More on the zinc connection.
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Cytokines↗
Biomedical subjects
R A Wapnir
Publications and source records attributed to R A Wapnir.
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↗
In vitro effect of furosemide on the chemiluminescence of polymorphonuclear neutrophils in preterm infants.
We tested the hypothesis that the phagocytic activity of polymorphonuclear neutrophils (PMNs) of neonates is more sensitive to furosemide (FU) in vitro than that of adults. Phagocytosis was monitored by chemiluminescence of PMNs in cord blood of full-term (n = 10) and preterm (n = 8) neonates in the presence of 0, 6, 9, and 12 micrograms/ml of FU. Venous blood from adults (n = 10) was used for comparison. Random motility and chemotaxis were also determined in the three groups. The peak chemiluminescence of PMNs in preterm neonates was significantly decreased at a FU concentration of either 6, 9, or 12 micrograms/ml when compared to full-term infants. In contrast, no difference was observed between full-term infants and adults. Random motility and chemotaxis were comparable in all groups, regardless of the FU concentration. The results of this study suggest that preterm infants may be more sensitive to FU, as indicated by the adverse effect of this drug on chemiluminescence activity of their PMNs, in vitro.
Adult↗
Cellulose derivatives and intestinal absorption of water and electrolytes: potential role in oral rehydration solutions.
The physicochemical and structural characteristics of several types of carboxymethylcellulose (CMC) and of methylcellulose (MC) were examined in relation to their capacity to modify water and sodium absorption in oral rehydration solutions (ORS) at various concentrations, using a jejunal perfusion procedure in rats. Comparison of intrinsic low-viscosity CMC of various degrees of substitution (DS) revealed that net water absorption increased as the DS was augmented. A stimulatory effect on sodium absorption occurred only at a low (2.5 g/l) CMC concentration. With products of medium DS, stimulation of net water and sodium absorption was observed only with low-viscosity CMC at 2.5 g/l, but not at 5.0 g/l. In perfusions with CMC of medium and high DS there was a reduction of water and sodium absorption, ultimately resulting in net sodium secretion with 5.0 g/l high-DS CMC. MC perfused at 5.0 or 10.0 g/l reduced net water absorption and reversed sodium transport from absorptive to secretory status. These results show that while low-viscosity-grade, low-DS CMC in low concentrations may facilitate solute uptake and concurrent water absorption from ORS by the jejunum, high intrinsic viscosity and possible chemical interaction of solutes with the modified celluloses tend to block water uptake and produce fluid stasis and electrolyte secretion. Thus, the data suggest that only certain types of CMC may be proabsorptive when added to ORS, while high-viscosity and high-DS CMC or MC induce electrolyte malabsorption and eventual catharsis.
Animals↗
Placental copper transport in the rat. II: Effect of maternal copper deficiency.
Copper (Cu) placental transport presents a steep downhill gradient from mother to fetus. This process could be altered by low-molecular-weight (LMW) ligands and maternal Cu deficiency. We compared the ratio of Cu transfer from dam-to-fetus in Cu-deficient (CuDf) and Cu-sufficient (CuSf) rats in the last day of gestation. Anaesthetized dams were iv injected 79 mumol/kg (5 mg/kg) of either Cu acetate [Cu (AcO)2]; Cu+L-histidine, 1:10. [Cu(His)10]; Cu-(glycyl-glycyl-L-histidine) [Cu(GGH)], or saline. Dam and fetal blood, as well as placentae were obtained at 0, 10, 20, 40 and 60 min. At time 0, CuDf dams had lower plasma Cu than CuSf dams (8.3 +/- 1.2 versus 26.7 +/- 1.1 mumol/l), but CuDf fetuses plasma Cu was unchanged. This resulted in a more favourable mean fetal: maternal plasma Cu ratio in the CuDf fetuses (0.61) than in the CuSf fetuses (0.21). Dam plasma Cu was unaffected by the chemical form of Cu injected. In CuDf fetuses lower plasma Cu was observed with Cu(GGH) and Cu (His)10 at 20 min than in the CuSf. In the presence of these LMW ligands CuDf placentae retained more Cu than those of the CuSf group. CuDf was associated ultrastructurally with extensive lipid deposition in dam hepatocytes and, to a lesser extent, in CuDf fetal liver. These results indicate that in CuDf, LMW ligands increase placental uptake of Cu, without improving placenta-fetus transport. Although the rat fetus is well adapted to intrauterine CuDf, it may also be susceptible to hepatic lipid infiltration when the dam is CuDf.
Animals↗
Oral rehydration solutions: enhanced sodium absorption with gum arabic.
OBJECTIVE: To assess whether the addition of gum arabic (GA) to oral rehydration solutions (ORS) of either 60 or 90 mM sodium enhances net water and sodium absorption in rats. METHODS: Perfusion of a jejunal segment of male juvenile rats under anesthesia, and determination of net water and sodium absorption, and unidirectional fluid movements using appropriate markers. RESULTS: Addition of 5 and 10 g/L of GA increased the rates of sodium removal from the intestinal lumen perfused with ORS containing either 60 or 90 mM sodium. Net water absorption was unaffected, although GA tended to facilitate bidirectional fluid movement. The alteration of solute transport rates by the addition of 10 g/L GA was associated with an expansion of the basolateral intercellular spaces. CONCLUSIONS: A soluble fiber such as GA appears to be an effective enhancer of sodium absorption from ORS when tested in experimental animals. Since GA does not affect viscosity, an alteration of solute diffusibility through the brush border membrane and changes in intercellular compartments may underlie the observed improvement of sodium absorption.
Animals↗
Enhancement of intestinal water absorption and sodium transport by glycerol in rats.
Glycerol (Gly) is a hydrophilic, absorbable, and energy-rich solute that could make water absorption more efficient. We investigated the use of Gly in a high-energy beverage containing corn syrup (CS) by using a small intestine perfusion procedure in the rat, an approach shown earlier to provide good preclinical information. The effectiveness of several formulations with Gly and CS was compared with commercial products and to experimental formulas where Gly substituted for glucose (Glc). The CS-Gly combination was more effective than preparations on the market containing sucrose and Glc-fructose syrups (G-P and G-L, respectively) in maintaining a net water absorption balance in the test jejunal segment [CS-Gly = 0.21 +/- 0.226, G-L = -1.516 +/- 0.467, and G-P = -0.299 +/- 0.106 (SE) microliter.min-1.cm-1 (P = 0.0113)] and in reducing sodium release into the lumen [CS-Gly = -133.2 +/- 16.2, G-L = -226.7 +/- 25.2, and G-P = -245.6 +/- 23.4 nmol.min-1.cm-1 (P = 0.0022)]. In other preparations, at equal CS concentrations (60 and 80 g/l, respectively), Gly clearly improved net water absorption over a comparable Glc-containing product [CS60-Gly = 0.422 +/- 0.136 and CS80-Gly = 0.666 +/- 0.378 vs. CS60-Glc = -0.282 +/- 0.200 and CS80-Glc = -1.046 +/- 0.480 microliters.min-1.cm-1 (P = 0.0019)]. On the basis of the data of this rat intestine perfusion model, Gly could be a useful ingredient in energy-rich beverages and might enhance fluid absorption in humans.
Animals↗
Copper intestinal absorption in the rat: effect of free fatty acids and triglycerides.
The absorption of some minerals has been shown to be affected by the presence of unhydrolyzed dietary triglycerides and free fatty acids generated from their partial hydrolysis. Since copper (Cu) can form poorly soluble soaps with long-chain fatty acids, we examined whether the uptake of Cu from the intestinal lumen is altered by the presence of fatty acids and triglycerides using an in vivo jejunal perfusion procedure. Long-chain fatty acids palmitate and stearate at 1.0 mM reduced Cu absorption rates compared with infusates without either fatty acid or triglycerides (means +/- SEM, controls: 104.4 +/- 8.8 pmole/min x cm vs palmitate: 12.5 +/- 17.6, P < 0.01; stearate:37.2 +/- 25.6, P < 0.05). Medium chain free fatty acids had no effect on Cu absorption (caprylate: 90.6 +/- 14.9, not significant; caproate: 69.5 +/- 14.2, not significant). Similarly, neither an emulsion of medium chain nor long-chain triglycerides at a total 1.0 or 2.5 mM concentration altered Cu absorption. The inhibitory effect of palmitate and stearate on Cu absorption was accompanied by a reduction in lumen-to-mucosa water influx (controls: 5.33 +/- 0.26 microl/min x cm vs palmitate: 3.20 +/- 0.70, P < 0.01; stearate: 3.36 +/- 0.52, P < 0.01). The data are consistent with a potential impairment of Cu intestinal absorption by long-chain free fatty acids which may accumulate in the jejunum following excessive fat intake and/or lipid malabsorption.
Animals↗
Placental copper transport in the rat: role of low-molecular-weight ligands.
In this study we investigated whether two low-molecular-weight (LMW) ligands with high affinity for copper (Cu) play a role in the transplacental transport of Cu in the rat. Dams on days 20-21 of gestation were anesthetized and injected via the femoral vein with 5 mg/kg (79 mumol/kg) Cu in 0.5 ml, as either the acetate [Cu(AcO)2], as a 1;10 mixture with L-histidine [Cu(His)10], or as the Cu-(glycyl-glycyl-L-histidine) [G-G-H] complex. Controls received saline. After laparotomy, several fetuses and their placentas were removed at 0, 10, 20, 40, and 60 min after injection, simultaneously with dam blood. Peak Cu concentration in dam plasma occurred at 10 min and was highest following Cu(AcO)2 injection. At 10 and 20 min the placentas from the Cu(AcO)2 and the Cu(G-G-H) groups had higher Cu levels than the controls. By 40 min placentas from all rats injected with Cu had similar Cu concentrations. In the Cu(AcO)2 group there was a positive correlation between dam plasma and placental Cu (r = 0.527, P < 0.05). A sharp downhill gradient was observed between dam and fetus. Fetal plasma Cu levels did not differ among all groups at any time. The data indicate that LMW ligands do not enhance overall maternal-to-fetal Cu transfer, but that an excess of His may inhibit the release of Cu from placenta to fetus.
Acetates↗
Copper deficiency: interaction with high-fructose and high-fat diets in rats.
The purpose of this study was to investigate whether a high fat intake would potentiate an excess of fructose in the diet of rats to alter energy metabolism and worsen the nutritional status for copper. Weanling male rats were fed diets with 45% fat and 20% cornstarch, 45% fat and 20% fructose, 5% fat and 60% cornstarch, or 5% fat and 60% fructose for 3 wk, with either sufficient (+) or deficient (-) amounts of copper. Copper deficiency, as demonstrated by low plasma copper and ceruloplasmin, caused a decrease of liver, heart, and testes copper; a decline of liver and heart zinc; and an increase of hepatic iron. High-fat diets reduced liver glucose-6-phosphate dehydrogenase (G6PDH) and, to a lesser extent, glycerophosphate dehydrogenase (GPDH). The interaction between high-fat and high-fructose diets, superimposed on copper deficiency, resulted in a lowering of G6PDH, GPDH, and malic enzyme. These results support the hypothesis that a high fat ingestion becomes an aggravating stress factor, which, in combination with a high-fructose intake in a copper-deficient diet, adversely alters key organ mineral content, with detrimental effects on copper nutritional status and intermediary metabolism.
Animals↗
Erythropoietin (EPO) levels in fetal rats after ritodrine and terbutaline administration.
Beta-2 sympathomimetics, such as terbutaline, have been shown to alter erythropoietin (EPO) secretion in animal studies. More recently introduced sympathomimetics, such as ritodrine, have been extensively used to inhibit uterine contractions in preterm labor. It has not been determined what effect ritodrine may have on EPO production. We investigated the effect of RD administered to rats in the last day of gestation on the dam and the fetuses' levels of EPO. Rats at the 20th day of gestation were given, under anesthesia, either 3000 micrograms/kg ritodrine over a 10-min period or a similar volume of saline as control (CTL). Fetuses were removed at 0 and 4 h after injection. Ritodrine administration produced a decrease of dam EPO (23.4 +/- 4.2 to 12.0 +/- 2.9 pmol/ml), while the CTL showed no changes. The fetuses from the ritodrine-injected dams exhibited a marked decline over the 4-h period, while the CTL fetuses did not change. In other experiments 500 micrograms terbutaline was administered daily during the last 5 days of rat gestation. The drug produced a significant decline in EPO at delivery time, but plasma EPO in the pups was unchanged. Blood hematocrits were comparable to those of controls. The data show that acute administration of ritodrine reduces fetal and dam plasma EPO, while long-term terbutaline treatment late in gestation alters maternal, but not fetal plasma EPO, indicating that neither drug has any direct regulatory effect on the erythropoietic ability of the fetuses.
Animals↗
Adventitious redox-active metals in Krebs-Henseleit buffer can contribute to Langendorff heart experimental results.
Adventitious redox-active metals in Krebs-Henseleit buffer exhibit a significant enhancement of damage to isolated rat hearts. Using atomic absorption spectroscopy, it was determined that Krebs-Henseleit buffer contains substantial amounts of contaminating iron and copper. Significant copper contamination was found in ACS Reagent grade sodium chloride and sodium bicarbonate; iron contamination in sodium chloride, potassium chloride, sodium bicarbonate, and calcium chloride. Chelating resin treatment of individual reagents was found to decrease copper content of Krebs-Henseleit buffer from 0.32 to 0.17 microM. Using salicylate as a probe for .OH formation, it was determined that considerable amounts of this radical are formed when 0.25 mM ascorbate is added to the buffer indicating significant metal-catalysed autoxidation. Isolated rat hearts, perfused with non-chelexed Krebs-Henseleit buffer plus 0.25 mM ascorbate for 60 min, sustained moderate injury with developed systolic pressure, +dP/dtmax and -dP/dtmax decreased by 30 to 35% by the end of experiment. Hearts perfused with chelating resin-treated Krebs-Henseleit buffer sustained no significant injury within the same time frame. Furthermore, it was observed that hearts perfused with non-chelexed Krebs-Henseleit buffer accumulate significant amounts of copper depending on the amount of contamination and length of perfusion. Significant effects on post-ischemic end diastolic pressure were observed in hearts perfused with a Krebs-Henseleit buffer subsequently found to be contaminated with high levels of copper. These results clearly demonstrate that adventitious redox-active transition metals may be a confounding factor in experimental results. Further, it is recommended that all perfusion media be routinely examined for adventitious metals and treated if deemed necessary.
Animals↗
Another step in the search for better oral rehydration solutions.
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Administration, Oral↗
Oral rehydration solutions (ORS): enhancement by a soluble fiber.
OBJECTIVE: This study was designed to test the hypothesis that, in an animal model of protein-energy malnutrition (PEM), carboxymethylcellulose (CMC), a viscous additive for the World Health Organization Oral Rehydration Solution (WHO-ORS), previously found to be effective in rats with osmotic diarrhea as an enhancer of water and sodium absorption, would also improve the performance of the WHO-ORS. This hypothesis was based on the changes in fluid and electrolyte transport that could be induced by an increase in the viscosity. METHODS: We evaluated CMC in young rats fed a low-protein, low-energy diet for 3 weeks to induce PEM. Control (CTL) rats were fed a nutritionally complete diet. The ORS were tested with an in vivo perfusion procedure under anesthesia. RESULTS: CMC addition (0, 2.5, 5.0 and 10.0 g/L) sharply increased the rates of net water and sodium absorption in both groups of rats, especially in the PEM animals. Net water absorption increased from (means +/- SEM) 0.75 +/- 0.06 to 2.21 +/- 0.18, 3.35 +/- 0.20 and 8.46 +/- 0.84 microL/min x cm in the PEM rats (0, 2.5, 5.0 and 10.0 g/L CMC, respectively). For the same CMC concentrations, sodium absorption improved from 178.8 +/- 20.3 to 402.4 +/- 18.4, 486.4 +/- 29.2 and 898.4 +/- 21.4 nmol/min x cm, respectively. CTL rats also showed marked increases. Rates of lumen-to-serosa water influx improved in both groups without major changes in water efflux. Net water and sodium absorption appeared related to the log of the ORS viscosity. CONCLUSIONS: The results further support the concept that increased viscosity induced by CMC enhances the effectiveness of ORS.
Absorption↗
Zinc improves postischemic recovery of isolated rat hearts through inhibition of oxidative stress.
We studied the cardiac protective qualities of zinc in the postischemic isolated rat heart. Hearts, perfused with Krebs-Henseleit buffer with or without zinc-bis-histidinate, were subjected to 20 min of "no-flow" normothermic global ischemia. Pre- and postischemic treatment with 0, 10, 20, or 30 microM zinc resulted in concentration-dependent enhancement of postischemic function as evidenced by decreased end-diastolic pressure (37 +/- 3, 25 +/- 5, 17 +/- 5, and 8 +/- 2 mmHg, respectively) and increased recovery of developed systolic pressure (41 +/- 6, 59 +/- 17, 76 +/- 18, and 87 +/- 16 mmHg, respectively) and maximum rate of rise in pressure (+dP/dtmax; 823 +/- 141, 1,413 +/- 396, 1,700 +/- 450, and 2,157 +/- 407 mmHg/s, respectively) as well as decreased lactate dehydrogenase efflux from the hearts (peak: 1,002%, 840%, 580%, and 440%, respectively). Only preischemic treatment resulted in an intermediate protective effect, whereas treatment starting at reperfusion worsened postischemic damage. In hearts perfused with zinc throughout the experiment, prolongation of the preischemic treatment interval further enhanced postischemic recovery. With the use of salicylate as a trap for .OH, it was determined that zinc virtually eliminated the early postischemic "burst" of this species normally observed in this preparation. Atomic absorption studies demonstrated that hearts treated with 30 microM zinc contained 27% less copper than control hearts by the end of the reperfusion period. In control hearts, electron microscopy revealed swollen mitochondria with marked loss of inner matrix density, whereas morphology of postischemic zinc-treated hearts was essentially normal. These studies indicate that zinc possesses cardiac cytoprotective qualities and support the concept that this metal can decrease .OH formation by affecting copper reactivity.
Animals↗
Oral rehydration solutions: increased water and sodium absorption by addition of a viscosity-enhancing agent in a rat model of chronic osmotic diarrhea.
Viscosity-enhancing agents such as carboxymethylcellulose (CMC) can alter absorption of solutes and fluid exchange in the small intestine. We investigated whether the standard World Health Organization oral rehydration solution (WHO-ORS) with the addition of CMC would improve net water and sodium absorption in rats using an in vivo intestinal perfusion technique. Four WHO-ORS, containing either 0, 2.5, 5.0, or 10.0 g/L of CMC, were perfused in rats with a well-tested model of cathartic-induced chronic osmotic diarrhea (D) and in normal controls (C). In D rats, the ORSs with CMC improved sodium absorption at the three concentrations used (p < 0.01). The same effect was shown in C rats. Net water absorption was also enhanced in D rats given ORSs with CMC, although the changes in C animals were less marked. The improvement in sodium and water absorption in both C and D rats positively correlated with the log of relative ORS viscosity. Ultrastructural examination of tissues perfused with 10 g/L of CMC showed an extended brush border glycocalyx. This study indicates that CMC added to WHO-ORS in the perfused rat jejunum improves the effectiveness of the solution by increasing sodium and water absorption.
Animals↗
Limitation of private attending pediatricians' neonatal intensive care privileges in level III institutions throughout the United States.
OBJECTIVE: To determine the privileges of Private Attending Pediatricians (PAP) in caring for newborns requiring intensive (ITC), intermediate (IMC), or continuing (CC) care in Level III neonatal intensive care units (NICUs) throughout the United States. DESIGN: A two-page mail questionnaire was sent to 429 Level III NICUs to obtain the statement best describing the PAPs' privileges, the number of PAP, and some of the PAPs' functions. Level III NICUs were classified by geographic region as Eastern, Central, or Western United States. RESULTS: Responses were received from 301 NICUs (70%) representing 48 states, the District of Columbia, and > 9000 PAP. Twenty-two institutions had no PAP. In the remaining 279 institutions, 96% (267/279) had restricted the PAPs' privileges partially or completely. In 32% (88/279), the PAP were not allowed to render any type of NICU care. In 18% (51/279) of the institutions, the PAP were allowed to render CC only. In 27% (76/279) of the institutions, the PAP were allowed to render IMC and CC only. Limitation of PAPs' privileges were reported in all geographic areas in the U.S., were more pronounced in the Eastern than the Central or Western sections of the country, and were noted in institutions with small (< or = 10) as well as large (> or = 60) numbers of PAP. Limitation of PAPs' privileges was determined by the PAP him/herself in many institutions. Proficiency in resuscitation was considered to be a needed skill. Communication with parents of an infant under the care of a neonatologist was encouraged. CONCLUSIONS: The PAPs' privileges were limited partially or completely in most Level III NICUs. Knowledge of this restricted role impacts significantly on curriculum design for pediatric house officers, number and type of health care providers required for Level III NICUs and future house officer's career choices.
Chi-Square Distribution↗
Development of copper intestinal absorption in the rat.
We investigated changes in the kinetic characteristics of copper absorption at three stages of rat development: suckling, weanling, and adolescence, as well as the inducibility of metallothionein (MT) in small intestine and kidney. Using an in vivo, single-pass intestinal perfusion procedure, we found that the rates of copper absorption in suckling and weanling rats were concentration-dependent and there was no difference between these two groups of rats. However, in adolescent rats, there was a saturable component, with an apparent Kt of 10-13 microM, and a nonsaturable component with a diffusion coefficient of 3.2 s-1 (3.2 x 10(-5) cm2/s). Intestinal copper retention was also concentration-dependent; the suckling rats showed much greater tissue levels of this element than the weanlings or the adolescents. MT intestinal content after stimulation with ip zinc chloride was significantly higher in the adolescent rats than that in the weanlings and sucklings, indicating that physiological mechanisms other than MT induction may play a role in copper retention early in life. The increase in MT levels in adolescence may be related to the onset of copper absorption saturability in the mature small intestine.
Age Factors↗