimming effects could be transferred to obese mice, a faecal microbial transplant (FMT) was carried out, showing that host bacteria grown under a HF diet could not be superseded by those from calcium-fed animals. Therefore, FMT was not able to transfer the beneficial effects of calcium. In conclusion, calcium modulated gut microbiota in a prebiotic manner, establishing a host cross-talk and promoting a healthier metabolic profile. However, lack of effectiveness of FMT suggests the need of further appropriate dietary factors in addition to the bacteria per se. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Alanyl-glutamine dipeptide-supplemented parenteral nutrition improves intestinal metabolism and prevents increased permeability in rats.

PubMed Central

Haque, S M; Chen, K; Usui, N; Iiboshi, Y; Okuyama, H; Masunari, A; Cui, L; Nezu, R; Takagi, Y; Okada, A

1996-01-01

OBJECTIVE: The authors determined the effects of alanyl-glutamine-supplemented total parenteral nutrition (TPN) on mucosal metabolism, integrity, and permeability of the small intestine in rats. METHODS: Male Sprague-Dawley rats were randomized to receive TPN supplemented with a conventional amino acids mixture (STD group) or the same solution supplemented with alanyl-glutamine; both solutions were isocaloric and isonitrogenous. On the seventh day of TPN, D-xylose and fluorescein isothiocyanate (FITC)-dextran were administered orally. One hour later, superior mesenteric vein (SMV) D-xylose and plasma FITC-dextran concentration were measured. Intestinal blood flow and calculated intestinal substrates flux were measured with ultrasonic transit time flowmetery. RESULTS: Plasma FITC-dextran increased significantly in the STD group. Intestinal blood flow and SMV D-xylose concentration did not differ between the groups. Mucosa weight, villus height, mucosal wall thickness, mucosal protein, and DNA and RNA content in jejunal mucosa were significantly increased in the alanyl-glutamine group. Jejunal mucosal glutaminase activity and net intestinal uptake of glutamine (glutamine flux) were significantly higher in the alanyl-glutamine group as compared with the STD group. CONCLUSION: Addition of alanyl-glutamine dipeptide to the TPN solution improves intestinal glutamine metabolism and prevents mucosal atrophy and deterioration of permeability. PMID:8604914

In utero exposure to perfluorooctanoate (PFOA) or perfluorooctane sulfonate (PFOS) did not increase body weight or intestinal tumorigenesis in multiple intestinal neoplasia (Min/+) mice.

PubMed

Ngo, Ha Thi; Hetland, Ragna Bogen; Sabaredzovic, Azemira; Haug, Line Småstuen; Steffensen, Inger-Lise

2014-07-01

We examined whether perfluorooctanoate (PFOA) or perfluorooctane sulfonate (PFOS) had obesogenic effects and if they increased spontaneous intestinal tumorigenesis in the mouse model C57BL/6J-Min/+ (multiple intestinal neoplasia) after in utero exposure. The dams were exposed to PFOA or PFOS (0.01, 0.1 or 3.0mg/kg bw/day) by po gavage on GD1-17. The Min/+ and wild-type offspring were terminated at week 11 for examination of intestinal tumorigenesis or at week 20 for obesogenic effect, respectively. Body weights of the dams and pups were recorded throughout life. Food intake was determined at week 6 and 10. Blood glucose (non-fasted) was measured at week 6 and 11. No obesogenic effect of PFOA or PFOS was observed up to 20 weeks of age. PFOA or PFOS did not increase the incidence or number of tumors in the small intestine or colon of the Min/+ mice or affect their location along the intestines. Feed intake was not affected. There were some indications of toxicity of PFOA, but not of PFOS. There was lower survival of pups after 3.0mg/kg PFOA, lower body weight in pups after 3.0 and possibly 0.1mg/kg PFOA, and increased relative liver weight after 0.01 and possibly 0.1mg/kg PFOA. Plasma glucose was lower after 0.01 and 0.1mg/kg PFOA. In conclusion, exposure to PFOA and PFOS in utero with the doses used did not have obesogenic effect on either Min/+ or wild-type mice, at least not up to 11 or 20 weeks of age, nor increased intestinal tumorigenesis in Min/+ mice. Copyright © 2014 Elsevier Inc. All rights reserved.

Diet, but not oral probiotics, effectively reduces urinary oxalate excretion and calcium oxalate supersaturation.

PubMed

Lieske, John C; Tremaine, William J; De Simone, Claudio; O'Connor, Helen M; Li, Xujian; Bergstralh, Eric J; Goldfarb, David S

2010-12-01

We examined the effect of a controlled diet and two probiotic preparations on urinary oxalate excretion, a risk factor for calcium oxalate kidney stone formation, in patients with mild hyperoxaluria. Patients were randomized to a placebo, a probiotic, or a synbiotic preparation. This tested whether these probiotic preparations can increase oxalate metabolism in the intestine and/or decrease oxalate absorption from the gut. Patients were maintained on a controlled diet to remove the confounding variable of differing oxalate intake from food. Urinary oxalate excretion and calcium oxalate supersaturation on the controlled diet were significantly lower compared with baseline on a free-choice diet. Neither study preparation reduced urinary oxalate excretion nor calcium oxalate supersaturation. Fecal lactobacilli colony counts increased on both preparations, whereas enterococcal and yeast colony counts were increased on the synbiotic. Total urine volume and the excretion of oxalate and calcium were all strong independent determinants of urinary calcium oxalate supersaturation. Hence, dietary oxalate restriction reduced urinary oxalate excretion, but the tested probiotics did not influence urinary oxalate levels in patients on a restricted oxalate diet. However, this study suggests that dietary oxalate restriction is useful for kidney stone prevention.

Thiazide increases serum calcium in anuric patients: the role of parathyroid hormone.

PubMed

Vasco, Raquel F V; Reis, Eduardo T; Moyses, Rosa M A; Elias, Rosilene M

2017-12-01

We evaluated the effect of hydrochlorothiazide in a sample of anuric patients on hemodialysis and found an increase in serum calcium, which occurred only in those with parathyroid hormone >300 pg/ml. This finding highlights the extra-renal effect of this diuretic and a possible role of parathyroid hormone in the mechanism. Thiazide diuretics are commonly used in patients with chronic kidney disease to treat hypertension. Their effects on calcium and bone metabolism are not well established, once calciuria may not fully explain levels of calcium and parathyroid hormone (PTH) in this population. A previous study has suggested that thiazides require the presence of PTH as a permissive condition for its renal action. In anuric patients, however, the role of PTH, if any, in the thiazide effect is unknown. To assess thiazide extra renal effect on serum calcium and whether such an effect is reliant on PTH, hydrochlorothiazide (HCTZ) 100 mg was given orally once a day to a sample of 19 anuric patients on hemodialysis for 2 weeks. Laboratories' analyses were obtained in three phases: baseline, after diuretic use, and after a 2-week washout phase. We demonstrated that serum calcium (Ca) increased in ten patients (52.6%) after HCTZ use, returning to previous levels after the washout period. Out of the 19 patients, ten presented PTH ≥ 300 pg/ml, and Ca has increased in eight of them, whereas in the other nine patients with PTH < 300 pg/ml, serum Ca has increased only in two individuals (RR risk of increase Ca 3.9; p = 0.012). HCTZ was capable of increasing serum Ca in a sample of anuric patients on hemodialysis and seems this effect is highly dependent on PTH levels. Caution is required while interpreting this result, as the small sample size might implicate in a finding caused by chance.

Timing of developmental reduction in epithelial glutathione redox potential is associated with increased epithelial proliferation in the immature murine intestine.

PubMed

Reid, Graham K; Berardinelli, Andrew J; Ray, Laurie; Jackson, Arena R; Neish, Andrew S; Hansen, Jason M; Denning, Patricia W

2017-08-01

BackgroundThe intracellular redox potential of the glutathione (GSH)/glutathione disulfide (GSSG) couple regulates cellular processes. In vitro studies indicate that a reduced GSH/GSSG redox potential favors proliferation, whereas a more oxidized redox potential favors differentiation. Intestinal growth depends upon an appropriate balance between the two. However, how the ontogeny of intestinal epithelial cellular (IEC) GSH/GSSG redox regulates these processes in the developing intestine has not been fully characterized in vivo.MethodsOntogeny of intestinal GSH redox potential and growth were measured in neonatal mice.ResultsWe show that IEC GSH/GSSG redox potential becomes increasingly reduced (primarily driven by increased GSH concentration) over the first 3 weeks of life. Increased intracellular GSH has been shown to drive proliferation through increased poly-ADP-ribose polymerase (PARP) activity. We show that increasing IEC poly-ADP-ribose chains can be measured over the first 3 weeks of life, indicating an increase in IEC PARP activity. These changes are accompanied by increased intestinal growth and IEC proliferation as assessed by villus height/crypt depth, intestinal length, and Ki67 staining.ConclusionUnderstanding how IEC GSH/GSSG redox potential is developmentally regulated may provide insight into how premature human intestinal redox states can be manipulated to optimize intestinal growth and adaptation.

Vitamin D supplementation increases calcium absorption without a threshold effect

USDA-ARS?s Scientific Manuscript database

The maximal calcium absorption in response to vitamin D has been proposed as a biomarker for vitamin D sufficiency. Our objective was to determine whether there is a threshold beyond which increasing doses of vitamin D, or concentrations of serum 25-hydroxyvitamin D [25(OH)D], no longer increase cal...

Role of calcium signaling in epithelial bicarbonate secretion.

PubMed

Jung, Jinsei; Lee, Min Goo

2014-06-01

Transepithelial bicarbonate secretion plays a key role in the maintenance of fluid and protein secretion from epithelial cells and the protection of the epithelial cell surface from various pathogens. Epithelial bicarbonate secretion is mainly under the control of cAMP and calcium signaling. While the physiological roles and molecular mechanisms of cAMP-induced bicarbonate secretion are relatively well defined, those induced by calcium signaling remain poorly understood in most epithelia. The present review summarizes the current status of knowledge on the role of calcium signaling in epithelial bicarbonate secretion. Specifically, this review introduces how cytosolic calcium signaling can increase bicarbonate secretion by regulating membrane transport proteins and how it synergizes with cAMP-induced mechanisms in epithelial cells. In addition, tissue-specific variations in the pancreas, salivary glands, intestines, bile ducts, and airways are discussed. We hope that the present report will stimulate further research into this important topic. These studies will provide the basis for future medicines for a wide spectrum of epithelial disorders including cystic fibrosis, Sjögren's syndrome, and chronic pancreatitis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Novel Peptide with Specific Calcium-Binding Capacity from Schizochytrium sp. Protein Hydrolysates and Calcium Bioavailability in Caco-2 Cells

PubMed Central

Cai, Xixi; Lin, Jiaping; Wang, Shaoyun

2016-01-01

Peptide-calcium can probably be a suitable supplement to improve calcium absorption in the human body. In this study, a specific peptide Phe-Tyr (FY) with calcium-binding capacity was purified from Schizochytrium sp. protein hydrolysates through gel filtration chromatography and reversed phase HPLC. The calcium-binding capacity of FY reached 128.77 ± 2.57 μg/mg. Results of ultraviolet spectroscopy, fluorescence spectroscopy, and infrared spectroscopy showed that carboxyl groups, amino groups, and amido groups were the major chelating sites. FY-Ca exhibited excellent thermal stability and solubility, which were beneficial to be absorbed and transported in the basic intestinal tract of the human body. Moreover, the calcium bioavailability in Caco-2 cells showed that FY-Ca could enhance calcium uptake efficiency by more than three times when compared with CaCl2, and protect calcium ions against dietary inhibitors, such as tannic acid, oxalate, phytate, and Zn2+. Our findings further the progress of algae-based peptide-calcium, suggesting that FY-Ca has the potential to be developed as functionally nutraceutical additives. PMID:28036002

Clostridium perfringens epsilon toxin increases the small intestinal permeability in mice and rats.

PubMed

Goldstein, Jorge; Morris, Winston E; Loidl, César Fabián; Tironi-Farinati, Carla; Tironi-Farinatti, Carla; McClane, Bruce A; Uzal, Francisco A; Fernandez Miyakawa, Mariano E

2009-09-18

Epsilon toxin is a potent neurotoxin produced by Clostridium perfringens types B and D, an anaerobic bacterium that causes enterotoxaemia in ruminants. In the affected animal, it causes oedema of the lungs and brain by damaging the endothelial cells, inducing physiological and morphological changes. Although it is believed to compromise the intestinal barrier, thus entering the gut vasculature, little is known about the mechanism underlying this process. This study characterizes the effects of epsilon toxin on fluid transport and bioelectrical parameters in the small intestine of mice and rats. The enteropooling and the intestinal loop tests, together with the single-pass perfusion assay and in vitro and ex vivo analysis in Ussing's chamber, were all used in combination with histological and ultrastructural analysis of mice and rat small intestine, challenged with or without C. perfringens epsilon toxin. Luminal epsilon toxin induced a time and concentration dependent intestinal fluid accumulation and fall of the transepithelial resistance. Although no evident histological changes were observed, opening of the mucosa tight junction in combination with apoptotic changes in the lamina propria were seen with transmission electron microscopy. These results indicate that C. perfringens epsilon toxin alters the intestinal permeability, predominantly by opening the mucosa tight junction, increasing its permeability to macromolecules, and inducing further degenerative changes in the lamina propria of the bowel.

Space-flight simulations of calcium metabolism using a mathematical model of calcium regulation

NASA Technical Reports Server (NTRS)

Brand, S. N.

1985-01-01

The results of a series of simulation studies of calcium matabolic changes which have been recorded during human exposure to bed rest and space flight are presented. Space flight and bed rest data demonstrate losses of total body calcium during exposure to hypogravic environments. These losses are evidenced by higher than normal rates of urine calcium excretion and by negative calcium balances. In addition, intestinal absorption rates and bone mineral content are assumed to decrease. The bed rest and space flight simulations were executed on a mathematical model of the calcium metabolic system. The purpose of the simulations is to theoretically test hypotheses and predict system responses which are occurring during given experimental stresses. In this case, hypogravity occurs through the comparison of simulation and experimental data and through the analysis of model structure and system responses. The model reliably simulates the responses of selected bed rest and space flight parameters. When experimental data are available, the simulated skeletal responses and regulatory factors involved in the responses agree with space flight data collected on rodents. In addition, areas within the model that need improvement are identified.

Demographic, dietary, and urinary factors and 24-h urinary calcium excretion.

PubMed

Taylor, Eric N; Curhan, Gary C

2009-12-01

Higher urinary calcium is a risk factor for nephrolithiasis. This study delineated associations between demographic, dietary, and urinary factors and 24-h urinary calcium. Cross-sectional studies were conducted of 2201 stone formers (SF) and 1167 nonstone formers (NSF) in the Health Professionals Follow-up Study (men) and Nurses' Health Studies I and II (older and younger women). Median urinary calcium was 182 mg/d in men, 182 mg/d in older women, and 192 mg/d in younger women. Compared with NSF, urinary calcium as a fraction of calcium intake was 33 to 38% higher in SF (P values < or =0.01). In regression analyses, participants were combined because associations with urinary calcium were similar in each cohort and in SF and NSF. After multivariate adjustment, participants in the highest quartile of calcium intake excreted 18 mg/d more urinary calcium than those in the lowest (P trend =0.01). Caffeine and family history of nephrolithiasis were positively associated, whereas urinary potassium, thiazides, gout, and age were inversely associated, with urinary calcium. After multivariate adjustment, participants in the highest quartiles of urinary magnesium, sodium, sulfate, citrate, phosphorus, and volume excreted 71 mg/d, 37 mg/d, 44 mg/d, 61 mg/d, 37 mg/d, and 24 mg/d more urinary calcium, respectively, than participants in the lowest (P values trend < or =0.01). Intestinal calcium absorption and/or negative calcium balance is greater in SF than NSF. Higher calcium intakes at levels typically observed in free-living individuals are associated with only small increases in urinary calcium.

Mammary-Specific Ablation of the Calcium-Sensing Receptor During Lactation Alters Maternal Calcium Metabolism, Milk Calcium Transport, and Neonatal Calcium Accrual

PubMed Central

Mamillapalli, Ramanaiah; VanHouten, Joshua; Dann, Pamela; Bikle, Daniel; Chang, Wenhan; Brown, Edward

2013-01-01

To meet the demands for milk calcium, the lactating mother adjusts systemic calcium and bone metabolism by increasing dietary calcium intake, increasing bone resorption, and reducing renal calcium excretion. As part of this adaptation, the lactating mammary gland secretes PTHrP into the maternal circulation to increase bone turnover and mobilize skeletal calcium stores. Previous data have suggested that, during lactation, the breast relies on the calcium-sensing receptor (CaSR) to coordinate PTHrP secretion and milk calcium transport with calcium availability. To test this idea genetically, we bred BLG-Cre mice with CaSR-floxed mice to ablate the CaSR specifically from mammary epithelial cells only at the onset of lactation (CaSR-cKO mice). Loss of the CaSR in the lactating mammary gland did not disrupt alveolar differentiation or milk production. However, it did increase the secretion of PTHrP into milk and decreased the transport of calcium from the circulation into milk. CaSR-cKO mice did not show accelerated bone resorption, but they did have a decrease in bone formation. Loss of the mammary gland CaSR resulted in hypercalcemia, decreased PTH secretion, and increased renal calcium excretion in lactating mothers. Finally, loss of the mammary gland CaSR resulted in decreased calcium accrual by suckling neonates, likely due to the combination of increased milk PTHrP and decreased milk calcium. These results demonstrate that the mammary gland CaSR coordinates maternal bone and calcium metabolism, calcium transport into milk, and neonatal calcium accrual during lactation. PMID:23782944

Alcohol, Intestinal Bacterial Growth, Intestinal Permeability to Endotoxin, and Medical Consequences

PubMed Central

Purohit, Vishnudutt; Bode, J. Christian; Bode, Christiane; Brenner, David A.; Choudhry, Mashkoor A.; Hamilton, Frank; Kang, Y. James; Keshavarzian, Ali; Rao, Radhakrishna; Sartor, R. Balfour; Swanson, Christine; Turner, Jerrold R.

2008-01-01

This report is a summary of the symposium on Alcohol, Intestinal Bacterial Growth, Intestinal Permeability to Endotoxin, and Medical Consequences, organized by National Institute on Alcohol Abuse and Alcoholism, Office of Dietary Supplements, and National Institute of Diabetes and Digestive and Kidney Diseases of National Institutes of Health in Rockville, Maryland, October 11, 2006. Alcohol exposure can promote the growth of Gram negative bacteria in the intestine which may result in accumulation of endotoxin. In addition, alcohol metabolism by Gram negative bacteria and intestinal epithelial cells can result in accumulation of acetaldehyde, which in turn can increase intestinal permeability to endotoxin by increasing tyrosine phosphorylation of tight junction and adherens junction proteins. Alcohol-induced generation of nitric oxide may also contribute to increased permeability to endotoxin by reacting with tubulin, which may cause damage to microtubule cytoskeleton and subsequent disruption of intestinal barrier function. Increased intestinal permeability can lead to increased transfer of endotoxin from the intestine to the liver and general circulation where endotoxin may trigger inflammatory changes in the liver and other organs. Alcohol may also increase intestinal permeability to peptidoglycan which can initiate inflammatory response in liver and other organs. In addition, acute alcohol exposure may potentiate the effect of burn injury on intestinal bacterial growth and permeability. Decreasing the number of Gram negative bacteria in the intestine can result in decreased production of endotoxin as well as acetaldehyde which is expected to decrease intestinal permeability to endotoxin. In addition, intestinal permeability may be preserved by administering epidermal growth factor, L-glutamine, oats supplementation, or zinc thereby preventing the transfer of endotoxin to the general circulation. Thus reducing the number of intestinal Gram negative bacteria and

INCREASES IN CYTOSOLIC CALCIUM ION LEVELS IN HUMAN NATURAL KILLER CELLS IN RESPONSE TO BUTYLTIN EXPOSURE

PubMed Central

Lane, Rhonda; Ghazi, Sabah O.; Whalen, Margaret M.

2009-01-01

This study investigated whether exposures to butyltins (BTs), tributylin (TBT) and dibutyltin (DBT) were able to alter cytosolic calcium levels in human natural killer (NK) cells. Additionally, the effects of cytosolic calcium ion increases on the activation state of mitogen activated protein kinases (MAPKs) in NK cells were also investigated. NK cells are an intital immune defense against the development of tumors or viral infections. TBT and DBT are widespread environmental contaminants, due to their various industrial applications. Both TBT and DBT have been shown to decrease the ability of NK cells to lyse tumor cells (lytic function). TBT has also been shown to activate MAPKs in NK cells. The results of this study indicated that TBT increased cytosolic calcium levels by as much as 100% after a 60 min exposure to 500 nM TBT while DBT increased cytosolic calcium levels to a much smaller extent (and required higher concentrations). The results also indicated that increases in cytosolic calcium could activate MAPKs but only for a short period of time (5 min), while previous studies showed that activation of MAPKs by TBT last for at least 6 hours. Thus, it appears that TBT stimulated increases in cytosolic calcium may contribute to, but are not fully responsible for, TBT-induced activation of MAPKs. PMID:19365649

Effects of age on intestinal phosphate transport and biochemical values of broiler chickens

PubMed Central

Li, Jianhui; Yuan, Jianmin; Miao, Zhiqiang; Guo, Yuming

2017-01-01

Objective The objective of this experiment was to characterize the mRNA expression profile of type IIb sodium-inorganic phosphate cotransporter (NaPi-IIb) and the biochemical values of serum alkaline phosphatase (AKP), calcium, inorganic phosphorus, tibial ash and minerals of broiler chickens with aging. Methods A total of 56 one-day-old Arbor Acres male broiler chickens were used. Broiler chickens were weighed and samples were collected weekly from day 1. Results The result showed that before the growth inflection point, ash, calcium, and phosphorus content in the tibia of broiler chickens increased with growth (before 3 weeks of age), although there were no significant differences in chicks at different ages in the later period of the experiment and weight gain rate was relatively slow at this stage (4 to 6 weeks). NaPi-IIb gene expression in the small intestine in the early growth stage was higher than that in the later growth stage. Expression of calbindin and the vitamin D receptor protein in the intestinal mucosa increased with age in the duodenum and jejunum. Serum AKP activity first increased and subsequently decreased after peaking at 1 week of age, but there was no significant difference after 3 weeks of age. Conclusion These results show that compared with the early growth stage, the weight-gain rate of broiler chickens in the late growth stage gradually decreased with gradual tibia maturation, along with weaker positive transport of phosphorus in the intestine and reinforced re-absorption of phosphorus in the kidney, which might be the reason that phosphorus requirement in the late growth stage was decreased. PMID:27703131

Cyclooxygenase-2 Deficiency Leads to Intestinal Barrier Dysfunction and Increased Mortality During Polymicrobial Sepsis 1

PubMed Central

Fredenburgh, Laura E.; Velandia, Margarita M. Suarez; Ma, Jun; Olszak, Torsten; Cernadas, Manuela; Englert, Joshua A.; Chung, Su Wol; Liu, Xiaoli; Begay, Cynthia; Padera, Robert F.; Blumberg, Richard S.; Walsh, Stephen R.; Baron, Rebecca M.; Perrella, Mark A.

2011-01-01

Sepsis remains the leading cause of death in critically ill patients despite modern advances in critical care. Intestinal barrier dysfunction may lead to secondary bacterial translocation and the development of the multiple organ dysfunction syndrome during sepsis. Cyclooxygenase-2 (COX-2) is highly upregulated in the intestine during sepsis and we hypothesized that it may be critical in the maintenance of intestinal epithelial barrier function during peritonitis-induced polymicrobial sepsis. COX-2−/− and COX-2+/+ BALB/c mice underwent cecal ligation and puncture (CLP) or sham surgery. Mice chimeric for COX-2 were derived by bone marrow transplantation and underwent CLP. C2BBe1 cells, an intestinal epithelial cell line, were treated with the COX-2 inhibitor NS-398, PGD2, or vehicle and stimulated with cytokines. COX-2−/− mice developed exaggerated bacteremia and increased mortality compared with COX-2+/+ mice following CLP. Mice chimeric for COX-2 exhibited the recipient phenotype suggesting that epithelial COX-2 expression in the ileum attenuates bacteremia following CLP. Absence of COX-2 significantly increased epithelial permeability of the ileum and reduced expression of the tight junction proteins zonula occludens-1 (ZO-1), occludin, and claudin-1 in the ileum following CLP. Furthermore, PGD2 attenuated cytokine-induced hyperpermeability and ZO-1 downregulation in NS-398-treated C2BBe1 cells. Our findings reveal that absence of COX-2 is associated with enhanced intestinal epithelial permeability and leads to exaggerated bacterial translocation and increased mortality during peritonitis-induced sepsis. Taken together, our results suggest that epithelial expression of COX-2 in the ileum is a critical modulator of tight junction protein expression and intestinal barrier function during sepsis. PMID:21967897

Vitamin D-mediated calcium absorption in patients with clinically stable Crohn's disease: a pilot study

USDA-ARS?s Scientific Manuscript database

Vitamin D is the critical hormone for intestinal absorption of calcium. Optimal calcium absorption is important for proper mineralization of bone in the prevention of osteoporosis and osteoporotic fractures, among other important functions. Diseases associated with gut inflammation, such as Crohn's ...

Corticosterone mediates stress-related increased intestinal permeability in a region-specific manner

PubMed Central

Zheng, Gen; Wu, Shu-Pei; Hu, Yongjun; Smith, David E; Wiley, John W.; Hong, Shuangsong

2012-01-01

Background Chronic psychological stress (CPS) is associated with increased intestinal epithelial permeability and visceral hyperalgesia. It is unknown whether corticosterone (CORT) plays a role in mediating alterations of epithelial permeability in response to CPS. Methods Male rats were subjected to 1-hour water avoidance (WA) stress or subcutaneous CORT injection daily for 10 consecutive days in the presence or absence of corticoid-receptor antagonist RU-486. The visceromotor response (VMR) to colorectal distension (CRD) was measured. The in situ single-pass intestinal perfusion was used to measure intestinal permeability in jejunum and colon simultaneously. Key Results We observed significant decreases in the levels of glucocorticoid receptor (GR) and tight junction proteins in the colon but not the jejunum in stressed rats. These changes were largely reproduced by serial CORT injections in control rats and were significantly reversed by RU-486. Stressed and CORT-injected rats demonstrated a 3-fold increase in permeability for PEG-400 (MW) in colon but not jejunum and significant increase in VMR to CRD, which was significantly reversed by RU-486. In addition, no differences in permeability to PEG-4,000 and PEG-35,000 were detected between control and WA groups. Conclusions & Inferences Our findings indicate that CPS was associated with region-specific decrease in epithelial tight junction protein levels in the colon, increased colon epithelial permeability to low-molecular weight macromolecules which were largely reproduced by CORT treatment in control rats and prevented by RU-486. These observations implicate a novel, region-specific role for CORT as a mediator of CPS-induced increased permeability to macromolecules across the colon epithelium. PMID:23336591

[Prevention of osteoporosis by foods and dietary supplements. Chocolate malt drink MILO: nutrition in children and calcium absorption].

PubMed

Fukushima, Yoichi; Kumagai, Akiko

2006-10-01

Calcium is not sufficiently consumed by Japanese at any age groups. Childhood is an important period, when they should earn bone minerals to reach higher peak bone mass for reducing the risk of osteoporosis in their later life. Children require higher calcium consumption per body weight than adults, and also establish their dietary pattern in this period. MILO has attracted widespread popularity as a good-taste chocolate-flavored malt drink with balanced nutrients for children. We developed FOSHU MILO with fructooligosaccharides (FOS) aiming at improving absorption of calcium, which is originally rich in the products. Using the calcium stable isotope (44)Ca, we found that the urinary excretion in the subject fed the products with FOS was higher than that of control product without FOS, suggesting that the FOSHU MILO is effective in promoting calcium absorption from the intestines. MILO could contribute to bone health by increasing consumption of calcium and/or improving the calcium bioavailability.

Osteomalacia and osteoporosis associated with primary intestinal lymphangiectasis.

PubMed

Li, Xin-Ping; Shen, Wen-Bin; Long, Ming-Qing; Meng, Xun-Wu; Lian, Xiao-Lan; Yu, Miao

2012-05-01

Primary Intestinal lymphangiectasia (PIL) is a common cause of protein losing enteropathy (PLE). It will affect enter-hepatic circulation of lipid-soluble vitamin, and absorption of electrolytes, cause malnutrition related osteomalacia or osteoporosis. While seldom health care workers noted to assess and treat osteomalacia or osteoporosis in PIL. Here we report a related case. We found increased parathyroid hormone, decreased 25(OH)D3, low bone mineral density, which indicated that the PIL patient had osteomalacia and/or osteoporosis. Adequate calcium and vitamin D supply can relieve the condition efficaciously. We should pay attention to osteomalacia and osteoporosis in PIL patients.

Demographic, Dietary, and Urinary Factors and 24-h Urinary Calcium Excretion

PubMed Central

Curhan, Gary C.

2009-01-01

Background and objectives: Higher urinary calcium is a risk factor for nephrolithiasis. This study delineated associations between demographic, dietary, and urinary factors and 24-h urinary calcium. Design, setting, participants, & measurements: Cross-sectional studies were conducted of 2201 stone formers (SF) and 1167 nonstone formers (NSF) in the Health Professionals Follow-up Study (men) and Nurses' Health Studies I and II (older and younger women). Results: Median urinary calcium was 182 mg/d in men, 182 mg/d in older women, and 192 mg/d in younger women. Compared with NSF, urinary calcium as a fraction of calcium intake was 33 to 38% higher in SF (P values ≤0.01). In regression analyses, participants were combined because associations with urinary calcium were similar in each cohort and in SF and NSF. After multivariate adjustment, participants in the highest quartile of calcium intake excreted 18 mg/d more urinary calcium than those in the lowest (P trend =0.01). Caffeine and family history of nephrolithiasis were positively associated, whereas urinary potassium, thiazides, gout, and age were inversely associated, with urinary calcium. After multivariate adjustment, participants in the highest quartiles of urinary magnesium, sodium, sulfate, citrate, phosphorus, and volume excreted 71 mg/d, 37 mg/d, 44 mg/d, 61 mg/d, 37 mg/d, and 24 mg/d more urinary calcium, respectively, than participants in the lowest (P values trend ≤0.01). Conclusions: Intestinal calcium absorption and/or negative calcium balance is greater in SF than NSF. Higher calcium intakes at levels typically observed in free-living individuals are associated with only small increases in urinary calcium. PMID:19820135

Sweet taste receptors in rat small intestine stimulate glucose absorption through apical GLUT2.

PubMed

Mace, Oliver J; Affleck, Julie; Patel, Nick; Kellett, George L

2007-07-01

Natural sugars and artificial sweeteners are sensed by receptors in taste buds. T2R bitter and T1R sweet taste receptors are coupled through G-proteins, alpha-gustducin and transducin, to activate phospholipase C beta2 and increase intracellular calcium concentration. Intestinal brush cells or solitary chemosensory cells (SCCs) have a structure similar to lingual taste cells and strongly express alpha-gustducin. It has therefore been suggested over the last decade that brush cells may participate in sugar sensing by a mechanism analogous to that in taste buds. We provide here functional evidence for an intestinal sensing system based on lingual taste receptors. Western blotting and immunocytochemistry revealed that all T1R members are expressed in rat jejunum at strategic locations including Paneth cells, SCCs or the apical membrane of enterocytes; T1Rs are colocalized with each other and with alpha-gustducin, transducin or phospholipase C beta2 to different extents. Intestinal glucose absorption consists of two components: one is classical active Na+-glucose cotransport, the other is the diffusive apical GLUT2 pathway. Artificial sweeteners increase glucose absorption in the order acesulfame potassium approximately sucralose > saccharin, in parallel with their ability to increase intracellular calcium concentration. Stimulation occurs within minutes by an increase in apical GLUT2, which correlates with reciprocal regulation of T1R2, T1R3 and alpha-gustducin versus T1R1, transducin and phospholipase C beta2. Our observation that artificial sweeteners are nutritionally active, because they can signal to a functional taste reception system to increase sugar absorption during a meal, has wide implications for nutrient sensing and nutrition in the treatment of obesity and diabetes.

Ezetimibe increases intestinal expression of the LDL receptor gene in dyslipidaemic men with insulin resistance.

PubMed

Drouin-Chartier, Jean-Philippe; Tremblay, André J; Lemelin, Valéry; Lépine, Marie-Claude; Lamarche, Benoît; Couture, Patrick

2016-12-01

To gain further insight into intestinal cholesterol homeostasis in dyslipidaemic men with insulin resistance (IR) by examining the impact of treatment with ezetimibe on the expression of key genes involved in cholesterol synthesis and LDL receptor (R)-mediated uptake of lipoproteins. A total of 25 men with dyslipidaemia and IR were recruited to participate in this double-blind, randomized, crossover, placebo-controlled trial. Participants received 10 mg/day ezetimibe or placebo for periods of 12 weeks each. Intestinal gene expression was measured by quantitative PCR in duodenal biopsy samples collected by gastroduodenoscopy at the end of each treatment. A total of 20 participants completed the protocol. Treatment with ezetimibe significantly increased intestinal LDLR (+16.2%; P = .01), 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoAR; +14.0%; P = .04) and acetyl-Coenzyme A acetyltransferase 2 (ACAT-2) mRNA expression (+12.5%; P = .03). Changes in sterol regulatory element-binding transcription factor 2 (SREBP-2) expression were significantly correlated with changes in HMG-CoAR (r = 0.55; P < .05), ACAT-2 (r = 0.69; P < .001) and proprotein convertase substilisin/kexin type 9 (PCSK9) expression (r = 0.45; P < .05). These results show that inhibition of intestinal cholesterol absorption by ezetimibe increases expression of the LDLR gene, supporting the concept that increased LDL clearance with ezetimibe treatment occurs not only in the liver but also in the small intestine. © 2016 John Wiley & Sons Ltd.

Toll-like receptor 4 increases intestinal permeability through up-regulation of membrane PKC activity in alcoholic steatohepatitis.

PubMed

Li, Xin; Wang, Chen; Nie, Jiao; Lv, Dong; Wang, Tianyi; Xu, Youqing

2013-09-01

Intestinal hyperpermeability is a causal factor for the development of alcoholic endotoxemia and steatohepatitis. However, the mechanisms governing this link remain unknown. The purpose of this study was to determine whether toll-like receptor 4 (TLR4) is involved in ethanol's deleterious effects on the intestinal barrier. Caco-2 cells were incubated in vitro with 1-10% ethanol. The results indicated that ethanol had a dose-dependent effect in increasing TLR4 expression and intercellular permeability. Then the effects of TLR4 on protein kinase C (PKC) and the intercellular junction protein occludin were assessed with and without pretreatment with a TLR4 inhibitor. The results indicated that TLR4 increased nonspecific PKC activity and reduced the expression of phosphorylated occludin in the membrane, which increased intercellular permeability. These effects were prevented by pretreatment with TLR4 mAb. Wild-type C57BL/6 mice were fed an ethanol or isocaloric liquid diet for 6 weeks. Hepatitis was diagnosed by the presence of an associated elevated blood endotoxin level. Chronic ethanol treatment significantly elevated blood endotoxin levels, intestinal permeability, and the expression of TLR4 in the ileum and colon. Moreover, ethanol exposure reduced the distribution of phosphorylated occludin in the intestinal epithelium because of PKC activation. In conclusion, chronic ethanol exposure induces a high response of TLR4 to lipopolysaccharide (LPS), and TLR4 increases intestinal permeability through down-regulation of phosphorylated occludin expression in the intestinal epithelial barrier, accompanied by membrane PKC hyperactivity. Copyright © 2013 Elsevier Inc. All rights reserved.

Intestine-specific deletion of microsomal triglyceride transfer protein increases mortality in aged mice.

PubMed

Liang, Zhe; Xie, Yan; Dominguez, Jessica A; Breed, Elise R; Yoseph, Benyam P; Burd, Eileen M; Farris, Alton B; Davidson, Nicholas O; Coopersmith, Craig M

2014-01-01

Mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO) exhibit a complete block in chylomicron assembly together with lipid malabsorption. Young (8-10 week) Mttp-IKO mice have improved survival when subjected to a murine model of Pseudomonas aeruginosa-induced sepsis. However, 80% of deaths in sepsis occur in patients over age 65. The purpose of this study was to determine whether age impacts outcome in Mttp-IKO mice subjected to sepsis. Aged (20-24 months) Mttp-IKO mice and WT mice underwent intratracheal injection with P. aeruginosa. Mice were either sacrificed 24 hours post-operatively for mechanistic studies or followed seven days for survival. In contrast to young septic Mttp-IKO mice, aged septic Mttp-IKO mice had a significantly higher mortality than aged septic WT mice (80% vs. 39%, p = 0.005). Aged septic Mttp-IKO mice exhibited increased gut epithelial apoptosis, increased jejunal Bax/Bcl-2 and Bax/Bcl-XL ratios yet simultaneously demonstrated increased crypt proliferation and villus length. Aged septic Mttp-IKO mice also manifested increased pulmonary myeloperoxidase levels, suggesting increased neutrophil infiltration, as well as decreased systemic TNFα compared to aged septic WT mice. Blocking intestinal chylomicron secretion alters mortality following sepsis in an age-dependent manner. Increases in gut apoptosis and pulmonary neutrophil infiltration, and decreased systemic TNFα represent potential mechanisms for why intestine-specific Mttp deletion is beneficial in young septic mice but harmful in aged mice as each of these parameters are altered differently in young and aged septic WT and Mttp-IKO mice.

Intestinal Cancer

MedlinePlus

... connects your stomach to your large intestine. Intestinal cancer is rare, but eating a high-fat diet ... increase your risk. Possible signs of small intestine cancer include Abdominal pain Weight loss for no reason ...

Milk with and without lactoferrin can influence intestinal damage in a pig model of malnutrition.

PubMed

Garas, Lydia C; Feltrin, Cristiano; Hamilton, M Kristina; Hagey, Jill V; Murray, James D; Bertolini, Luciana R; Bertolini, Marcelo; Raybould, Helen E; Maga, Elizabeth A

2016-02-01

Malnutrition remains a leading contributor to the morbidity and mortality of children under the age of five worldwide. However, the underlying mechanisms are not well understood necessitating an appropriate animal model to answer fundamental questions and conduct translational research into optimal interventions. One potential intervention is milk from livestock that more closely mimics human milk by increased levels of bioactive components that can promote a healthy intestinal epithelium. We tested the ability of cow milk and milk from transgenic cows expressing human lactoferrin at levels found in human milk (hLF milk) to mitigate the effects of malnutrition at the level of the intestine in a pig model of malnutrition. Weaned pigs (3 weeks old) were fed a protein and calorie restricted diet for five weeks, receiving cow, hLF or no milk supplementation daily from weeks 3-5. After three weeks, the restricted diet induced changes in growth, blood chemistry and intestinal structure including villous atrophy, increased ex vivo permeability and decreased expression of tight junction proteins. Addition of both cow and hLF milk to the diet increased growth rate and calcium and glucose levels while promoting growth of the intestinal epithelium. In the jejunum hLF milk restored intestinal morphology, reduced permeability and increased expression of anti-inflammatory IL-10. Overall, this pig model of malnutrition mimics salient aspects of the human condition and demonstrates that cow milk can stimulate the repair of damage to the intestinal epithelium caused by protein and calorie restriction with hLF milk improving this recovery to a greater extent.

Effect of Dietary Nutrient Density on Small Intestinal Phosphate Transport and Bone Mineralization of Broilers during the Growing Period.

PubMed

Li, Jianhui; Yuan, Jianmin; Miao, Zhiqiang; Song, Zhigang; Yang, Yu; Tian, Wenxia; Guo, Yuming

2016-01-01

A 2 × 4 factorial experiment was conducted to determine the effects of dietary nutrient density on growth performance, small intestinal epithelial phosphate transporter expression, and bone mineralization of broiler chicks fed with diets with different nutrient densities and nonphytate phosphorus (NPP) levels. The broilers were fed with the same starter diets from 0 to 21 days of age. In the grower phase (day 22 to 42), the broilers were randomly divided into eight groups according to body weight. Relatively high dietary nutrient density (HDND) and low dietary nutrient density (LDND) diets were assigned metabolic energy (ME) values of 3,150 and 2,950 kcal/kg, respectively. Crude protein and essential amino acid levels were maintained in the same proportion as ME to prepare the two diet types. NPP levels were 0.25%, 0.30%, 0.35%, and 0.40% of the diets. Results showed that a HDND diet significantly increased the body weight gain (BWG) of broilers and significantly decreased the feed conversion ratio and NPP consumed per BWG. HDND significantly decreased tibial P content of the broilers. Conversely, mRNA expression of NaPi-IIb and protein expression of calbindin were significantly increased in the intestine of broilers fed a HDND diet. HDND also increased vitamin D receptor (VDR) expression, especially at a relatively low dietary NPP level (0.25%). The mRNA expression of NaPi-IIa in the kidneys was significantly increased at a relatively low dietary NPP level (0.25%) to maintain P balance. Tibial P, calcium, and ash content were significantly decreased, as were calbindin and VDR expression levels in the intestine at a low NPP level. Therefore, HDND improved the growth rate of broilers and increased the expression of phosphate and calcium transporter in the small intestine, but adversely affected bone mineralization.

Lubiprostone Increases Small Intestinal Smooth Muscle Contractions Through a Prostaglandin E Receptor 1 (EP1)-mediated Pathway.

PubMed

Chan, Walter W; Mashimo, Hiroshi

2013-07-01

Lubiprostone, a chloride channel type 2 (ClC-2) activator, was thought to treat constipation by enhancing intestinal secretion. It has been associated with increased intestinal transit and delayed gastric emptying. Structurally similar to prostones with up to 54% prostaglandin E2 activity on prostaglandin E receptor 1 (EP1), lubiprostone may also exert EP1-mediated procontractile effect on intestinal smooth muscles. We investigated lubiprostone's effects on intestinal smooth muscle contractions and pyloric sphincter tone. Isolated murine small intestinal (longitudinal and circular) and pyloric tissues were mounted in organ baths with modified Krebs solution for isometric recording. Basal muscle tension and response to electrical field stimulation (EFS; 2 ms pulses/10 V/6 Hz/30 sec train) were measured with lubiprostone (10(-10)-10(-5) M) ± EP1 antagonist. Significance was established using Student t test and P < 0.05. Lubiprostone had no effect on the basal tension or EFS-induced contractions of longitudinal muscles. With circular muscles, lubiprostone caused a dose-dependent increase in EFS-induced contractions (2.11 ± 0.88 to 4.43 ± 1.38 N/g, P = 0.020) that was inhibited by pretreatment with EP1 antagonist (1.69 ± 0.70 vs. 4.43 ± 1.38 N/g, P = 0.030). Lubiprostone had no effect on circular muscle basal tension, but it induced a dose-dependent increase in pyloric basal tone (1.07 ± 0.01 to 1.97 ± 0.86 fold increase, P < 0.05) that was inhibited by EP1 antagonist. In mice, lubiprostone caused a dose-dependent and EP1-mediated increase in contractility of circular but not longitudinal small intestinal smooth muscles, and in basal tone of the pylorus. These findings suggest another mechanism for lubiprostone's observed clinical effects on gastrointestinal motility.

The effect of vitamin D2 and vitamin D3 on intestinal calcium absorption in Nigerian children with rickets

USDA-ARS?s Scientific Manuscript database

Children with calcium-deficiency rickets have high 1,25-dihydroxyvitamin D values. The objective of the study was to determine whether vitamin D increased calcium absorption. This was an experimental study. The study was conducted at a teaching hospital. Participants included 17 children with nutrit...

TRP channels in calcium homeostasis: from hormonal control to structure-function relationship of TRPV5 and TRPV6.

PubMed

van Goor, Mark K C; Hoenderop, Joost G J; van der Wijst, Jenny

2017-06-01

Maintaining plasma calcium levels within a narrow range is of vital importance for many physiological functions. Therefore, calcium transport processes in the intestine, bone and kidney are tightly regulated to fine-tune the rate of absorption, storage and excretion. The TRPV5 and TRPV6 calcium channels are viewed as the gatekeepers of epithelial calcium transport. Several calciotropic hormones control the channels at the level of transcription, membrane expression, and function. Recent technological advances have provided the first near-atomic resolution structural models of several TRPV channels, allowing insight into their architecture. While this field is still in its infancy, it has increased our understanding of molecular channel regulation and holds great promise for future structure-function studies of these ion channels. This review will summarize the mechanisms that control the systemic calcium balance, as well as extrapolate structural views to the molecular functioning of TRPV5/6 channels in epithelial calcium transport. Copyright © 2016. Published by Elsevier B.V.

Alpha Hemolysin Induces an Increase of Erythrocytes Calcium: A FLIM 2-Photon Phasor Analysis Approach

PubMed Central

Sanchez, Susana; Bakás, Laura; Gratton, Enrico; Herlax, Vanesa

2011-01-01

α-hemolysin (HlyA) from Escherichia coli is considered as the prototype of a family of toxins called RTX (repeat in toxin), a group of proteins that share genetic and structural features. HlyA is an important virulence factor in E. coli extraintestinal infections, such as meningitis, septicemia and urinary infections. High concentrations of the toxin cause the lysis of several cells such as erythrocytes, granulocytes, monocytes, endothelial and renal epithelial cells of different species. At low concentrations it induces the production of cytokines and apoptosis. Since many of the subcytolytic effects in other cells have been reported to be triggered by the increase of intracellular calcium, we followed the calcium concentration inside the erythrocytes while incubating with sublytic concentrations of HlyA. Calcium concentration was monitored using the calcium indicator Green 1, 2-photon excitation, and fluorescence lifetime imaging microscopy (FLIM). Data were analyzed using the phasor representation. In this report, we present evidence that, at sublytic concentrations, HlyA induces an increase of calcium concentration in rabbit erythrocytes in the first 10 s. Results are discussed in relation to the difficulties of measuring calcium concentrations in erythrocytes where hemoglobin is present, the contribution of the background and the heterogeneity of the response observed in individual cells. PMID:21698153

Interleukin-15 promotes intestinal dysbiosis with butyrate deficiency associated with increased susceptibility to colitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meisel, Marlies; Mayassi, Toufic; Fehlner-Peach, Hannah

2016-09-20

Dysbiosis resulting in gut-microbiome alterations with reduced butyrate production are thought to disrupt intestinal immune homeostasis and promote complex immune disorders. However, whether and how dysbiosis develops before the onset of overt pathology remains poorly defined. Interleukin 15 (IL-15) is upregulated in distressed tissue and its overexpression is thought to predispose susceptible individuals to and play a role in the pathogenesis of celiac disease and inflammatory bowel disease (IBD). While the immunological roles of IL-15 have been largely studied, its potential impact on the microbiota remains unexplored. Analysis of 16S rRNA-based inventories of bacterial communities in mice overexpressing IL-15 inmore » the intestinal epithelium (v-IL-15tg mice) shows distinct changes in the composition of the intestinal bacteria. While some alterations are specific to individual intestinal compartments, others are found across the ileum, cecum, and feces. In particular, IL-15 overexpression restructures the composition of the microbiota with a decrease in butyrate producing bacteria that is associated with a reduction in luminal butyrate levels across all intestinal compartments. Fecal microbiota transplant experiments of wild-type and v-IL-15tg microbiota into germ-free mice further indicate that diminishing butyrate concentration observed in the intestinal lumen of v-IL-15tg mice is the result of intrinsic alterations in the microbiota induced by IL-15. This reconfiguration of the microbiota is associated with increased susceptibility to dextran sodium sulfate induced colitis. Altogether, this study reveals that IL-15 impacts butyrate-producing bacteria and lowers butyrate levels in the absence of overt pathology, which represent events that precede and promote intestinal inflammatory diseases.« less

Dextran sulphate sodium (DSS) causes intestinal histopathology and inflammatory changes consistent with increased gut leakiness in chickens.

PubMed

Zou, X; Ji, J; Wang, J; Qu, H; Shu, D M; Guo, F Y; Luo, C L

2018-04-01

1. The clinical severity, histological changes, indicators of gut leakiness and inflammatory cytokine profiles were studied in chickens with dextran sulphate sodium (DSS)-induced intestinal inflammation. 2. The experimental groups (1.25%, 1.5% and 2.5% DSS) showed clinical signs, such as loose stools and weight loss, which increased with additional treatment days and, as expected, the effects of DSS-induced intestinal inflammation were time and dose-dependent. 3. After 10 d, histological manifestations were evident, including goblet cell depletion, mucus layer loss, significantly shorter villi and a thinner total ileal mucosa. 4. The d(-)-lactate value, which was used as a gut leakiness indicator, was significantly increased in the 2.5% DSS group. 5. Expression of the inflammatory cytokines interleukin-1Beta, tumour necrosis factor alpha and interleukin-10 in the serum significantly increased with DSS treatment. 6. This study indicates that the experimental intestinal inflammation induced by DSS is an ideal model to study the pathogenic mechanisms of intestinal inflammation in chickens and to test the efficacy of therapies.

[The functions of calcium-sensing receptor in regulating mineral metabolism.

PubMed

Kinoshita, Yuka

Calcium-sensing receptor(CaSR)which belongs to a G protein-coupled receptor family is one of the key elements in regulating calcium homeostasis. CaSR has been identified as a receptor to control parathyroid hormone(PTH)secretion in parathyroid glands according to serum calcium ion(Ca2+)levels. It has also been shown that CaSR controls reabsorption of water and several cations including Ca2+and magnesium ion(Mg2+)in renal tubular cells. This review summarizes the functions and roles of CaSR in mineral metabolism that are exerted in parathyroid glands, kidney, and intestine.

Insulin-Like Growth Factor Binding Proteins Increase Intracellular Calcium Levels in Two Different Cell Lines

PubMed Central

Seurin, Danielle; Lombet, Alain; Babajko, Sylvie; Godeau, François; Ricort, Jean-Marc

2013-01-01

Background Insulin-like growth factor binding proteins (IGFBPs) are six related secreted proteins that share IGF-dependent and -independent functions. If the former functions begin to be well described, the latter are somewhat more difficult to investigate and to characterize. At the cellular level, IGFBPs were shown to modulate numerous processes including cell growth, differentiation and apoptosis. However, the molecular mechanisms implicated remain largely unknown. We previously demonstrated that IGFBP-3, but not IGFBP-1 or IGFBP-5, increase intracellular calcium concentration in MCF-7 cells (Ricort J-M et al. (2002) FEBS lett 527: 293–297). Methodology/Principal Findings We perform a global analysis in which we studied, by two different approaches, the binding of each IGFBP isoform (i.e., IGFBP-1 to -6) to the surface of two different cellular models, MCF-7 breast adenocarcinoma cells and C2 myoblast proliferative cells, as well as the IGFBP-induced increase of intracellular calcium concentration. Using both confocal fluorescence microscopy and flow cytometry analysis, we showed that all IGFBPs bind to MCF-7 cell surface. By contrast, only four IGFBPs can bind to C2 cell surface since neither IGFBP-2 nor IGFBP-4 were detected. Among the six IGFBPs tested, only IGFBP-1 did not increased intracellular calcium concentration whatever the cellular model studied. By contrast, IGFBP-2, -3, -4 and -6, in MCF-7 cells, and IGFBP-3, -5 and -6, in C2 proliferative cells, induce a rapid and transient increase in intracellular free calcium concentration. Moreover, IGFBP-2 and -3 (in MCF-7 cells) and IGFBP-5 (in C2 cells) increase intracellular free calcium concentration by a pertussis toxin sensitive signaling pathway. Conclusions Our results demonstrate that IGFBPs are able to bind to cell surface and increase intracellular calcium concentration. By characterizing the IGFBPs-induced cell responses and intracellular couplings, we highlight the cellular specificity and

The Positive Inotropic Effect of Pyruvate Involves an Increase in Myofilament Calcium Sensitivity

PubMed Central

Torres, Carlos A. A.; Varian, Kenneth D.; Canan, Cynthia H.; Davis, Jonathan P.; Janssen, Paul M. L.

2013-01-01

Pyruvate is a metabolic fuel that is a potent inotropic agent. Despite its unique inotropic and antioxidant properties, the molecular mechanism of its inotropic mechanism is still largely unknown. To examine the inotropic effect of pyruvate in parallel with intracellular calcium handling under near physiological conditions, we measured pH, myofilament calcium sensitivity, developed force, and calcium transients in ultra thin rabbit heart trabeculae at 37 °C loaded iontophoretically with the calcium indicator bis-fura-2. By contrasting conditions of control versus sarcoplasmic reticulum block (with either cyclopiazonic acid and ryanodine or with thapsigargin) we were able to characterize and isolate the effects of pyruvate on sarcoplasmic reticulum calcium handling and developed force. A potassium contracture technique was subsequently utilized to assess the force-calcium relationship and thus the myofilament calcium sensitivity. Pyruvate consistently increased developed force whether or not the sarcoplasmic reticulum was blocked (16.8±3.5 to 24.5±5.1 vs. 6.9±2.6 to 12.5±4.4 mN/mm2, non-blocked vs. blocked sarcoplasmic reticulum respectively, p<0.001, n = 9). Furthermore, the sensitizing effect of pyruvate on the myofilaments was demonstrated by potassium contractures (EC50 at baseline versus 20 minutes of pyruvate infusion (peak force development) was 701±94 vs. 445±65 nM, p<0.01, n = 6). This study is the first to demonstrate that a leftward shift in myofilament calcium sensitivity is an important mediator of the inotropic effect of pyruvate. This finding can have important implications for future development of therapeutic strategies in the management of heart failure. PMID:23691074

Fructose-induced increases in expression of intestinal fructolytic and gluconeogenic genes are regulated by GLUT5 and KHK

PubMed Central

Patel, Chirag; Douard, Veronique; Yu, Shiyan; Tharabenjasin, Phuntila; Gao, Nan

2015-01-01

Marked increases in fructose consumption have been tightly linked to metabolic diseases. One-third of ingested fructose is metabolized in the small intestine, but the underlying mechanisms regulating expression of fructose-metabolizing enzymes are not known. We used genetic mouse models to test the hypothesis that fructose absorption via glucose transporter protein, member 5 (GLUT5), metabolism via ketohexokinase (KHK), as well as GLUT5 trafficking to the apical membrane via the Ras-related protein in brain 11a (Rab11a)-dependent endosomes are required for the regulation of intestinal fructolytic and gluconeogenic enzymes. Fructose feeding increased the intestinal mRNA and protein expression of these enzymes in the small intestine of adult wild-type (WT) mice compared with those gavage fed with lysine or glucose. Fructose did not increase expression of these enzymes in the GLUT5 knockout (KO) mice. Blocking intracellular fructose metabolism by KHK ablation also prevented fructose-induced upregulation. Glycolytic hexokinase I expression was similar between WT and GLUT5- or KHK-KO mice and did not vary with feeding solution. Gavage feeding with the fructose-specific metabolite glyceraldehyde did not increase enzyme expression, suggesting that signaling occurs before the hydrolysis of fructose to three-carbon compounds. Impeding GLUT5 trafficking to the apical membrane using intestinal epithelial cell-specific Rab11a-KO mice impaired fructose-induced upregulation. KHK expression was uniformly distributed along the villus but was localized mainly in the basal region of the cytosol of enterocytes. The feedforward upregulation of fructolytic and gluconeogenic enzymes specifically requires GLUT5 and KHK and may proactively enhance the intestine's ability to process anticipated increases in dietary fructose concentrations. PMID:26084694

Activation of calcium-sensing receptor increases TRPC3 expression in rat cardiomyocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng, Shan-Li; Sun, Ming-Rui; Li, Ting-Ting

Research highlights: {yields} Calcium-sensing receptor (CaR) activation stimulates TRP channels. {yields} CaR promoted transient receptor potential C3 (TRPC3) expression. {yields} Adult rat ventricular myocytes display capacitative calcium entry (CCE), which was operated by TRPCs. {yields} TRPC channels activation induced by CaR activator sustained the increased [Ca{sup 2+}]{sub i} to evoke cardiomyocytes apoptosis. -- Abstract: Transient receptor potential (TRP) channels are expressed in cardiomyocytes, which gate a type of influx of extracellular calcium, the capacitative calcium entry. TRP channels play a role in mediating Ca{sup 2+} overload in the heart. Calcium-sensing receptors (CaR) are also expressed in rat cardiac tissue andmore » promote the apoptosis of cardiomyocytes by Ca{sup 2+} overload. However, data about the link between CaR and TRP channels in rat heart are few. In this study, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were used to examine the expression of the TRP canonical proteins TRPC1 and TRPC3 in adult and neonatal rat cardiomyocytes. Laser scan confocal microscopy was used to detect intracellular [Ca{sup 2+}]{sub i} levels in isolated adult rat ventricular myocytes. The results showed that, in adult rat cardiomyocytes, the depletion of Ca{sup 2+} stores in the endoplasmic/sarcoplasmic reticulum (ER/SR) by thapsigargin induced a transient increase in [Ca{sup 2+}]{sub i} in the absence of [Ca{sup 2+}]{sub o} and the subsequent restoration of [Ca{sup 2+}]{sub o} sustained the increased [Ca{sup 2+}]{sub i} for a few minutes, whereas, the persisting elevation of [Ca{sup 2+}]{sub i} was reduced in the presence of the TRPC inhibitor SKF96365. The stimulation of CaR by its activator gadolinium chloride (GdCl{sub 3}) or spermine also resulted in the same effect and the duration of [Ca{sup 2+}]{sub i} increase was also shortened in the absence of [Ca{sup 2+}]{sub o}. In adult and neonatal rat cardiomyocytes, Gd

Calcium phosphate supplementation increases faecal Lactobacillus spp. in a randomised trial of young adults.

PubMed

Dahl, W J; Ford, A L; Coppola, J A; Lopez, D; Combs, W; Rohani, A; Ukhanova, M; Culpepper, T; Tompkins, T A; Christman, M; Mai, V

2016-02-01

The aim of the studies was to determine the effects of calcium carbonate and calcium phosphate supplementation on faecal Lactobacillus spp., with and without a probiotic supplement, in healthy adults. Study 1 comprised of a randomised, double-blind, crossover design; participants (n=15) received 2 capsules/d of 250 mg elemental calcium as calcium carbonate (Ca1) and calcium phosphate (Ca2) each for 2-week periods, with 2-week baseline and washout periods. Study 2 was a randomised, double-blind, crossover design; participants (n=17) received 2 capsules/d of Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011 (probiotic) alone, the probiotic with 2 capsules/d of Ca1, and probiotic with 2 capsules/d of Ca2 each for 2-week periods with 2-week baseline and washout periods. In both studies, stools were collected during the baseline, intervention and washout periods for Lactobacillus spp. quantification and qPCR analyses. Participants completed daily questionnaires of stool frequency and compliance. In Study 1, neither calcium supplement influenced viable counts of resident Lactobacillus spp., genome equivalents of lactic acid bacteria or stool frequency. In Study 2, faecal Lactobacillus spp. counts were significantly enhanced from baseline when the probiotic was administered with Ca2 (4.83±0.30, 5.79±0.31) (P=0.02), but not with Ca1 (4.98±0.31) or with the probiotic alone (5.36±0.31, 5.55±0.29) (not significant). Detection of L. helveticus R0052 and L. rhamnosus R0011 was significantly increased with all treatments, but did not differ among treatments. There were no changes in weekly stool frequency. Calcium phosphate co-administration may increase gastrointestinal survival of orally-administered Lactobacillus spp.

Matrix metalloproteinase 9-induced increase in intestinal epithelial tight junction permeability contributes to the severity of experimental DSS colitis

PubMed Central

Nighot, Prashant; Al-Sadi, Rana; Guo, Shuhong; Watterson, D. Martin; Ma, Thomas

2015-01-01

Recent studies have implicated a pathogenic role for matrix metalloproteinases 9 (MMP-9) in inflammatory bowel disease. Although loss of epithelial barrier function has been shown to be a key pathogenic factor for the development of intestinal inflammation, the role of MMP-9 in intestinal barrier function remains unclear. The aim of this study was to investigate the role of MMP-9 in intestinal barrier function and intestinal inflammation. Wild-type (WT) and MMP-9−/− mice were subjected to experimental dextran sodium sulfate (DSS) colitis by administration of 3% DSS in drinking water for 7 days. The mouse colonic permeability was measured in vivo by recycling perfusion of the entire colon using fluorescently labeled dextran. The DSS-induced increase in the colonic permeability was accompanied by an increase in intestinal epithelial cell MMP-9 expression in WT mice. The DSS-induced increase in intestinal permeability and the severity of DSS colitis was found to be attenuated in MMP-9−/− mice. The colonic protein expression of myosin light chain kinase (MLCK) and phospho-MLC was found to be significantly increased after DSS administration in WT mice but not in MMP-9−/− mice. The DSS-induced increase in colonic permeability and colonic inflammation was attenuated in MLCK−/− mice and MLCK inhibitor ML-7-treated WT mice. The DSS-induced increase in colonic surface epithelial cell MLCK mRNA was abolished in MMP-9−/− mice. Lastly, increased MMP-9 protein expression was detected within the colonic surface epithelial cells in ulcerative colitis cases. These data suggest a role of MMP-9 in modulation of colonic epithelial permeability and inflammation via MLCK. PMID:26514773

Cholinergic agonists increase intracellular calcium concentration in frog vestibular hair cells.

PubMed

Ohtani, M; Devau, G; Lehouelleur, J; Sans, A

1994-11-01

Acetylcholine (ACh) is usually considered to be the neurotransmitter of the efferent vestibular system. The nature and the localization of cholinergic receptors have been investigated on frog isolated vestibular hair cells (VHCs), by measuring variations of intracellular calcium concentration ([Ca2+]i), using calcium sensitive dye fura-2. Focal iontophoretic ACh (1 M, 300 nA.40 ms) application induced a rapid increase in [Ca2+]i, reaching a peak in 20 s and representing about 5-fold the resting level (from 61 +/- 6 to 320 +/- 26 nM). Applications of muscarinic agonists as methacholine and carbachol induced weaker calcium responses (from 78 +/- 25 to 238 +/- 53 nM) than the one obtained with ACh applications. These muscarinic agonists were efficient only in precise zones. Desensitization of muscarinic receptors to successive stimulations was significant. Perfusion of nicotine or 1,1-dimethyl-4-phenyl-piperazinium (DMPP), a nicotinic agonist, induced an increase in [Ca2+]i only in some cells (4/28 with DMPP). These results indicated the presence of cholinergic receptors on frog VHCs: muscarinic receptors were more responsive than nicotinic receptors. Presence of muscarinic and nicotinic receptors in the membrane of VHCs could indicate different modulations of VHCs activity mediated by [Ca2+]i and involving an efferent control which represents a central regulation of the vestibular afferent message.

Absorption-enhancing effects of gemini surfactant on the intestinal absorption of poorly absorbed hydrophilic drugs including peptide and protein drugs in rats.

PubMed

Alama, Tammam; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

2016-02-29

In general, the intestinal absorption of small hydrophilic molecules and macromolecules like peptides, after oral administration is very poor. Absorption enhancers are considered to be one of the most promising agents to enhance the intestinal absorption of drugs. In this research, we focused on a gemini surfactant, a new type of absorption enhancer. The intestinal absorption of drugs, with or without sodium dilauramidoglutamide lysine (SLG-30), a gemini surfactant, was examined by an in situ closed-loop method in rats. The intestinal absorption of 5(6)-carboxyfluorescein (CF) and fluorescein isothiocyanate-dextrans (FDs) was significantly enhanced in the presence of SLG-30, such effect being reversible. Furthermore, the calcium levels in the plasma significantly decreased when calcitonin was co-administered with SLG-30, suggestive of the increased intestinal absorption of calcitonin. In addition, no significant increase in the of lactate dehydrogenase (LDH) activity or in protein release from the intestinal epithelium was observed in the presence of SLG-30, suggestive of the safety of this compound. These findings indicate that SLG-30 is an effective absorption-enhancer for improving the intestinal absorption of poorly absorbed drugs, without causing serious damage to the intestinal epithelium. Copyright © 2015 Elsevier B.V. All rights reserved.

Increased calcium absorption from synthetic stable amorphous calcium carbonate: double-blind randomized crossover clinical trial in postmenopausal women.

PubMed

Vaisman, Nachum; Shaltiel, Galit; Daniely, Michal; Meiron, Oren E; Shechter, Assaf; Abrams, Steven A; Niv, Eva; Shapira, Yami; Sagi, Amir

2014-10-01

Calcium supplementation is a widely recognized strategy for achieving adequate calcium intake. We designed this blinded, randomized, crossover interventional trial to compare the bioavailability of a new stable synthetic amorphous calcium carbonate (ACC) with that of crystalline calcium carbonate (CCC) using the dual stable isotope technique. The study was conducted in the Unit of Clinical Nutrition, Tel Aviv Sourasky Medical Center, Israel. The study population included 15 early postmenopausal women aged 54.9 ± 2.8 (mean ± SD) years with no history of major medical illness or metabolic bone disorder, excess calcium intake, or vitamin D deficiency. Standardized breakfast was followed by randomly provided CCC or ACC capsules containing 192 mg elemental calcium labeled with 44Ca at intervals of at least 3 weeks. After swallowing the capsules, intravenous CaCl2 labeled with 42Ca on was administered on each occasion. Fractional calcium absorption (FCA) of ACC and CCC was calculated from the 24-hour urine collection following calcium administration. The results indicated that FCA of ACC was doubled (± 0.96 SD) on average compared to that of CCC (p < 0.02). The higher absorption of the synthetic stable ACC may serve as a more efficacious way of calcium supplementation. © 2014 American Society for Bone and Mineral Research.

25-Hydroxycholecalciferol as an antagonist of adverse corticosteroid effects on phosphate and calcium metabolism in man.

PubMed

Nuti, R; Vattimo, A; Turchetti, V; Righi, G

1984-10-01

The present study was performed in 30 patients who needed steroid therapy: courses of triamcinolone or DTM 8-15 given orally lasted 30 days. In 15 of these patients glucoactive corticosteroids were administered in combination with 5 micrograms/day of 25OH-vitamin D3 (25OHD3). 47Calcium oral test and 99mTc-MDP kinetics, as an index of bone turnover, were performed at the beginning of the therapy and after 30 days. At the end of treatment a significant improvement of intestinal radiocalcium transport together with a decrease in bone turnover in the group of patients treated with 25OHD3 was observed. As it concerns plasma calcium level, inorganic phosphate, the urinary excretion of calcium, phosphate and hydroxyproline no significant difference between the two groups examined were noticed. These results indicate that the adverse effects of glucoactive corticosteroids on intestinal calcium transport and bone turnover may be counteracted by the combined administration of physiological doses of 25OHD3.

Increased small intestinal permeability in ulcerative colitis: rather genetic than environmental and a risk factor for extensive disease?

PubMed

Büning, Carsten; Geissler, Nora; Prager, Matthias; Sturm, Andreas; Baumgart, Daniel C; Büttner, Janine; Bühner, Sabine; Haas, Verena; Lochs, Herbert

2012-10-01

A disturbed epithelial barrier could play a pivotal role in ulcerative colitis (UC). We performed a family-based study analyzing in vivo gastrointestinal permeability in patients with UC, their healthy relatives, spouses, and controls. In total, 89 patients with UC in remission, 35 first-degree relatives (UC-R), 24 nonrelated spouses (UC-NR), and 99 healthy controls (HC) were studied. Permeability was assessed by a sugar-drink test using sucrose (gastroduodenal permeability), lactulose/mannitol (intestinal permeability), and sucralose (colonic permeability). Data were correlated with clinical characteristics including medical treatment. Increased intestinal permeability was detected significantly more often in UC patients in remission (25/89, 28.1%) compared with HC (6/99, 6.1%; P < 0.001). Similar results were obtained in UC-R (7/35, 20.0%; P = 0.01 compared with HC) regardless of sharing the same household with the patients or not. No difference was found between UC-NR (3/24, 12.5%) and HC. Notably, in UC patients increased intestinal permeability was found in 12/28 patients (42.9%) with pancolitis, 7/30 (23.3%) patients with left-sided colitis, and in 2/19 (10.5%) patients with proctitis (P = 0.04). Gastroduodenal and colonic permeability were similar in all groups. Among patients on azathioprine, increased intestinal permeability was only seen in 1/18 (5.6%) patients. In contrast, in 24/70 (34.3%) patients without azathioprine, an increased intestinal permeability was found (P = 0.005). An increased intestinal but not colonic permeability was found in UC patients in clinical remission that could mark a new risk factor for extensive disease location. Similar findings in healthy relatives but not spouses suggest that this barrier defect is genetically determined. Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.

Effect of intravenous ranitidine and omeprazole on intestinal absorption of water, sodium, and macronutrients in patients with intestinal resection

PubMed Central

Jeppesen, P; Staun, M; Tjellesen, L; Mortensen, P

1998-01-01

Background—H2 receptor blockers and proton pump inhibitors reduce intestinal output in patients with short bowel syndrome. 
Aims—To evaluate the effect of intravenous omeprazole and ranitidine on water, electrolyte, macronutrient, and energy absorption in patients with intestinal resection. 
Methods—Thirteen patients with a faecal weight above 1.5 kg/day (range 1.7-5.7 kg/day and a median small bowel length of 100cm were studied. Omeprazole 40 mg twice daily or ranitidine 150mg twice daily were administered for five days in a randomised, double blind, crossover design followed by a three day control period with no treatment. Two patients with a segment of colon in continuation were excluded from analysis which, however, had no influence on the results. 
Results—Omeprazole increased median intestinal wet weight absorption compared with no treatment and ranitidine (p<0.03). The effect of ranitidine was not significant. Four patients with faecal volumes below 2.6 kg/day did not respond to omeprazole; in two absorption increased by 0.5-1 kg/day; and in five absorption increased by 1−2 kg/day. Absorption of sodium, calcium, magnesium, nitrogen, carbohydrate, fat, and total energy was unchanged. Four high responders continued on omeprazole for 12-15 months, but none could be weaned from parenteral nutrition. 
Conclusion—Omeprazole increased water absorption in patients with faecal output above 2.50 kg/day. The effect varied significantly and was greater in patients with a high output, but did not allow parenteral nutrition to be discontinued. Absorption of energy, macronutrients, electrolytes, and divalent cations was not improved. The effect of ranitidine was not significant, possibly because the dose was too low. 

 Keywords: short bowel syndrome; human; diarrhoea; ranitidine; omeprazole PMID:9824602

Na+/H+ exchanger 3 inhibitor diminishes hepcidin-enhanced duodenal calcium transport in hemizygous β-globin knockout thalassemic mice.

PubMed

Charoenphandhu, Narattaphol; Kraidith, Kamonshanok; Lertsuwan, Kornkamon; Sripong, Chanakarn; Suntornsaratoon, Panan; Svasti, Saovaros; Krishnamra, Nateetip; Wongdee, Kannikar

2017-03-01

Recent investigation has shown that the liver-derived iron-regulating hormone, hepcidin, can potentiate intestinal calcium absorption in hemizygous β-globin knockout thalassemic (BKO) mice. Since the upregulation of Fe 2+ and H + cotransporter, divalent metal transporter (DMT)-1, has been shown to correlate with thalassemia-induced intestinal calcium absorption impairment, the inhibition of the apical Na + /H + exchanger (NHE)-3 that is essential for cytoplasmic pH regulation and transepithelial sodium absorption was hypothesized to negatively affect hepcidin action. Herein, the positive effect of hepcidin on the duodenal calcium transport was evaluated using Ussing chamber technique. The results showed that BKO mice had lower absorptive surface area and duodenal calcium transport than wild-type mice. Besides, paracellular transport of zinc in BKO mice was compromised. Hepcidin administration completely restored calcium transport. Since this hepcidin action was totally abolished by inhibitors of the basolateral calcium transporters, Na + /Ca 2+ exchanger (NCX1) and plasma membrane Ca 2+ -ATPase (PMCA 1b ), the enhanced calcium flux potentially occurred through the transcellular pathway rather than paracellular pathway. Interestingly, the selective NHE3 inhibitor, 100 nM tenapanor, markedly inhibited hepcidin-enhanced calcium transport. Accordingly, hepcidin is one of the promising therapeutic agents for calcium malabsorption in β-thalassemia. It mainly stimulates the transcellular calcium transport across the duodenal epithelium in an NHE3-dependent manner.

Increased calcium absorption from synthetic stable amorphous calcium carbonate: Double-blind randomized crossover clinical trial in post-menopausal women

USDA-ARS?s Scientific Manuscript database

Calcium supplementation is a widely recognized strategy for achieving adequate calcium intake. We designed this blinded, randomized, crossover interventional trial to compare the bioavailability of a new stable synthetic amorphous calcium carbonate (ACC) with that of crystalline calcium carbonate (C...

Hypochlorhydria-induced calcium malabsorption does not affect fracture healing but increases post-traumatic bone loss in the intact skeleton.

PubMed

Haffner-Luntzer, Melanie; Heilmann, Aline; Heidler, Verena; Liedert, Astrid; Schinke, Thorsten; Amling, Michael; Yorgan, Timur Alexander; Vom Scheidt, Annika; Ignatius, Anita

2016-11-01

Efficient calcium absorption is essential for skeletal health. Patients with impaired gastric acidification display low bone mass and increased fracture risk because calcium absorption is dependent on gastric pH. We investigated fracture healing and post-traumatic bone turnover in mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells. Cckbr-/- mice display hypochlorhydria, calcium malabsorption, and osteopenia. Cckbr-/- and wildtype (WT) mice received a femur osteotomy and were fed either a standard or calcium-enriched diet. Healed and intact bones were assessed by biomechanical testing, histomorphometry, micro-computed tomography, and quantitative backscattering. Parathyroid hormone (PTH) serum levels were determined by enzyme-linked immunosorbent assay. Fracture healing was unaffected in Cckbr-/- mice. However, Cckbr-/- mice displayed increased calcium mobilization from the intact skeleton during bone healing, confirmed by significantly elevated PTH levels and osteoclast numbers compared to WT mice. Calcium supplementation significantly reduced secondary hyperparathyroidism and bone resorption in the intact skeleton in both genotypes, but more efficiently in WT mice. Furthermore, calcium administration improved bone healing in WT mice, indicated by significantly increased mechanical properties and bone mineral density of the fracture callus, whereas it had no significant effect in Cckbr-/- mice. Therefore, under conditions of hypochlorhydria-induced calcium malabsorption, calcium, which is essential for callus mineralization, appears to be increasingly mobilized from the intact skeleton in favor of fracture healing. Calcium supplementation during fracture healing prevented systemic calcium mobilization, thereby maintaining bone mass and improving fracture healing in healthy individuals whereas the effect was limited by gastric hypochlorhydria. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J

1-alpha,25-Dihydroxyvitamin D3 up-regulates the expression of 2 types of human intestinal alkaline phosphatase alternative splicing variants in Caco-2 cells and may be an important regulator of their expression in gut homeostasis.

PubMed

Noda, Seiko; Yamada, Asako; Nakaoka, Kanae; Goseki-Sone, Masae

2017-10-01

Vitamin D insufficiency is associated with a greater risk of osteoporosis and also influences skeletal muscle functions, differentiation, and development. The principal function of vitamin D in calcium homeostasis is to increase the absorption of calcium from the intestine, and the level of alkaline phosphatase (ALP) activity, a differentiation marker for intestinal epithelial cells, is regulated by vitamin D. Intestinal-type ALP is expressed at a high concentration in the brush border membrane of intestinal epithelial cells, and is known to be affected by several kinds of nutrients. Recent reviews have highlighted the importance of intestinal-type ALP in gut homeostasis. Intestinal-type ALP controls bacterial endotoxin-induced inflammation by dephosphorylating lipopolysaccharide and is a gut mucosal defense factor. In this study, we investigated the influence of vitamin D on the expression of 2 types of alternative mRNA variants encoding the human alkaline phosphatase, intestinal (ALPI) gene in human Caco-2 cells as an in vitro model of the small intestinal epithelium. After treatment with 1-alpha,25-dihydroxyvitamin D 3 , the biologically active form of vitamin D 3 , there were significant increases in the ALP activities of Caco-2 cells. Inhibitor and thermal inactivation experiments showed that the increased ALP had properties of intestinal-type ALP. Reverse transcription-polymerase chain reaction analysis revealed that expression of the 2 types of alternative mRNA variants from the ALPI gene was markedly enhanced by vitamin D in Caco-2 cells. In conclusion, these findings agree with the hypothesis: vitamin D up-regulated the expression of 2 types of human intestinal alkaline phosphatase alternative splicing variants in Caco-2 cells; vitamin D may be an important regulator of ALPI gene expression in gut homeostasis. Copyright © 2017 Elsevier Inc. All rights reserved.

Gene expression in human small intestinal mucosa in vivo is mediated by iron-induced oxidative stress.

PubMed

Troost, Freddy J; Brummer, Robert-Jan M; Haenen, Guido R M M; Bast, Aalt; van Haaften, Rachel I; Evelo, Chris T; Saris, Wim H M

2006-04-13

Iron-induced oxidative stress in the small intestine may alter gene expression in the intestinal mucosa. The present study aimed to determine which genes are mediated by an iron-induced oxidative challenge in the human small intestine. Eight healthy volunteers [22 yr(SD2)] were tested on two separate occasions in a randomized crossover design. After duodenal tissue sampling by gastroduodenoscopy, a perfusion catheter was inserted orogastrically to perfuse a 40-cm segment of the proximal small intestine with saline and, subsequently, with either 80 or 400 mg of iron as ferrous gluconate. After the intestinal perfusion, a second duodenal tissue sample was obtained. Thiobarbituric acid-reactive substances, an indicator of lipid peroxidation, in intestinal fluid samples increased significantly and dose dependently at 30 min after the start of perfusion with 80 or 400 mg of iron, respectively (P < 0.001). During the perfusion with 400 mg of iron, the increase in thiobarbituric acid-reactive substances was accompanied by a significant, momentary rise in trolox equivalent antioxidant capacity, an indicator of total antioxidant capacity (P < 0.05). The expression of 89 gene reporters was significantly altered by both iron interventions. Functional mapping showed that both iron dosages mediated six distinct processes. Three of those processes involved G-protein receptor coupled pathways. The other processes were associated with cell cycle, complement activation, and calcium channels. Iron administration in the small intestine induced dose-dependent lipid peroxidation and a momentary antioxidant response in the lumen, mediated the expression of at least 89 individual gene reporters, and affected at least six biological processes.

The calcium endocrine system of adolescent rhesus monkeys and controls before and after spaceflight

NASA Technical Reports Server (NTRS)

Arnaud, Sara B.; Navidi, Meena; Deftos, Leonard; Thierry-Palmer, Myrtle; Dotsenko, Rita; Bigbee, Allison; Grindeland, Richard E.

2002-01-01

The calcium endocrine system of nonhuman primates can be influenced by chairing for safety and the weightless environment of spaceflight. The serum of two rhesus monkeys flown on the Bion 11 mission was assayed pre- and postflight for vitamin D metabolites, parathyroid hormone, calcitonin, parameters of calcium homeostasis, cortisol, and indexes of renal function. Results were compared with the same measures from five monkeys before and after chairing for a flight simulation study. Concentrations of 1,25-dihydroxyvitamin D were 72% lower after the flight than before, and more than after chairing on the ground (57%, P < 0.05). Decreases in parathyroid hormone did not reach significance. Calcitonin showed modest decreases postflight (P < 0.02). Overall, effects of spaceflight on the calcium endocrine system were similar to the effects of chairing on the ground, but were more pronounced. Reduced intestinal calcium absorption, losses in body weight, increases in cortisol, and higher postflight blood urea nitrogen were the changes in flight monkeys that distinguished them from the flight simulation study animals.

My gut feeling says rest: Increased intestinal permeability contributes to chronic diseases in high-intensity exercisers.

PubMed

Van Houten, Jason M; Wessells, Robert J; Lujan, Heidi L; DiCarlo, Stephen E

2015-12-01

Chronic diseases are the leading cause of death and disability worldwide, and many of these conditions are linked to chronic inflammation. One potential cause of chronic inflammation is an increased intestinal epithelial permeability. Recent studies have demonstrated that parasympathetic stimulation via the efferent abdominal vagus nerve increases the expression and proper localization of tight junction proteins and decreases intestinal epithelial permeability. This finding may provide a novel approach for treating and preventing many chronic conditions. Importantly, physical activity is associated with increased resting parasympathetic (vagal) activity and lower risk of chronic diseases. However, high intensity long duration exercise can be harmful to overall health. Specifically, individuals who frequently exercise strenuously and for longer time intervals have the same mortality rates as sedentary individuals. This may be explained, in part, by longer periods of reduced vagal activity as vagal activity is markedly reduced both during and after intense exercise. We hypothesize that one mechanism by which exercise provides its health benefits is by increasing resting vagal activity and decreasing intestinal epithelial permeability, thus decreasing chronic inflammation. Additionally, we hypothesize that long periods of reduced vagal activity in individuals who exercise at high intensities and for longer durations, decrease the integrity of the intestinal barrier, putting them at greater risk of chronic inflammation and a host of chronic diseases. Thus, this hypothesis provides a conceptual link between the well-established benefits of frequent exercise and the paradoxical deleterious effects of prolonged, high-intensity exercise without adequate rest. Copyright © 2015. Published by Elsevier Ltd.

Nonprotein nitrogen is absorbed from the large intestine and increases nitrogen balance in growing pigs fed a valine-limiting diet.

PubMed

Columbus, Daniel A; Lapierre, Hélène; Htoo, John K; de Lange, Cornelis F M

2014-05-01

Nitrogen absorption from the large intestine, largely as ammonia and possibly as amino acids (AAs), is generally thought to be of little nutritional value to nonruminant animals and humans. Ammonia-nitrogen absorbed from the large intestine, however, may be recycled into the small intestine as urea and incorporated into microbial AAs, which may then be used by the host. A cecal infusion study was performed to determine the form in which nitrogen is absorbed from the large intestine and the impact of large intestine nitrogen supply on nitrogen balance in growing pigs. Eighteen cecally cannulated barrows (initial body weight: 22.4 ± 1.2 kg) were used to determine the effect of supplying nitrogen into the large intestine from either casein or urea on whole-body nitrogen retention and urea kinetics. Treatments were cecal infusions of saline (control), casein, or urea with nitrogen infused at a rate of 40% of nitrogen intake. In a subsample of 9 pigs, (15)N(15)N-urea was infused via i.v. during the nitrogen-balance period to determine urea kinetics. All pigs were fed a valine-limiting cornstarch-soybean meal-based diet. More than 80% of infused nitrogen was apparently absorbed. Urea flux and urinary nitrogen excretion increased (P ≤ 0.05) by the same amount for both nitrogen sources, but this increase did not fully account for the increase in nitrogen absorption from the large intestine. Whole-body nitrogen retention improved with nitrogen infusions (129 vs. 114 g/d; P < 0.01) and did not differ (P > 0.05) between nitrogen sources. Absorption of nitrogen from the large intestine appears to be in the form of nonprotein nitrogen, which appears to be returned to the small intestine via urea and used there for microbial AA production and should therefore be considered when determining nitrogen and AA supply and requirements.

Action of bradykinin potentiating factor (BPF) and dimercaprol (BAL) on the responses to bradykinin of isolated preparations of rat intestines.

PubMed

Camargo, A; Ferreira, S H

1971-06-01

BPF and BAL inhibited kininase activity of homogenates of rat intestine. However, BFP potentiated and BAL inhibited the contractions induced by bradykinin on rat isolated duodenum (low calcium solution) and terminal ileum (normal calcium solution). Neither BPF nor BAL affects the relaxation induced by bradykinin of rat duodenum bathed in normal Tyrode. These results suggest that two different types of pharmacological receptor are involved in the action of bradykinin on rat intestine, and that other factors besides the inhibition of agonist destruction participate in the mechanism of potentiation of kinin action by BPF.

Action of bradykinin potentiating factor (BPF) and dimercaprol (BAL) on the responses to bradykinin of isolated preparations of rat intestines

PubMed Central

Camargo, A.; Ferreira, S. H.

1971-01-01

BPF and BAL inhibited kininase activity of homogenates of rat intestine. However, BFP potentiated and BAL inhibited the contractions induced by bradykinin on rat isolated duodenum (low calcium solution) and terminal ileum (normal calcium solution). Neither BPF nor BAL affects the relaxation induced by bradykinin of rat duodenum bathed in normal Tyrode. These results suggest that two different types of pharmacological receptor are involved in the action of bradykinin on rat intestine, and that other factors besides the inhibition of agonist destruction participate in the mechanism of potentiation of kinin action by BPF. PMID:5091164

Pancreatic Digestive Enzyme Blockade in the Intestine Increases Survival After Experimental Shock

PubMed Central

DeLano, Frank A.; Hoyt, David B.; Schmid-Schönbein, Geert W.

2015-01-01

Shock, sepsis, and multiorgan failure are associated with inflammation, morbidity, and high mortality. The underlying pathophysiological mechanism is unknown, but evidence suggests that pancreatic enzymes in the intestinal lumen autodigest the intestine and generate systemic inflammation. Blocking these enzymes in the intestine reduces inflammation and multiorgan dysfunction. We investigated whether enzymatic blockade also reduces mortality after shock. Three rat shock models were used here: hemorrhagic shock, peritonitis shock induced by placement of cecal material into the peritoneum, and endotoxin shock. One hour after initiation of hemorrhagic, peritonitis, or endotoxin shock, animals were administered one of three different pancreatic enzyme inhibitors—6-amidino-2-naphtyl p-guanidinobenzoate di-methanesulfate, tranexamic acid, or aprotinin—into the lumen of the small intestine. In all forms of shock, blockade of digestive proteases with protease inhibitor attenuated entry of digestive enzymes into the wall of the intestine and subsequent autodigestion and morphological damage to the intestine, lung, and heart. Animals treated with protease inhibitors also survived in larger numbers than untreated controls over a period of 12 weeks. Surviving animals recovered completely and returned to normal weight within 14 days after shock. The results suggest that the active and concentrated digestive enzymes in the lumen of the intestine play a central role in shock and multi-organ failure, which can be treated with protease inhibitors that are currently available for use in the clinic. PMID:23345609

Dietary cadmium and benzo(a)pyrene increased intestinal metallothionein expression in the fish Fundulus heteroclitus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roesijadi, Guritno; Rezvankhah, Saeid; Perez-Matus, Alejandro

2008-10-17

To test the effect of dietary exposure to cadmium and benzo(a)pyrene on induction of metallothionein mRNA in the Fundulus heteroclitus, fish were individually fed a pelletized gel food containing cadmium, benzo(a)pyrene, or a combination of the two over a period of seven days, then analyzed for relative levels of metallothionein mRNA in the intestine, liver, and gill using real-time RT-qPCR. An initial experiment with only cadmium exposure showed an apparent 10-fold induction in the intestine, but no induction in liver or gill. Ingestion of contaminated pellets varied in individual fish, and because it was possible to monitor individual ingestion ratesmore » with our method, individual cadmium doses were estimated from the amount of ingested cadmium. When the levels of metallothionein mRNA were related to the dose to each fish, a linear dose-response relationship was observed for the intestine, but not the other organs, which showed no induction. In a second experiment, dose was controlled by placing the entire daily cadmium dose into a single contaminated pellet that was fed first (thereby, effectively controlling the effect of variable ingestion rates), and the interaction between cadmium and benzo(a)pyrene was also investigated. The intestine was again the primary organ for metallothionein induction by cadmium, with a 20-fold increase in metallothionein mRNA over control levels. When benzo(a)pyrene was administered together with cadmium, induction of metallothionein was potentiated by the presence of benzo(a)pyrene, with the main effect seen in the intestine, where already high levels of induction by cadmium alone increased by 1.74-fold when benzo(a)pyrene was present.« less

Age-related changes in the response of intestinal cells to parathyroid hormone.

PubMed

Russo de Boland, Ana

2004-12-01

The concept of the role(s) of parathyroid hormone (PTH), has expanded from that on acting on the classical target tissues, bone and kidney, to the intestine where its actions are of regulatory and developmental importance: regulation of intracellular calcium through modulation of second messengers and, activation of mitogenic cascades leading to cell proliferation. Several causes have been postulated to modify the hormone response in intestinal cells with ageing, among them, alterations of PTH receptor (PTHR1) binding sites, reduced expression of G proteins and hormone signal transduction changes. The current review summarizes the actual knowledge regarding the molecular and biochemical basis of age-impaired PTH receptor-mediated signaling in intestinal cells. A fundamental understanding of why PTH functions are impaired with age will enhance our understanding of its importance in intestinal cell physiology.

Chronic Trichuris muris Infection Decreases Diversity of the Intestinal Microbiota and Concomitantly Increases the Abundance of Lactobacilli.

PubMed

Holm, Jacob Bak; Sorobetea, Daniel; Kiilerich, Pia; Ramayo-Caldas, Yuliaxis; Estellé, Jordi; Ma, Tao; Madsen, Lise; Kristiansen, Karsten; Svensson-Frej, Marcus

2015-01-01

The intestinal microbiota is vital for shaping the local intestinal environment as well as host immunity and metabolism. At the same time, epidemiological and experimental evidence suggest an important role for parasitic worm infections in maintaining the inflammatory and regulatory balance of the immune system. In line with this, the prevalence of persistent worm infections is inversely correlated with the incidence of immune-associated diseases, prompting the use of controlled parasite infections for therapeutic purposes. Despite this, the impact of parasite infection on the intestinal microbiota, as well as potential downstream effects on the immune system, remain largely unknown. We have assessed the influence of chronic infection with the large-intestinal nematode Trichuris muris, a close relative of the human pathogen Trichuris trichiura, on the composition of the murine intestinal microbiota by 16S ribosomal-RNA gene-based sequencing. Our results demonstrate that persistent T. muris infection dramatically affects the large-intestinal microbiota, most notably with a drop in the diversity of bacterial communities, as well as a marked increase in the relative abundance of the Lactobacillus genus. In parallel, chronic T. muris infection resulted in a significant shift in the balance between regulatory and inflammatory T cells in the intestinal adaptive immune system, in favour of inflammatory cells. Together, these data demonstrate that chronic parasite infection strongly influences the intestinal microbiota and the adaptive immune system. Our results illustrate the complex interactions between these factors in the intestinal tract, and contribute to furthering the understanding of this interplay, which is of crucial importance considering that 500 million people globally are suffering from these infections and their potential use for therapeutic purposes.

The genetic composition of Oxalobacter formigenes and its relationship to colonization and calcium oxalate stone disease

PubMed Central

Knight, John; Deora, Rajendar; Assimos, Dean G.; Holmes, Ross P.

2013-01-01

Oxalobacter formigenes is a unique intestinal organism that relies on oxalate degradation to meet most of its energy and carbon needs. A lack of colonization is a risk factor for calcium oxalate stone disease. Protection against calcium oxalate stone disease appears to be due to the oxalate degradation that occurs in the gut on low calcium diets with a possible further contribution from intestinal oxalate secretion. Much remains to be learned about how the organism establishes and maintains gut colonization and the precise mechanisms by which it modifies stone risk. The sequencing and annotation of the genomes of a Group 1 and a Group 2 strain of O. formigenes should provide the informatic tools required for the identification of the genes and pathways associated with colonization and survival. In this review we have identified genes that may be involved and where appropriate suggested how they may be important in calcium oxalate stone disease. Elaborating the functional roles of these genes should accelerate our understanding of the organism and clarify its role in preventing stone formation. PMID:23632911

Effects of quercetin and menadione on intestinal calcium absorption and the underlying mechanisms.

PubMed

Marchionatti, Ana M; Pacciaroni, Adriana; Tolosa de Talamoni, Nori G

2013-01-01

Quercetin (QT) could be considered as a potential therapeutic agent for different diseases due to its antioxidant, anti-inflammatory, antiviral and anticancer properties. This study was designed to investigate the ability of QT to protect the chick intestine against menadione (MEN) induced injury in vivo and in vitro. Four-week old chicks (Gallus gallus) were treated i.p. with 2.5μmol of MEN/kg b.w. or with i.l. 50μM QT or both. QT protected the intestinal Ca(2+) absorption against the inhibition caused by MEN, but QT alone did not modify. Glutathione (GSH) depletion provoked by MEN in chick enterocytes was abolished by QT treatment, whereas QT alone did not modify the intestinal GSH content. The enhancement of GSH peroxidase activity produced by MEN was blocked by QT treatment. In contrast, superoxide dismutase activity remained high after simultaneous treatment of enterocytes with MEN and QT. The flavonol also avoided changes in the mitochondrial membrane permeability (swelling) produced by MEN. The FasL/Fas/caspase-3 pathway was activated by MEN, effect that was abrogated by QT. In conclusion, QT may be useful in preventing inhibition of chick intestinal Ca(2+) absorption caused by MEN or other substances that deplete GSH, by blocking the oxidative stress and the FasL/Fas/caspase-3 pathway activation. Copyright © 2012 Elsevier Inc. All rights reserved.

Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis

NASA Technical Reports Server (NTRS)

Beers, D. R.; Ho, B. K.; Siklos, L.; Alexianu, M. E.; Mosier, D. R.; Mohamed, A. H.; Otsuka, Y.; Kozovska, M. E.; McAlhany, R. E.; Smith, R. G.;

Age-related increases in F344 rat intestine microsomal quercetin glucuronidation

USDA-ARS?s Scientific Manuscript database

The objective of this study was to establish the extent age modifies intestinal quercetin glucuronidation capacity. Pooled microsomal fractions of three equidistant small intestine (SI) segments from 4, 12, 18, and 28 mo male F344 rats (n=8/group) were employed to model the enzyme kinetics of UDP-gl...

Parent/Child training to increase preteens' calcium, physical activity, and bone density: a controlled trial.

PubMed

Hovell, Melbourne F; Nichols, Jeanne F; Irvin, Veronica L; Schmitz, Katharine E; Rock, Cheryl L; Hofstetter, C Richard; Keating, Kristen; Stark, Lori J

2009-01-01

To test effects of parent/child training designed to increase calcium intake, bone-loading physical activity (PA), and bone density. Two-group randomized controlled trial. Family-based intervention delivered at research center. 117 healthy children aged 10-13 years (58.1% female, 42.7% Hispanic, 40.2% White). Ninety-seven percent of participants had at least one parent graduate from high school and 37.2 % had at least one parent graduate from a 4-year university. Children and parents were randomly assigned to diet and exercise (experimental) or injury prevention (control) interventions. Children were taught in eight weekly classes how to engage in bone-loading PA and eat calcium-rich foods or avoid injuries. Parents were taught behavior management techniques to modify children's behaviors. Measures at baseline and at 3, 9, and 12 months included 24-hour diet and PA recalls, and bone mineral density (BMD) by dual-energy x-ray absorptiometry. Analysis of variance and generalized estimating equations (GEE) assessed group by time differences. Comparisons were conducted separately for boys and girls. For boys, cross-sectional differences between experimental and control groups were achieved for 3- and 9-month calcium intake (1352 vs. 1052 mg/day, 1298 vs. 970 mg/day, p < .05). For girls, marginal cross-sectional differences were achieved for high-impact PA at 12 months (p < .10). For calcium intake, a significant group by time interaction was observed from pretest to posttest for the full sample (p = .008) and for girls (p = .006) but not for boys. No significant group by time differences in calcium were observed across the follow-up period. No group by time differences were observed for high-impact PA. Among boys, longitudinal group by time differences reached significance for total hip BMD (p = .045) and femoral neck BMD (p = .033), even after adjusting for skeletal growth. Similar differential increases were observed among boys for bone mineral content (BMC) at the

Parent/child training to increase preteens’ calcium, physical activity and bone density: A controlled trial

PubMed Central

Hovell, Melbourne F.; Nichols, Jeanne F.; Irvin, Veronica L.; Schmitz, Katharine E.; Rock, Cheryl L.; Hofstetter, C. Richard; Keating, Kristen; Stark, Lori

2012-01-01

PURPOSE To test effects of parent/child training designed to increase calcium intake, bone-loading physical activity (PA), and bone density. DESIGN Two-group randomized controlled trial. SETTING Family-based intervention delivered at research center. SUBJECTS 117 healthy children aged 10-13 years (58.1% female, 42.7% Hispanic, 40.2% White). Ninety-seven percent of participants had at least one parent graduate from high school and 37.2% had at least one parent graduate from a 4-year university. INTERVENTION Children and parents were randomly assigned to diet and exercise (experimental) or injury prevention (control) interventions. Children were taught in eight weekly classes how to engage in bone-loading PA and eat calcium-rich foods or avoid injuries. Parents were taught behavior management techniques to modify children’s behaviors. MEASURES Measures at baseline, three, nine and twelve months included 24-hour diet and PA recalls, and bone mineral density (BMD) by DXA. ANALYSIS ANOVA and Generalized Estimating Equations assessed group by time differences. Comparisons were conducted separately for boys and girls. RESULTS For boys, cross-sectional differences between experimental versus control group were achieved for 3 and 9-month calcium intake (1352 vs. 1052mg/day, 1298 vs. 970mg/day, p<0.05). For girls, marginal cross-sectional differences were achieved for high-impact PA at 12 months (p<0.10). For calcium intake, a significant group by time interaction was observed from pre to post test for the full sample (p=.008) and for girls (p=.006) but not for boys. No significant group by time differences in calcium were observed across the follow-up period. No group by time differences were observed for high impact physical activity. Among boys, longitudinal group by time differences reached significance for total hip BMD (p=.045) and femoral neck BMD (p=.033), even after adjusting for skeletal growth. Similar differential increases were observed among boys for BMC at

Decreased melatonin secretion is associated with increased intestinal permeability and marker of endotoxemia in alcoholics

PubMed Central

Gorenz, Annika; Shaikh, Maliha; Desai, Vishal; Forsyth, Christopher; Fogg, Louis; Burgess, Helen J.; Keshavarzian, Ali

2015-01-01

Chronic heavy alcohol use is known to cause gut leakiness and alcoholic liver disease (ALD), but only 30% of heavy drinkers develop increased intestinal permeability and ALD. The hypothesis of this study was that disruption of circadian rhythms is a potential risk factor in actively drinking alcoholics for gut leakiness and endotoxemia. We studied 20 subjects with alcohol use disorder (AD) and 17 healthy controls (HC, 6 day workers, 11 night workers). Subjects wore a wrist actiwatch for 7 days and underwent a 24-h dim light phase assessment and urine collection for intestinal permeability. The AD group had significantly less total sleep time and increased fragmentation of sleep (P < 0.05). AD also had significantly lower plasma melatonin levels compared with the HC [mean area under the curve (AUC) 322.78 ± 228.21 vs. 568.75 ± 304.26 pg/ml, P = 0.03]. In the AD group, AUC of melatonin was inversely correlated with small bowel and colonic intestinal permeability (lactulose-to-mannitol ratio, r = −0.39, P = 0.03; urinary sucralose, r = −0.47, P = 0.01). Cosinor analysis of lipopolysaccharide-binding protein (marker of endotoxemia) and lipopolysaccharide every 4 h for 24 h in HC and AD subjects had a midline estimating statistic of rhythm of 5,026.15 ± 409.56 vs. 6,818.02 ± 628.78 ng/ml (P < 0.01) and 0.09 ± 0.03 vs. 0.15 ± 0.19 EU/ml (P < 0.05), respectively. We found plasma melatonin was significantly lower in the AD group, and lower melatonin levels correlated with increased intestinal permeability and a marker of endotoxemia. Our study suggests the suppression of melatonin in AD may promote gut leakiness and endotoxemia. PMID:25907689

Dietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injury.

PubMed

Sureban, Sripathi M; May, Randal; Qu, Dongfeng; Chandrakesan, Parthasarathy; Weygant, Nathaniel; Ali, Naushad; Lightfoot, Stan A; Ding, Kai; Umar, Shahid; Schlosser, Michael J; Houchen, Courtney W

2015-01-01

Gastrointestinal (GI) mucosal damage is a devastating adverse effect of radiation therapy. We have recently reported that expression of Dclk1, a Tuft cell and tumor stem cell (TSC) marker, 24h after high dose total-body gamma-IR (TBI) can be used as a surrogate marker for crypt survival. Dietary pectin has been demonstrated to possess chemopreventive properties, whereas its radioprotective property has not been studied. The aim of this study was to determine the effects of dietary pectin on ionizing radiation (IR)-induced intestinal stem cell (ISC) deletion, crypt and overall survival following lethal TBI. C57BL/6 mice received a 6% pectin diet and 0.5% pectin drinking water (pre-IR mice received pectin one week before TBI until death; post-IR mice received pectin after TBI until death). Animals were exposed to TBI (14 Gy) and euthanized at 24 and 84h post-IR to assess ISC deletion and crypt survival respectively. Animals were also subjected to overall survival studies following TBI. In pre-IR treatment group, we observed a three-fold increase in ISC/crypt survival, a two-fold increase in Dclk1+ stem cells, increased overall survival (median 10d vs. 7d), and increased expression of Dclk1, Msi1, Lgr5, Bmi1, and Notch1 (in small intestine) post-TBI in pectin treated mice compared to controls. We also observed increased survival of mice treated with pectin (post-IR) compared to controls. Dietary pectin is a radioprotective agent; prevents IR-induced deletion of potential reserve ISCs; facilitates crypt regeneration; and ultimately promotes overall survival. Given the anti-cancer activity of pectin, our data support a potential role for dietary pectin as an agent that can be administered to patients receiving radiation therapy to protect against radiation-induces mucositis.

Excessive fructose intake causes 1,25-(OH)2D3-dependent inhibition of intestinal and renal calcium transport in growing rats

PubMed Central

Douard, Veronique; Sabbagh, Yves; Lee, Jacklyn; Patel, Chirag; Kemp, Francis W.; Bogden, John D.; Lin, Sheldon

2013-01-01

We recently discovered that chronic high fructose intake by lactating rats prevented adaptive increases in rates of active intestinal Ca2+ transport and in levels of 1,25-(OH)2D3, the active form of vitamin D. Since sufficient Ca2+ absorption is essential for skeletal growth, our discovery may explain findings that excessive consumption of sweeteners compromises bone integrity in children. We tested the hypothesis that 1,25-(OH)2D3 mediates the inhibitory effect of excessive fructose intake on active Ca2+ transport. First, compared with those fed glucose or starch, growing rats fed fructose for 4 wk had a marked reduction in intestinal Ca2+ transport rate as well as in expression of intestinal and renal Ca2+ transporters that was tightly associated with decreases in circulating levels of 1,25-(OH)2D3, bone length, and total bone ash weight but not with serum parathyroid hormone (PTH). Dietary fructose increased the expression of 24-hydroxylase (CYP24A1) and decreased that of 1α-hydroxylase (CYP27B1), suggesting that fructose might enhance the renal catabolism and impair the synthesis, respectively, of 1,25-(OH)2D3. Serum FGF23, which is secreted by osteocytes and inhibits CYP27B1 expression, was upregulated, suggesting a potential role of bone in mediating the fructose effects on 1,25-(OH)2D3 synthesis. Second, 1,25-(OH)2D3 treatment rescued the fructose effect and normalized intestinal and renal Ca2+ transporter expression. The mechanism underlying the deleterious effect of excessive fructose intake on intestinal and renal Ca2+ transporters is a reduction in serum levels of 1,25-(OH)2D3. This finding is significant because of the large amounts of fructose now consumed by Americans increasingly vulnerable to Ca2+ and vitamin D deficiency. PMID:23571713

A multi-component herbal preparation, STW 5, shows anti-apoptotic effects in radiation induced intestinal mucositis in rats.

PubMed

Khayyal, Mohamed T; Abdel-Naby, Doaa H; Abdel-Aziz, Heba; El-Ghazaly, Mona A

2014-09-25

Intestinal mucositis is a common adverse effect in patients undergoing radiotherapy and constitutes a treatment-limiting condition. Since no agents are yet known that can adequately guard against its development, the search continues to find safe and effective measures. The present study was intended to investigate whether the herbal preparation, STW 5, could offer a potentially effective agent in this respect. Intestinal mucositis was induced in rats by exposing them to whole body gamma-irradiation (6 Gy). Rats were treated orally with STW 5 (5 or 10 ml/kg) for five days before and two days after irradiation. One day later, rats were sacrificed and segments of small intestine were examined histologically. Intestinal homogenates and serum samples were used to assess relevant parameters for apoptosis and different markers for inflammation and oxidative stress. Exposure to radiation produced dose-dependent extents of intestinal injury associated with apoptotic changes with high radiation levels. Apoptosis was associated with an increase in cytosolic calcium, depletion of mitochondrial cytochrome c, B-cell lymphoma-2 and complex I. Oxidative stress parameters (reduced glutathione, thiobarbituric acid reactive substance and total nitrate/nitrite) were deranged. Inflammation markers (tumor necrosis factor and myeloperoxidase) and indices of intestinal damage (serum diamine oxidase) were increased. STW 5 protected to a large extent against histological changes and counteracted the deranged parameters. The findings provide experimental evidence for the potential beneficial use of STW5 in protecting against the development of radiation-induced intestinal mucositis and associated changes in tissue biomarkers. Copyright © 2014 The Authors. Published by Elsevier GmbH.. All rights reserved.

Effects of 1,25-dihydroxycholecalciferol on 47calcium absorption in post-menopausal osteoporosis.

PubMed

Caniggia, A; Vattimo, A

1979-07-01

Measurement of 47Calcium absorption was performed on eleven women with post-menopausal osteoporosis. The study was repeated after 10 days treatment with 1 microgram daily of 1,25(OH)2D3. These patients showed a statistically significant improvement of fractional calcium absorption that was inversely correlated to the basal values. The prompt improvement of the intestinal calcium transport in post-menopausal osteoporotic women, a few days after the administration of physiological doses of 1,25(OH)2D3, suggests that these patients synthesize inappropriately small amounts of 1,25(OH)2D3 because of their oestrogen deficiency. This could be an important pathogenetic factor in post-menopausal osteoporosis, as the efficiency of the adaptation of calcium absorption to low calcium intakes is dependent on 1,25(OH)2D3.

Sugars Increase Non-Heme Iron Bioavailability in Human Epithelial Intestinal and Liver Cells

PubMed Central

Christides, Tatiana; Sharp, Paul

2013-01-01

Previous studies have suggested that sugars enhance iron bioavailability, possibly through either chelation or altering the oxidation state of the metal, however, results have been inconclusive. Sugar intake in the last 20 years has increased dramatically, and iron status disorders are significant public health problems worldwide; therefore understanding the nutritional implications of iron-sugar interactions is particularly relevant. In this study we measured the effects of sugars on non-heme iron bioavailability in human intestinal Caco-2 cells and HepG2 hepatoma cells using ferritin formation as a surrogate marker for iron uptake. The effect of sugars on iron oxidation state was examined by measuring ferrous iron formation in different sugar-iron solutions with a ferrozine-based assay. Fructose significantly increased iron-induced ferritin formation in both Caco-2 and HepG2 cells. In addition, high-fructose corn syrup (HFCS-55) increased Caco-2 cell iron-induced ferritin; these effects were negated by the addition of either tannic acid or phytic acid. Fructose combined with FeCl3 increased ferrozine-chelatable ferrous iron levels by approximately 300%. In conclusion, fructose increases iron bioavailability in human intestinal Caco-2 and HepG2 cells. Given the large amount of simple and rapidly digestible sugars in the modern diet their effects on iron bioavailability may have important patho-physiological consequences. Further studies are warranted to characterize these interactions. PMID:24340076

Induction of defence gene expression by oligogalacturonic acid requires increases in both cytosolic calcium and hydrogen peroxide in Arabidopsis thaliana.

PubMed

Hu, Xiang Yang; Neill, Steven J; Cai, Wei Ming; Tang, Zhang Cheng

2004-06-01

Responses to oligogalacturonic acid (OGA) were determined in transgenic Arabidopsis thaliana seedlings expressing the calcium reporter protein aequorin. OGA stimulated a rapid, substantial and transient increase in the concentration of cytosolic calcium ([Ca2+]cyt) that peaked after ca. 15 s. This increase was dose-dependent, saturating at ca. 50 ug Gal equiv/ml of OGA. OGA also stimulated a rapid generation of H2O2. A small, rapid increase in H2O2 content was followed by a much larger oxidative burst, with H2O2 content peaking after ca. 60 min and declining thereafter. Induction of the oxidative burst by OGA was also dose-dependent, with a maximum response again being achieved at ca. 50 ug Gal equiv/mL. Inhibitors of calcium fluxes inhibited both increases in [Ca2+]cyt and [H2O2], whereas inhibitors of NADPH oxidase blocked only the oxidative burst. OGA increased strongly the expression of the defence-related genes CHS, GST, PAL and PR-1. This induction was suppressed by inhibitors of calcium flux or NADPH oxidase, indicating that increases in both cytosolic calcium and H2O2 are required for OGA-induced gene expression.

Increasing Soil Calcium Availability Alters Forest Soil Carbon Stocks

NASA Astrophysics Data System (ADS)

Melvin, A.; Goodale, C. L.

2011-12-01

Acid deposition in the Northeastern U.S. has been linked to a loss of soil base cations, especially calcium (Ca). While much research has addressed the effects of Ca depletion on soil and stream acidification, few studies have investigated its effects on ecosystem carbon (C) balance. We studied the long-term effects of increased Ca availability on C cycling in a northern hardwood forest in the Adirondack Park, NY. In 1989, calcium carbonate (lime) was added to ~ 100 ha of the Woods Lake Watershed to ameliorate the effects of soil Ca depletion. An additional 100 ha were maintained as controls. We hypothesized that the lime addition would improve forest health and that this improvement would be evident in increased tree biomass, leaf litter, and fine root production. Within the forest floor, we anticipated that the increased pH associated with liming would stimulate microbial activity resulting in increased decomposition and basal soil respiration, and reduced C stocks. Additionally, we hypothesized that increased Ca availability could enhance Ca-OM complexation in the upper mineral soils, leading to increased C stocks in these horizons. Eighteen years after liming, soil pH and exchangeable Ca pools remained elevated in the forest floor and upper mineral soil of the limed plots. Forest floor C stocks were significantly larger in limed plots (68 vs. 31 t C ha-1), and were driven primarily by greater C accumulation in the forest floor Oa horizon. Mineral soil C stocks did not differ between limed and control soils. Liming did not affect tree growth, however a net decline in biomass was observed across the entire watershed. There was a trend for larger fine root and foliar litter inputs in limed plots relative to controls, but the observed forest floor accumulation appears to be driven primarily by a suppression of decomposition. Liming reduced basal soil respiration rates by 17 and 43 % in the Oe and Oa horizons, respectively. This research suggests that Ca may

Cytokine gene expression in intestine of rat during the postnatal developmental period: increased IL-1 expression at weaning.

PubMed

Mengheri, E; Ciapponi, L; Vignolini, F; Nobili, F

1996-01-01

In the present study we have investigate whether cytokines are constitutively and differently expressed in intestine during the differentiative processes that take place at weaning. We have analyzed the expression of IL-1 beta, IL-2, IL-4 and IFN gamma by polymerase chain reaction in Peyer's patches (PP) and in intestine deprived of PP (I-PP) of rats from 16 to 30 days of age. The results showed a constitutive and marked expression of the cytokines already before weaning, with the exception of IL-2 in PP and IFN gamma in I-PP. IL-beta was the only cytokine to show a different expression at various ages with an initial increase at 19 days and a further elevation at 21 days when intestinal epithelium passes through major differentiative stages, suggesting an involvement of this cytokine in intestinal development. We have also tested whether treatment of rats with the immunosuppressor cyclosporin A (CsA) could affect intestinal differentiation. The results showed that only some markers of differentiation were affected (proliferation of staminal crypt cells and length of crypts). This was probably due to a direct effect rather than an immunomediated effect of CsA, since treatment of three intestinal cell lines (Caco-2, HT-29, FRIC) with CsA indicated that this drug can exert a cytostatic activity on intestinal cells.

Actin-interacting protein 1 controls assembly and permeability of intestinal epithelial apical junctions

PubMed Central

Baranwal, Somesh

2015-01-01

Adherens junctions (AJs) and tight junctions (TJs) are crucial regulators of the integrity and restitution of the intestinal epithelial barrier. The structure and function of epithelial junctions depend on their association with the cortical actin cytoskeleton that, in polarized epithelial cells, is represented by a prominent perijunctional actomyosin belt. The assembly and stability of the perijunctional cytoskeleton is controlled by constant turnover (disassembly and reassembly) of actin filaments. Actin-interacting protein (Aip) 1 is an emerging regulator of the actin cytoskeleton, playing a critical role in filament disassembly. In this study, we examined the roles of Aip1 in regulating the structure and remodeling of AJs and TJs in human intestinal epithelium. Aip1 was enriched at apical junctions in polarized human intestinal epithelial cells and normal mouse colonic mucosa. Knockdown of Aip1 by RNA interference increased the paracellular permeability of epithelial cell monolayers, decreased recruitment of AJ/TJ proteins to steady-state intercellular contacts, and attenuated junctional reassembly in a calcium-switch model. The observed defects of AJ/TJ structure and functions were accompanied by abnormal organization and dynamics of the perijunctional F-actin cytoskeleton. Moreover, loss of Aip1 impaired the apico-basal polarity of intestinal epithelial cell monolayers and inhibited formation of polarized epithelial cysts in 3-D Matrigel. Our findings demonstrate a previously unanticipated role of Aip1 in regulating the structure and remodeling of intestinal epithelial junctions and early steps of epithelial morphogenesis. PMID:25792565

Actin-interacting protein 1 controls assembly and permeability of intestinal epithelial apical junctions.

PubMed

Lechuga, Susana; Baranwal, Somesh; Ivanov, Andrei I

2015-05-01

Adherens junctions (AJs) and tight junctions (TJs) are crucial regulators of the integrity and restitution of the intestinal epithelial barrier. The structure and function of epithelial junctions depend on their association with the cortical actin cytoskeleton that, in polarized epithelial cells, is represented by a prominent perijunctional actomyosin belt. The assembly and stability of the perijunctional cytoskeleton is controlled by constant turnover (disassembly and reassembly) of actin filaments. Actin-interacting protein (Aip) 1 is an emerging regulator of the actin cytoskeleton, playing a critical role in filament disassembly. In this study, we examined the roles of Aip1 in regulating the structure and remodeling of AJs and TJs in human intestinal epithelium. Aip1 was enriched at apical junctions in polarized human intestinal epithelial cells and normal mouse colonic mucosa. Knockdown of Aip1 by RNA interference increased the paracellular permeability of epithelial cell monolayers, decreased recruitment of AJ/TJ proteins to steady-state intercellular contacts, and attenuated junctional reassembly in a calcium-switch model. The observed defects of AJ/TJ structure and functions were accompanied by abnormal organization and dynamics of the perijunctional F-actin cytoskeleton. Moreover, loss of Aip1 impaired the apico-basal polarity of intestinal epithelial cell monolayers and inhibited formation of polarized epithelial cysts in 3-D Matrigel. Our findings demonstrate a previously unanticipated role of Aip1 in regulating the structure and remodeling of intestinal epithelial junctions and early steps of epithelial morphogenesis. Copyright © 2015 the American Physiological Society.

In Inflamed Intestinal Tissues and Epithelial Cells, Interleukin 22 Signaling Increases Expression of H19 Long Noncoding RNA, Which Promotes Mucosal Regeneration.

PubMed

Geng, Hua; Bu, Heng-Fu; Liu, Fangyi; Wu, Longtao; Pfeifer, Karl; Chou, Pauline M; Wang, Xiao; Sun, Jiaren; Lu, Lu; Pandey, Ashutosh; Bartolomei, Marisa S; De Plaen, Isabelle G; Wang, Peng; Yu, Jindan; Qian, Jiaming; Tan, Xiao-Di

2018-04-03

Inflammation affects regeneration of the intestinal epithelia; long non-coding RNAs (lncRNAs) regulate cell functions, such as proliferation, differentiation, and migration. We investigated the mechanisms by which the lncRNA H19, imprinted maternally expressed transcript (H19) regulates regeneration of intestinal epithelium using cell cultures and mouse models of inflammation. We performed RNA-sequencing transcriptome analyses of intestinal tissues from mice with lipopolysaccharide (LPS)-induced sepsis to identify lncRNAs associated with inflammation; findings were confirmed by quantitative real-time polymerase chain reaction and in situ hybridization analyses of intestinal tissues from mice with sepsis or dextran sulfate sodium (DSS)-induced mucosal wound healing and patients with ulcerative colitis compared to healthy individuals (controls). We screened cytokines for their ability to induce expression of H19 in HT-29 cells and intestinal epithelial cells (IECs), and confirmed findings in crypt epithelial organoids derived from mouse small intestine. IECs were incubated with different signal transduction inhibitors and effects on H19 lncRNA levels were measured. We assessed intestinal epithelial proliferation or regeneration in H19 ΔEx1/+ mice given LPS or DSS vs wild-type littermates (control mice). H19 was overexpressed in IECs using lentiviral vectors and cell proliferation was measured. We performed RNA antisense purification, RNA immunoprecipitation, and luciferase reporter assays to study functions of H19 in IECs. In RNA-sequencing transcriptome analysis of lncRNA expression in intestinal tissues from mice, we found levels of H19 only changed significantly with LPS exposure. Levels of H19 lncRNA increased in intestinal tissues of patients with ulcerative colitis, mice with LPS-induced sepsis, or mice with DSS-induced colitis, compared with controls. Increased H19 lncRNA localized to epithelial cells in the intestine, regardless of Lgr5 messenger RNA

Studies on Inhibition of Intestinal Absorption of Radioactive Strontium

PubMed Central

Skoryna, Stanley C.; Paul, T. M.; Edward, Deirdre Waldron

1964-01-01

A method is reported which permits selective suppression of absorption of radioactive strontium from ingested food material, permitting the calcium to be available to the body. Studies were carried out in vivo by injection of Sr89 and Ca45 in the presence of inert carrier into ligated intestinal segments in rats, and the amount of absorption was measured by standard monitoring techniques. The pattern of absorption of both ions is very similar but the rate of absorption is different. It was found that the polyelectrolyte, sodium alginate, obtained from brown algae (Phaeophyceae), injected simultaneously with radiostrontium effectively reduces the absortion of Sr89 from all segments of the intestine by as much as 50-80% of the control values. No significant reduction in absorption of Ca45 was observed in equivalent concentrations. The reduction in blood levels of Sr89 and in bone uptake corresponded to the absorption pattern. The difference in the effect on strontium and calcium absorption may be due to differences in the binding capacity of sodium alginate from the two metal ions under the conditions present in vivo. PMID:14180534

Triiodothyronine increases calcium loss in a bed rest antigravity model for space flight.

PubMed

Smith, Steven R; Lovejoy, Jennifer C; Bray, George A; Rood, Jennifer; Most, Marlene M; Ryan, Donna H

2008-12-01

Bed rest has been used as a model to simulate the effects of space flight on bone metabolism. Thyroid hormones accelerate bone metabolism. Thus, supraphysiologic doses of this hormone might be used as a model to accelerate bone metabolism during bed rest and potentially simulate space flight. The objective of the study was to quantitate the changes in bone turnover after low doses of triiodothyronine (T(3)) added to short-term bed rest. Nine men and 5 women were restricted to bed rest for 28 days with their heads positioned 6 degrees below their feet. Subjects were randomly assigned to receive either placebo or oral T(3) at doses of 50 to 75 microg/d in a single-blind fashion. Calcium balance was measured over 5-day periods; and T(3), thyroxine, thyroid-stimulating hormone, immunoreactive parathyroid hormone, osteocalcin, bone alkaline phosphatase, and urinary deoxypyridinoline were measured weekly. Triiodothyronine increased 2-fold in the men and 5-fold in the women during treatment, suppressing both thyroxine and thyroid-stimulating hormone. Calcium balance was negative by 300 to 400 mg/d in the T(3)-treated volunteers, primarily because of the increased fecal loss that was not present in the placebo group. Urinary deoxypyridinoline to creatinine ratio, a marker of bone resorption, increased 60% in the placebo group during bed rest, but more than doubled in the T(3)-treated subjects (P < .01), suggesting that bone resorption was enhanced by treatment with T(3). Changes in serum osteocalcin and bone-specific alkaline phosphatase, markers of bone formation, were similar in T(3)- and placebo-treated subjects. Triiodothyronine increases bone resorption and fecal calcium loss in subjects at bed rest.

Influence of a low- and a high-oxalate vegetarian diet on intestinal oxalate absorption and urinary excretion.

PubMed

Thomas, E; von Unruh, G E; Hesse, A

2008-09-01

To compare quantitatively the effect of a low- and a high-oxalate vegetarian diet on intestinal oxalate absorption and urinary excretion. Eight healthy volunteers (three men and five women, mean age 28.6+/-6.3) were studied. Each volunteer performed the [(13)C(2)]oxalate absorption test thrice on a low-oxalate mixed diet, thrice on a low-oxalate vegetarian diet and thrice on a high-oxalate vegetarian diet. For each test, the volunteers had to adhere to an identical diet and collect their 24-h urines. In the morning of the second day, a capsule containing [(13)C(2)]oxalate was ingested. On the low-oxalate vegetarian diet, mean intestinal oxalate absorption and urinary oxalate excretion increased significantly to 15.8+/-2.9% (P=0.012) and 0.414+/-0.126 mmol/day (P=0.012), compared to the mixed diet. On the high-oxalate vegetarian diet, oxalate absorption (12.5+/-4.6%, P=0.161) and urinary excretion (0.340+/-0.077 mmol/day, P=0.093) did not change significantly, compared to the mixed diet. A vegetarian diet can only be recommended for calcium oxalate stone patients, if the diet (1) contains the recommended amounts of divalent cations such as calcium and its timing of ingestion to a meal rich in oxalate is considered and (2) excludes foodstuffs with a high content of nutritional factors, such as phytic acid, which are able to chelate calcium.

Intestinal Parasitoses.

ERIC Educational Resources Information Center

Lagardere, Bernard; Dumburgier, Elisabeth

1994-01-01

Intestinal parasites have become a serious public health problem in tropical countries because of the climate and the difficulty of achieving efficient hygiene. The objectives of this journal issue are to increase awareness of the individual and collective repercussions of intestinal parasites, describe the current conditions of contamination and…

Increased calcium supplementation is associated with morbidity and mortality in the infant postoperative cardiac patient.

PubMed

Dyke, Peter C; Yates, Andrew R; Cua, Clifford L; Hoffman, Timothy M; Hayes, John; Feltes, Timothy F; Springer, Michelle A; Taeed, Roozbeh

2007-05-01

study population. Greater calcium replacement is associated with increasing morbidity and mortality. Further investigation of the etiology and therapy of hypocalcemia in this population is warranted.

Nuclear factor of activated T-cells 5 increases intestinal goblet cell differentiation through an mTOR/Notch signaling pathway

PubMed Central

Zhou, Yuning; Wang, Qingding; Weiss, Heidi L.; Evers, B. Mark

2014-01-01

The intestinal mucosa undergoes a continual process of proliferation, differentiation, and apoptosis that is regulated by multiple signaling pathways. Previously, we have shown that the nuclear factor of activated T-cells 5 (NFAT5) is involved in the regulation of intestinal enterocyte differentiation. Here we show that treatment with sodium chloride (NaCl), which activates NFAT5 signaling, increased mTORC1 repressor regulated in development and DNA damage response 1 (REDD1) protein expression and inhibited mTOR signaling; these alterations were attenuated by knockdown of NFAT5. Knockdown of NFAT5 activated mammalian target of rapamycin (mTOR) signaling and significantly inhibited REDD1 mRNA expression and protein expression. Consistently, overexpression of NFAT5 increased REDD1 expression. In addition, knockdown of REDD1 activated mTOR and Notch signaling, whereas treatment with mTOR inhibitor rapamycin repressed Notch signaling and increased the expression of the goblet cell differentiation marker mucin 2 (MUC2). Moreover, knockdown of NFAT5 activated Notch signaling and decreased MUC2 expression, while overexpression of NFAT5 inhibited Notch signaling and increased MUC2 expression. Our results demonstrate a role for NFAT5 in the regulation of mTOR signaling in intestinal cells. Importantly, these data suggest that NFAT5 participates in the regulation of intestinal homeostasis via the suppression of mTORC1/Notch signaling pathway. PMID:25057011

Orally administered indomethacin acutely reduces cellular prion protein in the small intestine and modestly increases survival of mice exposed to infectious prions.

PubMed

Martin, Gary R; Sharkey, Keith A; Jirik, Frank R

2015-05-01

The oral uptake of infectious prions represents a common way to acquire a prion disease; thus, host factors, such as gut inflammation and intestinal "leakiness", have the potential to influence infectivity. For example, the ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) is known to induce intestinal inflammation and increase intestinal permeability. Previously, we reported that normal cellular prion protein (PrP(C)) expression was increased in experimental colitis, and since the level of PrP(C) expressed is a determinant of prion disease propagation, we hypothesized that NSAID administration prior to the oral inoculation of mice with infectious prions would increase intestinal PrP(C) expression and accelerate the onset of neurological disease. In the long-term experiments, one group of mice was gavaged with indomethacin, followed by a second gavage with brain homogenate containing mouse-adapted scrapie (ME7). Control mice received ME7 brain homogenate alone. Brain and splenic tissues were harvested at several time points for immunoblotting, including at the onset of clinical signs of disease. In a second series of experiments, mice were gavaged with indomethacin to assess the acute effects of this treatment on intestinal PrP(C) expression. Acutely, NSAID treatment reduced intestinal PrP(C) expression, and chronically, there was a modest delay in the onset of neurological disease. In contrast to our hypothesis, brief exposure to an NSAID decreased intestinal PrP(C) expression and led to a modest survival advantage following oral ingestion of infectious prions.

Calcium Balance in Mature Rats Exposed to a Space Flight Model

NASA Technical Reports Server (NTRS)

Wolinsky, Ira

1996-01-01

Negative calcium balances are seen in humans during spaceflight and bed rest, an analog of space flight. Due to the infrequency and costliness of space flight and the difficulties, cost, and restraints in using invasive procedures in bed rest studies, several ground based animal models of space flight have been employed. The most useful and well developed of these models is hind limb unloading in the rat. In this model the hind limbs are non-weight bearing (unloaded) but still mobile; there is a cephalad fluid shift similar to that seen in astronauts in flight; the animals are able to feed, groom and locomote using their front limbs; the procedure is reversible; and, importantly, the model has been validated by comparison to space flight. Several laboratories have studied calcium balance using rats in hind limb unweighting. Roer and Dillaman used young male rats to study calcium balance in this model for 25 days. They found no differences in dietary calcium intake, percent calcium absorption, urinary and fecal excretion, hence indicating no differences in calcium balance between control and unloaded rats. In another study, employing 120 day old females, rats' hind limbs were unloaded for 28 days. While negative calcium balances were observed during a 25 day recovery period no balance measurements were possible during unweighting since the researchers did not employ appropriate metabolic cages. In a recent study from this laboratory, using 200 g rats in the space flight model for two weeks, we found depressed intestinal calcium absorption and increased fecal calcium excretion (indicating less positive calcium balances) and lower circulating 1,25-dihydroxyvitamin D. The above studies indicate that there remains a dearth of information on calcium balance during the hind limb unloading rat space flight model, especially in mature rats, whose use is a better model for planned manned space flight than juvenile or growing animals. With the aid of a newly designed

Building better bones in childhood: a randomized controlled study to test the efficacy of a dietary intervention program to increase calcium intake.

PubMed

Weber, D R; Stark, L J; Ittenbach, R F; Stallings, V A; Zemel, B S

2017-06-01

Many children do not consume the recommended daily allowance of calcium. Inadequate calcium intake in childhood may limit bone accrual. The objective of this study was to determine if a behavioral modification and nutritional education (BM-NE) intervention improved dietary calcium intake and bone accrual in children. 139 (86 female) healthy children, 7-10 years of age, were enrolled in this randomized controlled trial conducted over 36 months. Participants randomized to the BM-NE intervention attended five sessions over a 6-week period designed to increase calcium intake to 1500 mg/day. Participants randomized to the usual care (UC) group received a single nutritional counseling session. The Calcium Counts Food Frequency Questionnaire was used to assess calcium intake; dual energy X-ray absorptiometry was used to assess areal bone mineral density (aBMD) and bone mineral content (BMC). Longitudinal mixed effects models were used to assess for an effect of the intervention on calcium intake, BMC and aBMD. BM-NE participants had greater increases in calcium intake that persisted for 12 months following the intervention compared with UC. The intervention had no effect on BMC or aBMD accrual. Secondary analyses found a negative association between calcium intake and adiposity such that greater calcium intake was associated with lesser gains in body mass index and fat mass index. A family-centered BM-NE intervention program in healthy children was successful in increasing calcium intake for up to 12 months but had no effect on bone accrual. A beneficial relationship between calcium intake and adiposity was observed and warrants future study.

The Hepatitis B Virus X Protein Elevates Cytosolic Calcium Signals by Modulating Mitochondrial Calcium Uptake

PubMed Central

Yang, Bei

2012-01-01

Chronic hepatitis B virus (HBV) infections are associated with the development of hepatocellular carcinoma (HCC). The HBV X protein (HBx) is thought to play an important role in the development of HBV-associated HCC. One fundamental HBx function is elevation of cytosolic calcium signals; this HBx activity has been linked to HBx stimulation of cell proliferation and transcription pathways, as well as HBV replication. Exactly how HBx elevates cytosolic calcium signals is not clear. The studies described here show that HBx stimulates calcium entry into cells, resulting in an increased plateau level of inositol 1,4,5-triphosphate (IP3)-linked calcium signals. This increased calcium plateau can be inhibited by blocking mitochondrial calcium uptake and store-operated calcium entry (SOCE). Blocking SOCE also reduced HBV replication. Finally, these studies also demonstrate that there is increased mitochondrial calcium uptake in HBx-expressing cells. Cumulatively, these studies suggest that HBx can increase mitochondrial calcium uptake and promote increased SOCE to sustain higher cytosolic calcium and stimulate HBV replication. PMID:22031934

Subchronic mild noise stress increases HRP permeability in rat small intestine in vitro.

PubMed

Bijlsma, P B; van Raaij, M T; Dobbe, C J; Timmerman, A; Kiliaan, A J; Taminiau, J A; Groot, J A

2001-05-01

Recently we reported an increased trans- and paracellular protein permeability in rat small intestine after acute cold restraint stress. In the present study, we applied randomized 95- or 105-dB white noise pulses during 45 min/h, 12 h/day, duration 8 days, as a milder, but more chronic stressor to male rats. At 8 days before the noise experiments, 50% of the animals were cannulated in the vena cava for blood sampling during the experimental period. The other 50% of the animals were sacrificed at Day 9, segments of ileum were mounted in Ussing chambers and perfused at 37 degrees C. Horseradish peroxidase (HRP) was added mucosally, serosal appearance was detected enzymatically and tissues were fixed for electron microscopy. In the animals exposed to 95-dB noise, plasma corticosterone levels were enhanced twofold compared to controls, and ileal HRP flux was enhanced twofold. Electron micrographs of tissue from stressed or control animals showed no detectable paracellular staining of HRP. Quantification of HRP-containing endosomes in enterocytes revealed a twofold increase in endosome number in the animals exposed to 95-db noise indicating that the increased HRP permeability was primarily due to increased endocytosis. In contrast to the animals exposed to 95-dB noise, rats exposed to 105-dB noise showed no increase in corticosterone levels and ileal HRP fluxes were not significantly different from controls. We conclude that mild subchronic noise stress may cause a decrease in intestinal barrier function by increased transcytosis of luminal antigens.

Prom1 Function in Development, Intestinal Inflammation, and Intestinal Tumorigenesis

PubMed Central

Karim, Baktiar O.; Rhee, Ki-Jong; Liu, Guosheng; Yun, Kyuson; Brant, Steven R.

2014-01-01

Prom1/CD133 has been identified in colorectal, hepatocellular, and pancreatic cancer as a cancer stem cell marker and has been used as such to predict colon cancer recurrence in humans. Its potential molecular function as well as its role as a marker of intestinal regeneration is still not fully known. We evaluated the role of Prom1 in intestinal regeneration in inflammatory bowel disease (IBD), determined the function of Prom1, and characterized the effect of a lack of Prom1 on intestinal tumor formation in animal models. Our results suggest that Apc mutations lead to an increase in Prom1 expressing cells in the intestinal crypt stem cell compartment and in early intestinal adenomas. Also, Prom1 knockout mice are more susceptible to intestinal tumor formation. We conclude that Prom1 likely plays a role in regulating intestinal homeostasis and that these results clearly illustrate the role of Prom1 in intestinal regeneration. We further conclude that Prom1 may provide a novel therapeutic target for patients with gastrointestinal conditions such as IBD, short bowel syndrome, and colorectal cancer. PMID:25452936

CaSR-mediated interactions between calcium and magnesium homeostasis in mice.

PubMed

Quinn, Stephen J; Thomsen, Alex R B; Egbuna, Ogo; Pang, Jian; Baxi, Khanjan; Goltzman, David; Pollak, Martin; Brown, Edward M

2013-04-01

Calcium (Ca) and magnesium (Mg) homeostasis are interrelated and share common regulatory hormones, including parathyroid hormone (PTH) and vitamin D. However, the role of the calcium-sensing receptor (CaSR) in Mg homeostasis in vivo is not well understood. We sought to investigate the interactions between Mg and Ca homeostasis using genetic mouse models with targeted inactivation of PTH (PTH KO) or both PTH and the calcium-sensing receptor (CaSR) (double knockout, DKO). Serum Mg is lower in PTH KO and DKO mice than in WT mice on standard chow, whereas supplemental dietary Ca leads to equivalent Mg levels for all three genotypes. Mg loading increases serum Mg in all genotypes; however, the increase in serum Mg is most pronounced in the DKO mice. Serum Ca is increased with Mg loading in the PTH KO and DKO mice but not in the WT mice. Here, too, the hypercalcemia is much greater in the DKO mice. Serum and especially urinary phosphate are reduced during Mg loading, which is likely due to intestinal chelation of phosphate by Mg. Mg loading decreases serum PTH in WT mice and increases serum calcitonin in both WT and PTH KO mice but not DKO mice. Furthermore, Mg loading elevates serum 1,25-dihydroxyvitamin D in all genotypes, with greater effects in PTH KO and DKO mice, possibly due to reduced levels of serum phosphorus and FGF23. These hormonal responses to Mg loading and the CaSR's role in regulating renal function may help to explain changes in serum Mg and Ca found during Mg loading.

Effect of excess dietary salt on calcium metabolism and bone mineral in a spaceflight rat model

NASA Technical Reports Server (NTRS)

Navidi, Meena; Wolinsky, Ira; Fung, Paul; Arnaud, Sara B.

1995-01-01

High levels of salt promote urinary calcium (UCa) loss and have the potential to cause bone mineral deficits if intestinal Ca absorption does not compensate for these losses. To determine the effect of excess dietary salt on the osteopenia that follows skeletal unloading, we used a spaceflight model that unloads the hindlimbs of 200-g rats by tail suspension (S). Rats were studied for 2 wk on diets containing high salt (4 and 8%) and normal calcium (0.45%) and for 4 wk on diets containing 8% salt (HiNa) and 0.2% Ca (LoCa). Final body weights were 9-11% lower in S than in control rats (C) in both experiments, reflecting lower growth rates in S than in C during pair feeding. UCa represented 12% of dietary Ca on HiNA diets and was twofold higher in S than in C transiently during unloading. Net intestinal Ca absorption was consistently 11-18% lower in S than in C. Serum 1,25-dihydroxyvitamin D was unaffected by either LoCa or HiNa diets in S but was increased by LoCa and HiNa diets in C. Despite depressed intestinal Ca absoption in S and a sluggish response of the Ca endocrine system to HiNa diets, UCa loss did not appear to affect the osteopenia induced by unloading. Although any deficit in bone mineral content from HiNa diets may have been too small to detect or the duration of the study too short to manifest, there were clear differences in Ca metabolism from control levels in the response of the spaceflight model to HiNa diets, indicated by depression of intestinal Ca absorption and its regulatory hormone.

Reversibility of increased intestinal permeability to 51Cr-EDTA in patients with gastrointestinal inflammatory diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jenkins, R.T.; Jones, D.B.; Goodacre, R.L.

1987-11-01

Intestinal permeability in adults with inflammatory gastrointestinal diseases was investigated by measuring the 24-h urinary excretion of orally administered /sup 51/Cr-EDTA. Eighty controls along with 100 patients with Crohn's disease, 46 patients with ulcerative colitis, 20 patients with gluten-sensitive enteropathy, and 18 patients with other diseases were studied. In controls, the median 24-h excretion was 1.34%/24 h of the oral dose. Patients with Crohn's disease (median 2.96%/24 h), ulcerative colitis (median 2.12%/24 h), and untreated gluten-sensitive enteropathy (median 3.56%/24 h) had significantly elevated urinary excretion of the probe compared to controls (p less than 0.0001). Increased 24-h urinary excretion ofmore » /sup 51/Cr-EDTA had a high association with intestinal inflammation (p less than 0.0001). Test specificity and sensitivity were 96% and 57%, respectively. A positive test has a 96% probability of correctly diagnosing the presence of intestinal inflammation, whereas a negative test has a 50% probability of predicting the absence of disease.« less

The site of net absorption of Ca from the intestinal tract of growing pigs and effect of phytic acid, Ca level and Ca source on Ca digestibility.

PubMed

González-Vega, J Caroline; Walk, Carrie L; Liu, Yanhong; Stein, Hans H

2014-01-01

An experiment was conducted to test the hypothesis that the standardised digestibility of Ca in calcium carbonate and Lithothamnium calcareum Ca is not different regardless of the level of dietary Ca, and that phytic acid affects the digestibility of Ca in these two ingredients to the same degree. The objectives were to determine where in the intestinal tract Ca absorption takes place and if there are measurable quantities of basal endogenous Ca fluxes in the stomach, small intestine or large intestine. Diets contained calcium carbonate or L. calcareum Ca as the sole source of Ca, 0% or 1% phytic acid and 0.4% or 0.8% Ca. A Ca-free diet was also formulated and used to measure endogenous fluxes and losses of Ca. Nine growing pigs (initial body weight 23.8 ± 1.3 kg) were cannulated in the duodenum and in the distal ileum, and faecal, ileal and duodenal samples were collected. Duodenal endogenous fluxes of Ca were greater (p < 0.05) than ileal endogenous fluxes and total tract endogenous losses of Ca, but ileal endogenous fluxes were less (p < 0.05) than total tract endogenous losses. Standardised digestibility of Ca was not affected by the level of phytic acid, but decreased (p < 0.05) as Ca level increased in L. calcareum Ca diets, but that was not the case if calcium carbonate was the source of Ca (interaction, p < 0.05). The standardised duodenal digestibility (SDD), standardised ileal digestibility (SID) and standardised total tract digestibility (STTD) of Ca were not different if calcium carbonate was the source of dietary Ca. However, the STTD of Ca in L. calcareum Ca was greater (p < 0.05) than the SID and SDD of Ca. The SDD, SID and STTD of Ca in calcium carbonate were greater (p < 0.05) than those of L. calcareum Ca. In conclusion, under the conditions of this experiment, standardised digestibility of Ca is not affected by the level of phytic acid, but may be affected by dietary Ca level depending on the Ca source. Calcium from calcium carbonate is mostly

Oxalate and Sucralose Absorption in Idiopathic Calcium Oxalate Stone Formers

PubMed Central

Knight, John; Jiang, Juquan; Wood, Kyle D.; Holmes, Ross P.; Assimos, Dean G.

2011-01-01

Objectives Oxalate has been hypothesized to undergo absorption in the large and small intestine by both paracellular and transepithelial transport. Sucralose is a chlorinated sugar that is absorbed by paracellular mechanisms. This study's objective was to better understand intestinal oxalate transport by correlating oxalate and sucralose absorption in idiopathic calcium oxalate stone formers. Methods Idiopathic calcium oxalate stone formers were recruited to provide urine specimens on both a self-selected diet and following a meal containing 90 mg of 13C2-oxalate and 5 grams of sucralose, and a stool sample for determination of Oxalobacter formigenes colonization. The 24 hour urine collections were fractionated into the first 6 hours and the subsequent 18 hours. Sucralose and oxalate excretion were measured during these periods and used to estimate absorption. Results A total of 38 subjects were evaluated. The majority of both the 13C2-oxalate and sucralose absorption occurred within the 0-6 hour collection. The 13C2-oxalate and sucralose absorptions were significantly correlated at the 0-6 hour, the 6-24 hour, and the total 24 hour time periods (p<0.04). All five oxalate hyperabsorbers(> 15% absorption) also absorbed significantly more sucralose during the 0-6 hour and whole 24 hour time points (p<0.04). Oxalobacter formigenes colonization did not significantly alter oxalate absorption. Conclusion The results suggest that the majority of oxalate is absorbed in the proximal portion of the gastrointestinal tract and that paracelluar transport is involved. Augmented paracellular transport, as evidenced by increased sucralose absorption, may also influence oxalate absorption. PMID:21676449

Calcium content of different compositions of gallstones and pathogenesis of calcium carbonate gallstones.

PubMed

Yu, Ji-Kuen; Pan, Huichin; Huang, Shing-Moo; Huang, Nan-Lan; Yao, Chung-Chin; Hsiao, Kuang-Ming; Wu, Chew-Wun

2013-01-01

Our aim was to investigate the calcium content of different gallstone compositions and the pathogenic mechanisms of calcium carbonate gallstones. Between August 2001 and July 2007, gallstones from 481 patients, including 68 calcium carbonate gallstones, were analyzed for total calcium content. Gallbladder bile samples from 33 cases and six controls were analyzed for pH, carbonate anion level, free-ionized calcium concentration and saturation index for calcium carbonate. Total calcium content averaged 75.6 %, 11.8 %, and 4.2 % for calcium carbonate, calcium bilirubinate and cholesterol gallstones. In 29.4 % of patients, chronic and/or intermittent cystic duct obstructions were caused by polypoid lesions in the neck region and 70.6 % were caused by stones. A total of 82 % of patients had chronic low-grade inflammation of the gallbladder wall and 18.0 % had acute inflammatory exacerbations. In the bile, we found the mean pH, mean carbonate anion, free-ionized calcium concentrations, and mean saturation index for calcium carbonate to be elevated in comparison to controls. From our study, we found chronic and/or intermittent cystic duct obstructions and low-grade GB wall inflammation lead to GB epithelium hydrogen secretion dysfunction. Increased calcium ion efflux into the GB lumen combined with increased carbonate anion presence increases SI_CaCO(3) from 1 to 22.4. Thus, in an alkaline milieu with pH 7.8, calcium carbonate begins to aggregate and precipitate. Copyright © 2012. Published by Elsevier B.V.

The calcium-sensing receptor regulates mammary gland parathyroid hormone–related protein production and calcium transport

PubMed Central

VanHouten, Joshua; Dann, Pamela; McGeoch, Grace; Brown, Edward M.; Krapcho, Karen; Neville, Margaret; Wysolmerski, John J.

2004-01-01

The transfer of calcium from mother to milk during lactation is poorly understood. In this report, we demonstrate that parathyroid hormone–related protein (PTHrP) production and calcium transport in mammary epithelial cells are regulated by extracellular calcium acting through the calcium-sensing receptor (CaR). The CaR becomes expressed on mammary epithelial cells at the transition from pregnancy to lactation. Increasing concentrations of calcium, neomycin, and a calcimimetic compound suppress PTHrP secretion by mammary epithelial cells in vitro, whereas in vivo, systemic hypocalcemia increases PTHrP production, an effect that can be prevented by treatment with a calcimimetic. Hypocalcemia also reduces overall milk production and calcium content, while increasing milk osmolality and protein concentrations. The changes in milk calcium content, milk osmolality, and milk protein concentration were mitigated by calcimimetic infusions. Finally, in a three-dimensional culture system that recapitulates the lactating alveolus, activation of the basolateral CaR increases transcellular calcium transport independent of its effect on PTHrP. We conclude that the lactating mammary gland can sense calcium and adjusts its secretion of calcium, PTHrP, and perhaps water in response to changes in extracellular calcium concentration. We believe this defines a homeostatic system that helps to match milk production to the availability of calcium. PMID:14966569

Increased intestinal macromolecular permeability and urine nitrite excretion associated with liver cirrhosis with ascites.

PubMed

Lee, Soong; Son, Seung-Cheol; Han, Moon-Jong; Kim, Woo-Jin; Kim, Soo-Hyun; Kim, Hye-Ran; Jeon, Woo-Kyu; Park, Ki-Hong; Shin, Myung-Geun

2008-06-28

To determine intestinal permeability, the serum tumor necrosis factor (TNF)-alpha level and urine nitric oxide (NO) metabolites are altered in liver cirrhosis (LC) with or without ascites. Fifty-three patients with LC and 26 healthy control subjects were enrolled in the study. The intestinal permeability value is expressed as the percentage of polyethylene glycol (PEG) 400 and 3350 retrieval in 8-h urine samples as determined by high performance liquid chromatography. Serum TNF-alpha concentrations and urine NO metabolites were determined using an enzyme-linked immunosorbent assay (ELISA) and Greiss reaction method, respectively. The intestinal permeability index was significantly higher in patients with LC with ascites than in healthy control subjects or patients with LC without ascites (0.88 +/- 0.12 vs 0.52 +/- 0.05 or 0.53 +/- 0.03, P < 0.05) and correlated with urine nitrite excretion (r = 0.98). Interestingly, the serum TNF-alpha concentration was significantly higher in LC without ascites than in control subjects or in LC with ascites (198.9 +/- 55.8 pg/mL vs 40.9 +/- 12.3 pg/mL or 32.1 +/- 13.3 pg/mL, P < 0.05). Urine nitrite excretion was significantly higher in LC with ascites than in the control subjects or in LC without ascites (1170.9 +/- 28.7 micromol/L vs 903.1 +/- 55.1 micromol/L or 956.7 +/- 47.7 micromol/L, P < 0.05). Increased intestinal macromolecular permeability and NO is probably of importance in the pathophysiology and progression of LC with ascites, but the serum TNF-alpha concentration was not related to LC with ascites.

Something more to say about calcium homeostasis: the role of vitamin K2 in vascular calcification and osteoporosis.

PubMed

Flore, R; Ponziani, F R; Di Rienzo, T A; Zocco, M A; Flex, A; Gerardino, L; Lupascu, A; Santoro, L; Santoliquido, A; Di Stasio, E; Chierici, E; Lanti, A; Tondi, P; Gasbarrini, A

2013-09-01

Vascular calcification and osteoporosis share similar etiopathogenetic mechanisms. Vitamin K2 deficiency could be responsible of the so called "calcium paradox", that is the lack of calcium in the bone and its storage in the vessel wall. These events may have clinically relevant consequences, such as cardiovascular accidents, and bone fractures. To review the biological function of vitamin K2 metabolism, the main factors related to its deficiency and the consequent clinical significance. Vitamin K2 is essential for the function of several proteins, involved in the maintenance of the normal structure of arterial wall, osteoarticular system, teeth, and for the regulation of cell growth. It has been demonstrated to have a pivotal role in the inhibition of vascular foci of calcification, and in the regulation of calcium deposition in the bone. Vitamin K2 deficiency is often subclinic in a large part of healthy population. This deficiency is related to the interaction of various factors, such as the reduced dietary intake, the alteration of intestinal absorption or production, with a possible role of intestinal microbiota and the increased consumption at the vessel wall. Vitamin K2 deficiency has recently been recognized as a protagonist in the development of vascular calcification and osteoporosis. Data reported so far are promising and, dietary supplementation seems a useful tool to contrast these diseases. However, large studies or solid clinical correlations regarding vitamin K2 deficiency and its pathologic consequences are needed to confirm these preliminary experiences.

Calcium intake is not associated with increased coronary artery calcification: The Framingham Study

USDA-ARS?s Scientific Manuscript database

Adequate calcium intake is known to protect the skeleton. However, studies that have reported adverse effects of calcium supplementation on vascular events have raised widespread concern. We assessed the association between calcium intake (from diet and supplements) and coronary artery calcification...

Osteocyte-derived RANKL is a critical mediator of the increased bone resorption caused by dietary calcium deficiency

PubMed Central

Xiong, Jinhu; Piemontese, Marilina; Thostenson, Jeff D.; Weinstein, Robert S.; Manolagas, Stavros C.; O’Brien, Charles A.

2014-01-01

Parathyroid hormone (PTH) excess stimulates bone resorption. This effect is associated with increased expression of the osteoclastogenic cytokine receptor activator of nuclear factor кB ligand (RANKL) in bone. However, several different cell types, including bone marrow stromal cells, osteocytes, and T lymphocytes, express both RANKL and the PTH receptor and it is unclear whether RANKL expression by any of these cell types is required for PTH-induced bone loss. Here we have used mice lacking the RANKL gene in osteocytes to determine whether RANKL produced by this cell type is required for the bone loss caused by secondary hyperparathyroidism induced by dietary calcium deficiency in adult mice. Thirty days of dietary calcium deficiency caused bone loss in control mice, but this effect was blunted in mice lacking RANKL in osteocytes. The increase in RANKL expression in bone and the increase in osteoclast number caused by dietary calcium deficiency were also blunted in mice lacking RANKL in osteocytes. These results demonstrate that RANKL produced by osteocytes contributes to the increased bone resorption and the bone loss caused by secondary hyperparathyroidism, strengthening the evidence that osteocytes are an important target cell for hormonal control of bone remodeling. PMID:24933342

Feeding 5-hydroxy-l-tryptophan during the transition from pregnancy to lactation increases calcium mobilization from bone in rats.

PubMed

Laporta, J; Peters, T L; Weaver, S R; Merriman, K E; Hernandez, L L

2013-05-01

An increasing demand for calcium during pregnancy and lactation can result in both clinical and subclinical hypocalcemia during the early lactation period in several mammalian species, in particular the dairy cow. Serotonin (5-HT) was recently identified as a regulator of lactation and bone turnover. The purpose of this study was to determine whether supplementation of the maternal diet with a 5-HT precursor would increase maternal bone turnover and calcium mobilization to maintain appropriate circulating maternal concentrations of ionized calcium during lactation. Female Sprague-Dawley rats (n = 30) were fed either a control diet (n = 15) or a diet supplemented with the 5-HT precursor 5-hydroxytryptophan (5-HTP, 0.2%; n = 15) from day 13 of pregnancy through day 9 of lactation. Maternal serum and plasma (day 1 and day 9 of lactation), milk and pup weight (daily), mammary gland and bone tissue (day 9 of lactation) were collected for analysis. The 5-HTP diet elevated circulating maternal concentrations of 5-HT on day 1 and day 9 of lactation and parathyroid hormone related-protein (PTHrP) on day 9 of lactation (P < 0.033). In addition, 5-HTP supplementation increased total serum calcium concentrations on day 1 of lactation and total milk calcium concentration on day 9 of lactation (P < 0.032). Supplemental 5-HTP did not alter milk yield, maternal body weight, mammary gland structure, or pup litter weights (P > 0.05). Supplemental 5-HTP also resulted in increased concentrations of mammary 5-HT and PTHrP, as well as increased mRNA expression of rate-limiting enzyme in 5-HT synthesis, tryptophan hydroxylase 1, and Pthrp mRNA on day 9 of lactation (P < 0.028). In addition, supplementation of 5-HTP resulted in increased mRNA expression of maternal mammary calcium transporters and resorption of bone in the femur, indicated by increase osteoclast number and diameter as well as mRNA expression of classical markers of bone resorption on day 9 of lactation (P < 0

Reduced active transcellular intestinal oxalate secretion contributes to the pathogenesis of obesity-associated hyperoxaluria.

PubMed

Amin, Ruhul; Asplin, John; Jung, Daniel; Bashir, Mohamed; Alshaikh, Altayeb; Ratakonda, Sireesha; Sharma, Sapna; Jeon, Sohee; Granja, Ignacio; Matern, Dietrich; Hassan, Hatim

2018-05-01

Most kidney stones are composed of calcium oxalate, and minor changes in urine oxalate affect the stone risk. Obesity is a risk factor for kidney stones and a positive correlation of unknown etiology between increased body size, and elevated urinary oxalate excretion has been reported. Here, we used obese ob/ob (ob) mice to elucidate the pathogenesis of obesity-associated hyperoxaluria. These ob mice have significant hyperoxaluria (3.3-fold) compared with control mice, which is not due to overeating as shown by pair-feeding studies. Dietary oxalate removal greatly ameliorated this hyperoxaluria, confirming that it is largely enteric in origin. Transporter SLC26A6 (A6) plays an essential role in active transcellular intestinal oxalate secretion, and ob mice have significantly reduced jejunal A6 mRNA (- 80%) and total protein (- 62%) expression. While net oxalate secretion was observed in control jejunal tissues mounted in Ussing chambers, net absorption was seen in ob tissues, due to significantly reduced secretion. We hypothesized that the obesity-associated increase in intestinal and systemic inflammation, as reflected by elevated proinflammatory cytokines, suppresses A6-mediated intestinal oxalate secretion and contributes to obesity-associated hyperoxaluria. Indeed, proinflammatory cytokines (elevated in ob mice) significantly decreased intestinal oxalate transport in vitro by reducing A6 mRNA and total protein expression. Proinflammatory cytokines also significantly reduced active mouse jejunal oxalate secretion, converting oxalate transport from net secretion in vehicle-treated tissues to net absorption in proinflammatory cytokines-treated tissues. Thus, reduced active intestinal oxalate secretion, likely secondary to local and systemic inflammation, contributes to the pathogenesis of obesity-associated hyperoxaluria. Hence, proinflammatory cytokines represent potential therapeutic targets. Copyright © 2017 International Society of Nephrology. Published by

Radiological study of the effect of low calcium diet on the mineral metabolism of bone tissue. With reference to mineralization in callus (in Japanese)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakamura, K.

1972-01-01

Deficiency of available food material due either to poor diet or to malabsorption may adversely affect the skeleton. To study the affection, DDN mice were fed low calcium diet to induce low calcium state corresponding to malabsorption of calcium from the intestine. The femur was fractured manually. Then, calcium deposition in the callus was observed by microradiography and tracer technics with /sup 47/Ca. Increase of the body weight in mice fed low calcium diet was much slower than in the control. The affection of the low calcium diet on bone tissue appeared as a decrease of precipitation of calcium salt.more » This tendency was also observed in callus, Tracer study with /sup 47/Ca was performed in mice fed the low calcium diet for 24 days. Incorporation activity of calcium was generally high in each organ except the kidney. Callus in the site of the fracture in mice fed a low calcium diet was formed to the same degree as the control, although the amount of precipitated calcium in it was significantly poorer. In summary, insufficient mineralization in relation to osteogenesis occurred when the supply of the requisite electrolytes was insufficient or inappropriate. On the other hand, the uptake rate of calcinm in the callus was elevated even in the calcium deficient state. (auth)« less

Calcium and Bone Metabolism Indices.

PubMed

Song, Lu

2017-01-01

Calcium and inorganic phosphate are of critical importance for many body functions, thus the regulations of their plasma concentrations are tightly controlled by the concerted actions of reabsorption/excretion in the kidney, absorption in the intestines, and exchange from bone, the major reservoir for calcium and phosphate in the body. Parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25(OH) 2 D) control calcium homeostasis, whereas PTH, 1,25(OH) 2 D, and bone-derived fibroblast growth factor 23 (FGF 23) control phosphate homeostasis. Hypoparathyroidism can cause hypocalcemia and hyperphosphatemia, whereas deficient vitamin D actions can cause osteomalacia in adults and rickets in children. Hyperparathyroidism, alternatively, can cause hypercalcemia and hypophosphatemia. Laboratory tests of calcium, phosphate, PTH, and 25-hydroxyvitamin D are very useful in the diagnosis of abnormalities associated with calcium and/or phosphate metabolisms. Bone is constantly remodeled throughout life in response to mechanical stress and a need for calcium in extracellular fluids. Metabolic bone diseases such as osteoporosis, osteomalacia in adults or rickets in children, and renal osteodystrophy develop when bone resorption exceeds bone formation. Bone turnover markers (BTM) such as serum N-terminal propeptide of type I procollagen (P1NP) and C-terminal collagen cross-link (CTX) may be useful in predicting future fracture risk or monitoring the response to anti-resorptive therapy. There is a need to standardize sample collection protocols because certain BTMs exhibit large circadian variations and tend to be influenced by food intakes. In the United States, a project to standardize BTM sample collection protocols and to establish the reference intervals for serum P1NP and serum CTX is ongoing. We anticipate the outcome of this project to shine lights on the standardization of BTM assays, sample collection protocols, reference intervals in relation to age, sex, and ethnic

Ablation of ceramide synthase 2 exacerbates dextran sodium sulphate-induced colitis in mice due to increased intestinal permeability.

PubMed

Kim, Ye-Ryung; Volpert, Giora; Shin, Kyong-Oh; Kim, So-Yeon; Shin, Sun-Hye; Lee, Younghay; Sung, Sun Hee; Lee, Yong-Moon; Ahn, Jung-Hyuck; Pewzner-Jung, Yael; Park, Woo-Jae; Futerman, Anthony H; Park, Joo-Won

2017-12-01

Ceramides mediate crucial cellular processes including cell death and inflammation and have recently been implicated in inflammatory bowel disease. Ceramides consist of a sphingoid long-chain base to which fatty acids of various length can be attached. We now investigate the effect of alerting the ceramide acyl chain length on a mouse model of colitis. Ceramide synthase (CerS) 2 null mice, which lack very-long acyl chain ceramides with concomitant increase of long chain bases and C16-ceramides, were more susceptible to dextran sodium sulphate-induced colitis, and their survival rate was markedly decreased compared with that of wild-type littermates. Using mixed bone-marrow chimeric mice, we showed that the host environment is primarily responsible for intestinal barrier dysfunction and increased intestinal permeability. In the colon of CerS2 null mice, the expression of junctional adhesion molecule-A was markedly decreased and the phosphorylation of myosin light chain 2 was increased. In vitro experiments using Caco-2 cells also confirmed an important role of CerS2 in maintaining epithelial barrier function; CerS2-knockdown via CRISPR-Cas9 technology impaired barrier function. In vivo myriocin administration, which normalized long-chain bases and C16-ceramides of the colon of CerS2 null mice, increased intestinal permeability as measured by serum FITC-dextran levels, indicating that altered SLs including deficiency of very-long-chain ceramides are critical for epithelial barrier function. In conclusion, deficiency of CerS2 influences intestinal barrier function and the severity of experimental colitis and may represent a potential mechanism for inflammatory bowel disease pathogenesis. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Canagliflozin Lowers Postprandial Glucose and Insulin by Delaying Intestinal Glucose Absorption in Addition to Increasing Urinary Glucose Excretion

PubMed Central

Polidori, David; Sha, Sue; Mudaliar, Sunder; Ciaraldi, Theodore P.; Ghosh, Atalanta; Vaccaro, Nicole; Farrell, Kristin; Rothenberg, Paul; Henry, Robert R.

2013-01-01

OBJECTIVE Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor, is also a low-potency SGLT1 inhibitor. This study tested the hypothesis that intestinal canagliflozin levels postdose are sufficiently high to transiently inhibit intestinal SGLT1, thereby delaying intestinal glucose absorption. RESEARCH DESIGN AND METHODS This two-period, crossover study evaluated effects of canagliflozin on intestinal glucose absorption in 20 healthy subjects using a dual-tracer method. Placebo or canagliflozin 300 mg was given 20 min before a 600-kcal mixed-meal tolerance test. Plasma glucose, 3H-glucose, 14C-glucose, and insulin were measured frequently for 6 h to calculate rates of appearance of oral glucose (RaO) in plasma, endogenous glucose production, and glucose disposal. RESULTS Compared with placebo, canagliflozin treatment reduced postprandial plasma glucose and insulin excursions (incremental 0- to 2-h area under the curve [AUC0–2h] reductions of 35% and 43%, respectively; P < 0.001 for both), increased 0- to 6-h urinary glucose excretion (UGE0–6h, 18.2 ± 5.6 vs. <0.2 g; P < 0.001), and delayed RaO. Canagliflozin reduced AUC RaO by 31% over 0 to 1 h (geometric means, 264 vs. 381 mg/kg; P < 0.001) and by 20% over 0 to 2 h (576 vs. 723 mg/kg; P = 0.002). Over 2 to 6 h, canagliflozin increased RaO such that total AUC RaO over 0 to 6 h was <6% lower versus placebo (960 vs. 1,018 mg/kg; P = 0.003). A modest (∼10%) reduction in acetaminophen absorption was observed over the first 2 h, but this difference was not sufficient to explain the reduction in RaO. Total glucose disposal over 0 to 6 h was similar across groups. CONCLUSIONS Canagliflozin reduces postprandial plasma glucose and insulin by increasing UGE (via renal SGLT2 inhibition) and delaying RaO, likely due to intestinal SGLT1 inhibition. PMID:23412078

MRP2 mediated drug-drug interaction: indomethacin increases sulfasalazine absorption in the small intestine, potentially decreasing its colonic targeting.

PubMed

Dahan, Arik; Amidon, Gordon L

2010-02-15

We have recently shown that efflux transport, mediated by multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP), is responsible for sulfasalazine low-permeability in the small intestine, thereby enabling its colonic targeting and therapeutic action. The purpose of the present study was to evaluate the potential pharmacokinetic interaction between indomethacin and sulfasalazine, in the mechanism of efflux transporter competition. The concentration-dependent effects of indomethacin on sulfasalazine intestinal epithelial transport were investigated across Caco-2 cell monolayers, in both apical to basolateral (AP-BL) and BL-AP directions. The interaction was then investigated in the in situ single-pass rat jejunal perfusion model. Sulfasalazine displayed 30-fold higher BL-AP than AP-BL Caco-2 permeability, indicative of net mucosal secretion. Indomethacin significantly increased AP-BL and decreased BL-AP sulfasalazine Caco-2 transport, in a concentration-dependent manner, with IC(50) values of 75 and 196 microM respectively. In the rat model, higher sulfasalazine concentrations resulted in higher intestinal permeability, consistent with saturation of efflux transporter. Without indomethacin, sulfasalazine demonstrated low rat jejunal permeability (vs. metoprolol). Indomethacin significantly increased sulfasalazine P(eff), effectively shifting it from BCS (biopharmaceutics classification system) Class IV to II. In conclusion, the data indicate that concomitant intake of indomethacin and sulfasalazine may lead to increased absorption of sulfasalazine in the small intestine, thereby reducing its colonic concentration and potentially altering its therapeutic effect. Copyright 2009 Elsevier B.V. All rights reserved.

Impaired Compensation for Salt-Induced Urinary Calcium Loss in a Space Flight Model

NASA Technical Reports Server (NTRS)

Navidi, Meena; Harper, J. S.; Evans, J.; Fung, P.; Wolinsky, I.; Arnaud, S. B.; Wade, Charles E. (Technical Monitor)

1994-01-01

The loss of urinary calcium (UCa) induced by high sodium (HiNa) diets is compensated for by an increase in net intestinal Ca absorption (abs.). To determine the capacity of the intestine to absorb Ca in a space flight model in which the formation of 1,25-dihydroxyvitamin D (1,25-D) is suppressed, we induced Ca loss with HiNa diets (8%) and restricted dietary Ca (0.2%). In 200 g rats with hind limbs unloaded by tail suspension (S), we examined intestinal Ca abs. by direct measurement in the duodenum (everted gut sac or S/M), vitamin D receptors (VDR) and Ca balance. We also measured serum ionized calcium (ICa), pH, parathyroid hormone (PTH) and 1,25D. PTH was related to ICa (r = -0.44, p is less than 0.02), pH (r = -0.47, p is less than 0.02) and %Ca abs. (r = -0.40, p is less than 0.05). 1,25-D was related to %Ca abs. (r = 0.60, p is less than 0.001) but not VDR or S/M. Effects of the model were lower serum 1,25-D (110 +/- 59 vs. 199 +/- 80 pg/ml, p is less than 0.005), %Ca abs. (83 +/- 6.9 vs. 93 +/- 3.2, p is less than 0.03) and Ca balance (27 +/- 0.2 vs. 30 +/- 0.3 mg/d, p is less than 0.001) in S than controls (C). The HiNa diet increased UCa excretion from 2 to 13% of dietary Ca. Responses to HiNa diets, compared to normal Na, revealed no differences in 1,25-D, Ca abs. or VDR. Ca balances were lower in HiNa (27 +/- 0.3 vs. 30 +/- 0.4 mg/d, p is less than 0.001) in spite of higher Ca intakes. The failure of S rats fed HiNa diets to increase Ca abs. in response to Na-induced Ca loss appears to be related to suppressed 1,25-D in the space flight model, the cause of which remains obscure.

Frequency of Celiac Disease in Patients With Increased Intestinal Gas (Flatulence).

PubMed

Masoodi, Mohsen; Mokhtare, Marjan; Agah, Shahram; Sina, Mohammad; Soltani-Kermanshahi, Mojtaba

2015-10-26

Excessive flatulence which impairs social performance in patients is one of the common reasons for referrals to gastroenterology clinics. Celiac Disease is a rare but important cause of increased intestinal gas (bloating) and if not diagnosed, patients face complications such as malabsorption, anemia, osteoporosis and even intestinal lymphoma. This study aimed to determine the frequency of Celiac Disease in patients with excessive flatulence.One hundred and fifty patients with a chief complaint of experiencing flatulence more than 15 times a day and lasting for three months were referred to the gastroenterology clinic of Rasoul-e-Akram Teaching Hospital. Serological tests for Celiac Disease, Anti TTG Ab (IgA-IgG) were requested and the patients with positive tests underwent upper GI endoscopy. Biopsies of the second part of the duodenum were then sent to the laboratory.From one hundred and thirty patients who completed the study, 92 (70.7%) were female. Mean age of the patients was 32 ± 13 years. Anti TTG Ab was found in 5 patients (3.85%). Only 2 patients (1.5%) had a documented positive pathology for Celiac Disease.According to the results of this study and other studies, we conclude that Celiac Disease is an uncommon etiology for excessive flatulence but it is of importance to investigate it in excessive flatulence patients.

Frequency of Celiac Disease in Patients with Increased Intestinal Gas (Flatulence)

PubMed Central

Masoodi, Mohsen; Mokhtare, Marjan; Agah, Shahram; Sina, Mohammad; Soltani-Kermanshahi, Mojtaba

2016-01-01

Excessive flatulence which impairs social performance in patients is one of the common reasons for referrals to gastroenterology clinics. Celiac Disease is a rare but important cause of increased intestinal gas (bloating) and if not diagnosed, patients face complications such as malabsorption, anemia, osteoporosis and even intestinal lymphoma. This study aimed to determine the frequency of Celiac Disease in patients with excessive flatulence. One hundred and fifty patients with a chief complaint of experiencing flatulence more than 15 times a day and lasting for three months were referred to the gastroenterology clinic of Rasoul-e-Akram Teaching Hospital. Serological tests for Celiac Disease, Anti TTG Ab (IgA-IgG) were requested and the patients with positive tests underwent upper GI endoscopy. Biopsies of the second part of the duodenum were then sent to the laboratory. From one hundred and thirty patients who completed the study, 92 (70.7%) were female. Mean age of the patients was 32 ± 13 years. Anti TTG Ab was found in 5 patients (3.85%). Only 2 patients (1.5%) had a documented positive pathology for Celiac Disease. According to the results of this study and other studies, we conclude that Celiac Disease is an uncommon etiology for excessive flatulence but it is of importance to investigate it in excessive flatulence patients. PMID:26755470

The common inhaled anesthetic isoflurane increases aggregation of huntingtin and alters calcium homeostasis in a cell model of Huntington's disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Qiujun; Department of Anesthesiology, The Third Clinical Hospital, Hebei Medical University, Shijiazhuang, Hebei 050051; Liang Ge

2011-02-01

Isoflurane is known to increase {beta}-amyloid aggregation and neuronal damage. We hypothesized that isoflurane will have similar effects on the polyglutamine huntingtin protein and will cause alterations in intracellular calcium homeostasis. We tested this hypothesis in striatal cells from the expanded glutamine huntingtin knock-in mouse (STHdh{sup Q111/Q111}) and wild type (STHdh{sup Q7/Q7}) striatal neurons. The primary cultured neurons were exposed for 24 h to equipotent concentrations of isoflurane, sevoflurane, and desflurane in the presence or absence of extracellular calcium and with or without xestospongin C, a potent endoplasmic reticulum inositol 1,4,5-trisphosphate (InsP{sub 3}) receptor antagonist. Aggregation of huntingtin protein, cellmore » viability, and calcium concentrations were measured. Isoflurane, sevoflurane, and desflurane all increased the aggregation of huntingtin in STHdh{sup Q111/Q111} cells, with isoflurane having the largest effect. Isoflurane induced greater calcium release from the ER and relatively more cell damage in the STHdh{sup Q111/Q111} huntingtin cells than in the wild type STHdh{sup Q7/Q7} striatal cells. However, sevoflurane and desflurane caused less calcium release from the ER and less cell damage. Xestospongin C inhibited the isoflurane-induced calcium release from the ER, aggregation of huntingtin, and cell damage in the STHdh{sup Q111/Q111} cells. In summary, the Q111 form of huntingtin increases the vulnerability of striatal neurons to isoflurane neurotoxicity through combined actions on the ER IP{sub 3} receptors. Calcium release from the ER contributes to the anesthetic induced huntingtin aggregation in STHdh{sup Q111/Q111} striatal cells.« less

Roux-en-Y Gastric Bypass Surgery Suppresses Hepatic Gluconeogenesis and Increases Intestinal Gluconeogenesis in a T2DM Rat Model.

PubMed

Yan, Yong; Zhou, Zhou; Kong, Fanzhi; Feng, Suibin; Li, Xuzhong; Sha, Yanhua; Zhang, Guangjun; Liu, Haijun; Zhang, Haiqing; Wang, Shiguang; Hu, Cheng; Zhang, Xueli

2016-11-01

Roux-en-Y gastric bypass (RYGB) is an effective surgical treatment for type 2 diabetes mellitus (T2DM). The present study aimed to investigate the effects of RYGB on glucose homeostasis, lipid metabolism, and intestinal morphological adaption, as well as hepatic and intestinal gluconeogenesis. Twenty adult male T2DM rats induced by high-fat diet and low dose of streptozotocin were randomly divided into sham and RYGB groups. The parameters of body weight, food intake, glucose tolerance, insulin sensitivity, and serum lipid profiles were assessed to evaluate metabolic changes. Intestinal sections were stained with hematoxylin and eosin (H&E) for light microscopy examination. The messenger RNA (mRNA) and protein expression levels of key regulatory enzymes of gluconeogenesis [phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase)] were determined through reverse-transcription PCR (RT-PCR) and Western blotting, respectively. RYGB induced significant improvements in glucose tolerance and insulin sensitivity, along with weight loss and decreased food intake. RYGB also decreased serum triglyceride (TG) and free fatty acid (FFA) levels. The jejunum and ileum exhibited a marked increase in the length and number of intestinal villi after RYGB. The RYGB group exhibited downregulated mRNA and protein expression levels of PEPCK and G6Pase in the liver and upregulated expression of these enzymes in the jejunum and ileum tissues. RYGB ameliorates glucose and lipid metabolism accompanied by weight loss and calorie restriction. The small intestine shows hyperplasia and hypertrophy after RYGB. Meanwhile, our study demonstrated that the reduced hepatic gluconeogenesis and increased intestinal gluconeogenesis may contribute to improved glucose homeostasis after RYGB.

Phenolic compounds increase the transcription of mouse intestinal maltase-glucoamylase and sucrase-isomaltase.

PubMed

Simsek, Meric; Quezada-Calvillo, Roberto; Nichols, Buford L; Hamaker, Bruce R

2017-05-24

Diverse natural phenolic compounds show inhibition activity of intestinal α-glucosidases, which may constitute the molecular basis for their ability to control systemic glycemia. Additionally, phenolics can modify mRNA expression for proteins involved in nutritional, metabolic or immune processes. To explore the possibility that phenolics can regulate the mRNA expression, enzymatic activity, and protein synthesis/processing of intestinal Maltase-Glucoamylase (MGAM) and Sucrase-Isomaltase (SI), small intestinal explants from Balb/c mice were cultured for 24 h in the presence or absence of gallic acid, caffeic acid, and (+)-catechin at 0.1, 0.5, and 1 mM. We measured the levels of MGAM and SI mRNA expression by qRT-PCR, maltase and sucrase activities by a standard colorimetric method and the molecular size distribution of MGAM and SI proteins by western blotting. mRNA expression for MGAM was induced by the three phenolic compounds at 0.1 mM. mRNA expression for SI was induced by caffeic and gallic acids, but not by (+)-catechin. Caffeic acid was the most effective inducer of mRNA expression of these enzymes. Total maltase and sucrase activities were not affected by treatment with phenolics. The proportion of high molecular size forms of MGAM was significantly increased by two of the three phenolic compounds, but little effect was observed on SI proteins. Thus, changes in the protein synthesis/processing, affecting the proportions of the different molecular forms of MGAM, may account for the lack of correlation between mRNA expression and enzymatic activity.

Intestinal lymphangiectasia in adults.

PubMed

Freeman, Hugh James; Nimmo, Michael

2011-02-15

Intestinal lymphangiectasia in the adult may be characterized as a disorder with dilated intestinal lacteals causing loss of lymph into the lumen of the small intestine and resultant hypoproteinemia, hypogammaglobulinemia, hypoalbuminemia and reduced number of circulating lymphocytes or lymphopenia. Most often, intestinal lymphangiectasia has been recorded in children, often in neonates, usually with other congenital abnormalities but initial definition in adults including the elderly has become increasingly more common. Shared clinical features with the pediatric population such as bilateral lower limb edema, sometimes with lymphedema, pleural effusion and chylous ascites may occur but these reflect the severe end of the clinical spectrum. In some, diarrhea occurs with steatorrhea along with increased fecal loss of protein, reflected in increased fecal alpha-1-antitrypsin levels, while others may present with iron deficiency anemia, sometimes associated with occult small intestinal bleeding. Most lymphangiectasia in adults detected in recent years, however, appears to have few or no clinical features of malabsorption. Diagnosis remains dependent on endoscopic changes confirmed by small bowel biopsy showing histological evidence of intestinal lymphangiectasia. In some, video capsule endoscopy and enteroscopy have revealed more extensive changes along the length of the small intestine. A critical diagnostic element in adults with lymphangiectasia is the exclusion of entities (e.g. malignancies including lymphoma) that might lead to obstruction of the lymphatic system and "secondary" changes in the small bowel biopsy. In addition, occult infectious (e.g. Whipple's disease from Tropheryma whipplei) or inflammatory disorders (e.g. Crohn's disease) may also present with profound changes in intestinal permeability and protein-losing enteropathy that also require exclusion. Conversely, rare B-cell type lymphomas have also been described even decades following initial

Intestinal lymphangiectasia in adults

PubMed Central

Freeman, Hugh James; Nimmo, Michael

2011-01-01

Intestinal lymphangiectasia in the adult may be characterized as a disorder with dilated intestinal lacteals causing loss of lymph into the lumen of the small intestine and resultant hypoproteinemia, hypogammaglobulinemia, hypoalbuminemia and reduced number of circulating lymphocytes or lymphopenia. Most often, intestinal lymphangiectasia has been recorded in children, often in neonates, usually with other congenital abnormalities but initial definition in adults including the elderly has become increasingly more common. Shared clinical features with the pediatric population such as bilateral lower limb edema, sometimes with lymphedema, pleural effusion and chylous ascites may occur but these reflect the severe end of the clinical spectrum. In some, diarrhea occurs with steatorrhea along with increased fecal loss of protein, reflected in increased fecal alpha-1-antitrypsin levels, while others may present with iron deficiency anemia, sometimes associated with occult small intestinal bleeding. Most lymphangiectasia in adults detected in recent years, however, appears to have few or no clinical features of malabsorption. Diagnosis remains dependent on endoscopic changes confirmed by small bowel biopsy showing histological evidence of intestinal lymphangiectasia. In some, video capsule endoscopy and enteroscopy have revealed more extensive changes along the length of the small intestine. A critical diagnostic element in adults with lymphangiectasia is the exclusion of entities (e.g. malignancies including lymphoma) that might lead to obstruction of the lymphatic system and “secondary” changes in the small bowel biopsy. In addition, occult infectious (e.g. Whipple’s disease from Tropheryma whipplei) or inflammatory disorders (e.g. Crohn’s disease) may also present with profound changes in intestinal permeability and protein-losing enteropathy that also require exclusion. Conversely, rare B-cell type lymphomas have also been described even decades following

A pharmacologic increase in activity of plasma transaminase derived from small intestine in animals receiving an acyl CoA: diacylglycerol transferase (DGAT) 1 inhibitor.

PubMed

Yokoyama, Hideaki; Kobayashi, Akio; Kondo, Kazuma; Oshida, Shin-Ichi; Takahashi, Tadakazu; Masuyama, Taku; Shoda, Toshiyuki; Sugai, Shoichiro

2018-01-01

Acyl CoA: diacylglycerol acyltransferase (DGAT) 1 is an enzyme that catalyzes the re-synthesis of triglycerides (TG) from free fatty acids and diacylglycerol. JTT-553 is a DGAT1 inhibitor and exhibits its pharmacological action (inhibition of re-synthesis of TG) in the enterocytes of the small intestine leading to suppression of a postprandial elevation of plasma lipids. After repeated oral dosing JTT-553 in rats and monkeys, plasma transaminase levels were increased but there were neither changes in other hepatic function parameters nor histopathological findings suggestive of hepatotoxicity. Based on the results of exploratory studies for investigation of the mechanism of the increase in transaminase levels, plasma transaminase levels were increased after dosing JTT-553 only when animals were fed after dosing and a main factor in the diet contributing to the increase in plasma transaminase levels was lipids. After dosing JTT-553, transaminase levels were increased in the small intestine but not in the liver, indicating that the origin of transaminase increased in the plasma was not the liver but the small intestine where JTT-553 exhibits its pharmacological action. The increase in small intestinal transaminase levels was due to increased enzyme protein synthesis and was suppressed by inhibiting fatty acid-transport to the enterocytes. In conclusion, the JTT-553-related increase in plasma transaminase levels is considered not to be due to release of the enzymes from injured cells into the circulation but to be phenomena resulting from enhancement of enzyme protein synthesis in the small intestine due to the pharmacological action of JTT-553 in this organ.

Synergistic Effect of Transient Receptor Potential Antagonist and Amiloride against Maitotoxin Induced Calcium Increase and Cytotoxicity in Human Neuronal Stem Cells.

PubMed

Boente-Juncal, Andrea; Vale, Carmen; Alfonso, Amparo; Botana, Luis M

2018-05-16

Maitotoxins (MTX) are among the most potent marine toxins identified to date causing cell death trough massive calcium influx. However, the exact mechanism for the MTX-induced calcium entry and cytotoxicity is still unknown. In this work, the effect of MTX-1 on the cytosolic free calcium concentration and cellular viability of human neuronal stem cells was evaluated. MTX elicited a concentration-dependent decrease in cell viability which was already evident after 1 h of treatment with 0.25 nM MTX; however, at a concentration of 0.1 nM, the toxin did not cause cell death even after 14 days of exposure. Moreover, the toxin caused a concentration dependent rise in the cytosolic calcium concentration which was maximal at toxin concentrations of 1 nM and dependent on the presence of extracellular calcium on the bathing solution. Several pharmacological approaches were employed to evaluate the role of canonical transient potential receptor channels (TRPC) on the MTX effects. The results presented here lead to the identification of the TRPC4 channels as contributors to the MTX effects in human neuronal cells. Both, the calcium increase and the cytotoxicity of MTX were either fully (for the calcium increase) or partially (in the case of cytotoxicity) reverted by the blockade of canonical TRPC4 receptors with the selective antagonist ML204. Furthermore, the sodium proton exchanger blocker amiloride also partially inhibited the calcium rise and the cell death elicited by MTX while the combination of amiloride and ML204 fully prevented both the cytotoxicity and the calcium rise elicited by the toxin.

Calcium Balance in Mature Rats Exposed to a Space Flight Model

NASA Technical Reports Server (NTRS)

Navidi, Meena; Evans, J.; Looft-Wilson, R.; Wolinsky, I.; Arnaud, S. B.; Hargens, Alan R. (Technical Monitor)

1996-01-01

Depressed intestinal calcium absorption (Ca abs.) and lower circulating 1,25-dihydroxyvitamin D (1,25-D) are associated with less positive calcium balance in young 200 g rats exposed to skeletal unloading by hind-limb suspension than controls (C) . To determine the effect of the space flight model on calcium balance in mature rats, we exposed 6 mo. old males weighing 492 +/- 12g to the model for 4 weeks (S) and compared Ca in the diet, urine, feces and 1,25-D in S and C. Rats were fed diets containing sufficient Ca to satisfy metabolic needs, but not to cause deficiency (0.1%). At the end of 4 weeks, there was a 5 percent weight loss in S, but not in C; and no differences in dietary, urine (UCa) or fecal Ca (FCa) in S and C. Net Ca abs. (0.1 vs 2.7 %), 1,25-D (50 +/- 16 vs 47 +/- 14 pg/ml) and Ca balances (-1.8 +/- 4 vs -1.0 +/- 2.9 mg/d) were similar in C and S. UCa loss was added to the model by inducing calciuria with 8% salt diets (HiNa). A 4-fold increase in UCa in C and S was transiently higher in S than C after 1 week. After 4 weeks, loss in BW was greater in S than C, Ca abs was higher in C than S (32 +/- 10 vs 3.5 +/- 16%, p less than .05), 1,25-D greater in S than C (98 +/- 15 vs 79 +/- 14 pg/ml p less than .05) and Ca balance less in S than C (-5.2 +/- 4 vs -1.7 +/- 2 mg/d, p less than .05). Ca balance in the mature rat is unaffected by the space flight model unless calciuria intervenes and reveals the failure of the intestine to enhance Ca abs. and compensate for UCa loss.

Identification of potent, nonabsorbable agonists of the calcium-sensing receptor for GI-specific administration.

PubMed

Sparks, Steven M; Spearing, Paul K; Diaz, Caroline J; Cowan, David J; Jayawickreme, Channa; Chen, Grace; Rimele, Thomas J; Generaux, Claudia; Harston, Lindsey T; Roller, Shane G

2017-10-15

Modulation of gastrointestinal nutrient sensing pathways provides a promising a new approach for the treatment of metabolic diseases including diabetes and obesity. The calcium-sensing receptor has been identified as a key receptor involved in mineral and amino acid nutrient sensing and thus is an attractive target for modulation in the intestine. Herein we describe the optimization of gastrointestinally restricted calcium-sensing receptor agonists starting from a 3-aminopyrrolidine-containing template leading to the identification of GI-restricted agonist 19 (GSK3004774). Copyright © 2017 Elsevier Ltd. All rights reserved.

Experience-dependent increase in spine calcium evoked by backpropagating action potentials in layer 2/3 pyramidal neurons in rat somatosensory cortex.

PubMed

Krieger, Patrik

2009-11-01

In spines on basal dendrites of layer 2/3 pyramidal neurons in somatosensory barrel cortex, calcium transients evoked by back-propagating action potentials (bAPs) were investigated (i) along the length of the basal dendrite, (ii) with postnatal development and (iii) with sensory deprivation during postnatal development. Layer 2/3 pyramidal neurons were investigated at three different ages. At all ages [postnatal day (P)8, P14, P21] the bAP-evoked calcium transient amplitude increased with distance from the soma with a peak at around 50 microm, followed by a gradual decline in amplitude. The effect of sensory deprivation on the bAP-evoked calcium was investigated using two different protocols. When all whiskers on one side of the rat snout were trimmed daily from P8 to P20-24 there was no difference in the bAP-evoked calcium transient between cells in the contralateral hemisphere, lacking sensory input from the whisker, and cells in the ipsilateral barrel cortex, with intact whisker activation. When, however, only the D-row whiskers on one side were trimmed the distribution of bAP-evoked calcium transients in spines was shifted towards larger amplitudes in cells located in the deprived D-column. In conclusion, (i) the bAP-evoked calcium transient gradient along the dendrite length is established at P8, (ii) the calcium transient increases in amplitude with age and (iii) this increase is enhanced in layer 2/3 pyramidal neurons located in a sensory-deprived barrel column that is bordered by non-deprived barrel columns.

Effects of dietary carbohydrates on metabolism of calcium and other minerals in normal subjects and patients with noninsulin-dependent diabetes mellitus.

PubMed

Garg, A; Bonanome, A; Grundy, S M; Unger, R H; Breslau, N A; Pak, C Y

1990-04-01

Transient hypercalciuria has been noted after high carbohydrate meals which is independent of dietary calcium and is probably due to impaired renal calcium reabsorption mediated by an increase in plasma insulin levels. Based on these observations, some investigators believe that long term intake of high carbohydrate diets may increase the risk of nephrolithiasis and possibly osteoporosis. Using a randomized cross-over design, we compared high carbohydrate diets (60% carbohydrate and 25% fat) with high fat diets (50% fat and 35% carbohydrate) for effects on metabolism of calcium and other minerals in eight normal subjects and eight euglycemic patients with noninsulin-dependent diabetes mellitus. All other dietary constituents, such as protein, fiber, fluid, minerals (including Ca, Mg, Na, K, and P), and caffeine intake, were kept constant. Despite higher daylong levels of plasma insulin on the high carbohydrate diets compared to the high fat diet in both normal and noninsulin-dependent diabetic subjects, no changes in daily urinary excretion of calcium or other constituents, associated with renal stone risk, were observed. Furthermore, there was no change in fractional intestinal 47Ca absorption. Although hypercalciuria may ensue transiently after high carbohydrate meals, we conclude that substitution of simple or complex carbohydrates for fats in an isocaloric manner for a longer duration does not result in significant urinary calcium loss, and therefore, high intakes of digestible carbohydrates may not increase the risk of nephrolithiasis or osteoporosis via this mechanism.

The regulation of K- and L-cell activity by GLUT2 and the calcium-sensing receptor CasR in rat small intestine

PubMed Central

Mace, Oliver J; Schindler, Marcus; Patel, Sonal

2012-01-01

Intestinal enteroendocrine cells (IECs) secrete gut peptides in response to both nutrients and non-nutrients. Glucose and amino acids both stimulate gut peptide secretion. Our hypothesis was that the facilitative glucose transporter, GLUT2, could act as a glucose sensor and the calcium-sensing receptor, CasR, could detect amino acids in the intestine to modify gut peptide secretion. We used isolated loops of rat small intestine to study the secretion of gluco-insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) secretion stimulated by luminal perfusion of nutrients or bile acid. Inhibition of the sodium-dependent glucose cotransporter 1 (SGLT1) with phloridzin partially inhibited GIP, GLP-1 and PYY secretion by 45%, suggesting another glucose sensor might be involved in modulating peptide secretion. The response was completely abolished in the presence of the GLUT2 inhibitors phloretin or cytochalasin B. Given that GLUT2 modified gut peptide secretion stimulated by glucose, we investigated whether it was involved in the secretion of gut peptide by other gut peptide secretagogues. Phloretin completely abolished gut peptide secretion stimulated by artificial sweetener (sucralose), dipeptide (glycylsarcosine), lipid (oleoylethanolamine), short chain fatty acid (propionate) and major rat bile acid (taurocholate) indicating a fundamental position for GLUT2 in the gut peptide secretory mechanism. We investigated how GLUT2 was able to influence gut peptide secretion mediated by a diverse range of stimulators and discovered that GLUT2 affected membrane depolarisation through the closure of K+ATP-sensitive channels. In the absence of SGLT1 activity (or presence of phloridzin), the secretion of GIP, GLP-1 and PYY was sensitive to K+ATP-sensitive channel modulators tolbutamide and diazoxide. l-Amino acids phenylalanine (Phe), tryptophan (Trp), asparagine (Asn), arginine (Arg) and glutamine (Gln) also stimulated GIP, GLP-1 and PYY

Two weeks of moderate-intensity continuous training, but not high-intensity interval training, increases insulin-stimulated intestinal glucose uptake

PubMed Central

Savolainen, Anna M.; Eskelinen, Jari-Joonas; Toivanen, Jussi; Ishizu, Tamiko; Yli-Karjanmaa, Minna; Virtanen, Kirsi A.; Parkkola, Riitta; Kapanen, Jukka; Grönroos, Tove J.; Haaparanta-Solin, Merja; Solin, Olof; Savisto, Nina; Ahotupa, Markku; Löyttyniemi, Eliisa; Knuuti, Juhani; Nuutila, Pirjo; Kalliokoski, Kari K.

2017-01-01

Similar to muscles, the intestine is also insulin resistant in obese subjects and subjects with impaired glucose tolerance. Exercise training improves muscle insulin sensitivity, but its effects on intestinal metabolism are not known. We studied the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on intestinal glucose and free fatty acid uptake from circulation in humans. Twenty-eight healthy, middle-aged, sedentary men were randomized for 2 wk of HIIT or MICT. Intestinal insulin-stimulated glucose uptake and fasting free fatty acid uptake from circulation were measured using positron emission tomography and [18F]FDG and [18F]FTHA. In addition, effects of HIIT and MICT on intestinal GLUT2 and CD36 protein expression were studied in rats. Training improved aerobic capacity (P = 0.001) and whole body insulin sensitivity (P = 0.04), but not differently between HIIT and MICT. Insulin-stimulated glucose uptake increased only after the MICT in the colon (HIIT = 0%; MICT = 37%) (P = 0.02 for time × training) and tended to increase in the jejunum (HIIT = −4%; MICT = 13%) (P = 0.08 for time × training). Fasting free fatty acid uptake decreased in the duodenum in both groups (HIIT = −6%; MICT = −48%) (P = 0.001 time) and tended to decrease in the colon in the MICT group (HIIT = 0%; MICT = −38%) (P = 0.08 for time × training). In rats, both training groups had higher GLUT2 and CD36 expression compared with control animals. This study shows that already 2 wk of MICT enhances insulin-stimulated glucose uptake, while both training modes reduce fasting free fatty acid uptake in the intestine in healthy, middle-aged men, providing an additional mechanism by which exercise training can improve whole body metabolism. NEW & NOTEWORTHY This is the first study where the effects of exercise training on the intestinal substrate uptake have been investigated using the most advanced techniques

Magnesium supplementation through seaweed calcium extract rather than synthetic magnesium oxide improves femur bone mineral density and strength in ovariectomized rats.

PubMed

Bae, Yun Jung; Bu, So Young; Kim, Jae Young; Yeon, Jee-Young; Sohn, Eun-Wha; Jang, Ki-Hyo; Lee, Jae-Cheol; Kim, Mi-Hyun

2011-12-01

Commercially available seaweed calcium extract can supply high amounts of calcium as well as significant amounts of magnesium and other microminerals. The purpose of this study was to investigate the degree to which the high levels of magnesium in seaweed calcium extract affects the calcium balance and the bone status in ovariectomized rats in comparison to rats supplemented with calcium carbonate and magnesium oxide. A total of 40 Sprague-Dawley female rats (7 weeks) were divided into four groups and bred for 12 weeks: sham-operated group (Sham), ovariectomized group (OVX), ovariectomized with inorganic calcium and magnesium supplementation group (OVX-Mg), and ovariectomized with seaweed calcium and magnesium supplementation group (OVX-SCa). All experimental diets contained 0.5% calcium. The magnesium content in the experimental diet was 0.05% of the diet in the Sham and OVX groups and 0.1% of the diet in the OVX-Mg and OVX-SCa groups. In the calcium balance study, the OVX-Mg and OVX-SCa groups were not significantly different in calcium absorption compared to the OVX group. However, the femoral bone mineral density and strength of the OVX-SCa group were higher than those of the OVX-Mg and OVX groups. Seaweed calcium with magnesium supplementation or magnesium supplementation alone did not affect the serum ALP and CTx levels in ovariectomized rats. In summary, consumption of seaweed calcium extract or inorganic calcium carbonate with magnesium oxide demonstrated the same degree of intestinal calcium absorption, but only the consumption of seaweed calcium extract resulted in increased femoral bone mineral density and strength in ovariectomized rats. Our results suggest that seaweed calcium extract is an effective calcium and magnesium source for improving bone health compared to synthetic calcium and magnesium supplementation.

Endocrine causes of calcium disorders.

PubMed

Greco, Deborah S

2012-11-01

Endocrine diseases that may cause hypercalcemia and hypocalcemia include hyperparathyroidism, hypoparathyroidism, thyroid disorders, hyperadrenocorticism, hypoadrenocorticism, and less commonly pheochromocytoma and multiple endocrine neoplasias. The differential diagnosis of hypercalcemia may include malignancy (lymphoma, anal sac carcinoma, and squamous cell carcinoma), hyperparathyroidism, vitamin D intoxication, chronic renal disease, hypoadrenocorticism, granulomatous disorders, osteolysis, or spurious causes. Hypocalcemia may be caused by puerperal tetany, pancreatitis, intestinal malabsorption, ethlyene glycol intoxication, acute renal failure, hypopararthyroidism, hypovitaminosis D, hypomagnesemia, and low albumin. This article focuses on the endocrine causes of calcium imbalance and provides diagnostic and therapeutic guidelines for identifying the cause of hypercalcemia and hypocalcemia in veterinary patients. Copyright © 2012 Elsevier Inc. All rights reserved.

Adult zebrafish intestine resection: a novel model of short bowel syndrome, adaptation, and intestinal stem cell regeneration.

PubMed

Schall, K A; Holoyda, K A; Grant, C N; Levin, D E; Torres, E R; Maxwell, A; Pollack, H A; Moats, R A; Frey, M R; Darehzereshki, A; Al Alam, D; Lien, C; Grikscheit, T C

2015-08-01

Loss of significant intestinal length from congenital anomaly or disease may lead to short bowel syndrome (SBS); intestinal failure may be partially offset by a gain in epithelial surface area, termed adaptation. Current in vivo models of SBS are costly and technically challenging. Operative times and survival rates have slowed extension to transgenic models. We created a new reproducible in vivo model of SBS in zebrafish, a tractable vertebrate model, to facilitate investigation of the mechanisms of intestinal adaptation. Proximal intestinal diversion at segment 1 (S1, equivalent to jejunum) was performed in adult male zebrafish. SBS fish emptied distal intestinal contents via stoma as in the human disease. After 2 wk, S1 was dilated compared with controls and villus ridges had increased complexity, contributing to greater villus epithelial perimeter. The number of intervillus pockets, the intestinal stem cell zone of the zebrafish increased and contained a higher number of bromodeoxyuridine (BrdU)-labeled cells after 2 wk of SBS. Egf receptor and a subset of its ligands, also drivers of adaptation, were upregulated in SBS fish. Igf has been reported as a driver of intestinal adaptation in other animal models, and SBS fish exposed to a pharmacological inhibitor of the Igf receptor failed to demonstrate signs of intestinal adaptation, such as increased inner epithelial perimeter and BrdU incorporation. We describe a technically feasible model of human SBS in the zebrafish, a faster and less expensive tool to investigate intestinal stem cell plasticity as well as the mechanisms that drive intestinal adaptation. Copyright © 2015 the American Physiological Society.

Adult zebrafish intestine resection: a novel model of short bowel syndrome, adaptation, and intestinal stem cell regeneration

PubMed Central

Schall, K. A.; Holoyda, K. A.; Grant, C. N.; Levin, D. E.; Torres, E. R.; Maxwell, A.; Pollack, H. A.; Moats, R. A.; Frey, M. R.; Darehzereshki, A.; Al Alam, D.; Lien, C.

2015-01-01

Loss of significant intestinal length from congenital anomaly or disease may lead to short bowel syndrome (SBS); intestinal failure may be partially offset by a gain in epithelial surface area, termed adaptation. Current in vivo models of SBS are costly and technically challenging. Operative times and survival rates have slowed extension to transgenic models. We created a new reproducible in vivo model of SBS in zebrafish, a tractable vertebrate model, to facilitate investigation of the mechanisms of intestinal adaptation. Proximal intestinal diversion at segment 1 (S1, equivalent to jejunum) was performed in adult male zebrafish. SBS fish emptied distal intestinal contents via stoma as in the human disease. After 2 wk, S1 was dilated compared with controls and villus ridges had increased complexity, contributing to greater villus epithelial perimeter. The number of intervillus pockets, the intestinal stem cell zone of the zebrafish increased and contained a higher number of bromodeoxyuridine (BrdU)-labeled cells after 2 wk of SBS. Egf receptor and a subset of its ligands, also drivers of adaptation, were upregulated in SBS fish. Igf has been reported as a driver of intestinal adaptation in other animal models, and SBS fish exposed to a pharmacological inhibitor of the Igf receptor failed to demonstrate signs of intestinal adaptation, such as increased inner epithelial perimeter and BrdU incorporation. We describe a technically feasible model of human SBS in the zebrafish, a faster and less expensive tool to investigate intestinal stem cell plasticity as well as the mechanisms that drive intestinal adaptation. PMID:26089336

Sorbitol increases muscle glucose uptake ex vivo and inhibits intestinal glucose absorption ex vivo and in normal and type 2 diabetic rats.

PubMed

Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

2017-04-01

Previous studies have suggested that sorbitol, a known polyol sweetener, possesses glycemic control potentials. However, the effect of sorbitol on intestinal glucose absorption and muscle glucose uptake still remains elusive. The present study investigated the effects of sorbitol on intestinal glucose absorption and muscle glucose uptake as possible anti-hyperglycemic or glycemic control potentials using ex vivo and in vivo experimental models. Sorbitol (2.5% to 20%) inhibited glucose absorption in isolated rat jejuna (IC 50 = 14.6% ± 4.6%) and increased glucose uptake in isolated rat psoas muscle with (GU 50 = 3.5% ± 1.6%) or without insulin (GU 50 = 7.0% ± 0.5%) in a concentration-dependent manner. Furthermore, sorbitol significantly delayed gastric emptying, accelerated digesta transit, inhibited intestinal glucose absorption, and reduced blood glucose increase in both normoglycemic and type 2 diabetic rats after 1 h of coingestion with glucose. Data of this study suggest that sorbitol exhibited anti-hyperglycemic potentials, possibly via increasing muscle glucose uptake ex vivo and reducing intestinal glucose absorption in normal and type 2 diabetic rats. Hence, sorbitol may be further investigated as a possible anti-hyperglycemic sweetener.

Calcium binding to Procambarus clarkii sarcoplasmic calcium binding protein splice variants.

PubMed

Rohrback, Suzanne E; Wheatly, Michele G; Gillen, Christopher M

2015-01-01

Sarcoplasmic calcium binding protein (SCP) is a high-affinity calcium buffering protein expressed in muscle of crayfish and other invertebrates. In previous work, we identified three splice variants of Procambarus clarkii SCP (pcSCP1a, pcSCP1b, and pcSCP1c) that differ in a 37 amino acid region that lies mainly between the 2nd and 3ed EF-hand calcium binding domain. To evaluate the function of the proteins encoded by the pcSCP1 transcripts, we produced recombinant pcSCP1 and used tryptophan fluorescence to characterize calcium binding. Tryptophan fluorescence of pcSCP1a decreased in response to increased calcium, while tryptophan fluorescence of the pcSCP1b and pcSCP1c variants increased. We estimated calcium binding constants and Hill coefficients with two different equations: the standard Hill equation and a modified Hill equation that accounts for contributions from two different tryptophans. The approaches gave similar results. Steady-state calcium binding constants (Kd) ranged from 2.7±0.7×10(-8)M to 5.6±0.1×10(-7)M, consistent with previous work. Variants displayed significantly different apparent calcium affinities, which were decreased in the presence of magnesium. Calcium Kd was lowest for pcSCP1a and highest for pcSCP1c. Site-directed mutagenesis of pcSCP1c residues to the amino acids of pcSCP1b decreased the calcium Kd, identifying residues outside the EF-hand domains that contribute to calcium binding in crayfish SCP. Copyright © 2014 Elsevier Inc. All rights reserved.

Curcuma longa L. as a therapeutic agent in intestinal motility disorders. 2: Safety profile in mouse.

PubMed

Micucci, Matteo; Aldini, Rita; Cevenini, Monica; Colliva, Carolina; Spinozzi, Silvia; Roda, Giulia; Montagnani, Marco; Camborata, Cecilia; Camarda, Luca; Chiarini, Alberto; Mazzella, Giuseppe; Budriesi, Roberta

2013-01-01

Curcuma extract exerts a myorelaxant effect on the mouse intestine. In view of a possible use of curcuma extract in motor functional disorders of the gastrointestinal tract, a safety profile study has been carried out in the mouse. Thirty mice were used to study the in vitro effect of curcuma on gallbladder, bladder, aorta and trachea smooth muscular layers and hearth inotropic and chronotropic activity. The myorelaxant effect on the intestine was also thoroughly investigated. Moreover, curcuma extract (200 mg/Kg/day) was orally administered to twenty mice over 28 days and serum liver and lipids parameters were evaluated. Serum, bile and liver bile acids qualitative and quantitative composition was were also studied. In the intestine, curcuma extract appeared as a not competitive inhibitor through cholinergic, histaminergic and serotoninergic receptors and showed spasmolytic effect on K(+) induced contraction at the level of L type calcium channels. No side effect was observed on bladder, aorta, trachea and heart when we used a dose that is effective on the intestine. An increase in gallbladder tone and contraction was observed. Serum liver and lipids parameters were normal, while a slight increase in serum and liver bile acids concentration and a decrease in bile were observed. Although these data are consistent with the safety of curcuma extract as far as its effect on the smooth muscular layers of different organs and on the heart, the mild cholestatic effect observed in absence of alteration of liver function tests must be further evaluated and the effective dose with minimal side effects considered.

Curcuma longa L. as a Therapeutic Agent in Intestinal Motility Disorders. 2: Safety Profile in Mouse

PubMed Central

Micucci, Matteo; Aldini, Rita; Cevenini, Monica; Colliva, Carolina; Spinozzi, Silvia; Roda, Giulia; Montagnani, Marco; Camborata, Cecilia; Camarda, Luca; Chiarini, Alberto; Mazzella, Giuseppe; Budriesi, Roberta

2013-01-01

Background Curcuma extract exerts a myorelaxant effect on the mouse intestine. In view of a possible use of curcuma extract in motor functional disorders of the gastrointestinal tract, a safety profile study has been carried out in the mouse. Methods Thirty mice were used to study the in vitro effect of curcuma on gallbladder, bladder, aorta and trachea smooth muscular layers and hearth inotropic and chronotropic activity. The myorelaxant effect on the intestine was also thoroughly investigated. Moreover, curcuma extract (200 mg/Kg/day) was orally administered to twenty mice over 28 days and serum liver and lipids parameters were evaluated. Serum, bile and liver bile acids qualitative and quantitative composition was were also studied. Results In the intestine, curcuma extract appeared as a not competitive inhibitor through cholinergic, histaminergic and serotoninergic receptors and showed spasmolytic effect on K+ induced contraction at the level of L type calcium channels. No side effect was observed on bladder, aorta, trachea and heart when we used a dose that is effective on the intestine. An increase in gallbladder tone and contraction was observed. Serum liver and lipids parameters were normal, while a slight increase in serum and liver bile acids concentration and a decrease in bile were observed. Conclusions Although these data are consistent with the safety of curcuma extract as far as its effect on the smooth muscular layers of different organs and on the heart, the mild cholestatic effect observed in absence of alteration of liver function tests must be further evaluated and the effective dose with minimal side effects considered. PMID:24260512

Reduced interstitial cells of Cajal and increased intraepithelial lymphocytes are associated with development of small intestinal bacterial overgrowth in post-infectious IBS mouse model.

PubMed

Chen, Binrui; Zhu, Shuwen; Du, Lijun; He, Huiqin; Kim, John J; Dai, Ning

2017-10-01

Intestinal dysmotility and immune activation are likely involved in the pathogenesis of small intestinal bacteria overgrowth (SIBO) in irritable bowel syndrome (IBS). We aimed at investigating the role of interstitial cells of Cajal (ICC) and intestinal inflammation in the development of SIBO using a post-infectious IBS (PI-IBS) mouse model. NIH mice were randomly infected with Trichinella spiralis. Visceral sensitivity and stool pattern were assessed at 8-weeks post-infection (PI). Intestinal bacteria counts from jejunum and ileum were measured by quantitative real-time PCR to evaluate the presence of SIBO. ICC density, intraepithelial lymphocytes (IELs) counts, and intestinal cytokine levels (IL1-β, IL-6, toll-like receptor-4 (TLR-4), IL-10) in the ileum were examined. PI-IBS mice demonstrated increased visceral sensitivity compared with the control group. One-third of the PI-IBS mice developed SIBO (SIBO+/PI-IBS) and was more likely to have abnormal stool form compared with SIBO negative PI-IBS (SIBO-/PI-IBS) mice but without difference in visceral sensitivity. SIBO+/PI-IBS mice had decreased ICC density and increased IELs counts in the ileum compared with SIBO-/PI-IBS mice. No difference in inflammatory cytokine expression levels were detected among the groups except for increased TLR-4 in PI-IBS mice compared with the control group. Development of SIBO in PI-IBS mice was associated with reduced ICC density and increased IELs counts in the ileum. Our findings support the role of intestinal dysmotility and inflammation in the pathogenesis of SIBO in IBS and may provide potential therapeutic targets.

Small intestinal permeability is increased in diarrhoea predominant IBS, while alterations in gastroduodenal permeability in all IBS subtypes are largely attributable to confounders.

PubMed

Mujagic, Z; Ludidi, S; Keszthelyi, D; Hesselink, M A M; Kruimel, J W; Lenaerts, K; Hanssen, N M J; Conchillo, J M; Jonkers, D M A E; Masclee, A A M

2014-08-01

Intestinal permeability has been studied in small groups of IBS patients with contrasting findings. To assess intestinal permeability at different sites of the GI tract in different subtypes of well-characterised IBS patients and healthy controls (HC), and to assess potential confounding factors. IBS patients and HC underwent a multi-sugar test to assess site-specific intestinal permeability. Sucrose excretion and lactulose/rhamnose ratio in 0-5 h urine indicated gastroduodenal and small intestinal permeability, respectively. Sucralose/erythritol ratio in 0-24 h and 5-24 h urine indicated whole gut and colonic permeability, respectively. Linear regression analysis was used to assess the association between IBS groups and intestinal permeability and to adjust for age, sex, BMI, anxiety or depression, smoking, alcohol intake and use of medication. Ninety-one IBS patients, i.e. 37% IBS-D, 23% IBS-C, 33% IBS-M and 7% IBS-U and 94 HC were enrolled. Urinary sucrose excretion was significantly increased in the total IBS group [μmol, median (Q1;Q3): 5.26 (1.82;11.03) vs. 2.44 (0.91;5.85), P < 0.05], as well as in IBS-C and IBS-D vs. HC. However, differences attenuated when adjusting for confounders. The lactulose/rhamnose ratio was increased in IBS-D vs. HC [0.023 (0.013;0.038) vs. 0.014 (0.008;0.025), P < 0.05], which remained significant after adjustment for confounders. No difference was found in 0-24 and 5-24 h sucralose/erythritol ratio between groups. Small intestinal permeability is increased in patients with IBS-D compared to healthy controls, irrespective of confounding factors. Adjustment for confounders is necessary when studying intestinal permeability, especially in a heterogeneous disorder such as IBS. © 2014 John Wiley & Sons Ltd.

The activity of calcium in calcium-metal-fluoride fluxes

NASA Astrophysics Data System (ADS)

Ochifuji, Yuichiro; Tsukihashi, Fumitaka; Sano, Nobuo

1995-08-01

The standard Gibbs energy of reaction Ca (1) + O (mass pct, in Zr) = CaO (s) has been determined as follows by equilibrating molten calcium with solid zirconium in a CaO crucible: Δ G° = -64,300(±700) + 19.8(±3.5) T J/mol (1373 to 1623 K) The activities of calcium in the CaOsatd-Ca- MF2 ( M: Ca, Ba, Mg) and CaOsatd-Ca-NaF systems were measured as a function of calcium composition at high calcium contents at 1473 K on the basis of the standard Gibbs energy. The activities of calcium increase in the order of CaF2, BaF2, and MgF2 at the same calcium fraction of these fluxes. The observed activities are compared with those estimated by using the Temkin model for ionic solutions. Furthermore, the possibility of the removal of tramp elements such as tin, arsenic, antimony, bismuth, and lead from carbon-saturated iron by using calcium-metal-fluoride fluxes is discussed.

Bone mineral content before and after intestinal bypass operation in obese patients.

PubMed

Rickers, H; Balslev, I; Foltved, H; Rødbro, P

1981-01-01

With the aim of investigating bone mineral loss after intestinal bypass operation, bone mineral content (BMC) was measured by two-dimensional scanning photon absorptiometry on the distal part of the forearm in 23 consecutive patients who had undergone intestinal bypass operation for obesity. Eleven patients (group 1) were investigated before and 12 months after operation, and 12 (group 2), who had been operated on 2-7 years earlier, were investigated two times at an interval of 12 months. No patient received therapeutic calcium or vitamin D supply. The predominant biochemical findings postoperatively were decreased serum values of calcium, magnesium, albumin, and total protein; there was no change in inorganic phosphate or alkaline phosphatase. Mean BMC was normal in both groups postoperatively as well as in group 1 before operation; there was no significant change in mean BMC during 12 months of observation. However, in BMC measurements on extremely obese subjects, a correction for the excessive fat layer on the forearm was necessary because of different attenuation properties of fat and soft tissues. Neglect of this problem will give a systematic underestimation of BMC, and may lead to false conclusions in cross-sectional as well as longitudinal studies.

Increased IGF-IEc expression and mechano-growth factor production in intestinal muscle of fibrostenotic Crohn's disease and smooth muscle hypertrophy

PubMed Central

Li, Chao; Vu, Kent; Hazelgrove, Krystina

2015-01-01

The igf1 gene is alternatively spliced as IGF-IEa and IGF-IEc variants in humans. In fibrostenotic Crohn's disease, the fibrogenic cytokine TGF-β1 induces IGF-IEa expression and IGF-I production in intestinal smooth muscle and results in muscle hyperplasia and collagen I production that contribute to stricture formation. Mechano-growth factor (MGF) derived from IGF-IEc induces skeletal and cardiac muscle hypertrophy following stress. We hypothesized that increased IGF-IEc expression and MGF production mediated smooth muscle hypertrophy also characteristic of fibrostenotic Crohn's disease. IGF-IEc transcripts and MGF protein were increased in muscle cells isolated from fibrostenotic intestine under regulation by endogenous TGF-β1. Erk5 and MEF2C were phosphorylated in vivo in fibrostenotic muscle; both were phosphorylated and colocalized to nucleus in response to synthetic MGF in vitro. Smooth muscle-specific protein expression of α-smooth muscle actin, γ-smooth muscle actin, and smoothelin was increased in affected intestine. Erk5 inhibition or MEF2C siRNA blocked smooth muscle-specific gene expression and hypertrophy induced by synthetic MGF. Conditioned media of cultured fibrostenotic muscle induced muscle hypertrophy that was inhibited by immunoneutralization of endogenous MGF or pro-IGF-IEc. The results indicate that TGF-β1-dependent IGF-IEc expression and MGF production in patients with fibrostenotic Crohn's disease regulates smooth muscle cell hypertrophy a critical factor that contributes to intestinal stricture formation. PMID:26428636

Increased IGF-IEc expression and mechano-growth factor production in intestinal muscle of fibrostenotic Crohn's disease and smooth muscle hypertrophy.

PubMed

Li, Chao; Vu, Kent; Hazelgrove, Krystina; Kuemmerle, John F

2015-12-01

The igf1 gene is alternatively spliced as IGF-IEa and IGF-IEc variants in humans. In fibrostenotic Crohn's disease, the fibrogenic cytokine TGF-β1 induces IGF-IEa expression and IGF-I production in intestinal smooth muscle and results in muscle hyperplasia and collagen I production that contribute to stricture formation. Mechano-growth factor (MGF) derived from IGF-IEc induces skeletal and cardiac muscle hypertrophy following stress. We hypothesized that increased IGF-IEc expression and MGF production mediated smooth muscle hypertrophy also characteristic of fibrostenotic Crohn's disease. IGF-IEc transcripts and MGF protein were increased in muscle cells isolated from fibrostenotic intestine under regulation by endogenous TGF-β1. Erk5 and MEF2C were phosphorylated in vivo in fibrostenotic muscle; both were phosphorylated and colocalized to nucleus in response to synthetic MGF in vitro. Smooth muscle-specific protein expression of α-smooth muscle actin, γ-smooth muscle actin, and smoothelin was increased in affected intestine. Erk5 inhibition or MEF2C siRNA blocked smooth muscle-specific gene expression and hypertrophy induced by synthetic MGF. Conditioned media of cultured fibrostenotic muscle induced muscle hypertrophy that was inhibited by immunoneutralization of endogenous MGF or pro-IGF-IEc. The results indicate that TGF-β1-dependent IGF-IEc expression and MGF production in patients with fibrostenotic Crohn's disease regulates smooth muscle cell hypertrophy a critical factor that contributes to intestinal stricture formation. Copyright © 2015 the American Physiological Society.

[The fasting calcium/creatinine ratio in patients with calcium stones and the relation with hypercalciuria and phosphocalcium metabolism].

PubMed

Arrabal-Polo, Miguel Ángel; del Carmen Cano-García, María; Arrabal-Martín, Miguel

2016-04-01

To determine the importance of fasting calcium/creatinine ratio in patients with calcium stones and its relation with hypercalciuria and phospho-calcium metabolism. Cross-sectional study including 143 patients divided into two groups according to fasting calcium/creatinine. Group 1: 66 patients (calcium/ creatinine<0.11); Group 2: 77 patients (calcium/ creatinine>0.11). A comparative study is performed between groups including phospho-calcium metabolism parameters and excretion of urinary lithogenic markers. Linear correlation studying calciuria and fasting calcium/ creatinine was performed. SPSS 17.0 statistical analysis software was used, considering p≤0.05. It is noteworthy that group 2 had increased 24 h urine calcium excretion in comparison to group 1 (229.3 vs 158.1; p=0.0001) and calcium/citrate (0.47 vs 0.34; p=0.001). There is a positive and significant correlation between calcium levels in 24 h urine and fasting calcium/creatinine (R=0.455; p=0.0001) and a cutoff is set at 0.127 (sensitivity 72%, specificity 66%) to determine hypercalciuria (>260 mg in 24 h). Increased fasting calcium/creatinine determines increased 24 hours calcium excretion, although the sensitivity and specificity to determine hypercalciuria is not high.

Genetically modified Medicago truncatula lacking calcium oxalate has increased calcium bioavailability and partially rescues vitamin D receptor knockout mice phenotypes

USDA-ARS?s Scientific Manuscript database

How the distribution and sequestered form of plant macro/micro-nutrients influence their bioavailability, and ultimately impact human health, is poorly understood. The legume Medicago truncatula has a portion of its tissue calcium sequestered in the form of the calcium oxalate crystal, which reduces...

Calcium metabolism and cardiovascular function after spaceflight

NASA Technical Reports Server (NTRS)

Hatton, Daniel C.; Yue, Qi; Dierickx, Jacqueline; Roullet, Chantal; Otsuka, Keiichi; Watanabe, Mitsuaki; Coste, Sarah; Roullet, Jean Baptiste; Phanouvang, Thongchan; Orwoll, Eric;

Intracellular Calcium Mobilization in Response to Ion Channel Regulators via a Calcium-Induced Calcium Release Mechanism

PubMed Central

Petrou, Terry; Olsen, Hervør L.; Thrasivoulou, Christopher; Masters, John R.; Ashmore, Jonathan F.

2017-01-01

Free intracellular calcium ([Ca2+]i), in addition to being an important second messenger, is a key regulator of many cellular processes including cell membrane potential, proliferation, and apoptosis. In many cases, the mobilization of [Ca2+]i is controlled by intracellular store activation and calcium influx. We have investigated the effect of several ion channel modulators, which have been used to treat a range of human diseases, on [Ca2+]i release, by ratiometric calcium imaging. We show that six such modulators [amiodarone (Ami), dofetilide, furosemide (Fur), minoxidil (Min), loxapine (Lox), and Nicorandil] initiate release of [Ca2+]i in prostate and breast cancer cell lines, PC3 and MCF7, respectively. Whole-cell currents in PC3 cells were inhibited by the compounds tested in patch-clamp experiments in a concentration-dependent manner. In all cases [Ca2+]i was increased by modulator concentrations comparable to those used clinically. The increase in [Ca2+]i in response to Ami, Fur, Lox, and Min was reduced significantly (P < 0.01) when the external calcium was reduced to nM concentration by chelation with EGTA. The data suggest that many ion channel regulators mobilize [Ca2+]i. We suggest a mechanism whereby calcium-induced calcium release is implicated; such a mechanism may be important for understanding the action of these compounds. PMID:27980039

Coral resistance to ocean acidification linked to increased calcium at the site of calcification.

PubMed

DeCarlo, T M; Comeau, S; Cornwall, C E; McCulloch, M T

2018-05-16

Ocean acidification threatens the persistence of biogenic calcium carbonate (CaCO 3 ) production on coral reefs. However, some coral genera show resistance to declines in seawater pH, potentially achieved by modulating the chemistry of the fluid where calcification occurs. We use two novel geochemical techniques based on boron systematics and Raman spectroscopy, which together provide the first constraints on the sensitivity of coral calcifying fluid calcium concentrations ([Formula: see text]) to changing seawater pH. In response to simulated end-of-century pH conditions, Pocillopora damicornis increased [Formula: see text] to as much as 25% above that of seawater and maintained constant calcification rates. Conversely, Acropora youngei displayed less control over [Formula: see text], and its calcification rates strongly declined at lower seawater pH. Although the role of [Formula: see text] in driving calcification has often been neglected, increasing [Formula: see text] may be a key mechanism enabling more resistant corals to cope with ocean acidification and continue to build CaCO 3 skeletons in a high-CO 2 world. © 2018 The Author(s).

Soluble corn fiber increases bone calcium retention in postmenopausal women in a dose-dependent manner: a randomized crossover trial.

PubMed

Jakeman, Steven A; Henry, Courtney N; Martin, Berdine R; McCabe, George P; McCabe, Linda D; Jackson, George S; Peacock, Munro; Weaver, Connie M

2016-09-01

Dietary soluble corn fiber (SCF) significantly improves calcium absorption in adolescents and the bone strength and architecture in rodent models. In this study, we aimed to determine the skeletal benefits of SCF in postmenopausal women. We used our novel technology of determining bone calcium retention by following the urinary appearance of (41)Ca, a rare long-lived radioisotope, from prelabeled bone to rapidly and sensitively evaluate the effectiveness of SCF in reducing bone loss. A randomized-order, crossover, double-blinded trial was performed in 14 healthy postmenopausal women to compare doses of 0, 10, and 20 g fiber from SCF/d for 50 d. A dose-response effect was shown with 10 and 20 g fiber from SCF/d, whereby bone calcium retention was improved by 4.8% (P < 0.05) and 7% (P < 0.04), respectively. The bone turnover biomarkers N-terminal telopeptide and osteocalcin were not changed by the interventions; however, a significant increase in bone-specific alkaline phosphatase, which is a bone-formation marker, was detected between 0 and 20 g fiber from SCF/d (8%; P = 0.035). Daily SCF consumption significantly increased bone calcium retention in postmenopausal women, which improved the bone calcium balance by an estimated 50 mg/d. This study was registered at clinicaltrials.gov as NCT02416947. © 2016 American Society for Nutrition.

Comparison of side effects of pentagastrin test and calcium stimulation test in patients with increased basal calcitonin concentration: the gender-specific differences.

PubMed

Ubl, Philipp; Gincu, Tatiana; Keilani, Mohammad; Ponhold, Lothar; Crevenna, Richard; Niederle, Bruno; Hacker, Marcus; Li, Shuren

2014-08-01

The aim of this study was to compare the side effects of the pentagastrin test and the calcium stimulation test in patients with increased basal calcitonin concentration, especially the gender-specific differences of side effects. A total of 256 patients (123 females and 133 males, mean age of 56 ± 27 years, range 21-83 years) had both pentagastrin and calcium stimulation tests. All patients filled in a questionnaire regarding the side effects within 30 min after completion of the stimulation tests. The differences of side effects between female and male patients as well as between the pentagastrin stimulation test and the calcium stimulation test were evaluated. Warmth feeling was the most frequent occurring side effect in all patients who had both pentagastrin and calcium stimulation tests, followed by nausea, altered gustatory sensation, and dizziness. The incidences of urgency to micturate (p < 0.05) and dizziness (p < 0.05) were significantly increased in the female patients as compared to male patients by calcium stimulation test. Significant higher incidences of urgency to micturate (p < 0.05) and warmth feeling (p < 0.05) were found by calcium stimulation test as compared with those by pentagastrin test in female patients. The incidences of nausea (p < 0.05) and abdominal cramping (p < 0.05) in male patients were significantly higher by pentagastrin stimulation test than by calcium stimulation test. There is a significant gender-specific difference in side effects induced by calcium stimulation test. Female patients have fewer side effects by pentagastrin test than by calcium stimulation test. Male patients may tolerate the calcium stimulation test better than the pentagastrin test.

Coupling of Rigor Mortis and Intestinal Necrosis during C. elegans Organismal Death.

PubMed

Galimov, Evgeniy R; Pryor, Rosina E; Poole, Sarah E; Benedetto, Alexandre; Pincus, Zachary; Gems, David

2018-03-06

Organismal death is a process of systemic collapse whose mechanisms are less well understood than those of cell death. We previously reported that death in C. elegans is accompanied by a calcium-propagated wave of intestinal necrosis, marked by a wave of blue autofluorescence (death fluorescence). Here, we describe another feature of organismal death, a wave of body wall muscle contraction, or death contraction (DC). This phenomenon is accompanied by a wave of intramuscular Ca 2+ release and, subsequently, of intestinal necrosis. Correlation of directions of the DC and intestinal necrosis waves implies coupling of these death processes. Long-lived insulin/IGF-1-signaling mutants show reduced DC and delayed intestinal necrosis, suggesting possible resistance to organismal death. DC resembles mammalian rigor mortis, a postmortem necrosis-related process in which Ca 2+ influx promotes muscle hyper-contraction. In contrast to mammals, DC is an early rather than a late event in C. elegans organismal death. VIDEO ABSTRACT. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

A grape-enriched diet increases bone calcium retention and cortical bone properties in ovariectomized rats.

PubMed

Hohman, Emily E; Weaver, Connie M

2015-02-01

Grapes and their associated phytochemicals have been investigated for beneficial effects on cardiovascular health, cancer prevention, and other chronic diseases, but the effect of grape consumption on bone health has not been fully determined. We previously found short-term benefits of grape products on reducing bone turnover in ovariectomized rats. The objective of this study was to determine the long-term benefits of a grape-enriched diet on bone in ovariectomized rats. Rats were ovariectomized at 3 mo of age and were administered a single dose of (45)Ca to prelabel bones at 4 mo of age. After a 1-mo equilibration period, baseline urinary (45)Ca excretion was determined. Rats (n = 22/group) were then randomly assigned to a modified AIN93M diet containing 25% freeze-dried grape powder or to a control diet for 8 wk. Urinary (45)Ca excretion was monitored throughout the study to determine changes in bone (45)Ca retention. Calcium balance was assessed after 1 and 8 wk of consuming the experimental diets, and a calcium kinetic study was performed at 8 wk. After 8 wk, femurs were collected for micro-computed tomographic imaging, 3-point bending, and reference point indentation. Rats fed the grape-enriched diet had 44% greater net bone calcium retention than did rats fed the control diet. There were no differences in calcium balance due to diet at either week 1 or week 8, but there was a significant increase in net calcium absorption (10.6%) and retention (5.7%) from week 1 to week 8 in the grape-enriched diet group only. Grape-enriched diet-fed rats had 3% greater cortical thickness and 11% greater breaking strength. There were no differences in femur bone mineral density, trabecular microarchitecture, or reference point indentation variables due to diet. This study of ovariectomized rats indicates that the consumption of grape products may improve calcium utilization and suppress bone turnover, resulting in improvements in bone quality. © 2015 American Society for

Effects of Hydration and Calcium Supplementation on Urine Calcium Concentration in Healthy Postmenopausal Women.

PubMed

Harris, Susan S; Dawson-Hughes, Bess

2015-01-01

The aim of this study was to determine whether calcium supplementation, compared with placebo, increases urine calcium concentrations to levels indicative of increased renal stone risk, and the role that fluid intake, as indicated by urine volume, may play in mitigating this risk. This is a secondary analysis of data from a randomized placebo-controlled trial of 500 mg/d calcium supplementation to prevent bone loss. Subjects were 240 white postmenopausal women age 40 to 70 years in good general health. Effects of supplementation on 1-year changes in 24h urine calcium concentration and urine volume were examined. Both treatment group and urine volume were strong independent predictors of urine calcium concentration (p < 0.001). Among subjects with urine volume under 2 L/24 h, more than half of placebo subjects were at lowest risk for renal stones compared with less than 35% of calcium-supplemented subjects. Among those with higher urine volumes, all placebo subjects and more than 80% of calcium supplemented subjects were at lowest risk. The increased risk of renal stones with calcium supplement use may be largely eliminated with adequate fluid intake, but older adults may not spontaneously consume adequate fluids to minimize this risk and should be counseled to do so.

Calcium Balance in Chronic Kidney Disease.

PubMed

Hill Gallant, Kathleen M; Spiegel, David M

2017-06-01

The kidneys play a critical role in the balance between the internal milieu and external environment. Kidney failure is known to disrupt a number of homeostatic mechanisms that control serum calcium and normal bone metabolism. However, our understanding of calcium balance throughout the stages of chronic kidney disease is limited and the concept of balance itself, especially with a cation as complex as calcium, is often misunderstood. Both negative and positive calcium balance have important implications in patients with chronic kidney disease, where negative balance may increase risk of osteoporosis and fracture and positive balance may increase risk of vascular calcification and cardiovascular events. Here, we examine the state of current knowledge about calcium balance in adults throughout the stages of chronic kidney disease and discuss recommendations for clinical strategies to maintain balance as well as future research needs in this area. Recent calcium balance studies in adult patients with chronic kidney disease show that neutral calcium balance is achieved with calcium intake near the recommended daily allowance. Increases in calcium through diet or supplements cause high positive calcium balance, which may put patients at risk for vascular calcification. However, heterogeneity in calcium balance exists among these patients. Given the available calcium balance data in this population, it appears clinically prudent to aim for recommended calcium intakes around 1000 mg/day to achieve neutral calcium balance and avoid adverse effects of either negative or positive calcium balance. Assessment of patients' dietary calcium intake could further equip clinicians to make individualized recommendations for meeting recommended intakes.

Intestinal double-positive CD4+CD8+ T cells are highly activated memory cells with an increased capacity to produce cytokines.

PubMed

Pahar, Bapi; Lackner, Andrew A; Veazey, Ronald S

2006-03-01

Peripheral blood and intestinal CD4+CD8+ double-positive (DP) T cells have been described in several species including humans, but their function and immunophenotypic characteristics are still not clearly understood. Here we demonstrate that DP T cells are abundant in the intestinal lamina propria of normal rhesus macaques (Macaca mulatta). Moreover, DP T cells have a memory phenotype and are capable of producing different and/or higher levels of cytokines and chemokines in response to mitogen stimulation compared to CD4+ single-positive T cells. Intestinal DP T cells are also highly activated and have higher expression of CCR5, which makes them preferred targets for simian immunodeficiency virus/HIV infection. Increased levels of CD69, CD25 and HLA-DR, and lower CD62L expression were found on intestinal DP T cells populations compared to CD4+ single-positive T cells. Collectively, these findings demonstrate that intestinal and peripheral blood DP T cells are effector cells and may be important in regulating immune responses, which distinguishes them from the immature DP cells found in the thymus. Finally, these intestinal DP T cells may be important target cells for HIV infection and replication due to their activation, memory phenotype and high expression of CCR5.

Kaiso overexpression promotes intestinal inflammation and potentiates intestinal tumorigenesis in Apc(Min/+) mice.

PubMed

Pierre, Christina C; Longo, Joseph; Mavor, Meaghan; Milosavljevic, Snezana B; Chaudhary, Roopali; Gilbreath, Ebony; Yates, Clayton; Daniel, Juliet M

2015-09-01

Constitutive Wnt/β-catenin signaling is a key contributor to colorectal cancer (CRC). Although inactivation of the tumor suppressor adenomatous polyposis coli (APC) is recognized as an early event in CRC development, it is the accumulation of multiple subsequent oncogenic insults facilitates malignant transformation. One potential contributor to colorectal carcinogenesis is the POZ-ZF transcription factor Kaiso, whose depletion extends lifespan and delays polyp onset in the widely used Apc(Min/+) mouse model of intestinal cancer. These findings suggested that Kaiso potentiates intestinal tumorigenesis, but this was paradoxical as Kaiso was previously implicated as a negative regulator of Wnt/β-catenin signaling. To resolve Kaiso's role in intestinal tumorigenesis and canonical Wnt signaling, we generated a transgenic mouse model (Kaiso(Tg/+)) expressing an intestinal-specific myc-tagged Kaiso transgene. We then mated Kaiso(Tg/+) and Apc(Min/+) mice to generate Kaiso(Tg/+):Apc(Min/+) mice for further characterization. Kaiso(Tg/+):Apc(Min/+) mice exhibited reduced lifespan and increased polyp multiplicity compared to Apc(Min/+) mice. Consistent with this murine phenotype, we found increased Kaiso expression in human CRC tissue, supporting a role for Kaiso in human CRC. Interestingly, Wnt target gene expression was increased in Kaiso(Tg/+):Apc(Min/+) mice, suggesting that Kaiso's function as a negative regulator of canonical Wnt signaling, as seen in Xenopus, is not maintained in this context. Notably, Kaiso(Tg/+):Apc(Min/+) mice exhibited increased inflammation and activation of NFκB signaling compared to their Apc(Min/+) counterparts. This phenotype was consistent with our previous report that Kaiso(Tg/+) mice exhibit chronic intestinal inflammation. Together our findings highlight a role for Kaiso in promoting Wnt signaling, inflammation and tumorigenesis in the mammalian intestine. Copyright © 2015 Elsevier B.V. All rights reserved.

MicroRNA-146a constrains multiple parameters of intestinal immunity and increases susceptibility to DSS colitis.

PubMed

Runtsch, Marah C; Hu, Ruozhen; Alexander, Margaret; Wallace, Jared; Kagele, Dominique; Petersen, Charisse; Valentine, John F; Welker, Noah C; Bronner, Mary P; Chen, Xinjian; Smith, Daniel P; Ajami, Nadim J; Petrosino, Joseph F; Round, June L; O'Connell, Ryan M

2015-10-06

Host-microbial interactions within the mammalian intestines must be properly regulated in order to promote host health and limit disease. Because the microbiota provide constant immunological signals to intestinal tissues, a variety of regulatory mechanisms have evolved to ensure proper immune responses to maintain homeostasis. However, many of the genes that comprise these regulatory pathways, including immune-modulating microRNAs (miRNAs), have not yet been identified or studied in the context of intestinal homeostasis. Here, we investigated the role of microRNA-146a (miR-146a) in regulating intestinal immunity and barrier function and found that this miRNA is expressed in a variety of gut tissues in adult mice. By comparing intestinal gene expression in WT and miR-146a-/- mice, we demonstrate that miR-146a represses a subset of gut barrier and inflammatory genes all within a network of immune-related signaling pathways. We also found that miR-146a restricts the expansion of intestinal T cell populations, including Th17, Tregs, and Tfh cells. GC B cells, Tfh ICOS expression, and the production of luminal IgA were also reduced by miR-146a in the gut. Consistent with an enhanced intestinal barrier, we found that miR-146a-/- mice are resistant to DSS-induced colitis, a model of Ulcerative Colitis (UC), and this correlated with elevated colonic miR-146a expression in human UC patients. Taken together, our data describe a role for miR-146a in constraining intestinal barrier function, a process that alters gut homeostasis and enhances at least some forms of intestinal disease in mice.

MicroRNA-146a constrains multiple parameters of intestinal immunity and increases susceptibility to DSS colitis

PubMed Central

Runtsch, Marah C.; Hu, Ruozhen; Alexander, Margaret; Wallace, Jared; Kagele, Dominique; Petersen, Charisse; Valentine, John F.; Welker, Noah C.; Bronner, Mary P.; Chen, Xinjian; Smith, Daniel P.; Ajami, Nadim J.; Petrosino, Joseph F.; Round, June L.; O'Connell, Ryan M.

2015-01-01

Host-microbial interactions within the mammalian intestines must be properly regulated in order to promote host health and limit disease. Because the microbiota provide constant immunological signals to intestinal tissues, a variety of regulatory mechanisms have evolved to ensure proper immune responses to maintain homeostasis. However, many of the genes that comprise these regulatory pathways, including immune-modulating microRNAs (miRNAs), have not yet been identified or studied in the context of intestinal homeostasis. Here, we investigated the role of microRNA-146a (miR-146a) in regulating intestinal immunity and barrier function and found that this miRNA is expressed in a variety of gut tissues in adult mice. By comparing intestinal gene expression in WT and miR-146a−/− mice, we demonstrate that miR-146a represses a subset of gut barrier and inflammatory genes all within a network of immune-related signaling pathways. We also found that miR-146a restricts the expansion of intestinal T cell populations, including Th17, Tregs, and Tfh cells. GC B cells, Tfh ICOS expression, and the production of luminal IgA were also reduced by miR-146a in the gut. Consistent with an enhanced intestinal barrier, we found that miR-146a−/− mice are resistant to DSS-induced colitis, a model of Ulcerative Colitis (UC), and this correlated with elevated colonic miR-146a expression in human UC patients. Taken together, our data describe a role for miR-146a in constraining intestinal barrier function, a process that alters gut homeostasis and enhances at least some forms of intestinal disease in mice. PMID:26456940

Intestinal absorption of strontium chloride in healthy volunteers: pharmacokinetics and reproducibility

PubMed Central

SIPS, A. J. A. M.; van der VIJGH, W. J. F.; BARTO, R.; NETELENBOS, J. C.

1996-01-01

1The absorption kinetics of orally administered strontium chloride and its reproducibility were investigated in healthy volunteers after administering strontium either under fasting conditions (study I, n=8) or in combination with a standardized meal (study II, n=8). Each subject received strontium orally at day 0, 14, and 28 and intravenously at day 42. The study was performed as part of a project in which a simple clinical test for measuring intestinal calcium absorption is being developed, based on the use of stable strontium as a marker. 2Plasma strontium concentration–time curves were analysed by noncompartment analysis and a four compartment disposition model. Within a volunteer each oral curve was fitted simultaneously with the intravenous curve, by which means a two segment model for absorption was revealed. 3Mean absolute bioavailability of strontium was 25% without a meal and 19% with a meal, whereas the intraindividual variation was 24% and 20%, respectively. 4Various limited sampling absorption parameters were determined in order to select a potential test parameter for measuring intestinal calcium absorption using strontium as a marker. Fractional absorption at 4 h (Fc240), obtained after co-ingestion of strontium with a meal, appeared to be the best test parameter, because it represented bioavailability well (r=0.90). PMID:8799520

The effects of 3,4-methylenedioxymethamphetamine (MDMA) on nicotinic receptors: Intracellular calcium increase, calpain/caspase 3 activation, and functional upregulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garcia-Rates, Sara; Camarasa, Jordi; Sanchez-Garcia, Ana I.

2010-05-01

Previous work by our group demonstrated that homomeric alpha7 nicotinic acetylcholine receptors (nAChR) play a role in the neurotoxicity induced by 3,4-methylenedioxymethamphetamine (MDMA), as well as the binding affinity of this drug to these receptors. Here we studied the effect of MDMA on the activation of nAChR subtypes, the consequent calcium mobilization, and calpain/caspase 3 activation because prolonged Ca{sup 2+} increase could contribute to cytotoxicity. As techniques, we used fluorimetry in Fluo-4-loaded PC12 cells and electrophysiology in Xenopus oocytes. MDMA produced a rapid and sustained increase in calcium without reaching the maximum effect induced by ACh. It also concentration-dependently inhibitedmore » the response induced by ACh, nicotine, and the specific alpha7 agonist PNU 282987 with IC{sub 50} values in the low micromolar range. Similarly, MDMA induced inward currents in Xenopus oocytes transfected with human alpha7 but not with alpha4beta2 nAChR and inhibited ACh-induced currents in both receptors in a concentration-dependent manner. The calcium response was inhibited by methyllycaconitine (MLA) and alpha-bungarotoxin but not by dihydro-beta-erythroidine. These results therefore indicate that MDMA acts as a partial agonist on alpha7 nAChRs and as an antagonist on the heteromeric subtypes. Subsequently, calcium-induced Ca{sup 2+} release from the endoplasmic reticulum and entry through voltage-operated calcium channels are also implicated as proved using specific antagonists. In addition, treatment with MDMA for 24 h significantly increased basal Ca{sup 2+} levels and induced an increase in alpha-spectrin breakdown products, which indicates that calpain and caspase 3 were activated. These effects were inhibited by pretreatment with MLA. Moreover, pretreatment with MDMA induced functional upregulation of calcium responses to specific agonists of both heteromeric and alpha7 nAChR. Sustained calcium entry and calpain activation could favor

Preinduced intestinal HSP70 improves visceral hypersensitivity and abnormal intestinal motility in PI-IBS mouse model.

PubMed

Lan, Cheng; Sun, Xiao-Ning; Zhou, Xu-Chun; Yang, Bo; Huang, Bai-Li; Deng, Tao-Zhi; He, Zhou-Tao; Han, Xiang-Yang

2016-03-01

To investigate the impact of the preinduced intestinal heat shock protein 70 (HSP70) on the visceral hypersensitivity and abnormal intestinal motility in a post-infectious irritable bowel syndrome (PI-IBS) mouse model. Eighty-four female C57BL/6 mice were randomly assigned to four groups: control group (n = 21) and induction + PI-IBS group (n = 21), PI-IBS group (n = 21) and induction group (n = 21). The mice in PI-IBS group were infected in vivo with Trichinella spiralis by oral administration. The visceral hypersensitivity and intestinal motility were evaluated respectively with abdominal withdrawal reflex and colon transportation test. The intestinal HSP70 protein and mRNA level was measured by Western blot and real-time PCR. Meanwhile, the intestinal proinflammatory cytokines IL-10 and TNF-α level was detected by ELISA. Compared with their counterparts in PI-IBS group, the animals in the Induction + PI-IBS group show significantly increased intestinal level of HSP70 and obviously ameliorative clinical figures, including abdominal withdrawal reflex score, intestine transportation time and Bristol scores (P < 0.05). Meanwhile, the intestinal post-inflammatory cytokines remarkably changed, including increased IL-10 level and decreased TNF-α level (P < 0.05). Intestinal HSP70 may play a potential protective role through improving the imbalance between the intestinal post-inflammatory and anti-inflammatory cytokines in PI-IBS. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kramer, L.

The effect of drugs such as glucocorticoids and thyroid extract on calcium metabolism is unknown. However, several other medications affect the excretion and intestinal absorption of calcium. A controlled study was carried out to investigate these aspects. Urinary calcium was determined for 3 months during the long-term intake of the antituberculous drug isoniazid (INH) and of the antibiotic tetracycline. The effect of the diuretics furosemide and hydrochlorothiazide, of several aluminum-containing antacids, of thyroid extract and of corticosteroids was also studied. Metabolic balances of calcium, phosphorus, magnesium and zinc were determined, as well as the intestinal absorption of calcium using Camore » 47. Plasma levels, urinary and fecal excretions of Ca 47 were determined. All drugs tested increased urinary calcium except for the diuretic hydrochlorothiazide. Regarding the effect of corticosteroids: the intestinal absorption of calcium was unchanged after the short-term use and was very high after long-term use. The studies have shown that several commonly used drugs induce an increase in urinary calcium excretion which may contribute to calcium loss, if this increase persists for prolonged periods of time. Urinary excretions of phosphorus, magnesium and zinc increased in some of the studies.« less

Increased calcium deposits and decreased Ca2+-ATPase in right ventricular myocardium of ascitic broiler chickens.

PubMed

Li, K; Qiao, J; Zhao, L; Dong, S; Ou, D; Wang, J; Wang, H; Xu, T

2006-11-01

Right ventricular hypertrophy and failure is an important step in the development of ascites syndrome (AS) in broiler chickens. Cytoplasmic calcium concentration is a major regulator of cardiac contractile function and various physiological processes in cardiac muscle cells. The purpose of this study was to measure the right ventricular pressure and investigate the precise ultrastructural location of Ca(2+) and Ca(2+)-ATPase in the right ventricular myocardium of chickens with AS induced by low ambient temperature. The results showed that the right ventricular diastolic pressure of ascitic broilers was significantly higher than that of control broilers (P < 0.01), and the maximum change ratio of right intraventricular pressure (RV +/- dp/dt(max)) of ascitic broilers was significantly lower than that of the controls (P < 0.01). Extensively increased calcium deposits were observed in the right ventricular myocardium of ascitic broilers, whereas in the age-matched control broilers, calcium deposits were much less. The Ca(2+)-ATPase reactive products were obviously found on the sarcoplasmic reticulum and mitochondrial membrane of the control right ventricular myocardium, but rarely observed in the ascitic broilers. The data suggest that in ascitic broilers there is the right ventricular diastolic dysfunction, in which the overload of intracellular calcium and the decreased Ca(2+)-ATPase activity might be the important factors.

Contribution of intestinal- and cereal-derived phytase activity on phytate degradation in young broilers.

PubMed

Morgan, N K; Walk, C L; Bedford, M R; Burton, E J

2015-07-01

There is little consensus as to the capability of poultry to utilize dietary phytate without supplemental phytase. Therefore, an experiment was conducted to examine the extent to which endogenous phytase of intestinal and cereal origin contributes to phytate degradation in birds aged 0 to 14 d posthatch. Ross 308 broilers (n = 720) were fed one of 4 experimental diets with differing dietary ingredient combinations and approximate total phytate levels of 10 g/kg, dietary phytase activity analyzed at 460 U/kg, dietary calcium (Ca) levels of 11 g/kg, and nonphytate-phosphorus (P) levels of 4 g/kg. Broiler performance, gizzard, duodenum, jejunum and ileum pH, Ca and P digestibility and solubility, amount of dietary phytate hydrolyzed in the gizzard, jejunum, and ileal digesta phytase activity were analyzed at d 4, 6, 8, 10, 12, and 14 posthatch. Intestinal endogenous phytase activity increased significantly (P < 0.001) between d 4 and 6, resulting in increased phytate hydrolysis in the gizzard (P = 0.003), jejunum (P < 0.001), and ileum (P < 0.001). Phytase activity and phytate hydrolysis continued to increase with age, with a greater phytase activity and associated increase in phytate hydrolysis and mineral utilization between d 10 and 12. Gizzard and jejunum Ca and P solubility and ileal Ca and P digestibility increased significantly (P < 0.001), and gastrointestinal pH decreased significantly (P < 0.001) between d 4 and 6. By d 14, phytase activity recovered in the ileum was approximately 45 U/kg. There were strong correlations between phytase activity measured in the ileum and phytate hydrolyzed in the gizzard (r = 0.905, P < 0.001), jejunum (r = 0.901, P = 0.023), and ileum (r = 0.938, P = 0.042). This study shows intestinal- and dietary-derived endogenous phytase activity is responsible for phytate-P hydrolysis in broilers. © 2015 Poultry Science Association Inc.

The effect of fucoidan on intestinal flora and intestinal barrier function in rats with breast cancer.

PubMed

Xue, Meilan; Ji, Xinqiang; Liang, Hui; Liu, Ying; Wang, Bing; Sun, Lingling; Li, Weiwei

2018-02-21

Recent research studies have shown that the intestinal flora are related to the occurrence and progress of breast cancer. This study investigates the effect of fucoidan on intestinal flora and intestinal barrier function in rats with 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancers. Sixty female Sprague-Dawley rats were randomly assigned to the control group, the model group, and the F1 and F2 groups, which were fed fucoidan at concentrations of 200 and 400 mg per kg bw (body weight), respectively. Intestinal histopathological analysis was performed and 16S rDNA high-throughput sequencing was used to provide an overview of the intestinal flora composition. The contents of d-lactic acid (d-LA), diamine oxidase (DAO) and endotoxin in plasma were detected by ELISA. Expression levels of the tight junction (TJ) proteins, phosphorylated p38 MAPK and ERK1/2 were measured using western blotting. Our results suggested that the intestinal wall of the model group was damaged. However, after fucoidan intervention, the villi were gradually restored. ELISA showed that the levels of plasma endotoxin, d-LA and DAO decreased in the F1 and F2 groups compared to those in the model group. Fucoidan treatment also increased the expressions of ZO-1, occludin, claudin-1 and claudin-8. Furthermore, the expression levels of phosphorylated p38 MAPK and ERK1/2 were upregulated in fucoidan treatment groups. The results of 16S rDNA high-throughput sequencing indicated that fucoidan increased the diversity of the intestinal microbiota and induced changes in microbial composition, with the increased Bacteroidetes/Firmicutes phylum ratio. In conclusion, the supplement of fucoidan could improve the fecal microbiota composition and repair the intestinal barrier function. The study suggested the use of fucoidan as an intestinal flora modulator for potential prevention of breast cancer.

Action of cholecystokinin and cholinergic agents on calcium transport in isolated pancreatic acinar cells.

PubMed Central

Gardner, J D; Conlon, T P; Kleveman, H L; Adams, T D; Ondetti, M A

1975-01-01

COOH-terminal octapeptide of cholecystokinin (CCK-octapeptide) and the cholinergic agent carbamylcholine each produced a fourfold stimulation of calcium outflux in guinea pig isolated pancreatic acinar cells. Neither agent altered calcium influx. Stimulation of calcium outflux was rapid and specific, was abolished by reducing the incubation temperature to 4 degrees C, and was a saturable function of the secretagogue concentration. The concentrations of CCK-octapeptide and carbamylcholine that produced half-maximal stimulation of calcium outflux were 3.1 x 10(-10) M and 4.9 x 10(-5) M, respectively. The cholinergic antagonist antropine competitively inhibited carbamylcholine stimulation of calcium outflux but did not alter stimulation produced by CCK-octapeptide. Stimulation of calcium outflux by maximal concentrations of carbamycholine plus CCK-octapeptide was the same as that produced by a maximal concentration of either agent alone.Calcium outflux became refractory to stimulation by secretagogues, and incubation with either CCK-ostapeptide or carbamylcholine produced a refractoriness to both agents. The relative potencies with CCK and its related fragments stimulated calcium outflux were CCK-octapeptide greater than heptapeptide greater than CCK greater than hexapeptide = gastrin. Secretin, glucagon, and vasoactive intestinal peptide, at concentrations as high as 10(-5) M, failed to alter calcium outflux and did not affect stimulation by CCK-octapeptide or by carbamycholine. Images PMID:1150877

Vasopressin regulates renal calcium excretion in humans

PubMed Central

Hanouna, Guillaume; Haymann, Jean-Philippe; Baud, Laurent; Letavernier, Emmanuel

2015-01-01

Antidiuretic hormone or arginine vasopressin (AVP) increases water reabsorption in the collecting ducts of the kidney. Three decades ago, experimental models have shown that AVP may increase calcium reabsorption in rat kidney. The objective of this study was to assess whether AVP modulates renal calcium excretion in humans. We analyzed calcium, potassium, and sodium fractional excretion in eight patients affected by insipidus diabetes (nephrogenic or central) under acute vasopressin receptor agonist action and in 10 patients undergoing oral water load test affected or not by inappropriate antidiuretic hormone secretion (SIADH). Synthetic V2 receptor agonist (dDAVP) reduced significantly calcium fractional excretion from 1.71% to 0.58% (P < 0.05) in patients with central diabetes insipidus. In patients with nephrogenic diabetes insipidus (resistant to AVP), calcium fractional excretion did not change significantly after injection (0.48–0.68%, P = NS). In normal subjects undergoing oral water load test, calcium fractional excretion increased significantly from 1.02% to 2.54% (P < 0.05). Patients affected by SIADH had a high calcium fractional excretion at baseline that remained stable during test from 3.30% to 3.33% (P = NS), possibly resulting from a reduced calcium absorption in renal proximal tubule. In both groups, there was a significant correlation between urine output and calcium renal excretion. In humans, dDAVP decreases calcium fractional excretion in the short term. Conversely, water intake, which lowers AVP concentration, increases calcium fractional excretion. The correlation between urine output and calcium excretion suggests that AVP-related antidiuresis increases calcium reabsorption in collecting ducts. PMID:26620256

Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia-Reperfusion in the Rat

PubMed Central

Onal, Ozkan; Yetisir, Fahri; Sarer, A. Ebru Salman; Zeybek, N. Dilara; Onal, C. Oztug; Yurekli, Banu; Celik, H. Tugrul; Sirma, Ayse; Kılıc, Mehmet

2015-01-01

Objectives. Intestinal ischemia-reperfusion injury is associated with mucosal damage and has a high rate of mortality. Various beneficial effects of ozone have been shown. The aim of the present study was to show the effects of ozone in ischemia reperfusion model in intestine. Material and Method. Twenty eight Wistar rats were randomized into four groups with seven rats in each group. Control group was administered serum physiologic (SF) intraperitoneally (ip) for five days. Ozone group was administered 1 mg/kg ozone ip for five days. Ischemia Reperfusion (IR) group underwent superior mesenteric artery occlusion for one hour and then reperfusion for two hours. Ozone + IR group was administered 1 mg/kg ozone ip for five days and at sixth day IR model was applied. Rats were anesthetized with ketamine∖xyzlazine and their intracardiac blood was drawn completely and they were sacrificed. Intestinal tissue samples were examined under light microscope. Levels of superoxide dismutase (SOD), catalase (CAT), glutathioneperoxidase (GSH-Px), malondyaldehide (MDA), and protein carbonyl (PCO) were analyzed in tissue samples. Total oxidant status (TOS), and total antioxidant capacity (TAC) were analyzed in blood samples. Data were evaluated statistically by Kruskal Wallis test. Results. In the ozone administered group, degree of intestinal injury was not different from the control group. IR caused an increase in intestinal injury score. The intestinal epithelium maintained its integrity and decrease in intestinal injury score was detected in Ozone + IR group. SOD, GSH-Px, and CAT values were high in ozone group and low in IR. TOS parameter was highest in the IR group and the TAC parameter was highest in the ozone group and lowest in the IR group. Conclusion. In the present study, IR model caused an increase in intestinal injury.In the present study, ozone administration had an effect improving IR associated tissue injury. In the present study, ozone therapy prevented

Calcium-induced calcium release in rod photoreceptor terminals boosts synaptic transmission during maintained depolarization

PubMed Central

Cadetti, Lucia; Bryson, Eric J.; Ciccone, Cory A.; Rabl, Katalin; Thoreson, Wallace B.

2008-01-01

We examined the contribution of calcium-induced calcium release (CICR) to synaptic transmission from rod photoreceptor terminals. Whole-cell recording and confocal calcium imaging experiments were conducted on rods with intact synaptic terminals in a retinal slice preparation from salamander. Low concentrations of ryanodine stimulated calcium increases in rod terminals, consistent with the presence of ryanodine receptors. Application of strong depolarizing steps (−70 to −10 mV) exceeding 200 ms or longer in duration evoked a wave of calcium that spread across the synaptic terminals of voltage-clamped rods. This secondary calcium increase was blocked by high concentrations of ryanodine, indicating it was due to CICR. Ryanodine (50 μM) had no significant effect on rod calcium current (Ica) although it slightly diminished rod light-evoked voltage responses. Bath application of 50 μM ryanodine strongly inhibited light-evoked currents in horizontal cells. Whether applied extracellularly or delivered into the rod cell through the patch pipette, ryanodine (50 μM) also inhibited excitatory post-synaptic currents (EPSCs) evoked in horizontal cells by depolarizing steps applied to rods. Ryanodine caused a preferential reduction in the later portions of EPSCs evoked by depolarizing steps of 200 ms or longer. These results indicate that CICR enhances calcium increases in rod terminals evoked by sustained depolarization, which in turn acts to boost synaptic exocytosis from rods. PMID:16819987

Disorder of endoplasmic reticulum calcium channel components is associated with the increased apoptotic potential in pale, soft, exudative pork.

PubMed

Guo, Bing; Zhang, Wangang; Tume, Ron K; Hudson, Nicholas J; Huang, Feng; Yin, Yan; Zhou, Guanghong

2016-05-01

Eight pale, soft and exudative (PSE) and eight reddish-pink, firm and non-exudative (RFN) porcine longissimus muscle samples were selected based on pH and L* at 1h postmortem (PM), and drip loss at 24h PM, and used to evaluate the cellular calcium and apoptosis status. We found that SERCA1 was decreased, while IP3R was decreased in PSE meat (P<0.05), indicative of the overloaded sarcoplasmic calcium status. In PSE meat, the pro-apoptotic factor BAX was increased while the anti-apoptotic factor Bcl-2 was decreased (P<0.05). The significantly increased activity of caspase 3 and the expression of its cleavage fragment suggested higher apoptotic potential in PSE meat compared with RFN meat (P<0.05). Moreover, the significantly higher expression level of cytochrome C (P<0.05) suggests the important role of mitochondria during apoptosis appearance in PSE meat. Taken together, our data inferred that the calcium channel disorder present in PSE meat was associated with the increased apoptotic potential. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced acute ileitis in mice harboring a human gut microbiota

PubMed Central

von Klitzing, Eliane; Ekmekciu, Ira; Kühl, Anja A.; Bereswill, Stefan

2017-01-01

Background Within seven days following peroral high dose infection with Toxoplasma gondii susceptible conventionally colonized mice develop acute ileitis due to an underlying T helper cell (Th) -1 type immunopathology. We here addressed whether mice harboring a human intestinal microbiota developed intestinal, extra-intestinal and systemic sequelae upon ileitis induction. Methodology/Principal findings Secondary abiotic mice were generated by broad-spectrum antibiotic treatment and associated with a complex human intestinal microbiota following peroral fecal microbiota transplantation. Within three weeks the human microbiota had stably established in the murine intestinal tract as assessed by quantitative cultural and culture-independent (i.e. molecular 16S rRNA based) methods. At day 7 post infection (p.i.) with 50 cysts of T. gondii strain ME49 by gavage human microbiota associated (hma) mice displayed severe clinical, macroscopic and microscopic sequelae indicating acute ileitis. In diseased hma mice increased numbers of innate and adaptive immune cells within the ileal mucosa and lamina propria and elevated intestinal secretion of pro-inflammatory mediators including IFN-γ, IL-12 and nitric oxide could be observed at day 7 p.i. Ileitis development was accompanied by substantial shifts in intestinal microbiota composition of hma mice characterized by elevated total bacterial loads and increased numbers of intestinal Gram-negative commensals such as enterobacteria and Bacteroides / Prevotella species overgrowing the small and large intestinal lumen. Furthermore, viable bacteria translocated from the inflamed ileum to extra-intestinal including systemic compartments. Notably, pro-inflammatory immune responses were not restricted to the intestinal tract as indicated by increased pro-inflammatory cytokine secretion in extra-intestinal (i.e. liver and kidney) and systemic compartments including spleen and serum. Conclusion/Significance With respect to the intestinal

Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced acute ileitis in mice harboring a human gut microbiota.

PubMed

von Klitzing, Eliane; Ekmekciu, Ira; Kühl, Anja A; Bereswill, Stefan; Heimesaat, Markus M

2017-01-01

Within seven days following peroral high dose infection with Toxoplasma gondii susceptible conventionally colonized mice develop acute ileitis due to an underlying T helper cell (Th) -1 type immunopathology. We here addressed whether mice harboring a human intestinal microbiota developed intestinal, extra-intestinal and systemic sequelae upon ileitis induction. Secondary abiotic mice were generated by broad-spectrum antibiotic treatment and associated with a complex human intestinal microbiota following peroral fecal microbiota transplantation. Within three weeks the human microbiota had stably established in the murine intestinal tract as assessed by quantitative cultural and culture-independent (i.e. molecular 16S rRNA based) methods. At day 7 post infection (p.i.) with 50 cysts of T. gondii strain ME49 by gavage human microbiota associated (hma) mice displayed severe clinical, macroscopic and microscopic sequelae indicating acute ileitis. In diseased hma mice increased numbers of innate and adaptive immune cells within the ileal mucosa and lamina propria and elevated intestinal secretion of pro-inflammatory mediators including IFN-γ, IL-12 and nitric oxide could be observed at day 7 p.i. Ileitis development was accompanied by substantial shifts in intestinal microbiota composition of hma mice characterized by elevated total bacterial loads and increased numbers of intestinal Gram-negative commensals such as enterobacteria and Bacteroides / Prevotella species overgrowing the small and large intestinal lumen. Furthermore, viable bacteria translocated from the inflamed ileum to extra-intestinal including systemic compartments. Notably, pro-inflammatory immune responses were not restricted to the intestinal tract as indicated by increased pro-inflammatory cytokine secretion in extra-intestinal (i.e. liver and kidney) and systemic compartments including spleen and serum. With respect to the intestinal microbiota composition "humanized" mice display acute ileitis

Polymer coated CaAl-layered double hydroxide nanomaterials for potential calcium supplement.

PubMed

Kim, Tae-Hyun; Lee, Jeong-A; Choi, Soo-Jin; Oh, Jae-Min

2014-12-05

We have successfully prepared layered double hydroxide (LDH) nanomaterials containing calcium and aluminum ions in the framework (CaAl-LDH). The surface of CaAl-LDH was coated with enteric polymer, Eudragit®L 100 in order to protect nanomaterials from fast dissolution under gastric condition of pH 1.2. The X-ray diffraction patterns, Fourier transform infrared spectroscopy, scanning electron and transmission electron microscopy revealed that the pristine LDH was well prepared having hydrocalumite structure, and that the polymer effectively coated the surface of LDH without disturbing structure. From thermal analysis, it was determined that only a small amount (less than 1%) of polymer was coated on the LDH surface. Metal dissolution from LDH nanomaterials was significantly reduced upon Eudragit®L 100 coating at pH 1.2, 6.8 and 7.4, which simulates gastric, enteric and plasma conditions, respectively, and the dissolution effect was the most suppressed at pH 1.2. The LDH nanomaterials did not exhibit any significant cytotoxicity up to 1000 μg/mL and intracellular calcium concentration significantly increased in LDH-treated human intestinal cells. Pharmacokinetic study demonstrated absorption efficiency of Eudragit®L 100 coated LDH following oral administration to rats. Moreover, the LDH nanomaterials did not cause acute toxic effect in vivo. All the results suggest the great potential of CaAl-LDH nanomaterials as a calcium supplement.

Functional Effects of Prebiotic Fructans in Colon Cancer and Calcium Metabolism in Animal Models.

PubMed

Rivera-Huerta, Marisol; Lizárraga-Grimes, Vania Lorena; Castro-Torres, Ibrahim Guillermo; Tinoco-Méndez, Mabel; Macías-Rosales, Lucía; Sánchez-Bartéz, Francisco; Tapia-Pérez, Graciela Guadalupe; Romero-Romero, Laura; Gracia-Mora, María Isabel

2017-01-01

Inulin-type fructans are polymers of fructose molecules and are known for their capacity to enhance absorption of calcium and magnesium, to modulate gut microbiota and energy metabolism, and to improve glycemia. We evaluated and compared the effects of Chicory inulin "Synergy 1®" and inulin from Mexican agave "Metlin®" in two experimental models of colon cancer and bone calcium metabolism in mice and rats. Inulins inhibited the development of dextran sulfate sodium-induced colitis and colon cancer in mice; these fructans reduced the concentration of tumor necrosis factor alpha and prevented the formation of intestinal polyps, villous atrophy, and lymphoid hyperplasia. On the other hand, inulin treatments significantly increased bone densitometry (femur and vertebra) in ovariectomized rats without altering the concentration of many serum biochemical parameters and urinary parameters. Histopathology results were compared between different experimental groups. There were no apparent histological changes in rats treated with inulins and a mixture of inulins-isoflavones. Our results showed that inulin-type fructans have health-promoting properties related to enhanced calcium absorption, potential anticancer properties, and anti-inflammatory effects. The use of inulin as a prebiotic can improve health and prevent development of chronic diseases such as cancer and osteoporosis.

Increased LDL electronegativity in chronic kidney disease disrupts calcium homeostasis resulting in cardiac dysfunction.

PubMed

Chang, Kuan-Cheng; Lee, An-Sheng; Chen, Wei-Yu; Lin, Yen-Nien; Hsu, Jing-Fang; Chan, Hua-Chen; Chang, Chia-Ming; Chang, Shih-Sheng; Pan, Chia-Chi; Sawamura, Tatsuya; Chang, Chi-Tzong; Su, Ming-Jai; Chen, Chu-Huang

2015-07-01

Chronic kidney disease (CKD), an independent risk factor for cardiovascular disease, is associated with abnormal lipoprotein metabolism. We examined whether electronegative low-density lipoprotein (LDL) is mechanistically linked to cardiac dysfunction in patients with early CKD. We compared echocardiographic parameters between patients with stage 2 CKD (n = 88) and normal controls (n = 89) and found that impaired relaxation was more common in CKD patients. Reduction in estimated glomerular filtration rate was an independent predictor of left ventricular relaxation dysfunction. We then examined cardiac function in a rat model of early CKD induced by unilateral nephrectomy (UNx) by analyzing pressure-volume loop data. The time constant of isovolumic pressure decay was longer and the maximal velocity of pressure fall was slower in UNx rats than in controls. When we investigated the mechanisms underlying relaxation dysfunction, we found that LDL from CKD patients and UNx rats was more electronegative than LDL from their respective controls and that LDL from UNx rats induced intracellular calcium overload in H9c2 cardiomyocytes in vitro. Furthermore, chronic administration of electronegative LDL, which signals through lectin-like oxidized LDL receptor-1 (LOX-1), induced relaxation dysfunction in wild-type but not LOX-1(-/-) mice. In in vitro and in vivo experiments, impaired cardiac relaxation was associated with increased calcium transient resulting from nitric oxide (NO)-dependent nitrosylation of SERCA2a due to increases in inducible NO synthase expression and endothelial NO synthase uncoupling. In conclusion, LDL becomes more electronegative in early CKD. This change disrupts SERCA2a-regulated calcium homeostasis, which may be the mechanism underlying cardiorenal syndrome. Copyright © 2015 Elsevier Ltd. All rights reserved.

Intestinal permeability defects: Is it time to treat?

PubMed Central

Odenwald, Matthew A.; Turner, Jerrold R.

2013-01-01

An essential role of the intestinal epithelium is to separate luminal contents from the interstitium, a function primarily determined by the integrity of the epithelium and the tight junction that seals the paracellular space. Intestinal tight junctions are selectively-permeable, and intestinal permeability can be increased physiologically in response to luminal nutrients or pathologically by mucosal immune cells and cytokines, the enteric nervous system, and pathogens. Compromised intestinal barrier function is associated with an array of clinical conditions, both intestinal and systemic. While most available data are correlative, some studies support a model where cycles of increased intestinal permeability, intestinal immune activation, and subsequent immune-mediated barrier loss contribute to disease progression. This model is applicable to intestinal and systemic diseases. However, it has not been proven and both mechanistic and therapeutic studies are ongoing. Nevertheless, the correlation between increased intestinal permeability and disease has caught the attention of the public, leading to a rise in popularity of the diagnosis of “leaky gut syndrome,” which encompasses a range of systemic disorders. Proponents claim that barrier restoration will cure underlying disease, but this has not been demonstrated in clinical trials. Moreover, human and mouse studies show that intestinal barrier loss alone is insufficient to initiate disease. It is therefore uncertain if increased permeability in these patients is a cause or effect of the underlying disorder. Although drug targets that may mediate barrier restoration have been proposed, none have been proven effective. As such, current treatments for barrier dysfunction should target the underlying disease. PMID:23851019

Indomethacin increases the formation of lipoxygenase products in calcium ionophore stimulated human neutrophils.

PubMed

Docherty, J C; Wilson, T W

1987-10-29

Arachidonic acid metabolism in human neutrophils stimulated in vitro with the calcium ionophore A23187 was studied using combined HPLC and radioimmunoassays. Indomethacin (0.1 and 1.0 microM) caused a 300% increase in LTB4 formation in neutrophils stimulated with A23187. 5-, 12- and 15-HETE levels were also increased. In the presence of exogenous arachidonic acid 1.0 microM Indomethacin caused a 37% increase in LTB4 formation. Acetyl Salicylic Acid and Ibuprofen had no effect on the formation of lipoxygenase metabolites. The effect of indomethacin on LTB4 formation does not appear to be due to a simple redirection of substrate arachidonic acid from the cyclooxygenase to the lipoxygenase pathways.

Substituting milk for apple juice does not increase kidney stone risk in most normocalciuric adults who form calcium oxalate stones.

PubMed

Massey, L K; Kynast-Gales, S A

1998-03-01

Increasing intake of dietary calcium from less than 400 mg to 800 mg daily may decrease the absorption of dietary oxalate, which in turn would decrease urinary oxalate excretion. The effect of substituting milk for apple juice on urine composition and risk of calcium oxalate precipitability was studied. Twenty-one normocalciuric adults with a history of at least 1 calcium oxalate stone and urinary oxalate excretion exceeding 275 micromol/day on their self-selected diet. Randomized crossover trial. Each participant consumed two moderate-oxalate (2,011 micromol/day) study diets, which were identical except that one contained 360 mL milk and the other contained 540 mL apple juice as the beverage with meals. Four days free-living then 2 days in the metabolic unit of a university nutrition department. Tiselius risk index for calcium oxalate precipitability calculated from urine composition. Paired t tests. Twenty-four hour urinary oxalate excretion was 18% lower (P<.0001) on the milk diet vs the juice diet: 423 vs 514 micromol, respectively. Calcium excretion was 17% higher (P<.05) on the milk vs juice diet: 4.7 vs 3.9 mmol, respectively. Urinary magnesium and citrate excretion, volume, and Tiselius risk index did not differ between diets. Substituting 360 mL milk daily for apple juice with meals in a diet containing moderate amounts of dietary oxalate from whole grains, legumes, fruits, and vegetables does not increase the risk index of calcium oxalate precipitability in most normocalciuric adults who form stones.

Slow wave contraction frequency plateaus in the small intestine are composed of discrete waves of interval increase associated with dislocations.

PubMed

Parsons, Sean P; Huizinga, Jan D

2018-06-03

What is the central question of this study? What is the nature of slow wave driven contraction frequency gradients in the small intestine? What is the main finding and its importance? Frequency plateaus are composed of discrete waves of increased interval, each wave associated with a contraction dislocation. Smooth frequency gradients are generated by localised neural modulation of wave frequency, leading to functionally important wave turbulence. Both patterns are emergent properties of a network of coupled oscillators, the interstitial cells of Cajal. A gut-wide network of interstitial cells of Cajal (ICC) generate electrical oscillations (slow waves) that orchestrate waves of muscle contraction. In the small intestine there is a gradient in slow wave frequency from high at the duodenum to low at the terminal ileum. Time-averaged measurements of frequency have suggested either a smooth or stepped (plateaued) gradient. We measured individual contraction intervals from diameter maps of the mouse small intestine to create interval maps (IMaps). IMaps showed that each frequency plateau was composed of discrete waves of increased interval. Each interval wave originated at a terminating contraction wave, a "dislocation", at the plateau's proximal boundary. In a model chain of coupled phase oscillators, interval wave frequency increased as coupling decreased or as the natural frequency gradient or noise increased. Injuring the intestine at a proximal point to destroy coupling, suppressed distal steps which then reappeared with gap junction block by carbenoxolone. This lent further support to our previous hypothesis that lines of dislocations were fixed by points of low coupling strength. Dislocations induced by electrical field pulses in the intestine and by equivalent phase shift in the model, were associated with interval waves. When the enteric nervous system was active, IMaps showed a chaotic, turbulent pattern of interval change with no frequency steps or plateaus

Calcium/calmodulin-dependent serine protein kinase CASK modulates the L-type calcium current.

PubMed

Nafzger, Sabine; Rougier, Jean-Sebastien

2017-01-01

The L-type voltage-gated calcium channel Ca v 1.2 mediates the calcium influx into cells upon membrane depolarization. The list of cardiopathies associated to Ca v 1.2 dysfunctions highlights the importance of this channel in cardiac physiology. Calcium/calmodulin-dependent serine protein kinase (CASK), expressed in cardiac cells, has been identified as a regulator of Ca v 2.2 channels in neurons, but no experiments have been performed to investigate its role in Ca v 1.2 regulation. Full length or the distal C-terminal truncated of the pore-forming Ca v 1.2 channel (Ca v 1.2α1c), both present in cardiac cells, were expressed in TsA-201 cells. In addition, a shRNA silencer, or scramble as negative control, of CASK was co-transfected in order to silence CASK endogenously expressed. Three days post-transfection, the barium current was increased only for the truncated form without alteration of the steady state activation and inactivation biophysical properties. The calcium current, however, was increased after CASK silencing with both types of Ca v 1.2α1c subunits suggesting that, in absence of calcium, the distal C-terminal counteracts the CASK effect. Biochemistry experiments did not reveals neither an alteration of Ca v 1.2 channel protein expression after CASK silencing nor an interaction between Ca v 1.2α1c subunits and CASK. Nevertheless, after CASK silencing, single calcium channel recordings have shown an increase of the voltage-gated calcium channel Ca v 1.2 open probability explaining the increase of the whole-cell current. This study suggests CASK as a novel regulator of Ca v 1.2 via a modulation of the voltage-gated calcium channel Ca v 1.2 open probability. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chamomile (Matricaria recutita L.) decoction extract inhibits in vitro intestinal glucose absorption and attenuates high fat diet-induced lipotoxicity and oxidative stress.

PubMed

Jabri, Mohamed-Amine; Sakly, Mohsen; Marzouki, Lamjed; Sebai, Hichem

2017-03-01

The present study aimed to investigate the inhibitory effect of chamomile decoction extract (CDE) on intestinal glucose absorption as well as its protective role against high fat diet (HFD)-induced obesity and lipotoxicity in rats. We used the Ussing chamber system to investigate the effect of CDE on intestinal transport of glucose. Male Wistar rats were fed HFD for six weeks to provoke obesity. CDE (100mg/kg, b.w. p.o.) has been per orally administered to HFD fed rats. Ex vivo, we found that CDE significantly and dose-dependently increased intestinal absorption of glucose. In vivo, HFD increased the body, liver and kidney weights, while CDE treatment showed a significant protective effects. High fat diet induced also a lipid profiles disorder and a disturbances in kidney and liver function parameters. Moreover liver and kidney lipotoxicity is accompanied by an oxidative stress status characterized by increased lipoperoxidation, depletion of antioxidant enzymes activity and non-enzymatic antioxidant (-SH groups and GSH) levels as well as increased levels of free iron, hydrogen peroxide (H 2 O 2 ) and calcium. However, treatment with CDE alleviated all the deleterious effects of HFD feed. These findings suggest that chamomile decoction extract can be used as functional beverage against obesity, hyperglycemia and hyperlipidemia. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Altered steady state pharmacokinetics of levofloxacin in adult cystic fibrosis patients receiving calcium carbonate.

PubMed

Pai, Manjunath P; Allen, Sarah E; Amsden, Guy W

2006-08-01

Levofloxacin is used in adult patients with cystic fibrosis but its pharmacokinetics is not well characterized in this population. Patients with cystic fibrosis use calcium routinely to prevent osteoporosis. A slower intestinal transit time is common in cystic fibrosis implying that the standard 2-h spacing of minerals and levofloxacin to prevent a chelation interaction may be insufficient. The objectives of this study were to characterize the steady state pharmacokinetics of oral levofloxacin 750 mg with and without 2-h spaced calcium carbonate in patients with cystic fibrosis compared to matched healthy volunteers. In an open-label, randomized, cross-over study of five patients with cystic fibrosis and five age, sex, race, and serum creatinine matched healthy volunteers received 750 mg of oral levofloxacin alone daily for 5 days and the same dose of levofloxacin with 2-h spaced calcium carbonate supplementation 500 mg po thrice daily with meals in random sequence. Blood was collected for plasma assay of levofloxacin pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, and 24h after the fifth levofloxacin dose. There was no significant interaction in healthy volunteers, however, when cystic fibrosis patients were given levofloxacin with 2-h spaced calcium, the maximum plasma concentration (Cmax) decreased by 19% and time to Cmax increased by 37% (p<0.05). This difference in peak concentrations resulted in a lack of bioequivalence (Cmax geometric mean ratio 81.6%, 90% confidence intervals: 71.8%, 91.4%) even when levofloxacin and calcium supplements were spaced by the standard 2h administration instruction in patients with cystic fibrosis. These results indicate that multivalent cations such as calcium should be maximally separated from oral levofloxacin administration in adult patients with cystic fibrosis to prevent this drug interaction, thereby better optimizing antibiotic efficacy and decreasing the potential for resistance development.

Calcium-dependent inactivation of calcium channels in cochlear hair cells of the chicken.

PubMed

Lee, Seunghwan; Briklin, Olga; Hiel, Hakim; Fuchs, Paul

2007-09-15

Voltage-gated calcium channels support both spontaneous and sound-evoked neurotransmitter release from ribbon synapses of cochlear hair cells. A variety of regulatory mechanisms must cooperate to ensure the appropriate level of activity in the restricted pool of synaptic calcium channels ( approximately 100) available to each synaptic ribbon. One potential feedback mechanism, calcium-dependent inactivation (CDI) of voltage-gated, L-type calcium channels, can be modulated by calmodulin-like calcium-binding proteins. CDI of voltage-gated calcium current was studied in hair cells of the chicken's basilar papilla (analogous to the mammalian cochlea) after blocking the predominant potassium conductances. For inactivating currents produced by 2.5 s steps to the peak of the current-voltage relation (1 mm EGTA internal calcium buffer), single exponential fits yielded an average decay time constant of 1.92 +/- 0.18 s (mean +/- s.e.m., n = 12) at 20-22 degrees C, while recovery occurred with a half-time of approximately 10 s. Inactivation produced no change in reversal potential, arguing that the observed relaxation did not result from alternative processes such as calcium accumulation or activation of residual potassium currents. Substitution of external calcium with barium greatly reduced inactivation, while inhibition of endoplasmic calcium pumps with t-benzohydroquinone (BHQ) or thapsigargin made inactivation occur faster and to a greater extent. Raising external calcium 10-fold (from 2 to 20 mm) increased peak current 3-fold, but did not alter the extent or time course of CDI. However, increasing levels of internal calcium buffer consistently reduced the rate and extent of inactivation. With 1 mm EGTA buffering and in 2 mm external calcium, the available pool of calcium channels was half-inactivated near the resting membrane potential (-50 mV). CDI may be further regulated by calmodulin-like calcium-binding proteins (CaBPs). mRNAs for several CaBPs are expressed in

[Adult intestinal malrotation associated with intestinal volvulus].

PubMed

Hernando-Almudí, Ernesto; Cerdán-Pascual, Rafael; Vallejo-Bernad, Cristina; Martín-Cuartero, Joaquín; Sánchez-Rubio, María; Casamayor-Franco, Carmen

Intestinal malrotation is a congenital anomaly of the intestinal rotation and fixation, and usually occurs in the neonatal age. Description of a clinical case associated with acute occlusive symptoms. A case of intestinal malrotation is presented in a previously asymptomatic woman of 46 years old with an intestinal obstruction, with radiology and surgical findings showing an absence of intestinal rotation. Intestinal malrotation in adults is often asymptomatic, and is diagnosed as a casual finding during a radiological examination performed for other reasons. Infrequently, it can be diagnosed in adults, associated with an acute abdomen. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Intestinal alkaline phosphatase deficiency leads to dysbiosis and bacterial translocation in the newborn intestine.

PubMed

Fawley, Jason; Koehler, Shannon; Cabrera, Susan; Lam, Vy; Fredrich, Katherine; Hessner, Martin; Salzman, Nita; Gourlay, David

2017-10-01

Intestinal alkaline phosphatase (IAP) has been shown to help maintain intestinal homeostasis. Decreased expression of IAP has been linked with pediatric intestinal diseases associated with bacterial overgrowth and subsequent inflammation. We hypothesize that the absence of IAP leads to dysbiosis, with increased inflammation and permeability of the newborn intestine. Sprague-Dawley heterozygote IAP cross-matches were bred. Pups were dam fed ad lib and euthanized at weaning. The microbiotas of terminal ileum (TI) and colon was determined by quantitative real-time polymerase chain reaction (qRT-PCR) of subphylum-specific bacterial 16S ribosomal RNA. RT-PCR was performed on TI for inflammatory cytokines. Intestinal permeability was quantified by fluorescein isothiocyanate-dextran permeability and bacterial translocation by qRT-PCR for bacterial 16S ribosomal RNA in mesenteric lymph nodes. Statistical analysis was done by chi-square analysis. All three genotypes had similar concentrations of bacteria in the TI and colon. However, IAP knockout (IAP-KO) had significantly decreased diversity of bacterial species in their colonic stool compared with heterozygous and wild-type (WT). IAP-KO pups had a nonstatistically significant 3.9-fold increased inducible nitric oxide synthase messenger RNA expression compared with WT (IAP-KO, 3.92 ± 1.36; WT, 1.0 ± 0.27; P = 0.03). IAP-KO also had significantly increased bacterial translocation to mesenteric lymph nodes occurred in IAP-KO (IAP-KO, 7625 RFU/g ± 3469; WT, 4957 RFU/g ± 1552; P = 0.04). Furthermore, IAP-KO had increased permeability (IAP-KO, 0.297 mg/mL ± 0.2; WT, 0.189 mg/mL ± 0.15 P = 0.07), but was not statistically significant. Deficiency of IAP in the newborn intestine is associated with dysbiosis and increased inflammation, permeability, and bacterial translocation. Copyright © 2017 Elsevier Inc. All rights reserved.

Requirement for digestible calcium by eleven- to twenty-five-kilogram pigs as determined by growth performance, bone ash concentration, calcium and phosphorus balances, and expression of genes involved in transport of calcium in intestinal and kidney cells.

PubMed

González-Vega, J C; Liu, Y; McCann, J C; Walk, C L; Loor, J J; Stein, H H

2016-08-01

Two experiments were conducted to determine the requirement for standardized total tract digestible (STTD) Ca by 11- to 25-kg pigs based on growth performance, bone ash, or Ca and P retention and to determine the effect of dietary Ca on expression of genes related to Ca transport in the jejunum and kidneys. Six diets were formulated to contain 0.36% STTD P and 0.32, 0.40, 0.48, 0.56, 0.64, or 0.72% STTD Ca by including increasing quantities of calcium carbonate in the diets at the expense of cornstarch. Two additional diets contained 0.72% STTD Ca and 0.33% or 0.40% STTD P to determine if 0.36% STTD P had negative effects on the Ca requirement. The same batch of all diets was used in both experiments. In Exp. 1, 256 pigs (11.39 ± 1.21 kg initial BW) were randomly allotted to the 8 diets with 4 pigs per pen and 8 replicate pens per diet in a randomized complete block design. On the last day of the experiment, 1 pig from each pen was euthanized and the right femur and intestine and kidney samples were collected. Results indicated that ADG and G:F started to decline (linear and quadratic, < 0.05) at 0.54 and 0.50% STTD Ca, respectively. In contrast, bone ash increased (quadratic, < 0.05) as dietary Ca increased and reached a plateau indicating that the requirement for STTD Ca to maximize bone ash was 0.48%. Bone ash, but not ADG or G:F, increased (linear, < 0.01) as STTD increased in the diets. The mRNA expression of genes related to transcellular Ca transport decreased (linear, < 0.01) in the jejunum and in kidneys (linear and quadratic, < 0.01) as dietary Ca increased. In Exp. 2, 80 pigs (13.12 ± 1.79 kg initial BW) were placed in metabolism crates and randomly allotted to the 8 diets with 10 replicate pigs per diet in a randomized complete block design. Fecal and urine samples were collected using the marker-to-marker approach. Results indicated that the requirement for STTD Ca to maximize Ca and P retention (g/d) was 0.60 and 0.49%, respectively. In conclusion

Calcium feedback mechanisms regulate oscillatory activity of a TRP-like Ca2+ conductance in C. elegans intestinal cells

PubMed Central

Estevez, Ana Y; Strange, Kevin

2005-01-01

Inositol-1,4,5-trisphosphate (IP3)-dependent Ca2+ oscillations in Caenorhabditis elegans intestinal epithelial cells regulate the nematode defecation cycle. The role of plasma membrane ion channels in intestinal cell oscillatory Ca2+ signalling is unknown. We have shown previously that cultured intestinal cells express a Ca2+-selective conductance, IORCa, that is biophysically similar to TRPM7 currents. IORCa activates slowly and stabilizes when cells are patch clamped with pipette solutions containing 10 mm BAPTA and free Ca2+ concentrations of ∼17 nm. However, when BAPTA concentration is lowered to 1 mm, IORCa oscillates. Oscillations in channel activity induced simultaneous oscillations in cytoplasmic Ca2+ levels. Removal of extracellular Ca2+ inhibited IORCa oscillations, whereas readdition of Ca2+ to the bath caused a rapid and transient reactivation of the current. Experimental manoeuvres that elevated intracellular Ca2+ blocked current oscillations. Elevation of intracellular Ca2+ in the presence of 10 mm BAPTA to block IORCa oscillations led to a dose-dependent increase in the rate of current activation. At intracellular Ca2+ concentrations of 250 nm, current activation was transient. Patch pipette solutions buffered with 1–4 mm of either BAPTA or EGTA gave rise to similar patterns of IORCa oscillations. We conclude that changes in Ca2+ concentration close to the intracellular opening of the channel pore regulate channel activity. Low concentrations of Ca2+ activate the channel. As Ca2+ enters and accumulates near the pore mouth, channel activity is inhibited. Oscillating plasma membrane Ca2+ entry may play a role in generating intracellular Ca2+ oscillations that regulate the C. elegans defecation rhythm. PMID:15961418

Examining urea flux across the intestine of the spiny dogfish, Squalus acanthias.

PubMed

Gary Anderson, W; McCabe, Chris; Brandt, Catherine; Wood, Chris M

2015-03-01

Recent examination of urea flux in the intestine of the spiny dogfish shark, Squalus acanthias, has shown that feeding significantly enhances urea uptake across the intestine, and this was significantly inhibited following mucosal addition of phloretin. The present study examined potential mechanisms of urea uptake across the dogfish intestine in starved and fed dogfish. Unidirectional flux chambers were used to examine the kinetics of urea uptake, and to determine the influence of sodium, ouabain, competitive urea analogues, and phloretin on urea uptake across the gut of fed dogfish. Intestinal epithelial preparations from starved and fed dogfish were mounted in Ussing chambers to examine the effect of phloretin on bidirectional solute transport across the intestine. In the unidirectional studies, the maximum uptake rate of urea was found to be 35.3±6.9 μmol.cm(-2).h(-1) and Km was found to be 291.8±9.6 mM in fed fish, and there was a mild inhibition of urea uptake following mucosal addition of competitive agonists. Addition of phloretin, Na-free Ringers and ouabain to the mucosal side of intestinal epithelia also led to a significant reduction in urea uptake in fed fish. In the Ussing chamber studies there was a net influx of urea in fed fish and a small insignificant efflux in starved fish. Addition of phloretin blocked urea uptake in fed fish when added to the mucosal side. Furthermore, phloretin had no effect on ion transport across the intestinal epithelia with the exception of the divalent cations, magnesium and calcium. Copyright © 2015 Elsevier Inc. All rights reserved.

Age-related changes in the response of intestinal cells to 1α,25(OH)2-vitamin D3.

PubMed

Gonzalez Pardo, Verónica; Russo de Boland, Ana

2013-01-01

The hormonally active form of vitamin D(3), 1α,25(OH)(2)-vitamin D(3), acts in intestine, its major target tissue, where its actions are of regulatory and developmental importance: regulation of intracellular calcium through modulation of second messengers and activation of mitogenic cascades leading to cell proliferation. Several causes have been postulated to modify the hormone response in intestinal cells with ageing, among them, alterations of vitamin D receptor (VDR) levels and binding sites, reduced expression of G-proteins and hormone signal transduction changes. The current review summarizes the actual knowledge regarding the molecular and biochemical basis of age-impaired 1α,25(OH)(2)-vitamin D(3) receptor-mediated signaling in intestinal cells. A fundamental understanding why the hormone functions are impaired with age will enhance our knowledge of its importance in intestinal cell physiology. Copyright © 2012 Elsevier B.V. All rights reserved.

Regulating intestinal function to reduce atherogenic lipoproteins.

PubMed

Hussain, M Mahmood; Leung, Tung Ming; Zhou, Liye; Abu-Merhi, Sarah

2013-08-01

Significant knowledge regarding different molecules involved in the transport of dietary fat into the circulation has been garnered. Studies point to the possibility that accumulation of intestine-derived lipoproteins in the plasma could contribute to atherosclerosis. This article provides a brief overview of dietary lipid metabolism and studies in mice supporting the hypothesis that intestinal lipoproteins contribute to atherosclerosis. Deficiencies in lipoprotein lipase and Gpihbp1, and overexpression of heparanse in mice, are associated with increases in atherosclerosis, suggesting that defects in catabolism of larger lipoproteins in the plasma contribute to atherosclerosis. Furthermore, inositol-requiring enzyme 1β-deficient mice that produce more intestinal lipoproteins also develop more atherosclerosis. Thus, increases in plasma intestinal lipoproteins due to either overproduction or reduced catabolism result in augmented atherosclerosis. Intestinal lipoproteins tend to adhere strongly to subendothelial proteoglycans, elicit an inflammatory response by endothelial cells and activate macrophages, contributing to the initiation and progression of the disease. Thus, molecules that reduce intestinal lipid absorption can be useful in lowering atherosclerosis.

Growth hormone favorably affects bone turnover and bone mineral density in patients with short bowel syndrome undergoing intestinal rehabilitation.

PubMed

Tangpricha, Vin; Luo, Menghua; Fernández-Estívariz, Concepción; Gu, Li H; Bazargan, Niloofar; Klapproth, Jan-Michael; Sitaraman, Shanthi V; Galloway, John R; Leader, Lorraine M; Ziegler, Thomas R

2006-01-01

Patients with short bowel syndrome (SBS) have a high prevalence of metabolic bone disease due to nutrient malabsorption and potential effects of parenteral nutrition (PN). Human growth hormone (hGH) has been shown in some studies to have anabolic effects on bone, but hGH effects on bone in patients with SBS are unknown. Adults with PN-dependent SBS underwent a 7-day period of baseline studies while receiving usual oral diet and PN and then began receiving modified diets designed to improve nutrient absorption and daily oral calcium/vitamin D supplements (1500 mg elemental calcium and 600 IU vitamin D, respectively). Subjects were randomized to receive in a double-blind manner either subcutaneous (sc) saline placebo as the control or hGH (0.1 mg/kg/d for 3 weeks, then 0.1 mg/kg 3 days a week for 8 subsequent weeks). Open-label hGH was given from week 13 to week 24 in subjects who required PN after completion of the 12-week double-blind phase. Markers of bone turnover (serum osteocalcin and urinary N-telopeptide [NTX]), vitamin D nutriture (serum calcium, 25-hydroxyvitamin D [25-OH D] and parathyroid hormone [PTH] concentrations), and intestinal calcium absorption were measured at baseline and at weeks 4 and 12. Dual x-ray absorptiometry (DXA) of the hip and spine was performed to determine bone mineral density (BMD) at baseline and weeks 12 and 24. The majority of subjects in each group exhibited evidence of vitamin D deficiency at baseline (25-OH D levels<30 ng/mL; 78% and 79% of control and hGH-treated subjects, respectively). Subjects treated with hGH demonstrated a significant increase from baseline in serum osteocalcin levels at 12 weeks (+62%; p<.05). The levels of NTX were increased over time in the hGH-treated group; however, this did not reach statistical significance. Both NTX and osteocalcin remained unchanged in control subjects. BMD of the spine and total hip was unchanged in subjects treated with placebo or hGH at 24 weeks. However, femoral neck BMD

Calcium balance in mature male rats with unloaded hindlimbs

NASA Technical Reports Server (NTRS)

Navidi, Meena; Evans, Juliann; Wolinsky, Ira; Arnaud, Sara B.

2004-01-01

BACKGROUND: Calcium balances, regulated by the calcium endocrine system, are negative during spaceflight but have not been reported in flight simulation models using fully mature small animals. METHODS: We conducted two calcium (Ca) balance studies in 6-mo-old male rats exposed to a model that unloads the hindlimbs (HU) for 4 wk. Control (C) and HU rats were fed diets with 0.5% Ca in the first and 0.1% Ca in the second study. Housing in metabolic cages enabled daily food and water intake measurements as well as collections of urine and fecal specimens. At necropsy, blood was obtained for measures of Ca-regulating hormones. RESULTS: Both C and HU rats adjusted to housing and diets with decreases in body weight and negative Ca balances during the first week of each experiment. Thereafter, averages of Ca balances were more negative in the unloaded rats than controls: -8.1 vs. -1.6 mg x d(-1) in rats fed 0.5% (p < 0.05). This difference was not due to urinary Ca excretion since it was lower in HU than C rats (1.27 +/- 0.51 mg x d(-1) vs. 2.35 +/- 0.82 mg x d(-1), p < 0.05). Fecal Ca in HU rats exceeded dietary Ca by 4-7%, Restricting dietary Ca to 0.1% was followed by an increase in serum 1,25-dihydroxyvitamin D (1,25-D) and greater intestinal Ca absorption than in rats fed 0.5% Ca. Ca balances in rats fed 0.1% Ca were also more negative in HU than C rats (-2.4 vs. -0.03 mg x d(-1), p < 0.05). Parathyroid hormone (PTH) was suppressed and 1,25-D increased in HU rats fed 0.5% Ca. C rats fed 0.1% Ca had increased PTH and 1,25-D was the same as in the HU group. CONCLUSION: After adaptation, Ca balances were more negative in mature male rats with unloaded hindlimbs than controls, an effect from increased secretion and loss of endogenous fecal Ca associated with increased 1,25-D in Ca-replete and Ca-restricted rats.

Immunoglobulin Fc gamma receptor promotes immunoglobulin uptake, immunoglobulin-mediated calcium increase, and neurotransmitter release in motor neurons

NASA Technical Reports Server (NTRS)

Mohamed, Habib A.; Mosier, Dennis R.; Zou, Ling L.; Siklos, Laszlo; Alexianu, Maria E.; Engelhardt, Jozsef I.; Beers, David R.; Le, Wei-dong; Appel, Stanley H.

2002-01-01

Receptors for the Fc portion of immunoglobulin G (IgG; FcgammaRs) facilitate IgG uptake by effector cells as well as cellular responses initiated by IgG binding. In earlier studies, we demonstrated that amyotrophic lateral sclerosis (ALS) patient IgG can be taken up by motor neuron terminals and transported retrogradely to the cell body and can alter the function of neuromuscular synapses, such as increasing intracellular calcium and spontaneous transmitter release from motor axon terminals after passive transfer. In the present study, we examined whether FcgammaR-mediated processes can contribute to these effects of ALS patient immunoglobulins. F(ab')(2) fragments (which lack the Fc portion) of ALS patient IgG were not taken up by motor axon terminals and were not retrogradely transported. Furthermore, in a genetically modified mouse lacking the gamma subunit of the FcR, the uptake of whole ALS IgG and its ability to enhance intracellular calcium and acetylcholine release were markedly attenuated. These data suggest that FcgammaRs appear to participate in IgG uptake into motor neurons as well as IgG-mediated increases in intracellular calcium and acetylcholine release from motor axon terminals. Copyright 2002 Wiley-Liss, Inc.

CD4 T Cells and Major Histocompatibility Complex Class II Expression Influence Worm Expulsion and Increased Intestinal Muscle Contraction during Trichinella spiralis Infection

PubMed Central

Vallance, Bruce A.; Galeazzi, Francesca; Collins, Stephen M.; Snider, Denis P.

1999-01-01

Expulsion of intestinal nematode parasites and the associated increased contraction by intestinal muscle are T cell dependent, since both are attenuated in athymic rodents. The CD4 T-cell subset has been strongly associated with worm expulsion; however, the relationship between these cells, antigen presentation, and worm expulsion is not definitive and the role of these factors in intestinal muscle hypercontractility has not been defined. We infected C57BL/6, athymic, CD4-deficient, CD8α-deficient, and major histocompatibility complex class II (MHC II)-deficient (C2d) mice with Trichinella spiralis larvae. We examined intestinal worm numbers, longitudinal muscle contraction, and MHC II expression. Numerous MHC II-positive cells were identified within the muscularis externa of infected but not uninfected C57BL/6 mice. C57BL/6 and CD8α-deficient mice developed large increases in muscle contraction, expelling the parasite by day 21. Athymic and C2d mice exhibited much smaller increases in muscle contraction and delayed parasite expulsion. CD4-deficient mice exhibited intermediate levels of muscle contraction and delayed parasite expulsion. To further examine the role of MHC II and CD4 T cells, we irradiated C2d mice and reconstituted them with C57BL/6 bone marrow alone or with C57BL/6 CD4 T cells. C57BL/6 bone marrow alone did not affect muscle function or worm expulsion in recipient C2d mice. Partial CD4 T-cell reconstitution was sufficient to restore increased muscle contraction but not worm expulsion. Thus, hematopoietic MHC II expression alone is insufficient for the development of muscle hypercontractility and worm expulsion, but the addition of even small numbers of CD4 T cells was sufficient to induce intestinal muscle pathophysiology. PMID:10531271

Dietary glutamine prevents the loss of intestinal barrier function and attenuates the increase in core body temperature induced by acute heat exposure.

PubMed

Soares, Anne D N; Costa, Kátia A; Wanner, Samuel P; Santos, Rosana G C; Fernandes, Simone O A; Martins, Flaviano S; Nicoli, Jacques R; Coimbra, Cândido C; Cardoso, Valbert N

2014-11-28

Dietary glutamine (Gln) supplementation improves intestinal function in several stressful conditions. Therefore, in the present study, the effects of dietary Gln supplementation on the core body temperature (T core), bacterial translocation (BT) and intestinal permeability of mice subjected to acute heat stress were evaluated. Male Swiss mice (4 weeks old) were implanted with an abdominal temperature sensor and randomly assigned to one of the following groups fed isoenergetic and isoproteic diets for 7 d before the experimental trials: group fed the standard AIN-93G diet and exposed to a high ambient temperature (39°C) for 2 h (H-NS); group fed the AIN-93G diet supplemented with l-Gln and exposed to a high temperature (H-Gln); group fed the standard AIN-93G diet and not exposed to a high temperature (control, C-NS). Mice were orally administered diethylenetriaminepentaacetic acid radiolabelled with technetium (99mTc) for the assessment of intestinal permeability or 99mTc-Escherichia coli for the assessment of BT. Heat exposure increased T core (approximately 41°C during the experimental trial), intestinal permeability and BT to the blood and liver (3 h after the experimental trial) in mice from the H-NS group relative to those from the C-NS group. Dietary Gln supplementation attenuated hyperthermia and prevented the increases in intestinal permeability and BT induced by heat exposure. No correlations were observed between the improvements in gastrointestinal function and the attenuation of hyperthermia by Gln. Our findings indicate that dietary Gln supplementation preserved the integrity of the intestinal barrier and reduced the severity of hyperthermia during heat exposure. The findings also indicate that these Gln-mediated effects occurred through independent mechanisms.

The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogawa, Eiichi; Hosokawa, Masaya; Faculty of Human Sciences, Tezukayama Gakuin University, Osaka

2011-01-07

Research highlights: {yields} Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. {yields} Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. {yields} The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic {beta} cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucosemore » absorption in vivo was measured by single-pass perfusion method. Incorporation of [{sup 14}C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [{sup 14}C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a

Cholinergic signaling inhibits oxalate transport by human intestinal T84 cells

PubMed Central

Cheng, Ming; Aronson, Peter S.

2012-01-01

Urolithiasis remains a very common disease in Western countries. Seventy to eighty percent of kidney stones are composed of calcium oxalate, and minor changes in urinary oxalate affect stone risk. Intestinal oxalate secretion mediated by anion exchanger SLC26A6 plays a major constitutive role in limiting net absorption of ingested oxalate, thereby preventing hyperoxaluria and calcium oxalate urolithiasis. Using the relatively selective PKC-δ inhibitor rottlerin, we had previously found that PKC-δ activation inhibits Slc26a6 activity in mouse duodenal tissue. To identify a model system to study physiologic agonists upstream of PKC-δ, we characterized the human intestinal cell line T84. Knockdown studies demonstrated that endogenous SLC26A6 mediates most of the oxalate transport by T84 cells. Cholinergic stimulation with carbachol modulates intestinal ion transport through signaling pathways including PKC activation. We therefore examined whether carbachol affects oxalate transport in T84 cells. We found that carbachol significantly inhibited oxalate transport by T84 cells, an effect blocked by rottlerin. Carbachol also led to significant translocation of PKC-δ from the cytosol to the membrane of T84 cells. Using pharmacological inhibitors, we observed that carbachol inhibits oxalate transport through the M3 muscarinic receptor and phospholipase C. Utilizing the Src inhibitor PP2 and phosphorylation studies, we found that the observed regulation downstream of PKC-δ is partially mediated by c-Src. Biotinylation studies revealed that carbachol inhibits oxalate transport by reducing SLC26A6 surface expression. We conclude that carbachol negatively regulates oxalate transport by reducing SLC26A6 surface expression in T84 cells through signaling pathways including the M3 muscarinic receptor, phospholipase C, PKC-δ, and c-Src. PMID:21956166

In vitro investigation of intestinal transport mechanism of silicon, supplied as orthosilicic acid-vanillin complex.

PubMed

Sergent, Thérèse; Croizet, Karine; Schneider, Yves-Jacques

2017-02-01

Silicon (Si) is one of the most abundant trace elements in the body. Although pharmacokinetics data described its absorption from the diet and its body excretion, the mechanisms involved in the uptake and transport of Si across the gut wall have not been established. Caco-2 cells were used as a well-accepted in vitro model of the human intestinal epithelium to investigate the transport, across the intestinal barrier in both the absorption and excretion directions, of Si supplied as orthosilicic acid stabilized by vanillin complex (OSA-VC). The transport of this species was found proportional to the initial concentration and to the duration of incubation, with absorption and excretion mean rates similar to those of Lucifer yellow, a marker of paracellular diffusion, and increasing in the presence of EGTA, a chelator of divalents cations including calcium. A cellular accumulation of Si, polarized from the apical side of cells, was furthermore detected. These results provide evidence that Si, ingested as a food supplement containing OSA-VC, crosses the intestinal mucosa by passive diffusion via the paracellular pathway through the intercellular tight junctions and accumulates intracellularly, probably by an uptake mechanism of facilitated diffusion. This study can help to further understand the kinetic of absorption of Si. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterisation of Fecal Soap Fatty Acids, Calcium Contents, Bacterial Community and Short-Chain Fatty Acids in Sprague Dawley Rats Fed with Different sn-2 Palmitic Triacylglycerols Diets.

PubMed

Wan, Jianchun; Hu, Songyou; Ni, Kefeng; Chang, Guifang; Sun, Xiangjun; Yu, Liangli

2016-01-01

The structure of dietary triacylglycerols is thought to influence fatty acid and calcium absorption, as well as intestinal microbiota population of the host. In the present study, we investigated the impact of palmitic acid (PA) esterified at the sn-2 position on absorption of fatty acid and calcium and composition of intestinal microorganisms in rats fed high-fat diets containing either low sn-2 PA (12.1%), medium sn-2 PA (40.4%) or high sn-2 PA (56.3%), respectively. Fecal fatty acid profiles in the soaps were measured by gas chromatography (GC), while fecal calcium concentration was detected by ICP-MS. The fecal microbial composition was assessed using a 16S rRNA high-throughput sequencing technology and fecal short-chain fatty acids were detected by ion chromatograph. Dietary supplementation with a high sn-2 PA fat significantly reduced total fecal contents of fatty acids soap and calcium compared with the medium or low sn-2 PA fat groups. Diet supplementation with sn-2 PA fat did not change the entire profile of the gut microbiota community at phylum level and the difference at genera level also were minimal in the three treatment groups. However, high sn-2 PA fat diet could potentially improve total short-chain fatty acids content in the feces, suggesting that high dietary sn-2 PA fat might have a beneficial effect on host intestinal health.

Calsequestrin mediates changes in spontaneous calcium release profiles.

PubMed

Tania, Nessy; Keener, James P

2010-08-07

Calsequestrin (CSQ) is the primary calcium buffer within the sarcoplasmic reticulum (SR) of cardiac cells. It has also been identified as a regulator of Ryanodine receptor (RyR) calcium release channels by serving as a SR luminal sensor. When calsequestrin is free and unbound to calcium, it can bind to RyR and desensitize the channel from cytoplasmic calcium activation. In this paper, we study the role of CSQ as a buffer and RyR luminal sensor using a mechanistic model of RyR-CSQ interaction. By using various asymptotic approximations and mean first exit time calculation, we derive a minimal model of a calcium release unit which includes CSQ dependence. Using this model, we then analyze the effect of changing CSQ expression on the calcium release profile and the rate of spontaneous calcium release. We show that because of its buffering capability, increasing CSQ increases the spark duration and size. However, because of luminal sensing effects, increasing CSQ depresses the basal spark rate and increases the critical SR level for calcium release termination. Finally, we show that with increased bulk cytoplasmic calcium concentration, the CRU model exhibits deterministic oscillations.

Risk of calcium oxalate nephrolithiasis in postmenopausal women supplemented with calcium or combined calcium and estrogen.

PubMed

Domrongkitchaiporn, Somnuek; Ongphiphadhanakul, Boonsong; Stitchantrakul, Wasana; Chansirikarn, Sirinthorn; Puavilai, Gobchai; Rajatanavin, Rajata

2002-02-26

AP(CaOx): 1.1 +/- 0.1 vs. 1.3 +/- 0.2 for group A and 1.2 +/- 0.2 vs. 1.1 +/- 0.1 for group B. There were eight and nine patients with high AP(CaOx), or >2, at baseline and after treatment, respectively. Calcium supplement with a meal or combined calcium supplement and estrogen therapy is not associated with a significant increased risk of calcium oxalate stone formation in the majority of postmenopausal osteoporotic patients. Determination of urinary saturation for calcium oxalate after calcium and estrogen supplements, especially at the initial phase of treatment, may be helpful in the avoidance of nephrolithiasis.

Dysbalance of Astrocyte Calcium under Hyperammonemic Conditions

PubMed Central

Haack, Nicole; Dublin, Pavel; Rose, Christine R.

2014-01-01

Increased brain ammonium (NH4 +/NH3) plays a central role in the manifestation of hepatic encephalopathy (HE), a complex syndrome associated with neurological and psychiatric alterations, which is primarily a disorder of astrocytes. Here, we analysed the influence of NH4 +/NH3 on the calcium concentration of astrocytes in situ and studied the underlying mechanisms of NH4 +/NH3-evoked calcium changes, employing fluorescence imaging with Fura-2 in acute tissue slices derived from different regions of the mouse brain. In the hippocampal stratum radiatum, perfusion with 5 mM NH4 +/NH3 for 30 minutes caused a transient calcium increase in about 40% of astrocytes lasting about 10 minutes. Furthermore, the vast majority of astrocytes (∼90%) experienced a persistent calcium increase by ∼50 nM. This persistent increase was already evoked at concentrations of 1–2 mM NH4 +/NH3, developed within 10–20 minutes and was maintained as long as the NH4 +/NH3 was present. Qualitatively similar changes were observed in astrocytes of different neocortical regions as well as in cerebellar Bergmann glia. Inhibition of glutamine synthetase resulted in significantly larger calcium increases in response to NH4 +/NH3, indicating that glutamine accumulation was not a primary cause. Calcium increases were not mimicked by changes in intracellular pH. Pharmacological inhibition of voltage-gated sodium channels, sodium-potassium-chloride-cotransporters (NKCC), the reverse mode of sodium/calcium exchange (NCX), AMPA- or mGluR5-receptors did not dampen NH4 +/NH3-induced calcium increases. They were, however, significantly reduced by inhibition of NMDA receptors and depletion of intracellular calcium stores. Taken together, our measurements show that sustained exposure to NH4 +/NH3 causes a sustained increase in intracellular calcium in astrocytes in situ, which is partly dependent on NMDA receptor activation and on release of calcium from intracellular stores. Our study furthermore suggests

Calcium-dependent inactivation of calcium channels in cochlear hair cells of the chicken

PubMed Central

Lee, Seunghwan; Briklin, Olga; Hiel, Hakim; Fuchs, Paul

2007-01-01

Voltage-gated calcium channels support both spontaneous and sound-evoked neurotransmitter release from ribbon synapses of cochlear hair cells. A variety of regulatory mechanisms must cooperate to ensure the appropriate level of activity in the restricted pool of synaptic calcium channels (∼100) available to each synaptic ribbon. One potential feedback mechanism, calcium-dependent inactivation (CDI) of voltage-gated, L-type calcium channels, can be modulated by calmodulin-like calcium-binding proteins. CDI of voltage-gated calcium current was studied in hair cells of the chicken's basilar papilla (analogous to the mammalian cochlea) after blocking the predominant potassium conductances. For inactivating currents produced by 2.5 s steps to the peak of the current–voltage relation (1 mm EGTA internal calcium buffer), single exponential fits yielded an average decay time constant of 1.92 ± 0.18 s (mean ±s.e.m., n = 12) at 20–22°C, while recovery occurred with a half-time of ∼10 s. Inactivation produced no change in reversal potential, arguing that the observed relaxation did not result from alternative processes such as calcium accumulation or activation of residual potassium currents. Substitution of external calcium with barium greatly reduced inactivation, while inhibition of endoplasmic calcium pumps with t-benzohydroquinone (BHQ) or thapsigargin made inactivation occur faster and to a greater extent. Raising external calcium 10-fold (from 2 to 20 mm) increased peak current 3-fold, but did not alter the extent or time course of CDI. However, increasing levels of internal calcium buffer consistently reduced the rate and extent of inactivation. With 1 mm EGTA buffering and in 2 mm external calcium, the available pool of calcium channels was half-inactivated near the resting membrane potential (−50 mV). CDI may be further regulated by calmodulin-like calcium-binding proteins (CaBPs). mRNAs for several CaBPs are expressed in chicken cochlear tissue, and

Surface characteristics of anodized and hydrothermally treated titatnium with an increasing concentration of calcium ion

NASA Astrophysics Data System (ADS)

Park, Il Song; Bae, Tae Sung; Seol, Kyeong Won

2006-10-01

Titanium is widely used as an implant material due to its good mechanical properties and the excellent biocompatibility of the oxide film on the surface. To modify the unstable oxide surface of pure titanium, plasma electrolytic oxidation was applied in this study. The electrolyte used for anodizing was a mixture of GP (glycerophosphate disodium salt) and CA (calcium acetate). In addition, a hydrothermal treatment was performed to precipitate a calcium phosphate crystal on the titanium oxide layer for bioactivity. The effect of the CA concentration of the electrolyte on the surface of titanium was investigated, with CA concentrations at 0.1 M, 0.2 M, and 0.3 M. A high concentration of CA results in a low breakdown voltage; hence many large micropores were formed on the anodized surface. Moreover, the size of the HA crystals was more minute in proportion to the increasing concentration of CA. The crystal phase of titanium dioxide was mainly anatase, and a rutile phase was also observed. As the size and/or amount of HA crystals increased, the surface roughness increased. However, the surface roughness could be decreased by fully and uniformly covering the surface with HA crystals. The corrosion resistance in the saline solution was increased by anodic spark oxidation. In addition, it was slightly increased by a hydrothermal treatment. It is considered that a more stable and thicker titanium oxide layer is formed by anodic oxidation and a hydrothermal treatment.

Deficient ryanodine receptor S-nitrosylation increases sarcoplasmic reticulum calcium leak and arrhythmogenesis in cardiomyocytes.

PubMed

Gonzalez, Daniel R; Beigi, Farideh; Treuer, Adriana V; Hare, Joshua M

2007-12-18

Altered Ca(2+) homeostasis is a salient feature of heart disease, where the calcium release channel ryanodine receptor (RyR) plays a major role. Accumulating data support the notion that neuronal nitric oxide synthase (NOS1) regulates the cardiac RyR via S-nitrosylation. We tested the hypothesis that NOS1 deficiency impairs RyR S-nitrosylation, leading to altered Ca(2+) homeostasis. Diastolic Ca(2+) levels are elevated in NOS1(-/-) and NOS1/NOS3(-/-) but not NOS3(-/-) myocytes compared with wild-type (WT), suggesting diastolic Ca(2+) leakage. Measured leak was increased in NOS1(-/-) and NOS1/NOS3(-/-) but not in NOS3(-/-) myocytes compared with WT. Importantly, NOS1(-/-) and NOS1/NOS3(-/-) myocytes also exhibited spontaneous calcium waves. Whereas the stoichiometry and binding of FK-binding protein 12.6 to RyR and the degree of RyR phosphorylation were not altered in NOS1(-/-) hearts, RyR2 S-nitrosylation was substantially decreased, and the level of thiol oxidation increased. Together, these findings demonstrate that NOS1 deficiency causes RyR2 hyponitrosylation, leading to diastolic Ca(2+) leak and a proarrhythmic phenotype. NOS1 dysregulation may be a proximate cause of key phenotypes associated with heart disease.

Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kosmidis, Georgios; Bellin, Milena; Ribeiro, Marcelo C.

One limitation in using human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) for disease modeling and cardiac safety pharmacology is their immature functional phenotype compared with adult cardiomyocytes. Here, we report that treatment of human embryonic stem cell derived cardiomyocytes (hESC-CMs) with dexamethasone, a synthetic glucocorticoid, activated glucocorticoid signaling which in turn improved their calcium handling properties and contractility. L-type calcium current and action potential properties were not affected by dexamethasone but significantly faster calcium decay, increased forces of contraction and sarcomeric lengths, were observed in hESC-CMs after dexamethasone exposure. Activating the glucocorticoid pathway can thus contribute to mediating hPSC-CMs maturation.more » - Highlights: • Dexamethasone accelerates Ca{sup 2+} transient decay in hESC-CMs. • Dexamethasone enhances SERCA and NCX function in hESC-CMs. • Dexamethasone increases force of contraction and sarcomere length in hESC-CMs. • Dexamethasone does not alter I{sub Ca,L} and action potential characteristics in hESC-CMs.« less

Intestinal permeability in a patient with liver cirrhosis

PubMed Central

Aguirre Valadez, Jonathan Manuel; Rivera-Espinosa, Liliana; Méndez-Guerrero, Osvely; Chávez-Pacheco, Juan Luis; García Juárez, Ignacio; Torre, Aldo

2016-01-01

Liver cirrhosis is a worldwide public health problem, and patients with this disease are at high risk of developing complications, bacterial translocation from the intestinal lumen to the mesenteric nodes, and systemic circulation, resulting in the development of severe complications related to high mortality rate. The intestinal barrier is a structure with a physical and biochemical activity to maintain balance between the external environment, including bacteria and their products, and the internal environment. Patients with liver cirrhosis develop a series of alterations in different components of the intestinal barrier directly associated with the severity of liver disease that finally increased intestinal permeability. A “leaky gut” is an effect produced by damaged intestinal barrier; alterations in the function of tight junction proteins are related to bacterial translocation and their products. Instead, increasing serum proinflammatory cytokines and hemodynamics modification, which results in the appearance of complications of liver cirrhosis such as hepatic encephalopathy, variceal hemorrhage, bacterial spontaneous peritonitis, and hepatorenal syndrome. The intestinal microbiota plays a fundamental role in maintaining the proper function of the intestinal barrier; bacterial overgrowth and dysbiosis are two phenomena often present in people with liver cirrhosis favoring bacterial translocation. Increased intestinal permeability has an important role in the genesis of these complications, and treating it could be the base for prevention and partial treatment of these complications. PMID:27920543

Soluble Corn Fiber Increases Calcium Absorption Associated with Shifts in the Gut Microbiome: A Randomized Dose-Response Trial in Free-Living Pubertal Females.

PubMed

Whisner, Corrie M; Martin, Berdine R; Nakatsu, Cindy H; Story, Jon A; MacDonald-Clarke, Claire J; McCabe, Linda D; McCabe, George P; Weaver, Connie M

2016-07-01

Soluble corn fiber (SCF; 12 g fiber/d) is shown to increase calcium absorption efficiency, associated with shifts in the gut microbiota in adolescent males and females who participated in a controlled feeding study. We evaluated the dose response of 0, 10, and 20 g fiber/d delivered by PROMITOR SCF 85 (85% fiber) on calcium absorption, biochemical bone properties, and the fecal microbiome in free-living adolescents. Healthy adolescent females (n = 28; aged 11-14 y) randomly assigned into a 3-phase, double-blind, crossover study consumed SCF for 4 wk at each dose (0, 10, and 20 g fiber/d from SCF) alongside their habitual diet and were followed by 3-d clinical visits and 3-wk washout periods. Stable isotope ((44)Ca and (43)Ca) enrichment in pooled urine was measured by inductively coupled plasma mass spectrometry. Fecal microbial community composition was assessed by high-throughput sequencing (Illumina) of polymerase chain reaction-amplified 16S rRNA genes. Mixed model ANOVA and Friedman analysis were used to determine effects of SCF on calcium absorption and to compare mean microbial proportions, respectively. Calcium absorption increased significantly with 10 (13.3% ± 5.3%; P = 0.042) and 20 g fiber/d (12.9% ± 3.6%; P = 0.026) from SCF relative to control. Significant differences in fecal microbial community diversity were found after consuming SCF (operational taxonomic unit measures of 601.4 ± 83.5, 634.5 ± 83.8, and 649.6 ± 75.5 for 0, 10, and 20 g fiber/d, respectively; P < 0.05). Proportions of the genus Parabacteroides significantly increased with SCF dose (1.1% ± 0.8%, 2.1% ± 1.6%, and 3.0% ± 2.0% for 0, 10, and 20 g fiber/d from SCF, respectively; P < 0.05). Increases in calcium absorption positively correlated with increases in Clostridium (r = 0.44, P = 0.023) and unclassified Clostridiaceae (r = 0.40, P = 0.040). SCF, a nondigestible carbohydrate, increased calcium absorption in free-living adolescent females. Two groups of bacteria may be

Modulation of small intestinal phosphate transporter by dietary supplements of mineral phosphorus and phytase in broilers.

PubMed

Huber, Korinna; Zeller, Ellen; Rodehutscord, Markus

2015-05-01

Dietary phosphorus (P) is known as a main modulator of phosphate (Pi) transporter expression. The effect of supplemented mineral P with or without phytase on protein expression of two sodium-dependent Pi (NaPi) transporters and a calcium channel was studied in the small intestine of broilers. Thirty-six broilers were randomly assigned to six different diets at 15 days of age. Two levels of total P (tP, adjusted by monocalcium phosphate (MCP) supplementation), 0.39% (BD-) and 0.47% (BD+) were fed until day 25; and at each tP level, three levels of phytase were used with 0, 500, and 12,500 FTU/kg of an E. coli phytase. Mucosa samples from jejunum and ileum were taken and apical membranes were isolated by MgCl2 precipitation. Protein expression of NaPi IIb, NaPi type III (PiT1) and the calcium channel TRPV6 were semiquantitatively measured by Western blotting and jejunal mucosal phytase activity by measurement of Pi release. The jejunal NaPi IIb transporter was expressed with two distinct bands, which were modulated differently by diet. NaPi IIb Band1 increased (P < 0.05) and Band2 decreased (P < 0.05) with phytase supplementation but was not affected by MCP supplementation. This inverse modulation of Band1 and Band2 was significantly related to the amount of net absorbed P with higher expression of Band1 at higher amounts of net absorbed P. In addition, a second Pi transporter, PiT1, was detected in which ileal expression decreased (P < 0.05) in response to higher phytase supplementation. The expression of the calcium channel TRPV6 was increased in BD+ groups. A trend for an interaction between MCP and phytase supplementation on mucosal phytase activity was observed (P = 0.079) with a decrease in activity when BD+ with 12,500 FTU/kg phytase was fed. Chicken intestinal epithelial cells responded to dietary supplemented phytase and MCP by changing the Pi transporter expression in apical membranes. In conclusion, availability of Pi is most likely the key modulator of

Conservation of body calcium by increased dietary intake of potassium: A potential measure to reduce the osteoporosis process during prolonged exposure to microgravity

NASA Technical Reports Server (NTRS)

Nechay, Bohdan R.

1989-01-01

During the 1988 NASA Summer Faculty Fellowship Program, it was proposed that the loss of skeletal calcium upon prolonged exposure to microgravity could be explained, in part, by a renal maladjustment characterized by an increased urinary excretion of calcium. It was theorized that because the conservation of body fluids and electrolytes depends upon the energy of adenosine triphosphate and enzymes that control the use of its energy for renal ion transport, an induction of renal sodium and potassium-dependent adenosine triphosphatase (Na + K ATPase) by oral loading with potassium would increase the reabsorption of sodium directly and that of calcium indirectly, leading to improved hydration and to reduced calcium loss. Preliminary studies showed the following. Rats drinking water containing 0.2 M potassium chloride for six to 13 days excreted in urine 22 muEq of calcium and 135 muEq of sodium per 100 grams of body weight per day. The corresponding values for control rats drinking tap water were 43 muEq and 269 muEq respectively. Renal Na + K ATPase activity in potassium loaded rats was higher than in controls. Thus, oral potassium loading resulted in increased Na + K ATPase activity and diminished urinary excretion of calcium and of sodium as predicted by the hypothesis. An extension of these studies to humans has the potential of resulting in development of harmless, non-invasive, drug-free, convenient measures to reduce bone loss and other electrolyte and fluid problems in space travelers exposed to prolonged periods of microgravity.

Intestinal Membrane Permeability and Hypersensitivity In the Irritable Bowel Syndrome

PubMed Central

Zhou, QiQi; Zhang, Buyi; Verne, G. Nicholas

2009-01-01

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the underlying pathophysiology is poorly understood; however, increased intestinal permeability in diarrhea-predominant IBS patients has been reported. Here we demonstrate diarrhea-predominant IBS patients (D-IBS) that display increased intestinal permeability. We have also found that increased intestinal membrane permeability is associated with visceral and thermal hypersensitivity in this subset of D-IBS patients. We evaluated 54 D-IBS patients and 22 controls for intestinal membrane permeability using the lactulose / mannitol method. All subjects ingested 5 g laclulose and 2 g mannitol in 100 ml of water after which their urine was collected. We also evaluated the mean mechanical visual analogue (MVAS) pain rating to nociceptive thermal and visceral stimulation in all subjects. All study participants also completed the FBDSI scale. Approximately 39% of diarrhea-predominant IBS patients have increased intestinal membrane permeability as measured by the lactulose / mannitol ratio. These IBS patients also demonstrated higher M-VAS pain intensity reading scale. Interestingly, the IBS patients with hypersensitivity and increased intestinal permeability had a higher FBDSI score (100.8±5.4) compared to IBS patients with normal membrane permeability and sensitivity (51.6±12.7) and controls (6.1 ± 5.6) (p<0.001). A subset of D-IBS patients have increased intestinal membrane permeability that is associated with an increased FBDSI score and increased hypersensitivity to visceral and thermal nociceptive pain stimuli. Thus, increased intestinal membrane permeability in D-IBS patients may lead to more severe IBS symptoms and hypersensitivity to somatic and visceral stimuli. PMID:19595511

Calcium distribution in Amoeba proteus

PubMed Central

1979-01-01

A preliminary investigation of the distribution of cellular calcium in Amoeba proteus was undertaken. Total cellular calcium under control conditions was found to be 4.59 mmol/kg of cells. When the external Ca++ concentration is increased from the control level of 0.03 to 20 mM, a net Ca++ influx results with a new steady-state cellular calcium level being achieved in integral of 3 h. At steady state the amount of calcium per unit weight of cells is higher than the amount of calcium per unit weight of external solution when the external concentration of Ca++ is below 10 mM. At external Ca++ concentrations above this level, total cellular calcium approaches the medium level of Ca++. Steady- state calcium exchange in Amoeba proteus was determined with 45Ca. There is an immediate and rapid exchange of integral of 0.84 mmol/kg of cells or 18% of the total cellular calcium with the labelled Ca++. Following this initial exchange, there was very little if any further exchange observed. Most of this exchanged calcium could be eliminated from the cell with 1 mM La+++, suggesting that the exchanged calcium is associated with the surface of the cell. Increase in either the external Ca++ concentration of pH raise the amount of exchangeable calcium associated with the cell. Calcium may be associated with the cell surface as a co-ion in the diffuse double layer or bound to fixed negative sites on the surface of the cell. If Ca++-binding sites do exist on the cell surface, there may be more than one type and they may have different dissociation constants. The cytoplasmic Ca++ ion activity is probably maintained at very low levels. PMID:512628

Silver ions increase plasma membrane permeability through modulation of intracellular calcium levels in tobacco BY-2 cells.

PubMed

Klíma, Petr; Laňková, Martina; Vandenbussche, Filip; Van Der Straeten, Dominique; Petrášek, Jan

2018-05-01

Silver ions increase plasma membrane permeability for water and small organic compounds through their stimulatory effect on plasma membrane calcium channels, with subsequent modulation of intracellular calcium levels and ion homeostasis. The action of silver ions at the plant plasma membrane is largely connected with the inhibition of ethylene signalling thanks to the ability of silver ion to replace the copper cofactor in the ethylene receptor. A link coupling the action of silver ions and cellular auxin efflux has been suggested earlier by their possible direct interaction with auxin efflux carriers or by influencing plasma membrane permeability. Using tobacco BY-2 cells, we demonstrate here that besides a dramatic increase of efflux of synthetic auxins 2,4-dichlorophenoxyacetic acid (2,4-D) and 1-naphthalene acetic acid (NAA), treatment with AgNO 3 resulted in enhanced efflux of the cytokinin trans-zeatin (tZ) as well as the auxin structural analogues tryptophan (Trp) and benzoic acid (BA). The application of AgNO 3 was accompanied by gradual water loss and plasmolysis. The observed effects were dependent on the availability of extracellular calcium ions (Ca 2+ ) as shown by comparison of transport assays in Ca 2+ -rich and Ca 2+ -free buffers and upon treatment with inhibitors of plasma membrane Ca 2+ -permeable channels Al 3+ and ruthenium red, both abolishing the effect of AgNO 3 . Confocal microscopy of Ca 2+ -sensitive fluorescence indicator Fluo-4FF, acetoxymethyl (AM) ester suggested that the extracellular Ca 2+ availability is necessary to trigger the response to silver ions and that the intracellular Ca 2+ pool alone is not sufficient for this effect. Altogether, our data suggest that in plant cells the effects of silver ions originate from the primal modification of the internal calcium levels, possibly by their interaction with Ca 2+ -permeable channels at the plasma membrane.

Synchrotron X-ray microscopy and spectroscopy analysis of iron in hemochromatosis liver and intestines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ko, J .Y. Peter; Sham, Tsun-Kong; Chakrabarti, Subrata

2009-12-01

Hemochromatosis is a genetic disorder that causes body to store excess iron in organs such as heart or liver. Distribution of iron, as well as copper, zinc and calcium, and chemical identity of iron in hemochromatosis liver and intestine were investigated by X-ray microprobe experiments, which consist of X-ray microscopy and micro-X-ray absorption fine structure. Our results show that iron concentration in hemochromatosis liver tissue is high, while much less Fe is found in intestinal tissue. Moreover, chemical identity of Fe in hemochromatosis liver can be identified. X-ray microprobe experiments allows for examining elemental distribution at an excellent spatial resolution.more » Moreover, chemical identity of element of interest can be obtained.« less

Rebamipide ameliorates radiation-induced intestinal injury in a mouse model.

PubMed

Shim, Sehwan; Jang, Hyo-Sun; Myung, Hyun-Wook; Myung, Jae Kyung; Kang, Jin-Kyu; Kim, Min-Jung; Lee, Seung Bum; Jang, Won-Suk; Lee, Sun-Joo; Jin, Young-Woo; Lee, Seung-Sook; Park, Sunhoo

2017-08-15

Radiation-induced enteritis is a major side effect in cancer patients undergoing abdominopelvic radiotherapy. Radiation exposure produces an uncontrolled inflammatory cascade and epithelial cell loss leading to impaired epithelial barrier function. The goal of this study was to determine the effect of rebamipide on regeneration of the intestinal epithelia after radiation injury. The abdomens of C57BL/6 mice were exposed to 13Gy of irradiation (IR) and then the mice were treated with rebamipide. Upon IR, intestinal epithelia were destroyed structurally at the microscopic level and bacterial translocation was increased. The intestinal damage reached a maximum level on day 6 post-IR and intestinal regeneration occurred thereafter. We found that rebamipide significantly ameliorated radiation-induced intestinal injury. In mice treated with rebamipide after IR, intestinal barrier function recovered and expression of the tight junction components of the intestinal barrier were upregulated. Rebamipide administration reduced radiation-induced intestinal mucosal injury. The levels of proinflammatory cytokines and matrix metallopeptidase 9 (MMP9) were significantly reduced upon rebamipide administration. Intestinal cell proliferation and β-catenin expression also increased upon rebamipide administration. These data demonstrate that rebamipide reverses impairment of the intestinal barrier by increasing intestinal cell proliferation and attenuating the inflammatory response by inhibiting MMP9 and proinflammatory cytokine expression in a murine model of radiation-induced enteritis. Copyright © 2017 Elsevier Inc. All rights reserved.

The Roles and Mechanisms of Intestinal Oxalate Transport in Oxalate Homeostasis

PubMed Central

Hatch, Marguerite; Freel, Robert W.

2008-01-01

The mammalian intestine has an important role in the dynamics of oxalate exchange and thereby is significant in the etiology of calcium oxalate nephrolithiasis. Here we review some of the phenomenological observations that have led to the conclusion that anion exchangers (antiporters) are important mediators of secondarily active, net oxalate transport along the intestine (both absorptive and secretory). Understanding the mechanisms of transepithelial oxalate transport has been radically advanced in recent years by the identification of the SLC26 family of anion transporters which has facilitated the identification of specific proteins mediating individual apical or basolateral oxalate transport pathways. Moreover, identification of specific exchangers has underscored their relative importance to oxalate homeostasis as revealed by using knockout mouse models and facilitated studies of oxalate transport regulation in heterologous expression systems. Finally, the significance of oxalate degrading bacteria to oxalate homeostasis is considered from basic and applied perspectives. PMID:18359395

SECONDARY HYPERPARATHYROIDISM AFTER BARIATRIC SURGERY: TREATMENT IS WITH CALCIUM CARBONATE OR CALCIUM CITRATE?

PubMed Central

BARETTA, Giorgio Alfredo Pedroso; CAMBI, Maria Paula Carlini; RODRIGUES, Arieli Luz; MENDES, Silvana Aparecida

2015-01-01

Background : Bariatric surgery, especially Roux-en-Y gastric bypass, can cause serious nutritional complications arising from poor absorption of essential nutrients. Secondary hyperparathyroidism is one such complications that leads to increased parathyroid hormone levels due to a decrease in calcium and vitamin D, which may compromise bone health. Aim : To compare calcium carbonate and calcium citrate in the treatment of secondary hyperparathyroidism. Method : Patients were selected on the basis of their abnormal biochemical test and treatment was randomly done with citrate or calcium carbonate. Results : After 60 days of supplementation, biochemical tests were repeated, showing improvement in both groups. Conclusion : Supplementation with calcium (citrate or carbonate) and vitamin D is recommended after surgery for prevention of secondary hyperparathyroidism. PMID:26537273

The effects of excess calcium on the handling and mechanical properties of hydrothermal derived calcium phosphate bone cement

NASA Astrophysics Data System (ADS)

Razali, N. N.; Sukardi, M. A.; Sopyan, I.; Mel, M.; Salleh, H. M.; Rahman, M. M.

2018-01-01

The objective of this study is to determine the effects of excess calcium on the handling and mechanical properties of hydrothermal derived calcium phosphate cement (CPC) for bone filling applications. Hydroxyapatite powder was synthesized via hydrothermal method using calcium oxide, CaO and ammonium dihydrogen phosphate, NH4H2PO4 as the calcium and phosphorus precursors respectively. The effects of calcium excess were evaluated by varying the CaO content at 0, 5 and 15 mole %. The precursors were then refluxed in distilled water at 90-100°C and dried overnight until the calcium phosphate powder was formed. CPC was then produced by mixing the synthesized powder with distilled water at the powder-to-liquid (P/L) ratio of 1.5. The result from the morphological properties of CPC shows the increase in agglomeration and particles size with 5 mole % of calcium excess but decreased with 15 mole % of calcium excess in CPC. This result was in agreement with the compressive strength result where the CPC increased its strength with 5 mole % of calcium excess but reduced with 15 mole % of calcium excess. The excess in calcium precursor also significantly improved the setting time but reduced the injectability of CPC.

Diuretics and disorders of calcium homeostasis.

PubMed

Grieff, Marvin; Bushinsky, David A

2011-11-01

Diuretics commonly are administered in disorders of sodium balance. Loop diuretics inhibit the Na-K-2Cl transporter and also increase calcium excretion. They are often used in the treatment of hypercalcemia. Thiazide diuretics block the thiazide-sensitive NaCl transporter in the distal convoluted tubule, and can decrease calcium excretion. They are often used in the treatment of nephrolithiasis. Carbonic anhydrase inhibitors decrease bicarbonate absorption and the resultant metabolic acidosis can increase calcium excretion. Their use can promote nephrocalcinosis and nephrolithiasis. This review will address the use of diuretics on disorders of calcium homeostasis. Copyright © 2011 Elsevier Inc. All rights reserved.

Extracellular nucleotides inhibit oxalate transport by human intestinal Caco-2-BBe cells through PKC-δ activation

PubMed Central

Amin, Ruhul; Sharma, Sapna; Ratakonda, Sireesha

2013-01-01

Nephrolithiasis remains a major health problem in Western countries. Seventy to 80% of kidney stones are composed of calcium oxalate, and small changes in urinary oxalate affect risk of kidney stone formation. Intestinal oxalate secretion mediated by the anion exchanger SLC26A6 plays an essential role in preventing hyperoxaluria and calcium oxalate nephrolithiasis, indicating that understanding the mechanisms regulating intestinal oxalate transport is critical for management of hyperoxaluria. Purinergic signaling modulates several intestinal processes through pathways including PKC activation, which we previously found to inhibit Slc26a6 activity in mouse duodenal tissue. We therefore examined whether purinergic stimulation with ATP and UTP affects oxalate transport by human intestinal Caco-2-BBe (C2) cells. We measured [14C]oxalate uptake in the presence of an outward Cl− gradient as an assay of Cl−/oxalate exchange activity, ≥50% of which is mediated by SLC26A6. We found that ATP and UTP significantly inhibited oxalate transport by C2 cells, an effect blocked by the PKC inhibitor Gö-6983. Utilizing pharmacological agonists and antagonists, as well as PKC-δ knockdown studies, we observed that ATP inhibits oxalate transport through the P2Y2 receptor, PLC, and PKC-δ. Biotinylation studies showed that ATP inhibits oxalate transport by lowering SLC26A6 surface expression. These findings are of potential relevance to pathophysiology of inflammatory bowel disease-associated hyperoxaluria, where supraphysiological levels of ATP/UTP are expected and overexpression of the P2Y2 receptor has been reported. We conclude that ATP and UTP inhibit oxalate transport by lowering SLC26A6 surface expression in C2 cells through signaling pathways including the P2Y2 purinergic receptor, PLC, and PKC-δ. PMID:23596171

Rebamipide inhibits indomethacin-induced small intestinal injury: possible involvement of intestinal microbiota modulation by upregulation of α-defensin 5.

PubMed

Tanigawa, Tetsuya; Watanabe, Toshio; Otani, Koji; Nadatani, Yuji; Ohkawa, Fumikazu; Sogawa, Mitsue; Yamagami, Hirokazu; Shiba, Masatsugu; Watanabe, Kenji; Tominaga, Kazunari; Fujiwara, Yasuhiro; Takeuchi, Koji; Arakawa, Tetsuo

2013-03-15

Enterobacteria play important roles in the pathophysiology of small intestinal injuries induced by nonsteroidal anti-inflammatory drugs (NSAIDs). We investigated the effects of rebamipide, a gastrointestinal mucoprotective drug, on indomethacin-induced small intestinal injuries, intestinal microbiota, and expression levels of α-defensin 5, which is a Paneth cell-specific antimicrobial peptide and is important for the regulation of intestinal microbiota. Indomethacin (10mg/kg) was orally administered to mice after oral administration of rebamipide (100 or 300 mg/kg) or vehicle for 1 week, and the small intestinal injuries were assessed. After oral administration of rebamipide, the small intestinal contents were subjected to terminal restriction fragment length polymorphism (T-RFLP) analysis to assess the intestinal microbiota composition. Further, the expression levels of mRNA and protein for α-defensin 5 in the ileal tissue were determined by real-time reverse transcription-polymerase chain reaction and western blotting analysis, respectively. Rebamipide inhibited indomethacin-induced small intestinal injuries and T-RFLP analysis showed that rebamipide increased the percentage of Lactobacillales and decreased the percentage of Bacteroides and Clostridium than that in vehicle-treated controls. The mice that were treated with rebamipide showed an increase in α-defensin 5 mRNA expression and protein levels in the ileal tissue compared to vehicle-treated control mice. Indomethacin reduced expression of α-defensin 5 mRNA in ileal tissue, while rebamipide reversed expression of α-defensin 5 mRNA. In conclusion, our study results suggest that rebamipide inhibits indomethacin-induced small intestinal injuries, possibly by modulating microbiota in the small intestine by upregulation of α-defensin 5. Copyright © 2013 Elsevier B.V. All rights reserved.

Calcium-pH crosstalks in rat mast cells: cytosolic alkalinization, but not intracellular calcium release, is a sufficient signal for degranulation

PubMed Central

Alfonso, A; Cabado, A G; Vieytes, M R; Botana, L M

2000-01-01

The aim of this work was to study the relationship between intracellular alkalinization, calcium fluxes and histamine release in rat mast cells. Intracellular alkalinization was induced by nigericin, a monovalent cation ionophore, and by NH4Cl (ammonium chloride). Calcium cytosolic and intracellular pH were measured by fluorescence digital imaging using Fura-2-AM and BCECF-AM.In rat mast cells, nigericin and NH4Cl induce a dose-dependent intracellular alkalinization, a dose-dependent increase in intracellular calcium levels by releasing calcium from intracellular pools, and an activation of capacitative calcium influx.The increase in both intracellular calcium and pH activates exocytosis (histamine release) in the absence of external calcium. Under the same conditions, thapsigargin does not activate exocytosis, the main difference being that thapsigargin does not alkalinize the cytosol.After alkalinization, histamine release is intracellular-calcium dependent. With 2.5 mM EGTA and thapsigargin the cell response decreases by 62%.The cytosolic alkalinization, in addition to the calcium increase it is enough signal to elicit the exocytotic process in rat mast cells. PMID:10952669

Sulfhydryl oxidation modifies the calcium dependence of ryanodine-sensitive calcium channels of excitable cells.

PubMed Central

Marengo, J J; Hidalgo, C; Bull, R

1998-01-01

The calcium dependence of ryanodine-sensitive single calcium channels was studied after fusing with planar lipid bilayers sarcoendoplasmic reticulum vesicles isolated from excitable tissues. Native channels from mammalian or amphibian skeletal muscle displayed three different calcium dependencies, cardiac (C), mammalian skeletal (MS), and low fractional open times (low Po), as reported for channels from brain cortex. Native channels from cardiac muscle presented only the MS and C dependencies. Channels with the MS or low Po behaviors showed bell-shaped calcium dependencies, but the latter had fractional open times of <0.1 at all [Ca2+]. Channels with C calcium dependence were activated by [Ca2+] < 10 microM and were not inhibited by increasing cis [Ca2+] up to 0.5 mM. After oxidation with 2,2'-dithiodipyridine or thimerosal, channels with low Po or MS dependencies increased their activity. These channels modified their calcium dependencies sequentially, from low Po to MS and C, or from MS to C. Reduction with glutathione of channels with C dependence (native or oxidized) decreased their fractional open times in 0.5 mM cis [Ca2+], from near unity to 0.1-0.3. These results show that all native channels displayed at least two calcium dependencies regardless of their origin, and that these changed after treatment with redox reagents. PMID:9512024

Targeting immunoproteasome and glutamine supplementation prevent intestinal hyperpermeability.

PubMed

Ghouzali, Ibtissem; Lemaitre, Caroline; Bahlouli, Wafa; Azhar, Saïda; Bôle-Feysot, Christine; Meleine, Mathieu; Ducrotté, Philippe; Déchelotte, Pierre; Coëffier, Moïse

2017-01-01

Intestinal hyperpermeability has been reported in several intestinal and non-intestinal disorders. We aimed to investigate the role of the ubiquitin proteasome system in gut barrier regulation in two mice models: the water avoidance stress model (WAS) and a post-inflammatory model (post-TNBS). Both models were applied in C57BL/6 male mice (n=7-8/group); Proteasome was targeted by injection of a selective proteasome inhibitor or by using knock-out mice for β2i proteasome subunit. Finally, glutamine supplementation was evaluated. In both models (WAS at day 10, post-TNBS at day 28), we observed an increase in proteasome trypsin-like activity and in inducible β2/constitutive β2 subunit protein expression ratio, associated with an increase in intestinal permeability. Moreover, intestinal hyperpermeability was blunted by intraperitoneal injection of selective proteasome inhibitor in WAS and post-TNBS mice. Of note, knock-out mice for the β2i subunit exhibited a significant decrease in intestinal permeability and fecal pellet output during WAS. Glutamine supplementation also improved colonic permeability in both models. In conclusion, the proteasome system is altered in the colonic mucosa of WAS and post-TNBS mice with increased trypsin-like activity. Associated intestinal hyperpermeability was blunted by immunoproteasome inhibition. Copyright © 2016 Elsevier B.V. All rights reserved.

Intestinal microbiota in liver disease.

PubMed

Haque, Tanvir R; Barritt, A Sidney

2016-02-01

The intestinal microbiota have emerged as a topic of intense interest in gastroenterology and hepatology. The liver is on the front line as the first filter of nutrients, toxins and bacterial metabolites from the intestines and we are becoming increasingly aware of interactions among the gut, liver and immune system as important mediators of liver health and disease. Manipulating the microbiota with therapeutic intent is a rapidly expanding field. In this review, we will describe what is known about the contribution of intestinal microbiota to liver homeostasis; the role of dysbiosis in the pathogenesis of liver disease including alcoholic and non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma; and the therapeutic manifestations of altering intestinal microbiota via antibiotics, prebiotics, probiotics and fecal microbiota transplantation. Copyright © 2016. Published by Elsevier Ltd.

Intestinal alkaline phosphatase at the crossroad of intestinal health and disease - a putative role in type 1 diabetes.

PubMed

Lassenius, M I; Fogarty, C L; Blaut, M; Haimila, K; Riittinen, L; Paju, A; Kirveskari, J; Järvelä, J; Ahola, A J; Gordin, D; Härma, M-A; Kumar, A; Hamarneh, S R; Hodin, R A; Sorsa, T; Tervahartiala, T; Hörkkö, S; Pussinen, P J; Forsblom, C; Jauhiainen, M; Taskinen, M-R; Groop, P-H; Lehto, M

2017-06-01

Patients with type 1 diabetes have shown an increase in circulating cytokines, altered lipoprotein metabolism and signs of vascular dysfunction in response to high-fat meals. Intestinal alkaline phosphatase (IAP) regulates lipid transport and inflammatory responses in the gastrointestinal tract. We therefore hypothesized that changes in IAP activity could have profound effects on gut metabolic homeostasis in patients with type 1 diabetes. Faecal samples of 41 nondiabetic controls and 46 patients with type 1 diabetes were analysed for IAP activity, calprotectin, immunoglobulins and short-chain fatty acids (SCFAs). The impact of oral IAP supplementation on intestinal immunoglobulin levels was evaluated in C57BL/6 mice exposed to high-fat diet for 11 weeks. Patients with type 1 diabetes exhibited signs of intestinal inflammation. Compared to controls, patients with diabetes had higher faecal calprotectin levels, lower faecal IAP activities accompanied by lower propionate and butyrate concentrations. Moreover, the amount of faecal IgA and the level of antibodies binding to oxidized LDL were decreased in patients with type 1 diabetes. In mice, oral IAP supplementation increased intestinal IgA levels markedly. Deprivation of protective intestinal factors may increase the risk of inflammation in the gut - a phenomenon that seems to be present already in patients with uncomplicated type 1 diabetes. Low levels of intestinal IgA and antibodies to oxidized lipid epitopes may predispose such patients to inflammation-driven complications such as cardiovascular disease and diabetic nephropathy. Importantly, oral IAP supplementation could have beneficial therapeutic effects on gut metabolic homeostasis, possibly through stimulation of intestinal IgA secretion. © 2017 The Association for the Publication of the Journal of Internal Medicine.

Impregnating Coal With Calcium Carbonate

NASA Technical Reports Server (NTRS)

Sharma, Pramod K.; Voecks, Gerald E.; Gavalas, George R.

1991-01-01

Relatively inexpensive process proposed for impregnating coal with calcium carbonate to increase rates of gasification and combustion of coal and to reduce emission of sulfur by trapping sulfur in calcium sulfide. Process involves aqueous-phase reactions between carbon dioxide (contained within pore network of coal) and calcium acetate. Coal impregnated with CO2 by exposing it to CO2 at high pressure.

Oncostatin M Mediates STAT3-Dependent Intestinal Epithelial Restitution via Increased Cell Proliferation, Decreased Apoptosis and Upregulation of SERPIN Family Members

PubMed Central

Beigel, Florian; Friedrich, Matthias; Probst, Corina; Sotlar, Karl; Göke, Burkhard; Diegelmann, Julia; Brand, Stephan

2014-01-01

Objective Oncostatin M (OSM) is produced by activated T cells, monocytes, and dendritic cells and signals through two distinct receptor complexes consisting of gp130 and LIFR (I) or OSMR-β and gp130 (II), respectively. Aim of this study was to analyze the role of OSM in intestinal epithelial cells (IEC) and intestinal inflammation. Methods OSM expression and OSM receptor distribution was analyzed by PCR and immunohistochemistry experiments, signal transduction by immunoblotting. Gene expression studies were performed by microarray analysis and RT-PCR. Apoptosis was measured by caspases-3/7 activity. IEC migration and proliferation was studied in wounding and water soluble tetrazolium assays. Results The IEC lines Caco-2, DLD-1, SW480, HCT116 and HT-29 express mRNA for the OSM receptor subunits gp130 and OSMR-β, while only HCT116, HT-29 and DLD-1 cells express LIFR mRNA. OSM binding to its receptor complex activates STAT1, STAT3, ERK-1/2, SAPK/JNK-1/2, and Akt. Microarray analysis revealed 79 genes that were significantly up-regulated (adj.-p≤0.05) by OSM in IEC. Most up-regulated genes belong to the functional categories “immunity and defense” (p = 2.1×10−7), “apoptosis” (p = 3.7×10−4) and “JAK/STAT cascade” (p = 3.4×10−6). Members of the SERPIN gene family were among the most strongly up-regulated genes. OSM significantly increased STAT3- and MEK1-dependent IEC cell proliferation (p<0.05) and wound healing (p = 3.9×10−5). OSM protein expression was increased in colonic biopsies of patients with active inflammatory bowel disease (IBD). Conclusions OSM promotes STAT3-dependent intestinal epithelial cell proliferation and wound healing in vitro. Considering the increased OSM expression in colonic biopsy specimens of patients with active IBD, OSM upregulation may modulate a barrier-protective host response in intestinal inflammation. Further in vivo studies are warranted to elucidate the exact role of OSM in intestinal

- Invited Review - Calcium Digestibility and Metabolism in Pigs*

PubMed Central

González-Vega, J. C.; Stein, H. H.

2014-01-01

Calcium (Ca) and phosphorus (P) are minerals that have important physiological functions in the body. For formulation of diets for pigs, it is necessary to consider an appropriate Ca:P ratio for an adequate absorption and utilization of both minerals. Although both minerals are important, much more research has been conducted on P digestibility than on Ca digestibility. Therefore, this review focuses on aspects that are important for the digestibility of Ca. Only values for apparent total tract digestibility (ATTD) of Ca have been reported in pigs, whereas values for both ATTD and standardized total tract digestibility (STTD) of P in feed ingredients have been reported. To be able to determine STTD values for Ca it is necessary to determine basal endogenous losses of Ca. Although most Ca is absorbed in the small intestine, there are indications that Ca may also be absorbed in the colon under some circumstances, but more research to verify the extent of Ca absorption in different parts of the intestinal tract is needed. Most P in plant ingredients is usually bound to phytate. Therefore, plant ingredients have low digestibility of P due to a lack of phytase secretion by pigs. During the last 2 decades, inclusion of microbial phytase in swine diets has improved P digestibility. However, it has been reported that a high inclusion of Ca reduces the efficacy of microbial phytase. It is possible that formation of insoluble calcium-phytate complexes, or Ca-P complexes, not only may affect the efficacy of phytase, but also the digestibility of P and Ca. Therefore, Ca, P, phytate, and phytase interactions are aspects that need to be considered in Ca digestibility studies. PMID:25049919

Preparation and preclinical evaluation of 68Ga-DOTA-amlodipine for L-type calcium channel imaging.

PubMed

Firuzyar, Tahereh; Jalilian, Amir Reza; Aboudzadeh, Mohammad Reza; Sadeghpour, Hossein; Shafiee-Ardestani, Mahdi; Khalaj, Ali

2016-01-01

In order to develop a possible tracer for L-type calcium channel imaging, we here report the development of a Ga-68 amlodipine derivative for possible PET imaging. Amlodipine DOTA conjugate was synthesized, characterized and went through calcium channel blockade, toxicity, apoptosis/necrosis tests. [ 68 Ga] DOTA AMLO was prepared at optimized conditions followed by stability tests, partition coefficient determination and biodistribution studies using tissue counting and co incidence imaging up to 2 h. [ 68 Ga] DOTA AMLO was prepared at pH 4-5 in 7-10 min at 95°C in high radiochemical purity (>99%, radio thin layer chromatography; specific activity: 1.9-2.1 GBq/mmol) and was stable up to 4 h with a log P of -0.94. Calcium channel rich tissues including myocardium, and tissues with smooth muscle cells such as colon, intestine, and lungs demonstrated significant uptake. Co incidence images supported the biodistribution data up to 2 h. The complex can be a candidate for further positron emission tomography imaging for L type calcium channels.

Effect of oral calcium and calcium + fluoride treatments on mouse bone properties during suspension

NASA Technical Reports Server (NTRS)

Simske, S. J.; Luttges, M. W.; Allen, K. A.; Spooner, B. S. (Principal Investigator)

1992-01-01

The bone effects of oral dosages of calcium chloride with or without supplementary sodium fluoride were assessed in antiorthostatically suspended mice. Two calcium dosages were used to replace half (3.1 mM) or all(6.3 mM) of the dietary calcium lost due to reduced food intake by the suspended mice. Two groups of 6.3 mM CaCl2-treated mice were additionally treated with 0.25 or 2.5 mM NaF. The results indicate that supplementation of the mouse drinking water with calcium salts prevents bone changes induced by short-term suspension, while calcium salts in combination with fluoride are less effective as fluoride dosage increases. However, the calcium supplements change the relationship between the femur mechanical properties and the mineral composition of the bone. Because of this, it appears that oral calcium supplements are effective through a mechanism other than simple dietary supplementation and may indicate a dependence of bone consistency on systemic and local fluid conditions.

Calcium binding properties of calcium dependent protein kinase 1 (CaCDPK1) from Cicer arietinum.

PubMed

Dixit, Ajay Kumar; Jayabaskaran, Chelliah

2015-05-01

Calcium plays a crucial role as a secondary messenger in all aspects of plant growth, development and survival. Calcium dependent protein kinases (CDPKs) are the major calcium decoders, which couple the changes in calcium level to an appropriate physiological response. The mechanism by which calcium regulates CDPK protein is not well understood. In this study, we investigated the interactions of Ca(2+) ions with the CDPK1 isoform of Cicer arietinum (CaCDPK1) using a combination of biophysical tools. CaCDPK1 has four different EF hands as predicted by protein sequence analysis. The fluorescence emission spectrum of CaCDPK1 showed quenching with a 5 nm red shift upon addition of calcium, indicating conformational changes in the tertiary structure. The plot of changes in intensity against calcium concentrations showed a biphasic curve with binding constants of 1.29 μM and 120 μM indicating two kinds of binding sites. Isothermal calorimetric (ITC) titration with CaCl2 also showed a biphasic curve with two binding constants of 0.027 μM and 1.7 μM. Circular dichroism (CD) spectra showed two prominent peaks at 208 and 222 nm indicating that CaCDPK1 is a α-helical rich protein. Calcium binding further increased the α-helical content of CaCDPK1 from 75 to 81%. Addition of calcium to CaCDPK1 also increased fluorescence of 8-anilinonaphthalene-1-sulfonic acid (ANS) indicating exposure of hydrophobic surfaces. Thus, on the whole this study provides evidence for calcium induced conformational changes, exposure of hydrophobic surfaces and heterogeneity of EF hands in CaCDPK1. Copyright © 2015 Elsevier GmbH. All rights reserved.

Biotic Nitrogen Enrichment Regulates Calcium Sources to Forests

NASA Astrophysics Data System (ADS)

Pett-Ridge, J. C.; Perakis, S. S.; Hynicka, J. D.

2015-12-01

Calcium is an essential nutrient in forest ecosystems that is susceptible to leaching loss and depletion. Calcium depletion can affect plant and animal productivity, soil acid buffering capacity, and fluxes of carbon and water. Excess nitrogen supply and associated soil acidification are often implicated in short-term calcium loss from soils, but the long-term role of nitrogen enrichment on calcium sources and resupply is unknown. Here we use strontium isotopes (87Sr/86Sr) as a proxy for calcium to investigate how soil nitrogen enrichment from biological nitrogen fixation interacts with bedrock calcium to regulate both short-term available supplies and the long-term sources of calcium in montane conifer forests. Our study examines 22 sites in western Oregon, spanning a 20-fold range of bedrock calcium on sedimentary and basaltic lithologies. In contrast to previous studies emphasizing abiotic control of weathering as a determinant of long-term ecosystem calcium dynamics and sources (via bedrock fertility, climate, or topographic/tectonic controls) we find instead that that biotic nitrogen enrichment of soil can strongly regulate calcium sources and supplies in forest ecosystems. For forests on calcium-rich basaltic bedrock, increasing nitrogen enrichment causes calcium sources to shift from rock-weathering to atmospheric dominance, with minimal influence from other major soil forming factors, despite regionally high rates of tectonic uplift and erosion that can rejuvenate weathering supply of soil minerals. For forests on calcium-poor sedimentary bedrock, we find that atmospheric inputs dominate regardless of degree of nitrogen enrichment. Short-term measures of soil and ecosystem calcium fertility are decoupled from calcium source sustainability, with fundamental implications for understanding nitrogen impacts, both in natural ecosystems and in the context of global change. Our finding that long-term nitrogen enrichment increases forest reliance on atmospheric

LX4211 increases serum glucagon-like peptide 1 and peptide YY levels by reducing sodium/glucose cotransporter 1 (SGLT1)-mediated absorption of intestinal glucose.

PubMed

Powell, David R; Smith, Melinda; Greer, Jennifer; Harris, Angela; Zhao, Sharon; DaCosta, Christopher; Mseeh, Faika; Shadoan, Melanie K; Sands, Arthur; Zambrowicz, Brian; Ding, Zhi-Ming

2013-05-01

LX4211 [(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol], a dual sodium/glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor, is thought to decrease both renal glucose reabsorption by inhibiting SGLT2 and intestinal glucose absorption by inhibiting SGLT1. In clinical trials in patients with type 2 diabetes mellitus (T2DM), LX4211 treatment improved glycemic control while increasing circulating levels of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). To better understand how LX4211 increases GLP-1 and PYY levels, we challenged SGLT1 knockout (-/-) mice, SGLT2-/- mice, and LX4211-treated mice with oral glucose. LX4211-treated mice and SGLT1-/- mice had increased levels of plasma GLP-1, plasma PYY, and intestinal glucose during the 6 hours after a glucose-containing meal, as reflected by area under the curve (AUC) values, whereas SGLT2-/- mice showed no response. LX4211-treated mice and SGLT1-/- mice also had increased GLP-1 AUC values, decreased glucose-dependent insulinotropic polypeptide (GIP) AUC values, and decreased blood glucose excursions during the 6 hours after a challenge with oral glucose alone. However, GLP-1 and GIP levels were not increased in LX4211-treated mice and were decreased in SGLT1-/- mice, 5 minutes after oral glucose, consistent with studies linking decreased intestinal SGLT1 activity with reduced GLP-1 and GIP levels 5 minutes after oral glucose. These data suggest that LX4211 reduces intestinal glucose absorption by inhibiting SGLT1, resulting in net increases in GLP-1 and PYY release and decreases in GIP release and blood glucose excursions. The ability to inhibit both intestinal SGLT1 and renal SGLT2 provides LX4211 with a novel dual mechanism of action for improving glycemic control in patients with T2DM.

Expression of intestinal trefoil factor, proliferating cell nuclear antigen and histological changes in intestine of rats after intrauterine asphyxia

PubMed Central

Xu, Ling-Fen; Li, Jun; Sun, Mei; Sun, Hong-Wei

2005-01-01

AIM: To study the expressions of intestinal trefoil factor (ITF) and proliferating cell nuclear antigen (PCNA) and histologic changes in intestine, to investigate the relationship between ITF and intestinal damage and repair after intrauterine hypoxia so as to understand the mechanism of intestinal injury and to find a new way to prevent and treat gastrointestinal diseases. METHODS: Wistar rats, pregnant for 21 d, were used to establish animal models of intrauterine asphyxia by clamping one side of vessels supplying blood to uterus for 20 min, another side was regarded as sham operation group. Intestinal tissues were taken away at 0, 24, 48 and 72 h after birth and stored in different styles. ITF mRNA was detected by RT-PCR. PCNA expression was measured by immunohistochemistry. Intestinal tissues were studied histologically by HE staining in order to observe the areas and degree of injury and to value the intestinal mucosa injury index (IMDI). RESULTS: ITF mRNA appeared in full-term rats and increased with age. After ischemia, ITF mRNA was decreased to the minimum (0.59±0.032) 24 h after birth, then began to increase higher after 72 h than it was in the control group (P<0.01). PCNA positive staining located in goblet cell nuclei. The PCNA level had a remarkable decline (53.29±1.97) 48 h after ischemia. Structure changes were obvious in 48-h group, IMDI (3.40±0.16) was significantly increased. Correlation analyses showed that IMDI had a negative correlation with ITF mRNA and PCNA (r = -0.543, P<0.05; r = -0.794, P<0.01, respectively). CONCLUSION: Intrauterine ischemia can result in an early decrease of ITF mRNA expression. ITF and PCNA may play an important role in the damage and repair of intestinal mucosa. PMID:15818741

A sensor for calcium uptake

PubMed Central

Collins, Sean; Meyer, Tobias

2011-01-01

Mitochondria — the cell’s power plants — increase their energy production in response to calcium signals in the cytoplasm. A regulator of the elusive mitochondrial calcium channel has now been identified. PMID:20844529

Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants.

PubMed

Jaeggi, Tanja; Kortman, Guus A M; Moretti, Diego; Chassard, Christophe; Holding, Penny; Dostal, Alexandra; Boekhorst, Jos; Timmerman, Harro M; Swinkels, Dorine W; Tjalsma, Harold; Njenga, Jane; Mwangi, Alice; Kvalsvig, Jane; Lacroix, Christophe; Zimmermann, Michael B

2015-05-01

In-home iron fortification for infants in developing countries is recommended for control of anaemia, but low absorption typically results in >80% of the iron passing into the colon. Iron is essential for growth and virulence of many pathogenic enterobacteria. We determined the effect of high and low dose in-home iron fortification on the infant gut microbiome and intestinal inflammation. We performed two double-blind randomised controlled trials in 6-month-old Kenyan infants (n=115) consuming home-fortified maize porridge daily for 4 months. In the first, infants received a micronutrient powder (MNP) containing 2.5 mg iron as NaFeEDTA or the MNP without iron. In the second, they received a different MNP containing 12.5 mg iron as ferrous fumarate or the MNP without the iron. The primary outcome was gut microbiome composition analysed by 16S pyrosequencing and targeted real-time PCR (qPCR). Secondary outcomes included faecal calprotectin (marker of intestinal inflammation) and incidence of diarrhoea. We analysed the trials separately and combined. At baseline, 63% of the total microbial 16S rRNA could be assigned to Bifidobacteriaceae but there were high prevalences of pathogens, including Salmonella Clostridium difficile, Clostridium perfringens, and pathogenic Escherichia coli. Using pyrosequencing, +FeMNPs increased enterobacteria, particularly Escherichia/Shigella (p=0.048), the enterobacteria/bifidobacteria ratio (p=0.020), and Clostridium (p=0.030). Most of these effects were confirmed using qPCR; for example, +FeMNPs increased pathogenic E. coli strains (p=0.029). +FeMNPs also increased faecal calprotectin (p=0.002). During the trial, 27.3% of infants in +12.5 mgFeMNP required treatment for diarrhoea versus 8.3% in -12.5 mgFeMNP (p=0.092). There were no study-related serious adverse events in either group. In this setting, provision of iron-containing MNPs to weaning infants adversely affects the gut microbiome, increasing pathogen abundance and

The calcium paradox phenomenon: a flow rate and volume response study of calcium-free perfusion.

PubMed

Oksendal, A N; Jynge, P; Sellevold, O F; Rotevatn, S; Saetersdal, T

1985-10-01

A dose-response study concerning the importance of the flow rate (0.5 to 12 ml/min) and volume (2.5 to 60 ml) of calcium-free coronary perfusion (duration 5 min) in the induction of a calcium paradox on reperfusion (duration 15 min) with calcium-containing medium has been performed in the isolated rat heart (37 degrees C). On the basis of enzymatic, physiological, and metabolic assessments three different levels of tissue injury were identified: a minimal paradox at 1.0 ml/min or 5 ml, a subtotal paradox at 2 ml/min or 10 ml and a total paradox at 9 ml/min or 45 ml. Ultrastructural examination revealed that cellular injury following calcium repletion was always severe, and that an increase in the flow rate and volume of calcium-free perfusion increased the number of severely injured cells. During calcium-free perfusion the external lamina largely remained intact over the surface coat of the sarcolemma, but variable degrees of separation of intercalated discs were observed. It is concluded that the calcium paradox model of myocardial injury presents a rather sharp threshold related to the flow rate or volume of calcium-free coronary perfusion and that on trespassing this threshold there is a narrow zone characterized by a decreasing number of viable cells. Furthermore, the study indicates that a separation of the external lamina from the surface coat of the sarcolemma is not a prerequisite for the induction of a calcium paradox, and that cell injury may occur in the presence of intact intercalated discs.

Increasing O-GlcNAcylation level on organ culture of soleus modulates the calcium activation parameters of muscle fibers.

PubMed

Cieniewski-Bernard, Caroline; Montel, Valerie; Berthoin, Serge; Bastide, Bruno

2012-01-01

O-N-acetylglucosaminylation is a reversible post-translational modification which presents a dynamic and highly regulated interplay with phosphorylation. New insights suggest that O-GlcNAcylation might be involved in striated muscle physiology, in particular in contractile properties such as the calcium activation parameters. By the inhibition of O-GlcNAcase, we investigated the effect of the increase of soleus O-GlcNAcylation level on the contractile properties by establishing T/pCa relationships. We increased the O-GlcNAcylation level on soleus biopsies performing an organ culture of soleus treated or not with PUGNAc or Thiamet-G, two O-GlcNAcase inhibitors. The enhancement of O-GlcNAcylation pattern was associated with an increase of calcium affinity on slow soleus skinned fibers. Analysis of the glycoproteins pattern showed that this effect is solely due to O-GlcNAcylation of proteins extracted from skinned biopsies. We also characterized the O-GlcNAcylated contractile proteins using a proteomic approach, and identified among others troponin T and I as being O-GlcNAc modified. We quantified the variation of O-GlcNAc level on all these identified proteins, and showed that several regulatory contractile proteins, predominantly fast isoforms, presented a drastic increase in their O-GlcNAc level. Since the only slow isoform of contractile protein presenting an increase of O-GlcNAc level was MLC2, the effect of enhanced O-GlcNAcylation pattern on calcium activation parameters could involve the O-GlcNAcylation of sMLC2, without excluding that an unidentified O-GlcNAc proteins, such as TnC, could be potentially involved in this mechanism. All these data strongly linked O-GlcNAcylation to the modulation of contractile activity of skeletal muscle.

Evaluation of isolation methods for pathogenic Yersinia enterocolitica from pig intestinal content.

PubMed

Laukkanen, R; Hakkinen, M; Lundén, J; Fredriksson-Ahomaa, M; Johansson, T; Korkeala, H

2010-03-01

The aim of this study was to evaluate the efficiency of four isolation methods for the detection of pathogenic Yersinia enterocolitica from pig intestinal content. The four methods comprised of 15 isolation steps using selective enrichments (irgasan-ticarcillin-potassium chlorate and modified Rappaport broth) and mildly selective enrichments at 4 or 25 degrees C. Salmonella-Shigella-desoxycholate-calcium chloride agar, cefsulodin-irgasan-novobiocin agar were used as plating media. The most sensitive method detected 78% (53/68) of the positive samples. Individual isolation steps using cold enrichment as the only enrichment or as a pre-enrichment step with further selective enrichment showed the highest sensitivities (55-66%). All isolation methods resulted in high numbers of suspected colonies not confirmed as pathogenic Y. enterocolitica. Cold enrichment should be used in the detection of pathogenic Y. enterocolitica from pig intestinal contents. In addition, more than one parallel isolation step is needed. The study shows that depending on the isolation method used for Y. enterocolitica, the detected prevalence of Y. enterocolitica in pig intestinal contents varies greatly. More selective and sensitive isolation methods need to be developed for pathogenic Y. enterocolitica.

A Specific Peptide with Calcium-Binding Capacity from Defatted Schizochytrium sp. Protein Hydrolysates and the Molecular Properties.

PubMed

Cai, Xixi; Yang, Qian; Lin, Jiaping; Fu, Nanyan; Wang, Shaoyun

2017-03-29

Marine microorganisms have been proposed as a new kind of protein source. Efforts are needed in order to transform the protein-rich biological wastes left after lipid extraction into value-added bio-products. Thus, the utilization of protein recovered from defatted Schizochytrium sp. by-products presents an opportunity. A specific peptide Tyr-Leu (YL) with calcium-binding capacity was purified from defatted Schizochytrium sp. protein hydrolysates through gel filtration chromatography and RP-HPLC. The calcium-binding activity of YL reached 126.34 ± 3.40 μg/mg. The calcium-binding mechanism was investigated through ultraviolet, fluorescence and infrared spectroscopy. The results showed that calcium ions could form dative bonds with carboxyl oxygen atoms and amino nitrogen atoms as well as the nitrogen and oxygen atoms of amide bonds. YL-Ca exhibited excellent thermal stability and solubility, which was beneficial for its absorption and transport in the basic intestinal tract of the human body. Moreover, the cellular uptake of calcium in Caco-2 cells showed that YL-Ca could enhance calcium uptake efficiency and protect calcium ions against precipitation caused by dietary inhibitors such as tannic acid, oxalate, phytate and metal ions. The findings indicate that the by-product of Schizochytrium sp. is a promising source for making peptide-calcium bio-products as algae-based functional supplements for human beings.

Mechanisms of decreased intestinal epithelial proliferation and increased apoptosis in murine acute lung injury.

PubMed

Husain, Kareem D; Stromberg, Paul E; Woolsey, Cheryl A; Turnbull, Isaiah R; Dunne, W Michael; Javadi, Pardis; Buchman, Timothy G; Karl, Irene E; Hotchkiss, Richard S; Coopersmith, Craig M

2005-10-01

The aim of this study was to determine the effects of acute lung injury on the gut epithelium and examine mechanisms underlying changes in crypt proliferation and apoptosis. The relationship between severity and timing of lung injury to intestinal pathology was also examined. Randomized, controlled study. University research laboratory. Genetically inbred mice. Following induction of acute lung injury, gut epithelial proliferation and apoptosis were assessed in a) C3H/HeN wild-type and C3H/HeJ mice, which lack functional Toll-like receptor 4 (n = 17); b) C57Bl/6 mice that received monoclonal anti-tumor necrosis factor-alpha or control antibody (n = 22); and c) C57Bl/6 wild-type and transgenic mice that overexpress Bcl-2 in their gut epithelium (n = 21). Intestinal epithelial proliferation and death were also examined in animals with differing degrees of lung inflammation (n = 24) as well as in a time course analysis following a fixed injury (n = 18). Acute lung injury caused decreased proliferation and increased apoptosis in crypt epithelial cells in all animals studied. C3H/HeJ mice had higher levels of proliferation than C3H/HeN animals without additional changes in apoptosis. Anti-tumor necrosis factor-alpha antibody had no effect on gut epithelial proliferation or death. Overexpression of Bcl-2 did not change proliferation despite decreasing gut apoptosis. Proliferation and apoptosis were not correlated to severity of lung injury, as gut alterations were lost in mice with more severe acute lung injury. Changes in both gut epithelial proliferation and death were apparent within 12 hrs, but proliferation was decreased 36 hrs following acute lung injury while apoptosis returned to normal. Acute lung injury causes disparate effects on crypt proliferation and apoptosis, which occur, at least in part, through differing mechanisms involving Toll-like receptor 4 and Bcl-2. Severity of lung injury does not correlate with perturbations in proliferation or death in the

Mechanisms of decreased intestinal epithelial proliferation and increased apoptosis in murine acute lung injury

PubMed Central

Husain, Kareem D.; Stromberg, Paul E.; Woolsey, Cheryl A.; Turnbull, Isaiah R.; Dunne, W. Michael; Javadi, Pardis; Buchman, Timothy G.; Karl, Irene E.; Hotchkiss, Richard S.; Coopersmith, Craig M.

2005-01-01

Objectives The aim of this study was to determine the effects of acute lung injury (ALI) on the gut epithelium and examine mechanisms underlying changes in crypt proliferation and apoptosis. The relationship between severity and timing of lung injury to intestinal pathology was also examined. Design Randomized, controlled study. Setting University research laboratory. Subjects Genetically inbred mice. Interventions Following induction of ALI, gut epithelial proliferation and apoptosis was assessed in a) C3H/HeN wild type and C3H/HeJ mice, that lack functional toll-like receptor 4 (TLR4, n=17), b) C57Bl/6 mice that received monoclonal anti-tumor necrosis factor-α (TNFα) or control antibody (n=22) and c) C57Bl/6 wild type and transgenic mice that overexpress Bcl-2 in their gut epithelium (n=21). Intestinal epithelial proliferation and death were also examined in animals with differing degrees of lung inflammation (n=24) as well as in a timecourse analysis following a fixed injury (n=18). Measurements and Main Results ALI caused decreased proliferation and increased apoptosis in crypt epithelial cells in all animals studied. C3H/HeJ mice had higher levels of proliferation than C3H/HeN animals without additional changes in apoptosis. Anti-TNFα antibody had no effect on gut epithelial proliferation or death. Overexpression of Bcl-2 did not change proliferation despite decreasing gut apoptosis. Proliferation and apoptosis were not correlated to severity of lung injury, as gut alterations were lost in mice with more severe ALI. Changes in both gut epithelial proliferation and death were apparent within 12 hours, but proliferation was decreased 36 hours following ALI while apoptosis returned to normal. Conclusions ALI causes disparate effects on crypt proliferation and apoptosis, which occur, at least in part, through differing mechanisms involving TLR4 and Bcl-2. Severity of lung injury does not correlate with perturbations in proliferation or death in the gut

Aluminum hydroxide, calcium carbonate and calcium acetate in chronic intermittent hemodialysis patients.

PubMed

Janssen, M J; van der Kuy, A; ter Wee, P M; van Boven, W P

1996-02-01

Prevention of secondary hyperparathyroidism in uremia necessitates correction of hyperphosphatemia and hypocalcemia. In order to avoid aluminum toxicity, calcium containing phosphate binders are used increasingly, instead of aluminium hydroxide. Recent studies have shown that calcium acetate has many characteristics of an ideal phosphate binder. It is, for instance, a more readily soluble salt compared with calcium carbonate. This advantage might, however, disappear if calcium carbonate is taken on an empty stomach, a few minutes before meals. We examined the efficacy of three different phosphate binding agents in a randomized prospective study of 53 patients on regular hemodialysis. Bicarbonate dialyses were performed with a dialysate calcium concentration of 1.75 mmol/l. After a three-week wash-out period, patients received either aluminum hydroxide (control group), calcium acetate, or calcium carbonate as their phosphate binder. Patients were instructed to take the calcium salts a few minutes before meals on an empty stomach, and aluminum hydroxide during meals. Serum calcium, phosphate, intact parathormone, and alkaline phosphatase levels were determined every month. Patient compliance was estimated every month by asking the patients which phosphate binder and what daily dose they had used. Aluminum hydroxide tended to be the most effective phosphate binder. The mean +/- SEM required daily dose of calcium acetate at 12 months was 5.04 +/- 0.60 g, corresponding to 10.1 +/- 1.20 tablets of 500 mg. Co-medication with aluminum hydroxide, however, was needed (1.29 +/- 0.54 g per day, corresponding to 2.6 +/- 1.08 tablets of 500 mg). The required daily calcium carbonate dose appeared to be 2.71 +/- 0.48 g, corresponding to 5.4 +/- 0.95 capsules of 500 mg, with an adjuvant daily aluminum hydroxide dose of 0.69 +/- 0.27 g, corresponding to 1.4 +/- 0.55 tablets of 500 mg (p = 0.0055). Thus, the mean daily doses of elemental calcium were comparable between the calcium

Alterations in Intestinal Permeability After Thermal Injury,

DTIC Science & Technology

1992-01-01

intestinal permeability has been documented in the infected group. Our finding of increased intestinal many clinical states, including celiac disease ...Crohn’s permeability before the episode of infection suggests, but disease , and other intestinal mucosal disorders.6,7 It was does not prove, a causal...permeability to sugars in patients with Crohn’s disease ofresult in endotoxemia only in those patients who develop the terminal ileus and colon. Digestion

Calcium regulates FGF-23 expression in bone.

PubMed

David, Valentin; Dai, Bing; Martin, Aline; Huang, Jinsong; Han, Xiaobin; Quarles, L Darryl

2013-12-01

Calcium has recently been shown to regulate fibroblast growth factor 23 (FGF-23), a bone-derived phosphate and vitamin D-regulating hormone. To better understand the regulation of FGF-23 by calcium, phosphorus, 1,25 dihydroxyvitamin D3 [1,25(OH)2D], and PTH, we examined FGF-23 expression under basal conditions and in response to PTH, doxercalciferol, or high-calcium diet treatment in Gcm2(-/-) and Cyp27b1(-/-) mutant mice. Gcm2(-/-) mice exhibited low serum PTH and 1,25(OH)2D concentrations, hypocalcemia, and hyperphosphatemia, whereas Cyp27b1(-/-) mice had high PTH, undetectable 1,25(OH)2D, hypocalcemia, and hypophosphatemia. Serum FGF-23 levels were decreased in both mutant models. Doxercalciferol administration increased serum FGF-23 levels in both mutant models. PTH administration to Gcm2(-/-) mice also increased serum FGF-23 levels, in association with an increase in both 1,25(OH)2D and calcium concentrations. Multiple regression analysis of pooled data indicated that changes in FGF-23 were positively correlated with serum calcium and 1,25(OH)2D but not related to changes in serum phosphate concentrations. A high-calcium diet also increased serum FGF-23 concentrations in Cyp27b1(-/-) mice in the absence of 1,25(OH)2D and in Gcm2(-/-) mice with low PTH. The addition of calcium to the culture media also stimulated FGF-23 message expression in MC3T3-E1 osteoblasts. In addition, FGF-23 promoter activity in cultured osteoblasts was inhibited by the L-calcium-channel inhibitor nifedipine and stimulated by calcium ionophores. The effects of chronic low calcium to prevent 1,25(OH)2D and PTH stimulation of FGF-23 in these mutant mouse models suggest that suppression of FGF-23 plays an important physiological adaptive response to hypocalcemia.

Pregnane X receptor agonists enhance intestinal epithelial wound healing and repair of the intestinal barrier following the induction of experimental colitis.

PubMed

Terc, Joshua; Hansen, Ashleigh; Alston, Laurie; Hirota, Simon A

2014-05-13

The intestinal epithelial barrier plays a key role in the maintenance of homeostasis within the gastrointestinal tract. Barrier dysfunction leading to increased epithelial permeability is associated with a number of gastrointestinal disorders including the inflammatory bowel diseases (IBD) - Crohn's disease and ulcerative colitis. It is thought that the increased permeability in patients with IBD may be driven by alterations in the epithelial wound healing response. To this end considerable study has been undertaken to identify signaling pathways that may accelerate intestinal epithelial wound healing and normalize the barrier dysfunction observed in IBD. In the current study we examined the role of the pregnane X receptor (PXR) in modulating the intestinal epithelial wound healing response. Mutations and reduced mucosal expression of the PXR are associated with IBD, and others have reported that PXR agonists can dampen intestinal inflammation. Furthermore, stimulation of the PXR has been associated with increased cell migration and proliferation, two of the key processes involved in wound healing. We hypothesized that PXR agonists would enhance intestinal epithelial repair. Stimulation of Caco-2 intestinal epithelial cells with rifaximin, rifampicin and SR12813, all potent agonists of the PXR, significantly increased wound closure. This effect was driven by p38 MAP kinase-dependent cell migration, and occurred in the absence of cell proliferation. Treating mice with a rodent specific PXR agonist, pregnenolone 16α-carbonitrile (PCN), attenuated the intestinal barrier dysfunction observed in the dextran sulphate sodium (DSS) model of experimental colitis, an effect that occurred independent of the known anti-inflammatory effects of PCN. Taken together our data indicate that the activation of the PXR can enhance intestinal epithelial repair and suggest that targeting the PXR may help to normalize intestinal barrier dysfunction observed in patients with IBD

Small intestinal bacterial overgrowth syndrome

PubMed Central

Bures, Jan; Cyrany, Jiri; Kohoutova, Darina; Förstl, Miroslav; Rejchrt, Stanislav; Kvetina, Jaroslav; Vorisek, Viktor; Kopacova, Marcela

2010-01-01

Human intestinal microbiota create a complex polymicrobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO). SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastrointestinal tract. There are several endogenous defence mechanisms for preventing bacterial overgrowth: gastric acid secretion, intestinal motility, intact ileo-caecal valve, immunoglobulins within intestinal secretion and bacteriostatic properties of pancreatic and biliary secretion. Aetiology of SIBO is usually complex, associated with disorders of protective antibacterial mechanisms (e.g. achlorhydria, pancreatic exocrine insufficiency, immunodeficiency syndromes), anatomical abnormalities (e.g. small intestinal obstruction, diverticula, fistulae, surgical blind loop, previous ileo-caecal resections) and/or motility disorders (e.g. scleroderma, autonomic neuropathy in diabetes mellitus, post-radiation enteropathy, small intestinal pseudo-obstruction). In some patients more than one factor may be involved. Symptoms related to SIBO are bloating, diarrhoea, malabsorption, weight loss and malnutrition. The gold standard for diagnosing SIBO is still microbial investigation of jejunal aspirates. Non-invasive hydrogen and methane breath tests are most commonly used for the diagnosis of SIBO using glucose or lactulose. Therapy for SIBO must be complex, addressing all causes, symptoms and complications, and fully individualised. It should include treatment of the underlying disease, nutritional support and cyclical gastro-intestinal selective antibiotics. Prognosis is usually serious, determined mostly by the underlying disease that led to SIBO. PMID:20572300

Sodium butyrate attenuates soybean oil-based lipid emulsion-induced increase in intestinal permeability of lipopolysaccharide by modulation of P-glycoprotein in Caco-2 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan, Jun-Kai; Gong, Zi-Zhen; Zhang, Tian

Down-regulation of intestinal P-glycoprotein (P-gp) by soybean oil-based lipid emulsion (SOLE) may cause elevated intestinal permeability of lipopolysaccharide (LPS) in patients with total parenteral nutrition, but the appropriate preventative treatment is currently limited. Recently, sodium butyrate (NaBut) has been demonstrated to regulate the expression of P-gp. Therefore, this study aimed to address whether treatment with NaBut could attenuate SOLE-induced increase in intestinal permeability of LPS by modulation of P-gp in vitro. Caco-2 cells were exposed to SOLE with or without NaBut. SOLE-induced down-regulation of P-gp was significantly attenuated by co-incubation with NaBut. Nuclear recruitment of FOXO 3a in response to NaButmore » was involved in P-gp regulation. Transport studies revealed that SOLE-induced increase in permeability of LPS was significantly attenuated by co-incubation with NaBut. Collectively, our results suggested that NaBut may be a potentially useful medication to prevent SOLE-induced increase in intestinal permeability of LPS. - Highlights: • Caco-2 cells were used as models for studying parenteral nutrition in vitro. • NaBut restored SOLE-induced down-regulation of P-gp in Caco-2 cells. • Regulation of P-gp by NaBut was mediated via nuclear recruitment of FOXO 3a. • NaBut modulated the permeability of LPS by P-gp function, not barrier function.« less