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Biomedical subjects

R A Wapnir

Publications and source records attributed to R A Wapnir.

At least 73 records · Page 4Linked to original sources
PubMed1987

Interstitial deletion of chromosome 2 (p23p25).

We report a patient with a de novo interstitial deletion of the short arm of chromosome 2 (p23p25). The patient had microcephaly with prominent forehead and occiput, narrow rectangular face, clinodactyly, failure to thrive, delayed psychomotor development, and seizures. Maternal serum alpha-fetoprotein was undetectable at 18 weeks of gestation. Heterozygosity at the red cell acid phosphatase locus (SRO-2p25) and normal levels of red cell malate dehydrogenase (SRO-2p23) are findings consistent with the presence of genetic material from bands 2p25 and 2p23.

Abnormalities, Multiple↗
PubMed1987

Regulation of hepatic gluconeogenesis and glycogenolysis by phosphorylated glycerol and glycolytic intermediates in diabetic and control Chinese hamsters.

Metabolic regulation of gluconeogenesis and glycogenolysis by two phosphorylated derivatives of glycerol, G3P, and DHAP, and by F2,6BP, was assessed in vitro in liver homogenates obtained from Chinese hamsters (C. griseus) of two types: diabetic animals from sublines with consistent glycosuria and hyperglycemia, and normoglycemic controls. Only FBPase was sensitive to inhibition by the phosphorylated metabolites. G3P was weakly inhibitory of FBPase. Addition of 7 X 10(-3) M DHAP halved FBPase activity in the diabetic hamsters and 4 X 10(-3) M DHAP produced the same effect in the controls. The other gluconeogenic enzymes and phosphorylase a were only negligibly inhibited. In contrast, F2,6BP inhibited FBPase at concentrations in the micromolar range. Liver homogenates from diabetic hamsters appeared significantly more sensitive to F2,6BP inhibition of FBPase than those from controls at concentrations 0.6 X 10(-6) M and higher. These data indicate that in well-fed hamsters phosphorylated glycerol derivatives are unlikely to regulate hepatic gluconeogenesis at physiologic concentrations. However, the effects of F2,6BP on gluconeogenesis and glycolysis may be linked to those mediated by insulin. Thus, the deficiency of insulin, elevated end-organ insulin resistance, the alteration in the glucagon-insulin interaction, or a combination of these possible causes can be involved in an abnormal regulation of glycolysis and gluconeogenesis at the FBPase step, associated with changes in F2,6BP concentration.

Animals↗
PubMed1987

Obesity-induced hyperplastic lung growth.

The effects of overnutrition on lung growth were studied in newborn male Long-Evans rats made obese by nursing in small litters with subsequent feeding of a high fat diet. Control rats were nursed in normal-sized litters and then fed standard rat chow. The animals were killed at 8 wk of age. When compared with control rats, obese rats had significant increases in body weight (24%); fat pad weight (118%); fat pad weight/body weight ratio (77%); snout-to-anus length (11%); total lung weight (11%); lung content of DNA (19%), protein (22%), RNA (22%), total lipids (31%), cholesterol (20%), and triglycerides (141%); and the lung triglyceride/DNA ratio (217%). Serum levels of insulin (71%), total lipids (60%), cholesterol (64%), and triglycerides (90%) were also elevated in obese rats as compared with those in control rats. Unchanged were the ratios of lung protein/DNA, RNA/DNA, lipid/DNA, and cholesterol/DNA; lung phospholipid content; and serum concentrations of glucose and phospholipids. The results indicate the presence of cellular hyperplasia in lungs of young rats made obese by diet. Lipid deposition in the obese lungs suggests metabolic alterations in pulmonary composition occurring with obesity.

Animals↗
PubMed1987

Intestinal absorption of copper: effect of sodium.

The mechanisms of copper (Cu) absorption from the small intestinal lumen are poorly understood. In this study we investigated the role of sodium (Na) during the removal of Cu from the lumen of jejunal and ileal segments, using an in situ perfusion procedure in the anesthetized rat. Intestinal absorption of Cu from a 31 microM solution was highest in the presence of an isotonic concentration of NaCl, as compared to solutions containing either glycerol (GRL) or N-methyl-D-glucamine (NMG) as osmotic agents. In the jejunum, mean +/- SEM Cu absorption rates in the presence of the following solutes were: with NaCl, 57.5 +/- 10.5 pmole/min X cm; with GRL, 13.3 +/- 14.7 (P less than 0.05); with NMG, 18.4 +/- 10.1 (P less than 0.05). In the ileum, copper absorption in the presence of NaCl was 64.4 +/- 9.6; with GRL, 24.3 +/- 10.1 (P less than 0.01); with NMG, 15.8 +/- 3.7 (P less than 0.001). Kinetic analysis of the carrier-mediated component of Cu absorption in rat jejunum yielded a Vmax = 47.5 pmole/min X cm and an apparent Kt = 21 microM. The diffusion coefficient was calculated to be 1.4 X 10(-5) cm2/sec. The absorption of Cu was independent of net water absorption, which was highest in the presence of GRL and abolished and reversed into secretion by NMG. The data obtained are indicative of a significant role of Na in the small intestinal transport of Cu, in vivo, although not directly related to unidirectional water fluxes. The cation specificity of Na in this process remains to be elucidated, although the results support earlier studies which postulated that mediated transport may constitute a major component of Cu absorption in the mammalian small intestine.

Absorption↗
PubMed1986

Zinc intestinal absorption in rats: specificity of amino acids as ligands.

The luminal phase of zinc intestinal absorption may be mediated by low-molecular-weight substances originated in digestive, metabolic or secretory processes. Amino acids are considered primary candidates for this role through the formation of complexes with zinc. However, structural characteristics that may be indispensable for this physiological function have not been explored in vivo. We investigated the comparative effectiveness of four amino acids and their respective chemically related homologues on the absorption of zinc by the jejunum, ileum and colon of the rat using a perfusion procedure. L-Tryptophan (Trp) allowed for significantly greater zinc absorption than tryptophol (Tpl) in all areas of the gut. L-Histidine (His) and imidazole (Imd) had similar effects in both the jejunum and the ileum. Imd allowed for much greater zinc absorption from the colon than did His (His, 388 +/- 31; Imd, 937 +/- 107 pmol/min X cm, P less than 0.001). Proline (Pro) was a more effective ligand than pyroglutamate (Pyr) in the ileum (Pro, 559 +/- 19; Pyr, 352 +/- 22 pmol/min X cm, P less than 0.001), but not in the jejunum or the colon. L-Cysteine was superior to N-acetyl-L-cysteine only in the ileum (508 +/- 45 vs. 348 +/- 25 pmol/min X cm, P less than 0.01). The greater zinc absorption achieved by amino acids than by non-amino acid homologues in the small intestine appeared to be due to the presence of both mediated and nonmediated transport mechanisms for amino acids but of only nonmediated zinc uptake for the homologues. In the colon, where amino acid absorption does not take place, high structural affinity for zinc, such as that exhibited by Imd, allowed for considerable absorption of the trace element.

Acetylcysteine↗
PubMed1986

Alterations in jejunal transport and (Na+-K+)-ATPase in an experimental model of hypoxia in rats.

Hypoxia was induced by exposing rats to an atmosphere of 93% N2, 7% O2 for 4-48 hr. The animals became hypoxic as indicated by a decreased blood PaO2 (mean +/- SEM: 48 +/- 10 mm Hg). Hypoxia was accompanied by metabolic acidosis (pH 7.22 +/- 0.02) and decreased serum bicarbonate levels (9.0 +/- 4.0 meq/liter). Hypoxic rats also showed evidence of tissue hypoxia; liver tryptophan oxygenase levels were increased to 21 +/- 2 nmole/min/mg protein. In the hypoxic animals there was decreased jejunal mucosal (Na+-K+)-ATPase activity and an inhibition of active intestinal transport of sodium, glucose, 3-O-methylglucose, galactose, tyrosine, phenylalanine, and glycine as determined by in vivo perfusion studies. Jejunal fructose transport, which has a large passive component, was unaffected by hypoxia. The electrolyte, carbohydrate, and amino acid transport alterations produced by hypoxia were seen in the absence of an effect on jejunal cell number, DNA synthesis, or cell turnover. There was also no evidence of histological or ultrastructural damage. Furthermore, studies with a luminal macromolecular tracer, horseradish peroxidase, indicated that the jejunal lumen-to-blood barrier to macromolecules was also unaltered in these hypoxic animals. In vitro local oxygenation of the jejunum, by bubbling of 95% O2:5% CO2, markedly improved sodium and glucose (but not 3-O-methylglucose) absorption in hypoxic rats and control rats. The (Na+-K+)-ATPase activity of the jejunal mucosa of hypoxic rats was significantly enhanced by the local bubbling of 95% O2:5% CO2. Overall, our data indicate that during relatively mild conditions of hypoxia there is an inhibition of jejunal (Na+-K+)-ATPase activity and related transport processes that is prevented by in situ oxygenation.

Amino Acids↗
PubMed1985

Regulation of gluconeogenesis by glycerol and its phosphorylated derivatives.

Glycerol, glycerol-3-phosphate (G3P), and dihydroxyacetone phosphate (DHAP) were evaluated as inhibitors of gluconeogenesis on rat liver enzymes in vitro, and for their effects on glucose formation in vivo in well-nourished and malnourished rats. DHAP was more potent as an inhibitor than G3P on fructose-1,6-diphosphatase (FDPase), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pase). The I50 for DHAP was 2, 8, and 9 x 10(-3) M, respectively. No effect was observed on rat liver pyruvate carboxylase (PC). Glycerol was a weak inhibitor of FDPase and PEPCK, but did not inhibit PC and G6Pase. In vivo, when G3P was injected before a parenteral L-alanine (Ala) challenge, it produced a hypoglycemic effect in malnourished rats and a lesser, but noticeable, blood glucose level reduction in well-fed animals. Glycerol caused a smaller reduction in glucose formation from Ala. No comparable effects were observed after a fructose pretreatment. These results underscore the potential hypoglycemic effects of phosphorylated glycerol metabolites and identify the steps in gluconeogenesis where this action is exerted. The study also stresses the nutritional component in the glycerol intolerance syndrome, apparent from the far more severe effects observed in malnourished rats given G3P or glycerol prior to Ala.

Alanine↗
PubMed1985

Oral hydration solutions: experimental optimization of water and sodium absorption.

Eight solutions of potential efficacy for hydration orally, which differed in composition, osmolality, and pH, were tested in an in vivo perfusion system on rat jejunum to assess the rate of water and sodium absorption or secretion. Optimal results were obtained with a preparation of the type recommended by the World Health Organization, containing 60 mEq/L sodium and 111 mM glucose; there was a maximum influx of both water and sodium, which may be ideal for rehydration. It appeared that the critical factor was the molar relationship between glucose and sodium at a 2:1 ratio. Sodium absorption was inversely correlated with glucose concentration in the perfusates. Osmolality and pH may also have a role in the regulation of fluxes across the mucosa. Citrate at concentrations up to 30 mEq/L did not interfere with water absorption. The data presented may thus contribute to a better rationale for the use of orally administered hydration solutions and guidelines for the preparation of more effective ready-to-use solutions.

Animals↗
PubMed1985

Cyclic AMP-mediated jejunal secretion in lactose-fed malnourished rats.

We evaluated the effects of a hyperosmolar lactose load on the functional properties of the jejunal mucosa of protein-energy malnourished rats. Malnourished animals exposed to an oral lactose load showed an enhanced loss of DNA, protein, and sodium into the intestinal lumen as compared to well nourished controls exposed to the same lactose load. Only the jejunum of lactose-fed malnourished rats showed increased levels of 3'-5' cyclic adenosine monophosphate (cAMP), that appeared principally due to an enhancement of adenyl cyclase. Overall, our data strongly suggest that the intestinal mucosa in malnutrition is more sensitive and responds to an osmotic stress by enhanced secretion.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1985

Differential absorption of zinc and low-molecular-weight ligands in the rat gut in protein-energy malnutrition.

The differences in zinc absorption in the presence of four low-molecular-weight ligands in the jejunum, ileum and colon of protein-energy malnourished juvenile rats (M), and their controls (C) were investigated. An in vivo perfusion procedure was applied to vascularly intact segments of the three areas of the gut. The absorption of L-proline and L-histidine, and a hydrolysis-resistant dipeptide, glycylsarcosine, were also determined. In certain instances, the M rats absorbed zinc at a lower rate than the C animals. This effect was especially consistent throughout the gut when glycylsarcosine was present in the perfusates. In the colon, zinc, but not the amino acids, was taken up. Glycylsarcosine was well absorbed by the colon in both the M and C rats. The data indicate that protein-energy deficiency may impair the absorption of zinc by the rat intestinal mucosa in the presence of low-molecular-weight substances of high affinity for zinc, without altering the absorption of amino acids, or of zinc organometallic complexes in which the metal is tightly bound. The two contrasting situations may be relevant to alleviating zinc deficiency in nutritionally compromised conditions.

Animals↗
PubMed1985

Magnesium metabolism studies in children with chronic inflammatory disease of the bowel.

Magnesium metabolism was studied in seven patients with severe chronic inflammatory disease of the bowel (CIDB), and in 20 children without intestinal pathology. Four of the CIDB patients had ulcerative colitis and three had granulomatous disease of the bowel. All had diarrhea as well as other gastrointestinal complaints for 1 to 6 years prior to the study. All were being treated with sulfasalazine and were also receiving corticosteroids intermittently. All but one had had intestinal surgery. Basal plasma and urine were obtained in all patients and, if surgery was performed, a piece of muscle was excised. The CIDB patients received an intravenous magnesium infusion of 2 mEq/kg/day for 4 days, 2 days postsurgery. Electrocardiograms were recorded throughout the study. The mean basal plasma magnesium levels were reduced in CIDB patients as compared with controls. Mild hypomagnesemia was observed in six of seven CIDB patients. The mean basal urine excretion of magnesium was also reduced in CIDB patients, but the muscle concentrations of this element were similar to controls. Basal hypomagnesuria was present in only two of the three patients with granulomatous disease and in one patient with ulcerative colitis. The three patients with granulomatous disease excreted minimal amounts of magnesium in the urine during intravenous administration of this ion. A positive magnesium balance persisted throughout the 4-day period of infusion. In contrast, only two of the four patients with ulcerative colitis had magnesium retention during the first day of intravenous administration, and all four had negative magnesium balances thereafter. The data suggest that hypomagnesemia in CIDB patients may occur with or without magnesium deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Osmolality and solute concentration--their relationship with oral hydration solution effectiveness: an experimental assessment.

The role of electrolyte, carbohydrate, and base composition, as well as osmolality, of oral hydration solutions (OHS), was investigated using a nonabsorbable marker and tritiated water in an in vivo intestinal perfusion system in rats. The OHS tested were the World Health Organization recommended formula, containing 90 mEq/liter sodium and 111 mM glucose, which was taken as the reference solution; five variants of this solution with different sodium and glucose concentrations; and two solutions without sodium, i.e. isotonic glucose and deionized water. Also tested were one solution with acetate in lieu of bicarbonate, and two commercial preparations where citrate substituted for bicarbonate. The best water absorption rates were obtained with World Health Organization-type OHS characterized by a combination of low osmolality and moderate sodium and glucose content. Hypotonic OHS (190, 220, and 155 mosmol/kg) in which the sodium:glucose ratios were 60:30, 60:60, and 30:55, respectively, produced mean jejunal water transport rates of 3.46, 3.20, and 2.91 microliter/min/cm, respectively, whereas the standard World Health Organization OHS (330 mosmol/kg) resulted in a rate of 1.36 microliter/min/cm (p less than 0.001). Similar good water absorption was achieved when Ac was the base (270 mosmol/kg and 60:111 sodium:glucose ratio) and with one of the commercial solutions (245 mosmol/kg and 50:111 sodium:glucose ratio). The reference World Health Organization OHS allowed for sodium absorption, as did the OHS with sodium:glucose ratios of 90:45, 60:30, 60:60, and acetate-containing 60:111. Sodium at a concentration of 30 mEq/liter or less resulted in the efflux of this electrolyte. High glucose concentration and lower osmolality exacerbated this effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Fetal glycerol metabolism in experimental maternal lipemia.

Maternal lipemia (L), one of the consequences of poorly controlled diabetes in gestation, was induced in pregnant rats by feedings of a diet containing 45% fat. The maternal condition was associated with fetal L and moderate ketonemia. L fetuses had an elevated liver glycerol kinase (EC 2.7.1.30), when assayed 1 day before term (L = 82.5 +/- 3.8 nmole/min X mg protein and controls (C) = 67.4 +/- 3.9 nmole/min X mg protein; means +/- SE, P less than 0.01). However, neither hepatic cytosolic glycerophosphate (GcPO4) dehydrogenase (EC 1.1.1.94) nor mitochondrial GcPO4 oxidase (EC 1.1.99.5) were altered. GcPO4 oxidase was lower in the striated muscle of L than in that of C fetuses (13.7 +/- 1.2 nmole/min X mg protein vs 17.2 +/- 0.5 nmole/min X mg protein, P less than 0.05). The results of the present study suggest that L, in utero, may cause an alteration in overall glycerol oxidative capacity in liver and GcPO4 in muscle. These changes appear to be compatible with a shift in the capacity of L fetuses to handle glycerol which may relate to postnatal fuel utilization by L offspring.

3-Hydroxybutyric Acid↗
PubMed1984

Intestinal absorption of manganese in experimental malnutrition.

We investigated possible changes in mechanisms of the intestinal absorption of Mn in rats malnourished with a low protein-low energy diet (M) for 4 weeks against controls fed a complete diet (C) during the same period. The absorption of Mn in the absence or in the presence of two small molecular weight ligands, citrate and L-histidine, was studied by an in vivo procedure. In both M and C rats, jejunal Mn absorption decreased linearly with time and was enhanced by the presence of the low molecular weight ligands. The initial rate of absorption, for Mn alone, was higher in M than in C rats, but it was indistinguishable between both groups in the presence of either citrate or L-histidine. Total Mn absorption, in midperfusion, was greater in M than in C animals with no ligands in the solutions (means +/- SEM, M = 2,969 +/- 923 vs. C = 654 +/- 218 pmol/cm, p less than 0.05). However, in the presence of citrate or L-histidine, the well-nourished rats absorbed more Mn than M rats. Also, water fluxes across the mucosa had a positive correlation with Mn transport when the ligands were present. This solvent drag of the trace element was not operant in the absence of citrate or L-histidine. These data indicate that the jejunal mucosa of M rats absorbs Mn more effectively than C animals, independently from water fluxes and the presence of small molecular weight chelators. These substances do not alter the uptake of Mn in growth-retarded rats, while they enhance the absorption of the trace metal in well-fed animals.

Animals↗
PubMed1984

Effects of lead on gamma-glutamyl transpeptidase and (Na+ -K+)-adenosine triphosphatase of the small intestinal mucosa.

Oral lead, when fed to young rats for 6 weeks, at a level of 0.50 in the diet, produced an increase in small intestinal mucosal gamma-glutamyl transpeptidase, an enzyme capable of catalyzing membrane translocation of amino acids and small peptides. However, a non-competitive inhibition with the glutamate acceptor used, glycylglycine, was demonstrated for lead, in vitro (l50 = 1.0 mM in purified brush border preparations). Lead ingestion caused a reduction of small intestinal mucosal (Na+ -K+)-ATPase (l50 = 0.4 - 0.6mM). At 0.2 mM concentration, lead was a competitive inhibitor for ATP in a (Na+ -K+)-ATPase assay system in vitro. A higher concentration of lead (0.5 mM) also produced an inhibitory, but non-competitive effect, with a decline of Vmax from 36.6 to 8.1 nmoles/min X cm.

Animals↗
PubMed1983

Tyrosine supplementation in chronic experimental uremia.

The occurrence of low tyrosine tissue levels in uremic subjects, possibly due to impaired phenylalanine hydroxylation, suggests that tyrosine may be an essential amino acid in uremia. Additional dietary tyrosine may thus re-dress the deficiency. This study examined growth and tyrosine/phenylalanine metabolism in uremic rats during tyrosine supplementation. Rats made uremic (U) by 7/8 nephrectomy were compared to pair-fed (CP) and ad libitum-fed (CA), sham-operated controls. Two sets of each group of rats were studied after 21 days on the respective diets: I = Purina Lab Chow; II = same + 3.5% tyrosine. Plasma tyrosine was below normal in U and CP-fed diet I. With diet II, the tyrosine:phenylalanine ratio in U was lower than both CA and CP. In rats fed diet II, the tyrosine:phenylalanine ratio became indistinguishable among the three groups. Growth parameters in U and CP were similar, regardless of the diet. Body weight gain, tibial length, muscle mass, and tissue protein did not improve in uremic animals supplemented with tyrosine. The specific activity of liver phenylalanine hydroxylase in U was not different from CA or CP. However, loss of cortical renal mass appeared to be the major determinant of decreased kidney phenylalanine hydroxylation in experimental uremia. This alteration is likely to be the greatest contributory factor to the alteration of plasma levels of tyrosine and phenylalanine. The data presented do not support a proposed essentiality of tyrosine in uremia.

Animals↗
PubMed1983

Intrauterine malnutrition in the rat: alterations of fetal glycerol metabolism.

This investigation intended to clarify the effects of malnutrition in utero on enzymes of glycerol metabolism and the stores of phosphorylated glycerol intermediates in liver, striated muscle, and brain in the rat. Pregnant Wistar rats were restricted to an intake of 50% (M) of ad libitum fed controls (C) from the seventh day of gestation onward. Fetuses were removed 2 days (-2), or 1 day (-1), before term, or at the day of birth (DOB) The M fetuses and newborn rats were stunted. Their hepatic alpha-glycerophosphate oxidase (GPO) levels were lower than those of C in utero (mean +/- SEM: M = 23.1 +/- 1.5, 15.8 +/- 1.1, and 31.6 +/- 4.5; C = 34.8 +/- 4.9, 39.8 +/- 7.0, and 23.6 +/- 5.0 nmol/min X cm at -2, -1, and DOB, respectively; F = 7.29 [1,57], P less than .01). In muscle, this enzyme, as well as liver and brain alpha-glycerophosphate dehydrogenase (GPD), alpha-glycerophosphate (GP), and dihydroxyacetone phosphate (DHAP), only varied with the developmental stage. Although the latter was a significant differential factor in all the determinations, maternal diet only affected brain DHAP stores (M = 1.85 +/- 0.36, 1.03 +/- 0.16, 0.74 +/- 0.10; C = 2.33 +/- 0.46, 1.87 +/- 0.21, 1.13 +/- 0.18 mumol/g at -2, -1, and DOB, respectively; F = 9.03 [1,53], P less than .01). These findings support the contention that intrauterine malnutrition can alter normal ontogenesis of glycerol metabolism enzymes in certain organs and become a negative factor disturbing normal gluconeogenesis and glycogenolysis, with potential disruption of energy homeostasis immediately after birth.

Animals↗