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Biomedical subjects

R A Wapnir

Publications and source records attributed to R A Wapnir.

At least 19 recordsLinked to original sources

Stimulation of non-sodium-dependent water, electrolyte, and glucose transport in rat small intestine by gum arabic.

In experimental models of gastroenterological disease, the soluble fiber gum arabic (GA) acts as a proabsorptive adjuvant. This study investigated which specific transport pathway(s) are affected by GA. Rat jejunum was perfused under anesthesia with a standardized oral rehydration solution (ORS) containing D-glucose, with or without GA (2.5 g/liter). In some preparations either phloridizin, a competitive inhibitor of Na+-coupled D-glucose transport, or phloretin, an inhibitor of basolateral glucose transport, were added to the ORS, with or without GA. Diffusion and paracellular transport changes due to GA were evaluated with L-glucose and [14C]polyethlyene glycol 4000 (PEG). GA partially reversed water, Na+, and D-glucose absorption inhibition induced by phloridzin and normalized water and Na+ absorption in the presence of phloretin. GA also increased absorption of water, Na+, and PEG from an L-glucose ORS. The data suggest that GA does not act via Na+ dependent mechanism(s), but stimulates transcellular and/or transjunctional transport pathways; therefore GA may be useful to increase absorption of solutes transported by diffusion.

Animals↗

Development of the intestinal SGLT1 transporter in rats.

Glucose absorption from the small intestine is largely mediated via the sodium-coupled glucose transporter (SGLT1). The goal of this study was to investigate the ontogenesis of the SGLT1, using the rat as an animal model at three stages of development: during lactation, at weaning, and at physiologic maturity. The techniques involved upper small intestinal perfusions with solutions containing 200 mM glucose and 50 mM NaCl, with or without 1 mM phloridzin (Phl), as an inhibitor of SGLT1. Molecular expression of the SGLT1 was also investigated via Western blot analysis from intestinal specimens of the three growth periods. Glucose absorption in weanling rats, in the absence of Phl, was several times higher than in sucklings and approximately double that of mature animals, and the effects of Phl were the greatest in weanlings. Furthermore, the physiologic data correlate to the molecular analysis of the SGLT1 which showed an increase in expression of the SGLT1 in both the weanlings and the adults compared to the sucklings. At all three stages of development Phl abolished Na absorption, and in sucklings there was a net outflow of Na. Due to the coupling between Na and water transport, net water absorption and the influx/efflux ratio, a more sensitive indicator of changes in unidirectional fluid movement, were similarly affected by Phl at the three stages of development. Net water absorption was highest in weanling animals. These findings are consistent with an early development of SGLT1 in rat small intestine and an apparent burst of activity at weaning. Less than complete maturity of other absorptive mechansims is occurring at this time.

Aging↗

Cholera toxin-induced secretion in rats is reduced by a soluble fiber, gum arabic.

Gum arabic (GA), a soluble fiber with emulsifying properties, enhances intestinal water and electrolyte absorption in normal and secreting rats. Our aim was to assess the effect of GA, 2.5 and 5.0 g/liter, on cholera toxin-induced water and electrolyte secretion in rat jejunum in vivo. After a 2-hr exposure to cholera toxin, jejunal segments of adult rats were perfused in vivo with at plasma electrolyte solution containing GA, 0, 2.5 or 5.0 g/liter. 24Na was used as a marker of sodium influx. Cholera toxin-induced secretion was reduced by GA, 2.5 and 5.0 g/liter. 24Na secretion into the lumen was reduced by GA. GA caused a morphological expansion of intercellular spaces in the villi but not crypts. In conclusion, GA promotes lumen to blood intestinal transport of water and sodium despite cholera toxin activation. These observations support a potential role for GA in enhancing the efficacy of ORS.

Animals↗

Zinc deficiency, malnutrition and the gastrointestinal tract.

Recent clinical and experimental findings have reinforced the link among zinc deficiency, malnutrition and diarrheal disease. Because there is a strong association between protein and zinc content in virtually all types of foods, insufficient protein intake may often be the cause of zinc deficiency. Compensatory mechanisms operating in monogastric species during malnutrition are less effective for the absorption of transition divalent elements such as zinc, which remain bound to ligands of dietary or endogenous origin. Both protein and zinc deficiencies are strong negative determinants for normal cellular immunity. In zinc deficiency, the organism is more susceptible to toxin-producing bacteria or enteroviral pathogens that activate guanylate and adenylate cyclases, stimulating chloride secretion, producing diarrhea and diminishing absorption of nutrients, thus exacerbating an already compromised mineral status. In addition, zinc deficiency may impair the absorption of water and electrolytes, delaying the termination of normally self-limiting gastrointestinal disease episodes. The gastrointestinal tract may be one of the first target areas where zinc insufficiency may be manifested. A prolonged low zinc intake deprives the organism of the local potential beneficial effects of zinc, including interactions with oxidative free radicals and nitric oxide metabolism. Nitric oxide is a second messenger that plays an important part in the triggering of diarrheal disease. The possible interrelationship among infection, inflammation, free radical damage and its quenching by potential scavengers, such as zinc, in the intestinal lumen or within the enterocyte should be more extensively studied.

Animals↗

Combined effect of high-fat diet and copper deficiency during gestation on fetal copper status in the rat.

We have previously shown that a low-copper (Cu) diet produced alterations in placental Cu transport and fetal Cu stores. Because Cu deficiency has been associated with lipid deposition in rat dam liver, we hypothesized that a high fat intake, a prevalent dietary habit in many populations, may worsen fetal Cu status and its closely linked iron (Fe) deposits. Pregnant rats were fed one of four diets during the second half of gestation: NFNCu: normal fat (7%), normal Cu (6 mg/kg); HFNCu: high fat (21%), normal Cu; NFLCu: normal fat, low Cu (0.6 mg/kg), and HFLCu: high fat, low Cu. One day before delivery, dams were anesthetized, and maternal as well as fetal plasma and tissues were obtained. Maternal, fetal, and placental weights were indistinguishable regardless of the group. Dam plasma Cu and placental Cu were lower in both LCu groups than in the NFNCu or the HFNCu groups. However, fetal plasma Cu was similar in all treatment groups. Dam and fetal liver Cu stores were reduced in the LCu groups compared to the NCu groups. This resulted in lower fetal/maternal liver Cu ratios in the NFLCu (1.79+/-0.14, p < 0.05) and HFLCu (1.59+/-0.21, p < 0.05) as compared to the NFNCu (4.12+/-0.44) and the HFNCu (4.15+/-0.27). Dam liver Fe was higher in the NFNCu than in HFNCu group (1.10+/-0.8 vs. 0.89+/-0.06 micromol/g, p < 0.05); fetal liver Fe from HFNCu and NFLCu dams was lower than that from NFNCu fetuses (NFNCu: 2.42+/-0.14; HFNCu: 1.92+/-0.15, p < 0.05; NFLCu: 1.81+/-0.10, p < 0.01). Fetuses of the HFLCu group had a lower heart Fe than the NFNCu group (0.56+/-0.03 vs. 44.0+/-3.0 microg/g, p < 0.01). These data indicate that a maternal high-fat diet can potentially aggravate the effects of Cu deficiency by further altering fetal Cu and Fe tissue stores.

Animals↗

Effect of gum arabic in an oral rehydration solution on recovery from diarrhea in rats.

BACKGROUND: It has been shown that gum arabic, a soluble fiber, enhances water, electrolyte, and glucose absorption from oral rehydration solutions in jejunal perfusion of healthy rats and in animals with theophylline-induced secretion or chronic osmotic-secretory diarrhea. This report concerns a study of the effectiveness of an oral rehydration solution supplemented with gum arabic, during recovery from chronic osmotic secretory diarrhea in free-living rats. METHODS: Chronic diarrhea was induced in 60- to 80-g juvenile rats by providing a magnesium citrate-phenolphthalein solution as the sole fluid source for 7 days. This led to diarrhea characterized by dehydration, soft stools, increased cecal volume, decreased food and fluid intake and failure to gain weight. After 7 days of diarrhea, rats recovered for 24 hours with either tap water or an oral rehydration solution (90 mM Na, 111 mM glucose, 20 mM K, 80 mM chloride, 20 mM citrate) with or without 2.5 g/l gum arabic. RESULTS: Although all three solutions improved the diarrhea, optimal recovery from diarrhea was achieved with the gum arabic-supplemented oral rehydration solution. After 4 hours and 24 hours, rats drinking the gum arabic-supplemented solution gained more weight and had lower fecal output than rats receiving water or the rehydration solution without gum arabic. All three solutions normalized plasma osmolality after 24 hours. CONCLUSIONS: The positive effects of the gum arabic-supplemented rehydration solution on fluid and electrolyte absorption seen during jejunal perfusion also occurred during recovery from chronic osmotic secretory diarrhea, when free-living animals drank the solution ad libitum.

Animals↗

Promotion of copper excretion from the isolated rat heart attenuates postischemic cardiac oxidative injury.

This study examined the role of Cu as a mediator of cardiac postischemic oxidative injury. Isolated rat hearts were subjected to 20 min of normothermic global ischemia, followed by 30 min of reperfusion; after 20 min of preischemic loading with Krebs-Henseleit buffer +/- 20 or 30 microM zinc-bis-histidinate (Zn-His2), 0.5 mM deferoxamine (DEF) or 42 microM neocuproine (NEO). Postischemic developed systolic pressure and rate-pressure product were highest and postischemic end-diastolic pressure was lowest in hearts treated with 20 or 30 microM Zn-His2 and 0.5 mM DEF. Cu efflux was significantly increased by 225 and 290% (end of preischemic loading), and 325 and 375% (immediate postischemic period) of control basal rates in hearts treated with 30 microM Zn-His2 and 0.5 mM DEF, respectively. NEO did not effect any of these parameters. By the end of ischemia, protein carbonyls were lowest in Zn-His2-treated hearts and highest in DEF-treated hearts when compared with control hearts. The results of this study suggest that removal of redox-active Cu before ischemia has beneficial effects, indicating a mediatory role in postischemic cardiac oxidative injury.

Animals↗

Modified starch enhances absorption and accelerates recovery in experimental diarrhea in rats.

Rice gruels have been used as home remedies to treat dehydration associated with diarrheal illness in developing countries. These preparations have produced conflicting results, most likely due to the heterogeneity of starch used. We investigated whether the modified tapioca starch, Textra (TX), at 5.0 or 10.0 g/L added to a 90 mmol/L Na+-111 mmol glucose oral rehydration solution (ORS) enhanced water and electrolyte absorption in two models of diarrhea. To induce a secretory state (model A), the jejunum of juvenile rats was perfused with 10 mmol/L theophylline (THEO) under anesthesia and then perfused with the solutions indicated above. To produce chronic osmotic-secretory diarrhea (model B), rats had a magnesium citrate-phenolphthalein solution as the sole fluid source for 1 wk, and then were perfused as the THEO-treated rats. Water, electrolyte, and glucose absorption were measured during both perfusions. As an extension of the perfusion studies, we compared how fast rats recovered from chronic osmotic diarrhea by offering them either water, ORS, or ORS containing 5.0 g/L TX along with solid food. Recovery rate markers were measured after 24 h and included weight gain, food and fluid intake, and stool output. In model A, addition of 5.0 g/L TX to ORS reversed Na+ secretion and improved net water as well as K+ and glucose absorption, compared with THEO-treated rats perfused with ORS without TX. In model B, addition of TX to ORS increased water, Na+, K+, and glucose absorption, compared with rats perfused without TX. Increasing TX from 5.0 to 10.0 g/L had no additional benefit. In recovery experiments, animals with free access to ORS with TX had significantly greater weight gain and decreased stool output compared with animals recovering with water or ORS without TX. Our experiments suggest that TX may be a useful additive to standard ORS to promote fluid and electrolyte absorption and may provide additional energy without increasing ORS osmotic load.

Animals↗

The role of dietary zinc in modifying the onset and severity of spontaneous diabetes in the BB Wistar rat.

The goal of this study was to determine whether zinc supplementation in the diet of diabetes-prone BB Wistar rats will delay or prevent the onset of overt diabetes. Male Wistar BB rats were fed diets containing either 1000 ppm (HZ), 50 ppm (NZ), or 1 ppm zinc (LZ) starting at 30 days of age. Non-diabetes-prone rats were fed NZ and designated as controls (NORM). Beginning at 60 days, the rats were checked for glycosuria and, if positive, were given an i.p. glucose tolerance test (IPGTT). All remaining animals underwent an IPGTT at 100 days and were sacrificed. At 90 days of age HZ rats had a lower incidence of diabetes (19%) than NZ (53%) or LZ (44%) animals (P < 0.015). By age 100 days, for the HZ group, there was a 60% reduction in the number of expected overt diabetic rats. HZ animals also had higher concentrations of both pancreatic and serum insulin and exhibited lower serum glucose and triglycerides. Immunohistochemistry of HZ rats was clearly different from NZ rats and showed evidence of nearly normal pancreatic endocrine activity. Data indicate that dietary treatment of diabetes-prone BB Wistar rats with zinc appears to be an effective approach for delaying or preventing the onset of diabetes in genetically predisposed rodents. This finding may suggest further experimental studies regarding dietary means for preservation of pancreatic function.

Adolescent↗

Placental copper transport in the rat. III: Interaction between copper and iron in maternal protein deficiency.

Copper (Cu) and iron (Fe) metabolism are linked in the haematopoietic process. There is also considerable evidence of a linkage between protein intake and mineral sufficiency. The present study tested the hypothesis that a low protein diet during the second half of gestation in the rat alters Cu and Fe transport across the placenta and affects the Cu and Fe status of the fetus. Pregnant rats were fed a normal commercial diet the first half of gestation, and then assigned either a 20 per cent protein (NP) or a 4 per cent protein diet (LP) during the second half of gestation. One day before delivery, rats were anaesthetized, fetuses removed and dam tissues and plasma obtained. Other pregnant rats were injected i.v. with 2.5 mg/kg Cu acetate and sequential samples of dam blood, fetal blood and placentae were taken from 0 to 60 min. The LP diet produced generalized maternal hypoproteinaemia, and although there was no difference in fetal plasma albumin, there was a generalized fetal hypoproteinaemia as well. Fetal haematocrit (Hct) of the LP litters was lower than that of the NP group, but dam Hct was unchanged. Dam plasma Fe and Cu showed no differences between diets. Dam liver Cu was unaltered but liver Fe stores were elevated significantly. Before and after a Cu bolus, the LP placentae retained Cu to a greater extent than those of the NP placentae. Fetal liver Cu and Fe were elevated in the LP litters compared to the NP group. In conclusion, the LP diet in the dam during the second half of gestation was associated with fetal anaemia, hypoproteinaemia, and increased Cu and Fe accumulation in fetal liver. The higher concentration of Cu and Fe retained in LP placentae during gestation, and confirmed in the Cu challenge, suggest that Cu and Fe delivery to the fetus is related to placental concentration and that maternal protein malnutrition is a regulatory factor in fetal mineral homeostasis.

Animals↗

Mineral composition of meconium: effect of prematurity.

OBJECTIVES: We hypothesized that the concentration of major essential mineral elements in meconium correlate with gestational age (GA) or birth weight. To verify this premise we determined the concentration in meconium of calcium, magnesium, phosphorus, copper, zinc, iron, and manganese. METHODS: Thirty-four appropriate for age singleton infants without major congenital anomalies were divided into four GA groups (in weeks): 24 to 28; 29 to 33; 34 to 37; 38 to 42, or in birth weight groups (in g): < 1500; 1500-1999; 2000-2499; > or = 2500. Meconium was collected until the appearance of transitional stools and lyophilized for analysis. RESULTS: When adjusted for birth weight, the concentrations of calcium, copper, iron and phosphorus were higher in the meconium of 24 to 28 week GA infants than in those of the 38 to 42 week GA newborns. Birth weight adjusted copper concentration was highest in the 29 to 33 week GA group, while the remaining elements did not change across the range of GA. Meconium copper concentration in infants born with < 2000 g was higher than in those born with a weight > or = 2500 g. CONCLUSIONS: These results could serve as normative data of a noninvasive examination of the mineral nutritional "history" of the fetus, and, eventually, to better evaluate possible neonatal deficiencies in infants with intrauterine growth retardation or other types of complicated intrauterine courses.

Birth Weight↗

Copper absorption and bioavailability.

The human gastrointestinal system can absorb 30-40% of ingested copper from the typical diets consumed in industrialized countries. Experimental data support the existence of a carrier-mediated transport mechanism with an affinity constant in the micromolar range. Aging probably decreases the efficiency of copper homeostasis, resulting in higher plasma copper concentrations in the elderly. Physiologic differences may account for the higher cupremia of females. Supplements of minerals with similar chemical characteristics could reduce copper absorption. This property has pharmacologic applications in Wilson disease. Manipulation of the fiber content of the diet may have an indirect effect on copper bioavailability by altering the bioavailability of mineral antagonists. Proteins and soluble carbohydrates tend to improve copper absorption and bioavailability by enhancing its solubility and intestinal bulk flow. Organic acids, other than ascorbic acid, or agents that form low-molecular-weight chelates, are likely to have a positive effect on overall copper absorption. Conditions associated with malabsorption of macronutrients and gastrointestinal disease can impair copper uptake and contribute to suboptimal copper status.

Animals↗

Placental copper transport in rats: effects of elevated dietary zinc on fetal copper, iron and metallothionein.

We hypothesized that the competition between zinc (Zn) and copper (Cu) during fetal accretion of copper could be discriminated at either the dam-to-placenta or placenta-to-fetus stage. This premise was tested by feeding dams a high Zn diet (1000 mg/kg, HZn) during the second half of gestation. One day before delivery, dams were anesthetized, fetuses removed and both maternal and fetal tissues and plasma obtained and assayed. Other rats were fed a normal Zn concentration diet (32.4 mg/kg, ND) throughout pregnancy. There were significantly lower fetal liver Cu concentrations and greater plasma Fe concentrations, but not plasma Cu concentrations or liver Fe concentrations in the HZn group. Both dam and fetal Zn liver concentrations were greater in the HZn than in the ND group. Plasma Cu levels were lower in the HZn-fed than in the ND-fed dams. Placental tissue from the HZn litters had a greater concentration of Zn and Fe than did the ND group, whereas no effect was noted for Cu concentration. Metallothionein (MT) levels were elevated in dam livers and placenta in the HZn group, but there were no differences in fetal liver MT. The dynamic assessment of placental transport was conducted by injecting 2.5 mg/kg Cu acetate intravenously into dams of both groups. Sequential samplings of dam and fetal blood and placentas were taken from 0 to 60 min. After the Cu bolus, there was a consistently higher plasma Cu concentration in the HZn than in the ND dams, but no alteration in the concentration of Cu in the placenta or fetal plasma. This study indicates that placental Cu uptake is not affected by a high Zn diet in the dam. In addition, the greater Zn concentration in the placenta of HZn than in ND litters results in abnormal fetal Cu, Fe and Zn concentrations, suggesting that an imbalanced maternal mineral consumption is deleterious to normal divalent metal accretion.

Animals↗

Proabsorptive effects of modified tapioca starch as an additive of oral rehydration solutions.

BACKGROUND: Partially hydrolyzed starches from staple cereals, obtained by heat or by enzymatic treatment, are often used in the formulation of homemade or extemporaneously used oral rehydration solutions used in developing countries. Conflicting or anecdotal results obtained thus far could be clarified with a standardized preparation tested under well-controlled laboratory conditions. METHODS: A modified commercial tapioca starch was tested. Textra (National Starch and Chemical Co. Bridgewater, NJ, U.S.A.) added at 0, 5 or 10 g/l to an oral rehydration solution with 90 mM sodium and 111 mM glucose, in 30 rats malnourished by a protein-deficient diet for 3 weeks and in 26 well-fed control animals, using a one-pass jejunal perfusion. RESULTS: In protein-deficient rats, Textra stimulated sodium absorption at 5 and 10 g/l (mean +/- SEM); 0 g/l Textra: 160 +/- 13 nmol/min x cm; 5 g/l Textra: 406 +/- 31 (p < 0.0001); and 10 g/l Textra 230 +/- 27 (p < 0.02). Potassium absorption was comparably increased. Textra also improved net water absorption and the water influx:efflux ratio. Glucose absorption was increased only at 10 g/l Textra. In control rats, Textra improved sodium and net water absorption at 5 g/l, but not at 10 g/l Textra; but the influx:efflux ratio and potassium absorption were unaltered. CONCLUSIONS: These data, obtained in normal and protein-deficient rats, support the view that modified starch is a potentially useful, energy-rich additive for oral rehydration solution, which does not introduce an osmotic penalty.

Animals↗

Gum arabic promotes rat jejunal sodium and water absorption from oral rehydration solutions in two models of diarrhea.

BACKGROUND & AIMS: We have shown that addition of gum arabic (GA) to a 90 mmol/L sodium-111 mmol/L glucose oral rehydration solution (ORS) enhances its effectiveness for water and electrolyte absorption in normal rats. The present study extends these observations on GA in ORS to two rat models of diarrheal disease. METHODS: Juvenile rats were either treated for 1 week with magnesium citrate-phenolphthalein to produce chronic osmotic-secretory diarrhea or luminally exposed to 10 mmol/L theophylline to induce jejunal secretion. In both models jejunal perfusion was used to assess absorption. RESULTS: Addition of 2.5 or 5.0 g/L GA to ORS increased roughly twofold absorption of sodium, potassium, and water in the model of chronic osmotic-secretory diarrhea. Rats perfused with GA-supplemented ORS showed an expansion of the basolateral intercellular spaces between villus absorptive epithelial cells and the lamina propria, reflecting enhanced water and sodium absorption. Similarly, addition of 2.5, 5.0, or 10.0 g/L GA to the ORS neutralized theophylline-induced abolition of net sodium and potassium absorption and reversed water and glucose malabsorption. CONCLUSIONS: These experimental studies in models of diarrhea suggest that GA may be a useful additive to ORS for the potentiation of water and electrolyte absorption.

Absorption↗

L-arginine in low concentration improves rat intestinal water and sodium absorption from oral rehydration solutions.

BACKGROUND: The nitric oxide (NO) precursor L-arginine has been shown to produce variable effects on intestinal absorptive function, including ion transport. AIMS: To determine whether there is an optimal concentration of L-arginine, promoting proabsorptive effects from oral rehydration solutions (ORS) with 90 or 60 mM sodium. SUBJECTS AND METHODS: In vivo perfusion of rat jejunum with determination of net water absorption, unidirectional fluid exchanges, sodium and calcium transport, and glucose absorption. RESULTS: L-Arginine (1 mM) added to the 90 mM sodium ORS increased intestinal absorption of both sodium and water. Higher concentrations of L-arginine (2 to 10 mM) lacked this stimulatory effect. At 20 mM, L-arginine decreased sodium absorption below baseline. With a 60 mM sodium ORS, 2 mM L-arginine had a maximal fluid and electrolyte proabsorptive effect. At 20 mM L-arginine, net water absorption was indistinguishable from that obtained in the absence of L-arginine, and lower than with 2 mM L-arginine. Sodium absorption remained raised above baseline in perfusions with 10 and 20 mM L-arginine. Morphologically, villi from perfusions with increased absorption showed a large expansion of intercellular and lamina propria intercellular spaces. CONCLUSIONS: Low concentrations of L-arginine seem to stimulate water and electrolyte absorption by the small intestine. This effect is consistent with NO induced vasodilation, may be vaso-constrictive and thereby reverse fluid and electrolyte transport.

Animals↗