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Sample records for intestinal oxalate absorption

  1. Fat Malabsorption and Increased Intestinal Oxalate Absorption are Common after Rouxen-Y Gastric Bypass Surgery

    PubMed Central

    Kumar, Rajiv; Lieske, John C.; Collazo-Clavell, Maria L.; Sarr, Michael G.; Olson, Ellen R.; Vrtiska, Terri J.; Bergstralh, Eric J.; Li, Xujian

    2010-01-01

    Background Hyperoxaluria and increased calcium oxalate stone formation occur after Rouxen- Y gastric bypass (RYGB) surgery for morbid obesity. The etiology of this hyperoxaluria is unknown. We hypothesized that after bariatric surgery, intestinal hyperabsorption of oxalate contributes to increases in plasma oxalate and urinary calcium oxalate supersaturation. Methods We prospectively examined oxalate metabolism in 11 morbidly obese subjects prior to and 6 and 12 months after RYGB (n = 9) and biliopancreatic diversion-duodenal switch (n =2). We measured 24 hour urinary supersaturations for calcium oxalate, apatite, brushite, uric acid, and sodium urate, fasting plasma oxalate, 72 hour fecal fat, and increases in urine oxalate following an oral oxalate load. Results Six and 12 months after RYGB surgery, plasma oxalate and urine calcium oxalate supersaturation increased significantly compared to similar measurements obtained prior to surgery (P values all ≤0.02). Fecal fat excretion at 6 and 12 months was increased (P-value, 0.026 and 0.055, 0 vs 6 and 12 months). An increase in urine oxalate excretion after an oral dose of oxalate was observed at 6 and 12 months (P-values ≤0.02 each). Therefore, after bariatric surgery, increases in fecal fat excretion, urinary oxalate excretion after an oral oxalate load, plasma oxalate, and urinary calcium oxalate supersaturation values were observed. Conclusions Enteric hyperoxaluria is often present in patients after the operations of RYGB and BPD-DS that utilize an element of intestinal malabsorption as a mechanism for weight loss. PMID:21295813

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. Origin of Urinary Oxalate

    NASA Astrophysics Data System (ADS)

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

    2007-04-01

    Urinary oxalate is mostly derived from the absorption of ingested oxalate and endogenous synthesis. The breakdown of vitamin C may also contribute small amounts to the urinary oxalate pool. The amount of oxalate absorbed is influenced by the oxalate content of the diet, the concentrations of divalent cations in the gut, the presence of oxalate-degrading organisms, transport characteristics of the intestinal epithelium, and other factors associated with the intestinal environment. Knowledge of pathways associated with endogenous oxalate synthesis is limited. Urinary oxalate excretion can be modified using strategies that limit dietary oxalate absorption and the ingestion of oxalogenic substrates such as hydroxyproline.

  7. 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

  8. 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

  9. Intestinal folate absorption

    PubMed Central

    Strum, Williamson; Nixon, Peter F.; Bertino, Joseph B.; Binder, Henry J.

    1971-01-01

    Intestinal absorption of the monoglutamate form of the principal dietary and circulating folate compound, 5-methyltetrahydrofolic acid (5-MTHF), was studied in the rat utilizing a synthetic highly purified radiolabeled diastereoisomer. Chromatography confirmed that the compound was not altered after transfer from the mucosa to the serosa. Accumulation against a concentration gradient was not observed in duodenal, jejunal, or ileal segments at 5-MTHF concentration from 0.5 to 500 nmoles/liter. Unidirectional transmural flux determination also did not indicate a significant net flux. Mucosal to serosal transfer of 5-MTHF was similar in all segments of the intestine and increased in a linear fashion with increased initial mucosal concentrations. Further, no alteration in 5-MTHF transfer was found when studied in the presence of metabolic inhibitors or folate compounds. These results indicate that 5-MTHF is not absorbed by the rat small intestine by a carrier-mediated system and suggest that 5-MTHF transfer most likely represents diffusion. Images PMID:5564397

  10. The Intestinal Absorption of Folates

    PubMed Central

    Visentin, Michele; Diop-Bove, Ndeye; Zhao, Rongbao; Goldman, I. David

    2014-01-01

    The properties of intestinal folate absorption were documented decades ago. However, it was only recently that the proton-coupled folate transporter (PCFT) was identified and its critical role in folate transport across the apical brush-border membrane of the proximal small intestine established by the loss-of-function mutations identified in the PCFT gene in subjects with hereditary folate malabsorption and, more recently, by the Pcft-null mouse. This article reviews the current understanding of the properties of PCFT-mediated transport and how they differ from those of the reduced folate carrier. Other processes that contribute to the transport of folates across the enterocyte, along with the contribution of the enterohepatic circulation, are considered. Important unresolved issues are addressed, including the mechanism of intestinal folate absorption in the absence of PCFT and regulation of PCFT gene expression. The impact of a variety of ions, organic molecules, and drugs on PCFT-mediated folate transport is described. PMID:24512081

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

    PubMed

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

    2010-12-01

    We examined the effect of a controlled diet and two probiotic preparations on urinary oxalate excretion, a risk factor for calcium oxalate kidney stone formation, in patients with mild hyperoxaluria. Patients were randomized to a placebo, a probiotic, or a synbiotic preparation. This tested whether these probiotic preparations can increase oxalate metabolism in the intestine and/or decrease oxalate absorption from the gut. Patients were maintained on a controlled diet to remove the confounding variable of differing oxalate intake from food. Urinary oxalate excretion and calcium oxalate supersaturation on the controlled diet were significantly lower compared with baseline on a free-choice diet. Neither study preparation reduced urinary oxalate excretion nor calcium oxalate supersaturation. Fecal lactobacilli colony counts increased on both preparations, whereas enterococcal and yeast colony counts were increased on the synbiotic. Total urine volume and the excretion of oxalate and calcium were all strong independent determinants of urinary calcium oxalate supersaturation. Hence, dietary oxalate restriction reduced urinary oxalate excretion, but the tested probiotics did not influence urinary oxalate levels in patients on a restricted oxalate diet. However, this study suggests that dietary oxalate restriction is useful for kidney stone prevention. PMID:20736987

  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)₂D₃] 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)₂D₃ 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. 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

  19. 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

  20. Normal and abnormal intestinal absorption by humans.

    PubMed

    Heizer, W D

    1979-12-01

    Adults eating a Western diet digest and absorb ingested food containing approximately 100 g fat, 350 g carbohydrate, and 75 g protein daily. Normal fat absorption requires adequate gastric, pancreatic, liver-biliary, mucosal, and lymphatic function. Carbohydrate and protein absorption is much less dependent on liver-biliary and lymphatic function. The intestine has a large reserve capacity for digestion and absorption of nutrients which is due to both excess function and to adaptive changes which increase function in one segment of the digestive-absorptive system when it is decreased or lost in another segment. The large reserve capacity explains why most of the prevalent intestinal diseases seldom cause clinically detectable changes in absorption. However, there are more than 30 less-common human diseases which cause malabsorption of one or more nutrients. Those that cause the malabsorption syndrome, i.e., steatorrhea and weight loss, can be conveniently categorized according to the major deficiency leading to the absorptive defect as follows: insufficient pancreatic enzyme activity, insufficient bile acid, disease of the small intestinal wall, multiple defects, mechanism unknown, and drug-induced malabsorption. A few diseases, most of which are congenital, cause malabsorption of only one or a few related nutrients such as lactose malabsorption in lactase deficiency. Most of the tests currently in use for detecting and diagnosing the cause of malabsorption are relatively insensitive and nonspecific. Chemical analysis of the fat in a three-day stool collection remains the single best test for diagnosing the malabsorption syndrome. However, a breath test using Triolein labeled with either the radioactive or stable isotope of carbon may be an important recent advance. Other breath tests are also currently being investigated for quantitating absorption or malabsorption of various substances including bile acids and various sugars. Studies of the function of the intestinal epithelial cells are usually best accomplished using tissue obtained by per oral biopsy. Biopsy specimens are used for many types of study including light and electron microscopic examination, chemical and enzymatic assays, tissue culture, and uptake of various radiolabeled compounds. PMID:540610

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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

  7. [Hydrolysis and absorption of lysozyme in the small intestine].

    PubMed

    Basova, N A; Mikelsone, V Ia; Tarvid, I L; Kushak, R I; Grigor'eva, V

    1992-01-01

    Preparations of chicken small intestine were used in the experiment in vitro simulating processes of membranous digestion (inverted intestinal segments) and absorption (inverted intestinal myasis). It was established that lysozyme was hydrolyzed on the internal mucosa surface regardless of its concentration in the gastro-intestinal tract, and only insignificant quantity of lysozyme (0.027%) penetrates the intestinal wall. The method of lysozyme determination through its action on the cellular wall of Micrococcus lisodeicticus, and highly efficient liquid chromatography were used to study the transport process. The data presented have evidenced that lysozyme is well hydrolyzed under the action of intestinal peptide hydrolyses, and only insignificant amounts of non-splitted lysozyme can penetrate the blood. PMID:1621381

  8. Exploring food effects on indinavir absorption with human intestinal fluids in the mouse intestine.

    PubMed

    Holmstock, Nico; De Bruyn, Tom; Bevernage, Jan; Annaert, Pieter; Mols, Raf; Tack, Jan; Augustijns, Patrick

    2013-04-11

    Food can have a significant impact on the pharmacokinetics of orally administered drugs, as it may affect drug solubility as well as permeability. Since fed state conditions cannot easily be implemented in the presently available permeability tools, including the frequently used Caco-2 system, exploring food effects during drug development can be quite challenging. In this study, we investigated the effect of fasted and fed state conditions on the intestinal absorption of the HIV protease inhibitor indinavir using simulated and human intestinal fluids in the in situ intestinal perfusion technique in mice. Although the solubility of indinavir was 6-fold higher in fed state human intestinal fluids (FeHIF) as compared to fasted state HIF (FaHIF), the intestinal permeation of indinavir was 22-fold lower in FeHIF as compared to FaHIF. Dialysis experiments showed that only a small fraction of indinavir is accessible for absorption in FeHIF due to micellar entrapment, possibly explaining its low intestinal permeation. The presence of ritonavir, a known P-gp inhibitor, increased the intestinal permeation of indinavir by 2-fold in FaHIF, while there was no increase when using FeHIF. These data confirm that drug-food interactions form a complex interplay between solubility and permeability effects. The use of HIF in in situ intestinal perfusions holds great promise for biorelevant absorption evaluation as it allows to directly explore this complex solubility/permeability interplay on drug absorption. PMID:23402972

  9. 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.

  10. The effect of some beverage extracts on intestinal iron absorption.

    PubMed

    el-Shobaki, F A; Saleh, Z A; Saleh, N

    1990-12-01

    The effect of some beverage extracts namely anise, mint, caraway, cumin, tilia, liquorice, karkade and tea, on the absorption of iron was tested in tied-off intestinal segments of rats. The rate of intestinal iron absorption was calculated in terms of an absorption index. The tannin, phytic acid and ascorbic acid contents of these beverages were analysed. The results show that anise, mint, caraway, cumin, tilia, liquorice, arranged in decreasing order of their effect, promoted the absorption of iron. Karkade did not exert an appreciable effect while tea inhibited absorption. The results are discussed in relation to the content of these beverages of tannins, phytic or ascorbic acids. It is recommended to offer these beverages to children and also to adults as a preventive agent to iron deficiency anemia. Also can be used for the preparation of bioavailable medicinal iron. PMID:2080638

  11. 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.

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

    PubMed

    Goncalves, Aurélie; Margier, Marielle; Roi, Stéphanie; 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 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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.

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

    PubMed Central

    2013-01-01

    Background Understanding the quantitative relationship between a drug’s 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 μm. 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

  2. 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

  3. 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

  4. 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

  5. Activation of rat intestinal mucosal mast cells by fat absorption.

    PubMed

    Ji, Yong; Sakata, Yasuhisa; Yang, Qing; Li, Xiaoming; Xu, Min; Yoder, Stephanie; Langhans, Wolfgang; Tso, Patrick

    2012-06-01

    Previous studies have linked certain types of gut mucosal immune cells with fat intake. We determined whether fat absorption activates intestinal mucosal mast cells (MMC), a key component of the gut mucosal immune system. Conscious intestinal lymph fistula rats were used. The mesenteric lymph ducts were cannulated, and the intraduodenal (i.d.) tubes were installed for the infusion of Liposyn II 20% (an intralipid emulsion). Lymphatic concentrations of histamine, rat MMC protease II (RMCPII), a specific marker of rat intestinal MMC degranulation, and prostaglandin D(2) (PGD(2)) were measured by ELISA. Intestinal MMC degranulation was visualized by immunofluorescent microscopy of jejunum sections taken at 1 h after Liposyn II gavage. Intraduodenal bolus infusion of Liposyn II 20% (4.4 kcal/3 ml) induced approximately a onefold increase in lymphatic histamine and PGD(2), ∼20-fold increase in lymphatic RMCPII, but only onefold increase in peripheral serum RMCPII concentrations. Release of RMCPII into lymph increased dose dependently with the amount of lipid fed. In addition, i.d. infusion of long-chain triacylglycerol trilinolein (C18:2 n-6, the major composite in Liposyn II) significantly increased the lymphatic RMCPII concentration, whereas medium-chain triacylglycerol tricaprylin (C8:0) did not alter lymph RMCPII secretion. Immunohistochemistry image revealed the degranulation of MMC into lamina propria after lipid feeding. These novel findings indicate that intestinal MMC are activated and degranulate to release MMC mediators to the circulation during fat absorption. This action of fatty acid is dose and chain length dependent. PMID:22461027

  6. 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

  7. 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 (0.2–2%). Gibbs free energy (ΔGtro) 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 (15 mg/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

  8. [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.

  9. [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

  10. 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

  11. An unusual cause of acute kidney injury due to oxalate nephropathy in systemic scleroderma.

    PubMed

    Mascio, Heather M; Joya, Christie A; Plasse, Richard A; Baker, Thomas P; Flessner, Michael F; Nee, Robert

    2015-08-01

    Oxalate nephropathy is an uncommon cause of acute kidney injury. Far rarer is its association with scleroderma, with only one other published case report in the literature. We report a case of a 75-year-old African-American female with a history of systemic scleroderma manifested by chronic pseudo-obstruction and small intestinal bacterial overgrowth (SIBO) treated with rifaximin, who presented with acute kidney injury with normal blood pressure. A renal biopsy demonstrated extensive acute tubular injury with numerous intratubular birefringent crystals, consistent with oxalate nephropathy. We hypothesize that her recent treatment with rifaximin for SIBO and decreased intestinal transit time in pseudo-obstruction may have significantly increased intestinal oxalate absorption, leading to acute kidney injury. Oxalate nephropathy should be considered in the differential diagnosis of acute kidney injury in scleroderma with normotension, and subsequent evaluation should be focused on bowel function to include alterations in gut flora due to antibiotic administration. PMID:25500295

  12. 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

  13. The mechanism of intestinal absorption of phosphatidylcholine in rats

    PubMed Central

    Parthasarathy, Sampath; Subbaiah, Papasani V.; Ganguly, Jagannath

    1974-01-01

    1. The mechanism of absorption of phosphatidylcholine was studied in rats by injecting into the intestine phosphatidylcholine specifically labelled either in the fatty acid or in the glycerol moiety or with 32P, when considerable amounts of 1-acyl-lysophosphatidylcholine were found in the intestinal lumen. 2-([14C]Acyl)phosphatidylcholine gave markedly more radioactive unesterified fatty acids in the lumen, compared with the 1-([14C]acyl) derivative. Some of the radioactivity from either the fatty acid or the glycerol moiety of the injected phosphatidylcholine appeared in the mucosal triacylglycerols. 2. Injection of 32P-labelled phosphatidylcholine or 32P-labelled lysophosphatidylcholine led to the appearance of radioactive glycerylphosphorylcholine, glycerophosphate and Pi in the mucosa. 3. Rat mucosa was found to contain a highly active glycerylphosphorylcholine diesterase. 4. It was concluded that the dietary phosphatidylcholine is hydrolysed in the intestinal lumen by the pancreatic phospholipase A to 1-acylglycerylphosphorylcholine, which on entering the mucosal cell is partly reacylated to phosphatidylcholine, and the rest is further hydrolysed to glycerylphosphorylcholine, glycerophosphate, glycerol and Pi. The fatty acids and glycerophosphate are then reassembled to give triacylglycerols via the Kennedy (1961) pathway. PMID:4374941

  14. Establishment of novel prediction system of intestinal absorption in humans using human intestinal tissues.

    PubMed

    Miyake, Masateru; Toguchi, Hajime; Nishibayashi, Toru; Higaki, Kazutaka; Sugita, Akira; Koganei, Kazutaka; Kamada, Nobuhiko; Kitazume, Mina T; Hisamatsu, Tadakazu; Sato, Toshiro; Okamoto, Susumu; Kanai, Takanori; Hibi, Toshifumi

    2013-08-01

    The objective of this study was to establish a novel prediction system of drug absorption in humans by utilizing human intestinal tissues. Based on the transport index (TI), a newly defined parameter, calculated by taking account of the change in drug concentrations because of precipitation on the apical side and the amounts accumulated in the tissue and transported to the basal side, the absorbability of drugs in rank order as well as the fraction of dose absorbed (Fa) in humans were estimated. Human intestinal tissues taken from ulcerative colitis or Crohn's disease patients were mounted in a mini-Ussing chamber and transport studies were performed to evaluate the permeation of drugs, including FD-4, a very low permeable marker, atenolol, a low permeable marker, and metoprolol, a high permeable marker. Although apparent permeability coefficients calculated by the conventional equation did not reflect human Fa values for FD-4, atenolol, and metoprolol, TI values were well correlated with Fa values, which are described by 100 · [1 - e (- f · (TI - α)) ]. Based on this equation, Fa values in humans for other test drugs were predicted successfully, indicating that our new system utilizing human intestinal tissues would be valuable for predicting oral drug absorption in humans. PMID:23686795

  15. 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.

  16. 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

  17. 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.

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

    PubMed Central

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

    2012-01-01

    SUMMARY 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 extra-intestinal 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

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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; Fernández-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

  4. Oxalate: Effect on calcium absorbability

    SciTech Connect

    Heaney, R.P.; Weaver, C.M. )

    1989-10-01

    Absorption of calcium from intrinsically labeled Ca oxalate was measured in 18 normal women and compared with absorption of Ca from milk in these same subjects, both when the test substances were ingested in separate meals and when ingested together. Fractional Ca absorption from oxalate averaged 0.100 +/- 0.043 when ingested alone and 0.140 +/- 0.063 when ingested together with milk. Absorption was, as expected, substantially lower than absorption from milk (0.358 +/- 0.113). Nevertheless Ca oxalate absorbability in these women was higher than we had previously found for spinach Ca. When milk and Ca oxalate were ingested together, there was no interference of oxalate in milk Ca absorption and no evidence of tracer exchange between the two labeled Ca species.

  5. 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

  6. In vitro intestinal co-culture cell model to evaluate intestinal absorption of edelfosine lipid nanoparticles.

    PubMed

    Lasa-Saracíbar, Beatriz; Guada, Melissa; Sebastián, Victor; Blanco-Prieto, Maria J

    2014-01-01

    Nanotechnology is providing a new therapeutic paradigm by enhancing drug efficacy and preventing side-effects. Edelfosine is a synthetic ether lipid analogue of platelet activating factor with high antitumor activity. The encapsulation of this potent antitumor drug in lipid nanoparticles increases its oral bioavailability; moreover, it prevents the hemolytic and gastrointestinal side-effects of the free drug. The literature points towards lymphatic absorption of lipid nanoparticles after oral administration, and previous in vitro and in vivo studies stress the protection against toxicity that these nanosystems provide. The present study is intended to assess the permeability of lipid nanoparticles across the intestinal barrier. Caco-2 monoculture and Caco-2/Raji co-culture were used as in vitro models of enterocytes and Microfold cells respectively. Results showed that free drug is internalized and possibly metabolized in enterocytes. These results do not correlate with those observed in vivo when edelfosine-lipid nanoparticles were administered orally in mice, which suggests that the microfold model is not a good model to study the absorption of edelfosine-lipid nanoparticles across the intestinal barrier in vitro. PMID:24678709

  7. Absorption of tetraethylammonium (TEA+) by perfused lobster intestine.

    PubMed

    Piersol, Megan C; Sterling, Kenneth M; Ahearn, Gregory A

    2007-03-01

    The organic cation, tetraethylammonium (TEA(+)), is actively secreted by mammalian nephrons and crustacean urinary bladders by similar processes in both animal groups. These mechanisms consist of a basolateral Organic Cation Transporter (OCT family) that employs the transmembrane electrical potential as a driving force for organic cation uptake from the blood and a brush border secondary active transport process that exchanges luminal protons for TEA(+). The present study examined the nature of (14)C-TEA(+) transport across the perfused intestinal epithelium of the American lobster, Homarus americanus, to ascertain whether the gut complemented the kidneys in the clearance of these organic metabolites from the blood. Unidirectional mucosa to serosa (M to S) (14)C-TEA(+) fluxes in anterior and posterior intestine were hyperbolic functions of luminal [TEA(+)] and significantly (P<0.01) exceeded the respective serosa to mucosa (S to M) fluxes. Luminal quinine (1 mM) significantly (P<0.05) inhibited M to S flux of the organic cation, while serosal addition of the drug had no effect on S to M transfer of TEA(+). Reducing serosal pH from 7.20 to 6.02 significantly (P<0.01) stimulated M to S transfer of 0.1 mM (14)C-TEA(+), but significantly (P<0.05) lowered S to M transfer of the metabolite. Addition of 2.0 mM unlabelled serosal TEA(+) trans-stimulated the M to S flux of 0.1 mM (14)C-TEA and doubled the transfer rate of the organic cation from lumen to blood compared to its transport in the absence of TEA(+) in the bath. Results suggest that this organic cation is absorbed across lobster intestine by the combination of a brush border OCT-1-like transporter coupled with a basolateral H(+)/TEA(+) exchanger. A working model is presented for intestinal organic cation absorption in crustaceans and compared to the secretory transport model for this class of metabolites previously reported for crustacean and mammalian kidneys. PMID:17397071

  8. Intestinal absorption of colostral lymphoid cells in newborn piglets.

    PubMed

    Tuboly, S; Bernáth, S; Glávits, R; Medveczky, I

    1988-12-01

    Intestinal absorption of colostral lymphoid cells was studied in 23 piglets of four sows (sows A, B, C and D). From the colostrum and blood of the sows the lymphoid cells were isolated with Ficoll-Paque and labelled with technetium (Na99mTcO4). In the 7th hour after birth, 5-ml volumes of the cell suspensions were injected, following laparotomy, directly into the stomach (piglets of sow A) or into the jejunum (piglets of sow B), whereas piglets of sows C and D received the suspensions through a naso-oesophageal tube. Cryostat sections of duodenum, jejunum and lymph node samples of piglets killed by bleeding 8 h after the treatment were examined by autoradiography. It was found that lymphoid cells present in the colostrum of a piglet's own mother were absorbed from the digestive tract and, via the lymphatic vessels, were transported to the mesenteric lymph nodes. Electron microscopy revealed that absorption took place intercellularly. Colostral cells of sows other than a piglet's own mother were observed only in the epithelial layer of the mucous membrane. The lymphoid cells isolated from the sows' blood and heat-treated colostral lymphoid cells were not absorbed. The results indicate that in the pig, an animal having an epitheliochorial placenta, the colostral lymphoid cells are absorbed from the digestive tract and, hence, they can confer an active cellular immunity on the newborn piglets. PMID:3238920

  9. [Recent knowledge about intestinal absorption and cleavage of carotenoids].

    PubMed

    Borel, P; Drai, J; Faure, H; Fayol, V; Galabert, C; Laromiguière, M; Le Moël, G

    2005-01-01

    Our knowledge about intestinal absorption and cleavage of carotenoids has rapidly grown during the last years. New facts about carotenoid absorption have emerged while some controversies about cleavage are close to end. The knowledge of the absorption and conversion processes is indispensable to understand and interpret the perturbations that can occur in the metabolism of carotenoids and vitamin A. Recently, it has been shown that the absorption of certain carotenoids is not passive - as believed for a long time - but is a facilitated process that requires, at least for lutein, the class B-type 1 scavenger receptor (SR-B1). Various epidemiological and clinical studies have shown wide variations in carotenoid absorption from one subject to another, such differences are now explained by the structure of the concerned carotenoid, by the nature of the food that is absorbed with the carotenoid, by diverse exogenous factors like the intake of medicines or interfering components, by diet factors, by genetic factors, and by the nutritional status of the subject. Recently, the precise mechanism of beta-carotene cleavage by betabeta-carotene 15,15' monooxygenase (EC 1.14.99.36) - formerly called beta-carotene 15,15' dioxygenase (ex EC 1.13.11.21) - has been discovered, and a second enzyme which cleaves asymmetrically the beta-carotene molecule has been found. beta-carotene 15,15' monooxygenase only acts on the 15,15' bond, thus forming two molecules of retinal from one molecule of beta-carotene by central cleavage. Even though the betabeta-carotene 15,15' monooxygenase is much more active on the beta-carotene molecule, a study has shown that it can act on all carotenoids. Searchers now agree that other enzymes that can catalyse an eccentric cleavage of carotenoids probably exist, but under physiological conditions the betabeta-carotene 15,15' monooxygenase is by far the most active, and it is mainly effective in the small bowel mucosa and in the liver. However the conversion of provitamin A carotenoids into vitamin A is only partial, and requires a satisfactory protein status. PMID:15771974

  10. Effect of intestinal fluid flux on ibuprofen absorption in the rat intestine.

    PubMed

    Lane, Majella E; Levis, Karl A; Corrigan, Owen I

    2006-02-17

    Previously the apparent permeability coefficient (P(app)) of ibuprofen was observed to vary depending on the perfusion medium employed. The present work explores the possible contributions to these differences. Studies were undertaken using an in situ single pass rat gut technique. Lumenal drug concentrations and plasma drug levels were assayed by HPLC. Absorption rate constants (k(0)) were determined from fractions of drug unabsorbed from the intestineat steady state. Plasma data were fitted to a two compartment open model with zero-order input. Significant differences in net fluid flux were observed between the various buffered perfusion media, with fluxes varying from -0.044+/-0.006 ml min(-1) to +0.057+/-0.013 ml min(-1), the lower and negative values occurring for lower pH media and the larger positive values tending to occur with media of higher pH. A linear relationship was found between the P(app) of ibuprofen and net water flux (y=1.13+11.3x; r(2)=0.80). Apparent zero-order rate constants for ibuprofen appearance in plasma correlated well with absorption rate constants estimated from steady state lumenal drug concentration [k(0(gut))]. From the linear relationship between P(app) and fluid flux a normalized P(app) for ibuprofen (i.e. the P(app) in the absence of net fluid flux) of 1.1 x 10(-4)cms(-1) was determined Net lumenal fluid flux is dependent on perfusion medium composition and significantly alters ibuprofen absorption. The differences observed for P(app) were reflected in systemic drug absorption concentrations. The findings of these studies underline the importance of standardizing the osmolarity of experimental media used for the determination of intestinal permeability data. PMID:16376032

  11. 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

  12. Pinoresinol of olive oil decreases vitamin D intestinal absorption.

    PubMed

    Goncalves, Aurélie; Margier, Marielle; Tagliaferri, Camille; Lebecque, Patrice; Georgé, Stéphane; Wittrant, Yohann; Coxam, Véronique; Amiot, Marie-Josèphe; Reboul, Emmanuelle

    2016-09-01

    Enriching oils, such as olive oil, could be one solution to tackle the worldwide epidemic of vitamin D deficiency and to better fit with omega 3 (DHA) recommendations. However, data regarding the interactions occurring at the intestinal level between vitamin D and phenols from olive oil are scarce. We first determined the effect of polyphenols from a virgin olive oil, and a virgin olive oil enriched with DHA, on vitamin D absorption in rats. We then investigated the effects of 3 main olive oil phenols (oleuropein, hydroxytyrosol and pinoresinol) on vitamin D uptake by Caco-2 cells. The presence of polyphenols in the olive oil supplemented with DHA inhibited vitamin D postprandial response in rats (-25%, p<0.05). Similar results were obtained with a mix of the 3 polyphenols delivered to Caco-2 cells. However, this inhibitory effect was due to the presence of pinoresinol only. As the pinoresinol content can highly vary between olive oils, the present results should be taken into account to formulate an appropriate oil product enriched in vitamin D. PMID:27041321

  13. The digestive adaptation of flying vertebrates: High intestinal paracellular absorption compensates for smaller guts

    PubMed Central

    Caviedes-Vidal, Enrique; McWhorter, Todd J.; Lavin, Shana R.; Chediack, Juan G.; Tracy, Christopher R.; Karasov, William H.

    2007-01-01

    Anecdotal evidence suggests that birds have smaller intestines than mammals. In the present analysis, we show that small birds and bats have significantly shorter small intestines and less small intestine nominal (smooth bore tube) surface area than similarly sized nonflying mammals. The corresponding >50% reduction in intestinal volume and hence mass of digesta carried is advantageous because the energetic costs of flight increase with load carried. But, a central dilemma is how birds and bats satisfy relatively high energy needs with less absorptive surface area. Here, we further show that an enhanced paracellular pathway for intestinal absorption of water-soluble nutrients such as glucose and amino acids may compensate for reduced small intestines in volant vertebrates. The evidence is that l-rhamnose and other similarly sized, metabolically inert, nonactively transported monosaccharides are absorbed significantly more in small birds and bats than in nonflying mammals. To broaden our comparison and test the veracity of our finding we surveyed the literature for other similar studies of paracellular absorption. The patterns found in our focal species held up when we included other species surveyed in our analysis. Significantly greater amplification of digestive surface area by villi in small birds, also uncovered by our analysis, may provide one mechanistic explanation for the observation of higher paracellular absorption relative to nonflying mammals. It appears that reduced intestinal size and relatively enhanced intestinal paracellular absorption can be added to the suite of adaptations that have evolved in actively flying vertebrates. PMID:18025481

  14. 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)

  15. Indirect evidence for cholinergic inhibition of intestinal bicarbonate absorption in humans

    PubMed Central

    Mellander, A; Sjovall, H

    1999-01-01

    BACKGROUND—The aim of the study was to test the hypothesis that in the fasting state, proximal intestinal HCO3 absorption, which depends on villus Na+/H+ exchanger activity, is tonically inhibited by a cholinergic atropine sensitive mechanism. 
SUBJECTS—The experiments were performed in 34 healthy volunteers and in eight patients with intestinal villus atrophy. 
METHODS—HCO3 absorption was measured with a modified triple lumen perfusion technique in the distal duodenum, the most proximal portion of the small intestine. The study was designed to compensate for the inhibitory effects of atropine on intestinal motor activity. 
RESULTS—Atropine had three effects on HCO3 transport: it reduced HCO3 concentration at the proximal aspiration site, it displaced the relation between HCO3 concentration and HCO3 absorption to the left, and it induced a significant acidification of the perfusate at the distal aspiration site. The magnitude of the stimulatory effect on HCO3 absorption was similar to the difference between patients with intestinal villus atrophy and healthy controls. 
CONCLUSION—The data suggest that, in the fasting state, duodenal HCO3 absorption, which depends on villus Na+/H+ exchanger activity, may be tonically inhibited by an atropine sensitive cholinergic mechanism. 

 Keywords: small intestine; absorption; cholinergic; muscarinic receptor; villus atrophy; coeliac disease PMID:10026320

  16. 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

  17. 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

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

    PubMed

    Sjögren, Erik; Dahlgren, David; Roos, Carl; Lennernäs, 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

  19. Reduction in intestinal cholesterol absorption by various food components: mechanisms and implications.

    PubMed

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

    2010-06-01

    A number of different food components are known to reduce plasma and LDL-cholesterol levels by affecting intestinal cholesterol absorption. They include: soluble fibers, phytosterols, saponins, phospholipids, soy protein and stearic acid. These compounds inhibit cholesterol absorption by affecting cholesterol solubilization in the intestinal lumen, interfering with diffusion of luminal cholesterol to the gut epithelium and/or inhibiting molecular mechanisms responsible for cholesterol uptake by the enterocyte. Cholesterol content of intestinal chylomicrons is subsequently reduced, less cholesterol is transported to the liver within chylomicron remnants, hepatic LDL-receptor activity is increased and plasma levels of LDL-cholesterol are decreased. Reduced hepatic VLDL production and less conversion of VLDL to LDL also contribute to lower LDL levels. Certain food components may also affect intestinal bile acid metabolism. Further investigation of the way in which these functional ingredients affect intestinal lipid metabolism will facilitate their use and application as cardiovascular nutraceuticals. PMID:20439167

  20. Effect of Lactobacillus casei on the absorption of nifedipine from rat small intestine.

    PubMed

    Kato, Ryuji; Yuasa, Hiroaki; Inoue, Katsuhisa; Iwao, Takahiro; Tanaka, Kazuhiko; Ooi, Kazuya; Hayashi, Yayoi

    2007-04-01

    Lactobacillus casei Shirota strain (L. casei) has a modulating effect on the production of cytokines, which often play important roles in drug metabolism, in the inflamed intestinal mucosa. We evaluated the effect of L. casei administered orally in advance for 4 weeks on the absorption of nifedipine from the rat small intestine. The maximum concentration of nifedipine in plasma after administration into the intestinal loop (0.8 mg/kg) was significantly higher in L. casei-treated rats (3.26 microg/mL) than in those untreated rats (2.33 microg/mL) by 40%. Accordingly, the bioavailability of nifedipine was tended to be higher in the former, while the effect of L. casei on the disposition of intravenously administered nifedipine was negligible. We also found that the availability of nifedipine for the passage through the intestinal mucosa was significantly increased in L. casei-treated rats from the single-pass intestinal perfusion experiments. Therefore, it is likely that the exposure to nifedipine after its administration into rat intestine was increased by oral ingestion of L. casei due to an increase in absorption by increased intestinal availability (decreased metabolic extraction) during passage through the intestinal mucosa. This study has suggested that L. casei has some effect on the metabolic activity in the intestinal mucosa, though it seems to be only mild. PMID:17495416

  1. Acute oxalate nephropathy associated with orlistat

    PubMed Central

    Humayun, Youshay; Ball, Kenneth C.; Lewin, Jack R.; Lerant, Anna A.; Fülöp, Tibor

    2016-01-01

    Background: Obesity is a major world-wide epidemic which has led to a surge of various weight loss-inducing medical or surgical treatments. Orlistat is a gastrointestinal lipase inhibitor used as an adjunct treatment of obesity and type 2 diabetes mellitus to induce clinically significant weight loss via fat malabsorption. Case Presentation: We describe a case of a 76-year-old female with past medical history of chronic kidney disease (baseline serum creatinine was 1.5-2.5 mg/dL), hypertension, gout and psoriatic arthritis, who was admitted for evaluation of elevated creatinine, peaking at 5.40 mg/dL. She was started on orlistat 120 mg three times a day six weeks earlier. Initial serologic work-up remained unremarkable. Percutaneous kidney biopsy revealed massive calcium oxalate crystal depositions with acute tubular necrosis and interstitial inflammation. Serum oxalate level returned elevated at 45 mm/l (normal <27). Timed 24-hour urine collection documented increased oxalate excretion repeatedly (54-96 mg/24 hour). After five renal dialysis sessions in eighth days she gradually regained her former baseline kidney function with creatinine around 2 mg/dL. Given coexisting proton-pump inhibitor therapy, only per os calcium-citrate provided effective intestinal oxalate chelation to control hyperoxaluria. Conclusions: Our case underscores the potential of medically induced fat malabsorption to lead to an excessive oxalate absorption and acute kidney injury (AKI), especially in subjects with pre-existing renal impairment. Further, it emphasizes the importance of kidney biopsy to facilitate early diagnosis and treatment. PMID:27152294

  2. 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

  3. Increased proliferative response of lymphocytes from intestinal lymph during long chain fatty acid absorption.

    PubMed Central

    Miura, S; Imaeda, H; Shiozaki, H; Ohkubo, N; Tashiro, H; Serizawa, H; Tsuchiya, M; Tso, P

    1993-01-01

    The effect of long chain and medium chain fatty acid absorption on transport and mitogen-induced blast transformation of lymphocytes in intestinal lymphatics was investigated. Intestinal lymph was collected from mesenteric lymph duct cannulated rats maintained in Bollman's cage. Following the intraduodenal administration of oleic acid (long chain fatty acid) or octanoic acid (medium chain fatty acid), only oleic acid produced a significant increase in lymphocyte flux and enhanced proliferative response of lymphocyte in intestinal lymph, without significant alteration of lymphocyte subsets. These changes appeared to be closely correlated with the appearance of radiolabelled oleic acid. Absorption of a medium chain fatty acid, octanoic acid, most of which appeared to be transported to portal blood, did not produce a significant elevation of lymphocyte flux or increased proliferative response of lymphocyte in intestinal lymph. Pluronic L-81, which is a potent inhibitor of the intracellular formation and secretion of chylomicron, significantly attenuated the increased lymphocyte flux and suppressed the enhancement of lymphocyte responsiveness to PHA in intestinal lymph after stimulation by oleic acid administration. There is a possibility that lymphocyte transport and proliferative response in intestinal lymph during oleic acid absorption are closely related to the process of chylomicron formation and secretion to lymphatics in the intestinal mucosa. PMID:8436400

  4. 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

  5. Conditional Gata4 deletion in mice induces bile acid absorption in the proximal small intestine

    PubMed Central

    Beuling, Eva; Kerkhof, Ilona M; Nicksa, Grace A; Giuffrida, Michael J; Haywood, Jamie; de Kerk, Daniel J aan; Piaseckyj, Christina M; Pu, William T; Buchmiller, Terry L; Dawson, Paul A; Krasinski, Stephen D

    2010-01-01

    Background and aims The transcription factor GATA4 is expressed throughout most of the small intestine except distal ileum, and restricts expression of the apical sodium-dependent bile acid transporter (ASBT), the rate-limiting intestinal bile acid transporter, to distal ileum. The hypothesis was tested that reduction of GATA4 activity in mouse small intestine results in an induction of bile acid transport in proximal small intestine sufficient to restore bile acid absorption and homeostasis after ileocaecal resection (ICR). Methods Bile acid homeostasis was characterised in non-surgical, sham or ICR mice using two recombinant Gata4 models in which Asbt expression is induced to different levels. Results Reduction of intestinal GATA4 activity resulted in an induction of ASBT expression, bile acid absorption and expression of bile acid-responsive genes in proximal small intestine, and a reduction of luminal bile acids in distal small intestine. While faecal bile acid excretion and bile acid pool size remained unchanged, the bile acid pool became more hydrophilic due to a relative increase in tauro-β-muricholate absorption. Furthermore, proximal induction of Asbt in both Gata4 mutant models corrected ICR-associated bile acid malabsorption, reversing the decrease in bile acid pool size and increase in faecal bile acid excretion and hepatic cholesterol 7α-hydroxylase expression. Conclusions Reduction of intestinal GATA4 activity induces bile acid absorption in proximal small intestine without inducing major changes in bile acid homeostasis. This induction is sufficient to correct bile acid malabsorption caused by ICR in mice. PMID:20581237

  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. Effects of DFA IV in rats: calcium absorption and metabolism of DFA IV by intestinal microorganisms.

    PubMed

    Saito, K; Hira, T; Suzuki, T; Hara, H; Yokota, A; Tomita, F

    1999-04-01

    Di-D-fructose-2,6':6,2'-dianhydride (DFA IV) is a disaccharide consisting of two fructose residues that can be prepared from levan by levan fructotransferase from Arthrobacter nicotinovorans GS-9, and it can be expected to have novel physiological functions from its unique structure. In this study, the effects of DFA IV on calcium absorption and the metabolism of DFA IV by intestinal microorganisms were studied in rats to examine the physiological functions of DFA IV. The apparent calcium absorption in rats fed with DFA IV was significantly higher than that in the control rats, and it seems that calcium absorption had almost been completed at the end of the small intestine. DFA IV also increased the calcium absorption in in vitro experiments, using everted jejunal and ileal sacs, and this result supports the finding obtained in the in vivo experiments. These results indicate that DFA IV may have a function for increasing the calcium absorption in the small intestine of rats. However, the effect in the large intestine could not be clearly observed because of the lack of calcium that reached there. The results of analyses of organic acids in the cecal and colonic contents and of DFA IV in the fecal, cecal, and colonic contents showed that the metabolism of DFA IV by microorganisms in the large intestine progressed gradually, and that DFA IV was converted mainly to acetate, butyrate, and lactate. PMID:10361678

  8. Effects of DFA IV in rats: calcium absorption and metabolism of DFA IV by intestinal microorganisms.

    TOXLINE Toxicology Bibliographic Information

    Saito K; Hira T; Suzuki T; Hara H; Yokota A; Tomita F

    1999-04-01

    Di-D-fructose-2,6':6,2'-dianhydride (DFA IV) is a disaccharide consisting of two fructose residues that can be prepared from levan by levan fructotransferase from Arthrobacter nicotinovorans GS-9, and it can be expected to have novel physiological functions from its unique structure. In this study, the effects of DFA IV on calcium absorption and the metabolism of DFA IV by intestinal microorganisms were studied in rats to examine the physiological functions of DFA IV. The apparent calcium absorption in rats fed with DFA IV was significantly higher than that in the control rats, and it seems that calcium absorption had almost been completed at the end of the small intestine. DFA IV also increased the calcium absorption in in vitro experiments, using everted jejunal and ileal sacs, and this result supports the finding obtained in the in vivo experiments. These results indicate that DFA IV may have a function for increasing the calcium absorption in the small intestine of rats. However, the effect in the large intestine could not be clearly observed because of the lack of calcium that reached there. The results of analyses of organic acids in the cecal and colonic contents and of DFA IV in the fecal, cecal, and colonic contents showed that the metabolism of DFA IV by microorganisms in the large intestine progressed gradually, and that DFA IV was converted mainly to acetate, butyrate, and lactate.

  9. Effects of difructose anhydride III on calcium absorption in small and large intestines of rats.

    PubMed

    Suzuki, T; Hara, H; Kasai, T; Tomita, F

    1998-05-01

    Difructose anhydride III (DFA III; di-D-fructo-furanose 1,2':2,3' dianhydride) was prepared from inulin with Arthrobacter sp. H65-7 inulin fructotransferase (depolymerizing (inulase II; EC 2.4.1.93). DFA III is not hydrolyzed by enzymes in the small intestine, but is metabolized by microorganisms in the large intestine. We investigated the effects of DFA III on calcium absorption in two experiments. In the in vivo experiment, we examined the effects of DFA III, fructooligosaccharides, and raffinose on calcium absorption in male Sprague-Dawley rats 5 weeks old at start of the experiment and given feed containing 3% of one of these oligosaccharides for two weeks. The apparent calcium absorption was significantly higher in rats fed any of these oligosaccharides than in control rats, and the increase with DFA III was the greatest. Absorption in both the small and large intestines was affected. In rats fed DFA III, the cecal wall thickened and soluble calcium and the amounts of some organic acids were higher than in the control groups. In an in vitro experiment with everted jejunal and ileal sacs of rats, calcium absorption was higher when DFA III was present in the mucosal fluid at all concentrations tested (up to 200 mM). In the jejunal sacs, the increase in calcium absorption depended on the DFA III concentration. In the ileal sacs, the absorption was maximum at 50 mM DFA III and did not increase further at higher concentrations. These results indicate that intact DFA III stimulates calcium absorption in the small intestine, and that cecal fermentation of DFA III may contribute to the increase in calcium absorption by the large intestine. PMID:9648212

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. Intestinal absorptive surface in mammals of different sizes.

    PubMed

    Snipes, R L

    1997-01-01

    The present treatise is primarily concerned with the structural and morphometric parameters of the cecum and large intestine of mammals. Over the past century, numerous accounts have visually presented the variation and diversity of the large intestine of mammals. This includes above all comprehensive works on the macroscopic anatomy. More recently, the microscopic anatomy of various animals at the light, electron, and scanning electron microscopy levels has been covered, especially for rodents and primates. In the past two decades, progress has been made by adding a new dimension to the previous structural studies, namely, the morphometrical analysis of the intestine of various animals and subsequent employment of this data in an analysis based on principles of scaling. The present account follows essentially this outline, but presented in a slightly different order. First, in the introductory section, the scientific aims and general prologue to this field of study are presented. Included in this section is a short, concise literature survey that deals with the major literature available on the subject of the large intestine at the macroscopical and microscopical level, as well as the most recent morphometric analyses of the intestines. The main focus of the present work is on the methodological; a new method is described to measure the intestines of animals ranging in size from the harvest mouse to the horse. This technique may also be applicable to other hollow or tube-like organs. Heretofore, previous techniques have been based on obtaining the area of the surface mucosa by measuring lengths and widths and calculating the area by multiplying the two measurements. Alternatively, some methods have taken probes and made measurements at the light microscopy level and then extrapolated these results to determine the entire area. The former method is inadequate, while the latter possesses the inherent disadvantages of all sampling techniques. The present technique has two levels: (1) obtaining the basal surface area of the entire intestine and (2) accounting for any increase in the mucosal surface area that is due to microscopically visible folds, villi, or other such structures. The former is accomplished by flattening appropriately sized pieces of intestine between two glass plates and tracing the contours onto transparent paper. The entire intestine is processed in this manner, resulting in a basal surface area, the contours having been submitted to analysis on a semi-automatic image analyzer to determine the area in square millimeters. The second-level measurements determine a factor of surface enlargement by calculating a ratio of the distance along the surface contour of the mucosa on a histological section cut perpendicular to the width of the intestine to a second distance (reference line) drawn straight beneath the mucosa but not tracing the enlargements. The measurements obtained at both levels are multiplied to give a final surface area. In addition to a detailed description of the technique complete with a flow sheet and pictorial diagram, the various aspects of proper fixation, tissue embedding, shrinkage, and determination of sampling sites (for the second level of measurement) are discussed. A pilot experiment to determine the surface enlargement due to microvilli is presented from material taken from the giant pouched rat. This was performed by measuring video sequences of microvilli taken from electron microscopy images. Cecal microvilli increase the surface area 15-fold, while in the colon the increase is approximately 19- to 20-fold. In the discussion, the choice of using three animals per group is discussed, based on simple statistical tests. Section 3 is entitled "Morphology of the Mammalian Cecum." Chronologically, it marks the onset of the entire investigation. Before having developed the method described in Sect. 2, these morphological investigations at the light, electron and scanning electron microscopy PMID:9308197

  16. 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

  17. 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

  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 situ absorption in rat intestinal tract of solid dispersion of annonaceous acetogenins.

    PubMed

    Dang, Yun-Jie; Feng, Han-Zhou; Zhang, Limei; Hu, Chun-Hui; Zhu, Chun-Yan

    2012-01-01

    Isolated from Annona squamosa L, Annonaceous acetogenins (ACGs) exhibit a broad range of biological properties yet absorbed badly due to the low solubility. Solid dispersion in polyethylene glycol 4000 (PEG 4000) has been developed to increase the solubility and oral absorption of ACGs. The formulation of ACGS-solid dispersion was optimized by a simplex lattice experiment design and carried out by a solvent-fusion method. We studied the absorption property of ACGs in rat's intestine, which showed there was a good absorption and uptake percentages with solid dispersion. The study on uptake percentage in different regions of rat's intestine attested that the duodenum had the best permeability, followed by jejunum, ileum, and colon in order with no significant differences. So the paper drew the conclusion that solid dispersion could improve the solubility and oral absorption of annonaceous acetogenins. PMID:22536222

  1. In Situ Absorption in Rat Intestinal Tract of Solid Dispersion of Annonaceous Acetogenins

    PubMed Central

    Dang, Yun-Jie; Feng, Han-Zhou; Zhang, Limei; Hu, Chun-Hui; Zhu, Chun-Yan

    2012-01-01

    Isolated from Annona squamosa L, Annonaceous acetogenins (ACGs) exhibit a broad range of biological properties yet absorbed badly due to the low solubility. Solid dispersion in polyethylene glycol 4000 (PEG 4000) has been developed to increase the solubility and oral absorption of ACGs. The formulation of ACGS-solid dispersion was optimized by a simplex lattice experiment design and carried out by a solvent-fusion method. We studied the absorption property of ACGs in rat's intestine, which showed there was a good absorption and uptake percentages with solid dispersion. The study on uptake percentage in different regions of rat's intestine attested that the duodenum had the best permeability, followed by jejunum, ileum, and colon in order with no significant differences. So the paper drew the conclusion that solid dispersion could improve the solubility and oral absorption of annonaceous acetogenins. PMID:22536222

  2. 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 NKCC2β and AQP1 genes whose expression was markedly upregulated after seawater acclimation. The SLC26A6 (anion exchanger) and NCCβ genes were also expressed in small amounts. Consistent with the inhibitors' effect, expression of NKCC2β was MI > PI, and that of NCCβ was MI < PI. The present study showed that GN not only inhibits the bumetanide-sensitive Na(+)-K(+)-Cl(-) transport system governed by NKCC2β, 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

  3. 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

  4. Heme in intestinal epithelial cell turnover, differentiation, detoxification, inflammation, carcinogenesis, absorption and motility

    PubMed Central

    Oates, Phillip S; West, Adrian R

    2006-01-01

    The gastrointestinal tract is lined by a simple epithelium that undergoes constant renewal involving cell division, differentiation and cell death. In addition, the epithelial lining separates the hostile processes of digestion and absorption that occur in the intestinal lumen from the aseptic environment of the internal milieu by defensive mechanisms that protect the epithelium from being breached. Central to these defensive processes is the synthesis of heme and its catabolism by heme oxygenase (HO). Dietary heme is also an important source of iron for the body which is taken up intact by the enterocyte. This review describes the recent literature on the diverse properties of heme/HO in the intestine tract. The roles of heme/HO in the regulation of the cell cycle/apoptosis, detoxification of xenobiotics, oxidative stress, inflammation, development of colon cancer, heme-iron absorption and intestinal motility are specifically examined. PMID:16865768

  5. 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

  6. Effect of abdominal surgery on the intestinal absorption of lipophilic drugs: possible role of the lymphatic transport.

    PubMed

    Gershkovich, Pavel; Itin, Constantin; Yacovan, Avihai; Amselem, Shimon; Hoffman, Amnon

    2009-06-01

    Although abdominal surgery is a routine procedure in clinical practice and in preclinical investigation, little is known regarding its effect on the intestinal absorption of drugs. The aim of this study was to investigate the effect of abdominal surgery on the intestinal absorption of highly lipophilic compounds with different absorption mechanisms following oral administration. The 2 compounds that were tested were biopharmaceutical classification system (BCS) class 2 model lipophilic cannabinoid derivatives, dexanabinol and PRS-211,220. Although dexanabinol is mostly absorbed via passive diffusion to the portal blood, PRS-211,220 is absorbed mostly via lymphatic transport. In this work, we compared the absorption of these compounds after abdominal surgery in rat with the absorption data obtained from naïve animals. The outcomes of this investigation showed that the abdominal surgery mostly affected the absorption process on the preenterocyte level, as indicated by the 2-fold increase in the extent of intestinal absorption of dexanabinol, which is a compound with a low degree of intestinal lymphatic transport. However, the lymphatic transport was not affected by the surgical procedure as evident by the absence of change in the extent of absorption of PRS-211,220, which is transported to the systemic circulation mainly by intestinal lymphatics. In conclusion, abdominal surgery can significantly affect the intestinal absorption of lipophilic drugs; however, intestinal lymphatic transport seems to be less affected by the abdominal surgery. PMID:19446284

  7. 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

  8. 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

  9. 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

  10. 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

  11. Amino acid modulation of in vivo intestinal zinc absorption in freshwater rainbow trout.

    PubMed

    Glover, Chris N; Hogstrand, Christer

    2002-01-01

    The composition of the intestinal lumen is likely to have considerable influence upon the absorption, and consequently the nutrition and/or toxicity, of ingested zinc in aquatic environments, where zinc is both a nutrient and a toxicant of importance. The effects of amino acids upon intestinal zinc uptake in freshwater rainbow trout (Oncorhynchus mykiss) were studied using an in vivo perfusion technique. The presence of histidine, cysteine and taurine had distinct modifying actions upon quantitative and qualitative zinc absorption, compared to perfusion of zinc alone. Alterations in zinc transport were not correlated with changes in levels of free zinc ion. The chemical nature of the zinc-amino acid chelate, rather than the chelation itself, appeared to have the most important influence upon zinc absorption. L-histidine, despite a strong zinc-chelating effect, maintained quantitative zinc uptake at control (zinc alone) levels. This effect correlated with the formation of Zn(His)(2) species. D-histidine at a luminal concentration of 100 mmol l(-1) significantly enhanced subepithelial zinc accumulation, but reduced the fraction of zinc that was retained and absorbed by the fish. The possibility of a Zn(His)(2)-mediated pathway for intestinal uptake is discussed. L-cysteine specifically stimulated the accumulation of zinc post-intestinally, an effect attributed to enhanced zinc accumulation in the blood. Taurine increased subepithelial zinc accumulation, but decreased the passage of zinc to post-intestinal compartments. Amino acids are proposed to have important roles in modifying intestinal zinc uptake with potential implications for environmental toxicity as well as aquaculture. PMID:11818421

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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.

  18. Electrical charge on protein regulates its absorption from the rat small intestine.

    PubMed

    Nishikawa, Makiya; Hasegawa, Susumu; Yamashita, Fumiyoshi; Takakura, Yoshinobu; Hashida, Mitsuru

    2002-04-01

    The effect of the electrical charge on the intestinal absorption of a protein was studied in normal adult rats. Chicken egg lysozyme (Lyz), a basic protein with a molecular weight of 14,300, was selected and several techniques for chemical modification were applied. Then the intestinal absorption of Lyz derivatives was evaluated by measuring the radioactivity in plasma and tissues, after the administration of an (111)In-labeled derivative to an in situ closed loop of the jejunum. After the administration of (111)In-Lyz, the level of radioactivity in plasma was comparable with the lytic activity of Lyz, supporting the fact that the radioactivity represents intact Lyz. (111)In-cationized Lyz showed a 2-3 times higher level of radioactivity in plasma, whereas the radioactivity of (111)In-anionized Lyz was much lower. The absorption rate of (111)In-Lyz derivatives calculated by a deconvolution method was correlated for the strength of their positive net charge. A similar relationship was observed using superoxide dismutase. These findings indicate that the intestinal absorption of a protein is, at least partially, determined by its electrical charge. PMID:11897631

  19. 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

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

    PubMed Central

    Li, Xingsheng; Ellis, Melissa L.

    2015-01-01

    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

  1. 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

  2. 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.

  3. 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

  4. 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 (μmol/(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 (μmol/(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

  5. 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.

  6. 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.

  7. Effects of a single dose of menadione on the intestinal calcium absorption and associated variables.

    PubMed

    Marchionatti, Ana M; Díaz de Barboza, Gabriela E; Centeno, Viviana A; Alisio, Arturo E; Tolosa de Talamoni, Nori G

    2003-08-01

    The effect of a single large dose of menadione on intestinal calcium absorption and associated variables was investigated in chicks fed a normal diet. The data show that 2.5 micro mol of menadione/kg of b.w. causes inhibition of calcium transfer from lumen-to-blood within 30 min. This effect seems to be related to oxidative stress provoked by menadione as judged by glutathione depletion and an increment in the total carbonyl group content produced at the same time. Two enzymes presumably involved in calcium transcellular movement, such as alkaline phosphatase, located in the brush border membrane, and Ca(2+)- pump ATPase, which sits in the basolateral membrane, were also inhibited. The enzyme inhibition could be due to alterations caused by the appearance of free hydroxyl groups, which are triggered by glutathione depletion. Addition of glutathione monoester to the duodenal loop caused reversion of the menadione effect on both intestinal calcium absorption and alkaline phosphatase activity. In conclusion, menadione shifts the balance of oxidative and reductive processes in the enterocyte towards oxidation causing deleterious effects on intestinal Ca(2+) absorption and associated variables, which could be prevented by administration of oral glutathione monoester. PMID:12948877

  8. 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

  9. 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.

  10. 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

  11. 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

  12. Melatonin not only restores but also prevents the inhibition of the intestinal Ca(2+) absorption caused by glutathione depleting drugs.

    PubMed

    Areco, Vanessa; Rodriguez, Valeria; Marchionatti, Ana; Carpentieri, Agata; Tolosa de Talamoni, Nori

    2016-07-01

    We have previously demonstrated that melatonin (MEL) blocks the inhibition of the intestinal Ca(2+) absorption caused by menadione (MEN). The purpose of this study were to determine whether MEL not only restores but also prevents the intestinal Ca(2+) absorption inhibited either by MEN or BSO, two drugs that deplete glutathione (GSH) in different ways, and to analyze the mechanisms by which MEN and MEL alter the movement of Ca(2+) across the duodenum. To know this, chicks were divided into four groups: 1) controls, 2) MEN treated, 3) MEL treated, and 4) treated sequentially with MEN and MEL or with MEN and MEL at the same time. In a set of experiments, chicks treated with BSO or sequentially with BSO and MEL or with BSO and MEL at the same time were used. MEL not only restored but also prevented the inhibition of the chick intestinal Ca(2+) absorption produced by either MEN or BSO. MEN altered the protein expression of molecules involved in the transcellular as well as in the paracellular pathway of the intestinal Ca(2+) absorption. MEL restored partially both pathways through normalization of the O2(-) levels. The nitrergic system was not altered by any treatment. In conclusion, MEL prevents or restores the inhibition of the intestinal Ca(2+) absorption caused by different GSH depleting drugs. It might become one drug for the treatment of intestinal Ca(2+) absorption under oxidant conditions having the advantage of low or null side effects. PMID:26970583

  13. Dietary oxidized n-3 PUFA induce oxidative stress and inflammation: role of intestinal absorption of 4-HHE and reactivity in intestinal cells[S

    PubMed Central

    Awada, Manar; Soulage, Christophe O.; Meynier, Anne; Debard, Cyrille; Plaisancié, Pascale; Benoit, Bérengère; Picard, Grégory; Loizon, Emmanuelle; Chauvin, Marie-Agnès; Estienne, Monique; Peretti, Noël; Guichardant, Michel; Lagarde, Michel; Genot, Claude; Michalski, Marie-Caroline

    2012-01-01

    Dietary intake of long-chain n-3 PUFA is now widely advised for public health and in medical practice. However, PUFA are highly prone to oxidation, producing potentially deleterious 4-hydroxy-2-alkenals. Even so, the impact of consuming oxidized n-3 PUFA on metabolic oxidative stress and inflammation is poorly described. We therefore studied such effects and hypothesized the involvement of the intestinal absorption of 4-hydroxy-2-hexenal (4-HHE), an oxidized n-3 PUFA end-product. In vivo, four groups of mice were fed for 8 weeks high-fat diets containing moderately oxidized or unoxidized n-3 PUFA. Other mice were orally administered 4-HHE and euthanized postprandially versus baseline mice. In vitro, human intestinal Caco-2/TC7 cells were incubated with 4-hydroxy-2-alkenals. Oxidized diets increased 4-HHE plasma levels in mice (up to 5-fold, P < 0.01) compared with unoxidized diets. Oxidized diets enhanced plasma inflammatory markers and activation of nuclear factor kappaB (NF-κB) in the small intestine along with decreasing Paneth cell number (up to −19% in the duodenum). Both in vivo and in vitro, intestinal absorption of 4-HHE was associated with formation of 4-HHE-protein adducts and increased expression of glutathione peroxidase 2 (GPx2) and glucose-regulated protein 78 (GRP78). Consumption of oxidized n-3 PUFA results in 4-HHE accumulation in blood after its intestinal absorption and triggers oxidative stress and inflammation in the upper intestine. PMID:22865918

  14. Pharmacokinetics, intestinal absorption and microbial metabolism of single platycodin D in comparison to Platycodi radix extract

    PubMed Central

    Shan, Jinjun; Zou, Jiashuang; Xie, Tong; Kang, An; Zhou, Wei; Deng, Haishan; Mao, Yancao; Di, Liuqing; Wang, Shouchuan

    2015-01-01

    Background: Platycodi radix, the dried root of Platycodon grandiflorum A. DC, has been widely used as food and herb medicine for treating cough, cold and other respiratory ailments, and platycodin D (PD) is one of the most important compounds in Platycodi Radix. Objective: The purpose of this study was to compare the pharmacokinetic characteristics, intestinal absorption and microbial metabolism of PD in monomer with that in Platycodi radix extract (PRE). Materials and Methods: In the pharmacokinetic study, the concentrations of PD in rat plasma were determined by ultra-performance liquid chromatography-tandem mass spectrometry and the main pharmacokinetic parameters were calculated by data analysis software (DAS). Besides, in vitro Caco-2 cells and fecal lysate were performed to investigate the intestinal absorption and metabolism, respectively. Results: The results from pharmacokinetics showed that the area under the curve, the peak concentration the time to reach peak concentration and mean residence time of PD in PRE were enhanced significantly compared with that in single PD. Caco-2 cells transport study indicated that the absorption of PD both in monomer and in PRE were poor owning that the permeability of PD were <1/106 cm/s. The hydrolysis degree of PD in PRE was significantly lower than that in monomer PD in fecal lysate, which might be illustrated by the other ingredients in PRE influenced the hydrolysis of PD via gut microbiota. Conclusion: These findings indicated that the difference of microbial metabolism, not apparent absorption in intestine for PD between in monomer and in PRE contributed to their pharmacokinetic difference. PMID:26600720

  15. 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.

  16. 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

  17. 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

  18. 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. The Vegfc-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

  19. Oxalates in some Indian green leafy vegetables.

    PubMed

    Radek, M; Savage, G P

    2008-05-01

    The soluble and total oxalate contents of 11 leafy vegetables grown in India were determined. Spinach, purple and green amaranth and colocasia contained high levels of total oxalates, which ranged from 5,138.0 +/- 37.6 mg/100 g dry matter up to 12,576.1 +/- 107.9 mg/100 g dry matter. Seven other leafy vegetables (curry, drumstick, shepu, fenugreek, coriander, radish and onion stalks) contained only insoluble oxalate, which ranged from 209.0 +/- 5.0 mg/100 g dry matter to 2,774.9 +/-18.4 mg/100 g dry matter. In vitro digestion of the samples showed that the gastric available oxalate was 10% lower than the values obtained from acid extraction and that intestinal available oxalate was 20% lower than the values obtained following hot water extraction. The percentage calcium bound in the insoluble oxalate fraction of the dried leafy vegetables ranged from 3.3% to 86.7% of the total calcium. Addition of four different sources of calcium (low fat milk, whole milk, calcium carbonate and calcium sulphate) resulted in a range of 32-100% reductions of intestinal available oxalate in the mixture. PMID:18335334

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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...

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. SLC26A6 and NaDC-1 Transporters Interact to Regulate Oxalate and Citrate Homeostasis

    PubMed Central

    Ohana, Ehud; Shcheynikov, Nikolay; Moe, Orson W.

    2013-01-01

    The combination of hyperoxaluria and hypocitraturia can trigger Ca2+-oxalate stone formation, even in the absence of hypercalciuria, but the molecular mechanisms that control urinary oxalate and citrate levels are not understood completely. Here, we examined the relationship between the oxalate transporter SLC26A6 and the citrate transporter NaDC-1 in citrate and oxalate homeostasis. Compared with wild-type mice, Slc26a6-null mice exhibited increased renal and intestinal sodium-dependent succinate uptake, as well as urinary hyperoxaluria and hypocitraturia, but no change in urinary pH, indicating enhanced transport activity of NaDC-1. When co-expressed in Xenopus oocytes, NaDC-1 enhanced Slc26a6 transport activity. In contrast, Slc26a6 inhibited NaDC-1 transport activity in an activity dependent manner to restricted tubular citrate absorption. Biochemical and physiologic analysis revealed that the STAS domain of Slc26a6 and the first intracellular loop of NaDC-1 mediated both the physical and functional interactions of these transporters. These findings reveal a molecular pathway that senses and tightly regulates oxalate and citrate levels and may control Ca2+-oxalate stone formation. PMID:23833257

  16. 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

  17. Effect of dietary phosphorus on intestinal phosphorus absorption in growing Holstein steers.

    PubMed

    Feng, X; Ronk, E; Hanigan, M D; Knowlton, K F; Schramm, H; McCann, M

    2015-05-01

    The effect of dietary P intake on intestinal P absorption was evaluated in growing Holstein steers. Diets varying in P content (0.15, 0.27, 0.36, and 0.45%, DM basis) were fed to 8 steers (174±10kg of BW) fitted with permanent duodenal and ileal cannulas in a replicated 4×4 Latin square with 14-d periods. Ytterbium-labeled corn silage and cobalt-EDTA were used as particulate and liquid phase markers, respectively, to measure digesta flow. Duodenal and ileal samples and spot urine samples were collected every 9 h from d 11 to 14. Total fecal collection was conducted on d 11 to 14 with fecal bags. Blood samples were collected from the coccygeal vessel on d 14. Feed, digesta, and fecal samples were analyzed for total P and inorganic P. Data were analyzed using PROC GLIMMIX in SAS with a model including treatment, square, period, and interaction of treatment and square. Preplanned contrasts were used to evaluate linear and quadratic treatment effects. Results were reported as least squares means. Dry matter intake (mean=4.90kg/d, 2.8% of BW) and apparent DM digestibility (mean=78.1%) were unaffected by treatment. Duodenal and ileal flow of total P increased linearly with increasing P intake (13.4, 18.5, 23.0, and 27.4g/d; 6.80, 7.87, 8.42, and 10.4g/d). Increasing P intake increased the quantity of P absorbed from the small intestine linearly (6.96, 11.1, 14.6, and 17.2g/d), but absorption efficiency was unchanged (mean=59.6%). Phosphorus was absorbed on a net basis from the large intestine, but this was not affected by treatment and was a small proportion of total P absorption. Blood inorganic P increased linearly with increased dietary P (4.36, 6.31, 7.68, and 8.5mg/dL) and salivary P secretion was unchanged (mean=5.79g/d), suggesting that rumen function was prioritized during short-term P deficiency. These data showing an absence of change in absorption efficiency and salivary P secretion in the face of short-term P deficiency may be used to improve published models of P digestion, absorption, and metabolism. PMID:25771046

  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. Human Milk Oligosaccharides in Premature Infants: Absorption, Excretion and Influence on the Intestinal Microbiota

    PubMed Central

    Underwood, Mark A.; Gaerlan, Stephanie; De Leoz, M. Lorna A.; Dimapasoc, Lauren; Kalanetra, Karen M.; Lemay, Danielle G.; German, J. Bruce; Mills, David A.; Lebrilla, Carlito B.

    2015-01-01

    Background Human milk oligosaccharides (HMOs) shape the intestinal microbiota in term infants. In premature infants, alterations in the intestinal microbiota (dysbiosis) are associated with risk of necrotizing enterocolitis and sepsis and the influence of HMOs on the microbiota is unclear. Methods Milk, urine, and stool specimens from 14 mother-premature infant dyads were investigated by mass spectrometry for HMO composition. The stools were analyzed by next-generation sequencing (NGS) to complement a previous analysis. Results Percentages of fucosylated and sialylated HMOs were highly variable between individuals but similar in urine, feces and milk within dyads. Differences in urine and fecal HMO composition suggest variability in absorption. Secretor status of the mother correlated with the urine and fecal content of specific HMO structures. Trends toward higher levels of Proteobacteria and lower levels of Firmicutes, were noted in premature infants of non-secretor mothers. Specific HMO structures in the milk, urine and feces were associated with alterations in fecal Proteobacteria and Firmicutes. Conclusion HMOs may influence the intestinal microbiota in premature infants. Specific HMOs, for example those associated with secretor mothers, may have a protective effect by decreasing pathogens associated with sepsis and necrotizing enterocolitis while other HMOs may increase dysbiosis in this population. PMID:26322410

  20. 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 1α-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

  1. Age-related decline of bone mass and intestinal calcium absorption in normal males.

    PubMed

    Agnusdei, D; Civitelli, R; Camporeale, A; Parisi, G; Gennari, L; Nardi, P; Gennari, C

    1998-09-01

    Although about 25% of all hip fractures occur in men, little is known about the pattern of their age-related bone loss and its main determinants. The aim of this cross-sectional study was to evaluate the age-related changes of intestinal calcium absorption, bone mass, and bone turnover in normal men. In 70 normal males (age 17-91 years), we measured spinal and forearm bone density (FBD) (by DXA), fractional intestinal calcium absorption (by oral test), serum immunoreactive parathyroid hormone (PTH), dietary calcium intake (diet records), biochemical markers of bone turnover (serum alkaline phosphatase (ALP), osteocalcin, urine calcium, creatinine, and hydroxyproline), and 1,25(OH)2D3 serum levels. Vertebral bone density (VBD) showed a modest decline before age 50 and a greater decline after age 50, whereas FBD presented a significant decrease with advancing age starting at age 40, suggesting a predominant age-related cortical bone loss. Intestinal calcium absorption (47CaFA) and serum 1,25(OH)2D3 also presented an age-related decline similar to FBD. Simple correlation analysis revealed that age was significantly related to 47CaFA (r = 0.60), calcium intake (r = 0.32), VBD and FBD (r = 0.79 and 0.63, respectively), serum 1,25(OH)2D3 (r = 0.69), and serum iPTH (r = 0.72). No significant correlation was found between age and biochemical markers of bone remodeling. Partial correlation and stepwise variable selection analyses, using 47CaFA and bone mass as dependent variables, showed that in normal males, serum 1,25(OH)2D3 and dietary calcium intake were the main contributors (64%) to 47CaFA variability, whereas only age accounted for 63% of VBD and age and dietary calcium accounted for 45% of FBD variability. These results indicate that bone loss in men accelerates after age 50 years and that among other factors, intestinal calcium malabsorption and 1,25(OH)2D3 serum levels play a role. PMID:9701622

  2. Absence of negative feedback on intestinal magnesium absorption on excessive magnesium administration in rats.

    PubMed

    Nakaya, Yumi; Suzuki, Masao; Uehara, Mariko; Katsumata, Shin-ichi; Suzuki, Kazuharu; Sakai, Kensuke; Ohnishi, Ryuko; Ohta, Atsutane

    2009-08-01

    This study aimed to clarify the regulatory mechanism of Mg homeostasis on administration of excessive Mg in rats. Six-week-old male Wistar rats (n=30) were fed a Mg-deficient diet (D) or a control diet (M) in addition to which they received subcutaneous injections of saline (S) or additional Mg (M) for 14 d. Feces and urine were collected from the rats for 4 d every week. Between the MS and MM rats and the DS and DM rats, the injection of additional Mg increased Mg retention, but intestinal Mg absorption did not differ. Urinary Mg excretion in the MM rats was significantly greater than that in the MS rats, but fecal Mg excretion did not increase. Mg retention in the DM rats was approximately 30% of that in the MS rats, and urinary Mg excretion did not differ between the 2 groups, although the serum Mg in DM rats was low. There was no significant difference in the femoral Mg between the MM and MS groups. The physiological Mg pool in the bone appears to be limited. Therefore, there is no physiological Mg pool for the storage of excessive Mg, and there appears to be no negative feedback mechanism on intestinal Mg absorption upon administration of excessive Mg in the rats. In conclusion, it appears that the kidney is the only organ that regulates Mg in the body; apart from this, regulatory mechanisms corresponding to the physiological Mg requirement do not exist or are weak. PMID:19763034

  3. 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

  4. 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

  5. Relevance of PepT1 in the Intestinal Permeability and Oral Absorption of Cefadroxil

    PubMed Central

    Posada, Maria M.; Smith, David E.

    2012-01-01

    Purpose To determine the contribution of intestinal PepT1 on the permeability and oral absorption of the β-lactam antibiotic drug cefadroxil. Methods The effective permeability (Peff) of cefadroxil was evaluated in wild-type and PepT1 knockout mice following in situ single-pass intestinal perfusions. The plasma concentration-time profiles of cefadroxil were also examined after oral gavage. Results The Peff (cm/s) of cefadroxil in wild-type mice was 0.49×10-4 in duodenum, 0.80×10-4 in jejunum, 0.88×10-4 in ileum and 0.064x10-4 in colon. The Peff (cm/s) in PepT1 knockout mice was significantly reduced in small intestine, but not in colon, as shown by values of 0.003×10-4, 0.090×10-4, 0.042×10-4 and 0.032×10-4, respectively. Jejunal uptake of cefadroxil was saturable (Km=2-4 mM) and significantly attenuated by the sodium-proton exchange inhibitor 5-(N,N-dimethyl)amiloride. Jejunal permeability of cefadroxil was not affected by L-histidine, glycine, cephalothin, p-aminohippurate or N-methylnicotinamide. In contrast, cefadroxil permeability was significantly reduced by glycylproline, glycylsarcosine, or cephalexin. Finally, PepT1 ablation resulted in 23-fold reductions in peak plasma concentrations and 14-fold reductions in systemic exposure of cefadroxil after oral dosing. Conclusions The findings are definitive in demonstrating that PepT1 is the major transporter responsible for the small intestinal permeability of cefadroxil as well as its enhanced oral drug performance. PMID:23224978

  6. Effect of glucose and lipids on intestinal absorption of sorbitol: role of gastric emptying.

    PubMed

    Beaugerie, L; Lémann, M; Jian, R; Flourié, B; Rain, J D; Rambaud, J C

    1996-09-01

    The aim of our study was to test the hypothesis that the better absorption of sorbitol when ingested with glucose could be related to a delayed gastric emptying. We tested the effect of the ingestion of glucose and lipids on the gastric emptying and intestinal absorption of sorbitol in six healthy volunteers, using gastric scintigraphy and hydrogen breath test. After an overnight fast, subjects ingested in random order, on 48-h test periods separated by at least one week, the following solutions: (a) 20 g sorbitol alone; (b) 20 g sorbitol and 20 g glucose; (c) 20 g sorbitol and 9 g lipids. Isotopic acquisitions were taken for 3 h following the ingestion of sorbitol labelled with 111Indium. Hydrogen concentration was measured in end-expiratory samples during 5 h, and the areas under the breath hydrogen curve, reflecting the amounts of sorbitol unabsorbed in the small bowel, were compared between periods. Mean area under the curve was 397 +/- 159 when sorbitol was ingested alone, and this was significantly lower when ingested with glucose or lipids (313 +/- 181 and 337 +/- 135, respectively; P < 0.05). The three curves of sorbitol gastric emptying differed significantly from each other, the gastric emptying being the slowest for sorbitol plus lipids, and the fastest for sorbitol taken alone. We found a positive correlation between the half-emptying time and the hydrogen areas under the curve (r = 0.46, P = 0.05). In conclusion, our study demonstrates that adding glucose or lipids to a solution of sorbitol slows the gastric emptying of sorbitol, resulting in a better intestinal absorption of sorbitol. PMID:8878083

  7. 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

  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. 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

  12. 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

  13. 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.

  14. Dentin Hypersensitivity and Oxalates

    PubMed Central

    Cunha-Cruz, J.; Stout, J.R.; Heaton, L.J.; Wataha, J.C.

    2011-01-01

    Treatment of dentin hypersensitivity with oxalates is common, but oxalate efficacy remains unclear. Our objective was to systematically review clinical trials reporting an oxalate treatment compared with no treatment or placebo with a dentin hypersensitivity outcome. Risk-of-bias assessment and data extraction were performed independently by two reviewers. Standardized mean differences (SMD) were estimated by random-effects meta-analysis. Of 677 unique citations, 12 studies with high risk-of-bias were included. The summary SMD for 3% monohydrogen-monopotassium oxalate (n = 8 studies) was -0.71 [95% Confidence Interval: -1.48, 0.06]. Other treatments, including 30% dipotassium oxalate (n = 1), 30% dipotassium oxalate plus 3% monohydrogen monopotassium oxalate (n = 3), 6% monohydrogen monopotassium oxalate (n = 1), 6.8% ferric oxalate (n = 1), and oxalate-containing resin (n = 1), also were not statistically significantly different from placebo treatments. With the possible exception of 3% monohydrogen monopotassium oxalate, available evidence currently does not support the recommendation of dentin hypersensitivity treatment with oxalates. PMID:21191127

  15. 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...

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

    PubMed Central

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

    2010-01-01

    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 β,β-carotene to the retinoic acid precursor, retinaldehyde. Using BCMO1-knockout mice, we demonstrated increased intestinal SR-BI expression and systemic β,β-carotene accumulation. SR-BI-dependent accumulation of β,β-carotene was prevented by dietary retinoids that induced ISX expression. Thus, our study revealed a diet-responsive regulatory network that controls β,β-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.—Lobo, G. P., Hessel, S., Eichinger, A., Noy, N., Moise, A. R., Wyss, A., Palczewski, K., von Lintig, J. ISX is a retinoic acid-sensitive gatekeeper that controls intestinal β,β-carotene absorption and vitamin A production. PMID:20061533

  17. 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.

  18. 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

  19. Effect of cadmium and zinc on intestinal absorption of xylose and tryptophan in the fresh water teleost fish, Heteropneustes fossilis

    SciTech Connect

    Sastry, K.V.; Subhadra, S.

    1984-01-01

    The effect of cadmium and of zinc on the rate of uptake of a pentose sugar xylose and an aminoacid tryptophan by the intestine of a teleost fish, Heteropneustes fossilis was studied under two experimental conditions. In the first, four concentration of cadmium or zinc mixed with the nutrient solution were filled in the intestinal sacs, and the rate of absorption was recorded after 1 h at 23/sup 0/C. In the second experiment fish were exposed by bath to a sublethal concentrations of cadmium or zinc for 15 and 30 days and the rate of absorption of the two nutrients was measured. The activity of intestinal Na/sup +/, K/sup +/ activated adenosine triphosphatase was also assayed. The two heavy metals at all the four concentrations decreased the rate of intestinal transport of nutrients. The rate of intestinal absorption of the two nutrients was also reduced by exposure of fish to the heavy metals in vivo. The activity of Na/sup +/, K/sup +/ ATPase decreased in vitro with all four concentrations of cadmium and zinc and was diminished in fish exposed for 15 and 30 days.

  20. Region-dependent absorption of faropenem shared with foscarnet, a phosphate transporter substrate, in the rat small intestine.

    PubMed

    Saitoh, Hiroshi; Sawazaki, Rinako; Oda, Masako; Kobayashi, Michiya

    2008-09-01

    Faropenem, a penem antibiotic, is orally active despite its hydrophilic nature. However, its intestinal absorption has not yet been characterised in detail. This study was undertaken to determine the factors regulating faropenem absorption using intestinal loops prepared in the rat duodenum, jejunum and terminal ileum. Faropenem disappearance was much greater than that of cefotaxime and meropenem, and faropenem disappeared more extensively from the terminal ileum than from the jejunum or duodenum. In contrast to faropenem, the disappearance of ceftibuten was much greater from the duodenum and jejunum than from the terminal ileum. As the accumulation and enzymatic degradation of faropenem was minimal in the intestinal mucosa, faropenem was considered to enter the portal vein smoothly after its disappearance from the intestinal loops. Faropenem disappearance was not significantly influenced by the presence of monocarboxylic acids, amino acids or bile acid. Dipeptides such as L-carnosine and glycylglycine slightly but significantly lowered faropenem disappearance from the terminal ileum. On the other hand, foscarnet exerted a marked inhibitory effect on faropenem disappearance, but the antiviral agent did not modulate ceftibuten absorption. The present results suggest that faropenem is in part absorbed via a phosphate transporter present in the rat small intestine. PMID:18614339

  1. 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

  2. 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.

  3. 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...

  4. Intestinal Calcium Absorption and Serum Vitamin D Metabolites in Normal Subjects and Osteoporotic Patients

    PubMed Central

    Gallagher, J. C.; Riggs, B. Lawrence; Eisman, John; Hamstra, Alan; Arnaud, Sara B.; Deluca, Hector F.

    1979-01-01

    Intestinal calcium absorption assessed by a double-isotope method, decreased significantly with aging in 94 normal subjects (r = −0.22, P < 0.025). In 52 untreated patients with postmenopausal osteoporosis, calcium absorption was significantly lower than normal when either age or habitual calcium intake was used as a covariable (P < 0.001). Serum 25-hydroxyvitamin D (25-OH-D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured in 44 normal subjects and 27 osteoporotic patients. For all normals, calcium absorption and serum 1,25(OH)2D were positively correlated (r = 0.50, P < 0.001). In nonelderly normal subjects (ages 30-65 yr), dietary calcium intake correlated inversely with both calcium absorption (r = −0.39, P < 0.01) and with serum 1,25(OH)2D (r = −0.50, P < 0.01). Both osteoporotic patients and elderly normal subjects (ages 65-90 yr) differed from nonelderly normals in that these correlations were not present. In addition although serum 25-OH-D was normal, serum 1,25(OH)2D was significantly decreased in both osteoporotic patients and elderly normals (P < 0.001). In osteoporotic patients, calcium absorption increased significantly (P < 0.001) after 7 d administration of a small dose (0.4 μg/d) of synthetic 1,25(OH)2D3. In osteoporotics mean serum immunoreactive parathyroid hormone was either normal (COOH-terminal assay) or low (NH2-terminal assay) relative to age-matched controls, and mean serum phosphate was increased. The data suggest that inadequate metabolism of 25-OH-D to 1,25(OH)2D contributes significantly to decreased calcium absorption and adaptation in both osteoporotics and elderly normal subjects. In patients with osteoporosis this abnormality could result from a decrease in factors that normally stimulate 1,25(OH)2D production, such as the decreased parathyroid hormone secretion and increased serum phosphate demonstrated in this group. In elderly subjects a primary abnormality in metabolism of 25-OH-D to 1,25(OH)2D, analagous to that seen in aging rats, cannot be excluded. Images PMID:468987

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. Bioavailability of dietary (poly)phenols: a study with ileostomists to discriminate between absorption in small and large intestine.

    PubMed

    Borges, Gina; Lean, Michael E J; Roberts, Susan A; Crozier, Alan

    2013-04-30

    A feeding study was carried out in which six healthy ileostomists ingested a juice drink containing a diversity of dietary (poly)phenols derived from green tea, apples, grapes and citrus fruit. Ileal fluid and urine collected at intervals over the ensuing 24 h period were then analysed by HPLC-MS. Urinary excretions were compared with results obtained in an earlier study in which the juice drink was ingested by ten healthy control subjects with an intact colon. Some polyphenol components, such as (epi)catechins and (epi)gallocatechin(s), were excreted in urine in similar amounts in ileostomists and subjects with an intact colon, demonstrating that absorption took place principally in the small intestine. In the urine of ileostomists, there were reduced levels of other constituents, including hesperetin-7-O-rutinoside, 5-O-caffeoylquinic acid and dihydrochalcones, indicating their absorption in both the small and large intestine. Ileal fluid analysis revealed that even when absorption occurred in the small intestine, in subjects with a functioning colon a substantial proportion of the ingested components still pass from the small into the large intestine, where they may be either absorbed before or after catabolism by colonic bacteria. PMID:23471276

  10. Absorption and metabolism of flavonoids in the caco-2 cell culture model and a perused rat intestinal model.

    PubMed

    Liu, Yan; Hu, Ming

    2002-04-01

    The purpose of present study was to determine the intestinal absorption and metabolism of genistein and its analogs to better understand the mechanisms responsible for their low oral bioavailability. The Caco-2 cell culture model and a perfused rat intestinal model were used for the study. In both models, permeabilities of aglycones (e.g., genistein) were comparable to well absorbed compounds, such as testosterone and propranolol. In the Caco-2 model, permeabilities of aglycones were at least 5 times higher (p < 0.05) than their corresponding glycosides (e.g., genistin), and the vectorial transport of aglycones was similar (p > 0.05). In contrast, vectorial transport of glucosides favored excretion (p < 0.05). Limited hydrolysis of glycosides was observed in the Caco-2 model, which was completely inhibited (p < 0.05) by 20 mM gluconolactone, a broad specificity glycosidase inhibitor. In the perfused rat intestinal model, genistin was rapidly hydrolyzed (about 40% in 15 min) in the upper intestine but was not hydrolyzed at all in the colon. Aglycones were rapidly absorbed (P*(eff) > 1.5), and absorbed aglycones underwent extensive (40% maximum) phase II metabolism via glucuronidation and sulfation in the upper small intestine. Similar to the hydrolysis, recovery of conjugated genistein was also region-dependent, with jejunum having the highest and colon the lowest (p < 0.05). This difference in conjugate recovery could be due to the difference in the activities of enzymes or efflux transporters, and the results of studies tend to suggest that both of these factors were involved. In conclusion, genistein and its analogs are well absorbed in both intestinal models, and therefore, poor absorption is not the reason for its low bioavailability. On the other hand, extensive phase II metabolism in the intestine significantly contributes to its low bioavailability. PMID:11901089

  11. [Analysis and comparison of intestinal absorption of components of Gegenqinlian decoction in different combinations based on pharmacokinetic parameters].

    PubMed

    Zhang, Yi-Zhu; An, Rui; Yuan, Jin; Wang, Yue; Gu, Qing-Qing; Wang, Xin-Hong

    2013-10-01

    To analyse and compare the characteristics of the intestinal absorption of puerarin, baicalin, berberine and liquiritin in different combinations of Gegenqinlian decoction based on pharmacokinetic parameters, a sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was applied for the quantification of four components in rat's plasma. And pharmacokinetic parameters were determined from the plasma concentration-time data with the DAS software package. The influence of different combinations on pharmacokinetics of four components was studied to analyse and compare the absorption difference of four components, together with the results of the in vitro everted gut model and the rat single pass intestinal perfusion model. The results showed that compared with other combinations, the AUC values of puerarin, baicalin and berberine were increased significantly in Gegenqinlian decoction group, while the AUC value of liquiritin was reduced. Moreover, the absorption of four components was increased significantly supported by the results from the in vitro everted gut model and the rat single pass intestinal perfusion model, which indicated that the Gegenqinlian decoction may promote the absorption of four components and accelerate the metabolism of liquiritin by the cytochrome P450. PMID:24417090

  12. 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

  13. 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).

  14. Gastric intrinsic factor: the gastric and small intestinal stages of cobalamin absorption. a personal journey.

    PubMed

    Alpers, David H; Russell-Jones, Greg

    2013-05-01

    Intrinsic factor (IF) was first identified as a component of the gastric mucosa that reacted with an extrinsic factor, later discovered to be vitamin B12 (VB12). IF has been extensively characterized, and its cloned cDNA used to produce sufficient IF to produce high quality antibodies, and to elucidate its 3-dimensional structure bound to cobalamin (Cbl, VB12). The absorption of the IF-Cbl complex involves internalization by endocytosis, incorporation into multivesicular/lysosomal bodies, release of Cbl by lysosomal proteolysis and pH effects, with subsequent binding to transcobalamin (TC). Hereditary IF deficiency is rare, consistent with the need for IF to absorb Cbl, a vitamin essential for cell replication. When mutations occur, they are most often associated with loss of function, but some mutations occur outside the coding region. The IF-mediated intestinal uptake of Cbl has been harnessed for use as a transporter for peptides, proteins and even nanoparticles. Nanoparticle (NP) technology has produced Cbl-coated NPs that can incorporate peptides (insulin, IgG) that can be absorbed orally to function as hormones and antibodies in rodent models, but these systems are not yet ready for clinical use. PMID:23274574

  15. 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 P(app) and K(a) 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. PMID:26514546

  16. Relationships between human intestinal absorption and polar interactions drug/phospholipids estimated by IAM-HPLC.

    PubMed

    Grumetto, Lucia; Russo, Giacomo; Barbato, Francesco

    2015-07-15

    Phospholipid affinity indexes (logkW(IAM)) for 15 structurally non-related basic, acidic, ampholytic, and neutral drugs were measured by HPLC on two different phospholipid stationary phases (immobilized artificial membrane - IAM). According to a method we previously proposed, polar and electrostatic forces involved in drug/membrane interactions were quantified both as ΔlogkW(IAM) and as Δ(')logkW(IAM). These values are the differences between the experimental logkW(IAM) and the values expected for a neutral compound having the lipophilicity value equal to either that of the neutral form of the analyte (logP(N)) or that of the mixture of charged and neutral forms of the analyte at jejunum pH 6.5 (logD(6.5)), respectively. Jejunum absorption values, logPeff, measured by the Loc-I-Gut technique, did not relate with logkW(IAM) values. A moderate linear relationship was observed with logP(N) values for all the analytes and a weak parabolic relationship was observed with logD(6.5) values, but only after the exclusion of two analytes. In contrast, a highly significant linear inverse relationship was observed with ΔlogkW(IAM) values. Therefore, differently from the results of our recent studies on blood-brain barrier passage, the intestinal absorption data for not only bases and zwitterions but also for acids relate significantly with ΔlogkW(IAM) and not with Δ(')logkW(IAM) values. The results suggest that membrane passage at jejunum level can be described according to the "flip-flop" model; indeed, the lipophilicity of the neutral forms (logP(N)) appears related to the passage through the non-polar inner moieties of phospholipids whereas ΔlogkW(IAM) parameter appears related to the "trapping" forces at their polar surfaces. The method, easy to perform and at medium throughput, could be of use for preliminary screening of new drugs based on oral absorption potential. PMID:25917756

  17. 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

  18. Effect of oral supplementation of Lactobacillus reuteri in reduction of intestinal absorption of aflatoxin B(1) in rats.

    PubMed

    Hernandez-Mendoza, Adrián; González-Córdova, Aarón Fernando; Vallejo-Cordoba, Belinda; Garcia, Hugo Sergio

    2011-06-01

    The goals of this work were to assess the ability of Lactobacillus reuteri to bind aflatoxin B(1) in the intestinal tract and determine its effect on intestinal absorption of the toxin dispensed in either single or multiple doses in a murine model. Male Wistar rats were used, and two experiments were conducted after bacteria were implanted. Experiment one involved a single-oral dose of toxin, and the subsequent flow cytometric analysis of bacteria isolated from the small intestine and treated with specific FITC-labeled AFB(1) antibodies. The second experiment was carried out supplying the toxin in 7 oral sub-doses, and the later quantification of AFB(1)-Lys adducts in blood samples by ELISA assay. The results demonstrated that L. reuteri was able to bind AFB(1) in the intestinal tract, mostly in the duodenum. Furthermore, the AFB(1)-Lys adducts were present at significantly lower levels in those animals receiving AFB(1) plus bacteria than in those receiving only AFB(1). Our findings confirm that probiotic bacteria could act as biological barriers in normal intestinal conditions thereby reducing the bioavailability of AFB(1) ingested orally in a single or multiple doses, thus avoiding its toxic effects. PMID:21298677

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

    PubMed

    Carvalho, Edison S M; Gregório, Sílvia F; Canário, 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 μmol l(-1)) or the phospholipase C inhibitor (U73122, 10 μmol 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 μmol l(-1)) and was insensitive to the phospholipase C inhibitor (U73122, 10 μmol 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

  20. 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

  1. 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

  2. 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...

  3. 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

  4. 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

  5. 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

  6. Intestinal absorption of nutrients is not influenced by soy fiber and does not differ between oligomeric and polymeric enteral diets.

    PubMed

    Ehrlein, H; Stockmann, A

    1998-09-01

    Enteric feeding is often associated with diarrhea. To avoid this side effect, isoosmotic and fiber-supplemented enteral diets are recommended. The aims of this study were to determine whether supplementing enteral diets with soy fiber influences nutrient absorption and whether in enteric feeding absorption of nutrients and water fluxes differ between hyperosmotic oligomeric and isoosmotic polymeric diets. In mini pigs intestinal absorption and water fluxes were measured by perfusing a 150-cm length of jejunum. Six noncommercial iso- and hyperosmotic oligomeric and polymeric diets and six commercial polymeric diets, either fiber-free or supplemented with soy fiber, were used. Pancreatic enzymes were infused concomitantly with the polymeric diets. The absorption of nutrients and energy did not differ between oligomeric and polymeric diets. Oligomeric diets of high energy density produced a pronounced secretion of water. Despite lower initial osmolality, polymeric diets produced a similar secretion of water due to rapid pancreatic hydrolysis. Supplementing diets with largely insoluble soy fiber increased viscosity only between 4.6 and 14.5 mPa x sec. Soy fiber did not influence absorption of nutrients and energy and had also no effects on luminal transit and flow rate. The lack of effects was not due to dilution of chyme by intestinal secretion of water because no differences existed between isoosmotic and hyperosmotic oligomeric diets. In conclusion, supplementing enteral diets with soy fiber does not impair the absorption of nutrients. Enteric feeding with isoosmotic polymeric diets provides no advantage compared with hyperosmotic oligomeric diets with respect to absorption of nutrients and secretion of water. PMID:9753279

  7. 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

  8. Villin Promoter-Mediated Transgenic Expression of TRPV6 Increases Intestinal Calcium Absorption in Wild-type and VDR Knockout Mice

    PubMed Central

    Cui, Min; Li, Qiang; Johnson, Robert; Fleet, James C.

    2012-01-01

    Transient receptor potential cation channel, subfamily V, member 6 (TRPV6) is an apical membrane calcium (Ca) channel in the small intestine proposed to be essential for vitamin D regulated intestinal Ca absorption. Recent studies have challenged the proposed role for TRPV6 in Ca absorption. We directly tested intestinal TRPV6 function in Ca and bone metabolism in wild-type (WT) and vitamin D receptor knockout (VDRKO) mice. Transgenic mice (TG) were made with intestinal epithelium-specific expression of a 3X flag-tagged human TRPV6 protein. TG and VDRKO mice were crossed to make TG-VDRKO mice. Ca and bone metabolism was examined in WT, TG, VDRKO, and TG-VDRKO mice. TG mice developed hypercalcemia and soft tissue calcification on a chow diet. In TG mice fed a 0.25% Ca diet, Ca absorption was >3 fold higher and femur bone mineral density (BMD) was 26% higher than WT. Renal CYP27B1 mRNA and intestinal expression of the natural mouse TRPV6 gene were reduced to <10% of WT but small intestine calbindin-D9k expression was elevated >15X in TG mice. TG-VDRKO mice had high Ca absorption that prevented the low serum Ca, high renal CYP27B1 mRNA, and low BMD and abnormal bone microarchitecture seen in VDRKO mice. In addition, small intestinal calbindin D9K mRNA and protein levels were elevated in TG-VDRKO. Transgenic TRPV6 expression in intestine is sufficient to increase Ca absorption and bone density, even in VDRKO mice. VDR independent up-regulation of intestinal calbindin D9k in TG-VDRKO suggests this protein may buffer intracellular Ca during Ca absorption. PMID:22589201

  9. Effect of various absorption enhancers based on tight junctions on the intestinal absorption of forsythoside A in Shuang-Huang-Lian, application to its antivirus activity

    PubMed Central

    Zhou, Wei; Zhu, Xuan Xuan; Yin, Ai Ling; Cai, Bao Chang; Wang, Hai Dan; Di, Liuqing; Shan, Jin Jun

    2014-01-01

    Background: Forsythoside A (FTA), one of the main active ingredients in Shuang–Huang–Lian (SHL), possesses strong antibacterial, antioxidant and antiviral effects, and its pharmacological effects was higher than that of other ingredients, but the absolute bioavailability orally was approximately 0.72%, which was significantly low, influencing clinical efficacies of its oral preparations seriously. Materials and Methods: In vitro Caco-2 cell and in vivo pharmacokinetics study were simultaneously performed to investigate the effects of absorption enhancers based on tight junctions: sodium caprate and water-soluble chitosan on the intestinal absorption of FTA, and the eventual mucosal epithelial damage resulted from absorption enhancers was evaluated by MTT test and morphology observation, respectively. The pharmacological effects such as antivirus activity improvement by absorption enhancers were verified by MDCK damage inhibition rate after influenza virus propagation. Results: The observations from in vitro Caco-2 cell showed that the absorption of FTA in SHL could be improved by absorption enhancers. Meanwhile, the absorption enhancing effect of water-soluble chitosan may be almost saturable up to 0.0032% (w/v), and sodium caprate at concentrations up to 0.64 mg/mL was safe, but water-soluble chitosan at different concentrations was all safe for these cells. In pharmacokinetics study, water-soluble chitosan at dosage of 50 mg/kg improved the bioavailability of FTA in SHL to the greatest extent, and was safe for gastrointestine from morphological observation. Besides, treatment with SHL with water-soluble chitosan at dosage of 50 mg/kg prevented MDCK damage after influenza virus propagation better significantly than that of control. Conclusion: Water-soluble chitosan at dosage of 50 mg/kg might be safe and effective absorption enhancer for improving the bioavailability of FTA and the antivirus activity in vitro in SHL. PMID:24695554

  10. Involvement of drinking and intestinal sodium absorption in hyponatremic effect of atrial natriuretic peptide in seawater eels.

    PubMed

    Tsukada, Takehiro; Rankin, J Cliff; Takei, Yoshio

    2005-01-01

    Atrial natriuretic peptide (ANP) decreases plasma Na+ concentration and promtes seawater (SW) adaptation in eels. The hyponatremia may most probably be caused by increased branchial extrusion of Na+, but the mechanism has not been determined yet. The present study examined initially the effects of ANP on branchial Na+ efflux in vivo using isotopic 22Na. However, the efflux rate was not altered by infusion of a hyponatremic dose of ANP (5 pmol.kg(-1).min(-1)). Therefore, we sought to examine whether the ANP-mediated hyponatremia is caused by a decrease in the uptake of Na+ from the environment. Since a decrease in drinking was highly correlated with a degree of hyponatremia, conscious SW eels were infused with dilute SW into the stomach at a normal drinking rate to offset the antidipsogenic effect of ANP. Under this regimen, the hyponatremic effect of ANP was abolished. Then, we examined the site of Na+ absorption in the alimentary tract by measuring the changes in ion composition of intraluminal fluid along the tract. Since Na+ was absorbed at the esophagus and anterior/middle intestine, a sac was prepared at each site and the effects of ANP were examined in situ in conscious SW eels. ANP infusion did not alter Na+ absorption at the esophagus, but it profoundly reduced the absorption at the intestine. Together with our previous finding that ANP does not alter renal Na+ excretion, we propose that ANP reduces plasma Na+ concentration in SW eels by inhibiting drinking and subsequent absorption of Na+ by the intestine. PMID:15684587

  11. Targeted disruption of the murine cholecystokinin-1 receptor promotes intestinal cholesterol absorption and susceptibility to cholesterol cholelithiasis

    PubMed Central

    Wang, David Q.-H.; Schmitz, Frank; Kopin, Alan S.; Carey, Martin C.

    2004-01-01

    Cholecystokinin (CCK) modulates contractility of the gallbladder, the sphincter of Oddi, and the stomach. These effects are mediated through activation of gastrointestinal smooth muscle as well as enteric neuron CCK-1 receptors (CCK-1Rs). To investigate the potential physiological and pathophysiological functions linked to CCK-1R–mediated signaling, we compared male WT and CCK-1R–deficient mice (129/SvEv). After 12 weeks on either a standard mouse chow or a lithogenic diet (containing 1% cholesterol, 0.5% cholic acid, and 15% dairy fat), small-intestinal transit time, intestinal cholesterol absorption, biliary cholesterol secretion, and cholesterol gallstone prevalence were compared in knockout versus WT animals. Analysis of mice on either the chow or the lithogenic diet revealed that CCK-1R–/– animals had larger gallbladder volumes (predisposing to bile stasis), significant retardation of small-intestinal transit times (resulting in increased cholesterol absorption), and increased biliary cholesterol secretion rates. The elevation in bile cholesterol, coupled with a tendency toward gallbladder stasis (due to the absence of CCK-induced contraction), facilitates nucleation, growth, and agglomeration of cholesterol monohydrate crystals; this sequence of events in turn results in a significantly higher prevalence of cholesterol gallstones in the CCK-1R–null mice. PMID:15314689

  12. P-glycoprotein limits the absorption of the anti-HIV drug zidovudine through rat intestinal segments.

    PubMed

    Quevedo, Mario A; Nieto, Leandro E; Briñón, Margarita C

    2011-06-14

    Zidovudine (AZT) was the first drug approved for the treatment of Acquired Immunodeficiency Syndrome (AIDS) in humans, and although its clinical efficacy has been demonstrated, suboptimal pharmacokinetic aspects still remain a concern. To assess the basis of its highly variable oral bioavailability, this work deals with the study of AZT intestinal absorption by applying the gut sac technique. Permeation through the rat jejunum and ileum segments was analyzed at different drug concentrations and gut regions, with higher apparent permeability coefficients (P(app)) being found for the proximal regions of the small intestine compared to distal ones. Bi-directional permeation assays demonstrated that AZT is subjected to efflux mechanisms in distal regions of small intestine, which are blocked by verapamil (VER), thus demonstrating a P-glycoprotein (P-gp) mediated mechanism. The efficiency of AZT efflux increased in the distal ileum as consequence of exposure to AZT, with the amount of drug permeating from the mucosal to the serosal side diminishing after 35 min. Molecular modeling techniques were applied to analyze the binding mode of AZT to P-gp, which was compared to that of VER and AZT-Ac, a novel prodrug of AZT. The energy required for their solvation was found to constitute a critical feature in their binding to this efflux protein. The present work updates the impact of P-gp in AZT oral bioavailability, highlighting the need for further study of the dynamic nature of its expression at intestinal level. PMID:21540109

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

    PubMed

    Dahan, Arik; Amidon, Gordon L

    2010-02-15

    We have recently shown that efflux transport, mediated by multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP), is responsible for sulfasalazine low-permeability in the small intestine, thereby enabling its colonic targeting and therapeutic action. The purpose of the present study was to evaluate the potential pharmacokinetic interaction between indomethacin and sulfasalazine, in the mechanism of efflux transporter competition. The concentration-dependent effects of indomethacin on sulfasalazine intestinal epithelial transport were investigated across Caco-2 cell monolayers, in both apical to basolateral (AP-BL) and BL-AP directions. The interaction was then investigated in the in situ single-pass rat jejunal perfusion model. Sulfasalazine displayed 30-fold higher BL-AP than AP-BL Caco-2 permeability, indicative of net mucosal secretion. Indomethacin significantly increased AP-BL and decreased BL-AP sulfasalazine Caco-2 transport, in a concentration-dependent manner, with IC(50) values of 75 and 196 microM respectively. In the rat model, higher sulfasalazine concentrations resulted in higher intestinal permeability, consistent with saturation of efflux transporter. Without indomethacin, sulfasalazine demonstrated low rat jejunal permeability (vs. metoprolol). Indomethacin significantly increased sulfasalazine P(eff), effectively shifting it from BCS (biopharmaceutics classification system) Class IV to II. In conclusion, the data indicate that concomitant intake of indomethacin and sulfasalazine may lead to increased absorption of sulfasalazine in the small intestine, thereby reducing its colonic concentration and potentially altering its therapeutic effect. PMID:19944137

  14. [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

  15. In vitro-in vivo correlation of the effect of supersaturation on the intestinal absorption of BCS Class 2 drugs.

    PubMed

    Higashino, Haruki; Hasegawa, Tsubasa; Yamamoto, Mari; Matsui, Rie; Masaoka, Yoshie; Kataoka, Makoto; Sakuma, Shinji; Yamashita, Shinji

    2014-03-01

    The aim of this study was to establish an in vitro method for evaluating the effect of supersaturation on oral absorption of poorly water-soluble drugs in vivo. Albendazole, dipyridamole, gefitinib, and ketoconazole were used as model drugs. Supersaturation of each drug was induced by diluting its stock solution by fasted state simulated intestinal fluid (FaSSIF) (solvent-shift method), then dissolution and precipitation profile of the drug was observed in vitro. The crystalline form of the precipitate was checked by differential scanning calorimetry (DSC). For comparison, control suspension was prepared by suspending a drug powder directly into FaSSIF (powder-suspending method). In vivo intestinal absorption of the drug was observed in rats by determined the plasma concentration after intraduodenal administration of drug suspensions. For all drugs, suspensions prepared by solvent-shift method showed significantly higher dissolved concentration in vitro than that prepared by powder-suspending method, clearly indicated the induction of supersaturation. DSC analysis revealed that crystalline form of the precipitate profoundly affects the extent and the duration of supersaturation. A rat in vivo study confirmed that the supersaturation of these drugs increased the fraction absorbed from the intestine, which corresponded well to the in vitro dissolution and precipitation profile of drugs except for ketoconazole. For ketoconazole, an in vivo absorption study was performed in rats pretreated with 1-aminobenzotriazole, a potent inhibitor of CYP mediated metabolism. CYP inhibition study suggested that the high luminal concentration of ketoconazole caused by supersaturation saturated the metabolic enzymes and further increased the systemic exposure of the absorbed drug. The additional effects of supersaturation on the absorption of ketoconazole are consistent with previous studies in humans under differing gastric pH conditions. In conclusion, effects of supersaturation on the intestinal absorption of poorly water-soluble drugs could be predicted from in vitro dissolution and a precipitation study. However if supersaturation affects the pharmacokinetic profiles of drugs, such as a first-pass metabolism, a combination with in vivo study should be required to evaluate its impact on oral bioavailability. PMID:24460473

  16. Evaluation of the Intestinal Absorption Mechanism of Casearin X in Caco-2 Cells with Modified Carboxylesterase Activity.

    PubMed

    Moreira da Silva, Rodrigo; Verjee, Sheela; de Gaitani, Cristiane Masetto; Moraes de Oliveira, Anderson Rodrigo; Pires Bueno, Paula Carolina; Cavalheiro, Alberto José; Peporine Lopes, Norberto; Butterweck, Veronika

    2016-04-22

    The clerodane diterpene casearin X (1), isolated from the leaves of Casearia sylvestris, is a potential new drug candidate due to its potent in vitro cytotoxic activity. In this work, the intestinal absorption mechanism of 1 was evaluated using Caco-2 cells with and without active carboxylesterases (CES). An LC-MS method was developed and validated for the quantification of 1. The estimation of permeability coefficients was possible only under CES-inhibited conditions in which 1 is able to cross the Caco-2 cell monolayer. The mechanism is probably by active transport, with no significant efflux, but with a high retention of the compound inside the cells. The enzymatic hydrolysis assay demonstrates the susceptibility of 1 to first-pass metabolism as substrate for specific CES expressed in human intestine. PMID:26990770

  17. 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 (48.5±15.6 μg/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

  18. 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

  19. 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

  20. Green tea as inhibitor of the intestinal absorption of lipids: potential mechanism for its lipid-lowering effect.

    PubMed

    Koo, Sung I; Noh, Sang K

    2007-03-01

    Animal and epidemiological studies suggest that green tea catechins may reduce the risk of cardiovascular diseases [e.g., coronary heart disease (CHD)]. The health benefit of green tea has been attributed to its antioxidant and anti-inflammatory properties; however, considerable evidence suggests that green tea and its catechins may reduce the risk of CHD by lowering the plasma levels of cholesterol and triglyceride. Although the mechanism underlying such effect of green tea is yet to be determined, it is evident from in vitro and in vivo studies that green tea or catechins inhibit the intestinal absorption of dietary lipids. Studies in vitro indicate that green tea catechins, particularly (-)-epigallocatechin gallate, interfere with the emulsification, digestion, and micellar solubilization of lipids, critical steps involved in the intestinal absorption of dietary fat, cholesterol, and other lipids. Based on the observations, it is likely that green tea or its catechins lower the absorption and tissue accumulation of other lipophilic organic compounds. The available information strongly suggests that green tea or its catechins may be used as safe and effective lipid-lowering therapeutic agents. PMID:17296491

  1. 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

  2. Improvement of intestinal absorption of peptides: adsorption of B1-Phe monoglucosylated insulin to rat intestinal brush-border membrane vesicles.

    PubMed

    Hashimoto, T; Nomoto, M; Komatsu, K; Haga, M; Hayashi, M

    2000-09-01

    In a previous study we glycosylated insulin to improve its intestinal absorption. When the glycosylated product, p-(succinylamido)-phenyl-alpha-D-glucopyranoside (SAPG)-substituted insulin (SAPG-INS), was administered intra-intestinally to rats, it showed a greater hypoglycemic effect than native bovine insulin. The enhanced hypoglycemic effect of SAPG-INS was considered to be due to an increase in membrane permeability as well as an increase in resistance to enzymatic degradation. In particular, membrane permeability may be related to an interaction with the Na(+)-dependent D-glucose transporter (SGLT-1) which is located in the brush-border membrane of epithelial cells. The insulin product used in the previous study, however, comprised a mixture of mono-, di- and tri-SAPG-substituted insulin. In this study SAPG-INS with a defined substitution number and position was synthesized to examine the interaction between the transporter and glycosylated insulin in more detail. The new product was mono-SAPG-substituted insulin substituted at the B1-phenylalanine position (B1-SAPG-INS) and was selectively synthesized after protection of the A1-glycine and varepsilonB29-lysine amino acids. The hypoglycemic effect of B1-SAPG-INS in rats after an intravenous dose of 71 microg/kg was almost the same as that of native bovine insulin at a dose of 1 U/kg and B1-SAPG-INS retained about 60% of the immunoreactivity of native bovine insulin. The interaction of B1-SAPG-INS with the intestinal transporter was examined by a rapid filtration technique using (125)I-labeled B1-SAPG-INS and brush-border membrane vesicles (BBMVs) which were prepared from rat small intestine by the Mg-precipitation method. The amount of B1-SAPG-INS adsorbed or absorbed by BBMVs in the presence of an inward Na(+)-gradient into BBMVs was greater than that of native bovine insulin. This adsorption/absorption was significantly inhibited by the presence of 1 mM phloridzin. A similar inhibition was observed when Na(+) was replaced with K(+) and when B1-SAPG-INS was incubated with BBMVs at 4 degrees C. From the effect of osmolarity on the extent of adsorption/absorption, it was considered that B1-SAPG-INS was not taken up into the intravesicular space but adsorbed onto the external membrane surface of BBMVs. These findings suggested that B1-SAPG-INS was adsorbed specifically onto the transporter. The hypoglycemic effect of insulin was enhanced by glycosylation at the B1 position in in situ experiments using normal and diabetic rats. Consequently, it is suggested that B1-SAPG-INS was adsorbed specifically onto the glucose transporter of intestinal BBM. This specific adsorption may be involved in the mechanism of the enhanced hypoglycemic effect of B1-SAPG-INS both in normal and diabetic rats. PMID:10962227

  3. Relative contribution of small and large intestine to deglycosylation and absorption of flavonoids from Chrysanthemun morifolium extract.

    PubMed

    Lu, Xin-Yan; Sun, Dong-Li; Chen, Zhong-Jian; Chen, Ting; Li, Li-Ping; Xu, Zheng-Hao; Jiang, Hui-Di; Zeng, Su

    2010-10-13

    The flower of Chrysanthemum morifolium Ramat (CM) is an established part of traditional Chinese medicine (TCM). Luteolin and apigenin flavonoids are the effective components of the CM extract (CME); however, they exist in the orally consumed CME as glycosides. The present study was carried out to determine the relative contribution of the small and large intestine to the deglycosylation and absorption of flavonoids from CME using a rat model system. The distribution of luteolin and apigenin in rat gastrointestinal (GI) luminal contents, tissues, and plasmas was assessed after the oral administration of CME. The hydrolysis and absorption of CME flavonoids in different rat GI segments were further evaluated by using in situ ligated models and cell-free extracts prepared from rat GI segments. The results demonstrated that after the oral administration of CME, the magnitude of deglycosylation in rats was surprisingly high (about 30%) in the stomach and upper intestine within the first 5 min after ingestion, and early absorption in the plasma was detected. The results from site-limited administration revealed that the stomach was the initial hydrolysis site, while the duodenum was the first effective absorption site for CME flavonoids. Diminishing microbial flora in the jejunum had no significant effect on the hydrolysis of the flavonoids from CME, but the cell-free extracts prepared from rat GI segments demonstrated a strong ability to hydrolyze. Taken together, our findings suggest that enteric disposition contributes to the pharmacokinetics of luteolin and apigenin after oral administration of CME. Moreover, the upper digestive tract plays a key role in the hydrolysis and absorption of flavonoids in CME. PMID:20853834

  4. 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

  5. Conditional (intestinal-specific) knockout of the riboflavin transporter-3 (RFVT-3) impairs riboflavin absorption.

    PubMed

    Subramanian, Veedamali S; Lambrecht, Nils; Lytle, Christian; Said, Hamid M

    2016-02-15

    Riboflavin (RF) is indispensable for normal cell metabolism, proliferation, and growth. The RFVT-3 protein (product of the Slc52a3 gene) is expressed in the gut with the expression being restricted to the apical membrane domain of the polarized intestinal epithelial cells. The relative contribution of RFVT-3 to total carrier-mediated RF uptake in the native intestine, however, is not clear. We addressed this issue in the current investigation using a conditional (intestinal-specific) RFVT-3 knockout (cKO) mouse model developed by the Cre/Lox approach. All RFVT-3 cKO mice were found to be RF deficient and showed a significant growth and development retardation; also, nearly two-thirds of them died prematurely between the age of 6 and 12 wk. In vivo (intestinal and colonic loops) and in vitro (native isolated intestinal epithelial cells) uptake studies showed a severe inhibition in carrier-mediated RF uptake in the cKO mice compared with control littermates. We also observed a significant increase in the level of expression of oxidative stress-responsive genes in the intestine of the cKO mice compared with control littermates. Supplementation of the RFVT-3 cKO mice with pharmacological doses of RF led to a complete correction of the growth retardation and to normalization in the level of expression of the oxidative stress-responsive genes in the gut. These results show, for the first time, that the RFVT-3 system is the main transporter involved in carrier-mediated RF uptake in the native mouse small and large intestine, and that its dysfunction impairs normal RF body homeostasis. PMID:26660539

  6. 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

  7. Absorption characteristic of paeoniflorin-6'-O-benzene sulfonate (CP-25) in in situ single-pass intestinal perfusion in rats.

    PubMed

    Yang, Xiao-Dan; Wang, Chun; Zhou, Peng; Yu, Jun; Asenso, James; Ma, Yong; Wei, Wei

    2016-09-01

    1. Paeoniflorin-6'-O-benzene sulfonate (CP-25) was synthesized to improve the poor oral absorption of paeoniflorin (Pae). 2. This study was performed to investigate the absorptive behavior and mechanism of CP-25 in in situ single-pass intestinal perfusion in rats, using Pae as a control. 3. The results showed that intestinal absorption of CP-25 was neither segmental nor sex dependent. However, the main segment of intestine that absorbed Pae was the duodenum. Furthermore, passive transport was confirmed to be the main absorption pattern of CP-25. More importantly, the absorption of CP-25 was much higher than Pae in the small intestine. 4. Among the ABC transporter inhibitors, the absorption rate of Pae increased in the presence of P-gp inhibitors verapamil and GF120918, which indicated that Pae was a substrate of P-glycoprotein (P-gp), however, such was not observed in the presence of breast cancer resistance protein and multidrug resistance-associated protein 2. Finally, the ABC transporter inhibitors did not have any significant impact on CP-25 as demonstrated in the parallel studies. 5. CP-25 could improve the poor absorption of Pae, which may be attributed to both the lipid solubility enhancement and its resistance to P-gp-mediated efflux. PMID:26711120

  8. 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

  9. 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

  10. 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

  11. Stability of bovine lactoferrin in luminal extracts and mucosal homogenates from rat intestine: a prelude to oral absorption.

    PubMed

    Yao, Xudong; Bunt, Craig; Cornish, Jillian; Quek, Siew-Young; Wen, Jingyuan

    2014-12-01

    Oral delivery is the most common method for bovine lactoferrin (bLf) administration. However, the presence of proteolytic enzymes in the stomach and intestine limits the effective absorption of bLf within the gastrointestinal (GI) tract. To determine the extent of bLf proteolysis, several digestion models were developed using luminal extracts and mucosal homogenates isolated from four regions of rat intestine: duodenum, jejunum, ileum, and proximal colon. The kinetics of bLf degradation followed a pseudo-first-order rate, and almost complete hydrolysis of bLf was observed in the luminal extracts, indicating that bLf is more susceptive to luminal peptidases rather than mucosal enzymes. Moreover, a significant reduction in bLf proteolysis was observed in the presence of soybean trypsin inhibitor (SBTI), bestatin, and bacitracin, suggesting that there exist trypsin-like and aminopeptidase-like proteases, which play a key role in the degradation of bLf in the intestine. Lactoferrin was then encapsulated in several lipid-based delivery systems including liposomes and solid lipid particles (SLPs) with polymer modification, showing at least 50% of intact bLf remaining after 6 h of digestion compared with native bLf. These findings suggest that particle encapsulation may modulate protein digestion and possibly achieve sufficient oral bioavailability of bLf. PMID:24890384

  12. 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.

  13. Ouabain-sensitive bicarbonate secretion and acid absorption by the marine teleost fish intestine play a role in osmoregulation.

    PubMed

    Grosell, M; Genz, J

    2006-10-01

    The gulf toadfish (Opsanus beta) intestine secretes base mainly in the form of HCO3- via apical anion exchange to serve Cl- and water absorption for osmoregulatory purposes. Luminal HCO3- secretion rates measured by pH-stat techniques in Ussing chambers rely on oxidative energy metabolism and are highly temperature sensitive. At 25 degrees C under in vivo-like conditions, secretion rates averaged 0.45 micromol x cm(-2) x h(-1), of which 0.25 micromol x cm(-2) x h(-1) can be accounted for by hydration of endogenous CO2 partly catalyzed by carbonic anhydrase. Complete polarity of secretion of HCO3- and H+ arising from the CO2 hydration reaction is evident from equal rates of luminal HCO3- secretion via anion exchange and basolateral H+ extrusion. When basolateral H+ extrusion is partly inhibited by reduction of serosal pH, luminal HCO3- secretion is reduced. Basolateral H+ secretion occurs in exchange for Na+ via an ethylisopropylamiloride-insensitive mechanism and is ultimately fueled by the activity of the basolateral Na+-K+-ATPase. Fluid absorption by the toadfish intestine to oppose diffusive water loss to the concentrated marine environment is accompanied by a substantial basolateral H+ extrusion, intimately linking osmoregulation and acid-base balance. PMID:16709644

  14. 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

  15. 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...

  16. 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 ...

  17. 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...

  18. 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...

  19. 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

  20. Intestinal expression of human apolipoprotein A-IV in transgenic mice fails to influence dietary lipid absorption or feeding behavior.

    PubMed Central

    Aalto-Setälä, K; Bisgaier, C L; Ho, A; Kieft, K A; Traber, M G; Kayden, H J; Ramakrishnan, R; Walsh, A; Essenburg, A D; Breslow, J L

    1994-01-01

    Two transgenic mouse lines, expressing low or high amounts of human apo A-IV were created. In low and high expressor HuAIVTg mice on a chow diet, serum human apo A-IV levels were 6 and 25 times the normal human level and on a high fat diet, they were 12 and 77 times higher. Human apo A-IV was equally distributed between lipoprotein (mainly HDL) and lipid-free fractions. Intestinal absorption of radiolabeled cholesterol and triglycerides was unaffected in HuAIVTg mice. Vitamin A, carried exclusively in chylomicrons and their remnants, was catabolized normally. When an intragastric vitamin E bolus is given to the HuAIVTg mice, the initial absorption and appearance in triglyceride-rich lipoproteins was similar to that observed in normal mice. However, elevated amounts of vitamin E were subsequently observed in the VLDL of the HuAIVTg mice. Furthermore, in the fed state, serum VLDL triglycerides were markedly elevated in HuAIVTg mice. This effect was greater in high expressor mice. Serum total cholesterol was not elevated, but the distribution was altered in the HuAIVTg mice; VLDL-C was increased at the expense of VLDL-C. Kinetic studies suggested a delayed clearance of VLDL in HuAIVTg mice. Apo A-IV has been suggested to be a satiety factor, but no effect on feeding behavior or weight gain was observed in these HuAIVTg mice. In summary, our studies with HuAIVTg mice show that additional apo A-IV does not effect intestinal absorption of fat and fat-soluble vitamins, and at least chronic elevation of plasma apo A-IV does not effect feeding behavior in this model system. Images PMID:8163677

  1. Pathophysiology of intestinal uptake and absorption of antigens in food allergy.

    PubMed

    Walker, W A

    1987-11-01

    An important adaptation of the gastrointestinal tract to the extrauterine environment is its development of a mucosal barrier against the penetration of proteins and protein fragments. To combat the potential danger of invasion across the mucosal barrier, the infant must develop within the lumen and on the luminal mucosal surface an elaborate system of defense mechanisms that act to control and maintain the epithelium as an impermeable barrier to the uptake of macromolecular antigens. These defenses include a unique local immunologic system adapted to function in the complicated milieu of the intestine as well as other nonimmunologic processes such as a gastric barrier, intestinal surface secretions, peristaltic movement, etc, all of which help to provide maximum protection for the intestinal surface. Unfortunately, during the immediate postpartum period, especially for premature and "small-for-date" infants, this elaborate local defense system is incompletely developed. As a result of the delay in the maturation of the mucosal barrier, newborn infants are particularly vulnerable to pathologic penetration by harmful intraluminal substances. The consequences of altered defense are susceptibility to infection and the potential for hypersensitivity reactions and the formation of immune complexes. With these reactions comes the potential for developing life-threatening diseases such as necrotizing enterocolitis, sepsis, and hepatitis. Fortunately, nature has provided a means for passively protecting the "vulnerable" newborn against the dangers of a deficient intestinal defense system: human milk. It is now increasingly apparent that human milk contains not only antibodies and viable leukocytes, but many other substances that can interfere with bacterial colonization and prevent antigen penetration. PMID:3318588

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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?

  7. 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

  8. 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.

  9. 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

  10. Aqueous extracts of husks of Plantago ovata reduce hyperglycaemia in type 1 and type 2 diabetes by inhibition of intestinal glucose absorption.

    PubMed

    Hannan, J M A; Ali, L; Khaleque, J; Akhter, M; Flatt, P R; Abdel-Wahab, Y H A

    2006-07-01

    Plantago ovata has been reported to reduce postprandial glucose concentrations in diabetic patients. In the present study, the efficacy and possible modes of action of hot-water extracts of husk of P. ovata were evaluated. The administration of P. ovata (0.5 g/kg body weight) significantly improved glucose tolerance in normal, type 1 and type 2 diabetic rat models. When the extract was administered orally with sucrose solution, it suppressed postprandial blood glucose and retarded small intestinal absorption without inducing the influx of sucrose into the large intestine. The extract significantly reduced glucose absorption in the gut during in situ perfusion of small intestine in non-diabetic rats. In 28 d chronic feeding studies in type 2 diabetic rat models, the extract reduced serum atherogenic lipids and NEFA but had no effect on plasma insulin and total antioxidant status. No effect of the extract was evident on intestinal disaccharidase activity. Furthermore, the extract did not stimulate insulin secretion in perfused rat pancreas, isolated rat islets or clonal beta cells. Neither did the extract affect glucose transport in 3T3 adipocytes. In conclusion, aqueous extracts of P. ovata reduce hyperglycaemia in diabetes via inhibition of intestinal glucose absorption and enhancement of motility. These attributes indicate that P. ovata may be a useful source of active components to provide new opportunities for diabetes therapy. PMID:16870001

  11. 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 120 min 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

  12. Effect of the antiprotozoal agent metronidazole (Flagyl) on absorptive and digestive functions of the rat intestine.

    PubMed

    Sanyal, S N; Jamba, L; Channan, M

    1992-01-01

    Metronidazole (Flagyl), an antibiotic commonly used in treating intestinal infections, when administered orally at a dose level of 100 mg/kg body weight daily for 7 days to rats brought about a significant elevation of the uptake of end-product nutrients like D-glucose, L-alanine, L-aspartic acid and L-leucine in the intestinal segments. Brush border membrane-bound hydrolytic enzymes, i.e. sucrase, lactase, maltase, alkaline phosphatase and leucine aminopeptidase levels, were also elevated. Substrate kinetic analysis of the uptake of nutrients as well as the enzymes indicated that the drug increased the maximum of apparent initial velocity, while the substrate affinity constants did not change. Studies of the temperature-dependent parameters of the nutrient uptake and the enzyme activity revealed that metronidazole did not induce any shift in the transition temperature (T(o)) for the uptake but the energy of activation (Ea) was reduced in all the cases except those of maltase and leucine aminopeptidase, which registered an increase in Ea and a marginal shift in T(o), respectively. A significant elevation was seen in the levels of membrane cholesterol, phospholipid, ganglioside and plasmalogen in metronidazole-treated animals, while triglycerides and the non-esterified fatty acids remained unaffected. The effects produced by metronidazole treatment persisted in the animals, which were allowed a recovery period of 7 days after the drug regimen. PMID:1471860

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

    PubMed Central

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

    2008-01-01

    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 α-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

  14. 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...

  15. 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

  16. 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

  17. 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.

  18. [Kinetics of inactivation of calf intestine alkaline phosphatase by EDTA with absorption spectrum method].

    PubMed

    Wang, J Y; Peng, X J; Yang, D; An, L J; Hu, J H; Zheng, X F

    2001-10-01

    Calf intestinal alkaline phosphatase (EC.3.1.3.1) is a dimeric metalloenzyme composed of two identical subunits, the each active site of which contains a tight cluster of two zinc ions and one magnesium ion. The kinetic theory of the substrate reaction during irreversible inhibition of enzyme activity previously described by Tsou has been applied for a study on the kinetics of the course of inactivation of the enzyme by EDTA. The kinetics of the substrate reaction with different concentrations of the substrate p-nitrophenylphosphate (PNPP) and inactivator EDTA suggested a competitive complexing mechanism for inactivation by EDTA, and the process of inactivation composed of the rapid initial formation of an enzyme-EDTA complex, in which the conformation of enzyme has been changed, and then zinc ions are finally removed from the enzyme. PMID:12945337

  19. 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

  20. 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

  1. Prediction of the Passive Intestinal Absorption of Medicinal Plant Extract Constituents with the Parallel Artificial Membrane Permeability Assay (PAMPA).

    PubMed

    Petit, Charlotte; Bujard, Alban; Skalicka-Woźniak, Krystyna; Cretton, Sylvian; Houriet, Joëlle; Christen, Philippe; Carrupt, Pierre-Alain; Wolfender, Jean-Luc

    2016-03-01

    At the early drug discovery stage, the high-throughput parallel artificial membrane permeability assay is one of the most frequently used in vitro models to predict transcellular passive absorption. While thousands of new chemical entities have been screened with the parallel artificial membrane permeability assay, in general, permeation properties of natural products have been scarcely evaluated. In this study, the parallel artificial membrane permeability assay through a hexadecane membrane was used to predict the passive intestinal absorption of a representative set of frequently occurring natural products. Since natural products are usually ingested for medicinal use as components of complex extracts in traditional herbal preparations or as phytopharmaceuticals, the applicability of such an assay to study the constituents directly in medicinal crude plant extracts was further investigated. Three representative crude plant extracts with different natural product compositions were chosen for this study. The first extract was composed of furanocoumarins (Angelica archangelica), the second extract included alkaloids (Waltheria indica), and the third extract contained flavonoid glycosides (Pueraria montana var. lobata). For each medicinal plant, the effective passive permeability values Pe (cm/s) of the main natural products of interest were rapidly calculated thanks to a generic ultrahigh-pressure liquid chromatography-UV detection method and because Pe calculations do not require knowing precisely the concentration of each natural product within the extracts. The original parallel artificial membrane permeability assay through a hexadecane membrane was found to keep its predictive power when applied to constituents directly in crude plant extracts provided that higher quantities of the extract were initially loaded in the assay in order to ensure suitable detection of the individual constituents of the extracts. Such an approach is thus valuable for the high-throughput, cost-effective, and early evaluation of passive intestinal absorption of active principles in medicinal plants. In phytochemical studies, obtaining effective passive permeability values of pharmacologically active natural products is important to predict if natural products showing interesting activities in vitro may have a chance to reach their target in vivo. PMID:26872320

  2. Influence of age and hormonal treatment on intestinal absorption of magnesium in ovariectomised rats.

    PubMed

    Coudray, C; Gaumet, N; Bellanger, J; Coxam, V; Barlet, J P; Rayssiguier, Y

    1999-06-01

    This study was designed to assess the effect of age, ovariectomy and estrogen treatment on the absorption and the balance of Mg in the rat. Three groups of fifteen 6- (mature), 12- (old), and 30-month-old female rats (senescent), fed a diet containing 1.5 g of Mg/kg were used in the present study. Within each group, 10 rats were surgically ovariectomized (OVX). From day 2 until day 60 after OVX, they were s.c. injected with either solvant or 17 beta-estradiol (E: 10 mg/kg bw/48 h, n = 5). Five other rats were sham operated (SH, n = 5) and received solvent alone. Animals were pair fed 6 g/100 g bw/day and distilled water was available ad libitum. Food intake, urine and feces from each individual rat were measured 1 day per week, during the last 5 weeks. The results clearly showed that apparent Mg absorption (per cent) was not significantly altered with aging. Moreover, whatever the age, neither OVX nor E treatment had any significant effect on Mg apparent absorption. PMID:10423705

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. Transport properties of puerarin and effect of extract of Radix Angelicae dahuricae on puerarin intestinal absorption using in situ and in vitro models.

    PubMed

    Liao, Zheng-Gen; Liang, Xin-Li; Zhu, Jing-Yun; Zhao, Guo-Wei; Guan, Yong-Mei; Cao, Yun-Chao; Zhao, Li-Jun

    2014-09-01

    The root of Angelica dahurica (Radix Angelicae Dahuricae, RAD), which contains coumarins and volatile oil as its main classes of active components, is often given in conjunction with Pueraria root (Radix Puerariae, RP), which contains the phytoestrogen puerarin. The two herbs are considered to be compatible 'herb-pairs' in traditional Chinese medicine. The present investigation investigates the absorption of puerarin from RP and the effect of the total coumarins and volatile oil from RAD on its absorption. The everted gut sac and single-pass intestinal perfusion methods were used, respectively. The results showed that the absorption of puerarin in the jejunum was significantly increased in the presence of the coumarins and/or volatile oil. The absorption rate constant (K(a)) of puerarin increased gradually until the concentration reached 160 µg · mL(-1), after which its absorption became saturated and the apparent permeability (P(app)) values significantly decreased. The results showed that the intestinal absorption mechanisms of puerarin involved active transportation processes and that puerarin is likely to be a substrate of P-gp because verapamil significantly affected its P(app) and K(a). The absorption of puerarin significantly increased (p < 0.01) when combined with RAD extracts, as shown by the increase in concentration of puerarin in blood from the hepatic portal vein, supporting the concept of RAD and RP as a compatible herb-pair. PMID:24756954

  9. Absorption of protein and protein fragments in the developing intestine: role in immunologic/allergic reactions.

    PubMed

    Walker, W A

    1985-01-01

    An important adaptation of the gastrointestinal tract to the extrauterine environment is its development of a mucosal barrier against the penetration of proteins and protein fragments. To combat the potential danger of invasion across the mucosal barrier the newborn infant must develop within the lumen and on the luminal mucosal surface an elaborate system of defense mechanisms which act to control and maintain the epithelium as an impermeable barrier to the uptake of macromolecular antigens. As a result of a delay in the maturation of the mucosal barrier, newborn infants are particularly vulnerable to pathologic penetration by harmful intraluminal substances. The consequences of altered defense are susceptibility to infection and the potential for hypersensitivity reactions and the formation of immune complexes. With these reactions comes the potential for developing life-threatening diseases such as necrotizing enterocolitis, sepsis, and hepatitis. Fortunately, "nature" has provided a means for passively protecting the "vulnerable" newborn against the dangers of a deficient intestinal defense system, namely human milk. It is now increasingly apparent that human milk contains not only antibodies and viable leukocytes but many other substances that can interfere with bacterial colonization and prevent antigen penetration. PMID:3966050

  10. 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.

  11. 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.

  12. Studies on digestion and absorption in the intestines of growing pigs. 6. Measurements of the flow of amino acids.

    PubMed

    Low, A G

    1979-01-01

    1. Digesta were collected from seventeen pigs initially of 30 kg live weight fitted with single re-entrant cannulas in either the duodenum, jejunum or ileum. A further twenty-four pigs were used in a conventional digestibility trial. 2. The pigs received three types of diet containing: barley, fine wheat offal, white fish meal, minerals and vitamins (diet BWF); starch, sucrose, maize, oil, cellulose, minerals and vitamins and either groundnut (diet SSG) or casein (diet SSC). 3. Amino acids were measured in samples representative of the digesta flow in 24 h periods and in the faeces collected in 5 d periods. 4. For each diet the total flow in 24 h periods in the duodenum for aspartic acid, threonine, serine and glycine exceeded or equalled intake, while the amounts of the other amino acids were usually rather less than intake. 5. For each diet in the jejunum, the amounts of glycine and cystine exceeded intake in 24 h periods, while methionine, arginine and tyrosine were the most rapidly absorbed amino acids anterior to the cannula site. On average 0.22, 0.25 and 0.31 of the dietary amino acids were absorbed anterior to the cannula site for diets BWF, SSG and SSC, respectively. 6. For each diet in the ileum, the least apparently absorbed dietary amino acids were glycine and cystine. On average 0.81, 0.83 and 0.95 of the dietary amino acids were absorbed anterior to the cannula site for diets BWF, SSG and SSC, respectively. 7. There was net disappearance of most amino acids in the large intestine, but some net accumulation occurred in this region. 8. The results are discussed in relation to the amino acid composition of endogenous secretions (particularly glycine in bile), protease and peptidase specificity, free amino acid absorption and the role of the microflora in the large intestine. PMID:420746

  13. 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

  14. 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

  15. [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

  16. 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 μg mL(-1) BAK-SME formulation in rat intestinal segments of duodenum, jejunum, ileum and colon were 30.91 × 10(-3), 23.61 × 10(-3), 29.43 × 10(-3) and 23.62 × 10(-3) cm min(-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 150 mg kg(-1) was determined in rats. The Cmax and the AUC(0-24h) were 515.4 ng mL(-1) and 4,327.2 h ng mL(-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

  17. 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...

  18. 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

  19. 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...

  20. 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

  1. Enhancing the intestinal absorption of molecules containing the polar guanidino functionality: a double-targeted prodrug approach.

    PubMed

    Sun, Jing; Dahan, Arik; Amidon, Gordon L

    2010-01-28

    A prodrug strategy was applied to guanidino-containing analogues to increase oral absorption via hPEPT1 and hVACVase. l-Valine, l-isoleucine, and l-phenylalanine esters of [3-(hydroxymethyl)phenyl]guanidine (3-HPG) were synthesized and evaluated for transport and activation. In HeLa/hPEPT1 cells, Val-3-HPG and Ile-3-HPG exhibited high affinity to hPEPT1 (IC(50): 0.65 and 0.63 mM, respectively), and all three l-amino acid esters showed higher uptake (2.6- to 9-fold) than the parent compound 3-HPG. Val-3-HPG and Ile-3-HPG demonstrated remarkable Caco-2 permeability enhancement, and Val-3-HPG exhibited comparable permeability to valacyclovir. In rat perfusion studies, Val-3-HPG and Ile-3-HPG permeabilities were significantly higher than 3-HPG and exceeded/matched the high-permeability standard metoprolol, respectively. All the l-amino acid 3-HPG esters were effectively activated in HeLa and Caco-2 cell homogenates and were found to be good substrates of hVACVase (k(cat)/K(m) in mM(-1) x s(-1): Val-3-HPG, 3370; Ile-3-HPG, 1580; Phe-3-HPG, 1660). In conclusion, a prodrug strategy is effective at increasing the intestinal permeability of polar guanidino analogues via targeting hPEPT1 for transport and hVACVase for activation. PMID:19957998

  2. 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

  3. Intestinal absorption of dietary cadmium in women depends on body iron stores and fiber intake.

    PubMed Central

    Berglund, M; Akesson, A; Nermell, B; Vahter, M

    1994-01-01

    Measurements of intake and uptake of cadmium in relation to diet composition were carried out in 57 nonsmoking women, 20-50 years of age. A vegetarian/high-fiber diet and a mixed-diet group were constructed based on results from a food frequency questionnaire. Duplicate diets and the corresponding feces were collected during 4 consecutive days in parallel with dietary recording of type and amount of food ingested for determination of the dietary intake of cadmium and various nutrients. Blood and 24-hr urine samples were collected for determination of cadmium, hemoglobin, ferritin, and zinc. There were no differences in the intake of nutrients between the mixed-diet and the high-fiber diet groups, except for a significantly higher intake of fiber (p < 0.001) and cadmium (p < 0.002) in the high-fiber group. Fecal cadmium corresponded to 98% in the mixed-diet group and 100% in the high-fiber diet group. No differences in blood cadmium (BCd) or urinary cadmium (UCd) between groups could be detected. There was a tendency toward higher BCd and UCd concentrations with increasing fiber intake; however, the concentrations were not statistically significant at the 5% level, indicating an inhibitory effect of fiber on the gastrointestinal absorption of cadmium. Sixty-seven percent of the women had serum ferritin < 30 micrograms/l, indicating reduced body iron stores, which were highly associated with higher BCd (irrespective of fiber intake). BCd was mainly correlated with UCd, serum ferritin, age, anf fibre intake. UCd and serum ferritin explained almost 60% of the variation in BCd.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1. Figure 2. Figure 3. A Figure 3. B Figure 4. Figure 5. PMID:7713018

  4. Impaired Intestinal Calcium Absorption in Protein 4.1R-deficient Mice Due to Altered Expression of Plasma Membrane Calcium ATPase 1b (PMCA1b)*

    PubMed Central

    Liu, Congrong; Weng, Haibao; Chen, Lixiang; Yang, Shaomin; Wang, Hua; Debnath, Gargi; Guo, Xinhua; Wu, Liancheng; Mohandas, Narla; An, Xiuli

    2013-01-01

    Protein 4.1R was first identified in the erythrocyte membrane skeleton. It is now known that the protein is expressed in a variety of epithelial cell lines and in the epithelia of many tissues, including the small intestine. However, the physiological function of 4.1R in the epithelial cells of the small intestine has not so far been explored. Here, we show that 4.1R knock-out mice exhibited a significantly impaired small intestinal calcium absorption that resulted in secondary hyperparathyroidism as evidenced by increased serum 1,25-(OH)2-vitamin D3 and parathyroid hormone levels, decreased serum calcium levels, hyperplasia of the parathyroid, and demineralization of the bones. 4.1R is located on the basolateral membrane of enterocytes, where it co-localizes with PMCA1b (plasma membrane calcium ATPase 1b). Expression of PMCA1b in enterocytes was decreased in 4.1−/− mice. 4.1R directly associated with PMCA1b, and the association involved the membrane-binding domain of 4.1R and the second intracellular loop and C terminus of PMCA1b. Our findings have enabled us to define a functional role for 4.1R in small intestinal calcium absorption through regulation of membrane expression of PMCA1b. PMID:23460639

  5. Intestinal absorption, blood transport and hepatic and muscle metabolism of fatty acids in preruminant and ruminant animals.

    PubMed

    Hocquette, J F; Bauchart, D

    1999-01-01

    Current research on lipid metabolism in ruminants aims to improve the growth and health of the animals and the muscle characteristics associated with meat quality. This review, therefore, focuses on fatty acid (FA) metabolism from absorption to partitioning between tissues and metabolic pathways. In young calves, which were given high-fat milk diets, lipid absorption is delayed because the coagulation of milk caseins results in the retention of dietary fat as an insoluble clot in the abomasum. After weaning, the calves were fed forage- and cereal-based diets containing low levels of long-chain fatty acids (LCFA) but leading to high levels of volatile fatty acid (VFA) production by the rumen microflora. Such differences in dietary FA affect: i) the lipid transport system via the production of lipoproteins by the intestine and the liver, and (ii) the subsequent metabolism of lipids and FA by tissues. In preruminant calves, high-fat feed stimulates the secretion of triacylglycerols (TG)-rich lipoproteins (chylomicrons, very-low density lipoproteins (VLDL)). Diets rich in polyunsaturated FA (PUFA) stimulate the production of chylomicrons by the intestine (at peak lipid absorption) and of high density lipoproteins by the liver, leading to high blood concentrations of cholesterol. High levels of non-esterified FA (NEFA) uptake by the liver in high-yielding dairy cows in early lactation leads to TG infiltration of the hepatocytes (fatty liver). This is due to the low chronic capacity of the liver to synthesise and secrete VLDL particles. This abnormality in hepatic FA metabolism involves defects in apolipoprotein B synthesis and low availability of apolipoproteins and lipids for VLDL packaging. Fatty liver in calves is also caused by milk containing either soybean oil (rich in n-6 PUFA), or coconut oil (rich in C12:0 and C14:0). The ability of muscle tissue to use FA as an energy source depends on its mitochondrial content and, hence, on many physiological factors. The uptake and partitioning of LCFA between oxidation and storage in muscle is regulated by the activity of key intracellular enzymes and binding proteins. One such protein, carnitine palmitoyltransferase I (CPT I) controls the transport of LCFA into mitochondria. Metabolites derived from LCFA inhibit glucose oxidation, decrease the activity of CPT I and decrease the efficiency of ATP production by mitochondria. Most research on tissue lipid metabolism in ruminants is focused on: i) the partitioning of FA oxidation between intracellular peroxisomes and mitochondria in the liver and in muscles; (ii) the regulation of lipid metabolism by leptin, a recently discovered hormone secreted by mature adipocytes; and iii) the effects of activation of the nuclear receptors (PPARs and RXR) by LCFA or by phytol metabolites derived from chlorophyll. PMID:10222498

  6. Small intestine (image)

    MedlinePlus

    The small intestine is the portion of the digestive system most responsible for absorption of nutrients from food into ... the duodenum. This short first portion of the small intestine is followed by the jejunum and the ...

  7. 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

  8. 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

  9. [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

  10. Predicting both passive intestinal absorption and the dissociation constant toward albumin using the PAMPA technique.

    PubMed

    Bujard, Alban; Sol, Marine; Carrupt, Pierre-Alain; Martel, Sophie

    2014-10-15

    The parallel artificial membrane permeability assay (PAMPA) is a high-throughput screening (HTS) method that is widely used to predict in vivo passive permeability through biological barriers, such as the skin, the blood brain barrier (BBB) and the gastrointestinal tract (GIT). The PAMPA technique has also been used to predict the dissociation constant (Kd) between a compound and human serum albumin (HSA) while disregarding passive permeability. Furthermore, the assay is based on the use of two separate 5-point kinetic experiments, which increases the analysis time. In the present study, we adapted the hexadecane membrane (HDM)-PAMPA assay to both predict passive gastrointestinal absorption via the permeability coefficient logPe value and determine the Kd. Two assays were performed: one in the presence and one in the absence of HSA in the acceptor compartment. In the absence of HSA, logPe values were determined after a 4-h incubation time, as originally described, but the dimethylsulfoxide (DMSO) percentage and pH were altered to be compatible with the protein. In parallel, a second PAMPA assay was performed in the presence of HSA during a 16-h incubation period. By adding HSA, a variation in the amount of compound crossing the membrane was observed compared to the permeability measured in the absence of HSA. The concentration of compound reaching the acceptor compartment in each case was used to determine both parameters (logPe and logKd) using numerical simulations, which highlighted the originality of this method because these calculations required only two endpoint measurements instead of a complete kinetic study. It should be noted that the amount of compound that reaches the acceptor compartment in the presence of HSA is modulated by complex dissociation in the receptor compartment. Only compounds that are moderately bound to albumin (-3

  11. Lgr5 positive stem cells sorted from small intestines of diabetic mice differentiate into higher proportion of absorptive cells and Paneth cells in vitro.

    PubMed

    Zhong, Xian-Yang; Yu, Tao; Zhong, Wa; Li, Jie-Yao; Xia, Zhong-Sheng; Yuan, Yu-Hong; Yu, Zhong; Chen, Qi-Kui

    2015-08-01

    Intestinal epithelial stem cells (IESCs) can differentiate into all types of intestinal epithelial cells (IECs) and Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) is a marker for IESC. Previous studies reported enhanced proliferation of IECs in diabetic mice. In this study, the in vitro differentiation of Lgr5 positive IESCs sorted from diabetic mice was further investigated. The diabetic mouse model was induced by streptozotocin (STZ), and crypt IECs were isolated from small intestines. Subsequently, Lgr5 positive IESCs were detected by flow cytometry (FCM) and sorted by magnetic activated cell sorting (MACS). Differentiation of the sorted IESCs was investigated by detecting the IEC markers in the diabetic mice using immunostaining, quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR), and Western blot analysis, which was compared with normal mice. We found that the proportion of Lgr5 positive cells in the crypt IECs of diabetic mice was higher than that of control mice (P < 0.05). Lgr5 positive IESCs could be significantly enriched in Lgr5 positive cell fraction sorted by MACS. Furthermore, the absorptive cell marker sucrase-isomaltase (SI) and the Paneth cell marker lysozyme 1 (Lyz1) were more highly expressed in the differentiated cells derived from Lgr5 positive IESCs of diabetic mice in vitro (P < 0.05). We demonstrate that the number of Lgr5 positive IESCs is significantly increased in the small intestines of STZ-induced diabetic mice. Lgr5 positive IESCs sorted from the diabetic mice can differentiate into a higher proportion of absorptive cells and Paneth cells in vitro. We characterized the expression of Lgr5 in the small intestine of diabetic mice, and sorted Lgr5 positive intestinal epithelial stem cells (IESCs) for investigating their differentiation in vitro. We proved that the quantity of Lgr5 positive IESCs was significantly increased in the small intestines of diabetic mice. IESCs sorted from the diabetic mice can differentiate into a higher proportion of absorptive cells and Paneth cells in vitro. PMID:26122164

  12. [Treatment of intestinal failure in adults. I. Dietary measures].

    PubMed

    Wanten, G; Sauerwein, H P; van den Broek, P; Kristinsson, J

    2007-08-18

    Patients with intestinal failure, predominantly caused by short-bowel syndrome, have impaired quality of life due to the frequent development of complications. Dietary modifications have an established role in the treatment of short-bowel syndrome. Treatment of short-bowel syndrome includes optimising the balance of fluids and nutrients in the presence of reduced absorption. The population is heterogeneous due to differences in anatomical structure and the functional status of the remaining intestine. Diet must therefore be tailored to the individual patient. Determining the appropriate amount of carbohydrates is based on the presence of the colon, because carbohydrates are processed in the colon by bacterial fermentation. Patients with a jejunostomy rapidly become dehydrated because they lose more sodium and fluids than are taken up enterally. The jejunum rapidly absorbs solutions with high salt concentrations, such as the WHO-recommended oral rehydration solution. Replacement of long-chain fatty acids with water-soluble medium-chain fatty acids increases the energy intake in patients with short-bowel syndrome and a colon. Extra attention should be given to electrolytes, trace elements and vitamins. Patients with short-bowel syndrome and a colon are at risk for oxalate nephropathy. For these patients, a low oxalate diet is recommended. With these interventions, many patients with intestinal failure will ultimately become independent of total parenteral nutrition. PMID:17874637

  13. 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

  14. 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 µM) 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

  15. Effects of Polyoxyethylene Alkyl Ethers on the Intestinal Transport and Absorption of Rhodamine 123: A P-glycoprotein Substrate by In Vitro and In Vivo Studies.

    PubMed

    Zhao, Wanting; Uehera, Sachiyo; Tanaka, Keiichiro; Tadokoro, Shuhei; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2016-04-01

    We examined the effects of polyoxyethylene alkyl ethers (Brijs) on the intestinal transport and absorption of rhodamine 123, a P-glycoprotein (P-gp) substrate, by in vitro and in vivo studies. Brijs increased the absorptive transport of rhodamine 123 and decreased its secretory transport in the in vitro diffusion chamber method. However, Brijs did not change the transport of 5(6)-carboxyfluorescein, a non-P-gp substrate, indicating that the effect of Brijs on the transport of drugs was P-gp substrate-specific. The effects of Brijs on rhodamine 123 transport across Caco-2 cell monolayers were also examined. Secretory transport of rhodamine 123 was enhanced and its absorptive transport was significantly reduced in the presence of Brijs. Furthermore, in the in vivo studies, Brijs also enhanced the intestinal absorption of rhodamine 123 in rats. The intestinal membrane damage produced by Brijs was also evaluated by measuring the activity of lactate dehydrogenase and the release of protein. We found almost no intestinal damage in the presence of various Brijs. These findings suggest that Brijs might inhibit the function of intestinal P-gp, thereby increasing the intestinal transport and absorption of P-gp substrates without serious intestinal membrane damage. PMID:26968974

  16. 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

  17. 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

  18. 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.

  19. 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

  20. Multiple efflux pumps are involved in the transepithelial transport of colchicine: combined effect of p-glycoprotein and multidrug resistance-associated protein 2 leads to decreased intestinal absorption throughout the entire small intestine.

    PubMed

    Dahan, Arik; Sabit, Hairat; Amidon, Gordon L

    2009-10-01

    The purpose of this study was to thoroughly characterize the efflux transporters involved in the intestinal permeability of the oral microtubule polymerization inhibitor colchicine and to evaluate the role of these transporters in limiting its oral absorption. The effects of P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) inhibitors on colchicine bidirectional permeability were studied across Caco-2 cell monolayers, inhibiting one versus multiple transporters simultaneously. Colchicine permeability was then investigated in different regions of the rat small intestine by in situ single-pass perfusion. Correlation with the P-gp/MRP2 expression level throughout different intestinal segments was investigated by immunoblotting. P-gp inhibitors [N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918), verapamil, and quinidine], and MRP2 inhibitors [3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK571), indomethacin, and p-aminohippuric acid (p-AH)] significantly increased apical (AP)-basolateral (BL) and decreased BL-AP Caco-2 transport in a concentration-dependent manner. No effect was obtained by the BCRP inhibitors fumitremorgin C (FTC) and pantoprazole. P-gp/MRP2 inhibitors combinations greatly reduced colchicine mucosal secretion, including complete abolishment of efflux (GF120918/MK571). Colchicine displayed low (versus metoprolol) and constant permeability along the rat small-intestine. GF120918 significantly increased colchicine permeability in the ileum with no effect in the jejunum, whereas MK571 augmented jejunal permeability without changing the ileal transport. The GF120918/MK571 combination caused an effect similar to that of MK571 alone in the jejunum and to that of GF120918 alone in the ileum. P-gp expression followed a gradient increasing from proximal to distal segments, whereas MRP2 decreased from proximal to distal small intestinal regions. Overall, it was revealed that the combined effect of P-gp and MRP2, but not BCRP, dominates colchicine transepithelial transport, leading to complete coverage of the entire small intestine, and makes the efflux transport dominate the intestinal permeability process. PMID:19589874

  1. Mechanisms of calcium absorption by anterior and posterior segments of the intestinal tract of juvenile lake sturgeon.

    PubMed

    Genz, Janet; Carriere, Benjamin; Anderson, W Gary

    2013-10-01

    Rapid growth in juvenile fish increases calcium demand, and the intestine may play a role in calcium homeostasis at this life stage, in addition to branchial and renal transport. This study examined calcium flux in the gastrointestinal tract (GIT) of freshwater juvenile lake sturgeon acclimated to 0.14, 0.34, and 2.26mmol L(-1) environmental calcium. Net Ca(2+) flux did not differ due to environmental [Ca(2+)] in either the anterior or posterior intestine. Blocking the apical epithelial calcium channel (ECaC) with ruthenium red (RR, 8.5μmol L(-1)) significantly decreased Ca(2+) influx in the anterior intestine, but exposure to the plasma membrane Ca(2+)-ATP-ase (PMCA) inhibitor trifluoperazine (TFP, 10mmol L(-1)) had no effect at any environmental [Ca(2+)], nor did inhibition of the Na(+)-Ca(2+) exchanger (NCX) with KB-R7943 (10μmol L(-1)). Neither RR nor TFP affected Ca(2+) uptake by the posterior intestine in any of the treatment groups, but KB-R7943 reduced net calcium flux in the posterior intestine at all environmental [Ca(2+)]. Thus, basolateral Ca(2+) influx in the posterior GIT of lake sturgeon relies more heavily on NCX than PMCA. Furthermore, the differing pharmacological effects in the anterior and posterior intestine suggest that the dominant transporters responsible for calcium uptake vary over the length of the GIT in lake sturgeon. PMID:23831300

  2. 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

  3. 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 Kützing (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-1α, 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

  4. Impact of Peptide Transporter 1 on the Intestinal Absorption and Pharmacokinetics of Valacyclovir after Oral Dose Escalation in Wild-Type and PepT1 Knockout Mice

    PubMed Central

    Yang, Bei; Hu, Yongjun

    2013-01-01

    The primary objective of this study was to determine the in vivo absorption properties of valacyclovir, including the potential for saturable proton-coupled oligopeptide transporter 1 (PepT1)-mediated intestinal uptake, after escalating oral doses of prodrug within the clinical dose range. A secondary aim was to characterize the role of PepT1 on the tissue distribution of its active metabolite, acyclovir. [3H]Valacyclovir was administered to wild-type (WT) and PepT1 knockout (KO) mice by oral gavage at doses of 10, 25, 50, and 100 nmol/g. Serial blood samples were collected over 180 minutes, and tissue distribution studies were performed 20 minutes after a 25-nmol/g oral dose of valacyclovir. We found that the Cmax and area under the curve (AUC)0–180 of acyclovir were 4- to 6-fold and 2- to 3-fold lower, respectively, in KO mice for all four oral doses of valacyclovir. The time to peak concentration of acyclovir was 3- to 10-fold longer in KO compared with WT mice. There was dose proportionality in the Cmax and AUC0–180 of acyclovir in WT and KO mice over the valacyclovir oral dose range of 10–100 nmol/g (i.e., linear absorption kinetics). No differences were observed in the peripheral tissue distribution of acyclovir once these tissues were adjusted for differences in perfusing drug concentrations in the systemic circulation. In contrast, some differences were observed between genotypes in the concentrations of acyclovir in the distal intestine. Collectively, the findings demonstrate a critical role of intestinal PepT1 in improving the rate and extent of oral absorption for valacyclovir. Moreover, this study provides definitive evidence for the rational development of a PepT1-targeted prodrug strategy. PMID:23924683

  5. Impact of peptide transporter 1 on the intestinal absorption and pharmacokinetics of valacyclovir after oral dose escalation in wild-type and PepT1 knockout mice.

    PubMed

    Yang, Bei; Hu, Yongjun; Smith, David E

    2013-10-01

    The primary objective of this study was to determine the in vivo absorption properties of valacyclovir, including the potential for saturable proton-coupled oligopeptide transporter 1 (PepT1)-mediated intestinal uptake, after escalating oral doses of prodrug within the clinical dose range. A secondary aim was to characterize the role of PepT1 on the tissue distribution of its active metabolite, acyclovir. [³H]Valacyclovir was administered to wild-type (WT) and PepT1 knockout (KO) mice by oral gavage at doses of 10, 25, 50, and 100 nmol/g. Serial blood samples were collected over 180 minutes, and tissue distribution studies were performed 20 minutes after a 25-nmol/g oral dose of valacyclovir. We found that the C(max) and area under the curve (AUC)₀₋₁₈₀ of acyclovir were 4- to 6-fold and 2- to 3-fold lower, respectively, in KO mice for all four oral doses of valacyclovir. The time to peak concentration of acyclovir was 3- to 10-fold longer in KO compared with WT mice. There was dose proportionality in the C(max) and AUC₀₋₁₈₀ of acyclovir in WT and KO mice over the valacyclovir oral dose range of 10-100 nmol/g (i.e., linear absorption kinetics). No differences were observed in the peripheral tissue distribution of acyclovir once these tissues were adjusted for differences in perfusing drug concentrations in the systemic circulation. In contrast, some differences were observed between genotypes in the concentrations of acyclovir in the distal intestine. Collectively, the findings demonstrate a critical role of intestinal PepT1 in improving the rate and extent of oral absorption for valacyclovir. Moreover, this study provides definitive evidence for the rational development of a PepT1-targeted prodrug strategy. PMID:23924683

  6. Hydrogen bonded structures in organic amine oxalates

    NASA Astrophysics Data System (ADS)

    Vaidhyanathan, R.; Natarajan, S.; Rao, C. N. R.

    2002-05-01

    Oxalates of n-propylamine, n-butylamine, ethylenediamine, 1,4-butanediamine, piperazine, guanidine and 1,4-diazabicyclo[2,2,2]octane (DABCO) have been synthesized and characterized by single crystal X-ray diffraction and other techniques. The amine oxalates show different types of hydrogen bonded networks, linear hydrogen bonded chains characterizing the oxalates of the first five amines. Guanidinium oxalate has a sheet like structure while DABCO oxalate has dimeric hydrogen bonded rings. Hydrogen bonded structures of these oxalates are discussed in detail, besides relating their thermal stability to the strengths of the networks.

  7. [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

  8. Effect of oxalic acid treatment on sediment arsenic concentrations and lability under reducing conditions.

    PubMed

    Sun, Jing; Bostick, Benjamin C; Mailloux, Brian J; Ross, James M; Chillrud, Steven N

    2016-07-01

    Oxalic acid enhances arsenic (As) mobilization by dissolving As host minerals and competing for sorption sites. Oxalic acid amendments thus could potentially improve the efficiency of widely used pump-and-treat (P&T) remediation. This study investigates the effectiveness of oxalic acid on As mobilization from contaminated sediments with different As input sources and redox conditions, and examines whether residual sediment As after oxalic acid treatment can still be reductively mobilized. Batch extraction, column, and microcosm experiments were performed in the laboratory using sediments from the Dover Municipal Landfill and the Vineland Chemical Company Superfund sites. Oxalic acid mobilized As from both Dover and Vineland sediments, although the efficiency rates were different. The residual As in both Dover and Vineland sediments after oxalic acid treatment was less vulnerable to microbial reduction than before the treatment. Oxalic acid could thus improve the efficiency of P&T. X-ray absorption spectroscopy analysis indicated that the Vineland sediment samples still contained reactive Fe(III) minerals after oxalic acid treatment, and thus released more As into solution under reducing conditions than the treated Dover samples. Therefore, the efficacy of enhanced P&T must consider sediment Fe mineralogy when evaluating its overall potential for remediating groundwater As. PMID:26970042

  9. In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen.

    PubMed

    Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L

    2012-10-01

    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, in particular, BCS class II weak acids. However, a discrepancy between the in vivo BE results and in vitro dissolution results for 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 of 6.0. Further the experimental dissolution of ibuprofen tablets in a low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol l (-1) /pH) was dramatically reduced compared with the dissolution in SIF (the average buffer capacity 12.6 mmol l (-1) /pH). Thus these predictions for the oral absorption of BCS class II acids indicate that the absorption patterns depend largely on the intestinal pH and buffer strength and must be considered carefully for a bioequivalence test. Simulation software may be a very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. PMID:22815122

  10. 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

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

    PubMed

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

    2015-08-01

    Although a high number of chickens carry Campylobacter jejuni, the mechanistic action of colonization in the intestine is still poorly understood. The current study was therefore designed to investigate the effects of C. jejuni on glucose uptake, amino acids availability in digesta, and intracellular calcium [Ca(2+)]i signaling in the intestines of broiler chickens. For this, we compared: control birds (n = 60) and C. jejuni-infected birds (n = 60; infected orally with 1 × 10(8) CFU of C. jejuni NCTC 12744 at 14 days of age). Our results showed that glucose uptake was reduced due to C. jejuni infection in isolated jejunal, but not in cecal mucosa at 14 days postinfection (dpi). The decrease in intestinal glucose absorption coincided with a decrease in body weight gain during the 2-week post-infectious period. A reduction in the amount of the amino acids (serine, proline, valine, leucine, phenylalanine, arginine, histidine, and lysine) in ileal digesta of the infected birds at 2 and/or 7 dpi was found, indicating that Campylobacter utilizes amino acids as a carbon source for their multiplication. Applying the cell-permeable Ca(2+) indicator Fluo-4 and two-photon microscopy, we revealed that [Ca(2+)]i was increased in the jejunal and cecal mucosa of infected birds. The muscarinic agonist carbachol induced an increase in [Ca(2+)]i in jejunum and cecum mucosa of control chickens, a response absent in the mucosa of infected chickens, demonstrating that the modulation of [Ca(2+)]i by Campylobacter might be involved in facilitating the necessary cytoskeletal rearrangements that occur during the bacterial invasion of epithelial cells. In conclusion, this study demonstrates the multifaceted interactions of C. jejuni with the gastrointestinal mucosa of broiler chickens. For the first time, it could be shown that a Campylobacter infection could interfere with intracellular Ca(2+) signaling and nutrient absorption in the small intestine with consequences on intestinal function, performance, and Campylobacter colonization. Altogether, these findings indicate that Campylobacter is not entirely a commensal and can be recognized as an important factor contributing to an impaired chicken gut health. PMID:25825050

  12. 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.

  13. 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

  14. Coassimilation of dietary fat and benzo(a)pyrene in the small intestine: an absorption model using the killifish

    SciTech Connect

    Vetter, R.D.; Carey, M.C.; Patton, J.S.

    1985-04-01

    Benzo(a)pyrene (BP) was dissolved in dietary fat and fed in a single dose to killifish (Fundulus heteroclitus). Fluorescence microscopic examinations of small intestinal content and frozen sections of whole small intestine revealed that during fat digestion BP was codispersed in liquid crystalline product phases produced during lipolysis and then coabsorbed with dietary lipid followed by its reappearance in intracellular fat droplets. During the time that the absorbed fat remained in the enterocytes, BP fluorescence was initially concentrated in the intracellular fat droplets and then spread throughout the cytosol of the enterocytes. Tissue analyses showed that BP was rapidly metabolized in the intestine and transported to the gallbladder. These studies show that separation of a dissolved hydrophobic carcinogen from dietary fat occurs primarily after the fat has been digested, dispersed, absorbed, and reassembled in the enterocyte. The inability of the enterocyte to discriminate between dietary fat and dissolved carcinogenic compounds may be a partial explanation of the observed link between high fat diets and the incidence of some cancers. In vertebrates, the intestine and not the liver, appears to be the major site of metabolism of dietary polycyclic aromatic hydrocarbons (PAHs).

  15. 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…

  16. Effect of the abrasive properties of sedges on the intestinal absorptive surface and resting metabolic rate of root voles.

    PubMed

    Wieczorek, Monika; Szafrańska, Paulina A; Labecka, Anna Maria; Lázaro, 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

  17. OXALATE PROCESS FOR SEPARATING ELEMENT 94

    DOEpatents

    Gofman, J.W.

    1959-01-01

    A process is presented for separating plutonium values in the tetravalent state from hexavalent uranium with which it is associated in aqueous solutions. This separation is aceomplished by forming a thorium oxalate precipitate in order to carry only the plutonium. By carefully regulating the acidity of the solution and the oxalate ion concentration, the precipitation of uranium oxalate may be avoided.

  18. Feed supplemented with organic acids does not affect starch digestibility, nor intestinal absorptive or secretory function in broiler chickens.

    PubMed

    Ruhnke, I; Röhe, 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 μm phloridzin, 100 μm histamine and 100 μm 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 (ΔIsc ) 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

  19. 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

  20. Acute oral calcium-sodium citrate load in healthy males. Effects on acid-base and mineral metabolism, oxalate and other risk factors of stone formation in urine.

    PubMed

    Schwille, P O; Schmiedl, A; Herrmann, U; Schwille, R; Fink, E; Manoharan, M

    1997-01-01

    The currently preferred calcium preparations for supplementation of food vary widely with respect to calcium availability, effects on systemic mineral metabolism, acid-base status, and the calciuria-induced risk of urinary tract stone formation. In eight healthy males we studied the response to an acute load with alkali(sodium)-containing soluble calcium citrate (CSC) (molar ratio calcium/sodium/citrate approx. = 1/1/1), when taken in three different doses (10, 20, 30 mmol calcium) together with a continental breakfast. Intestinal calcium absorption, serum calcium, calcitonin, parathyroid hormone (PTH) other markers of bone metabolism, net acid excretion and calcium oxalate crystallization in urine were evaluated. CSC evoked a dose-dependent increase in calcium absorption, calcium in serum and urine, but no overt hypercalcemia, and calciuria was low relative to the excess calcium ingested; PTH fell and calcitonin rose (p < 0.05 vs. breakfast alone), but the diet-independent markers of bone resorption declined only insignificantly, while the markers of bone formation and turnover remained unchanged. There was a significant "once-daily" effect (= cumulative 24 h postload response) of CSC: a decrease in urinary cyclic AMP, phosphorus, and ammonium, and an increase in urinary bicarbonate. Soon after CSC intake, urinary calcium oxalate and hydroxyapatite supersaturation increased dose-dependently, the calcium oxalate crystal diameter was increased, but crystal aggregation time, which is crucial for stone formation, remained statistically unchanged. Thus, CSC provides calcium in a bioavailable form, creates mild systemic alkalinisation and inhibition of bone resorption, but leaves the risk of developing urinary stones unchanged. Comparative long-term studies on bone growth and the maintenance of bone health, using alkali-containing versus alkali-free calcium citrate, appear worthwhile. PMID:9385591

  1. 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.

  2. [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

  3. 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 μCi) 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

  4. 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

  5. Effect of γ-aminobutyric acid on digestive enzymes, absorption function, and immune function of intestinal mucosa in heat-stressed chicken.

    PubMed

    Chen, Z; Xie, J; Wang, B; Tang, J

    2014-10-01

    To explore the effect of dietary γ-aminobutyric acid (GABA) on digestive enzyme activity, absorption function and immune function of intestinal mucosa in heat-stressed Wenchang chicken were studied. One-day-old male Wenchang chickens were randomly divided into a control group (CK), heat stress group (HS), and GABA+HS group. The chickens from the GABA+HS group were administered with 0.2 mL of GABA solution daily. Chickens from HS and GABA+HS groups were subjected to heat stress treatment at 40 ± 0.5°C for 2 h during 1300 to 1500 h every day. Blood was drawn and 0.5 cm-long duodenum, jejunum, and ileum were collected from the chickens on d 3, 5, 7, 9, 12, and 15. Results showed that the activity of Ca²⁺-Mg²⁺-adenosine triphosphatase (ATPase), Na⁺-K⁺-ATPase, maltase, sucrase, and alkaline phosphatase, the contents of secretory IgA, glutathione, and d-xylose, and the number of lymphocytes in HS group were significantly lower than those in the CK group. Among them, some were rescued after the treatment of GABA as the time extension. For maltase, d-xylose, alkaline phosphatase, and Na⁺-K⁺-ATPase, it required 5 to 7 d for achieving the significant effect. For sucrase, 12 d for the alleviation effect was required. In the case of other parameters, no alleviation was observed during the whole period of the study. We have concluded that HS can inhibit the activity of digestive enzymes and reduce absorption and immune functions of intestinal mucosa. γ-Aminobutyric acid can effectively alleviate these inhibitory effects. PMID:25085934

  6. 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

  7. 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.

  8. 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...

  9. 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

  10. 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

  11. 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.

  12. Effect of pentobarbital anaesthesia on intestinal absorption and hepatic first-pass metabolism of oxacillin in rats, evaluated by portal-systemic concentration difference.

    PubMed

    Ueda, S; Yamaoka, K; Nakagawa, T

    1999-05-01

    The effects of anaesthesia on intestinal drug absorption and hepatic first-pass metabolism in rats were investigated by observing the difference in the drug concentration between portal and systemic bloods. Oxacillin and pentobarbital were selected as a model drug and as an anaesthetic, respectively. Rats were divided into a conscious control group and an anaesthetized group. All rats were cannulated simultaneously in the portal vein and in the femoral artery, and oxacillin was orally administered after its intra-arterial injection (double dosing). For the anaesthetized group, pentobarbital was intrasubcutaneously administered twice, first before intra-arterial injection and again before oral administration of oxacillin. The arterial blood alone was sampled from the cannula in the femoral artery before oral administration, whereas the arterial and portal bloods were simultaneously sampled from both cannulated sites after oral administration. Oxacillin concentrations in plasma were assayed by HPLC. The anaesthesia increased the absolute bioavailability (F), the mean absorption time (MAT) and the hepatic recovery ratio (F(H)), but caused little change in the local absorption ratio into the portal system (Fa) and the total clearance (CL). The hepatic clearance (CL(H)) was significantly decreased, resulting in an apparent small change in CL-CL(H) which is considered to be renal clearance. By this method, it was shown directly that an increase in F due to pentobarbital anaesthesia was attributable to the significant increase in F(H). It is expected that the method is useful not only to evaluate the effect of anaesthesia on the first-pass effect, but also to assess the effect of co-administration of drugs on first-pass metabolism. PMID:10411218

  13. 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.

  14. 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

  15. Human microsomal cyttrochrome P450-mediated reduction of oxysophocarpine, an active and highly toxic constituent derived from Sophora flavescens species, and its intestinal absorption and metabolism in rat.

    PubMed

    Wu, Lili; Zhong, Wanping; Liu, Junjin; Han, Weichao; Zhong, Shilong; Wei, Qiang; Liu, Shuwen; Tang, Lan

    2015-09-01

    Oxysophocarpine (OSC), an active and toxic quinolizidine alkaloid, is highly valued in Sophora flavescens Ait. and Subprostrate sophora Root. OSC is used to treat inflammation and hepatitis for thousands of years in China. This study aims to investigate the CYP450-mediated reduction responsible for metabolizing OSC and to evaluate the absorption and metabolism of OSC in rat in situ. Four metabolites were identified, with sophocarpine (SC) as the major metabolite. SC formation was rapid in human and rat liver microsomes (HLMs and RLMs, respectively). The reduction rates in the liver are two fold higher than in the intestine, both in humans and rats. In HLMs, inhibitors of CYP2C9, 3A4/5, 2D6, and 2B6 had strong inhibitory effects on SC formation. Meanwhile, inhibitors of CYP3A and CYP2D6 had significant inhibition on SC formation in RLMs. Human recombinant CYP3A4/5, 2B6, 2D6, and 2C9 contributed significantly to SC production. The permeability in rat intestine and the excretion rates of metabolites were highest in the duodenum (p<0.05), and the absorbed amount of OSC in duodenum and jejunum was concentration-dependent. The metabolism could be significantly decreased by CYP3A inhibitor ketoconazole. In conclusion, the liver was the main organ responsible for OSC metabolism. First-pass metabolism via CYP3A4/5, 2B6, 2D6, and 2C9 may be the main reason for the poor OSC bioavailability. PMID:26045316

  16. 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

  17. 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 ...

  18. 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

  19. 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

  20. 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...

  1. Engineering calcium oxalate crystal formation in Arabidopsis.

    PubMed

    Nakata, Paul A

    2012-07-01

    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 this approach hinged on the ability to transform Arabidopsis genetically into a calcium oxalate crystal-accumulating plant. To accomplish this transformation, two oxalic acid biosynthetic genes, obcA and obcB, from the oxalate-secreting phytopathogen, Burkholderia glumae were inserted into the Arabidopsis genome. The co-expression of these two bacterial genes in Arabidopsis conferred the ability not only to produce a measurable amount of oxalate but also to form crystals of calcium oxalate. Biochemical and cellular studies of crystal accumulation in Arabidopsis revealed features that are similar to those observed in the cells of crystal-forming plants. Thus, it appears that at least some of the basic components that comprise the calcium oxalate crystal formation machinery are conserved even in non-crystal-accumulating plants. PMID:22576773

  2. 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.

  3. Enabling the intestinal absorption of highly polar antiviral agents: ion-pair facilitated membrane permeation of zanamivir heptyl ester and guanidino oseltamivir.

    PubMed

    Miller, Jonathan M; Dahan, Arik; Gupta, Deepak; Varghese, Sheeba; Amidon, Gordon L

    2010-08-01

    Antiviral drugs often suffer from poor intestinal permeability, preventing their delivery via the oral route. The goal of this work was to enhance the intestinal absorption of the low-permeability antiviral agents zanamivir heptyl ester (ZHE) and guanidino oseltamivir (GO) utilizing an ion-pairing approach, as a critical step toward making them oral drugs. The counterion 1-hydroxy-2-naphthoic acid (HNAP) was utilized to enhance the lipophilicity and permeability of the highly polar drugs. HNAP substantially increased the log P of the drugs by up to 3.7 log units. Binding constants (K(11(aq))) of 388 M(-1) for ZHE-HNAP and 2.91 M(-1) for GO-HNAP were obtained by applying a quasi-equilibrium transport model to double-reciprocal plots of apparent octanol-buffer distribution coefficients versus HNAP concentration. HNAP enhanced the apparent permeability (P(app)) of both compounds across Caco-2 cell monolayers in a concentration-dependent manner, as substantial P(app) (0.8-3.0 x 10(-6) cm/s) was observed in the presence of 6-24 mM HNAP, whereas no detectable transport was observed without counterion. Consistent with a quasi-equilibrium transport model, a linear relationship with slope near 1 was obtained from a log-log plot of Caco-2 P(app) versus HNAP concentration, supporting the ion-pair mechanism behind the permeability enhancement. In the rat jejunal perfusion assay, the addition of HNAP failed to increase the effective permeability (P(eff)) of GO. However, the rat jejunal permeability of ZHE was significantly enhanced by the addition of HNAP in a concentration-dependent manner, from essentially zero without HNAP to 4.0 x 10(-5) cm/s with 10 mM HNAP, matching the P(eff) of the high-permeability standard metoprolol. The success of ZHE-HNAP was explained by its >100-fold stronger K(11(aq)) versus GO-HNAP, making ZHE-HNAP less prone to dissociation and ion-exchange with competing endogenous anions and able to remain intact during membrane permeation. Overall, this work presents a novel approach to enable the oral delivery of highly polar antiviral drugs, and provides new insights into the underlying mechanisms governing the success or failure of the ion-pairing strategy to increase oral absorption. PMID:20536260

  4. In utero and postnatal exposure to long chain (n-3) PUFA enhances intestinal glucose absorption and energy stores in weanling pigs.

    PubMed

    Gabler, Nicholas K; Spencer, Joel D; Webel, Doug M; Spurlock, Michael E

    2007-11-01

    The aim of this research was to determine whether feeding gestating and lactating sows (n-3) PUFA [eicosapentaenoic acid (EPA) and/or docosahexenoic acid (DHA)] or coconut fat (saturated fat) influences ex vivo glucose absorption in the proximal jejunum and glucose and glycogen concentration of liver and muscle of their offspring at weaning. Sows were fed 1 of 4 diets for 150 d, which included the entire gestation and lactation periods. The diets consisted of basal corn/soybean meal (CONT), CONT + protected EPA and DHA-rich fish oil (PFO), CONT + DHA Gold fat (DHAGF), and CONT + coconut fat (COCO). All tissues were collected from piglets (n = 4 per treatment) following a 24-h period of food deprivation, which was initiated at weaning. Proximal jejunum samples were mounted in modified Ussing chambers for transport determinations. Relative to the CONT (7 muA/cm(2)), active glucose transport was greater (P = 0.013) in piglets from sows fed the PFO (30 microA/cm(2)) and DHAGF (40 microA/cm(2)) diets, but not the COCO diet (19 microA/cm(2); pooled SEM = 5). Likewise, jejunum expression of glucose transporter 2 and sodium glucose transporter 1 protein tended (P < 0.10) to be greater in piglets from dams fed the PFO and DHAGF diets, as did AMP-activated protein kinase activity. Piglets' muscle glycogen was greater than in CONT (34 +/- 5.2 mg/g wet tissue) only in piglets from dams fed the DHAGF (46 +/- 5.2 mg/g wet tissue; P < 0.05). These results indicate that (n-3) PUFA, particularly DHA, improves intestinal glucose absorption and muscle glycogen concentrations in newly weaned pigs. These findings may also have important implications for human mothers and infants. PMID:17951469

  5. Enhancing the intestinal absorption of low molecular weight chondroitin sulfate by conjugation with α-linolenic acid and the transport mechanism of the conjugates.

    PubMed

    Xiao, Yuliang; Li, Pingli; Cheng, Yanna; Zhang, Xinke; Sheng, Juzheng; Wang, Decai; Li, Juan; Zhang, Qian; Zhong, Chuanqing; Cao, Rui; Wang, Fengshan

    2014-04-25

    The purpose of this report was to demonstrate the effect of amphiphilic polysaccharides-based self-assembling micelles on enhancing the oral absorption of low molecular weight chondroitin sulfate (LMCS) in vitro and in vivo, and identify the transepithelial transport mechanism of LMCS micelles across the intestinal barrier. α-Linolenic acid-low molecular weight chondroitin sulfate polymers(α-LNA-LMCS) were successfully synthesized, and characterized by FTIR, (1)HNMR, TGA/DSC, TEM, laser light scattering and zeta potential. The significant oral absorption enhancement and elimination half-life (t₁/₂) extension of LNA-LMCS2 in rats were evidenced by intragastric administration in comparison with CS and LMCS. Caco-2 transport studies demonstrated that the apparent permeability coefficient (Papp) of LNA-LMCS2 was significantly higher than that of CS and LMCS (p<0.001), and no significant effects on the overall integrity of the monolayer were observed during the transport process. In addition, α-LNA-LMCS micelles accumulated around the cell membrane and intercellular space observed by confocal laser scanning microscope (CLSM). Furthermore, evident alterations in the F-actin cytoskeleton were detected by CLSM observation following the treatment of the cell monolayers with α-LNA-LMCS micelles, which further certified the capacity of α-LNA-LMCS micelles to open the intercellular tight junctions rather than disrupt the overall integrity of the monolayer. Therefore, LNA-LMCS2 with low cytotoxicity and high bioavailability might be a promising substitute for CS in clinical use, such as treating osteoarthritis, atherosclerosis, etc. PMID:24524826

  6. 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 ...

  7. 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...

  8. Unexpected similarity of intestinal sugar absorption by SGLT1 and apical GLUT2 in an insect (Aphidius ervi, Hymenoptera) and mammals.

    PubMed

    Caccia, S; Casartelli, M; Grimaldi, A; Losa, E; de Eguileor, M; Pennacchio, F; Giordana, B

    2007-06-01

    Sugars are critical substrates for insect metabolism, but little is known about the transporters and epithelial routes that ensure their constant supply from dietary resources. We have characterized glucose and fructose uptakes across the apical and basolateral membranes of the isolated larval midgut of the aphid parasitoid Aphidius ervi. The uptake of radiolabeled glucose at the basal side of the epithelium was almost suppressed by 200 microM cytochalasin B, uninhibited by phlorizin, and showed the following decreasing rank of specificity for the tested substrates: glucose > glucosamine > fructose, with no recognition of galactose. These functional properties well agree with the expression of GLUT2-like transporters in this membrane. When the apical surface of the epithelium was also exposed to the labeled medium, a cation-dependent glucose uptake, inhibited by 10 microM phlorizin and by an excess of galactose, was detected suggesting the presence in the apical membrane of a cation-dependent cotransporter. Radiolabeled fructose uptakes were only partially inhibited by cytochalasin B. SGLT1-like and GLUT5-like transporters were detected in the apical membranes of the epithelial cell by immunocytochemical experiments. These results, along with the presence of GLUT2-like transporters both in the apical and basolateral cell membranes of the midgut, as we recently demonstrated, allow us to conclude that the model for sugar transepithelial transport in A. ervi midgut appears to be unexpectedly similar to that recently proposed for sugar intestinal absorption in mammals. PMID:17322115

  9. Inclusion of ancient Latin-American crops in bread formulation improves intestinal iron absorption and modulates inflammatory markers.

    PubMed

    Laparra, José Moisés; 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

  10. The intestine is a blender

    NASA Astrophysics Data System (ADS)

    Yang, Patricia; Lamarca, Morgan; Hu, David

    2015-11-01

    According to the U.S. Department of Health and Human Services, digestive disease affects 60 to 70 million people and costs over 140 billion annually. Despite the significance of the gastrointestinal tract to human health, the physics of digestion remains poorly understood. In this study, we ask a simple question: what sets the frequency of intestinal contractions? We measure the frequency of intestinal contractions in rats, as a function of distance down the intestine. We find that intestines contract radially ten times faster than longitudinally. This motion promotes mixing and, in turn, absorption of food products by the intestinal wall. We calculate viscous dissipation in the intestinal fluid to rationalize the relationship between frequency of intestinal contraction and the viscosity of the intestinal contents. Our findings may help to understand the evolution of the intestine as an ideal mixer.

  11. The intestine is a blender

    NASA Astrophysics Data System (ADS)

    Yang, Patricia; Lamarca, Morgan; Kravets, Victoria; Hu, David

    According to the U.S. Department of Health and Human Services, digestive disease affects 60 to 70 million people and costs over 140 billion annually. Despite the significance of the gastrointestinal tract to human health, the physics of digestion remains poorly understood. In this study, we ask a simple question: what sets the frequency of intestinal contractions? We measure the frequency of intestinal contractions in rats, as a function of distance down the intestine. We find that intestines Contract radially ten times faster than longitudinally. This motion promotes mixing and, in turn, absorption of food products by the intestinal wall. We calculate viscous dissipation in the intestinal fluid to rationalize the relationship between frequency of intestinal contraction and the viscosity of the intestinal contents. Our findings may help to understand the evolution of the intestine as an ideal mixer.

  12. CONCENTRATION OF Pu USING OXALATE TYPE CARRIER

    DOEpatents

    Ritter, D.M.; Black, R.P.S.

    1960-04-19

    A method is given for dissolving and reprecipitating an oxalate carrier precipitate in a carrier precipitation process for separating and recovering plutonium from an aqueous solution. Uranous oxalate, together with plutonium being carried thereby, is dissolved in an aqueous alkaline solution. Suitable alkaline reagents are the carbonates and oxulates of the alkali metals and ammonium. An oxidizing agent selected from hydroxylamine and hydrogen peroxide is then added to the alkaline solution, thereby oxidizing uranium to the hexavalent state. The resulting solution is then acidified and a source of uranous ions provided in the acidified solution, thereby forming a second plutoniumcarrying uranous oxalate precipitate.

  13. Artificial photosynthesis of oxalate and oxalate-based polymer by a photovoltaic reactor

    NASA Astrophysics Data System (ADS)

    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.

  14. 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

  15. Metabolic Conversion of l-Ascorbic Acid to Oxalic Acid in Oxalate-accumulating Plants 1

    PubMed Central

    Yang, Joan C.; Loewus, Frank A.

    1975-01-01

    l-Ascorbic acid-1-14C and its oxidation product, dehydro-l-ascorbic acid, produced labeled oxalic acid in oxalate-accumulating plants such as spinach seedlings (Spinacia oleracea) and the detached leaves of woodsorrel (Oxalis stricta and O. oregana), shamrock (Oxalis adenopylla), and begonia (Begonia evansiana). In O. oregana, conversion occurred equally well in the presence or absence of light. This relationship between l-ascorbic acid metabolism and oxalic acid formation must be given careful consideration in attempts to explain oxalic accumulation in plants. PMID:16659288

  16. 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

  17. 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

  18. Modeling the Adsorption of Oxalate onto Montmorillonite.

    PubMed

    Ramos, M Elena; Emiroglu, Caglayan; García, David; Sainz-Díaz, 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

  19. 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.

  20. Increased protein intake on controlled oxalate diets does not increase urinary oxalate excretion.

    PubMed

    Knight, John; Easter, Linda H; Neiberg, Rebecca; Assimos, Dean G; Holmes, Ross P

    2009-04-01

    High animal protein intake is a risk factor for calcium oxalate stone disease. The effect of dietary protein on the urinary excretion of calcium, acid and citrate is well established. However, its effect on oxalate excretion is unclear, due in part to an inadequate control of dietary oxalate intake in previous studies. This relationship warrants clarification due to the proposed important role of the metabolism of amino acids in endogenous oxalate synthesis. In this study, 11 normal subjects consumed controlled oxalate diets containing 0.6, 1.2 and 1.8 g protein/kg body weight/day. The analysis of 24 h urine collections confirmed that as protein intake increased, urinary calcium and glycolate increased and urinary pH and citrate decreased. The increased glycolate excretion was due in part to an increased hydroxyproline, but not glycolate consumption. Total daily urinary oxalate excretion did not change. When indexed to creatinine there was a small but significant decrease in oxalate excretion. This is most likely due to hyperfiltration. These results indicate that as dietary protein intake increases, the catabolism of diet-derived amino acids is not associated with an increased endogenous oxalate synthesis in normal subjects. PMID:19183980

  1. 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

  2. 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 ...

  3. 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.

  4. 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.

  5. 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...

  6. 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 0–24 h urine MgA value alone (ρ = 0.95, P < 0.001) or the mean of the 0–24 h urine and the 3-h (ρ = 0.93, P < 0.001) or 5-h (ρ = 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 0–24 h urine and 3-h serum MgA values. We conclude that means of 0–24 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

  7. 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.

  8. 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

  9. Vacuolar deposition of ascorbate-derived oxalic acid in barley

    SciTech Connect

    Wagner, G.J.

    1981-03-01

    L-(1-/sup 14/C)Ascorbic acid was supplied to detached barley seedlings to determine the subcellular location of oxalic acid, one of its metabolic products. Intact vacuoles isolated from protoplasts of labeled leaves contained (/sup 14/C)oxalic acid which accounted for about 70% of the intraprotoplast soluble oxalic acid. Tracer-labeled oxalate accounted for 36 and 72% of the /sup 14/C associated with leaf vacuoles of seedlings labeled for 22 and 96 hours, respectively.

  10. 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

  11. 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

  12. 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...

  13. 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...

  14. 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

  15. 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

  16. 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

  17. Photolytic destruction of oxalate in aqueous mixed waste

    SciTech Connect

    Wang, F.T.; Lum, B.Y.

    1995-03-01

    In aqueous plutonium processing, residual oxalic acid can be destroyed (oxalate kill) by UV light with hydrogen peroxide (H{sub 2}O{sub 2}) in 1 M HCl solutions. By controlling the amount of H{sub 2}O{sub 2}, the oxalate kill process will not affect the chloride concentration. In nitric acid solutions, UV light alone can destroy the oxalic acid. However, with H{sub 2}O{sub 2}, the rate of destruction is faster. After the destruction of oxalic acid, the acidic solutions may be reusable without further purification process.

  18. 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 ...

  19. 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

  20. 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

  1. 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.

  2. Oligomeric proanthocyanidins protect against HK-2 cell injury induced by oxalate and calcium oxalate monohydrate crystals.

    PubMed

    Wang, Shuo; Du, Peng; Zhang, Ning; Liu, Jia; Tang, Xingxing; Zhao, Qiang; Yang, Yong

    2016-06-01

    The purpose of the study was to test whether the antioxidants oligomeric proanthocyanidins (OPCs) could provide protection against oxalate and calcium oxalate monohydrate crystals (COM) toxicity in HK-2 cells. Four groups were chosen for the study: negative control group, positive control group (COM + oxalate), OPCs group (OPCs + COM + oxalate), Vit E group (Vit E + COM + oxalate). HK-2 cells were exposed for 4, 8, 12 and 24 h. The activity of HK-2 cell was assessed by MTT. Cellular injury was assessed by activity of Na(+)/K(+) ATP enzyme. Peroxidation level was assessed by malondialdehyde (MDA) content in medium and activity of superoxide dismutase (SOD). Morphological changes of HK-2 cell after exposed for 4 and 12 h in each group were observed under Transmission electron microscope (TEM). The effects of OPCs and VitE on oxalate- and COM-exposed cells were tested. After exposed to oxalate and COM crystals, activity of cells, Na(+)/K(+) ATP enzyme and SOD enzyme showed a significant reduction, and MDA content in medium was significantly increased. OPCs group: the addition of OPCs significantly increased activity of cell, SOD and Na(+)/K(+) ATP enzyme while MDA content was significantly decreased compared with the positive control group. VitE group: compared with the positive control group, activity of HK-2 cell, Na(+)/K(+) ATP enzyme was not significantly changed while SOD activity was restored, and MDA content was significantly decreased after the addition of Vit E. Morphological structure of HK-2 cell was extremely changed as observed under TEM after exposure to high level of COM crystals and oxalate. After the addition of OPCs or Vit E, amounts of cells with vacuoles formed in cytoplasms, karyotheca dissolved and nucleolus disappeared were less than in positive control group. The morphological structure changing in OPCs group was slighter than that in Vit E group. OPCs and vitamin E administration may prevent oxalate- and COM-mediated peroxidative injury, restoring intracellular antioxidant enzyme activity. The protection rendered by OPCs was greater than that of vitamin E. PMID:26446157

  3. 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.

  4. 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.

  5. 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

  6. Urinary metabolic phenotyping the slc26a6 (chloride-oxalate exchanger) null mouse model.

    PubMed

    Garcia-Perez, Isabel; Villaseñor, Alma; Wijeyesekera, Anisha; Posma, Joram M; Jiang, Zhirong; Stamler, Jeremiah; Aronson, Peter; Unwin, Robert; Barbas, Coral; Elliott, Paul; Nicholson, Jeremy; Holmes, Elaine

    2012-09-01

    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 cometabolic activities. Gender-related metabotypes were also observed in both wild type and slc26a6 null groups. Urinary metabolites that showed a sex-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 different composition of microbial metabolites in the slc26a6 null mice 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

  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. Evidence that serum calcium oxalate supersaturation is a consequence of oxalate retention in patients with chronic renal failure.

    PubMed Central

    Worcester, E M; Nakagawa, Y; Bushinsky, D A; Coe, F L

    1986-01-01

    Serum oxalate rises in uremia because of decreased renal clearance, and crystals of calcium oxalate occur in the tissues of uremic patients. Crystal formation suggests that either uremic serum is supersaturated with calcium oxalate, or local oxalate production or accumulation causes regional supersaturation. To test the first alternative, we ultrafiltered uremic serum and measured supersaturation with two different methods previously used to study supersaturation in urine. First, the relative saturation ratio (RSR), the ratio of the dissolved calcium oxalate complex to the thermodynamic calcium oxalate solubility product, was estimated for 11 uremic (before and after dialysis) and 4 normal serum samples using a computer program. Mean ultrafiltrate oxalate predialysis was 89 +/- 8 microM/liter (+/- SEM), 31 +/- 4 postdialysis, and 10 +/- 3 in normals. Mean RSR was 1.7 +/- 0.1 (predialysis), 0.7 +/- 0.1 (postdialysis), and 0.2 +/- 0.1 (normal), where values greater than 1 denote supersaturation, less than 1, undersaturation. Second, the concentration product ratio (CPR), the ratio of the measured calcium oxalate concentration product before to that after incubation of the sample with calcium oxalate monohydrate crystal, was measured in seven uremic and seven normal serum ultrafiltrates. Mean oxalate was 91 +/- 11 (uremic) and 8 +/- 3 (normal). Mean CPR was 1.4 +/- 0.2 (uremic) and 0.2 +/- 0.1 (normal). Predialysis, 17 of 18 uremic ultrafiltrates were supersaturated with respect to calcium oxalate. The degree of supersaturation was correlated with ultrafiltrate oxalate (RSR, r = 0.99, r = 29, P less than 0.001; CPR, r = 0.75, n = 11, P less than 0.001). A value of ultrafiltrate oxalate of 50 microM/liter separated undersaturated from supersaturated samples and occurred at a creatinine of approximately 9.0 mg/dl. PMID:3711339

  9. 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

  10. 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.

  11. Absorption and metabolism of the food contaminant 3-chloro-1,2-propanediol (3-MCPD) and its fatty acid esters by human intestinal Caco-2 cells.

    PubMed

    Buhrke, Thorsten; Weisshaar, Rüdiger; Lampen, Alfonso

    2011-10-01

    3-Chloro-1,2-propanediol (3-MCPD) fatty acid esters are formed upon thermal processing of fat-containing foods in the presence of chloride ions. Upon hydrolytic cleavage, these substances could release free 3-MCPD. This compound is toxicologically well characterised and displayed cancerogenic potential in rodent models. Recently, serious contaminations of different food products with 3-MCPD fatty acid esters have been reported. In regard to a risk assessment, the key question is to which degree these 3-MCPD fatty acid esters are hydrolysed in the human gut. Therefore, the aim of the present project was to examine the hydrolysis of 3-MCPD fatty acid esters and the resulting release of free 3-MCPD by using differentiated Caco-2 cells, a cellular in vitro model for the human intestinal barrier. Here, we show that 3-MCPD fatty acid esters at a concentration of 100 μM were neither absorbed by the cells nor the esters were transported via a Caco-2 monolayer. 3-MCPD-1-monoesters were hydrolysed in the presence of Caco-2 cells. In contrast, a 3-MCPD-1,2-diester used in this study was obviously absorbed and metabolised by the cells. Free 3-MCPD was not absorbed by the cells, but the substance migrated through a Caco-2 monolayer by paracellular diffusion. From these in vitro studies, we conclude that 3-MCPD-1-monoesters are likely to be hydrolysed in the human intestine, thereby increasing the burden with free 3-MCPD. In contrast, intestinal cells seem to have the capacity to metabolise 3-MCPD diesters, thereby detoxifying the 3-MCPD moiety. PMID:21327620

  12. Effect of the microbial lactase (EC 3.2.1.23) activity in yoghurt on the intestinal absorption of lactose: an in vivo study in lactase-deficient humans.

    PubMed

    Marteau, P; Flourie, B; Pochart, P; Chastang, C; Desjeux, J F; Rambaud, J C

    1990-07-01

    Breath hydrogen excretion was measured in eight lactase (EC 3.2.1.108)-deficient volunteers ingesting 18 g lactose in the form of milk, yoghurt and heated yoghurt. Total excess hydrogen excretion (area under curve) was significantly lower after yoghurt and heated yoghurt, than after milk: 103 (SE 29), 191 (SE 32), and 439 (SE 69) respectively (P less than 0.001). The oro-caecal transit time of fermentable components from yoghurt and heated yoghurt (mainly lactose) was longer than that from milk: 165 (SE 17), 206 (SE 19), v. 103 (SE 19) min (P less than 0.01). An intestinal perfusion technique was used in the same subjects after ingestion on two consecutive days of 18 g lactose in yoghurt and heated yoghurt. Significantly less lactose was recovered from the terminal ileum after yoghurt than after heated yoghurt meals: 1740 (SE 260) v. 2825 (SE 461) mg (P less than 0.05), and approximately one-fifth of the lactase activity contained in yoghurt reached the terminal ileum. These findings indicate that more than 90% of the lactose in yoghurt is digested in the small intestine of lactase-deficient subjects and suggest that both the lactase activity contained in the viable starter culture and a slow oro-caecal transit time are responsible for this excellent absorption. PMID:2119224

  13. 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

  14. Acquired causes of intestinal malabsorption.

    PubMed

    van der Heide, F

    2016-04-01

    This review focuses on the acquired causes, diagnosis, and treatment of intestinal malabsorption. Intestinal absorption is a complex process that depends on many variables, including the digestion of nutrients within the intestinal lumen, the absorptive surface of the small intestine, the membrane transport systems, and the epithelial absorptive enzymes. Acquired causes of malabsorption are classified by focussing on the three phases of digestion and absorption: 1) luminal/digestive phase, 2) mucosal/absorptive phase, and 3) transport phase. Most acquired diseases affect the luminal/digestive phase. These include short bowel syndrome, extensive small bowel inflammation, motility disorders, and deficiencies of digestive enzymes or bile salts. Diagnosis depends on symptoms, physical examination, and blood and stool tests. There is no gold standard for the diagnosis of malabsorption. Further testing should be based on the specific clinical context and the suspected underlying disease. Therapy is directed at nutritional support by enteral or parenteral feeding and screening for and supplementation of deficiencies in vitamins and minerals. Early enteral feeding is important for intestinal adaptation in short bowel syndrome. Medicinal treatment options for diarrhoea in malabsorption include loperamide, codeine, cholestyramine, or antibiotics. PMID:27086886

  15. Screening of Indigenous Oxalate Degrading Lactic Acid Bacteria from Human Faeces and South Indian Fermented Foods: Assessment of Probiotic Potential

    PubMed Central

    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

  16. Inhibition of Intestinal α-Glucosidase and Glucose Absorption by Feruloylated Arabinoxylan Mono- and Oligosaccharides from Corn Bran and Wheat Aleurone

    PubMed Central

    Malunga, Lovemore Nkhata; Eck, Peter; Beta, Trust

    2016-01-01

    The effect of feruloylated arabinoxylan mono- and oligosaccharides (FAXmo) on mammalian α-glucosidase and glucose transporters was investigated using human Caco-2 cells, rat intestinal acetone powder, and Xenopus laevis oocytes. The isolated FAXmo from wheat aleurone and corn bran were identified to have degree of polymerization (DP) of 4 and 1, respectively, by HPLC-MS. Both FAXmo extracts were effective inhibitors of sucrase and maltase functions of the α-glucosidase. The IC50 for FAXmo extracts on Caco-2 cells and rat intestinal α-glucosidase was 1.03–1.65 mg/mL and 2.6–6.5 mg/mL, respectively. Similarly, glucose uptake in Caco-2 cells was inhibited up to 40%. The inhibitory effect of FAXmo was dependent on their ferulic acid (FA) content (R = 0.95). Sodium independent glucose transporter 2 (GLUT2) activity was completely inhibited by FAXmo in oocytes injected to express GLUT2. Our results suggest that ferulic acid and feruloylated arabinoxylan mono-/oligosaccharides have potential for use in diabetes management. PMID:27073693

  17. 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, UV–vis, FT-IR and TG–DTA. - 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. UV–vis and FT-IR spectroscopies were also used to characterize the electrodeposited nanoparticles. The TG–DTA studies of the nanoparticles indicated that the main thermal degradation occurs in two steps over a temperature range of 350–430 °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.

  18. Hydroxyproline ingestion and urinary oxalate and glycolate excretion.

    PubMed

    Knight, J; Jiang, J; Assimos, D G; Holmes, R P

    2006-12-01

    Endogenous synthesis of oxalate is an important contributor to calcium oxalate stone formation and renal impairment associated with primary hyperoxaluria. Although the principal precursor of oxalate is believed to be glyoxylate, pathways in humans resulting in glyoxylate synthesis are not well defined. Hydroxyproline, a component amino acid of collagen, is a potential glyoxylate precursor. We have investigated the contribution of dietary hydroxyproline derived from gelatin to urinary oxalate and glycolate excretion. Responses to the ingestion of 30 g of gelatin or whey protein were compared on controlled oxalate diets. The time course of metabolism of a 10 g gelatin load was determined as well as the response to varying gelatin loads. Urinary glycolate excretion was 5.3-fold higher on the gelatin diet compared to the whey diet and urinary oxalate excretion was 43% higher. Significant changes in plasma hydroxyproline and urinary oxalate and glycolate were observed with 5 and 10 g gelatin loads, but not 1 and 2 g loads. Extrapolation of these results to daily anticipated collagen turnover and hydroxyproline intake suggests that hydroxyproline metabolism contributes 20-50% of glycolate excreted in urine and 5-20% of urinary oxalate derived from endogenous synthesis. Our results also revealed that the kidney absorbs significant quantities of hydroxyproline and glycolate, and their metabolism to oxalate in this tissue warrants further consideration. PMID:17021603

  19. 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.

  20. 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.

  1. [Calcium oxalate microcrystalline arthropathy in primary oxalosis].

    PubMed

    Benhamou, C L; Laoussadi, S; Geslin, N; Pierre, D; Luthier, F; Maitre, F; Bouille, G; Amor, B

    1985-04-01

    This paper dealt with the case of a 53 years old man, affected by a chronic renal failure as the initial symptom of a primary oxalosis and treated by hemodialysis three years ago. Two years after the onset of renal failure, the left knee was painful and swollen but no cartilage or bone joint lesion was observed. Presence of intra synovial calcium oxalate crystals suggests that this arthropathy may be related to the primary oxalosis. However the role of other calcium salts under identification evidenced by synovial electron microscopy (apatite ? pyrophosphate ?) is discussed. PMID:4001817

  2. 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

  3. 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…

  4. 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.

  5. 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

  6. 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…

  7. 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

  8. 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 ...

  9. 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

  10. [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

  11. Adipose triglyceride lipase is a TG hydrolase of the small intestine and regulates intestinal PPARα signaling

    PubMed Central

    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

    2013-01-01

    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 α (PPARα). 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 [3H]trioleate resulted in the accumulation of radioactive TG in the intestine, whereas absorption into the systemic circulation was unchanged. Intraperitoneally injected [3H]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 PPARα 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 PPARα-dependent processes also in the small intestine. PMID:23220585

  12. 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.

  13. 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

  14. In vitro effects of deoxynivalenol on small intestinal D-glucose uptake and absorption of deoxynivalenol across the isolated jejunal epithelium of laying hens.

    PubMed

    Awad, W A; Aschenbach, J R; Setyabudi, F M C S; Razzazi-Fazeli, E; Böhm, J; Zentek, J

    2007-01-01

    Deoxynivalenol (DON) is a common mycotoxin contaminant in feedstuffs. It has been shown to cause diverse toxic effects in animals. The aim of the present study was to evaluate the effects of DON on the glucose transport capacity in chickens' jejunum and to investigate the permeation of DON itself by the Ussing chamber technique. Glucose uptake into chicken jejunal epithelia was measured after the addition of 200 mumol/L of (14)C-labeled glucose to the mucosal solution. Glucose uptake under control condition was 3.28 +/- 0.53 nmol/cm(2) x min. The contribution of sodium glucose-linked transporter 1 (SGLT-1) to total glucose uptake was estimated by inhibiting SGLT-1 with phlorizin (100 micromol/L). In the presence of phlorizin, glucose uptake was reduced (P < 0.05) to 1.21 +/- 0.19 nmol/cm(2) x min. Deoxynivalenol decreased (P < 0.05) the glucose uptake in the absence of phlorizin to 1.81 +/- 0.24 nmol/cm(2) x min but had no additional effect on the glucose uptake in the presence of phlorizin (0.97 +/- 0.17 nmol/cm(2) x min). Mucosal-to-serosal permeation of DON was proportional to the initial DON concentration over a concentration range from 1 to 10 mug/mL on the mucosal side. Apparent permeability at 10 microg/mL of DON measured 60 to 90 min after DON application was 1.7 x 10(-05) cm/s. It can be concluded that DON (10 mg/L) decreases glucose uptake almost as efficiently as phlorizin. The similarity between the effects of phlorizin and DON on glucose uptake evidences their common ability to inhibit Na(+)-D-glucose cotransport. In addition to local effects, DON can be absorbed from the jejunum. A predominant part of DON passes across the chicken intestinal epithelium by passive diffusion, which is likely on the paracellular pathway. The results imply that the exposure to DON-contaminated feeds may negatively affect animal health and performance by local (i.e., inhibition of intestinal SGLT-1) and systemic effects. PMID:17179409

  15. 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,...

  16. Concurrent determination of topotecan and model permeability markers (atenolol, antipyrine, propranolol and furosemide) by reversed phase liquid chromatography: utility in Caco-2 intestinal absorption studies.

    PubMed

    Bansal, Tripta; Singh, Manoj; Mishra, Gautam; Talegaonkar, Sushama; Khar, Roop K; Jaggi, Manu; Mukherjee, Rama

    2007-11-15

    A simple, sensitive, specific and high-resolution reversed-phase liquid chromatographic method utilizing ultraviolet detection has been developed and validated for simultaneous determination of topotecan and four intestinal permeability markers (atenolol, antipyrine, propranolol and furosemide) as suggested by US-FDA. Chromatography was carried out on C-18 column with mobile phase comprising water (pH 3.0) and acetonitrile gradient pumped at a flow rate of 1 ml min(-1). The validation parameters included specificity, accuracy, precision, sensitivity and stability studies. Topotecan, an anti-cancer drug widely used in metastatic carcinoma, is a P-glycoprotein substrate having oral bioavailability of 30% with large inter-patient variability. The present method was successfully applied for demonstrating P-gp mediated transport of topotecan and its inhibition using verapamil in Caco-2 cell monolayer. The method can be used in identification of novel P-gp inhibitors for topotecan and estimating the contribution of P-gp in affecting oral bioavailability of topotecan. The other applications of method include its use in validation of Caco-2 monolayer assay for getting biowaiver based on Biopharmaceutic Classification System and its extrapolation to in situ and/or in vivo studies. PMID:17936093

  17. 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

  18. Metal oxalates in paints: a Raman investigation on the relative reactivities of different pigments to oxalic acid solutions.

    PubMed

    Zoppi, A; Lofrumento, C; Mendes, N F C; Castellucci, E M

    2010-05-01

    One degradation phenomenon that occurs in artworks is the formation of metal oxalates on their surfaces. In order to gain insight into the inclination of pigments to produce oxalates, nine pigments including Na, Ca, Fe, Pb and Cu cations were selected to react with oxalic acid solutions at different concentrations (1 M, 0.1 M, 0.01 M and 0.005 M). Micro-Raman spectroscopy was used to detect the different reaction products. Pigments containing calcium (calcite, gypsum and Volterra gypsum) showed a high tendency to form weddellite as well as whewellite, especially at high acidic concentrations; among copper-based pigments (malachite, azurite, verdigris), the formation of moolooite was observed for high concentrations of acid and down to the lowest concentration (0.005 M) in the case of verdigris. Lead oxalate was detected on lead white. No iron oxalates were observed for hematite; the formation of calcium oxalate crystals was observed instead. Ultramarine blue reacted to produce elemental sulfur. According to the results obtained, calcite and verdigris showed the highest reactivity in oxalic acid environments, resulting in a high tendency to form calcium and copper oxalates, even at very low acidic concentrations; this behavior seems to arise from the high solubilities of these pigments in acidic environments. PMID:20225056

  19. 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

  20. 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

  1. Inhibition of Pancreatic Lipase and Triacylglycerol Intestinal Absorption by a Pinhão Coat (Araucaria angustifolia) Extract Rich in Condensed Tannin

    PubMed Central

    Oliveira, Roselene Ferreira; Gonçalves, Geferson Almeida; Inácio, Fabíola Dorneles; Koehnlein, Eloá Angélica; 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 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, K¯i1 and K¯i2, 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

  2. Characterization of the intestinal absorption of seven flavonoids from the flowers of Trollius chinensis using the Caco-2 cell monolayer model.

    PubMed

    Liu, Lijia; Guo, Lina; 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

  3. 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

  4. 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

  5. Intestinal Obstruction

    MedlinePlus

    ... sounds Swelling of the abdomen Inability to pass gas Constipation A complete intestinal obstruction is a medical emergency. It often requires surgery. NIH: National Institute of Diabetes and Digestive and Kidney Diseases

  6. Intestinal obstruction

    MedlinePlus

    Obstruction of the bowel may due to: A mechanical cause, which means something is in the way ... lung disease Use of certain medicines, especially narcotics Mechanical causes of intestinal obstruction may include: Adhesions or ...

  7. Aging and the intestine

    PubMed Central

    Drozdowski, Laurie; Thomson, Alan BR

    2006-01-01

    Over the lifetime of the animal, there are many changes in the function of the body’s organ systems. In the gastrointestinal tract there is a general modest decline in the function of the esophagus, stomach, colon, pancreas and liver. In the small intestine, there may be subtle alterations in the intestinal morphology, as well as a decline in the uptake of fatty acids and sugars. The malabsorption may be partially reversed by aging glucagon-like peptide 2 (GLP2) or dexamethasone. Modifications in the type of lipids in the diet will influence the intestinal absorption of nutrients: for example, in mature rats a diet enriched with saturated as compared with polysaturated fatty acids will enhance lipid and sugar uptake, whereas in older animals the opposite effect is observed. Thus, the results of studies of the intestinal adaptation performed in mature rats does not necessarily apply in older animals. The age-associated malabsorption of nutrients that occurs with aging may be one of the several factors which contribute to the malnutrition that occurs with aging. PMID:17171784

  8. The Intestinal Tract: Structure, Function, Disorders and Related Medication.

    ERIC Educational Resources Information Center

    Wagner, Dianne M.

    This instructional guide is intended for use within inservice or continuing education programs for people who work in long-term care facilities. This module includes an overview of the normal functions of the small and large intestines and discusses the structures of the intestines, absorption in the intestines, and commonly occurring conditions…

  9. STUDIES ON INHIBITION OF INTESTINAL ABSORPTION OF RADIOACTIVE STRONTIUM. II. EFFECTS OF ADMINISTRATION OF SODIUM ALGINATE BY OROGASTRIC INTUBATION AND FEEDING.

    PubMed

    PAUL, T M; EDWARD, D W; SKORYNA, S C

    1964-09-01

    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 Sr(89) and Ca(45) 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

  10. Quinoa extract enriched in 20-hydroxyecdysone affects energy homeostasis and intestinal fat absorption in mice fed a high-fat diet.

    PubMed

    Foucault, Anne-Sophie; Even, Patrick; Lafont, René; Dioh, Waly; Veillet, Stanislas; Tomé, Daniel; Huneau, Jean-François; Hermier, Dominique; Quignard-Boulangé, Annie

    2014-04-10

    In a previous study, we have demonstrated that a supplementation of a high-fat diet with a quinoa extract enriched in 20-hydroxyecdysone (QE) or pure 20-hydroxyecdysone (20E) could prevent the development of obesity. In line with the anti-obesity effect of QE, we used indirect calorimetry to examine the effect of dietary QE and 20E in high-fat fed mice on different components of energy metabolism. Mice were fed a high-fat (HF) diet with or without supplementation by QE or pure 20E for 3 weeks. As compared to mice maintained on a low-fat diet, HF feeding resulted in a marked physiological shift in energy homeostasis, associating a decrease in global energy expenditure (EE) and an increase in lipid utilization as assessed by the lower respiratory quotient (RQ). Supplementation with 20E increased energy expenditure while food intake and activity were not affected. Furthermore QE and 20E promoted a higher rate of glucose oxidation leading to an increased RQ value. In QE and 20E-treated HFD fed mice, there was an increase in fecal lipid excretion without any change in stool amount. Our study indicates that anti-obesity effect of QE can be explained by a global increase in energy expenditure, a shift in glucose metabolism towards oxidation to the detriment of lipogenesis and a decrease in dietary lipid absorption leading to reduced dietary lipid storage in adipose tissue. PMID:24534167

  11. Bile acids in regulation of intestinal physiology.

    PubMed

    Keating, Niamh; Keely, Stephen J

    2009-10-01

    In addition to their roles in facilitating lipid digestion and absorption, bile acids are recognized as important regulators of intestinal function. Exposure to bile acids can dramatically influence intestinal transport and barrier properties; in recent years, they have also become appreciated as important factors in regulating cell growth and survival. Indeed, few cells reside within the intestinal mucosa that are not altered to some degree by exposure to bile acids. The past decade saw great advances in the knowledge of how bile acids exert their actions at the cellular and molecular levels. In this review, we summarize the current understanding of the role of bile acids in regulation of intestinal physiology. PMID:19765365

  12. Polar interactions drug/phospholipids estimated by IAM-HPLC vs cultured cell line passage data: Their relationships and comparison of their effectiveness in predicting drug human intestinal absorption.

    PubMed

    Grumetto, Lucia; Russo, Giacomo; Barbato, Francesco

    2016-03-16

    The relationships between data of passage through Caco-2 cultured cell lines (logPapp), taken from the literature, for 38 structurally unrelated compounds and both n-octanol lipophilicity parameters (logP(N) and logD(7.4)) and phospholipid affinity indexes were investigated. Phospholipid affinity(logkW(IAM)) was experimentally determined by HPLC on two different phospholipid stationary phases and the polar/electrostatic interaction component drug/phospholipids (Δlog kW(IAM)) was calculated according to a method we previously proposed. LogPapp moderately related to lipophilicity values measured at pH 7.4 (logD(7.4)), according to a parabolic pattern, but poorly related with log kW(IAM). Furthermore, a significant inverse linear relationship with Δlog kW(IAM) values was only observed for the analytes with m.w. >300Da, for which paracellular diffusion can be considered a minor transport route in vivo. Indeed, it has been reported that Caco-2 passage data also encode secondary passage mechanisms, which participate in a different extent to the jejunal absorption in vivo and cannot be directly equated to the corresponding human in situ logPeff values, unless a normalization is performed. In an attempt to elucidate this issue, 47 structurally unrelated compounds whose cultured cell line passage data were corrected for the effects of the aqueous boundary layer and paracellular permeability, so as to express transcellular intrinsic permeability, logP0(Caco-2/MDCK), were also considered. Highly significant inverse linear relationships were observed between logP0(Caco-2/MDCK) and ΔlogkW(IAM) values from both IAM.PC.MG (r(2)=0.765) and IAM.PC.DD2 (r(2)=0.806) stationary phases whereas the relationships with either lipophilicity in n-octanol or logkW(IAM) values were very poor. The results of the present study, in complete agreement with those of our recent study on the relationships between jejunal absorption data measured in situ and ΔlogkW(IAM) values, confirm the soundness of ΔlogkW(IAM) parameters in the prediction of the intestinal absorption of drugs. From a mechanistic point of view, they suggest that the polar/electrostatic forces between drugs and phospholipids play a major role in the passage through biomembranes. PMID:26780120

  13. The enzymes of oxalate metabolism: unexpected structures and mechanisms.

    PubMed

    Svedruzić, Drazenka; Jónsson, Stefán; Toyota, Cory G; Reinhardt, Laurie A; Ricagno, Stefano; Lindqvist, Ylva; Richards, Nigel G J

    2005-01-01

    Oxalate degrading enzymes have a number of potential applications, including medical diagnosis and treatments for hyperoxaluria and other oxalate-related diseases, the production of transgenic plants for human consumption, and bioremediation of the environment. This review seeks to provide a brief overview of current knowledge regarding the major classes of enzymes and related proteins that are employed in plants, fungi, and bacteria to convert oxalate into CO(2) and/or formate. Not only do these enzymes employ intriguing chemical strategies for cleaving the chemically unreactive C-C bond in oxalate, but they also offer the prospect of providing new insights into the molecular processes that underpin the evolution of biological catalysts. PMID:15581576

  14. Apoptosis, Necrosis, and Necroptosis in the Gut and Intestinal Homeostasis

    PubMed Central

    Negroni, Anna; Cucchiara, Salvatore; Stronati, Laura

    2015-01-01

    Intestinal epithelial cells (IECs) form a physiochemical barrier that separates the intestinal lumen from the host's internal milieu and is critical for electrolyte passage, nutrient absorption, and interaction with commensal microbiota. Moreover, IECs are strongly involved in the intestinal mucosal inflammatory response as well as in mucosal innate and adaptive immune responses. Cell death in the intestinal barrier is finely controlled, since alterations may lead to severe disorders, including inflammatory diseases. The emerging picture indicates that intestinal epithelial cell death is strictly related to the maintenance of tissue homeostasis. This review is focused on previous reports on different forms of cell death in intestinal epithelium. PMID:26483605

  15. Multiorgan crystal deposition following intravenous oxalate infusion in rat

    SciTech Connect

    Blumenfrucht, M.J.; Cheeks, C.; Wedeen, R.P.

    1986-06-01

    Deposition of calcium oxalate is responsible for the pathologic manifestations of oxalosis and may contribute to multiorgan dysfunction in uremia and to the progression of renal damage after renal failure is established. We have developed a rat model of oxalosis using a single intravenous injection of sodium oxalate, 0.3 mmol./kg. body weight, in rats. Polarized light microscopy and section freeze-dry autoradiography were used to identify /sup 14/C-oxalate within the renal parenchyma and in extrarenal organs. /sup 14/C-oxalate crystals under three mu in length were identified within one min. of injection in proximal tubule lumens. Section freeze-dry autoradiography showed occasional minute crystals within glomeruli, heart, lung and liver at one hr. In contrast to concentrative cellular uptake demonstrated in rat renal cortical slices in vitro, intracellular accumulation of /sup 14/C-oxalate could not be detected in vivo. Within the first 24 hr., renal oxalate retention reached a maximum of 25 +/- 4 per cent of the injected dose/gm. kidney compared to a maximum of only 7 +/- 3 per cent/gm. kidney after intraperitoneal administration. Although less than one per cent dose/gm. kidney remained after one week, crystal fragments were scattered throughout the cortex and medulla, often surrounded by foci of interstitial nephritis. The retention of crystals in kidney and other body organs following i.v. oxalate provides a model of oxalosis which stimulates pathophysiologic events in a variety of clinical situations characterized by transiently or persistently elevated serum oxalate.

  16. Oxalate nephropathy in free-living American bullfrog tadpoles.

    PubMed

    Tokiwa, Toshihiro; Kadekaru, Sho; Ito, Masao; Yoshida, Makoto; Une, Yumi

    2015-10-27

    In February 2014, wild American bullfrog Lithobates catesbeianus tadpoles from an artificial pond in the Kyusyu region, Japan, presented with coelomic and subcutaneous edema and erythema within the skin. A pathological examination of 57 tadpoles of American bullfrogs in the region was conducted to evaluate the disease. Crystal deposition of varying degrees was found in the kidneys of 35 tadpoles (61.4%). The crystals were transparent, pleomorphic in shape, highly birefringent in polarized light, and arranged in a radial pattern within the renal tubular lumen. Using Alizarin Red S stain and liquid chromatography, these crystals were identified as calcium oxalate. Severe coelomic and subcutaneous edema was observed in 7 of these 35 tadpoles (20.0%). Ammonia levels in coelomic fluid were extremely elevated (>1000 µg dl(-1)) in 4 tadpoles examined. These findings suggest that oxalate deposition in kidneys causes metabolic disorder with renal nephropathy. The source of the oxalate could not be determined; however, the presence of calcium oxalates in pond sediments, as revealed by liquid chromatography, suggested that the deposition was most likely due to ingestion of oxalate materials from the environment. This is the first report of oxalate nephropathy in free-living amphibians. PMID:26503774

  17. Aluminum Citrate Prevents Renal Injury from Calcium Oxalate Crystal Deposition

    PubMed Central

    Besenhofer, Lauren M.; Cain, Marie C.; Dunning, Cody

    2012-01-01

    Calcium oxalate monohydrate crystals are responsible for the kidney injury associated with exposure to ethylene glycol or severe hyperoxaluria. Current treatment strategies target the formation of calcium oxalate but not its interaction with kidney tissue. Because aluminum citrate blocks calcium oxalate binding and toxicity in human kidney cells, it may provide a different therapeutic approach to calcium oxalate-induced injury. Here, we tested the effects of aluminum citrate and sodium citrate in a Wistar rat model of acute high-dose ethylene glycol exposure. Aluminum citrate, but not sodium citrate, attenuated increases in urea nitrogen, creatinine, and the ratio of kidney to body weight in ethylene glycol–treated rats. Compared with ethylene glycol alone, the addition of aluminum citrate significantly increased the urinary excretion of both crystalline calcium and crystalline oxalate and decreased the deposition of crystals in renal tissue. In vitro, aluminum citrate interacted directly with oxalate crystals to inhibit their uptake by proximal tubule cells. These results suggest that treating with aluminum citrate attenuates renal injury in rats with severe ethylene glycol toxicity, apparently by inhibiting calcium oxalate’s interaction with, and retention by, the kidney epithelium. PMID:23138489

  18. Use of Microfocused X-ray Techniques to Investigate the Mobilization of As by Oxalic Acid

    PubMed Central

    Wovkulich, Karen; Mailloux, Brian J.; Bostick, Benjamin C.; Dong, Hailiang; Bishop, Michael E.; Chillrud, Steven N.

    2012-01-01

    Improved linkages between aqueous phase transport and solid-phase reactions are needed to better predict and model transport of contaminants through the subsurface. Here we develop and apply a new method for measuring As mobilization in situ within soil columns that utilizes synchrotron-based X-ray fluorescence. By performing these measurements in situ during column transport experiments, we simultaneously monitor grain-scale solid phase reactions and column-scale transport. Arsenic may be effectively mobilized by oxalic acid but the geochemical and mineralogical factors that influence the rate and extent of mobilization are not well understood. Column experiments (~4 cm long × 0.635 cm ID) using As contaminated sediments from the Vineland Chemical Company Superfund site were performed on the laboratory bench as well as in the synchrotron beamline. Microfocused synchrotron X-ray fluorescence (μSXRF) maps for As and Fe were collected at the same location in the columns (<1 mm2) before and during treatment with 10 mM oxalic acid. The fraction of As and Fe removed by oxalic acid treatment was calculated from the change in flux-normalized counts for each pixel in the map images, and these data were used to calculate kinetic parameters over the studied area. Between 79% and 83% of the As was removed from the sediments by the oxalic acid treatment based on μSXRF data; these removal percentages agreed well with laboratory data based on column effluent (88–95%). Considerably less Fe was removed by oxalic acid treatment, 14–25% based on μSXRF counts, which is somewhat higher than the 7–9% calculated from laboratory column effluent concentrations. Microfocused X-ray absorption near edge spectroscopy (μXANES) on a subset of points indicates most of the Fe was oxidized and present as a mixture of goethite, hematite, and ferrihydrite on sand grain coatings. Treatment with oxalic acid led to subtle shifts in Fe (III) species following oxalic acid treatment, either removing ferrihydrite or transforming it to more stable oxides; however, Fe redox states were not impacted. Kinetics information extracted from μSXRF data compared favorably with rates of As removal from observed As breakthrough curves. The average pseudo-first order As removal rate constant was calculated to be 0.015 min−1 ± 0.002 (± average standard error, N=400) based on changes in μSXRF counts over time. The spatial variation observed in the rate constant is likely a result of differences in the mineral substrate or As retention mechanism. Geochemical models created using the calculated As removal rate constants showed agreement with As breakthrough curves for both a small column (4.25 cm × 0.635 cm ID) and a larger column (23.5 cm × 4.2 cm ID), indicating that the processes studied using the microprobe are representative and often can be predictive of larger systems. While this work was used to understand the processes that regulate As release and transport, the methods developed here could be used to study a wide variety of reaction processes, including contaminant removal due to chemical treatment, mineral precipitation due to changing redox characteristics, and solid phase transformations. PMID:23175572

  19. Use of Microfocused X-ray Techniques to Investigate the Mobilization of As by Oxalic Acid.

    PubMed

    Wovkulich, Karen; Mailloux, Brian J; Bostick, Benjamin C; Dong, Hailiang; Bishop, Michael E; Chillrud, Steven N

    2012-08-15

    Improved linkages between aqueous phase transport and solid-phase reactions are needed to better predict and model transport of contaminants through the subsurface. Here we develop and apply a new method for measuring As mobilization in situ within soil columns that utilizes synchrotron-based X-ray fluorescence. By performing these measurements in situ during column transport experiments, we simultaneously monitor grain-scale solid phase reactions and column-scale transport. Arsenic may be effectively mobilized by oxalic acid but the geochemical and mineralogical factors that influence the rate and extent of mobilization are not well understood. Column experiments (~4 cm long × 0.635 cm ID) using As contaminated sediments from the Vineland Chemical Company Superfund site were performed on the laboratory bench as well as in the synchrotron beamline. Microfocused synchrotron X-ray fluorescence (μSXRF) maps for As and Fe were collected at the same location in the columns (<1 mm(2)) before and during treatment with 10 mM oxalic acid. The fraction of As and Fe removed by oxalic acid treatment was calculated from the change in flux-normalized counts for each pixel in the map images, and these data were used to calculate kinetic parameters over the studied area. Between 79% and 83% of the As was removed from the sediments by the oxalic acid treatment based on μSXRF data; these removal percentages agreed well with laboratory data based on column effluent (88-95%). Considerably less Fe was removed by oxalic acid treatment, 14-25% based on μSXRF counts, which is somewhat higher than the 7-9% calculated from laboratory column effluent concentrations. Microfocused X-ray absorption near edge spectroscopy (μXANES) on a subset of points indicates most of the Fe was oxidized and present as a mixture of goethite, hematite, and ferrihydrite on sand grain coatings. Treatment with oxalic acid led to subtle shifts in Fe (III) species following oxalic acid treatment, either removing ferrihydrite or transforming it to more stable oxides; however, Fe redox states were not impacted. Kinetics information extracted from μSXRF data compared favorably with rates of As removal from observed As breakthrough curves. The average pseudo-first order As removal rate constant was calculated to be 0.015 min(-1) ± 0.002 (± average standard error, N=400) based on changes in μSXRF counts over time. The spatial variation observed in the rate constant is likely a result of differences in the mineral substrate or As retention mechanism. Geochemical models created using the calculated As removal rate constants showed agreement with As breakthrough curves for both a small column (4.25 cm × 0.635 cm ID) and a larger column (23.5 cm × 4.2 cm ID), indicating that the processes studied using the microprobe are representative and often can be predictive of larger systems. While this work was used to understand the processes that regulate As release and transport, the methods developed here could be used to study a wide variety of reaction processes, including contaminant removal due to chemical treatment, mineral precipitation due to changing redox characteristics, and solid phase transformations. PMID:23175572

  20. Use of microfocused X-ray techniques to investigate the mobilization of arsenic by oxalic acid

    NASA Astrophysics Data System (ADS)

    Wovkulich, Karen; Mailloux, Brian J.; Bostick, Benjamin C.; Dong, Hailiang; Bishop, Michael E.; Chillrud, Steven N.

    2012-08-01

    Improved linkages between aqueous phase transport and solid-phase reactions are needed to better predict and model transport of contaminants through the subsurface. Here we develop and apply a new method for measuring As mobilization in situ within soil columns that utilizes synchrotron-based X-ray fluorescence. By performing these measurements in situ during column transport experiments, we simultaneously monitor grain-scale solid phase reactions and column-scale transport. Arsenic may be effectively mobilized by oxalic acid but the geochemical and mineralogical factors that influence the rate and extent of mobilization are not well understood. Column experiments (4 cm long 0.635 cm ID) using As contaminated sediments from the Vineland Chemical Company Superfund site were performed on the laboratory bench as well as in the synchrotron beamline. Microfocused synchrotron X-ray fluorescence (?SXRF) maps for As and Fe were collected at the same location in the columns (<1 mm2) before and during treatment with 10 mM oxalic acid. The fraction of As and Fe removed by oxalic acid treatment was calculated from the change in flux-normalized counts for each pixel in the map images, and these data were used to calculate kinetic parameters over the studied area. Between 79% and 83% of the As was removed from the sediments by the oxalic acid treatment based on ?SXRF data; these removal percentages agreed well with laboratory data based on column effluent (88-95%). Considerably less Fe was removed by oxalic acid treatment, 14-25% based on ?SXRF counts, which is somewhat higher than the 7-9% calculated from laboratory column effluent concentrations. Microfocused X-ray absorption near edge spectroscopy (?XANES) on a subset of points indicates most of the Fe was oxidized and present as a mixture of goethite, hematite, and ferrihydrite on sand grain coatings. Treatment with oxalic acid led to subtle shifts in Fe (III) species following oxalic acid treatment, either removing ferrihydrite or transforming it to more stable oxides; however, Fe redox states were not impacted. Kinetics information extracted from ?SXRF data compared favorably with rates of As removal from observed As breakthrough curves. The average pseudo-first order As removal rate constant was calculated to be 0.015 min-1 0.002 ( average standard error, N = 400) based on changes in ?SXRF counts over time. The spatial variation observed in the rate constant is likely a result of differences in the mineral substrate or As retention mechanism. Geochemical models created using the calculated As removal rate constants showed agreement with As breakthrough curves for both a small column (4.25 cm 0.635 cm ID) and a larger column (23.5 cm 4.2 cm ID), indicating that the processes studied using the microprobe are representative and often can be predictive of larger systems. While this work was used to understand the processes that regulate As release and transport, the methods developed here could be used to study a wide variety of reaction processes, including contaminant removal due to chemical treatment, mineral precipitation due to changing redox characteristics, and solid phase transformations.

  1. Isolation and some characteristics of anaerobic oxalate-degrading bacteria from the rumen.

    PubMed Central

    Dawson, K A; Allison, M J; Hartman, P A

    1980-01-01

    Obligately anaerobic oxalate-degrading bacteria were isolated from an enriched population of rumen bacteria in an oxalate-containing medium that had been depleted of other readily metabolized substrates. These organisms, which are the first reported anaerobic oxalate degraders isolated from the rumen, were gram negative, nonmotile rods. They grew in a medium containing sodium oxalate, yeast extract, cysteine, and minerals. The only substrate that supported growth was oxalate. Growth was directly related to the concentration of oxalate in the medium (1 to 111 mM), and cell yields were approximately 1.1 g (dry weight)/mol of oxalate degraded. Oxalate was stoichiometrically degraded to CO2 and formate. These anaerobes occupy a unique ecological niche and are distinct from any previously described oxalate-degrading bacteria. Images PMID:7425628

  2. Contribution of calcium oxalate to soil-exchangeable calcium

    USGS Publications Warehouse

    Dauer, Jenny M.; Perakis, Steven S.

    2013-01-01

    Acid deposition and repeated biomass harvest have decreased soil calcium (Ca) availability in many temperate forests worldwide, yet existing methods for assessing available soil Ca do not fully characterize soil Ca forms. To account for discrepancies in ecosystem Ca budgets, it has been hypothesized that the highly insoluble biomineral Ca oxalate might represent an additional soil Ca pool that is not detected in standard measures of soil-exchangeable Ca. We asked whether several standard method extractants for soil-exchangeable Ca could also access Ca held in Ca oxalate crystals using spike recovery tests in both pure solutions and soil extractions. In solutions of the extractants ammonium chloride, ammonium acetate, and barium chloride, we observed 2% to 104% dissolution of Ca oxalate crystals, with dissolution increasing with both solution molarity and ionic potential of cation extractant. In spike recovery tests using a low-Ca soil, we estimate that 1 M ammonium acetate extraction dissolved sufficient Ca oxalate to contribute an additional 52% to standard measurements of soil-exchangeable Ca. However, in a high-Ca soil, the amount of Ca oxalate spike that would dissolve in 1 M ammonium acetate extraction was difficult to detect against the large pool of exchangeable Ca. We conclude that Ca oxalate can contribute substantially to standard estimates of soil-exchangeable Ca in acid forest soils with low soil-exchangeable Ca. Consequently, measures of exchangeable Ca are unlikely to fully resolve discrepancies in ecosystem Ca mass balance unless the contribution of Ca oxalate to exchangeable Ca is also assessed.

  3. [Absorption of extractive Polygonum orientale in rat everted gut sacs].

    PubMed

    Liu, Yue; Tang, Li; Cao, Xu; Zheng, Lin; Wang, Ai-Min; Huang, Yong

    2014-06-01

    Using in vitro everted gut to investigate the intestinal absorption of the extracts from Polygonum orientale at different concentration. UPLC-MS/MS was used to detect the content of protocatechuic acid, isoorientin, orientin, vitexin, cynaroside, quercitrin, kaempferol-rhamnoside in different intestinal segments, then compared the results with the absorption of chemical components of extractive P. orientale in each intestinal segments, and calculated the absorption parameter. We took the statistic analysis with SPSS statistic software. The influence significance of each factors were analyzed to describe the character of absorption. The absorption of each component is linearity in different intestinal segments and different dose, and the square of coeficient correlation exceed 0.95, which consistent with zero order rate process. The K(a) increase along with the raised dosage of the extractive P. orientale (R2 > 0.95), indicated it is the passive absorption; different intestinal segments have different absorption. And the absorption trend in intestinal is duodenum, jejunum, ileum are greater than the colon. As ingredients are selectively absorbed in intestinal sac, the everted intestinal sac method is selected to assess the intestinal absorption charcteristics of ingredients of extractive P. orientale. PMID:25272855

  4. Oxalate content of some common foods: determination by an enzymatic method.

    PubMed

    Kasidas, G P; Rose, G A

    1980-08-01

    A specific enzymatic method was used to determine the oxalate content of some common foods. No preliminary isolation of oxalate was required and recoveries ranging from 95-110 per cent were obtained. Spinach, rhubarb, peanuts, chocolates, parsley and tea were found to contain high levels of oxalate as previously described by others. On the other hand the oxalate content of beetroot was found to be five times as high as previously reported, but coca-cola and beer were almost free from oxalate. Cereals and meat were either low or deficient in oxalate. PMID:7410821

  5. [Determination of glyoxalate and oxalate by capillary zone electrophoresis].

    PubMed

    Guan, Jin; Wang, Huize; Ren, Liyan; Niu, Qiuling

    2012-01-01

    A method for the simultaneous determination of glyoxalate and oxalate by capillary zone electrophoresis (CZE) was developed. The influences of type, concentration and pH of the running buffer, and the applied voltage on separation were investigated. Glyoxalate and oxalate were separated within 11 min under the conditions of 20 mmol/L borax-5.5 mmol/L potassium hydrogen phthalate (pH 9.0), applied voltage of 20 kV, and detected wavelength of 212 nm. The calibration curves of glyoxalate and oxalate showed good linearity in the ranges of 0.8 -20 g/L and 1.2-20 g/L, respectively. The correlation coefficients were 0.999 3 and 0.997 5, respectively. The limits of detection for glyoxalate and oxalate were 0.2 and 0.4 g/L (S/N = 3), respectively. The average recoveries at three spiked levels were 98.3%-102.5% with acceptable relative standard deviations of 0.35%-0.61%. This method is simple, low cost and high performance. The method was successfully used for the determination of glyoxalate and oxalate in real samples, and the assay results were satisfactory. PMID:22667103

  6. Intestinal spirochaetosis

    PubMed Central

    Lee, F. D.; Kraszewski, A.; Gordon, J.; Howie, J. G. R.; McSeveney, D.; Harland, W. A.

    1971-01-01

    An abnormal condition of the large intestine is described in which the surface epithelium is infested by short spirochaetes. Diagnosis can be made by light microscopy. A review of 14 cases diagnosed by rectal biopsy and 62 cases involving the appendix shows no consistent symptom complex. The possible significance is discussed. ImagesFig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 1 PMID:5548558

  7. The relative effects of supplemental dietary calcium and oxalate on urine composition and calcium oxalate relative supersaturation in healthy adult dogs.

    PubMed

    Stevenson, A E; Hynds, W K; Markwell, P J

    2003-08-01

    The aim of this study was to establish the relative effects of dietary calcium and oxalate (in the form of oxalic acid) on the composition of urine produced by healthy adult Cairn Terriers and Miniature Schnauzers. A nutritionally complete dry dog food was fed to 7 dogs (4 Cairn terriers and 3 Miniature schnauzers) for 24 weeks. The dogs were fed the diet alone, or supplemented with six different combinations of dietary calcium (as carbonate and sulphate) and oxalate (as oxalic acid) commonly found in dry commercially prepared dog foods. Urine pH, volume, specific gravity, and concentrations of 12 analytes were measured for each dog; urinary relative supersaturation (RSS) with calcium oxalate (CaOx) was calculated from these values. The effects of supplemental calcium and oxalate were established using two-way analysis of variance and multiple range tests (least significant difference); P<0.05 was considered significant. The lowest level of dietary calcium and oxalate resulted in the lowest CaOx RSS. The high calcium, low oxalate diet resulted in the highest CaOx RSS, a low calcium diet with increased dietary oxalate also tended to increase CaOx RSS although results were highly variable. Urinary calcium concentration increased significantly with dietary calcium; urinary oxalate increased, although inconsistently, with dietary oxalic acid only when dietary calcium was low. Measures to reduce both calcium and oxalate should be considered when implementing dietary changes to reduce the risk of calcium oxalate formation in dogs. A reduction in dietary calcium without a concomitant decrease in dietary oxalate may increase the risk of CaOx crystallisation in susceptible dogs. PMID:12801461

  8. Differentiation of Calcium Oxalate Monohydrate and Calcium Oxalate Dihydrate Stones Using Quantitative Morphological Information from Micro-Computerized and Clinical Computerized Tomography

    PubMed Central

    Duan, Xinhui; Qu, Mingliang; Wang, Jia; Trevathan, James; Vrtiska, Terri; Williams, James C.; Krambeck, Amy; Lieske, John; McCollough, Cynthia

    2014-01-01

    Purpose We differentiated calcium oxalate monohydrate and calcium oxalate dihydrate kidney stones using micro and clinical computerized tomography images. Materials and Methods A total of 22 calcium oxalate monohydrate and 15 calcium oxalate dihydrate human kidney stones were scanned using a commercial micro-computerized tomography scanner with a pixel size of 7 to 23 μm. Under an institutional review board approved protocol, image data on 10 calcium oxalate monohydrate and 9 calcium oxalate dihydrate stones greater than 5 mm were retrieved from a total of 80 patients who underwent clinical dual energy computerized tomography for clinical indications and had stones available for infrared spectroscopic compositional analysis. Micro and clinical computerized tomography images were processed using in-house software, which quantified stone surface morphology with curvature based calculations. A shape index was generated as a quantitative shape metric to differentiate calcium oxalate monohydrate from calcium oxalate dihydrate stones. Statistical tests were used to test the performance of the shape index. Results On micro-computerized tomography images the shape index of calcium oxalate monohydrate and calcium oxalate dihydrate stones significantly differed (ROC curve AUC 0.92, p <0.0001). At the optimal cutoff sensitivity was 0.93 and specificity was 0.91. On clinical computerized tomography images a significant morphological difference was also detected (p = 0.007). AUC, sensitivity and specificity were 0.90, 1 and 0.73, respectively. Conclusions On micro and clinical computerized tomography images a morphological difference was detectable in calcium oxalate monohydrate and calcium oxalate dihydrate stones larger than 5 mm. The shape index is a highly promising method that can distinguish calcium oxalate monohydrate and calcium oxalate dihydrate stones with reasonable accuracy. PMID:23142201

  9. Changes in oxalate and some mineral concentrations of Setaria sphacelata under cutting and uncutting conditions.

    PubMed

    Rahman, M M; Tateyama, M; Niimi, M; Abdullah, R B; Khadijah, W E Wan; Kawamura, O

    2014-04-01

    Oxalate concentration in forage plants is important, because it results mineral deficiency in ruminants. Data on oxalate concentration in forage plants in conjunction with cutting and uncutting conditions throughout the growing period are limited. This study was aimed to investigate the changes in oxalate and some mineral concentrations of setaria (Setaria sphacelata). The plants were harvested at different stages (vegetative, boot, pre-flowering, flowering and seed) of maturity and at about 50 cm in length of regrowth (second to sixth cuttings) for evaluation of soluble oxalate, insoluble oxalate and some mineral concentrations. Soluble oxalate and total oxalate concentrations, as well as mineral concentrations, decreased with advancing maturity. Both oxalate concentrations (soluble or insoluble) were higher in leaf compared to stem. Soluble oxalate and total oxalate concentrations of regrowth were the highest at third cutting and lowest at sixth cutting. Insoluble oxalate concentration of regrowth was almost similar in all cuttings, except for the sixth cutting. The highest concentrations of potassium, sodium and magnesium of regrowth were observed at third cutting, while the highest concentration of calcium was observed at sixth cutting. A relationship between oxalate and mineral concentrations was partially observed. Results suggest that cutting materials of setaria from June to October could achieve oxalate levels that are toxic to ruminants. PMID:25911853

  10. Vibrational dynamics of a non-degenerate ultrafast rotor: The (C12,C13)-oxalate ion

    PubMed Central

    Kuroda, Daniel G.; Abdo, Mohannad; Chuntonov, Lev; Smith, Amos B.; Hochstrasser, Robin M.

    2013-01-01

    Molecular ions undergoing ultrafast conformational changes on the same time scale of water motions are of significant importance in condensed phase dynamics. However, the characterization of systems with fast molecular motions has proven to be both experimentally and theoretically challenging. Here, we report the vibrational dynamics of the non-degenerate (C12,C13)-oxalate anion, an ultrafast rotor, in aqueous solution. The infrared absorption spectrum of the (C12,C13)-oxalate ion in solution reveals two vibrational transitions separated by approximately 40 cm?1 in the 15001600 cm?1 region. These two transitions are assigned to vibrational modes mainly localized in each of the carboxylate asymmetric stretch of the ion. Two-dimensional infrared spectra reveal the presence and growth of cross-peaks between these two transitions which are indicative of coupling and population transfer, respectively. A characteristic time of sub-picosecond cross-peaks growth is observed. Ultrafast pump-probe anisotropy studies reveal essentially the same characteristic time for the dipole reorientation. All the experimental data are well modeled in terms of a system undergoing ultrafast population transfer between localized states. Comparison of the experimental observations with simulations reveal a reasonable agreement, although a mechanism including only the fluctuations of the coupling caused by the changes in the dihedral angle of the rotor, is not sufficient to explain the observed ultrafast population transfer. PMID:24182056

  11. Microelectrophoretic study of calcium oxalate monohydrate in macromolecular solutions

    NASA Technical Reports Server (NTRS)

    Curreri, P. A.; Onoda, G. Y., Jr.; Finlayson, B.

    1987-01-01

    Electrophoretic mobilities were measured for calcium oxalate monohydrate (COM) in solutions containing macromolecules. Two mucopolysaccharides (sodium heparin and chondroitin sulfate) and two proteins (positively charged lysozyme and negatively charged bovine serum albumin) were studied as adsorbates. The effects of pH, calcium oxalate surface charge (varied by calcium or oxalate ion activity), and citrate concentration were investigated. All four macromolecules showed evidence for adsorption. The macromolecule concentrations needed for reversing the surface charge indicated that the mucopolysaccharides have greater affinity for the COM surface than the proteins. Citrate ions at high concentrations appear to compete effectively with the negative protein for surface sites but show no evidence for competing with the positively charged protein.

  12. Effect of Tribulus terrestris on oxalate metabolism in rats.

    PubMed

    Sangeeta, D; Sidhu, H; Thind, S K; Nath, R

    1994-10-01

    This study concerns the effect of an aqueous extract of Tribulus terrestris on the metabolism of oxalate in male rats fed sodium glycolate. Glycolate feeding resulted in hyperoxaluria as well as increased activities of oxalate synthesizing enzymes of the liver i.e. glycolate oxidase (GAO), glycolate dehydrogenase (GAD) and lactate dehydrogenase (LDH), and decreased kidney LDH activity. T. terrestris administration to sodium glycolate fed rats produced a significant decrease in urinary oxalate excretion, and a significant increase in urinary glyoxylate excretion, as compared to sodium glycolate fed animals. The supplementation of T. terrestris with sodium glycolate also caused a reduction in liver GAO and GAD activities, whereas liver LDH activity remained unaltered. The isoenzyme pattern of kidney LDH revealed that normalization of kidney LDH by T. terrestris feeding was mainly due to an increase in the LDH 5 fraction. The LDH 1 isoenzyme remained unchanged in all the groups. PMID:7853865

  13. The influence of scale inhibitors on calcium oxalate

    SciTech Connect

    Gill, J.S.

    1999-11-01

    Precipitation of calcium oxalate is a common occurrence in mammalian urinary tract deposits and in various industrial processes such as paper making, brewery fermentation, sugar evaporation, and tannin concentration. Between pH 3.5 to 4.5 the driving force for calcium oxalate precipitation increases almost by three fold. It is a complicated process to predict both the nature of a deposit and at which stage of a multi-effect evaporator a particular mineral will deposit, as this depends on temperature, pH, total solids, and kinetics of mineralization. It is quite a challenge to inhibit calcium oxalate precipitation in the pH range of 4--6. Al{sup 3+} ions provide excellent threshold inhibition in this pH range and can be used to augment traditional inhibitors such as polyphosphates and polycarboxylates.

  14. Characterization of wheat germin (oxalate oxidase) expressed by Pichia pastoris

    SciTech Connect

    Pan, Heng-Yen; Whittaker, Mei M.; Bouveret, Romaric; Berna, Anne; Bernier, Francois; Whittaker, James W. . E-mail: jim@ebs.ogi.edu

    2007-05-18

    High-level secretory expression of wheat (Triticum aestivum) germin/oxalate oxidase was achieved in Pichia pastoris fermentation cultures as an {alpha}-mating factor signal peptide fusion, based on the native wheat cDNA coding sequence. The oxalate oxidase activity of the recombinant enzyme is substantially increased (7-fold) by treatment with sodium periodate, followed by ascorbate reduction. Using these methods, approximately 1 g (4 x 10{sup 4} U) of purified, activated enzyme was obtained following eight days of induction of a high density Pichia fermentation culture, demonstrating suitability for large-scale production of oxalate oxidase for biotechnological applications. Characterization of the recombinant protein shows that it is glycosylated, with N-linked glycan attached at Asn47. For potential biomedical applications, a nonglycosylated (S49A) variant was also prepared which retains essentially full enzyme activity, but exhibits altered protein-protein interactions.

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

    PubMed

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

    2016-03-24

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

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

    PubMed Central

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

    2016-01-01

    Inadequate absorptive surface area poses a great challenge to the patients suffering a variety of intestinal diseases causing short bowel syndrome. To date, these patients are managed with total parenteral nutrition or intestinal transplantation. However, these carry significant morbidity and mortality. Currently, by emergence of tissue engineering, anticipations to utilize an alternative method to increase the intestinal absorptive surface area are increasing. In this paper, we will review the improvements made over time in attempting elongating the intestine with surgical techniques as well as using intestinal bioengineering. Performing sequential intestinal lengthening was the preliminary method applied in humans. However, these methods did not reach widespread use and has limited outcome. Subsequent experimental methods were developed utilizing scaffolds to regenerate intestinal tissue and organoids unit from the intestinal epithelium. Stem cells also have been studied and applied in all types of tissue engineering. Biomaterials were utilized as a structural support for naive cells to produce bio-engineered tissue that can achieve a near-normal anatomical structure. A promising novel approach is the elongation of the intestine with an acellular biologic sca