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Sample records for intestinal oxalate absorption

  1. Acute probiotic ingestion reduces gastrointestinal oxalate absorption in healthy subjects.

    PubMed

    Al-Wahsh, Ismail; Wu, Yan; Liebman, Michael

    2012-06-01

    Both a high dietary oxalate intake and increased intestinal absorption appear to be major causes of elevated urine oxalate, a risk factor for kidney stone formation. A number of recent studies have assessed whether daily ingestion of a probiotic containing oxalate-degrading bacteria could lead to sufficient gut colonization to increase oxalate degradation, thereby reducing urinary oxalate. In contrast, the present study assessed whether simultaneous ingestion of oxalate-degrading probiotic bacteria with a 176 mg oxalate load could lead to decreased urinary oxalate in a population of 11 healthy non-stone formers (8 females, 3 males), aged 21-45 years. The results indicated that both the single and double doses of VSL#3(®) probiotic solutions were effective in reducing urinary oxalate and estimated oxalate absorption with no significant difference between the two probiotic doses. The timing of the reduction in urinary oxalate suggested a small intestinal and possibly gastric reduction in oxalate absorption. Similar to what had been reported for chronic or daily probiotic ingestion, individuals characterized by high oxalate absorption were most likely to experience clinically significant reductions in urinary oxalate in response to acute probiotic ingestion. PMID:21874572

  2. Acute probiotic ingestion reduces gastrointestinal oxalate absorption in healthy subjects.

    TOXLINE Toxicology Bibliographic Information

    Al-Wahsh I; Wu Y; Liebman M

    2012-06-01

    Both a high dietary oxalate intake and increased intestinal absorption appear to be major causes of elevated urine oxalate, a risk factor for kidney stone formation. A number of recent studies have assessed whether daily ingestion of a probiotic containing oxalate-degrading bacteria could lead to sufficient gut colonization to increase oxalate degradation, thereby reducing urinary oxalate. In contrast, the present study assessed whether simultaneous ingestion of oxalate-degrading probiotic bacteria with a 176 mg oxalate load could lead to decreased urinary oxalate in a population of 11 healthy non-stone formers (8 females, 3 males), aged 21-45 years. The results indicated that both the single and double doses of VSL#3(®) probiotic solutions were effective in reducing urinary oxalate and estimated oxalate absorption with no significant difference between the two probiotic doses. The timing of the reduction in urinary oxalate suggested a small intestinal and possibly gastric reduction in oxalate absorption. Similar to what had been reported for chronic or daily probiotic ingestion, individuals characterized by high oxalate absorption were most likely to experience clinically significant reductions in urinary oxalate in response to acute probiotic ingestion.

  3. Absorption kinetics of oxalate from oxalate-rich food in man

    SciTech Connect

    Prenen, J.A.; Boer, P.; Dorhout Mees, E.J.

    1984-11-01

    The absorption of oxalate was investigated in a healthy subject after ingestion of oxalate-rich meals (spinach and rhubarb) with and without addition of /sup 14/C-labeled oxalic acid and calcium oxalate, and after oxalate-free meals with addition of nonlabeled sodium oxalate and calcium oxalate. Under these conditions, calcium oxalate was absorbed to the same extent as soluble oxalate; only a small percentage (2.4 +/- 0.7) of the total oxalate load was absorbed. Significant oxalate absorption occurred within 1 to 8 h after ingestion. The results suggest that under normal conditions the proximal part of the small bowel is a major absorption site.

  4. Oxalic acid decreases calcium absorption in rats

    SciTech Connect

    Weaver, C.M.; Martin, B.R.; Ebner, J.S.; Krueger, C.A.

    1987-11-01

    Calcium absorption from salts and foods intrinsically labeled with /sup 45/Ca was determined in the rat model. Calcium bioavailability was nearly 10 times greater for low oxalate kale, CaCO/sub 3/ and CaCl/sub 2/ than from CaC/sub 2/O/sub 4/ (calcium oxalate) and spinach (high in oxalates). Extrinsic and intrinsic labeling techniques gave a similar assessment of calcium bioavailability from kale but not from spinach.

  5. 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

  6. Probiotics and Other Key Determinants of Dietary Oxalate Absorption1

    PubMed Central

    Liebman, Michael; Al-Wahsh, Ismail A.

    2011-01-01

    Oxalate is a common component of many foods of plant origin, including nuts, fruits, vegetables, grains, and legumes, and is typically present as a salt of oxalic acid. Because virtually all absorbed oxalic acid is excreted in the urine and hyperoxaluria is known to be a considerable risk factor for urolithiasis, it is important to understand the factors that have the potential to alter the efficiency of oxalate absorption. Oxalate bioavailability, a term that has been used to refer to that portion of food-derived oxalate that is absorbed from the gastrointestinal tract (GIT), is estimated to range from 2 to 15% for different foods. Oxalate bioavailability appears to be decreased by concomitant food ingestion due to interactions between oxalate and coingested food components that likely result in less oxalic acid remaining in a soluble form. There is a lack of consensus in the literature as to whether efficiency of oxalate absorption is dependent on the proportion of total dietary oxalate that is in a soluble form. However, studies that directly compared foods of varying soluble oxalate contents have generally supported the proposition that the amount of soluble oxalate in food is an important determinant of oxalate bioavailability. Oxalate degradation by oxalate-degrading bacteria within the GIT is another key factor that could affect oxalate absorption and degree of oxaluria. Studies that have assessed the efficacy of oral ingestion of probiotics that provide bacteria with oxalate-degrading capacity have led to promising but generally mixed results, and this remains a fertile area for future studies. PMID:22332057

  7. Intestinal absorptive function.

    PubMed Central

    Spiller, R C

    1994-01-01

    The normal gut is adapted to intermittent feeding with complex macromolecular substrates of low sodium content. The high permeability of the upper small intestine to sodium, together with sodium rich saliva and pancreaticobiliary secretions results in large sodium fluxes into the lumen. These substantial sodium influxes are matched by equally large effluxes from the ileum and proximal colon, which are comparatively impermeable to sodium and capable of active sodium absorption. Resection of these distal, sodium absorbing regions of the intestine, lead to problems with sodium depletion. Controlled transit of chyme is essential to permit time for optimum digestion and absorption and a range of feedback control mechanisms exist. Partially digested nutrients, both in the duodenum and ileum, exert inhibitory feedback to delay delivery of further nutrients and here again surgery may compromise these reflexes. Brush border hydrolase values are strongly influenced by luminal nutrient concentrations, being impaired by malnutrition and total parenteral nutrition, but restored by enteral feeding. Viscous fibre slows absorption and may delay transit through mechanisms that are as yet uncertain. Whether and how novel substrates activate normal control mechanisms will be important factors determining their effectiveness and patient acceptability. PMID:8125391

  8. Effects of acid-base variables and the role of carbonic anhydrase on oxalate secretion by the mouse intestine invitro

    PubMed Central

    Whittamore, Jonathan M; Frost, Susan C; Hatch, Marguerite

    2015-01-01

    Hyperoxaluria is a major risk factor for calcium oxalate kidney stones and the intestine is recognized as an important extra-renal pathway for eliminating oxalate. The membrane-bound chloride/bicarbonate (Cl?/) exchangers are involved in the transcellular movement of oxalate, but little is understood about how they might be regulated. , CO2, and pH are established modulators of intestinal NaCl cotransport, involving Na+/H+ and Cl?/ exchange, but their influence on oxalate transport is unknown. Measuring 14C-oxalate and 36Cl fluxes across isolated, short-circuited segments of the mouse distal ileum and distal colon we examined the role of these acid-base variables and carbonic anhydrase (CA) in oxalate and Cl? transport. In standard buffer both segments performed net oxalate secretion (and Cl? absorption), but only the colon, and the secretory pathway were responsive to and CO2. Ethoxzolamide abolished net oxalate secretion by the distal colon, and when used in tandem with an impermeant CA inhibitor, signaled an intracellular CA isozyme was required for secretion. There was a clear dependence on as their removal eliminated secretion, while at 42mmol/L was also decreased and eradicated. Independent of pH, raising Pco2 from 28 to 64 mmHg acutely stimulated net oxalate secretion 41%. In summary, oxalate secretion by the distal colon was dependent on , CA and specifically modulated by CO2, whereas the ileum was remarkably unresponsive. These findings highlight the distinct segmental heterogeneity along the intestine, providing new insights into the oxalate transport mechanism and how it might be regulated. PMID:25716924

  9. Intestinal absorption of Serratia protease

    SciTech Connect

    Miyata, K.; Hirai, S.; Yashiki, T.; Tomoda, K.

    1980-04-01

    The intestinal absorption of Serratia protease (TSP) was studied in vivo with adult rats and dogs. After intraduodenal administration of TSP, the TSP levels in the blood and lymph were determined periodically by radioimmunoassay. The maximum concentration of TSP was observed within 1 h after administration in both the blood and lymph; it was higher in the latter. An apparent saturation phenomenon was observed in the absorption of TSP.

  10. [Renal oxalate excretion following oral oxalate load in patients with urinary calculus disease and healthy controls].

    PubMed

    Ebisuno, S; Morimoto, S; Yoshida, T; Fukatani, T; Yasukawa, S; Okawa, T

    1986-12-01

    Oral oxalate loading using sodium oxalate or a vegetable juice was done to evaluate the intestinal absorption of exogenous oxalate in 30 patients with renal stones and 13 healthy controls. Fifteen calcium oxalate stone formers, 7 non-oxalate stone formers and 10 healthy volunteers were given an oral loading of sodium oxalate (500 mg). Urinary oxalate increased promptly, reaching a peak value within 4 to 8 hours after administration of a synthetic oxalate orally in a fasting state. In calcium oxalate stone formers, the mean increment of urinary oxalate and the bioavailability following oral sodium oxalate load were significantly higher than in the healthy controls and non-oxalate stone formers. Furthermore, intestinal hyperabsorption of oxalate in our criterion was defined in six patients with calcium oxalate stones (40%). On the other hand, eight calcium oxalate stone formers and three healthy controls were given vegetable juice. Urinary oxalate was increased only slightly after the ingestion, and there was no difference between calcium oxalate stone formers and normal controls. These results suggest that a certain hyperoxaluria might be induced by intestinal absorption of exogenous oxalate, and that the hyperabsorption might indicate a possible risk factor for calcium oxalate stone formation. PMID:3825824

  11. Intestinal lipid absorption.

    PubMed

    Iqbal, Jahangir; Hussain, M Mahmood

    2009-06-01

    Our knowledge of the uptake and transport of dietary fat and fat-soluble vitamins has advanced considerably. Researchers have identified several new mechanisms by which lipids are taken up by enterocytes and packaged as chylomicrons for export into the lymphatic system or clarified the actions of mechanisms previously known to participate in these processes. Fatty acids are taken up by enterocytes involving protein-mediated as well as protein-independent processes. Net cholesterol uptake depends on the competing activities of NPC1L1, ABCG5, and ABCG8 present in the apical membrane. We have considerably more detailed information about the uptake of products of lipid hydrolysis, the active transport systems by which they reach the endoplasmic reticulum, the mechanisms by which they are resynthesized into neutral lipids and utilized within the endoplasmic reticulum to form lipoproteins, and the mechanisms by which lipoproteins are secreted from the basolateral side of the enterocyte. apoB and MTP are known to be central to the efficient assembly and secretion of lipoproteins. In recent studies, investigators found that cholesterol, phospholipids, and vitamin E can also be secreted from enterocytes as components of high-density apoB-free/apoAI-containing lipoproteins. Several of these advances will probably be investigated further for their potential as targets for the development of drugs that can suppress cholesterol absorption, thereby reducing the risk of hypercholesterolemia and cardiovascular disease. PMID:19158321

  12. Vitamin D and Intestinal Calcium Absorption

    PubMed Central

    Christakos, Sylvia; Dhawan, Puneet; Porta, Angela; Mady, Leila J.; Seth, Tanya

    2012-01-01

    The principal function of vitamin D in calcium homeostasis is to increase calcium absorption from the intestine. Calcium is absorbed by both an active transcellular pathway, which is energy dependent, and by a passive paracellular pathway through tight junctions. 1,25Dihydroxyvitamin D3 (1,25(OH)2D3) the hormonally active form of vitamin D, through its genomic actions, is the major stimulator of active intestinal calcium absorption which involves calcium influx, translocation of calcium through the interior of the enterocyte and basolateral extrusion of calcium by the intestinal plasma membrane pump. This article reviews recent studies that have challenged the traditional model of vitamin D mediated transcellular calcium absorption and the crucial role of specific calcium transport proteins in intestinal calcium absorption. There is also increasing evidence that 1,25(OH)2D3 can enhance paracellular calcium diffusion. The influence of estrogen, prolactin, glucocorticoids and aging on intestinal calcium absorption and the role of the distal intestine in vitamin D mediated intestinal calcium absorption are also discussed. PMID:21664413

  13. Neural regulation of intestinal nutrient absorption.

    PubMed

    Mourad, Fadi H; Saadé, Nayef E

    2011-10-01

    The nervous system and the gastrointestinal (GI) tract share several common features including reciprocal interconnections and several neurotransmitters and peptides known as gut peptides, neuropeptides or hormones. The processes of digestion, secretion of digestive enzymes and then absorption are regulated by the neuro-endocrine system. Luminal glucose enhances its own absorption through a neuronal reflex that involves capsaicin sensitive primary afferent (CSPA) fibres. Absorbed glucose stimulates insulin release that activates hepatoenteric neural pathways leading to an increase in the expression of glucose transporters. Adrenergic innervation increases glucose absorption through α1 and β receptors and decreases absorption through activation of α2 receptors. The vagus nerve plays an important role in the regulation of diurnal variation in transporter expression and in anticipation to food intake. Vagal CSPAs exert tonic inhibitory effects on amino acid absorption. It also plays an important role in the mediation of the inhibitory effect of intestinal amino acids on their own absorption at the level of proximal or distal segment. However, chronic extrinsic denervation leads to a decrease in intestinal amino acid absorption. Conversely, adrenergic agonists as well as activation of CSPA fibres enhance peptides uptake through the peptide transporter PEPT1. Finally, intestinal innervation plays a minimal role in the absorption of fat digestion products. Intestinal absorption of nutrients is a basic vital mechanism that depends essentially on the function of intestinal mucosa. However, intrinsic and extrinsic neural mechanisms that rely on several redundant loops are involved in immediate and long-term control of the outcome of intestinal function. PMID:21854830

  14. Intestinal absorption and metabolism of xenobiotics

    PubMed Central

    Chhabra, Rajendra S.

    1979-01-01

    There are five possible processes of intestinal absorption of xenobiotics. These are active transport, passive diffusions, pinocytosis, filtration through pores, and lymphatic absorption. The passive diffusion is major process for transport of foreign chemicals across the intestine. Though the lymphatic absorption of drugs is not of any major therapeutic significance, the uptake of toxic chemicals such as 3-MC, benzpyrene, and DDT through lymphatics may enhance their toxicity, since they are distributed to other organ systems in the body without being metabolized by liver. A number of factors such as diet, motility of intestine, interference with gastrointestinal flora, changes in the rate of gastric emptying, age of the animal, and dissolution rate of xenobiotic can alter the rate of absorption of chemicals. Liver is the major site of metabolism of xenobiotics, but the contribution of intestinal metabolism of xenobiotic can influence the overall bioavailability of chemicals. The xenobiotic metabolizing enzymes located in endoplasmic reticulum of intestine possess biochemical characteristics similar to that of liver. In general, the rate of metabolism of xenobiotics by intestinal microsomal preparation is lower than that observed with similar hepatic microsomal preparations. The in vitro intestinal metabolism of xenobiotics is affected by several factors including age, sex, diurnal variations, species, and nutritional status of the animal. The intestinal xenobiotic metabolizing enzymes are stimulated by the pretreatment of animals with foreign chemicals, but this depends on the route of administration of chemicals, drug substrate and the animal species used. Rabbit intestinal drug metabolizing enzymes seem to be resistant to induction by foreign chemicals. PMID:540626

  15. Intestinal absorption and biomagnification of organochlorines

    SciTech Connect

    Gobas, F.A.P.C. ); McCorquodale, J.R.; Haffner, G.D. )

    1993-03-01

    Dietary uptake rates of several organochlorines from diets with different lipid contents were measured in goldfish (Carassius auratus) to investigate the mechanism of intestinal absorption and biomagnification of organic chemical. The results suggest that intestinal absorption is predominantly controlled by chemical diffusion rather than lipid cotransport. Data for chemical uptake in human infants are presented to illustrate that biomagnification is caused by the digestion of food in the gastrointestinal tract. The findings are discussed in the context of two conflicting theories for the mechanism of biomagnification, and a mechanistic model is presented for the dietary uptake and biomagnification of organic chemicals in fish and mammals.

  16. Molecular aspects of intestinal calcium absorption.

    PubMed

    Diaz de Barboza, Gabriela; Guizzardi, Solange; Tolosa de Talamoni, Nori

    2015-06-21

    Intestinal Ca(2+) absorption is a crucial physiological process for maintaining bone mineralization and Ca(2+) homeostasis. It occurs through the transcellular and paracellular pathways. The first route comprises 3 steps: the entrance of Ca(2+) across the brush border membranes (BBM) of enterocytes through epithelial Ca(2+) channels TRPV6, TRPV5, and Cav1.3; Ca(2+) movement from the BBM to the basolateral membranes by binding proteins with high Ca(2+) affinity (such as CB9k); and Ca(2+) extrusion into the blood. Plasma membrane Ca(2+) ATPase (PMCA1b) and sodium calcium exchanger (NCX1) are mainly involved in the exit of Ca(2+) from enterocytes. A novel molecule, the 4.1R protein, seems to be a partner of PMCA1b, since both molecules co-localize and interact. The paracellular pathway consists of Ca(2+) transport through transmembrane proteins of tight junction structures, such as claudins 2, 12, and 15. There is evidence of crosstalk between the transcellular and paracellular pathways in intestinal Ca(2+) transport. When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways that inhibit intestinal Ca(2+) absorption. Normalization of redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid, or melatonin return intestinal Ca(2+) transport to control values. Calcitriol [1,25(OH)?D?] is the major controlling hormone of intestinal Ca(2+) transport. It increases the gene and protein expression of most of the molecules involved in both pathways. PTH, thyroid hormones, estrogens, prolactin, growth hormone, and glucocorticoids apparently also regulate Ca(2+) transport by direct action, indirect mechanism mediated by the increase of renal 1,25(OH)?D? production, or both. Different physiological conditions, such as growth, pregnancy, lactation, and aging, adjust intestinal Ca(2+) absorption according to Ca(2+) demands. Better knowledge of the molecular details of intestinal Ca(2+) absorption could lead to the development of nutritional and medical strategies for optimizing the efficiency of intestinal Ca(2+) absorption and preventing osteoporosis and other pathologies related to Ca(2+) metabolism. PMID:26109800

  17. Molecular aspects of intestinal calcium absorption

    PubMed Central

    Diaz de Barboza, Gabriela; Guizzardi, Solange; Tolosa de Talamoni, Nori

    2015-01-01

    Intestinal Ca2+ absorption is a crucial physiological process for maintaining bone mineralization and Ca2+ homeostasis. It occurs through the transcellular and paracellular pathways. The first route comprises 3 steps: the entrance of Ca2+ across the brush border membranes (BBM) of enterocytes through epithelial Ca2+ channels TRPV6, TRPV5, and Cav1.3; Ca2+ movement from the BBM to the basolateral membranes by binding proteins with high Ca2+ affinity (such as CB9k); and Ca2+ extrusion into the blood. Plasma membrane Ca2+ ATPase (PMCA1b) and sodium calcium exchanger (NCX1) are mainly involved in the exit of Ca2+ from enterocytes. A novel molecule, the 4.1R protein, seems to be a partner of PMCA1b, since both molecules co-localize and interact. The paracellular pathway consists of Ca2+ transport through transmembrane proteins of tight junction structures, such as claudins 2, 12, and 15. There is evidence of crosstalk between the transcellular and paracellular pathways in intestinal Ca2+ transport. When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways that inhibit intestinal Ca2+ absorption. Normalization of redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid, or melatonin return intestinal Ca2+ transport to control values. Calcitriol [1,25(OH)2D3] is the major controlling hormone of intestinal Ca2+ transport. It increases the gene and protein expression of most of the molecules involved in both pathways. PTH, thyroid hormones, estrogens, prolactin, growth hormone, and glucocorticoids apparently also regulate Ca2+ transport by direct action, indirect mechanism mediated by the increase of renal 1,25(OH)2D3 production, or both. Different physiological conditions, such as growth, pregnancy, lactation, and aging, adjust intestinal Ca2+ absorption according to Ca2+ demands. Better knowledge of the molecular details of intestinal Ca2+ absorption could lead to the development of nutritional and medical strategies for optimizing the efficiency of intestinal Ca2+ absorption and preventing osteoporosis and other pathologies related to Ca2+ metabolism. PMID:26109800

  18. Biotin absorption by distal rat intestine

    SciTech Connect

    Bowman, B.B.; Rosenberg, I.H.

    1987-12-01

    We used the in vivo intestinal loop approach, with short (10-min) and long (3-h) incubations, to examine biotin absorption in proximal jejunum, distal ileum, cecum and proximal colon. In short-term studies, luminal biotin disappearance from rat ileum was about half that observed in the jejunum, whereas absorption by proximal colon was about 12% of that in the jejunum. In 3-h closed-loop studies, the absorption of 1.0 microM biotin varied regionally. Biotin absorption was nearly complete in the small intestine after 3 h; however, only about 15% of the dose had been absorbed in the cecum and 27% in the proximal colon after 3 h. Independent of site of administration, the major fraction of absorbed biotin was recovered in the liver; measurable amounts of radioactive biotin were also present in kidney and plasma. The results support the potential nutritional significance for the rat of biotin synthesized by bacteria in the distal intestine, by demonstrating directly an absorptive capability of mammalian large bowel for this vitamin.

  19. Mechanisms of oxalate absorption and secretion across the rabbit distal colon.

    PubMed

    Hatch, M; Freel, R W; Vaziri, N D

    1994-01-01

    To further evaluate the mechanisms of oxalate (Ox2-) transport in the intestine the following studies were performed using isolated, short-circuited segments of the rabbit distal colon (DC). In control buffer, the DC absorbed Ox2- (net Ox2- flux, JNetOx = 5.4 +/- 0.7 pmol.cm-1.h-1). Replacement of Na+ with N-methyl-D-glucamine (NMDG+) abolished Ox2- absorption by decreasing mucosal to serosal Ox2- flux (JmsOx), without affecting Cl- transport, while gluconate substitution for Cl- did not affect JNetOx or net Na+ flux (JNetNa). Addition of Na+ to the serosal side of tissues bathed by NMDG+ buffer increased JmsOx 40% without altering mucosal to serosal Cl- flux (JmsCl). Serosal amiloride or dimethyl amiloride (10(-3) M) abolished JNetOx by decreasing JmsOx, it increased serosal to muscosal Cl- flux (JsmCl) and it gradually inhibited short-circuit current (Isc). Mucosal amiloride (10(-4) M) abolished Ise but had no effect on Ox2- or Cl- fluxes. Serosal 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS, 10(-6) M) reduced JmsOx by 20% and JNetOx by 43% without affecting JmsCl or JNetCl. Dibutyryl cyclic adenosine monophosphate (dB-cAMP, 5 x 10(-4) M, both sides) stimulated Ox2- secretion (JNetOx = -12.6 +/- 3.3 pmol.cm-2.h-1). The dB-cAMP-induced secretion of Ox2- and Cl- were fully abolished by serosal furosemide (10(-4) M) and partially inhibited (35%) by 5 x 10(-4) M mucosal NPPB [5-nitro-2-(3-phenylpropylamino)-benzoic acid], a putative Cl- channel blocker.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8146012

  20. Intestinal absorption of copper: effect of sodium

    SciTech Connect

    Wapnir, R.A.; Stiel, L.

    1987-07-01

    The mechanisms of copper (Cu) absorption from the small intestinal lumen are poorly understood. In this study the authors investigated the role of sodium (Na) during the removal of Cu from the lumen of jejunal and ileal segments. Intestinal absorption of Cu from a 31 M solution was highest in the presence of an isotonic concentration of NaCl, as compared to solutions containing either glycerol (GRL) or N-methyl-D-glucamine (NMG) as osmotic agents. In the jejunum, mean +/- SEM Cu absorption rates in the presence of the following solutes were: with NaCl, 57.5 +/- 10.5 pmole/min x cm; with GRL, 13.3 +/- 14.7; with NMG, 18.4 +/- 10.1. In the ileum, copper absorption in the presence of NaCl was 64.4 +/- 9.6; with GRL, 24.3 +/- 10.1 with NMG, 15.8 +/- 3.7. Kinetic analysis of the carrier-mediated component of Cu absorption in rat jejunum yielded a V/sub max/ = 47.5 pmole/min x cm and an apparent K/sub t/ = 21 M. The diffusion coefficient was calculated to be 1.4 x 10 V cmS/sec. The absorption of Cu was independent of net water absorption, which was highest in the presence of GRL and abolished and reversed into secretion by NMG. The data obtained are indicative of a significant role of Na in the small intestinal transport of Cu, in vivo, although not directly related to unidirectional water fluxes. The cation specificity of Na in this process remains to be elucidated.

  1. Intestinal absorption of calcium and phosphorus

    SciTech Connect

    Wasserman, R.H.

    1981-01-01

    The intestinal absorption of calcium and phosphorus has received considerable attention in recent years. The evidence has clearly indicated that calcium is absorbed by two processes: active transport and diffusion. Vitamin D appears to affect both processes, and has a significant effect at the brush border of the intestinal cell. Several proposed models to account for the transmural movement of calcium are discussed. The active transport of phosphate is under the control of vitamin D and is located at the brush border region of the intestinal cell. This transport system, like several others, appears to be sodium-dependent and inhibited by ouabain. In-transit phosphate does not mix with the cellular phosphate pool. Emphasized in the presentation is current knowledge of the transport mechanisms and macromolecular changes that potentially account for the stimulatory effect of vitamin D on calcium and phosphate transport.

  2. Dietary Phospholipids and Intestinal Cholesterol Absorption

    PubMed Central

    Cohn, Jeffrey S.; Kamili, Alvin; Wat, Elaine; Chung, Rosanna W. S.; Tandy, Sally

    2010-01-01

    Experiments carried out with cultured cells and in experimental animals have consistently shown that phospholipids (PLs) can inhibit intestinal cholesterol absorption. Limited evidence from clinical studies suggests that dietary PL supplementation has a similar effect in man. A number of biological mechanisms have been proposed in order to explain how PL in the gut lumen is able to affect cholesterol uptake by the gut mucosa. Further research is however required to establish whether the ability of PLs to inhibit cholesterol absorption is of therapeutic benefit. PMID:22254012

  3. Development and physiological regulation of intestinal lipid absorption. III. Intestinal transporters and cholesterol absorption.

    PubMed

    Hui, David Y; Labonté, Eric D; Howles, Philip N

    2008-04-01

    Intestinal cholesterol absorption is modulated by transport proteins in enterocytes. Cholesterol uptake from intestinal lumen requires several proteins on apical brush-border membranes, including Niemann-Pick C1-like 1 (NPC1L1), scavenger receptor B-I, and CD36, whereas two ATP-binding cassette half transporters, ABCG5 and ABCG8, on apical membranes work together for cholesterol efflux back to the intestinal lumen to limit cholesterol absorption. NPC1L1 is essential for cholesterol absorption, but its function as a cell surface transporter or an intracellular cholesterol transport protein needs clarification. Another ATP transporter, ABCA1, is present in the basolateral membrane to mediate HDL secretion from enterocytes. PMID:18276831

  4. Intestinal absorption of calcium and phosphorus

    SciTech Connect

    Wasserman, R.H.

    1981-01-01

    The intestinal absorption of calcium and phosphorus has received considerable attention in recent years. The evidence has clearly indicated that calcium is absorbed by two processes: active transport and diffusion. Vitamin D appears to affect both processes, and has a significant effect at the brush border of the intestinal cell. Vitamin D also affects the release of calcium from the intestinal cell to the lamina propria. Several proposed models to account for the transmural movement of calcium are discussed. The active transport of phosphate is under the control of vitamin D and is located at the brush border region of the intestinal cell. This transport system, like several others, appears to be sodium-dependent and inhibited by ouabain. In-transit phosphate does not mix with the cellular phosphate pool, implying that phosphate is moving through the cell as a distinct packet or through specialized channels, or possibly a phosphorylated derivative. Emphasized in the presentation is current knowledge of the transport mechanisms and macromolecular changes that potentially account for the stimulatory effect of vitamin D on calcium and phosphate transport.

  5. Combinatorial QSAR modeling of human intestinal absorption.

    PubMed

    Suenderhauf, Claudia; Hammann, Felix; Maunz, Andreas; Helma, Christoph; Huwyler, Jörg

    2011-02-01

    Intestinal drug absorption in humans is a central topic in drug discovery. In this study, we use a broad selection of machine learning and statistical methods for the classification and numerical prediction of this key end point. Our data set is based on a selection of 458 small druglike compounds with FDA approval. Using easily available tools, we calculated one- to three-dimensional physicochemical descriptors and used various methods of feature selection (best-first backward selection, correlation analysis, and decision tree analysis). We then used decision tree induction (DTI), fragment-based lazy-learning (LAZAR), support vector machine classification, multilayer perceptrons, random forests, k-nearest neighbor and Naïve Bayes analysis to model absorption ratios and binary classification (well-absorbed and poorly absorbed compounds). Best performance for classification was seen with DTI using the chi-squared analysis interaction detector (CHAID) algorithm, yielding corrected classification rate of 88% (Matthews correlation coefficient of 75%). In numeric predictions, the multilayer perceptron performed best, achieving a root mean squared error of 25.823 and a coefficient of determination of 0.6. In line with current understanding is the importance of descriptors such as lipophilic partition coefficients (log P) and hydrogen bonding. However, we are able to highlight the utility of gravitational indices and moments of inertia, reflecting the role of structural symmetry in oral absorption. Our models are based on a diverse data set of marketed drugs representing a broad chemical space. These models therefore contribute substantially to the molecular understanding of human intestinal drug absorption and qualify for a generalized use in drug discovery and lead optimization. PMID:21142073

  6. Intestinal absorption of biotin in the rat

    SciTech Connect

    Bowman, B.B.; Selhub, J.; Rosenberg, I.H.

    1986-07-01

    We examined the absorption of biotin using the in vivo intestinal loop technique. Jejunal segments from male rats were filled with solutions containing (/sup 3/H)biotin and (/sup 14/C)inulin in Krebs-Ringer phosphate buffer, pH 6.5. Absorption was determined on the basis of luminal tritium disappearance after correction for inulin recovery. At biotin concentrations of 0.1 and 5.0 microM, luminal biotin disappearance was linear for at least 10 min. At biotin concentrations ranging from 2.3 nM to 75 microM, 10-28% of the administered dose was absorbed in 10 min. The concentration dependence of luminal biotin disappearance is consistent with the presence of both saturable and nonsaturable (linear) components of biotin uptake, with estimated Km = 9.6 microM and Jmax = 75.2 pmol/(2.5 cm loop X min). The rate constant for nonsaturable uptake is 3.1 pmol/(2.5 cm loop X min X microM). We conclude that at biotin concentrations less than 5 microM, biotin absorption proceeds largely by the saturable process, whereas at concentrations above 25 microM, nonsaturable uptake predominates. Additional studies demonstrated significantly less biotin uptake in the ileum than in the jejunum, a finding in agreement with previous in vitro studies.

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

    SciTech Connect

    Ogawa, Eiichi; Hosokawa, Masaya; Faculty of Human Sciences, Tezukayama Gakuin University, Osaka ; Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito; Tsukiyama, Katsushi; Yamada, Yuichiro; Department of Internal Medicine, Division of Endocrinology, Diabetes and Geriatric Medicine, Akita University School of Medicine, Akita ; Seino, Yutaka; Kansai Electric Power Hospital, Osaka ; Inagaki, Nobuya; CREST of Japan Science and Technology Cooperation , Kyoto

    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 glucose 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 somatostatin-mediated pathway rather than through a GLP-1-mediated pathway.

  8. Intestinal Cgi-58 deficiency reduces postprandial lipid absorption.

    PubMed

    Xie, Ping; Guo, Feng; Ma, Yinyan; Zhu, Hongling; Wang, Freddy; Xue, Bingzhong; Shi, Hang; Yang, Jian; Yu, Liqing

    2014-01-01

    Comparative Gene Identification-58 (CGI-58), a lipid droplet (LD)-associated protein, promotes intracellular triglyceride (TG) hydrolysis in vitro. Mutations in human CGI-58 cause TG accumulation in numerous tissues including intestine. Enterocytes are thought not to store TG-rich LDs, but a fatty meal does induce temporary cytosolic accumulation of LDs. Accumulated LDs are eventually cleared out, implying existence of TG hydrolytic machinery in enterocytes. However, identities of proteins responsible for LD-TG hydrolysis remain unknown. Here we report that intestine-specific inactivation of CGI-58 in mice significantly reduces postprandial plasma TG concentrations and intestinal TG hydrolase activity, which is associated with a 4-fold increase in intestinal TG content and large cytosolic LD accumulation in absorptive enterocytes during the fasting state. Intestine-specific CGI-58 knockout mice also display mild yet significant decreases in intestinal fatty acid absorption and oxidation. Surprisingly, inactivation of CGI-58 in intestine significantly raises plasma and intestinal cholesterol, and reduces hepatic cholesterol, without altering intestinal cholesterol absorption and fecal neutral sterol excretion. In conclusion, intestinal CGI-58 is required for efficient postprandial lipoprotein-TG secretion and for maintaining hepatic and plasma lipid homeostasis. Our animal model will serve as a valuable tool to further define how intestinal fat metabolism influences the pathogenesis of metabolic disorders, such as obesity and type 2 diabetes. PMID:24618586

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

    PubMed Central

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

    2014-01-01

    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. PMID:20736987

  10. Paracetamol absorption from different sites in the human small intestine.

    PubMed

    Gramatt, T; Richter, K

    1994-06-01

    Site-specificity in the small intestinal absorption of paracetamol was investigated using a segmental intestinal steady state perfusion technique (triple-lumen tubing system) combined with simultaneous measurements of serum drug concentrations. Dissolved paracetamol was perfused over 160 min into different parts of the small intestine (65-210 cm beyond the teeth). Each of the four healthy subjects was studied twice with a proximal and a more distal site of perfusion. Serum drug concentrations were similar after proximal and distal perfusions. Mean drug absorption rates calculated from intestinal aspirate concentrations were similar in both parts of the intestine--proximal: 869 micrograms 30 cm-1 min-1 (95% CI: 659-1079) vs distal: 941 micrograms 30 cm-1 min-1 (794-1088). The absorption rate was related directly to the amount of paracetamol perfused per unit time as well as to the rate of transmucosal water fluxes. PMID:7917782

  11. [Intestinal glucose absorption in rats of different ages (author's transl)].

    PubMed

    Tolu, W; Fadda, F; Carbini, L; Padalino, A

    1975-01-01

    We studied the intestinal glucose absorption in a colony of rats at different ages. The experiment was carried out on animals of the following ages: 3, 5, 10 and 20 months. All rats were fasted 48 hr prior to the administration of 2 ml. 50% glucose solution by an oesophageal sound. After one hour the animals were killed, the intestine was washed with a determinated quantity of distilled water and homogenized, to find out any trace of glucose in mucose cells. Glucose absorption was calculated as the difference between the quantity introduced and that left in the intestine. The results of this experiment show that glucose absorption expressed as mg/100 gm. body weight/hr decrease significantly during the first 10 months, with no marked changes there after. Absorption rapidly increase during the first 16 month, if expressed as mg/hr. This is probably due to a remarkable weight increase without a proportional increase of intestinal length. PMID:1243975

  12. [Intestinal absorption of berberine alone and in combinations by rats single pass intestinal perfusion in situ].

    PubMed

    Zhang, Yan; Zhu, Hua-Xu; Guo, Li-Wei

    2012-02-01

    The aim of the study is to investigate the effects of concentration, intestinal segments, pH, inhibitors of proteins (P-gp), Na(+)-dependent glucose transporter (SGLT1) on the intestinal absorption of berberine, and to compare intestinal absorption of berberine in combinations. With phenol red as the indicator, in situ single pass intestinal perfusion (SPIP) model was used and intestinal absorption of pure berberine at concentrations of 36.70, 46.17 and 92.33 microg x mL(-1), simulated system of HLJDT (mixture of berberine, baicalin and geniposide), HLJDT with the concentration of berberine 92.33 microg x mL(-1) in perfusion solution of different intestinal segments (duodenum, jejunum, ileum, and colon) were determined by HPLC in combination with diode array detection (DAD). The results indicated that Ka values ofberberine at different concentrations had little significant difference among that obtained after perfusing via duodenum, jejunum, ileum and colon indicating that the absorption of berberine was mainly the passive diffusion. It was also suggested that SGLT1 and P-gp might exert some effects on the absorption of berberine. Ka and Peff values of berberine in a mixture of pure compounds and HLJDT for different intestine segments of rat showed an increasing tendency and was significantly different (P < 0.05) indicating that berberine in a mixture of pure compounds and HLJDT was assimilated better in small intestine. These results indicate that the intestinal absorption of berberine may be affected by compatibility of compounds. Additionally, berberine has wide absorption window and better absorption in colon. PMID:22512037

  13. Biopharmaceutics classification and intestinal absorption study of apigenin.

    PubMed

    Zhang, Jianjun; Liu, Dapeng; Huang, Yanting; Gao, Yuan; Qian, Shuai

    2012-10-15

    The aim of the study was to characterize the biopharmaceutics classification system (BCS) category of apigenin (AP) using intrinsic dissolution rate (IDR) and rat intestinal permeability, and to investigate the intestinal absorption mechanism of AP in rats. In the present investigation, equilibrium solubility and intrinsic dissolution rate (IDR) of AP were estimated in phosphate buffers. Effective intestinal permeability (P(eff)) of AP was determined using single-pass intestinal perfusion (SPIP) technique in four segments (duodenum, jejunum, ileum and colon) of rat intestine at three concentrations (10, 50 and 100 ?g/ml). The aqueous solubility of AP in tested phosphate buffers was very poor with maximum solubility of 2.16 ?g/ml at pH 7.5. The IDR of AP was very low with a value of 0.006 mg/min/cm(2). The minimum and maximum P(eff)s determined by SPIP were 0.19810(-4) and 0.71310(-4) cm/s at jejunum and duodenum site, respectively. In addition, the concentration-dependent permeability behavior was observed in the duodenum and jejunum, which suggested that AP was transported by both passive and active carrier-mediated saturable mechanism in these two intestinal segments. However, the observed concentration-independent permeability behavior in ileum and colon indicated primarily passive transport mechanism of absorption of AP in the last two intestinal segments. AP was classified as class II drug of the BCS due to its low solubility and high intestinal permeability. AP could be well absorbed in the whole intestine with the main absorption site at duodenum. The absorption of AP in four intestinal segments exhibited different transport mechanisms. PMID:22796171

  14. Effect of zinc supplements on the intestinal absorption of calcium

    SciTech Connect

    Spencer, H.; Rubio, N.; Kramer, L.; Norris, C.; Osis, D.

    1987-02-01

    Pharmacologic doses of zinc are widely used as zinc supplements. As calcium and zinc may compete for common absorption sites, a study was carried out on the effect of a pharmacologic dose of zinc on the intestinal absorption of calcium in adult males. The analyzed dietary zinc intake in the control studies was normal, averaging 14.6 mg/day. During the high zinc study, 140 mg zinc as the sulfate was added daily for time periods ranging from 17 to 71 days. The studies were carried out during both a low calcium intake averaging 230 mg/day and during a normal calcium intake of 800 mg/day. Calcium absorption studies were carried out during the normal and high zinc intake by using an oral tracer dose of Ca-47 and determining plasma levels and urinary and fecal excretions of Ca-47. The study has shown that, during zinc supplementation, the intestinal absorption of calcium was significantly lower during a low calcium intake than in the control study, 39.3% vs 61% respectively, p less than 0.001. However, during a normal calcium intake of 800 mg/day, the high zinc intake had no significant effect on the intestinal absorption of calcium. These studies have shown that the high zinc intake decreased the intestinal absorption of calcium during a low calcium intake but not during a normal calcium intake.

  15. Bifidobacterium animalis subsp. lactis decreases urinary oxalate excretion in a mouse model of primary hyperoxaluria.

    PubMed

    Klimesova, Klara; Whittamore, Jonathan M; Hatch, Marguerite

    2015-04-01

    Hyperoxaluria significantly increases the risk of calcium oxalate kidney stone formation. Since several bacteria have been shown to metabolize oxalate in vitro, including probiotic bifidobacteria, we focused on the efficiency and possible mechanisms by which bifidobacteria can influence oxalate handling in vivo, especially in the intestines, and compared these results with the reported effects of Oxalobacter formigenes. Bifidobacterium animalis subsp. lactis DSM 10140 and B. adolescentis ATCC 15703 were administered to wild-type (WT) mice and to mice deficient in the hepatic enzyme alanine-glyoxylate aminotransferase (Agxt(-/-), a mouse model of Primary Hyperoxaluria) that were fed an oxalate-supplemented diet. The administration of B. animalis subsp. lactis led to a significant decrease in urinary oxalate excretion in WT and Agxt(-/-) mice when compared to treatment with B. adolescentis. Detection of B. animalis subsp. lactis in feces revealed that 3 weeks after oral gavage with the bacteria 64% of WT mice, but only 37% of Agxt(-/-) mice were colonized. Examining intestinal oxalate fluxes showed there were no significant changes to net oxalate secretion in colonized animals and were therefore not associated with the changes in urinary oxalate excretion. These results indicate that colonization with B. animalis subsp. lactis decreased urinary oxalate excretion by degrading dietary oxalate thus limiting its absorption across the intestine but it did not promote enteric oxalate excretion as reported for O. formigenes. Preventive or therapeutic administration of B. animalis subsp. lactis appears to have some potential to beneficially influence dietary hyperoxaluria in mice. PMID:25269440

  16. In vivo studies of biotin absorption in distal rat intestine

    SciTech Connect

    Bowman, B.B.; Rosenberg, I.H.

    1986-03-01

    The authors have extended their previous studies of biotin absorption in rat proximal jejunum (PJ) to examine biotin absorptive capacity of rat ileum (I) and proximal colon (PC) using in vivo intestinal loop technique. Intestinal loops (2.5 cm) were filled with 0.3 ml of solution containing (/sup 3/H)-biotin and (/sup 14/C)-inulin in phosphate buffer, pH 6.5. Biotin absorption was determined on the basis of luminal biotin disappearance after correction for inulin recovery and averaged (pmol/loop-10 min; X +/- SEM). In related experiments, 5-cm loops of PJ, distal I (DI), or PC were filled with 0.5 ml of solution of similar composition (1.0 ..mu..M biotin). The abdominal cavity was closed and the rats were allowed to recover from anesthesia, then sacrificed 3 hr after injection. Biotin absorption averaged 96.2% (PJ), 93.2% (DI), and 25.8% (PC) of the dose administered. These differences were reflected in the radioactive biotin content of plasma and intestinal loop, kidney, and liver. These data demonstrate significant biotin absorption in rat DI and PC, as required if the intestinal microflora are to be considered as a source of biotin for the host.

  17. Intestinal scavenger receptors are involved in vitamin K1 absorption.

    PubMed

    Goncalves, Aurlie; Margier, Marielle; Roi, Stphanie; Collet, Xavier; Niot, Isabelle; Goupy, Pascale; Caris-Veyrat, Catherine; Reboul, Emmanuelle

    2014-10-31

    Vitamin K1 (phylloquinone) intestinal absorption is thought to be mediated by a carrier protein that still remains to be identified. Apical transport of vitamin K1 was examined using Caco-2 TC-7 cell monolayers as a model of human intestinal epithelium and in transfected HEK cells. Phylloquinone uptake was then measured ex vivo using mouse intestinal explants. Finally, vitamin K1 absorption was compared between wild-type mice and mice overexpressing scavenger receptor class B type I (SR-BI) in the intestine and mice deficient in cluster determinant 36 (CD36). Phylloquinone uptake by Caco-2 cells was saturable and was significantly impaired by co-incubation with ?-tocopherol (and vice versa). Anti-human SR-BI antibodies and BLT1 (a chemical inhibitor of lipid transport via SR-BI) blocked up to 85% of vitamin K1 uptake. BLT1 also decreased phylloquinone apical efflux by ?80%. Transfection of HEK cells with SR-BI and CD36 significantly enhanced vitamin K1 uptake, which was subsequently decreased by the addition of BLT1 or sulfo-N-succinimidyl oleate (CD36 inhibitor), respectively. Similar results were obtained in mouse intestinal explants. In vivo, the phylloquinone postprandial response was significantly higher, and the proximal intestine mucosa phylloquinone content 4 h after gavage was increased in mice overexpressing SR-BI compared with controls. Phylloquinone postprandial response was also significantly increased in CD36-deficient mice compared with wild-type mice, but their vitamin K1 intestinal content remained unchanged. Overall, the present data demonstrate for the first time that intestinal scavenger receptors participate in the absorption of dietary phylloquinone. PMID:25228690

  18. Intestinal Scavenger Receptors Are Involved in Vitamin K1 Absorption*

    PubMed Central

    Goncalves, Aurélie; Margier, Marielle; Roi, Stéphanie; Collet, Xavier; Niot, Isabelle; Goupy, Pascale; Caris-Veyrat, Catherine; Reboul, Emmanuelle

    2014-01-01

    Vitamin K1 (phylloquinone) intestinal absorption is thought to be mediated by a carrier protein that still remains to be identified. Apical transport of vitamin K1 was examined using Caco-2 TC-7 cell monolayers as a model of human intestinal epithelium and in transfected HEK cells. Phylloquinone uptake was then measured ex vivo using mouse intestinal explants. Finally, vitamin K1 absorption was compared between wild-type mice and mice overexpressing scavenger receptor class B type I (SR-BI) in the intestine and mice deficient in cluster determinant 36 (CD36). Phylloquinone uptake by Caco-2 cells was saturable and was significantly impaired by co-incubation with α-tocopherol (and vice versa). Anti-human SR-BI antibodies and BLT1 (a chemical inhibitor of lipid transport via SR-BI) blocked up to 85% of vitamin K1 uptake. BLT1 also decreased phylloquinone apical efflux by ∼80%. Transfection of HEK cells with SR-BI and CD36 significantly enhanced vitamin K1 uptake, which was subsequently decreased by the addition of BLT1 or sulfo-N-succinimidyl oleate (CD36 inhibitor), respectively. Similar results were obtained in mouse intestinal explants. In vivo, the phylloquinone postprandial response was significantly higher, and the proximal intestine mucosa phylloquinone content 4 h after gavage was increased in mice overexpressing SR-BI compared with controls. Phylloquinone postprandial response was also significantly increased in CD36-deficient mice compared with wild-type mice, but their vitamin K1 intestinal content remained unchanged. Overall, the present data demonstrate for the first time that intestinal scavenger receptors participate in the absorption of dietary phylloquinone. PMID:25228690

  19. Regulation of Intestinal Glucose Absorption by Ion Channels and Transporters

    PubMed Central

    Chen, Lihong; Tuo, Biguang; Dong, Hui

    2016-01-01

    The absorption of glucose is electrogenic in the small intestinal epithelium. The major route for the transport of dietary glucose from intestinal lumen into enterocytes is the Na+/glucose cotransporter (SGLT1), although glucose transporter type 2 (GLUT2) may also play a role. The membrane potential of small intestinal epithelial cells (IEC) is important to regulate the activity of SGLT1. The maintenance of membrane potential mainly depends on the activities of cation channels and transporters. While the importance of SGLT1 in glucose absorption has been systemically studied in detail, little is currently known about the regulation of SGLT1 activity by cation channels and transporters. A growing line of evidence suggests that cytosolic calcium ([Ca2+]cyt) can regulate the absorption of glucose by adjusting GLUT2 and SGLT1. Moreover, the absorption of glucose and homeostasis of Ca2+ in IEC are regulated by cation channels and transporters, such as Ca2+ channels, K+ channels, Na+/Ca2+ exchangers, and Na+/H+ exchangers. In this review, we consider the involvement of these cation channels and transporters in the regulation of glucose uptake in the small intestine. Modulation of them may be a potential strategy for the management of obesity and diabetes. PMID:26784222

  20. Regulation of Intestinal Glucose Absorption by Ion Channels and Transporters.

    PubMed

    Chen, Lihong; Tuo, Biguang; Dong, Hui

    2016-01-01

    The absorption of glucose is electrogenic in the small intestinal epithelium. The major route for the transport of dietary glucose from intestinal lumen into enterocytes is the Na?/glucose cotransporter (SGLT1), although glucose transporter type 2 (GLUT2) may also play a role. The membrane potential of small intestinal epithelial cells (IEC) is important to regulate the activity of SGLT1. The maintenance of membrane potential mainly depends on the activities of cation channels and transporters. While the importance of SGLT1 in glucose absorption has been systemically studied in detail, little is currently known about the regulation of SGLT1 activity by cation channels and transporters. A growing line of evidence suggests that cytosolic calcium ([Ca(2+)]cyt) can regulate the absorption of glucose by adjusting GLUT2 and SGLT1. Moreover, the absorption of glucose and homeostasis of Ca(2+) in IEC are regulated by cation channels and transporters, such as Ca(2+) channels, K? channels, Na?/Ca(2+) exchangers, and Na?/H? exchangers. In this review, we consider the involvement of these cation channels and transporters in the regulation of glucose uptake in the small intestine. Modulation of them may be a potential strategy for the management of obesity and diabetes. PMID:26784222

  1. Modulation of ganciclovir intestinal absorption in presence of absorption enhancers.

    PubMed

    Shah, Pranav; Jogani, Viral; Mishra, Pushpa; Mishra, Anil Kumar; Bagchi, Tamishraha; Misra, Ambikanandan

    2007-10-01

    The purpose of this investigation was to study the influences of absorption enhancers in increasing oral bioavailability of Ganciclovir (GAN) by assessing the transepithelial permeation across cell monolayers in vitro and bioavailability in rats in vivo. The permeation of GAN across Caco-2 and MDCK cell monolayers in the absence/presence of dimethyl-beta-cyclodextrin (DMbetaCD), chitosan hydrochloride (CH), sodium lauryl sulphate (SLS), and their combinations was studied for a 2-h period. GAN was administered to rats in absence/presence of absorption enhancers and drug contents in plasma were estimated. We found that the apparent permeability coefficient (Papp) of GAN in absence of absorption enhancers (control) were 0.261 +/- 0.072 x 10(-6) and 0.486 +/- 0.063 x 10(-6) cm/s in Caco-2 and MDCK cell monolayers, respectively, whereas in the presence of DMbetaCD, CH, SLS, and their combinations, Papp of GAN increased by 5- to 25-fold and 7- to 33-fold as compared to control in Caco-2 and MDCK cell monolayers, respectively. However, in rats, the maximum enhancement in bioavailability of GAN during coadministration of these absorption enhancers was only fivefold compared to GAN control. To conclude, the absorption enhancers-DMbetaCD, CH, SLS, and their combinations demonstrated significant improvement in transepithelial permeation and bioavailability of GAN. PMID:17680662

  2. Nonlinear intestinal absorption kinetics of cefuroxime axetil in rats.

    PubMed Central

    Ruiz-Balaguer, N; Nacher, A; Casabo, V G; Merino, M

    1997-01-01

    Cefuroxime is commercially available for parenteral administration as a sodium salt and for oral administration as cefuroxime axetil, the 1-(acetoxy)ethyl ester of the drug. Cefuroxime axetil is a prodrug of cefuroxime and has little, if any, antibacterial activity until hydrolyzed in vivo to cefuroxime. In this study, the absorption of cefuroxime axetil in the small intestines of anesthetized rats was investigated in situ, by perfusion at four concentrations (11.8, 5, 118 and 200 microM). Oral absorption of cefuroxime axetil can apparently be described as a specialized transport mechanism which obeys Michaelis-Menten kinetics. Parameters characterizing absorption of prodrug in free solution were obtained: maximum rate of absorption (Vmax) = 289.08 +/- 46.26 microM h-1, and Km = 162.77 +/- 31.17 microM. Cefuroxime axetil transport was significantly reduced in the presence of the enzymatic inhibitor sodium azide. On the other hand, the prodrug was metabolized in the gut wall through contact with membrane-bound enzymes in the brush border membrane before absorption occurred. This process reduces the prodrug fraction directly available for absorption. From a bioavailability point of view, therefore, the effects mentioned above can explain the variable and poor bioavailability following oral administration of cefuroxime axetil. Thus, future strategies in oral cefuroxime axetil absorption should focus on increasing the stability of the prodrug in the intestine by modifying the prodrug structure and/or targeting the compound to the absorption site. PMID:9021205

  3. Sugar absorption in the intestine: the role of GLUT2.

    PubMed

    Kellett, George L; Brot-Laroche, Edith; Mace, Oliver J; Leturque, Armelle

    2008-01-01

    Intestinal glucose absorption comprises two components. One is classical active absorption mediated by the Na+/glucose cotransporter. The other is a diffusive component, formerly attributed to paracellular flow. Recent evidence, however, indicates that the diffusive component is mediated by the transient insertion of glucose transporter type 2 (GLUT2) into the apical membrane. This apical GLUT2 pathway of intestinal sugar absorption is present in species from insect to human, providing a major route at high sugar concentrations. The pathway is regulated by rapid trafficking of GLUT2 to the apical membrane induced by glucose during assimilation of a meal. Apical GLUT2 is therefore a target for multiple short-term and long-term nutrient-sensing mechanisms. These include regulation by a newly recognized pathway of calcium absorption through the nonclassical neuroendocrine l-type channel Cav1.3 operating during digestion, activation of intestinal sweet taste receptors by natural sugars and artificial sweeteners, paracrine and endocrine hormones, especially insulin and GLP-2, and stress. Permanent apical GLUT2, resulting in increased sugar absorption, is a characteristic of experimental diabetes and of insulin-resistant states induced by fructose and fat. The nutritional consequences of apical and basolateral GLUT2 regulation are discussed in the context of Western diet, processed foods containing artificial sweeteners, obesity, and diabetes. PMID:18393659

  4. 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

  5. A new approach to predict human intestinal absorption using porcine intestinal tissue and biorelevant matrices.

    PubMed

    Westerhout, Joost; van de Steeg, Evita; Grossouw, Dimitri; Zeijdner, Evelijn E; Krul, Cyrille A M; Verwei, Miriam; Wortelboer, Heleen M

    2014-10-15

    A reliable prediction of the oral bioavailability in humans is crucial and of high interest for pharmaceutical and food industry. The predictive value of currently used in silico methods, in vitro cell lines, ex vivo intestinal tissue and/or in vivo animal studies for human intestinal absorption, however, is often insufficient, especially when food-drug interactions are evaluated. Ideally, for this purpose healthy human intestinal tissue is used, but due to its limited availability there is a need for alternatives. The aim of this study was to evaluate the applicability of healthy porcine intestinal tissue mounted in a newly developed InTESTine™ system to predict human intestinal absorption of compounds with different chemical characteristics, and within biorelevant matrices. To that end, first, a representative set of compounds was chosen of which the apparent permeability (Papp) data in both Caco-2 cells and human intestinal tissue mounted in the Ussing chamber system, and absolute human oral bioavailability were reported. Thereafter, Papp values of the subset were determined in both porcine jejunal tissue and our own Caco-2 cells. In addition, the feasibility of this new approach to study regional differences (duodenum, jejunum, and ileum) in permeability of compounds and to study the effects of luminal factors on permeability was also investigated. For the latter, a comparison was made between the compatibility of porcine intestinal tissue, Caco-2 cells, and Caco-2 cells co-cultured with the mucin producing HT29-MTX cells with biorelevant samples as collected from an in vitro dynamic gastrointestinal model (TIM). The results demonstrated that for the paracellularly transported compounds atenolol, cimetidine, mannitol and ranitidine porcine Papp values are within 3-fold difference of human Papp values, whereas the Caco-2 Papp values are beyond 3-fold difference. Overall, the porcine intestinal tissue Papp values are more comparable to human Papp values (9 out of 12 are within 3-fold difference), compared to Caco-2 Papp values (4 out of 12 are within 3-fold difference). In addition, for the selected hydrophilic compounds a significant increase in the permeability was observed from duodenum to ileum. Finally, this study indicated that porcine jejunal tissue segments can be used with undiluted luminal samples to predict human intestinal permeability and the effect of biorelevant matrices on this. In conclusion, viable porcine intestinal tissue mounted in the InTESTine™ system can be applied as a reliable tool for the assessment of intestinal permeability in the absence and presence of biorelevant samples. This would enable an accessible opportunity for a reliable prediction of human intestinal absorption, and the effect of luminal compounds such as digested foods, early in drug development. PMID:25046168

  6. Determination of Oxalate Content in Herbal Remedies and Dietary Supplements Based on Plant Extracts.

    PubMed

    Siener, Roswitha; López-Mesas, Montserrat; Valiente, Manuel; Blanco, Francisco

    2016-02-01

    Lifestyle, especially diet, is a prominent risk factor that affects the formation of calcium oxalate stones. Urinary oxalate excretion is directly related to the amount of oral intake and intestinal absorption rate of oxalate. This work evaluated the possibility of increasing oxalate ingestion, which could lead to secondary hyperoxaluria, associated with the intake of herbal remedies and dietary supplements containing plant extracts. A wide variety of 17 commercially available drugs and dietary supplements were analyzed using ion chromatography. The results showed remarkable differences in oxalate contents of the extracts. Total oxalate concentrations ranged from 0.03 to 2.2 mg/g in solid samples and from 0.005 to 0.073 mg/mL in liquid samples. The selected herbal remedies and dietary supplements containing plant extracts represent only a low risk for calcium oxalate stone formers, if the recommended daily dose is not exceeded. PMID:26670692

  7. Contribution of dietary oxalate to urinary oxalate excretion

    NASA Technical Reports Server (NTRS)

    Holmes, R. P.; Goodman, H. O.; Assimos, D. G.

    2001-01-01

    BACKGROUND: The amount of oxalate excreted in urine has a significant impact on calcium oxalate supersaturation and stone formation. Dietary oxalate is believed to make only a minor (10 to 20%) contribution to the amount of oxalate excreted in urine, but the validity of the experimental observations that support this conclusion can be questioned. An understanding of the actual contribution of dietary oxalate to urinary oxalate excretion is important, as it is potentially modifiable. METHODS: We varied the amount of dietary oxalate consumed by a group of adult individuals using formula diets and controlled, solid-food diets with a known oxalate content, determined by a recently developed analytical procedure. Controlled solid-food diets were consumed containing 10, 50, and 250 mg of oxalate/2500 kcal, as well as formula diets containing 0 and 180 mg oxalate/2500 kcal. Changes in the content of oxalate and other ions were assessed in 24-hour urine collections. RESULTS: Urinary oxalate excretion increased as dietary oxalate intake increased. With oxalate-containing diets, the mean contribution of dietary oxalate to urinary oxalate excretion ranged from 24.4 +/- 15.5% on the 10 mg/2500 kcal/day diet to 41.5 +/- 9.1% on the 250 mg/2500 kcal/day diet, much higher than previously estimated. When the calcium content of a diet containing 250 mg of oxalate was reduced from 1002 mg to 391 mg, urinary oxalate excretion increased by a mean of 28.2 +/- 4.8%, and the mean dietary contribution increased to 52.6 +/- 8.6%. CONCLUSIONS: These results suggest that dietary oxalate makes a much greater contribution to urinary oxalate excretion than previously recognized, that dietary calcium influences the bioavailability of ingested oxalate, and that the absorption of dietary oxalate may be an important factor in calcium oxalate stone formation.

  8. Quantitation of small intestinal permeability during normal human drug absorption

    PubMed Central

    2013-01-01

    Background Understanding the quantitative relationship between a drugs physical chemical properties and its rate of intestinal absorption (QSAR) is critical for selecting candidate drugs. Because of limited experimental human small intestinal permeability data, approximate surrogates such as the fraction absorbed or Caco-2 permeability are used, both of which have limitations. Methods Given the blood concentration following an oral and intravenous dose, the time course of intestinal absorption in humans was determined by deconvolution and related to the intestinal permeability by the use of a new 3 parameter model function (Averaged Model (AM)). The theoretical validity of this AM model was evaluated by comparing it to the standard diffusion-convection model (DC). This analysis was applied to 90 drugs using previously published data. Only drugs that were administered in oral solution form to fasting subjects were considered so that the rate of gastric emptying was approximately known. All the calculations are carried out using the freely available routine PKQuest Java (http://www.pkquest.com) which has an easy to use, simple interface. Results Theoretically, the AM permeability provides an accurate estimate of the intestinal DC permeability for solutes whose absorption ranges from 1% to 99%. The experimental human AM permeabilities determined by deconvolution are similar to those determined by direct human jejunal perfusion. The small intestinal pH varies with position and the results are interpreted in terms of the pH dependent octanol partition. The permeability versus partition relations are presented separately for the uncharged, basic, acidic and charged solutes. The small uncharged solutes caffeine, acetaminophen and antipyrine have very high permeabilities (about 20 x 10-4?cm/sec) corresponding to an unstirred layer of only 45??m. The weak acid aspirin also has a large AM permeability despite its low octanol partition at pH?7.4, suggesting that it is nearly completely absorbed in the first part of the intestine where the pH is about 5.4. Conclusions The AM deconvolution method provides an accurate estimate of the human intestinal permeability. The results for these 90 drugs should provide a useful benchmark for evaluating QSAR models. PMID:23800230

  9. Variability of Oxalobacter Formigenes and Oxalate in Stool Samples

    PubMed Central

    Prokopovich, Sergey; Knight, John; Assimos, Dean G.; Holmes, Ross P.

    2009-01-01

    Purpose The intestinal organism Oxalobacter formigenes is unique in using oxalate as its primary carbon and energy source. Intestinal colonization with O. formigenes may have clinical significance by decreasing intestinal oxalate and its absorption, thereby influencing the concentration of oxalate in plasma and urine, and the development of calcium oxalate stone disease. Because the oxalate content of the diet varies considerably, we hypothesized that the number of O. formigenes and amount of oxalate would vary in feces. Materials and Methods To enumerate the number of O. formigenes in feces an accurate and reproducible real-time polymerase chain reaction assay was developed to quantify O. formigenes DNA. Stool samples were obtained from 10 colonized individuals to determine the levels of O. formigenes by this assay and the oxalate content by ion chromatography. Results Concentrations of O. formigenes ranged from lower than the limit of detection of 5 103 to 1.04 109 cells per gm stool. The total oxalate content of stool samples varied from 0.1 to 1.8 mg/gm and fecal water oxalate varied from 60 to 600 ?M. All parameters measured varied within each stool collection, among stool collections on different days and among individuals. Notably in 7 of 10 individuals at least 1 stool sample contained no detectable O. formigenes. In addition, 7 of 10 subjects had a fecal colonization of less than 4 104 per gm stool. Conclusions This study demonstrates that there is intrastool and interstool sample variability in the amount of O. formigenes measured by real-time polymerase chain reaction that did not correlate with the quantity of oxalate in stool. Most subjects had a fecal colonization of less than 4 104 per gm stool. PMID:17870112

  10. A simplified method for the determination of intestinal calcium absorption.

    PubMed

    Kapitola, J; Hrba, J; Vilimovská, D

    1979-06-01

    The double-isotope technique for the estimation of intestinal calcium absorption was simplified by using the scintillation liquid Insta-Gel. The urine was mixed with Insta-Gel without any previous preparation. A suitable constitution of the sample was ascertained by preliminary experiments (1 ml urine + 10 ml Insta-Gel); the stability of the samples, the correctness of 45Ca (counting separately as well as mixed with 47Ca) and the linearity of the counting rates of 45Ca obtained in a range of doses over four orders was proved. In 43 subjects aged 20 to 65 years and without any disturbance of calcium metabolism or intestinal function, the average normal value of fractional calcium absorption was 45.9 +/- 1.6% (SEM). PMID:503873

  11. Genetic analysis of intestinal cholesterol absorption in inbred mice.

    PubMed

    Schwarz, M; Davis, D L; Vick, B R; Russell, D W

    2001-11-01

    A genetic mapping strategy was employed to identify chromosomal regions harboring genes that influence the absorption of intestinal cholesterol in the mouse. Analysis of seven inbred strains of male mice (129P3, AKR, BALB/c, C3H/He, C57BL/6, DBA/2, and SJL, all from Jackson Laboratories) revealed substantial differences in their abilities to absorb a bolus of cholesterol delivered by gavage. Crosses between high (AKR, 129) and low (DBA/2, SJL) absorbing strains revealed evidence for the presence of dominant genes that increase and decrease cholesterol absorption. Backcrosses between F1 offspring and parental strains (DBA/2xAKD2F1 and 129xSJL129F1) followed by linkage analyses revealed four quantitative trait loci that influenced cholesterol absorption. Analyses of recombinant inbred strains identified an additional three loci affecting this phenotype. These seven quantitative trait loci, which map to different chromosomes and are termed Cholesterol absorption 1-7 (Chab1-7) loci, together influence the absorption of intestinal cholesterol in mice and are likely to be involved in different steps of this complex pathway. PMID:11714849

  12. Glutathione plays a role in the chick intestinal calcium absorption.

    PubMed

    Tolosa de Talamoni, N; Marchionatti, A; Baudino, V; Alisio, A

    1996-10-01

    DL-buthionine-S,R-sulfoximine (BSO) administration to vitamin D-deficient chicks treated with cholecalciferol produces a rapid decrease in the Ca2+ transfer from lumen-to-plasma and in the intestinal glutathione content. This response was reversed by addition of glutathione monoester to the intestinal sac. Variables related to the Ca2+ homeostasis such as plasma Ca and P, and intestinal calbindin D28k were not modified by BSO given to vitamin D-deficient chicks treated with cholecalciferol. Intestinal alkaline phosphatase activity, on the contrary, was highly reduced by BSO in vitamin D-deficient chicks treated with vitamin D3. This effect showed time and dose-dependency. Although the mechanism/s of action of BSO on the intestinal Ca absorption is unknown, it is quite possible that thiol groups of protein involved in the Ca2+ transport are affected by the GSH depletion and/or by block of the antioxidant ability of vitamin D3. Thus, reactive oxygen compounds would be increased and, therefore, the Ca2+ movement from lumen to plasma decreases. PMID:8916550

  13. Intestinal absorptive capacity, intestinal permeability and jejunal histology in HIV and their relation to diarrhoea.

    PubMed Central

    Keating, J; Bjarnason, I; Somasundaram, S; Macpherson, A; Francis, N; Price, A B; Sharpstone, D; Smithson, J; Menzies, I S; Gazzard, B G

    1995-01-01

    Intestinal function is poorly defined in patients with HIV infection. Absorptive capacity and intestinal permeability were assessed using 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose in 88 HIV infected patients and the findings were correlated with the degree of immunosuppression (CD4 counts), diarrhoea, wasting, intestinal pathogen status, and histomorphometric analysis of jejunal biopsy samples. Malabsorption of 3-O-methyl-D-glucose and D-xylose was prevalent in all groups of patients with AIDS but not in asymptomatic, well patients with HIV. Malabsorption correlated significantly (r = 0.34-0.56, p < 0.005) with the degree of immune suppression and with body mass index. Increased intestinal permeability was found in all subgroups of patients. The changes in absorption-permeability were of comparable severity to those found in patients with untreated coeliac disease. Jejunal histology, however, showed only mild changes in the villus height/crypt depth ratio as compared with subtotal villus atrophy in coeliac disease. Malabsorption and increased intestinal permeability are common in AIDS patients. Malabsorption, which has nutritional implications, relates more to immune suppression than jejunal morphological changes. PMID:8549936

  14. Intestinal absorption-partition relationships: a tentative functional nonlinear model.

    PubMed

    Plá-Delfina, J M; Moreno, J

    1981-04-01

    Models and equations designed to elucidate passive intestinal absorption mechanisms by analysis of the relationship between the absorption rate constant (ka) and either the partition coefficients (P) or a related partition constant for homologous series of substances, are reviewed. Classical nonlinear physical models, such as those which assume the existence of a nonstirred layer or equilibrium extraction, predict sigmoidal or hyperbolic relationships between ka and P, whereas other models, which regard the membrane as a heterogeneous multicompartment system, predict parabolic or bilinear relationships between log ka and log P. In the present paper, an alternative model is proposed, which incorporates the Wagner-Sedman equilibrium extraction model together with the existence of pores, which play a fundamental role for compounds below 250 in molecular weight. Several apparently contradictory absorption-partition literature data are shown to be highly consistent with the tentative model proposed. PMID:7277209

  15. Enhanced solubility and intestinal absorption of candesartan cilexetil solid dispersions using everted rat intestinal sacs

    PubMed Central

    Gurunath, S.; Nanjwade, Baswaraj K.; Patila, P.A.

    2013-01-01

    Objective Candesartan cilexetil (CAN) is a poor aqueous soluble compound and a P-glycoprotein (P-gp) efflux pump substrate. These key factors are responsible for its incomplete intestinal absorption. Methods In this study, we investigated to enhance the absorption of CAN by improving its solubility and inhibiting intestinal P-gp activity. A phase solubility method was used to evaluate the aqueous solubility of CAN in PVP K30 (0.22%). Gibbs free energy (?Gtro) values were all negative. Solubility was enhanced by the freeze drying technique. The in vitro dissolution was evaluated using the USP paddle method. The interaction between drug and carrier was evaluated by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and Differential scanning calorimetry (DSC) studies. Naringin was selected as P-gp inhibitor. Absorption studies were performed using the everted gut sac model from rat jejunum. The drug analysis was performed by HPLC. Results FTIR spectra revealed no interaction between drug and PVP K30. From XRD and DSC data, CAN was in the amorphous form, which explains the cumulative release of drug from its prepared systems. We noticed an enhancement of CAN absorption by improving its solubility and inhibiting the P-gp activity. The significant results (p<0.05) were obtained for freeze dried solid dispersions in the presence of P-gp inhibitor than without naringin (15mg/kg) with an absorption enhancement of 8-fold. Conclusion Naringin, a natural flavonoid, has no undesirable side effects. Therefore, it could be employed as an excipient in the form of solid dispersions to increase CAN intestinal absorption and its oral bioavailability. PMID:25067902

  16. Analysis of sequential events in intestinal absorption of folylpolyglutamate

    SciTech Connect

    Darcy-Vrillon, B.; Selhub, J.; Rosenberg, I.H.

    1988-09-01

    Although it is clear that the intestinal absorption of folylpolyglutamates is associated with hydrolysis to monoglutamyl folate, the precise sequence and relative velocity of the events involved in this absorption are not fully elucidated. In the present study, we used biosynthetic, radiolabeled folylpolyglutamates purified by affinity chromatography to analyze the relationship of hydrolysis and transport in rat jejunal loops in vivo. Absorption was best described by a series of first-order processes: luminal hydrolysis to monoglutamyl folate followed by tissue uptake of the product. The rate of hydrolysis in vivo was twice as high as the rate of transport. The latter value was identical to that measured for folic acid administered separately. The relevance of this sequential model was confirmed by data obtained using inhibitors of the individual steps in absorption of ''natural'' folate. Heparin and sulfasalazine were both effective in decreasing absorption. The former affected hydrolysis solely, whereas the latter acted as a competitive inhibitor of transport of monoglutamyl folate. These studies confirm that hydrolysis is obligatory and that the product is subsequently taken up by a transport process, common to monoglutamyl folates, that is the rate-determining step in transepithelial absorption.

  17. [Intestinal absorption of fats in children using serum turbidity and triglyceride absorption tests].

    TOXLINE Toxicology Bibliographic Information

    Costa CD; Schmidt BJ; de Barros FJ; Tamega I das E

    1985-10-01

    Intestinal fat absorption was studied, using serum turbidity and serum triglyceride levels, which were determined before and after a test meal of 2 g neutral fat per kg b.w. in 33 children: 25 controls, four with cystic fibrosis, and four with celiac disease. The results proved that the easy-to-perform serum turbidity test was superior to the triglyceride absorption test in characterizing fat digestion and absorption. The most substantial increase in both tests occurred about three hours after the oral fat load.

  18. [Intestinal absorption of fats in children using serum turbidity and triglyceride absorption tests].

    PubMed

    Costa, C D; Schmidt, B J; de Barros, F J; Tamega I das, E

    1985-01-01

    Intestinal fat absorption was studied, using serum turbidity and serum triglyceride levels, which were determined before and after a test meal of 2 g neutral fat per kg b.w. in 33 children: 25 controls, four with cystic fibrosis, and four with celiac disease. The results proved that the easy-to-perform serum turbidity test was superior to the triglyceride absorption test in characterizing fat digestion and absorption. The most substantial increase in both tests occurred about three hours after the oral fat load. PMID:3837660

  19. Intestinal absorption of raltitrexed and evaluation of the effects of absorption enhancers.

    PubMed

    Yu, Yong; Lu, Yiling; Zhao, Xianmei; Li, Xiaosi; Yin, Zongning

    2013-09-01

    Raltitrexed (RTX) has shown clinical activity in a variety of advanced solid tumours. Its oral bioavailability is low and its intestinal absorption mechanism is not clear. In the present study, the absorption mechanism of RTX in the small intestine was investigated, and the effects of absorption enhancers and efflux transporter inhibitors were evaluated by in vitro transport studies using the Caco-2 cell model and in situ perfusion experiments in rats. Oral bioavailability of RTX in rats in the presence or absence of enhancers were also investigated. The results of in vitro and in situ experiments indicated that the kinetic model of combined mechanism (active and passive transport) fitted the concentration-time data of RTX best with the highest R2 and lowest SSE (Sum of Squares for Error). The apparent or effective permeability coefficient (P(app) or P(eff)) of RTX remained statistically constant in a certain concentration range, then decreased when the concentration increased. But the decrease trend did not continue with further increase in concentration. And folic acid could competitively inhibit RTX absorption. These results suggested that a combined absorption mechanism for RTX existed. Furthermore, within certain concentration ranges, Carbomer 934P and sodium caprate (Cap-Na) exhibited significant absorption enhancement effects with low toxicity, whereas the enhancement effects of sodium deoxycholate (Deo-Na) were accompanied with acute toxicities. Moreover, probenecid and pantoprazole obviously enhanced RTX absorption, demonstrating that RTX is a substrate of the multidrug resistance protein (MRP) and breast cancer resistance protein (BCRP). A secretion experiment indicated that RTX could be effluxed into the intestines both with bile and by active efflux action. Oral bioavailability of RTX was significantly improved by the investigated absorption enhancers and transporter inhibitors, which is consistent with the in vitro and in situ experiments. PMID:24147341

  20. Mechanistic and regulatory aspects of intestinal iron absorption

    PubMed Central

    Gulec, Sukru; Anderson, Gregory J.

    2014-01-01

    Iron is an essential trace mineral that plays a number of important physiological roles in humans, including oxygen transport, energy metabolism, and neurotransmitter synthesis. Iron absorption by the proximal small bowel is a critical checkpoint in the maintenance of whole-body iron levels since, unlike most other essential nutrients, no regulated excretory systems exist for iron in humans. Maintaining proper iron levels is critical to avoid the adverse physiological consequences of either low or high tissue iron concentrations, as commonly occurs in iron-deficiency anemia and hereditary hemochromatosis, respectively. Exquisite regulatory mechanisms have thus evolved to modulate how much iron is acquired from the diet. Systemic sensing of iron levels is accomplished by a network of molecules that regulate transcription of the HAMP gene in hepatocytes, thus modulating levels of the serum-borne, iron-regulatory hormone hepcidin. Hepcidin decreases intestinal iron absorption by binding to the iron exporter ferroportin 1 on the basolateral surface of duodenal enterocytes, causing its internalization and degradation. Mucosal regulation of iron transport also occurs during low-iron states, via transcriptional (by hypoxia-inducible factor 2α) and posttranscriptional (by the iron-sensing iron-regulatory protein/iron-responsive element system) mechanisms. Recent studies demonstrated that these regulatory loops function in tandem to control expression or activity of key modulators of iron homeostasis. In health, body iron levels are maintained at appropriate levels; however, in several inherited disorders and in other pathophysiological states, iron sensing is perturbed and intestinal iron absorption is dysregulated. The iron-related phenotypes of these diseases exemplify the necessity of precisely regulating iron absorption to meet body demands. PMID:24994858

  1. Intestinal Absorption of Calcium-47 after Treatment with Oral Oestrogen-gestogens in Senile Osteoporosis

    PubMed Central

    1970-01-01

    Intestinal absorption of radiocalcium was measured in 15 postmenopausal women with osteoporosis before and after six months' treatment with an oral oestrogen-gestogen combination. Comparison with a control group indicated a significant improvement in intestinal absorption after treatment. Though there is no evidence that oestrogens have an anabolic effect on human bone, these results indicate that they affect the intestinal absorption of calcium directly. PMID:5470432

  2. Intestinal absorption of chromium as affected by wheat bran

    SciTech Connect

    Keim, K.S.; Holloway, C.L.; Hegsted, M.

    1986-03-01

    This study was designed to investigate the influence of dietary fiber, as found in wheat bran, on the absorption of chromium. Twenty male Sprague-Dawley rats were divided into two groups of 10. The control was fed a semi-purified diet containing casein, methionine, cornstarch, sucrose, corn oil, mineral and vitamin mix, and choline bitartrate. The experimental group was fed the same diet but with soft red winter wheat bran added to a level of 35% of the diet at the expense of sucrose. To determine chromium absorption and uptake by selected tissues, rats were fasted for 24 hr, fed 5 g of the respective diet, 2 hr later intubated with 100..mu..Ci of Cr-51of sacrificed 24 hr later. The rats wee housed in metabolic cages after the Cr-51 intubation. The addition of wheat brand to the diet did not significantly affect chromium absorption as measured by percent dose of Cr-51 in the 24 hr urine. The percent dose in the control group was 0.68 +/- 0.20% (mean +/- SEM) and in the experimental group 0.63 +/- 0.24% (mean +/-SEM) (N.S.). The cr-51 uptake of liver, spleen, jejunum, and blood was not statistically different between groups. These results indicate that dietary fiber as found in wheat bran does not impair intestinal absorption of chromium.

  3. Effect of diet upon intestinal disaccharidases and disaccharide absorption.

    PubMed

    Deren, J J; Broitman, S A; Zamcheck, N

    1967-02-01

    The administration of a carbohydrate-containing diet for 24 hours to rats previously fasted for 3 days led to a twofold increase in total intestinal sucrase and sucrase specific activity. The specific activity of maltase was similarly increased, but lactase activity was unaffected. The sucrose-containing diet led to a greater increase in sucrase than maltase activity, whereas the converse was true of the maltose-containing diet. A carbohydrate-free isocaloric diet led to a slight increase in the total intestinal sucrase, but sucrase specific activity was unchanged. Assay of sucrase activity of mixed homogenates from casein-fed and sucrose-fed rats or fasted and sucrose-fed animals yielded activities that were additive. The Michaelis constant (Km) of the enzyme hydrolyzing sucrose was similar in the fasted, casein-fed, and sucrose-fed rats. The maximal velocity (Vmax) was twice greater in sucrose-fed as compared to casein-fed or fasted rats, suggesting an increased quantity of enzyme subsequent to sucrose feeding. Adrenalectomized rats maintained on 1.0% salt intake had sucrase and maltase levels comparable to those of controls. Steroid administration did not significantly increase their activities. The response to sucrose feeding was similar in both control and adrenalectomized rats, indicative of the absence of steroidal control on sucrase and maltase activity in the adult animal. Studies using intestinal ring preparations indicated that sucrose hydrolysis by the intact cells proceeded more rapidly when animals were fed sucrose. Additional corroboration of the physiologic significance of the increased enzyme levels in homogenates was afforded by intestinal perfusion studies. Sucrose hydrolysis increased twofold and fructose absorption fourfold in animals fed sucrose when compared to either fasted or casein-fed rats. PMID:6018758

  4. Absorption of thiamine and nicotinic acid in the rat intestine during fasting and immobilization stress

    NASA Technical Reports Server (NTRS)

    Kirilyuk, O. G.; Khmelevskiy, Y. V.

    1980-01-01

    By perfusion of isolated sections of intestine with a solution containing thiamine at a concentration of 3.1 micromole, it was established that thiamine absorption in animals fasted for 72 hours decreased by 28 percent, whereas absorption increased by 12 percent in rats after 24 hour immobilization. After immobilization, absorption of label in the intestinal mucosa increased. Na K ATPase activity in the intestinal mucosa decreased by 10 percent during fasting, and it increased with immobilization of the animals. Activity of Na K ATPase in the intestinal mucosa cells determined the absorption rate of thiamine and nicotinic acid at the level of vitamin transport through the plasma membranes of the enterocytes.

  5. In vivo kinetics of intestinal absorption of riboflavin in rats

    SciTech Connect

    Feder, S.; Daniel, H.; Rehner, G. )

    1991-01-01

    To investigate absorption kinetics of riboflavin under in vivo conditions, with blood and lymph circulation intact, the small intestine of anesthetized rats was perfused with ({sup 14}C)riboflavin in a concentration range between 0.31 and 10.00 mumol/L. Apart from the uptake of riboflavin from the perfusate, passage of the vitamin into the portal (vena portae) and peripheral (vena femoralis) blood was determined. The absorption proved to be a dual process: at low substrate concentrations (less than 2 mumol/L) a saturable component predominated; at higher concentrations simple diffusion was found to be the prevailing uptake mechanism. The apparent transport constant of the saturable component was calculated to be 0.38 mumol/L. ({sup 14}C)flavin concentrations in the portal and peripheral blood were estimated as a function of the riboflavin concentration of the perfusion media. The dual character of the absorption was reflected by the portal blood flavin levels. Due to the high retaining and equalizing capacity of the liver, the ({sup 14}C)flavin level of the peripheral blood was relatively low and obeyed saturation kinetics. Constants of elimination, determined by pharmacokinetic calculations, were different for the two blood compartments but independent of the concentration of riboflavin in the perfusion media.

  6. Improvement of intestinal absorption of water-soluble macromolecules by various polyamines: intestinal mucosal toxicity and absorption-enhancing mechanism of spermine.

    PubMed

    Gao, Yang; He, Lin; Katsumi, Hidemasa; Sakane, Toshiyasu; Fujita, Takuya; Yamamoto, Akira

    2008-04-16

    The absorption-enhancing effects of three different polyamines, spermine (SPM), spermidine (SPD) and putrescine (PUT) on the intestinal absorption of water-soluble macromolecules were examined in rats. Fluorescein isothiocyanate-labeled dextrans (FDs) with different average molecular weights were chosen as models of water-soluble macromolecules and intestinal absorption of FDs with or without these polyamines was examined by an in situ closed loop method. The intestinal absorption of fluorescein isothiocyanate-labeled dextran with an average molecular weight of 4400 (FD4) was relatively low in the absence of these polyamines. However, its absorption was improved in the presence of 5-10mM SPM and 10mM SPD in the jejunum and 10mM SPM in the colon, while 10mM PUT had almost no absorption-enhancing effect on the intestinal absorption of FD4. Overall, the enhancing effects of these polyamines were greater in the jejunal membranes than in the colonic membranes. The absorption-enhancing effect of SPM decreased as the molecular weights of FDs increased. The intestinal membrane toxicity of 10mM SPM was evaluated by measuring the amount of protein and activity of lactate dehydrogenase (LDH) released from the intestinal epithelial cells. We also observed the morphological changes of intestinal mucosa in the presence or absence of SPM. The results indicated that the amount of protein and LDH was not changed in the presence of 10mM SPM, although we observed a significant increase in these biological markers in the presence of 3% Triton X-100, as a positive control. Furthermore, we found no significant change in the intestinal membrane with 10mM SPM by the morphological observation. These findings suggested that 10mM SPM did not cause any significant membrane damage to the intestinal epithelium. To investigate the absorption-enhancing mechanism of SPM, the transepithelial electrical resistance (TEER) of the rat jejunal membranes was studied by using a diffusion chamber method. SPM decreased the TEER values in a concentration dependent manner and 10mM SPM had almost the same effect to decrease the TEER value compared with 10mM EDTA as a positive control. These findings suggest that SPM may loosen the tight junction of the epithelium, thereby increasing the intestinal absorption of drugs via a paracellular route. In summary, polyamines, especially SPM would be one of the suitable absorption enhancers with high effectiveness and low intestinal membrane toxicity. PMID:18206325

  7. Improvement of intestinal absorption of water-soluble macromolecules by various polyamines: intestinal mucosal toxicity and absorption-enhancing mechanism of spermine.

    TOXLINE Toxicology Bibliographic Information

    Gao Y; He L; Katsumi H; Sakane T; Fujita T; Yamamoto A

    2008-04-16

    The absorption-enhancing effects of three different polyamines, spermine (SPM), spermidine (SPD) and putrescine (PUT) on the intestinal absorption of water-soluble macromolecules were examined in rats. Fluorescein isothiocyanate-labeled dextrans (FDs) with different average molecular weights were chosen as models of water-soluble macromolecules and intestinal absorption of FDs with or without these polyamines was examined by an in situ closed loop method. The intestinal absorption of fluorescein isothiocyanate-labeled dextran with an average molecular weight of 4400 (FD4) was relatively low in the absence of these polyamines. However, its absorption was improved in the presence of 5-10mM SPM and 10mM SPD in the jejunum and 10mM SPM in the colon, while 10mM PUT had almost no absorption-enhancing effect on the intestinal absorption of FD4. Overall, the enhancing effects of these polyamines were greater in the jejunal membranes than in the colonic membranes. The absorption-enhancing effect of SPM decreased as the molecular weights of FDs increased. The intestinal membrane toxicity of 10mM SPM was evaluated by measuring the amount of protein and activity of lactate dehydrogenase (LDH) released from the intestinal epithelial cells. We also observed the morphological changes of intestinal mucosa in the presence or absence of SPM. The results indicated that the amount of protein and LDH was not changed in the presence of 10mM SPM, although we observed a significant increase in these biological markers in the presence of 3% Triton X-100, as a positive control. Furthermore, we found no significant change in the intestinal membrane with 10mM SPM by the morphological observation. These findings suggested that 10mM SPM did not cause any significant membrane damage to the intestinal epithelium. To investigate the absorption-enhancing mechanism of SPM, the transepithelial electrical resistance (TEER) of the rat jejunal membranes was studied by using a diffusion chamber method. SPM decreased the TEER values in a concentration dependent manner and 10mM SPM had almost the same effect to decrease the TEER value compared with 10mM EDTA as a positive control. These findings suggest that SPM may loosen the tight junction of the epithelium, thereby increasing the intestinal absorption of drugs via a paracellular route. In summary, polyamines, especially SPM would be one of the suitable absorption enhancers with high effectiveness and low intestinal membrane toxicity.

  8. Bifidobacterium animalis subsp. lactis decreases urinary oxalate excretion in a mouse model of primary hyperoxaluria

    PubMed Central

    Whittamore, Jonathan M.; Hatch, Marguerite

    2015-01-01

    Hyperoxaluria significantly increases the risk of calcium oxalate kidney stone formation. Since several bacteria have been shown to metabolize oxalate in vitro, including probiotic bifidobacteria, we focused on the efficiency and possible mechanisms by which bifidobacteria can infuence oxalate handling in vivo, especially in the intestines, and compared these results with the reported effects of Oxalobacter formigenes. Bifidobacterium animalis subsp. lactis DSM 10140 and B. adolescentis ATCC 15703 were administered to wild-type (WT) mice and to mice defcient in the hepatic enzyme alanine-glyoxylate aminotransferase (Agxt−/−, a mouse model of Primary Hyperoxaluria) that were fed an oxalate-supplemented diet. The administration of B. animalis subsp. lactis led to a significant decrease in urinary oxalate excretion in WT and Agxt−/− mice when compared to treatment with B. adolescent-is. Detection of B. animalis subsp. lactis in feces revealed that 3 weeks after oral gavage with the bacteria 64 % of WT mice, but only 37 % of Agxt−/− mice were colonized. Examining intestinal oxalate fuxes showed there were no significant changes to net oxalate secretion in colonized animals and were therefore not associated with the changes in urinary oxalate excretion. These results indicate that colonization with B. animalis subsp. lactis decreased urinary oxalate excretion by degrading dietary oxalate thus limiting its absorption across the intestine but it did not promote enteric oxalate excretion as reported for O. formigenes. Preventive or therapeutic administration of B. animalis subsp. lactis appears to have some potential to beneficially infuence dietary hyperoxaluria in mice. PMID:25269440

  9. Intestinal Water Absorption Varies with Expected Dietary Water Load among Bats but Does Not Drive Paracellular Nutrient Absorption.

    PubMed

    Price, Edwin R; Brun, Antonio; Gontero-Fourcade, Manuel; Fernndez-Marinone, Guido; Cruz-Neto, Ariovaldo P; Karasov, William H; Caviedes-Vidal, Enrique

    2015-01-01

    Rapid absorption and elimination of dietary water should be particularly important to flying species and were predicted to vary with the water content of the natural diet. Additionally, high water absorption capacity was predicted to be associated with high paracellular nutrient absorption due to solvent drag. We compared the water absorption rates of sanguivorous, nectarivorous, frugivorous, and insectivorous bats in intestinal luminal perfusions. High water absorption rates were associated with high expected dietary water load but were not highly correlated with previously measured rates of (paracellular) arabinose clearance. In conjunction with these tests, we measured water absorption and the paracellular absorption of nutrients in the intestine and stomach of vampire bats using luminal perfusions to test the hypothesis that the unique elongated vampire stomach is a critical site of water absorption. Vampire bats' gastric water absorption was high compared to mice but not compared to their intestines. We therefore conclude that (1) dietary water content has influenced the evolution of intestinal water absorption capacity in bats, (2) solvent drag is not the only driver of paracellular nutrient absorption, and (3) the vampire stomach is a capable but not critical location for water absorption. PMID:26658415

  10. Microbiota regulate intestinal absorption and metabolism of fatty acids in the zebrafish.

    PubMed

    Semova, Ivana; Carten, Juliana D; Stombaugh, Jesse; Mackey, Lantz C; Knight, Rob; Farber, Steven A; Rawls, John F

    2012-09-13

    Regulation of intestinal dietary fat absorption is critical to maintaining energy balance. While intestinal microbiota clearly impact the host's energy balance, their role in intestinal absorption and extraintestinal metabolism of dietary fat is less clear. Using in vivo imaging of fluorescent fatty acid (FA) analogs delivered to gnotobiotic zebrafish hosts, we reveal that microbiota stimulate FA uptake and lipid droplet (LD) formation in the intestinal epithelium and liver. Microbiota increase epithelial LD number in a diet-dependent manner. The presence of food led to the intestinal enrichment of bacteria from the phylum Firmicutes. Diet-enriched Firmicutes and their products were sufficient to increase epithelial LD number, whereas LD size was increased by other bacterial types. Thus, different members of the intestinal microbiota promote FA absorption via distinct mechanisms. Diet-induced alterations in microbiota composition might influence fat absorption, providing mechanistic insight into how microbiota-diet interactions regulate host energy balance. PMID:22980325

  11. Proximal small intestinal mucosal injury. Maintenance of glucose and glucose polymer absorption, attenuation of disaccharide absorption.

    PubMed

    Palacios, M; Madariaga, H; Heitlinger, L; Lee, P C; Lebenthal, E

    1989-03-01

    The effect of chronic intragastric infusion of hypertonic mannitol on small intestinal mucosal structure and function was studied in adult rats. Animals were gavage-fed 20% mannitol (1300 mosm) at a dose of 5 ml/100 g body weight daily for seven days. Control animals were gavage-fed tap water on the same schedule. On day 8, the animals were anesthetized, the duodenum cannulated, and a test sugar (glucose, glucose polymer, lactose, sucrose, or maltose) was infused at a dose of 0.5 g/kg body weight in 2.5 ml distilled water over less than 1 min. Portal vein glucose was measured at 30-min intervals from 0 to 120 min. Mannitol treatment resulted in histologic and biochemical alterations (reduced lactase, sucrase, maltase) limited to the proximal small intestine compared to the control group. The absorption of glucose and glucose polymers was similar in mannitol-treated and control animals. In contrast, digestion and absorption of lactose, sucrose, and maltose was significantly diminished in mannitol-treated animals when compared to controls. No changes in permeability to polyethylene glycol 4000 or Na+-coupled glucose transport were observed in mannitol-treated animals compared to controls. These data suggest that when the intestinal mucosa is exposed to hyperosmolar loads that the digestive capacity for disaccharides is suppressed more than its glucose absorptive capacities. Furthermore, glucose oligomers may be more readily digested and absorbed than disaccharides, in this setting, due, in part, to the proximal injury and less pronounced proximal-distal gradient for glucoamylase than other brush-border carbohydrases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2493365

  12. [Study on intestinal absorption of formononetin in Millettia nitita var. hirsutissima in rats].

    PubMed

    Liu, Ya-Li; Xiong, Xian-Bing; Su, Dan; Song, Yong-Gui; Zhang, Ling; Yang, Shi-Lin

    2013-10-01

    To use the single-pass intestine perfusion (SPIP) model and HPLC to determine the concentration of formononetin, the effect of quality concentrations of formononetin, different intestinal segments and P-glycoprotein inhibitor on intestinal absorption of formononetin, in order to observe the intestinal absorption mechanism of formononetin from Millettia nitita var. hirsutissima in rats. The experimental results showed that the qulaity concentration of formononetin in the perfusate had no significant effect on the absorption rate constant (K(a)) and the apparent absorption coefficient (P(app)); K(a) and P(app) of formononetin in duodenum, jejunum and ileum showed no significant difference. However, K(a) was significantly higher than that in colon (P < 0.05), with significant difference between that in intestinum tenue and colon. P-glycoprotein inhibitor verapamil showed significant difference in K(a) and P(app) in intestinal segments (P < 0.05). This indicated that the absorption mechanism of formononein in rat intestinal tracts passive diffusion, without any saturated absorption. Formononein is absorbed well in all intestines. Their absorption windows were mainly concentrated in the intestinum tenue, without specific absorption sites. Formononein may be the substrate of P-glycoprotein. PMID:24490575

  13. Intestinal absorption of the intact peptide carnosine in man, and comparison with intestinal permeability to lactulose.

    PubMed Central

    Gardner, M L; Illingworth, K M; Kelleher, J; Wood, D

    1991-01-01

    1. Healthy humans ingested the dipeptide carnosine (L-beta-alanyl-L-histidine). Their plasma levels and urinary outputs of carnosine and beta-alanine were monitored over the following 5 h. 2. Large amounts of intact carnosine (up to 14% of the ingested dose) were recovered in the urine over the 5 h after ingestion. However, carnosine was undetectable in the plasma unless precautions were taken to inhibit blood carnosinase activity ex vivo during and after blood collection. 3. The amount of carnosine recovered in urine varied substantially between subjects. It correlated negatively with carnosinase enzymic activity in the plasma. Highest carnosinase activities were observed in those subjects who regularly underwent physical training. 4. Urinary recovery of the disaccharide lactulose also varied considerably between subjects, but was substantially lower than that of carnosine. There was no significant correlation between the recoveries of carnosine and lactulose. 5. When lactulose was ingested with a hypertonic solution, the urinary recovery of lactulose was generally increased. When carnosine was ingested with a hypertonic solution, the urinary recovery of carnosine was reduced: hence the paracellular route probably is not dominant for absorption of intact carnosine. 6. Intact carnosine must have crossed the intestine to an extent much greater than hitherto recognized. Rapid post-absorptive hydrolysis is a severe obstacle to quantification of intact peptide absorption. PMID:1910085

  14. Permeability for intestinal absorption: Caco-2 assay and related issues.

    PubMed

    Press, Barry; Di Grandi, Deanna

    2008-11-01

    In vitro permeability assays remain a valuable tool of screening scientists for lead compound optimization. As a majority of discovery projects are focused on the development of orally bioavailable drugs, the need for predictability and correlation of in vitro permeability data to in vivo absorption results has never been greater. For more than a decade, the Caco-2 screening assay has remained a popular, in vitro system to test compounds for intestinal permeability and efflux liability. Despite advances in artificial membrane technology and in silico modeling systems, drug compounds still benefit from testing in cell-based epithelial monolayer assays for lead optimization and SAR. This review discusses the strengths and limitations of the Caco-2 permeability assay, and puts into context the power of combining multiple assays and approaches to improve predictability and rank-ordering for lead compound optimization. Technical information for dealing with some of the most pressing issues with in vitro permeability assays (i.e. low aqueous solubility and low post-assay recovery) is also discussed. Insights are offered to help researchers avoid common pitfalls in the interpretation of in vitro permeability data, which can often lead to the perception of misleading results for correlation to in vivo data. In addition, the advantages of addressing the issue of efflux liability early in the drug development process is discussed, detailing the usefulness of Caco-2 cells for this type of screening paradigm. PMID:18991586

  15. Factors contributing to the variation in feline urinary oxalate excretion rate.

    PubMed

    Dijcker, J C; Hagen-Plantinga, E A; Everts, H; Queau, Y; Biourge, V; Hendriks, W H

    2014-03-01

    This study aimed to identify factors (season, animal, and diet) contributing to the variation in urinary oxalate (Uox) excretion rate, Uox concentration, and urine volume in healthy adult cats. A data set (1,940 observations) containing information on Uox excretion rate of 65 cats fed 252 diets (i.e., each diet was fed to a group of 6 to 8 cats), with known dietary oxalate concentrations, collected over a 6 yr period at a feline nutrition facility, were retrospectively analyzed. Data related to season, animal (i.e., age, gender, body weight, and breed), and diet (i.e., nutrient content) characteristics were subjected to stepwise multivariate regression analysis to identify factors significantly correlated to Uox excretion rate (?mol/(kg BW(0.67)d)) and concentration (mmol/L) as well as urine volume (mL/(kg BW(0.67)d)). Independent factors significantly (P < 0.05) associated with lower Uox concentration (mmol/L) included greater ash, Ca, and Na intake and lower nitrogen-free extract, total dietary fiber, P, and oxalate intake, and a body weight <5 kg. Factors significantly associated with lower Uox excretion rate (?mol/(kg BW(0.67)d)) included greater crude fat and Ca intake and lower CP, total dietary fiber, P, and oxalate intake. However, a considerable part of the variation in Uox excretion rate remained unexplained. The majority of the unexplained variation in Uox excretion rate is likely to be related to factors involved in endogenous oxalate synthesis, as the majority of the dietary factors involved in intestinal oxalate absorption were included in the model. Apparent intestinal oxalate absorption was estimated to be 6.2% on average; however, much variation was present. Future research on Uox excretion rate in cats should focus on the influence of dietary protein sources, amino acid composition, vitamin C (that was not included in the present study), and variations in apparent intestinal oxalate absorption. PMID:24496844

  16. Update: The Digestion and Absorption of Carbohydrate and Protein: Role of the Small Intestine.

    ERIC Educational Resources Information Center

    Leese, H. J.

    1984-01-01

    Discusses the role of the small intestine in the digestion and absorption of carbohydrates and proteins. Indicates as outdated the view that these materials must be broken down to monomeric units before absorption and that the gut secretes a mixture of digestive juices which brings about absorption. (JN)

  17. Mechanisms of intestinal absorption of the carcinogen MNNG (N-Methyl-N'-nitro-N-nitrosoguanidine)

    SciTech Connect

    Koyama, S.Y.; Hollander, D.; Dadufalza, V.

    1988-06-01

    The authors studied the characteristics and mechanisms of MNNG (N-methyl-N'-nitro-N-nitrosoguanidine) intestinal absorption and the interaction between bile acids and fatty acids and MNNG absorption rat in vivo in male Sprague-Dawley rats. They found that MNNG was absorbed by simple passive diffusion. Transport of MNNG was the highest at pH 6.0. The addition of the bile salt, taurocholate by itself, greatly increased MNNG absorption, while the addition of the long-chain unsaturated fatty acids, oleic and linoleic, decreased the rate of absorption of MNNG. The phospholipid lecithin addition to the perfusate did not change the rate of MNNG absorption. Induction of dietary vitamin A deficiency (serum vitamin A level decreased from 40.9 to 13.7 ..mu..g/dl) did not change the absorption rate of MNNG. These studies demonstrate that bile acids, dietary fatty acids, and the pH of the intestinal content can modify the rate of absorption of this carcinogen by the small intestine. Since initial intestinal absorption determines serum levels and subsequent reabsorption and enterohepatic cycling determines long-term lumenal levels, serum levels, and total body content, factors which modify the rate of intestinal absorption of MNNG could also modify its carcinogenicity.

  18. Effects of resection on absorption and secretion of divalent cations by small intestine of rat.

    PubMed

    Aliaga, I L; Miller, D L; Wilson, H D; Schedl, H P

    1990-11-01

    Resection increases villus height and crypt depth of remaining intestine. We examined functional consequences of resection by measuring absorption of strontium and secretion of calcium and magnesium by proximal and distal segments remaining after resecting 70% of mid small intestine. Compared with the transected control group, resection decreased strontium absorption per unit weight of mucosa (specific absorption) in the proximal segment. The decreased specific absorption was compensated by increased mucosal growth in the resected group so that absorption per unit length of segment (per cm) was the same in both groups. Resection increased secretion of calcium and magnesium by 66% per unit weight of mucosa and by 145%/cm in the distal segment. Comparing proximal with distal segments in the resected group, secretion was greater in distal for calcium and in proximal for magnesium. Intestinal resection causes responses in absorption and secretion of divalent cations important in mineral homeostasis. PMID:2239763

  19. Intestinal triacylglycerol synthesis in fat absorption and systemic energy metabolism

    PubMed Central

    Yen, Chi-Liang Eric; Nelson, David W.; Yen, Mei-I

    2015-01-01

    The intestine plays a prominent role in the biosynthesis of triacylglycerol (triglyceride; TAG). Digested dietary TAG is repackaged in the intestine to form the hydrophobic core of chylomicrons, which deliver metabolic fuels, essential fatty acids, and other lipid-soluble nutrients to the peripheral tissues. By controlling the flux of dietary fat into the circulation, intestinal TAG synthesis can greatly impact systemic metabolism. Genes encoding many of the enzymes involved in TAG synthesis have been identified. Among TAG synthesis enzymes, acyl-CoA:monoacylglycerol acyltransferase 2 and acyl-CoA:diacylglycerol acyltransferase (DGAT)1 are highly expressed in the intestine. Their physiological functions have been examined in the context of whole organisms using genetically engineered mice and, in the case of DGAT1, specific inhibitors. An emerging theme from recent findings is that limiting the rate of TAG synthesis in the intestine can modulate gut hormone secretion, lipid metabolism, and systemic energy balance. The underlying mechanisms and their implications for humans are yet to be explored. Pharmacological inhibition of TAG hydrolysis in the intestinal lumen has been employed to combat obesity and associated disorders with modest efficacy and unwanted side effects. The therapeutic potential of inhibiting specific enzymes involved in intestinal TAG synthesis warrants further investigation. PMID:25231105

  20. Intestinal triacylglycerol synthesis in fat absorption and systemic energy metabolism.

    PubMed

    Yen, Chi-Liang Eric; Nelson, David W; Yen, Mei-I

    2015-03-01

    The intestine plays a prominent role in the biosynthesis of triacylglycerol (triglyceride; TAG). Digested dietary TAG is repackaged in the intestine to form the hydrophobic core of chylomicrons, which deliver metabolic fuels, essential fatty acids, and other lipid-soluble nutrients to the peripheral tissues. By controlling the flux of dietary fat into the circulation, intestinal TAG synthesis can greatly impact systemic metabolism. Genes encoding many of the enzymes involved in TAG synthesis have been identified. Among TAG synthesis enzymes, acyl-CoA:monoacylglycerol acyltransferase 2 and acyl-CoA:diacylglycerol acyltransferase (DGAT)1 are highly expressed in the intestine. Their physiological functions have been examined in the context of whole organisms using genetically engineered mice and, in the case of DGAT1, specific inhibitors. An emerging theme from recent findings is that limiting the rate of TAG synthesis in the intestine can modulate gut hormone secretion, lipid metabolism, and systemic energy balance. The underlying mechanisms and their implications for humans are yet to be explored. Pharmacological inhibition of TAG hydrolysis in the intestinal lumen has been employed to combat obesity and associated disorders with modest efficacy and unwanted side effects. The therapeutic potential of inhibiting specific enzymes involved in intestinal TAG synthesis warrants further investigation. PMID:25231105

  1. Human in vivo regional intestinal permeability: quantitation using site-specific drug absorption data.

    PubMed

    Sjgren, Erik; Dahlgren, David; Roos, Carl; Lennerns, Hans

    2015-06-01

    Application of information on regional intestinal permeability has been identified as a key aspect of successful pharmaceutical product development. This study presents the results and evaluation of an approach for the indirect estimation of site-specific in vivo intestinal effective permeability (Peff) in humans. Plasma concentration-time profiles from 15 clinical studies that administered drug solutions to specific intestinal regions were collected and analyzed. The intestinal absorption rate for each drug was acquired by deconvolution, using historical intravenous data as reference, and used with the intestinal surface area and the dose remaining in the lumen to estimate the Peff. Forty-three new Peff values were estimated (15 from the proximal small intestine, 11 from the distal small intestine, and 17 from the large intestine) for 14 active pharmaceutical ingredients representing a wide range of biopharmaceutical properties. A good correlation (r(2) = 0.96, slope = 1.24, intercept = 0.030) was established between these indirect jejunal Peff estimates and jejunal Peff measurements determined directly using the single-pass perfusion double balloon technique. On average, Peff estimates from the distal small intestine and large intestine were 90% and 40%, respectively, of those from the proximal small intestine. These results support the use of the evaluated deconvolution method for indirectly estimating regional intestinal Peff in humans. This study presents the first comprehensive data set of estimated human regional intestinal permeability values for a range of drugs. These biopharmaceutical data can be used to improve the accuracy of gastrointestinal absorption predictions used in drug development decision-making. PMID:25919764

  2. Inhibitory effect and mechanism of acarbose combined with gymnemic acid on maltose absorption in rat intestine

    PubMed Central

    Luo, Hong; Wang, Le Feng; Imoto, Toshiaki; Hiji, Yasutake

    2001-01-01

    AIM: To compare the combinative and individual effect of acarbose and gymnemic acid (GA) on maltose absorption and hydrolysis in small intestine to determine whether nutrient control in diabetic care can be improved by combination of them. METHODS: The absorption and hydrolysis of maltose were studied by cyclic perfusion of intestinal loops in situ and motility of the intestine was recorded with the intestinal ring in vitro using Wistar rats. RESULTS: The total inhibitory rate of maltose absorption was improved by the combination of GA (0.1 g/L-1.0 g/L) and acarbose (0.1 mmol/L-2.0 mmol/L) throughout their effective duration (P < 0.05, U test of Mann-Whitney), although the improvement only could be seen at a low dosage during the first hour. With the combination, inhibitory duration of acarbose on maltose absorption was prolonged to 3 h and the inhibitory effect onset of GA was fastened to 15 min. GA suppressed the intestinal mobility with a good correlation (r = 0.98) to the inhibitory effect of GA on maltose absorption and the inhibitory effect of 2 mmol/L (high dose) acarbose on maltose hydrolysis was dual modulated by 1 g/L GA in vivo indicating that the combined effects involved the functional alteration of intestinal barriers. CONCLUSION: There are augmented effects of acarbose and GA, which involve pre-cellular and paracellular barriers. Diabetic care can be improved by employing the combination. PMID:11819725

  3. New insights into the molecular mechanism of intestinal fatty acid absorption

    PubMed Central

    Wang, Tony Y.; Liu, Min; Portincasa, Piero; Wang, David Q.-H.

    2013-01-01

    Background Dietary fat is the most important energy source of all the nutrients. Fatty acids, stored as triacylglycerols in the body, are an important reservoir of stored energy and derive primarily from animal fats and vegetable oils. Design Although the molecular mechanisms for the transport of water-insoluble amphipathic fatty acids across cell membranes have been debated for many years, it is now believed that the dominant means for intestinal fatty acid uptake is via membrane-associated fatty acid-binding proteins, i.e., fatty acid transporters on the apical membrane of enterocytes. Results These findings indicate that intestinal fatty acid absorption is a multistep process that is regulated by multiple genes at the enterocyte level, and intestinal fatty acid absorption efficiency could be determined by factors influencing intraluminal fatty acid molecules across the brush border membrane of enterocytes. To facilitate research on intestinal, hepatic and plasma triacylglycerol metabolism, it is imperative to establish standard protocols for precisely and accurately measuring the efficiency of intestinal fatty acid absorption in humans and animal models. In this review, we will discuss the chemical structure and nomenclature of fatty acids and summarize recent progress in investigating the molecular mechanisms underlying the intestinal absorption of fatty acids, with a particular emphasis on the physical-chemistry of intestinal lipids and the molecular physiology of intestinal fatty acid transporters. Conclusions A better understanding of the molecular mechanism of intestinal fatty acid absorption should lead to novel approaches to the treatment and the prevention of fatty acid-related metabolic diseases that are prevalent worldwide. PMID:24102389

  4. Fatty acid transport protein 4 is dispensable for intestinal lipid absorption in mice.

    PubMed

    Shim, Jien; Moulson, Casey L; Newberry, Elizabeth P; Lin, Meei-Hua; Xie, Yan; Kennedy, Susan M; Miner, Jeffrey H; Davidson, Nicholas O

    2009-03-01

    FA transport protein 4 (FATP4), one member of a multigene family of FA transporters, was proposed as a major FA transporter in intestinal lipid absorption. Due to the fact that Fatp4(-/-) mice die because of a perinatal skin defect, we rescued the skin phenotype using an FATP4 transgene driven by a keratinocyte-specific promoter (Fatp4(-/-);Ivl-Fatp4(tg/+) mice) to elucidate the role of intestinal FATP4 in dietary lipid absorption. Fatp4(-/-);Ivl-Fatp4(tg/+) mice and wild-type littermates displayed indistinguishable food consumption, growth, and weight gain on either low or high fat (Western) diets, with no differences in intestinal triglyceride (TG) absorption or fecal fat losses. Cholesterol absorption and intestinal TG absorption kinetics were indistinguishable between the genotypes, although Western diet fed Fatp4(-/-);Ivl-Fatp4(tg/+) mice showed a significant increase in enterocyte TG and FA content. There was no compensatory upregulation of other FATP family members or any other FA or cholesterol transporters in Fatp4(-/-);Ivl-Fatp4(tg/+) mice. Furthermore, although serum cholesterol levels were lower in Fatp4(-/-);Ivl-Fatp4(tg/+) mice, there was no difference in hepatic VLDL secretion in-vivo or in hepatic lipid content on either a chow or Western diet. Taken together, our studies find no evidence for a physiological role of intestinal FATP4 in dietary lipid absorption in mice. PMID:18843142

  5. Effects of pentagastrin on intestinal absorption and blood flow in the anaesthetized dog.

    PubMed Central

    Mailman, D

    1980-01-01

    1. Pentagastrin (1, 10 micrograms/min) was infused I.V. into fed and fasted anaesthetized dogs and the intestinal absorption of NaCl and H2O and blood flow were determined. The influence of pentagastrin-induced cardiovascular changes on absorption was investigated. 2. 22Na and 3H2O were used to determine the unidirectional Na and H2O fluxes from saline perfused through the ileal lumen and the clearances of 3H2O were used to calculate total and absorptive site blood flow. 3. Ileal absorption of Na and H2O was reduced by 10 micrograms/min pentagastrin due primarily to significant increases in the secretory flux of Na and decreases in the absorptive flux of H2O in both fed and fasted animals. 4. Neither total intestinal blood flow, arterial nor mesenteric vein pressure were changed by pentagastrin but absorptive site blood flow was decreased in fasted but not in fed dogs. 5. Pretreatment with atropine reduced the effects of pentagastrin but pretreatment with guanethidine potentiated the effects of pentagastrin. 6. Absorptive site blood flow was positively linearly correlated with the absorptive fluxes of both Na and H2O. The relationships between the secretory fluxes of Na and H2O and estimated capillary pressure were changed from a positive relationship in control periods to a less positive or negative relationship following pentagastrin. 7. It was concluded that pentagastrin reduces intestinal absorption through both a cardiovascular effect and an effect on the intestinal epithelium. Also, there is a strong autonomic component in the effects of pentagastrin on intestinal absorption. PMID:7205671

  6. Effect of vitamin D on the intestinal absorption of 203Pb and 47Ca in chicks

    SciTech Connect

    Mykkaenen, H.M.; Wasserman, R.H.

    1982-03-01

    The transfer of 203Pb and/or 47Ca across the intestinal epithelium of the chick was investigated, with emphasis given to the functional role of cholecalciferol (vitamin D-3). 203Pb, after introduction in the intestinal lumen, is rapidly accumulated by the intestinal tissue, and only a fraction of 203Pb is translocated parenterally (absorbed). Cholecalciferol did not significantly affect the accumulation of 203Pb by intestinal tissue but did accelerate 203Pb movement across the basal-lateral membrane. In contrast, cholecalciferol both decreased 47Ca tissue levels and increased 47Ca absorption. In rachitic chicks, the rate of absorption of 203Pb was greater in the distal than in the proximal segments of the intestine; after cholecalciferol repletion, the degree of absorption in al segments was similar, indicting the order of cholecalciferol effectiveness as duodenum greater than or equal to jejunum greater than ileum. An acute dose of 1,25(OH)2D3 to rachitic chicks also enhanced both 203Pb and 47Ca absorption, but the time course and pattern of absorption of these metal cations differed. The time at which the absorption of 203Pb peaked and returned to base-line occurred sooner than for 47Ca. Also the back-flux (blood leads to intestinal lumen) of 47Ca was enhanced by cholecalciferol, whereas no effect on the back-flux of 203Pb was noted. These studies show that cholecalciferol and 1,25(OH)2D3 affects both the 203Pb and 47Ca absorptive processes, but the nature of these responses are not identical, suggesting differences in the transport path or the macromolecular interactions of these metal ions during the course of absorption, or both.

  7. 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. PMID:26707414

  8. Intestinal absorption characteristics of imperialine: in vitro and in situ assessments

    PubMed Central

    Lin, Qing; Ling, Li-qin; Guo, Ling; Gong, Tao; Sun, Xun; Zhang, Zhi-rong

    2015-01-01

    Aim: Imperialine is an effective compound in the traditional Chinese medicine chuanbeimu (Bulbus Fritillariae Cirrhosae) that has been used as antitussive/expectorant in a clinical setting. In this study we investigated the absorption characteristics of imperialine in intestinal segments based on an evaluation of its physicochemical properties. Methods: Caco-2 cells were used to examine uptake and transport of imperialine in vitro, and a rat in situ intestinal perfusion model was used to characterize the absorption of imperialine. The amount of imperialine in the samples was quantified using LC-MS/MS. Results: The aqueous solubility and oil/water partition coefficient of imperialine were determined. This compound demonstrated a relatively weak alkalinity with a pKa of 8.467±0.028. In Caco-2 cells, the uptake of imperialine was increased with increasing pH in medium, but not affected by temperature. The apparent absorptive and secretive coefficient was (8.39±0.12)×10−6 cm/s and (7.78±0.09)×10−6 cm/s, respectively. Furthermore, neither the P-glycoprotein inhibitor verapamil nor Niemann-Pick C1-Like 1 transporter inhibitor ezetimibe affected the absorption and secretion of imperialine in vitro. The in situ intestinal perfusion study showed that the absorption parameters of imperialine varied in 4 intestinal segments (duodenum, jejunum, ileum and colon) with the highest ones in the colon, where a greater number of non-ionized form of imperialine was present. Conclusion: The intestinal absorptive characteristics of imperialine are closely related to its physicochemical properties. The passive membrane diffusion dominates the intestinal absorption of imperialine. PMID:26051111

  9. Intestinal absorption of water-soluble vitamins in health and disease

    PubMed Central

    Said, Hamid M.

    2014-01-01

    Our knowledge of the mechanisms and regulation of intestinal absorption of water-soluble vitamins under normal physiological conditions, and of the factors/conditions that affect and interfere with theses processes has been significantly expanded in recent years as a result of the availability of a host of valuable molecular/cellular tools. Although structurally and functionally unrelated, the water-soluble vitamins share the feature of being essential for normal cellular functions, growth and development, and that their deficiency leads to a variety of clinical abnormalities that range from anaemia to growth retardation and neurological disorders. Humans cannot synthesize water-soluble vitamins (with the exception of some endogenous synthesis of niacin) and must obtain these micronutrients from exogenous sources. Thus body homoeostasis of these micronutrients depends on their normal absorption in the intestine. Interference with absorption, which occurs in a variety of conditions (e.g. congenital defects in the digestive or absorptive system, intestinal disease/resection, drug interaction and chronic alcohol use), leads to the development of deficiency (and sub-optimal status) and results in clinical abnormalities. It is well established now that intestinal absorption of the water-soluble vitamins ascorbate, biotin, folate, niacin, pantothenic acid, pyridoxine, riboflavin and thiamin is via specific carrier-mediated processes. These processes are regulated by a variety of factors and conditions, and the regulation involves transcriptional and/or post-transcriptional mechanisms. Also well recognized now is the fact that the large intestine possesses specific and efficient uptake systems to absorb a number of water-soluble vitamins that are synthesized by the normal microflora. This source may contribute to total body vitamin nutrition, and especially towards the cellular nutrition and health of the local colonocytes. The present review aims to outline our current understanding of the mechanisms involved in intestinal absorption of water-soluble vitamins, their regulation, the cell biology of the carriers involved and the factors that negatively affect these absorptive events. PMID:21749321

  10. Enhanced ex vivo intestinal absorption of olmesartan medoxomil nanosuspension: Preparation by combinative technology

    PubMed Central

    Attari, Zenab; Bhandari, Amita; Jagadish, P.C.; Lewis, Shaila

    2015-01-01

    The purpose of this study was to develop nanosuspension based on combinative technology to enhance the intestinal absorption of Olmesartan medoxomil (OLM), a potent antihypertensive agent with limited oral bioavailability. Two combinative approaches were employed and then characterized. In vitro intestinal absorption of OLM nanosuspension and plain OLM was studied using non-everted rat intestinal sac model. Optimal OLM nanosuspension was prepared by a combination of ball milling and probe sonication using stabilizer, Poloxamer 407. The formula exhibited particle size of 469.9 nm and zeta potential of −19.1 mV, which was subjected to ex vivo studies. The flux and apparent permeability coefficient in intestine from OLM nanosuspension was higher than the plain drug, thereby suggesting better drug delivery. PMID:26903769

  11. Enhanced ex vivo intestinal absorption of olmesartan medoxomil nanosuspension: Preparation by combinative technology.

    PubMed

    Attari, Zenab; Bhandari, Amita; Jagadish, P C; Lewis, Shaila

    2016-01-01

    The purpose of this study was to develop nanosuspension based on combinative technology to enhance the intestinal absorption of Olmesartan medoxomil (OLM), a potent antihypertensive agent with limited oral bioavailability. Two combinative approaches were employed and then characterized. In vitro intestinal absorption of OLM nanosuspension and plain OLM was studied using non-everted rat intestinal sac model. Optimal OLM nanosuspension was prepared by a combination of ball milling and probe sonication using stabilizer, Poloxamer 407. The formula exhibited particle size of 469.9 nm and zeta potential of -19.1 mV, which was subjected to ex vivo studies. The flux and apparent permeability coefficient in intestine from OLM nanosuspension was higher than the plain drug, thereby suggesting better drug delivery. PMID:26903769

  12. Lysoglyceroglycolipids Improve the Intestinal Absorption of Micellar Fucoxanthin by Caco-2 Cells.

    PubMed

    Kotake-Nara, Eiichi; Yonekura, Lina; Nagao, Akihiko

    2015-01-01

    To improve the intestinal absorption of fucoxanthin, we evaluated the effects of dietary glyceroglycolipids on the uptake and secretion of fucoxanthin solubilized in mixed micelles by human intestinal Caco-2 cells. Although digalactosyldiacylglycerol and sulfoquinovosyldiacylglycerol suppressed fucoxanthin uptake and secretion, their lyso-types, digalactosylmonoacylglycerol and sulfoquinovosylmonoa cylglycerol, remarkably enhanced them. Thus, some dietary glyceroglycolipids may be potential enhancers of fucoxanthin bioavailability in humans. PMID:26468234

  13. DIGESTION AND INTESTINAL ABSORPTION OF DIETARY CAROTENOIDS AND VITAMIN A.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin A deficiency affects more than 100 million children throughout the world. Thus, knowledge about the mechanisms of absorption of vitamin A can lead to better approaches for enhancing its absorption and could be helpful in ameliorating some of the deficiencies. The major sources of vitamin A...

  14. Functional involvement of RFVT3/SLC52A3 in intestinal riboflavin absorption.

    PubMed

    Yoshimatsu, Hiroki; Yonezawa, Atsushi; Yao, Yoshiaki; Sugano, Kumiko; Nakagawa, Shunsaku; Omura, Tomohiro; Matsubara, Kazuo

    2014-01-01

    Riboflavin, also known as vitamin B2, is transported across the biological membrane into various organs by transport systems. Riboflavin transporter RFVT3 is expressed in the small intestine and has been suggested to localize in the apical membranes of the intestinal epithelial cells. In this study, we investigated the functional involvement of RFVT3 in riboflavin absorption using intestinal epithelial T84 cells and mouse small intestine. T84 cells expressed RFVT3 and conserved unidirectional riboflavin transport corresponding to intestinal absorption. Apical [(3)H]riboflavin uptake was pH-dependent in T84 cells. This uptake was not affected by Na(+) depletion at apical pH 6.0, although it was significantly decreased at apical pH 7.4. The [(3)H]riboflavin uptake from the apical side of T84 cells was prominently inhibited by the RFVT3 selective inhibitor methylene blue and significantly decreased by transfection of RFVT3-small-interfering RNA. In the gastrointestinal tract, RFVT3 was expressed in the jejunum and ileum. Mouse jejunal and ileal permeabilities of [(3)H]riboflavin were measured by the in situ closed-loop method and were significantly reduced by methylene blue. These results strongly suggest that RFVT3 would functionally be involved in riboflavin absorption in the apical membranes of intestinal epithelial cells. PMID:24264046

  15. The assessment of absorption of periplocin in situ via intestinal perfusion of rats by HPLC.

    PubMed

    Xie, Yue-Sheng; Ren, Xiao-Liang; Pan, Gui-Xiang; Gao, Xiu-Mei; Liu, Chang-Xiao

    2008-02-01

    Periplocin is an important compound of Cortex Periplocae, which shows poor absorption when administered orally. The effective intestinal permeability of periplocin was investigated using single-pass intestinal perfusion technique in male Wistar rats. SPIP was performed in rat jejunum. The samples of perfusate were collected at the designated time points after rat intestinal perfusion and analyzed by HPLC. The specificity of this method was demonstrated by the absence of interference of the drug peak with the intestinal sac artifacts and the components of the KRB solution. Recovery studies, as well as the intra-day and inter-day variations, were within statistical limits. This technique was applied to the study of the intestinal absorption of periplocin. The determined fraction absorbed (F(a)) of periplocin was 0.151 +/- 0.072 (n = 6) at a concentration of 6 microg/mL; the absorption rate constant (K(a)) was 0.0102 +/- 0.0039/min and the effective permeability coefficient (P(eff)) was 0.0021 +/- 0.0012 cm/min. These data suggest that periplocin has high permeability and might be absorbed in rat intestine. PMID:18059065

  16. The role of P-glycoprotein in limiting intestinal regional absorption of digoxin in rats.

    PubMed

    Sababi, M; Borg, O; Hultkvist-Bengtsson, U

    2001-08-01

    The objective of this work was to study the role of regional intestinal efflux activity of P-glycoprotein (Pgp) in situ in anesthetized rats in limiting the absorption of digoxin. A 10-cm portion of duodenum or jejunum, or 5-cm of colon was perfused single-pass with saline containing [(3)H]digoxin while the appearance of radioactivity in the blood was measured. Verapamil in the perfusate was used as a modulator of Pgp in the intestinal mucosa. Net water absorption, mucosal integrity, and intestinal motility of the isolated segment were monitored, as well as heart rate and blood pressure. Excretion of i.v. administered unlabelled digoxin, 1 mg/kg, into the intestine while perfusing the duodenum-proximal jejunum region, was studied for comparison. At a perfusate concentration of 1 mM, verapamil caused a dramatic increase in [(3)H]digoxin absorption rate from duodenum and jejunum, while the effect in colon was insignificant. At concentrations of 0.1, 1, and 2.5 mM in the duodenal perfusate, verapamil increased the absorption rate of [(3)H]digoxin in a dose-dependent manner. The lowest concentration almost doubled the rate without having any significant effects on the cardiovascular system, intestinal motility, or net absorption of water. The excretion rate of unlabelled digoxin from the blood into the gut lumen was found to be halved in the presence of 0.5 mM verapamil in the perfusate. Absorption rate of [(3)H]digoxin in the rat is likely limited by Pgp-mediated efflux. The data indicate that Pgp plays an important role for digoxin efflux in the small intestine only. PMID:11457646

  17. Enhanced glucose absorption in the rat small intestine following repeated doses of 5-fluorouracil.

    PubMed

    Tomimatsu, Takashi; Horie, Toshiharu

    2005-08-15

    Many studies demonstrated that 5-fluorouracil (5-FU) treatment of rodents caused the damage of small intestine, resulting in the malabsorption, while we recently found that repeated administration of 5-FU to rats increased Na(+)-dependent glucose absorption in the small intestine. This study investigated the cause of enhanced glucose absorption. 3-O-methyl-d-glucose (3-OMG) absorption was examined using the everted intestine technique. d-Glucose uptake, phlorizin binding, Western blot analysis and membrane fluidity were examined using small intestinal brush-border membrane vesicles (BBMV). Repeated oral administration of 5-FU to rats increased Na(+)-dependent 3-OMG absorption in the small intestine, while alkaline phosphatase activity in the small intestine decreased. Na(+)/K(+)-ATPase activity of 5-FU-treated rats was about three-fold higher than that of control rats. Although the amount of Na(+)-dependent glucose co-transporter (SGLT1) in 5-FU-treated rats decreased, the overshoot magnitude of d-glucose uptake in BBMV was not altered. Maximum binding of phlorizin in 5-FU-treated rats was 1.5-fold larger than that of control rats, but not altered the maximal rate of d-glucose absorption, Michaelis constant of d-glucose and dissociation constant of phlorizin. The membrane fluidity of 5-FU-treated rats increased. The enhanced d-glucose absorption in 5-FU-treated rats seems to occur secondarily due to the activation of Na(+)/K(+)-ATPase activity in basolateral membranes (BLM). Because the amounts of SGLT1 in 5-FU-treated rats decreased, the increase of turnover rate of SGLT1 and/or an expression of unknown Na(+)-dependent glucose co-transporter with high affinity for d-glucose and phlorizin sensitivity would contribute to the enhancement of d-glucose transport in 5-FU-treated rats. PMID:15996645

  18. Intestinal absorption of 5 chromium compounds in young black ducks (Anas rubripes)

    USGS Publications Warehouse

    Eastin, W.C., Jr.; Haseltine, S.D.; Murray, H.C.

    1980-01-01

    An in vivo intestinal perfusion technique was used to measure the absorption rates of five Cr compounds in black ducks. Cr was absorbed from saline solutions of KCr(SO4 )2 and CrO3 at a rate about 1.5 to 2.0 times greater than from solutions of Cr, Cr(NO3 )3, and Cr(C5H7O2)3. These results suggest the ionic form of Cr in solution may be an important factor in determining absorption of Cr compounds from the small intestine.

  19. Intestinal folate binding protein (FBP) and folate absorption in the suckling rat

    SciTech Connect

    Mason, J.B.; Selhub, J.

    1986-03-01

    The folate in milk is bound to high affinity FBPs but it is unknown whether this binding affects intestinal transport of milk folate in the suckling rat. The authors examined the FBP activity of segments of the GI tract in fed and fasting states. Under fed conditions, the FBP activity in the mucosa of the stomach and proximal small intestine were similar (0.28 and 0.32 pMole folic acid binding/mg protein, N.S.). Both demonstrated less activity than the mucosa of the distal small intestine (1.31 pMole/mg protein, P < .001). A 6 hr fast produced no change in the FBP activity in the stomach or proximal small intestine but resulted in a 42% decrease in the distal small intestine (p < .01). Intestinal transport of unbound and FB-bound H/sup 3/pteryolmonoglutamate (H/sup 3/PGA) was examined in suckling rats by the intestinal loop model. Unbound H/sup 3/PGA demonstrated greater lumenal disappearance in the proximal segment of the small intestine compared to the distal segment (79% vs. 56%, P < .001) whereas the bound H/sup 3/PGA demonstrated greater lumenal disappearance in the distal segment (36% vs. 21%, p < .005). That porton of FBP activity in the distal small intestine that disappears with fasting may represent FBP absorbed from the lumen of the intestine. The FBP-bound folate in milk appears to be absorbed in the suckling rat by a mechanism that favors the distal small intestine and is different from the mechanism responsible for absorption of the unbound folate.

  20. In vitro intestinal absorption and first-pass intestinal and hepatic metabolism of cycloastragenol, a potent small molecule telomerase activator.

    PubMed

    Zhu, Jing; Lee, Stephanie; Ho, Maurice K C; Hu, Yueqing; Pang, Haihong; Ip, Fanny C F; Chin, Allison C; Harley, Calvin B; Ip, Nancy Y; Wong, Yung H

    2010-01-01

    Cycloastragenol (CAG) is the aglycone derivative of astragaloside IV which has recently been demonstrated to activate telomerase and represents a potential drug candidate for the treatment of degenerative diseases. In the present study, intestinal absorption and metabolism of CAG were examined using the Caco-2 model and liver microsomes, respectively. The results showed that CAG rapidly passes through the Caco-2 cell monolayer by passive diffusion. Four different glucuronide conjugates and two oxidized CAG metabolites were found in the apical and basolateral sides of Caco-2 monolayer, suggesting that first-pass intestinal metabolism of CAG might occur upon passage through the intestinal epithelium. CAG underwent extensive metabolism in rat and human liver microsomes with only 17.4% and 8.2%, respectively, of the starting amount of CAG remaining after 30 min of incubation. Monohydroxylation of the parent and oxidization of the hydroxylated CAG were found in the liver samples. The present study indicates that CAG is efficiently absorbed through intestinal epithelium. However, extensive first-pass hepatic metabolism would limit the oral bioavailability of this compound. PMID:20877137

  1. [In situ rats single pass perfusion intestinal absorption of the effectivein components in Radix Angelicae Pubescentis].

    PubMed

    Wu, Ya-Na; Luan, Li-Biao

    2008-01-01

    In order to study the intestinal absorption behaviors of three active constituents, columbianetin acetate, osthole and columbianadin in Radix Angelicae Pubescentis extracts, in situ rat single pass intestine perfusion (SPIP) was carried out by the perfusion solution of the extract I containing less than 10% total coumarins. The absorption of extract II containing more than 60% total coumarins was compared with that of extract I by rat colon SPIP to elucidate the influence on absorption of the different coumarin content extracts of the Chinese traditional medicine. The samples of the perfusion solution were collected in certain intervals. The concentrations of three active components in the perfusion samples were determined by HPLC method. The results demonstrated that the absorption rate constants (Ka) or apparent permeability coefficients (Papp) of columbianetin acetate, osthole and columbianadin from extract I had no significant difference among concentration ranges of 62-555 microg x mL(-1), 101-887 microg x mL(-1), 19-186 microg x mL(-1), respectively. The absorption quantity of three components was proportional to its concentration respectively and the saturate absorption phenomena were not observed. This suggested that the absorption of columbianetin acetate, osthole and columbianadin showed the passive diffusion process. Three components could be absorbed in whole intestinal sections. The Ka and Papp of three components all showed colon > duodenum > jejunum > ileum in four different regions of rat intestine. At colon, Ka and P app were significant different from the others. The Ka or Papp of three components from the extract I was significantly more than that of same components from extract II. The extract I redounded to increase the absorption of three active components. PMID:18357742

  2. Intestinal Caveolin-1 Is Important for Dietary Fatty Acid Absorption

    PubMed Central

    Siddiqi, Shahzad; Sheth, Atur; Patel, Feenalie; Barnes, Matthew; Mansbach, Charles M.

    2013-01-01

    SUMMARY How dietary fatty acids are absorbed into the enterocyte and transported to the ER is not established. We tested the possibility that caveolin-1 containing lipid rafts and endocytic vesicles were involved. Apical brush border membranes took up 15% of albumin bound 3H-oleate whereas brush border membranes from caveolin-1 KO mice took up only 1%. In brush border membranes, the 3H-oleate was in the detergent resistant fraction of an OptiPrep gradient. On OptiPrep gradients of intestinal cytosol, we also found the 3H-oleate in the detergent resistant fraction, separate from OptiPrep gradients spiked with 3H-oleate or 3H-triacylglycerol. Caveolin-1 immuno-depletion of cytosol removed 91% of absorbed 3H-oleate whereas immuno-depletion using IgG, or anti-caveolin-2 or ?3 or anti-clathrin antibodies removed 20%. Electron microscopy showed the presence of caveolin-1 containing vesicles in WT mouse cytosol that were 4 fold increased by feeding intestinal sacs 1 mM oleate. No vesicles were seen in caveolin-1 KO mouse cytosol. Caveolin-1 KO mice gained less weight on a 23% fat diet and had increased fat in their stool compared to WT mice. We conclude that dietary fatty acids are absorbed by caveolae in enterocyte brush border membranes, are endocytosed, and transported in cytosol in caveolin-1 containing endocytic vesicles. PMID:23665238

  3. Intestinal caveolin-1 is important for dietary fatty acid absorption.

    PubMed

    Siddiqi, Shahzad; Sheth, Atur; Patel, Feenalie; Barnes, Matthew; Mansbach, Charles M

    2013-08-01

    How dietary fatty acids are absorbed into the enterocyte and transported to the ER is not established. We tested the possibility that caveolin-1 containing lipid rafts and endocytic vesicles were involved. Apical brush border membranes took up 15% of albumin bound (3)H-oleate whereas brush border membranes from caveolin-1 KO mice took up only 1%. In brush border membranes, the (3)H-oleate was in the detergent resistant fraction of an OptiPrep gradient. On OptiPrep gradients of intestinal cytosol, we also found the (3)H-oleate in the detergent resistant fraction, separate from OptiPrep gradients spiked with (3)H-oleate or (3)H-triacylglycerol. Caveolin-1 immuno-depletion of cytosol removed 91% of absorbed (3)H-oleate whereas immuno-depletion using IgG, or anti-caveolin-2 or -3 or anti-clathrin antibodies removed 20%. Electron microscopy showed the presence of caveolin-1 containing vesicles in WT mouse cytosol that were 4 fold increased by feeding intestinal sacs 1mM oleate. No vesicles were seen in caveolin-1 KO mouse cytosol. Caveolin-1 KO mice gained less weight on a 23% fat diet and had increased fat in their stool compared to WT mice. We conclude that dietary fatty acids are absorbed by caveolae in enterocyte brush border membranes, are endocytosed, and transported in cytosol in caveolin-1 containing endocytic vesicles. PMID:23665238

  4. Mechanisms of guanylin action on water and ion absorption at different regions of seawater eel intestine.

    PubMed

    Ando, Masaaki; Wong, Marty K S; Takei, Yoshio

    2014-09-15

    Guanylin (GN) inhibited water absorption and short-circuit current (Isc) in seawater eel intestine. Similar inhibition was observed after bumetanide, and the effect of bumetanide was abolished by GN or vice versa, suggesting that both act on the same target, Na(+)-K(+)-2Cl(-) cotransporter (NKCC), which is a key player for the Na(+)-K(+)-Cl(-) transport system responsible for water absorption in marine teleost intestine. However, effect of GN was always greater than that of bumetanide: 10% greater in middle intestine (MI) and 40% in posterior intestine (PI) for Isc, and 25% greater in MI and 34% in PI for water absorption. After treatment with GN, Isc decreased to zero, but 20-30% water absorption still remained. The remainder may be due to the Cl(-)/HCO3 (-) exchanger and Na(+)-Cl(-) cotransporter (NCC), since inhibitors for these transporters almost nullified the remaining water absorption. Quantitative PCR analysis revealed the presence of major proteins involved in water absorption; the NKCC2? and AQP1 genes whose expression was markedly upregulated after seawater acclimation. The SLC26A6 (anion exchanger) and NCC? genes were also expressed in small amounts. Consistent with the inhibitors' effect, expression of NKCC2? was MI > PI, and that of NCC? was MI < PI. The present study showed that GN not only inhibits the bumetanide-sensitive Na(+)-K(+)-Cl(-) transport system governed by NKCC2?, but also regulates unknown ion transporters different from GN-insensitive SLC26A6 and NCC. A candidate is cystic fibrosis transmembrane conductance regulator Cl(-) channel, as demonstrated in mammals, but its expression is low in eel intestine, and its role may be minor, as indicated by the small effect of its inhibitors. PMID:24990857

  5. The effects of inhibition of haem biosynthesis by griseofulvin on intestinal iron absorption.

    PubMed

    Laftah, Abas H; Raja, Kishor B; Beaumont, Nick; Simpson, Robert J; Deacon, Allan; Solanky, Nita; Srai, Surjit Kaila S; Peters, Timothy J

    2004-04-01

    The relationship between haem biosynthesis and intestinal iron absorption in mice was investigated by ascertaining the effect of the haem synthesis inhibitor, griseofulvin, on duodenal iron absorption using both in vivo and in vitro measurements. Urinary 5-aminolaevulinic acid levels were increased within 24 hr of feeding mice with griseofulvin diet (2.5% w/w), with more marked increases seen after 3-7 days. Urinary porphobilinogen levels also showed a similar trend. In vivo intestinal iron absorption was significantly reduced (P<0.05) in experimental mice, mainly due to reduction in the transfer of 59Fe from the enterocytes to the portal circulation. In vitro studies using isolated duodenal fragments also exhibited marked decreases in both iron uptake and Fe (III) reduction. Changes in mucosal Divalent Metal Transporter 1 (DMT-1), Dcytb and Ireg1 (iron regulated protein 1) mRNA levels paralleled the changes in iron absorption. The reduction in iron absorption after griseofulvin treatment was normalised when mice were simultaneously injected with haem-arginate. These data support the hypothesis that intermediates in haem biosynthesis, particularly 5-aminolaevulinic acid, regulate intestinal iron absorption. PMID:15078340

  6. Intestinal alkaline phosphatase: selective endocytosis from the enterocyte brush border during fat absorption.

    PubMed

    Hansen, Gert H; Niels-Christiansen, Lise-Lotte; Immerdal, Lissi; Nystrøm, Birthe T; Danielsen, E Michael

    2007-12-01

    Absorption of dietary fat in the small intestine is accompanied by a rise of intestinal alkaline phosphatase (IAP) in the serum and of secretion of IAP-containing surfactant-like particles from the enterocytes. In the present work, fat absorption was studied in organ cultured mouse intestinal explants. By immunofluorescence microscopy, fat absorption caused a translocation of IAP from the enterocyte brush border to the interior of the cell, whereas other brush-border enzymes were unaffected. By electron microscopy, the translocation occurred by a rapid (5 min) induction of endocytosis via clathrin-coated pits. By 60 min, IAP was seen in subapical endosomes and along membranes surrounding fat droplets. IAP is a well-known lipid raft-associated protein, and fat absorption was accompanied by a marked change in the density and morphology of the detergent-resistant membranes harboring IAP. A lipid analysis revealed that fat absorption caused a marked increase in the microvillar membrane contents of free fatty acids. In conclusion, fat absorption rapidly induces a transient clathrin-dependent endocytosis via coated pits from the enterocyte brush border. The process selectively internalizes IAP and may contribute to the appearance of the enzyme in serum and surfactant-like particles. PMID:17947448

  7. Consensus hologram QSAR modeling for the prediction of human intestinal absorption.

    PubMed

    Moda, Tiago L; Andricopulo, Adriano D

    2012-04-15

    Consistent in silico models for ADME properties are useful tools in early drug discovery. Here, we report the hologram QSAR modeling of human intestinal absorption using a dataset of 638 compounds with experimental data associated. The final validated models are consistent and robust for the consensus prediction of this important pharmacokinetic property and are suitable for virtual screening applications. PMID:22425566

  8. Eicosapentaenoic acid inhibits intestinal ?-carotene absorption by downregulation of lipid transporter expression via PPAR-? dependent mechanism.

    PubMed

    Mashurabad, Purna Chandra; Kondaiah, Palsa; Palika, Ravindranadh; Ghosh, Sudip; Nair, Madhavan K; Raghu, Pullakhandam

    2016-01-15

    The involvement of lipid transporters, the scavenger receptor class B, type I (SR-BI) and Niemann-Pick type C1 Like 1 protein (NPC1L1) in carotenoid absorption is demonstrated in intestinal cells and animal models. Dietary ?-3 fatty acids are known to possess antilipidemic properties, which could be mediated by activation of PPAR family transcription factors. The present study was conducted to determine the effect of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on intestinal ?-carotene absorption. ?-carotene uptake in Caco-2/TC7 cells was inhibited by EPA (p<0.01) and PPAR? agonist (P<0.01), but not by DHA, PPAR? or PPAR? agonists. Despite unaltered ?-carotene uptake, both DHA and PPAR? agonists inhibited the NPC1L1 expression. Further, EPA also induced the expression of carnitine palmitoyl transferase 1A (CPT1A) expression, a PPAR? target gene. Interestingly, EPA induced inhibition of ?-carotene uptake and SR B1 expression were abrogated by specific PPAR? antagonist, but not by PPAR? antagonist. EPA and PPAR? agonist also inhibited the basolateral secretion of ?-carotene from Caco-2 cells grown on permeable supports. These results suggest that EPA inhibits intestinal ?-carotene absorption by down regulation of SR B1 expression via PPAR? dependent mechanism and provide an evidence for dietary modulation of intestinal ?-carotene absorption. PMID:26577021

  9. Intestinal Absorption of Fucoidan Extracted from the Brown Seaweed, Cladosiphon okamuranus

    PubMed Central

    Nagamine, Takeaki; Nakazato, Kyoumi; Tomioka, Satoru; Iha, Masahiko; Nakajima, Katsuyuki

    2014-01-01

    The aim of this study was to examine the absorption of fucoidan through the intestinal tract. Fucoidan (0.1, 0.5, 1.0, 1.5 and 2.0 mg/mL) was added to Transwell inserts containing Caco-2 cells. The transport of fucoidan across Caco-2 cells increased in a dose-dependent manner up to 1.0 mg/mL. It reached a maximum after 1 h and then rapidly decreased. In another experiment, rats were fed standard chow containing 2% fucoidan for one or two weeks. Immunohistochemical staining revealed that fucoidan accumulated in jejunal epithelial cells, mononuclear cells in the jejunal lamina propria and sinusoidal non-parenchymal cells in the liver. Since we previously speculated that nitrosamine may enhance the intestinal absorption of fucoidan, its absorption was estimated in rats administered N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in their drinking water. Rats were fed 0.2% fucoidan chow (BBN + 0.2% fucoidan rats), 2% fucoidan chow (BBN + 2% fucoidan rats) and standard chow for eight weeks. The uptake of fucoidan through the intestinal tract seemed to be low, but was measurable by our ELISA method. Fucoidan-positive cells were abundant in the small intestinal mucosa of BBN + 2% fucoidan rats. Most fucoidan-positive cells also stained positive for ED1, suggesting that fucoidan was incorporated into intestinal macrophages. The uptake of fucoidan by Kupffer cells was observed in the livers of BBN + 2% fucoidan rats. In conclusion, the absorption of fucoidan through the small intestine was demonstrated both in vivo and in vitro. PMID:25546518

  10. [Intestinal absorption of aloe-emodin using single-passintestinal perfusion method in rat].

    PubMed

    Wang, Jinrong; Wang, Ping; Yang, Yongmao; Meng, Xianli; Zhang, Yan

    2011-09-01

    The intestinal absorption of aloe-emodin was investigated using the single pass intestinal perfusion (SPIP) technique in S/D rats. SPIP was performed in each isolated segment of the intestine (i.e., duodenum, jejunum, ileum and colon) and the different concentrations inhibitor group of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP2) with the concentrations of aloe-emodin (0.238 mg x L(-1)) at a flow rate of 0.28 mL x min(-1). The effective absorption rate constant (Ka) and apparent absorption coefficient (Papp) of aloe-emodin for each segment were determined before and after treated with different concentrations of inhibitors of P-gp and MRP2 respectively. Aloe-emodin exhibits a high intestinal permeability except the the ileum, indicative that the compounds are well absorbed. Decreases of Ka and Papp values in the duodenum, jejunum, colon and ileum, furthermore, the duodenum has significant increased compared with the ileum, there are have no significant difference in other isolated region of the intestine. Compared with the group which have no inhibitor of P-gp, the Ka and Papp were significantly increased in inhibitor of P-gp groups. Compared with the group of no inhibitor of MRP2, the Ka and Papp were significantly increased in inhibitor of MRP2 groups with the highest and the middle concentration. The results suggested that the inhibitors of P-gp and MRP2 all can promote the intestinal absorption of aloe-emodin. PMID:22121810

  11. In situ intestinal absorption of cyclosporine A solid dispersion in rats.

    PubMed

    Liu, Chen; Zhu, Saijie; Zhou, Ying; Wei, Yupu; Pei, Yuanying

    2008-06-01

    Effects of concentration of Polyoxyethylene (40) stearate, Na(+) and P-gp inhibitor on cyclosporin A (CyA-SD) absorption were investigated by in situ circulation method. The results showed that the absorption of CyA increased linearly with its concentration, indicating a passive diffusion process was dominated. CyA absorption decreased with the carrier concentration. The concentration of Na(+) didn't influence the drug absorbed (P > 0.05). The P-gp inhibitor enhanced the CyA absorption significantly (P < 0.05). The passive diffusion process during the intestinal absorption indicated that the solubility enhancement of CyA is one of the mechanisms for the absorption of this water insoluble drug. PMID:18568913

  12. Intestinal absorption of aloin, aloe-emodin, and aloesin; A comparative study using two in vitro absorption models.

    PubMed

    Park, Mi-Young; Kwon, Hoon-Jeong; Sung, Mi-Kyung

    2009-01-01

    Aloe products are one of the top selling health-functional foods in Korea, however the adequate level of intake to achieve desirable effects are not well understood. The objective of this study was to determine the intestinal uptake and metabolism of physiologically active aloe components using in vitro intestinal absorption model. The Caco-2 cell monolayer and the everted gut sac were incubated with 5-50 microM of aloin, aloe-emodin, and aloesin. The basolateral appearance of test compounds and their glucuronosyl or sulfated forms were quantified using HPLC. The % absorption of aloin, aloe-emodin, and aloesin was ranged from 5.51% to 6.60%, 6.60% to 11.32%, and 7.61% to 13.64%, respectively. Up to 18.15%, 18.18%, and 38.86% of aloin, aloe-emodin, and aloesin, respectively, was absorbed as glucuronidated or sulfated form. These results suggest that a significant amount is transformed during absorption. The absorption rate of test compounds except aloesin was similar in two models; more aloesin was absorbed in the everted gut sac than in the Caco-2 monolayer. These results provide information to establish adequate intake level of aloe supplements to maintain effective plasma level. PMID:20016696

  13. Intestinal absorption of aloin, aloe-emodin, and aloesin; A comparative study using two in vitro absorption models

    PubMed Central

    Park, Mi-Young; Kwon, Hoon-Jeong

    2009-01-01

    Aloe products are one of the top selling health-functional foods in Korea, however the adequate level of intake to achieve desirable effects are not well understood. The objective of this study was to determine the intestinal uptake and metabolism of physiologically active aloe components using in vitro intestinal absorption model. The Caco-2 cell monolayer and the everted gut sac were incubated with 5-50 M of aloin, aloe-emodin, and aloesin. The basolateral appearance of test compounds and their glucuronosyl or sulfated forms were quantified using HPLC. The % absorption of aloin, aloe-emodin, and aloesin was ranged from 5.51% to 6.60%, 6.60% to 11.32%, and 7.61% to 13.64%, respectively. Up to 18.15%, 18.18%, and 38.86% of aloin, aloe-emodin, and aloesin, respectively, was absorbed as glucuronidated or sulfated form. These results suggest that a significant amount is transformed during absorption. The absorption rate of test compounds except aloesin was similar in two models; more aloesin was absorbed in the everted gut sac than in the Caco-2 monolayer. These results provide information to establish adequate intake level of aloe supplements to maintain effective plasma level. PMID:20016696

  14. Unique insights into the intestinal absorption, transit, and subsequent biodistribution of polymer-derived microspheres.

    PubMed

    Reineke, Joshua J; Cho, Daniel Y; Dingle, Yu-Ting; Morello, A Peter; Jacob, Jules; Thanos, Christopher G; Mathiowitz, Edith

    2013-08-20

    Polymeric microspheres (MSs) have received attention for their potential to improve the delivery of drugs with poor oral bioavailability. Although MSs can be absorbed into the absorptive epithelium of the small intestine, little is known about the physiologic mechanisms that are responsible for their cellular trafficking. In these experiments, nonbiodegradable polystyrene MSs (diameter range: 500 nm to 5 µm) were delivered locally to the jejunum or ileum or by oral administration to young male rats. Following administration, MSs were taken up rapidly (≤ 5 min) by the small intestine and were detected by transmission electron microscopy and confocal laser scanning microscopy. Gel permeation chromatography confirmed that polymer was present in all tissue samples, including the brain. These results confirm that MSs (diameter range: 500 nm to 5 µm) were absorbed by the small intestine and distributed throughout the rat. After delivering MSs to the jejunum or ileum, high concentrations of polystyrene were detected in the liver, kidneys, and lungs. The pharmacologic inhibitors chlorpromazine, phorbol 12-myristate 13-acetate, and cytochalasin D caused a reduction in the total number of MSs absorbed in the jejunum and ileum, demonstrating that nonphagocytic processes (including endocytosis) direct the uptake of MSs in the small intestine. These results challenge the convention that phagocytic cells such as the microfold cells solely facilitate MS absorption in the small intestine. PMID:23922388

  15. Unique insights into the intestinal absorption, transit, and subsequent biodistribution of polymer-derived microspheres

    PubMed Central

    Reineke, Joshua J.; Cho, Daniel Y.; Dingle, Yu-Ting; Morello, A. Peter; Jacob, Jules; Thanos, Christopher G.; Mathiowitz, Edith

    2013-01-01

    Polymeric microspheres (MSs) have received attention for their potential to improve the delivery of drugs with poor oral bioavailability. Although MSs can be absorbed into the absorptive epithelium of the small intestine, little is known about the physiologic mechanisms that are responsible for their cellular trafficking. In these experiments, nonbiodegradable polystyrene MSs (diameter range: 500 nm to 5 m) were delivered locally to the jejunum or ileum or by oral administration to young male rats. Following administration, MSs were taken up rapidly (?5 min) by the small intestine and were detected by transmission electron microscopy and confocal laser scanning microscopy. Gel permeation chromatography confirmed that polymer was present in all tissue samples, including the brain. These results confirm that MSs (diameter range: 500 nm to 5 m) were absorbed by the small intestine and distributed throughout the rat. After delivering MSs to the jejunum or ileum, high concentrations of polystyrene were detected in the liver, kidneys, and lungs. The pharmacologic inhibitors chlorpromazine, phorbol 12-myristate 13-acetate, and cytochalasin D caused a reduction in the total number of MSs absorbed in the jejunum and ileum, demonstrating that nonphagocytic processes (including endocytosis) direct the uptake of MSs in the small intestine. These results challenge the convention that phagocytic cells such as the microfold cells solely facilitate MS absorption in the small intestine. PMID:23922388

  16. Peptide derivation of poorly absorbable drug allows intestinal absorption via peptide transporter.

    PubMed

    Kikuchi, Akihiro; Tomoyasu, Takahiro; Tanaka, Michinori; Kanamitsu, Kayoko; Sasabe, Hiroyuki; Maeda, Tomoji; Odomi, Masaaki; Tamai, Ikumi

    2009-05-01

    The purpose of the present study was to examine whether the intestinal absorption of low-permeability drugs could be improved by utilization of the intestinal influx transporter PEPT1. We investigated whether peptide derivatives of poorly absorbable nonamino acid-like drugs might be substrates of PEPT1, using rebamipide (Reb) as a model drug. We synthesized several peptide derivatives of rebamipide and examined their inhibitory effect on the uptake of [(3)H]Gly-Sar by PEPT1-expressing HeLa cells. Some of the peptide derivatives inhibited PEPT1-mediated uptake of [(3)H]Gly-Sar. Next, uptake of the inhibitory peptide derivatives was evaluated in PEPT1-expressing Xenopus oocytes and HeLa cells. Ser(Reb)-Gly exhibited significantly increased uptake by PEPT1-expressing cells in comparison with that by mock cells. The permeability of Ser(Reb)-Gly across a Caco-2 cell monolayer was significantly higher than that of rebamipide itself, and the transport was decreased in the presence of PEPT1 substrates. Further, a rat intestinal perfusion study revealed increased absorption of Ser(Reb)-Gly compared with rebamipide. These results demonstrate that the addition of a dipeptide moiety to a poorly absorbable nonpeptide/nonamino acid-like drug can result in absorption via the intestinal transporter PEPT1, though there is some selectivity as regards the structure of the added peptide moiety. PMID:18781650

  17. Development and physiological regulation of intestinal lipid absorption. I. Development of intestinal lipid absorption: cellular events in chylomicron assembly and secretion.

    PubMed

    Black, Dennis D

    2007-09-01

    The newborn mammal must efficiently absorb dietary fat, predominantly as triacylglycerol, and produce chylomicrons to deliver this lipid to peripheral tissues. The cellular mechanisms involved in enterocyte chylomicron assembly have recently been elucidated, and data on their regulation in the immature gut are beginning to emerge. This review focuses on key proteins involved in chylomicron assembly: apolipoprotein B-48, microsomal triglyceride transfer protein, and apolipoprotein A-IV. Recent studies support a role for apolipoprotein A-IV in enhancing chylomicron secretion by promoting production of larger particles. These proteins are regulated in a manner to maximize the lipid absorptive capacity of the newborn intestine. PMID:17495031

  18. A Sensitive Medium-Throughput Method to Predict Intestinal Absorption in Humans Using Rat Intestinal Tissue Segments.

    PubMed

    Da Silva, Las Cristina; Da Silva, Taynara Loureno; Antunes, Alisson Henrique; Rezende, Knnia Rocha

    2015-09-01

    A range of in vitro, ex vivo, and in vivo approaches are currently used for drug development. Highly predictive human intestinal absorption models remain lagging behind the times because of numerous variables concerning permeability through gastrointestinal tract in humans. However, there is a clear need for a drug permeability model early in the drug development process that can balance the requirements for high throughput and effective predictive potential. The present study developed a medium throughput screening Snapwell (MTS-Snapwell) ex vivo model to provide an alternative method to classify drug permeability. Rat small intestine tissue segments were mounted in commercial Snapwell inserts. Unidirectional drug transport (A-B) was measured by collecting samples at different time points. Viability of intestinal tissue segments was measured by examining transepithelial electric resistance (TEER) and phenol red and caffeine transport. As a result, the apparent permeability (Papp; 10(-6) cm/s) was determined for atenolol (10.7 1.2), caffeine (17.6 3.1), cimetidine (6.9 0.1), metoprolol (12.6 0.7), theophylline (15.3 1.6) and, ranitidine (3.8 0.4). All drugs were classified in high/low permeability according to Biopharmaceutics Classification System showing high correlation with human data (r = 0.89). These findings showed a high correlation with human data (r = 0.89), suggesting that this model has potential predictive capacity for paracellular and transcellular passively absorbed molecules. PMID:25690454

  19. Studies on inhibition of intestinal absorption of radioactive strontium. IX. Relationship between biological activity and electron microscopic appearance of alginic acid components.

    PubMed

    Tanaka, Y; Inoue, S; Skoryna, S C

    1970-09-12

    The inhibitory action of alginate on intestinal absorption of radioactive strontium was investigated in order to correlate the biological activity with the chemical composition. Alginate from Laminaria hyperborea was partially hydrolyzed with oxalic acid and the degradation products were fractionated into polymannuronic and polyguluronic acid. The activity of these products was assessed biologically in rats and morphologically by electron microscopy. Sodium polymannuronate was found to be less effective than sodium polyguluronate in preventing absorption of radiostrontium. The inhibition of absorption of radio-calcium was low and not affected by hydrolysis or fractionation. When dried from dilute aqueous solutions, the polymannuronate retained the original helical structure of alginate, while the polyguluronate showed a strong tendency to coagulate, forming granules. The variation in the biological activity was attributed to the morphological differences between these alginic acid components and it is suggested that the degree of uncoiling of the polyguluronate chain in water is greater than that of the polymannuronate chain, thus making the carboxylate ions more accessible to strontium. PMID:5469618

  20. Intestinal SR-BI does not impact cholesterol absorption or transintestinal cholesterol efflux in mice.

    PubMed

    Bura, Kanwardeep S; Lord, Caleb; Marshall, Stephanie; McDaniel, Allison; Thomas, Gwyn; Warrier, Manya; Zhang, Jun; Davis, Matthew A; Sawyer, Janet K; Shah, Ramesh; Wilson, Martha D; Dikkers, Arne; Tietge, Uwe J F; Collet, Xavier; Rudel, Lawrence L; Temel, Ryan E; Brown, J Mark

    2013-06-01

    Reverse cholesterol transport (RCT) can proceed through the classic hepatobiliary route or through the nonbiliary transintestinal cholesterol efflux (TICE) pathway. Scavenger receptor class B type I (SR-BI) plays a critical role in the classic hepatobiliary route of RCT. However, the role of SR-BI in TICE has not been studied. To examine the role of intestinal SR-BI in TICE, sterol balance was measured in control mice and mice transgenically overexpressing SR-BI in the proximal small intestine (SR-BI(hApoCIII-ApoAIV-Tg)). SR-BI(hApoCIII-ApoAIV-Tg) mice had significantly lower plasma cholesterol levels compared with wild-type controls, yet SR-BI(hApoCIII-ApoAIV-Tg) mice had normal fractional cholesterol absorption and fecal neutral sterol excretion. Both in the absence or presence of ezetimibe, intestinal SR-BI overexpression had no impact on the amount of cholesterol excreted in the feces. To specifically study effects of intestinal SR-BI on TICE we crossed SR-BI(hApoCIII-ApoAIV-Tg) mice into a mouse model that preferentially utilized the TICE pathway for RCT (Niemann-Pick C1-like 1 liver transgenic), and likewise found no alterations in cholesterol absorption or fecal sterol excretion. Finally, mice lacking SR-BI in all tissues also exhibited normal cholesterol absorption and fecal cholesterol disposal. Collectively, these results suggest that SR-BI is not rate limiting for intestinal cholesterol absorption or for fecal neutral sterol loss through the TICE pathway. PMID:23564696

  1. LXR driven induction of HDL-cholesterol is independent of intestinal cholesterol absorption and ABCA1 protein expression.

    PubMed

    Kannisto, Kristina; Gfvels, Mats; Jiang, Zhao-Yan; Sltis, Katharina; Hu, Xiaoli; Jorns, Carl; Steffensen, Knut R; Eggertsen, Gsta

    2014-01-01

    We investigated whether: (1) liver X receptor (LXR)-driven induction of high-density lipoprotein cholesterol (HDL-C) and other LXR-mediated effects on cholesterol metabolism depend on intestinal cholesterol absorption; and (2) combined treatment with the LXR agonist GW3965 and the cholesterol absorption inhibitor ezetimibe results in synergistic effects on cholesterol metabolism that could be beneficial for treatment of atherosclerosis. Mice were fed 0.2% cholesterol and treated with GW3965+ezetimibe, GW3965 or ezetimibe. GW3965+ezetimibe treatment elevated serum HDL-C and Apolipoprotein (Apo) AI, effectively reduced the intestinal cholesterol absorption and increased the excretion of faecal neutral sterols. No changes in intestinal ATP-binding cassette (ABC) A1 or ABCG5 protein expression were observed, despite increased mRNA expression, while hepatic ABCA1 was slightly reduced. The combined treatment caused a pronounced down-regulation of intestinal Niemann-Pick C1-like 1 (NPC1L1) and reduced hepatic and intestinal cholesterol levels. GW3965 did not affect the intestinal cholesterol absorption, but increased serum HDL-C and ApoAI levels. GW3965 also increased Apoa1 mRNA levels in primary mouse hepatocytes and HEPA1-6 cells. Ezetimibe reduced the intestinal cholesterol absorption, ABCA1 and ABCG5, but did not affect the serum HDL-C or ApoAI levels. Thus, the LXR-driven induction of HDL-C and ApoAI was independent of the intestinal cholesterol absorption and increased expression of intestinal or hepatic ABCA1 was not required. Inhibited influx of cholesterol via NPC1L1 and/or low levels of intracellular cholesterol prevented post-transcriptional expression of intestinal ABCA1 and ABCG5, despite increased mRNA levels. Combined LXR activation and blocked intestinal cholesterol absorption induced effective faecal elimination of cholesterol. PMID:24163219

  2. Intestinal absorptive transport of Genkwanin from Flos genkwa using a single-pass intestinal perfusion rat model.

    PubMed

    Jiang, Cui-Ping; He, Xin; Yang, Xiao-Lin; Zhang, Su-Li; Li, Hui; Song, Zi-Jing; Zhang, Chun-Feng; Yang, Zhong-Lin; Li, Ping

    2014-01-01

    To investigate the absorptive transport behavior of genkwanin and the beneficial effects of monoterpene enhancers with different functional groups, the single-pass intestinal perfusion (SPIP) of rats was used. The results showed that genkwanin was segmentally-dependent and the best absorptive site was the duodenum. The effective permeability coefficient (P eff ) was 1.97 10(-4) cm/s and the absorption rate constant (Ka) was 0.62 10(-2) s(-1). Transepithelial transportation descended with increasing concentrations of genkwanin. This was a 1.4-fold increase in P eff by probenecid, whereas a 1.4-fold or 1.6-fold decrease was observed by verapamil and pantoprazole, respectively. Furthermore, among the absorption enhancers, the enhancement with carbonyl (camphor and menthone) was higher than that with hydroxyl (borneol and menthol). The concentration-independent permeability and enhancement by coperfusion of probenecid indicated that genkwanin was transported by both passive diffusion and multidrug resistance protein (MDR)-mediated efflux mechanisms. PMID:24707867

  3. Anthocyanin Absorption and Metabolism by Human Intestinal Caco-2 Cells--A Review.

    PubMed

    Kamiloglu, Senem; Capanoglu, Esra; Grootaert, Charlotte; Van Camp, John

    2015-01-01

    Anthocyanins from different plant sources have been shown to possess health beneficial effects against a number of chronic diseases. To obtain any influence in a specific tissue or organ, these bioactive compounds must be bioavailable, i.e., effectively absorbed from the gut into the circulation and transferred to the appropriate location within the body while still maintaining their bioactivity. One of the key factors affecting the bioavailability of anthocyanins is their transport through the gut epithelium. The Caco-2 cell line, a human intestinal epithelial cell model derived from a colon carcinoma, has been proven to be a good alternative to animal studies for predicting intestinal absorption of anthocyanins. Studies investigating anthocyanin absorption by Caco-2 cells report very low absorption of these compounds. However, the bioavailability of anthocyanins may be underestimated since the metabolites formed in the course of digestion could be responsible for the health benefits associated with anthocyanins. In this review, we critically discuss recent findings reported on the anthocyanin absorption and metabolism by human intestinal Caco-2 cells. PMID:26370977

  4. Intestinal absorption of dietary fat from a liquid diet perfused in rats at a submaximum level

    SciTech Connect

    Simko, V.; Kelley, R.E.

    1988-02-01

    The small intestine of rats was perfused in vivo for 2 h with a nutritionally complete liquid diet (68% calories from fat as corn oil). As the perfusion increased from 106 mg/2 h, the intestinal disappearance of the /sup 14/C-triolein marker remained proportional to the load up to 2359 mg fat/2 h. Despite a decrease in absorption from 70 to 17%, this represents a very large fat intake. Fat absorption improved when medium-chain triglycerides or octanoic acid replaced corn oil (both p less than 0.01). Linoleic acid was absorbed from the diet less than corn oil (p less than 0.01). Dry ox bile reduced fat absorption (p less than 0.05); lipase and an antacid had no effect. Corn oil perfused alone was absorbed better than from the diet (p less than 0.01). Data with /sup 14/C-triolein was confirmed by dry-weight disappearance of the diet and by net intestinal water balance. Usual feeding underutilizes a large reserve for fat absorption. This reserve should be considered in therapeutic nutrition.

  5. Anthocyanin Absorption and Metabolism by Human Intestinal Caco-2 Cells—A Review

    PubMed Central

    Kamiloglu, Senem; Capanoglu, Esra; Grootaert, Charlotte; Van Camp, John

    2015-01-01

    Anthocyanins from different plant sources have been shown to possess health beneficial effects against a number of chronic diseases. To obtain any influence in a specific tissue or organ, these bioactive compounds must be bioavailable, i.e., effectively absorbed from the gut into the circulation and transferred to the appropriate location within the body while still maintaining their bioactivity. One of the key factors affecting the bioavailability of anthocyanins is their transport through the gut epithelium. The Caco-2 cell line, a human intestinal epithelial cell model derived from a colon carcinoma, has been proven to be a good alternative to animal studies for predicting intestinal absorption of anthocyanins. Studies investigating anthocyanin absorption by Caco-2 cells report very low absorption of these compounds. However, the bioavailability of anthocyanins may be underestimated since the metabolites formed in the course of digestion could be responsible for the health benefits associated with anthocyanins. In this review, we critically discuss recent findings reported on the anthocyanin absorption and metabolism by human intestinal Caco-2 cells. PMID:26370977

  6. Intestinal fluid absorption in anadromous salmonids: importance of tight junctions and aquaporins

    PubMed Central

    Sundell, Kristina S.; Sundh, Henrik

    2012-01-01

    The anadromous salmonid life cycle includes both fresh water (FW) and seawater (SW) stages. The parr-smolt transformation (smoltification) pre-adapt the fish to SW while still in FW. The osmoregulatory organs change their mode of action from a role of preventing water inflow in FW, to absorb ions to replace water lost by osmosis in SW. During smoltification, the drinking rate increases, in the intestine the ion and fluid transport increases and is further elevated after SW entry. In SW, the intestine absorbs ions to create an inwardly directed water flow which is accomplished by increased Na+, K+-ATPase (NKA) activity in the basolateral membrane, driving ion absorption via ion channels and/or co-transporters. This review will aim at discussing the expression patterns of the ion transporting proteins involved in intestinal fluid absorption in the FW stage, during smoltification and after SW entry. Of equal importance for intestinal fluid absorption as the active absorption of ions is the permeability of the epithelium to ions and water. During the smoltification the increase in NKA activity and water uptake in SW is accompanied by decreased paracellular permeability suggesting a redirection of the fluid movement from a paracellular route in FW, to a transcellular route in SW. Increased transcellular fluid absorption could be achieved by incorporation of aquaporins (AQPs) into the enterocyte membranes and/or by a change in fatty acid profile of the enterocyte lipid bilayer. An increased incorporation of unsaturated fatty acids into the membrane phospholipids will increase water permeability by enhancing the fluidity of the membrane. A second aim of the present review is therefore to discuss the presence and regulation of expression of AQPs in the enterocyte membrane as well as to discuss the profile of fatty acids present in the membrane phospholipids during different stages of the salmonid lifecycle. PMID:23060812

  7. Intestinal fluid absorption in anadromous salmonids: importance of tight junctions and aquaporins.

    PubMed

    Sundell, Kristina S; Sundh, Henrik

    2012-01-01

    The anadromous salmonid life cycle includes both fresh water (FW) and seawater (SW) stages. The parr-smolt transformation (smoltification) pre-adapt the fish to SW while still in FW. The osmoregulatory organs change their mode of action from a role of preventing water inflow in FW, to absorb ions to replace water lost by osmosis in SW. During smoltification, the drinking rate increases, in the intestine the ion and fluid transport increases and is further elevated after SW entry. In SW, the intestine absorbs ions to create an inwardly directed water flow which is accomplished by increased Na(+), K(+)-ATPase (NKA) activity in the basolateral membrane, driving ion absorption via ion channels and/or co-transporters. This review will aim at discussing the expression patterns of the ion transporting proteins involved in intestinal fluid absorption in the FW stage, during smoltification and after SW entry. Of equal importance for intestinal fluid absorption as the active absorption of ions is the permeability of the epithelium to ions and water. During the smoltification the increase in NKA activity and water uptake in SW is accompanied by decreased paracellular permeability suggesting a redirection of the fluid movement from a paracellular route in FW, to a transcellular route in SW. Increased transcellular fluid absorption could be achieved by incorporation of aquaporins (AQPs) into the enterocyte membranes and/or by a change in fatty acid profile of the enterocyte lipid bilayer. An increased incorporation of unsaturated fatty acids into the membrane phospholipids will increase water permeability by enhancing the fluidity of the membrane. A second aim of the present review is therefore to discuss the presence and regulation of expression of AQPs in the enterocyte membrane as well as to discuss the profile of fatty acids present in the membrane phospholipids during different stages of the salmonid lifecycle. PMID:23060812

  8. Novel norcantharidin-loaded liver targeting chitosan nanoparticles to enhance intestinal absorption.

    PubMed

    Bei, Yong-yan; Chen, Xiao-yan; Liu, Yang; Xu, Jing-yu; Wang, Wen-juan; Gu, Zong-lin; Xing, Kong-lang; Zhu, Ai-jun; Chen, Wei-liang; Shi, Lin-seng; Wang, Qin; Zhang, Xue-nong; Zhang, Qiang

    2012-01-01

    In this paper, two novel liver-targeting nanoparticles, norcantharidin-loaded chitosan nanoparticles (NCTD-CS-NPs) and norcantharidin-associated galactosylated chitosan nanoparticles (NCTD-GC-NPs), were prepared using ionic cross-linkage. The physical properties, particle size, encapsulation efficiency, and drug release characteristics of the nanoparticles were investigated in vitro. To investigate the intestinal absorption mechanisms of the two preparations, a series of experiments was carried out, including in situ circulation method, in vitro everted gut sacs, and Ussing chamber perfusion technique. The absorption rate constants (Ka) of NCTD at different segments were found to be duodenum > jejunum > ileum > colon. The concentration had no distinctive effect on absorption kinetics, suggesting that drug absorption is not dose-dependent. The transport of NCTD was found to be inhibited by P-glycoprotein (P-gp) inhibitor, indicating that NCTD might be the substrate of P-gp. The order of the absorption enhancer effects were as follows: low molecular weight chitosan (CS-8kDa) > high molecular weight chitosan (CS-30kDa) > Poloxamer > sodium dodecyl sulfate (SDS) > sodium deoxycholate (SDCh). The results indicate that the chitosan nanoparticles can improve intestinal absorption of NCTD. PMID:22619530

  9. Update on Oxalate Crystal Disease

    PubMed Central

    Lorenz, Elizabeth C.; Michet, Claude J.; Milliner, Dawn S.; Lieske, John C.

    2013-01-01

    Oxalate arthropathy is a rare cause of arthritis characterized by deposition of calcium oxalate crystals within synovial fluid. This condition typically occurs in patients with underlying primary or secondary hyperoxaluria. Primary hyperoxaluria constitutes a group of genetic disorders resulting in endogenous overproduction of oxalate, whereas secondary hyperoxaluria results from gastrointestinal disorders associated with fat malabsorption and increased absorption of dietary oxalate. In both conditions oxalate crystals can deposit in the kidney leading to renal failure. Since oxalate is primarily renally eliminated, it accumulates throughout the body in renal failure, a state termed oxalosis. Affected organs can include bones, joints, heart, eyes and skin. Since patients can present with renal failure and oxalosis before the underlying diagnosis of hyperoxaluria has been made, it is important to consider hyperoxaluria in patients who present with unexplained soft tissue crystal deposition. The best treatment of oxalosis is prevention. If patients present with advanced disease, treatment of oxalate arthritis consists of symptom management and control of the underlying disease process. PMID:23666469

  10. Studies on Inhibition of Intestinal Absorption of Radioactive Strontium

    PubMed Central

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

    1964-01-01

    A method is reported that enables selective suppression of absorption of radioactive strontium from ingested food material, permitting calcium to remain available to the body. Studies were carried out by measuring blood levels and bone uptake of Sr89 and Ca45 at different time intervals after orogastric intubation of rats. The addition of sodium alginate, derived from brown marine algae, to the radioactive isotopes increased the overall physiological discrimination against strontium by amounts up to 60% after 24 hours. This discrimination was further increased by feeding sodium alginate mixed with standard diet in the proportions of 20:80 and 30:70. The observed ratio was reduced by administration of sodium alginate from 0.25 to 0.09. Determination of the limiting dosage in rats is restricted to the amounts which rats will consume. In the event of an inadvertent release of radioactive strontium, human subjects probably could increase their intake of alginate at will, permitting a greater effectiveness of sodium alginate than could be obtained in experimental animals. PMID:14176062

  11. Intestinal absorption of triglyceride and vitamin D3 in aged and young rats

    SciTech Connect

    Holt, P.R.; Dominguez, A.A.

    1981-12-01

    (3H)Trioleyl glycerol (TO) and (14C)vitamin D3 were perfused intraduodenally for 5 hr in aged (19-21 months) and young adult (4-5 months) Sprague-Dawley rats. The rate of intestinal uptake from the gastrointestinal lumen and transport into the body of these lipids were decreased in the aged animals. Since the distribution of TO lipolytic products in the lumen was unchanged, reduced intestinal uptake rate probably occurred at the mucosal membrane. Furthermore, in the aged rats, the rate of transintestinal transport of both trioleyl glycerol and vitamin D3 was impaired. No evidence for impaired mucosal TO reesterification or for accumulation of vitamin D3 metabolites was found, suggesting that intestinal lipid accumulation resulted from a defect in lipoprotein assembly or in discharge from the mucosal cell. Impaired absorption of lipids may contribute to malnutrition and osteopenia of advancing age.

  12. Bile salts enhance the intestinal absorption of lipophilic drug loaded lipid nanocarriers: mechanism and effect in rats.

    PubMed

    Zhang, Zhiwen; Gao, Fang; Jiang, Shijun; Chen, Lingli; Liu, Zeying; Yu, Haijun; Li, Yaping

    2013-08-16

    The purpose of this study was to elucidate the effect and possible mechanism of bile salts on the intestinal absorption of lipophilic drug loaded lipid nanocarriers in rats. Effects of sodium cholate (SC) on the characteristics, intestinal absorption, cellular uptake in Caco-2 cell monolayers and intestinal lymphatic transport of candesartan cilexetil loaded lipid nanocarriers (CLN) were investigated to clarify the possible mechanism. The intestinal absorption of candesartan from CLN was evidently improved over 16-fold compared with free drug suspension, and further significantly enhanced 1.79-fold after the addition of SC. The cellular uptake of CLN in Caco-2 cell monolayers at 37?C and its colocalization with endoplasmic reticulum were obviously increased in the presence of SC. Moreover, the intestinal lymphatic transport of CLN was obviously enhanced by SC. These results implicated that bile salts could improve the cellular uptake of CLN in Caco-2 cell monolayers via the active processes and promote the intestinal absorption of CLN through the intestinal lymphatic pathway. Therefore, bile salts could be an important physiological factor affecting the intestinal absorption of lipophilic drugs loaded lipid nanocarriers. PMID:23694804

  13. Calorie Restriction Increases P-Glycoprotein and Decreases Intestinal Absorption of Digoxin in Mice.

    PubMed

    Renaud, Helen J; Klaassen, Curtis D; Csanaky, Iván L

    2016-03-01

    There is wide variation in how patients respond to therapeutics. Factors that contribute to pharmacokinetic variations include disease, genetics, drugs, age, and diet. The purpose of this study was to determine the effect of calorie restriction on the expression of Abcb1a in the intestine and whether calorie restriction can alter the absorption of an Abcb1a substrate (i.e., digoxin) in mice. Ten-week-old C57BL/6 mice were given either an ad libitum diet or a 25% calorie-restricted diet for 3 weeks. To determine digoxin absorption, mice were administered [(3)H]-labeled digoxin by oral gavage. Blood and intestine with contents were collected at 1, 2, 4, and 12 hours after digoxin administration. Concentrations of [(3)H]-digoxin in plasma and tissues were determined by liquid scintillation. Calorie restriction decreased plasma digoxin concentrations (about 60%) at 1, 2, and 4 hours after administration. Additionally, digoxin concentrations in the small intestine of calorie-restricted mice were elevated at 4 and 12 hours after administration. Furthermore, calorie restriction increased Abcb1a transcripts in the duodenum (4.5-fold) and jejunum (12.5-fold). To confirm a role of Abcb1a in the altered digoxin pharmacokinetics induced by calorie restriction, the experiment was repeated in Abcb1a/b-null mice 4 hours after drug administration. No difference in intestine or plasma digoxin concentrations were observed between ad libitum-fed and calorie-restricted Abcb1a/b-null mice. Thus, these findings support the hypothesis that calorie restriction increases intestinal Abcb1a expression, leading to decreased absorption of digoxin in mice. Because Abcb1a transports a wide variety of therapeutics, these results may be of important clinical significance. PMID:26744253

  14. In vitro study of transporters involved in intestinal absorption of inorganic arsenic.

    PubMed

    Calatayud, Marta; Barrios, Julio A; Vlez, Dinoraz; Devesa, Vicenta

    2012-02-20

    Inorganic arsenic (iAs) [As(III)+As(V)] is a drinking water contaminant, and human exposure to these arsenic species has been linked with a wide range of health effects. The main path of exposure is the oral route, and the intestinal epithelium is the first physiological barrier that iAs must cross in order to be absorbed. However, there is a lack of information about intestinal iAs absorption. The aim of this study was to evaluate the participation of certain transporters [glucose transporters (GLUT and SGLT), organic anion transporting polypeptides (OATPs), aquaporins (AQPs), and phosphate transporters (NaPi and PiT)] in intestinal absorption of As(V) and As(III), using the Caco-2 cell line as a model of the intestinal epithelium. For this purpose, the effects of chemical inhibition and gene silencing of the transporters of interest on iAs uptake were evaluated, and also the differential expression of these transporters after treatment with iAs. The results show that chemical inhibition using rifamycin SV (OATP inhibitor), phloridzin (SGLT inhibitor), phloretin (GLUT and AQP inhibitor), and copper sulfate (AQP inhibitor) leads to a significant reduction in the apparent permeability and cellular retention of As(III). RT-qPCR indicates up-regulation of GLUT2, GLUT5, OATPB, AQP3, and AQP10 after exposure to As(III), while exposure to As(V) increases the expression of sodium-dependent phosphate transporters, especially NaPiIIb. Gene silencing of OATPB, AQP10, and GLUT5 for As(III) and NaPiIIb for As(V) significantly reduces uptake of the inorganic forms. These results indicate that these transporters may be involved in intestinal absorption of iAs. PMID:22214486

  15. Oxalobacter formigenes Colonization and Oxalate Dynamics in a Mouse Model.

    PubMed

    Li, Xingsheng; Ellis, Melissa L; Knight, John

    2015-08-01

    Animal and human studies have provided compelling evidence that colonization of the intestine with Oxalobacter formigenes reduces urinary oxalate excretion and lowers the risk of forming calcium oxalate kidney stones. The mechanism providing protection appears to be related to the unique ability of O. formigenes to rely on oxalate as a major source of carbon and energy for growth. However, much is not known about the factors that influence colonization and host-bacterium interactions. We have colonized mice with O. formigenes OxCC13 and systematically investigated the impacts of diets with different levels of calcium and oxalate on O. formigenes intestinal densities and urinary and intestinal oxalate levels. Measurement of intestinal oxalate levels in mice colonized or not colonized with O. formigenes demonstrated the highly efficient degradation of soluble oxalate by O. formigenes relative to other microbiota. The ratio of calcium to oxalate in diets was important in determining colonization densities and conditions where urinary oxalate and fecal oxalate excretion were modified, and the results were consistent with those from studies we have performed with colonized and noncolonized humans. The use of low-oxalate purified diets showed that 80% of animals retained O. formigenes colonization after a 1-week dietary oxalate deprivation. Animals not colonized with O. formigenes excreted two times more oxalate in feces than they had ingested. This nondietary source of oxalate may play an important role in the survival of O. formigenes during periods of dietary oxalate deprivation. These studies suggest that the mouse will be a useful model to further characterize interactions between O. formigenes and the host and factors that impact colonization. PMID:25979889

  16. Avian species differences in the intestinal absorption of xenobiotics (PCB, dieldrin, Hg2+)

    USGS Publications Warehouse

    Serafin, J.A.

    1984-01-01

    Intestinal absorption of a polychlorinated biphenyl, dieldrin, and mercury (from HgCl2) was measured in adult Northern bobwhites, Eastern screech owls, American kestrels, black-crowned night-herons and mallards in vivo by an in situ luminal perfusion technique. bobwhites, screech owls and kestrels absorbed much more of each xenobiotic than black-crowned night-herons and mallards. Mallards absorbed less dieldrin and mercury than black-crowned night-herons. Mercury absorption by kestrels was more than twice that in screech owls and eight times that observed in mallards. Pronounced differences in xenobiotic absorption rates between bobwhites, screech owls and kestrels on the one hand, and black-crowned night-herons and mallards on the other, raise the possibility that absorptive ability may be associated with the phylogenetic classification of birds.

  17. Effect of absorbable and nonabsorbable sugars on intestinal calcium absorption in humans

    SciTech Connect

    Griessen, M.; Speich, P.V.; Infante, F.; Bartholdi, P.; Cochet, B.; Donath, A.; Courvoisier, B.; Bonjour, J.P.

    1989-03-01

    The effects of glucose, galactose, and lactitol on intestinal calcium absorption and gastric emptying were studied in 9, 8, and 20 healthy subjects, respectively. Calcium absorption was measured by using a double-isotope technique and the kinetic parameters were obtained by a deconvolution method. The gastric emptying rate was determined with /sup 99m/Tc-diethylenetriaminepentaacetic acid and was expressed as the half-time of the emptying curve. Each subject was studied under two conditions: (a) with calcium alone and (b) with calcium plus sugar. Glucose and galactose increased the calcium mean transit time and improved the total fractional calcium absorption by 30% (p less than 0.02). Lactitol decreased the mean rate of absorption (p less than 0.001) and reduced the total fractional calcium absorption by 15% (p less than 0.001). The gastric emptying rate did not appear to influence directly the kinetic parameters of calcium absorption. These results show that both glucose and galactose exert the same stimulatory effect as lactose on calcium absorption in subjects with normal lactase whereas lactitol mimics the effects of lactose in lactase-deficient patients. Thus the absorbability of sugars determines their effect on calcium absorption.

  18. Enhancing effect of hydroxypropyl-?-cyclodextrin on the intestinal absorption process of genipin.

    TOXLINE Toxicology Bibliographic Information

    Zhang Y; Meng FC; Cui YL; Song YF

    2011-10-26

    The purpose of this work is to investigate the effect of the genipin/hydroxypropyl-?-cyclodextrin (HP-?-CD) inclusion complex on the intestinal absorption of genipin and identify its mechanism of action. The phase solubility profile was classified as A(L) type, indicating the formulation of a 1:1 stoichiometry inclusion complex. Fourier transform infrared spectroscopy, Differential scanning calorimetry, X-ray powder diffractometry, and (1)H nuclear magnetic resonance (NMR) and two-dimensional (2D) (1)H rotating-frame Overhauser enhancement (ROESY) NMR spectroscopies further confirmed the formulation of the inclusion complex with superior dissolution properties than the drug alone. The results of single-pass intestinal perfusion showed that the intestinal absorption of genipin was affected by P-glycoprotein (Pgp). The absorption rate and permeability value of the inclusion complex were significantly higher than the free drug, suggesting that its enhancing effect was involved in its solubilizing effect and Pgp inhibitory effect. The mechanisms of HP-?-CD on Pgp inhibition were demonstrated by restraining the Pgp ATPase activity rather than changing the fluidity of the cell membrane.

  19. Changes in the intestinal absorption mechanism of icariin in the nanocavities of cyclodextrins

    PubMed Central

    Zhang, Ye; Wang, Qiang-Song; Cui, Yuan-Lu; Meng, Fan-Cui; Lin, Ke-Ming

    2012-01-01

    Icariin is a bioactive herbal ingredient isolated from Herba epimedii, which has been widely used for the treatment of osteoporosis and male sexual dysfunction in traditional Chinese medicine. The major objective of this work is to investigate the different enhancing effects of ?-cyclodextrin (?-CD) and hydroxypropyl-?-cyclodextrin (HP-?-CD) on the intestinal absorption of icariin, and to identify the molecular mechanisms of this action. Hostguest-type interactions of icariin with cyclodextrins nanocavities were unambiguously demonstrated by the phase-solubility diagram, ultraviolet spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray powder diffractometry, and two dimensional proton nuclear magnetic resonance rotating-frame Overhauser effect spectroscopy. These results were further supported using molecular modeling studies. The rat single-pass intestinal perfusion model showed that the absorption of icariin was affected by P-glycoprotein (Pgp). The icariin/HP-?-CD inclusion complex provided greater enhancement in the intestinal absorption than the icariin/?-CD inclusion complex. Therefore, the enhancing effect was involved in a solubilizing effect and/or Pgp inhibitory effect. Finally, fluorescence anisotropy measurements and Pgp adenosine triphosphatase (ATPase) assay demonstrated that ?-CD exhibited no effect on Pgp, while HP-?-CD showed inhibition by restraining the Pgp ATPase activity rather than changing the fluidity of cell membrane. PMID:22904630

  20. Bioadhesive polysaccharide in protein delivery system: chitosan nanoparticles improve the intestinal absorption of insulin in vivo.

    PubMed

    Pan, Yan; Li, Ying-jian; Zhao, Hui-ying; Zheng, Jun-min; Xu, Hui; Wei, Gang; Hao, Jin-song; Cui, Fu-de

    2002-12-01

    There are many ongoing investigations to improve the oral bioavailability of peptide and protein formulations. Bioadhesive polysaccharide chitosan nanoparticles (CS-NPs) would seem to further enhance intestinal absorption of them. In this study, Insulin-loaded CS-NPs were prepared by ionotropic gelation of CS with tripolyphosphate anions. Its particle size distribution and zeta potential were determined by photon correction spectroscopy and laser Dopper anemometry. The ability of CS-NPs to enhance intestinal absorption of insulin and increase the relative pharmacological bioavailability of insulin was investigated by monitoring the plasma glucose level of alloxan-induced diabetic rats after oral administration of various doses of insulin-loaded CS-NPs. CS-NPs had a particle size in the range of 250-400 nm and its polydispersity index was smaller than 0.1, positively charged, stable. Insulin association was found up to 80% and its in vitro release showed a great initial burst with a pH-sensitivity property. CS-NPs enhanced the intestinal absorption of insulin to a greater extent than the aqueous solution of CS in vivo. Above all, after administration of 21 I.U./kg insulin in the CS-NPs, the hypoglycemia was prolonged over 15 h and the average pharmacological bioavailability relative to SC injection of insulin solution was up to 14.9%. PMID:12433442

  1. Calcium absorption in rat large intestine in vivo: availability of dietary calcium

    SciTech Connect

    Ammann, P.; Rizzoli, R.; Fleisch, H.

    1986-07-01

    Calcium absorption in the large intestine of the rat was investigated in vivo. After a single injection of /sup 45/CaCl/sub 2/ into the cecum, 26.0 +/- 2.5% (mean +/- SE, n = 9) of the /sup 45/CaCl/sub 2/ injected disappeared. This absorption was modulated by 1,25-dihydroxyvitamin D3, increased to 64.0 +/- 4.2% under a low-Ca diet, and increased under low-Pi diet. In contrast, when the difference of nonradioactive Ca in the cecal content and the feces was measured, only 4.1 +/- 4.6% (not significant) was absorbed. Secretion of intravenously injected /sup 45/Ca into the lumen was small and not altered by any of the conditions tested. When cecum contents were placed into duodenal tied loops, 14 +/- 6.2% were absorbed in situ when /sup 45/Ca was given orally, whereas when /sup 45/Ca was directly added to the content 35.6 +/- 4.6% were absorbed (P less than 0.02). These results indicate that the large intestine has an important vitamin D-dependent Ca absorptive system detectable if /sup 45/Ca is injected into the cecum. However, it is not effective in vivo because the Ca arriving in the large intestine appears to be no longer in an absorbable form.

  2. Water and solute absorption from carbohydrate-electrolyte solutions in the human proximal small intestine: a review and statistical analysis.

    PubMed

    Shi, Xiaocai; Passe, Dennis H

    2010-10-01

    The purpose of this study is to summarize water, carbohydrate (CHO), and electrolyte absorption from carbohydrate-electrolyte (CHO-E) solutions based on all of the triple-lumen-perfusion studies in humans since the early 1960s. The current statistical analysis included 30 reports from which were obtained information on water absorption, CHO absorption, total solute absorption, CHO concentration, CHO type, osmolality, sodium concentration, and sodium absorption in the different gut segments during exercise and at rest. Mean differences were assessed using independent-samples t tests. Exploratory multiple-regression analyses were conducted to create prediction models for intestinal water absorption. The factors influencing water and solute absorption are carefully evaluated and extensively discussed. The authors suggest that in the human proximal small intestine, water absorption is related to both total solute and CHO absorption; osmolality exerts various impacts on water absorption in the different segments; the multiple types of CHO in the ingested CHO-E solutions play a critical role in stimulating CHO, sodium, total solute, and water absorption; CHO concentration is negatively related to water absorption; and exercise may result in greater water absorption than rest. A potential regression model for predicting water absorption is also proposed for future research and practical application. In conclusion, water absorption in the human small intestine is influenced by osmolality, solute absorption, and the anatomical structures of gut segments. Multiple types of CHO in a CHO-E solution facilitate water absorption by stimulating CHO and solute absorption and lowering osmolality in the intestinal lumen. PMID:20975111

  3. Multifaceted interplay among mediators and regulators of intestinal glucose absorption: potential impacts on diabetes research and treatment.

    PubMed

    Chan, Leo Ka Yu; Leung, Po Sing

    2015-12-01

    Glucose is the prominent molecule that characterizes diabetes and, like the vast majority of nutrients in our diet, it is absorbed and enters the bloodstream directly through the small intestine; hence, small intestine physiology impacts blood glucose levels directly. Accordingly, intestinal regulatory modulators represent a promising avenue through which diabetic blood glucose levels might be moderated clinically. Despite the critical role of small intestine in blood glucose homeostasis, most physiological diabetes research has focused on other organs, such as the pancreas, kidney, and liver. We contend that an improved understanding of intestinal regulatory mediators may be fundamental for the development of first-line preventive and therapeutic interventions in patients with diabetes and diabetes-related diseases. This review summarizes the major important intestinal regulatory mediators, discusses how they influence intestinal glucose absorption, and suggests possible candidates for future diabetes research and the development of antidiabetic therapeutic agents. PMID:26487007

  4. Role of glucose transporters in the intestinal absorption of gastrodin, a highly water-soluble drug with good oral bioavailability.

    PubMed

    Cai, Zheng; Huang, Juan; Luo, Hui; Lei, Xiaolu; Yang, Zhaoxiang; Mai, Yang; Liu, Zhongqiu

    2013-07-01

    Gastrodin, a sedative drug, is a highly water-soluble phenolic glucoside with poor liposolubility but exhibits good oral bioavailability. The current study aims to investigate whether glucose transporters (GLTs) are involved in the intestinal absorption of gastrodin. The intestinal absorption kinetics of gastrodin was determined using the rat everted gut sac model, the Caco-2 cell culture model and the perfused rat intestinal model. In vivo pharmacokinetic studies using diabetic rats with high GLT expression were performed. Saturable intestinal absorption of gastrodin was observed in rat everted gut sacs. The apparent permeability (Papp) of gastrodin from the apical (A) to basolateral (B) side in Caco-2 cells was two-fold higher than that from B to A. Glucose or phlorizin, a sodium-dependent GLT (SGLT) inhibitor, reduced the absorption rates of gastrodin from perfused rat intestines. In vivo pharmacokinetic studies showed that the time of maximum plasma gastrodin concentration (Tmax) was prolonged from 28 to 72 min when orally co-administered with four times higher dose of glucose. However, the Tmax of gastrodin in diabetic rats was significantly lowered to 20 min because of the high intestinal SGLT1 level. In conclusion, our findings indicate that SGLT1 can facilitate the intestinal absorption of gastrodin. PMID:23480725

  5. Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

    PubMed Central

    Ventrucci, Gislaine; de Mello, Maria Alice Roston; Gomes-Marcondes, Maria Cristina Cintra

    2002-01-01

    Background It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. Methods To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein): pregnant (N), tumor-bearing (WN), pair-fed rats (Np). Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine): leucine (L), tumor-bearing (WL) and pair-fed with leucine (Lp). Non pregnant rats (C), which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. Results Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. Conclusions Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones. PMID:11955290

  6. Soybean ?-conglycinin induces inflammation and oxidation and causes dysfunction of intestinal digestion and absorption in fish.

    PubMed

    Zhang, Jin-Xiu; Guo, Lin-Ying; Feng, Lin; Jiang, Wei-Dan; Kuang, Sheng-Yao; Liu, Yang; Hu, Kai; Jiang, Jun; Li, Shu-Hong; Tang, Ling; Zhou, Xiao-Qiu

    2013-01-01

    ?-Conglycinin has been identified as one of the major feed allergens. However, studies of ?-conglycinin on fish are scarce. This study investigated the effects of ?-conglycinin on the growth, digestive and absorptive ability, inflammatory response, oxidative status and gene expression of juvenile Jian carp (Cyprinus carpio var. Jian) in vivo and their enterocytes in vitro. The results indicated that the specific growth rate (SGR), feed intake, and feed efficiency were reduced by ?-conglycinin. In addition, activities of trypsin, chymotrypsin, lipase, creatine kinase, Na(+),K(+)-ATPase and alkaline phosphatase in the intestine showed similar tendencies. The protein content of the hepatopancreas and intestines, and the weight and length of the intestines were all reduced by ?-conglycinin. ?-Conglycinin increased lipid and protein oxidation in the detected tissues and cells. However, ?-conglycinin decreased superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GR) activities and glutathione (GSH) content in the intestine and enterocytes. Similar antioxidant activity in the hepatopancreas was observed, except for GST. The expression of target of rapamycin (TOR) gene was reduced by ?-conglycinin. Furthermore, mRNA levels of interleukin-8 (IL-8), tumor necrosis factor-? (TNF-?), and transforming growth factor-? (TGF-?) genes were increased by ?-conglycinin. However, ?-conglycinin increased CuZnSOD, MnSOD, CAT, and GPx1b gene expression. In conclusion, this study indicates that ?-conglycinin induces inflammation and oxidation, and causes dysfunction of intestinal digestion and absorption in fish, and finally reduces fish growth. The results of this study provide some information to the mechanism of ?-conglycinin-induced negative effects. PMID:23520488

  7. Effect of undernutrition and hormone treatments on the absorption of proteins in suckling rat intestine

    SciTech Connect

    Babbar, H.S.; Jaswal, V.M.; Mahmood, A. )

    1990-02-01

    The absorption of {sup 125}I-labeled BSA and gamma-globulin was significantly (P less than 0.01) elevated in UN pups compared to the controls. Administration of pharmacological doses of cortisone, thyroxine, and insulin markedly (P less than 0.001) reduced the absorption of BSA and gamma-globulin in UN pups. There was no significant difference in the binding of {sup 125}I-labeled BSA and gamma-globulin to microvillus membrane in the control and experimental animals. However, the degradation of labeled BSA and gamma-globulin by luminal content was considerably higher (55-70%) in controls compared to UN pups. This suggested that observed increase in the absorption of proteins in nutritionally deprived pups was unrelated to their binding to the microvillus surface but presumably it is a consequence of reduced luminal degradation together with delayed maturational development as suggested by the pattern of brush border enzymes in the UN intestinal tissue.

  8. Intestinal synthesis and absorption of vitamin B-12 in channel catfish

    SciTech Connect

    Limsuwan, T.; Lovell, R.T.

    1981-12-01

    A feeding experiment conducted in a controlled environment and using a vitamin B12-deficient, but otherwise nutritionally complete, purified diet revealed that intestinal microorganisms in channel catfish synthesized approximately 1.4 ng of vitamin B12 per gram of bodyweight per day. Removal of cobalt from the diet or supplementation with an antibiotic (succinylsulfathiazole) significantly reduced the rate of intestinal synthesis and liver stores of vitamin B12. Radiolabeled vitamin B12 in the blood, liver, kidneys, and spleen of fish fed 60Co in the diet indicated that the intestinally synthesized vitamin was absorbed by the fish. The primary route of absorption was directly from the digestive tract into the blood because coprophagy was prevented in the rearing aquariums and the amount of vitamin B12 dissolved in the aquarium water was too low for gill absorption. Dietary supplementation of vitamin B12 was not necessary for normal growth and erythrocyte formation in channel catfish in a 24-week feeding period. A longer period, however, may have caused a vitamin deficiency since liver-stored vitamin B 12 decreased between the 2nd and 24th weeks.

  9. Translating molecular physiology of intestinal transport into pharmacologic treatment of diarrhea: stimulation of Na+ absorption.

    PubMed

    Singh, Varsha; Yang, Jianbo; Chen, Tiane-e; Zachos, Nicholas C; Kovbasnjuk, Olga; Verkman, Alan S; Donowitz, Mark

    2014-01-01

    Diarrheal diseases remain a leading cause of morbidity and mortality for children in developing countries, while representing an important cause of morbidity worldwide. The World Health Organization recommended that low osmolarity oral rehydration solutions plus zinc save lives in patients with acute diarrhea, but there are no approved, safe drugs that have been shown to be effective against most causes of acute diarrhea. Identification of abnormalities in electrolyte handling by the intestine in diarrhea, including increased intestinal anion secretion and reduced Na(+) absorption, suggest a number of potential drug targets. This is based on the view that successful drug therapy for diarrhea will result from correcting the abnormalities in electrolyte transport that are pathophysiologic for diarrhea. We review the molecular mechanisms of physiologic regulation of intestinal ion transport and changes that occur in diarrhea and the status of drugs being developed to correct the transport abnormalities in Na(+) absorption that occur in diarrhea. Mechanisms of Cl(-) secretion and approaches to anti-Cl(-) secretory therapies of diarrhea are discussed in a companion review. PMID:24184676

  10. Intestinal Absorption of Ergostane and Lanostane Triterpenoids from Antrodia cinnamomea Using Caco-2 Cell Monolayer Model.

    PubMed

    Wang, Qi; Qiao, Xue; Qian, Yi; Li, Zi-Wei; Tzeng, Yew-Min; Zhou, De-Min; Guo, De-An; Ye, Min

    2015-10-01

    Antrodia cinnamomea is a precious medicinal mushroom. It exhibits promising therapeutic effects on cancer, intoxication, hypertension, hepatitis, and inflammation. Its major bioactive constituents are ergostane and lanostane triterpenoids. In this study, we used intestinal Caco-2 cell monolayer model to reveal the intestinal absorption property of 14 representative triterpenoids from A. cinnamomea. The bidirectional transport through the monolayer at different time points was monitored by a fully validated LC/MS/MS method. In the case of pure compounds, ergostanes 5 (25R-antcin H), 6 (25S-antcin H) and 10 (25R-antcin B) could readily pass through the Caco-2 cell layer, whereas lanostanes 13 (dehydroeburicoic acid) and 14 (eburicoic acid) could hardly pass through. When the cells were treated with A. cinnamomea extract, antcins A, B, C, H and K (1-6 and 9-11) were absorbed via passive transcellular diffusion, and showed high P AB and P BA values (>2.5נ10(-5)cm/s). Meanwhile, the lanostanes dehydrosulphurenic acid (8), 15?-acetyldehydrosulphurenic acid (12), 13 and 14 exhibited poor permeability. Transport features of these compounds were consistent with their pharmacokinetic behaviors in rats. This study could also be helpful in predicting the intestinal absorption of A. cinnamomea in human. PMID:26411834

  11. VEGF-C is required for intestinal lymphatic vessel maintenance and lipid absorption

    PubMed Central

    Nurmi, Harri; Saharinen, Pipsa; Zarkada, Georgia; Zheng, Wei; Robciuc, Marius R; Alitalo, Kari

    2015-01-01

    Vascular endothelial growth factor C (VEGF-C) binding to its tyrosine kinase receptor VEGFR-3 drives lymphatic vessel growth during development and in pathological processes. Although the VEGF-C/VEGFR-3 pathway provides a target for treatment of cancer and lymphedema, the physiological functions of VEGF-C in adult vasculature are unknown. We show here that VEGF-C is necessary for perinatal lymphangiogenesis, but required for adult lymphatic vessel maintenance only in the intestine. Following Vegfc gene deletion in adult mice, the intestinal lymphatic vessels, including the lacteal vessels, underwent gradual atrophy, which was aggravated when also Vegfd was deleted. VEGF-C was expressed by a subset of smooth muscle cells adjacent to the lacteals in the villus and in the intestinal wall. TheVegfc-deleted mice showed defective lipid absorption and increased fecal excretion of dietary cholesterol and fatty acids. When fed a high-fat diet, the Vegfc-deficient mice were resistant to obesity and had improved glucose metabolism. Our findings indicate that the lymphangiogenic growth factors provide trophic and dynamic regulation of the intestinal lymphatic vasculature, which could be especially important in the dietary regulation of adiposity and cholesterol metabolism. PMID:26459520

  12. VEGF-C is required for intestinal lymphatic vessel maintenance and lipid absorption.

    PubMed

    Nurmi, Harri; Saharinen, Pipsa; Zarkada, Georgia; Zheng, Wei; Robciuc, Marius R; Alitalo, Kari

    2015-01-01

    Vascular endothelial growth factor C (VEGF-C) binding to its tyrosine kinase receptor VEGFR-3 drives lymphatic vessel growth during development and in pathological processes. Although the VEGF-C/VEGFR-3 pathway provides a target for treatment of cancer and lymphedema, the physiological functions of VEGF-C in adult vasculature are unknown. We show here that VEGF-C is necessary for perinatal lymphangiogenesis, but required for adult lymphatic vessel maintenance only in the intestine. Following Vegfc gene deletion in adult mice, the intestinal lymphatic vessels, including the lacteal vessels, underwent gradual atrophy, which was aggravated when also Vegfd was deleted. VEGF-C was expressed by a subset of smooth muscle cells adjacent to the lacteals in the villus and in the intestinal wall. TheVegfc-deleted mice showed defective lipid absorption and increased fecal excretion of dietary cholesterol and fatty acids. When fed a high-fat diet, the Vegfc-deficient mice were resistant to obesity and had improved glucose metabolism. Our findings indicate that the lymphangiogenic growth factors provide trophic and dynamic regulation of the intestinal lymphatic vasculature, which could be especially important in the dietary regulation of adiposity and cholesterol metabolism. PMID:26459520

  13. Food oxalate: factors affecting measurement, biological variation, and bioavailability.

    PubMed

    Massey, Linda K

    2007-07-01

    Food and nutrition professionals provide medical nutrition therapy for patients with kidney stones. If the stones contain oxalate or the patient has been diagnosed with hyperoxaluria, reduction of dietary oxalate may be appropriate. Differences in oxalate values for a single food may be due to analytical methods, and/or biological variation from several sources, including cultivar, time of harvest, and growing conditions. Bioavailability of food oxalate and, thus, urine oxalate, will also be affected by salt forms of oxalate, food processing and cooking methods, meal composition, and the presence of Oxalabacter formigenes in the patient's gut. Dietary advice for reducing urinary oxalate should include both reduction of dietary oxalate and simultaneous consumption of calcium-rich food or supplement to reduce oxalate absorption. PMID:17604750

  14. Drug-nutrient interactions: inhibition of amino acid intestinal absorption by fluoxetine.

    PubMed

    Urdaneta, E; Idoate, I; Larralde, J

    1998-05-01

    Fluoxetine is one of the most widely used antidepressants and nowadays it is also being used to manage obesity problems. In our laboratory we demonstrated that the drug inhibited sugar absorption (Monteiro et al. 1993). The aim of the present work was to determine the effect of fluoxetine on intestinal leucine absorption. Using a procedure of successive absorptions in vivo the drug diminished amino acid absorption by 30% (P < 0.001). Experiments in vitro in isolated jejunum also revealed a reduction in leucine uptake of 37% (P < 0.001). In both cases fluoxetine only affected mediated transport without altering diffusion. In a preparation enriched in basolateral membrane, fluoxetine inhibited the Na+,K(+)-ATPase (EC 3.6.1.37) activity (55%; P < 0.001) in a non-competitive manner with an inhibition constant (Ki) value of 0.92 mM. Leucine uptake by brush-border membrane vesicles was diminished by the drug (a reduction of 48% was observed at 30s, P < 0.001); only the apical Na(+)-dependent transport system of the amino acid was modified and the inhibition was non-competitive. Leucine uptake in the presence of lysine indicated that transporter B was involved. These results suggest that fluoxetine reduces leucine absorption by its action on the basolateral and apical membrane of the enterocyte; the nutritional status of the patients under drug treatment may be affected as neutral amino acid absorption is decreased. PMID:9682663

  15. Characterization of the oral absorption of several aminopenicillins: determination of intrinsic membrane absorption parameters in the rat intestine in situ

    NASA Technical Reports Server (NTRS)

    Sinko, P. J.; Amidon, G. L.

    1992-01-01

    The absorption mechanism of several penicillins was characterized using in situ single-pass intestinal perfusion in the rat. The intrinsic membrane parameters were determined using a modified boundary layer model (fitted value +/- S.E.): Jmax* = 11.78 +/- 1.88 mM, Km = 15.80 +/- 2.92 mM, Pm* = 0, Pc* = 0.75 +/- 0.04 for ampicillin; Jmax* = 0.044 +/- 0.018 mM, Km = 0.058 +/- 0.026 mM, Pm* = 0.558 +/- 0.051, Pc* = 0.757 +/- 0.088 for amoxicillin; and Jmax* = 16.30 +/- 3.40 mM, Km = 14.00 +/- 3.30 mM, Pm* = 0, Pc* = 1.14 +/- 0.05 for cyclacillin. All of the aminopenicillins studied demonstrated saturable absorption kinetics as indicated by their concentration-dependent wall permeabilities. Inhibition studies were performed to confirm the existence of a nonpassive absorption mechanism. The intrinsic wall permeability (Pw*) of 0.01 mM ampicillin was significantly lowered by 1 mM amoxicillin and the Pw* of 0.01 mM amoxicillin was reduced by 2 mM cephradine consistent with competitive inhibition.

  16. Intestine.

    PubMed

    Smith, J M; Skeans, M A; Horslen, S P; Edwards, E B; Harper, A M; Snyder, J J; Israni, A K; Kasiske, B L

    2016-01-01

    Intestine and intestine-liver transplant plays an important role in the treatment of intestinal failure, despite decreased morbidity associated with parenteral nutrition. In 2014, 210 new patients were added to the intestine transplant waiting list. Among prevalent patients on the list at the end of 2014, 65% were waiting for an intestine transplant and 35% were waiting for an intestine-liver transplant. The pretransplant mortality rate decreased dramatically over time for all age groups. Pretransplant mortality was highest for adult candidates, at 22.1 per 100 waitlist years compared with less than 3 per 100 waitlist years for pediatric candidates, and notably higher for candidates for intestine-liver transplant than for candidates for intestine transplant without a liver. Numbers of intestine transplants without a liver increased from a low of 51 in 2013 to 67 in 2014. Intestine-liver transplants increased from a low of 44 in 2012 to 72 in 2014. Short-gut syndrome (congenital and other) was the main cause of disease leading to both intestine and intestine-liver transplant. Graft survival improved over the past decade. Patient survival was lowest for adult intestine-liver recipients and highest for pediatric intestine recipients. PMID:26755265

  17. Intestinal Absorption and First-Pass Metabolism of Polyphenol Compounds in Rat and Their Transport Dynamics in Caco-2 Cells

    PubMed Central

    Zhang, Feng; Huan, Menglei; Cao, Weidong; Li, Kangchu; Yang, Jingyue; Cao, Dayong; Zhou, Siyuan; Mei, Qibing

    2012-01-01

    Background Polyphenols, a group of complex naturally occurring compounds, are widely distributed throughout the plant kingdom and are therefore readily consumed by humans. The relationship between their chemical structure and intestinal absorption, transport, and first-pass metabolism remains unresolved, however. Methods Here, we investigated the intestinal absorption and first-pass metabolism of four polyphenol compounds, apigenin, resveratrol, emodin and chrysophanol, using the in vitro Caco-2 cell monolayer model system and in situ intestinal perfusion and in vivo pharmacokinetic studies in rats, so as to better understand the relationship between the chemical structure and biological fate of the dietary polyphenols. Conclusion After oral administration, emodin and chrysophanol exhibited different absorptive and metabolic behaviours compared to apigenin and resveratrol. The differences in their chemical structures presumably resulted in differing affinities for drug-metabolizing enzymes, such as glucuronidase and sulphatase, and transporters, such as MRP2, SGLT1, and P-glycoprotein, which are found in intestinal epithelial cells. PMID:22253753

  18. Intestinal Absorption of Fibrinolytic and Proteolytic Lumbrokinase Extracted from Earthworm, Eisenia andrei

    PubMed Central

    Yan, Xiang Mei; Kim, Chung-Hyo; Lee, Chul Kyu; Shin, Jang Sik; Cho, Il Hwan

    2010-01-01

    To investigate the intestinal absorption of a fibrinolytic and proteolytic lumbrokinase extracted from Eisenia andrei, we used rat everted gut sacs and an in situ closed-loop recirculation method. We extracted lumbrokinase from Eisenia andrei, and then raised polyclonal antibody against lumbrokinase. Fibrinolytic activity and proteolytic activity in the serosal side of rat everted gut sacs incubated with lumbrokinase showed dose- and time-dependent patterns. Immunological results obtained by western blotting serosal side solution using rat everted gut sacs method showed that lumbrokinase proteins between 33.6 and 54.7 kDa are absorbed mostly by the intestinal epithelium. Furthermore, MALDI-TOF mass spectrometric analysis of plasma fractions obtained by in situ recirculation method confirmed that lumbrokinase F1 is absorbed into blood. These results support the notion that lumbrokinase can be absorbed from mucosal lumen into blood by oral administration. PMID:20473377

  19. The Use of Low Molecular Weight Protamine Chemical Chimera to Enhance Monomeric Insulin Intestinal Absorption

    PubMed Central

    He, Huining; Sheng, Jianyong; David, Allan E.; Kwon, Young Min; Zhang, Jian; Huang, Yongzhuo; Wang, Jianxin; Yang, Victor C.

    2013-01-01

    Although oral delivery of insulin offers a number of unmatched advantages, it nevertheless is beset by the poor permeability of insulin molecules through the epithelial cell membranes of the intestinal mucosal layer. We previously reported the development of low molecular weight protamine (LMWP) as a nontoxic yet potent cell penetrating peptide, of which via covalent linkage was capable of translocating protein cargos through the membranes of almost all cell types. It is therefore hypothesized that LMWP could be practically employed as a safe and effective tool to deliver insulin across the intestinal mucosal membrane, thereby augmenting its absorption through the GI tract. However, formulating 1:1 monomeric insulin/LMWP conjugate presents a tall order of challenge, as the acidic insulin and basic LMWP would automatically form tight aggregates through electrostatic interactions. In this paper, we developed an innovative conjugation strategy to solve this problem, by using succinimidyl-[(N-maleimidopropionamido)-polyethyleneglycol] ester (NHS-PEG-MAL) as an intermediate cross-linker during the coupling process. Both SDS-PAGE and MALDI-TOF mass spectroscopy confirmed the formation of a homogeneous, monomeric (1:1 ratio) insulin/LMWP conjugate without encountering the conventional problem of substrate aggregation. Cell culture studies demonstrated that transport of the Insulin-PEG-LMWP conjugate across the intestinal mucosal monolayer was augmented by almost five folds compared to native insulin. Furthermore, results from the in situ loop absorption tests in rats showed that systemic pharmacological bioavailability of insulin was significantly enhanced after its conjugation with LMWP. Overall, the presented chemical conjugation with LMWP could offer a reliable and safe means to improve the intestinal permeability of therapeutic peptides/proteins, shedding light of the possibility for their effective oral delivery. PMID:23863452

  20. Disordered Control of Intestinal Sweet Taste Receptor Expression and Glucose Absorption in Type 2 Diabetes

    PubMed Central

    Young, Richard L.; Chia, Bridgette; Isaacs, Nicole J.; Ma, Jing; Khoo, Joan; Wu, Tongzhi; Horowitz, Michael; Rayner, Christopher K.

    2013-01-01

    We previously established that the intestinal sweet taste receptors (STRs), T1R2 and T1R3, were expressed in distinct epithelial cells in the human proximal intestine and that their transcript levels varied with glycemic status in patients with type 2 diabetes. Here we determined whether STR expression was 1) acutely regulated by changes in luminal and systemic glucose levels, 2) disordered in type 2 diabetes, and 3) linked to glucose absorption. Fourteen healthy subjects and 13 patients with type 2 diabetes were studied twice, at euglycemia (5.2 0.2 mmol/L) or hyperglycemia (12.3 0.2 mmol/L). Endoscopic biopsy specimens were collected from the duodenum at baseline and after a 30-min intraduodenal glucose infusion of 30 g/150 mL water plus 3 g 3-O-methylglucose (3-OMG). STR transcripts were quantified by RT-PCR, and plasma was assayed for 3-OMG concentration. Intestinal STR transcript levels at baseline were unaffected by acute variations in glycemia in healthy subjects and in type 2 diabetic patients. T1R2 transcript levels increased after luminal glucose infusion in both groups during euglycemia (+5.8 104 and +5.8 104 copies, respectively) but decreased in healthy subjects during hyperglycemia (?1.4 104 copies). T1R2 levels increased significantly in type 2 diabetic patients under the same conditions (+6.9 105 copies). Plasma 3-OMG concentrations were significantly higher in type 2 diabetic patients than in healthy control subjects during acute hyperglycemia. Intestinal T1R2 expression is reciprocally regulated by luminal glucose in health according to glycemic status but is disordered in type 2 diabetes during acute hyperglycemia. This defect may enhance glucose absorption in type 2 diabetic patients and exacerbate postprandial hyperglycemia. PMID:23761104

  1. A comparison of absorption of glycerol tristearate and glycerol trioleate by rat small intestine

    SciTech Connect

    Bergstedt, S.E.; Hayashi, H.; Kritchevsky, D.; Tso, P. )

    1990-09-01

    Generally, fats rich in saturated fatty acids raise serum cholesterol, whereas fats rich in polyunsaturated fatty acids lower it. There appear to be exceptions; e.g., stearic acid (18:0)-rich fats have little or no effect on serum cholesterol concentrations. This apparent lack of cholesterolemic effect of stearic acid-rich fat could be because intestinal absorption of fat is poor or subsequent plasma and/or tissue metabolism of fat is different. To investigate mechanisms involved, we compared intestinal digestion, uptake, and lymphatic transport of glycerol tristearate (TS) and glycerol trioleate (TO, 18:1). Two groups of rats bearing intestinal lymph fistulas were used. TO rats were fed intraduodenally for 8 h at a constant rate a lipid emulsion of 25 mumols/h of TO (labeled with glycerol tri(9,10 (n)-3H)oleate), 7.8 mumols of egg phosphatidylcholine, and 57 mumols of sodium taurocholate in 3 ml of phosphate-buffered saline. TS rats were fed the same lipid emulsion except that TS replaced TO and the emulsion was labeled with glyceryl (1,3-14C)tristearate. The lymph triglyceride and radioactivity were determined. After infusion, the luminal and mucosal radioactive lipid content was analyzed. The results showed that there was significantly less lipid transported in the lymph of TS rats compared with TO rats. The results also showed a significant decrease in the absorption of TS as compared with TO. This was due in part to poor lipolysis. In addition, the lipid absorbed by the intestine of the TS rats was transported into lymph less efficiently than in TO rats.

  2. Lysophosphatidylcholine for Efficient Intestinal Lipid Absorption And Lipoprotein Secretion in Caco-2 Cells

    PubMed Central

    Nakano, Takanari; Inoue, Ikuo; Katayama, Shigehiro; Seo, Makoto; Takahashi, Seiichiro; Hokari, Shigeru; Shinozaki, Rina; Hatayama, Kazuhisa; Komoda, Tsugikazu

    2009-01-01

    Phosphatidylcholine (PC) and its hydrolysates are considered to stimulate intestinal lipid absorption, however, their exact effects on lipoproteins and apolipoprotein (apo) metabolism remain ambiguous. This study aimed to further differentiate the effects of them using fully differentiated enterocyte-like Caco-2 cells. Lipid micelles (oleic acid 0.6, cholesterol 0.05, monooleylglycerol 0.2, taurocholate 2 in mmol/l) with or without choline, PC, and lysoPC (0.2 mmol/l each) were applied apically to Caco-2 cells. 3H-oleic acid and 14C-cholesterol were added to the micelles when necessary. Secreted lipoproteins were analyzed by a HPLC method. LysoPC had the most potent promoting effect on lipid uptake, and lipoprotein and apolipoprotein B-48 secretion among the molecules tested. LysoPC doubled the output of cholesterol and triglyceride as the lipoprotein component, but PC did not. On the other hand, PC only increased the secretion of apoA-IV in the presence of lipid micelles. These findings confirm that the alteration of PC by PLA2 hydrolysis is intrinsically involved in the intestinal lipid absorption process and suggest that PC and its hydrolysis are coordinately associated with not only lipid absorption efficiency but also lipoprotein output and metabolism. PMID:19794933

  3. Lysophosphatidylcholine for efficient intestinal lipid absorption and lipoprotein secretion in caco-2 cells.

    PubMed

    Nakano, Takanari; Inoue, Ikuo; Katayama, Shigehiro; Seo, Makoto; Takahashi, Seiichiro; Hokari, Shigeru; Shinozaki, Rina; Hatayama, Kazuhisa; Komoda, Tsugikazu

    2009-09-01

    Phosphatidylcholine (PC) and its hydrolysates are considered to stimulate intestinal lipid absorption, however, their exact effects on lipoproteins and apolipoprotein (apo) metabolism remain ambiguous. This study aimed to further differentiate the effects of them using fully differentiated enterocyte-like Caco-2 cells. Lipid micelles (oleic acid 0.6, cholesterol 0.05, monooleylglycerol 0.2, taurocholate 2 in mmol/l) with or without choline, PC, and lysoPC (0.2 mmol/l each) were applied apically to Caco-2 cells. (3)H-oleic acid and (14)C-cholesterol were added to the micelles when necessary. Secreted lipoproteins were analyzed by a HPLC method. LysoPC had the most potent promoting effect on lipid uptake, and lipoprotein and apolipoprotein B-48 secretion among the molecules tested. LysoPC doubled the output of cholesterol and triglyceride as the lipoprotein component, but PC did not. On the other hand, PC only increased the secretion of apoA-IV in the presence of lipid micelles. These findings confirm that the alteration of PC by PLA(2) hydrolysis is intrinsically involved in the intestinal lipid absorption process and suggest that PC and its hydrolysis are coordinately associated with not only lipid absorption efficiency but also lipoprotein output and metabolism. PMID:19794933

  4. Effect of ezetimibe on incretin secretion in response to the intestinal absorption of a mixed meal.

    PubMed

    Yang, Li; Li, Xiaoming; Ji, Yong; Kohan, Alison B; Wang, David Q-H; Howles, Philip N; Hui, David Y; Lai, Jianghua; Tso, Patrick

    2010-11-01

    Ezetimibe is a potent inhibitor of cholesterol absorption by enterocytes. Although ezetimibe minimally affects the absorption of triglyceride, it is unknown whether ezetimibe affects the secretion of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). It has been shown that ezetimibe-treated mice are protected from diet-induced insulin resistance. Since GIP and GLP-1 promote the actions of insulin, we hypothesized that ezetimibe may affect the secretion of GIP and GLP-1 by enteroendocrine cells into lymph in response to the intestinal absorption of a mixed meal (Ensure). To test this hypothesis, we used the lymph fistula rat model to determine GIP and GLP-1 concentrations in lymph during the 2 h after the infusion of Ensure. Ezetimibe significantly reduced lymphatic cholesterol output during fasting, without coincident decreases in glucose, protein, and triglyceride outputs. However, ezetimibe did not influence cholesterol output after infusion of Ensure. Interestingly, ezetimibe significantly reduced the secretion of both GIP and GLP-1 into lymph after the infusion of Ensure. Therefore, the inhibitory effect of ezetimibe on GIP and GLP-1 secretion by enteroendocrine cells occurs outside of the effects of glucose, protein, or triglyceride secretion by the intestine. PMID:20651007

  5. Effect of ezetimibe on incretin secretion in response to the intestinal absorption of a mixed meal

    PubMed Central

    Yang, Li; Li, Xiaoming; Ji, Yong; Kohan, Alison B.; Wang, David Q.-H.; Howles, Philip N.; Hui, David Y.; Lai, Jianghua

    2010-01-01

    Ezetimibe is a potent inhibitor of cholesterol absorption by enterocytes. Although ezetimibe minimally affects the absorption of triglyceride, it is unknown whether ezetimibe affects the secretion of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). It has been shown that ezetimibe-treated mice are protected from diet-induced insulin resistance. Since GIP and GLP-1 promote the actions of insulin, we hypothesized that ezetimibe may affect the secretion of GIP and GLP-1 by enteroendocrine cells into lymph in response to the intestinal absorption of a mixed meal (Ensure). To test this hypothesis, we used the lymph fistula rat model to determine GIP and GLP-1 concentrations in lymph during the 2 h after the infusion of Ensure. Ezetimibe significantly reduced lymphatic cholesterol output during fasting, without coincident decreases in glucose, protein, and triglyceride outputs. However, ezetimibe did not influence cholesterol output after infusion of Ensure. Interestingly, ezetimibe significantly reduced the secretion of both GIP and GLP-1 into lymph after the infusion of Ensure. Therefore, the inhibitory effect of ezetimibe on GIP and GLP-1 secretion by enteroendocrine cells occurs outside of the effects of glucose, protein, or triglyceride secretion by the intestine. PMID:20651007

  6. Low zinc status and absorption exist in infants with jejunostomies or ileostomies which persists after intestinal repair

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is very little data regarding trace mineral nutrition in infants with small intestinal ostomies. Here we evaluated 14 infants with jejunal or ileal ostomies to measure their zinc absorption and retention and biochemical zinc and copper status. Zinc absorption was measured using a dual-tracer s...

  7. Ferroportin mediates the intestinal absorption of iron from a nanoparticulate ferritin core mimetic in mice

    PubMed Central

    Aslam, Mohamad F.; Frazer, David M.; Faria, Nuno; Bruggraber, Sylvaine F. A.; Wilkins, Sarah J.; Mirciov, Cornel; Powell, Jonathan J.; Anderson, Greg J.; Pereira, Dora I. A.

    2014-01-01

    The ferritin core is composed of fine nanoparticulate Fe3+ oxohydroxide, and we have developed a synthetic mimetic, nanoparticulate Fe3+ polyoxohydroxide (nanoFe3+). The aim of this study was to determine how dietary iron derived in this fashion is absorbed in the duodenum. Following a 4 wk run-in on an Fe-deficient diet, mice with intestinal-specific disruption of the Fpn-1 gene (Fpn-KO), or littermate wild-type (WT) controls, were supplemented with Fe2+ sulfate (FeSO4), nanoFe3+, or no added Fe for a further 4 wk. A control group was Fe sufficient throughout. Direct intestinal absorption of nanoFe3+ was investigated using isolated duodenal loops. Our data show that FeSO4 and nanoFe3+ are equally bioavailable in WT mice, and at wk 8 the mean sem hemoglobin increase was 18 7 g/L in the FeSO4 group and 30 5 g/L in the nanoFe3+ group. Oral iron failed to be utilized by Fpn-KO mice and was retained in enterocytes, irrespective of the iron source. In summary, although nanoFe3+ is taken up directly by the duodenum its homeostasis is under the normal regulatory control of dietary iron absorption, namely via ferroportin-dependent efflux from enterocytes, and thus offers potential as a novel oral iron supplement.Aslam, M. F., Frazer, D. M., Faria, N., Bruggraber, S. F. A., Wilkins, S. J., Mirciov, C., Powell, J. J., Anderson, G. J., Pereira, D. I. A. Ferroportin mediates the intestinal absorption of iron from a nanoparticulate ferritin core mimetic in mice. PMID:24776745

  8. 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

  9. Nonruminant Nutrition Symposium: intestinal glucose sensing and regulation of glucose absorption: implications for swine nutrition.

    PubMed

    Shirazi-Beechey, S P; Moran, A W; Bravo, D; Al-Rammahi, M

    2011-06-01

    The Na(+/)glucose cotransporter (SGLT1) is the major route for the transport of dietary sugars from the lumen of the intestine into enterocytes. Regulation of this protein is essential for the provision of glucose to the body and avoidance of intestinal malabsorption. This has important nutritional implications in particular for young and growing animals. It has been demonstrated that dietary sugars and artificial sweeteners increase SGLT1 expression and the capacity of the gut to absorb monosaccharides. Furthermore, diets supplemented with artificial sweeteners have been shown to improve growth and performance of weaning piglets. In this review, after describing the organization of intestinal epithelium, the type of gut hormones released in response to dietary carbohydrates, the mechanism underlying the transcellular transport of glucose in the intestine is outlined. Next, a historical background to the work carried out in various laboratories aimed at identifying molecular mechanisms involved in regulation of intestinal glucose transporter, SGLT1, is described. Subsequently, the more recent data on the role of intestinal glucose, or sweet, sensor T1R2 + T1R3, a G protein-coupled receptor, required for upregulation of SGLT1 by dietary sugars and artificial sweeteners, are presented. The glucose sensor subunits, T1R2 + T1R3, are members of the taste receptor family 1, T1R, and are expressed in the gut enteroendocrine cells. Sensing of dietary sugars and artificial sweeteners by T1R2 + T1R3 activates a pathway in endocrine cells leading to secretion of gut hormones. Finally, after describing molecular mechanisms by which a specific gut hormone released by endocrine cells may regulate SGLT1 expression in the neighboring absorptive enterocytes, the application of these findings to enhancing intestinal capacity to absorb dietary sugars in weaning piglets is presented. A better understanding of the molecular events involved in regulation of SGLT1 will allow the identification of nutritional targets with attendant promise of avoiding nutrient malabsorption and enhancing growth and well-being of species. PMID:21278108

  10. Effect of vitamin D on the intestinal absorption of /sup 203/Pb and /sup 47/Ca in chicks

    SciTech Connect

    Mykkaenen, H.M.; Wasserman, R.H.

    1982-03-01

    The transfer of /sup 203/Pb and/or /sup 47/Ca across the intestinal epithelium of the chick was investigated, with emphasis given to the functional role of cholecalciferol (vitamin D-3). /sup 203/Pb, after introduction in the intestinal lumen, is rapidly accumulated by the intestinal tissue, and only a fraction of /sup 203/ Pb is translocated parenterally (absorbed). Cholecalciferol did not significantly affect the accumulation of /sup 203/Pb by intestinal tissue but did accelerate /sup 203/Pb movement across the basal-lateral membrane. In contrast, cholecalciferol both decreased /sup 47/Ca tissue levels and increased /sup 47/Ca absorption. In rachitic chicks, the rate of absorption of /sup 203/Pb was greater in the distal than in the proximal segments of the intestine; after cholecalciferol repletion, the degree of absorption in all segments was similar, indicating the order of cholecalciferol effectiveness as duodenum greater than or equal to jejunum > ileum. An acute dose of 1,25(OH)/sub 2/D/sub 3/ to rachitic chicks also enhanced both /sup 203/Pb and /sup 47/Ca absorption, but the time course and pattern of absorption of these metal cations differed. The time at which the absorption of /sup 203/Pb peaked and returned to base-line occurred sooner than for /sup 47/Ca. Also the back-flux (blood ..-->.. intestinal lumen) of /sup 47/Ca was enhanced by cholecalciferol, whereas no effect on the back-flux of /sup 203/Pb was noted. These studies show that cholecalciferol and 1,25(OH)/sub 2/D/sub 3/ affects both the /sup 203/Pb and /sup 47/Ca absorptive processes, but the nature of these responses are not identical, suggesting differences in the transport path or the macromolecular interactions of these metal ions during the course of absorption, or both.

  11. Intestine-specific MTP and global ACAT2 deficiency lowers acute cholesterol absorption with chylomicrons and HDLs

    PubMed Central

    Boutjdir, Mohamed; Rudel, Lawrence L.; Hussain, M. Mahmood

    2014-01-01

    Intestinal cholesterol absorption involves the chylomicron and HDL pathways and is dependent on microsomal triglyceride transfer protein (MTP) and ABCA1, respectively. Chylomicrons transport free and esterified cholesterol, whereas HDLs transport free cholesterol. ACAT2 esterifies cholesterol for secretion with chylomicrons. We hypothesized that free cholesterol accumulated during ACAT2 deficiency may be secreted with HDLs when chylomicron assembly is blocked. To test this, we studied cholesterol absorption in mice deficient in intestinal MTP, global ACAT2, and both intestinal MTP and global ACAT2. Intestinal MTP ablation significantly increased intestinal triglyceride and cholesterol levels and reduced their transport with chylomicrons. In contrast, global ACAT2 deficiency had no effect on triglyceride absorption but significantly reduced cholesterol absorption with chylomicrons and increased cellular free cholesterol. Their combined deficiency reduced cholesterol secretion with both chylomicrons and HDLs. Thus, contrary to our hypothesis, free cholesterol accumulated in the absence of MTP and ACAT2 is unavailable for secretion with HDLs. Global ACAT2 deficiency causes mild hypertriglyceridemia and reduces hepatosteatosis in mice fed high cholesterol diets by increasing hepatic lipoprotein production by unknown mechanisms. We show that this phenotype is preserved in the absence of intestinal MTP in global ACAT2-deficient mice fed a Western diet. Further, we observed increases in hepatic MTP activity in these mice. Thus, ACAT2 deficiency might increase MTP expression to avoid hepatosteatosis in cholesterol-fed animals. Therefore, ACAT2 inhibition might avert hepatosteatosis associated with high cholesterol diets by increasing hepatic MTP expression and lipoprotein production. PMID:25030663

  12. Intestine-specific MTP and global ACAT2 deficiency lowers acute cholesterol absorption with chylomicrons and HDLs.

    PubMed

    Iqbal, Jahangir; Boutjdir, Mohamed; Rudel, Lawrence L; Hussain, M Mahmood

    2014-11-01

    Intestinal cholesterol absorption involves the chylomicron and HDL pathways and is dependent on microsomal triglyceride transfer protein (MTP) and ABCA1, respectively. Chylomicrons transport free and esterified cholesterol, whereas HDLs transport free cholesterol. ACAT2 esterifies cholesterol for secretion with chylomicrons. We hypothesized that free cholesterol accumulated during ACAT2 deficiency may be secreted with HDLs when chylomicron assembly is blocked. To test this, we studied cholesterol absorption in mice deficient in intestinal MTP, global ACAT2, and both intestinal MTP and global ACAT2. Intestinal MTP ablation significantly increased intestinal triglyceride and cholesterol levels and reduced their transport with chylomicrons. In contrast, global ACAT2 deficiency had no effect on triglyceride absorption but significantly reduced cholesterol absorption with chylomicrons and increased cellular free cholesterol. Their combined deficiency reduced cholesterol secretion with both chylomicrons and HDLs. Thus, contrary to our hypothesis, free cholesterol accumulated in the absence of MTP and ACAT2 is unavailable for secretion with HDLs. Global ACAT2 deficiency causes mild hypertriglyceridemia and reduces hepatosteatosis in mice fed high cholesterol diets by increasing hepatic lipoprotein production by unknown mechanisms. We show that this phenotype is preserved in the absence of intestinal MTP in global ACAT2-deficient mice fed a Western diet. Further, we observed increases in hepatic MTP activity in these mice. Thus, ACAT2 deficiency might increase MTP expression to avoid hepatosteatosis in cholesterol-fed animals. Therefore, ACAT2 inhibition might avert hepatosteatosis associated with high cholesterol diets by increasing hepatic MTP expression and lipoprotein production. PMID:25030663

  13. Absorption of Cholesterol from a Micellar Solution: Intestinal Perfusion Studies in Man*

    PubMed Central

    Simmonds, Wilfred J.; Hofmann, Alan F.; Theodor, Emanuel

    1967-01-01

    The absorption of cholesterol has been studied in man by perfusing the upper jejunum with a micellar solution of bile salt, 1-monoglyceride, and cholesterol-14C, with a triple lumen tube with collection sites 50 cm apart. The absorption of micellar components between the collection sites was calculated from their concentration changes relative to those of the watersoluble marker, polyethylene glycol. Control experiments were performed with cholesterol-free perfusions of saline or bile salt-monoglyceride solutions. Steady state conditions were obtained. Each of the components of the micelle was absorbed to a different extent during passage through the test segment of jejunum. Bile salt was not absorbed (mean, -3%), but micellar monoglyceride was rapidly hydrolyzed and absorbed almost completely (mean, 98%). Cholesterol radioactivity was absorbed to an intermediate extent (mean, 73%), and the absorption of chemically determined cholesterol (mean, 46%) indicated that much of the disappearance of radioactivity represented true absorption and not simple exchange. The specific activity of the perfused cholesterol fell during passage through the loop. This fall was interpreted as signifying the continuous addition of nonradioactive endogenous cholesterol by the test segment. However, the decrease in specific activity may also be considered to signify exchange, in that nonradioactive molecules entered the lumen as radioactive molecules were absorbed. Plant sterols appeared in the intestinal contents during the perfusion and must have been contributed by the perfused segment. The perfusate and samples taken from the upper and lower collection sites were examined by ultracentrifugation to define the physical state of cholesterol. It was found that cholesterol in the perfusate or upper collection site samples did not sediment, but that 23% of the cholesterol in the lower collection site samples was sedimentable (mean of three experiments); bile salt, as control, was not sedimentable. Solubility experiments in model systems showed that cholesterol possessed low solubility in bile salt solution; its solubility increased markedly and in linear proportion to the amount of fatty acid or monoglyceride or both that was added to the bile salt solution. These findings suggest that polar lipid such as fatty acid or monoglyceride as well as bile salt is essential for normal micellar solubilization of cholesterol in intestinal content. They suggest the necessity of considering an insoluble sedimentable phase of particulate sterol in intestinal content as well as an oil and micellar phase for a complete description of sterol absorption. The marked difference in the rates of absorption of individual micellar components suggests that micellar lipid is not absorbed as an intact aggregate and is consistent with the view that polar lipid such as fatty acid is absorbed in molecular form by diffusion from a micellar solution. The experiments confirm previous findings demonstrating that fat absorption without bile salt absorption occurs in the upper small intestine in man. Images PMID:6025488

  14. Differential subcompartmentation of terminal glycosylation in the Golgi apparatus of intestinal absorptive and goblet cells.

    PubMed

    Roth, J; Taatjes, D J; Weinstein, J; Paulson, J C; Greenwell, P; Watkins, W M

    1986-10-25

    Two terminal glycosyltransferases, a sialyltransferase and the blood group A alpha 1,3 N-acetylgalactosaminyltransferase, were found to exhibit differential subcompartmentation in the Golgi apparatus of intestinal goblet and absorptive cells. As expected from their role in terminal glycosylation, the two glycosyltransferases and their products, sialic acid residues and blood group A substance, were localized in the trans cisternae of the Golgi apparatus of goblet cells. In contrast, however, they were found throughout the Golgi apparatus stack of adjacent absorptive cells, with the exception of the fenestrated first cis cisterna. The results are in contrast to the general view that enzymes in the glycosylation pathway are arranged in a cis to trans gradient across the Golgi apparatus and that such polarized distributions may instead be cell type-specific. PMID:3095318

  15. Human chorionic gonadotropin promotes expression of protein absorption factors in the intestine of goldfish (Carassius auratus).

    PubMed

    Zhou, Y; Hao, G; Zhong, H; Wu, Q; Lu, S Q; Zhao, Q; Liu, Z

    2015-01-01

    Protein use is crucial for the ovulation and spawning of fish. Currently, limited information is available regarding the expression of protein absorption factors during the breeding seasons of teleosts and thus how various proteins involved in this process is not well-understood. The expression of CDX2, CREB, gluatamate dehydrogenase, LAT2, aminopeptidase N, PepT1, and SP1 were significantly elevated from the non-breeding season to the breeding season in female goldfish, and all proteins except PepT1 and SP1 were elevated in male goldfish. Injection of human chorionic gonadotropin upregulated the expression of all proteins except for aminopeptidase N in female goldfish and SP1 in male goldfish, suggesting a luteinizing hormone-inductive effect on protein absorption factors. Protein use in the intestine is increased during the breeding seasons as a result of increased luteinizing hormone. PMID:26345757

  16. [Intestinal absorption of the effective components of Schisandra chinensis Baill by rats single-pass perfusion in situ].

    PubMed

    Chen, Xin-Min; Li, Jun-Song; Li, Wen; Han, Lei; Liu, Xun-Hong; Di, Liu-Qing; Cai, Bao-Chang

    2010-05-01

    The aim of the study is to investigate rat intestinal absorption behavior of three main active components, schisandrol A, schisandrin A and schisandrin B in Schisandra chinensis Baill extracts in intestine of rats. With phenol red as the indicator, in situ single pass intestinal perfusion (SPIP) model was used and the concentrations of three main active components in perfusion solution of different intestinal segments (duodenum, jejunum, ileum, and colon) were determined by HPLC in combination with diode array detection. The results showed that the absorption rate constant (Ka) and effective permeability values (Peff) of three main active components in Schisandra chinensis Baill extracts had significant difference (P < 0.05) at different concentrations of perfusion solution, the Ka and Peff first increased and then decreased with the increase of drug concentration, the middle concentration was higher than those of the other two concentrations. The saturate absorption phenomena were observed, and it suggested that the transport mechanisms of three main active components in vivo were similar to active transport or facilitated diffusion. Three active components can be well absorbed in all of the intestinal segments, while duodenum is the best absorption region. The Ka and Peff of three active components in jejunum and ileum had no significant difference (P > 0.05). The absorption of the three active components displayed significant difference (P < 0.05) at different intestinal segments of rats. Schisandrin A had the best absorption in duodenum. The Ka and Peff among three active components were sequenced as follows: schisandrin A > schisandrin B > schisandrol A in other intestinal segments, and there is significant difference (P < 0.05) between them. PMID:20931771

  17. Dietary Fructose Inhibits Intestinal Calcium Absorption and Induces Vitamin D Insufficiency in CKD

    PubMed Central

    Douard, Veronique; Asgerally, Abbas; Sabbagh, Yves; Sugiura, Shozo; Shapses, Sue A.; Casirola, Donatella

    2010-01-01

    Renal disease leads to perturbations in calcium and phosphate homeostasis and vitamin D metabolism. Dietary fructose aggravates chronic kidney disease (CKD), but whether it also worsens CKD-induced derangements in calcium and phosphate homeostasis is unknown. Here, we fed rats diets containing 60% glucose or fructose for 1 mo beginning 6 wk after 5/6 nephrectomy or sham operation. Nephrectomized rats had markedly greater kidney weight, blood urea nitrogen, and serum levels of creatinine, phosphate, and calcium-phosphate product; dietary fructose significantly exacerbated all of these outcomes. Expression and activity of intestinal phosphate transporter, which did not change after nephrectomy or dietary fructose, did not correlate with hyperphosphatemia in 5/6-nephrectomized rats. Intestinal transport of calcium, however, decreased with dietary fructose, probably because of fructose-mediated downregulation of calbindin 9k. Serum calcium levels, however, were unaffected by nephrectomy and diet. Finally, only 5/6-nephrectomized rats that received dietary fructose demonstrated marked reductions in 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 levels, despite upregulation of 1?-hydroxylase. In summary, excess dietary fructose inhibits intestinal calcium absorption, induces marked vitamin D insufficiency in CKD, and exacerbates other classical symptoms of the disease. Future studies should evaluate the relevance of monitoring fructose consumption in patients with CKD. PMID:19959720

  18. Improved intestinal absorption of calcitonin by mucoadhesive delivery of novel pectin-liposome nanocomplexes.

    PubMed

    Thirawong, Nartaya; Thongborisute, Jringjai; Takeuchi, Hirofumi; Sriamornsak, Pornsak

    2008-02-11

    Self-assembling pectin-liposome nanocomplexes (PLNs) were prepared by a simple mixing of cationic liposomes with pectin solution, in order to improve intestinal absorption of calcitonin (eCT). Both in-vitro and in-vivo evaluations for PLNs were evaluated. The results showed that average particle size of PLNs was significantly larger than that of initial cationic liposomes. The surface charges were shifted from positive to negative after mixing with pectin. The PLNs made of high degree of esterification (DE) pectin showed less negatively charged values than those made of low DE pectin. The entrapment efficiency in cationic liposomes was in the same range even if the drug loading was increased. The in-vivo mucoadhesive test of pectin by confocal laser scanning microscopy demonstrated stronger mucoadhesive properties of PLNs made of low DE pectin, compared to cationic liposomes and PLNs made of other pectins. Moreover, high intensities of a fluorescent marker could be observed throughout the small intestines (i.e. duodenum, jejunum and ileum) and remained at the site of mucoadhesion even after 6 h of administration of PLNs made of low DE pectin. The eCT-loaded PLNs demonstrated a strong pharmacological action over the eCT solution and eCT-loaded liposomes, in which an enhanced and prolonged reduction in plasma calcium concentration of rats was observed. This was attributed to the ability of pectin to adhere to the mucus layer and prolong retention in the intestinal mucosa. PMID:18082282

  19. Mrp2-related efflux of scutellarin in the intestinal absorption in rats.

    PubMed

    Cao, Feng; Zhang, Haiyan; Guo, Jianxin; Ping, Qineng

    2008-01-01

    This study was conducted to investigate the role of P-glycoprotein (P-gp) and Multidrug resistance-associated protein 2(Mrp2) in the rat intestinal absorption of scutellarin and explore the possible reasons for its low oral bioavailability. Verapamil had little effect on the transport amount of scutellarin shown by in vitro everted sac experiments and the apparent permeability of the drug demonstrated by in situ single-pass intestinal perfusion experiments (SPIP). Leukotriene C4 (LTC4) added to the mucosal side significantly enhanced the transport of scutellarin to the serosal side. The Papp value of scutellarin increased gradually on raising the L-Buthionine-[S,R]-sulfoximine (BSO) concentration to 0.5 mM in the perfusion solution (P < 0.05). When probenecid (1 mM) was coperfused, a 1.34-fold increase in the Papp was observed (P < 0.05). Coperfusion of 0.5 mM BSO and 1 mM probenecid with 4.33 microM scutellarin, the Papp is 2.24 times than that of the control rats (p < 0.01). As shown by in silico experiments the spatial structure of scutellarin was in good agreement with the pharmacophore of Mrp2. The efflux of Mrp2, not P-gp, in the intestinal of the rats may be one of the reasons that lead to the low oral bioavailability of scutellarin. PMID:18271309

  20. In vivo measurement of the absorption of strontium in the rumen and small intestine of sheep as an index of calcium absorption capacity.

    PubMed

    Hyde, Michelle L; Fraser, David R

    2014-09-14

    In the present study, a method was developed for determining the alimentary tract Ca absorption capacity of ruminant animals by measuring the absorption rate of Sr after the administration of an oral dose of strontium chloride acting as a tracer analogue of Ca. A close correlation between the absorption rates of the two tracers was observed upon simultaneous administration of an oral dose of stable Sr and radioactive calcium (r 098). The Ca absorption capacity of the rumen and small intestine was determined separately by either directing the solution into the rumen or by diverting it into the post-ruminal tract by vasopressin-induced closure of the ruminoreticular groove. The animals were treated with 1?-hydroxyvitamin D3 administered via subcutaneously implanted mini-osmotic pumps. The effect of elevated plasma 1,25-dihydroxycholecalciferol concentrations on the Ca absorption capacity of the alimentary tract was then determined. An increased rate of Sr absorption was observed in both the rumen and small intestine of sheep after treatment, although it is unclear whether the rumen possesses the same vitamin D-dependent Ca absorption pathway as the small intestine. PMID:24998300

  1. Mechanisms involved in the intestinal absorption of dietary vitamin A and provitamin A carotenoids?

    PubMed Central

    Harrison, Earl H.

    2012-01-01

    Vitamin A is an essential nutrient for humans and is converted to the visual chromophore, 11-cis-retinal, and to the hormone, retinoic acid. Vitamin A in animal-derived foods is found as long chain acyl esters of retinol and these are digested to free fatty acids and retinol before uptake by the intestinal mucosal cell. The retinol is then reesterified to retinyl esters for incorporation into chlylomicrons and absorbed via the lymphatics or effluxed into the portal circulation facilitated by the lipid transporter, ABCA1. Provitamin A carotenoids such as ?-carotene are found in plant-derived foods. These and other carotenoids are transported into the mucosal cell by scavenger receptor class B type I (SR-BI). Provitamin A carotenoids are partly converted to retinol by oxygenase and reductase enzymes and the retinol so produced is available for absorption via the two pathways described above. The efficiency of vitamin A and carotenoid intestinal absorption is determined by the regulation of a number of proteins involved in the process. Polymorphisms in genes for these proteins lead to individual variability in the metabolism and transport of vitamin A and carotenoids. This article is part of a Special Issue entitled Retinoid and Lipid Metabolism. PMID:21718801

  2. Absorption of 3(2H)-furanones by human intestinal epithelial Caco-2 cells.

    PubMed

    Stadler, Nicole Christina; Somoza, Veronika; Schwab, Wilfried

    2009-05-13

    A number of 3(2H)-furanones are synthesized by fruits and have been found in cooked foodstuffs, where they impart flavor and odor because of their low perception thresholds. They show genotoxic properties in model studies but are also ranked among the antioxidants and anticarcinogens. This study examined the efficiency of intestinal absorption and metabolic conversion of 3(2H)-furanones by using Caco-2 cell monolayers as an intestinal epithelial cell model. The permeability of each agent was measured in both the apical to basal and basal to apical directions. 2,5-Dimethyl-4-methoxy-3(2H)-furanone (DMMF) showed the highest absorption rate in all experiments, while similar amounts of 4-hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF), 4-hydroxy-2(or 5)-ethyl-5(or 2)-methyl-3(2H)-furanone (HEMF), and 4-hydroxy-5-methyl-3(2H)-furanone (HMF) were taken up. HDMF-glucoside was almost not absorbed but was hydrolyzed to a small extent. The transport of 3(2H)-furanones could not be saturated even at levels of 500 microM and occurred in both directions. Because the uptake was only slightly reduced by apical hyperosmolarity, passive diffusion by paracellular transport is proposed. PMID:19338346

  3. Ferroportin mediates the intestinal absorption of iron from a nanoparticulate ferritin core mimetic in mice.

    PubMed

    Aslam, Mohamad F; Frazer, David M; Faria, Nuno; Bruggraber, Sylvaine F A; Wilkins, Sarah J; Mirciov, Cornel; Powell, Jonathan J; Anderson, Greg J; Pereira, Dora I A

    2014-08-01

    The ferritin core is composed of fine nanoparticulate Fe(3+) oxohydroxide, and we have developed a synthetic mimetic, nanoparticulate Fe(3+) polyoxohydroxide (nanoFe(3+)). The aim of this study was to determine how dietary iron derived in this fashion is absorbed in the duodenum. Following a 4 wk run-in on an Fe-deficient diet, mice with intestinal-specific disruption of the Fpn-1 gene (Fpn-KO), or littermate wild-type (WT) controls, were supplemented with Fe(2+) sulfate (FeSO4), nanoFe(3+), or no added Fe for a further 4 wk. A control group was Fe sufficient throughout. Direct intestinal absorption of nanoFe(3+) was investigated using isolated duodenal loops. Our data show that FeSO4 and nanoFe(3+) are equally bioavailable in WT mice, and at wk 8 the mean SEM hemoglobin increase was 18 7 g/L in the FeSO4 group and 30 5 g/L in the nanoFe(3+) group. Oral iron failed to be utilized by Fpn-KO mice and was retained in enterocytes, irrespective of the iron source. In summary, although nanoFe(3+) is taken up directly by the duodenum its homeostasis is under the normal regulatory control of dietary iron absorption, namely via ferroportin-dependent efflux from enterocytes, and thus offers potential as a novel oral iron supplement. PMID:24776745

  4. Extensive gut metabolism limits the intestinal absorption of excessive supplemental dietary glutamate loads in infant pigs.

    PubMed

    Janeczko, Michael J; Stoll, Barbara; Chang, Xiaoyan; Guan, Xinfu; Burrin, Douglas G

    2007-11-01

    Glutamate (Glu) is a major intestinal oxidative fuel, key neurotransmitter, and may be a useful dietary supplement to augment health of the infant gut. We quantified the metabolic fate of various supplemental dietary Glu intakes in young pigs surgically implanted with vascular, intraduodenal (ID), or intragastric (IG) catheters and a portal blood flow probe. Piglets were acutely fed a range of dietary Glu intakes using a basal milk formula (100%) supplemented with varying amounts of monosodium Glu (up to 400%) via ID or IG routes. We quantified the gastrointestinal metabolic fate of dietary Glu using [U-(13)C] Glu tracer. The Glu net absorption in the basal 100% group was low in both ID and IG groups, ranging from 13 to 17% of intake. Enteral Glu supplementation significantly increased the absolute absorption rate and arterial concentration of Glu. In both the ID and IG groups, enteral [(13)C]Glu absorption was limited (<5% tracer input) at the basal Glu intake (100%) but increased nearly 4-fold ( approximately 20% input) in the 300% intake group. A substantial fraction (33-50%) of the enteral [(13)C]Glu input was oxidized by the gut to (13)CO(2) in both the 100 and 300% intake groups. We conclude that extensive gut metabolism limits the absorption of supplemental dietary Glu even at excessive intakes. PMID:17951474

  5. Developing intestine is injured during absorption of oleic acid but not its ethyl ester.

    PubMed Central

    Velasquez, O R; Place, A R; Tso, P; Crissinger, K D

    1994-01-01

    Although lipids are essential nutrients in the mammalian diet, we have shown that fatty acids are injurious to epithelial cells of developing piglet intestine during luminal perfusion. Furthermore, the intestine of young animals sustains greater injury than that of older piglets. In an effort to understand the mechanism for this developmental injury, we investigated whether changes in the chemical configuration of oleic acid would alter this damage. Mucosal permeability, as quantitated by the plasma-to-lumen clearance of 51chromium EDTA, was evaluated during luminal perfusion with oleic acid as compared with its ethyl (ethyl oleate) and glyceryl (glycerol-1-mono-oleate) esters, solubilized with taurocholic acid, in jejunum of 1-d-, 3-d-, 2-wk-, and 1-mo-old piglets. 51Chromium EDTA clearance increased significantly during oleic acid and glycerol-1-mono-oleate perfusion, but did not increase during perfusion with ethyl oleate or saline. This result was not secondary to failure of absorption of ethyl oleate, as [14C]oleic acid and ethyl [1-14C]oleate were absorbed to a similar extent. Furthermore, developing intestine was able to remove the ethyl group and then re-esterify the fatty acid to form triacyglycerol. These studies indicate that oleic acid-induced mucosal injury can be abolished when the carboxylic group of the fatty acid is esterified with an ethyl, but not a glycerol, group. Since the ethyl ester is also absorbed and metabolized similarly to the free fatty acid, this may provide a means of supplying long-chain fatty acids to developing intestine without causing mucosal damage. Images PMID:8113387

  6. Quercetin Inhibits Intestinal Iron Absorption and Ferroportin Transporter Expression In Vivo and In Vitro

    PubMed Central

    Balesaria, Sara; Skinner, Vernon; Debnam, Edward S.; Srai, Surjit K. S.; Sharp, Paul A.

    2014-01-01

    Balancing systemic iron levels within narrow limits is critical for maintaining human health. There are no known pathways to eliminate excess iron from the body and therefore iron homeostasis is maintained by modifying dietary absorption so that it matches daily obligatory losses. Several dietary factors can modify iron absorption. Polyphenols are plentiful in human diet and many compounds, including quercetin the most abundant dietary polyphenol are potent iron chelators. The aim of this study was to investigate the acute and longer-term effects of quercetin on intestinal iron metabolism. Acute exposure of rat duodenal mucosa to quercetin increased apical iron uptake but decreased subsequent basolateral iron efflux into the circulation. Quercetin binds iron between its 3-hydroxyl and 4-carbonyl groups and methylation of the 3-hydroxyl group negated both the increase in apical uptake and the inhibition of basolateral iron release, suggesting that the acute effects of quercetin on iron transport were due to iron chelation. In longer-term studies, rats were administered quercetin by a single gavage and iron transporter expression measured 18 h later. Duodenal FPN expression was decreased in quercetin-treated rats. This effect was recapitulated in Caco-2 cells exposed to quercetin for 18 h. Reporter assays in Caco-2 cells indicated that repression of FPN by quercetin was not a transcriptional event but might be mediated by miRNA interaction with the FPN 3?UTR. Our study highlights a novel mechanism for the regulation of iron bioavailability by dietary polyphenols. Potentially, diets rich in polyphenols might be beneficial for patients groups at risk of iron loading by limiting the rate of intestinal iron absorption. PMID:25058155

  7. Regional distribution and variation of gamma-globulin absorption from the small intestine of the neonatal calf

    SciTech Connect

    Fetcher, A.; Gay, C.C.; McGuire, T.C.; Barbee, D.D.; Parish, S.M.

    1983-11-01

    125I-labeled immunoglobulin (Ig)G1 in colostral whey was used to determine the region of maximum absorption of Ig from the small intestine of the neonatal calf and the variation in Ig absorption among calves at the intestinal level. In experiment 1, 5 segments (approx 5%, 35%, 60%, 80%, and 95% of the duodenocecal length) were formed in the small intestine of 9 colostrum-deprived calves shortly after birth. These segments were injected with colostral whey containing 125I-IgG1 4 hours after birth, and uptake, transfer, and absorption (defined as uptake plus transfer) were determined for each segment 2 hours later. Raw data were adjusted for the milligrams of IgG1 injected per gram of intestinal tissue to obtain the least squares mean (LSM) value. The LSM values for absorption of IgG1 from distal segments 3, 4, and 5 were significantly greater (P less than 0.05) than those values for proximal segments 1 and 2. The region of the maximum IgG1 absorption was the lower small intestine, 60% to 80% of the duodenocecal length. There was also an indication of independence between uptake and transfer in each of the segments. Significant differences (P less than 0.05) were present among calves in the LSM values for uptake and absorption, but not for transfer. In experiment 2, thoracic ducts of 8 newborn calves were cannulated 4 to 5 hours after birth. At 6 hours after birth, colostral whey with 125I-IgG1 was injected into an intestinal segment (approx 60% to 80% of the duodenocecal length).

  8. ISX is a retinoic acid-sensitive gatekeeper that controls intestinal beta,beta-carotene absorption and vitamin A production.

    PubMed

    Lobo, Glenn P; Hessel, Susanne; Eichinger, Anne; Noy, Noa; Moise, Alexander R; Wyss, Adrian; Palczewski, Krzysztof; von Lintig, Johannes

    2010-06-01

    The uptake of dietary lipids from the small intestine is a complex process that depends on the activities of specific membrane receptors with yet unknown regulatory mechanisms. Using both mouse models and human cell lines, we show here that intestinal lipid absorption by the scavenger receptor class B type 1 (SR-BI) is subject to control by retinoid signaling. Retinoic acid via retinoic acid receptors induced expression of the intestinal transcription factor ISX. ISX then repressed the expression of SR-B1 and the carotenoid-15,15'-oxygenase Bcmo1. BCMO1 acts downstream of SR-BI and converts absorbed beta,beta-carotene to the retinoic acid precursor, retinaldehyde. Using BCMO1-knockout mice, we demonstrated increased intestinal SR-BI expression and systemic beta,beta-carotene accumulation. SR-BI-dependent accumulation of beta,beta-carotene was prevented by dietary retinoids that induced ISX expression. Thus, our study revealed a diet-responsive regulatory network that controls beta,beta-carotene absorption and vitamin A production by negative feedback regulation. The role of SR-BI in the intestinal absorption of other dietary lipids, including cholesterol, fatty acids, and tocopherols, implicates retinoid signaling in the regulation of lipid absorption more generally and has clinical implications for diseases associated with dyslipidemia. PMID:20061533

  9. Diet effects on glucose absorption in the small intestine of neonatal calves: importance of intestinal mucosal growth, lactase activity, and glucose transporters.

    PubMed

    Steinhoff-Wagner, Julia; Zitnan, Rudolf; Schönhusen, Ulrike; Pfannkuche, Helga; Hudakova, Monika; Metges, Cornelia C; Hammon, Harald M

    2014-10-01

    Colostrum (C) feeding in neonatal calves improves glucose status and stimulates intestinal absorptive capacity, leading to greater glucose absorption when compared with milk-based formula feeding. In this study, diet effects on gut growth, lactase activity, and glucose transporters were investigated in several gut segments of the small intestine. Fourteen male German Holstein calves received either C of milkings 1, 3, and 5 (d 1, 2, and 3 in milk) or respective formulas (F) twice daily from d 1 to d 3 after birth. Nutrient content, and especially lactose content, of C and respective F were the same. On d 4, calves were fed C of milking 5 or respective F and calves were slaughtered 2h after feeding. Tissue samples from duodenum and proximal, mid-, and distal jejunum were taken to measure villus size and crypt depth, mucosa and brush border membrane vesicles (BBMV) were taken to determine protein content, and mRNA expression and activity of lactase and mRNA expression of sodium-dependent glucose co-transporter-1 (SGLT1) and facilitative glucose transporter (GLUT2) were determined from mucosal tissue. Additionally, protein expression of SGLT1 in BBMV and GLUT2 in crude mucosal membranes and BBMV were determined, as well as immunochemically localized GLUT2 in the intestinal mucosa. Villus circumference, area, and height were greater, whereas crypt depth was smaller in C than in F. Lactase activity tended to be greater in C than in F. Protein expression of SGLT1 was greater in F than in C. Parameters of villus size, lactase activity, SGLT1 protein expression, as well as apical and basolateral GLUT2 localization in the enterocytes differed among gut segments. In conclusion, C feeding, when compared with F feeding, enhances glucose absorption in neonatal calves primarily by stimulating mucosal growth and increasing absorptive capacity in the small intestine, but not by stimulating abundance of intestinal glucose transporters. PMID:25108868

  10. Effect of petroleum vapors inhalation on intestinal absorption of glucose and some amino acids in the rat

    SciTech Connect

    Szablicka, E.; Oledzka, R.

    1989-02-01

    The proper intestinal absorption of nutrients, particularly sugars and amino acids, is necessary to keep the organism healthy. It is well known that various toxic compounds present in the environment can have an unfavorable influence. On the other hand it is also known that crude oil which pollutes the aqueous environment affects birds' gastrointestinal tract. Little is known about the influence of petroleum vapors on the gastrointestinal tract of animals and humans. The present study was undertaken to determine the effect of petroleum vapors inhalation on intestinal absorption of some nutrients (glucose, leucine, methionine) in rats.

  11. Intestinal absorption of retinol and retinyl palmitate in the rat. Effects of tetrahydrolipstatin

    SciTech Connect

    Fernandez, E.; Borgstroem, B. )

    1990-09-01

    The aim of the present study was to characterize the intestinal absorption of retinol and retinyl palmitate in thoracic duct and bile duct fistulated rats and to investigate the effect of a simultaneously administered lipase inhibitor, tetrahydrolipstatin (THL). Absorption was determined as lymphatic recovery over a 24-hr period, including an initial 12-hr continuous intraduodenal infusion of either (11,12-3H)retinol or (11,12-3H)retinyl palmitate given in emulsified glyceryl trioleate or in mixed micellar solution of monoolein and oleic acid. From micellar dispersion, labeled retinol and retinyl palmitate were recovered in the lymph to 50-60% and both to the same extent. Administered in emulsified form, labeled retinol from fed retinyl palmitate was recovered to 47%, but retinol from fed retinol to only 18%. THL (10(-4) M) in the infusate had no significant effect on the recovery of 14C-labeled oleic acid. The recovery of label from emulsified glyceryl tri(1-14C)oleate was significantly decreased at this concentration of THL (76.5% vs 19.6% recovery). When administered in emulsified form, retinol absorption was not significantly affected by THL at 10(-4) M, while retinyl palmitate absorption was very significantly decreased (5.0% compared to 47.8%). In the presence of THL, retinol absorption from retinyl palmitate in micellar solution was decreased (from 58% to 17%). Most of the retinol in the lymph extracts (72.2 to 91.3) was present as retinyl ester, regardless of the chemical and physical form of administration. Furthermore, THL did not induce any change in this pattern.

  12. Deoxynivalenol as a contaminant of broiler feed: intestinal development, absorptive functionality, and metabolism of the mycotoxin.

    PubMed

    Yunus, A W; Blajet-Kosicka, A; Kosicki, R; Khan, M Z; Rehman, H; Böhm, J

    2012-04-01

    Deoxynivalenol (DON) has been recently documented to deteriorate intestinal morphology in chickens at dietary doses that are regarded as safe for this species. The present trial was conducted to explore the significance of these morphological changes in relation to intestinal absorptive functionality and DON metabolism. Ross broilers at 7 d of age were fed either a basal diet (0.265 ± 0.048 mg of DON/kg; 0.013 ± 0.001 mg of zearalenone/kg), a low DON diet (1.68 mg of DON/kg; 0.145 ± 0.007 mg of zearalenone/kg), or a high DON diet (12.209 ± 1.149 mg of DON/kg; 1.094 ± 0.244 mg of zearalenone/kg). The DON diets (to variable degrees) progressively decreased the relative density (weight:length) of the small intestine with increasing exposure length, which could be correlated with a decrease in villus height in the small intestine. Short circuit current of the jejunal epithelium, reflecting transport function of the epithelium per unit area, was reduced (P = 0.001) in the birds fed the high DON diet. The increasing dietary level of DON linearly (P = 0.035) increased the length of the jejunum in wk 4 of exposure, resulting in conservation of macronutrient retention. Upon challenging the birds with a fixed amount of DON after wk 5 of exposure, higher (P ≤ 0.033) amounts of DON and the detoxification metabolite (de-epoxy-DON) were found at 5 h postchallenge in the guts of birds raised on the DON diets. The increasing level of previous exposure to DON linearly (P = 0.040) decreased the plasma level of DON in the birds at 1 h postchallenge. The amounts of zearalenone and its analogs in the gut and plasma also followed a trend similar to that for DON. These data suggest that intestines in chickens may adapt to a chronic DON challenge by morphological and functional modifications. The birds having previous exposure to Fusarium mycotoxins showed moderate detoxification coupled with reduced transfer of the mycotoxins to systemic circulation. Some metabolites of zearalenone found in this study were previously unknown for chickens. PMID:22399724

  13. Intestinal absorption of amino acids in the Pacific bluefin tuna (Thunnus orientalis): in vitro lysine-arginine interaction using the everted intestine system.

    PubMed

    Martínez-Montaño, Emmanuel; Peña, Emyr; Viana, María Teresa

    2013-04-01

    The interaction between lysine (Lys) and arginine (Arg) in the proximal intestinal region of Pacific bluefin tuna (Thunnus orientalis) was evaluated using the everted intestine method. This in vitro intestinal system has been shown to be an effective tool for studying the nutrient absorption without the need to handle the tuna fish in marine cages as needed for digestibility and amino acid (AA) absorption. We used a factorial design with two sets of variables: low and high Lys concentration (10 and 75 mM) and four different Arg concentrations (3, 10, 20, and 30 mM). Both amino acids were dissolved in marine Ringer solution with a basal amino acidic composition consisting of a tryptone solution (9 mg mL(-1)). No interaction was observed between the absorption of Lys and Arg during the first 10 min of the experiment when low concentration of Lys and Arg was used in the hydrolyzate solution. However, there seemed to be a positive effect on Lys absorption when both amino acids were at high concentrations (30 and 75 mM, respectively). This type of studies will led us to test different formulations and/or additives to better understand the efficiency of AA supplementation as an alternative to in situ studies that are difficult to follow to design with the Pacific Bluefin Tuna. PMID:23001589

  14. Absorption of calcium measured by intubation and perfusion of the intact human small intestine

    PubMed Central

    Wensel, Ronald H.; Rich, Clayton; Brown, Arthur C.; Volwiler, Wade

    1969-01-01

    Absorption of calcium was measured by direct intubation and perfusion of the small intestine in 10 volunteer normal adult subjects, two adults with celiac-sprue, and one with a parathyroid adenoma. A total of 60 studies were completed using one of two different levels, duodenojejunum or ileum. Solutions containing stable calcium, radiocalcium47, and a nonabsorbable dilution-concentration marker, polyethylene glycol, were infused at a uniform rate via the proximal lumen of a triple-lumen polyvinyl tube. The mixed intraluminal contents were continuously sampled by siphonage from two distal sites, 10 and 60 cm below the point of infusion. Unidirectional flux rates, lumen to blood and blood to lumen, and net absorption of calcium for the 50 cm segment of small intestine between the two collection sites were calculated from the measured changes in concentration of stable calcium, calcium-47, and polyethylene glycol. Flux of calcium from lumen to blood in the duodenojejunum of normal subjects was appreciable even when the concentration of calcium in the perfusate was below that of extracellular fluid and, as the intraluminal concentration of calcium was increased through a range of 0.5-3.5 ?moles/ml, was positively correlated, ranging from 1.9 to 7.0 ?moles/min per 50 cm. Repeated studies of individual subjects demonstrated a consistent pattern of absorptive efficiency in each, but significant variability from person to person. Flux from lumen to blood in the ileal segment occurred at a much lower rate than that found in the proximal intestine, and there was not a significant dependence upon intraluminal calcium concentration. The opposite flux, from blood to lumen, was low both in the duodenojejunum and ileum (average 0.76 ?moles/min per 50 cm) and was independent of the intraluminal calcium concentration. Unidirectional flux, lumen to blood, from the duodenojejunum was not altered by parathyroid extract administered at the time of the infusion, but was accelerated in the subject with a parathyroid adenoma and markedly reduced in the two subjects with celiac-sprue. PMID:5822585

  15. Time dependent changes in the intestinal Ca? absorption in rats with type I diabetes mellitus are associated with alterations in the intestinal redox state.

    PubMed

    Rivoira, Mara; Rodrguez, Valeria; Lpez, Mara Peralta; Tolosa de Talamoni, Nori

    2015-03-01

    The aim was to determine the intestinal Ca? absorption in type I diabetic rats after different times of STZ induction, as well as the gene and protein expression of molecules involved in both the transcellular and paracellular Ca? pathways. The redox state and the antioxidant enzymes of the enterocytes were also evaluated in duodenum from either diabetic or insulin-treated diabetic rats as compared to control rats. Male Wistar rats (150-200 g) were divided into two groups: 1) controls and 2) STZ-induced diabetic rats (60 mg/kg b.w.). A group of diabetic rats received insulin for five days. The insulin was adjusted daily to maintain a normal blood glucose level. Five 5 d after STZ injection, there was a reduction in the intestinal Ca? absorption, which was maintained for 30 d and disappeared at 60 d. Similar changes occurred in the GSH and (?)O(2)(-) levels. The protein expression of molecules involved in the transcellular pathway increased at 5 and 30 d returning to control values at 60 d. Their mRNA levels declined considerably at 60 d. The gene and protein expression of claudin 2 was upregulated at 30 d. Catalase activity increased at 5 and 30 d normalizing at 60 d. To conclude, type I D.m. inhibits the intestinal Ca? absorption, which is transient leading to a time dependent adaptation and returning the absorptive process to normal values. The inhibition is accompanied by oxidative stress. When insulin is administered, the duodenal redox state returns to control values and the intestinal Ca? absorption normalizes. PMID:25459228

  16. Impact of murine intestinal apolipoprotein A-IV expression on regional lipid absorption, gene expression, and growth

    PubMed Central

    Simon, Trang; Cook, Victoria R.; Rao, Anuradha; Weinberg, Richard B.

    2011-01-01

    Apolipoprotein A-IV (apoA-IV) is synthesized by intestinal enterocytes during lipid absorption and secreted into lymph on the surface of nascent chylomicrons. A compelling body of evidence supports a central role of apoA-IV in facilitating intestinal lipid absorption and in regulating satiety, yet a longstanding conundrum is that no abnormalities in fat absorption, feeding behavior, or weight gain were observed in chow-fed apoA-IV knockout (A4KO) mice. Herein we reevaluated the impact of apoA-IV expression in C57BL6 and A4KO mice fed a high-fat diet. Fat balance and lymph cannulation studies found no effect of intestinal apoA-IV gene expression on the efficiency of fatty acid absorption, but gut sac transport studies revealed that apoA-IV differentially modulates lipid transport and the number and size of secreted triglyceride-rich lipoproteins in different anatomic regions of the small bowel. ApoA-IV gene deletion increased expression of other genes involved in chylomicron assembly, impaired the ability of A4KO mice to gain weight and increase adipose tissue mass, and increased the distal gut hormone response to a high-fat diet. Together these findings suggest that apoA-IV may play a unique role in integrating feeding behavior, intestinal lipid absorption, and energy storage. PMID:21840868

  17. Oral absorption of anti-AIDS nucleoside analogues. 1. Intestinal transport of didanosine in rat and rabbit preparations.

    PubMed

    Sinko, P J; Hu, P; Waclawski, A P; Patel, N R

    1995-08-01

    The intestinal transport of didanosine (ddl), a nucleoside analog used in the treatment of human immunodeficiency virus (HIV) infection, was characterized using in situ and in vitro techniques. The zero-trans uptake of ddl in rat intestinal brush border membrane vesicles (BBMV) was linear over the range of 1 microM to 50 mM, ruling out a significant carrier-mediated absorption component. The lack of carrier-mediated transport was confirmed in a second species (rabbit). In order to quantitate the convective (Pconv) and diffusive (Pdiff) components of ddl intestinal permeability, the steady state wall permeability (P*w) was determined using an established perfusion technique in rats. Even though baseline P*w (pH 6.5, 290 mosm/kg, no modulator) and fluid absorption results were similar to those of furosemide, the ratios (ddl:furosemide) of Pdiff and phi, the sieving coefficient, were 0.31:1 and 1.70:1, respectively, demonstrating that ddl's Pdiff is low and Pconv is high relative to furosemide's, suggesting significant paracellular absorption of ddl. The apparent diffusive absorptive clearances (P'app) of ddl and furosemide were determined in BBMV, which lack functional tight junctions, and the ratios (ddl:furosemide) of P'app in rat and rabbit were 0.23:1 and 0.24:1, respectively. The BBMV results demonstrate that the majority of ddl intestinal transport does not occur by passive membrane diffusion, confirming the single pass intestinal perfusion (SPIP) findings. The results of these studies suggest that ddl is transported by nonfacilitated membrane and paracellular diffusion with paracellular transport being responsible for the majority of ddl absorption from the intestine. PMID:7500281

  18. Metabolic effects of intestinal absorption and enterohepatic cycling of bile acids.

    PubMed

    Ferrebee, Courtney B; Dawson, Paul A

    2015-03-01

    The classical functions of bile acids include acting as detergents to facilitate the digestion and absorption of nutrients in the gut. In addition, bile acids also act as signaling molecules to regulate glucose homeostasis, lipid metabolism and energy expenditure. The signaling potential of bile acids in compartments such as the systemic circulation is regulated in part by an efficient enterohepatic circulation that functions to conserve and channel the pool of bile acids within the intestinal and hepatobiliary compartments. Changes in hepatobiliary and intestinal bile acid transport can alter the composition, size, and distribution of the bile acid pool. These alterations in turn can have significant effects on bile acid signaling and their downstream metabolic targets. This review discusses recent advances in our understanding of the inter-relationship between the enterohepatic cycling of bile acids and the metabolic consequences of signaling via bile acid-activated receptors, such as farnesoid X nuclear receptor (FXR) and the G-protein-coupled bile acid receptor (TGR5). PMID:26579438

  19. Metabolic effects of intestinal absorption and enterohepatic cycling of bile acids

    PubMed Central

    Ferrebee, Courtney B.; Dawson, Paul A.

    2015-01-01

    The classical functions of bile acids include acting as detergents to facilitate the digestion and absorption of nutrients in the gut. In addition, bile acids also act as signaling molecules to regulate glucose homeostasis, lipid metabolism and energy expenditure. The signaling potential of bile acids in compartments such as the systemic circulation is regulated in part by an efficient enterohepatic circulation that functions to conserve and channel the pool of bile acids within the intestinal and hepatobiliary compartments. Changes in hepatobiliary and intestinal bile acid transport can alter the composition, size, and distribution of the bile acid pool. These alterations in turn can have significant effects on bile acid signaling and their downstream metabolic targets. This review discusses recent advances in our understanding of the inter-relationship between the enterohepatic cycling of bile acids and the metabolic consequences of signaling via bile acid-activated receptors, such as farnesoid X nuclear receptor (FXR) and the G-protein-coupled bile acid receptor (TGR5). PMID:26579438

  20. Intestinal absorption and tissue distribution of ( sup 14 C)pyrroloquinoline quinone in mice

    SciTech Connect

    Smidt, C.R.; Unkefer, C.J.; Houck, D.R.; Rucker, R.B. )

    1991-05-01

    Pyrroloquinoline quinone (PQQ) functions as a cofactor for prokaryotic oxidoreductases, such as methanol dehydrogenase and membrane-bound glucose dehydrogenase. In animals fed chemically defined diets, PQQ improves reproductive outcome and neonatal growth. Consequently, the present study was undertaken to determine the extent to which PQQ is absorbed by the intestine, its tissue distribution, and route of excretion. About 28 micrograms of PQQ (0.42 microCi/mumol), labeled with {sup 14}C derived from L-tyrosine, was administered orally to Swiss-Webster mice (18-20 g) to estimate absorption. PQQ was readily absorbed (62%, range 19-89%) in the lower intestine, and was excreted by the kidneys (81% of the absorbed dose) within 24 hr. The only tissues that retained significant amounts of ({sup 14}C)PQQ at 24 hr were skin and kidney. For kidney, it was assumed that retention of ({sup 14}C)PQQ represented primarily PQQ destined for excretion. For skin, the concentration of ({sup 14}C)PQQ increased from 0.3% of the absorbed dose at 6 hr to 1.3% at 24 hr. Furthermore, most of the ({sup 14}C)PQQ in blood (greater than 95%) was associated with the blood cell fraction, rather than plasma.

  1. Oligoarginine-modified biodegradable nanoparticles improve the intestinal absorption of insulin.

    PubMed

    Liu, Xiaoli; Liu, Chang; Zhang, Wenjian; Xie, Cao; Wei, Gang; Lu, Weiyue

    2013-05-01

    The strategy of oral administration of bioactive macromolecules using cell-penetrating peptides (CPPs) is restricted to covalent linkage or electrostatic interaction between the cargo and CPPs. In the present study, we devised an approach utilizing CPP-functionalized poly(lactic-co-glycolic acid) (PLGA) nanoparticles as a carrier for oral delivery of insulin. Pegylated PLGA nanoparticles were modified with poly(arginine)8 enantiomers (l-R8 and d-R8) via a maleimide-mediated covalent conjugating procedure. The physical and chemical features of the nanoparticles were characterized, which confirmed the successful immobilization of R8 to the nanoparticles. Using a Caco-2 cell monolayer model, R8-modified nanoparticles were found to exhibit significantly increased cellular uptake and transportation. Pharmacokinetics and pharmacodynamics of the insulin-loaded nanoparticles were evaluated with rats by intestinal administration. Compared to the unmodified nanoparticles, l-R8 and d-R8 modified-nanoparticles increased the relative bioavailabilities of insulin by 3.2- and 4.4-times, meanwhile, improved the hypoglycemic effects by 2.5- and 3.7-times, respectively. Neither of the R8-modified nanoparticles caused perceptible histological toxicities. The results implied that surface modification of biodegradable nanoparticles with poly(arginine)8, especially with the d-form enantiomer, showed remarkable advancement in promoting the intestinal absorption of insulin. This delivery system is also promising for the delivery of a wide variety of bioactive macromolecules by oral administration. PMID:23538098

  2. Intestinal Calcium Absorption Decreases Dramatically After Gastric Bypass Surgery Despite Optimization of Vitamin D Status.

    PubMed

    Schafer, Anne L; Weaver, Connie M; Black, Dennis M; Wheeler, Amber L; Chang, Hanling; Szefc, Gina V; Stewart, Lygia; Rogers, Stanley J; Carter, Jonathan T; Posselt, Andrew M; Shoback, Dolores M; Sellmeyer, Deborah E

    2015-08-01

    Roux-en-Y gastric bypass (RYGB) surgery has negative effects on bone, mediated in part by effects on nutrient absorption. Not only can RYGB result in vitamin D malabsorption, but the bypassed duodenum and proximal jejunum are also the predominant sites of active, transcellular, 1,25(OH)2 D-mediated calcium (Ca) uptake. However, Ca absorption occurs throughout the intestine, and those who undergo RYGB might maintain sufficient Ca absorption, particularly if vitamin D status and Ca intake are robust. We determined the effects of RYGB on intestinal fractional Ca absorption (FCA) while maintaining ample 25OHD levels (goal ?30?ng/mL) and Ca intake (1200?mg daily) in a prospective cohort of 33 obese adults (BMI 44.7??7.4?kg/m(2)). FCA was measured preoperatively and 6 months postoperatively with a dual stable isotope method. Other measures included calciotropic hormones, bone turnover markers, and BMD by DXA and QCT. Mean 6-month weight loss was 32.5??8.4?kg (25.8%??5.2% of preoperative weight). FCA decreased from 32.7%??14.0% preoperatively to 6.9%??3.8% postoperatively (p?

  3. Efficacy of different hexacyanoferrates(II) in inhibiting the intestinal absorption of radiocaesium in rats.

    PubMed

    Dresow, B; Nielsen, P; Heinrich, H C

    1990-06-01

    The inhibitory effect of various oral doses of different hexacyanoferrate(II) compounds (HCF) and the influence of the time interval of HCF-administration on intestinal 134Cs-absorption was studied in rats. Optimum inhibition was obtained by administration of HCF together with or 2 min before oral 134Cs loading. Using appropriate low amounts (0.1-0.5 mg) of the different HCF compounds, the inhibitory effect increased in the sequence KZnHCF less than KCuHCF less than FeHCF less than KCoHCF = KNiHCF less than NH4FeHCF = KFeHCF. Oral administration of 5 mg (0.5 mg) of KFeHCF, together with 134CsCl loading, reduces 134Cs-absorption from 41% (control) to 0.8% (2.8%). Zinc-, copper-, cobalt, and nickel hexacyanoferrates(II), despite showing a high caesium sorption capacity in vitro, were less effective in rats and are not suited for in vivo application, also because they may produce toxic side effects. As a consequence, the orally administered colloidal-soluble iron(III) hexacyanoferrates(II) (NH4Fe[Fe(CN)6] and KFe[Fe(CN)6]) have to be considered as the most valuable countermeasure against radiocaesium absorption for humans and domestic animals in the case of a severe nuclear accident in the future. Manganese oxide, a non-hexacyanoferrate(II) compound with known in vitro caesium binding capacity, showed no inhibitory effect on radiocaesium absorption in rats. PMID:2400470

  4. Oxalate catabolism in Arabidopsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxalic acid is found in most plant species and can serve beneficial roles that protect the plant from a variety of environmental stresses. Excessive amounts of oxalate, however, can be detrimental to plant health. Thus, careful coordination of oxalate metabolism is needed. Despite the important impa...

  5. Orlistat limits cholesterol intestinal absorption by Niemann-pick C1-like 1 (NPC1L1) inhibition.

    PubMed

    Alqahtani, Saeed; Qosa, Hisham; Primeaux, Brian; Kaddoumi, Amal

    2015-09-01

    The known mechanism by which orlistat decreases the absorption of dietary cholesterol is by inhibition of intestinal lipases. The aim of this study was to investigate the ability of orlistat to limit cholesterol absorption by inhibition of the cholesterol transport protein Niemann-Pick C1-like 1 (NPC1L1) as another mechanism of action. In situ rat intestinal perfusion studies were conducted to study the effect of orlistat on jejunal cholesterol absorption. Inhibition kinetic parameters were calculated from in vitro inhibition studies using Caco2 and NPC1L1 transfected cell lines. The in situ studies demonstrated that intestinal perfusion of orlistat (100M) was able to reduce cholesterol absorption by three-fold when compared to control (i.e. in the absence of orlistat, P<0.01). In vitro studies using Caco2 cells demonstrated orlistat to reduce the cellular uptake of cholesterol by 30%. Additionally, orlistat reduced the cellular uptake of cholesterol in dose dependent manner in NPC1L1 transfected cell line with an IC50=1.2M. Lineweaver-Burk plot indicated a noncompetitive inhibition of NPC1L1 by orlistat. Beside the already established mechanism by which orlistat reduces the absorption of cholesterol, we demonstrated for the first time that orlistat limits cholesterol absorption by the inhibition of NPC1L1 transport protein. PMID:26048312

  6. Uptake of Gold Nanoparticles by Intestinal Epithelial Cells: Impact of Particle Size on Their Absorption, Accumulation, and Toxicity.

    PubMed

    Yao, Mingfei; He, Lili; McClements, David Julian; Xiao, Hang

    2015-09-16

    Inorganic nanomaterials have been increasingly utilized in many consumer products, which has led to concerns about their potential toxicity. At present, there is limited knowledge about the gastrointestinal fate and cytotoxicity of ingested inorganic nanoparticles. This study determined the influence of particle size and concentration of gold nanoparticles (AuNPs) on their absorption, accumulation, and cytotoxicity in model intestinal epithelial cells. As the mean particle diameter of the AuNPs decreased (from 100 to 50 to 15 nm), their rate of absorption by the intestinal epithelium cells increased, but their cellular accumulation in the epithelial cells decreased. Moreover, accumulation of AuNPs caused cytotoxicity in the intestinal epithelial cells, which was evidenced by depolarization of mitochondria membranes. These results provide important insights into the relationship between the dimensions of AuNPs and their gastrointestinal uptake and potential cytotoxicity. PMID:26313743

  7. Folate-binding protein and the absorption of folic acid in the small intestine of the suckling rat

    SciTech Connect

    Mason, J.B.; Selhub, J.

    1988-09-01

    The folate in milk is largely bound to high-affinity folate-binding protein (FBP). With an in vivo intestinal loop technique, we examined the absorption of folic acid bound to FBP (FA-FBP) in the small intestine of the suckling rat. In contrast to unbound folic acid (FA), FA-FBP is absorbed more avidly in the ileum than in the jejunum (p less than 0.025) and its absorption is not inhibited by 1 mmol sulfasalazine/L. Folate-binding activities in the mucosa of the proximal (duodenum and jejunum combined) and distal (ileum) small intestine were also examined and found to be 0.32 and 1.31 pmol/mg protein, respectively (p less than 0.001). A 6-h fast produced a 42% decrease in folate-binding activity in the distal small intestine (p less than 0.01) but did not change activity in the proximal portion. Collectively, these observations suggest that FA-FBP is absorbed by a mechanism that is distinct from that responsible for the absorption of FA and that absorption does not require prior dissociation of the vitamin-binding protein complex.

  8. Effect of cadmium administration on intestinal calcium absorption and vitamin D-dependent calcium-binding protein

    SciTech Connect

    Fullmer, C.S.; Oku, T.; Wasserman, R.H.

    1980-08-01

    The effects of cadmium on intestinal calcium absorption and calcium-binding protein (CaBP) were investigated in chicks by means of the in situ ligated duodenal loop technique. Dietary cadmium, administered in the feed or by gastric intubation, resulted in significant declines in intestinal calcium absorption and mucosal calcium-binding protein concentrations. Cadmium chloride injected directly into the ligated loop of naive chicks also diminished calcium absorption and CaBP concentrations in an apparently dose-response related fashion. No adverse effects of cadmium administration on either the 25- or 1..cap alpha..-hydroxylation reactions of vitamin D were observed. While the general effect of cadmium administration was a reduction in intestinal calcium absorption, plasma calcium levels were consistently elevated in Cd-treated chicks, with the exception of those also maintained on diets low in Ca. The results indicate that cadmium toxicity exerts at least two effects on Ca metabolism, one at the intestinal level and another at the level of the bone, kidney, or both.

  9. Effects of oligofructose-enriched inulin on intestinal absorption of calcium and magnesium and bone turnover markers in postmenopausal women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Deficiency of oestrogen at menopause decreases intestinal Ca absorption, contributing to a negative Ca balance and bone loss. Mg deficiency has also been associated with bone loss. The purpose of the present investigation was to test the hypothesis that treatment with a spray-dried mixture of chicor...

  10. Low zinc status and absorption exist in infants with jejunostomies or ileostomies which persists after intestinal repair.

    PubMed

    Balay, Kimberly S; Hawthorne, Keli M; Hicks, Penni D; Chen, Zhensheng; Griffin, Ian J; Abrams, Steven A

    2012-09-01

    There is very little data regarding trace mineral nutrition in infants with small intestinal ostomies. Here we evaluated 14 infants with jejunal or ileal ostomies to measure their zinc absorption and retention and biochemical zinc and copper status. Zinc absorption was measured using a dual-tracer stable isotope technique at two different time points when possible. The first study was conducted when the subject was receiving maximal tolerated feeds enterally while the ostomy remained in place. A second study was performed as soon as feasible after full feeds were achieved after intestinal repair. We found biochemical evidence of deficiencies of both zinc and copper in infants with small intestinal ostomies at both time points. Fractional zinc absorption with an ostomy in place was 10.9% 5.3%. After reanastamosis, fractional zinc absorption was 9.4% 5.7%. Net zinc balance was negative prior to reanastamosis. In conclusion, our data demonstrate that infants with a jejunostomy or ileostomy are at high risk for zinc and copper deficiency before and after intestinal reanastamosis. Additional supplementation, especially of zinc, should be considered during this time period. PMID:23112915

  11. Improvement in site-specific intestinal absorption of furosemide by Eudragit L100-55.

    PubMed

    Terao, T; Matsuda, K; Shouji, H

    2001-04-01

    Furosemide (frusemide) is a weakly acidic diuretic drug. Its absorption is poor and variable, in part due to its restricted sites of absorption, mainly the stomach. The narrow absorption window of this drug can be explained by pH partition theory. The purpose of this study was to investigate the feasibility of widening the absorption window of furosemide by controlling the pH in distal portions of the gastrointestinal tract with officially used additives. Methacrylate copolymer (Eudragit L100-55), hydroxypropylmethylcellulose phthalate (HP-55) and hydroxypropylmethylcellulose acetate succinate (AS-MF) were selected as additives. The pH of suspensions of these additives was about 4, and the pH was adjusted to about 6-7 by the addition of NaOH. The Eudragit L100-55 suspension was found to be the most resistant to NaOH titration. When Eudragit L100-55 was used in an in-situ ileal loop experiment in rats, the pH of the intestinal contents was significantly reduced, from 7.9+/-0.1 to 5.7+/-0.1, and the plasma concentration of furosemide 15 min after administration was about 3 times higher than that in controls, 1.81+/- 0.42microg mL(-1) vs 0.63+/-0.08 microg mL(-1). However, the plasma concentration of [14C] mannitol was not changed by the co-administration of Eudragit L100-55. Furthermore, the AUC of furosemide was significantly increased by a factor of about 1.6 relative to that in controls by the co-administration of Eudragit L100-55, to 21.4+/-4.0 microg h mL(-1) from 13.3+/- 3.9 microg h mL(-1), and the gastrointestinal pH in the midgut and ileum was significantly reduced, with most of the furosemide remaining in these segments at 2 h following the oral administration of furosemide with Eudragit L100-55 to rats. These findings clearly demonstrate that the addition of Eudragit L100-55 can increase the absorption of furosemide in distal portions of the gastrointestinal tract. In conclusion, it is feasible to widen the absorption window of furosemide by controlling the pH in distal portions of the gastrointestinal tract by the co-administration of Eudragit L100-55. PMID:11341359

  12. High paracellular nutrient absorption in intact bats is associated with high paracellular permeability in perfused intestinal segments.

    PubMed

    Brun, Antonio; Price, Edwin R; Gontero-Fourcade, Manuel N; Fernandez-Marinone, Guido; Cruz-Neto, Ariovaldo P; Karasov, William H; Caviedes-Vidal, Enrique

    2014-09-15

    Water-soluble nutrients are absorbed by the small intestine via transcellular and paracellular mechanisms. Based on a few previous studies, the capacity for paracellular nutrient absorption seems greater in flying mammals than in nonflying mammals, but there has been little investigation of the mechanisms driving this difference. Therefore, we studied three species each of bats (Artibeus lituratus, Sturnira lilium and Carollia perspicillata) and nonflying mammals (Akodon montensis, Mus musculus and Rattus norvegicus). Using standard pharmacokinetic techniques in intact animals, we confirmed the greater paracellular nutrient absorption in the fliers, comparing one species in each group. Then we conducted in situ intestinal perfusions on individuals of all species. In both approaches, we measured the absorption of 3OMD-glucose, a nonmetabolizable glucose analog absorbed both paracellularly and transcellularly, as well as L-arabinose, which has no mediated transport. Fractional absorption of L-arabinose was three times higher in the bat (S. lilium: 1.20.24) than in the rodent (A. montensis: 0.350.04), whereas fractional absorption of 3OMD-glucose was complete in both species (1.460.4 and 0.970.12, respectively). In agreement, bats exhibited two to 12 times higher l-arabinose clearance per square centimeter nominal surface area than rodents in intestinal perfusions. Using L-arabinose, we estimated that the contribution of the paracellular pathway to total glucose absorption was higher in all three bats (109-137%) than in the rodents (13-39%). These findings contribute to an emerging picture that reliance on the paracellular pathway for nutrient absorption is much greater in bats relative to nonflying mammals and that this difference is driven by differences in intestinal permeability to nutrient-sized molecules. PMID:25104759

  13. Increases in intestinal glucose absorption and hepatic glucose uptake elicited by luminal but not vascular glutamine in the jointly perfused small intestine and liver of the rat.

    PubMed Central

    Gardemann, A; Watanabe, Y; Grosse, V; Hesse, S; Jungermann, K

    1992-01-01

    1. Previous studies have shown that an arterial-to-portal glucose concentration gradient may be an important signal for insulin-dependent net hepatic glucose uptake. It is not known whether intestinal factors also contribute to the regulation of hepatic glucose utilization. This problem was studied in a newly developed model which allows luminal perfusion of the small intestine via the pyloric sphincter and a combined vascular perfusion of the small intestine via the gastroduodenal artery and superior mesenteric artery, and of the liver via the hepatic artery and portal vein. 2. In both the presence and the absence of 1 mM-glutamine in the vascular perfusate, only about 7% of a luminal bolus of 5500 mumol (1 g) of glucose was absorbed by the small intestine, and nothing was taken up by the liver. 3. With small doses of 75-380 mumol (11-55 mg) of luminal glutamine, but not with 300 mumol of alanine, the intestinal absorption of the luminal glucose bolus was increased almost linearly from 7% to a maximum of 40% and the hepatic uptake from 0% to a maximum of 22%. 4. The increase of hepatic glucose uptake caused by luminal glutamine was only observed when the glucose load was applied into the intestinal lumen, rather than into the superior mesenteric artery. 5. The relative hepatic glucose uptake (uptake/portal supply) was enhanced from 0% to 55% with an increase in portal supply by luminal glutamine, whereas with a similar range of portal glucose supply the relative hepatic uptake by the isolated liver, perfused simultaneously via the hepatic artery and portal vein, was slightly decreased, from 20% to 15%. 6. Addition of various amounts of portal glutamine and/or alterations in the Na+ content of the portal perfusate failed to mimic the luminal glutamine-dependent activation of hepatic glucose uptake. Therefore the luminal-glutamine-elicited activation of hepatic glucose uptake was apparently not caused by a simple increase in the portal-arterial glucose gradient, by glutamine itself or by Na(+)-dependent alterations in hepatic cell volume. The results suggest that luminal glutamine caused not only an increase in intestinal glucose absorption by unknown mechanisms but also the generation of one or more humoral or nervous 'hepatotropic' signals in the small intestine which enhanced the hepatic uptake of absorbed glucose. Images Fig. 1. PMID:1590766

  14. Transport, metabolism, and endosomal trafficking-dependent regulation of intestinal fructose absorption.

    PubMed

    Patel, Chirag; Douard, Veronique; Yu, Shiyan; Gao, Nan; Ferraris, Ronaldo P

    2015-09-01

    Dietary fructose that is linked to metabolic abnormalities can up-regulate its own absorption, but the underlying regulatory mechanisms are not known. We hypothesized that glucose transporter (GLUT) protein, member 5 (GLUT5) is the primary fructose transporter and that fructose absorption via GLUT5, metabolism via ketohexokinase (KHK), as well as GLUT5 trafficking to the apical membrane via the Ras-related protein-in-brain 11 (Rab11)a-dependent endosomes are each required for regulation. Introducing fructose but not lysine and glucose solutions into the lumen increased by 2- to 10-fold the heterogeneous nuclear RNA, mRNA, protein, and activity levels of GLUT5 in adult wild-type mice consuming chow. Levels of GLUT5 were >100-fold that of candidate apical fructose transporters GLUTs 7, 8, and 12 whose expression, and that of GLUT 2 and the sodium-dependent glucose transporter protein 1 (SGLT1), was not regulated by luminal fructose. GLUT5-knockout (KO) mice exhibited no facilitative fructose transport and no compensatory increases in activity and expression of SGLT1 and other GLUTs. Fructose could not up-regulate GLUT5 in GLUT5-KO, KHK-KO, and intestinal epithelial cell-specific Rab11a-KO mice. The fructose-specific metabolite glyceraldehyde did not increase GLUT5 expression. GLUT5 is the primary transporter responsible for facilitative absorption of fructose, and its regulation specifically requires fructose uptake and metabolism and normal GLUT5 trafficking to the apical membrane. PMID:26071406

  15. Intestinal nutrient absorption - A biomarker for deleterious heavy metals in aquatic environments

    SciTech Connect

    Farmanfarmaian, A. )

    1988-09-01

    The deleterious effects of heavy metals on absorptive processes at the membrane surface will be summarized. Among the deleterious heavy metal chlorides (HgCl{sub 2}, CH{sub 3}HgCl, CdCl{sub 2}, CoCl{sub 2}, SrCl{sub 2}) tested HgCl{sub 2}, CH{sub 3}HgCl, and CdCl{sub 2} inhibit the absorption of several amino acids and sugars (L-leucine, L-methionine, L-isoleucine, L-lysine, cyclolencine, D-glucose, and D-galactose). The dose dependent inhibition of L-leucine uptake by HgCl{sub 2} is shown in a number of fish from different collection sites representing nektonic plankton feeders as well as demersal carnivores. The same type of data is shown for both HgCl{sub 2} and HC{sub 3}HgCl in the case of the commercially important summer flounder. Since the overall rate of intestinal absorption of amino acids and sugars involves the three processes of simple diffusion, protein-mediated facilitated diffusions, and protein-mediated sodium dependent active transport, the inhibition of the overall rate may not be sensitive enough as a biomarker. However, the active component, which alone accumulates essential amino acids in the tissue, appears to be very sensitive and can be used as a biomarker. The terminal tissue-to-medium (T/M) ratio of L-leucine concentration shows a 2-3 fold accumulation in the absence of mercury. Since the diffusional components can at best equilibrate L-leucine across the membrane % inhibition of the active component can be calculated after subtracting 1 from the experimental T/M values. The resulting inhibition is very sever ranging from approximately 50-100% for HgCl{sub 2} and 20-70% for CH{sub 3}HgCl over a range of 5-20 ppm of mercury.

  16. Effect of cholecalciferol and 1,25-dihydroxycholecalciferol on the intestinal absorption of zinc in the chick

    SciTech Connect

    Koo, S.I.; Fullmer, C.S.; Wasserman, R.H.

    1980-09-01

    The effect of cholecalciferol on the intestinal absorption of /sup 65/Zn was assessed in zinc-deficient and zinc-replete rachitic chicks, using the in situ ligated loop techniques. Cholecalciferol did not significantly affect /sup 65/Zn absorption in either group, although the synthesis of the intestinal calcium-binding protein (CaBP) in both groups was similar. In an analogous study, 1,25-dihydroxycholecalciferol increased /sup 47/Ca absorption and induced the synthesis of CaBP but exerted no effect on /sup 65/Zn absorption in zinc-deficient rachitic chicks. When fed a diet adequate in cholecalciferol, more CaBP was present in the intestine of the zinc-adequate group than in the zinc-deficient group, possibly due to the greater rate of growth and therefore the greater need for calcium by the former group. These results suggest that cholecalciferol and its most active metabolite do not directly affect zinc absorption and, by inference, that the vitamin D-dependent transport mechanism is not involved in zinc homeostasis, or in the interaction between calcium and zinc.

  17. Ezetimibe selectively inhibits intestinal cholesterol absorption in rodents in the presence and absence of exocrine pancreatic function

    PubMed Central

    van Heek, Margaret; Farley, Constance; Compton, Douglas S; Hoos, Lizbeth; Davis, Harry R

    2001-01-01

    Ezetimibe potently inhibits the transport of cholesterol across the intestinal wall, thereby reducing plasma cholesterol in preclinical animal models of hypercholesterolemia. The effect of ezetimibe on known absorptive processes was determined in the present studies.Experiments were conducted in the hamster and/or rat to determine whether ezetimibe would affect the absorption of molecules other than free cholesterol, namely cholesteryl ester, triglyceride, ethinylestradiol, progesterone, vitamins A and D, and taurocholic acid. In addition, to determine whether exocrine pancreatic function is involved in the mechanism of action of ezetimibe, a biliary anastomosis model, which eliminates exocrine pancreatic function from the intestine while maintaining bile flow, was established in the rat.Ezetimibe reduced plasma cholesterol and hepatic cholesterol accumulation in cholesterol-fed hamsters with an ED50 of 0.04?mg kg?1. Utilizing cholesteryl esters labelled on either the cholesterol or the fatty acid moiety, we demonstrated that ezetimibe did not affect cholesteryl ester hydrolysis and the absorption of fatty acid thus generated in both hamsters and rats. The free cholesterol from this hydrolysis, however, was not absorbed (92??96% inhibition) in the presence of ezetimibe. Eliminating pancreatic function in rats abolished hydrolysis of cholesteryl esters, but did not affect the ability of ezetimibe to block absorption of free cholesterol (?94%). Ezetimibe did not affect the absorption of triglyceride, ethinylestradiol, progesterone, vitamins A and D, and taurocholic acid in rats.Ezetimibe is a potent inhibitor of intestinal free cholesterol absorption that does not require exocrine pancreatic function for activity. Ezetimibe does not affect the absorption of triglyceride as a pancreatic lipase inhibitor (Orlistat) would, nor does it affect the absorption of vitamin A, D or taurocholate, as a bile acid sequestrant (cholestyramine) would. PMID:11564660

  18. The effect of haem biosynthesis inhibitors and inducers on intestinal iron absorption and liver haem biosynthetic enzyme activities

    SciTech Connect

    Laftah, A.H.; Simpson, R.J. Peters, T.J.; Raja, K.B.

    2008-06-15

    The relation between haem biosynthesis and intestinal iron absorption is not well understood, we therefore investigated the effect of compounds that alter haem metabolism on duodenal iron absorption. CD1 mice were treated with either an inhibitor (succinyl acetone (SA)) or stimulator (2-allyl-2-isopropylacetamide (AIA)) of haem biosynthesis. 5-Aminolaevulinic acid (ALA) dehydratase and urinary ALA and porphobilinogen (PBG) levels, were determined. Intestinal iron absorption was assayed with in vivo and in vitro techniques. Liver hepcidin (Hamp1) and duodenal iron transporter mRNA levels were measured using RT-PCR. AIA caused increased hepatic ALA synthase (1.6-fold) and ALA dehydratase (1.4-fold, both p < 0.005) activities and increased urinary ALA and PBG excretion (2.1- and 1.4-fold, p < 0.005, p < 0.05, respectively). In vivo intestinal iron absorption was reduced to 49% of control (p < 0.005). Mice treated with SA showed decreased urinary ALA and PBG levels (75 and 55% control, both p < 0.005) and reductions in both ALA synthase and ALA dehydratase activities (77 and 56% control, p < 0.05, p < 0.005, respectively) in the liver. Liver and duodenal haem and cytochrome oxidase levels were not significantly decreased. Iron absorption was enhanced (1.26-fold, p < 0.05) and hepatic Hamp1 mRNA was reduced (53% of control, p < 0.05). In vitro duodenal iron uptake after mice were injected with SA also demonstrated an increase in Fe(III) reduction and uptake (1.27- and 1.41-fold, p < 0.01 respectively). Simultaneous injections of SA and ALA blocked the enhancing effect on iron absorption seen with SA alone. We conclude that alterations in haem biosynthesis can influence iron absorption and in particular, the intermediate ALA seems to be an inhibitor of iron absorption.

  19. In situ intestinal permeability and in vivo absorption characteristics of olmesartan medoxomil in self-microemulsifying drug delivery system.

    PubMed

    Kang, Myung J; Kim, Hyung S; Jeon, Ho S; Park, Jong H; Lee, Bong S; Ahn, Byeong K; Moon, Ki Y; Choi, Young W

    2012-05-01

    To characterize the intestinal absorption behavior of olmesartan medoxomil (OLM) and to evaluate the absorption-improving potential of a self-microemulsifying drug delivery system (SMEDDS), we performed in situ single-pass intestinal perfusion (SPIP) and in vivo pharmacokinetic studies in rats. The SPIP study revealed that OLM is absorbed throughout whole intestinal regions, favoring proximal segments, at drug levels of 10-90 ?M. The greatest value for effective permeability coefficient (P(eff)) was 11.4 10(-6) cm/s in the duodenum (90 ?M); the lowest value was 2.9 10(-6) cm/s in the ileum (10 ?M). A SMEDDS formulation consisting of Capryol 90, Labrasol, and Transcutol, which has a droplet size of 200 nm and self-dispersion time of 21 s, doubled upper intestinal permeability of OLM. The SMEDDS also improved oral bioavailability of OLM in vivo: a 2.7-fold increase in the area under the curve (AUC) with elevated maximum plasma concentration (C(max)) and shortened peak time (T(max)) compared to an OLM suspension. A strong correlation (r(2) = 0.955) was also found between the in situ jejunal P(eff) and the in vivo AUC values. Our study illustrates that the SMEDDS formulation holds great potential as an alternative to increased oral absorption of OLM. PMID:21988221

  20. Recent Advances in Our Understanding of 1,25-Dihydroxyvitamin D3 Regulation of Intestinal Calcium Absorption

    PubMed Central

    Christakos, Sylvia

    2012-01-01

    Calcium is required for many cellular processes including muscle contraction, nerve pulse transmission, stimulus secretion coupling and bone formation. The principal source of new calcium to meet these essential functions is from the diet. Intestinal absorption of calcium occurs by an active transcellular path and by a non-saturable paracellular path. The major factor influencing intestinal calcium absorption is vitamin D and more specifically the hormonally active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). This article emphasizes studies that have provided new insight related to the mechanisms involved in the intestinal actions of 1,25(OH)2D3. The following are discussed: recent studies, including those using knock out mice, that suggest that 1,25(OH)2D3 mediated calcium absorption is more complex than the traditional transcellular model; evidence for 1,25(OH)2D3 mediated active transport of calcium by distal as well as proximal segments of the intestine; 1,25(OH)2D3 regulation of paracellular calcium transport and the role of 1,25(OH)2D3 in protection against mucosal injury. PMID:22230327

  1. Intestinal absorption and intestinal lymphatic transport of sirolimus from self-microemulsifying drug delivery systems assessed using the single-pass intestinal perfusion (SPIP) technique and a chylomicron flow blocking approach: linear correlation with oral bioavailabilities in rats.

    PubMed

    Sun, Minghui; Zhai, Xuezhen; Xue, Kewen; Hu, Lei; Yang, Xiangliang; Li, Gao; Si, Luqin

    2011-06-14

    This work aims to investigate the impact of different amount of oil or surfactant included in self-microemulsifying drug delivery systems on the intestinal lymphatic transport of sirolimus using the single-pass intestinal perfusion (SPIP) technique and a chylomicron flow blocking approach. Male Sprague-Dawley rats were pretreated intraperitoneally with 3.0mg/kg cycloheximide or saline. One hour later, single-pass intestinal perfusion experiments in jejunum and ileum and in vivo bioavailability studies were carried out to calculate the effective permeability coefficient and pharmacokinetic parameters, respectively. Drug absorption from oil-free formulation was mostly via the portal blood. In contrast, for the SMEDDS formulations containing ?25% MCT, the lymphatic transport of sirolimus was a major contributor to oral bioavailability. The formulation including more content of oil presented higher lymphatic transport of drug and further exhibited the increased oral bioavailability. Besides, distal ileum presented much more lymphatic transport of drug compared to proximal jejunum. Furthermore, even though the smaller droplet size of resultant microemulsions and more surfactant content also can positively influence the intestinal absorption of drug, their influences on the drug intestinal lymphatic transport were relatively weaker than that of more oil content. In addition, there was a high linear correlation between the AUC values and the mean of P(eff) values in jejunum and ileum. PMID:21530655

  2. Intestinal water absorption through aquaporin 1 expressed in the apical membrane of mucosal epithelial cells in seawater-adapted Japanese eel.

    PubMed

    Aoki, Mayumi; Kaneko, Toyoji; Katoh, Fumi; Hasegawa, Sanae; Tsutsui, Naoaki; Aida, Katsumi

    2003-10-01

    To elucidate the mechanisms associated with water absorption in the intestine, we compared drinking and intestinal water absorption in freshwater- and seawater-adapted Japanese eels, and investigated a possible involvement of aquaporin (AQP) in the absorption of water in the intestine. Seawater eels ingested more water than freshwater eels, the drinking rate being 0.02 ml kg(-1) h(-1) in fresh water and 0.82 ml kg(-1) h(-1) in sea water. In intestinal sacs prepared from freshwater and seawater eels, water absorption increased in time- and hydrostatic pressure-dependent manners. The water absorption rates were greater in seawater sacs than in freshwater sacs, and also greater in the posterior intestine than in the anterior. In view of the enhanced water permeability in the intestine of seawater eel, we cloned two cDNAs encoding AQP from the seawater eel intestine, and identified two eel homologues (S-AQP and L-AQP) of mammalian AQP1. S-AQP and L-AQP possessed the same amino acid sequence, except that one amino acid was lacking in S-AQP and two amino acids were substituted. Eel AQP1 was expressed predominantly in the intestine, and the expression levels were higher in seawater eel than in freshwater eel. Immunocytochemical studies revealed intense AQP1 immunoreaction in the apical surface of columnar epithelial cells in seawater eel, in which the immunoreaction was stronger in the posterior intestine than in the anterior. In contrast, the immunoreaction was faint in the freshwater eel intestine. Preferential localization of AQP1 in the apical membrane of epithelial cells in the posterior intestine of seawater eel indicates that this region of the intestine is responsible for water absorption, and that AQP1 may act as a water entry site in the epithelial cells. PMID:12939380

  3. Elimination of oxalate by fat sand rats (Psammomys obesus): wild and laboratory-bred animals compared.

    PubMed

    Palgi, Niv; Taleisnik, Hanna; Pinshow, Berry

    2008-02-01

    Wild fat sand rats (Psammomys obesus) can feed exclusively on plants containing much oxalate, but little calcium; oxalate intake may exceed 300 mg/d, while calcium intake is approximately 30 mg/day. By contrast, for generations, laboratory bred P. obesus have been fed a low-oxalate (<100 mg/day), high-calcium (approximately 150 mg/day) rodent chow. We compared oxalate intake and excretion between wild and laboratory-bred animals, both fed the natural high-oxalate diet, to determine whether these different dietary histories are reflected in the animal's ability to eliminate dietary oxalate. Since both wild and laboratory-bred P. obesus harbor intestinal oxalate-degrading bacteria, we predicted that their oxalate intake and excretion would be similar. Indeed, we found no significant differences in oxalate intake or excretion between the groups fed either saltbush or alfalfa (p>0.05). However, due to the differences in dietary calcium intake between the two diets, in both groups only part (23-25%) of the ingested oxalate was excreted when the animals were fed the oxalate-rich saltbush, yet most (87-90%) was excreted when feeding on calcium-rich alfalfa. Thus, even after generations of feeding on a commercial low-oxalate diet, fat sand rats maintain intestinal oxalate-degrading bacteria that appear to increase in number and activity when presented with their natural diet. PMID:18187353

  4. Prediction of in vivo intestinal absorption enhancement on P-glycoprotein inhibition, from rat in situ permeability.

    PubMed

    Varma, Manthena V S; Panchagnula, Ramesh

    2005-08-01

    The purpose of this study is to determine the functional role of P-glycoprotein (P-gp) in intestinal absorption of drugs and to quantitatively predict the in vivo absorption enhancement on P-gp inhibition. In situ single-pass rat ileum permeability and aqueous solubility were measured for a set of 16 compounds. Permeability studies were also carried out in the presence of P-gp inhibitor to estimate the permeability enhancement on P-gp inhibition. A significant correlation was obtained between rat ileum permeability and the literature human intestinal absorption (HIA), F(a,human) (r = 0.891; p < 0.01). Compounds with permeability >0.2 x 10(-4) cm/s are completely absorbed; however, few practically insoluble compounds were overestimated with this relationship. Inhibition of P-gp increased the permeability (p < 0.05) of three moderately and three highly permeable compounds. Efflux inhibition ratio (EIR), the ratio of permeability due to P-gp-mediated efflux activity and passive permeability only, for these compounds was in the order of digoxin > paclitaxel > fexofenadine > quinidine > verapamil > cyclosporine. Integration of EIR with permeability versus F(a,human) predicted that modulation of P-gp has no significant effect on the absorption of highly permeable compounds (quinidine, verapamil, and cyclosporine A), while for moderately permeable compounds (digoxin, paclitaxel, and fexofenadine), P-gp profoundly influences the intestinal permeability. The in situ permeability in rat ileum may be used to predict the in vivo P-gp function and its quantitative contribution to intestinal drug absorption. Integration of the functional activity of P-gp with the characteristics of BCS may explain drug interactions and explore the possible pharmacokinetic advantage on P-gp inhibition. PMID:15986467

  5. Mass balance approaches for estimating the intestinal absorption and metabolism of peptides and analogues: theoretical development and applications

    NASA Technical Reports Server (NTRS)

    Sinko, P. J.; Leesman, G. D.; Amidon, G. L.

    1993-01-01

    A theoretical analysis for estimating the extent of intestinal peptide and peptide analogue absorption was developed on the basis of a mass balance approach that incorporates convection, permeability, and reaction. The macroscopic mass balance analysis (MMBA) was extended to include chemical and enzymatic degradation. A microscopic mass balance analysis, a numerical approach, was also developed and the results compared to the MMBA. The mass balance equations for the fraction of a drug absorbed and reacted in the tube were derived from the general steady state mass balance in a tube: [formula: see text] where M is mass, z is the length of the tube, R is the tube radius, Pw is the intestinal wall permeability, kr is the reaction rate constant, C is the concentration of drug in the volume element over which the mass balance is taken, VL is the volume of the tube, and vz is the axial velocity of drug. The theory was first applied to the oral absorption of two tripeptide analogues, cefaclor (CCL) and cefatrizine (CZN), which degrade and dimerize in the intestine. Simulations using the mass balance equations, the experimental absorption parameters, and the literature stability rate constants yielded a mean estimated extent of CCL (250-mg dose) and CZN (1000-mg dose) absorption of 89 and 51%, respectively, which was similar to the mean extent of absorption reported in humans (90 and 50%). It was proposed previously that 15% of the CCL dose spontaneously degraded systematically; however, our simulations suggest that significant CCL degradation occurs (8 to 17%) presystemically in the intestinal lumen.(ABSTRACT TRUNCATED AT 250 WORDS).

  6. Insulin down-regulates the Na+/K+ ATPase in enterocytes but increases intestinal glucose absorption.

    PubMed

    Serhan, Maya F; Kreydiyyeh, Sawsan I

    2010-06-01

    The effect of insulin on [(14)C] 3-O-methyl-d-glucose (3OMG) absorption in the rat jejunum was studied using an in situ perfusion technique. Insulin increased apical glucose entry into the cells and decreased intestinal retention suggesting that serosal glucose transport was enhanced by the hormone. This enhanced uptake was ascribed to an increase in the expression of glucose transporters as confirmed by Western blot analysis and not to a higher sodium gradient, since insulin reduced the activity and protein expression of the Na(+)/K(+) ATPase. To separate the glycemic from the insulinemic effect on glucose transport, the effect of the hormone was investigated in vitro using cultured Caco-2 cells. The cells also showed an increase in [(14)C] 3OMG uptake and intracellular glucose levels when treated with insulin and a lower Na(+)/K(+) ATPase activity. Phloretin, an inhibitor of GLUT2 was used to determine if these transporters are targeted by the hormone. The results showed that the effect of insulin on glucose uptake and intracellular glucose was still enhanced in presence of phloretin. Considering the inhibitory effect of the hormone on the Na(+)/K(+) ATPase, it was concluded that insulin acts by increasing the number of glucose transporters, a hypothesis that was confirmed by Western blot analysis. PMID:20303969

  7. Bioactive Dietary Polyphenols Inhibit Heme Iron Absorption in A Dose-Dependent Manner in Human Intestinal Caco-2 cells

    PubMed Central

    Ma, Qianyi; Kim, Eun-Young; Lindsay, Elizabeth Ann; Han, Okhee

    2011-01-01

    Although heme iron is an important form of dietary iron, its intestinal absorption mechanism remains elusive. Our previous work revealed that (?)-epigallocatechin-3-gallate (EGCG) and grape seed extract (GSE) markedly inhibited intestinal heme iron absorption by reducing the basolateral iron export in Caco-2 cells. The aims of this study were to examine whether small amounts of EGCG, GSE and green tea extract (GT) could inhibit heme iron absorption, and to test whether the inhibitory action of polyphenols could be offset by ascorbic acid. A heme-55Fe absorption study was conducted by adding various concentrations of EGCG, GSE and GT to Caco-2 cells in the absence and presence of ascorbic acid. Polyphenolic compounds significantly inhibited heme-55Fe absorption in a dose-dependent manner. The addition of ascorbic acid did not modulate the inhibitory effect of dietary polyphenols on heme iron absorption when the cells were treated with polyphenols at a concentration of 46 mg/L. However, ascorbic acid was able to offset or reverse the inhibitory effects of polyphenolic compounds when lower concentrations of polyphenols were added (? 4.6 mg/L). Ascorbic acid modulated the heme iron absorption without changing the apical heme uptake, the expression of the proteins involved in heme metabolism and basolateral iron transport, and heme oxygenase activity, indicating that ascorbic acid may enhance heme iron absorption by modulating the intracellular distribution of 55Fe. These results imply that the regular consumption of dietary ascorbic acid can easily counteract the inhibitory effects of low concentrations of dietary polyphenols on heme iron absorption but cannot counteract the inhibitory actions of high concentrations of polyphenols. PMID:22417433

  8. Ex Vivo and In Situ Evaluation of 'Dispelling-Wind' Chinese Medicine Herb-Drugs on Intestinal Absorption of Chlorogenic Acid.

    PubMed

    Zhai, Lixiang; Shi, Jun; Xu, Weitong; Heinrich, Michael; Wang, Jianying; Deng, Wenji

    2015-12-01

    This study aims to investigate the additive or synergistic effects and mechanism of intestinal absorption of extracts from two commonly used 'dispelling-wind' TCM botanical drugs [roots of Angelica dahurica (Hoffm.) Benth. & Hook. f. ex Franch. & Sav. (RAD) and Saposhnikovia divaricata (Turcz.) Schischk. (RSD)] using chlorogenic acid as a marker substance. Ex vivo everted intestinal sac and in situ single pass perfusion methods using rats were employed to investigate the effects of two TCM botanical drugs extracts on the intestinal absorption of chlorogenic acid. Both the extracts of RAD and RSD showed synergistic properties on the intestinal absorption of chlorogenic acid. The verapamil (a P-gp inhibitor) and intestinal dysbacteriosis model induced by norfloxacin increased the Papp and Ka of intestinal absorption of chlorogenic acid. These synergistic effects on intestinal absorption in a rat model can be correlated with the inhibition of P-gp and regulation of gut microbiota. This experimental approach has helped to better understand changes in the absorption of chlorogenic acid under different conditions. Copyright 2015 John Wiley & Sons, Ltd. PMID:26514546

  9. Human and mouse tissue-engineered small intestine both demonstrate digestive and absorptive function.

    PubMed

    Grant, Christa N; Mojica, Salvador Garcia; Sala, Frederic G; Hill, J Ryan; Levin, Daniel E; Speer, Allison L; Barthel, Erik R; Shimada, Hiroyuki; Zachos, Nicholas C; Grikscheit, Tracy C

    2015-04-15

    Short bowel syndrome (SBS) is a devastating condition in which insufficient small intestinal surface area results in malnutrition and dependence on intravenous parenteral nutrition. There is an increasing incidence of SBS, particularly in premature babies and newborns with congenital intestinal anomalies. Tissue-engineered small intestine (TESI) offers a therapeutic alternative to the current standard treatment, intestinal transplantation, and has the potential to solve its biggest challenges, namely donor shortage and life-long immunosuppression. We have previously demonstrated that TESI can be generated from mouse and human small intestine and histologically replicates key components of native intestine. We hypothesized that TESI also recapitulates native small intestine function. Organoid units were generated from mouse or human donor intestine and implanted into genetically identical or immunodeficient host mice. After 4 wk, TESI was harvested and either fixed and paraffin embedded or immediately subjected to assays to illustrate function. We demonstrated that both mouse and human tissue-engineered small intestine grew into an appropriately polarized sphere of intact epithelium facing a lumen, contiguous with supporting mesenchyme, muscle, and stem/progenitor cells. The epithelium demonstrated major ultrastructural components, including tight junctions and microvilli, transporters, and functional brush-border and digestive enzymes. This study demonstrates that tissue-engineered small intestine possesses a well-differentiated epithelium with intact ion transporters/channels, functional brush-border enzymes, and similar ultrastructural components to native tissue, including progenitor cells, whether derived from mouse or human cells. PMID:25573173

  10. Dietary glutamine supplementation effects on amino acid metabolism, intestinal nutrient absorption capacity and antioxidant response of gilthead sea bream (Sparus aurata) juveniles.

    PubMed

    Coutinho, F; Castro, C; Rufino-Palomares, E; Ordez-Grande, B; Gallardo, M A; Oliva-Teles, A; Peres, H

    2016-01-01

    A study was undertaken to evaluate dietary glutamine supplementation effects on gilthead sea bream performance, intestinal nutrient absorption capacity, hepatic and intestinal glutamine metabolism and oxidative status. For that purpose gilthead sea bream juveniles (mean weight 13.0g) were fed four isolipidic (18% lipid) and isonitrogenous (43% protein) diets supplemented with 0, 0.5, 1 and 2% glutamine for 6weeks. Fish performance, body composition and intestinal nutrient absorption capacity were not affected by dietary glutamine levels. Hepatic and intestinal glutaminase (GlNase), glutamine synthetase (GSase), alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase activities were also unaffected by dietary glutamine supplementation. In the intestine GlNase activity was higher and GSase/GlNase ratio was two-fold lower than in the liver, suggesting a higher use of glutamine for energy production by the intestine than by the liver. The liver showed higher catalase and glucose-6-phosphate dehydrogenase activities, while the intestine presented higher glutathione peroxidase and glutathione reductase activities and oxidised glutathione content, which seems to reveal a higher glutathione dependency of the intestinal antioxidant response. Total and reduced glutathione contents in liver and intestine and superoxide dismutase activity in the intestine were enhanced by dietary glutamine, though lipid peroxidation values were not affected. Overall, differences between liver and intestine glutamine metabolism and antioxidant response were identified and the potential of dietary glutamine supplementation to gilthead sea bream's antioxidant response was elucidated. PMID:26424608

  11. NPC1L1 is a key regulator of intestinal vitamin K absorption and a modulator of warfarin therapy.

    PubMed

    Takada, Tappei; Yamanashi, Yoshihide; Konishi, Kentaro; Yamamoto, Takehito; Toyoda, Yu; Masuo, Yusuke; Yamamoto, Hideaki; Suzuki, Hiroshi

    2015-02-18

    Vitamin K (VK) is a micronutrient that facilitates blood coagulation. VK antagonists, such as warfarin, are used in the clinic to prevent thromboembolism. Because VK is not synthesized in the body, its intestinal absorption is crucial for maintaining whole-body VK levels. However, the molecular mechanism of this absorption is unclear. We demonstrate that Niemann-Pick C1-like 1 (NPC1L1) protein, a cholesterol transporter, plays a central role in intestinal VK uptake and modulates the anticoagulant effect of warfarin. In vitro studies using NPC1L1-overexpressing intestinal cells and in vivo studies with Npc1l1-knockout mice revealed that intestinal VK absorption is NPC1L1-dependent and inhibited by ezetimibe, an NPC1L1-selective inhibitor clinically used for dyslipidemia. In addition, in vivo pharmacological studies demonstrated that the coadministration of ezetimibe and warfarin caused a reduction in hepatic VK levels and enhanced the pharmacological effect of warfarin. Adverse events caused by the coadministration of ezetimibe and warfarin were rescued by oral VK supplementation, suggesting that the drug-drug interaction effects observed were the consequence of ezetimibe-mediated VK malabsorption. This mechanism was supported by a retrospective evaluation of clinical data showing that, in more than 85% of warfarin-treated patients, the anticoagulant activity was enhanced by cotreatment with ezetimibe. Our findings provide insight into the molecular mechanism of VK absorption. This new drug-drug interaction mechanism between ezetimibe (a cholesterol transport inhibitor) and warfarin (a VK antagonist and anticoagulant) could inform clinical care of patients on these medications, such as by altering the kinetics of essential, fat-soluble vitamins. PMID:25696002

  12. Evaluation of a single-pass intestinal-perfusion method in rat for the prediction of absorption in man.

    PubMed

    Salphati, L; Childers, K; Pan, L; Tsutsui, K; Takahashi, L

    2001-07-01

    Prediction of the fraction of dose absorbed from the intestine (Fa) in man is essential in the early drug discovery stage. In-vitro assays in Caco-2 and MDCK cells are routinely used for that purpose, and their predictive value has been reported. However, in-situ techniques might provide a more accurate estimation of Fa. In this study, we evaluated a single-pass intestinal-perfusion (SPIP) method in the rat for its use in the prediction of absorption in man and compared it with a previous report using cell-based assays. Effective permeability coefficients (Peff) were determined in rats for 14 compounds, and ranged from 0.043x 10(-4) cm s(-1) to 1.67 x 10(-4) cm s(-1). These values strongly correlated (r2 = 0.88) with reported Peff values for man. In addition, the Spearman rank correlation coefficient calculated for in-situ-derived Peff and absorption in man was 0.92 while for the previously tested in-vitro Caco-2 and MDCK systems vs absorption in man, the correlation coefficients were 0.61 and 0.59, respectively. SPIP provided a better prediction of human absorption than the cell-based assays. This method, although time consuming, could be used as a secondary test for studying the mechanisms governing the absorption of new compounds, and for predicting more accurately the fraction absorbed in man. PMID:11480535

  13. PTHrP regulates water absorption and aquaporin expression in the intestine of the marine sea bream (Sparus aurata, L.).

    PubMed

    Carvalho, Edison S M; Gregrio, Slvia F; Canrio, Adelino V M; Power, Deborah M; Fuentes, Juan

    2015-03-01

    Water ingestion by drinking is fundamental for ion homeostasis in marine fish. However, the fluid ingested requires processing to allow net water absorption in the intestine. The formation of luminal carbonate aggregates impacts on calcium homeostasis and requires epithelial HCO3(-) secretion to enable water absorption. In light of its endocrine importance in calcium handling and the indication of involvement in HCO3(-) secretion the present study was designed to expose the role of the parathyroid hormone-related protein (PTHrP) in HCO3(-) secretion, water absorption and the regulation of aqp1 gene expression in the anterior intestine of the sea bream. HCO3(-) secretion rapidly decreased when PTHrP(1-34) was added to anterior intestine of the sea bream mounted in Ussing chambers. The effect achieved a maximum inhibition of 60% of basal secretion rates, showing a threshold effective dose of 0.1 ng ml(-1) compatible with reported plasma values of PTHrP. When applied in combination with the adenylate cyclase inhibitor (SQ 22.536, 100 ?mol l(-1)) or the phospholipase C inhibitor (U73122, 10 ?mol l(-1)) the effect of PTHrP(1-34) on HCO3(-) secretion was reduced by about 50% in both cases. In parallel, bulk water absorption measured in intestinal sacs was sensitive to inhibition by PTHrP. The inhibitory action conforms to a typical dose-response curve in the range of 0.1-1000 ng ml(-1), achieves a maximal effect of 60-65% inhibition from basal rates and shows threshold significant effects at hormone levels of 0.1 ng ml(-1). The action of PTHrP in water absorption was completely abolished in the presence of the adenylate cyclase inhibitor (SQ 22.536, 100 ?mol l(-1)) and was insensitive to the phospholipase C inhibitor (U73122, 10 ?mol l(-1)). In vivo injections of PTHrP(1-34) or the PTH/PTHrP receptor antagonist PTHrP(7-34) evoked respectively, a significant decrease or increase of aqp1ab, but not aqp1a. Overall the present results suggest that PTHrP acts as a key regulator of carbonate aggregate formation in the intestine of marine fish via its actions on water absorption, calcium regulation and HCO3(-) secretion. PMID:25562629

  14. The role of Niemann-Pick C1 Like 1 (NPC1L1) in intestinal sterol absorption

    PubMed Central

    Turley, Stephen D.

    2008-01-01

    The absorption of cholesterol by the proximal small intestine represents a major pathway for the entry of cholesterol into the body pools. This cholesterol is derived primarily from the bile and the diet. In adult humans, typically several hundred milligrams of cholesterol reach the liver from the intestine daily, with the potential to impact the plasma low density lipoprotein-cholesterol (LDL-C) concentration. There are three main phases involved in cholesterol absorption. The first occurs intraluminally and culminates in micellar solubilization of unesterified cholesterol which facilitates its movement up to the brush border membrane (BBM) of the enterocyte. The second phase involves the transport of cholesterol across the BBM by Niemann-Pick C1 Like-1 (NPC1L1), while the third phase entails a series of steps within the enterocyte involving the esterification of cholesterol and its incorporation, along with other lipids and apolipoprotein B48 (apo B48), into nascent chylomicrons (CM). The discovery of the role of NPC1L1 in intestinal sterol transport occurred directly as a consequence of efforts to identify the molecular target of ezetimibe, a novel, potent, and specific inhibitor of sterol absorption that is now widely used in combination therapy with statins for the management of hypercholesterolemia in the general population. Some aspects of the role of NPC1L1 in cholesterol absorption nevertheless remain controversial and are the subject of ongoing research. For example, one report suggests that NPC1L1 is located not in the plasma membrane but intracellularly where it is thought to be involved in cytosolic trafficking of cholesterol, while another concludes that a protein other than NPC1L1 is responsible for the high affinity binding of cholesterol on intestinal BBM. However, other new studies which show that the in vivo responsiveness of different species to ezetimibe correlates with NPC1L1 binding affinity further support the widely held belief that NPC1L1 does facilitate sterol uptake by the enterocyte and is the target of ezetimibe. Added to this is the unequivocal finding that deletion of the gene for NPC1L1 in mice results in a near complete prevention of cholesterol absorption and an accelerated rate of fecal neutral sterol excretion. In summary, the development of ezetimibe and the identification of NPC1L1 as a key player in sterol absorption have taken research on the molecular control of this pathway to an exciting new level. From this it is hoped that we will now be able to determine more precisely what effect, if any, other classes of lipid lowering agents, particularly the statins, might exert on the amount of intestinal cholesterol reaching the liver. PMID:18496605

  15. Surface-modified solid lipid nanoparticles for oral delivery of docetaxel: enhanced intestinal absorption and lymphatic uptake

    PubMed Central

    Cho, Hyun-Jong; Park, Jin Woo; Yoon, In-Soo; Kim, Dae-Duk

    2014-01-01

    Docetaxel is a potent anticancer drug, but development of an oral formulation has been hindered mainly due to its poor oral bioavailability. In this study, solid lipid nanoparticles (SLNs) surface-modified by Tween 80 or D-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS 1000) were prepared and evaluated in terms of their feasibility as oral delivery systems for docetaxel. Tween 80-emulsified and TPGS 1000-emulsified tristearin-based lipidic nanoparticles were prepared by a solvent-diffusion method, and their particle size distribution, zeta potential, drug loading, and particle morphology were characterized. An in vitro release study showed a sustained-release profile of docetaxel from the SLNs compared with an intravenous docetaxel formulation (Taxotere®). Tween 80-emulsified SLNs showed enhanced intestinal absorption, lymphatic uptake, and relative oral bioavailability of docetaxel compared with Taxotere in rats. These results may be attributable to the absorption-enhancing effects of the tristearin nanoparticle. Moreover, compared with Tween 80-emulsified SLNs, the intestinal absorption and relative oral bioavailability of docetaxel in rats were further improved in TPGS 1000-emulsified SLNs, probably due to better inhibition of drug efflux by TPGS 1000, along with intestinal lymphatic uptake. Taken together, it is worth noting that these surface-modified SLNs may serve as efficient oral delivery systems for docetaxel. PMID:24531717

  16. Does 'sugar' permeability reflect macromolecular absorption? A comparison of the gastro-intestinal uptake of lactulose and beta-lactoglobulin in the neonatal guinea pig.

    PubMed

    Weaver, L T; Coombs, R R

    1988-01-01

    Intestinal closure to cow's milk beta-lactoglobulin occurs within 6 days of birth in the guinea pig. Passive intestinal permeability to lactulose persists through the suckling period. The uptake of small water-soluble markers does not reflect macromolecular absorption, and has no place in the measurement of immunologic protein handling by the gut. PMID:3338854

  17. DETERMINATION OF OXALATE ION DOPANT LEVEL IN POLYPYRROLE USING FT-IR

    PubMed Central

    Benally, Kristal J.; GreyEyes, Shawn D.; McKenzie, Jason T.

    2014-01-01

    A pellet method using standard addition and FT-IR was used to estimate oxalate ion doping levels in electrosynthesized polypyrrole. The method is useful for materials where removal of analyte from an insoluble material is problematic. Here, electrosynthesized oxalate doped polypyrrole is dispersed in potassium bromide. Spikes of sodium oxalate are added and the mixtures pressed into pellets. The oxalate carbonyl absorption peak is then used to quantify the amount of oxalate present in the polypyrrole. The mass fraction of oxalate dopant in polypyrrole was determined to be 0.4 0.1 % and coincides with the original synthesis solution composition. PMID:25598749

  18. Intestinal cholesterol absorption inhibitor ezetimibe added to cholestyramine for sitosterolemia and xanthomatosis.

    PubMed

    Salen, Gerald; Starc, Thomas; Sisk, Christine McCrary; Patel, Shailendra B

    2006-05-01

    Sitosterolemia is a rare, recessively inherited disorder characterized by increased absorption and delayed removal of noncholesterol sterols, which is associated with accelerated atherosclerosis, premature coronary artery disease, hemolysis, and xanthomatosis. Treatments include low-sterol diet and bile salt-binding resins; however, these often do not reduce the xanthomatosis. We examined the effects of the intestinal cholesterol/phytosterol transporter inhibitor ezetimibe added to cholestyramine in a young female patient with sitosterolemia and associated xanthomatosis. The patient was an 11-year-old female with sitosterolemia presenting with prominent xanthomas in the subcutaneous tissue of both elbows who was receiving treatment with cholestyramine 2 g once daily. Bilateral carotid bruits were audible, and a grade II/VI systolic murmur was detected at the left upper sternal border. She also had a low platelet count of 111,000/microL. Ezetimibe 10 mg once daily was added to the patient's ongoing cholestyramine regimen, and she was evaluated for 1 year. The patient followed an unrestricted diet during the 1-year treatment period. After 1 year of treatment with ezetimibe added to ongoing cholestyramine therapy, the patient's plasma sitosterol and campesterol levels decreased by approximately 50%. Her carotid bruits completely resolved, her systolic murmur diminished, and her platelet count rose to 268,000/microL. More remarkably, the tuberous xanthomas on her elbows had completely regressed. Ezetimibe added to ongoing low-dose cholestyramine therapy led to a marked improvement in plasma sterol concentrations, complete regression of xanthomatosis, resolution of carotid bruits, and improvement in cardiac murmur in a young female patient with sitosterolemia. PMID:16697747

  19. Predicting human intestinal absorption of diverse chemicals using ensemble learning based QSAR modeling approaches.

    PubMed

    Basant, Nikita; Gupta, Shikha; Singh, Kunwar P

    2016-04-01

    Human intestinal absorption (HIA) of the drugs administered through the oral route constitutes an important criterion for the candidate molecules. The computational approach for predicting the HIA of molecules may potentiate the screening of new drugs. In this study, ensemble learning (EL) based qualitative and quantitative structure-activity relationship (SAR) models (gradient boosted tree, GBT and bagged decision tree, BDT) have been established for the binary classification and HIA prediction of the chemicals, using the selected molecular descriptors. The structural diversity of the chemicals and the nonlinear structure in the considered data were tested by the similarity index and Brock-Dechert-Scheinkman statistics. The external predictive power of the developed SAR models was evaluated through the internal and external validation procedures recommended in the literature. All the statistical criteria parameters derived for the performance of the constructed SAR models were above their respective thresholds suggesting for their robustness for future applications. In complete data, the qualitative SAR models rendered classification accuracy of >99%, while the quantitative SAR models yielded correlation (R(2)) of >0.91 between the measured and predicted HIA values. The performances of the EL-based SAR models were also compared with the linear models (linear discriminant analysis, LDA and multiple linear regression, MLR). The GBT and BDT SAR models performed better than the LDA and MLR methods. A comparison of our models with the previously reported QSARs for HIA prediction suggested for their better performance. The results suggest for the appropriateness of the developed SAR models to reliably predict the HIA of structurally diverse chemicals and can serve as useful tools for the initial screening of the molecules in the drug development process. PMID:26881740

  20. Evaluation of Oxalate Concentration in the U.S. Spinach Germplasm Collection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In addition to its high nutrient content, spinach (Spinacia oleracea L.) is also known to have greater amount of oxalic acid than most crops. Oxalic acid may form crystals with minerals to reduce the bioavailability and absorption of calcium and iron in diets, and calcium oxalate may deposit in the...

  1. Soybean β-Conglycinin Induces Inflammation and Oxidation and Causes Dysfunction of Intestinal Digestion and Absorption in Fish

    PubMed Central

    Zhang, Jin-Xiu; Guo, Lin-Ying; Feng, Lin; Jiang, Wei-Dan; Kuang, Sheng-Yao; Liu, Yang; Hu, Kai; Jiang, Jun; Li, Shu-Hong; Tang, Ling; Zhou, Xiao-Qiu

    2013-01-01

    β-conglycinin has been identified as one of the major feed allergens. However, studies of β-conglycinin on fish are scarce. This study investigated the effects of β-conglycinin on the growth, digestive and absorptive ability, inflammatory response, oxidative status and gene expression of juvenile Jian carp (Cyprinus carpio var. Jian) in vivo and their enterocytes in vitro. The results indicated that the specific growth rate (SGR), feed intake, and feed efficiency were reduced by β-conglycinin. In addition, activities of trypsin, chymotrypsin, lipase, creatine kinase, Na+,K+-ATPase and alkaline phosphatase in the intestine showed similar tendencies. The protein content of the hepatopancreas and intestines, and the weight and length of the intestines were all reduced by β-conglycinin. β-conglycinin increased lipid and protein oxidation in the detected tissues and cells. However, β-conglycinin decreased superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GR) activities and glutathione (GSH) content in the intestine and enterocytes. Similar antioxidant activity in the hepatopancreas was observed, except for GST. The expression of target of rapamycin (TOR) gene was reduced by β-conglycinin. Furthermore, mRNA levels of interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β) genes were increased by β-conglycinin. However, β-conglycinin increased CuZnSOD, MnSOD, CAT, and GPx1b gene expression. In conclusion, this study indicates that β-conglycinin induces inflammation and oxidation, and causes dysfunction of intestinal digestion and absorption in fish, and finally reduces fish growth. The results of this study provide some information to the mechanism of β-conglycinin-induced negative effects. PMID:23520488

  2. Effect of resistant and digestible starch on intestinal absorption of calcium, iron, and zinc in infant pigs.

    PubMed

    Morais, M B; Feste, A; Miller, R G; Lifschitz, C H

    1996-05-01

    The first nonmilk foods that are given to infants contain high levels of starch, a fraction of which is resistant to enzyme hydrolysis. Incomplete digestion of starch may interfere with the absorption of certain minerals. A fraction of dietary starch which is resistant to in vitro enzymatic hydrolysis has been termed resistant starch. The aim of this study was to compare the intestinal apparent absorption of calcium, phosphorus, iron, and zinc in the presence of either resistant or digestible starch. Twelve 7-10-d-old piglets were fitted with a T-tube inserted into the intestine approximately 3 m distal to the duodenum. Animals received in random order 200 mL of a test meal of cooked, cooled, high amylose corn starch (16.4% resistant starch), or cooked rice starch (digestible starch) administered by an orogastric tube. Both meals contained the same amount of calcium, phosphorus, iron, and zinc. The test meal also contained tracer amounts of 59Fe and 65Zn, as well as polyethylene glycol 3350, as a nonabsorbable marker. Intestinal apparent absorption of starch was greater the meal with digestible starch (71.0 +/- 17.0%) than after the meal with resistant starch (49.2 +/- 10.3) (p < 0.001). After feeding the meals with resistant and digestible starch, mineral apparent absorption was, respectively: calcium, 40.2 +/- 11.8% versus 28.1 +/- 16.4% (p < 0.05); phosphorus, 73.2 +/- 14.0% versus 67.8 +/- 18% (NS); iron, 24.1 +/- 12.2% versus 12.6 +/- 10.6% (p < 0.01), and zinc, 35.0 +/- 13.0% versus 30.6 +/- 8.22% (NS). In conclusion, a meal containing 16.4% resistant starch resulted in a greater apparent absorption of calcium and iron compared with a completely digestible starch meal. If this finding holds true for the whole bowel, administration of resistant starches could have a positive effect on intestinal calcium and iron absorption. PMID:8726244

  3. Increased intestinal vitamin D receptor in genetic hypercalciuric rats. A cause of intestinal calcium hyperabsorption.

    PubMed

    Li, X Q; Tembe, V; Horwitz, G M; Bushinsky, D A; Favus, M J

    1993-02-01

    In humans, familial or idiopathic hypercalciuria (IH) is a common cause of hypercalciuria and predisposes to calcium oxalate nephrolithiasis. Intestinal calcium hyperabsorption is a constant feature of IH and may be due to either a vitamin D-independent process in the intestine, a primary overproduction of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], or a defect in renal tubular calcium reabsorption. Selective breeding of spontaneously hypercalciuric male and female Sprague-Dawley rats resulted in offspring with hypercalciuria, increased intestinal calcium absorption, and normal serum 1,25(OH)2D3 levels. The role of the vitamin D receptor (VDR) in the regulation of intestinal calcium absorption was explored in 10th generation male genetic IH rats and normocalciuric controls. Urine calcium excretion was greater in IH rats than controls (2.9 +/- 0.3 vs. 0.7 +/- 0.2 mg/24 h, P < 0.001). IH rat intestine contained twice the abundance of VDR compared with normocalciuric controls (536 +/- 73 vs. 243 +/- 42 nmol/mg protein, P < 0.001), with no difference in the affinity of the receptor for its ligand. Comparable migration of IH and normal intestinal VDR on Western blots and of intestinal VDR mRNA by Northern analysis suggests that the VDR in IH rat intestine is not due to large deletion or addition mutations of the wild-type VDR. IH rat intestine contained greater concentrations of vitamin D-dependent calbindin 9-kD protein. The present studies strongly suggest that increased intestinal VDR number and normal levels of circulating 1,25(OH)2D3 result in increased functional VDR-1,25(OH)2D3 complexes, which exert biological actions in enterocytes to increase intestinal calcium transport. Intestinal calcium hyperabsorption in the IH rat may be the first example of a genetic disorder resulting from a pathologic increase in VDR. PMID:8381825

  4. Mechanisms Involved in Vitamin D Mediated Intestinal Calcium Absorption and in Non-Classical Actions of Vitamin D

    PubMed Central

    Christakos, Sylvia; Dhawan, Puneet; Ajibade, Dare; Benn, Bryan S.; Feng, Jingjing; Joshi, Sneha S.

    2010-01-01

    Recent studies in our laboratory using calbindin-D9k null mutant mice as well as mice lacking the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) inducible epithelial calcium channel TRPV6 provide evidence for calbindin-D9k and TRPV6 independent regulation of active intestinal calcium absorption. These findings suggest that in the knock out (KO) mice there is compensation by another calcium channel or protein and that other novel factors are involved in 1,25(OH)2D3 mediated active intestinal calcium absorption. In addition, 1,25(OH)2D3 mediated paracellular transport of calcium may have contributed to the normalization of serum calcium in the null mutant mice. 1,25(OH)2D3 downregulates cadherin-17 and upregulates claudin-2 and claudin-12 in the intestine, suggesting that 1,25(OH)2D3, by regulating these epithelial cell junction proteins, can route calcium through the paracellular path. With regard to non-classical actions, 1,25(OH)2D3 has been reported to inhibit the proliferation of a number of malignant cells and to regulate adaptive as well as innate immunity. This article will review new developments related to the function and regulation of vitamin D target proteins in classical and non-classical vitamin D target tissues that have provided novel insight into mechanisms of vitamin D action. PMID:20214989

  5. Contribution of solvent drag through intercellular junctions to absorption of nutrients by the small intestine of the rat.

    PubMed

    Pappenheimer, J R; Reiss, K Z

    1987-01-01

    The lumen of the small intestine in anesthetized rats was recirculated with 50 ml perfusion fluid containing normal salts, 25 mM glucose and low concentrations of hydrophilic solutes ranging in size from creatinine (mol wt 113) to Inulin (mol wt 5500). Ferrocyanide, a nontoxic, quadrupally charged anion was not absorbed; it could therefore be used as an osmotically active solute with reflection coefficient of 1.0 to adjust rates of fluid absorption, Jv, and to measure the coefficient of osmotic flow, Lp. The clearances from the perfusion fluid of all other test solutes were approximately proportional to Jv. From Lp and rates of clearances as a function of Jv and molecular size we estimate (a) the fraction of fluid absorption which passes paracellularly (approx. 50%), (b) coefficients of solvent drag of various solutes within intercellular junctions, (c) the equivalent pore radius of intercellular junctions (50 A) and their cross sectional area per unit path length (4.3 cm per cm length of intestine). Glucose absorption also varied as a function of Jv. From this relationship and the clearances of inert markers we calculate the rate of active transport of glucose, the amount of glucose carried paracellularly by solvent drag or back-diffusion at any given Jv and luminal glucose concentration and the concentration of glucose in the absorbate. The results indicate that solvent drag through paracellular channels is the principal route for intestinal transport of glucose or amino acids at physiological rates of fluid absorption and concentration. In the absence of luminal glucose the rate of fluid absorption and the clearances of all inert hydrophilic solutes were greatly reduced. It is proposed that Na-coupled transport of organic solutes from lumen to intercellular spaces provides the principal osmotic force for fluid absorption and triggers widening of intercellular junctions, thus promoting bulk absorption of nutrients by solvent drag. Further evidence for regulation of channel width is provided in accompanying papers on changes in electrical impedance and ultrastructure of junctions during Na-coupled solute transport. PMID:3430569

  6. [Application of a potential difference to evaluate the absorptive faculty in the small intestine. The changes in potential differences, uptake of sugars and amino acid and electrical transmural resistance in injured intestine].

    PubMed

    Ohkohchi, N; Kasai, M; Ohi, R; Igarashi, Y; Naganuma, H

    1985-12-01

    Since there was no effective method for evaluating the absorptive capacity in the small intestine, we devised a test for evaluating the absorptive capacity with potential difference. Potential difference is provided by electrical resistance of intestine and flux of substances. Previously, we reported that the electrical resistance of the small intestine in the guinea pigs had changed very slightly throughout the entire life, and that sugars and neutral amino acids have been transported completely activity from the birth. In addition, potential difference of glycyl-glycine reflected the uptake of the intestine after the period of weanling. We experimentally studied the electrical transmural resistance and absorptive capacity of the small intestine with various damages to the small intestine by 5-Fu, ischemia and long fasting. Histologically, swelling of nucleus, intracellular edema, dilatation of capillary vein, dropping of epithelial cells, etc., were seen in these models. But the electrical resistance was slightly changed in 10% of the cases. Potential differences by sugars or neutral amino acid ingestion accurately reflected their real flux. These facts suggest that the potential differences deficiently reflect the uptake of sugars and amino acids in the small intestine under conditions with malabsorption. PMID:4088187

  7. Intestinal absorption, organ distribution, and urinary excretion of the rare sugar D-psicose

    PubMed Central

    Tsukamoto, Ikuko; Hossain, Akram; Yamaguchi, Fuminori; Hirata, Yuko; Dong, Youyi; Kamitori, Kazuyo; Sui, Li; Nonaka, Machiko; Ueno, Masaki; Nishimoto, Kazuyuki; Suda, Hirofumi; Morimoto, Kenji; Shimonishi, Tsuyoshi; Saito, Madoka; Song, Tao; Konishi, Ryoji; Tokuda, Masaaki

    2014-01-01

    Background The purpose of this study was to evaluate intestinal absorption, organ distribution, and urinary elimination of the rare sugar D-psicose, a 3-carbon stereoisomer of D-fructose that is currently being investigated and which has been found to be strongly effective against hyperglycemia and hyperlipidemia. Methods This study was performed using radioactive D-psicose, which was synthesized enzymatically from radioactive D-allose. Concentrations in whole blood, urine, and organs were measured at different time points until 2 hours after both oral and intravenous administrations and 7 days after a single oral administration (100 mg/kg body weight) to Wistar rats. Autoradiography was also performed by injecting 100 mg/kg body weight of 14C-labeled D-psicose or glucose intravenously to C3H mice. Results Following oral administration, D-psicose easily moved to blood. The maximum blood concentration (48.515.6 ?g/g) was observed at 1 hour. Excretion to urine was 20% within 1 hour and 33% within 2 hours. Accumulation to organs was detected only in the liver. Following intravenous administration, blood concentration was decreased with the half-life=57 minutes, and the excretion to urine was up to almost 50% within 1 hour. Similarly to the results obtained with oral administration, accumulation to organs was detected only in the liver. Seven days after the single-dose oral administration, the remaining amounts in the whole body were less than 1%. Autoradiography of mice showed results similar to those in rats. High signals of 14C-labeled D-psicose were observed in liver, kidney, and bladder. Interestingly, no accumulation of D-psicose was observed in the brain. Conclusion D-psicose was absorbed well after oral administration and eliminated rapidly after both oral and intravenous administrations, with short duration of action. The study provides valuable pharmacokinetic data for further drug development of D-psicose. Because the findings were mainly based on animal study, it is necessary to implement human trials to study the metabolism pathway, which would give an important guide for human intake and food application of D-psicose. PMID:25378908

  8. Modulation of NaCl absorption by [HCO3?] in the marine teleost intestine is mediated by soluble adenylyl cyclase

    PubMed Central

    Levin, Lonny R.; Buck, Jochen; Grosell, Martin

    2010-01-01

    Intestinal HCO3? secretion and NaCl absorption are essential for counteracting dehydration in marine teleost fish. We investigated how these two processes are coordinated in toadfish. HCO3? stimulated a luminal positive short-circuit current (Isc) in intestine mounted in Ussing chamber, bathed with the same saline solution on the external and internal sides of the epithelium. The Isc increased proportionally to the [HCO3?] in the bath up to 80 mM NaHCO3, and it did not occur when NaHCO3 was replaced with Na+-gluconate or with NaHCO3 in Cl?-free saline. HCO3? (20 mM) induced a ?2.5-fold stimulation of Isc, and this [HCO3?] was used in all subsequent experiments. The HCO3?-stimulated Isc was prevented or abolished by apical application of 10 ?M bumetanide (a specific inhibitor of NKCC) and by 30 ?M 4-catechol estrogen [CE; an inhibitor of soluble adenylyl cyclase (sAC)]. The inhibitory effects of bumetanide and CE were not additive. The HCO3?-stimulated Isc was prevented by apical bafilomycin (1 ?M) and etoxolamide (1 mM), indicating involvement of V-H+-ATPase and carbonic anhydrases, respectively. Immunohistochemistry and Western blot analysis confirmed the presence of an NKCC2-like protein in the apical membrane and subapical area of epithelial intestinal cells, of Na+/K+-ATPase in basolateral membranes, and of an sAC-like protein in the cytoplasm. We propose that sAC regulates NKCC activity in response to luminal HCO3?, and that V-H+-ATPase and intracellular carbonic anhydrase are essential for transducing luminal HCO3? into the cell by CO2/HCO3? hydration/dehydration. This mechanism putatively coordinates HCO3? secretion with NaCl and water absorption in toadfish intestine. PMID:20410468

  9. Na+-d-glucose Cotransporter SGLT1 is Pivotal for Intestinal Glucose Absorption and Glucose-Dependent Incretin Secretion

    PubMed Central

    Gorboulev, Valentin; Schürmann, Annette; Vallon, Volker; Kipp, Helmut; Jaschke, Alexander; Klessen, Dirk; Friedrich, Alexandra; Scherneck, Stephan; Rieg, Timo; Cunard, Robyn; Veyhl-Wichmann, Maike; Srinivasan, Aruna; Balen, Daniela; Breljak, Davorka; Rexhepaj, Rexhep; Parker, Helen E.; Gribble, Fiona M.; Reimann, Frank; Lang, Florian; Wiese, Stefan; Sabolic, Ivan; Sendtner, Michael; Koepsell, Hermann

    2012-01-01

    To clarify the physiological role of Na+-d-glucose cotransporter SGLT1 in small intestine and kidney, Sglt1−/− mice were generated and characterized phenotypically. After gavage of d-glucose, small intestinal glucose absorption across the brush-border membrane (BBM) via SGLT1 and GLUT2 were analyzed. Glucose-induced secretion of insulinotropic hormone (GIP) and glucagon-like peptide 1 (GLP-1) in wild-type and Sglt1−/− mice were compared. The impact of SGLT1 on renal glucose handling was investigated by micropuncture studies. It was observed that Sglt1−/− mice developed a glucose-galactose malabsorption syndrome but thrive normally when fed a glucose-galactose–free diet. In wild-type mice, passage of d-glucose across the intestinal BBM was predominantly mediated by SGLT1, independent the glucose load. High glucose concentrations increased the amounts of SGLT1 and GLUT2 in the BBM, and SGLT1 was required for upregulation of GLUT2. SGLT1 was located in luminal membranes of cells immunopositive for GIP and GLP-1, and Sglt1−/− mice exhibited reduced glucose-triggered GIP and GLP-1 levels. In the kidney, SGLT1 reabsorbed ∼3% of the filtered glucose under normoglycemic conditions. The data indicate that SGLT1 is 1) pivotal for intestinal mass absorption of d-glucose, 2) triggers the glucose-induced secretion of GIP and GLP-1, and 3) triggers the upregulation of GLUT2. PMID:22124465

  10. Lactobacillus acidophilus ATCC 4356 prevents atherosclerosis via inhibition of intestinal cholesterol absorption in apolipoprotein E-knockout mice.

    PubMed

    Huang, Ying; Wang, Jinfeng; Quan, Guihua; Wang, Xiaojun; Yang, Longfei; Zhong, Lili

    2014-12-01

    The objective of this study was to investigate the effect of Lactobacillus acidophilus ATCC 4356 on the development of atherosclerosis in apolipoprotein E-knockout (ApoE(-/-)) mice. Eight-week-old ApoE(-/-) mice were fed a Western diet with or without L. acidophilus ATCC 4356 daily for 16 weeks. L. acidophilus ATCC 4356 protected ApoE(-/-) mice from atherosclerosis by reducing their plasma cholesterol levels from 923 44 to 581 18 mg/dl, likely via a marked decrease in cholesterol absorption caused by modulation of Niemann-Pick C1-like 1 (NPC1L1). In addition, suppression of cholesterol absorption induced reverse cholesterol transport (RCT) in macrophages through the peroxisome proliferator-activated receptor/liver X receptor (PPAR/LXR) pathway. Fecal lactobacillus and bifidobacterium counts were significantly (P < 0.05) higher in the L. acidophilus ATCC 4356 treatment groups than in the control groups. Furthermore, L. acidophilus ATCC 4356 was detected in the rat small intestine, colon, and feces during the feeding trial. The bacterial levels remained high even after the administration of lactic acid bacteria had been stopped for 2 weeks. These results suggest that administration of L. acidophilus ATCC 4356 can protect against atherosclerosis through the inhibition of intestinal cholesterol absorption. Therefore, L. acidophilus ATCC 4356 may be a potential therapeutic material for preventing the progression of atherosclerosis. PMID:25261526

  11. Lactobacillus acidophilus ATCC 4356 Prevents Atherosclerosis via Inhibition of Intestinal Cholesterol Absorption in Apolipoprotein E-Knockout Mice

    PubMed Central

    Wang, Jinfeng; Quan, Guihua; Wang, Xiaojun; Yang, Longfei; Zhong, Lili

    2014-01-01

    The objective of this study was to investigate the effect of Lactobacillus acidophilus ATCC 4356 on the development of atherosclerosis in apolipoprotein E-knockout (ApoE−/−) mice. Eight-week-old ApoE−/− mice were fed a Western diet with or without L. acidophilus ATCC 4356 daily for 16 weeks. L. acidophilus ATCC 4356 protected ApoE−/− mice from atherosclerosis by reducing their plasma cholesterol levels from 923 ± 44 to 581 ± 18 mg/dl, likely via a marked decrease in cholesterol absorption caused by modulation of Niemann-Pick C1-like 1 (NPC1L1). In addition, suppression of cholesterol absorption induced reverse cholesterol transport (RCT) in macrophages through the peroxisome proliferator-activated receptor/liver X receptor (PPAR/LXR) pathway. Fecal lactobacillus and bifidobacterium counts were significantly (P < 0.05) higher in the L. acidophilus ATCC 4356 treatment groups than in the control groups. Furthermore, L. acidophilus ATCC 4356 was detected in the rat small intestine, colon, and feces during the feeding trial. The bacterial levels remained high even after the administration of lactic acid bacteria had been stopped for 2 weeks. These results suggest that administration of L. acidophilus ATCC 4356 can protect against atherosclerosis through the inhibition of intestinal cholesterol absorption. Therefore, L. acidophilus ATCC 4356 may be a potential therapeutic material for preventing the progression of atherosclerosis. PMID:25261526

  12. Assessment of hypolactasia and site-specific intestinal permeability by differential sugar absorption of raffinose, lactose, sucrose and mannitol.

    PubMed

    Hessels, Jan; Eidhof, Harry H M; Steggink, Jan; Roeloffzen, Wilfried W H; Wu, Kalung; Tan, Guy; van de Stadt, Jan; van Bergeijk, Leo

    2003-08-01

    The sugar absorption test is a non-invasive test for investigating intestinal permeability by simultaneous measurement of four probe sugars. In this study, we evaluated the utility of raffinose, lactose, sucrose and mannitol as probe sugars and calculated their urinary recovery as a percentage of ingested dose (mol/mol) and the recovery ratios of raffinose/mannitol, lactose/ raffinose and sucrose/raffinose. The reference ranges for these ratios, established from 39 healthy volunteers, are 0.005-0.015, 0.13-0.63 and 0.09-0.47, respectively. This sugar absorption test was performed in three patient groups. i) In 109 patients with aspecific gastrointestinal symptoms of whom intestinal histology was studied by duodenal biopsies: the urinary raffinose/mannitol recovery ratio highly correlated with gradation of duodenal damage; the sensitivity and specificity of the raffinose/mannitol ratio for detection of intestinal damage were 93% and 91%, respectively, using a cut-off level of 0.020. ii) In 70 patients in whom intestinal lactase activity was investigated by the lactose tolerance test: the urinary lactose/raffinose recovery ratio provided high diagnostic accuracy for hypolactasia (sensitivity 81% and specificity 89% at a cut-off level of 0.70). In analogy with the lactose/raffinose ratio, we suppose that the sucrose/raffinose ratio can be used as a marker of hyposucrasia. iii) In 40 patients with localized small intestinal damage, Crohn's disease of the ileum (n = 21) and celiac disease with histologically proven duodenal damage (n = 19): the raffinose/mannitol recovery ratio was increased in 100% of patients with celiac disease and in 81% of patients with Crohn's disease; increased lactose/raffinose recovery ratio (hypolactasia) and increased sucrose/raffinose (hyposucrasia) were present in 89% and 95% of celiac patients and 19% and 0% of Crohn's disease patients, respectively. The combination of the raffinose/mannitol ratio and sucrose/raffinose ratio appears to be an indication of the distribution of intestinal damage. PMID:12964814

  13. Supplementation with difructose anhydride III promotes passive calcium absorption in the small intestine immediately after calving in dairy cows.

    PubMed

    Teramura, M; Wynn, S; Reshalaitihan, M; Kyuno, W; Sato, T; Ohtani, M; Kawashima, C; Hanada, M

    2015-12-01

    The incidence of hypocalcemia increases in high-parity dairy cows because resorption of bone Ca is delayed in these animals, and they appear to have a reduced ability to absorb Ca from the intestine during the early postpartum period. Difructose anhydride (DFA) III has been shown to promote the absorption of intestinal Ca via a paracellular pathway. However, past studies have not reported this effect in peripartum dairy cows. Therefore, we investigated the effect of DFA III supplementation on Ca metabolism during the peripartum period to determine whether DFA III promotes intestinal Ca absorption via this route. Seventy-four multiparous Holstein cows were separated into DFA and control groups based on their parity and body weight. The feed of the DFA group was supplemented with 40g/d of DFA III from -14 to 6d relative to calving. The control group did not receive DFA III. At calving (0h relative to calving), serum Ca declined below 9mg/dL in both groups. However, serum Ca concentrations were greater in the DFA group than in the control group at 6, 12, 24, and 48h relative to calving, and the time required for serum Ca to recover to 9mg/dL during the postpartum period was shorter in the high-parity cows in the DFA group than in those in the control group. Parathyroid hormone concentrations increased immediately after calving in both groups and were greater in the control group than in the DFA group at 12 and 24h relative to calving. Serum 1,25-dihydroxyvitamin D concentrations increased at 0 and 12h relative to calving in both groups and were higher in the control group than in the DFA group at 72h relative to calving. Serum concentrations of the bone-resorption marker cross-linked N-telopeptide of type I collagen (NTX) were not different between the groups during peripartum period, and serum NTX in all cows was lower at 0, 6, 12, 24, 48, and 72h relative to calving than at -21, 4, and 5d relative to calving. Thus, DFA treatment induced faster recovery of serum Ca, although bone resorption was restrained. In conclusion, DFA III promotes intestinal passive Ca absorption via the paracellular pathway during the early postpartum period; this absorption is unaffected by aging. PMID:26454295

  14. Acidic fermentation in the caecum increases absorption of calcium and magnesium in the large intestine of the rat.

    PubMed

    Younes, H; Demigné, C; Rémésy, C

    1996-02-01

    The effect of fermentation on colonic absorption of Ca and Mg was investigated in 8-week-old rats adapted to diets containing either digestible wheat starch (DS diets) or including resistant starch, i.e. 350 g raw potato starch/kg (RS diets). The dietary Ca level of the DS and RS diets was 2.5 or 7.5 g/kg. RS diets resulted in enlargements of the caecum together with hypertrophy of the caecal wall. Acidification of the caecal contents by microbial fermentation of RS was influenced by the dietary Ca level. Very acidic pH conditions and relatively low concentrations of short-chain fatty acids, in the presence of lactic acid fermentation, were observed with the 2.5 g Ca/kg level. Rats fed on RS diets had a higher percentage of soluble Ca (and inorganic phosphate) in the caecum, particularly of rats adapted to the high Ca level. As a result of the hypertrophy of the caecal wall and of an elevated concentration of soluble Ca, the caecal absorption of Ca was 5-6-fold higher in the RS groups than in the DS groups. The difference between dietary intake and faecal excretion (DI-FE) of Ca was higher in rats fed on RS diets than in those fed on DS diets, when the dietary Ca level was 2.5 g/kg. With the higher Ca intake the elevated rate of Ca absorption from the caecum in RS-fed rats was not paralleled by an enhanced DI-EE difference: this suggests a shift of the Ca absorption towards the large intestine. Feeding RS diets also enhanced Mg caecal absorption, resulting in a substantially higher DI-FE difference for Mg, especially with the 2.5 g Ca/kg diets, because a high Ca intake tends to inhibit Mg absorption. The present findings support the view that the large intestine may represent a major site of Ca (and Mg) absorption when acidic fermentations take place. This process could improve the digestive Ca balance when the dietary Ca supply is low; when the Ca supply is affluent, it rather shifts Ca absorption towards a more distal site of the digestive tract. PMID:8785206

  15. Effect of Dietary Calcium and Age on Jejunal Calcium Absorption in Humans Studied by Intestinal Perfusion

    PubMed Central

    Ireland, Patricia; Fordtran, John S.

    1973-01-01

    Jejunal calcium absorption was measured from test solutions containing 1.0, 2.5, 5, and 10 mM calcium (as calcium gluconate). Absorption rates increased progressively as luminal calcium concentration was increased, although there was a tendency toward saturation of the absorptive process at the higher concentrations. Calcium absorption was higher in normal young adults than in normal subjects over age 60. In both groups a 300 mg calcium diet for 4-8 wk enhanced calcium absorption relative to absorption rates after 4-8 wk on a 2,000 mg calcium diet. This adaptation was more definite and dramatic in the young than in the old subjects. Indirect estimates suggest that adaptation to a low calcium diet and the higher absorption in young than old normal subjects are mediated by an increased Vmax rather than a decreased Km. PMID:4748506

  16. The survey of the use of QSAR methods to determine intestinal absorption and oral bioavailability during drug design.

    PubMed

    Silva, Fredson Torres; Trossini, Gustavo H G

    2014-01-01

    Only 10% of all compounds developed by pharmaceutical companies make it to the market. Of the 90% that do not make it to the market, 50% either have toxicity or pharmacokinetic issues. Thus, the need for ADMET (absorption, distribution, metabolism, excretion and toxicity) optimization during the early stages of drug development is clear. In silico tools may be promising for this use due to their lower cost and time requirements. This review aims to evaluate the predictive power of intestinal absorption and oral bioavailability prediction methods using different statistical approaches over time. Improvement, refinement and diversification of these methods have been observed over the past few years. Nevertheless, some elements related to the quality of the biological data, disclosure of the data used and description of validation methods, that could contribute to building new, better and more reliable models have been ignored by researchers or restricted by the technical limitations of various laboratories. PMID:24730584

  17. Relation between dietary-induced increase of intestinal lactase activity and lactose digestion and absorption in adult rats.

    PubMed

    Leichter, J; Goda, T; Bhandari, S D; Bustamante, S; Koldovsk, O

    1984-12-01

    To study the relation between dietary-induced increase of intestinal lactase activity and lactose absorption, 11-wk-old rats were fed either a high-starch (70 cal%), low-fat (7 cal%) diet or a low-starch (5 cal%), high-fat (73 cal%) diet for 7 days. Food intake and body weight changes were similar in the two dietary groups. In the first experiment, lactose absorption was studied in vivo after oral administration of 600 mg lactose (10% solution in water with added [3H]PEG) to rats fasted for 16 h. Groups of rats were killed at time 0 and at 1-h intervals for the next 3 h. Lactase activity and lactose absorption were significantly higher (P less than 0.01) in the high-starch group than in the low-starch group. In the subsequent experiment, 9-wk-old rats were fed the two isocaloric diets for 3 days. By use of the everted sac technique, we have demonstrated a significantly higher absorption of monosaccharides from lactose in the high-starch diet group; also, glucose transport was higher in the high-starch diet-fed animals. When Tris, an inhibitor of lactase, was added into the mucosal fluid, absorption of lactose was abolished and no effect was seen on glucose absorption (in vivo and in vitro). In both experiments, significant linear regression was established between lactase activity and lactose absorption. Our results thus show that the increase in lactase activity, induced by feeding a high-starch diet to adult rats, is accompanied by an increased capacity to hydrolyze lactose and absorb the constituent monosaccharides. PMID:6439052

  18. Intestinal absorption of luteolin from peanut hull extract is more efficient than that from individual pure luteolin.

    PubMed

    Zhou, Ping; Li, Li-Ping; Luo, Shu-Qing; Jiang, Hui-Di; Zeng, Su

    2008-01-01

    Luteoin is one of the main flavones and the crucial effective component of peanut hull extract (PHE). The present paper aims to elucidate the absorption mechanism of luteolin and clarify whether its absorption occurs primarily at a specific site of the intestine by an in situ single-pass intestinal perfusion (SPIP) model. Moreover, the paper investigates the difference in absorption of luteolin when it is administered in PHE form and as pure luteolin by the SPIP model and in vivo pharmacokinetics studies. Results showed that the effective permeability ( P eff) and absorption rate constant ( k a) of pure luteolin(5.0 microg/mL) in duodenum and jejunum were not significantly different, but markedly higher than that in the colon and ileum. The P eff and k a of luteolin in jejunum were concentration-independent, and the ATP inhibitor (DNP) did not influence P eff and k a of pure luteolin. However, the P eff and k a of luteolin in PHE were significantly greater than that of pure luteolin. The pharmacokinetics study showed that following oral administration of a single dose of pure luteolin (14.3 mg/kg) or PHE (= 14.3 mg/kg of luteolin) in rats, the peak concentration of luteolin in plasma ( C max) and the area under the concentration curve (AUC) for pure luteolin were 1.97 +/- 0.15 microg/mL and 10.7 +/- 2.2 microg/mL.h, respectively. These parameters were significantly lower than those of the PHE group ( P < 0.05), C max = 8.34 +/- 0.98 microg/mL and AUC = 20.3 +/- 1.3 microg/mL.h, respectively. It can be concluded that luteolin is absorbed passively in the intestine of rats and that its absorption is more efficient in the jejunum and duodenum than in the colon and ileum. The bioavailability of luteolin in PHE form is significantly greater than that of pure luteolin. PMID:18052241

  19. A new in vitro system for evaluation of passive intestinal drug absorption: establishment of a double artificial membrane permeation assay.

    PubMed

    Kataoka, Makoto; Tsuneishi, Saki; Maeda, Yukako; Masaoka, Yoshie; Sakuma, Shinji; Yamashita, Shinji

    2014-11-01

    The aim of this present study was to establish a new in vitro assay, double artificial membrane permeation assay (DAMPA), to evaluate the human intestinal permeability of drugs. A double artificial membrane with an intracellular compartment was constructed in side-by-side chambers by sandwiching a filter containing buffer solution with impregnated lipophilic filters with dodecane containing 2w/v% phosphatidylcholine. Permeation data of ionic compounds clearly indicated that not only the pH value of the apical solution but also that of the intracellular compartment affected the permeability across the double artificial membrane. DAMPA was performed with 20 compounds at physiological pH (apical; 6.5, intracellular and basal; 7.4). Paracellular and transcellular permeabilities of compounds in human epithelium were estimated based on the characteristics of the paracellular pathway using physicochemical properties of compounds with the Renkin function and the area factor i.e. the difference in the effective surface area between human epithelium and the double artificial membrane, respectively. The human intestinal permeability of each compound was predicted by the sum of estimated transcellular and paracellular permeabilities. Predicted human intestinal permeability was significantly correlated with the fraction of absorbed dose in humans, indicating that DAMPA has the potential to predict oral absorption of drugs in humans. PMID:25304077

  20. Brown algae fucoxanthin is hydrolyzed to fucoxanthinol during absorption by Caco-2 human intestinal cells and mice.

    PubMed

    Sugawara, Tatsuya; Baskaran, Vallikannan; Tsuzuki, Wakako; Nagao, Akihiko

    2002-05-01

    The metabolic fate in mammals of dietary fucoxanthin, a major carotenoid in brown algae, is not known. We investigated the absorption and metabolism of fucoxanthin in differentiated Caco-2 human intestinal cells, a useful model for studying the absorption of dietary compounds by intestinal cells. Fucoxanthin was taken up by Caco-2 cells incubated with micellar fucoxanthin composed of 1 micromol/L fucoxanthin, 2 mmol/L sodium taurocholate, 100 micromol/L monoacylglycerol, 33.3 micromol/L fatty acids and 50 micromol/L lysophosphatidylcholine. Fucoxanthinol, the deacetylated product of fucoxanthin, was also found in both medium and cells, with its level increasing significantly in a time-dependent manner. No conjugated forms of fucoxanthin and fucoxanthinol were found in either medium or cells. In the animal study, fucoxanthinol (10.4 +/- 5.3 nmol/L plasma, n = 4) was detected in plasma of mice 1 h after intubation of 40 nmol fucoxanthin. These results indicate that dietary fucoxanthin is incorporated as fucoxanthinol, the deacetylated form, from the digestive tract into the blood circulation system in mammals. PMID:11983819

  1. Dietary iodide controls its own absorption through post-transcriptional regulation of the intestinal Na+/I- symporter.

    PubMed

    Nicola, Juan Pablo; Reyna-Neyra, Andrea; Carrasco, Nancy; Masini-Repiso, Ana Maria

    2012-12-01

    Dietary I(-) absorption in the gastrointestinal tract is the first step in I(-) metabolism. Given that I(-) is an essential constituent of the thyroid hormones, its concentrating mechanism is of significant physiological importance. We recently described the expression of the Na(+)/I(-) symporter (NIS) on the apical surface of the intestinal epithelium as a central component of the I(-) absorption system and reported reduced intestinal NIS expression in response to an I(-)-rich diet in vivo. Here, we evaluated the mechanism involved in the regulation of NIS expression by I(-) itself in enterocytes. Excess I(-) reduced NIS-mediated I(-) uptake in IEC-6 cells in a dose- and time-dependent fashion, which was correlated with a reduction of NIS expression at the plasma membrane. Perchlorate, a competitive inhibitor of NIS, prevented these effects, indicating that an increase in intracellular I(-) regulates NIS. Iodide induced rapid intracellular recruitment of plasma membrane NIS molecules and NIS protein degradation. Lower NIS mRNA levels were detected in response to I(-) treatment, although no transcriptional effect was observed. Interestingly, I(-) decreased NIS mRNA stability, affecting NIS translation. Heterologous green fluorescent protein-based reporter constructs revealed a significant repressive effect of the I(-)-targeting NIS mRNA 3 untranslated region. In conclusion, excess I(-) downregulates NIS expression in enterocytes by virtue of a complex mechanism. Our data suggest that I(-) regulates intestinal NIS mRNA expression at the post-transcriptional level as part of an autoregulatory effect of I(-) on its own metabolism. PMID:23006481

  2. Dietary iodide controls its own absorption through post-transcriptional regulation of the intestinal Na+/I− symporter

    PubMed Central

    Nicola, Juan Pablo; Reyna-Neyra, Andrea; Carrasco, Nancy; Masini-Repiso, Ana Maria

    2012-01-01

    Dietary I− absorption in the gastrointestinal tract is the first step in I− metabolism. Given that I− is an essential constituent of the thyroid hormones, its concentrating mechanism is of significant physiological importance. We recently described the expression of the Na+/I− symporter (NIS) on the apical surface of the intestinal epithelium as a central component of the I− absorption system and reported reduced intestinal NIS expression in response to an I−-rich diet in vivo. Here, we evaluated the mechanism involved in the regulation of NIS expression by I− itself in enterocytes. Excess I− reduced NIS-mediated I− uptake in IEC-6 cells in a dose- and time-dependent fashion, which was correlated with a reduction of NIS expression at the plasma membrane. Perchlorate, a competitive inhibitor of NIS, prevented these effects, indicating that an increase in intracellular I− regulates NIS. Iodide induced rapid intracellular recruitment of plasma membrane NIS molecules and NIS protein degradation. Lower NIS mRNA levels were detected in response to I− treatment, although no transcriptional effect was observed. Interestingly, I− decreased NIS mRNA stability, affecting NIS translation. Heterologous green fluorescent protein-based reporter constructs revealed a significant repressive effect of the I−-targeting NIS mRNA 3′ untranslated region. In conclusion, excess I− downregulates NIS expression in enterocytes by virtue of a complex mechanism. Our data suggest that I− regulates intestinal NIS mRNA expression at the post-transcriptional level as part of an autoregulatory effect of I− on its own metabolism. PMID:23006481

  3. Extensive gut metabolism limits the intestinal absorption of excessive supplemental dietary glutamate loads in infant pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Glutamate (Glu) is a major intestinal oxidative fuel, key neurotransmitter, and may be a useful dietary supplement to augment health of the infant gut. We quantified the metabolic fate of various supplemental dietary Glu intakes in young pigs surgically implanted with vascular, intraduodenal (ID), o...

  4. Oxalate minerals on Mars?

    NASA Astrophysics Data System (ADS)

    Applin, D. M.; Izawa, M. R. M.; Cloutis, E. A.; Goltz, D.; Johnson, J. R.

    2015-06-01

    Small amounts of unidentified organic compounds have only recently been inferred on Mars despite strong reasons to expect significant concentrations and decades of searching. Based on X-ray diffraction and reflectance spectroscopic analyses we show that solid oxalic acid and its most common mineral salts are stable under the pressure and ultraviolet irradiation environment of the surface of Mars, and could represent a heretofore largely overlooked reservoir of organic carbon in the martian near-surface. In addition to the delivery to Mars by carbonaceous chondrites, oxalate minerals are among the predicted breakdown products of meteoritic organic matter delivered to the martian surface, as well as any endogenic organic carbon reaching the martian surface from the interior. A reinterpretation of pyrolysis experiments from the Viking, Phoenix, and Mars Science Laboratory missions shows that all are consistent with the presence of significant concentrations of oxalate minerals. Oxalate minerals could be important in numerous martian geochemical processes, including acting as a possible nitrogen sink (as ammonium oxalate), and contributing to the formation of organic carbonates, methane, and hydroxyl radicals.

  5. Adolescence: How do we increase intestinal calcium absorption to allow for bone mineral mass accumulation?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An increase in calcium absorptive efficiency (fractional absorption of dietary calcium) during adolescence is associated with a rapid increase in total body bone mineral mass (BMM) accumulation. This increase occurs across a range of calcium intakes. It appears to be principally mediated by hormonal...

  6. First-pass metabolism limits the intestinal absorption of enteral alpha-ketoglutarate in young pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our results in a previous study indicated that the portal absorption of intragastrically fed alpha-ketoglutarate (AKG) was limited in young pigs. Our aim was to quantify the net portal absorption, first-pass metabolism, and whole-body flux of enterally infused AKG. In study 1, we quantified the net ...

  7. IRON DISSOCIATES FROM THE NAFEEDTA COMPLEX PRIOR TO OR DURING INTESTINAL ABSORPTION IN RATS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sodium Iron EDTA (NaFeEDTA) has superior iron bioavailability especially in foods containing iron absorption inhibitors. However, mechanisms involved in the absorption and subsequent partitioning of iron complexed with EDTA are poorly understood. Our objectives were to compare retention and tissue...

  8. HCO3? secretion and CaCO3 precipitation play major roles in intestinal water absorption in marine teleost fish in vivo

    PubMed Central

    Cooper, Christopher A.; Wilson, Rod W.

    2010-01-01

    The intestine of marine teleosts must effectively absorb fluid from ingested seawater to avoid dehydration. This fluid transport has been almost exclusively characterized as driven by NaCl absorption. However, an additional feature of the osmoregulatory role of the intestine is substantial net HCO3? secretion. This is suggested to drive additional fluid absorption directly (via Cl?/HCO3? exchange) and indirectly by precipitating ingested Ca2+ as CaCO3, thus creating the osmotic gradient for additional fluid absorption. The present study tested this hypothesis by perfusing the intestine of the European flounder in vivo with varying [Ca2+]: 10 (control), 40, and 90 mM. Fractional fluid absorption increased from 47% (control) to 73% (90 mM Ca2+), where almost all secreted HCO3? was excreted as CaCO3. This additional fluid absorption could not be explained by NaCl cotransport. Instead, a significant positive relationship between Na+-independent fluid absorption and total HCO3? secretion was consistent with the predicted roles for anion exchange and CaCO3 precipitation. Further analysis suggested that Na+-independent fluid absorption could be accounted for by net Cl? and H+ absorption (from Cl?/HCO3? exchange and CO2 hydration, respectively). There was no evidence to suggest that CaCO3 alone was responsible for driving fluid absorption. However, by preventing the accumulation of luminal Ca2+ it played a vital role by dynamically maintaining a favorable osmotic gradient all along the intestine, which permits substantially higher rates of solute-linked fluid absorption. To overcome the resulting hyperosmotic and highly acidic absorbate, it is proposed that plasma HCO3? buffers the absorbed H+ (from HCO3? production), and consequently reduces the osmolarity of the absorbed fluid entering the body. PMID:20130226

  9. Intestinal Complications of IBD

    MedlinePLUS

    ... dietary intake, intestinal loss of protein, and poor absorption of nutrients. Medical treatment is usually effective in ... disease. This is the principal area for intestinal absorption of bile acids, compounds that help transport and ...

  10. Contrasting effects of the stomach and small intestine of rats on copper absorption

    SciTech Connect

    Fields, M.; Craft, N.; Lewis, C.; Holbrook, J.; Rose, A.; Reiser, S.; Smith, J.C.

    1986-11-01

    Since the severity of copper deficiency has been shown to be enhanced by feeding diets containing fructose but ameliorated by diets containing starch, we decided to investigate the effect of fructose or starch on copper absorption. As copper transport has been reported to occur also from the stomach, it was possible that copper absorption is inhibited by fructose already from that tissue. Under anesthesia, stomachs of 72 rats fed copper-deficient or supplemented diets containing fructose or starch were ligated prior to the oral administration of /sup 64/Cu. Gastric absorption of /sup 64/Cu was studied when the isotope was administered by gastric tube either in diet containing fructose or starch or in water. /sup 64/Cu was not absorbed from the stomach regardless of the type of dietary treatment, copper status or whether the copper was administered either in diet or in water. In addition, the absorption of /sup 64/Cu from a diet containing either fructose or starch or from a saline solution was studied using the isolated ligated duodenal loop. When /sup 64/Cu was administered with dietary fructose /sup 64/Cu retention and absorption were impaired when compared to starch. When /sup 64/Cu was administered in saline solution, differences in retention and absorption between the four dietary groups disappeared. It is suggested that the requirements for copper rather than the decreased absorption of copper are responsible at least in part for the more pronounced severity of copper deficiency in rats fed fructose compared to those fed starch.

  11. Cerium oxalate precipitation

    SciTech Connect

    Chang, T.P.

    1987-02-01

    Cerium, a nonradioactive, common stand-in for plutonium in development work, has been used to simulate several plutonium precipitation processes at the Savannah River Laboratory. There are similarities between the plutonium trifluoride and the cerium oxalate precipitations in particle size and extent of plating, but not particle morphology. The equilibrium solubility, precipitation kinetics, particle size, extent of plating, and dissolution characteristics of cerium oxalate have been investigated. Interpretations of particle size and plating based on precipitation kinetics (i.e., nucleation and crystal growth) are presented. 16 refs., 7 figs., 6 tabs.

  12. Effect of carbachol on intestinal mucosal blood flow, activity of Na+-K+-ATPase, expression of aquaporin-1, and intestinal absorption rate during enteral resuscitation of burn shock in rats.

    PubMed

    Bao, Chengmei; Hu, Sen; Zhou, Guoyong; Tian, Yijun; Wu, Yan; Sheng, Zhiyong

    2010-01-01

    We investigated the effect of carbachol (CAR, a cholinergic agent) on intestinal mucosal blood flow (IMBF), activity of Na-K-ATPase, expression of aquaporin (AQP)-1, and intestinal absorption rate during enteral resuscitation of a 35%TBSA scald in rats with a glucose electrolyte solution (GES). One hundred male Wistar rats were randomly divided into five groups: sham scald (N group); scald without fluid resuscitation (S group); scald resuscitated with enteral GES alone (GES group); scald resuscitated with enteral CAR alone (CAR group); and scald resuscitated with enteral CAR plus GES (GES/CAR group). The rats were inflicted 35%TBSA third degree of scald injury on the back with boiling water (100 degrees C, 15 seconds) in all groups, except the sham scald group. A catheter was inserted into the proximal duodenum (5 cm distal to pylorus) and distal ileum (5 cm proximal to cecum), of each rats through laparotomy, thus a segment of intestine was virtually isolated to form a loop for inlet and outlet of introduced fluid. In N, GES, and GES/CAR groups, fluids were introduced 30 minutes after scald injury. The speed of fluid infusion was 4 ml/kg/1%TBSA for 4 hours. CAR (60 microg/kg) was injected into the intestinal lumen at 30-minute after injury in CAR and GES/CAR groups. At 2 and 4 hours after scald, intestinal absorption rate of water and Na, and IMBF were determined, respectively. Then, animals were killed, and specimens of intestinal tissue were obtained for the determination of the activity of Na-K-ATPase, hematoxylin-eosin coloring, and expression of AQP-1. The intestinal absorption rate was reduced markedly in GES group compared with sham scald group at 2 and 4 hours after scald, and absorption rate of small intestine in GES/CAR was significantly higher than that in GES group (P < .05). It was also found that there was significant decrease in IMBF, activity of Na-K-ATPase, and expression of AQP-1 in scald group compared with the sham group. However, in GES/CAR group, the levels of these parameters were significantly increased compared with scald groups (P < .05). The results indicate that CAR promotes intestinal absorption rate of water and Na by improving IMBF, ATPase activity, and AQP-1 expression in gut mucosa during resuscitation with enteral GES of burn shock in rats. PMID:20061857

  13. A preparation of perfused small intestine for the study of absorption in amphibia

    PubMed Central

    Parsons, D. S.; Prichard, J. S.

    1968-01-01

    1. A preparation of amphibian small intestine perfused through its vascular system is described. Vascular perfusion with a bicarbonate Ringer solution containing a colloid is used to control the composition of the environment of the submucosal faces of the absorbing cells and to carry away for collection any material extruded from these cells. Oxygenation of the mucosal cells is derived primarily from fluid circulated through the intestinal lumen. The preparation exhibits physiological properties of transport for periods of up to 5 hr. After 5 hr perfusion the epithelial cells show no signs of gross cellular damage when examined either by light or by electron microscopy. 2. The relationship between the hydrostatic pressure at the mesenteric artery and the rate of perfusion through the vascular bed is substantially linear. The pressureflow relationships in the mesenteric bed, including an apparent `critical closing pressure', are primarily determined by the hydrostatic pressure in the intestinal lumen. Alterations in the hydrostatic pressure in the intestinal lumen also change the relative proportions of the vascular infusate which appear in the portal venous effluent and in the fluid exuded from the serosal surface of the preparation (`sweat'). Hydrostatic distension pressures above about 10 cm H2O reduce the rate of collection of fluid from the portal vein and increase the rate of collection of `sweat'. 3. An increase in the rate of vascular perfusion increases the total rate of glucose appearance although the glucose concentrations in both the portal effluent and the `sweat' are reduced. 4. The glucose translocation rate is related in an alinear saturable fashion to the luminal concentration of glucose. By making a correction for metabolic loss of glucose during its passage through the intestinal cell, the relationship existing between the lumen concentration and the uptake of the sugar by the mucosal cells has been calculated. This relationship is found to fit MichaelisMenten type kinetics. The Km of the intestinal translocation process for glucose in Rana pipiens was 045 013 (4) ?M. The mean Vmax was 1375 353 (4) ?M/hr/g fat-free dry wt. 5. When phlorrhizin (10-5 M) is added to the vascular perfusate, no inhibition of glucose transport is seen for at least 60 min. When strophanthin is added to the vascular perfusate (5 10-5 M), a markedly greater inhibition of glucose transport is observed than when it is introduced to the luminal circulation. 6. Earlier studies of the vascular perfusion of isolated small intestine are tabulated. The experimental findings are discussed in relation to a model of the mode of action of the epithelial cell for glucose transport. Images(a)(b)(c)(a)(b) PMID:5698278

  14. Intestinal Absorption Mechanisms of Prenylated Flavonoids Present in the Heat-Processed Epimedium koreanum Nakai (Yin Yanghuo)

    PubMed Central

    Chen, Yan; Zhao, Yan Hong; Jia, Xiao Bin; Hu, Ming

    2008-01-01

    Purpose The purpose is to determine absorption mechanism of five bioactive prenylated flavonoids (baohuoside I, icariin, epimedine A, B, and C) present in heat-processed Epimedium koreanum Nakai (Yin Yanghuo). Methods Transport of five prenylated flavonoids present in heat-processed herbs were studied in the human intestinal Caco-2 model and the perfused rat intestinal model. Results In the perfused rat intestinal model, prenylated flavonoids with a monoglucosidic bond (e.g., icariin) was rapidly hydrolyzed into corresponding metabolites (e.g., baohuoside I). In the Caco-2 model, apical to basolateral permeability of a monoglycoside baohuoside I (1.46 10?6 cm/sec) was more than 2 folds greater than four prenylated flavonoids with 2 or more sugar moieties (<0.610?6 cm/sec). The slow apical to basolateral transport of baohuoside I was the result of efflux. This efflux was carrier-mediated and active since its transport was vectorial, concentration- and temperature-dependent with activation energies greater than 15 kcal/mol. Efflux of baohuoside I was significantly suppressed by inhibitors of BCRP and MRP2, whereas efflux of icariin was significantly inhibited only by p-glycoprotein inhibitor verapamil. Because YHH is often heat-processed for better efficacy, we determined and found the optimal condition for increasing contents of more bioavailable flavonoids (i.e., baohuoside I) to be 160170C for 57 min. Conclusions Poor bioavailability of prenylated flavonoids results from their poor intrinsic permeation and transporter-mediated efflux. Heat processing parameters may be optimized to preserve the herbs bioavailable flavonoids, which help retain and improve its efficacy during processing. PMID:18459036

  15. Intestinal paracellular absorption is necessary to support the sugar oxidation cascade in nectarivorous bats.

    PubMed

    Rodriguez-Peña, Nelly; Price, Edwin R; Caviedes-Vidal, Enrique; Flores-Ortiz, Cesar M; Karasov, William H

    2016-03-15

    We made the first measurements of the capacity for paracellular nutrient absorption in intact nectarivorous bats. Leptonycteris yerbabuenae (20 g mass) were injected with or fed inert carbohydrate probes l-rhamnose and d(+)-cellobiose, which are absorbed exclusively by the paracellular route, and 3-O-methyl-d-glucose (3OMD-glucose), which is absorbed both paracellularly and transcellularly. Using a standard pharmacokinetic technique, we collected blood samples for 2 h after probe administration. As predicted, fractional absorption (f) of paracellular probes declined with increasing Mr in the order of rhamnose (f=0.71)>cellobiose (f=0.23). Absorption of 3OMD-glucose was complete (f=0.85; not different from unity). Integrating our data with those for glucose absorption and oxidation in another nectarivorous bat, we conclude that passive paracellular absorption of glucose is extensive in nectarivorous bat species, as in other bats and small birds, and necessary to support high glucose fluxes hypothesized for the sugar oxidation cascade. PMID:26985050

  16. Digestion and absorption of an egg white ACE-inhibitory peptide in human intestinal Caco-2 cell monolayers.

    PubMed

    Ding, Long; Wang, Liying; Yu, Zhipeng; Zhang, Ting; Liu, Jingbo

    2016-03-01

    The objective of this study was to investigate the digestion and absorption of egg white-derived angiotensin I-converting enzyme (ACE)-inhibitory peptide TNGIIR in human intestinal Caco-2 cell monolayers. Results showed that the digestion of TNGIIR to simulated gastrointestinal enzymes and brush border membrane peptidases were 5.87% 1.92% and 17.17% 0.64%, respectively (p?

  17. Enhancement of intestinal absorption of poorly absorbed hydrophilic compounds by simultaneous use of mucolytic agent and non-ionic surfactant.

    PubMed

    Takatsuka, Shinya; Kitazawa, Takeo; Morita, Takahiro; Horikiri, Yuji; Yoshino, Hiroyuki

    2006-01-01

    The effect of co-administration of a mucolytic agent with a penetration enhancer was assessed on the intestinal absorption of poorly absorbed hydrophilic compounds. Fluorescein isothiocyanate-labeled dextran with average molecular weight of ca. 4.4 kDa (FD-4) was used as a model compound, and N-acetylcysteine (NAC) was used as a mucolytic agent. Sodium caprate (C10), tartaric acid (TA), sodium taurodeoxycholate (TDC), sodium dodecyl sulfate (SDS), p-t-octyl phenol polyoxyethylene-9.5 (Triton X-100, TX-100) were selected as penetration enhancers with different mechanisms of action. Various dosing solutions containing a penetration enhancer in the absence or in the presence of NAC were directly administered into the exposed rat jejunum, and the bioavailability of FD-4 up to 2 h was determined. The extent of improvement by co-administration was highly dependent on the penetration enhancer species applied. The observed enhancement was thought to result from the mucolytic activity of NAC, which can reduce the mucus viscosity and facilitate the penetration of FD-4 to mucosal membrane. Among the combinations tested, the simultaneous administration of NAC and TX-100 provided the highest enhancement (22.5-fold) of intestinal FD-4 absorption compared to the control. Although the detailed mechanism for the observed drastic improvement is unclear, one possible reason was thought to be due to the improved diffusivity of TX-100 micellar system in the mucus layer. All these results suggest that the combination of a mucolytic agent and a non-ionic surfactant may have potential as an enhancing system for peroral delivery of poorly absorbed hydrophilic compounds like protein and peptide drugs. PMID:16289777

  18. Nitrogen absorption and endogenous nitrogen along the intestinal tract of chicks.

    PubMed

    Bielorai, R; Iosif, B; Neumark, H

    1985-05-01

    Six groups of 15 chicks each were fed ad libitum experimental diets that contained between 0.4 and 35 g nitrogen/kg, from 10 to 16 d of age. Soybean meal was the only source of protein, and the marker was magnesium ferrite. The calculated absorption values obtained by regression analysis were higher than the determined apparent values, mainly in the duodenum and upper jejunum, due to elimination of endogenous nitrogen secretion. At the lower ileum, the calculated and the measured (apparent) absorption values were almost identical; thus, with soybean as the protein source in a diet containing a normal level of protein (18-35 N/kg diet), there is no need for endogenous nitrogen correction. Absorption of the endogenous nitrogen in chicks fed ad libitum a nitrogen-free diet was almost completed at the lower ileum (95%). PMID:3998858

  19. The effect of canola meal tannins on the intestinal absorption capacity of broilers using a D-xylose test.

    PubMed

    Mansoori, B; Rogiewicz, A; Slominski, B A

    2015-12-01

    In three D-xylose absorption experiments, the effect of 1% HCl/methanol, 70% methanol or 70% acetone extracts of canola meal (CM) or 70% acetone extract of soybean meal (SBM) containing polyphenols, phenolic acids, tannins and phytic acid on intestinal absorption capacity of broilers was determined. In Exp. 1, the experimental groups received orally D-xylose solution alone or with methanol/HCl, methanol or acetone extracts of CM. In Exp. 2, the experimental groups received D-xylose alone or with acetone extracts of CM or SBM. In Exp. 3, the experimental groups received D-xylose plus sucrose solution or D-xylose plus acetone extracts of CM or SBM. In Exps. 2 and 3, the CM extracts contained 2.7 and 2.6, 2.4 and 2.3, 3.2 and 3.2, and 2.4 and 2.2 times higher polyphenols, phenolic acids, tannins and condensed tannins than the corresponding SBM extracts respectively. Blood samples were collected in 40-min intervals, and plasma D-xylose was measured. Compared to the Control, plasma D-xylose in Exp. 1 was lower (p<0.001) by 81, 69 and 73% at 40-min, by 41, 44 and 37% at 80-min and by 22, 31, and 23% at 120-min post-ingestion of the HCl/methanol, methanol and acetone extracts respectively. In both Exps. 2 and 3, plasma D-xylose level was lower (p<0.001) in groups dosed with CM extract or SBM extract at each time of blood collection, when compared to the respective Control group. However, in Exp. 3, birds dosed with SBM extract had higher plasma D-xylose than CM extract-dosed birds by 28, 8 and 21% at 40, 80 and 120min respectively (p<0.01). In conclusion, although CM extract caused a lower absorption of D-xylose, based on 5 to 10% of CM inclusion levels in practical broiler rations, the soluble bioactive components of CM will likely have minor impact on the absorption capacity of the chicken intestine. PMID:25865561

  20. Thorium oxalate solubility and morphology

    SciTech Connect

    Monson, P.R. Jr.; Hall, R.

    1981-10-01

    Thorium was used as a stand-in for studying the solubility and precipitation of neptunium and plutonium oxalates. Thorium oxalate solubility was determined over a range of 0.001 to 10.0 in the concentration parameter (H/sub 2/C/sub 2/O/sub 4/)/(HNO/sub 3/)/sup 2/. Morphology of thorium oxide made from the oxalate precipitates was characterized by scanning electron microscopy. The different morphologies found for oxalate-lean and oxalate-rich precipitations were in agreement with predictions based on precipitation theory.

  1. Binding of navy bean (Phaseolus vulgaris) lectin to the intestinal cells of the rat and its effect on the absorption of glucose

    SciTech Connect

    Donatucci, D.A.; Liener, I.E.; Gross, C.J.

    1987-12-01

    The main objectives of this investigation were to study the binding of a lectin from navy beans with the epithelial cells of the rat intestine and to assess the effect of such binding on the ability of the intestine to absorb glucose. A Scatchard plot, based on the binding of /sup 125/I-labeled lectin to isolated intestinal epithelial cells, was used to calculate an association constant (Ka) of 15 x 10(6)M-1 and the number of binding sites per cell, 12 x 10(6). Metabolic studies were conducted over a period of 5 d on groups of rats fed raw or autoclaved navy bean flour and casein with or without the purified lectin. Growth, protein digestibility, biological value and net protein utilization were significantly lower in animals that had been fed raw navy bean flour or casein plus lectin than in control groups fed diets containing autoclaved navy bean flour or casein alone. Vascular perfusion was used to measure the rate of uptake of glucose by the intestines of rats that had received the various dietary treatments. The rate of absorption of (/sup 14/C)glucose by intestines from rats fed raw navy bean flour or casein plus lectin was approximately one-half that of their counterparts fed the autoclaved flour or casein alone. These results provide evidence that the lectin, by virtue of its interference with intestinal absorption, is responsible, at least in part, for the nutritional inferiority of raw navy beans.

  2. Acute oxalate nephropathy due to pancreatic atrophy in newly diagnosed pancreatic carcinoma.

    PubMed

    Moinuddin, Irfan; Bala, Asif; Ali, Butool; Khan, Husna; Bracamonte, Erika; Sussman, Amy

    2016-02-01

    Acute oxalate nephropathy can occur due to primary hyperoxaluria and secondary hyperoxaluria. The primary hyperoxalurias are a group of autosomal recessive disorders of endogenous oxalate overproduction. Secondary hyperoxaluria may occur as a result of excess dietary intake, poisoning with oxalate precursors (ethylene glycol), or enteric hyperoxaluria. The differential diagnosis of enteric hyperoxaluria includes inflammatory bowel disease, short bowel syndrome, bariatric surgery (with jejunoileal bypass or Roux-en-Y gastric bypass), celiac disease, partial colectomy, and chronic pancreatitis. The common etiology in all these processes is fat malabsorption, steatorrhea, saponification of calcium, and absorption of free oxalate. Hyperoxaluria causes increased urinary oxalate excretion, urolithiasis (promoted by hypovolemia, decreased urinary pH caused by metabolic acidosis, and decreased citrate and magnesium concentrations in urine), tubulointerstitial oxalate deposits, and tubulointerstitial nephritis. We report a rare case of acute oxalate nephropathy due to pancreatic atrophy and exocrine insufficiency caused by newly diagnosed pancreatic cancer. PMID:26614399

  3. Intestinal absorption of free oral hyperalimentation in the very short bowel syndrome.

    PubMed

    Messing, B; Pigot, F; Rongier, M; Morin, M C; Ndeïndoum, U; Rambaud, J C

    1991-06-01

    Ten adult ambulatory patients with the nonactive digestive disease short bowel syndrome were prospectively studied to quantitatively assess their free oral intake and their net digestive absorption of total calories, fat, protein, and carbohydrate during a 3-day period at least 6 months after a resection. The remaining portions of small bowel had a mean length of 75 cm (range, 0-200 cm); the remaining colon lengths had a mean of 67% of normal (range, 0%-100%). The experimental diets were formulated according to a home dietary inquiry. During the study period, pooled intakes and digestive losses were measured for total calories, fat, and protein using the bomb calorimetry, Van de Kamer, and Kjeldahl techniques, respectively. The ingested diet provided 58 +/- 14 kcal.kg-1.day-1 (mean +/- SD) and consisted of 46% carbohydrate, 31% fat, and 23% protein. Net digestive absorption was 67% +/- 12% for total calories, 79% +/- 15% for carbohydrate, 52% +/- 16% for fat, and 61% +/- 19% for protein. The larger net digestive absorption of carbohydrate (P less than or equal to 0.004) compared with fat and protein suggests salvage of colonic cholesterol in short bowel syndrome patients. It is concluded that these patients with the short bowel syndrome adapted to a hypercaloric, hyperprotein diet to compensate for increased fecal losses and that this hyperphagia does not seem to have impaired their net digestive absorption. PMID:1850371

  4. Differential intestinal absorption of two fatty acid isomers: Elaidic and oleic acids

    SciTech Connect

    Bernard, A.; Echinard, B.; Carlier, H. )

    1987-12-01

    The absorption of {sup 14}C-labeled oleic acid and {sup 14}C-labeled elaidic acid was studied in bile- and pancreatic juice-diverted adult rats. In some cases these acids were compared with {sup 14}C-labeled palmitic acid absorption. Sodium taurocholate-emulsified test infusates containing an equimolar mixture of monopalmitin and two fatty acids (oleic and elaidic or palmitic), one of which was {sup 14}C labeled, were infused through a duodenal canula. The chyle was collected from the mesenteric lymphatic vessel by plastic tubing. Among the three fatty acids studied, oleic acid exhibited the highest lymphatic recovery rate. Elaidic and palmitic acids appeared more slowly and in lesser amounts. Simultaneously, the highest amount of chylomicrons was observed when the lipid emulsion contained oleic acid alone; the lowest was observed when elaidic acid was the only unsaturated fatty acid. Experimental data have also shown that compared with elaidic acid, oleic acid is preferentially incorporated into the lymph triglycerides. The authors conclude from the data presented that the enterocytic enzymes involved in the absorption of lipids show a high degree of specificity related to the fatty acid isomery, since the absorption of elaidic acid differs markedly from its isomer oleic acid.

  5. Aldosterone regulation of intestinal Na absorption involves SGK-mediated changes in NHE3 and Na+ pump activity.

    PubMed

    Musch, Mark W; Lucioni, Alvaro; Chang, Eugene B

    2008-11-01

    Aldosterone-induced intestinal Na(+) absorption is mediated by increased activities of apical membrane Na(+)/H(+) exchange (aNHE3) and basolateral membrane Na(+)-K(+)-ATPase (BLM-Na(+)-K(+)-ATPase) activities. Because the processes coordinating these events were not well understood, we investigated human intestinal Caco-2BBE cells where aldosterone increases within 2-4 h of aNHE3 and alpha-subunit of BLM-Na(+)-K(+)-ATPase, but not total abundance of these proteins. Although aldosterone activated Akt2 and serum glucorticoid kinase-1 (SGK-1), the latter through stimulation of phosphatidylinositol 3-kinase (PI3K), only the SGK-1 pathway mediated its effects on Na(+)-K(+)-ATPase. Ouabain inhibition of the early increase in aldosterone-induced Na(+)-K(+)-ATPase activation blocked most of the apical NHE3 insertion, possibly by inhibiting Na(+)-K(+)-ATPase-induced changes in intracellular sodium concentration ([Na](i)). Over the next 6-48 h, further increases in aNHE3 and BLM-Na(+)-K(+)-ATPase activity and total protein expression were observed to be largely mediated by aldosterone-activated SGK-1 pathway. Aldosterone-induced increases in NHE3 mRNA, for instance, could be inhibited by RNA silencing of SGK-1, but not Akt2. Additionally, aldosterone-induced increases in NHE3 promoter activity were blocked by silencing SGK-1 as well as pharmacological inhibition of PI3K. In conclusion, aldosterone-stimulated intestinal Na(+) absorption involves two phases. The first phase involves stimulation of PI3K, which increases SGK-dependent insertion and function of BLM-Na(+)-K(+)-ATPase and subsequent increased membrane insertion of aNHE3. The latter may be caused by Na(+)-K(+)-ATPase-induced changes in [Na] or transcellular Na flux. The second phase involves SGK-dependent increases in total NHE3 and Na(+)-K(+)-ATPase protein expression and activities. The coordination of apical and BLM transporters after aldosterone stimulation is therefore a complex process that requires multiple time- and interdependent cellular processes. PMID:18801914

  6. Isotope concentrations from 24-h urine and 3-h serum samples can be used to measure intestinal magnesium absorption in postmenopausal women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies suggest a link between magnesium status and osteoporosis. One barrier to more conclusive research on the potential relation is measuring intestinal magnesium absorption (MgA), which requires the use of stable isotopes and a >/= 6-d stool or 3-d urine collection. We evaluated alternative meth...

  7. Perilipin-2 Modulates Lipid Absorption and Microbiome Responses in the Mouse Intestine.

    PubMed

    Frank, Daniel N; Bales, Elise S; Monks, Jenifer; Jackman, Matthew J; MacLean, Paul S; Ir, Diana; Robertson, Charles E; Orlicky, David J; McManaman, James L

    2015-01-01

    Obesity and its co-morbidities, such as fatty liver disease, are increasingly prevalent worldwide health problems. Intestinal microorganisms have emerged as critical factors linking diet to host physiology and metabolic function, particularly in the context of lipid homeostasis. We previously demonstrated that deletion of the cytoplasmic lipid drop (CLD) protein Perilipin-2 (Plin2) in mice largely abrogates long-term deleterious effects of a high fat (HF) diet. Here we test the hypotheses that Plin2 function impacts the earliest steps of HF diet-mediated pathogenesis as well as the dynamics of diet-associated changes in gut microbiome diversity and function. WT and perilipin-2 null mice raised on a standard chow diet were randomized to either low fat (LF) or HF diets. After four days, animals were assessed for changes in physiological (body weight, energy balance, and fecal triglyceride levels), histochemical (enterocyte CLD content), and fecal microbiome parameters. Plin2-null mice had significantly lower respiratory exchange ratios, diminished frequencies of enterocyte CLDs, and increased fecal triglyceride levels compared with WT mice. Microbiome analyses, employing both 16S rRNA profiling and metagenomic deep sequencing, indicated that dietary fat content and Plin2 genotype were significantly and independently associated with gut microbiome composition, diversity, and functional differences. These data demonstrate that Plin2 modulates rapid effects of diet on fecal lipid levels, enterocyte CLD contents, and fuel utilization properties of mice that correlate with structural and functional differences in their gut microbial communities. Collectively, the data provide evidence of Plin2 regulated intestinal lipid uptake, which contributes to rapid changes in the gut microbial communities implicated in diet-induced obesity. PMID:26147095

  8. Perilipin-2 Modulates Lipid Absorption and Microbiome Responses in the Mouse Intestine

    PubMed Central

    Frank, Daniel N.; Bales, Elise S.; Monks, Jenifer; Jackman, Matthew J.; MacLean, Paul S.; Ir, Diana; Robertson, Charles E.; Orlicky, David J.; McManaman, James L.

    2015-01-01

    Obesity and its co-morbidities, such as fatty liver disease, are increasingly prevalent worldwide health problems. Intestinal microorganisms have emerged as critical factors linking diet to host physiology and metabolic function, particularly in the context of lipid homeostasis. We previously demonstrated that deletion of the cytoplasmic lipid drop (CLD) protein Perilipin-2 (Plin2) in mice largely abrogates long-term deleterious effects of a high fat (HF) diet. Here we test the hypotheses that Plin2 function impacts the earliest steps of HF diet-mediated pathogenesis as well as the dynamics of diet-associated changes in gut microbiome diversity and function. WT and perilipin-2 null mice raised on a standard chow diet were randomized to either low fat (LF) or HF diets. After four days, animals were assessed for changes in physiological (body weight, energy balance, and fecal triglyceride levels), histochemical (enterocyte CLD content), and fecal microbiome parameters. Plin2-null mice had significantly lower respiratory exchange ratios, diminished frequencies of enterocyte CLDs, and increased fecal triglyceride levels compared with WT mice. Microbiome analyses, employing both 16S rRNA profiling and metagenomic deep sequencing, indicated that dietary fat content and Plin2 genotype were significantly and independently associated with gut microbiome composition, diversity, and functional differences. These data demonstrate that Plin2 modulates rapid effects of diet on fecal lipid levels, enterocyte CLD contents, and fuel utilization properties of mice that correlate with structural and functional differences in their gut microbial communities. Collectively, the data provide evidence of Plin2 regulated intestinal lipid uptake, which contributes to rapid changes in the gut microbial communities implicated in diet-induced obesity. PMID:26147095

  9. Characteristics of the transport of oxalate and other ions across rabbit proximal colon.

    PubMed

    Hatch, M; Freel, R W; Vaziri, N D

    1993-05-01

    In order to characterize oxalate handling by the P2 segment of the rabbit proximal colon, the fluxes of [14C]oxalate, 22Na+, and 36Cl- were measured in vitro using conventional short-circuiting techniques. In standard buffer the proximal colon exhibited net secretion of Na+ (-2.31 +/- 0.64 mu equiv cm-2 h-1), negligible net Cl- transport, and net secretion of oxalate (-12.7 +/- 1.6 pmol cm-2 h-1). Replacement of buffer Na+ or Cl- abolished net oxalate secretion, while HCO(3-)-free media revealed a net absorption of oxalate (19.3 +/- 4.2 pmol cm-2 h-1) and stimulated NaCl absorption. Mucosal amiloride and dimethylamiloride (1 mM) significantly reduced the unidirectional fluxes of oxalate and enhanced sodium secretion by decreasing JNams. The anion exchange inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS; 0.1 mM, both sides) reduced the unidirectional fluxes of oxalate and chloride. Serosal epinephrine (50 microM) stimulated oxalate absorption (21.3 +/- 6.3 pmol cm-2 h-1) and sodium absorption (5.71 +/- 1.20 mu equiv cm-2 h-1), whereas dibutyryl-cAMP enhanced oxalate secretion (-43.4 +/- 6.9 pmol cm-2 h-1) and stimulated chloride secretion (-7.27 +/- 0.64 mu equiv cm-2 h-1). These results indicate that the P2 segment of the proximal colon possesses (a) secretory as well as absorptive capacities, (b) oxalate fluxes that are mediated by pathways involving Na+, Cl-, HCO3- transport and (c) a net oxalate flux that is sensitive to absorptive and secretory stimuli. PMID:8391680

  10. Inhibition of steady-state intestinal absorption of long-chain triglyceride by medium-chain triglyceride in the unanesthetized rat

    PubMed Central

    Clark, Susanne Bennett; Holt, Peter R.

    1969-01-01

    Maximal steady-state intestinal absorption rates in unanesthetized rats for triolein, a long-chain triglyceride, and for trioctanoin, a medium-chain triglyceride, are known to differ. Both these lipids are hydrolyzed in the intestinal lumen but the products of hydrolysis are metabolized differently by the mucosal cell. Intraduodenal infusion of trioctanoin was found to reduce steady-state triolein absorption. Luminal lipolysis was shown not to be rate-controlling. High rates of trioctanoin infusion significantly lowered the pH of the luminal aqueous phase and altered the partition of oleic acid between aqueous and oil phases. Two possible mechanisms for the inhibition of triolein uptake are considered. In the intestinal lumen medium chain lipids might have lowered the activity of oleic acid monomers in the aqueous phase and reduced passive diffusion into mucosal cells. Alternatively, competition between long and medium chain fatty acids for some common receptor during transport into the intestinal mucosal cell may have occurred. Despite significant inhibition of triolein absorption by high levels of trioctanoin, the maximum number of calories absorbed from mixtures of triglycerides exceeded the maxima from either glyceride alone. The optimum proportion of triolein to trioctanoin in lipid infusion mixtures was about 3:4 by weight and the optimum dosages about half maximal for each triglyceride, which represented a caloric intake of 4 kcal/rat per 2 hr. The absorption coefficient for this lipid mixture was about 90%. It is suggested that in patients who have a limited intestinal absorptive capacity dietary fat intake might be doubled with a caloric supplement of medium-chain triglycerides without increase in steatorrhea of long-chain fat. PMID:5355337

  11. Lowering urinary oxalate excretion to decrease calcium oxalate stone disease.

    PubMed

    Holmes, Ross P; Knight, John; Assimos, Dean G

    2016-02-01

    Dietary modifications should be considered as a first line approach in the treatment of idiopathic calcium oxalate nephrolithiasis. The amounts of oxalate and calcium consumed in the diet are significant factors in the development of the disease due to their impact on urinary oxalate excretion. There are a number of strategies that can be employed to reduce oxalate excretion. The consumption of oxalate-rich foods should be avoided and calcium intake adjusted to 1000-1200mg/day. To encourage compliance it should be emphasized to patients that they be vigilant with this diet as a deviation in any meal or snack could potentially result in significant stone growth. The evidence underlying these two modifications is outlined and other strategies to reduce urinary oxalate excretion are reviewed. PMID:26614109

  12. Literature review for oxalate oxidation processes and plutonium oxalate solubility

    SciTech Connect

    Nash, C. A.

    2015-10-01

    A literature review of oxalate oxidation processes finds that manganese(II)-catalyzed nitric acid oxidation of oxalate in precipitate filtrate is a viable and well-documented process. The process has been operated on the large scale at Savannah River in the past, including oxidation of 20 tons of oxalic acid in F-Canyon. Research data under a variety of conditions show the process to be robust. This process is recommended for oxalate destruction in H-Canyon in the upcoming program to produce feed for the MOX facility. Prevention of plutonium oxalate precipitation in filtrate can be achieved by concentrated nitric acid/ferric nitrate sequestration of oxalate. Organic complexants do not appear practical to sequester plutonium. Testing is proposed to confirm the literature and calculation findings of this review at projected operating conditions for the upcoming campaign.

  13. 25-Hydroxyvitamin D level does not reflect intestinal calcium absorption: an assay using strontium as a surrogate marker.

    PubMed

    Camargo, Marília Brasilio Rodrigues; Vilaça, Tatiane; Hayashi, Lilian Fukusima; Rocha, Olguita G Ferreira; Lazaretti-Castro, Marise

    2015-05-01

    There is conflicting evidence as to the optimal serum 25-hydroxyvitamin D [25(OH)D] concentration for intestinal calcium absorption (Abs-Ca). Our purpose was to assess the relationship between vitamin D status and Abs-Ca in postmenopausal women. Fifty volunteers with low bone mass were grouped according to their serum 25(OH)D concentration as follows: mild deficient, <50 nmol/L (DEF) and sufficient, ≥75 nmol/L (SUF). The subjects were submitted to an oral strontium overload test to assess their Abs-Ca. Fasting blood samples were obtained to perform the relevant hormonal and biochemical tests. After the subjects received the test solution, blood samples were drawn at 30, 60, 120, and 240 min to determine the strontium concentrations. Abs-Ca was indirectly expressed as the area under the serum strontium concentration curve (AUC). A repeated measures ANOVA was performed to determine the differences among the groups. Pearson's correlation and multiple linear regression analysis were used to study the associations between the variables. The mean 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations differed between the groups (SUF vs. DEF) as follows: 98.7 ± 18.2 vs. 38.4 ± 8.5 nmol/L (p < 0.001) and 36.2 ± 10.2 vs. 24.9 ± 4.6 pg/mL (p < 0.001), respectively. There was no statistically significant difference between the groups for parathyroid hormone and AUC. Only 1,25(OH)2D influenced the strontium absorption in the last 2 h of the test. In the studied population, no correlation between levels of 25(OH)D and Abs-Ca was found. Only 1,25(OH)2D influenced Abs-Ca as measured by a strontium absorption test. PMID:24858975

  14. Red wine alcohol promotes quercetin absorption and directs its metabolism towards isorhamnetin and tamarixetin in rat intestine in vitro

    PubMed Central

    Dragoni, Stefania; Gee, Jennifer; Bennett, Richard; Valoti, Massimo; Sgaragli, Giampietro

    2006-01-01

    Moderate consumption of red wine has been associated with beneficial effects on human health, and this has been attributed to the flavonoid content. Factors that influence the bioavailability of this group of polyphenolic compounds are therefore important. Using the rat cannulated everted jejunal sac technique, we have investigated the effect of alcohol on the intestinal absorption of quercetin and its 3-O-glucoside from red wine. Tissue preparations were incubated in whole or dealcoholised red wine, diluted 1 : 1 with Krebs buffer for 20 min at 37°C, after which the mucosa was removed and processed for HPLC analysis. Tissues exposed to red wine had significantly higher amounts of both quercetin (× 3; P<0.001) and quercetin-3-O-glucoside (× 1.5; P<0.01) associated with them, compared with sacs incubated in the dealcoholised equivalent. In addition, both tamarixetin (T) and isorhamnetin (I), in the mucosal tissue from sacs exposed to the whole wine, were significantly elevated approximately two fold (P<0.05; P<0.01, respectively). Similar results were obtained when sacs were incubated in Krebs buffer containing a mixture of pure quercetin and quercetin-3-O-glucoside with or without alcohol, and, although effects on the apparent absorption of Q and Q-3-G were not so marked, concentrations of the metabolites quercetin-3-O-glucuronide and I were significantly increased by the presence of alcohol (P<0.01 and P<0.001, respectively). It is therefore plausible that the moderate alcohol content of red wine contributes to its beneficial health effects in humans by both increasing the absorption of quercetin and quercetin-3-O-glucoside and by channelling their metabolism towards O-methylation to yield compounds (T and I), which have potential protective effects against cancer and cardiovascular diseases. PMID:16444288

  15. SGLT-1 Transport and Deglycosylation inside Intestinal Cells Are Key Steps in the Absorption and Disposition of Calycosin-7-O-β-d-Glucoside in Rats.

    PubMed

    Shi, Jian; Zheng, Haihui; Yu, Jia; Zhu, Lijun; Yan, Tongmeng; Wu, Peng; Lu, Linlin; Wang, Ying; Hu, Ming; Liu, Zhongqiu

    2016-03-01

    Hydrolysis by lactase-phloridzin hydrolase (LPH) is the first and critical step in the absorption of isoflavonoid glucosides. However, the absorption characteristics of calycosin-7-O-β-d-glucoside (CG) slightly differ from other isoflavonoid glucosides. In this study, we used the rat intestinal perfusion model and performed pharmacokinetic studies and in vitro experiments to determine the factors influencing CG absorption and disposition. After oral administration of isoflavonoid glucosides, LPH was found to play minimal or no role on the hydrolysis of CG, in contrast to that of daidzin. CG was mainly transported into the small intestinal cells by sodium-dependent glucose transporter 1 (SGLT-1) as intact. This pathway could be the main mechanism underlying the high permeability of CG in the small intestine. CG was likely to be hydrolyzed in enterocytes to its aglycone calycosin by broad-specific β-glucuronides (BSβG) and glucocerebrosidase or rapidly metabolized. Calycosin was also rapidly and extensively metabolized to 3'-glucuronide in the enterocytes and liver, and the glucuronidation rates of calycosin and CG were much higher in the former. The metabolites were also transported into lumen by breast cancer resistance protein and multidrug resistance-associated protein 2. In conclusion, the enterocytes could be an important site for CG absorption, deglycosylation, and metabolism in rats. This study could contribute to the theoretical foundation and mechanism of absorption and disposition of flavonoid compounds. PMID:26658676

  16. Absorption barriers in the rat intestinal mucosa: 2. Application of physiologically based mathematical models to quantify mechanisms of drug permeation and metabolism.

    PubMed

    Mudra, Daniel R; Jin, Jin Y; Borchardt, Ronald T

    2010-02-01

    The absorption of drug molecules is often investigated using in vitro or in situ models of the intestinal mucosa; however, few studies have quantified the kinetics that limit absorption. The objective of this study was to quantify kinetic rates of rat intestinal absorption, metabolism, and efflux using nonlinear mixed effects modeling. A multicompartment model accurately described the absorption and distribution of atenolol and verapamil as well as the metabolism of verapamil and distribution of the metabolite, norverapamil. The accurate description of atenolol data required inclusion of an intermediate compartment in addition to paracellular clearance, whereas verapamil and norverapamil were modeled in the absence of paracellular clearance. The absorption of verapamil was well characterized by linear kinetics, whereas the formation and distribution of norverapamil were well characterized by Michaelis-Menten kinetics. The model identified EDTA as a modulator of physical barriers, ketoconazole as an inhibitor of cytochrome P450 3A and P-glycoprotein (P-gp), and PSC-833 and GF-120918 as specific P-gp inhibitors. These results demonstrate the utility of a physiologically based model to characterize (i) the drug distribution across the in situ perfused rat intestine and (ii) the effect of chemical modulators in this biological system. PMID:19798765

  17. Effect of dietary fat on plasma glutathione peroxidase levels and intestinal absorption of /sup 75/Se-labeled sodium selenite in chicks

    SciTech Connect

    Mutanen, M.L.; Mykkaenen, H.M.

    1984-05-01

    The effect of dietary fat on the availability of selenium was investigated in chicks fed either 4 or 20% butter, olive oil, rape oil, corn oil or sunflower oil in the diet for 3 weeks after hatching. Plasma glutathione peroxidase (GSH-Px) activity was used as an indicator of the body selenium status. In addition, the intestinal absorption of sodium selenite (/sup 75/Se-labeled) was determined by using both the in vivo ligated loop procedure and oral administration of the isotope. The plasma GSH-Px levels increased with increasing proportion of the polyunsaturated fatty acids in the diet. Increasing the amount of fat from 4 to 20% significantly enhanced the GSH-Px activity in the groups receiving butter or olive oil, but had no effect in animals fed the unsaturated fats. The absorption of (/sup 75/Se)selenite from the ligated duodenal loops tended to be reduced in chicks fed corn oil or sunflower oil as compared to the animals receiving butter in their diet. On the other hand, the type of dietary fat did not appear to affect the absorption of the orally administered selenite. The present study demonstrates that the type of dietary fat can affect the plasma GSH-Px levels in chicks without altering the intestinal absorption of selenite. However, the results on the absorption of the intraduodenally injected sodium selenite suggest that dietary fat plays some role in the intestinal transport of selenium.

  18. The effect of different fatty acids on the intestinal lymphatic absorption of cyclosporin-A after oral administration in the rat

    SciTech Connect

    Jensen, B.K.

    1988-01-01

    Four studies were conducted in male Sprague-Dawley rats to evaluate the effect of saturated fatty acids (FA) of varying chain lengths on cyclosporin-A (CSA) intestinal lymphatic absorption. {sup 3}H-CSA was given to thoracic duct-ligated and sham rats in a nonlipid-(NL) or busyric (BA), octanoic (OA), lauric (LA), palmitic (PA), or stearic (SA) acid dosage form ({sup 14}C-FA) in an oral absorption study. The dosage forms were given to thoracic duct cannulated (TDC) rats to assess CSA intestinal lymphatic absorption. CSA blood-to-lymph transfer was assessed by intravenous {sup 3}H-CSA in TDC rats. Colchicine pretreated TDC rats received CSA in the NL and PA dosage forms. CSA and FA concentrations in blood and lymph were measured radiometrically. CSA and FA in the chylomicron and aqueous fractions were determined from ultracentrifugation of pooled lymph samples.

  19. Role of P-glycoprotein in the intestinal absorption of glabridin, an active flavonoid from the root of Glycyrrhiza glabra.

    PubMed

    Cao, Jie; Chen, Xiao; Liang, Jun; Yu, Xue-Qing; Xu, An-Long; Chan, Eli; Wei, Duan; Huang, Min; Wen, Jing-Yuan; Yu, Xi-Yong; Li, Xiao-Tian; Sheu, Fwu-Shan; Zhou, Shu-Feng

    2007-04-01

    Glabridin is a major constituent of the root of Glycyrrhiza glabra, which is commonly used in the treatment of cardiovascular and central nervous system diseases. This study aimed to investigate the role of P-glycoprotein (PgP/MDR1) in the intestinal absorption of glabridin. The systemic bioavailability of glabridin was approximately 7.5% in rats, but increased when combined with verapamil. In single-pass perfused rat ileum with mesenteric vein cannulation, the permeability coefficient of glabridin based on drug disappearance in luminal perfusates (P(lumen)) was approximately 7-fold higher than that based on drug appearance in the blood (P(blood)). Glabridin was mainly metabolized by glucuronidation, and the metabolic capacity of intestine microsomes was 1/15 to 1/20 of that in liver microsomes. Polarized transport of glabridin was found in Caco-2 and MDCKII monolayers. Addition of verapamil in both apical (AP) and basolateral (BL) sides abolished the polarized transport of glabridin across Caco-2 cells. Incubation of verapamil significantly altered the intracellular accumulation and efflux of glabridin in Caco-2 cells. The transport of glabridin in the BL-AP direction was significantly higher in MDCKII cells overexpressing PgP/MDR1 than in the control cells. Glabridin inhibited PgP-mediated transport of digoxin with an IC(50) value of 2.56 microM, but stimulated PgP/MDR1 ATPase activity with a K(m) of 25.1 microM. The plasma AUC(0-24h) of glabridin in mdr1a(-/-) mice was 3.8-fold higher than that in wild-type mice. These findings indicate that glabridin is a substrate for PgP and that both PgP/MDR1-mediated efflux and first-pass metabolism contribute to the low oral bioavailability of glabridin. PMID:17220245

  20. Effects of steroids and sex reversal on intestinal absorption of L-(/sup 14/C)leucine in vivo, in rainbow trout, Salmo gairdneri

    SciTech Connect

    Habibi, H.R.; Ince, B.W.

    1983-12-01

    The effects of steroids (17 alpha-methyltestosterone (MT), 17 beta-oestradiol (E2)), and of sex reversal (XX male) on intestinal absorption and accumulation of L-(/sup 14/C)leucine (5 mM), were investigated in unanaesthetized rainbow trout (Salmo gairdneri), using an in vivo gut perfusion technique. Each steroid was luminally perfused through the gut at a concentration of 50 micrograms/ml perfusate, during five separate perfusions carried out on the same fish at 30-min intervals (perfusion periods 1 to 5), for a total of 120 min at 14 degrees. Experiments were also conducted on masculinized, genetically female trout (XX male) with steroid-free perfusate. MT treatment significantly increased the intestinal absorption of radioleucine during periods 1 and 2, whilst E2 was without effect. Neither MT nor E2 influenced intestinal accumulation (mid- and hindgut) of radioleucine, and accumulation of /sup 14/C-solutes in skeletal muscle. Sex reversal, however, whilst having no effect on leucine absorption, nevertheless significantly increased intestinal accumulation of radioleucine, and accumulation of /sup 14/C-solutes in skeletal muscle. The effects observed in the present study are in agreement with previous work in trout using everted gut sac preparations. It is suggested that the growth-promoting effects of anabolic-androgenic steroids in fish may be partly explained by their action on gastrointestinal function.

  1. Enhanced intestinal absorption of etoposide by self-microemulsifying drug delivery systems: roles of P-glycoprotein and cytochrome P450 3A inhibition.

    PubMed

    Zhao, Gang; Huang, Jiangeng; Xue, Kewen; Si, Luqin; Li, Gao

    2013-11-20

    Etoposide is recognized as a dual P-glycoprotein (P-gp) and cytochrome P450 3A (CYP3A) substrate drug with poor water-solubility. To improve its solubility and bioavailability, three novel self-microemulsifying drug delivery systems (SMEDDS) contained the known P-gp and CYP3A inhibitory surfactants, Cremophor RH40, Cremophor EL, or Polysorbate 80, were prepared. This work aims to evaluate the enhanced intestinal absorption of etoposide SMEDDS as well as to explore the roles of P-gp and CYP3A inhibition in the absorption process. Etoposide SMEDDS were orally administered to rats for in vivo bioavailability investigation. In situ single-pass intestinal perfusion with mesenteric vein cannulation was employed to study the drug permeability and intestinal metabolism. In vitro Caco-2 cell models were applied to study the effects of P-gp and CYP3A inhibition by SMEDDS on the cellular accumulation of etoposide. It was found that the bioavailability and in situ intestinal absorption were significantly enhanced by SMEDDS with the order of Polysorbate 80-based SMEDDS>Cremophor EL-based SMEDDS>Cremophor RH40-based SMEDDS. In addition, there was a dramatically high linear correlation between the AUC0-t values and the apparent permeability coefficient values based on the appearance of the drug in mesenteric vein blood. Cellular uptake studies demonstrated that P-gp inhibition by SMEDDS played an important role in etoposide uptake. Moreover, etoposide metabolism was demonstrated to be dramatically inhibited by the three kinds of SMEDDS. These finding may assist in the improvement of the intestinal absorption of P-gp and/or CYP3A substrate drugs. PMID:23981337

  2. [Development of an oligoarginine peptide displaying rapid cell penetration for improved intestinal absorption].

    PubMed

    Takayama, Kentaro

    2014-01-01

    Arginine-rich peptides, including oligoarginines (Rn, n=7-12) are cell penetrating peptides (CPPs) and are useful for the intracellular delivery of membrane-impermeable substances. Endocytosed arginine-rich peptides can become trapped in endosomes, and the avoidance of endosomal retention is necessary for achieving effective cytosolic translocation. Our group has succeeded in enhancing the cellular uptake of oligoarginines by introducing short hydrophobic penetration accelerating sequences (Pas). The effectiveness of a Pas segment in improving the oligoarginine-mediated intracellular delivery of a biofunctional peptide was demonstrated through the efficient inhibition of glioma cell growth by a p53 C-terminal-derived retro-inverso peptide. The CPPs were expected to increase the penetration efficiency of low-permeability drugs through the intestinal epithelial cell layer into blood. Drugs conjugated to oligoarginines via a chemically stable linker tend to be retained in the negatively charged intracellular compartment due to the strongly cationic peptides. Our group has proposed the use of a self-cleavable linker strategy that effectively releases the drugs from the oligoarginine peptide. Chemical-triggered self-cleavage produces the parent drug via intramolecular imide formation under physiological conditions. The designed model drug-oligoarginine conjugates were converted with the half-life (t1/2) values of 9-100 min. Conjugates possessing a short t1/2 of 9-10 min improved the transport rate of the parent model drug in a Caco-2 monolayer permeation assay. The Pas attachment to the oligoarginine was also found to be effective in this permeation assay. The Pas attachment may provide a new platform for facilitating arginine-rich CPP-mediated cargo transport. PMID:24389618

  3. Self-micro emulsifying formulation improved intestinal absorption and oral bioavailability of bakuchiol.

    PubMed

    Pi, Jiaxin; Gao, Xu; Yu, Yue; Zheng, Yin; Zhu, Zhuangzhi; Wang, Yajing

    2014-10-18

    Bakuchiol (BAK), isolated from the seeds of Psoralea corylifolia L., recently presents a variety of pharmacologic activities. However, the poor oral bioavailability limits its further development and clinical use. The purpose of this study was to establish a self-microemulsifying (SME) formulation for oral delivery improvement of BAK. The optimized liquid SME formulation was comprised of BAK (40%), Cremophor RH 40 (30%) and Labrasol (30%). The emulsion droplets were spherical in shape, and particle size and zeta potential were determined. The in vitro dissolution test of BAK-SME formulation illustrated faster dissolution rate than the bulk drug. The permeabilities of 40?gmL(-1) BAK-SME formulation in rat intestinal segments of duodenum, jejunum, ileum and colon were 30.91נ10(-3), 23.61נ10(-3), 29.43נ10(-3) and 23.62נ10(-3) cmmin(-1), respectively, exhibiting 3.99 times in duodenum, 2.59 times in ileum and 2.31 times in colon greater than BAK perfusate. The oral bioavailability of BAK-SME formulation at a dose of 150mgkg(-1) was determined in rats. The Cmax and the AUC(0-24h) were 515.4ngmL(-1) and 4,327.2hngmL(-1), respectively, which were 1.90 fold and 1.73 fold greater than the value of BAK suspension. All these results clearly stated that BAK-SME formulation performed well-improvement on oral bioavailability of BAK. PMID:25325927

  4. Effect of compounds affecting ABCA1 expression and CETP activity on the HDL pathway involved in intestinal absorption of lutein and zeaxanthin.

    PubMed

    Niesor, Eric J; Chaput, Evelyne; Mary, Jean-Luc; Staempfli, Andreas; Topp, Andreas; Stauffer, Andrea; Wang, Haiyan; Durrwell, Alexandre

    2014-12-01

    The antioxidant xanthophylls lutein and zeaxanthin are absorbed from the diet in a process involving lipoprotein formation. Selective mechanisms exist for their intestinal uptake and tissue-selective distribution, but these are poorly understood. We investigated the role of high-density lipoprotein (HDL), apolipoprotein (apo) A1 and ATP-binding cassette transporter (ABC) A1 in intestinal uptake of lutein in a human polarized intestinal cell culture and a hamster model. Animals received dietary lutein and zeaxanthin and either a liver X receptor (LXR) agonist or statin, which up- or down-regulate intestinal ABCA1 expression, respectively. The role of HDL was studied following treatment with the cholesteryl ester transfer protein (CETP) modulator dalcetrapib or the CETP inhibitor anacetrapib. In vitro, intestinal ABCA1 at the basolateral surface of enterocytes transferred lutein and zeaxanthin to apoA1, not to mature HDL. In hamsters, plasma lutein and zeaxanthin levels were markedly increased with the LXR agonist and decreased with simvastatin. Dalcetrapib, but not anacetrapib, increased plasma and liver lutein and zeaxanthin levels. ABCA1 expression and apoA1 acceptor activity are important initial steps in intestinal uptake and maintenance of lutein and zeaxanthin levels by an HDL-dependent pathway. Their absorption may be improved by physiological and pharmacological interventions affecting HDL metabolism. PMID:25300953

  5. Further studies on the perfusion method for measuring intestinal absorption in man: The effects of a proximal occlusive balloon and a mixing segment

    PubMed Central

    Sladen, G. E.; Dawson, A. M.

    1970-01-01

    The reliability and accuracy of the two-lumen tube perfusion method for measuring intestinal absorption in man has been assessed by the use of a proximal occlusive balloon in nine normal volunteers. Luminal occlusion significantly reduced the variability of individual glucose and water absorption rates, and reduced the variability of triplicate marker concentrations within individual studies. Mean absorption rates of glucose, water, sodium, and chloride were not significantly affected by luminal occlusion. Absorption rates obtained with the triple-lumen tube method were rather more variable both within and between individuals, but a statistical comparison of the accuracy of the two methods could not be made. These results are discussed in relation to the contribution of endogenous gut secretion and proximal reflux of infused fluid to the variability of absorption rates obtained by the perfusion technique. ImagesFig. 1 PMID:5492251

  6. Role of rat intestinal glucoamylase in glucose polymer hydrolysis and absorption.

    PubMed

    Azad, M A; Lebenthal, E

    1990-08-01

    Rice starch is a main source of energy in many lesser developed countries. We studied different chain-lengths of rice glucose polymers (GP) to evaluate their possible use in feeding infants in developing countries. The initial GP of rice (G1 = 4.6, G2 = 4.5, G3 = 15.4, G4 = 7.3, G5 = 17.4, G6-G9 = 9.61 and greater than G9 = 31.3%) was analyzed by HPLC and then separated in a Bio-Gel P-2 column and compared to its short-chain GP of rice (G2 = 22.7, G3 = 28.2, G4 = 14.0, G5 = 16.6, G6 = 11.6, G7-G9 = 6.9%), long-chain GP of rice (greater than G9 = 100%), and D-glucose. Intraduodenal bolus infusion of 10% solution of short-chain rice GP when compared with long-chain rice GP, the initial rice GP, or D-glucose showed significantly higher values at peak absorption time (0 to 30 min) in the portal venous blood glucose response. The portal venous glycemic response of short-chain rice GP compared with D-glucose was as follows: 2.5 +/- 0.1 versus 2.0 +/- 0.2 cm2, area under the portal blood glucose curve at 0-30 min (p less than 0.01). Glucoamylase, the key enzyme for brush-border hydrolysis of short-chain GP, was assessed with a newly modified glucoamylase assay using GP G5-G8 as substrate. Our finding of faster glucose absorption with short-chain rice GP compared with isocaloric D-glucose might have important physiologic implications for carbohydrate absorption. The osmolality of short-chain rice GP is nearly one-fourth that of glucose. This might have important bearing in the design of infant feeding where increased caloric density with low osmolality is desirable. PMID:2118618

  7. LITERATURE REVIEW FOR OXALATE OXIDATION PROCESSES AND PLUTONIUM OXALATE SOLUBILITY

    SciTech Connect

    Nash, C.

    2012-02-03

    A literature review of oxalate oxidation processes finds that manganese(II)-catalyzed nitric acid oxidation of oxalate in precipitate filtrate is a viable and well-documented process. The process has been operated on the large scale at Savannah River in the past, including oxidation of 20 tons of oxalic acid in F-Canyon. Research data under a variety of conditions show the process to be robust. This process is recommended for oxalate destruction in H-Canyon in the upcoming program to produce feed for the MOX facility. Prevention of plutonium oxalate precipitation in filtrate can be achieved by concentrated nitric acid/ferric nitrate sequestration of oxalate. Organic complexants do not appear practical to sequester plutonium. Testing is proposed to confirm the literature and calculation findings of this review at projected operating conditions for the upcoming campaign. H Canyon plans to commence conversion of plutonium metal to low-fired plutonium oxide in 2012 for eventual use in the Mixed Oxide Fuel (MOX) Facility. The flowsheet includes sequential operations of metal dissolution, ion exchange, elution, oxalate precipitation, filtration, and calcination. All processes beyond dissolution will occur in HB-Line. The filtration step produces an aqueous filtrate that may have as much as 4 M nitric acid and 0.15 M oxalate. The oxalate needs to be removed from the stream to prevent possible downstream precipitation of residual plutonium when the solution is processed in H Canyon. In addition, sending the oxalate to the waste tank farm is undesirable. This report addresses the processing options for destroying the oxalate in existing H Canyon equipment.

  8. Secretin receptor-knockout mice are resistant to high-fat diet-induced obesity and exhibit impaired intestinal lipid absorption.

    PubMed

    Sekar, Revathi; Chow, Billy K C

    2014-08-01

    Secretin, a classical gastrointestinal hormone released from S cells in response to acid and dietary lipid, regulates pleiotropic physiological functions, such as exocrine pancreatic secretion and gastric motility. Subsequent to recently proposed revisit on secretin's metabolic effects, we have confirmed lipolytic actions of secretin during starvation and discovered a hormone-sensitive lipase-mediated mechanistic pathway behind. In this study, a 12 wk high-fat diet (HFD) feeding to secretin receptor-knockout (SCTR(-/-)) mice and their wild-type (SCTR(+/+)) littermates revealed that, despite similar food intake, SCTR(-/-) mice gained significantly less weight (SCTR(+/+): 49.6±0.9 g; SCTR(-/-): 44.7±1.4 g; P<0.05) and exhibited lower body fat content. These SCTR(-/-) mice have corresponding alleviated HFD-associated hyperleptinemia and improved glucose/insulin tolerance. Further analyses indicate that SCTR(-/-) have impaired intestinal fatty acid absorption while having similar energy expenditure and locomotor activity. Reduced fat absorption in the intestine is further supported by lowered postprandial triglyceride concentrations in circulation in SCTR(-/-) mice. In jejunal cells, transcript and protein levels of a key fat absorption regulator, cluster of differentiation 36 (CD36), was reduced in knockout mice, while transcript of Cd36 and fatty-acid uptake in isolated enterocytes was stimulated by secretin. Based on our findings, a novel positive feedback pathway involving secretin and CD36 to enhance intestinal lipid absorption is being proposed. PMID:24769669

  9. Calcium oxalate content affects the nutritional availability of calcium from Medicago truncatula leaves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is known that oxalate, present in edible plants, can bind calcium in a crystalline form that reduces the availability of the bound calcium for nutritional absorption by humans. It is unknown, however, the degree to which the calcium oxalate content of a plant can be genetically altered and how mu...

  10. Kinetic analysis of hexose transport to determine the mechanism of amygdalin and prunasin absorption in the intestine.

    PubMed

    Wagner, Brent; Galey, William R

    2003-01-01

    Evidence is accumulating that glucose-conjugated compounds may be carried across the gut mucosa via the epithelial sodium-dependent monosaccharide transporter SGLT1. A modification of the everted intestinal sac technique was utilized to study the transport of the cyanogenic glycoside amygdalin (D-mandelonitrile beta-D-gentiobioside) and its metabolite D-mandelontrile beta-D-glucoside (prunasin). Everted sacs of rat jejunum and ileum were bathed in isotonic oxygenated sodium chloride-potassium phosphate buffer containing 2.8 microCi D-[(3)H]-mannose and 0.187 microCi D-[(14)C]-glucose. For treatment groups, buffers contained phloridzin, galactose, amygdalin or prunasin. The rate constant (k) for the transport process was calculated. Compared with the control (n = 33), phloridzin (n = 25) significantly reduced the rate constants of both D-[(14)C]-glucose and D-[(3)H]-mannose. Substitution of sodium with choline and incremental galactose treatments similarly reduced D-[(14)C]-glucose influx, indicating that a fraction of the transport is carrier-mediated. Treatment with amygdalin did not significantly affect the rate constants of D-[(14)C]-glucose or D-[(3)H]-mannose transport. However, treatment with 1 mM prunasin (n = 16) did reduce the influx of D-[(14)C]-glucose without affecting D-[(3)H]-mannose values. This is consistent with the reports finding that glycoside absorption may be mediated by SGLT1. PMID:12975776

  11. Improved intestinal absorption of a poorly water-soluble oral drug using mannitol microparticles containing a nanosolid drug dispersion.

    PubMed

    Nishino, Yukiko; Kubota, Aya; Kanazawa, Takanori; Takashima, Yuuki; Ozeki, Tetsuya; Okada, Hiroaki

    2012-11-01

    A nozzle for a spray dryer that can prepare microparticles of water-soluble carriers containing various nanoparticles in a single step was previously developed in our laboratory. To enhance the solubility and intestinal absorption of poorly water-soluble drugs, we used probucol (PBL) as a poorly water-soluble drug, mannitol (MAN) as a water-soluble carrier for the microparticles, and EUDRAGIT (EUD) as a polymer vehicle for the solid dispersion. PBL-EUD-acetone-methanol and aqueous MAN solutions were simultaneously supplied through different liquid passages of the spray nozzle and dried together. PBL-EUD solid dispersion was nanoprecipitated in the MAN solution using an antisolvent mechanism and rapidly dried by surrounding it with MAN. PBL in the dispersion vehicle was amorphous and had higher physical stability according to powder X-ray diffraction and differential scanning calorimetry analysis. The bioavailability of PBL in PBL-EUD S-100-MAN microparticles after oral administration in rats was markedly higher (14- and 6.2-fold, respectively) than that of the original PBL powder and PBL-MAN microparticles. These results demonstrate that the composite microparticles containing a nanosized solid dispersion of a poorly water-soluble drug prepared using the spray nozzle developed by us should be useful to increase the solubility and bioavailability of drugs after oral administration. PMID:22864998

  12. Absorption of fumonisin B1 and aminopentol on an in vitro model of intestinal epithelium; the role of P-glycoprotein.

    PubMed

    De Angelis, I; Frigg, G; Raimondi, F; Stammati, A; Zucco, F; Caloni, F

    2005-03-01

    The aim of the present paper is to evaluate the absorption of fumonisin B1 and its principal metabolite, aminopentol on a human intestinal model, Caco-2 cells, cultured on semi-permeable inserts, that reproduces the two different intestinal compartments: luminal (apical) and serosal (basolateral) side. Following separate exposure in apical and in basolateral compartments, aminopentol passage through the cell layer (in particular from basolateral to apical direction) was shown, while it was not observed for the parent compound. The different aminopentol distribution between the two compartments of the culture system, and its variation in presence of verapamil or probenecid (P-gp and MRP inhibitors respectively), strongly suggests the involvement of P-glycoprotein in the influx/efflux mechanisms of aminopentol in the intestinal cells, reducing its oral bioavailability. PMID:15683866

  13. In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation.

    PubMed

    Franek, F; Jarlfors, A; Larsen, F; Holm, P; Steffansen, B

    2015-09-18

    Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq(), an extended release formulation (ERF). Semi-mechanistic models of desvenlafaxine were built (using SimCyp()) by combining in vitro data on dissolution and permeation (mechanistic part of model) with clinical data (obtained from literature) on distribution and clearance (non-mechanistic part of model). The model predictions of desvenlafaxine pharmacokinetics after IRF and ERF administration were compared with published clinical data from 14 trials. Desvenlafaxine in vivo dissolution from the IRF and ERF was predicted from in vitro solubility studies and biorelevant dissolution studies (using the USP3 dissolution apparatus), respectively. Desvenlafaxine apparent permeability (Papp) at varying apical pH was investigated using the Caco-2 cell line and extrapolated to effective intestinal permeability (Peff) in human duodenum, jejunum, ileum and colon. Desvenlafaxine pKa-values and octanol-water partition coefficients (Do:w) were determined experimentally. Due to predicted rapid dissolution after IRF administration, desvenlafaxine was predicted to be available for permeation in the duodenum. Desvenlafaxine Do:w and Papp increased approximately 13-fold when increasing apical pH from 5.5 to 7.4. Desvenlafaxine Peff thus increased with pH down the small intestine. Consequently, desvenlafaxine absorption from an IRF appears rate-limited by low Peff in the upper small intestine, which "delays" the predicted time to the maximal plasma concentration (tmax), consistent with clinical data. Conversely, desvenlafaxine absorption from the ERF appears rate-limited by dissolution due to the formulation, which tends to negate the influence of pH-dependent permeability on absorption. We suggest that desvenlafaxine Peff is mainly driven by transcellular diffusion of the unionized form. In the case of desvenlafaxine, poor metabolism does not imply low intestinal permeability, as indicated by the BDDCS, merely low duodenal/jejunal permeability. PMID:26091569

  14. OXALATE DEPOSITION ON ASBESTOS BODIES

    EPA Science Inventory

    The clinical and histopathologic findings in three patients with a deposition of calcium oxalate crystals on ferruginous bodies after occupational exposure to asbestos are provided. In addition, we test the hypothesis that this oxalate can be generated through a nonenzymatic o...

  15. Lycopene absorption in human intestinal cells and in mice involves scavenger receptor class B type I but not Niemann-Pick C1-like 1.

    PubMed

    Moussa, Myriam; Landrier, Jean-Franois; Reboul, Emmanuelle; Ghiringhelli, Odette; Comra, Christine; Collet, Xavier; Frhlich, Kati; Bhm, Volker; Borel, Patrick

    2008-08-01

    Cholesterol membrane transporters scavenger receptor class B type I (SR-BI) and (cluster determinant 36) are involved in intestinal uptake of lutein and beta-carotene, 2 of the 3 main carotenoids of the human diet. The aim of this work was therefore to determine whether SR-BI and NPC1L1 (Niemann-Pick C1-like 1), another cholesterol transporter, are implicated in absorption of lycopene, the 3rd main carotenoid of the human diet. Anti-human SR-BI antibody and block lipid transport 1 (BLT1) (a chemical inhibitor of lipid transport by SR-BI) impaired up to 60% (all-E) and (5Z)-lycopene uptake (P < 0.05) by Caco-2 cell monolayers, which were used as a model of human intestinal epithelium. The involvement of SR-BI in lycopene absorption in vivo was then verified by comparing plasma lycopene concentrations in wild-type and SR-BI transgenic mice that were fed a diet enriched with 0.25 g/kg (all-E)-lycopene for 1 mo. Plasma lycopene concentrations were approximately 10-fold higher (P < 0.001) in mice overexpressing SR-BI in the intestine than in wild-type mice, confirming the involvement of SR-BI in lycopene absorption. Further experiments showed that (all-E)-lycopene did not affect SR-BI mRNA levels in Caco-2 cells or mouse intestine. In contrast to SR-BI, neither anti-human NPC1L1 antibody nor ezetimibe, used as inhibitors of lycopene uptake via NPC1L1, significantly impaired (all-E) or (5Z)-lycopene uptake by Caco-2 monolayers. Thus, the present data show that lycopene absorption is, at least in part, mediated by SR-BI but not by NPC1L1. PMID:18641187

  16. Feeding rates affect growth, intestinal digestive and absorptive capabilities and endocrine functions of juvenile blunt snout bream Megalobrama amblycephala.

    PubMed

    Xu, Chao; Li, Xiang-Fei; Tian, Hong-Yan; Jiang, Guang-Zhen; Liu, Wen-Bin

    2016-04-01

    This study aimed to investigate the optimal feeding rate for juvenile blunt snout bream (average initial weight 23.74 ± 0.09 g) based on the results on growth performance, intestinal digestive and absorptive capabilities and endocrine functions. A total of 840 fish were randomly distributed into 24 cages and fed a commercial feed at six feeding rates ranging from 2.0 to 7.0 % body weight (BW)/day. The results indicated that weight gain rate increased significantly (P < 0.05) as feeding rates increased from 2.0 to 5.0 % BW/day, but decreased with the further increasing feeding rates (P > 0.05). Protein efficiency ratio and nitrogen and energy retention all showed a similar trend. However, feed conversion ratio increased significantly (P < 0.05) with increasing feeding rates. Feeding rates have little effects (P > 0.05) on whole-body moisture, ash and protein contents, but significantly (P < 0.05) affect both lipid and energy contents with the highest values both observed in fish fed 4.0 % BW/day. In addition, moderate ration sizes (2.0-4.0 % BW/day) resulted in the enhanced activities of intestinal enzymes, including lipase, protease, Na(+), K(+)-ATPase, alkaline phosphatase and creatine kinase. Furthermore, the mRNA levels of growth hormone, insulin-like growth factors-I, growth hormone receptor and neuropeptide all increased significantly (P < 0.05) as feeding rates increased from 2.0 to 5.0 % and 6.0 % BW/day, but decreased significantly (P < 0.05) with the further increase in feeding rates, whereas both leptin and cholecystokinin expressions showed an opposite trend. Based on the broken-line regression analysis of SGR against feeding rates, the optimal feeding rate for juvenile blunt snout bream was estimated to be 4.57 % BW/day. PMID:26597852

  17. [Traditional Chinese medicine pairs (III)--effect of extract of Ginseng Radix et Rhizoma and Puerariae Lobatae Radix on intestinal absorption in rats].

    PubMed

    Chen, Yi-hang; Li, Meng-xuan; Meng, Zhao-qing; Yang, Jiao-jiao; Huang, Wen-zhe; Wang, Zhen-zhong; Wang, Yue-sheng; Xiao, Wei

    2015-08-01

    This study focused on the intestinal absorption of traditional Chinese medicines (TCM) to reveal the scientific connotation of the compatibility of TCM pairs. The single pass intestinal perfusion (SPIP) was used in rats to compare the absorption of single extracts from Puerariae Lobatae Radix, single extracts from Ginseng Radix et Rhizoma, combined extracts from Puerariae Lobatae Radix and Ginseng Radix et Rhizoma and Puerariae Lobatae Radix and Ginseng Radix et Rhizoma mixture in rats. The content of puerarin, ginsenoside Rg1, ginsenoside Re and ginsenoside Rb1 in liquid were tested by HPLC. The speed constant (Ka) and apparent permeability coefficients (Papp) were calculated and compared. Specifically, the order of puerarin Ka and Papp values from high to low was Ginseng Radix et Rhizoma and Puerariae Lobatae Radix mixture > single extracts from Puerariae Lobatae Radix > combined extracts from Ginseng Radix et Rhizoma and Puerariae Lobatae Radix; the order of ginsenosides Ka and Papp values from high to low was Ginseng Radix et Rhizoma and Puerariae Lobatae Radix mixture > single extracts from Ginseng Radix et Rhizoma > combined extracts from Ginseng Radix et Rhizoma and Puerariae Lobatae Radix. The combined administration of Ginseng Radix et Rhizoma and Puerariae Lobatae Radix may improve the absorption in the intestinal tract. PMID:26677717

  18. Intestinal Failure (Short Bowel Syndrome)

    MedlinePLUS

    ... N Vitamin deficiencies as a result of poor absorption in the intestine N Electrolyte and mineral deficiencies ... N Kidney stones or gallstones due to poor absorption of calcium or bile How is intestinal failure ...

  19. Bioavailability of soluble oxalate from spinach eaten with and without milk products.

    PubMed

    Brogren, Madelene; Savage, Geoffrey P

    2003-01-01

    Leafy vegetables such as spinach (Spinacia oleracea) are known to contain moderate amounts of soluble and insoluble oxalates. Frozen commercially available spinach in New Zealand contains 736.6+/-20.4 mg/100g wet matter (WM) soluble oxalate and 220.1+/-96.5mg/100g WM insoluble oxalate. The frozen spinach contained 90mg total calcium/100g WM, 76.7%of this calcium was unavailable as it was bound to oxalate as insoluble oxalate. The oxalate/calcium (mEq) ratio of the frozen spinach was 4.73. When frozen convenience food is grilled there is no opportunity for the soluble oxalates to be leached out into the cooking water and discarded. Soluble oxalates, when consumed, have the ability to bind to calcium in the spinach and any calcium in foods consumed with the spinach, reducing the absorption of soluble oxalate. In this experiment 10 volunteers ingested 100g grilled spinach alone or with 100g additions of cottage cheese, sour cream and sour cream with Calci-Trim milk (180 g) and finally, with 20g olive oil. The availability of oxalate in the spinach was determined by measuring the oxalate output in the urine over a 6-hour and 24-hour period after intake of the test meal. The mean bioavailability of soluble oxalate in the grilled spinach was 0.75+/-0.48% over a 6-hour period after intake and was 1.93+/-0.85% measured over a 24-hour period. Addition of sour cream and Calci-Trim milk reduced the availability of the oxalate in the spinach significantly (P<0.05) in both the 6-hour and 24-hour collection periods. PMID:12810415

  20. Use of NBD-cholesterol to identify a minor but NPC1L1-independent cholesterol absorption pathway in mouse intestine.

    PubMed

    Adams, Michelle R; Konaniah, Eddy; Cash, James G; Hui, David Y

    2011-01-01

    The importance of Niemann-Pick C1 Like-1 (NPC1L1) protein in intestinal absorption of dietary sterols, including both cholesterol and phytosterols, is well documented. However, the exact mechanism by which NPC1L1 facilitates cholesterol transport remains controversial. This study administered 22-(N(-7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol) and [(3)H]cholesterol to Npc1l1(+/+) and Npc1l1(-/-) mice to determine whether NPC1L1 facilitates dietary sterol uptake by enterocytes and/or participates in intracellular sterol delivery to the endoplasmic reticulum (ER) for lipoprotein assembly before secretion into plasma circulation. Results showed that [(3)H]cholesterol absorption was reduced but not abolished in Npc1l1(-/-) mice compared with Npc1l1(+/+) mice. In the presence of Pluronic L-81 to block pre-chylomicron exit from the ER, significant amounts of [(3)H]cholesterol were found to be associated with lipid droplets in the intestinal mucosa of both Npc1l1(+/+) and Npc1l1(-/-) mice, and the intracellular [(3)H]cholesterol can be esterified to cholesteryl esters. These results provided evidence indicating that the main function of NPC1L1 is to promote cholesterol uptake from the intestinal lumen but that it is not necessary for intracellular cholesterol transport to the ER. Surprisingly, NBD-cholesterol was taken up by intestinal mucosa, esterified to NBD-cholesteryl esters, and transported to plasma circulation to similar extent between Npc1l1(+/+) and Npc1l1(-/-) mice. Ezetimibe treatment also had no impact on NBD-cholesterol absorption by Npc1l1(+/+) mice. Thus, NBD-cholesterol absorption proceeds through an NPC1L1-independent and ezetimibe-insensitive sterol absorption mechanism. Taken together, these results indicate that NBD-cholesterol can be used to trace the alternative cholesterol absorption pathway but is not suitable for tracking NPC1L1-mediated cholesterol absorption. PMID:21071508

  1. An Approach to Improve Intestinal Absorption of Poorly Absorbed Water-Insoluble Components via Niemann-Pick C1-Like 1.

    PubMed

    Takekawa, Yuto; Sato, Yuki; Yamaki, Yoshiaki; Imai, Mei; Noto, Kazuma; Sumi, Masato; Takekuma, Yoh; Iseki, Ken; Sugawara, Mitsuru

    2016-01-01

    Dietary and biliary cholesterol absorption contributes to the maintenance of tight control of cholesterol homeostasis. Cholesterol is present as mixed micelles formed by bile salts and phospholipids in the intestinal lumen. Recently, Niemann-Pick C1-Like 1 (NPC1L1) transporter was identified as being critical for cholesterol absorption. However, the uptake mechanism of an enveloped substrate of NPC1L1 in whole lipid emulsion particles remains unclear. In this study, we investigated the uptake mechanism of a substrate of NPC1L1 in lipid emulsion particles. We also investigated whether these particles containing cholesterol can improve the intestinal absorption of other lipophilic components via NPC1L1. The uptake of lysophosphatidylcholine (LPC)-4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-propionic acid saccinimidyl ester (BODIPY), a fluorescently labeled phospholipid, in lipid emulsion particles containing cholesterol (1?M) was significantly increased compared to that without cholesterol in Caco-2 cells. On the other hand, its increased uptake was significantly inhibited by ezetimibe, a selective inhibitor of NPC1L1. These results suggested that not only cholesterol but also some components in lipid emulsion particles are taken up into enterocytes via NPC1L1. We also examined an approach to improve intestinal absorption of a poorly absorbed water-insoluble component, coenzyme Q10 (CoQ10), by this mechanism. The uptake of CoQ10 in lipid emulsion particles containing cholesterol was significantly increased compared to that without cholesterol. Its increased uptake was significantly inhibited by ezetimibe. Though it is still not clear whether CoQ10 is a substrate of NPC1L1, there is a potential for improvement of the absorption of poorly absorbed components by lipid emulsion particles containing cholesterol. PMID:26934923

  2. Short communication: Casein hydrolysate and whey proteins as excipients for cyanocobalamin to increase intestinal absorption in the lactating dairy cow.

    PubMed

    Artegoitia, V M; de Veth, M J; Harte, F; Ouellet, D R; Girard, C L

    2015-11-01

    Bioavailability of vitamin B12 is low in humans and animals. Improving vitamin B12 absorption is important for optimal performance in dairy cows and for increasing vitamin B12 concentrations in milk for human consumption. However, when supplemented in the diet, 80% of synthetic vitamin B12, cyanocobalamin (CN-CBL), is degraded in the rumen of dairy cows and only 25% of the amount escaping destruction in the rumen disappears from the small intestine between the duodenal and ileal cannulas. In pigs, vitamin B12 from milk is more efficiently absorbed than synthetic CN-CBL. The objective of this study was to determine the efficacy of casein hydrolysate and whey proteins as excipients for CN-CBL to increase portal-drained viscera (PDV) flux of the vitamin in lactating dairy cows. Four multiparous lactating Holstein cows (237 ± 17 DIM) equipped with a rumen cannula and catheters in the portal vein and a mesenteric artery were used in a randomized Youden square design. They were fed every 2 h to maintain steady digesta flow. On experimental days, they received a postruminal bolus of (1) CN-CBL alone (0.1 g), (2) CN-CBL (0.1 g) + casein hydrolysate (10 g), or (3) CN-CBL (0.1 g) + whey proteins (10 g). Starting 30 min after the bolus, blood samples were taken simultaneously from the 2 catheters every 15 min during the first 2 h and then every 2 h until 24 h postbolus. Milk yield, DMI, and vitamin B12 portal-arterial difference and PDV flux were analyzed using the MIXED procedure of SAS. Milk yield and DMI were not affected by treatments. The portal-arterial difference of vitamin B12 during the 24-h period following the bolus of vitamin was greater when the vitamin was given in solution with casein hydrolysate (2.9 ± 4.6 pg/mL) than alone (-17.5 ± 5.2 pg/mL) or with whey protein (-13.4 ± 4.2 pg/mL). The treatment effects were similar for the PDV flux. The present results suggest that CN-CBL given with casein hydrolysate increases vitamin B12 absorption as compared with CN-CBL given alone. PMID:26364097

  3. Gene expression profiles in rat intestine identify pathways for 1,25-dihydroxyvitamin D(3) stimulated calcium absorption and clarify its immunomodulatory properties.

    PubMed

    Kutuzova, Galina D; Deluca, Hector F

    2004-12-15

    Microarray technology has been used to discover 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) induced gene expression changes in rat small intestine in vivo. Here, we report gene expression changes related to intestinal absorption or transport, the immune system and angiogenesis in response to 1,25-(OH)(2)D(3). Vitamin D deficient rats were intrajugularly given vehicle or vehicle containing 730 ng of 1,25-(OH)(2)D(3)/kg of body weight. Intestinal mRNA was harvested from duodenal mucosa at 15 min, 1, 3, and 6 h post-injection and studied by Affymetrix microarrays. Genes significantly affected by 1,25-(OH)(2)D(3) were confirmed by quantitative RT-PCR with remarkable agreement. The most strongly affected gene in intestine was CYP24 with 97-fold increase at 6 h post-1,25-(OH)(2)D(3) treatment. Intestinal calcium absorption genes: TRPV5, TRPV6, calbindin D(9k), and Ca(2+) dependent ATPase all were up-regulated in response to 1,25-(OH)(2)D(3), supporting the currently accepted mechanism of 1,25-(OH)(2)D(3) induced transcellular calcium transport. However, a 1,25-(OH)(2)D(3) suppression of several intra-/intercellular matrix modeling proteins such as sodium/potassium ATPase, claudin 3, aquaporin 8, cadherin 17, and RhoA suggests a vitamin D regulation of tight junction permeability and paracellular calcium transport. Several other genes related to the immune system and angiogenesis whose expression was changed in response to 1,25-(OH)(2)D(3) provided evidence for an immunomodulatory and anti-angiogenic role of 1,25-(OH)(2)D(3). PMID:15542054

  4. Oxalate, calcium and ash intake and excretion balances in fat sand rats (Psammomys obesus) feeding on two different diets.

    PubMed

    Palgi, Niv; Vatnick, Itzick; Pinshow, Berry

    2005-05-01

    Fat sand rats Psammomys obesus feed exclusively on plants of the family Chenopodiaceae, which contain high concentrations of chloride salts (NaCl, KCl) and oxalate salts. Ingestion of large quantities of oxalate is challenging for mammals because oxalate chelates Ca(2+) cations, reducing Ca(2+) availability. Oxalate is a metabolic end-point in mammalian metabolism, however it can be broken-down by intestinal bacteria. We predicted that in fat sand rats microbial breakdown of oxalate will be substantial due to the high dietary load. In addition, since a high concentration of soluble chloride salts increases the solubility of calcium oxalate in solution, we examined whether a change in the intake of chloride salts affects microbial oxalate breakdown and calcium excretion in fat sand rats. We measured oxalate, calcium and other inorganic matter (ash) intake and excretion in fat sand rats feeding on two different diets: saltbush (Atriplex halimus), their natural diet, and goose-foot (Chenopodium album), a non-native chenopod on which fat sand rats will readily feed and that has a similar oxalate content to saltbush but only 2/3 of the ash content. In animals feeding on both diets, 65-80% of the oxalate ingested did not appear in urine or faeces. In animals consuming the more saline saltbush, significantly more oxalate was apparently degraded (p<0.001), while significantly less oxalate was excreted in urine (p<0.01) and in faeces (p<0.05). We propose, therefore, that fat sand rats rely on symbiotic bacteria to remove a large portion of the oxalates ingested with their diet, and that the high dietary salt intake may play a beneficial role in their oxalate and calcium metabolism. PMID:15922640

  5. Transport of sennosides and sennidines from Cassia angustifolia and Cassia senna across Caco-2 monolayers--an in vitro model for intestinal absorption.

    PubMed

    Waltenberger, B; Avula, B; Ganzera, M; Khan, I A; Stuppner, H; Khan, S I

    2008-05-01

    Laxative effects of Senna preparations are mainly mediated by rheinanthrone, a metabolite formed in the intestinal flora from dianthrones. Nevertheless, it was not clear whether dianthrones are bioavailable at all and contribute to the overall effects of this important medicinal plant. Using the Caco-2 human colonic cell line as an in vitro model of the human intestinal mucosal barrier, the bioavailability of dianthrones was studied in apical to basolateral (absorptive) and basolateral to apical (secretive) direction. Permeability coefficients (P(c)) and percent transport were calculated based on quantitations by HPLC. From the data obtained it was concluded that sennosides A and B, as well as their aglycones sennidine A and B are transported through the Caco-2 monolayers in a concentration-dependent manner and their transport was linear with time. The absorption in apical to basolateral direction was poor and P(c) values were comparable to mannitol. The transport was higher in the secretory direction, indicating a significant efflux (e.g. by efflux pumps) of the (poorly) absorbed compounds in the intestinal lumen again. Our findings support the general understanding that the laxative effects of Senna are explainable mainly by metabolites and not by the natively present dianthrones. PMID:17481875

  6. Absorption

    PubMed Central

    Menzies, Victoria; Taylor, Ann Gill; Bourguignon, Cheryl

    2009-01-01

    Given that mindbody interventions constitute a major portion of complementary and alternative medicine used by the public, it seems important to explore those human characteristics that may contribute to the efficacy of mindbody interventions in those who are most likely to benefit. One such characteristic, absorption, reflects an individuals cognitive capacity for involvement in sensory and imaginative experiences in ways that alter an individuals perception, memory, and mood with behavioral and biological consequences. Thus, ones level of absorption may potentially create differential treatment effects in mindbody intervention outcomes. Conducting practical clinical trials helps address the challenge of determining whether a specific mindbody modality intervention may be effective. Such trials may be strengthened by including measures of personality dimensions such as absorption. PMID:19126883

  7. Medical therapy, calcium oxalate urolithiasis

    NASA Technical Reports Server (NTRS)

    Ruml, L. A.; Pearle, M. S.; Pak, C. Y.

    1997-01-01

    The development of diagnostic protocols that identify specific risk factors for calcium oxalate nephrolithiasis has led to the formulation of directed medical regimens that are aimed at correcting the underlying metabolic disturbances. Initiation of these treatment programs has reduced markedly the rate of stone formation in the majority of patients who form stones. This article discusses the rationale that underlies the choice of medical therapy for the various pathophysiologic causes of calcium oxalate nephrolithiasis and the appropriate use of available medications.

  8. Medical therapy, calcium oxalate urolithiasis.

    PubMed

    Ruml, L A; Pearle, M S; Pak, C Y

    1997-02-01

    The development of diagnostic protocols that identify specific risk factors for calcium oxalate nephrolithiasis has led to the formulation of directed medical regimens that are aimed at correcting the underlying metabolic disturbances. Initiation of these treatment programs has reduced markedly the rate of stone formation in the majority of patients who form stones. This article discusses the rationale that underlies the choice of medical therapy for the various pathophysiologic causes of calcium oxalate nephrolithiasis and the appropriate use of available medications. PMID:9048856

  9. Caco-2/TC7 cell line characterization for intestinal absorption: how reliable is this in vitro model for the prediction of the oral dose fraction absorbed in human?

    PubMed

    Turco, Laura; Catone, Tiziana; Caloni, Francesca; Di Consiglio, Emma; Testai, Emanuela; Stammati, Annalaura

    2011-02-01

    Caco-2 cell line is one of the most used in vitro model to study intestinal absorption of compounds at screening level. Several clones have been isolated from Caco-2 cell line and characterized for their activities. Among them, TC7 clone was isolated from a late passage of the parental Caco-2 line and has shown to consist of a more homogeneous population with respect to the most representative functions of the small intestinal enterocytes, with more developed intercellular junctions. On the basis of these characteristics, it was selected within the framework of the EU A-Cute-Tox project to check its suitability to predict intestinal transport. In the present study, drugs, synthetic or natural chemicals have been characterized for their absorption profile in TC7 cells cultivated on semi-permeable filters for 21 days. The absorption experiments have been performed with the highest nontoxic concentration as determined in a preliminary set of cytotoxicity tests. The apparent permeability coefficient (P(app)) has been extrapolated by calculating the passage of the test compound from the donor to the receiver compartment as a time function. The samples have been collected at different time intervals and the concentration of the test compounds analyzed by analytical methods (HPLC, GC, GC/MS). The P(app) obtained with the TC7 clone are comparable to those obtained with the parental cell line. However, some drawbacks related to the experimental system have been highlighted (i.e. low mass balance, adsorption to the plastics), on the basis of which some compounds were excluded from the analysis. In order to check the predictability of the model, a regression analysis has been performed by plotting P(app) values vs. the fraction absorbed in humans (FA, expressed as % of the administered dose). Additional elaborations have highlighted that the specific absorption pathway (passive, active and carrier-mediated) and other factors (i.e. efflux proteins and/or metabolic activity) can strongly affect the robustness of the prediction model. On the basis of the obtained results, TC7 clone has shown to be a model for passive diffusion as reliable as the parental cell line. However, we have remarked the non-suitability of the TC7 cells to predict intestinal absorption: (i) for highly lipophilic compounds; (ii) for poorly absorbed compounds; or (iii) when transporter-mediated routes and/or first pass metabolism are involved. The preliminary study of those factors likely influencing compound biokinetics, as well as the characterization of the cellular model with respect to metabolic and transporter competence, would help in the interpretation of data. PMID:20732406

  10. Circadian Regulation of Intestinal Lipid Absorption by Apolipoprotein AIV Involves Forkhead Transcription Factors A2 and O1 and Microsomal Triglyceride Transfer Protein*

    PubMed Central

    Pan, Xiaoyue; Munshi, Mohamed Khalid; Iqbal, Jahangir; Queiroz, Joyce; Sirwi, Alaa Ahmed; Shah, Shrenik; Younus, Abdullah; Hussain, M. Mahmood

    2013-01-01

    We have shown previously that Clock, microsomal triglyceride transfer protein (MTP), and nocturnin are involved in the circadian regulation of intestinal lipid absorption. Here, we clarified the role of apolipoprotein AIV (apoAIV) in the diurnal regulation of plasma lipids and intestinal lipid absorption in mice. Plasma triglyceride in apoAIV−/− mice showed diurnal variations similar to apoAIV+/+ mice; however, the increases in plasma triglyceride at night were significantly lower in these mice. ApoAIV−/− mice absorbed fewer lipids at night and showed blunted response to daytime feeding. To explain reasons for these lower responses, we measured MTP expression; intestinal MTP was low at night, and its induction after food entrainment was less in apoAIV−/− mice. Conversely, apoAIV overexpression increased MTP mRNA in hepatoma cells, indicating transcriptional regulation. Mechanistic studies revealed that sequences between −204/−775 bp in the MTP promoter respond to apoAIV and that apoAIV enhances expression of FoxA2 and FoxO1 transcription factors and their binding to the identified cis elements in the MTP promoter at night. Knockdown of FoxA2 and FoxO1 abolished apoAIV-mediated MTP induction. Similarly, knockdown of apoAIV in differentiated Caco-2 cells reduced MTP, FoxA2, and FoxO1 mRNA levels, cellular MTP activity, and media apoB. Moreover, FoxA2 and FoxO1 expression showed diurnal variations, and their expression was significantly lower in apoAIV−/− mice. These data indicate that apoAIV modulates diurnal changes in lipid absorption by regulating forkhead transcription factors and MTP and that inhibition of apoAIV expression might reduce plasma lipids. PMID:23729668

  11. Hypolipidemic Effect of a Blue-Green Alga (Nostoc commune) Is Attributed to Its Nonlipid Fraction by Decreasing Intestinal Cholesterol Absorption in C57BL/6J Mice.

    PubMed

    Ku, Chai Siah; Kim, Bohkyung; Pham, Tho X; Yang, Yue; Weller, Curtis L; Carr, Timothy P; Park, Young-Ki; Lee, Ji-Young

    2015-11-01

    We previously demonstrated that Nostoc commune var. sphaeroids Ktzing (NO), a blue-green alga (BGA), exerts a hypolipidemic effect in vivo and its lipid extract regulates the expression of genes involved in cholesterol and lipid metabolism in vitro. The objective of this study was to investigate whether the hypolipidemic effect of NO is attributed to an algal lipid or a delipidated fraction in vivo compared with Spirulina platensis (SP). Male C57BL/6J mice were fed an AIN-93M diet containing 2.5% or 5% of BGA (w/w) or a lipid extract equivalent to 5% of BGA for 4 weeks to measure plasma and liver lipids, hepatic gene expression, intestinal cholesterol absorption, and fecal sterol excretion. Plasma total cholesterol (TC) was significantly lower in 2.5% and 5% NO-fed groups, while plasma triglyceride (TG) levels were decreased in the 5% NO group compared with controls. However, neither NO organic extract (NOE) nor SP-fed groups altered plasma lipids. Hepatic mRNA levels of sterol regulatory element-binding protein 2, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), carnitine palmitoyltransferase-1?, and acyl-CoA oxidase 1 were induced in 5% NO-fed mice, while there were no significant changes in hepatic lipogenic gene expression between groups. NO, but not NOE and SP groups, significantly decreased intestinal cholesterol absorption. When HepG2 cells and primary mouse hepatocytes were incubated with NOE and SP organic extract (SPE), there were marked decreases in protein levels of HMGR, low-density lipoprotein receptor, and fatty acid synthase. In conclusion, the nonlipid fraction of NO exerts TC and TG-lowering effects primarily by inhibiting intestinal cholesterol absorption and by increasing hepatic fatty acid oxidation, respectively. PMID:26161942

  12. Oxalate content of cereals and cereal products.

    PubMed

    Siener, Roswitha; Hnow, Ruth; Voss, Susanne; Seidler, Ana; Hesse, Albrecht

    2006-04-19

    Detailed knowledge of food oxalate content is of essential importance for dietary treatment of recurrent calcium oxalate urolithiasis. Dietary oxalate can contribute considerably to the amount of urinary oxalate excretion. Because cereal foods play an important role in daily nutrition, the soluble and total oxalate contents of various types of cereal grains, milling products, bread, pastries, and pasta were analyzed using an HPLC-enzyme-reactor method. A high total oxalate content (>50 mg/100 g) was found in whole grain wheat species Triticum durum (76.6 mg/100 g), Triticum sativum (71.2 mg/100 g), and Triticum aestivum (53.3 mg/100 g). Total oxalate content was comparably high in whole grain products of T. aestivum, that is, wheat flakes and flour, as well as in whole grain products of T. durum, that is, couscous, bulgur, and pasta. The highest oxalate content was demonstrated for wheat bran (457.4 mg/100 g). The higher oxalate content in whole grain than in refined grain cereals suggests that oxalic acid is primarily located in the outer layers of cereal grains. Cereals and cereal products contribute to the daily oxalate intake to a considerable extent. Vegetarian diets may contain high amounts of oxalate when whole grain wheat and wheat products are ingested. Recommendations for prevention of recurrence of calcium oxalate stone disease have to take into account the oxalate content of these foodstuffs. PMID:16608223

  13. Human biokinetics of strontium. Part I: intestinal absorption rate and its impact on the dose coefficient of 90Sr after ingestion.

    PubMed

    Li, Wei Bo; Hllriegl, Vera; Roth, Paul; Oeh, Uwe

    2006-07-01

    Intestinal absorption of strontium (Sr) in thirteen healthy adult German volunteers has been investigated by simultaneous oral and intravenous administration of two stable tracer isotopes, i.e. (84)Sr and (86)Sr. The measured Sr tracer concentration in plasma was analyzed using the convolution integral technique to obtain the intestinal absorption rate. The results showed that the Sr labeled in different foodstuffs was absorbed into the body fluids in a large range of difference. The maximum Sr absorption rates were observed within 60-120 min after administration. The rate of absorption is used to evaluate the intestinal absorption fraction, i.e. the f (1) value for various foodstuffs. The equivalent and effective dose coefficients for ingestion of (90)Sr were calculated using these f (1) values, and they were compared with those recommended by the International Commission on Radiological Protection (ICRP). The geometric and arithmetic means of the f (1) values are 0.38 and 0.45 associated with a geometric standard deviation and a standard deviation of 1.88 and 0.22, respectively. The 90% confidence interval of the f (1) values obtained in the present study ranges from 0.13 to 0.98. Expressed as the ratio of the 95 and 50% percentiles of the estimated probability, the uncertainty for the f (1) value corresponds to a factor of 2.58. The effective dose coefficients of (90)Sr after ingestion are 6.1 x 10(-9) Sv Bq(-1) for an f(1) value of 0.05, 1.0 x 10(-8) Sv Bq(-1) for 0.1, 1.9 x 10(-8) Sv Bq(-1) for 0.2, 2.8 x 10(-8) Sv Bq(-1) for 0.3, 3.6 x 10(-8) Sv Bq(-1) for 0.4, 5.3 x 10(-8) Sv Bq(-1) for 0.6, 7.1 x 10(-8) Sv Bq(-1) for 0.8, and 7.9 x 10(-8) Sv Bq(-1) for 0.9, respectively. Taking the effective dose coefficient of 2.8 x 10(-8) Sv Bq(-1) for an f (1) value of 0.3, which is recommended by the ICRP, as a reference, the effective dose coefficient of (90)Sr after ingestion varies by a factor of 2.8 when the f (1) value changes by a factor of 3, i.e. it decreases from 0.3 to 0.1 or increases from 0.3 to 0.9, respectively. PMID:16733723

  14. In Silico Prediction of Drug Dissolution and Absorption with variation in Intestinal pH for BCS Class II Weak Acid Drugs: Ibuprofen and Ketoprofen

    PubMed Central

    Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L.

    2012-01-01

    The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS Class III and BCS class II have been proposed, particularly, BCS class II weak acids. However, a discrepancy between the in vivo- BE results and in vitro- dissolution results for a BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH=6.0. Further the experimental dissolution of ibuprofen tablets in the low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol L-1/pH) was dramatically reduced compared to the dissolution in SIF (the average buffer capacity 12.6 mmol L -1/pH). Thus these predictions for oral absorption of BCS class II acids indicate that the absorption patterns largely depend on the intestinal pH and buffer strength and must be carefully considered for a bioequivalence test. Simulation software may be very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. PMID:22815122

  15. [A modification of the estimation of urinary oxalate using a Sigma kit].

    PubMed

    Ebisuno, S; Ohkawa, T

    1988-02-01

    The Sigma kit for estimating urinary oxalate is an enzymatic procedure. However, some errors were encountered using the standard assay system of the kit. Firstly, an overestimate of oxalate may arise from the oxidation of ascorbate during the alkaline wash stage of the extraction of oxalate from urine. Secondly, an underestimate of oxalate may occur because of incomplete extraction of oxalate. A modified assay system for measurement of urinary oxalate using the kit is reported. The following points were modified: urine was diluted two-fold with 0.2 M EDTA and and 0.2 M citrate buffer (pH 3.0), oxalate from urine was extracted with 0.06 N sodium hydroxide to prevent the overestimation by the oxidation of ascorbate, and a plate mixer and addition of a small magnet to the vial were used in the steps of both absorption and extraction of oxalate to keep the accuracy of the estimation. The linearity of standard curve, reproducibility and recovery rates of the modified method were studied, and good results were obtained (linearity; r = 0.999, CV of reproducibility; 5.3%, recovery rate; 101% (300 microM) and 103% (600 microM). A good correlation was seen between the modified Sigma method and high performance liquid chromatography (r = 0.991). PMID:3376811

  16. Increased paracellular absorption by bile salts and P-glycoprotein stimulated efflux of otilonium bromide in Caco-2 cells monolayers as a model of intestinal barrier.

    PubMed

    Catalioto, Rose-Marie; Triolo, Antonio; Giuliani, Sandro; Altamura, Maria; Evangelista, Stefano; Maggi, Carlo Alberto

    2008-09-01

    The present study investigates the intestinal permeability of otilonium bromide, a spasmolytic drug used to treat irritable bowel syndrome, across Caco-2 cell monolayers. The amount of otilonium bromide transported was determined by high-performance liquid chromatography-mass spectrometry. Epithelial barrier integrity was estimated by measuring transepithelial electrical resistance and the transport of reference compounds, P-glycoprotein activity by measuring rhodamine 123 efflux. Results showed that the apparent permeability of otilonium bromide was comparable to that of our zero permeability marker, inulin, in the apical-to-basal direction and similar to that of rhodamine 123 in the basal-to-apical direction. The P-glycoprotein substrate, verapamil, prevented otilonium bromide efflux and, conversely, otilonium bromide inhibited P-glycoprotein activity. Bile salts induced a transient opening of tight junctions, as measured by selective increase of paracellular transport, and significantly enhanced the absorption of otilonium bromide. In turn otilonium bromide potentiates the effect of bile salts on tight junctions without modifying their critical micellar concentration or altering cell viability. In conclusion, otilonium bromide is a paracellularly transported drug whose absorption, in amounts sufficient to exert a spasmolytic effect, is favoured by bile salts. P-glycoprotein, by stimulating efflux, contributes to remove excess compound, restraining its distribution and site of action to the intestinal wall. PMID:18200532

  17. Effect of colchicine on rat small intestinal absorptive cells. II. Distribution of label after incorporation of (/sup 3/H)fucose into plasma membrane glycoproteins

    SciTech Connect

    Ellinger, A.; Pavelka, M.; Gangl, A.

    1983-12-01

    By means of radioautography the influence was tested of various periods (5, 15, 30, 40 min, 2 hr) of pretreatment with colchicine, administered intraperitoneally to rats at a dosage of 0.5 mg/100 g of body weight, on the intracellular pathway of (/sup 3/H)fucose in absorptive cells of the small intestine. Administration of colchicine for 30 min and longer time intervals causes delay in the insertion of (/sup 3/H)fucose into the oligosaccharide chains of glycoconjugates in the Golgi apparatus, and results in redistribution of the label apparent over the different portions of the plasma membrane. In controls, at 2 and 4 hr after administration of (/sup 3/H)fucose the apical plasma membrane is strongly labeled. Colchicine causes equalization of the reaction of apical and basolateral regions of the plasma membrane: the number of silver grains attributable to the apical plasma membrane is reduced; following treatment with colchicine, apical portions of the plasma membrane comprise 31.6 +/- 1.8% of the silver grains, 38.6 +/- 3.8% are attributable to basolateral membrane regions. The colchicine-induced equalization of the density of label of apical and basolateral regions of the plasma membrane, in addition to the occurrence of basolateral microvillus borders, suggests microtubules to be important in the maintenance of the polar organization of small intestinal absorptive cells.

  18. Lactoferrin supplementation of the neonatal calf has no impact on immunoglobulin G absorption and intestinal development in the first days of life.

    PubMed

    Connelly, R A; Erickson, P S

    2016-01-01

    The objectives of this study were to determine if newborn calves receiving supplemental lactoferrin (LF) had improved IgG uptake and if supplemental LF enhanced intestinal development through estimation of xylose uptake. Twenty-four newborn Holstein bull calves were randomly assigned to 1 of 2 treatments: 0 or 1 g/d of supplemental LF. Calves were fed pooled maternal colostrum from 9 cows in 2 feedings: at birth and 12 h later. Calves consumed in excess of 200 g of IgG. Blood samples were taken before colostrum feeding (0 h) and at 12, 18, and 24 h after birth. Blood samples were analyzed for IgG concentration. On d 2 of life, calves were fed milk replacer with the added LF and 0.5 g/kg of BW xylose to determine if supplemental LF affected intestinal development. Blood was sampled at 0, 0.5, 1, 2, 3, 4, 6, 8, and 12 h after the xylose dose. All calves attained passive transfer and supplemental LF did not affect IgG uptake ( ? 0.36) or apparent efficiency of absorption of IgG ( = 0.49). Lactoferrin did not enhance rate of absorption at any time point ( ? 0.36). There were no differences in xylose ( = 0.28) or glucose ( = 0.27) area under the curve values in calves supplemented with either 0 or 1 g/d LF. Lactoferrin did not enhance IgG uptake during the first 24 h or intestinal development in calves on the second day of life. PMID:26812326

  19. Comparison of a Computer Simulation Program and a Traditional Laboratory Practical Class for Teaching the Principles of Intestinal Absorption.

    ERIC Educational Resources Information Center

    Dewhurst, D. G.; And Others

    1994-01-01

    Evaluates the effectiveness of an interactive computer-assisted learning program for undergraduate students that simulates experiments performed using isolated, everted sacs of rat small intestine. The program is designed to offer an alternative student-centered approach to traditional laboratory-based practical classes. Knowledge gain of students

  20. Effect of the abrasive properties of sedges on the intestinal absorptive surface and resting metabolic rate of root voles.

    PubMed

    Wieczorek, Monika; Szafra?ska, Paulina A; Labecka, Anna Maria; Lzaro, Javier; Konarzewski, Marek

    2015-01-15

    Recent studies on grasses and sedges suggest that the induction of a mechanism reducing digestibility of plant tissues in response to herbivore damage may drive rodent population cycles. This defence mechanism seems to rely on the abrasive properties of ingested plants. However, the underlying mechanism has not been demonstrated in small wild herbivores. Therefore, we carried out an experiment in which we determined the joint effect of abrasive sedge components on the histological structure of small intestine as well as resting metabolic rate (RMR) of the root vole (Microtus oeconomus). Histological examination revealed that voles fed with a sedge-dominated diet had shorter villi composed from narrower enterocytes in duodenum, jejunum and ileum. Reduction in the height of villi decreased along the small intestine. Activity of the mucus secretion increased along the small intestine and was significantly higher in the ileum. The intestinal abrasion exceeded the compensatory capabilities of voles, which responded to a sedge-dominated diet by a reduction of body mass and a concomitant decrease in whole body RMR. These results explain the inverse association between body mass and the probability of winter survival observed in voles inhabiting homogenous sedge wetlands. PMID:25524975

  1. Comparison of a Computer Simulation Program and a Traditional Laboratory Practical Class for Teaching the Principles of Intestinal Absorption.

    ERIC Educational Resources Information Center

    Dewhurst, D. G.; And Others

    1994-01-01

    Evaluates the effectiveness of an interactive computer-assisted learning program for undergraduate students that simulates experiments performed using isolated, everted sacs of rat small intestine. The program is designed to offer an alternative student-centered approach to traditional laboratory-based practical classes. Knowledge gain of students…

  2. Relevance of irinotecan hydrochloride-induced diarrhea to the level of prostaglandin E2 and water absorption of large intestine in rats.

    PubMed

    Kase, Y; Hayakawa, T; Togashi, Y; Kamataki, T

    1997-12-01

    For characterization of the mechanism(s) of severe diarrhea due to the anticancer agent, irinotecan hydrochloride (CPT-11), examination was made of the relation of CPT-11-related diarrhea to colonic prostaglandin E2 (PGE2) and water absorption in rats. Acute diarrheal symptoms were observed within 1 hr after the administration of CPT-11 to rats, with increased PGE2 and decreased water absorption in the colon. Treatment with atropine at 1 mg/kg, s.c. was noted to inhibit intestinal PGE2 and the CPT-11-related acute diarrheal symptoms, indicating that these diarrheal symptoms were mediated through the cholinergic nervous system accelerated functionally by CPT-11. On the other hand, daily treatment of CPT-11 at the same dose resulted in chronic diarrheal symptoms in all animals 3 days after CPT-11 treatment. Histopathological changes observed in the descending colon and ileum of the rats included degeneration and necrosis of villi and cryptal cells and a decrease in the number of the goblet cells. Significantly increased PGE2 and impaired water absorption of the descending colon were also observed during the chronic diarrheal stage. It can be considered that the chronic diarrheal symptoms appear as a consequence of the gastrointestinal injury characterized by significant increase in PGE2 accompanied by impaired water absorption. PMID:9469646

  3. Absolute abundance and function of intestinal drug transporters: a prerequisite for fully mechanistic in vitro-in vivo extrapolation of oral drug absorption.

    PubMed

    Harwood, M D; Neuhoff, S; Carlson, G L; Warhurst, G; Rostami-Hodjegan, A

    2013-01-01

    The use of whole body physiological-based pharmacokinetic (PBPK) models linked with in vitro-in vivo extrapolation (IVIVE) of kinetic parameters from laboratory experiments, has become embedded within many of the pharmaceutical industry and is used even as part of regulatory submissions. These include the influence of transporter proteins on drug disposition, a subject for which we have witnessed an increasing awareness. A combination of the development of high-powered analytical techniques and antibody-based technology, together with a realization that an understanding of absolute transporter protein abundances together with activity can potentially enhance the modelling of transporter kinetics by PBPK-IVIVE link models. This review summarizes the mechanistic approaches to integrate suitable non-biased in vitro transporter kinetic data relevant to the intestine (i.e. 'intrinsic' K(i) , 'intrinsic' K(m) ), by in vitro system modelling for these kinetic inputs with the advantages of, and challenges for, generating these data for input into PBPK models. This step is considered as a prerequisite for mechanistic modelling of the oral absorption for drugs that are substrates for transporters. Various approaches are provided to integrate intestinal transporter expression into PBPK models with a perspective on the incorporation of the absolute abundance/activity of transporters to enhance the predictive power of the models. We define the key intestinal tissue and functional expression-based scaling factors required. The objective is to use these for facilitating the extrapolation from in vitro intestinal transporter assays to the in vivo system, using absolute quantification methodologies. The models could be used to elucidate the complex relationship and relative importance of metabolizing enzymes and transporters in drug disposition and toxicity. PMID:22927116

  4. Feed supplemented with organic acids does not affect starch digestibility, nor intestinal absorptive or secretory function in broiler chickens.

    PubMed

    Ruhnke, I; Rhe, I; Goodarzi Boroojeni, F; Knorr, F; Mader, A; Hafeez, A; Zentek, J

    2015-04-01

    The current study aimed to determine the impact of acidified feed on apparent ileal starch digestibility, intestinal transport and barrier function and intestinal glucose transporter expression. The experiment included a control group and a treatment group with broilers fed a standard diet without or with 1.5% of a commercial organic acid product (64% formic acid, 25% propionic acid, 11% water). Broilers were fed with the experimental diets from hatching until days 32-35. Starch digestibility was determined using 0.2% titanium dioxide as ingestible marker. Gene expressions of the intestinal sodium glucose transporter 1 (SGLT-1) and glucose transporter 2 (GLUT-2) were analysed using qPCR analysis. Additionally, SGLT-1 function and chloride secretion were analysed in Ussing chamber experiments. Jejunal samples were sequentially exposed to 10 mm glucose, 100 ?m phloridzin, 100 ?m histamine and 100 ?m carbachol. Apparent ileal starch digestibility (SEM) of the control group (97.5 0.35%) and the acid-treated group (97.0 0.59%) did not differ (p = 0.674). The mean tissue conductance of intestinal samples obtained from the control group and the treatment group was similar [10.6 mS/cm(2) (0.68) and 9.4 mS/cm(2) (0.80) respectively (p = 0.147)]. The mean short-circuit currents (?Isc ) of the samples exposed to glucose, phloridzin, histamine and carbachol did not differ (p > 0.05). Additionally, no differences in the expression of SGLT-1 and GLUT-2 could be observed (p = 0.942, p = 0.413). Based on this study, the consumption of feed supplemented with organic acids was not associated with effects on ileal starch digestibility and functional traits of jejunal tissues, indicating that these additives have no major impact on the small intestinal function in broilers. PMID:25865420

  5. Motility Disorders of the Small Intestine

    MedlinePLUS

    ... Contact Us Donate Motility Disorders of the Small Intestine The general function of the small intestine is the absorption of the food we eat. During and after a meal, the intestine normally shows very irregular or unsynchronized contractions. The ...

  6. Oral absorption of anti-acquired immune deficiency syndrome nucleoside analogues. 2. Carrier-mediated intestinal transport of stavudine in rat and rabbit preparations.

    PubMed

    Waclawski, A P; Sinko, P J

    1996-05-01

    The intestinal transport and metabolism of stavudine (d4T), a nucleoside analogue of thymidine used in the treatment of AIDS, was studied using single-pass intestinal perfusion (SPIP), intestinal brush-border membrane vesicles (BBMV), and mucosal homogenates in rats and rabbits. In the SPIP, d4T demonstrated concentration-dependent mean wall permeability (P+/-w) at perfusate concentrations ranging from 0.001 to 25 mM. In coperfusion studies using 0.1 mM thymidine, 1 mM formycin B, or 5 microM NBTI as putative inhibitors of d4T transport, the P+/-w of 5 microM d4T was reduced to 48%, 62%, and 70% of the control value, respectively, suggesting the involvement of multiple nucleoside carriers in the intestinal uptake of d4T. d4T uptake in rat BBMV was significantly greater in the presence of a sodium ion gradient compared with a sodium-free (choline) gradient. The permeability of d4T, in the presence of a sodium gradient, was concentration-dependent and inhibited by 10 mM thymidine but not significantly reduced by 10 mM formycin B. In the presence of 10 microM NBTI, the permeability of d4T was not inhibited; however; the binding of d4T to rat and rabbit BBMV was significantly reduced. Formycin B did not significantly reduce the d4T uptake in rat or rabbit BBMV suggesting that d4T does not interact with the purine-selective N1 nucleoside carrier. However, because formycin B inhibited d4T uptake in the SPIP and since d4T inhibited formycin B uptake in rat but not rabbit BBMV, it appears to interact with the N3 carrier which has been demonstrated in rat but not rabbit intestine. Also, an interaction with the sodium-independent facilitative transporter at the basolateral membrane cannot be ruled out. The low hybrid K(m) and high passive permeability of d4T likely account for the lack of saturable absorption behavior observed in humans, whereas the brush-border and intracellular stability of d4T preserve the high bioavailability observed after oral dosing. PMID:8742938

  7. Acylation of acylglycerols by acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1). Functional importance of DGAT1 in the intestinal fat absorption.

    PubMed

    Cheng, Dong; Iqbal, Jahangir; Devenny, James; Chu, Ching-Hsuen; Chen, Luping; Dong, Jessica; Seethala, Ramakrishna; Keim, William J; Azzara, Anthony V; Lawrence, R Michael; Pelleymounter, Mary Ann; Hussain, M Mahmood

    2008-10-31

    Acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) is one of the four intestinal membrane bound acyltransferases implicated in dietary fat absorption. Recently, it was found that, in addition to acylating diacylglycerol (DAG), DGAT1 also possesses robust enzymatic activity for acylating monoacylglycerol (MAG) (Yen, C. L., Monetti, M., Burri, B. J., and Farese, R. V., Jr. (2005) J. Lipid Res. 46, 1502-1511). In the current paper, we have conducted a detailed characterization of this reaction in test tube, intact cell culture, and animal models. Enzymatically, we found that triacylglycerol (TAG) synthesis from MAG by DGAT1 does not behave according to classic Michaelis-Menten kinetics. At low concentrations of 2-MAG (<50 microm), the major acylation product by DGAT1 was TAG; however, increased concentrations of 2-MAG (50-200 microm) resulted in decreased TAG formation. This unique product/substrate relationship is similar to MGAT3 but distinct from DGAT2 and MGAT2. We have also found that XP620 is an inhibitor that selectively inhibits the acylation of MAG by DGAT1 (IC(50) of human DGAT1: 16.6+/-4.0 nM (MAG as substrate) and 1499+/-318 nM (DAG as substrate); IC(50) values of human DGAT2, MGAT2, and MGAT3 are >30,000 nM). Using this pharmacological tool, we have shown that approximately 76 and approximately 89% of the in vitro TAG synthesis initiated from MAG is mediated by DGAT1 in Caco-2 cell and rat intestinal mucosal membranes, respectively. When applied to intact cultured cells, XP620 substantially decreased but did not abolish apoB secretion in differentiated Caco-2 cells. It also decreased TAG and DAG syntheses in primary enterocytes. Last, when delivered orally to rats, XP620 decreased absorption of orally administered lipids by approximately 50%. Based on these data, we conclude that the acylation of acylglycerols by DGAT1 is important for dietary fat absorption in the intestine. PMID:18768481

  8. Absorption, Metabolism, Excretion, and the Contribution of Intestinal Metabolism to the Oral Disposition of [14C]Cobimetinib, a MEK Inhibitor, in Humans.

    PubMed

    Takahashi, Ryan H; Choo, Edna F; Ma, Shuguang; Wong, Susan; Halladay, Jason; Deng, Yuzhong; Rooney, Isabelle; Gates, Mary; Hop, Cornelis E C A; Khojasteh, S Cyrus; Dresser, Mark J; Musib, Luna

    2016-01-01

    The pharmacokinetics, metabolism, and excretion of cobimetinib, a MEK inhibitor, were characterized in healthy male subjects (n = 6) following a single 20 mg (200 ?Ci) oral dose. Unchanged cobimetinib and M16 (glycine conjugate of hydrolyzed cobimetinib) were the major circulating species, accounting for 20.5% and 18.3% of the drug-related material in plasma up to 48 hours postdose, respectively. Other circulating metabolites were minor, accounting for less than 10% of drug-related material in plasma. The total recovery of the administered radioactivity was 94.3% (1.6%, S.D.) with 76.5% (2.3%) in feces and 17.8% (2.5%) in urine. Metabolite profiling indicated that cobimetinib had been extensively metabolized with only 1.6% and 6.6% of the dose remaining as unchanged drug in urine and feces, respectively. In vitro phenotyping experiments indicated that CYP3A4 was predominantly responsible for metabolizing cobimetinib. From this study, we concluded that cobimetinib had been well absorbed (fraction absorbed, Fa = 0.88). Given this good absorption and the previously determined low hepatic clearance, the systemic exposures were lower than expected (bioavailability, F = 0.28). We hypothesized that intestinal metabolism had strongly attenuated the oral bioavailability of cobimetinib. Supporting this hypothesis, the fraction escaping gut wall elimination (Fg) was estimated to be 0.37 based on F and Fa from this study and the fraction escaping hepatic elimination (Fh) from the absolute bioavailability study (F = Fa Fh Fg). Physiologically based pharmacokinetics modeling also showed that intestinal clearance had to be included to adequately describe the oral profile. These collective data suggested that cobimetinib was well absorbed following oral administration and extensively metabolized with intestinal first-pass metabolism contributing to its disposition. PMID:26451002

  9. Fructans of Jerusalem artichokes: intestinal transport, absorption, fermentation, and influence on blood glucose, insulin, and C-peptide responses in healthy subjects.

    PubMed

    Rumessen, J J; Bod, S; Hamberg, O; Gudmand-Hyer, E

    1990-10-01

    Fructans are naturally occurring plant oligosaccharides with sweetening properties. Fructans (FAs) isolated from Jerusalem artichokes (Helianthus tuberosus) were studied with respect to intestinal handling and influence on blood glucose (BG), insulin, and C-peptide responses in eight healthy subjects. The responses were compared with those for fructose ingestion. The effect of FAs added to a wheat-starch meal was also studied. Standardized breath-hydrogen excretion indicated that FAs were completely malabsorbed and, after a 20-g dose, traces of FA were detected in 24-h urine collections in one subject only. Orocecal transit times were longer for FAs than for lactulose and fructose. The BG and insulin increments were very low after FA ingestion, lower than after fructose ingestion, whereas hydrogen production was much higher. Areas under BG curves tended to be smaller when 10 g FA was added to a 50-g wheat-starch meal, but there was no apparent interference with starch absorption. PMID:2206038

  10. CaSR function in the intestine: Hormone secretion, electrolyte absorption and secretion, paracrine non-canonical Wnt signaling and colonic crypt cell proliferation.

    PubMed

    Macleod, R John

    2013-06-01

    Expression and function of the CaSR have been shown in some mammalian taste buds and basal cells of the esophagus. Signaling cascades responsible for CaSR-mediated stimulation of H(+)-K(+)-ATPase on human parietal cells have been defined. Transgenic mice and reductionistic cell culture models have shown that the CaSR promotes gastrin secretion from G cells, cholecystokinin (CCK) secretion from duodenal I cells and BMP-2 secretion from sub-epithelial myofibroblasts. In addition, the CaSR mediates a novel paracrine relationship between myofibroblasts and overlying epithelial cells in the colon. Thus, CaSR activators stimulate secretion of Wnt5a from myofibroblasts and expression of the Wnt5a receptor Ror2 in epithelial cells. CaSR-mediated Wnt5a/Ror2 engagement stimulates epithelial differentiation and reduces expression of the receptor for tumor necrosis factor (TNFR1). CaSR activators also modulate intestinal motility, inhibit Cl(-) secretion and stimulate Na(+) absorption in both the small intestine and colon. Colonic epithelia from conditional and global CaSR knockout mice exhibit increased proliferation with increased Wnt/?-catenin signaling, demonstrating that the CaSR negatively modulates colonic epithelial growth. PMID:23856267

  11. Study on the Main Components Interaction from Flos Lonicerae and Fructus Forsythiae and Their Dissolution In Vitro and Intestinal Absorption in Rats

    PubMed Central

    Zhou, Wei; Tan, Xiaobin; Shan, Jinjun; Wang, Shouchuan; Yin, Ailing; Cai, Baochang; Di, Liuqing

    2014-01-01

    The Flos Lonicerae-Fructus Forsythiae herb couple is the basic components of Chinese herbal preparations (Shuang-Huang-Lian tablet, Yin-Qiao-Jie-Du tablet and Fufang Qin-Lan oral liquid), and its pharmacological effects were significantly higher than that in Flos Lonicerae or Fructus Forsythiae, but the reasons remained unknown. In the present study, pattern recognition analysis (hierarchical cluster analysis (HCA) and principal component analysis (PCA)) combined with UHPLC-ESI/LTQ-Orbitrap MS system were performed to study the chemical constitution difference between co-decoction and mixed decoction in the term of chemistry. Besides, the pharmacokinetics in vivo and intestinal absorption in vitro combined with pattern recognition analysis were used to reveal the discrepancy between herb couple and single herbs in the view of biology. The observation from the chemical view in vitro showed that there was significant difference in quantity between co-decoction and mixed decoction by HCA, and the exposure level of isoforsythoside and 3, 5-dicaffeoylquinic acid in co-decoction, higher than that in mixed decoction, directly resulted in the discrepancy between co-decoction and mixed decoction using both PCA and HCA. The observation from the pharmacokinetics displayed that the exposure level in vivo of neochlorogenic acid, 3, 4-dicaffeoylquinic acid, isoforsythoside and forsythoside A, higher than that in single herbs, was the main factor contributing to the difference by both PCA and HCA, interestingly consistent with the results obtained from Caco-2 cells in vitro, which indicated that it was because of intestinal absorption improvement of neochlorogenic acid, 3, 4-dicaffeoylquinic acid, isoforsythoside and forsythoside A that resulted in a better efficacy of herb couple than that of single herbs from the perspective of biology. The results above illustrated that caffeic acid derivatives in Flos Lonicerae-Fructus Forsythiae herb couple could be considered as chemical markers for quality control of its preparations. PMID:25275510

  12. Estimation of the oxalate content of foods and daily oxalate intake

    NASA Technical Reports Server (NTRS)

    Holmes, R. P.; Kennedy, M.

    2000-01-01

    BACKGROUND: The amount of oxalate ingested may be an important risk factor in the development of idiopathic calcium oxalate nephrolithiasis. Reliable food tables listing the oxalate content of foods are currently not available. The aim of this research was to develop an accurate and reliable method to measure the food content of oxalate. METHODS: Capillary electrophoresis (CE) and ion chromatography (IC) were compared as direct techniques for the estimation of the oxalate content of foods. Foods were thoroughly homogenized in acid, heat extracted, and clarified by centrifugation and filtration before dilution in water for analysis. Five individuals consuming self-selected diets maintained food records for three days to determine their mean daily oxalate intakes. RESULTS: Both techniques were capable of adequately measuring the oxalate in foods with a significant oxalate content. With foods of very low oxalate content (<1.8 mg/100 g), IC was more reliable than CE. The mean daily intake of oxalate by the five individuals tested was 152 +/- 83 mg, ranging from 44 to 352 mg/day. CONCLUSIONS: CE appears to be the method of choice over IC for estimating the oxalate content of foods with a medium (>10 mg/100 g) to high oxalate content due to a faster analysis time and lower running costs, whereas IC may be better suited for the analysis of foods with a low oxalate content. Accurate estimates of the oxalate content of foods should permit the role of dietary oxalate in urinary oxalate excretion and stone formation to be clarified. Other factors, apart from the amount of oxalate ingested, appear to exert a major influence over the amount of oxalate excreted in the urine.

  13. Determination of trace amount of oxalic acid with zirconium(IV)-(DBS-arsenazo) by spectrophotometry

    NASA Astrophysics Data System (ADS)

    Zhai, Qing-Zhou

    2008-11-01

    A novel method is proposed for the determination of trace amount of oxalic acid in the present article. In 1.0 M hydrochloric acid medium, oxalic acid can react with the zirconium(IV) in Zr(IV)-(DBS-arsenazo) complex and replaces the DBS-arsenazo to produce a hyperchromic effect at 520 nm. The hyperchromic degree is proportional to the concentration of the oxalic acid added over a defined range. Based on this property, a new method for the spectrophotometric determination of trace oxalic acid was developed. Beer's law is held over the concentration range of 9.0 10 -6 to 5.0 10 -4 M for oxalic acid with a correlation coefficient of 0.9995. The apparent molar absorptivity of the method is ?520 nm = 1.16 10 3 L mol -1 cm -1 and the detection limit for oxalic acid is 0.815 ?g/mL. The developed method was directly applied to the determination of oxalic acid in tomato samples with satisfactory results.

  14. Role of Oxalic Acid Overexcretion in Transformations of Toxic Metal Minerals by Beauveria caledonica

    PubMed Central

    Fomina, M.; Hillier, S.; Charnock, J. M.; Melville, K.; Alexander, I. J.; Gadd, G. M.

    2005-01-01

    The fungus Beauveria caledonica was highly tolerant to toxic metals and solubilized cadmium, copper, lead, and zinc minerals, converting them into oxalates. This fungus was found to overexcrete organic acids with strong metal-chelating properties (oxalic and citric acids), suggesting that a ligand-promoted mechanism was the main mechanism of mineral dissolution. Our data also suggested that oxalic acid was the main mineral-transforming agent. Cadmium, copper, and zinc oxalates were precipitated by the fungus in the local environment and also in association with the mycelium. The presence of toxic metal minerals often led to the formation of mycelial cords, and in the presence of copper-containing minerals, these cords exhibited enhanced excretion of oxalic acid, which resulted in considerable encrustation of the cords by copper oxalate hydrate (moolooite). It was found that B. caledonica hyphae and cords were covered by a thick hydrated mucilaginous sheath which provided a microenvironment for chemical reactions, crystal deposition, and growth. Cryo-scanning electron microscopy revealed that mycogenic metal oxalates overgrew parental fungal hyphae, leaving a labyrinth of fungal tunnels within the newly formed mineral matter. X-ray absorption spectroscopy revealed that oxygen ligands played a major role in metal coordination within the fungal biomass during the accumulation of mobilized toxic metals by B. caledonica mycelium; these ligands were carboxylic groups in copper phosphate-containing medium and phosphate groups in pyromorphite-containing medium. PMID:15640211

  15. [Oxalobacter formigenes--characteristics and role in development of calcium oxalate urolithiasis].

    PubMed

    Torzewska, Agnieszka

    2013-01-01

    Microorganisms are one of the important factors for urinary calculi formation. While urease-positive bacteria and nanobacteria contribute to stone formation, Oxalobacter formigenes rods play a protective role against the development of urolithiasis. Proteus mirabilis alkaline environment of the urinary tract and cause crystallization mainly of struvite (magnesium ammonium phosphate). However, nanobacteria, due to the possibility of apatite deposition on the surface of their cells, have long been considered as an etiological factor of urinary calculi consisting of calcium phosphates. O. formigenes is an anaerobe using oxalate as the main source of carbon and energy and occurs as natural gastrointestinal microflora of humans and animals. These bacteria control the amount of oxalate excretion degrading oxalates and regulating their transport by intestinal epithelium. Lower colonization of the human colon by O. formigenes can cause increased oxalate excretion and lead to the development of oxalate urolithiasis. Due to the positive influence of O. formigenes, there is ongoing research into the use of this microorganism as a probiotic in the prophylaxis or treatment of hyperoxaluria, both secondary and primary. The results of these studies are very promising, but they still require continuation. Future studies focus on the exact characteristics of O. formigenes including their metabolism and the development of methods for applying as a therapeutic agent the bacteria or their enzymes degrading the oxalate. PMID:24379255

  16. Role of the Lower and Upper Intestine in the Production and Absorption of Gut Microbiota-Derived PUFA Metabolites

    PubMed Central

    Druart, Cline; Neyrinck, Audrey M.; Vlaeminck, Bruno; Fievez, Veerle; Cani, Patrice D.; Delzenne, Nathalie M.

    2014-01-01

    In vitro studies have suggested that isolated gut bacteria are able to metabolize PUFA into CLA (conjugated linoleic acids) and CLnA (conjugated linolenic acids). However, the bioavailability of fatty acid metabolites produced in vivo by the gut microbes remains to be studied. Therefore, we measured intestinal concentration and plasma accumulation of bacterial metabolites produced from dietary PUFA in mice, first injected with a lipoprotein lipase inhibitor, then force-fed with either sunflower oil (200 l) rich in n-6 PUFA or linseed oil (200 l) rich in n-3 PUFA. The greatest production of bacterial metabolites was observed in the caecum and colon, and at a much lesser extent in the jejunum and ileum. In the caecal content, CLA proportions were higher in sunflower oil force-fed mice whereas CLnA proportions were higher in linseed oil force-fed mice. The accumulation of the main metabolites (CLA cis-9,trans-11-18:2 and CLnA cis-9,trans-11,cis-15-18:3) in the caecal tissue was not associated with their increase in the plasma, therefore suggesting that, if endogenously produced CLA and CLnA have any biological role in host metabolism regulation, their effect would be confined at the intestinal level, where the microbiota is abundant. PMID:24475308

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  18. P-glycoprotein is responsible for the poor intestinal absorption and low toxicity of oral aconitine: In vitro, in situ, in vivo and in silico studies

    SciTech Connect

    Yang, Cuiping Zhang, Tianhong Li, Zheng Xu, Liang Liu, Fei Ruan, Jinxiu Liu, Keliang Zhang, Zhenqing

    2013-12-15

    Aconitine (AC) is a highly toxic alkaloid from bioactive plants of the genus Aconitum, some of which have been widely used as medicinal herbs for thousands of years. In this study, we systematically evaluated the potential role of P-glycoprotein (P-gp) in the mechanisms underlying the low and variable bioavailability of oral AC. First, the bidirectional transport of AC across Caco-2 and MDCKII-MDR1 cells was investigated. The efflux of AC across monolayers of these two cell lines was greater than its influx. Additionally, the P-gp inhibitors, verapamil and cyclosporin A, significantly decreased the efflux of AC. An in situ intestinal perfusion study in rats showed that verapamil co-perfusion caused a significant increase in the intestinal permeability of AC, from 0.22 × 10{sup −5} to 2.85 × 10{sup −5} cm/s. Then, the pharmacokinetic profile of orally administered AC with or without pre-treatment with verapamil was determined in rats. With pre-treatment of verapamil, the maximum plasma concentration (C{sub max}) of AC increased sharply, from 39.43 to 1490.7 ng/ml. Accordingly, a 6.7-fold increase in the area under the plasma concentration–time curve (AUC{sub 0–12} {sub h}) of AC was observed when co-administered with verapamil. In silico docking analyses suggested that AC and verapamil possess similar P-gp recognition mechanisms. This work demonstrated that P-gp is involved in limiting the intestinal absorption of AC and attenuating its toxicity to humans. Our data indicate that potential P-gp-mediated drug–drug interactions should be considered carefully in the clinical application of aconite and formulations containing AC. - Highlights: • Verapamil and cyclosporin A decreased the efflux of aconitine across Caco-2 cells. • Both inhibitors decreased the efflux of aconitine across MDCKII-MDR1 cells. • Co-perfusion with verapamil increased the intestinal permeability of aconitine. • Co-administration with verapamil sharply increased the C{sub max} and AUC of aconitine. • P-gp interacted with both verapamil and aconitine and recognized them similarly.

  19. The mechanism of salt and water absorption in the intestine of the eel (Anguilla anguilla) adapted to waters of various salinities

    PubMed Central

    Skadhauge, Erik

    1969-01-01

    1. The absorption of NaCl and water was studied by intraluminal in vivo perfusion of the intestine of the yellow European eel (Anguilla anguilla) adapted to fresh water (FW), to sea water (SW), and to double strength SW (DSW). 2. The net lumen to plasma NaCl transport from diluted SW perfusion fluids was independent of the NaCl concentration in the Na+ concentration range tested. The NaCl absorption (expressed as μ-equiv/100 g.hr.) increased from FW (mean ± S.E.): Na+ 166 ± 17, Cl- 205 ± 24 to SW: Na+ 363 ± 33, Cl- 423 ± 37, and again in DSW: Na+ 640 ± 110, Cl- 676 ± 149. 3. The osmolality of the perfusion fluid which resulted in zero net water transport was higher than plasma osmolality by 73 ± 3 m-osmole in FW, 126 ± 5 m-osmole in SW, and 244 ± 32 m-osmole in DSW (mean ± S.E.). A fairly constant ratio between net NaCl transport and this osmolality difference prevailed. 4. The general osmotic permeability to water in the serosa—mucosa direction (expressed as μl./100 g. hr. m-osmole) measured from experiments with impermeant solute increased from FW: 3·7 ± 0·5 to SW: 7·2 ± 1·0 (mean ± S.E.). 5. These results are compatible with the interpretation that the water flow occurring in the absence of a general transmural osmotic gradient, the `solute-linked water flow', is linearly related both to net NaCl transport and to the osmotic permeability to water. The findings support the view that the `solute-linked water flow' is, indeed, secondary to the salt movement and is due to osmotic force. 6. The amount of water absorbed from dilute SW perfusion fluids isosmotic with plasma was larger than in most other intestinal epithelia. FW: 650, SW: 1620 μl./100 g. hr. The NaCl concentration of the absorbate was hypertonic to plasma. 7. The passive permeability of the intestine to NaCl was very low, and the reflexion coefficient was close to unity. Therefore metabolic energy will be used to absorb NaCl, even when the NaCl concentration in the gut is higher than that of plasma due to ingestion of SW. There appears to be a limited interaction in the intestinal wall between passive salt and water flow. 8. In DSW the Na+ ingestion with the oral intake of the surrounding fluid matched the gut absorption capacity. Since DSW is close to the tolerance limit, it is concluded that the gut NaCl transport capacity may be one of the factors limiting the tolerance to water or higher salinity. PMID:5352039

  20. Comparison of the gravimetric, phenol red, and 14C-PEG-3350 methods to determine water absorption in the rat single-pass intestinal perfusion model.

    PubMed

    Sutton, S C; Rinaldi, M T; Vukovinsky, K E

    2001-01-01

    This study was undertaken to determine whether the gravimetric method provided an accurate measure of water flux correction and to compare the gravimetric method with methods that employ nonabsorbed markers (eg, phenol red and 14C-PEG-3350). Phenol red,14C-PEG-3350, and 4-[2-[[2-(6-amino-3-pyridinyl)-2-hydroxyethyl]amino]ethoxy]-, methyl ester, (R)-benzene acetic acid (Compound I) were co-perfused in situ through the jejunum of 9 anesthetized rats (single-pass intestinal perfusion [SPIP]). Water absorption was determined from the phenol red,14C-PEG-3350, and gravimetric methods. The absorption rate constant (ka) for Compound I was calculated. Both phenol red and 14C-PEG-3350 were appreciably absorbed, underestimating the extent of water flux in the SPIP model. The average +/- SD water flux microg/h/cm) for the 3 methods were 68.9 +/- 28.2 (gravimetric), 26.8 +/- 49.2 (phenol red), and 34.9 +/- 21.9 (14C-PEG-3350). The (average +/- SD) ka for Compound I (uncorrected for water flux) was 0.024 +/- 0.005 min(-1). For the corrected, gravimetric method, the average +/- SD was 0.031 +/- 0.001 min(-1). The gravimetric method for correcting water flux was as accurate as the 2 "nonabsorbed" marker methods. PMID:11741276

  1. Synthesis, structural and spectroscopic investigations of nanostructured samarium oxalate crystals

    NASA Astrophysics Data System (ADS)

    Vimal, G.; Mani, Kamal P.; Biju, P. R.; Joseph, Cyriac; Unnikrishnan, N. V.; Ittyachen, M. A.

    2014-03-01

    Nanostructured samarium oxalate crystals were prepared via microwave assisted co-precipitation method. The crystal structure and morphology of the sample were analyzed using X-ray powder diffraction, Scanning electron microscopy and Transmission electron microscopy. The presence of functional groups is ascertained by Fourier transform infrared spectroscopy. Samarium oxalate nanocrystals of average size 20 nm were aggregated together to form nano-plate structure in sub-microrange. Detailed spectroscopic investigation of the prepared phosphor material was carried out by Judd-Ofelt analysis based on the UV-Visible-NIR absorption spectra and photoluminescence emission spectra. The analysis reveals that the transition from energy level 4G5/2 to 6H7/2 of Sm3+ ion has maximum branching ratio and the corresponding orange emission can be used for display applications.

  2. Anthranoid laxatives influence the absorption of poorly permeable drugs in human intestinal cell culture model (Caco-2).

    PubMed

    Laitinen, Leena; Takala, Elina; Vuorela, Heikki; Vuorela, Pia; Kaukonen, Ann Marie; Marvola, Martti

    2007-04-01

    Interactions between widely used anthranoid laxatives and other simultaneously administered drugs are not known. In this paper, the influence of rhein, danthron, sennidins A/B, sennosides A/B, and senna leaf infusion was investigated on the permeability of furosemide, ketoprofen, paracetamol, propranolol, verapamil, digoxin, and Rhodamine 123 across Caco-2 monolayers. The effects on monolayer integrity ([(14)C]mannitol permeability, TEER) were also determined. The in vitro absorption of highly permeable drugs was not strongly affected during co-administration of the laxatives. Furosemide permeability was enhanced by rhein and danthron (3.6 and 3.0-fold), which may partly be due to opening of the paracellular spaces and/or effects on active efflux. However, the secretory permeability of digoxin and Rho 123 was not strongly affected by rhein and danthron, suggesting that inhibition of MDR1 was not responsible for the increased permeation of furosemide. The absorptive permeability of digoxin was decreased by rhein and danthron, offering evidence for effects on apical membranes. The effects on monolayer integrity were detectable, but reversible. According to presented experiments, daily use of laxatives with well-absorbing drugs would seem unlikely to affect drug permeability, but the effects on the absorption of poorly permeable drugs cannot be excluded. PMID:17098405

  3. Proteome Dynamics of the Specialist Oxalate Degrader Oxalobacter formigenes

    PubMed Central

    Ellis, Melissa E; Mobley, James A; Holmes, Ross P; Knight, John

    2016-01-01

    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 kidney stone disease. The release of the genome sequence of O. formigenes has provided an opportunity to increase our understanding of the biology of O. formigenes. This study used mass spectrometry based shotgun proteomics to examine changes in protein levels associated with the transition of growth from log to stationary phase. Of the 1867 unique protein coding genes in the genome of O. formigenes strain OxCC13, 1822 proteins were detected, which is at the lower end of the range of 1500–7500 proteins found in free-living bacteria. From the protein datasets presented here it is clear that O. formigenes contains a repertoire of metabolic pathways expected of an intestinal microbe that permit it to survive and adapt to new environments. Although further experimental testing is needed to confirm the physiological and regulatory processes that mediate adaptation with nutrient shifts, the O. formigenes protein datasets presented here can be used as a reference for studying proteome dynamics under different conditions and have significant potential for hypothesis development. PMID:26924912

  4. Comparison of sulfuric and oxalic acid anodizing for preparation of thermal control coatings for spacecraft

    NASA Technical Reports Server (NTRS)

    Le, Huong G.; Watcher, John M.; Smith, Charles A.

    1988-01-01

    The development of thermal control surfaces, which maintain stable solar absorptivity and infrared emissivity over long periods, is challenging due to severe conditions in low-Earth orbit (LEO). Some candidate coatings are second-surface silver-coated Teflon; second-surface, silvered optical solar reflectors made of glass or quartz; and anodized aluminum. Sulfuric acid anodized and oxalic acid anodized aluminum was evaluated under simulated LEO conditions. Oxalic acid anodizing shows promise of greater stability in LEO over long missions, such as the 30 years planned for the Space Station. However, sulfuric acid anodizing shows lower solar absorptivity.

  5. A new drug delivery system targeting ileal epithelial cells induced electrogenic sodium absorption: possible promotion of intestinal adaptation.

    PubMed

    Haneda, Sho; Fukushima, Kouhei; Funayama, Yuji; Shibata, Chikashi; Takahashi, Ken-Ichi; Tabata, Yasuhiko; Sasaki, Iwao

    2007-05-01

    We previously demonstrated the induction of the epithelial sodium channel, prostasin, and 11beta-hydroxysteroid dehydrogenase type 2 and activation of sodium transport mediated by those molecules in the remnant ileum after total proctocolectomy. The aims of the present study were to develop a new drug delivery system that targets ileal epithelial cells and to enhance local mineralocorticoid action without systemic effects. Orally administered D-aldosterone-containing D,L-lactide/glycolide acid copolymer microspheres are absorbed in the rat terminal ileum and released aldosterone. Blood and terminal ileal tissues were collected 2 weeks after the administration of the microspheres, and the aldosterone concentrations, mRNA, and protein expressions of the above molecules and sodium transport were evaluated. Significantly high levels of tissue aldosterone in the absence of elevated plasma levels were detected in the microspheres-treated rats. Epithelial mRNA and protein expression of the above molecules increased significantly in the microspheres-treated animals. Electrogenic sodium transport in the ileum was enhanced in the microspheres-treated rats. Aldosterone-containing microspheres successfully induced the expression of the above molecules and activated sodium transport in the ileal mucosa, both of which are essential for intestinal adaptation. Pre- and/or postoperative treatment with this drug may compensate for the excessive loss of sodium and water following proctocolectomy. PMID:17468916

  6. Transcriptional analysis of porcine intestinal mucosa infected with Salmonella Typhimurium revealed a massive inflammatory response and disruption of bile acid absorption in ileum.

    PubMed

    Uribe, Juber Herrera; Collado-Romero, Melania; Zaldívar-López, Sara; Arce, Cristina; Bautista, Rocío; Carvajal, Ana; Cirera, Susanna; Claros, M Gonzalo; Garrido, Juan J

    2016-01-01

    Infected pork meat is an important source of non-typhoidal human salmonellosis. Understanding of molecular mechanisms involved in disease pathogenesis is important for the development of therapeutic and preventive strategies. Thus, hereby we study the transcriptional profiles along the porcine intestine during infection with Salmonella Typhimurium, as well as post-transcriptional gene modulation by microRNAs (miRNA). Sixteen piglets were orally challenged with S. Typhimurium. Samples from jejunum, ileum and colon, collected 1, 2 and 6 days post infection (dpi) were hybridized to mRNA and miRNA expression microarrays and analyzed. Jejunum showed a reduced transcriptional response indicating mild inflammation only at 2 dpi. In ileum inflammatory genes were overexpressed (e.g., IL-1B, IL-6, IL-8, IL1RAP, TNFα), indicating a strong immune response at all times of infection. Infection also down-regulated genes of the FXR pathway (e.g., NR1H4, FABP6, APOA1, SLC10A2), indicating disruption of the bile acid absorption in ileum. This result was confirmed by decreased high-density lipoprotein cholesterol in serum of infected pigs. Ileal inflammatory gene expression changes peaked at 2 dpi and tended to resolve at 6 dpi. Furthermore, miRNA analysis of ileum at 2 dpi revealed 62 miRNAs potentially regulating target genes involved in this inflammatory process (e.g., miR-374 and miR-451). In colon, genes involved in epithelial adherence, proliferation and cellular reorganization were down-regulated at 2 and 6 dpi. In summary, here we show the transcriptional changes occurring at the intestine at different time points of the infection, which are mainly related to inflammation and disruption of the bile acid metabolism. PMID:26738723

  7. A saturable transport mechanism in the intestinal absorption of gabapentin is the underlying cause of the lack of proportionality between increasing dose and drug levels in plasma.

    PubMed

    Stewart, B H; Kugler, A R; Thompson, P R; Bockbrader, H N

    1993-02-01

    Gabapentin (1-(aminomethyl)cyclohexaneacetic acid) is a neuroprotective agent with antiepileptic properties. The structure is small (molecular weight less than 200), is zwitterionic, and resembles an amino acid with the exception that it does not contain a chiral carbon and the amino group is not alpha to the carboxylate functionality. Gabapentin is not metabolized by humans, and thus, the amount of gabapentin excreted by the renal route represents the fraction of dose absorbed. Clinical trials have reported dose-dependent bioavailabilities ranging from 73.8 +/- 18.3 to 35.7 +/- 18.3% when the dose was increased from 100 to 1600 mg. The permeability of gabapentin in the rat intestinal perfusion system was consistent with carrier-mediated absorption, i.e., a 75 to 80% decrease in permeability when the drug concentration was increased from 0.01 to 50 mM (0.46 +/- 0.05 to 0.12 +/- 0.04). Excellent agreement was obtained between the actual clinical values and the predicted values from in situ results for the fraction of dose absorbed calculated using the theoretically derived correlation, Fabs = 1 - exp(-2Peff) by Amidon et al. (Pharm. Res. 5:651-654, 1988). The permeability values obtained for gabapentin correspond to 67.4 and 30.2% of the dose absorbed at the low and high concentrations, respectively. In the everted rat intestinal ring system, gabapentin shared an inhibition profile similar to that of L-phenylalanine. Characteristics of gabapentin uptake included cross-inhibition with L-Phe, sensitivity to inhibition by L-Leu, stereoselectivity as evidenced by incomplete inhibition by D-Phe, and lack of effect by Gly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8456077

  8. Inhibition of Pancreatic Lipase and Triacylglycerol Intestinal Absorption by a Pinho Coat (Araucaria angustifolia) Extract Rich in Condensed Tannin

    PubMed Central

    Oliveira, Roselene Ferreira; Gonalves, Geferson Almeida; Incio, Fabola Dorneles; Koehnlein, Elo Anglica; de Souza, Cristina Giatti Marques; Bracht, Adelar; Peralta, Rosane Marina

    2015-01-01

    The purpose of the present work was to characterize the possible inhibition of pancreatic lipase by a tannin-rich extract obtained from the pinho (Araucaria angustifolia seed) coat, based on the previous observation that this preparation inhibits ?-amylases. Kinetic measurements of pancreatic lipase revealed that the pinho coat tannin is an effective inhibitor. Inhibition was of the parabolic non-competitive type. The inhibition constants, Ki1 and Ki2, were equal to 332.7 146.1 ?g/mL and 321.2 93.0 ?g/mL, respectively, corresponding roughly to the inhibitor concentration producing 50% inhibition ([I]50). Consistently, the pinho coat extract was also effective at diminishing the plasma triglyceride levels in mice after an olive oil load; 50% diminution of the area under the plasma concentration versus the time curve occurred at a dose of 250 mg/kg. This observation is most probably the consequence of an indirect inhibition of triglyceride absorption via inhibition of pancreatic lipase. For the pinho coat tannin, this is the second report of a biological activity, the first one being a similar inhibition of the absorption of glucose derived from starch as a consequence of an inhibitory action on ?-amylases. Taken together, these effects represent a potential anti-obesity action, as suggested for other polyphenol or tannin-rich preparations. PMID:26184295

  9. Inhibition of food intake in the rat following complete absorption of glucose delivered into the stomach, intestine or liver.

    PubMed Central

    Booth, D A; Jarman, S P

    1976-01-01

    1. Solutions of glucose or other carbohydrates were administered during the dark or light period of the circadian cycle to rats which had been only briefly deprived of food. 2. food was restored to the animals at various times after administration of a glucose load by stomach tube. With delays between loading and access to food of up to 3 hr by night and 2 hr by day, subsequent food intake was less than intake after non-nutritive loads. 3. measurement of the glucose content of the gastrointestinal tract at various times after glucose loading showed that this depression of intake was still apparent even when the rat was offered food some time after complete absorption of the stomach load. 4. infusion of a glucose solution into the duodenum or the hepatic protal vein also inhibited subsequent food intake. 5. in all cases, the inhibition of food intake was expressed as a decrease in the size of the first meal after restoring access to food. 6. these results provide the first demonstration that the entry of normal amounts of carbohydrate into the body by the physiological route is followed by depression of food intake which lasts until after absorption is complete. PMID:957255

  10. D-xylose absorption

    MedlinePLUS

    D-xylose absorption is a laboratory test to determine how well the intestines absorb a simple sugar (D-xylose). The test ... test is primarily used to determine if nutrient absorption problems are due to a disease of the ...

  11. 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

    Gonzlez-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 absorbed before the duodenum, but Ca from L. calcareum Ca is mostly absorbed in the jejunum and ileum. PMID:24646151

  12. Formation of superconducting Bi sub 2-y Pb sub y Sr sub 2 Ca sub 2 Cu sub 3 O sub x from coprecipitated oxalates

    SciTech Connect

    Bernhard, K.; Gritzner, G.; Wang, Xianzhong; Baeuerle, D. )

    1990-06-01

    The conditions for the coprecipitation of Bi{sup 3+}, Pb{sup 2+}, Ca{sup 2+} as oxalates are reported. These oxalates were used as precursors for the formation of Bi{sub 2-y}Pb{sub y}Sr{sub 2}Ca{sub 2}Cu{sub 3}O{sub x} superconducting ceramics. The behavior of the oxalates upon heat treatment was studied by thermogravimetry. Both the oxalates and the superconducting oxides were analyzed and characterized by atomic absorption spectroscopy and by X-ray diffraction.

  13. Peanut-induced acute oxalate nephropathy with acute kidney injury

    PubMed Central

    Park, Hyeoncheol; Eom, Minseob; Won Yang, Jae; Geun Han, Byoung; Ok Choi, Seung; Kim, Jae Seok

    2014-01-01

    Oxalate nephropathy is commonly caused by ethylene glycol, vitamin C, and foods like star fruit that contain a lot of oxalate. Peanuts also have high oxalate contents. However, case reports of peanut-induced oxalate nephropathy are not common. Here, we describe a case of peanut-induced acute oxalate nephropathy with acute kidney injury and intend to demonstrate the conditions under which peanut-induced oxalate nephropathy is likely to occur. PMID:26877960

  14. Engineering calcium oxalate crystal formation in Arabidopsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many plants accumulate crystals of calcium oxalate. Just how these crystals form remains unknown. To gain insight into the mechanisms regulating calcium oxalate crystal formation, a crystal engineering approach was initiated utilizing the non-crystal accumulating plant, Arabidopsis. The success of t...

  15. The effect of several crude oils and some petroleum distillation fractions on intestinal absorption in ducklings (Anas platyhynchos).

    PubMed

    Crocker, A D; Cronshaw, J; Holmes, W N

    1975-01-01

    Ducklings given hypertonic saline drinking water show significant increases in the rates of Na+ and water transfer across the intestinal mucosa. These increased rates of transfer are maintained as long as the birds are fed dypertonic saline. Oral administration of a single small dose of crude oil had no effect on the basal rate of mucosal transfer in freshwater-maintained ducklings but the adaptive response of the mucosa is suppressed in birds given hypertonic saline. When crude oils from eight different geographical locations were tested, the degree of inhibition varied between them; the greatest and smallest degrees of inhibition being observed following administration of Kuwait and North Slope, Alaska, crude oils respectively. The effects of distallation fractions derived from two chemically different crude oils were also examined. The volume of each distallation fraction administered corresponded to its relative abundance in the crude oil from which it was derived. The inhibitory effect was not associated exclusively with the same distallation fractions from each oil. A highly naphthenic crude oil from the San Joaquin Valley, California, showed the greatest inhibitory activity in the least abundant (2%), low boiling point (smaller than 245 degrees C) fraction and the least inhibitory activity in the highest boiling point (greater than 482 degrees C) most abundant (47%) fraction. In contrast, a highly paraffinic crude oil from Paradox Basin, Utah, showed the greatest inhibitory effect with the highest boiling point fraction and a minimal effect with the lowest boiling point fraction; the relative abundances of these two fractions in the crude oil represented 27 and 28% respectively. Water-soluble extracts of both crude oils also had inhibitory effects on mucosal transfer rates and these roughly proportionate to the inhibitory potency of the low boiling point fraction of each oil. Weathered samples of San Joaquin Valley, California, and the Paradox Basin, Utah, oils showed greater effects than corresponding samples of unweathered oils even though most of the low molecular weight material from both oils was either evaporated or solubilized in the underlying water during the 36-h weathering period. PMID:1149720

  16. Neptunium (IV) oxalate solubility. [22, 45, 60/sup 0/C

    SciTech Connect

    Luerkens, D W

    1983-07-01

    The equilibrium solubility of neptunium (IV) oxalate in nitric/oxalic acid solutions was determined at 22/sup 0/C, 45/sup 0/C, and 60/sup 0/C. The concentrations of nitric/oxalic acid solutions represented a wide range of free oxalate ion concentration. A mathematical solubility model was developed which is based on the formation of the known complexes of neptunium (IV) oxalate. the solubility model uses a simplified concentration parameter which is proportional to the free oxalate ion concentration. The solubility model can be used to estimate the equilibrium solubility of neptunium (IV) oxalate over a wide range of oxalic and nitric acid concentrations at each temperature.

  17. Biogenesis of Oxalate in Plant Tissues

    PubMed Central

    Chang, Chi-Cheng; Beevers, Harry

    1968-01-01

    Red beet root discs aerated in potassium phosphate for 2 to 3 days and young spinach leaves actively produce oxalate. A series of labeled compounds was supplied to each of these tissues to determine the extent of conversion to oxalate. Similar results were obtained with the 2 tissues except that in the leaf tissue glyoxylate and glycolate were outstandingly good precursors. Carbon from glucose, acetate, and particularly from some acids of the tricarboxylic acid cycle was recovered in oxalate. Extracts from both tissues were found to contain an enzyme which converts oxaloacetate to oxalate and acetate. The enzyme was partially purified and some of its properties are described. A pathway of oxalate synthesis which does not include glycolate or its oxidase is therefore proposed. PMID:16656975

  18. Inclusion of ancient Latin-American crops in bread formulation improves intestinal iron absorption and modulates inflammatory markers.

    PubMed

    Laparra, Jos Moiss; Haros, Monika

    2016-02-17

    This study compares iron (Fe) absorption in Fe-deficient animals from bread formulations prepared by substitution of white wheat flour (WB) by whole wheat flour (WWB), amaranth flour (Amaranthus hypochondriacus, 25%) (AB) and quinoa flour (Chenopodium quinoa, 25%) (QB), or chia flour (Salvia hispanica L, 5%) (ChB). Hematological parameters of Fe homeostasis, plasmatic active hepcidin peptide production (LC coupled to Ms/Ms), and liver TfR-2 and IL-6 expression (RT-qPCR) were determined. The different bread formulations increased Fe content between 14% and 83% relative to white bread. Only animals fed with WWB, AB and ChB increased haemoglobin concentrations significantly. Feeding the different bread formulations did not increase hepcidin levels, but down-regulated transferrin receptor 2 (TfR2) (apart from WWB) and IL-6 (apart from QB) expression levels. Only AB and ChB had a significant influence on Fe bioavailability at the investigated level of substitution. The potential contribution of these flours would not differ considerably from that of WWB. PMID:26787109

  19. Lack of acyl-CoA:diacylglycerol acyltransferase 1 reduces intestinal cholesterol absorption and attenuates atherosclerosis in apolipoprotein E knockout mice

    PubMed Central

    Chandak, Prakash G.; Obrowsky, Sascha; Radovic, Branislav; Doddapattar, Prakash; Aflaki, Elma; Kratzer, Adelheid; Doshi, Lalit S.; Povoden, Silvia; Ahammer, Helmut; Hoefler, Gerald; Levak-Frank, Sanja; Kratky, Dagmar

    2011-01-01

    Triacylglycerols (TG) are the major storage molecules of metabolic energy and fatty acids in several tissues. The final step in TG biosynthesis is catalyzed by acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes. Lack of whole body DGAT1 is associated with reduced lipid-induced inflammation. Since one major component of atherosclerosis is chronic inflammation we hypothesized that DGAT1 deficiency might ameliorate atherosclerotic lesion development. We therefore crossbred Apolipoprotein E-deficient (ApoE?/?) mice with Dgat1?/? mice. ApoE?/? and ApoE?/?Dgat1?/? mice were fed Western-type diet (WTD) for 9weeks and thereafter examined for plaque formation. The mean atherosclerotic lesion area was substantially reduced in ApoE?/?Dgat1?/? compared with ApoE?/? mice in en face and aortic valve section analyses. The reduced lesion size was associated with decreased cholesterol uptake and absorption by the intestine, reduced plasma TG and cholesterol concentrations and increased cholesterol efflux from macrophages. The expression of adhesion molecules was reduced in aortas of ApoE?/?Dgat1?/? mice, which might be the reason for less migration capacities of monocytes and macrophages and the observed decreased amount of macrophages within the plaques. From our results we conclude that the lack of DGAT1 is atheroprotective, implicating an additional application of DGAT1 inhibitors with regard to maintaining cholesterol homeostasis and attenuating atherosclerosis. PMID:21924378

  20. Comparison of the enhanced steady-state diffusion of calcium by calbindin-D9K and calmodulin: possible importance in intestinal calcium absorption.

    PubMed

    Feher, J J; Fullmer, C S; Fritzsch, G K

    1989-01-01

    The diffusion of calcium was measured using the unidirectional flux of 45Ca across an aqueous layer. The aqueous layer was bounded by two dialysis membranes and convection was eliminated by gelling the aqueous layer with agarose. The apparent self-diffusion coefficient was determined by the dependence of the tracer flux on the diffusion distance. The apparent self-diffusion coefficient increased linearly with the concentration of calbindin-D9K and calmodulin, but the effect of calmodulin was markedly less than that of calbindin-D9K. This difference is attributed to the lower association constant for calmodulin. The ion-exchange resin Chelex-100 also increased the steady-state of 45Ca, but the effect of Chelex-100 was much less efficient than the effect of calbindin-D9K. The mechanism of enhanced diffusion was attributed to an enhanced gradient of total 45Ca. These results indicate that the steady-state unidirectional calcium flux is a superposition of free calcium diffusion and bound calcium diffusion, with only a small contribution due to a 'bucket brigade' mechanism. We suggest that this phenomenon may be important in calcium absorption across the intestine. PMID:2776187

  1. Human biokinetics of strontium--part II: Final data evaluation of intestinal absorption and urinary excretion of strontium in human subjects after stable tracer administration.

    PubMed

    Hllriegl, Vera; Li, Wei Bo; Oeh, Uwe

    2006-09-01

    Fractional intestinal absorption (f1 value) and urinary excretion of strontium in healthy human volunteers has been measured by simultaneous oral and intravenous administration of the stable isotopes 86Sr and 84Sr using the double-isotope method. Final evaluation of the complete data set confirmed that ingestion of different foodstuff and nutritional factors could influence the fractional gut uptake of strontium. In some cases, significant deviations from the f1 value adopted by the International Commission on Radiological Protection (ICRP) were found. The arithmetic mean (+/- standard deviation) of the f1 values of all experiments performed was determined to be 0.46 (+/- 0.24). The probability distribution function of the f1 values is represented by a lognormal curve with a geometric mean of 0.38 and a geometric standard deviation of 2.06. Urinary excretion in all subjects varied depending on the administered foodstuff in a wide range and differs from the ICRP model, up to 2 days after tracer administration. No age or gender dependence of the absorbed strontium fraction and of the urinary excretion of strontium after an oral load was found. PMID:16897061

  2. Sitagliptin promotes macrophage-to-faeces reverse cholesterol transport through reduced intestinal cholesterol absorption in obese insulin resistant CETP-apoB100 transgenic mice.

    PubMed

    Briand, F; Thieblemont, Q; Burcelin, R; Sulpice, T

    2012-07-01

    Dipeptidyl peptidase-4 inhibitors (DPP-4i) improve glycaemic control in type 2 diabetes, but their benefits on reverse cholesterol transport (RCT) remain unknown. We evaluated the effects of DPP-4i sitagliptin 500 mg/kg/day on RCT in obese insulin-resistant CETP-apoB100 transgenic mice. Metformin 300 mg/kg/day orally was used as a reference compound. Both metformin and sitagliptin showed the expected effects on glucose parameters. Although no significant effect was observed on total cholesterol and high-density lipoprotein (HDL) cholesterol levels, sitagliptin, but not metformin, increased faecal cholesterol mass excretion by 132% (p < 0.001 vs. vehicle), suggesting a potent effect on cholesterol metabolism. Mice were then injected i.p. with (3) H-cholesterol labelled macrophages to measure RCT over 48 h. Compared with vehicle, sitagliptin significantly increased macrophage-derived (3) H-cholesterol faecal excretion by 39%. Administration of (14) C-cholesterol labelled olive oil orally showed a significant reduction of (14) C-tracer plasma appearance over time with sitagliptin, indicating that this drug promotes RCT through reduced intestinal cholesterol absorption. PMID:22268579

  3. In vitro prediction of human intestinal absorption and blood-brain barrier partitioning: development of a lipid analog for micellar liquid chromatography.

    PubMed

    De Vrieze, Mike; Janssens, Pieter; Szucs, Roman; Van der Eycken, Johan; Lynen, Frdric

    2015-09-01

    Over the past decades, several in vitro methods have been tested for their ability to predict either human intestinal absorption (HIA) or penetration across the blood-brain barrier (BBB) of drugs. Micellar liquid chromatography (MLC) has been a successful approach for retention time measurements of drugs to establish models together with other molecular descriptors. Thus far, MLC approaches have only made use of commercial surfactants such as sodium dodecyl sulfate (SDS) and polyoxyethylene (23) lauryl ether (Brij35), which are not representative for the phospholipids present in human membranes. Miltefosine, a phosphocholine-based lipid, is presented here as an alternative surfactant for MLC measurements. By using the obtained retention factors and several computed descriptors for a set of 48 compounds, two models were constructed: one for the prediction of HIA and another for the prediction of penetration across the BBB expressed as log BB. All data were correlated to experimental HIA and log BB values, and the performance of the models was evaluated. Log BB prediction performed better than HIA prediction, although HIA prediction was also improved a lot (from 0.5530 to 0.7175) compared to in silico predicted HIA values. PMID:26277183

  4. A GENETIC MUTATION THAT REDUCES CALCIUM OXALATE CONTENT INCREASES CALCIUM AVAILABILITY IN MEDICAGO TRUNCATULA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxalate is considered an antinutrient that renders calcium unavailable for nutritional absorption by humans. Efforts have been made to generate and identify edible plants with decreased levels of this antinutrient. The extent to which a food can be nutritionally improved through genetic alterations ...

  5. A GENETIC MUTATION THAT REDUCES CALCIUM OXALATE CONTENT INCREASES CALCIUM AVAILABILITY IN MEDICAGO TRUNCATULA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxalate is considered an antinutrient that renders calcium unavailable for nutritional absorption by humans. Efforts have been made to generate and identify edible plants with decreased levels of this antinutrient. The extent to which a food can be nutritionally improved through genetic alteration...

  6. The interactive effect of phytase and coccidia on the gross lesions as well as the absorption capacity of intestine in broilers fed with diets low in calcium and available phosphorous.

    PubMed

    Mansoori, Behzad; Modirsanei, Mehrdad; Nodeh, Hassan; Rahbari, Sadegh

    2010-02-26

    In an experiment with 2x2 factorial design, the influence of dietary phytase on the intestinal lesions as well as the absorption capacity of intestine for D-xylose in broiler chickens provided with a diet low in calcium (Ca) and available phosphorus (aP) and challenged with Eimeria oocysts, was evaluated. Four groups of 20 1-day-old male broiler were provided with diets low in total Ca and aP (8 and 3g/kg instead of 10 and 5g/kg of Ca and aP in the diet, respectively). On day 10, 10 chicks from each group were randomly kept in individual raised floor wire cages to adopt environmental conditions. The experimental groups were as follows, Group 1: received no Eimeria oocysts (negative control), Group 2: received oocysts of mixed Eimeria species on day 15 to create an experimental coccidiosis (positive control), Group 3: negative control received phytase enzyme in their diet, from the first day of life, and Group 4: positive control received phytase enzyme in the diet. On day 20, after 12h fasting, the D-xylose absorption test was performed and immediately after that, the intestinal lesion scoring was carried out. The results showed that coccidiosis in Groups 2 and 4 produced progressive lesions in intestinal tract and reduced the concentration of plasma D-xylose in Group 2 when compared to Groups 1 and 3. Dietary phytase had no influence on the concentration of plasma D-xylose in un-infected birds. The enzyme had no influence on the intestinal lesions caused by coccidiosis as well. However, it increased the plasma D-xylose concentration of Group 4 to the level that it was comparable with Groups 1 and 3, at 45 and 90min post-ingestion of the solution. It was concluded that the addition of phytase enzyme to the low Ca and aP diet, increased indirectly the absorption capacity of intestine for D-xylose in infected chickens most probably through the improvement of mechanisms involved in the absorption and transport of D-xylose. PMID:19942351

  7. Automated homogeneous oxalate precipitation of Pu(III)

    SciTech Connect

    Yarbro, S.L.; Schreiber, S.B.; Dunn, S.L.; Mills, C.W.

    1990-01-01

    Homogeneous oxalate precipitation using diethyl oxalate was compared to precipitating Pu(III) oxalate with solid oxalic acid. The diethyl oxalate technique at 75{degree}C is better because it gives 50% less plutonium in the filtrate with a reasonable filtering time. Also, the procedure for the homogeneous precipitation is easier to automate because the liquid diethyl oxalate is simpler to introduce into the precipitator than solid oxalic acid. It also provides flexibility because the hydrolysis rate and therefore the precipitation rate can be controlled by varying the temperature. 5 refs., 3 figs., 3 tabs.

  8. Artificial photosynthesis of oxalate and oxalate-based polymer by a photovoltaic reactor

    PubMed Central

    Nong, Guangzai; Chen, Shan; Xu, Yuanjin; Huang, Lijie; Zou, Qingsong; Li, Shiqiang; Mo, Haitao; Zhu, Pingchuan; Cen, Weijian; Wang, Shuangfei

    2014-01-01

    A photovoltaic reactor was designed for artificial photosynthesis, based on the reactions involved in high energy hydrogen atoms, which were produced from water electrolysis. Water and CO2, under the conditions studied, were converted to oxalate (H2C2O4) and a polymer. This was the first time that the oxalates and oxalate-based polymer were produced from the artificial photosynthesis process. PMID:24389750

  9. In vivo oxalate degradation by liposome encapsulated oxalate oxidase in rat model of hyperoxaluria

    PubMed Central

    Dahiya, Tulika; Pundir, C.S.

    2013-01-01

    Background & objectives: High level of urinary oxalate substantially increases the risk of hyperoxaluria, a significant risk factor for urolithiasis. The primary goal of this study was to reduce urinary oxalate excretion employing liposome encapsulated oxalate oxidase in animal model. Methods: A membrane bound oxalate oxidase was purified from Bougainvillea leaves. The enzyme in its native form was less effective at the physiological pH of the recipient animal. To increase its functional viability, the enzyme was immobilized on to ethylene maleic anhydride (EMA). Rats were injected with liposome encapsulated EMA- oxalate oxidase and the effect was observed on degradation of oxalic acid. Results: The enzyme was purified to apparent homogeneity with 60-fold purification and 31 per cent yield. The optimum pH of EMA-derivative enzyme was 6.0 and it showed 70 per cent of its optimal activity at pH 7.0. The EMA-bound enzyme encapsulated into liposome showed greater oxalate degradation in 15 per cent casein vitamin B6 deficient fed rats as compared with 30 per cent casein vitamin B6 deficient fed rats and control rats. Interpretation & conclusions: EMA-oxalate oxidase encapsulated liposome caused oxalate degradation in experimental hyperoxaluria indicating that the enzyme could be used as a therapeutic agent in hyperoxaluria leading to urinary stones. PMID:23481063

  10. Photoconductivity of Yttrium Neodymium Gadolinium Oxalate Crystals

    NASA Astrophysics Data System (ADS)

    Kuryan, Soosy; Abraham, Rosalin; Isac, Jayakumari

    2007-03-01

    Crystals are pillars of modern technology..Yttrium Neodymium Gadolinium oxalate (YNdGaOx) crystals were grown by gel method by the diffusion of Yttrium Chloride, Neodymium Chloride, and Gadolinium Chloride into the set gel containing Oxalic acid. Silica gel method is capable of yielding crystals of high optical perfection and wide morphology. The growing crystals are held in the gel medium in a strain free manner and at the same time nucleation and super saturation are well controlled. Photo conductivity studies of these crystals revealed negative photoconductivity nature. The photocurrent is found to be less than the dark current at every applied electric field. Rare Earth compounds are known for their interesting electric, magnetic and luminescent properties. Recent investigations on the fluorescence of some rare earth oxalates suggest their potentiality for their optical applications. Rare Earth oxalates evoked greater attention because of their ionic conduction.

  11. Photoconductivity of Yttrium Praseodymium Gadolinium Oxalate Crystals

    NASA Astrophysics Data System (ADS)

    Kuryan, Soosy; Abraham, Rosalin; Isac, Jayakumari

    2007-06-01

    Crystals are pillars of modern technology. Yttrium Praseodymium Gadolinium oxalate (YPrGaOx) crystals were grown by gel method by the diffusion of Yttrium Chloride, Praseodymium Chloride, and Gadolinium Chloride into the set gel containing Oxalic acid. Silica gel method is capable of yielding crystals of high optical perfection and wide morphology. The growing crystals are held in the gel medium in a strain free manner and at the same time nucleation and super saturation are well controlled. Photo conductivity studies of these crystals revealed negative photoconductivity nature. The photocurrent is found to be less than the dark current at every applied electric field. Rare Earth compounds are known for their interesting electric, magnetic and luminescent properties. Recent investigations on the fluorescence of some rare earth oxalates suggest their potentiality for their optical applications. Rare Earth oxalates evoked greater attention because of their ionic conduction.

  12. Chaga mushroom-induced oxalate nephropathy.

    PubMed

    Kikuchi, Yuko; Seta, Koichi; Ogawa, Yayoi; Takayama, Tatsuya; Nagata, Masao; Taguchi, Takashi; Yahata, Kensei

    2014-06-01

    Chaga mushrooms have been used in folk and botanical medicine as a remedy for cancer, gastritis, ulcers, and tuberculosis of the bones. A 72-year-old Japanese female had been diagnosed with liver cancer 1 year prior to presenting at our department. She underwent hepatectomy of the left lobe 3 months later. Chaga mushroom powder (4 - 5 teaspoons per day) had been ingested for the past 6 months for liver cancer. Renal function decreased and hemodialysis was initiated. Renal biopsy specimens showed diffuse tubular atrophy and interstitial fibrosis. Oxalate crystals were detected in the tubular lumina and urinary sediment and oxalate nephropathy was diagnosed. Chaga mushrooms contain extremely high oxalate concentrations. This is the first report of a case of oxalate nephropathy associated with ingestion of Chaga mushrooms. PMID:23149251

  13. Modeling the Adsorption of Oxalate onto Montmorillonite.

    PubMed

    Ramos, M Elena; Emiroglu, Caglayan; Garca, David; Sainz-Daz, C Ignacio; Huertas, F Javier

    2015-11-01

    In this work, a multiscale modeling of the interaction of oxalate with clay mineral surfaces from macroscale thermodynamic equilibria simulations to atomistic calculations is presented. Previous results from macroscopic adsorption data of oxalate on montmorillonite in 0.01 M KNO3 media at 25 C within the pH range from 2.5 to 9 have been used to develop a surface complexation model. The experimental adsorption edge data were fitted using the triple-layer model (TLM) with the aid of the FITEQL 4.0 computer program. Surface complexation of oxalate is described by two reactions: >AlOH + Ox(2-) + 2H(+) = >AlOxH + H2O (log K = 14.39) and >AlOH + Ox(2-) + H(+) = >AlOx(-) + H2O (log K = 10.39). The monodentate complex >AlOxH dominated adsorption below pH 4, and the bidentate complex >AlOx(-) was predominant at higher pH values. Both of the proposed inner-sphere oxalate species are qualitatively consistent with previously published diffuse reflectance FTIR spectroscopic results for oxalate on montmorillonite edge surface (Chem. Geol. 2014, 363, 283-292). Atomistic computational studies have been performed to understand the interactions at the molecular level between adsorbates and mineral surface, showing the atomic structures and IR frequency shifts of the adsorption complexes of oxalate with the edge surface of a periodic montmorillonite model. PMID:26444928

  14. Spectroscopic study of the inhibition of calcium oxalate calculi by Larrea tridentata

    NASA Astrophysics Data System (ADS)

    Pinales, Luis Alonso

    The causes of urolithiasis include such influences as diet, metabolic disorders, and genetic factors which have been documented as sources that aggravate urinary calculi depositions and aggregations, and, implicitly, as causes of urolithiasis. This study endeavors to detail the scientific mechanisms involved in calcium oxalate calculi formation, and, more importantly, their inhibition under growth conditions imposed by the traditional medicinal approach using the herbal extract, Larrea tridentata. The calculi were synthesized without and with Larrea tridentata infusion by employing the single diffusion gel technique. A visible decrease in calcium oxalate crystal growth with increasing amounts of Larrea tridentata herbal infusion was observed in photomicrographs, as well as a color change from white-transparent for pure crystals to light orange-brown for crystals with inhibitor. Analysis of the samples, which includes Raman, infrared absorption, scanning electron microscopy (SEM), and X-ray powder diffraction (XRD) techniques, demonstrate an overall transition in morphology of the crystals from monohydrate without herbal extract to dihydrate with inhibitor. Furthermore, the resulting data from Raman and infrared absorption support the possibilities of the influences, in this complex process, of NDGA and its derivative compounds from Larrea tridentata, and of the bonding of the magnesium of the inhibitor with the oxalate ion on the surface of the calculi crystals. This assumption corroborates well with the micrographs obtained under higher magnification, which show that the separated small crystallites consist of darker brownish cores, which we attribute to the dominance of growth inhibition by NDGA, surrounded by light transparent thin shells, which possibly correspond to passivation of the crystals by magnesium oxalate. The SEM results reveal the transformation from the dominant monoclinic structure of the calcium oxalate crystals grown alone to the tetragonal dipyramidal crystal structure of the calcium oxalate crystals grown with Larrea tridentata. Comparison between XRD experimental and simulated data, besides corroborating with our previous results, show that each sample is a combination of different structures.

  15. Intestinal failure: Pathophysiological elements and clinical diseases

    PubMed Central

    Ding, Lian-An; Li, Jie-Shou

    2004-01-01

    There are two main functions of gastrointestinal tract, digestion and absorption, and barrier function. The latter has an important defensive effect, which keeps the body away from the invading and damaging of bacteria and endotoxin. It maintains the systemic homeostasis. Intestinal dysfunction would happen when body suffers from diseases or harmful stimulations. The lesser dysfunction of GI tract manifests only disorder of digestion and absorption, whereas the more serious intestinal disorders would harm the intestinal protective mechanism, or intestinal barrier function, and bacterial/endotoxin translocation, of intestinal failure (IF) would ensue. This review disscussed the theory of the intestinal failure, aiming at attracting recognition and valuable comments by clinicians. PMID:15052668

  16. High-fat diet intake from senescence inhibits the attenuation of cell functions and the degeneration of villi with aging in the small intestine, and inhibits the attenuation of lipid absorption ability in SAMP8 mice

    PubMed Central

    Yamamoto, Kazushi; E, Shuang; Hatakeyama, Yu; Sakamoto, Yu; Tsuduki, Tsuyoshi

    2015-01-01

    We examined the effect of a high-fat diet from senescence as a means of preventing malnutrition among the elderly. The senescence-accelerated mouse P8 was used and divided into three groups. The 6C group was given a normal diet until 6 months old. The 12N group was given a normal diet until 12 months old. The 12F group was given a normal diet until 6 months old and then a high-fat diet until 12 months old. In the oral fat tolerance test, there was a decrease in area under the curve for serum triacylglycerol level in the 12N group and a significant increase in the 12F group, suggesting that the attenuation of lipid absorption ability with aging was delayed by a high-fat diet from senescence. To examine this mechanism, histological analysis in the small intestine was performed. As a result, the degeneration of villi with aging was inhibited by the high-fat diet. There was also a significant decrease in length of villus in the small intestine in the 12N group and a significant increase in the 12F group. The high-fat diet from senescence inhibited the degeneration of villi with aging in the small intestine, and inhibited the attenuation of lipid absorption ability. PMID:26566305

  17. Circadian Regulation of Macronutrient Absorption.

    PubMed

    Hussain, M Mahmood; Pan, Xiaoyue

    2015-12-01

    Various intestinal functions exhibit circadian rhythmicity. Disruptions in these rhythms as in shift workers and transcontinental travelers are associated with intestinal discomfort. Circadian rhythms are controlled at the molecular level by core clock and clock-controlled genes. These clock genes are expressed in intestinal cells, suggesting that they might participate in the circadian regulation of intestinal functions. A major function of the intestine is nutrient absorption. Here, we will review absorption of proteins, carbohydrates, and lipids and circadian regulation of various transporters involved in their absorption. A better understanding of circadian regulation of intestinal absorption might help control several metabolic disorders and attenuate intestinal discomfort associated with disruptions in sleep-wake cycles. PMID:26269217

  18. 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 ...

  19. Isotope Concentrations from 24-h Urine and 3-h Serum Samples Can Be Used to Measure Intestinal Magnesium Absorption in Postmenopausal Women123

    PubMed Central

    Hansen, Karen E.; Nabak, Andrea C.; Johnson, Rachael Erin; Marvdashti, Sheeva; Keuler, Nicholas S.; Shafer, Martin M.; Abrams, Steven A.

    2014-01-01

    Studies suggest a link between magnesium status and osteoporosis. One barrier to more conclusive research on the potential relation is measuring intestinal magnesium absorption (MgA), which requires the use of stable isotopes and a ?6-d stool or 3-d urine collection. We evaluated alternative methods of measuring MgA. We administered 2 stable magnesium isotopes to 15 postmenopausal women (cohort 1) aged 62 8 y with a dietary magnesium intake of 345 72 mg/d. Participants fasted from 1200 h to 0700 h and then consumed breakfast with ?23 mg of oral 26Mg and ?11 mg of i.v. 25Mg. We measured magnesium isotope concentrations in 72-h urine, spot urine (36, 48, 60, and 72 h), and spot serum (1, 3, and 5 h) samples collected after isotope dosing. We calculated MgA using the dose-corrected fraction of isotope concentrations from the 72-h urine collection. We validated new methods in 10 postmenopausal women (cohort 2) aged 59 5 y with a dietary magnesium intake of 325 122 mg/d. In cohort 1, MgA based on the 72-h urine collection was 0.28 0.08. The 72-h MgA correlated most highly with 024 h urine MgA value alone (? = 0.95, P < 0.001) or the mean of the 024 h urine and the 3-h (? = 0.93, P < 0.001) or 5-h (? = 0.96, P < 0.001) serum MgA values. In cohort 2, Bland-Altman bias was lowest (?0.003, P = 0.82) using means of the 024 h urine and 3-h serum MgA values. We conclude that means of 024 h urine and 3-h serum MgA provide a reasonable estimate of 72-h MgA. However, if researchers seek to identify small changes in MgA, we recommend a 3-d urine or extended stool collection. This trial was registered at clinicaltrials.gov as NCT01593501. PMID:24500940

  20. Cinnamon polyphenols regulate multiple metabolic pathways involved in intestinal lipid metabolism of primary small intestinal enterocytes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing evidence suggests that dietary factors may affect the expression of multiple genes and signaling pathways including those that regulate intestinal lipoprotein metabolism. The small intestine is actively involved in the regulation of dietary lipid absorption, intracellular transport and me...

  1. High variability of the heterogeneous ice nucleation potential of oxalic acid dihydrate and sodium oxalate

    NASA Astrophysics Data System (ADS)

    Wagner, R.; Möhler, O.; Saathoff, H.; Schnaiter, M.; Leisner, T.

    2010-04-01

    The heterogeneous ice nucleation potential of airborne oxalic acid dihydrate and sodium oxalate particles in the deposition and condensation mode has been investigated by controlled expansion cooling cycles in the AIDA aerosol and cloud chamber of the Karlsruhe Institute of Technology at temperatures between 244 and 228 K. Previous laboratory studies have highlighted the particular role of oxalic acid dihydrate as the only species amongst a variety of other investigated dicarboxylic acids to be capable of acting as a heterogeneous ice nucleus in both the deposition and immersion mode. We could confirm a high deposition mode ice activity for 0.03 to 0.8 μm sized oxalic acid dihydrate particles that were either formed by nucleation from a gaseous oxalic acid/air mixture or by rapid crystallisation of highly supersaturated aqueous oxalic acid solution droplets. The critical saturation ratio with respect to ice required for deposition nucleation was found to be less than 1.1 and the size-dependent ice-active fraction of the aerosol population was in the range from 0.1 to 22%. In contrast, oxalic acid dihydrate particles that had crystallised from less supersaturated solution droplets and had been allowed to slowly grow in a supersaturated environment from still unfrozen oxalic acid solution droplets over a time period of several hours were found to be much poorer heterogeneous ice nuclei. We speculate that under these conditions a crystal surface structure with less-active sites for the initiation of ice nucleation was generated. Such particles partially proved to be almost ice-inactive in both the deposition and condensation mode. At times, the heterogeneous ice nucleation ability of oxalic acid dihydrate significantly changed when the particles had been processed in preceding cloud droplet activation steps. Such behaviour was also observed for the second investigated species, namely sodium oxalate. Our experiments address the atmospheric scenario that coating layers of oxalic acid or its salts may be formed by physical and chemical processing on pre-existing particulates such as mineral dust and soot. Given the broad diversity of the observed heterogeneous ice nucleability of the oxalate species, it is not straightforward to predict whether an oxalate coating layer will improve or reduce the ice nucleation ability of the seed aerosol particles.

  2. High variability of the heterogeneous ice nucleation potential of oxalic acid dihydrate and sodium oxalate

    NASA Astrophysics Data System (ADS)

    Wagner, R.; Möhler, O.; Saathoff, H.; Schnaiter, M.; Leisner, T.

    2010-08-01

    The heterogeneous ice nucleation potential of airborne oxalic acid dihydrate and sodium oxalate particles in the deposition and condensation mode has been investigated by controlled expansion cooling cycles in the AIDA aerosol and cloud chamber of the Karlsruhe Institute of Technology at temperatures between 244 and 228 K. Previous laboratory studies have highlighted the particular role of oxalic acid dihydrate as the only species amongst a variety of other investigated dicarboxylic acids to be capable of acting as a heterogeneous ice nucleus in both the deposition and immersion mode. We could confirm a high deposition mode ice activity for 0.03 to 0.8 μm sized oxalic acid dihydrate particles that were either formed by nucleation from a gaseous oxalic acid/air mixture or by rapid crystallisation of highly supersaturated aqueous oxalic acid solution droplets. The critical saturation ratio with respect to ice required for deposition nucleation was found to be less than 1.1 and the size-dependent ice-active fraction of the aerosol population was in the range from 0.1 to 22%. In contrast, oxalic acid dihydrate particles that had crystallised from less supersaturated solution droplets and had been allowed to slowly grow in a supersaturated environment from still unfrozen oxalic acid solution droplets over a time period of several hours were found to be much poorer heterogeneous ice nuclei. We speculate that under these conditions a crystal surface structure with less-active sites for the initiation of ice nucleation was generated. Such particles partially proved to be almost ice-inactive in both the deposition and condensation mode. At times, the heterogeneous ice nucleation ability of oxalic acid dihydrate significantly changed when the particles had been processed in preceding cloud droplet activation steps. Such behaviour was also observed for the second investigated species, namely sodium oxalate. Our experiments address the atmospheric scenario that coating layers of oxalic acid or its salts may be formed by physical and chemical processing on pre-existing particulates such as mineral dust and soot. Given the broad diversity of the observed heterogeneous ice nucleability of the oxalate species, it is not straightforward to predict whether an oxalate coating layer will improve or reduce the ice nucleation ability of the seed aerosol particles.

  3. ADVANCED OXIDATION: OXALATE DECOMPOSITION TESTING WITH OZONE

    SciTech Connect

    Ketusky, E.; Subramanian, K.

    2012-02-29

    At the Savannah River Site (SRS), oxalic acid is currently considered the preferred agent for chemically cleaning the large underground Liquid Radioactive Waste Tanks. It is applied only in the final stages of emptying a tank when generally less than 5,000 kg of waste solids remain, and slurrying based removal methods are no-longer effective. The use of oxalic acid is preferred because of its combined dissolution and chelating properties, as well as the fact that corrosion to the carbon steel tank walls can be controlled. Although oxalic acid is the preferred agent, there are significant potential downstream impacts. Impacts include: (1) Degraded evaporator operation; (2) Resultant oxalate precipitates taking away critically needed operating volume; and (3) Eventual creation of significant volumes of additional feed to salt processing. As an alternative to dealing with the downstream impacts, oxalate decomposition using variations of ozone based Advanced Oxidation Process (AOP) were investigated. In general AOPs use ozone or peroxide and a catalyst to create hydroxyl radicals. Hydroxyl radicals have among the highest oxidation potentials, and are commonly used to decompose organics. Although oxalate is considered among the most difficult organic to decompose, the ability of hydroxyl radicals to decompose oxalate is considered to be well demonstrated. In addition, as AOPs are considered to be 'green' their use enables any net chemical additions to the waste to be minimized. In order to test the ability to decompose the oxalate and determine the decomposition rates, a test rig was designed, where 10 vol% ozone would be educted into a spent oxalic acid decomposition loop, with the loop maintained at 70 C and recirculated at 40L/min. Each of the spent oxalic acid streams would be created from three oxalic acid strikes of an F-area simulant (i.e., Purex = high Fe/Al concentration) and H-area simulant (i.e., H area modified Purex = high Al/Fe concentration) after nearing dissolution equilibrium, and then decomposed to {le} 100 Parts per Million (ppm) oxalate. Since AOP technology largely originated on using ultraviolet (UV) light as a primary catalyst, decomposition of the spent oxalic acid, well exposed to a medium pressure mercury vapor light was considered the benchmark. However, with multi-valent metals already contained in the feed, and maintenance of the UV light a concern; testing was conducted to evaluate the impact from removing the UV light. Using current AOP terminology, the test without the UV light would likely be considered an ozone based, dark, ferrioxalate type, decomposition process. Specifically, as part of the testing, the impacts from the following were investigated: (1) Importance of the UV light on the decomposition rates when decomposing 1 wt% spent oxalic acid; (2) Impact of increasing the oxalic acid strength from 1 to 2.5 wt% on the decomposition rates; and (3) For F-area testing, the advantage of increasing the spent oxalic acid flowrate from 40 L/min (liters/minute) to 50 L/min during decomposition of the 2.5 wt% spent oxalic acid. The results showed that removal of the UV light (from 1 wt% testing) slowed the decomposition rates in both the F & H testing. Specifically, for F-Area Strike 1, the time increased from about 6 hours to 8 hours. In H-Area, the impact was not as significant, with the time required for Strike 1 to be decomposed to less than 100 ppm increasing slightly, from 5.4 to 6.4 hours. For the spent 2.5 wt% oxalic acid decomposition tests (all) without the UV light, the F-area decompositions required approx. 10 to 13 hours, while the corresponding required H-Area decompositions times ranged from 10 to 21 hours. For the 2.5 wt% F-Area sludge, the increased availability of iron likely caused the increased decomposition rates compared to the 1 wt% oxalic acid based tests. In addition, for the F-testing, increasing the recirculation flow rates from 40 liter/minute to 50 liter/minute resulted in an increased decomposition rate, suggesting a better use of ozone.

  4. Fish Oil Supplementation and Urinary Oxalate Excretion in Normal Subjects on a Low-oxalate Diet

    PubMed Central

    Lange, Jessica N.; Mufarrij, Patrick W.; Easter, Linda; Knight, John; Holmes, Ross P.; Assimos, Dean G.

    2014-01-01

    OBJECTIVE To determine if fish oil supplementation reduces endogenous oxalate synthesis in healthy subjects. MATERIALS AND METHODS Fifteen healthy nonstone-forming adults participated in this study. Subjects first abstained from using vitamins, medications, or foods enriched in omega-3 fatty acids for 30 days. Next, they collected two 24-hour urine specimens while consuming a self-selected diet. Subjects consumed an extremely low-oxalate and normal-calcium diet for 5 days and collected 24-hour urine specimens on the last 3 days of this diet. Next, the subjects took 2 fish oil capsules containing 650-mg eicosapentaenoic acid and 450-mg docosahexaenoic acid twice daily for 30 days. They consumed a self-selected diet on days 125 and the controlled diet on days 2630. Twenty-four-hour urine samples were collected on days 2830. Excretion levels of urinary analytes including oxalate and glycolate were analyzed. RESULTS Although there was a significant reduction in urinary oxalate, magnesium, and potassium excretions and an increase in uric acid excretion during the controlled dietary phases compared with the self-selected diet, there were no significant differences in their excretion during controlled diet phases with and without fish oil supplementation. CONCLUSION These results suggest that fish oil supplementation does not reduce endogenous oxalate synthesis or urinary oxalate excretion in normal adults during periods of extremely low oxalate intake. However, these results do not challenge the previously described reduction in urinary oxalate excretion demonstrated in normal subjects consuming a moderate amount of oxalate in conjunction with fish oil. PMID:25102784

  5. 3-Cyanoanilinium hydrogen oxalate hemihydrate

    PubMed Central

    Chen, Xin-Yuan

    2012-01-01

    In the title hydrated molecular salt, C7H7N2 +C2HO4 ?0.5H2O, contains a 3-cyanoanilinium cation, a hydrogen oxalate anion and half a water molecule in an asymmetric unit. The dihedral angle between the CO2(H) and CO2 planes of the hydrogen oxalate ion is 7.96?(1). In the crystal, the components are linked by NH?O and OH?O hydrogen bonds, forming a layer lying parallel to the ac plane. PMID:22719472

  6. The impact of in vitro digestion on bioaccessibility of polyphenols from potatoes and sweet potatoes and their influence on iron absorption by human intestinal cells.

    PubMed

    Miranda, Lisa; Deußer, Hannah; Evers, Danièle

    2013-11-01

    The composition of potatoes as determined by chemical extraction has been described extensively. It is thus quite well known that, among other compounds, potato is rich in polyphenols, vitamins and in some minerals. This paper underlines the important role of simulated gastro-intestinal in vitro digestion in the bioaccessibility of polyphenols (chlorogenic acid and derivatives, and rutin) from potatoes and sweet potatoes and their impact on iron uptake. Concentrations of polyphenols in the flesh of two potato cultivars (Nicola, white potato, and Vitelotte, purple potato) and sweet potato were measured by Ultra Performance Liquid Chromatography after boiling and after in vitro digestion. Chemical extraction underestimates polyphenol amounts that can be released during digestion and that are actually bioaccessible. Iron uptake, as evaluated by a ferritin assay, by intestinal human cells was decreased after incubation with the intestinal phase of in vitro digestion, presumably due to the presence of polyphenols. PMID:24056541

  7. The Interaction between Enterobacteriaceae and Calcium Oxalate Deposits

    PubMed Central

    Barr-Beare, Evan; Saxena, Vijay; Hilt, Evann E.; Thomas-White, Krystal; Schober, Megan; Li, Birong; Becknell, Brian; Hains, David S.; Wolfe, Alan J.; Schwaderer, Andrew L.

    2015-01-01

    Background The role of calcium oxalate crystals and deposits in UTI pathogenesis has not been established. The objectives of this study were to identify bacteria present in pediatric urolithiasis and, using in vitro and in vivo models, to determine the relevance of calcium oxalate deposits during experimental pyelonephritis. Methods Pediatric kidney stones and urine were collected and both cultured and sequenced for bacteria. Bacterial adhesion to calcium oxalate was compared. Murine kidney calcium oxalate deposits were induced by intraperitoneal glyoxalate injection and kidneys were transurethrally inoculated with uropathogenic Escherichia coli to induce pyelonephritis Results E. coli of the family Enterobacteriaceae was identified in patients by calcium oxalate stone culture. Additionally Enterobacteriaceae DNA was sequenced from multiple calcium oxalate kidney stones. E. coli selectively aggregated on and around calcium oxalate monohydrate crystals. Mice inoculated with glyoxalate and uropathogenic E. coli had higher bacterial burdens, increased kidney calcium oxalate deposits and an increased kidney innate immune response compared to mice with only calcium oxalate deposits or only pyelonephritis. Conclusions In a murine model, the presence of calcium oxalate deposits increases pyelonephritis risk, likely due to preferential aggregation of bacteria on and around calcium oxalate crystals. When both calcium oxalate deposits and uropathogenic bacteria were present, calcium oxalate deposit number increased along with renal gene transcription of inner stone core matrix proteins increased. Therefore renal calcium oxalate deposits may be a modifiable risk factor for infections of the kidney and urinary tract. Furthermore, bacteria may be present in calcium oxalate deposits and potentially contribute to calcium oxalate renal disease. PMID:26448465

  8. Comparative structural modeling and docking studies of oxalate oxidase: Possible implication in enzyme supplementation therapy for urolithiasis.

    PubMed

    Khobragade, C N; Beedkar, Supriya D; Bodade, Ragini G; Vinchurkar, Aruna S

    2011-04-01

    In humans oxalate is end product of protein metabolism, with no enzyme present to act on it. In conditions of its enhanced endogenous synthesis or increased absorption from the diet, oxalate accumulation leads to hyperoxaluria which can further lead to a number of pathological conditions including urolithiasis. Urolithiasis has been a perplexing problem due to its high incidence and rate of recurrence after treatment like Extracorporeal-shock wave lithotripsy (ESWL). Hence other prophylactic treatment becomes necessary. One of the newer approaches of curing such metabolic disorders is the enzyme supplementation therapy. Oxalate oxidase (OxOx) is a commonly occurring enzyme in plants, bacteria and fungi that catalyses oxidative cleavage of oxalate to CO(2) with reduction of dioxygen to H(2)O(2). Present study, used Hordeum vulgare OxOx crystal structure (PDB ID 2ET1A) as a template for constructing 3D models of OxOx from Triticum aestivum, Arabidopsis thaliana, Sclerotiana sclerotiarum. Similarly Homology models for isoforms Ceriporiopsis subvermispora 336, C. subvermispora 422 were constructed by using template Bacillus subtilis oxalate decarboxylase (Oxdc) (PDB ID 2UY8A) by comparative modeling approach in SWISS MODEL, MODELLER, 3D JIGSAW and GENO 3D program server. Based on overall stereochemical quality (PROCHECK, PROSA, VARIFY 3D), best models were selected, energy minimized, refined and characterized for active site in BioMed CaChe V 6.1 workspace. Selected models were further studied for structure function relationship with substrate (oxalate) and its analogue (glycolate) by using docking approach. Calculated interaction energy between the oxalate and constructed enzyme indicated that homology models for OxOx of T. aestivum, A. thaliana and S. sclerotiarum, can account for better regio-specificity of this enzyme towards oxalate. That supports the interested metabolism and thus may further implement in enzyme supplementation therapy for urolithiasis. PMID:21255608

  9. Comparative study on intestinal metabolism and absorption in vivo of ginsenosides in sulphur-fumigated and non-fumigated ginseng by ultra performance liquid chromatography quadruple time-of-flight mass spectrometry based chemical profiling approach.

    PubMed

    Zhu, He; Shen, Hong; Xu, Jun; Xu, Jin-Di; Zhu, Ling-Ying; Wu, Jie; Chen, Hu-Biao; Li, Song-Lin

    2015-04-01

    Our previous study indicated that sulphur-fumigation of ginseng in post-harvest handling processes could induce chemical transformation of ginsenosides to generate multiple ginsenoside sulphur derivatives. In this study, the influence of sulphur-fumigation on intestinal metabolism and absorption in vivo of ginsenosides in ginseng was sequentially studied. The intestinal metabolic and absorbed profiles of ginsenosides in rats after intra-gastric (i.g.) administration of sulphur-fumigated ginseng (SFG) and non-fumigated ginseng (NFG) were comparatively characterized by a newly established ultra performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) with electrospray ionization negative (ESI-) mode. A novel strategy based on the characteristic product ions and fragmentation pathways of different types of aglycones (saponin skeletons) and glycosyl moieties was proposed and successfully applied to rapid structural identification of ginsenoside sulphur derivatives and relevant metabolites. In total, 18 ginsenoside sulphur derivatives and 26 ginsenoside sulphur derivative metabolites in the faeces together with six ginsenoside sulphur derivatives in the plasma were identified in the SFG-administrated group but not in the NFG-administrated group. The results clearly demonstrated that the intestinal metabolic and absorbed profiles of ginsenosides in sulphur-fumigated and non-fumigated ginseng were quite different, which inspired that sulphur-fumigation of ginseng should not be recommended before the bioactivity and toxicity of the ginsenoside sulphur derivatives were systematically evaluated. PMID:24853104

  10. 40 CFR 721.10628 - Mixed metal oxalate (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Mixed metal oxalate (generic). 721... Substances § 721.10628 Mixed metal oxalate (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as mixed metal oxalate (PMN...

  11. 40 CFR 721.10628 - Mixed metal oxalate (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Mixed metal oxalate (generic). 721... Substances § 721.10628 Mixed metal oxalate (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as mixed metal oxalate (PMN...

  12. Theoretical calculation of zero field splitting parameters of Cr3+ doped ammonium oxalate monohydrate

    NASA Astrophysics Data System (ADS)

    Kripal, Ram; Yadav, Awadhesh Kumar

    2015-06-01

    Zero field splitting parameters (ZFSPs) D and E of Cr3+ ion doped ammonium oxalate monohydrate (AOM) are calculated with formula using the superposition model. The theoretically calculated ZFSPs for Cr3+ in AOM crystal are compared with the experimental value obtained by electron paramagnetic resonance (EPR). Theoretical ZFSPs are in good agreement with the experimental ones. The energy band positions of optical absorption spectra of Cr3+ in AOM crystal calculated with CFA package are in good match with the experimental values.

  13. Role of magnesium in the growth of calcium oxalate monohydrate and calcium oxalate dihydrate crystals.

    PubMed

    Oka, T; Yoshioka, T; Koide, T; Takaha, M; Sonoda, T

    1987-01-01

    Since about 85% of synthesized calcium oxalate dihydrate (COD) crystals proved not to have changed into calcium oxalate monohydrate (COM) crystals at 30 min of incubation time at 37 degrees C when our evaluation method of the COD-to-COM ratio was being used, we made a comparative study of the inhibitory effects of magnesium, one of the well-known inhibitors of calcium oxalate stone formation, on the growth of seeded COM and COD crystals. The results demonstrated that magnesium in identical concentrations might have stronger inhibitory effects on the growth of COM crystals than on that of COD crystals and suggested that these different effects of magnesium on the growth of COM and COD crystals might arise not only from the difference between the specific surface areas of COM and COD crystals, but also from that between the direct inhibitory effects of magnesium on these two types of calcium oxalate crystal growth. PMID:3617248

  14. Direct carbothermic reduction of actinide oxalates: Example of Nd(III) oxalate-carbon mixtures conversion

    NASA Astrophysics Data System (ADS)

    Handschuh, A.; Dubois, S.; Vaudez, S.; Grandjean, S.; Leturcq, G.; Abraham, F.

    2009-03-01

    Mixed uranium-plutonium monocarbide was obtained by carbothermic reduction of mixture of UO 2, PuO 2 and C at around 1500 C under vacuum or argon for 4 h followed by sintering at around 1650 C under mixture of Ar + 8%H 2 for 10 h. Moreover, PuO 2 was synthesized by oxalic precipitation followed by calcination at around 700 C (PUREX process). This work deals with a process simplification, i.e. fabrication of carbide by calcination of actinide oxalate, precipitated in presence of carbon, at 1600 C for 13 h under argon. In this preliminary study, neodymium was used as a surrogate of actinides. No carbon influence was noticed during calcination of neodymium oxalate into oxide. Carbon content was the same before and after calcination making possible conversion to carbide directly from mixture of neodymium oxalate and C.

  15. Use of hydrogen gas (H2) analysis to assess intestinal absorption. Studies in normal rats and in rats infected with the nematode, Nippostrongylus brasiliensis.

    PubMed

    Carter, E A; Bloch, K J; Cohen, S; Isselbacher, K J; Walker, W A

    1981-12-01

    The in vitro and in vivo production of hydrogen gas (H2) from various carbohydrates or proteins has been examined in normal rats and in rats infected with the nematode Nippostrongylus brasiliensis. Normal rat fecal homogenates were capable of producing H2 in vitro from glucose, sucrose, xylose, lactulose, bovine serum albumin, or casein hydrolysate. Direct injection of glucose, sucrose, xylose, lactulose, bovine serum albumin, or casein hydrolysate into the cecum of normal rats resulted in approximately twice as much H2 production in vivo than when these same carbohydrates or proteins were administered to the normal rats by gavage. Partial small intestinal villous atrophy was produced by infecting rats with the nematode N. brasiliensis. Impaired small intestinal cell function and evidence of malabsorption in the nematode-infected rats included: (a) decreased activity of intestinal cell lactase (-43%), sucrase (-33%), and alkaline phosphatase (-46%); (b) decreased gut sac uptake of 3-O-(methyl-3H]-D-glucose (-21%) or 1-[carboxyl-14C]-aminocyclopentane-1-carboxylic acid (-28%); and (c) increased (+ 64%-561%) 14CO2 production after D-[U-14C]xylose administration. These rats produced approximately twice as much H2 after gavage administration of glucose, sucrose, xylose, bovine serum albumin, or casein hydrolysate compared with normal rats. The present study suggests that H2 analysis may be useful in the evaluation of small intestinal malabsorption states in rats. PMID:7286587

  16. Aripiprazole salts. III. Bis(aripiprazolium) oxalate-oxalic acid (1/1).

    PubMed

    Freire, Eleonora; Polla, Griselda; Baggio, Ricardo

    2013-02-01

    The asymmetric unit of the title salt [systematic name: bis(4-(2,3-dichlorophenyl)-1-{4-[(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)oxy]butyl}piperazin-1-ium) oxalate-oxalic acid (1/1)], 2C(23)H(28)Cl(2)N(3)O(2)(+)C(2)O(4)(2-)C(2)H(2)O(4), consists of one protonated aripiprazole unit (HArip(+)), half an oxalate dianion and half an oxalic acid molecule, the latter two lying on inversion centres. The conformation of the HArip(+) cation differs from that in other reported salts and resembles more the conformation of neutral Arip units in reported polymorphs and solvates. The intermolecular interaction linking HArip(+) cations is also similar to those in reported Arip compounds crystallizing in the space group P1, with head-to-head N-HO hydrogen bonds generating centrosymmetric dimers, which are further organized into planar ribbons parallel to (012). The oxalate anions and oxalic acid molecules form hydrogen-bonded chains running along [010], which 'pierce' the planar ribbons, interacting with them through a number of stronger N-HO and weaker C-HO hydrogen bonds, forming a three-dimensional network. PMID:23377689

  17. Oxalate-degrading microorganisms or oxalate-degrading enzymes: which is the future therapy for enzymatic dissolution of calcium-oxalate uroliths in recurrent stone disease?

    PubMed

    Peck, Ammon B; Canales, Benjamin K; Nguyen, Cuong Q

    2016-02-01

    Renal urolithiasis is a pathological condition common to a multitude of genetic, physiological and nutritional disorders, ranging from general hyperoxaluria to obesity. The concept of quickly dissolving renal uroliths via chemolysis, especially calcium-oxalate kidney stones, has long been a clinical goal, but yet to be achieved. Over the past 25 years, there has been a serious effort to examine the prospects of using plant and microbial oxalate-degrading enzymes known to catabolize oxalic acid and oxalate salts. While evidence is emerging that bacterial probiotics can reduce recurrent calcium-oxalate kidney stone disease by lowering systemic hyperoxaluria, the possible use of free oxalate-degrading enzyme therapy remains a challenge with several hurdles to overcome before reaching clinical practice. PMID:26645869

  18. Investigation of the role of oligopeptide transporter PEPT1 and sodium/glucose cotransporter SGLT1 in intestinal absorption of their substrates using small GTP-binding protein Rab8-null mice.

    PubMed

    Kato, Yukio; Sugiura, Tomoko; Nakadera, Yasuhito; Sugiura, Mikihiro; Kubo, Yoshiyuki; Sato, Takashi; Harada, Akihiro; Tsuji, Akira

    2009-03-01

    A small GTP-binding protein, Rab8, is essential for apical localization of oligopeptide transporter PEPT1/SLC15A1 and sodium/glucose cotransporter SGLT1/SLC5A1 in small intestine; deficiency of rab8 gene results in mislocalization and reduced expression of these transporters. Here, we examined the role of PEPT1 and SGLT1 in vivo in gastrointestinal absorption of a beta-lactam antibiotic, cefixime, and alpha-methyl-d-glycopyranoside (alpha-MDG), respectively, using rab8 gene knockout [rab8(-/-)] mice as experimental animals deficient in those transporters. Plasma concentration of cefixime and alpha-MDG after oral administration in rab8(-/-) mice was much lower than that in wild-type mice, whereas such reduction in oral absorption was not observed for antipyrine, membrane permeation of which is not transporter-mediated. Uptake of cefixime from the apical side of isolated small intestine assessed by means of the everted sac method in wild-type mice was decreased in the presence of excess unlabeled glycylsarcosine, a PEPT1 substrate. In contrast, the uptake in rab8(-/-) mice was much lower than that in wild-type mice and comparable with that of an extracellular marker, mannitol, suggesting that the apical membrane permeability of cefixime was reduced in rab8(-/-) mice. Uptake of cefixime in wild-type mice was pH-dependent, being higher at lower pH, whereas that in rab8(-/-) mice remained at the background level at all pH values examined. These results suggest that PEPT1 and SGLT1 play an important role in gastrointestinal absorption of cefixime and alpha-MDG, respectively, in vivo in mice. The present findings also illustrate the pharmacokinetic influence of the sorting machinery protein Rab8. PMID:19074526

  19. Intestinal Obstruction

    MedlinePLUS

    ... Abscesses Abdominal Wall Hernias Inguinal Hernia Acute Mesenteric Ischemia Appendicitis Ileus Intestinal Obstruction Ischemic Colitis Perforation of ... Abscesses Abdominal Wall Hernias Inguinal Hernia Acute Mesenteric Ischemia Appendicitis Ileus Intestinal Obstruction Ischemic Colitis Perforation of ...

  20. Intestinal Malrotation

    MedlinePLUS

    ... the intestines don't position themselves normally during fetal development and aren't attached inside properly as a result. The exact reason this occurs is unknown. When a fetus develops in the womb, the intestines start out ...

  1. Intestinal Obstruction

    MedlinePLUS

    ... Acute Mesenteric Ischemia Appendicitis Ileus Intestinal Obstruction Ischemic Colitis Perforation of the Digestive Tract An obstruction of ... Acute Mesenteric Ischemia Appendicitis Ileus Intestinal Obstruction Ischemic Colitis Perforation of the Digestive Tract NOTE: This is ...

  2. Transient changes of the intestinal absorption of sodium and chloride in the rainbow trout after abrupt transfer into sea-water.

    PubMed

    Nonnotte, G; Aubree-Pelletier, A; Colin, D A

    1987-01-01

    1. Unidirectional fluxes of Na+ and Cl-, ouabain-sensitive Na+,K+-ATPase activity and the protein content have been determined in the intestine of trout in fresh water (FW) and 1, 2, 7 days after sea-water (SW) transfer. 2. After abrupt transfer in SW the Na+ and Cl- transports follow in two phases: first, a permeabilization of the epithelium during the first day; secondly, a transient impermeabilization and increase of the protein content of the mucosa (2 days after SW transfer) and a progressive increase of both the unidirectional Na+, Cl- fluxes and the Na+,K+-ATPase activity (7 days after SW transfer). 3. After 7 days SW the adaptation of the enterocytes which is different for Na+ and Cl- and for the middle and the posterior intestine is not achieved. PMID:2892617

  3. Estimating intestinal absorption of inorganic and organic selenium compounds by in vitro flux and biotransformation studies in Caco-2 cells and ICP-MS detection.

    PubMed

    Gammelgaard, Bente; Rasmussen, Laura Hyrup; Gabel-Jensen, Charlotte; Steffansen, Bente

    2012-02-01

    The aim of the present work was to compare and estimate absorption and biotransformation of selected selenium compounds by studying their fluxes across Caco-2 cells. Five different selenium compounds, selenomethionine (SeMet), Se-methylselenocysteine (MeSeCys), selenate, selenite, and methylseleninic acid (MeSeA), were applied to Caco-2 cells in a concentration of 10 μM, and fluxes in both directions were studied for 2 h. Fluxes of selenite and MeSeA in the presence of excess reduced glutathione (selenite + GSH and MeSeA + GSH) and flux of MeSeA in the presence of excess cysteine (MeSeA + Cys) were also studied. Selenium absorptive and exsorptive fluxes and accumulation in cell cytosol were analyzed by means of flow injection inductively coupled plasma mass spectrometry (ICP-MS). Absorptive flux of SeMet, MeSeCys, and selenate showed values correlating to complete in vivo absorption, while selenite and MeSeA fluxes correlated to poor in vivo absorption. Speciation analysis of cell lysate and donor and receptor solutions by LC-ICP-MS showed limited transformation of all selenium compounds. Extensive transformation as well as significantly increased absorptive flux was observed when co-administering selenite with glutathione compared to administering selenite alone. These observations are possibly due to formation of selenodiglutathione (GS-Se-SG) which may be absorbed differently than selenite. Concomitant application of GSH or cysteine with MeSeA resulted in extensive transformation of MeSeA, including volatile species, whereas no significant increases in fluxes were observed. In summary, the absorption of selenite selenate and the selenoamino acids is considered complete under physiological conditions, but the absorption mechanisms and metabolism of the compounds are different. PMID:21863324

  4. XPS study of reductive dissolution of birnessite by oxalate: rates and mechanistic aspects of dissolution and redox processes

    NASA Astrophysics Data System (ADS)

    Banerjee, D.; Nesbitt, H. W.

    1999-10-01

    Reductive dissolution of synthetic 7-birnessite [MnO1.7(OH)0.25 or MnO1.95] by Na-oxalate produces a Mn(III) intermediate reaction product (here represented as MnOOH?) which subsequently reacts with sorbed (COO)2-2 to form an unreactive Mn(III)-oxalate surface complex at the solution-mineral interface according to the reactions: 2MnO2+(COO)2-2+2H+=2MnOOH?+2CO2? (1)2MnOOH?+(COO)2-2=2[MnOOH-COO]-(2) X-ray Photoelectron Spectroscopy (XPS) results from Mn2p3/2, C1s and O1s spectra of reacted surfaces reveal that initially rapid production of CO2 via Eqn. (1) results in accumulation of CO2 at the reaction interface. After about 15 min, the reaction rate decreases to the point where CO2 desorption keeps pace with accumulation. Surface concentrations of CO2 suggest that the rate of CO2 production decreases with time, until after 10 hr of reaction, it is undetectable. Reduction of Mn(IV) to Mn(III) suggests that the MnO2-oxalate redox reaction proceeds as a transfer of one electron per metal centre. There is no XPS evidence for reduction of Mn(III) from birnessite to Mn(II) in the presence of oxalate. Although this reaction proceeds in presence of arsenite, it is inhibited by oxalate, probably through formation of a strong Mn(III)-oxalate surface complex (either monodentate or bidentate). This hypothesis is consistent with Mn3+(aq) stabilization by oxalate in aqueous solutions. Further study using X-ray absorption spectroscopy (XAS) is required for a better understanding of the structure of the surface complexes. Rate of release of soluble Mn(II) to dilute oxalate solutions (5 10-4 M) is lower by an order of magnitude than the rate of release to aerated, distilled water at similar pH. Apparently, the process of proton-promoted dissolution of the soluble Mn(II) component of birnessite in distilled water is impeded by the addition of oxalate, probably by formation of a binuclear, bidentate surface complex between Mn(II, III) and adsorbed oxalate ions.

  5. Red facts: Oxalic acid. Fact sheet

    SciTech Connect

    Not Available

    1992-12-01

    All pesticides sold or used in the United States must be registered by EPA, based on scientific studies showing that they can be used without posing unreasonable risks to people or the environment. Because of advances in scientific knowledge, the law requires that pesticides which were first registered years ago be reregistered to ensure that they meet today's more stringent standards. Oxalic acid is registered for use as a disinfectant to control bacteria and germs, and as a sanitizer, in toilet bowls, urinals and bathroom premises. Oxalic acid also has many diverse, non-pesticidal, manufacturing and industrial uses including use in fabric printing and dyeing; bleaching straw hats; removing paint, varnish, rust or ink stains; and cleaning wood.

  6. Modification of cement systems with oxalic aldehyde

    NASA Astrophysics Data System (ADS)

    Subbotina, N. V.; Gorlenko, N. P.; Sarkisov, Ju S.; Naumova, L. B.; Minakova, T. S.

    2015-01-01

    The experimental results of physical-chemical properties of composite materials on the basis of cement and wood waste modified by an aquatic solution of oxalic aldehyde are presented in this paper. The injection of a chemical addition agent being in optimal concentration is shown to result in the increase of compressive strength of a cement stone by 30%, that of wood-cement composition - in 7 times. IR spectroscopy investigations, microphotographs of structures, kinetics of samples strength changes are shown.

  7. Evidence for a role of prolactin in calcium homeostasis: regulation of intestinal transient receptor potential vanilloid type 6, intestinal calcium absorption, and the 25-hydroxyvitamin D(3) 1alpha hydroxylase gene by prolactin.

    PubMed

    Ajibade, Dare V; Dhawan, Puneet; Fechner, Adam J; Meyer, Mark B; Pike, J Wesley; Christakos, Sylvia

    2010-07-01

    Increased calcium transport has been observed in vitamin D-deficient pregnant and lactating rats, indicating that another factor besides 1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is involved in intestinal calcium transport. To investigate prolactin as a hormone involved in calcium homeostasis, vitamin D-deficient male mice were injected with 1,25(OH)(2)D(3), prolactin, or prolactin + 1,25(OH)(2)D(3). Prolactin alone (1 microg/g body weight 48, 24, and 4 h before termination) significantly induced duodenal transient receptor potential vanilloid type 6 (TRPV6) mRNA (4-fold) but caused no change in calbindin-D(9k). Combined treatment with 1,25(OH)(2)D(3) and prolactin resulted in an enhancement of the 1,25(OH)(2)D(3) induction of duodenal TRPV6 mRNA, calbindin-D(9k) mRNA, and an induction of duodenal calcium transport [P < 0.05 compared with 1,25(OH)(2)D(3) alone]. Because lactation is associated with an increase in circulating 1,25(OH)(2)D(3), experiments were done to determine whether prolactin also has a direct effect on induction of 25-hydroxyvitamin D(3) 1alpha hydroxylase [1alpha(OH)ase]. Using AOK B-50 cells cotransfected with the prolactin receptor and the mouse 1alpha(OH)ase promoter -1651/+22 cooperative effects between prolactin and signal transducer and activator of transcription 5 were observed in the regulation of 1alpha(OH)ase. In addition, in prolactin receptor transfected AOK B-50 cells, prolactin treatment (400 ng/ml) and signal transducer and activator of transcription 5 significantly induced 1alpha(OH)ase protein as determined by Western blot analysis. Thus, prolactin, by multiple mechanisms, including regulation of vitamin D metabolism, induction of TRPV6 mRNA, and cooperation with 1,25(OH)(2)D(3) in induction of intestinal calcium transport genes and intestinal calcium transport, can act as an important modulator of vitamin D-regulated calcium homeostasis. PMID:20463051

  8. OXALATE MASS BALANCE DURING CHEMICAL CLEANING IN TANK 6F

    SciTech Connect

    Poirier, M.; Fink, S.

    2011-07-22

    The Savannah River Remediation (SRR) is preparing Tank 6F for closure. The first step in preparing the tank for closure is mechanical sludge removal. Following mechanical sludge removal, SRS performed chemical cleaning with oxalic acid to remove the sludge heel. Personnel are currently assessing the effectiveness of the chemical cleaning to determine whether the tank is ready for closure. SRR personnel collected liquid samples during chemical cleaning and submitted them to Savannah River National Laboratory (SRNL) for analysis. Following chemical cleaning, they collected a solid sample (also known as 'process sample') and submitted it to SRNL for analysis. The authors analyzed these samples to assess the effectiveness of the chemical cleaning process. Analysis of the anions showed the measured oxalate removed from Tank 6F to be approximately 50% of the amount added in the oxalic acid. To close the oxalate mass balance, the author collected solid samples, leached them with nitric acid, and measured the concentration of cations and anions in the leachate. Some conclusions from this work are: (1) Approximately 65% of the oxalate added as oxalic acid was removed with the decanted liquid. (2) Approximately 1% of the oxalate (added to the tank as oxalic acid) formed precipitates with compounds such as nickel, manganese, sodium, and iron (II), and was dissolved with nitric acid. (3) As much as 30% of the oxalate may have decomposed forming carbon dioxide. The balance does not fully account for all the oxalate added. The offset represents the combined uncertainty in the analyses and sampling.

  9. Urinary metabolic phenotyping the slc26a6 (chloride-oxalate exchanger) null mouse model

    PubMed Central

    Garcia-Perez, Isabel; Villaseor, Alma; Wijeyesekera, Anisha; Posma, Joram M.; Stamler, Jeremiah; Aronson, Peter; Unwin, Robert; Barbas, Coral; Elliott, Paul; Nicholson, Jeremy; Holmes, Elaine

    2014-01-01

    The prevalence of renal stone disease is increasing, although it remains higher in men than in women when matched for age. While still somewhat controversial, several studies have reported an association between renal stone disease and hypertension, but this may be confounded by a shared link with obesity. However, independent of obesity, hyperoxaluria has been shown to be associated with hypertension in stone-formers and the most common type of renal stone is composed of calcium oxalate. The chloride-oxalate exchanger slc26a6 (also known as CFEX or PAT-1), located in the renal proximal tubule, was originally thought to have an important role in sodium homeostasis and thereby blood pressure control, but it has recently been shown to have a key function in oxalate balance by mediating oxalate secretion in the gut. We have applied two orthogonal analytical platforms (NMR spectroscopy and capillary-electrophoresis with UV detection) in parallel to characterize the urinary metabolic signatures related to the loss of the renal chloride-oxalate exchanger in slc26a6 null mice. Clear metabolic differentiation between the urinary profiles of the slc26a6 null and the wild type mice were observed using both methods, with the combination of NMR and CE-UV providing extensive coverage of the urinary metabolome. Key discriminating metabolites included oxalate, m-hydroxyphenylpropionylsulfate (m-HPPS), trimethylamine-N-oxide, glycolate and scyllo-inositol (higher in SLC26A6 null mice) and hippurate, taurine, trimethylamine, and citrate (lower in slc26a6 null mice). In addition to the reduced efficiency of anion transport, several of these metabolites (hippurate, m-HPPS, methylamines) reflect alteration in gut microbial co-metabolic activities. Gender-related metabotypes were also observed in both wild type and slc26a6 null groups. Other urinary chemicals that showed a gender-specific pattern included trimethylamine, trimethylamine-N-oxide, citrate, spermidine, guanidinoacetate, and 2-oxoisocaproate. The gender-dependent metabolic expression of the consequences of slc26a6 deletion might have relevance to the difference in prevalence of renal stone formation in men and women. The modification of the microbial metabolites is consistent with the fact that the slc26a6 transporter is found in a range of tissues, including the kidney and intestine, and provides further evidence for the long reach of the microbiota in physiological and pathological processes. PMID:22594923

  10. Generation of enterocyte-like cells from human induced pluripotent stem cells for drug absorption and metabolism studies in human small intestine

    PubMed Central

    Ozawa, Tatsuya; Takayama, Kazuo; Okamoto, Ryota; Negoro, Ryosuke; Sakurai, Fuminori; Tachibana, Masashi; Kawabata, Kenji; Mizuguchi, Hiroyuki

    2015-01-01

    Enterocytes play an important role in drug absorption and metabolism. However, a widely used enterocyte model, Caco-2 cell, has difficulty in evaluating both drug absorption and metabolism because the expression levels of some drug absorption and metabolism-related genes in these cells differ largely from those of human enterocytes. Therefore, we decided to generate the enterocyte-like cells from human induced pluripotent stem (iPS) cells (hiPS-ELCs), which are applicable to drug absorption and metabolism studies. The efficiency of enterocyte differentiation from human iPS cells was significantly improved by using EGF, SB431542, and Wnt3A, and extending the differentiation period. The gene expression levels of cytochrome P450 3A4 (CYP3A4) and peptide transporter 1 in the hiPS-ELCs were higher than those in Caco-2 cells. In addition, CYP3A4 expression in the hiPS-ELCs was induced by treatment with 1, 25-dihydroxyvitamin D3 or rifampicin, which are known to induce CYP3A4 expression, indicating that the hiPS-ELCs have CYP3A4 induction potency. Moreover, the transendothelial electrical resistance (TEER) value of the hiPS-ELC monolayer was approximately 240 Ω*cm2, suggesting that the hiPS-ELC monolayer could form a barrier. In conclusion, we succeeded in establishing an enterocyte model from human iPS cells which have potential to be applied for drug absorption and metabolism studies. PMID:26559489

  11. Formation and structure of copper(II) oxalate layers on carboxy-terminated self-assembled monolayers.

    PubMed

    Schrader, I; Wittig, L; Richter, K; Vieker, H; Beyer, A; Glzhuser, A; Hartwig, A; Swiderek, P

    2014-10-14

    Copper(II) oxalate was grown on carboxy-terminated self-assembled monolayers using a step-by-step approach by dipping the surfaces alternately in ethanolic solutions of copper(II) acetate and oxalic acid with intermediate thorough rinsing steps. The deposition was monitored by reflection absorption infrared spectroscopy (RAIRS), a quartz microbalance with dissipation measurement (QCM-D), scanning electron microscopy (SEM), and helium ion microscopy (HIM). Amounts of material corresponding to a coverage of 75% of a monolayer are deposited in each dipping step in copper(II) acetate solution while deposition of oxalic acid produces a viscoelastic layer that is partially removed by rinsing. This points toward initial aggregation but acid not bound to Cu(2+) ions as oxalate ions is removed by the rinsing steps. RAIRS further indicates that the material grows as copper(II) oxalate ribbons similar to the crystal structure but with ribbons oriented roughly parallel to the surface. SEM and HIM give evidence of the formation of needle-shaped structures which are a possible explanation for the viscoelastic behavior of the layer. PMID:25225717

  12. Thermodynamical and structural study of protactinium(V) oxalate complexes in solution.

    PubMed

    Mendes, Mickaël; Hamadi, Séna; Le Naour, Claire; Roques, Jérôme; Jeanson, Aurélie; Den Auwer, Christophe; Moisy, Philippe; Topin, Sylvain; Aupiais, Jean; Hennig, Christoph; Di Giandomenico, Maria-Vita

    2010-11-01

    The complexation of protactinium(V) by oxalate was studied by X-ray absorption spectroscopy (XAS), density functional theory (DFT) calculations, capillary electrophoresis coupled with inductively coupled plasma mass spectrometry (CE-ICP-MS) and solvent extraction. XAS measurements showed unambiguously the presence of a short single oxo-bond, and the deduced structure agrees with theoretical calculations. CE-ICP-MS results indicated the formation of a highly charged anionic complex. The formation constants of PaO(C(2)O(4))(+), PaO(C(2)O(4))(2)(-), and PaO(C(2)O(4))(3)(3-) were determined from solvent extraction data by using protactinium at tracer scale (C(Pa) < 10(-10) M). Complexation reactions of Pa(V) with oxalate were found to be exothermic with relatively high positive entropic variation. PMID:20883035

  13. Growth Conditions To Reduce Oxalic Acid Content of Spinach

    NASA Technical Reports Server (NTRS)

    Johnson-Rutzke, Corinne

    2003-01-01

    A controlled-environment agricultural (CEA) technique to increase the nutritive value of spinach has been developed. This technique makes it possible to reduce the concentration of oxalic acid in spinach leaves. It is desirable to reduce the oxalic acid content because oxalic acid acts as an anti-nutritive calcium-binding component. More than 30 years ago, an enzyme (an oxidase) that breaks down oxalic acid into CO2 and H2O2 was discovered and found to be naturally present in spinach leaves. However, nitrate, which can also be present because of the use of common nitratebased fertilizers, inactivates the enzyme. In the CEA technique, one cuts off the supply of nitrate and keeps the spinach plants cool while providing sufficient oxygen. This technique provides the precise environment that enables the enzyme to naturally break down oxalate. The result of application of this technique is that the oxalate content is reduced by 2/3 in one week.

  14. Screening of indigenous oxalate degrading lactic acid bacteria from human faeces and South Indian fermented foods: assessment of probiotic potential.

    PubMed

    Gomathi, Sivasamy; Sasikumar, Ponnusamy; Anbazhagan, Kolandaswamy; Sasikumar, Sundaresan; Kavitha, Murugan; Selvi, M S; Selvam, Govindan Sadasivam

    2014-01-01

    Lactic acid bacteria (LAB) have the potential to degrade intestinal oxalate and this is increasingly being studied as a promising probiotic solution to manage kidney stone disease. In this study, oxalate degrading LAB were isolated from human faeces and south Indian fermented foods, subsequently assessed for potential probiotic property in vitro and in vivo. Based on preliminary characteristics, 251 out of 673 bacterial isolates were identified as LAB. A total of 17 strains were found to degrade oxalate significantly between 40.38% and 62.90% and were subjected to acid and bile tolerance test. Among them, nine strains exhibited considerable tolerance up to pH 3.0 and at 0.3% bile. These were identified as Lactobacillus fermentum and Lactobacillus salivarius using 16S rDNA sequencing. Three strains, Lactobacillus fermentum TY5, Lactobacillus fermentum AB1, and Lactobacillus salivarius AB11, exhibited good adhesion to HT-29 cells and strong antimicrobial activity. They also conferred resistance to kanamycin, rifampicin, and ampicillin, but were sensitive to chloramphenicol and erythromycin. The faecal recovery rate of these strains was observed as 15.16% (TY5), 6.71% (AB1), and 9.3% (AB11) which indicates the colonization ability. In conclusion, three efficient oxalate degrading LAB were identified and their safety assessments suggest that they may serve as good probiotic candidates for preventing hyperoxaluria. PMID:24723820

  15. The oxalic acid: 2-chloroacetamide crystallization: A new revelation

    NASA Astrophysics Data System (ADS)

    Chitra, R.; Choudhury, R. R.; Capet, Frederic; Roussel, Pascal

    2013-02-01

    The OH of COOH can acts as both donor and acceptor of hydrogen bond. OH of COOH as an acceptor was primarily observed in Oxalic acid Amide complexes. In order to further understand the packing in these complexes, oxalic acid was complexed with 2-tricholoroacetamide. This crystallization resulted in the formation of ammonium tetraoxalate dehydrate. A result similar to what was observed in complexation of oxalic acid with amide containing amino acids (asparagine and glutamine). Interestingly in all these cases, the amide bond is broken, to form the ammonium ion when trying to complex with oxalic acid.

  16. Electrochemical synthesis and characterization of zinc oxalate nanoparticles

    SciTech Connect

    Shamsipur, Mojtaba; Roushani, Mahmoud; Pourmortazavi, Seied Mahdi

    2013-03-15

    Highlights: ? Synthesis of zinc oxalate nanoparticles via electrolysis of a zinc plate anode in sodium oxalate solutions. ? Design of a Taguchi orthogonal array to identify the optimal experimental conditions. ? Controlling the size and shape of particles via applied voltage and oxalate concentration. ? Characterization of zinc oxalate nanoparticles by SEM, UVvis, FT-IR and TGDTA. - Abstract: A rapid, clean and simple electrodeposition method was designed for the synthesis of zinc oxalate nanoparticles. Zinc oxalate nanoparticles in different size and shapes were electrodeposited by electrolysis of a zinc plate anode in sodium oxalate aqueous solutions. It was found that the size and shape of the product could be tuned by electrolysis voltage, oxalate ion concentration, and stirring rate of electrolyte solution. A Taguchi orthogonal array design was designed to identify the optimal experimental conditions. The morphological characterization of the product was carried out by scanning electron microscopy. UVvis and FT-IR spectroscopies were also used to characterize the electrodeposited nanoparticles. The TGDTA studies of the nanoparticles indicated that the main thermal degradation occurs in two steps over a temperature range of 350430 C. In contrast to the existing methods, the present study describes a process which can be easily scaled up for the production of nano-sized zinc oxalate powder.

  17. Metal Dependence of Oxalate Decarboxylase Activity

    PubMed Central

    Moomaw, Ellen W.; Angerhofer, Alexander; Moussatche, Patricia; Ozarowski, Andrew; Garca-Rubio, Ins; Richards, Nigel G. J.

    2009-01-01

    Bacillus subtilis oxalate decarboxylase (OxDC) catalyzes the conversion of oxalate into CO2 and formate. The enzyme is composed of two cupin domains, each of which contains a Mn(II) ion. Although there is general agreement that Mn(II) in the N-terminal domain mediates OxDC-catalyzed decarboxylation, legitimate questions have been raised concerning the function (if any) of the Mn(II) bound in the C-terminal cupin domain. We have investigated this problem using a series of OxDC mutants in which Mn(II) binding is perturbed by mutagenesis of Glu-101 and Glu-280, which coordinate the metal in the N-terminal and C-terminal domains, respectively. We now demonstrate that decarboxylase activity and total manganese content are sensitive to modifications in either metal-binding glutamate residue. These findings, in combination with EPR measurements, raise the possibility that the C-terminal Mn(II) center can catalyze the decarboxylation reaction. Further support for this conclusion has been provided from a combination of in vivo and in vitro strategies for preparing wild-type OxDC in which Mn(II) is incorporated to a variety of extents. Kinetic characterization of these variants shows that OxDC activity is linearly correlated with manganese content, as might be expected if both sites can catalyze the breakdown of oxalate into formate and CO2. These studies also represent the first unequivocal demonstration that OxDC activity is uniquely mediated by manganese. PMID:19473032

  18. Abortiporus biennis tolerance to insoluble metal oxides: oxalate secretion, oxalate oxidase activity, and mycelial morphology.

    TOXLINE Toxicology Bibliographic Information

    Graz M; Jarosz-Wilko?azka A; Pawlikowska-Pawlega B

    2009-06-01

    The ability of Abortiporus biennis to tolerate and solubilize toxic metal oxides (Cu(2)O, Al(2)O(3), ZnO, CuFe(2)O(4)Zn, CdO, and MnO(2)) incorporated into agar media was investigated and the growth rate, oxalic acid secretion, and mycelial morphology were monitored. Among the tested metal oxides, formation of clear zones underneath the mycelium growing on Cu(2)O- and ZnO-amended plates was observed. ZnO, CdO and Cu(2)O caused the highest rate of fungal growth inhibition. An increased level of oxalic acid concentration was detected as a response of A. biennis to the presence of Cu(2)O, MnO(2), ZnO and CuFe(2)O(4)Zn in growth medium. The oxalate oxidase (OXO) was found to be responsible for oxalic acid degradation in A. biennis cultivated in metal-amended media. An increased level of OXO was observed in media amended with Cu(2)O, ZnO and MnO(2). Confocal microscopy used in this study revealed changes in mycelial morphology which appeared as increased hyphal branching, increased septation and increased spore number.

  19. Reregistration eligibility document (RED): Oxalic acid

    SciTech Connect

    Not Available

    1992-12-01

    EPA is directed by the Federal Insecticide, Fungicide, and Rodenticide Act as amended in 1988 (FIFRA '88) to review all pesticide products containing active ingredients initially registered before November 1, 1984, and to reregister those products that have a substantially complete data base and do not pose unreasonable adverse effects to people or the environment. This pesticide reregistration program is to be completed by the late 1990's. The Reregistration Eligibility Document (or RED) for oxalic acid discusses the scientific data and other information supporting EPA's regulatory conclusion that products containing a pesticide do not pose unreasonable risks when used as directed by Agency-approved labeling, and are eligible for reregistration.

  20. Intestinal hormones and growth factors: Effects on the small intestine

    PubMed Central

    Drozdowski, Laurie; Thomson, Alan BR

    2009-01-01

    There are various hormones and growth factors which may modify the intestinal absorption of nutrients, and which might thereby be useful in a therapeutic setting, such as in persons with short bowel syndrome. In partI, we focus first on insulin-like growth factors, epidermal and transferring growth factors, thyroid hormones and glucocorticosteroids. Part II will detail the effects of glucagon-like peptide (GLP)-2 on intestinal absorption and adaptation, and the potential for an additive effect of GLP2 plus steroids. PMID:19152442

  1. Claudin-related intestinal diseases.

    PubMed

    Barmeyer, Christian; Schulzke, Jrg D; Fromm, Michael

    2015-06-01

    With up to 200 m(2) the human intestine is the organ with the largest absorptive surface of the body. It is lined by a single layer of epithelial cells that separates the host from the environment. The intestinal epithelium provides both, selective absorption of nutrients, ions, and water but also a highly effective barrier function which includes the first line of defense against environmental antigens. The paracellular part of this barrier function is provided by tight junction (TJ) proteins, especially the large family of claudins. Changes in abundance or molecular structure of claudins can generally result in three typical effects, (i) decreased absorptive passage, (ii) increased secretory passage of small solutes and water causing leak flux diarrhea and (iii) increased absorptive passage of macromolecules which may induce inflammatory processes. Several intestinal diseases are associated with such changes that can result in intestinal inflammation and symptoms like weight loss, abdominal pain or diarrhea. This review summarizes our current knowledge on barrier dysfunction and claudin dysregulation in several intestinal diseases gastroenterologists are often faced with, like inflammatory bowel disease, microscopic colitis, celiac disease, irritable bowel syndrome, gallstones and infectious diseases like HIV enteropathy, Campylobacter jejuni and Clostridium perfringens infection. PMID:25999319

  2. 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…

  3. Synthetic Small Intestinal Scaffolds for Improved Studies of Intestinal Differentiation

    PubMed Central

    Costello, Cait M.; Hongpeng, Jia; Shaffiey, Shahab; Yu, Jiajie; Jain, Nina K.; Hackam, David

    2014-01-01

    In vitro intestinal models can provide new insights into small intestinal function, including cellular growth and proliferation mechanisms, drug absorption capabilities, and host-microbial interactions. These models are typically formed with cells cultured on 2D scaffolds or transwell inserts, but it is widely understood that epithelial cells cultured in 3D environments exhibit different phenotypes that are more reflective of native tissue. Our focus was to develop a porous, synthetic 3D tissue scaffold with villous features that could support the culture of epithelial cell types to mimic the natural microenvironment of the small intestine. We demonstrated that our scaffold could support the co-culture of Caco-2 cells with a mucus-producing cell line, HT29-MTX, as well as small intestinal crypts from mice for extended periods. By recreating the surface topography with accurately sized intestinal villi, we enable cellular differentiation along the villous axis in a similar manner to native intestines. In addition, we show that the biochemical microenvironments of the intestine can be further simulated via a combination of apical and basolateral feeding of intestinal cell types cultured on the 3D models. PMID:24390638

  4. Adipose triglyceride lipase is a TG hydrolase of the small intestine and regulates intestinal PPAR? signaling.

    PubMed

    Obrowsky, Sascha; Chandak, Prakash G; Patankar, Jay V; Povoden, Silvia; Schlager, Stefanie; Kershaw, Erin E; Bogner-Strauss, Juliane G; Hoefler, Gerald; Levak-Frank, Sanja; Kratky, Dagmar

    2013-02-01

    Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme mediating triglyceride (TG) hydrolysis. The lack of ATGL results in TG accumulation in multiple tissues, underscoring the critical role of ATGL in maintaining lipid homeostasis. Recent evidence suggests that ATGL affects TG metabolism via activation of peroxisome proliferator-activated receptor ? (PPAR?). To investigate specific effects of intestinal ATGL on lipid metabolism we generated mice lacking ATGL exclusively in the intestine (ATGLiKO). We found decreased TG hydrolase activity and increased intracellular TG content in ATGLiKO small intestines. Intragastric administration of [(3)H]trioleate resulted in the accumulation of radioactive TG in the intestine, whereas absorption into the systemic circulation was unchanged. Intraperitoneally injected [(3)H]oleate also accumulated within TG in ATGLiKO intestines, indicating that ATGL mobilizes fatty acids from the systemic circulation absorbed by the basolateral side from the blood. Down-regulation of PPAR? target genes suggested modulation of cholesterol absorption by intestinal ATGL. Accordingly, ATGL deficiency in the intestine resulted in delayed cholesterol absorption. Importantly, this study provides evidence that ATGL has no impact on intestinal TG absorption but hydrolyzes TGs taken up from the intestinal lumen and systemic circulation. Our data support the role of ATGL in modulating PPAR?-dependent processes also in the small intestine. PMID:23220585

  5. [The quantitative study of inhibitory effect of pentosan polysulfate and chlorophyllin on the experimental calcium oxalate stone].

    PubMed

    Miyazawa, K; Suzuki, K; Tsugawa, R

    1989-06-01

    The purpose of this study is to evaluate the effect of sodium pentosan polysulfate (SPP) and sodium copper chlorophyllin (SCC) on the formation, growth and aggregation of calcium oxalate crystals in vivo, and to measure the number and the volume of crystals formed in the rat kidney, quantitatively, with a Coulter counter TA-II. The deposition of calcium oxalate crystals in the rat kidney was induced by intraperitoneal injection of 2.5 g per Kg of body weight of hydroxy-L-proline and administration of 0.4% ethylene glycol as the drinking fluid ad libitum for 7 days. Daily excretions of urinary oxalate, calcium (ratio to urinary creatinine) and urinary volume were measured. Both kidneys were removed after protocol. The kidneys were homogenized with 0.2 M Tris-buffer (pH 8.0) and subsequently digested in soluene-100. After calcium oxalate crystals were collected, they were suspended in saline saturated with calcium oxalate. The crystal size distribution was measured with a Coulter counter TA-II. In addition, the renal calcium content was measured by atomic absorption spectrometry, and the kidneys were examined by optical microscopy and scanning electron microscopy. The crystals formed in the rats' kidneys were analyzed by infrared spectroscopy. The results were as follows: 1. There was no deposition of crystals in the kidney of the rats which were not treated. There was intratubular deposition of crystals in the kidneys of the rats injected with hydroxy-L-proline and administered 0.4% ethylene glycol. They consisted of calcium oxalate monohydrate. 2. Renal calcium content was significantly higher in the groups with induced crystals than the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2477580

  6. Oxalic acid production and aluminum tolerance in Pseudomonas fluorescens.

    PubMed

    Hamel, R; Levasseur, R; Appanna, V D

    1999-08-30

    13C NMR studies on intact cells from Al-stressed Pseudomonas fluorescens incubated with citric acid or Al-citrate yielded peaks at 158 and 166 ppm that were attributable to free and complexed oxalic acid, respectively. The presence of oxalic acid was further confirmed with the aid of oxalate oxidase. These peaks were not discernable in experiments performed with cells taken from control cultures. Enzymatic analyses of cell fractions showed the highest production of oxalic acid in the inner membrane fraction of Al-stressed cells incubated with glyoxylate. There was an eight-fold increase in the synthesis of oxalic acid in the inner membrane fraction from the Al-stressed cells compared to the control cells. Although oxalic acid production was observed when citrate, Al-citrate and isocitrate were utilized as substrates, the inner membrane fraction did not mediate the formation of oxalic acid from glycine/pyruvate, glycolic acid, oxaloacetate or ascorbate. These data suggest that the increased oxalic acid production in response to Al stress is effected via the oxidation of glyoxylate. PMID:10612061

  7. Characterization of Medicago truncatula reduced calcium oxalate crystal mutant alleles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Calcium oxalate crystal formation is common in plants. Formation of these crystals has been shown to function in plant defense, calcium regulation, and aluminum tolerance. Although calcium oxalate is common and plays important roles in plant development, our understanding of how these crystals form ...

  8. Oxalate Synthesis and Pyrolysis: A Colorful Introduction to Stoichiometry

    ERIC Educational Resources Information Center

    Vannatta, Michael W.; Richards-Babb, Michelle; Sweeney, Robert J.

    2010-01-01

    Metal oxalate synthesis and pyrolysis provides an opportunity for students to (i) learn stoichiometry, (ii) experience the consequences of proper stoichiometric calculations and experimental techniques, and (iii) be introduced to the relevance of chemistry by highlighting oxalates in context, for example, usages and health effects. At our…

  9. Oxalate Synthesis and Pyrolysis: A Colorful Introduction to Stoichiometry

    ERIC Educational Resources Information Center

    Vannatta, Michael W.; Richards-Babb, Michelle; Sweeney, Robert J.

    2010-01-01

    Metal oxalate synthesis and pyrolysis provides an opportunity for students to (i) learn stoichiometry, (ii) experience the consequences of proper stoichiometric calculations and experimental techniques, and (iii) be introduced to the relevance of chemistry by highlighting oxalates in context, for example, usages and health effects. At our

  10. Calcium Oxalate Accumulation in Malpighian Tubules of Silkworm (Bombyx mori)

    NASA Astrophysics Data System (ADS)

    Wyman, Aaron J.; Webb, Mary Alice

    2007-04-01

    Silkworm provides an ideal model system for study of calcium oxalate crystallization in kidney-like organs, called Malpighian tubules. During their growth and development, silkworm larvae accumulate massive amounts of calcium oxalate crystals in their Malpighian tubules with no apparent harm to the organism. This manuscript reports studies of crystal structure in the tubules along with analyses identifying molecular constituents of tubule exudate.

  11. Total and soluble oxalate content of some Indian spices.

    PubMed

    Ghosh Das, Sumana; Savage, G P

    2012-06-01

    Spices, such as cinnamon, cloves, cardamom, garlic, ginger, cumin, coriander and turmeric are used all over the world as flavouring and colouring ingredients in Indian foods. Previous studies have shown that spices contain variable amounts of total oxalates but there are few reports of soluble oxalate contents. In this study, the total, soluble and insoluble oxalate contents of ten different spices commonly used in Indian cuisine were measured. Total oxalate content ranged from 194 (nutmeg) to 4,014 (green cardamom) mg/100 g DM, while the soluble oxalate contents ranged from 41 (nutmeg) to 3,977 (green cardamom) mg/100 g DM. Overall, the percentage of soluble oxalate content of the spices ranged from 4.7 to 99.1% of the total oxalate content which suggests that some spices present no risk to people liable to kidney stone formation, while other spices can supply significant amounts of soluble oxalates and therefore should be used in moderation. PMID:22492273

  12. The adsorption and photodegradation of oxalic acid at the TiO2 surface.

    PubMed

    Mendive, Cecilia B; Blesa, Miguel A; Bahnemann, Detlef

    2007-01-01

    ATR-FTIR measurements in combination with quantum chemical calculations were performed to study chemical reactions taking place at the surface of a thin TiO2 layer immersed in an aqueous oxalic acid solution under UV(A) illumination. It was found that the adsorption of oxalic acid on TiO2 in the dark can be explained in terms of two surface complexes for the anatase phase. Under UV(A) illumination, one of the adsorbed species on the anatase phase preferably undergoes photo-degradation and at the same time more molecules of oxalic acid are adsorbed at the TiO2 surface which is thus enriched in the second complexation mode. The spectral changes observed under UV(A) illumination are explained in the light of different theories: photo-desorption of water molecules as a thermal mechanism induced by the absorption of photons, surface reconstruction, and newly exposed surface area provided by the de-aggregation of the TiO2 particles. PMID:17674840

  13. Effects of hydroxyethyl cellulose and oxalic acid on the properties of cement

    SciTech Connect

    Singh, N.K.; Mishra, P.C.; Singh, V.K.; Narang, K.K

    2003-09-01

    Effects of hydroxyethyl cellulose (HEC), oxalic acid and their binary mixtures {l_brace}1:1, 1:2, 1:3 and 1:4 (by mass){r_brace} on the properties of ordinary Portland cement have been studied using up to 4% admixtures. Variations in setting time, heat of hydration, strength, hardness and fracture toughness have been determined. FT-IR and XRD have been utilized to determine the phase compositions of the material. Corrosion resistance against H{sub 2}SO{sub 4}, HCl and seawater has been studied by determining the loss in mass of cement mortars. It was found that HEC acts as a retarder and oxalic acid as an accelerator. The binary mixture (1:3) has increased the heat of hydration, strength, hardness, fracture toughness and corrosion resistance. Interaction between HEC, oxalic acid and cement hydration products takes place, and new phases are formed in the presence of water, which lead to the formation of stronger bonds and the sealing of the pores in the resulting product causing decreased water absorption as compared to ordinary Portland cement.

  14. Spectra investigation on surface characteristics of graphene oxide nanosheets treated with tartaric, malic and oxalic acids

    NASA Astrophysics Data System (ADS)

    Teng, Xiyao; Yan, Manqing; Bi, Hong

    2014-01-01

    The surface characteristics of graphene oxide nanosheets (GO) treated respectively with tartaric acid, malic acid and oxalic acid, have been investigated by mainly using optical spectroscopic methods including Fourier transform infrared spectroscopy (FT-IR), Ultraviolet-visible (UV-Vis) absorption and Raman spectroscopy. Additionally, the electrochemical property of the products has also been studied. The data revealed that oxygen-containing groups such as sbnd OH, sbnd COOH and sbnd Cdbnd O on the GO surface have been almost removed and thus reduced graphene oxide nanosheets (RGN) were obtained. Interestingly, the number of sp2 domains of RGN increases as treated by tartaric acid < malic acid < oxalic acid whereas the steric hindrance (SH) decreases and the ionization constant (IC) differs among these three acids. Furthermore, the specific capacitances (Cs) of GO have been greatly promoted from 2.4 F g-1 to 100.8, 112.4, and 147 F g-1 after treated with tartaric, malic and oxalic acids, respectively. This finding agrees well with the spectra result of the tendency of surface conjugated degree alteration. We claim that the difference in both SH and IC among these acids is the main reason for the diverse surface characteristics as well as the improved Cs of the RGN.

  15. Inhibition of Pancreatic Lipase and Triacylglycerol Intestinal Absorption by a Pinhão Coat (Araucaria angustifolia) Extract Rich in Condensed Tannin.

    PubMed

    Oliveira, Roselene Ferreira; Gonçalves, Geferson Almeida; Inácio, Fabíola Dorneles; Koehnlein, Eloá Angélica; de Souza, Cristina Giatti Marques; Bracht, Adelar; Peralta, Rosane Marina

    2015-07-01

    The purpose of the present work was to characterize the possible inhibition of pancreatic lipase by a tannin-rich extract obtained from the pinhão (Araucaria angustifolia seed) coat, based on the previous observation that this preparation inhibits α-amylases. Kinetic measurements of pancreatic lipase revealed that the pinhão coat tannin is an effective inhibitor. Inhibition was of the parabolic non-competitive type. The inhibition constants, Ki1 and Ki2, were equal to 332.7 ± 146.1 μg/mL and 321.2 ± 93.0 μg/mL, respectively, corresponding roughly to the inhibitor concentration producing 50% inhibition ([I]50). Consistently, the pinhão coat extract was also effective at diminishing the plasma triglyceride levels in mice after an olive oil load; 50% diminution of the area under the plasma concentration versus the time curve occurred at a dose of 250 mg/kg. This observation is most probably the consequence of an indirect inhibition of triglyceride absorption via inhibition of pancreatic lipase. For the pinhão coat tannin, this is the second report of a biological activity, the first one being a similar inhibition of the absorption of glucose derived from starch as a consequence of an inhibitory action on α-amylases. Taken together, these effects represent a potential anti-obesity action, as suggested for other polyphenol or tannin-rich preparations. PMID:26184295

  16. Characterization of the Intestinal Absorption of Seven Flavonoids from the Flowers of Trollius chinensis Using the Caco-2 Cell Monolayer Model

    PubMed Central

    Zhao, Can; Wu, Xiuwen; Wang, Rufeng; Liu, Chen

    2015-01-01

    The human Caco-2 cell monolayer model was used to investigate the absorption property, mechanism, and structure-property relationship of seven representative flavonoids, namely, orientin, vitexin, 2”-O-β-L-galactopyranosylorientin, 2”-O-β-L-galactopyranosylvitexin, isoswertisin, isoswertiajaponin, and 2”-O-(2”‘-methylbutanoyl)isoswertisin from the flowers of Trollius chinensis. The results showed that these flavonoids were hardly transported through the Caco-2 cell monolayer. The compounds with 7-OCH3 including isoswertisin, isoswertiajaponin and 2”-O-(2”‘-methylbutanoyl)isoswertisin were absorbed in a passive diffusion manner, and their absorbability was increased in the same order as their polarity. The absorption of the remaining compounds with 7-OH including orientin, vitexin, 2”-O-β-L-galactopyranosylorientin, and 2”-O-β-L-galactopyranosylvitexin involved transporter mediated efflux in addition to passive diffusion. Among the four compounds with 7-OH, those with a free hydroxyl group at C-2” such as orientin and vitexin were the substrates of P-glycoprotein (P-gp) and that with a free hydroxyl group at C-2’ such as 2”-O-β-L-galactopyranosylorientin was the substrate of multidrug resistance protein 2 (MRP2). The results of this study also implied that the absorbability of the flavonoids should be taken into account when estimating the effective components of T. chinensis. PMID:25789809

  17. Acute oxalate nephropathy caused by ethylene glycol poisoning

    PubMed Central

    Seo, Jung Woong; Lee, Jong-Ho; Son, In Sung; Kim, Yong Jin; Kim, Do Young; Hwang, Yong; Chung, Hyun Ah; Choi, Hong Seok; Lim, So Dug

    2012-01-01

    Ethylene glycol (EG) is a sweet-tasting, odorless organic solvent found in many agents, such as anti-freeze. EG is composed of four organic acids: glycoaldehyde, glycolic acid, glyoxylic acid and oxalic acid in vivo. These metabolites are cellular toxins that can cause cardio-pulmonary failure, life-threatening metabolic acidosis, central nervous system depression, and kidney injury. Oxalic acid is the end product of EG, which can precipitate to crystals of calcium oxalate monohydrate in the tubular lumen and has been linked to acute kidney injury. We report a case of EG-induced oxalate nephropathy, with the diagnosis confirmed by kidney biopsy, which showed acute tubular injury of the kidneys with extensive intracellular and intraluminal calcium oxalate monohydrate crystal depositions.

  18. GLUCAGON-LIKE PEPTIDE-2 PROTECTS AGAINST TPN-INDUCED INTESTINAL HEXOSE MALABSORPTION IN ENTERALLY RE-FED PIGLETS.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Premature infants receiving chronic total parenteral nutrition (TPN) due to feeding intolerance develop intestinal atrophy and reduced nutrient absorption. Although providing the intestinal trophic hormone glucagon-like peptide 2 (GLP-2) during chronic TPN improves intestinal growth and morphology,...

  19. The Ileal Lipid Binding Protein Is Required for Efficient Absorption and Transport of Bile Acids in the Distal Portion of the Murine Small Intestine

    PubMed Central

    Praslickova, Dana; Torchia, Enrique C.; Sugiyama, Michael G.; Magrane, Elijah J.; Zwicker, Brittnee L.; Kolodzieyski, Lev; Agellon, Luis B.

    2012-01-01

    The ileal lipid binding protein (ilbp) is a cytoplasmic protein that binds bile acids with high affinity. However evidence demonstrating the role of this protein in bile acid transport and homeostasis is missing. We created a mouse strain lacking ilbp (Fabp6?/? mice) and assessed the impact of ilbp deficiency on bile acid homeostasis and transport in vivo. Elimination of ilbp increased fecal bile acid excretion (54.2%, P<0.05) in female but not male Fabp6?/? mice. The activity of cholesterol 7?-hydroxylase (cyp7a1), the rate-controlling enzyme of the classical bile acid biosynthetic pathway, was significantly increased in female (63.5%, P<0.05) but not in male Fabp6?/? mice. The amount of [3H]taurocholic acid (TCA) excreted by 24 h after oral administration was 102% (P<0.025) higher for female Fabp6?/? mice whereas it was 57.3% (P<0.01) lower for male Fabp6?/? mice, compared to wild-type mice. The retained fraction of the [3H]TCA localized in the small and large intestines was increased by 22% (P<0.02) and decreased by 62.7% (P<0.01), respectively, in male Fabp6?/? mice relative wild-type mice, whereas no changes were seen in female Fabp6?/? mice. Mucosal to serosal bile acid transport using everted distal gut sacs was decreased by 74% (P<0.03) in both sexes of Fabp6?/? mice as compared to wild-type mice. The results demonstrate that ilbp is involved in the apical to basolateral transport of bile acids in ileal enterocytes, and is vital for the maintenance of bile acid homeostasis in the enterohepatic circulation (EHC) in mice. PMID:23251388

  20. Reduction of Oxalate Levels in Tomato Fruit and Consequent Metabolic Remodeling Following Overexpression of a Fungal Oxalate Decarboxylase1[W

    PubMed Central

    Chakraborty, Niranjan; Ghosh, Rajgourab; Ghosh, Sudip; Narula, Kanika; Tayal, Rajul; Datta, Asis; Chakraborty, Subhra

    2013-01-01

    The plant metabolite oxalic acid is increasingly recognized as a food toxin with negative effects on human nutrition. Decarboxylative degradation of oxalic acid is catalyzed, in a substrate-specific reaction, by oxalate decarboxylase (OXDC), forming formic acid and carbon dioxide. Attempts to date to reduce oxalic acid levels and to understand the biological significance of OXDC in crop plants have met with little success. To investigate the role of OXDC and the metabolic consequences of oxalate down-regulation in a heterotrophic, oxalic acid-accumulating fruit, we generated transgenic tomato (Solanum lycopersicum) plants expressing an OXDC (FvOXDC) from the fungus Flammulina velutipes specifically in the fruit. These E8.2-OXDC fruit showed up to a 90% reduction in oxalate content, which correlated with concomitant increases in calcium, iron, and citrate. Expression of OXDC affected neither carbon dioxide assimilation rates nor resulted in any detectable morphological differences in the transgenic plants. Comparative proteomic analysis suggested that metabolic remodeling was associated with the decrease in oxalate content in transgenic fruit. Examination of the E8.2-OXDC fruit proteome revealed that OXDC-responsive proteins involved in metabolism and stress responses represented the most substantially up- and down-regulated categories, respectively, in the transgenic fruit, compared with those of wild-type plants. Collectively, our study provides insights into OXDC-regulated metabolic networks and may provide a widely applicable strategy for enhancing crop nutritional value. PMID:23482874

  1. Reduction of oxalate levels in tomato fruit and consequent metabolic remodeling following overexpression of a fungal oxalate decarboxylase.

    PubMed

    Chakraborty, Niranjan; Ghosh, Rajgourab; Ghosh, Sudip; Narula, Kanika; Tayal, Rajul; Datta, Asis; Chakraborty, Subhra

    2013-05-01

    The plant metabolite oxalic acid is increasingly recognized as a food toxin with negative effects on human nutrition. Decarboxylative degradation of oxalic acid is catalyzed, in a substrate-specific reaction, by oxalate decarboxylase (OXDC), forming formic acid and carbon dioxide. Attempts to date to reduce oxalic acid levels and to understand the biological significance of OXDC in crop plants have met with little success. To investigate the role of OXDC and the metabolic consequences of oxalate down-regulation in a heterotrophic, oxalic acid-accumulating fruit, we generated transgenic tomato (Solanum lycopersicum) plants expressing an OXDC (FvOXDC) from the fungus Flammulina velutipes specifically in the fruit. These E8.2-OXDC fruit showed up to a 90% reduction in oxalate content, which correlated with concomitant increases in calcium, iron, and citrate. Expression of OXDC affected neither carbon dioxide assimilation rates nor resulted in any detectable morphological differences in the transgenic plants. Comparative proteomic analysis suggested that metabolic remodeling was associated with the decrease in oxalate content in transgenic fruit. Examination of the E8.2-OXDC fruit proteome revealed that OXDC-responsive proteins involved in metabolism and stress responses represented the most substantially up- and down-regulated categories, respectively, in the transgenic fruit, compared with those of wild-type plants. Collectively, our study provides insights into OXDC-regulated metabolic networks and may provide a widely applicable strategy for enhancing crop nutritional value. PMID:23482874

  2. Intestinal Malrotation

    MedlinePLUS