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Biomedical subjects

F Varga

Publications and source records attributed to F Varga.

At least 91 records · Page 5Linked to original sources

Postnatal development of renal sodium handling in premature infants.

To estimate the contribution of the specific defect in proximal and distal tubular reabsorption of sodium to renal salt wasting, fractional sodium excretion, distal tubular sodium delivery, and distal tubular sodium reabsorption were determined in 11 healthy premature infants. The study was performed on the seventh day and at weekly intervals thereafter up to the sixth week of life. Sodium clearance and fractional sodium excretion decreased significantly with increasing postnatal age (P less than 0.001). There was no significant alteration in either osmolar or free-water clearances. Distal tubular sodium delivery steadily decreased from 4.96 +/- 0.66 (mean +/- SE) in the first week to 3.3 +/- 0.41 ml/minute/dl GFR in the sixth week of life (P less than 0.05). Distal tubular sodium reabsorption was 69.5 +/- 2.36% in the first week, then rose significantly to reach a value of 83.7 +/- 1.85% in the second week (P less than 0.001) and remained practically unchanged thereafter. It is suggested that the rapid improvement of distal tubular sodium reabsorption in premature infants might result from forced stimulation by the excessively activated renin-angiotensin-aldosterone system.

Age Factors↗

Relationship between maturity, electrolyte balance and the function of the renin-angiotensin-aldosterone system in newborn infants.

Simultaneous measurement of plasma renin activity (PRA), plasma aldosterone concentration (PA) and urinary aldosterone excretion (UAE) was made using the RIA method along with determination of Na and K balance in 1-week-old neonates with gestational age of 30-41 weeks (mean 35.9 weeks) and birth weight of 1,160-4,670 g (mean 2,680 g). It was demonstrated that PRA decreased from the value of 36.3 +/- 6.3 ng/ml/h (mean +/- SE) to a level of 10.2 +/- 2.1 ng/ml/h (p less than 0.001), PA did not change and UAE increased from 3.3 +/- 0.8 to 7.8 +/- 1.4 microgram/day (p less than 0.01) as the gestational age advanced from 30-32 to 39-41 weeks. There was no correlation between either PRA and PA and UAE. PRA showed a significant positive correlation with urinary Na excretion (p less than 0.001) and plasma K concentration (p less than 0.05), but it was negatively related to Na balance (p less than 0.001). Significant negative correlations were found between UAE and urinary Na excretion (p less than 0.05), urinary Na/K ratio (p less than 0.01 (and plasma K concentration (p less than 0.05); however, UAE positively correlated with Na balance (p less than 0.01). It is concluded that, in response to renal salt wasting and to the subsequent negative salt balance, premature infants can augment their PRA above values found for full-term infants. Their adrenals, however, failed to respond adequately to this stimulation.

Aldosterone↗

Postnatal development of renin-angiotensin-aldosterone system, RAAS, in relation to electrolyte balance in premature infants.

In an attempt to provide information about the role of RAAS in development of late hyponatremia in low-birthweight neonates, simultaneous measurement of plasma renin activity, (PRA), plasma aldosterone concentration (PA), and urinary aldosterone excretion (UAE) was made using RIA methods along with determination of Na and K balance weekly up to the 6th week of life. Seven healthy male infants with mean birthweight of 1580 g, range: 1160-1850 g, and mean gestational age of 31 weeks, range: 30-32 weeks, were selected for the study. Due to the increased urinary Na loss, negative Na balance developed in the first 2 weeks followed positive balance thereafter. PRA, PA, and UAE increased tremendously from the initially high values of 18.2 +/- 4.1 ng/ml/hr, 1.7 +/- 0.5 ng/ml, and 2.6 +/- 0.4 microgram/day, mean and SEM, to their maximum of 78.6 +/- 18.1 ng/ml/hr, p less than 0.01, 6.8 +/- 3.7 ng/ml, p less than 0.05, and 26.4 +/- 2.9 microgram/dayp less than 0.01, in the 3rd week, respectively. Later on, gradual declines occurred, however, PRA, PA, and UAE remained highly elevated even at the 6th week with values of 45.5 +/- 15 ng/ml/hr, 1.6 +/- 0.5 ng/ml, and 14.5 +/- 1.4 microgram/day, respectively. It is suggested that late hyponatremia of premature infants is due to tubular unresponsiveness to aldosterone and not to inadequate response of RAAS to stimulation.

Aldosterone↗

Effect of sodium taurocholate on the hepatic transport of bromsulphthalein in rats.

In anaesthetized, bile duct-cannulated rats the hepatic transport of bromsulphthalein (BSP) showed a dose-dependent increase in response to simultaneous administration of taurocholate (TC). The excretion rates of both free (BSP) and conjugated bromsulphthalein (BSP-GSH) were significantly elevated by TC. The simultaneously given TC decreased the hepatic uptake of BSP and BSP-GSH, but did not influence the conjugation of BSP with glutathione (GSH) or the biliary excretion rate of exogenous BSP-GSH. When the liver was depleted of GSH by pretreatment with diethyl-maleate (DEM), TC increased the excretion of free BSP. In DEM-treated rats free BSP markedly depressed the biliary excretion of exogenous BSP-GSH. When TC was given simultaneously with BSP, the inhibitory effect of BSP on the excretion of exogenous BSP-GSH was significantly reduced. TC also diminished the depressing effect of BSP on state III respiration of liver mitochondria in vitro. It is concluded that this effect of TC may play a role also in the increased biliary excretion of intraphepatic conjugated BSP.

Animals↗

Hepatic storage and biliary excretion of rose bengal in the rat.

The distribution of intravenously administered rose bengal (RB) depends on its dose. At a low dose (10 mg/kg), RB can be found almost solely in the liver and plasma. However, at higher doses (from 25 up to 200 mg/kg) the amount of RB found in extra-hepatic tissues gradually increases. In this experiment the hepatic transfer maximum of RB amounted to 146 micrograms/kg/min. By increasing the dose from 10 to 200 mg/kg, the hepatic concentration of RB also approached a maximum (1250 micrograms/g). The storage capacity of the liver, however, did not limit the transfer maximum of RB.

Animals↗

Effect of 3-methylcholanthrene on the biliary excretion of bromsulphthalein and eosine in newborn rats.

The biliary excretion rates of bromsulphthalein (BSP), bromsulphthalein-glutathione conjugate (BSP-GSH) and eosine have been studied in 3-methylcholanthrene (3-MC)-pretreated (100 mg/kg i.p.) and control rats aged 10 days. Liver weight was invariably increased after 3-MC treatment, associated with enhanced biliary excretion of total BSP. The increase in the biliary excretion of total BSP was due solely to the increased excretion of BSP-GSH. Following 3-MC pretreatment, BSP-GSH and eosine appeared in the bile in the same amount as in the control rats after i.v. administration of BSP-GSH and eosine. Pretreatment with 3-MC increased the ratio of BSP-GSH to BSP in the liver and bile. Our results suggest that the increased biliary excretion of total BSP following 3-MC treatment was due to an enhanced conjugation of BSP with GSH.

Animals↗

Correlation between hepatic transport of cholephilic organic anions and their effect on hepatic mitochondrial respiration.

The maximum biliary excretion rate (Tm) of some nonmetabolized organic anions was investigated in anaesthetized male rats and was found to increase in the following order: indocyanine green (ICG), rose bengal (RB), bromsulphthalein (BSP; its conjugation with glutathione was prevented by diethyl maleate), bromcresol green (BCG), eosine (E), BSP-glutathione conjugate (BSP-GSH), iodoxamic acid (IA) and amaranth (A). The accumulation of ICG, RB, BSP and BCG in liver was relatively high, whereas E, BSP-GSH,IA and A were taken up by the liver in a lower concentration. ICG, RB, BSP and BCG decreased the biliary flow, however, E, BSP-GSH, IA and A stimulated it. ICG, RB and BSP had a strong, BCG and E a moderate, inhibitory effect on hepatic mitochondrial respiration stimulated by ADP, DNP and glutamate-malate, whereas BSP-GSH, IA and A had no effect on this process. Our results suggest that the depressing effect of cholephilic organic anions on bile production and their low biliary excretion rates are connected with their inhibitory effects on mitochondrial respiration.

Amaranth Dye↗

Hepatic microsomal induction and hepatic transport.

Hepatic microsomal induction (hexobarbital sleeping time, cytochrome P-450 and microsomal protein concentration, liver weight) and hepatic transport (hepatic uptake, biotransformation, biliary excretion) have been studied in rats. Phenobarbital pretreatment (75 mg/kg i.p. daily for 5 days) produced microsomal induction in the liver and enhanced biliary excretion of bromcresol green, eosine, bromsulphthaleine glutathione conjugate (BSP-GSH), amaranth and iodoxamic acid. However, biliary excretion of indocyanine green was unchanged after phenobarbital pretreatment. Biotransformation of bromsulphthalein (BSP) with glutathione was also increased by phenobarbital. The hepatic concentration of these organic anions was not influenced uniformly after phenobarbital pretreatment: the concentration of indocyanine green, bromcresol green, eosin and BSP-GSH in the liver was unchanged, that of amaranth and iodoxamic acid was enhanced following phenobarbital pretreatment. Investigation of the effect of pretreatment with other barbiturates showed that barbital, butobarbital, pentobarbital and amobarbital produced microsomal induction. Only baribtal and butobarbital stimulated biliary excretion of organic anions, whereas pentobarbital and amobarbital proved to be ineffective in this parameter. The results seem to indicate that the enhanced biliary excretion of exogenous organic anions produced by barbiturates is independent of microsomal enzyme induction.

Amaranth Dye↗

Bile flow and biliary excretion rate of some organic anions in phenobarbital-pretreated rats.

Bile flow and the biliary excretion of indocyanine green, bromcresol green, eosine, bromsulphthalein-glutathione conjugate (BSP-GSH), amaranth and iodoxamic acid were investigated in control and phenobarbital-pretreated rats (75 mg/kg i.p. daily for 5 days). The bile flow was increased by phenobarbital from an average of 50.6 to 77.7 microliter/kg/min. Depending on the dose, the biliary excretion rate of bromcresol green was increased by 48-496% and that of eosine by 30-149%. After phenobarbital pretreatment the excretion of BSP-GSH was also enhanced by 34-52%, that of amaranth by 37-53% and that of iodoxamic acid by 40-56%. However, the biliary excretion of indocyanine green remained unchanged. There was no parallelism between the increase in bile flow and biliary excretion of the drugs.

Amaranth Dye↗

Relationship of renal threshold for bicarbonate reabsorption to urinary sodium excretion in premature infants.

Renal threshold for bicarbonate reabsorption and urinary sodium excretion of nine healthy male premature infants with a mean birth weight of 1734 g (range 1650-1900) was determined on the 7th day of life, and subsequently weekly for 6 consecutive weeks, by applying a repeated NH4Cl load. A close negative correlation was found between bicarbonate threshold and urinary sodium excretion (p less than 0.01). It is suggested that the limited renal capacity to reabsorb sodium may account for the low bicarbonate threshold in premature infants.

Ammonium Chloride↗

Relationship of metabolic acidosis to urinary sodium excretion in the newborn infant.

The relationship between birth weight, postnatal age and acidosis-induced urinary sodium excretion was studied in 43 one-week-old newborn infants with birth weights of 1000-4300 g and gestational age of 28-41 weeks; and in 13 premature infants with birth weights of 1000-1970 g (mean 1620 g) and gestational age of 29-35 weeks (mean, 31.4 weeks) during the first six weeks of life. Developmental changes were found in acidosis-induced urinary sodium excretion. Newborns with higher birth weight and postnatal age excreted significantly more sodium in response to acidosis than their lighter and younger matches. It is suggested that the degree of acidosis must be taken into account when estimating the sodium requirement of newborn infants different in birth weight and postnatal age.

Acidosis↗

Tracer kinetic studies on in vivo fatty acid metabolism in white adipose tissue of well-fed and starving newborn rabbits during acute or prolonged exposure to cold.

Pool size (M), and specific radioactivities (SA) of lipids of white adipose tissue (WAT), as well as the flow rates (ms) of free fatty acids (FFA) from plasma into WAT were studied by injecting 14C-1-palmitate (20.10(6) cpm/100 g body weight) into 7-day-old rabbits reared in a thermoneutral (Group I) or a cold environment (Group II) or subjected to starvation at an ambient temperature (Ta) of 35 degrees C (Group III) or at Ta 20 degrees C (Group IV). Experiments were carried out at Ta 20 degrees C in all four groups of rabbits. The pool size of esterified and non-esterified fatty acids of WAT was reduced in both the well-fed animals raised in the cold and in the starving ones. The SA of tissue FFA and phospholipid fatty acid (PL-FA) was highest in Group III and Group IV indicating an increased FFA metabolism of WAT in animals subjected to starvation prior to acute exposure to cold. The flow rate (ms) of FFA between plasma and WAT increased twofold in Group IV but remained about one fifth that of the ms between plasma and brown adipose tissue (BAT) indicating that the contribution of WAT to cold-induced calorigenesis of the whole animal must be regarded as of secondary importance.

Adipose Tissue↗

Changes in the blood supply of the gastrointestinal tract in rats with age.

Regional blood flow of the gastrointestinal (GI) tract and cardiac output have been determined in male Sprague-Dawley rats weighing from 30-726 g. The cardiac output (ml/min per kg) was highest in rats weighing 80-100 g. In heavier rats the cardiac output decreased proportionally with the body weight. The gradient of blood flow to the different parts of the GI tract develops step by step. In the weaning period the blood flow (ml/min per g tissue) through the stomach was less than that through the distal parts of the GI tract. However, the blood flow through the small intestine, cecum and large intestine was uniform at this age. In rats weighing 80-100 g the blood flow through both the cecum and large intestine was less than that through the small intestine. The gradient in blood flow through the various segments of small intestine developed last.

Age Factors↗

Transit time changes with age in the gastrointestinal tract of the rat.

Using 85Sr-labelled microspheres as nonabsorbable markers, the effect of age on gastrointestinal propulsion motility was determined in conscious rats. There was no significant correlation between the gastric emptying rate or the propulsion motility of the small intestine and the age of the rats. However, the transit time of the intestinal content in the caecum in adult (17- to 20-month-old) rats was about fivefold the value found in weanling (19-day-old) rats. Also the transit time of the large intestine was found to be prolonged by about 70% during the life span investigated.

Age Factors↗

Studies on plasma free-fatty-acid metabolism and triglyceride synthesis of brown adipose tissue in vivo during cold-induced thermogenesis of the newborn rabbit.

Parameters of plasma free fatty acid metabolism (pool size, half time, disappearance rate, turnover time and absolute turnover rate), the influx of plasma free fatty acids into the glycerides of brown adipose tissue and the pathway of triglyceride synthesis in brown adipose tissue (glycerol-1-phosphate versus monoglyceride pathway) were examined after intravenous injection of [1-14C]palmitate in newborn rabbits. In the thermoneutral environment of 35 degrees C the turnover rate of plasma free fatty acids was 10.20 mumol/min per 100 g body weight and its flux into the glycerides of brown adipose tissue 0.367 mumol/min per 100 g body weight. Cold exposure at an ambient temperature of 20 degrees C caused a decrease to 5.84 mumol/min and 0.207 mumol/min per 100 g body weight, respectively. Both under basal conditions at an ambient temperature of 35 degrees C and under cold-induced thermogenesis at an ambient temperature of 20 degrees C triglyceride synthesis in brown adipose tissue ran through the glycerol 1-phosphate pathway.

Adipose Tissue, Brown↗