Biomedical subjects

M Jeevanandam

Publications and source records attributed to M Jeevanandam.

At least 73 records · Page 4Linked to original sources

PubMed1987

Altered peripheral amino acid uptake in obstructive jaundice.

To characterize amino acid metabolism in obstructive jaundice, the amino acid uptake in tissues of bile duct-ligated (BDL) rats was determined. Fischer 344 rats underwent either bile duct ligation or sham laparotomy and were pair fed for 72 hr. Amino acid uptake was determined in peripheral skeletal muscle (quadriceps femoris, soleus, and rectus abdominis), liver, blood, and other tissues by accumulation of alpha-[14C]-aminoisobutyric acid following intracardiac injection. Although total hepatic amino acid uptake was unaltered in the BDL animals compared with the sham-operated controls, amino acid uptake in peripheral skeletal muscle was significantly decreased in all muscle groups studied in the BDL rats. The relative concentration (percentage dose per gram normalized to the animal mass) for quadriceps femoris was 0.16 +/- 0.02 for BDL and 0.32 +/- 0.04 for sham-operated rats, P less than 0.005. Muscle protein was lower in BDL animals when compared with sham-operated rats (P less than 0.05). Total trunk blood amino acid levels were not significantly different in the two groups; however, there was a decreased serum level of branched-chain amino acids in the BDL group, P less than 0.05. No differences in plasma glucose or serum insulin were found in the two groups; lactate levels were lower in the BDL group, and plasma triglyceride levels were three times higher in the BDL animals. These data suggest that obstructive jaundice in the rat is associated with organ-specific metabolic abnormalities consistent with impaired peripheral amino acid uptake.

Amino Acids↗

PubMed1987

Metabolic efficacy of enteral feeding in malnourished cancer and noncancer patients.

Total parenteral nutrition and enteral nutrition are the two available methods for supplementary nutritional support of malnourished patients. Although supplemental alimentation is beneficial in malnourished patients, it is unclear whether malnourished cancer bearing patients are successfully replenished with similar nutritional support. We studied the efficacy of 2 weeks of enteral nutrition on intermediary glucose and protein metabolism in malnourished tumor-bearing (TB) and non-tumor bearing (NTB) patients. Both TB and NTB patients showed equivalent suppression of endogenous glucose production (2.13 +/- 0.23 to 0.35 +/- 0.16 mg/kg/min and 2.35 +/- 0.18 to 0 mg/kg/min), suppression of alanine to glucose conversion (43.8 +/- 10.6% to 0.75 +/- 0.41% and 37.0 +/- 10.7% to 0.11 +/- 0.09%), attainment of positive nitrogen balance (-2.15 +/- 1.18 to 4.26 +/- 1.37 gN/d and -2.25 +/- 0.63 to 4.32 +/- 0.44 gN/d) and suppression of protein catabolism (2.39 +/- 0.13 to 1.10 +/- 0.27 gP/kg/d and 2.23 +/- 0.04 to 1.34 +/- 0.22 gP/kg/d). Following 2 weeks of enteral support, the TB patients differed from the NTB group with significantly elevated lactate levels (80 +/- 8 v 48 +/- 7 mg/L) and depressed plasma glycine levels (264 +/- 12 v 356 +/- 27 mumol/L plasma) and inability to replenish fat stores (triceps skin fold, 7.6 +/- 1.5 to 7.1 +/- 1.5 mm in TB v 5.9 +/- 0.7 to 8.0 +/- 1.2 mm in NTB). A significant reduction in whole body protein synthesis (2.08 +/- 0.19 to 1.84 +/- 0.18 gP/kg/d) in TB patients was obtained while NTB showed no significant change (1.86 +/- 1.3 to 1.91 +/- 0.26 gP/kg/d).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

PubMed1987

Whole body lipid and energy metabolism in the cancer patient.

The relationship between whole-body energy and lipid kinetics in eight cancer patients was investigated after an overnight fast. Respiratory gas exchange and indirect calorimetry were used to obtain resting energy expenditure (REE) and net substrate oxidation rates. Free fatty acid (FFA) turnover, oxidation, and clearance rates were obtained after a primed-constant infusion of albumin bound 1-14C-Na palmitate. This was followed by a primed-constant, two-stage infusion of unlabeled glycerol to measure plasma glycerol turnover and clearance. The REE was 1.3 times the predicted (by the Harris-Benedict equation) basal energy expenditure. FFA and glycerol, plasma concentrations, and turnover rates were higher in these depleted but hypermetabolic cancer patients, compared to reported values for healthy normals. The ratio of FFA turnover to glycerol turnover was 3.14 +/- 0.38, which is close to the theoretical value of 3, suggesting complete hydrolysis of triglycerides and the absence of any extensive reesterification of FFA in adipose tissue. The net fat oxidation accounts for 53 +/- 5% of fat mobilized and 29 +/- 3% of the FFA turnover was converted to CO2 in the process of supplying energy in cancer patients. The results suggest that fat is efficiently mobilized and utilized as a fuel source in hypermetabolic cancer patients in the postabsorptive state.

Adult↗

PubMed1987

Effect of the route of nutrient administration on whole-body protein kinetics in man.

The kinetic mechanism resulting in nitrogen (N) retention during oral or continuous intravenous feeding (IVF) was investigated in normal subjects and hospitalized patients. The whole-body protein turnover rate (Q) in these adult subjects was estimated using a primed-constant infusion of 15N-glycine and measuring the isotope enrichments in urinary urea and ammonia. Based on a stochastic model, the total protein synthesis (S) and breakdown (C) rates were calculated from N excretion and intake. These protein kinetic responses were studied either after brief (two or three days) or extended (ten days) fasting or during the fourth day of defined formula oral feeding or the tenth to 14th day of parenteral repletion by IVF. The mean daily intake during feeding was 270 +/- 7 mg N/kg and 28 +/- 2 nonprotein kcal/kg. The results from a total of 120 studies are summarized. In the absence of any N intake, depleted patients with cancer demonstrated a higher Q (+16%), with increased S (+25%) than depleted patients without cancer or acutely depleted normals. In all groups, protein kinetics were increased to a greater extent by oral feeding, compared to IVF. All subjects are in positive N balance during feeding and the mean N retention is 32 +/- 3%, which is not different among groups. Protein accretion during oral feeding is due to an increase in S and a similar decrease in C of body protein. During IVF this is achieved by a larger decrease in C with relatively little or no change in S.

Administration, Oral↗

PubMed1987

Muscle amino acid flux in patients receiving branched-chain amino acid solutions after surgery.

The metabolism and efficacy of branched-chain amino acids (BCAAs)-enriched parenteral solutions in patients after surgery are unclear. This prospective clinical study compared two groups of patients (n = 13) receiving either a 25% BCAA solution or a 45% BCAA solution at 30 kcal/kg/day and 1.5 gm protein/kg/day for 7 days after operation. Whole-body nitrogen balance and forearm muscle amino acid and ketoacid flux were measured. There were no significant differences between the two groups in mean cumulative nitrogen balance (+13.1 gm versus +18.0 gm) between the two groups. Patients receiving the 45% BCAA solution had significant mean uptake of total BCAA, leucine, and isoleucine compared with results in patients receiving the 25% BCAA solution. Despite this increased uptake of BCAA in the 45% BCAA group, there was no increased efflux of alanine, glutamine, or the BCAA ketoacids, ketoisocaproic, ketoisovaleric, or ketomethylvaleric. However, increased release of aspartate was noted in the 45% BCAA group compared with the 25% BCAA group. Thus use of a 45% BCAA-enriched solution infused in patients after surgery results in a significant increase in forearm muscle uptake of the BCAA that is not demonstrated in whole-body nitrogen economics.

Adult↗

PubMed1987

Extremity blood flow in man: comparison between strain-gauge and capacitance plethysmography.

Metabolic studies with substrate limb flux determinations require an accurate and simple method for measuring blood flow through the extremity. Two common, noninvasive methods used in recent studies are strain-gauge and capacitance venous occlusion plethysmography. The values obtained for forearm blood flow by these two methods are highly correlated in normal resting and seriously ill patients. The use of a fixed percentage of cardiac output as a measure of extremity flow was not indicative of the measured flow by either capacitance or strain-gauge plethysmography. Capacitance and strain-gauge plethysmography are comparable, noninvasive indicators of change in extremity blood flow in humans.

Cardiac Output↗

PubMed1986

Stimulatory effect of interleukin-1 upon hepatic metabolism.

The liver plays an important role in the acute-phase response to sepsis and injury, and host survival often depends upon an adequate hepatic response. Many of the metabolic sequelae to sepsis and injury are mediated by interleukin-1. This study was undertaken to investigate the impact of interleukin-1 upon hepatic metabolism and whether this mediator acted directly upon the liver. Interleukin-1 (5 rabbit pyrogen dose units) was administered to male Fisher F344 rats (175 to 200 g), and hepatocytes were isolated at three time periods; 2 to 4, 6 to 10, and 12 to 14 hours following an intraperitoneal injection. Alanine transport, gluconeogenesis, nonsecretory protein synthesis, and oxygen consumption were measured simultaneously in freshly isolated hepatocytes. Interleukin-1 stimulated initial rates of alanine uptake over a four-minute period. Peak stimulation of gluconeogenesis occurred at six to ten hours (0.52 +/- .14 v 0.08 +/- .01 nmol alanine converted/10(6) cells/min, P less than 0.05); nonsecretory protein synthesis was significantly stimulated at 12 to 14 hours (2.1 +/- .7 v 0.7 +/- 0.1 nmol valine converted/10(6) cells/min, P less than 0.05). These enhanced metabolic processes were associated with an increased oxygen consumption, with peak oxygen utilization occurring at six to ten hours (69 +/- 2 v 25 +/- 7 nmol of oxygen consumed 10(6) cells/min, P less than 0.05). In order to examine if interleukin-1 exerted its effect directly upon the liver, hepatocytes from normal rats were incubated in vitro with this mediator for two hours. Under these experimental conditions, interleukin-1 did not reproduce the stimulatory effect obtained following in vivo administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗

PubMed1986

Cancer cachexia and the rate of whole body lipolysis in man.

While malnutrition attending cancer cachexia may be associated with variable losses of body fat, lipid metabolism has been only minimally studied. To clarify potential aberrations of lipid metabolism in weight losing cancer patients, the whole body rate of lipolysis was determined in 9 cancer patients in the postabsorptive state and compared to that in 5 normal subjects. A primed-three stage infusion of glycerol was used to measure plasma glycerol clearance and turnover. A positive correlation between glycerol turnover and plasma concentration was demonstrated in both cancer patients (r = 0.72) and in normal subjects (r = 0.81). Glycerol turnover rate in cancer patients (2.05 +/- 0.14 mumol X kg-1 X min-1) was not different from that in normals (2.31 +/- 0.50); while glycerol clearance in cancer patients (1.72 +/- 0.13 L/min) was significantly lower (P less than 0.025) by 32% than that in normals. This study demonstrates that the whole body lipolytic rate in cancer patients is not different from healthy normals. As a consequence, the loss of body fat in patients with cancer cachexia may be due to a reduced rate of lipogenesis rather than augmented lipolysis as is observed in nonmalignant malnutrition, starvation, or injury.

Adult↗

PubMed1986

Influence of increasing dietary intake on whole body protein kinetics in normal man.

The whole body protein kinetic response to increasing dietary intake was studied in 20 normal adult male subjects receiving a defined formula diet orally. Each person received the same amount for 5 days at the rate ranging from 150 to 330 mgN/kg. day and 16 to 34 kcal/kg. day, keeping the calorie to nitrogen ratio as constant. Whole body protein flux was measured using a primed constant infusion of 15N glycine and determining isotopic enrichments in the urinary urea and ammonia. Whole body protein synthesis and breakdown rates were calculated from the flux measurement and nitrogen excretion and intake. The mean protein turnover (Q), synthesis (S) and breakdown (C) rates for all subjects were 3.72+/-0.42, 2.47+/-0.47 and 2.12+/-0.39 g protein/kg. day. These values increased with increasing dietary nitrogen intake up to 270+/-4 mgN/kg. day which is twice the daily recommended protein requirement for a normal adult man and then tended to decrease. Nitrogen intake in the range of 150 to 270 mg N/kg. day showed significant positive correlations with nitrogen balance, Q, S and S/C and the protein accretion was due to a relatively large increase in S compared to that in C. When the intake rate exceeded 270 mg N/kg. day, the nitrogen balance was still positive but now due to a larger decrease in C. These results show that the kinetic parameters of whole body protein metabolism in adult man appear to exhibit a maximum at a dietary nitrogen intake twice the daily requirement level. The mechanism of the maintenance of protein balance changes at this threshold.

Journal Article↗

PubMed1986

Basal glucagon replacement in chronic glucagon deficiency increases insulin resistance.

To evaluate the role of glucagon in insulin-mediated glucose metabolism, we studied four men and four women, ranging in age from 30-73 yr (mean +/- SEM, 54 +/- 5) who had undergone complete pancreatic resection for cancer or chronic pancreatitis 16-58 mo previously. The patients had undetectable C-peptide levels and established lack of biologically active 3500 mol wt glucagon. Euglycemic insulin clamp studies were performed with a 40 mU X m-2 X min-1 insulin infusion in the basal, post-absorptive, insulin-withdrawn state, before and during the last 3 h of a 72-h glucagon replacement-dose infusion (1.25 ng X kg-1 X min-1). In four patients, hepatic glucose production was determined by a primed-constant infusion of 3-[3H]glucose. Monocyte insulin-binding studies, pre- and postglucagon, were performed in all patients. The 72-h glucagon infusion, resulting in mean plasma glucagon levels of 124 +/- 7 pg/ml, caused a significant rise in the mean plasma glucose level (249 +/- 8 versus 170 +/- 13 mg/dl preglucagon) and a sixfold increase in mean 24-h glucose excretion. Both with and without glucagon, euglycemic hyperinsulinemia achieved identical and complete suppression of hepatic glucose production. The mean glucose utilization rate (4.70 +/- 0.36 mg X kg-1 X min-1 preglucagon) was significantly decreased by glucagon replacement (3.83 +/- 0.31 mg X kg-1 X min-1, P less than 0.02). Mean glucose clearance was also diminished with glucagon (4.49 +/- 0.32 versus 5.73 +/- 0.45 ml X kg-1 X min-1 preglucagon, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1986

Body protein kinetics during perioperative intravenous nutritional support.

The kinetics of whole body protein metabolism in eight patients with benign disease were evaluated during perioperative isocaloric and isonitrogenous intravenous feedings. A prime infusion of 15N-glycine with determination of urinary end product enrichment and stochastic analysis was used to determine protein kinetics. Surgically induced increases in body protein turnover, synthesis and breakdown were evident on the fifth postoperative day. Abdominal operation was associated with a rise in urinary 3-methylhistidine (3MH) excretion. The postoperative alteration in the relationship between 3MH excretion and body protein breakdown suggests that even mild to moderate surgical injury induces tissue specific changes in protein metabolism. Resting energy expenditure remained unchanged from that of the preoperative levels on the fifth postoperative day. Despite significant changes in body and tissue specific protein kinetics, there is no change in the apparent efficiency of oxygen use for protein homeostasis postoperatively. The failure to observe a relationship between energy expenditure and protein metabolism suggests that only a small proportion of body oxygen uptake is directed toward protein homeostasis after elective surgical procedures. A comparison of perioperative complete intravenous feeding to hypocaloric regimens will be necessary to evaluate more fully the impact of protein and energy balance upon cellular and body protein homeostasis after injury.

Aged↗

PubMed1986

Impaired metabolic response to endotoxin in obstructive jaundice.

Surgical management of extrahepatic cholestasis is frequently complicated by sepsis, which can be explained in part by diminished function of the reticuloendothelial system. We have explored the possibility that the metabolic response to infection may also be abnormal. Fischer 344 rats underwent either bile duct ligation (BDL) or sham operation and were studied 3 days after operation. Hepatic amino acid uptake measured in vivo by the accumulation of 14C-alpha-aminoisobutyric acid or in vitro by the rate of transport of 14C-alanine by isolated hepatocytes was unaltered in the BDL animals, while gluconeogenesis from alanine by viable hepatocytes from BDL rats was actually enhanced. However, the expected increase in hepatic amino acid uptake in response to endotoxin was diminished in the BDL animals. In addition, we observed impaired responses of the jaundiced animals to glucagon and interleukin-1, two mediators of the hepatic acute phase response to endotoxin. These data suggest that while hepatic amino acid transport is normal in the basal state, the rat with extrahepatic biliary obstruction does not respond appropriately to stress and that this defect cannot be explained solely on the basis of altered handling of endotoxin by the reticuloendothelial system.

Alanine↗

PubMed1985

Tracer priming in human protein turnover studies with [15N]glycine.

Sixty-three studies in healthy normal volunteers (n = 29), malnourished cancer (n = 8) or non-cancer patients (n = 9), and postoperative radical cystectomy patients (n = 17) were conducted to evaluate the primed constant infusion labeling technique for the estimation of whole-body protein turnover under a variety of dietary conditions. [15N]Glycine was used as the tracer with a prime to infusion ratio of 1300 to 3300 min and a continuous-infusion rate of 0.11 to 0.33 micrograms 15N . kg-1 . min-1 for 24 to 36 hr. The isotopic steady-state enrichment was reached in all subjects both in urinary urea and ammonia between 10 and 26 hr (mean 18 +/- 2). During protein calorie fasting the attainment of isotopic steady state is much quicker (10 to 18 hr) with a primed constant infusion than with a constant infusion alone (approximately 38 hr). A P/I ratio greater or less than 1800 (min) usually resulted in a delay of plateau attainment without affecting the protein turnover values. Reliable estimates of protein kinetics in humans can be made in clinical conditions with a 26-hr infusion of glycine at the rate of 0.28 microgram 15N . kg-1 . min-1 with a P/I ratio of 1800 min, collecting six urine samples every 2 hr from 16 hr and analyzing for both urinary urea and ammonia enrichments.

Ammonia↗

PubMed1985

Elevated energy expenditure in hepatocytes from tumor-bearing rats.

Mechanisms for the development of cancer cachexia are not well defined. Oxygen consumption and the capacity of the host liver to metabolize lactate were studied in isolated hepatocytes from sarcoma-bearing rats (TIH) and pair-fed controls (CH). Basal oxygen consumption (without exogenous substrate) is significantly increased by 65% in the TIH as compared to the CH. The addition of a physiologic concentration of lactate stimulated oxygen consumption over the already stimulated basal state by 13% in the TIH compared to 5% in the CH. When the hepatocytes are incubated with 1.5 mM of [U-14C]lactate, glucose production, lactate oxidation, and entry of lactate carbons into nonsecretory protein are significantly increased in the TIH. Associated with this stimulation is a significant decrease in lactate incorporation into glycogen and lipid in the TIH. This study suggests that the tumor-influenced liver utilizes lactate at an increased rate and its intermediary metabolism is directed toward energy utilization rather than energy storage. The enhanced metabolic processes in the tumor-influenced liver are associated with an increased oxygen consumption which may be a contributory factor to the negative energy balance, a characteristic of cancer cachexia.

Animals↗

PubMed1985

Orotic acid excretion during starvation and refeeding in normal men.

The effects of acute food deprivation and subsequent refeeding on urinary orotic acid excretion were examined in nine healthy adult male subjects. During inpatient metabolic ward conditions, the volunteers were fed a nutritionally complete, pyrimidine- and purine-free diet for three days and subsequently underwent a ten-day fast followed by a ten-day period of refeeding by total parenteral nutrition. Mean daily excretion of 4.33 +/- 0.23 mg (2.77 +/- 0.12 mg/g creatinine) of orotic acid during the enterally fed state was significantly reduced (mean 46 +/- 5%) in all subjects during starvation. This reduction in the excretion of orotic acid during starvation is more likely related to a lowered rate of production and utilization. The starvation adaptation of orotate excretion occurred more rapidly than did the decrease in urinary nitrogen loss. All subjects showed an increase (mean 48 +/- 14%) in the excretion of orotic acid during the first day of refeeding which continued throughout the refeeding phase. A significant positive correlation was shown between the daily orotic acid excretion and nitrogen intake (r = 0.98) or protein balance (r = 0.83). The response to refeeding of acutely malnourished normal male is an increase in orotic acid excretion with a decrease in whole body protein catabolism.

Adult↗

PubMed1985

Whole-body protein breakdown and 3-methylhistidine excretion during brief fasting, starvation, and intravenous repletion in man.

Simultaneous whole-body protein breakdown (using 15N-glycine) and urinary 3-methylhistidine (3MH) excretion rates were determined in six hospitalized normal volunteers after 10 days of starvation and a subsequent 10-day period of total parental nutrition (TPN). These data were contrasted to whole-body protein breakdown and urinary 3MH excretion in ten depleted (14.8% body weight loss) patients with benign intraabdominal disease studied in the basal (48 hours without nutrient intake) and intravenously refed states. The rates of whole-body protein breakdown were significantly reduced from basal (brief fasting or starvation) conditions in both normal volunteers (p less than 0.01) and depleted patients (p less than 0.01) during TPN. The rate of protein catabolism normalized for creatinine excretion in patients was higher than that observed in normal subjects during both basal (p less than 0.05) and intravenous feeding conditions. Daily urinary 3MH excretion was reduced during intravenous feeding in both starved normal volunteer (235 +/- 13 mumol/d to 197 +/- 9 mumol/d p less than 0.05) and in depleted patients (209 +/- 31 mumol/d to 140 +/- 35 mumol/d), and an apparent linear relationship between protein breakdown and urinary 3MH, normalized for creatinine excretion, was obtained in both volunteer and patient (r = 0.85) populations during fasting-refeeding. However, separate regression analysis of the protein breakdown and 3MH responses of both volunteer and patient groups under conditions of fasting, starvation, and refeeding revealed significant differences between volunteer and patient populations during intravenous refeeding (p less than 0.01). Further analysis of 3MH excretion in relationship to nitrogen balance during refeeding suggests a complex relationship between urinary 3MH excretion and whole-body protein metabolism that may be partly related to the degree of antecedent malnutrition.

Adult↗

PubMed1985

Protein synthesis in the tumor-influenced hepatocyte.

Total body protein turnover is elevated in the Fischer 344 rat bearing a subcutaneous transplantable methylcholanthrene-induced sarcoma. To assess the contribution of the liver, we have measured protein synthesis by hepatocytes freshly isolated from tumor-bearing animals over a range of tumor burdens and from sham-inoculated nontumor bearers. Synthetic rates of total hepatocyte protein were more than twofold greater in hepatocytes from tumor-bearing animals (P less than 0.005) and the increase was proportional to the tumor burden in individual animals (n = 19; r = 0.68; p less than 0.005). When compared with pair-fed nontumor bearers, the differences in rates of total hepatocyte protein synthesis reached statistical significance only when the tumor burden exceeded 5% of total body weight. The stimulation in synthetic rates applied equally to secretory and nonsecretory hepatocyte protein. Furthermore, a lack of net protein accrual in the livers of tumor-bearing animals suggests a concomitant increase in the rate of hepatic protein degradation.

Animals↗

PubMed1984

Cancer cachexia and protein metabolism.

Metabolic abnormalities arising from malnutrition and malignancy are seen in patients with cancer cachexia. To discriminate between the effects of pure malnutrition and tumour-specific metabolic alterations, the kinetics of whole-body metabolism were determined in 7 untreated, malnourished cancer patients and in 11 patients with benign disease, also malnourished, by means of primed constant infusion of 15N-glycine. Patients in both groups received 500 kcal/day as 5% glucose solution without any nitrogen. Whole-body protein turnover was 32% and 35% higher in the cancer patients than in the non-cancer patients and starved normal subjects respectively. Similarly, the rate of protein synthesis was 35% and 54% higher in the cancer patients than in the non-cancer patients and starved normal subjects respectively. Our study supports the view that aberrations of host metabolism in patients with cancer cachexia are different from those in non-cancer patients suffering equivalent weight loss.

Aged↗