Distribution volume, metabolic clearance and plasma half disappearance time of exogenous luteinizing hormone releasing hormone in normal women and women with obesity and anorexia nervosa

1981 ◽  
Vol 96 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Kazumasa Chikamori ◽  
Fumie Suehiro ◽  
Toshiki Ogawa ◽  
Kei Sato ◽  
Hiroyoshi Mori ◽  
...  
Keyword(s):  
Body Weight ◽  
Anorexia Nervosa ◽  
Normal Subjects ◽  
Distribution Volume ◽  
Metabolic Clearance ◽  
Obese Patients ◽  
Metabolic Clearance Rate ◽  
Provocation Tests ◽  
Disappearance Time ◽  
Normal Women

Abstract. Synthetic LRH was infused into normal women and women with obesity and anorexia nervosa to determine the distribution volume (DV), metabolic clearance rate (MCR) and half disappearance time (t½) of plasma LRH. In normal women, the DV of LRH was 12.1 ± 0.9 (mean ± se) l, the MCR was 1478.9 ± 39.8 ml/min (28.5 ± 1.2 ml/min/kg body weight) and the initial t½ was 5.6 ± 0.4 min. In obese patients the DV (20.6 ± 1.5 l) was significantly higher than that in normal subjects (P < 0.005), but the MCR and t½ were not significantly different from those in normal subjects. In patients with anorexia nervosa the DV and MCR were 6.5 ± 1.1 l and 621.8 ± 110.5 ml/min (17.9 ± 2.4 ml/ min/kg body weight), respectively, which were both significantly lower than those in normal subjects (P < 0.02), while the t½ (7.3 ± 0.1 min) was longer than in normal subjects (P < 0.02). These data suggest that 1) the abnormal responses of some hormones to provocation tests observed in obese patients and patients with anorexia nervosa should be evaluated in consideration of changes in the DV and metabolic clearance of hormones in these conditions, and 2) in patients with anorexia nervosa changes in MCR and t½ may reflect low metabolism of LRH.

A Comparative Study on the Metabolism of Human Insulin and Porcine Proinsulin in Man

1973 ◽  
Vol 45 (5) ◽  
pp. 633-654 ◽  
Author(s):  
P. H. Sönksen ◽  
Christine V. Tompkins ◽  
M. C. Srivastava ◽  
J. D. N. Nabarro
Keyword(s):  
Human Insulin ◽  
Normal Subjects ◽  
Constant Infusion ◽  
Metabolic Clearance ◽  
Priming Dose ◽  
Metabolic Clearance Rate ◽  
Serum Growth Hormone ◽  
Biological Potency ◽  
Infusion Technique ◽  
Apparent Distribution

1. The metabolism of unlabelled monocomponent human insulin and porcine proinsulin was studied in ten normal subjects (five males and five females) by using a priming dose-constant-infusion technique. In each subject, the metabolic clearance rate (MCR) was measured at four separate steady-state hormone concentrations averaging 16–216 μunits/ml (insulin) and 4·2–42·8 ng/ml (proinsulin). 2. For insulin the MCR fell progressively from 34 ml kg−1 min−1 at a mean fasting insulin concentration of 3·8 μunits/ml to 11·4 ml kg−1 min−1 at the highest concentration achieved (280 μunits/ml); for proinsulin MCR averaged 3·7 ml kg−1 min−1 at a mean plasma concentration of 4·2 ng/ml and fell to 2·71 ml kg−1 min−1 at 10·7 ng/ml, remaining constant thereafter at concentrations up to 71 ng/ml. 3. The half-disappearance time (T½) from the plasma, after the end of the infusion, averaged 4·3 min for insulin and 25·6 min for proinsulin. 4. The apparent distribution space (DS) was similar for both hormones (83 ml/kg of insulin and 98·9 ml/kg of proinsulin). 5. There was a direct correlation between T½ and DS for both hormones. 6. Although the higher MCR of insulin was reflected in its shorter T½ there was, for each hormone, no relationship between MCR and T½. 7. The biological potency of porcine proinsulin, as judged by its effect on plasma glucose, was approximately 5% of that of insulin. 8. The responses of serum growth hormone and Cortisol were shown to be directly related to the degree of hypoglycaemia induced.

In Vivo Catabolism of Human Fibrinogen Fragment D in Normal Subjects and Patients with Liver Cirrhosis

1979 ◽  
Author(s):  
N. Ardaillou ◽  
J. Yvart ◽  
M.J. Larrieu
Keyword(s):  
Liver Cirrhosis ◽  
Polyacrylamide Gel Electrophoresis ◽  
Normal Subjects ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Compartment System ◽  
Human Fibrinogen ◽  
Chloramine T ◽  
Disappearance Curve

The in vivo catabolism of purified 131-I-fragment D (Fg D) was studied in comparison with that of 125-I-Fibrinogen (Fg) simultaneously injected in 6 controls and 8 patients with liver cirrhosis. Fg D, M.W. 85,000, was obtained following prolonged (24 hours) plasmin digestion of human Fg. Labelling was performed using the chloramine T method. Linlabelled and labelled Fg and Fg D were characterized hy immunoelectrophoresis and SDS Polyacrylamide gel electrophoresis. Radioactivity was measured in thrombin-clottable (Fg) and TCA-precipitable (Fg D) proteins from plasma. Labelled Fg D present in plasma samples 1, 6 and 12 hours following injection eluted from Sephadex G 2D0 at the same position as native Fg D. A two compartment system was derived from the corresponding plasma disappearance curves for both Fg and Fg D in controls and patients. In controls, the first component of Fg D disappearance curve represented 54.1±13.4% of the total clearance with T 1/2 of 2.5±0.9 hours. The T 1/2 of the second component was 3.9±1.0 hours, Fg D disappeared more rapidly from plasma than Fg, and the ratio of Fg D to Fg was 0.11-0,02. In patients with liver cirrhosis, there was a significant (p<0.005) increase of T 1/2 of the second component (13.6±2.6 hours), whereas the in vivo survival of Fg was normal (4 cases) or decreased (2 cases). These results suggest that the liver interfers with the metabolic clearance rate of Fg D.

A primed-infusion technique for rapid estimation of the metabolic clearance rate of 1,25(OH)2D3

1987 ◽  
Vol 253 (3) ◽  
pp. E246-E250
Author(s):  
R. Eastell ◽  
B. L. Riggs ◽  
R. Kumar
Keyword(s):  
Production Rate ◽  
Clearance Rate ◽  
Human Subjects ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Study Interval ◽  
Normal Women ◽  
Infusion Technique

We have developed a rapid primed-infusion technique for the measurement of the metabolic clearance and production rate of 1,25-dihydroxyvitamin D3 in normal human subjects and experimental animals. With this method, an estimate of the metabolic clearance rate of 1,25-dihydroxyvitamin D3 can generally be made within 3 to 4 h. Initial studies in five dogs using 1,25-[3H]-dihydroxyvitamin D3 (180 Ci/mmol) allowed us to determine the optimal ratio of loading dose to infusion rate that resulted in the most rapid attainment of steady-state levels of plasma radioactivity. By use of this technique we found that the metabolic clearance rate of 1,25-dihydroxyvitamin D3 in dogs was 6.3 +/- 1.2 ml/min (mean +/- SD); the production rate of the hormone was 0.40 +/- 0.25 microgram/day (20.4 +/- 14.4 ng . kg-1 . day-1). In eight normal women, aged 28-51 yr, the metabolic clearance rate for 1,25-dihydroxyvitamin D3 was 25.9 +/- 4.7 ml/min; the production rate was 1.38 +/- 0.45 microgram/day (20.7 ng . kg-1 . day-1). The advantages of this method relative to ones used in the past are that it can be performed quickly (generally within 3-4 h) with the use of only tracer amounts of this hormone (equivalent to 1.1% of the production rate). With this method, no assumptions about the most appropriate model to which to fit the data need to be made. Because of its rapidity, no metabolites of the injected 1,25-dihydroxyvitamin D3 are formed during the study interval.

scholarly journals Effects of free fatty acids on ACTH and cortisol secretion in anorexia nervosa

2006 ◽  
Vol 154 (5) ◽  
pp. 731-738 ◽  
Author(s):  
Fabio Lanfranco ◽  
Laura Gianotti ◽  
Andreea Picu ◽  
Roberta Giordano ◽  
Giovanni Abbate Daga ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Anorexia Nervosa ◽  
Free Fatty Acids ◽  
Hpa Axis ◽  
Normal Subjects ◽  
Inhibitory Effect ◽  
Saline Infusion ◽  
Cortisol Secretion ◽  
Cortisol Levels ◽  
Normal Women

Objective: Free fatty acids (FFAs) exert a stimulatory effect on the hypothalamic–pituitary–adrenal (HPA) axis in animals and inhibit spontaneous ACTH and cortisol secretion in humans. Patients with anorexia nervosa display concomitant HPA axis hyperactivity and increased lipolysis. We studied the effects of a lipid load on ACTH and cortisol secretion in patients with anorexia nervosa in comparison with normal subjects. Design: Eight women with anorexia nervosa (ANW; means ± s.e.m.: 23.9 ± 2.3 years of age; body mass index (BMI): 14.9 ± 0.6 kg/m2) and seven normal women (NW; 25.6 ± 2.3 years of age; BMI: 22.8 ± 1.9 kg/m2) had FFA, ACTH, cortisol, glucose and insulin levels measured in the morning every 30 min for 180 min during i.v. saline or lipid-heparin emulsion (LHE) infusion. Results: During saline infusion, ACTH and cortisol levels decreased spontaneously in both groups, ACTH and cortisol levels in ANW being higher than in NW. LHE infusion led to increased FFA levels in both groups (P < 0.005). The ACTH and cortisol decrease in NW was more marked than during saline infusion (P < 0.05). LHE infusion in ANW was associated with a more pronounced decrease in ACTH levels than during saline infusion (P < 0.05), while cortisol levels were unchanged. At the end of the LHE infusion, a progressive decrease in FFA levels was associated with an increase in ACTH and cortisol concentrations in NW (P < 0.05) but not in ANW in whom FFA levels decreased to a lesser extent (P < 0.05). Conclusions: This study showed that corticotroph sensitivity to the inhibitory effect of an FFA load is preserved in patients with anorexia nervosa, in spite of persistent adrenal hyperactivity.

Response of ketone body metabolism to exercise during transition from postabsorptive to fasted state

1986 ◽  
Vol 250 (5) ◽  
pp. E495-E501 ◽  
Author(s):  
F. Fery ◽  
E. O. Balasse
Keyword(s):  
Clearance Rate ◽  
Ketone Body ◽  
Turnover Rate ◽  
Ketone Bodies ◽  
Normal Subjects ◽  
Moderate Intensity ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Fasted State ◽  
The Brain

This study examines the effects of a 2-h exercise of moderate intensity (50% of VO2 max) on the tracer-determined turnover rate of ketone bodies (KB) in 21 normal subjects fasted for 16 h, 5 days, whose basal ketonemia ranged between 0.09 and 6.16 mM. The KB response observed at the end of exercise is a function of the initial degree of ketosis. When basal ketonemia is below 0.6 mM, exercise enhances ketogenesis (Ra), the amplitude of this process being positively correlated with KB level. There is a concomitant acceleration of the metabolic clearance rate (MCR) of KB attaining 40-50%. When ketonemia exceeds 2.5 mM, the stimulatory effects of exercise on Ra and on MCR become less marked as basal ketonemia rises and are completely abolished or even reversed when initial KB level is higher than 3-4 mM. The pattern of changes in the concentration and in the overall disposal rate of KB were similar to that of Ra. It is suggested that the parallel inhibition of the stimulatory effect of work on hepatic ketogenesis and on muscular extraction of ketones associated with increasing degrees of fasting hyperketonemia has two physiological implications: it maintains the preferential utilization of KB by nonmuscular tissues (presumably the brain) and prevents the development of uncontrolled hyperketonemia, despite the intense catabolic situation created by the combination of exercise and starvation.

The Kinetics of Plasma Noradrenaline in Normal and Hypertensive Subjects

1978 ◽  
Vol 55 (s4) ◽  
pp. 89s-92s ◽  
Author(s):  
S. Ghione ◽  
C. Palombo ◽  
M. Pellegrini ◽  
E. Fommei ◽  
A. Pilo ◽  
...  
Keyword(s):  
Clearance Rate ◽  
Normal Subjects ◽  
Plasma Noradrenaline ◽  
Metabolic Clearance ◽  
Venous Sampling ◽  
Metabolic Clearance Rate ◽  
Hypertensive Patients ◽  
Arterial Blood ◽  
Endogenous Noradrenaline ◽  
Kinetics Of

1. The kinetics of plasma noradrenaline have been determined in normal and essential hypertensive patients by intravenous injection of tritiated noradrenaline and serial mixed venous sampling. 2. The metabolic clearance rate of plasma noradrenaline in normal subjects was approximately 1·1 min−1 m−2, whereas in essential hypertensive patients it was significantly reduced to approximately 0·61 min−1 m−2. 3. Metabolic clearance rate was negatively correlated to mean arterial blood pressure and total peripheral resistances. 4. Particularly low values of metabolic clearance rate were found in two patients with congestive heart failure and one with phaeochromocytoma. 5. We propose that the access of plasma noradrenaline to the main removal mechanisms takes place in competition with the flow of unlabelled endogenous noradrenaline directly released by nerve endings. The slower removal of plasma noradrenaline in essential hypertension could then express a larger release of endogenous noradrenaline in this condition.

An Estimate of the Endogenous Secretion Rate of Calcitonin in Man

1982 ◽  
Vol 63 (2) ◽  
pp. 145-152 ◽  
Author(s):  
J. A. Kanis ◽  
G. Heynen ◽  
T. Cundy ◽  
F. Cornet ◽  
A. Paterson ◽  
...  
Keyword(s):  
Paget’S Disease ◽  
Normal Subjects ◽  
Paget's Disease ◽  
Secretion Rate ◽  
Human Calcitonin ◽  
Metabolic Clearance ◽  
Disappearance Rate ◽  
Metabolic Clearance Rate ◽  
Day Range ◽  
Basal Plasma

1. The metabolic clearance rate (MCR) of human calcitonin was measured in 12 normal subjects and four patients with Paget's disease by the infusion of synthetic human calcitonin (15–40 μg/h for 2–24 h), and in 10 additional patients with Paget's disease from the disappearance rate of immunoreactive calcitonin from plasma after the intravenous injection of large doses of synthetic human calcitonin (0·5–1·0 mg). 2. The estimated MCR during the infusion studies (range 531–1224 litres/day) was similar to that calculated from the disappearance of large doses of synthetic human calcitonin injected intravenously in patients with Paget's disease (mean = 1035 litres/day; range = 593–1408 litres/day). 3. An eightfold range in the basal values of plasma immunoreactive calcitonin, in spite of the presence of a relatively constant MCR, suggests that the variation in basal plasma calcitonin was due principally to variation in the endogenous secretion rate for calcitonin. 4. The results suggest that the endogenous secretion rate for calcitonin is low in normal subjects (mean 124 ± sem 24 μg/day), and give a basis for selecting the doses of calcitonin which can be considered physiological.

Metabolic clearance rate of adrenocorticotropin in the rat

1977 ◽  
Vol 55 (5) ◽  
pp. 1079-1083 ◽  
Author(s):  
Josée Lalonde ◽  
Maurice Normand
Keyword(s):  
Body Weight ◽  
Steady State ◽  
Clearance Rate ◽  
Intravenous Infusion ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Plasma Acth ◽  
Adrenal Cells ◽  
Acth Concentration ◽  
Acth Release

The metabolic clearance rate (MCR) of adrenocorticotropin (ACTH) was estimated after the intravenous infusion of graded rates of the hormone (40–2560 μU/min per 100 g body weight) in rats pretreated with chlorpromazine, morphine, and Nembutal, a preparation which proved effective in blocking endogenous ACTH release. The hormone was infused over a period of 45 min, at which time the plasma ACTH concentration had reached a steady state. A specific and sensitive bioassay, based on the corticosterone production of dispersed adrenal cells, was used to measure the plasma ACTH concentration. With increasing infusion rates of ACTH, a threefold decrease in the MCR of ACTH was observed. Previous studies of our group have shown that the MCR of corticosterone increases as a function of the infusion rate of the steroid. It appears, therefore, that the metabolism of these two hormonal links of the hypothalarno–pituitary–adrenocortical axis vary in opposite fashions as a function of the secretion rate of the hormone.

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