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Biomedical subjects

R Ramakrishnan

Publications and source records attributed to R Ramakrishnan.

At least 127 records · Page 7Linked to original sources
PubMed1988

Growth, nutrient retention, and metabolic response in low birth weight infants fed varying intakes of protein and energy.

Growth, nutrient retention, and metabolic response were determined in low birth weight (LBW) infants fed daily protein and energy intakes, respectively, of 2.8 gm/kg and 119 kcal/kg (group 1), 3.8 gm/kg and 120 kcal/kg (group 2), and 3.9 gm/kg and 142 kcal/kg (group 3). The mean rates of both weight gain and nitrogen retention in group 1 were somewhat greater than intrauterine rates; plasma concentrations of transthyretin and albumin also were acceptable. Thus the lower protein intake appeared to be adequate. On the other hand, the rates of weight gain and nitrogen retention in groups 2 and 3 were greater than those in group 1, supporting the efficacy of the higher protein intake with respect to growth. However, blood urea nitrogen and plasma amino acid concentrations also were higher in groups 2 and 3; both were higher in group 2 than in group 3, reflecting the positive effect of the higher energy intake on protein utilization. This observation, combined with data from an earlier study, indicates that protein intakes in excess of 3 gm/100 kcal will not be utilized completely. Energy expenditure in group 3 was greater than in group 1 but not group 2, raising the possibility that protein intakes not utilized completely contribute to diet-induced thermogenesis. The higher energy intake in group 3 vs group 2 did not affect rate of weight gain significantly, but energy storage in group 3, and hence fat accretion, was greater than that of other groups. In all groups the ratio of protein accretion to fat accretion reflected dietary proportions of protein and energy.

Child Development↗
PubMed1987

Energy expenditure, energy balance, and composition of weight gain in low birth weight infants fed diets of different protein and energy content.

The effect of energy and protein intakes on energy expenditure, energy balance, and amount and relative rate of both protein and fat deposition in new tissue was investigated in 19 low birth weight infants whose mean protein and energy intakes, respectively, were 2.24 g/kg/d and 113 kcal/kg/d (formula A, n = 8), 3.6 g/kg/d and 115 kcal/kg/d (formula B, n = 5), and 3.5 g/kg/d and 149 kcal/kg/d (formula C, n = 6). The higher energy intake (formula C) but not the higher protein intake (formula B) resulted in greater energy expenditure. Both the higher protein (formula B vs formula A) and higher energy intakes (formula C vs formula B) resulted in greater weight gain secondary, in group B, to a greater absolute rate of protein deposition and, in group C, to a greater absolute rate of fat deposition. The relative composition of the new tissue deposited reflected the proportional intakes of protein and energy. The numerical value of the protein/fat ratio (g/g) of the new tissue deposited by infants fed formulas A and C, the protein contents of which were low relative to energy contents, were similar and significantly lower than the numerical value of the protein/fat ratio of the new tissue deposited by infants fed formula B, which had a higher protein content relative to energy content. These findings suggest that the composition of weight gain is related to both the absolute amounts and the proportions of dietary protein and energy; thus, both must be considered in formulation of nutritional regimens for LBW infants.

Body Weight↗
PubMed1987

Suppression of apolipoprotein B production during treatment of cholesteryl ester storage disease with lovastatin. Implications for regulation of apolipoprotein B synthesis.

Cholesteryl ester storage disease (CESD) is characterized by the deficient activity of lysosomal cholesteryl ester (CE) hydrolase, accumulation of LDL-derived CE in lysosomes, and hyperlipidemia. We studied the kinetics of VLDL and LDL apolipoprotein B (apoB), using 125I-VLDL and 131I-LDL, in a 9-yr-old female with CESD and elevated total cholesterol (TC) (271.0 +/- 4.4 mg/dl), triglyceride (TG) (150.0 +/- 7.8 mg/dl), and LDL cholesterol (184.7 +/- 3.4 mg/dl). These studies demonstrated a markedly elevated production rate (PR) of apoB, primarily in LDL, with normal fractional catabolism of apoB in VLDL and LDL. Urine mevalonate levels were elevated, indicative of increased synthesis of endogenous cholesterol. Treatment with lovastatin, a competitive inhibitor of hydroxymethylglutaryl coenzyme A reductase, resulted in significant reductions in TC (196.8 +/- 7.9 mg/dl), TG (100.8 +/- 20.6 mg/dl), and LDL cholesterol (102.0 +/- 10.9 mg/dl). Therapy reduced VLDL apoB PR (5.2 vs. 12.2 mg/kg per d pretreatment) and LDL apoB PR (12.7 vs. 24.2 mg/kg per d pretreatment). Urine mevalonate levels also decreased during therapy. These results indicate that, in CESD, the inability to release free cholesterol from lysosomal CE resulted in elevated synthesis of endogenous cholesterol and increased production of apoB-containing lipoproteins. Lovastatin reduced both the rate of cholesterol synthesis and the secretion of apoB-containing lipoproteins.

Apolipoproteins B↗
PubMed1986

Umbilical cord length in Down's syndrome.

Fetal motor activity is believed to influence umbilical cord growth. As Down's syndrome is associated with hypotonicity and reduced fetal activity, we hypothesized that newborn infants with this syndrome have short umbilical cords. We identified 21 infants with Down's syndrome and compared each individual cord length to mean standard values derived from the same population and matched for sex, race, and gestational age. Infants with Down's syndrome were found to have significantly shorter umbilical cords (mean of 45.1 cm compared with 57.3 cm for matched standards). It is not clear whether their cords are shorter on the basis of decreased fetal activity, genetics, or both. If it is on the basis of decreased fetal activity, it would be interesting to see if those with the shortest cords (presumed to have been the most hypoactive in utero) could be predicted to have worse neurodevelopmental outcomes.

Down Syndrome↗
PubMed1986

Effects of varying protein and energy intakes on growth and metabolic response in low birth weight infants.

Growth (weight, length, head circumference, and skinfold thickness), retention of major nutrients (nitrogen, sodium, potassium, chloride, calcium, and phosphorus), and chemical indices of protein adequacy (plasma albumin and transthyretin concentrations) and excess (blood urea nitrogen concentration and acid-base status; plasma amino acid concentrations) were determined serially from the time desired intake was tolerated until discharge weight (2200 gm) was reached in low birth weight infants (birth weight 900 to 1750 gm) fed one of three formulas, which provided protein and energy intakes, respectively, of 2.24 gm/kg/day and 115 kcal/kg/day (group 1), 3.6 gm/kg/day and 115 kcal/kg/day (group 2), and 3.5 gm/kg/day and 149 kcal/kg/day (group 3). Weight gain and rate of increase in length and head circumference were less in group 1 than in groups 2 and 3. Retention of most major nutrients also was less in group 1, as was blood urea nitrogen concentration, plasma albumin and transthyretin concentrations, and plasma concentrations of several amino acids. The rate of weight gain was not significantly greater in group 3 than in group 2, but the rate of increase in skinfold thickness was greater in this group. Neither nutrient retention nor metabolic indices differed between groups 2 and 3. These results suggest that a protein intake of 2.24 gm/kg/day is inadequate for the type of LBW infants studied, that the higher protein intakes are well tolerated, and that an energy intake of 149 vs 115 kcal/kg/day does not enhance utilization of the higher protein intakes studied.

Acid-Base Equilibrium↗
PubMed1986

An analysis of the variability in estimates of bioenergetic variables in preterm infants.

Estimates of average daily energy expenditure and minimal observed oxygen consumption are commonly used to characterize the energy metabolism of neonates. Yet, the errors inherent in these estimates have not been defined. Using measurements of oxygen consumption and carbon dioxide production made in healthy growing low birth weight infants during eight consecutive 3-h interfeeding epochs, we have determined the variability in the mean oxygen consumption, carbon dioxide production, respiratory quotient, total daily energy expenditure, and the minimal observed oxygen consumption among the feeding epochs. The coefficient of variation for oxygen consumption ranged from 3.1 to 9.1%, for minimal observed oxygen consumption from 3.7 to 16.7%, for carbon dioxide production from 3.3 to 7.4%, and for total daily energy expenditure from 2.9 to 7.6%. The SDs for respiratory quotient ranged from 0.008 to 0.066. From these 24-h data we have calculated the error in predicting daily estimates of the mean values for these variables if observations are made for less than 24 h. As expected, this error decreases with increasing duration of observation. These data should prove useful in the design and interpretation of investigations of neonatal energy expenditure.

Carbon Dioxide↗
PubMed1986

Lack of relationship in humans of the parameters of body cholesterol metabolism with plasma levels of subfractions of HDL or LDL, or with apoE isoform phenotype.

The factors involved in regulating parameters of whole body cholesterol metabolism in humans have been explored in a series of investigations. Several physiological variables have been identified (weight, excess weight, plasma cholesterol, and age) that can predict 53-76% of the variation in production rate (PR) and in the sizes of the rapidly exchanging pool of body cholesterol (M1) and of the minimum estimates of the slowly exchanging pool of body cholesterol (M3min) and of total body cholesterol (Mtotmin). Surprisingly, measurements of the plasma levels of HDL cholesterol and of the major HDL apolipoproteins (apoA-I, A-II, and E) did not provide additional information useful in predicting parameters of whole body cholesterol metabolism. A study was therefore conducted to investigate possible relationships of the plasma levels of subfractions of lipoproteins, determined by analytic ultracentrifugation, and of apoprotein E phenotype, with the parameters of whole body cholesterol metabolism. Ultracentrifugal analysis of plasma lipoprotein subfractions was performed at the Donner Laboratory in 49 subjects; all of these subjects were currently undergoing whole body cholesterol turnover studies or had previously had such studies and were in a similar metabolic state as judged by plasma lipid and lipoprotein values. Apoprotein E phenotyping was carried out in 71 subjects. Differences in model parameters were sought among subjects with various apoprotein E phenotypes. Ultracentrifugal LDL subfractions Sof 0-2 (the region of LPa), Sof 0-7 (smaller LDL), Sof 7-12 (larger LDL), Sof 12-20 (IDL), and ultracentrifugal HDL subfractions Fo1.20 0-1.5 (smaller HDL3), Fo1.20 2-9 (larger HDL3 plus HDL2), and Fo1.20 5-9 (larger HDL2 or HDL2b) were examined for correlations with each other and with parameters of whole body cholesterol metabolism.

Adolescent↗
PubMed1985

A rat model for the study of transplacental pharmacokinetics and its assessment with antipyrine and aminoisobutyric acid.

The suitability of a pregnant rat model for the study of transplacental pharmacokinetics was assessed by two test agents, antipyrine, which freely equilibrates in the maternal and fetal blood, and aminoisobutyric acid, which is actively transported from mother to fetus. In accordance with an ideal protocol for a two-compartment model solved for bolus injections, unlabeled antipyrine was injected into the mother (day 20 of gestation), and labeled antipyrine was injected into its fetuses following exteriorization under ether anesthesia. Maternal and fetal blood samples (2-3 fetuses removed at each time period) were collected sequentially under brief periods (2-3 min) of ether anesthesia up to 9-12 hr. In separate studies it was found that sequential removal of fetuses did not significantly alter maternal or fetal serum drug concentrations. As expected, placental clearances (ml/h-1/kg-1) of antipyrine from mother to fetus (392 +/- 86) and from fetus to mother (448 +/- 107) did not significantly differ. As an alternate approach, (3H)aminoisobutyric acid was either injected into the mother or into the fetuses, and maternal and fetal blood samples were sequentially collected in each case; the clearance of this agent from fetus to mother was 53 ml/h-1/kg-1, and, as expected, was much lower than that from mother to fetus (168 ml/h-1/kg-1). It is suggested that the pregnant rat model can be used as a substitute for the chronically catheterized pregnant sheep model for the study of pharmacokinetics in the maternal-fetal unit.

Aminoisobutyric Acids↗
PubMed1985

A convenient six-point blood sampling schedule for determining whole body cholesterol kinetics in humans.

Parameters of total body cholesterol metabolism in humans can be determined by using a three-pool model to analyze the turnover of plasma cholesterol following the injection of radiolabeled cholesterol. In the past this required a rigorous schedule of approximately 36 blood samples over a 10-month period. We have developed a convenient sampling schedule involving only six large samples, each analyzed in sextuplicate. Such a reduction in the frequency of samples is possible only when considerable confidence in the model is available. In general, the simplified sampling strategy depends upon considerable prior experience with the model, only moderate biological error, and estimatable subject to subject variation in model parameters. Because the timing of the samples is critical and because the optimal times will differ for different subjects, the six-point strategy involves using the first three samples (drawn at days 1, 7, and 24 or, for hypercholesterolemic subjects, at days 1, 8, and 28) in conjunction with results from previous studies to set the time for the next sample; the process is reiterated for the last two points. In this study, we have compared parameter estimates obtained by the new six-point schedule with those obtained simultaneously (in the same, single turnover study) by the old 36-point schedule in the same 26 subjects. Both schedules gave comparable values. In particular, the coefficients of variation between values obtained by the two methods for each of the four parameters for which we have developed predictive equations were quite low: PR 1.5%, M1 4.1%, M3min 13%, Mtot min 4.3%. The simplified six-point schedule makes it feasible to study long-term cholesterol turnover in substantial numbers of patients.

Blood Specimen Collection↗
PubMed1985

Whole body and tissue cholesterol turnover in the baboon.

Cholesterol turnover was studied in four baboons by injecting [14C]cholesterol 186 days and [3H]cholesterol 4 days before necropsy, and fitting a two- or three-pool model to the resulting specific activity-time data. At necropsy, cholesterol mass and specific activity were determined for the total body (minus the central nervous system) and for many tissues. A pool model permits the estimation, from the plasma specific activity-time curve alone, of total body cholesterol within a limited range, depending upon the extent of side pool synthesis. The principal aim of this study was to estimate the extent of cholesterol synthesis in the side pools of the model, by computing the amount of side pool synthesis needed to equal the measured total body cholesterol. Central pool synthesis varied from 61 to 89% of the total cholesterol production rate. Thus, approximately 25% (11 to 39%) of the production rate arose from peripheral (pool 3 for the three-pool, and pool 2 for the two-pool model) cholesterol synthesis. Moreover, the finding that the measured total body cholesterol fell within the range obtained from the kinetic analysis by using reasonable assumptions (namely, that zero or that half the production rate occurred in the side pools), provides evidence for the physiological validity of the model. A second aim of this study was to explore cholesterol turnover in various tissues. A pool model predicts that rapidly turning over tissues will have higher specific activities at early times and lower specific activities at later times after injection of tracer relative to slowly turning over tissues, except where significant synthesis occurs. Tissues were ranked 1 to 17 for 3H and 17 to 1 for 14C cholesterol specific activity values. Except for the GI tract and testis, the tissues had similar ranks for both 3H and 14C, further validating model predictions. Results in all four baboons were similar. Turnover rates for the different tissues loosely fell into three groups which were turning over at fast, intermediate, and slow rates. Finally, the magnitude of variation of cholesterol specific activity was moderate for several distributed tissues (fat, muscle, arteries, and the alimentary tract), but was small for liver. Cholesterol turnover in serial biopsies of skin, muscle, and fat could, however, be fitted with a single pool to estimate tissue turnover rates.

Animals↗
PubMed1985

Relationship of the parameters of body cholesterol metabolism with plasma levels of HDL cholesterol and the major HDL apoproteins.

The inverse relationship between plasma levels of high density lipoprotein (HDL) and coronary heart disease rates has suggested that HDL might influence body stores of cholesterol. Therefore, we have investigated potential relationships between the parameters of body cholesterol metabolism and the plasma levels of HDL cholesterol and the major HDL apoproteins. The study involved 55 human subjects who underwent long-term cholesterol turnover studies, as well as plasma lipoprotein and apolipoprotein assays. In order to maximize the likelihood of detecting existing relationships, the subjects were selected to span a wide range of plasma levels of lipids, lipoproteins, and apolipoproteins. Single univariate correlation analyses suggested weak but statistically significant inverse relationships of HDL cholesterol and apoA-I levels with the following model parameters: production rate (PR), the mass of rapidly exchanging body cholesterol (M1), the minimum estimate of the mass of slowly exchanging body cholesterol (M3min), and of the mass of total exchangeable body cholesterol (Mtotmin). These correlations, however, were quantitatively quite small (/r/ = 0.28-0.42) in comparison to the strength of the univariate relationships between body weight and PR (r = 0.76), M1 (r = 0.61), M3min (r = 0.58), and Mtotmin (r = 0.78). Correlations for apoA-II and apoE levels were even smaller than those for apoA-I and HDL cholesterol. In additional analyses using multivariate approaches, HDL cholesterol, apoA-I, apoA-II, and apoE levels were all found not to be independent determinants of the parameters of body cholesterol metabolism (/partial r/ less than 0.17, P greater than 0.3 in all cases). Thus the weak univariate correlations reflect relationships of HDL cholesterol and apoA-I levels with physiological variables, such as body size, which are primarily related to the model parameters. We conclude that plasma levels of HDL cholesterol and apoproteins A-I, A-II, and E are not quantitatively important independent determinants of the mass of slowly exchanging body cholesterol or of other parameters of long-term cholesterol turnover in humans. These studies give no support to the hypothesis that the inverse relationship between HDL cholesterol levels and coronary heart disease rates is mediated via an influence of HDL on body stores of cholesterol.

Aged↗
PubMed1983

Cholesterol turnover and metabolism in two patients with abetalipoproteinemia.

Total body turnover of cholesterol was studied in two patients with abetalipoproteinemia, a 32-year-old man and a 31-year-old woman. The patients received [14C]cholesterol intravenously, and the resulting specific activity-time curves (for 40 and 30 weeks, respectively) were fitted with a three-pool model. Parameters were compared with those from studies of cholesterol turnover in 82 normal and hyperlipidemic subjects. A three-pool model gave the best fit for the abetalipoproteinemic patients, as well as for the 82 previously studied subjects, suggesting general applicability of this model. Cholesterol production rates in the two abetalipoproteinemic subjects (0.82 and 0.89 g/day) were close to values predicted for persons of their body weight. Thus, total body turnover rate of cholesterol was quite normal in abetalipoproteinemia, confirming previous reports. Very low values (9.2 and 8.4 g) were found for M1, the size of the rapidly exchanging compartment pool 1, in the two abetalipoproteinemic subjects. These values were well below the values predicted (from the comparison study population) for normal persons of this size with low plasma cholesterol levels. For one patient, total body exchangeable cholesterol was very low, although not significantly below the predicted values for a person of his size. In the second patient, the observed estimate for total body exchangeable cholesterol was well within the range of values predicted for persons of her size with low to extremely low cholesterol levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Abetalipoproteinemia↗
PubMed1981

On determining the extent of side-pool synthesis in a three-pool model for whole body cholesterol kinetics.

Whole body cholesterol turnover is well described by a three-pool model. This model has eight unknown parameters: three masses, three synthesis rates, and two intercompartmental exchange rates. Only six parameters can be estimated by fitting the model to the plasma specific radioactivity-time curve which results from the intravenous injection of labeled cholesterol. Additional information is obtained if a precursor of cholesterol, labeled with a different isotope, is also injected. Equations are derived to enable the calculation of all eight model parameters from the two sum-of-exponentials equations that are fitted to the two tracer curves. The characteristics of a satisfactory precursor are discussed.

Animals↗