PubMed HealthSearch

Biomedical subjects

A Pilo

Publications and source records attributed to A Pilo.

At least 73 records · Page 4Linked to original sources

[125I]hGH metabolism in acromegaly: effects of chronic treatment with 2-Br-alpha-ergocryptine.

To assess the effects of 2-Br-alpha-ergocryptine (CB-154 Sandoz) on hGH metabolism, six acromegalic women were studied before and after 2 months of treatment with 10 mg bromocriptine/day. GH kinetics were evaluated by noncompartmental analysis of the plasma disappearance curve of immunoprecipitable [125I]human GH after pulse administration of the labeled hormone. MCR was increased in all acromegalics after treatment; the difference between the means [153 +/- 11 vs. 200 +/- 16 ml/min . m2 (mean +/- SE)] was highly significant. Secretion rate (SR), measured as the product of MCR by integrated 12-h concentration, was decreased in four patients after treatment, while it was slightly increased in the other two. No change was found after treatment, either initial distribution volume [2.0 +/-0.1 before (B) vs. 2.1 +/- 0.1 liters/m2 after (A)] or total distribution volume [5.0 +/- 0.3 (B) vs. 5.4 +/- 0.4 liters/m2 (A)]. Diffusion of GH from the intravascular pool, measured as reentry rate, was unchanged with treatment [66 +/- 4 (B) vs. 76 +/- 11 ml/min . m2 (A)]. In conclusion, our study shows that in acromegaly, by increasing the MCR of the hormone, and 2) by reducing the SR. The mechanisms by which bromocriptine increased MCR of the GH are also suggested on the basis of kinetic results; like dopamine, bromocriptine could induce a redistribution of blood flows to different organs, thus resulting in a net increase of blood flow to the liver and kidneys which are the major catabolic sites of GH.

Acromegaly

Insulin kinetics after portal and peripheral injection of [125I] insulin. I. Data analysis and modeling.

The kinetics of insulin are commonly investigated by intravenous administration of labeled hormone, whereas native insulin is removed by the liver to some extent before mixing in the systemic circulation. A mathematical model has been developed which makes it possible to interpret the experimental data obtained by peripheral plasma sampling after portal and peripheral injection of the tracer. Equations are given that allow for the computation of metabolic clearance rate, initial distribution volume, production rate, and body mass of insulin. It is demonstrated that hepatic extraction can be calculated from the difference between the clearance rate values obtained after portal and peripheral injection of the tracer; an estimate of total hepatic catabolism is also derived. The assumptions and limitations underlying this mathematical analysis are discussed.

Infusions, Parenteral

Insulin kinetics after portal and peripheral injection of [125I] insulin: II. Experiments in the intact dog.

Insulin metabolism in man is usually investigated by peripheral injection of the hormone, whereas native insulin undergoes hepatic extraction prior to mixing in the general circulation. To quantify this difference, in 10 dogs [125I] insulin was injected into a peripheral vein, and the initial distribution volume (IDV), the metabolic clearance rate (MCR), and the mean transit time (t) were computed from the plasma disappearance curve of the immunoprecipitable activity. The splenic vein was then cannulated under pentobarbital anesthesia, and the parameters were again computed from the peripheral activity after portal introduction of the tracer. The MCR after portal injection [15.1 +/- (SE) 1.1 ml/min per kg] was greater (P is less than 0.001) than the MCR after peripheral administration (13.4 +/- 0.9 ml/min per kg). Also, IDV was larger (P is less than 0.01) after portal injection (167 +/- 12 vs. 138 +/- 10 ml/kg). Mean transit times did not change significantly. Insulin secretion rate (0.29 +/-0.04 mU/min per kg) and body insulin mass (7.03 +/- 1.5 mU/kg) were also measured. An estimate of hepatic extraction was obtained from the difference between the clearance rate values calculated following portal and peripheral injection. Under our experimental conditions, hepatic retention of insulin was found to be 19.6% (range 9.6-36.2%). The method is recommended for investigations in man.

Animals

Automatic treatment of radioimmunoassay data: an experimental validation of the results.

A computational method for the automatic treatment of radioimmunoassay data has been developed and a computer program has been written in accordance. The main features of the approach used are the following: (a) a constant ratio between the bound fraction and its variance is assumed and estimated in each assay; (b) the points of the dose-response curve are fitted using the three-parameter function y' equals b1/(1 plus b2x(-b)3) where y' equals bound - nonspecific counts and x is the amount of hormone; the fitting is performed using the nonlinear, least-squares technique; (c) the values of the unknown samples are evaluated from the fitted standard curve; their confidence limits are computed taking into account both the variance of the bound replicates and the variance of the parameters of the dose-response curve. Experimental data that support the validity of the assumption on the variance of bound measurement and the suitability of the chosen function to fit the points of the standard curve are presented. A comparison between the confidence limits of the unknowns experimentally obtained and those computed by the program is reported and discussed.

Analysis of Variance

Mechanisms of albumin loss during peritoneal dialysis in man.

Albumin loss in the dialysate was evaluated during a total of 5 peritoneal dialyses carried out on 3 uraemic patients. The measurements were made by two different methods, the first based on the evaluation in the dialysate of intravenously injected radioiodinated albumin, the second one based on a radioimmunoassay of the protein in the dialysate. The results obtained showed three main mechanisms of protein loss during peritoneal dialysis: 1) albumin shift from extravascular sites adjacent to the peritoneum, 2) direct passage of albumin from blood stream to peritoneal cavity, and 3) tendency of the inter-dialysis peritoneal fluid to equilibrate with plasma proteins. Furthermore, the observations made on a patient with evident peritonitis proved the importance of the intrinsic biological properties of the peritoneum in determining the amplitude of protein wasting by the dialysate.

Ascitic Fluid

Double isotope measurement of peritoneal clearance of iodide and albumin loss during peritoneal dialysis in man (labelled albumin loss in peritoneal dialysis).

131I-labelled Human Serum Albumin and 125I-sodium iodide were used to measure protein loss from the peritoneum and peritoneal clearance of iodide in a group of 8 uraemic patients, each one being studied after a different number of dialyses. Both albumin loss and iodide clearance reached a maximum at about the 10th dialytic treatment and then tended towards the initial levels. Protein loss as determined isotopically was markedly lower than indicated by direct radioimmunoassay measurements performed in three cases. Fitting experimental points by a model which assumes direct passage of protein from plasma to peritoneal cavity suggests the presence of a "delay" pool between plasma and the peritoneal cavity itself (extravascular sites adjacent to peritoneum?). The shorter retention time of the dialysis solution in the abdomen (4-8 minutes) seemed to us to cause lower protein losses than reported by authors using longer retention times.

Adult

Effects of long-term low protein diet on albumin metabolism in chronic uremia.

The effects of long-term low protein diet on albumin metabolism of uremic patients were evaluated. Studies were performed on 62 patients divided into two groups depending on the duration of the diet (35 subjects from 6 to 30 days, 27 subjects from 6 months to 5 years). All patients received a diet containing at least 20 g of high biological value proteins per day. Albumin catabolism and distribution were measured by the two-tracer technique, after simultaneous i.v. injection of 131I-human serum albumin and of free 125I-iodide. Albumin synthesis was directly determined in 10 patients by two tracers, 14C-carbonate and 131I-albumin, according to the xanthydrol technique for specific activities of urea and albumin guanido carbon in plasma. The main features of albumin metabolism observed in both groups studied were: normal intravascular albumin mass, marked reduction of extravascular and total albumin pools, with proportionally reduced catabolism. No significant turnover difference was found between the first group and the patients on diet from 0.5 to 5 years, thus suggesting that dietary treatment per se is not responsible for the albumin depletion observed in chronic uremia.

Adolescent

Growth hormone kinetics in diabetic patients.

Several reports have shown that average plasma GH concentrations in insulin-treated and in juvenile diabetics are elevated in respect to normal values: these findings have been alternatively attributed to an increased pituitary GH secretion or to a lower GH catabolism induced by the disease. To reinvestigate the problem we studied GH kinetics in twenty-four diabetics using 125-I-GH. The patients were all normal in body weight and their fasting blood sugar did not exceed 190 mg. per 100 ml.; fourteen normal subjects were included as a control group. After single injection of the tracer, the plasma disappearance curve of labeled hormone was obtained. Starting from this curve, metabolic clearance rate (MCR), fractional catabolic rate (FCR), initial distribution volume (IDV), and total distribution volume (TDV) were computed; MCR and plasma concentration of endogenous GH in plasma samples were used to estimate the amount of hormone irreversibly lost during the experiment (IHL240). The major points that result from the comparison of the values obtained in diabetic patients with those in the normal group are: MCR values in diabetics do not differ from those found in normals (63.6 plus or minus 19.6 and 64.6 plus or minus 24.3 ml./min./m.-2 respectively). The higher plasma concentrations of endogenous GH in diabetics together with a normal MCR, yield hormone loss values (IHL240) significantly larger than normal (46.4 plus or minus 29.5 mug/240 min. as compared to 23.7 plus or minus 24.5) thus indicating that an increased GH secretion is present in diabetics. TDV, fairly constant in normals, (5.8 plus or minus 0.9 L./ml-2) tends to decrease in diagetic patients as the disease progesses; in fact the values of TDV are significantly reduced (P less than 0.005) in long-term diabetics (greater than 10 yrs. of disease) while TDV of short-term diabetics (less than 10 yrs.) does not differ from the normal value (4.6 plus or minus 1.16 L./m.-2 and 5.8 plus or minus 0.9 L./m.-2, respectively).

Adolescent