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Biomedical subjects

R A Wapnir

Publications and source records attributed to R A Wapnir.

At least 55 records · Page 3Linked to original sources
PubMed1993

Dietary regulation of copper absorption and storage in rats: effects of sodium, zinc and histidine-zinc.

Zinc (Zn) and L-histidine (His) are known competitors of intestinal copper (Cu) uptake. Sodium (Na) appears to be an enhancer of the luminal phase of Cu absorption. We investigated whether dietary treatment with these modifiers would alter Cu absorption and tissue stores of Zn and Cu in rats. Juvenile male rats were fed semipurified diets with adequate amounts of Cu, Zn and Na (Ctl), or with the addition of either excess Na (Hi Na), Zn (Hi Zn), or Zn plus His (Hi Zn+His) for 3 weeks. The jejunum was perfused in situ with 0.1 mM Cu, 1 mM His to determine Cu and water absorption rates. The lowest Cu absorption rate was observed in the Hi Zn+His group, and both the Hi Zn and Hi Zn+His had greater Cu accumulation in the small intestine than did Ctl or Hi Na rats. Hi Na had no effect on Cu transport. There was excess Cu accumulation in the kidneys of Hi Zn+His rats, and hepatic and kidney metallothioneins were also elevated. These results indicate that while a high Na intake does not affect Cu absorption, excess dietary Zn and His have greater effect than does Zn only in the limitation of Cu uptake.

Absorption↗
PubMed1993

In vitro effect of indomethacin on polymorphonuclear leukocyte function in preterm infants.

Random motility and chemotaxis of polymorphonuclear leukocytes (PMN) was evaluated after in vitro exposure to 0, 300, 600, and 900 ng/mL (0.84, 1.68, and 2.52 mumol/L) of indomethacin. PMN were obtained from cord blood of 22 preterm infants of less than 37 wk gestation. For comparison, PMN were obtained from cord blood of seven healthy full-term infants and from venous blood of 10 normal adults. In preterm infants, a significant decrease of random motility and chemotaxis of PMN was noted at all three drug concentrations; impairment of PMN function was dose dependent in the three groups (p < 0.0001), with the greatest effect seen at 900 ng/mL (2.52 mumol/L). Significant impairment of random motility was noted in full-term infants when compared with adults at all indomethacin concentrations and in chemotaxis at 300 and 600 ng/mL (0.84 and 1.68 mumol/L). The study indicates that indomethacin has an adverse effect on PMN random motility and chemotaxis, which is more pronounced in preterm infants.

Adult↗
PubMed1993

Effect of maternal labor and mode of delivery on polymorphonuclear leukocyte function in healthy neonates.

In this study, effect of maternal labor and mode of delivery on polymorphonuclear leukocyte (PMN) chemiluminescence and random and chemotactic motility was evaluated in healthy full-term neonates. PMN were obtained from cord blood of three groups of neonates: group I, 24 vaginally delivered neonates; group II, 22 neonates delivered by elective cesarean section without labor; and group III, 18 neonates delivered by cesarean section after labor. In group III, six neonates were delivered by cesarean section for fetal distress with acidemia and 12 for failure of progression of labor. Peak chemiluminescence of PMN in group III was depressed compared with groups I and II (p < 0.01). There was no difference in the peak chemiluminescence of PMN from neonates in group I versus group II. Random motility of PMN in group III was increased compared with the random motility in groups I and II (p < 0.05). Chemotactic motility of PMN was comparable in all three groups. In group III, a negative correlation was noted between peak chemiluminescence of PMN and the duration of labor (p < 0.001), whereas no such correlation was observed in group I despite a similar duration of labor. There was no correlation between duration of labor and random and chemotactic motility of PMN in groups I and III. The results of this study indicate that labor and mode of delivery per se have no effect on PMN function and that factors other than labor such as fetal acidemia, fetal distress, arrested labor, or maternal administration of drugs may play a role in alteration of PMN function.

Cell Movement↗
PubMed1993

Zinc absorption in experimental osmotic diarrhea: effect of long-chain fatty acids.

The effect of free fatty acids on zinc absorption was studied in a rat model of chronic osmotic diarrhea induced with magnesium citrate and phenolphthalein. In vivo rates of zinc removal from the lumen and analysis of tissue for zinc uptake and metallothionein alterations were monitored. One mmol/L stearate enhanced zinc absorption in rats with or without diarrhea, from 207 +/- 22 and 353 +/- 13 pmol/min x cm to 676 +/- 34 and 610 +/- 26 pmol/min x cm, respectively. Palmitate was only effective in normal rats. Zinc absorption inversely correlated with mucosal zinc content in the perfused intestinal segments, in both type of rats. Hepatic metallothionein was enhanced by zinc and even more by oleate plus zinc in both groups; kidney metallothionein in animals with diarrhea was normalized by either oleate or zinc. The data support previous reports on the effect of long-chain fatty acids on the enhancement of zinc absorption: saturation and a longer chain appear to be positive factors. A membrane modification role of long-chain fatty acids could have nutritional implications in the formulation of special diets.

Animals↗
PubMed1992

Distinct mechanisms of zinc uptake at the apical and basolateral membranes of caco-2 cells.

Zinc uptake mechanisms at the apical and basolateral membrane borders of caco-2 cells were examined. This human-derived cell line possesses many morphological and functional characteristics of absorptive small intestinal cells. By day 14, confluent and well-differentiated monolayers were formed when the cells were grown on porous polycarbonate filters. Labelled zinc was placed on the apical or basal side of the monolayer and its uptake by the cells, as well as its transport across the monolayer, were measured. Zinc uptake by the cells from the apical side was found to be a saturable process (Kt = 41 microM; Vmax = 0.3 nmols/cm2/10 min) with a diffusional term at higher concentrations (1.0 sec/cm). Apical uptake was not affected by metabolic inhibitors or potential zinc ligands. Zinc uptake from the basolateral side was concentration dependent (Kd = 1.3 sec/cm) and was partially inhibited (30%) by ouabain and vanadate, suggesting that the (Na-K)-ATPase on the basolateral membrane is involved in the serosal uptake of zinc by the cell. Transport of zinc across the monolayers from the apical or basolateral compartment was concentration dependent and was not affected by metabolic inhibitors. Zinc transport from the basolateral side was greater than 2-fold greater than apical transport. Hence, separate mechanisms can be distinguished with respect to zinc uptake at the apical and basolateral membranes of caco-2 cells.

Biological Transport↗
PubMed1992

Intestinal absorption of copper: influence of carbohydrates.

Macronutrients can modulate the intestinal absorption of trace elements by binding the metal or altering mucosal function. We investigated whether certain simple and complex carbohydrates modify copper (Cu) absorption, using an in vivo perfusion technique in the rat. Corn syrup solids, which contain a mixture of glucose polymers of diverse length, added at either 20 or 50 mosm/kg enhanced Cu absorption from a 31.5 microM (2 mg/liter) Cu solution (128 +/- 11 and 130 +/- 11 pmol/min x cm, respectively, vs 101 +/- 4 pmol/min x cm, P less than 0.05, in the absence of carbohydrate). This was concomitant with a stimulation of net water absorption (1.05 +/- 0.08 and 0.84 +/- 0.08 microliter/min x cm, respectively, vs 0.63 +/- 0.02 microliter/min x cm with no carbohydrate, P less than 0.05). Glucose, fructose, lactose, or sucrose had no influence on Cu absorption, although they altered water exchanges, an effect attributable to a reduction of the outflow component of fluid recirculation. Low concentrations of lactose resulted in a greater accumulation of Cu in the intestinal mucosa (8.75 +/- 0.71 micrograms/g vs 5.77 +/- 0.68 micrograms/g for controls, P less than 0.05). Hence, solutes that moderately stimulate mucosa-to-serosa fluid influx in a progressive manner, such as glucose polymers, may contribute to functionally increase Cu absorption. Conversely, conditions which tend to reduce water inflow or increase water outflow across the small intestinal mucosa, as may occur with high lactose diets or in cases of chronic diarrhea, may have negative effects.

Animals↗
PubMed1992

Development of the neonatal rat small intestinal barrier to nonspecific macromolecular absorption. II. Role of dietary corticosterone.

The role of oral corticosterone (C) in the maturation of the neonatal rat jejunal barrier to the absorption of nonspecific macromolecules was evaluated. This was done by adding C to the diet of rat pups weaned at an early age, 17 d, from maternal milk (MM) to either a protein hydrolysate (PH) or soy (S) artificial formula. Both PH and S are known to cause a delay in small intestinal closure to the absorption of a 40-kD glycoprotein tracer, horseradish peroxidase (HRP), on d 21 of age. C was added to PH and S formulas from d 17 to 21 at 0.26 mumol/L (10 micrograms/dL), a level found in the MM of lactating rat dams, or at 10.29 mumol/L (400 micrograms/dL) (PH + 10C, PH + 400C) (S + 10C, S + 400C). Controls consisted of rat pups fed PH or S without C and animals remaining with the dam on MM. The delay in jejunal closure to HRP on d 21 in both PH- and S-fed pups was prevented by C supplementation at both the higher and lower concentrations. Geometric mean (95% confidence intervals) jejunal HRP absorption in PH + 10C pups was 74 (32,167) IU HRP/mL x cm x min, less than in pups fed PH without C [353 (200,615); p less than 0.05] and indistinguishable from HRP absorption in MM-fed animals [111 (79,154)]. HRP absorption in PH + 400C pups [52 (23,115)] was also less than that in animals fed PH without C (p less than 0.01) and indistinguishable from those fed MM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Inhibition of copper absorption by zinc. Effect of histidine.

Copper and zinc interact at the intestinal mucosal level, affecting copper absorption. Amino acids, such as histidine, may affect the absorption of these two elements by chelating these cations. The two mechanisms could have additive potential. This possibility was investigated using a duodenal-jejunal single-pass perfusion procedure in anesthetized rats. Copper absorption and tissue retention from solutions containing 0.1 mM copper were determined in the presence of either no zinc or equimolar zinc, or at a zinc/copper ratio of 10/1, either without histidine or with histidine at a 10/1 or 20/1 ratio to copper. Copper removal from the intestinal lumen was decreased by zinc, and further reduced by increasing concentrations of histidine. There was a greater accumulation of copper in the small intestine, reaching a maximum with a 10-fold excess of histidine. With zinc at a 10/1 ratio to copper, the addition of a 10- or 20-fold molar excess of histidine further decreased the net uptake of copper from the perfusate while greater copper accumulation in the tissue occurred. Histidine thus enhances the inhibitory effects of zinc on copper absorption, suggesting the application of convergent mechanisms for diminishing copper uptake. This could be relevant for the treatment of Wilson's disease.

Animals↗
PubMed1991

Zinc-induced metallothionein synthesis by Caco-2 cells.

Caco-2 cells possess many morphological and biochemical characteristics of intestinal absorptive cells, including the ability to transport zinc. In the present study, metallothionein (MT) synthesis in response to increased levels of zinc was examined. Increased incorporation of [35S]cysteine into MTs was observed when excess ZnCl2 was added to the medium. The rate of MT synthesis was found to be concentration dependent. Also, induction of MT synthesis was greater early in the culture, before the cells were fully differentiated. Incubation of the monolayers with 65Zn and 200 microM zinc revealed that approximately 50% of the zinc incorporated into the cells was associated with MTs. The remainder was associated with large proteins as well as amino acids and small peptides. Actinomycin D and cycloheximide both inhibited the induction of MT synthesis, suggesting that the newly synthesized MTs are a result of expression of MT genes. Hence, Caco-2 cells, a model of intestinal absorptive cells, may be used to examine the role of MTs in zinc absorption.

Animals↗
PubMed1991

Improved water and sodium absorption from oral rehydration solutions based on rice syrup in a rat model of osmotic diarrhea.

Rice syrup solids, rice protein, and casein hydrolysate were added to experimental oral rehydration solutions in various combinations and tested in a rat intestinal perfusion system. Chronic osmotic diarrhea was induced in juvenile rats by supplying the cathartic agents, magnesium citrate and phenolphthalein, in their drinking water for 1 week. The experimental oral rehydration solutions were compared with standard oral rehydration solutions containing 20 gm/L or 30 gm/L of glucose and with each other to determine if there were significant differences in net water, sodium, or potassium absorption. An oral rehydration solution containing 30 gm/L of rice syrup solids had a net water absorption rate significantly higher than that of the standard 20 gm/L glucose-based oral rehydration solution (2.1 +/- 0.62 versus 1.5 +/- 0.48 microliters/[min x cm], p less than 0.05). Casein hydrolysate did not significantly affect net water absorption. However, combinations of 30 gm/L rice syrup solids and 5 gm/L casein hydrolysate significantly increased (p less than 0.05) net sodium and potassium absorption compared with the 20 gm/L glucose-based oral rehydration solution but not versus rice syrup solids alone. Oral rehydration solutions containing 30 gm/L rice syrup solids plus 5 gm/L rice protein, and 30 gm/L rice syrup solids plus 5 gm/L casein hydrolysate, had net water absorption rates significantly higher than the rate of a 30 gm/L glucose-based oral rehydration solution (2.5 +/- 0.36 and 2.4 +/- 0.38, respectively, versus 0.87 +/- 0.40 microliters/[min x cm], p less than 0.05). Rice protein and casein hydrolysate, however, did not significantly affect net water, sodium, or potassium absorption when added to rice protein glucose-based oral rehydration solutions. An inverse correlation between osmolality and net water absorption was observed (r = -0.653, p less than 0.02). The data suggest that substitution of rice syrup solids for glucose in oral rehydration solutions will improve water absorption and that rice syrup solids in combination with protein hydrolysates may, in addition, promote better sodium and potassium uptake.

Administration, Oral↗
PubMed1991

Copper-sodium linkage during intestinal absorption: inhibition by amiloride.

The possible association between copper and sodium small intestinal absorption in the rat was investigated in the presence or absence of the electrolyte transport inhibitors amiloride, acetazolamide, and furosemide, at pharmacologic concentrations, using an in situ perfusion procedure. Amiloride (1 mM) produced a significant decrease in copper, net water, and sodium absorption, in solutions with sodium. Copper tissue retention was not altered, but was much higher in the absence of sodium. Acetazolamide and furosemide (1 mM), in separate experiments, had no effect on copper removal from the lumen, but generally reduced sodium and water transport. The presence or absence of sodium in the perfusate influenced rates of copper uptake. These data are compatible with a more effective passage of copper across the enterocyte basolateral membrane in the presence of sodium than in its absence.

Acetazolamide↗
PubMed1990

Alanine stimulation of water and sodium absorption in a model of secretory diarrhea.

We investigated the effectiveness of L-alanine (Ala) addition to oral hydration solutions (OHSs) during secretory conditions induced by ileal instillation of 10 mM theophylline in anesthetized rats using a perfusion procedure, and monitoring water and sodium transport. Ala was added to two hypotonic OHSs in which the sodium:glucose ratio was 2:1, and compared with the OHS recommended by the World Health Organization (WHO), which has a sodium:glucose ratio of 0.81:1. Theophylline had the expected secretory effect on water and sodium absorption in the WHO-recommended OHS, and on sodium transport in a formula containing 60 mM sodium and 30 mM glucose. However, an OHS with 90 mM sodium and 45 mM glucose canceled the secretory effect of theophylline and yielded a greater rate of net water absorption than the WHO formula. Addition to this solution of either 15 or 30 mM Ala enhanced water and sodium absorption of both control and theophylline-treated rats. In the hypotonic OHS with 60 mM sodium and 30 mM glucose, Ala had little effect on both sodium and water transport. Therefore, the data support the view that Ala added to solutions with 90 mM sodium, containing sufficient glucose to maintain a sodium:glucose ratio of not less than 2:1, is most effective at compensating fluid and sodium losses under secretory conditions. Ala presumably exerts its sodium-sparing effect because of its cotransport with sodium and the consequent water influx into the intestinal cells.

Absorption↗
PubMed1990

Development of the neonatal rat small intestinal barrier to nonspecific macromolecular absorption: effect of early weaning to artificial diets.

We studied the effect of early weaning from maternal breast milk to artificial diets on rat jejunal absorption of an exogenous 40-kD glycoprotein, horseradish peroxidase (HRP). Rat pups, fed maternal milk (MM) from birth, received one of three diets for the last 4 d before weaning (d 17-21): MM, protein hydrolysate formula (PH), or soy formula (S). Some rats were pretreated on d 14 with intraperitoneal hydrocortisone (5 mg/rat). In MM-fed rat pups, jejunal HRP absorption was markedly higher on d 17 than on d 21. [Geometric means (95% confidence interval) were: d 17, 626.4 (461.3, 850.6) versus d 21, 90.6 (48.2, 170.5) IU HRP/mL x cm x min, p less than 0.01.] By contrast, 21-d-old PH- and S-fed pups maintained elevated absorption of the tracer [PH, 292.3 (177.5, 480.6), p less than 0.05 versus MM pups, S, 340.8 (164.4, 704.8), p less than 0.01 versus MM pups]. Wt-matched control studies indicate that the difference in HRP absorption was not due to the smaller body wt of formula-fed pups. The increased absorption in formula-fed animals was suppressed by hydrocortisone. In S-fed pups, the increased macromolecular absorption appeared, in part, to be the result of diffusion across altered villus absorptive cells. In PH-fed pups, there was no evidence of damage and HRP absorption appeared to occur by vesicle-mediated transport. Delay in the normal maturation of small intestinal "closure" appears to be associated with early weaning to artificial diets. This may lead to increased nonspecific macromolecular permeability that could result in immune-mediated sensitization and food intolerance.

Age Factors↗
PubMed1989

Intestinal absorption of zinc: sodium-metal-ligand interactions.

The characteristics of zinc small intestinal absorption were investigated with the purpose of clarifying the role of sodium and the possible interaction among certain amino acids, oligopeptides, and zinc with electrolyte and water absorption. A perfusion procedure was used in anesthetized rats. Physiological concentrations of zinc with no ligands, or with twice the zinc levels of either Trp, His, Pro, or a protein hydrolysate (PrH) were pumped through jejunal or ileal segments. PrH was also used at a 10: 1 ratio to zinc. The osmotic solutes were either sodium chloride, glycerol, or NMG at isotonic concentrations. In the absence of LMW ligands, zinc transport appeared to occur only by diffusion, except in the ileum and in the presence of glycerol, where at low zinc concentrations a low affinity mediated transport component could be identified (Kt = 0.67 mM; Vmax = 1,160 pmole/min.cm. Glycerol generally elicited a greater overall zinc absorption rate as well as an enhanced net water uptake than when sodium chloride was the osmotic agent when either Trp, His, or Pro was present. The data indicate that sodium is not a requirement for zinc transport. In the presence of LMW ligands, which may also be from endogenous origin, bulk flow may be a major contributor of zinc translocation across the mammalian small intestinal mucosa.

Amino Acids↗
PubMed1989

Zinc uptake by isolated rat enterocytes: effect of low molecular weight ligands.

The luminal phase of zinc intestinal absorption has not been well characterized. This study was intended to elucidate the possible role of low molecular weight (LMW) ligands in zinc intestinal transport in an isolated rat enterocyte system. Under these in vitro conditions, zinc uptake by the isolated enterocytes was rapid, leveling off within 1 min. Kinetic analysis revealed that both a mediated and diffusion component were involved in zinc uptake in the absence of LMW ligands by the cells. For the mediated component of zinc transport, the Kt and Vmax were 64.1 microM and 13.9 nmol/20 sec/mg protein, respectively. Zinc uptake was not affected by the addition of metabolic inhibitors. In the presence of histidine or cysteine (2:1 ligand:zinc molar ratio), zinc uptake was greatly reduced and occurred solely via mediated transport. Zinc uptake was also significantly decreased upon the addition of EDTA to the assay media. Other amino acids tested had no effect on zinc uptake by the cells. Albumin markedly reduced zinc uptake by the cells. Histidine and other potential LMW ligands were unable to facilitate albumin-inhibited zinc uptake. The results of this study suggest that the intestinal absorption of zinc may not be effected in the form of chelates with LMW ligands. Amino acids such as histidine and cysteine significantly reduce the uptake of the metal by isolated rat enterocytes, making questionable their putative role as necessary vehicles in the luminal phase of zinc absorption.

Albumins↗
PubMed1989

Morphologic and functional alterations in absorptive epithelial cells during L-tryptophan induced inhibition of net sodium and fluid absorption in the rat ileum.

L-Tryptophan (L-Trp) has been reported to suppress jejunal fluid and electrolyte transport in vitro, at a 20 mM concentration, whereas other amino acids enhance that absorption at the same concentration. The effect of L-Trp, glycine (Gly) and L-phenylalanine (L-Phe) on in vivo ileal and jejunal fluid and sodium transport, and their morphologic correlates, were investigated in the rat. In the ileum, morphology as well as fluid and sodium transport were more readily altered by L-Trp than in the jejunum. The ileal effects were rapid; morphologic and transport changes were seen within 2.5 minutes. The changes were stereospecific; they occurred only with the levo, but not with the dextro isomer of Trp. There was a concentration dependence; 20 mM levels of L-Trp were required, whereas lower concentrations of the amino acid often stimulated net absorption. Morphologic alterations produced by L-Trp were restricted to absorptive epithelial cells, whereas goblet cells appeared unaffected. Morphologically, L-Trp treatment led to the formation of clear basal vacuoles in ileal absorptive epithelial cells at 2.5 minutes, and extensive vacuolization and loss of the lumenal permeability barrier to macromolecules at 30 minutes. Since L-Trp can be hydroxylated in the small intestine, we assessed the effects of L-5 = OH tryptophan and 5-hydroxytryptamine on small intestinal transport and morphology in this experimental system. L-5-OH tryptophan inhibited fluid transport and produced some epithelial cell vacuolization. However, 5-hydroxytryptamine, which most severely decreased transport, had none of the morphologic effects of L-Trp. We hypothesize that L-Trp may inhibit transport as a result of its intracellular accumulation in absorptive epithelial cells.

Animals↗
PubMed1988

Oral hydration solutions in experimental osmotic diarrhea: enhancement by alanine and other amino acids and oligopeptides.

Improvement of sodium absorption during the administration of oral hydration solutions (OHS) could increase the efficacy of formulations used in the treatment of infantile diarrhea. To test this hypothesis, selected protein breakdown products were evaluated as absorption enhancers in OHS of different osmolalities and Na-to-glucose ratios in an animal model of osmotic diarrhea induced by cathartics. A very significant increase in water and Na absorption occurred in rats with diarrhea when they were perfused with a 90-mmol/L-Na, 111-mmol/L-glucose OHS containing 30 mmol/L of L-alanine (Ala). The same effect on Na retention was observed with a protein hydrolysate (PrH) in rats with diarrhea. Glycine was not effective. Other experimental OHS were ineffective in rats with diarrhea. The data indicate that in this animal model of chronic diarrhea Na transport enhancers, such as Ala and a PrH, are most efficacious in the presence of higher Na concentration.

Absorption↗