PubMed Health⌕ Search

Biomedical subjects

I Zelikovic

Publications and source records attributed to I Zelikovic.

At least 37 records · Page 2Linked to original sources
PubMed1990

Taurine depletion in very low birth weight infants receiving prolonged total parenteral nutrition: role of renal immaturity.

In a prospective, controlled study, plasma and urinary taurine concentrations were determined weekly, between postnatal weeks 3 and 18, in (1) seven sick infants (gestational age less than 28 weeks, birth weight less than or equal to 1000 gm) who received a taurine-free total parenteral nutrition solution for 32 to 49 days (group P) and who subsequently were formula fed and (2) eight sick infants matched by gestational age and birth weight, who received formula or human milk from day 3 to 4 of life (group E). Ten healthy full-term infants ranging in age from 1 to 18 weeks and fed with formula provided normal values (group C). Significantly lower mean plasma taurine values (range 1.59 to 3.43 mumol/dl) were found between postnatal weeks 3 and 7 in group P compared with group E (range 5.54 to 6.97 mumol/dl) and with group C (5.6 +/- 0.34 mumol/dl). After initiation of feeding, plasma taurine concentrations in group P increased to normal. Markedly elevated values of mean fractional excretion of taurine, 38% to 56%, were found between weeks 3 and 5 in group P and E compared with group C (15.5 +/- 3.2%). In contrast, during the same period, low urinary taurine values (4.9% to 6.7%) were found in two larger, older infants receiving total parenteral nutrition whose plasma taurine values were in the normal range. After week 5, urinary taurine values were in the control range in all groups. We conclude that the absence of taurine in total parenteral nutrition solutions administered to very low birth weight infants and the limited ability of the immature kidney to adapt to low taurine intake by "up-regulation" of tubular taurine reabsorption may result in depleted taurine body pools during the first weeks of life. This inability to conserve taurine by the immature nephron could potentially have a deleterious effect on the developing brain and retina in these infants, and indicates a possible need for taurine supplementation.

Enteral Nutrition↗
PubMed1989

Ionic requirements for amino acid transport.

The reabsorption of amino acids by the proximal tubule is remarkably efficient. Current evidence indicates that this process occurs by Na+-amino acid cotransport or symport. The energy for amino acid entry is derived from the chemical and voltage gradient for Na+ entry across the apical surface of the renal cell maintained by pumping Na+ out of the cell by Na+-K+-adenosine triphosphatase (ATPase) activity at the basolateral membrane. We chose the beta-amino acid taurine to study the anionic requirements as well as voltage- and pH-dependence of Na+-taurine symport into rat proximal tubule brush border membrane vesicles. Maximal uptake was found when Cl- or Br- were the anions. The addition of various ionophores (amiloride, carbonyl cyanide-n chlorophenyl-hydrazone, and valinomycin) under pH-equilibrated conditions did not change taurine entry into the vesicle. Hill equation analysis of the initial rate of taurine uptake into vesicles indicates that transport operates by means of a 2 Na+:1 Cl-:1 taurine-carrier complex. Because taurine is a zwitterion, this complex has a net positive charge. Its entry into the vesicle is favored by the imposition of an outwardly directed K+ gradient in the presence of valinomycin. The movement of a quaternary complex of this type across the apical surface of the proximal tubular cell would assure that the movement of both Cl- and the amino acid is energized by the Na+ gradient. Because most amino acids are zwitterions at physiologic pH this complex would be positively charged, favoring entry into the voltage negative renal cell interior.

Animals↗
PubMed1989

Sodium-coupled amino acid transport in renal tubule.

Amino acids are reabsorbed from the tubular lumen by a saturable, carrier-mediated, concentrative transport mechanism driven by a Na+ electrochemical gradient across the luminal membrane. This process is followed by efflux mainly via carrier-mediated, Na+-independent facilitated diffusion across the basolateral membrane. Individual amino acids may have two or more Na+-dependent transport systems with different kinetic characteristics along the luminal membrane of the proximal tubule, thereby enabling very efficient amino acid reabsorption. Dual Na+-coupled transport pathways for some amino acids located in both the luminal and the peritubular membranes may operate in concert to provide the tubular epithelial cell with essential nutrients. One or more Na+ ions, H+, Cl- and in the case of acidic amino acids, K+ ion, may be involved in the translocation of the carrier complex. For most amino acids this process is electrogenic positive, favored by a negative cell interior. At least seven distinct, but largely interacting, Na+-dependent amino acid transport systems have been identified in the brush border membrane. A diet-induced adaptation in Na+-coupled taurine transport and acidosis-induced adaptive response in Na+-dependent glutamine transport are expressed at the luminal and the basolateral membrane surfaces, respectively. The aminoaciduria of early life may be related to a rapid dissipation of the Na+ electrochemical gradient necessary for amino acid reabsorption.

Amino Acids↗
PubMed1989

Increased Na+-taurine symporter in rat renal brush border membranes: preformed or newly synthesized?

The renal adaptive response to a varied intake of sulfur amino acids is demonstrated by an increase in the initial rate of Na+-taurine symport (cotransport) by rat renal brush border membrane vesicles (BBMVs) after 8-14 days of a low methionine diet. A high (3%) taurine diet reduces Na+-taurine symport. Fasting for 3 days, which depletes renal tubule cell taurine content, also enhances Na+-taurine symport both initially (15 s) and throughout the overshoot. In this study we examine the possibility that a rapid-onset adaptive response is expressed in BBMV, with the increased Na+-taurine symport reflecting the incorporation of preformed symporter into membranes rather than new synthesis. Rats fed the low methionine diet for 14 days were placed on the high taurine diet for 12-18 h; Na+-taurine symport activity fell by 40%. Fasting for 4 h restored low methionine diet levels of Na+-taurine symport activity (92 pmol.mg protein-1.15 s-1), defining a rapidly induced rise in uptake. Colchicine (0.6 mg) was injected prior to fasting in a group of rats because it blocks the incorporation (import) of preformed symporter into the membrane. Animals injected with colchicine had a pattern of BBMV uptake similar to that found in animals switched to the high taurine diet for 18 h. This agent blocked the rapidly induced rise in uptake. Feeding with the high taurine diet for 4 h caused a fall in uptake of 16.5%; colchicine blocked this reduction in uptake. These results indicate that the nephron can respond rapidly to changes in the intake of amino acids, conserving taurine in periods of nutrient lack and excreting excess taurine within 4 h in periods of surfeit. This rapid response is expressed at the brush border surface. The use of cholchicine indicates that the increase or reduction in Na+-taurine symport activity is due to incorporation (import) of transporter into the BBMV rather than to de novo synthesis.

Amino Acids, Sulfur↗
PubMed1989

Anion dependence of taurine transport by rat renal brush-border membrane vesicles.

The anionic requirements and the stoichiometric relationships of Na+-taurine cotransport into rat renal brush-border membrane vesicles (BBMV) were evaluated. External Cl- (100 mM) or Br- (100 mM) gradients supported the full overshoot of Na+-taurine symport and yielded similar high-affinity transport systems for taurine uptake. No active uptake of taurine was evident in the presence of external (100 mM) NaF, NaI, Na gluconate, or Na p-aminohippurate (PAH). Na+:taurine stoichiometry was 2.18:1 in the presence of Cl- and 1.60:1 in the presence of Br-. When the external anion gluconate was employed, Na+-dependent taurine uptake was negligible over the whole range of Na+ concentrations examined. Cl-:taurine and Br-:taurine stoichiometries in the presence of external Na+ were 0.97:1 and 0.81:1, respectively. External furosemide (1 mM) or bumetanide (1 mM) did not change taurine accumulation and kinetic parameters. The anionic transport inhibitors 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (5 x 10(-4) M), N-(4-azido-2-nitrophenyl)-2-aminoethylsulfonate (10(-3) M) and p-chloromercuribenzoate (5 x 10(-4) M) significantly decreased initial rate of taurine uptake by 48, 31, and 31%, respectively. These data suggest that Na+-taurine cotransport into rat renal BBMV is Cl- or Br- dependent and probably operates by means of 2 Na+:1 Cl- or Br-:1 taurine carrier complex. Na+-taurine symport across the rat renal brush-border membrane surface is not affected by diuretics that influence NaCl cotransport but is affected by selected anionic transport inhibitors. An intact anionic binding site may be needed for this translocation process.

Amino Acid Transport Systems↗
PubMed1989

Pre- and postoperative fluid management in infancy.

The fluid and electrolyte management of the infant either before or following surgery is not difficult if the several principles are carefully followed: (1) Fluid requirements include maintenance therapy, correction of ongoing losses, and replacement of deficit losses. (2) Calculation for fluid requirements in the postoperative period will include maintenance therapy, correction of ongoing losses, and provision of fluid lost by internal shifts. (3) Maintenance needs for fluid in infants equals 100 to 120 mL/kg per 24 hours, and Na+ at 3 mEq/kg per 24 hours and K+ at 2 to 3 mEq/kg per 24 hours are needed. (4) Infants with pyloric stenosis should be anticipated to have hypokalemic, hypochloremic metabolic alkalosis, and dehydration. These electrolyte abnormalities should be corrected before surgery is performed. A pyloromyotomy is not an emergency procedure. (5) Ileostomy losses can equal 90 mEq/L of Na+ and up to 110 mEq/L of HCO3. Thus, adequate fluid replacement results in volume depletion and metabolic acidosis. (6) Children whose nutritional status is marginal and whose bowels cannot be used for nutrient absorption should receive their fluid and electrolyte needs as part of a total parenteral nutrition program.

Energy Metabolism↗
PubMed1988

Development of beta-amino acid transport in the kidney.

This study focuses on the maturation of the renal beta-amino acid transport system and uses dietary manipulation as a probe. The epithelial surface of the renal proximal tubule is responsible for the conservation of ions and organic solutes including beta-amino acids. This beta-amino acid transport system is stimulated during periods of reduced dietary intake and permits increased excretion following dietary excess. We have examined transport of the sulfur-containing beta-amino acid, taurine, as a measure of this renal adaptive response to fluctuations in dietary sulfur amino acid intake and as a substrate for the beta-amino acid transport system. A precession of taurine uptake values by brush border membrane vesicles (BBMV) prepared from nursing rats from youngest to oldest was evident. However, these membranes demonstrate the full renal adaptive response to altered sulfur amino acid intake after the first week of life. This adaptive response is expressed at the brush border surface by transport changes in both directions ("up regulation" and "down regulation"), through changes in the initial rate (15 sec) of Na+-taurine cotransport. No alterations in the lipid microenvironment of the membrane, as detected by altered membrane fluidity, were uncovered. Although vesicles from 7-day-old pups demonstrate adaptation and accumulate taurine to a limited extent, the accumulation of Na+, which energizes uptake, may be altered, thereby preventing full expression of the adaptive response and of transport capacity at this age.

Amino Acids↗
PubMed1988

Good outcome in prune-belly syndrome despite associated severe anomalies.

A boy aged 4.5 years with prune-belly syndrome and associated urethral stenosis, oligohydramnios, imperforate anus and vesicosigmoid fistula is described. In contrast to the anticipated poor prognosis, vesicostomy and divided transverse colostomy performed after birth followed by prophylaxis of infection and bicarbonate supplementation have resulted in a good outcome. The vesicosigmoid fistula might have served in utero as a "natural diversion" protecting from pressure-induced renal damage. It is suggested that the main determinant of prognosis in PBS is the presence and degree of kidney dysplasia at birth as reflected by the neonatal renal function after performance of an indicated urinary diversion procedure rather than the presence of severe associated anomalies.

Anus, Imperforate↗
PubMed1988

Renal adaptation to dietary amino acid alteration is expressed in immature renal brush border membranes.

The transport of ions and solutes at the epithelial surface of the renal proximal tubule increases during periods of reduced dietary intake and decreases with dietary excess. We have used the sulfur-containing beta-amino acid, taurine, as a probe of this renal adaptive response to altered dietary sulfur amino acid intake to better understand the mechanisms of renal amino acid reabsorption. There exists an age-related precession of taurine uptake values by brush border membrane vesicles prepared from nursing rats from youngest to oldest. However, despite the immaturity of this transport mechanism, epithelial membranes become able to display a full renal adaptive response to altered sulfur amino acid intake sometime between the 7th and 14th day of life. This adaptive response is expressed in both "up regulation" and "down regulation" by means of a change in the initial rate of Na(+)-taurine cotransport. No changes in the lipid microenvironment of the membrane, as assessed by measurements of membrane fluidity, are evident. The lack of adaptation observed in 7-day-old pups may be due to immaturity of the Na+ transporting mechanism which energizes the uptake of amino acids.

Adaptation, Physiological↗
PubMed1987

Developmental aspects of renal beta-amino acid transport. VI. The role of membrane fluidity and phospholipid composition in the renal adaptive response in nursing animals.

Accumulation of the beta-amino acid taurine is higher in adult rat renal brush border membrane vesicles than in nursing animals, which relates to a higher initial rate Vmax. A low sulfur amino acid diet increases and a 3% taurine diet reduces the Vmax of Na+-taurine cotransport in brush border membrane vesicles at all ages after 7 days as compared to values on a normal diet. To determine if changes in membrane fluidity account for these developmental and adaptive events, the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene was used to measure fluorescence anisotropy. A two-component, single break curve fit the data over the range 4 to 56 degrees C. Values for the break temperature centered around 23 degrees C, not different than a break temperature determined in adult membranes. The values for membrane polarization range from 0.311 to 0.329 in membranes from 7-, 14-, and 21-day-old pups exposed to each of the three diets, significantly lower than the value in adult membranes (p less than 0.02). The slopes of each component, equivalent to the apparent energy of activation, did not differ in relation to diet. The ontogenic changes in taurine uptake by brush border membrane vesicles related to the exposure to different dietary sulfur amino acid levels are not related to changes in membrane fluidity using 1,6-diphenyl-1,3,5-hexatriene as a probe. However, there is a decrease in fluidity with age. Total phospholipid content falls postweaning, and the percent of total content of phosphatidyl choline and glycerol phosphate fall, and phosphatidyl serine and ethanolamine rise as the rat ages.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1987

Severe renal osteodystrophy without elevated serum immunoreactive parathyroid hormone concentrations in hypomagnesemia due to renal magnesium wasting.

An 8 1/2-year-old girl presented with a long history of seizures, growth retardation, muscle weakness, gait disturbance, and hearing loss. Her evaluation revealed chronic moderate renal failure (serum creatinine 2.2 mg/dL), severe hypocalcemia (5 mg/dL), hyperphosphatemia (8.1 mg/dL), hypomagnesemia (1.5 mg/dL), increased urinary magnesium excretion (2 mg/kg/d), high fractional excretion of magnesium (21.7%), hypokalemia (3.2 mEq/L), and hyperkaliuria (26 mEq/L). Low circulating immunoreactive parathyroid hormone levels for the degree of the hypocalcemia (serum N-parathyroid hormone 212 pg/mL) and severe rickets without evidence of osteitis fibrosa cystica were found. The patient probably has primary renal leak hypomagnesemia (magnesuric hypomagnesemia) which caused impaired secretion of immunoreactive parathyroid hormone leading to severe hypocalcemia and calcium deficiency rickets. Treatment with magnesium and calcium supplements, calcitriol, and aluminum hydroxide resulted in marked clinical, biochemical, and radiologic improvement. Calcium deficiency rickets due to primary or secondary renal magnesium wasting in conjunction with moderate renal failure represents a largely unrecognized metabolic bone disease.

Aluminum Hydroxide↗