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Biomedical subjects

J Girard

Publications and source records attributed to J Girard.

At least 253 records · Page 14Linked to original sources
PubMed1987

Growth hormone in urine: development of an ultrasensitive assay applicable to plasma and urine.

A radiometric assay for human growth hormone (HGH) was developed based on a polyclonal goat anti-HGH antiserum covalently coupled to nonsedimenting polyacrylamide particles. HGH can be specifically immunoextracted from sample volumes of up to 10 ml. Subsequently, bound HGH is identified and quantitatively measured by a 125I-labelled monoclonal anti-HGH antibody. The assay is insensitive to plasma proteins from 10 to greater than 90%, to changing NaCl and urea molarities and to pH ranges from 6 to 8. The sensitivity in the second incubation is 2 pg/tube, corresponding to a maximum sensitivity of 300 fg/ml of a sample volume of 10 ml (urine) or of 40 pg/ml, if a volume of 50 microliter (plasma) is assayed. In healthy children, a mean HGH excretion of 6.5 ng/24 h was found with a large interindividual range from undetectable to 37.4 ng. An important intraindividual night-to-night variation of HGH excretion was found in several subsequent first morning void samples in healthy children. The mean excretion in 13 HGH-deficient children was 0.9 ng/24 h off therapy and increased to a mean of 6.9 ng/24 h on therapy. In acromegalic patients, the excreted HGH amounted to 73-208 ng/24 h. Preliminary results suggest that the ultrasensitive assay applied to plasma and urine could be a considerable improvement of diagnosis and follow-up of disorders of HGH secretion.

Adolescent↗
PubMed1987

Glucose metabolism in pregnancy.

Pregnancy is characterized by a number of maternal metabolic modifications in order to meet the energy requirements of the growing fetus. A progressive alteration of maternal glucose homeostasis develops throughout gestation and becomes maximal during the last trimester. A relative hypoglycemia is observed during the postabsorptive period despite an elevated plasma insulin concentration and an enhanced hepatic glucose production. In addition, the glucose utilization rate by peripheral maternal tissues is lowered in late gestation indicating that the mother supplies glucose to the fetus at the expense of her own tissues. Concomitantly, an insulin-resistant state develops in the mother to help sparing glucose for the pregnant uterus. It involves both glucose-producing (liver) and glucose-utilizing tissues. So far, the factor(s) responsible for the development of pregnancy-induced insulin resistance has not been identified although a number of circulating hormones are known to counteract insulin effects.

Adipose Tissue↗
PubMed1987

Glucose utilization by the placenta of anesthetized rats: effect of insulin, glucose, and ketone bodies.

Placental glucose metabolism and its regulation have been investigated in vivo in the rat using the radioactive 2-deoxyglucose technique. In the basal state, placental glucose utilization rates were similar on days 19 and 21 of gestation: 139 +/- 5 and 155 +/- 22 nmol/min/g at maternal blood glucose concentrations of 4.3 +/- 0.1 and 4.2 +/- 0.1 mmol/1. During hyperglycemic clamps, maternal glycemia was raised to 5.5 mmol/liter, a value similar to that during a meal in the rat. In this condition, the rate of placental glucose utilization at 19 days of gestation was increased by 85%. This was due not only to hyperglycemia but also to glucose-induced hyperinsulinemia. Indeed during hyperinsulinemic euglycemic clamps, placental glucose utilization showed a dose-response relationship to insulin (400 and 5000 microU/ml). At 21 days of gestation, placental glucose utilization was not affected by hyperglycemia or by hyperinsulinemia suggesting that in term placenta, glucose metabolism is no longer regulated. When 19-day pregnant rats were fasted for 48 and 96 h, the resulting low blood glucose and plasma insulin concentrations and the high ketone body concentrations induced, respectively, a 40 and 47% reduction of placental glucose utilization. The decrease in placental glucose utilization probably was due to both maternal hypoglycemia and long term adaptation to hyperketonemia. Indeed, the acute hyperketonemia in fed rats did not alter glucose utilization rate in placenta at 19 days of gestation. These data suggest that glucose metabolism in the preterm rat placenta is modulated in vivo by the maternal metabolic environment, particularly by maternal blood glucose and insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Uterine metabolism of the conscious gilt during late pregnancy.

The present study provides some metabolic features of the gravid uterus in the nonanesthetized gilt during the last fourth portion of pregnancy. Substrate and oxygen arteriovenous differences across the uterus were determined in eight gilts with chronically implanted arterial and uterine venous catheters. Glucose represents the main substrate taken up by the conceptus and glucose extraction amounts to 8.3 +/- 0.5%. By contrast, there is a constant release of lactate from the pregnant uterus. The coefficient of extraction of oxygen is 20.2 +/- 1.9%. Glucose plus lactate/oxygen quotient is high (1.3 +/- 0.2), suggesting that glucose alone is sufficient to account for the oxidative metabolism of the pig uterus. Nonesterified fatty acid and ketone body are not significantly extracted by the pig uterus whereas a significant amino acid extraction occurs in late pregnancy. Uterine uptake of amino acids depends on maternal arterial concentrations and a great part (78%) of this uterine uptake is represented by neutral amino acids and especially glutamine.

Amino Acids↗
PubMed1987

Development of obesity in Zucker rats. Early insulin resistance in muscles but normal sensitivity in white adipose tissue.

Euglycemic-hyperinsulinemic clamps were performed on 4- and 12-wk-old anesthetized lean and obese Zucker rats. During the clamp studies, total glucose production and utilization were assessed with a 3-[3H]glucose perfusion, whereas local glucose utilization was determined by measuring 2-deoxy-1-[3H]glucose 6-phosphate accumulation in various tissues. In the basal state, 4 wk-old obese rats were hyperinsulinemic (159 +/- 8 vs. 82 +/- 9 microU/ml), whereas glucose turnover rate was similar to that observed in lean rats (14.9 +/- 1.9 vs. 12.5 +/- 1.9 mg X min-1 X kg-1). Glucose utilization was identical in skeletal muscles, whereas it was increased in white adipose tissue of obese rats (22 +/- 4 vs. 8 +/- 2 ng X min-1 X mg-1). At plasma insulin level of 500 microU/ml, glucose production was totally suppressed in both groups, whereas overall glucose utilization was slightly less in 4-wk-old obese than in lean rats. This was due to a reduced stimulation of glucose utilization in skeletal muscles and brown adipose tissue. In contrast, glucose utilization in periovarian white adipose tissue was similarly increased in lean and obese rats. For a maximal insulin concentration (1500 microU/ml), all the differences were abolished between lean and obese young Zucker rats. In older (12-wk-old) obese rats, glucose utilization in various tissues was markedly reduced at maximal insulin level compared with that observed in age-matched lean animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1986

Evidence that the development of hepatic fatty acid oxidation at birth in the rat is concomitant with an increased intramitochondrial CoA concentration.

The development of hepatic fatty acid oxidation during the perinatal period in the rat was studied using isolated mitochondria. Ketone body synthesis from substrates entering at different levels of beta-oxidation was 2-3 times lower in mitochondria isolated from term-fetal liver than in 16-h-old newborn or adult liver mitochondria. The low rate of palmitoyl-L-carnitine oxidation in term-fetal mitochondria was linked neither to the low capacity of the respiratory chain nor to the removal of acetyl-CoA in the hydroxymethylglutaryl-CoA synthase pathway. The 2.5-times lower concentration of CoA found in term-fetal liver mitochondria when compared to 16-h-old or adult liver mitochondria might be the factor responsible for the low rate of fatty acid oxidation in term-fetal liver mitochondria.

2,4-Dinitrophenol↗
PubMed1986

Effect of lactation on insulin sensitivity of glucose metabolism in rat adipocytes.

During lactation glucose metabolism in paraovarian adipocytes is characterized by a 40 and 80% decrease of glucose incorporation into CO2 and fatty acids in the presence of insulin. In contrast with the stimulation by insulin of glucose incorporation into lactate, glycerol remains unchanged. As a result, insulin sensitivity of total glucose metabolism (oxidation and lipid synthesis) is not altered in adipocytes from lactating rats.

Adipose Tissue↗
PubMed1986

Glucose utilization in vivo and insulin-sensitivity of rat brown adipose tissue in various physiological and pathological conditions.

Brown-adipose-tissue glucose utilization rate and its insulin-sensitivity were measured in vivo in the anaesthetized rat by a 2-deoxy[1-3H]glucose technique. Glucose utilization can be increased 60-fold by insulin, to reach extremely high rates. Glucose utilization and its insulin-sensitivity are modulated in accordance with physiological or pathological conditions.

Adipose Tissue, Brown↗
PubMed1986

The significance of postnatal gonadotropin surge for testicular development in normal and cryptorchid testes.

Testicular biopsies from 29 infants with cryptorchidism between birth (gestational age as early as 36 weeks) and 9 months of age were compared to 34 biopsies from the testes of boys at postmortem examination, or during operation for a hydrocele or hernia. The total number of germ cells was similar in both groups but normal testes showed a transformation of gonocytes into spermatogonia to an extent that was not seen in the cryptorchid testes. Cryptorchid testes also showed markedly reduced numbers of Leydig cells compared to normal. These postnatal changes occurred in the normal testes at the same time that the increase is seen in luteinizing and follicle-stimulating hormones during the first few months of life and they are believed to be a consequence of this hormonal activity. It is postulated that the postnatal surge of gonadotropins may be responsible for priming the testes for subsequent development and fertility.

Biopsy↗
PubMed1986

Changes in energy metabolism during the suckling and weaning period in the newborn.

In most of the mammals, birth and weaning are two periods of nutritional transitions. Whereas the fetus oxidizes mainly glucose, lactate and aminoacids, the newborn is fed with milk, a high fat, low carbohydrate diet. At weaning, milk is replaced progressively by the adult diet which contains less fat and more carbohydrate. In the hours and days following birth, the newborn adapts itself to the new nutritional environment by increasing its capacity to produce glucose de novo (gluconeogenesis) in order to satisfy its high glucose needs. Oxidation of fatty acids is enhanced in the liver and at the peripheral level. Ketone bodies synthetized from fatty acids in the liver in large amounts are utilized by other tissues and specially the brain where they can met energetic and synthetic needs. In the rat, during the suckling period, lipogenesis is decreased in the liver and in white adipose tissue and triglyceride accretion is minimized. At weaning, these adaptations are reversed: decreased gluconeogenic and oxidative capacity of the liver, decrease of the role of ketone bodies, increase of the lipogenic rate in the liver and the adipose tissue, storage of triglycerides. The nutritional and hormonal factors involved in these metabolic adaptations are numerous but insulin and glucagon might play a major role.

Absorption↗
PubMed1986

Corticotrophin-releasing factor-test used with bilateral, simultaneous inferior petrosal sinus blood-sampling for the diagnosis of pituitary-dependent Cushing's disease.

Bilateral, simultaneous inferior petrosal sinus blood-sampling for determinations of ACTH levels has improved the ability to establish a differential diagnosis of Cushing's disease, particularly in patients whose endocrinological studies show equivocal results and whose computed tomography scans yield negative or inconclusive findings. Individual anatomical variations in the configuration of the sinus and insignificant differences between the ACTH levels obtained from its two sides may be a problem. Seven patients with clinically and biochemically typical Cushing's disease and one with atypical Cushing's disease were examined. An alternative approach for catheterization of the inferior petrosal sinus through the deep vertebral venous plexus was used in those patients who did not have direct connections between the sinus and the internal jugular vein. In two of the eight patients, only ACTH secretion stimulated with corticotrophin-releasing factor could unmask a significant difference between the ACTH levels on the two sides which was not obvious from the basal ACTH levels. Beta-lipotrophin values showed a behaviour similar to that of ACTH values, but because of a slower turn-over rate, the CRF-induced peaks were better visible. The aetiology of Cushing's disease was established from the results of this examination and corresponded with the surgical findings in this series, with the exception of one in which the patient had a highly atypical form of the disease. The abnormal ACTH source was found later to be a thymus carcinoid.

Adenoma↗
PubMed1986

Increased insulin sensitivity and responsiveness during lactation in rats.

In 12-day lactating rats blood glucose and plasma insulin were decreased by, respectively, 20 and 35% when compared with nonlactating rats, despite a 25% increase of their glucose turnover rate. Then, by using the euglycemic hyperinsulinemic clamp technique, dose-response curves for the effects of insulin on glucose production and utilization in lactating and nonlactating rats were performed. Glucose production rate was totally suppressed at 250 microU/ml of insulin in lactating rats and for plasma insulin concentrations higher than 500 microU/ml in nonlactating rats. Plasma insulin level inducing half-maximal inhibition of glucose production was decreased by 60% during lactation. The maximal effect of insulin on glucose utilization rate and glucose metabolic clearance rate was, respectively, increased 1.5- and 2.4-fold during lactation and was obtained for plasma insulin concentrations lower in lactating than in nonlactating rats (250 vs. 500 microU/ml). Insulin concentrations inducing half-maximal stimulation of glucose utilization and glucose metabolic clearance were decreased by 50% during lactation. In conclusion, this study has shown that insulin sensitivity and responsiveness of liver and peripheral tissues are improved at peak lactation in the rat.

Animals↗
PubMed1986

Gluconeogenesis in late fetal and early neonatal life.

Birth in most mammalian species represents an abrupt change from a high-carbohydrate and low-fat diet to a high-fat and low-carbohydrate diet. Gluconeogenesis is absent from the liver of the fetus of well fed mothers, but can be induced prematurely by prolonged fasting of the mother. Gluconeogenesis increases rapidly in the liver of newborn mammals in parallel with the appearance of phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme of this pathway. The rise in plasma glucagon and the fall in plasma insulin which occur immediately after birth are the main determinants of liver PEPCK induction. When liver PEPCK has reached its adult value, i.e. 24 h after birth, other factors are involved in the regulation of hepatic gluconeogensis. In order to maintain a high gluconeogenic rate, the newborn liver must be supplied with sufficient amount of gluconeogenic substrates and free fatty acids. An active hepatic fatty acid oxidation is necessary to support hepatic gluconeogenesis by providing essential cofactors such as acetyl CoA and NADH. The relevance of animal studies for the understanding of neonatal glucose homeostasis in man is discussed.

Animals↗
PubMed1986

Effect of weaning on different diets on hepatic gluconeogenesis in the rat.

The capacity of gluconeogenesis from lactate (10 mmol/l) was studied on isolated hepatocytes in 15-day-old suckling and in 28-day-old rats weaned at the age of 19 days on various diets. Weaning on a high-fat carbohydrate-free diet allowed to maintain a high gluconeogenic rate. By contrast, as soon as the carbohydrate content of the weaning diet was sufficient to meet the glucose needs of the newborn, the gluconeogenic capacity was reduced. The amount of fat in the weaning diet had no influence on the gluconeogenic capacity. Changes in the hepatic gluconeogenic rate at weaning were inversely correlated with the plasma insulin/glucagon molar ratio.

Animals↗
PubMed1986

Plasma ACTH in diagnosis and control of adrenal disorders.

Unstimulated plasma ACTH concentrations remain at or below the detection limit of conventional immunoassays. Grossly elevated ACTH concentrations are diagnostic in suspected adrenal insufficiency, remain elevated well above 200 ng/l during substitution therapy and obviate the need of further tests. For the diagnosis of secondary adrenal failure, plasma ACTH, cortisol and 11-desoxycortisol response to a single midnight dose of metyrapone (1.2 g/m2 = 30 mg/kg) discriminates between a normal (morning ACTH above 100 ng/l), diminished (morning ACTH detectable, but below 100 ng/l), and an absent (ACTH below 20 - 40 ng/l) ACTH reserve. In congenital adrenal hyperplasia, plasma ACTH concentrations mirror, together with 17-alpha-hydroxyprogesterone, the extent of ACTH suppression. Elevated ACTH concentrations were suppressed by prednisolone (25%), dexamethasone (2% of the hydrocortisone dose) or by addition of cyproterone acetate (100 mg/m2/day). Using selective venous catheterisation in clinically and biochemically proven Cushing's syndromes, a pituitary adenoma could be identified and localized in 6 of 8 patients by measuring ACTH concentrations in the left and right petrosal sinus before and after stimulation with corticotrophin releasing hormone.

17-alpha-Hydroxyprogesterone↗
PubMed1986

Steroidogenic activity of highly potent melanotropic peptides in the adrenal cortex of the rat.

Highly purified ACTH and MSH peptides were studied in isolated rat glomerulosa and inner zone cells and their activity compared with that in an Anolis melanophore assay. While both ACTH1-39 and ACTH1-24 were almost equally potent steroidogenic peptides in the two cell types (ED50 between 1 and 4 X 10(-12) M), alpha-MSH displayed only weak steroidogenic activity. Although it was a full agonist, it was about 10(4)-fold less potent in both capsular and inner zone cells. beta-MSH (porcine) was even 10-fold less active in capsular cells than alpha-MSH, and in inner zone cells it was a partial agonist. Highly potent melanotropic peptides, such as (Nle4, D-Phe7)-alpha-MSH or cyclic (Cys4, Cys10)-alpha-MSH were either inactive or exhibited only a very slight partial steroidogenic activity in both cell types. Comparison of the activity profile of additional compounds, such as des-acetyl alpha-MSH, (Tyr(I)2)-alpha-MSH, (Trp(For)9)-alpha-MSH or (Nva12)-alpha-MSH, in the adrenocortical and pigment cell assays led to the conclusion that alpha-MSH does not exert its steroidogenic effect through a typical melanocyte-type of MSH receptor, but rather through a low affinity-type of ACTH receptor.

Adrenal Cortex↗
PubMed1986

Glucose utilization rates and insulin sensitivity in vivo in tissues of virgin and pregnant rats.

In vivo studies have shown that insulin resistance in late pregnancy results from a decreased sensitivity of liver and peripheral tissues. In the present study, measurements of the rates of glucose utilization by skeletal muscles (soleus, extensor digitorum longus, epitrochlearis, and diaphragm), white adipose tissue, and brain of virgin and 19-day pregnant rats were performed in the basal condition and during a euglycemic, hyperinsulinemic (400 microU/ml) clamp to quantify the partition of glucose utilization and to identify the tissues other than liver responsible for insulin resistance. Fetal and placental glucose utilization rates were also measured in pregnant rats. The fetal glucose utilization rate (22 mg/min/kg) was very high and was not stimulated by physiologic maternal hyperinsulinemia. By contrast, the placental glucose utilization rate (29 mg/min/kg) was increased by 30% during hyperinsulinemia. The glucose utilization rate of the conceptus represented 23% of the maternal glucose utilization rate in the basal state. Glucose utilization rates in the basal condition were not statistically altered by pregnancy in brain, skeletal muscles, and white adipose tissue. During hyperinsulinemia (400 microU/ml), glucose utilization rates in extensor digitorum longus, epitrochlearis, and white adipose tissue were 30-70% lower in pregnant than in virgin rats. Insulin sensitivity of glucose metabolism in all the tissues tested other than brain was 50% lower in pregnant than in virgin rats. We conclude that skeletal muscles and, to a smaller extent, adipose tissue are involved in the insulin resistance of late pregnancy.

Adipose Tissue↗