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Biomedical subjects

J Girard

Publications and source records attributed to J Girard.

At least 307 records · Page 17Linked to original sources
PubMed1983

[Evaluation of the optimal thyroxine dose with the TRH test for replacement and suppression therapy].

53 patients with overt hypothyroidism (group 1), 17 patients with "preclinical hypothyroidism" (group 2), 22 patients with a euthyroid goiter (group 3) and 13 patients who had undergone total elimination of the thyroid gland for thyroid cancer (group 4) were treated with thyroxine. Basal levels of T4, T3, TSH and the TSH-response to 40 mg oral TRH were measured during treatment. For replacement therapy in hypothyroid patients of group 1 and 2 the dose was adjusted until the TSH response to TRH was within the normal range (3.5-38 mU/l). In groups 3 and 4 the thyroxine dose was increased to suppress the TSH response to TRH in the presence of euthyroid T4 and T3 levels (suppressive dose). Average thyroxine replacement doses were 128 micrograms per day in overt hypothyroidism and 101 micrograms/day in preclinical hypothyroidism. Suppressive doses of thyroxine were on average 119 micrograms/day in patients with euthyroid goiter and 183 micrograms thyroxine per day in patients with total thyroid ablation. In all 4 groups of patients a wide interindividual variation of the optimal thyroxine dose was found.

Goiter↗
PubMed1983

Development and regulation of ketogenesis in hepatocytes isolated from newborn rats.

The development of fatty acid metabolism was studied in isolated hepatocytes from newborn rats. Ketone-body production from oleate is increased 6-fold between 0 and 16 h after birth. This increase is related to an enhanced beta-oxidation rather than to a channeling of acetyl-CoA from the tricarboxylic acid cycle to ketone-body synthesis. The increase in oleate oxidation is not related to a decreased esterification rate, as the latter is already low at birth and does not decrease further. At birth, lipogenic rate is 2-3-fold lower than in fed adult rats and it decreases to undetectable values in 16 h-old rats. A 90% inhibition of lipogenesis in hepatocytes of newborn rats (0 h) by glucagon and 5-(tetradecyloxy)-2-furoic acid does not lead to an increased oxidation of non-esterified fatty acids. This suggests that the inverse relationship between lipogenesis and ketogenesis in the starved newborn rat is not responsible for the switch-on of fatty acid oxidation at birth. Moreover, ketogenesis from octanoate, a medium-chain fatty acid the oxidation of which is independent of carnitine acyltransferase, follows the same developmental pattern at birth as that from oleate.

Animals↗
PubMed1983

Metabolic fate of non-esterified fatty acids in isolated hepatocytes from newborn and young pigs. Evidence for a limited capacity for oxidation and increased capacity for esterification.

In hepatocytes isolated from 48 h-old starved of suckling newborn pigs or from 15-day-old starved piglets, the rate of ketogenesis from oleate or from octanoate is very low. This is not due to an inappropriate fatty acid uptake by the isolated liver cells, but results from a limited capacity for fatty acid oxidation. Some 80-95% of oleate taken up is converted into esterified fats, whatever the age or the nutritional conditions. Three lines of indirect evidences suggest that fatty acid oxidation is not controlled primarily by malonyl-CoA concentration in newborn pig liver. Firstly, the addition of glucagon does not increase fatty acid oxidation or ketogenesis. Secondly, the rate of lipogenesis is very low in isolated hepatocytes from newborn pigs. Thirdly, the rates of oxidation and ketogenesis from octanoate are also decreased in isolated hepatocytes from newborn and young piglets. The huge rate of esterification of fatty acids in the liver of the newborn pigs probably represents a species-specific difference in intrahepatic fatty acid metabolism.

Age Factors↗
PubMed1983

[Increase of circulating thyroid hormones following oral administration of TRH in preclinical hyperthyroidism. Biological efficacy of minimal TSH stimulation].

In patients with multinodular goiter and preclinical hyperthyroidism (euthyroid values of free T4-index, free T3-index, free T4, absent TSH response to oral TRH (40 mg), i.e. TSH after TRH less than 1.0 microU/ml) a statistical increase in the serum-T3 (free T3-index), serum-T4 (free T4-index) and free T4 was observed after oral TRH. No thyroid response to oral TRH occurred in multinodular goiter patients with hyperthyroidism or in preclinically hyperthyroid +athyrotic patients under T4. The thyroid response in patients with a preclinically hyperthyroid goiter was significantly lower than the response in goiter patients with a normal TSH reserve and in controls. The results demonstrate that (1) in euthyroid TRH-TSH unresponsiveness the pituitary TSH-reserve may not be completely suppressed; (2) very small variations in TSH not detectable by the available radioimmunologic assay may be of biological importance. In euthyroid TRH-TSH-unresponsive patients under T4 (simple goiter, differentiated thyroid carcinoma) thyrotropic function may not be completely suppressed. In euthyroid TRH-TSH-unresponsive patients with an autonomously functioning adenoma, additional exogenous suppression should be evaluated for protection of paranodular tissue before ablative radioiodine is given.

Administration, Oral↗
PubMed1983

Role of the mitochondrial metabolism of pyruvate on the regulation of ketogenesis in rat hepatocytes.

In hepatocytes isolated from fed rats the inhibition of lipogenesis (-80%) by 5-tetradecyloxy-2-furoate (an inhibitor of acetylCoA carboxylase) and alpha-cyano-3-hydroxycinnamate (an inhibitor of pyruvate entry into mitochondria) increases the oxidation of 0.35 mM oleate respectively by 70% and 90%. 5-tetradecyloxy-2-furoate increases ketone body production from oleate only by 30% and has no effect on ketogenesis from octanoate, whereas alpha-cyano-3-hydroxycinnamate mimics the effects of fasting on ketone body production: It increases ketogenesis from 0.35 mM oleate by 90%, from 0.78 mM oleate by 25% and from 1.57 mM butyrate by 37%. alpha-cyano-3-hydroxycinnamate also decreases the activity of tricarboxylic acid cycle and the production of malate and citrate. In hepatocytes from fasted rats, alpha-cyano-3-hydroxycinnamate does not modify ketogenesis from oleate, unless cells are incubated with a mixture of lactate and pyruvate. A lactate and pyruvate mixture decreases ketogenesis from oleate and octanoate and increases citrate and malate production without modifying the uptake of fatty acids. This effect is potentiated by 3-mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase. The results cannot be interpreted only by the effects of malonylCoA on carnitine acyltransferase. They are discussed with respect to the possible involvement of mitochondrial oxaloacetate concentration in the regulation of ketogenesis.

Animals↗
PubMed1983

A method for quantifying insulin sensitivity in vivo in the anesthetized rat: the euglycemic insulin clamp technique coupled with isotopic measurement of glucose turnover.

The euglycemic insulin clamp technique coupled with isotopic measurement of the glucose utilization rate ([3-3H] glucose), described previously in man, has been adapted to characterize and quantify insulin sensitivity in vivo in the rat. Only 30 min were needed for the exogenous glucose infusion rate, the specific activity of [3-3H] glucose and the plasma insulin to reach a steady-state value. During the next 30 min of the experiment, blood glucose was maintained at a constant basal level with a coefficient of variation of 2.3%. Plasma insulin was 48 +/- 4 microU/ml and glucose utilization was 1.84 +/- 0.07 mg/min in anesthetized female rats in the basal state. During euglycemic insulin clamp, plasma insulin was 302 +/- 24 microU/ml, glucose utilisation was increased by 53 +/- 10% and endogenous glucose production was decreased by 76 +/- 3%. By studying several insulin concentrations in different groups of rats, we hope to be able to characterize insulin resistance during pregnancy and to determine whether hepatic or peripheral tissues are responsible for this insulin resistance.

Animals↗
PubMed1983

Development of gluconeogenesis in isolated hepatocytes from the rabbit.

Gluconeogenesis from 10 mM lactate has been studied in isolated hepatocytes from fetal, newborn, and 70-day-old rabbits. Gluconeogenesis proceeds to a very low rate in fetal rabbit hepatocytes despite substantial activities of all gluconeogenic enzymes including mitochondrial phosphoenolpyruvate carboxykinase. A tenfold increase in the rate of gluconeogenesis occurs in hepatocytes from 1- or 2-day-old fasting or suckling newborn rabbits. The emergence of gluconeogenic capacity in newborn rabbit hepatocytes is triggered by birth itself and not by a chronological factor, and it is primarily controlled by an increase in the activity of cytosolic phosphoenolpyruvate carboxykinase. Moreover, an active fatty acid oxidation is essential to support a high rate of gluconeogenesis in hepatocytes from newborn rabbits.

Aging↗
PubMed1983

Effects of medium-chain triglyceride feeding on glucose homeostasis in the newborn rat.

The mechanism of the profound hypoglycemia that develops in newborn rats during a fast of 16-h beginning at birth has been investigated. This fasting hypoglycemia was completely reversed by giving oral medium-chain fatty acids (MCT). The rise in blood glucose induced by MCT feeding was not secondary to a decreased uptake of glucose by peripheral tissues because [6-3H]glucose turnover rate was increased in MCT-fed neonates. Several lines of evidence strongly suggest that MCT feeding was associated with a stimulation of hepatic gluconeogenesis. 1) The rate of [6-3H]glucose turnover was enhanced after MCT feeding. 2) A fivefold increase in the conversion of labeled lactate into glucose was observed in vivo after MCT feeding. 3) The rise in blood glucose induced by MCT feeding was totally suppressed by an inhibitor of gluconeogenesis (3-mercaptopicolinate). Despite their utilization for glucose synthesis, blood levels of lactate, alanine, and pyruvate were increased two- to threefold after MCT feeding. When MCT feeding was given in association with dichloroacetate, an activator of pyruvate dehydrogenase (PDH), no increase in blood lactate, alanine, and pyruvate was observed and the rise in glycemia was prevented. This suggested that hyperketonemia due to MCT feeding could decrease the oxidation of 3-carbon glucose precursors in peripheral tissues, secondary to an inhibition of PDH, and thus enhanced their release in blood. These data indicate that MCT feeding stimulates glucose production in the newborn rat, both by increasing the availability of gluconeogenic precursors and by a direct effect on hepatic gluconeogenesis.

Animals↗
PubMed1983

Glucose metabolism during lactation in the rat: quantitative and regulatory aspects.

Glucose metabolism was studied in anesthetized lactating rats in the postabsorptive state. Basal levels of blood glucose and plasma insulin were lower in 12-day-lactating rats than in age-matched nonlactating rats. When the pups were removed for 24 h, the maternal blood glucose level reached a value intermediate between lactating and nonlactating values, and the plasma insulin level was the same as in nonlactating rats. Glucose turnover was increased from 3 days postpartum on in lactating rats compared with nonlactating rats. At peak lactation (12-19 days) glucose turnover was 80% higher in lactating than in nonlactating rats. In the lactating rats weaned for 24 h, glucose turnover returned to the value of the nonlactating rats. Insulin secretion in response to an intravenous glucose load (IVGTT) was not modified in lactating rats compared with nonlactating rats but was increased threefold in weaned rats. This suggests that nonlactating tissues are insulin resistant during lactation. During euglycemic hyperinsulinemic clamp, glucose clearance was increased threefold in lactating and in nonlactating rats and twofold in weaned rats, suggesting that glucose metabolism in the mammary gland is affected by insulin. Measurement of lipogenesis gave direct evidence for the insulin responsiveness of the mammary gland and for the insulin resistance of adipose tissue during lactation.

Animals↗
PubMed1983

Long-term effects of betamethasone on blood pressure and hypothalamo-pituitary-adrenocortical function in spontaneously hypertensive and normotensive rats.

An enhanced hypothalamo-pituitary-adrenocortical (HPA) activity has been described during onset of elevated blood pressure in spontaneously hypertensive rats (SHR). An instability of the HPA axis could thus contribute to the development of hypertension in these animals. Glucocorticoid effects on blood pressure and HPA function were studied therefore in SHR and normotensive Wistar-Kyoto (WKY) and Wistar rats. Beginning at 4 weeks of age, the rats were treated with 0.1 and 0.5 microgram betamethasone per milliliter drinking water for 7 weeks. SHR and WKY responded with a significant elevation in average blood pressure. In SHR, mean blood pressure rose from 181.4 +/- 3.9 (mean +/- SEM) to 203.1 +/- 2.8 mm Hg in response to the lower dose of betamethasone and to 209.2 +/- 4.0 mm Hg in response to 0.5 microgram betamethasone per milliliter drinking water. In WKY, blood pressure increased from 134.4 +/- 3.3 to 148.2 +/- 3.0 and 157.9 +/- 4.5 mm Hg in response to the lower and higher dose of betamethasone, respectively. No significant effect was seen in Wistar rats, where the mean blood pressure values changed insignificantly from 133.8 +/- 2.1 to 136.3 +/- 3.2 and 135.6 +/- 2.4 mm Hg. Stress-induced secretion of corticosterone was significantly suppressed in a dose-dependent manner in all three strains. Stress-induced secretion of adrenocorticotropin was markedly reduced by 0.5 microgram betamethasone per milliliter in SHR and by both doses in WKY. No significant effect, however, was seen in Wistar rats. A predisposition to the hypertensiogenic actions of glucocorticoids was found therefore in SHR and WKY, but not in Wistar rats.

Animals↗
PubMed1983

The relationship of serum thyrotropin (TSH) to the thyroid hormones after oral TSH-releasing hormone in patients with preclinical hypothyroidism.

Serum thyroid hormone and TSH concentrations were measured before and after oral TRH (40 mg) administration in 46 women with preclinical hypothyroidism. Preclinical hypothyroidism was defined as serum T4 in the normal range, a normal or elevated basal serum TSH, and an exaggerated serum TSH response to TRH, in the absence of clinical manifestations of hypothyroidism. The results were compared to those in 22 normal women of the same age and body mass index. Overall, the patients had significantly lower mean values for basal T4 [total T4, free T4 index (FT4 index), and free T4] but not for T3; all indices of T4 were lower in those with an elevated basal TSH, but only the FT4 was lower in patients who had normal basal TSH levels and exaggerated TSH responses to TRH. Thyroid reserve, or the increase in serum thyroid hormones after TRH (delta T4, delta FT4, and delta T3) showed an inverse correlation with basal TSH (for delta T4, r = -0.518 and P less than 0.001; for delta FT4, r = -0.442 and P less than 0.05; for delta T3, r = -0.645 and P less than 0.001). Thyroid reserve was lower than normal in those with elevated basal TSH levels, but was normal in those with exaggerated TSH responses to TRH who had normal basal TSH levels. Thus, an elevated basal TSH level, even with basal serum T4 and T3 levels in the normal range, indicates deficient thyroid reserve.

Administration, Oral↗
PubMed1983

Preclinical hyperthyroidism--a graded condition.

In 65 consecutive surgical patients with multinodular goitre and with preclinical hyperthyroidism (TRH-resistant suppression of TSH in the presence of normal circulating thyroid hormones) the individual values of the FT4-index (FT4-I) and FT3-index (FT3-I) showed a wide range form low normal to high normal with mean values not differing from those in TRH-responsive goitre patients and from controls. Thirty-five patients underwent repeated pre-operative TRH tests: 11 (group A) were TRH-unresponsive on one occasion, and TRH-responsive at another time. Fifteen (group B) were TRH-unresponsive on two occasions. Nine patients (group C) were preclinically hyperthyroid on one occasion and had supranormal individual thyroid hormone concentrations at another time. In multinodular goitre patients with preclinical hyperthyroidism a significant T3 increase was observed after oral TRH. In spite of a TRH-resistant suppression of TSH small amounts of TSH are thus still secreted. The degree of TSH suppression may be the result of a varying degree and pattern of continued, fluctuating or elapsed increase in thyroid hormone supply. The T3 response to oral TRH depends not only on the degree of TSH suppression, but also subtlely on the thyroidal reserve: in euthyroid TRH-TSH negative goitre patients a decrease of the TSH-regulated follicular mass by goitre resection abolished the pre-operatively significant T3 response to TRH during the post-operative phase of transient TSH deficiency.

Goiter, Nodular↗
PubMed1983

Stress-induced secretion of ACTH and corticosterone during development of spontaneous hypertension in rats.

Plasma ACTH and corticosterone response to ether inhalation was examined in spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto (WKY) and Wistar control rats at 4, 8, 12 and 16 weeks of age. In SHR, blood pressure rose to hypertensive levels (above 150 mm Hg) between 5 and 8 weeks, whereas, in control animals, it did not exceed 140 mm Hg. Maximum plasma ACTH concentrations were measured 5 min after exposure to ether and plasma corticosterone values attained their maximum at 20 min. Stress-induced ACTH release was significantly elevated in SHR at 4 and 8 weeks. At 16 weeks of age, no difference in the ACTH response between the three strains could be detected. Correspondingly, 4-week-old SHR showed a more pronounced corticosterone release than Wistar and WKY, whereas 16-week-old SHR and control rats responded similarly. Hypothalamo-pituitary-adrenocortical response to ether stress is thus markedly enhanced in SHR during early development of hypertension.

Adrenocorticotropic Hormone↗
PubMed1983

Alpha-human chorionic gonadotropin and neuron-specific enolase as markers for malignancy and neuroendocrine nature of pancreatic endocrine tumors.

Human chorionic gonadotropin (HCG) or its alpha and beta subunits have been proposed as markers for malignancy in pancreatic endocrine tumors. Since proof of malignancy of pancreatic endocrine tumors is difficult early in the course of the disease, we tested retrospectively a series of 157 pancreatic endocrine tumors for the presence of alpha- or beta-HCG by immunocytochemistry. In addition, antiserum against neuron-specific enolase (NSE) was applied to these tumors, in order to demonstrate their neuroendocrine nature, alpha-HCG-immunoreactive cells were present in 42/56 (75%) functioning malignant pancreatic endocrine tumors, but in only 1, possibly benign, glucagonoma out of 67 functioning benign tumors, in only 1/17 nonfunctioning malignant, and in 0/17 nonfunctioning benign tumors. We were not able to localize beta-HCG-immunoreactivity in the tumors. In all but 1 tumor NSE was observed. It is concluded that alpha-HCG represents a reliable marker for malignancy in functioning pancreatic endocrine tumors, and that the presence of NSE establishes the neuroendocrine nature of the tumors.

Adenoma, Islet Cell↗
PubMed1983

Fuel metabolism and energy stores in fasting or suckling newborn guinea pigs.

Newborn guinea-pigs delivered by Caesarean section at term were fasted for 48h at 35 degrees C and compared with suckling neonates. For the first 18h of fasting, blood glucose concentration remains at a normal level: a rapid liver glycogenolysis contributes to glucose production but indirect evidence suggests also that active gluconeogenesis from lactate, alanine and glycerol occurs at this time. Despite high liver triacylglycerol levels at birth and increased plasma free fatty acids the blood ketone body concentration remains very low which suggests that free fatty acid availability is not the only factor controlling the onset of ketogenesis at birth. After 24h of fasting, blood glucose concentration decreases whereas suckling newborns remain normoglycaemic. A mild hypoglycaemia is observed in fasting newborn which is not related to an unavailability of fat-derived substrates since mobilization of fat stores induces an increase of plasma free fatty acid levels and high blood concentration of ketone bodies. This relative hypoglycaemia is probably related to the lack of glucose and/or gluconeogenic substrate intake strengthened by an unavailability of some endogenous gluconeogenic precursors since a lack of a mobilization of protein stores characterizes this period. The maintenance of glucose homeostasis in suckling neonates reflects an active gluconeogenesis; a theoretical calculation shows an important contribution of each milk constituent including amino acids to sustain an endogenous glucose production.

Acetoacetates↗
PubMed1982

[TRH-TSH regulation in the aged and in patients with senile dementia].

TRH-TSH-thyroid regulation has been studied in clinically euthyroid elderly patients (average age 80 years) with senile dementia (27 women, 35 men) and normal controls (18 women, 10 men). TRH (40 mg) given by mouth did not stimulate TSH in one third of all subjects. Both sexes were equally affected. No relation to senile dementia or to goiter could be established. All groups, including the group without measurable TSH response (1 mE/1) showed an increase in peripheral thyroid hormone concentration after TRH. It is suggested that the low TSH response to TRH is a consequence of diminished pituitary responsiveness to TRH. Evaluation of thyroid function and diagnosis of hyperthyroidism in the elderly after TRH should be carried out with great caution.

Aged↗
PubMed1982

[The action of bromazepam on anxiety (author's transl)].

The action of bromazepam was assessed in 30 patients whose dominant symptom was anxiety in clinical presentations of neurosis, depression, drug-addiction or alcoholism, senile dementia or oligophrenia. The doses administered ranged from 6 to 12 mg/day and in some cases from 18 to 36 mg/day. Distinct improvement was noted in 20 patients, the effects of the drug on anxiety being manifested within 2 to 3 days. The somatic symptoms of anxiety and sleep disturbances were also improved. However, depressive and psychotic symptoms remained unchanged and it was necessary to combine diazepam with other drugs. Side-effects consisted of daytime somnolence in 2 cases and feeling of dizziness in 3 cases.

Adult↗