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C R Krishnamurti

Publications and source records attributed to C R Krishnamurti.

At least 19 recordsLinked to original sources

A compartmental model depicting short-term kinetic changes in selenium metabolism in ewes fed hay containing normal or inadequate levels of selenium.

Changes in Se metabolism were studied in ewes fed hay containing normal or inadequate levels of Se. After intravenous injection of 75Se-sodium selenite, blood, feces and urine were collected at different times, and the concentrations of labeled and unlabeled Se were determined. Ewes were killed 1, 5, 9 or 14 d after tracer injection, and tissues were obtained for determination of radioactivity and Se concentration. The data were fitted to a compartmental model using the SAAM/CONSAM computer program, and kinetic parameters and steady-state transport rates were estimated. Daily Se intake (Vi) and fecal excretion (VF) were significantly (P < 0.001) higher in the ewes fed normal hay (6.06 +/- 1.09 and 3.36 +/- 0.88 mumol/d, respectively) than in those fed Se-deficient hay (0.64 +/- 0.18 and 0.26 +/- 0.15 mumol/d). The net absorption (Va) of Se was significantly higher in ewes fed normal hay [3.19 +/- 0.82 mumol/d by the balance method, Va = Vi-(VF -Vf) (Vf = endogenous fecal Se) and 1.05 +/- 0.38 mumol/d by using the model (plasma entry rate, U(1))] than in those fed hay deficient in Se [0.57 +/- 0.33 mumol/d (balance) and 0.28 +/- 0.08 mumol/d (model)]. The efficiency of absorption [alpha = U(1) divided by Vi] was significantly higher (0.46 +/- 0.19) in ewes fed Se-deficient hay than in those fed normal hay (0.18 +/- 0.09). Simultaneous fitting of the tracer data of both the groups showed that changes in hepatic extraction and urinary and fecal excretion were sufficient and necessary to account for the kinetic differences observed between treatments.

Animals↗

Application of models to determination of nutrient requirements: experimental techniques employing tracers.

This paper concerns some issues involved in the design of tracer experiments for the development of whole-body compartmental models of nutrient metabolism. It focuses on tracer administration protocol, use of multiple tracers, sampling strategy, measurement types and experiment duration in a pragmatic approach to obtaining data suitable for analysis and interpretation with use of models.

Animals↗

Kinetic modeling of selenium metabolism in nonpregnant ewes.

The kinetics of selenium metabolism in three nonpregnant ewes were studied by the intravenous injection of 75Se-sodium selenite and measurement of radioactivity responses in blood, tissues and excreta. Stable selenium measurements were also made to determine selenium intake, excretion in feces and urine, and mass of selenium in tissues. Immediately following tracer injection, there was a rapid disappearance of radioactivity from plasma reflecting the uptake of the element by the liver and blood cells. The decrease in plasma radioactivity ceased abruptly by 30-45 min, and was followed by an increase to a peak by 3-4 h and a more gradual biphasic decline thereafter. A kinetic model of selenium metabolism in the whole animal was constructed employing the SAAM/CONSAM computer program. The multiphasic response of plasma radioactivity during a physiological steady state was explained on the basis of rapid hepatic uptake of selenium and its subsequent reappearance in the circulation in protein-bound form followed by further metabolism and excretion of the element. The model provides reference parameter values for 75Se-sodium selenite kinetics in selenium-replete, mature nonpregnant ewes for comparison with the kinetics in animals whose selenium status may be altered.

Animals↗

Determination of leucine metabolism and protein turnover in sheep, using gas-liquid chromatography-mass spectrometry.

1. Whole-body protein synthetic rates in non-pregnant ewes were determined by the continuous infusion of L-[15N]- and [1-13C]leucine and measuring the plasma enrichment of leucine, alpha-ketoisocaproate (alpha-KIC) and expired carbon dioxide by gas-liquid chromatography-mass spectrometry. 2. The mean whole-body protein synthesis estimated from plasma leucine flux corrected for oxidation was 5.38 (SE 0.54) g/kg per d. 3. Under the conditions of the present study leucine oxidation was 0.323 (SE 0.067) mmol/kg per d and accounted for 10.71 (SE 2.26) % of plasma [13C]leucine flux. Deamination of leucine was 0.55 (SE 0.035) mmol/kg per d and accounted for approximately 17% of plasma [15N]leucine flux. 4. The rate of alpha-KIC reamination to leucine, calculated by subtracting 13C flux from 15N flux, was 0.228 (SE 0.101) mmol/kg per d. 5. The rate of whole-body protein degradation was 4.49 (SE 0.54) g/kg per d and there was a net protein gain of 0.89 (SE 0.21) g/kg per d.

Animals↗

Application of reversed-phase high-performance liquid chromatography using pre-column derivatization with o-phthaldialdehyde for the quantitative analysis of amino acids in adult and fetal sheep plasma, animal feeds and tissues.

The concentration of amino acids in adult and fetal sheep plasma, liver, muscle and animal feeds was determined by reversed-phase high-performance liquid chromatography using an automated data acquisition system and pre-column o-phthaldialdehyde derivatization. Of the seventeen amino acids in the standard mixture, fifteen including glycine and threonine were completely resolved in a total analysis time of 50 min. The clear resolution, high degree of precision and accuracy, relatively rapid analysis and the lack of interference from chemical contaminants in feed and tissue hydrolysates render this technique suitable for routine analysis of large numbers of biological samples of nutritional interest.

Aldehydes↗

Whole body and tissue fractional protein synthesis in the ovine fetus in utero.

Whole-body and tissue fractional protein synthesis rates were determined in chronically-catheterized ovine fetuses at 120-130 d of gestation following an 8 h continuous infusion of L-[U-14C]- or L-[2,3,5,6-3H]tyrosine. From the net utilization of tyrosine by the fetus, corrected for apparent oxidation, and tyrosine concentration in the fetal carcass protein, whole-body protein synthesis was estimated to be 63 g/d per kg. Following 8 h of infusion of labelled tyrosine the ewes were killed and fetal tissues were removed for the determination of tyrosine specific activity. The fractional rate of protein synthesis (ks) was calculated from the specific activity ratio, protein bound:intracellular free tyrosine. Tissue ks values for the liver, kidney, lungs, brain, skeletal muscle and small intestine were 78, 45, 65, 37, 26 and 93%/d respectively. The absolute rate of synthesis was calculated by multiplying the tissue protein content by ks. Muscles, gastrointestinal tract, liver and lungs contributed approximately 20.5, 20.5, 14.4 and 9.4% respectively to whole-body protein synthesis. The efficiency of protein synthesis as expressed by the RNA activity was higher in liver, lung and brain followed by kidney, skeletal and cardiac muscle.

Animals↗

Effect of maternal starvation on fetal tissue nucleic acid, plasma amino acid and growth hormone concentration in sheep.

The measurement of nucleic acids in fetal tissues as well as plasma growth hormone and amino acids was used in conjunction with fractional protein synthetic rates to investigate the mechanism of reduced fetal protein synthesis following acute maternal starvation. The nucleic acid analysis of fetal tissues from fed and 48 h starved ewes (120-130 days gestation) demonstrated a significant reduction in kidney RNA and heart DNA concentration in the starved fetuses. The RNA synthetic capacity (RNA/protein) was also seen to decrease in the starved fetuses both for liver and kidney tissue as was the protein/DNA in the lung tissue. Most revealing, however, were the measurements of RNA and DNA activity or the extent to which the protein synthesizing capacity was realized (g protein/g RNA or DNA/day). Significant reductions were observed in liver and brain RNA activity as well as the DNA activity of liver, lung, kidney and muscle. Plasma aminograms demonstrated reductions in maternal histidine, methionine and isoleucine as well as reductions in fetal glutamate and phenylalanine following starvation. Conversely, the fetal growth hormone levels were seen to rise under the influence of maternal starvation. The impact of maternal nutrient deprivation during gestation on fetal metabolism appears to depend on the ontogenic stage of development of specific tissues at the time the deprivation occurs.

Amino Acids↗

Protein synthesis in the gastrointestinal tissues of the ovine fetus.

An isotope dilution procedure employing an 8h continuous infusion of L-[2,3,5,6-3H] tyrosine was used to determine fractional protein synthetic rates in the gastrointestinal tissues of ovine fetuses. The infusions were made into the inferior vena cava of the fetuses at 120-130 days of gestation. Immediately following the termination of the infusion the ewes were sacrificed and fetal tissues were collected, frozen in liquid nitrogen and stored at -20 C. The specific activity of the intracellular free and protein bound amino acid pools was determined from which the fractional synthetic rates (%/day) were calculated. These rates were as follows: reticulo-rumen, 49%; omasum, 10%; abomasum, 14%; proximal duodenum, 93%; and distal colon, 15%. The contribution of duodenum to the whole body protein synthesis was 10.5% while the contribution of the entire GIT (13.9%) was very close to that of liver (14.4%). The specific activity of tyrosine in the amniotic fluid and fetal ruminal fluid averaged 22% and 36% respectively of the specific activity in the plasma. The high turnover of tissue proteins in the fetal gastrointestinal tract as well as the presence of labelled tyrosine in the ruminal fluid indicate the functional importance of gastrointestinal activity in utero preparing the gastrointestinal tract for post-natal life.

Animals↗

Effect of acute maternal starvation on tyrosine metabolism and protein synthesis in fetal sheep.

To determine the effects of acute maternal starvation on intrauterine growth, tyrosine concentration and specific activity values in plasma, intracellular free and protein bound pools were determined in catheterized ovine fetuses following an 8 h continuous infusion of L-[2,3,5,6 3H] or L-[U-14C] tyrosine into the ewe and fetus respectively at 115-125 days of gestation. From the kinetic data the rates of whole body and tissue fractional protein synthesis were calculated. Although placental protein synthesis was not significantly changed as a result of acute maternal starvation, fetal whole body protein synthesis was reduced from 63 g/d/kg in the fed to 25 g/d/kg in the starved condition. There was also a 10 fold reduction in the net placental transfer of tyrosine to the fetus in the starved ewes. In addition, a three fold increase was observed in the quantity of tyrosine used for oxidation by the fetuses of starved ewes, changing from 5.2% of tyrosine net utilization in the fed to 13.7% in the starved condition. Significant reductions in tissue fractional protein synthesis rates were also seen in the liver, brain, lung kidney and GIT tissues from 78, 37, 65, 45 and 71%/d respectively in the fed to 12, 10, 23, 22 and 35%/d in the fetuses of starved ewes. The data indicate that during acute maternal starvation the sheep fetus utilizes more tyrosine for oxidation and less for anabolic purposes which is reflected in a decrease both in whole body and tissue fractional rates of protein synthesis.

Animals↗

Myoelectrical changes in the uterus of the sheep around parturition.

Myoelectrical activity in the uterus of late-pregnant sheep was recorded by the chronic implantation of bipolar electrodes in the myometrium. Three distinct patterns of electrical activity were recognizable: irregular trains of action potentials (greater than 120 sec), long spike bursts (7--120 sec), or short spike bursts (less than 7 sec) each exhibiting high (greater than 100 muV) or low (50--100 muV) amplitude. The duration of spike activity was expressed as the myoelectrical index (MI), i.e. the fraction of the hour during which a given category of activity is exhibited. The increase in the overall MI which represents daily average values regardless of the class of amplitude from 72 h pre partum up to parturition was significantly (P less than 0.05) more pronounced in the uterine horn than in the body of the uterus. During the last 6--7 days of gestation high-amplitude irregular trains and long spike bursts were significantly (P less than 0.05) more frequent than these activity patterns with low amplitude. Regardless of the amplitude, the incidence of irregular trains began to decline rapidly 48 h pre partum with an abrupt cessation following parturition. The frequency of long spike bursts increased 72 h pre partum to reach a maximum which coincided with parturition.

Action Potentials↗

Kinetics of amino acid metabolism in the ovine fetus in utero.

The recycling of amino acids in chronically catheterized ovine fetuses was determined using a single intravenous injection of a mixture of fifteen (U-14C) amino acids. The specific activity--time data were fitted to a three exponential curve which best represented the disappearance of the tracer from the fetal blood plasma. Based on the rates of total entry and irreversible disposal of amino acid carbon, it was determined that 85% of the free amino acid pool was recycled. In addition, 23.6% of the administered label was recovered in fetal blood 14CO2. No radioactivity was detectable in the maternal plasma after the injection of tracer into the fetus. The mean total residence time of the label in the fetuses studied was 7.22 +/- 0.89 minutes and corresponded to 6.46 +/- 0.93 metabolic cycles. The high rate of recycling of amino acids in the plasma pool is a reflection of the rapid turnover of proteins in the actively growing fetus.

Amino Acids↗

Role of chlorinated hydrocarbon pesticides in abortions and premature labour.

Premature labour and abortion possibly due to the high concentration of organochlorine pesticides have been investigated. Considerably higher amounts of organochlorine pesticide residues have been detected by gas liquid chromatography in the circulating blood and placental tissue of the women undergoing abortion or premature labour as compared with pregnant women in full term labour. The differences are highly significant for all pesticides estimated.

Abortion, Spontaneous↗