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R Gopinath

Publications and source records attributed to R Gopinath.

35 records · Page 2Linked to original sources
PubMed1989

Administration of recombinant human insulin-like growth factor I to pigs: determination of circulating half-lives and chromatographic profiles.

Recombinant human insulin-like growth factor I (IGF-I) was injected daily (4 or 8 mg/pig) as an intra-arterial bolus into pigs for 3 consecutive days and the serum IGF-I concentration was measured to determine disappearance profiles. IGF-I partitioned to a fast component (half-life, t 1/2 = 5.7 min) and a slow component (t 1/2 = 253 min) in pig serum. Chromatography of serum revealed that the fast component comprised unbound IGF-I, whereas the slow component comprised IGF-I bound to 40- and 150-kD serum IGF-binding proteins. In addition, administration of exogenous IGF-I caused significant hypoglycemia.

Animals↗
PubMed1989

An acid-stable insulin-like growth factor (IGF)-binding protein from pig serum inhibits binding of IGF-I and IGF-II to vascular endothelial cells.

The effects of a porcine insulin-like growth factor (IGF)-binding protein on binding of IGF-I and IGF-II to porcine aortic endothelial cells (PAEC) were determined. Binding of 125I-labelled IGF-I and -II to IGF receptors was inhibited by IGF-binding protein. IGF-binding protein inhibited binding of IGF-I and -II in a dose-dependent manner with half-maximal inhibition occurring at 5.43 and 108 micrograms/l respectively. A 125I-labelled IGF-I--IGF-binding protein complex, formed by incubating 125I-labelled IGF-I with IGF-binding protein overnight at 4 degrees C, did not effectively bind to endothelial IGF receptors. Addition of IGF-binding protein to PAEC previously incubated with IGF-I caused a marked dissociation of bound IGF-I (47% dissociation within 12h). These results indicate that the acid-stable IGF-binding protein which appears to be a part of the 150 kDa GH-dependent binding protein, blocks binding of IGF-I and -II by the IGF receptors and appears to exhibit a higher affinity for IGF-I than the endothelial type-I IGF receptor. The ramifications of this latter point with respect to transfer of circulating IGFs (bound to their IGF-binding proteins) across the vascular endothelium are not clear.

Animals↗
PubMed1989

Effects of porcine growth hormone on glucose metabolism of pigs: I. Acute and chronic effects on plasma glucose and insulin status.

The acute and chronic effects of porcine growth hormone (pGH) administration on glucose homeostasis of pigs were investigated in the present study. Twelve Yorkshire barrows (average BW = 65 kg) fitted with femoral artery catheters were allotted to three groups. Pigs received acute, intra-arterial injections of either pituitary pGH, a recombinantly derived pGH analog (ppGH or rpGH, 100 micrograms/kg BW) or saline. Acute injection of pGH did not affect fasting plasma glucose or insulin status. Pigs then were treated daily by i.m. injection for 24 d with 70 micrograms ppGH/kg BW. Serum glucose and insulin concentrations during the fed and fasted states were higher in pGH-treated than in control pigs. On d 25, an acute intra-arterial injection of ppGH (100 micrograms/kg BW) elicited increases in plasma glucose and insulin in pigs chronically treated with pGH. The area circumscribed by the glucose and insulin response curves 5 min to 7 h postinjection was 40% (P less than .005) and 177% (P less than .001), respectively, higher in ppGH-treated than in control pigs. These data indicate that pGH does increase plasma glucose and insulin in the fed and fasted states; however, this response is only observed after chronic pGH administration. In addition, pGH is capable of increasing plasma glucose and insulin acutely in the pig. This effect, however, only is observed in pigs treated chronically with pGH. The mechanisms by which pGH elicit these effects on glucose homeostasis are not known.

Animals↗
PubMed1989

Effects of porcine growth hormone on glucose metabolism of pigs: II. Glucose tolerance, peripheral tissue insulin sensitivity and glucose kinetics.

This study was conducted to determine whether the increase in serum glucose observed in pigs treated chronically with pGH is due to an increase in hepatic glucose output or to an impairment in glucose clearance. Barrows (n = 4 per treatment) were treated with pituitary derived pGH (ppGH), recombinant pGH analog (rpGH) or vehicle. Pigs were treated for 28 d by daily i.m. injections. Insulin tolerance and glucose tolerance tests (GTT) were performed on d 19 and 21, respectively, following treatment with pGH. Glucose turnover was quantified on d 28 using [6-3H]glucose. Chronically treating pigs with pGH resulted in a significant decrease (26%; P less than .05) in glucose clearance, as determined by the GTT. Glucose clearance was affected similarly by ppGH and rpGH. Intra-arterial glucose infusion markedly increased plasma insulin concentration in pGH-treated pigs. Peak plasma insulin response was 87% and 58%, respectively, higher (P less than .05) in ppGH- and rpGH-treated than in control pigs. Insulin infusion elicited a marked hypoglycemia in pigs; however, the extent and duration of hypoglycemia were significantly less in pGH-treated pigs (ppGH or rpGH). Glucose production rates were 23% higher (P = .085) in ppGH-treated than in control pigs. These results establish that the hyperglycemia induced by pGH is the result of an increase in hepatic glucose output and a concurrent impairment in glucose clearance.

Animals↗
PubMed1989

Porcine insulin-like growth factor (IGF) binding protein blocks IGF-I action on porcine adipose tissue.

A growth hormone-dependent insulin-like growth factor (IGF) binding protein (IGFBP) purified from porcine serum specifically blocked the acute insulin-like effects of IGF-I on lipogenesis and glucose oxidation in porcine adipose tissue. This inhibition was dose dependent with half-maximal effective concentrations of IGFBP of 530 ng/ml for lipogenesis and 590 ng/ml for glucose oxidation in the presence of 10(-8) M IGF-I. The IGFBP also caused decreased rates of lipogenesis following a 1-hr preincubation of tissue with IGF-I (10(-8) M). The IGFBP had no effect on insulin action on porcine adipose tissue. These findings demonstrate the inhibitory effects of a highly purified porcine serum IGFBP on the biologic effects of IGF-I in vitro, and provide evidence that the growth hormone-dependent IGFBP blocks the acute insulin-like actions of IGF-I in vivo.

Adipose Tissue↗
PubMed1984

Growth, N tau-methylhistidine excretion and muscle protein degradation in growing beef steers.

The urinary excretion of N tau-methylhistidine (N tau-MH) was studied quantitatively in growing Hereford steers to measure muscle protein degradation (MPD) at different stages of growth. The amount of MPD and the fractional rate of protein breakdown (FBR) on 28, 42, 56 and 63 d of the experiment were calculated from the 24-h urinary N tau-MH excretion. The steers grew rapidly during the initial phase of the study; the growth rate was higher on d 56 (P less than .01) than on d 42 of the study. On d 63, there was a reduction in the growth rate compared with d 56 (P less than .05). Daily urinary N tau-MH excretion increased gradually as the animals gained weight and on an average, it was 1,957 +/- 88 mumol/d during the entire experimental period. Urinary creatinine excretion was not different at different growth stages, but the urinary N tau-MH: creatinine ratio was higher (P less than .05) on d 56 than on the other days. The amount of MPD per day increased gradually as the animals gained weight and was higher on d 56 than on d 42. Mean MPD and FBR values during the entire experimental period were 557 +/- 25 g/d and 2.44 +/- .09%/d, respectively. Half-life of the myofibrillar proteins decreased as the steers gained weight. These results indicate that the rapid growth in steers is accompanied by a high rate of MPD and demonstrate the usefulness of urinary N tau-MH excretion as a rapid, nondestructive method for measuring muscle protein degradation in large animals.

Analysis of Variance↗
PubMed1984

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↗
PubMed1984

Plasma thyroid hormone concentrations in growing beef steers implanted with estrogenic anabolic growth promotants.

The effect of estrogenic anabolic compounds on plasma thyroid hormone concentrations was investigated in growing beef steers. Sixteen Hereford beef steers, weighing approximately 380 kg, were randomly placed into four groups and assigned to one of the following treatments: 36 mg implant of Zeranol, 36 mg implant of diethylstilbestrol (DES), one implant of Synovex-S and an unimplanted control. Total thyroxine (T4) and triiodothyronine (T3) concentrations were analyzed from plasma samples collected at different periods following the implantation using a solid phase radioimmunoassay. Free thyroxine concentration was estimated indirectly as free thyroxine assessment (FTA) from total T4 concentration and the binding capacity of thyroxine binding globulin (TBG-RDA). Overall mean plasma T4 concentration was higher in steers implanted with Synovex-S (23%, P less than 0.05) and DES (18%, P = 0.08) than the controls. When compared to controls, a slight increase (2.2%, P greater than 0.05) was observed in steers implanted with zeranol. The TBG-RDA values were lower (P less than 0.05) and the FTA values were higher (P less than 0.05) in steers implanted with estrogenic anabolic compounds than the controls. The FTA values were significantly increased by Synovex-S (57%, P less than 0.05) and were found to be non-significantly increased by DES (37%) and zeranol (30%) when compared to the control values. Mean plasma T3 concentration was not affected (P greater than 0.05) by DES, Synovex-S or zeranol implantation. These data indicate increased plasma total and free T4 concentration in steers due to the implantation of Synovex-S, a non-significant increase due to DES implantation and suggest that it could be one of the mechanisms by which they improve growth and metabolism. Zeranol seems to have a weaker influence on the thyroid gland than Synovex-S or DES. Plasma T3 concentration appears to be unaffected by estrogenic anabolic compounds in steers. While previous investigators have reported a suppression of thyroid gland activity in ruminants treated with androgenic anabolic compounds, the present study indicates a stimulation of thyroid gland activity, as reflected by the elevated T4 concentration, in steers treated with estrogenic anabolic compounds, especially Synovex-S and DES.

Animals↗
PubMed1984

Growth hormone secretion and clearance rates in growing beef steers implanted with estrogenic anabolic compounds.

The effect of estrogenic anabolic compounds on the kinetic parameters of metabolism of growth hormone (GH) was studied in growing beef steers. Twenty-four beef steers were randomly placed into four groups and assigned to one of the following four treatment groups: zeranol, diethylstilbestrol (DES), Synovex-S and an unimplanted control. GH metabolism was studied from eight steers on day 20 following the implantation of anabolic compounds. The animals were rapidly injected with a solution of bGH (NIH-GH-B18) and the disappearance of injected GH from the plasma was monitored up to 120 min following the injection. The plasma GH disappearance curve displayed an initial rapid phase lasting 5 min and a slow disappearance phase lasting 42 min; the fractional turnover rate from the two compartments were 0.167 and 0.017 min-1, respectively. The average volume of distribution of GH in steers was 6% of the body weight. Mean values of metabolic clearance and secretion rates of GH in steers were 21 liters/h and 252 micrograms/h or 74.5 ml/kg/h and 0.91 microgram/kg/h, respectively. Steers implanted with anabolic compounds gained more rapidly (P less than 0.05) than the controls. Plasma basal GH concentration appeared to be higher in all the implanted than in the control steers. The secretion rate of GH was increased (P less than 0.05) in steers implanted with anabolic compounds when compared to control steers. The secretion rate (microgram/kg/h) was about 96% (P less than 0.05), 107% (P less than 0.05) and 81% (P less than 0.05) higher in steers implanted with DES, zeranol and Synovex-S, respectively, than in the control steers. All the compounds studied were equally effective in increasing the secretion of GH on day 20 following their implantation. Metabolic clearance rate of GH was not affected by anabolic compound implantation in steers. There was, however, a slight reduction in metabolic clearance rate due to DES and a slight elevation due to zeranol and Synovex-S when compared to control steers. There was a positive correlation between growth rate and GH secretion rate (r = 0.78; P less than 0.05). The results indicate that the implantation of estrogenic anabolic compounds increases the secretion rate of GH from the pituitary gland and suggest that their mechanism of action is mediated through increased GH secretion.

Animals↗
PubMedDate not supplied

Issues in the design of a multirate model-based controller for a nonlinear drug infusion system.

Multivariable controller design for the regulation of mean arterial pressure (MAP) and cardiac output (CO) in congestive heart failure patients is restricted by the limited frequency of CO sampling. Performance criteria for the controller specify maximum allowable transient settling times for both variables, and the design should account for the inherent multirate nature of the process in order to satisfy these criteria. We present a multirate model predictive control (MPC) design for MAP and CO regulation by combined infusion of sodium nitroprusside and dopamine, based on a comprehensive nonlinear model of the system. The multirate MPC algorithm is based on nonlinear quadratic dynamic matrix control. To reduce computation time, we introduce a selective linearization technique that linearizes the model on the basis of trends in the plant-model mismatch. The problem is complicated by restrictions on initial dopamine infusion, prescribed to avoid extremely slow responses. We present a novel rule-based override (RBO) to the MPC controller that uses a set of heuristics to initialize dopamine. The performance of the MPC/RBO controller is illustrated using simulation results.

Algorithms↗