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Biomedical subjects

F Lifshitz

Publications and source records attributed to F Lifshitz.

At least 91 records · Page 5Linked to original sources

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↗

Tolerance to glucose polymers in malnourished infants with diarrhea and disaccharide intolerance.

The response of infants with diarrhea and lactose intolerance to feedings containing soy protein and sucrose (Sobee), and/or to a carbohydrate free formula (RCF), to which glucose polymers (GP) were added, was assessed in twenty patients. They all were less than ten months of age and had varying degrees of malnutrition. Eleven had acute diarrhea and nine had chronic diarrhea. None of them had classical enteropathogenic strains and parasites in the stools. All had lactose intolerance when feedings were begun with cow's milk formula and some also had sucrose intolerance when fed sucrose containing soy formulas. They had persistent loose stools and excreted feces with an acid pH and with carbohydrates, thus they were given dietary treatment with RCF with GP. There were 9 patients with acute diarrhea and lactose intolerance (1 of them also had sucrose intolerance), who improved on RCF with GP feedings; but 2 patients (lactose and sucrose intolerant) failed to respond to this diet. There were six patients with chronic diarrhea and lactose intolerance (four of them also had sucrose intolerance), who improved on RCF with GP formula, but there were three patients who failed on this treatment. These data show that some infants with diarrhea, malnutrition, and lactose-sucrose intolerance may also develop intolerance to GP and require further dietary management with glucose as the source of carbohydrate in the diet.

Acute Disease↗

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↗

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↗

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↗

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↗

Impaired somatomedin generation test in children with insulin-dependent diabetes mellitus.

Recent studies have suggested a partial block in somatomedin (SM) production or growth hormone (GH) action in IDDM. Twelve well-nourished diabetic children (9 males and 3 females with a mean age of 11.2 +/- 3.3 yr), six with an HbA1c of 7.9-11.2% (group A) and six with an HbA1c of 12.5-15.6% (group B), were studied as follows: the GH response after 100 micrograms of oral clonidine and the SM generation capacity after i.m. administration of 0.2 U/kg/dose of human growth hormone (hGH) for 4 days. Group B diabetic subjects had a significantly higher mean +/- SD GH increase after clonidine than did group A patients (delta of 17.4 +/- 4.9 versus 5.7 +/- 6.0 ng/ml, P less than 0.01); the basal GH of both groups were similar (1.6 +/- 0.7 versus 2.3 +/- 1.4 ng/ml). In contrast, the SM response to hGH was significantly decreased in group B children as compared with those in group A (delta of 0.3 +/- 0.3 versus 1.2 +/- 0.4 U/ml, P less than 0.01). The basal SM levels of both groups were normal for age. GH and SM correlated with HbA1c levels (r = +0.80, P less than 0.01; r = -0.79, P less than 0.01, respectively); there was no correlation with plasma and urine glucose or serum cholesterol, cortisol, and transferrin. Our data indicate a blunted SM response to hGH in group B diabetic subjects; this defect in SM generation is apparently not present in group A subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Abnormalities of thyroid function in infants with Down syndrome.

We describe 12 of 1130 infants with Down syndrome in whom various degrees of thyroid dysfunction were detected by neonatal screening. These aberrations were confirmed subsequently in 11 patients. In eight of 11 children, persistent primary hypothyroidism, was diagnosed, whereas in the remaining three patients transient thyroid abnormalities were noted. The twelfth patient died and could not be retested. We found an incidence of persistent primary congenital hypothyroidism in infants with Down syndrome of 1:141, or about 28 times more than in the general population. The cause of thyroid aberrations in these infants remains unclear; none of the studied patients had agenesis or ectopia of the thyroid gland. On initial screening most infants with Down syndrome had only mild biochemical abnormalities, with gradual decompensation occurring thereafter. Infants with Down syndrome are therefore at high risk for congenital hypothyroidism and should have careful follow-up to prevent further deterioration of their mental development or growth.

Child, Preschool↗

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↗

Fear of obesity. A cause of short stature and delayed puberty.

We evaluated 201 children for short stature or delayed puberty or both. Fourteen of them (nine boys and five girls, aged 9 to 17 years) fit a pattern of growth failure due to malnutrition, which was the result of a self-imposed restriction of caloric intake arising from a fear of becoming obese. All 14 patients underwent a complete history, physical examination, diagnostic laboratory evaluation, and psychiatric assessment. They were all below the fifth percentile for weight, and 11 of them were also below the fifth percentile for height. The deficit of weight for height ranged from 5 to 23 per cent. Seven of the older patients also had delayed puberty. All 14 patients had deteriorating linear growth, which was preceded by at least one to two years of inadequate weight gain. They ingested only 32 to 91 per cent of the recommended caloric intake for their age and frequently skipped meals. No gross psychiatric disease or anorexia nervosa was found; on the whole, they were good students with rather compulsive, shy personalities observed in an open-ended interview. The Diagnostic Interview for Children and Adolescents, which was conducted with seven patients, also revealed no psychiatric disease. After nutritional and psychiatric counseling, the patients resumed an adequate caloric intake for their age, and recovery occurred, as demonstrated by increased linear growth and sexual development.

Adolescent↗

In vivo intestinal absorption of manganese in the rat.

The mechanisms of intestinal absorption of Mn in rats and the effects of low-molecular-weight ligands in this process were investigated using an in vivo perfusion system. Segments of either jejunum or ileum were perfused with isotonic solutions containing 0.0125 to 0.1 mM MnSO4 X 7H2O, in the presence or absence of double its concentration of either L-histidine (His) or citrate (Cit). In all cases the absorption of Mn declined with time; for example, in the absence of ligand Mn absorption fell from (means +/- SEM) 16.0 +/- 2.2 at 30 minutes to 2.3 +/- 4.1 pmol/(minute X cm) after 90 minutes of perfusion. Comparable declines occurred both in the jejunum and in the ileum in the presence of His or Cit. The initial absorption rates of Mn, obtained by extrapolation, were higher in the jejunum when His or Cit were present than when no ligands were included in the perfusate [means +/- SD, with His, 66.4 +/- 11.9; with Cit, 79.5 +/- 6.2; none = 17.8 +/- 3.3 pmol/(minute X cm)]. In the ileum, optimum absorption with His was observed between pH 7 and 8. The kinetics of in vivo Mn ileal absorption in the presence of His yielded a Kt of 0.056 mM and an estimated Vmax of 158 pmol/(minute X cm). The coefficient of diffusion was calculated to be 1.5 X 10(-3) cm2/minute. These data are compatible with a high affinity, low capacity, active transport mechanism for Mn in the rat intestine and suggest a limited role for small-molecular-weight ligands associated with both diffusional or active translocation processes.

Animals↗

Absorption of zinc by the rat ileum: effects of histidine and other low-molecular-weight ligands.

The role of certain amino acids, dipeptides and organic acids as ligands to facilitate the intestinal absorption of zinc was investigated by using an in vivo procedure on ileal segments of adult rats. Ligand:zinc ratios equal to or less than 3:1 were optimal for amino acids and dipeptides such as L-glutamate, glycine, L-histidine, L-tryptophan and glycylglycine. An excess of ligand reduced zinc absorption. At a 130:1 L-histidine:zinc ratio the absorption of zinc was less than one-fourth that obtained at a 3:1 ratio. Picolinate was a less effective ligand. The kinetics of the complex L-histidine:zinc at a 2:1 ratio and at pH 7.5 were determined in the absence and presence of a 20 mM excess of amino acid in a zinc concentration range between 0.038 mM and 6.00 mM. In both cases the Vmax was 2200 pmol/(minute . cm), but the Kt increased from 0.54 mM to 1.46 mM in the presence of the L-histidine excess. These data suggest a competitive inhibition of the L-histidine:zinc complex by the amino acid. Such an effect was dependent on the stereoisomerism of histidine, since the unnatural D-isomer was far less effective than the natural L-isomer in facilitating zinc absorption. The presence of an intact protein (bovine serum albumin) sharply decreased the ileal absorption of the L-histidine:zinc complex.

Amino Acids↗

Altered jejunal macromolecular barrier induced by alpha-dihydroxy deconjugated bile salts.

The effect of deconjugated bile salt hydroxy group position and numbers on the ability of these agents to alter the normal lumen-to-blood jejunal barrier to intact protein penetration was analyzed. Only in vivo jejunal perfusion with 0.5 mM alpha-dihydroxy deconjugated bile salts chenodeoxycholate and deoxycholate led to increased penetration of the 40,000-molecular-weight protein horseradish peroxidase (HRP). This increased absorption of HRP with 0.5 mM chenodeoxycholate and deoxycholate was detectable biochemically, as well as by light and electron microscopic cytochemistry, and occurred in the absence of demonstrable histological or ultrastructural damage to the epithelium. Conjugation of chenodeoxycholate with glycine, epimerization of chenodeoxycholate from 7 alpha-hydroxy to 7 beta-hydroxy as in ursodeoxycholate, or addition of a third hydroxyl group as in cholate all eliminated the increase in jejunal HRP penetration and led to HRP absorption levels like those in bile salt-free preparations. The effect of chenodeoxycholate and deoxycholate on HRP absorption was paralleled by their production of net jejunal water secretion. The observations suggest that the naturally occurring alpha-dihydroxy bile salts may lead to an increase in intact antigen or toxin absorption during bacterial stasis syndromes.

Animals↗

Disaccharide feedings enhance rat jejunal macromolecular absorption.

Disaccharide feedings to post-weaning rats alters their jejunal barrier to macromolecular absorption. Penetration of horseradish peroxidase (HRP) across the jejunum was enhanced after short-term high concentration gavage (30 g . kg-1 . day-1) of lactose that produces weight loss, osmotic diarrhea, and jejunal mucosal damage. HRP absorption was also increased by longer term feedings of lower levels of disaccharide that did not produce body weight alterations, diarrhea, or cell damage. Rats without diarrhea and gavaged with 7.5 g . kg-1 . day-1 of either lactose or maltose showed an increase in lumen to blood HRP absorption after 21 days of feedings. Also, lactose or maltose in the solid food diet at 30 g . kg-1 . day-1 for 21 days did not lead to diarrhea but produced an increase in jejunal lumen to blood HRP absorption. Rats having no diarrhea and receiving 15 g . kg-1 . day-1 of lactose or maltose in the drinking water for 21 days, showed an increase in jejunal HRP absorption. When rats were fed either lactose or maltose for 21 days glucose absorption became totally dependent upon the sugar concentration in the perfusion medium. The kinetics of this glucose absorption are compatible with a decrease in the "unstirred" layer. Disaccharide-induced HRP absorption may be mediated by transport from endocytotic vesicles across the jejunal epithelium.

Animals↗

Jejunal transport in experimental nephrotic syndrome.

In vivo jejunal transport of amino acids, monosaccharides, sodium, and electrolytes were studied in rats made nephrotic with puromycin aminonucleoside (PAN) and in pair-fed controls. Studies were performed 14 days after a single intravenous dose of PAN when rats were no longer edematous, but were still hypoproteinemic. There was decreased absorption of glucose, 3-0-methyl glucose, glycine, phenylalanine, histidine, water, and sodium in the nephrotic animals but transport of fructose, lysine and potassium was similar in the nephrotic and control animals. Enzyme kinetic studies for glucose transport showed a mixed type of inhibition affecting both Vm and Km. The jejunal mucosa of nephrotic and control rats had similar ATP content and enzyme activity for lactase, sucrase, maltase and (Na-K)-ATPase and the ratios of RNA to DNA were similar in the nephrotic and control rats. No abnormality of the jejunum was detected by light or electron microscopy. The data suggest that the impairment of absorption is a result of decreased activity of jejunal membrane carrier mechanisms. The altered transport may be secondary to effects related to the metabolic consequences of nephrotic syndrome and does not appear to be related to acute purine aminonucleoside toxicity, edema or malnutrition.

3-O-Methylglucose↗