Biomedical subjects

P A Desaulles

Publications and source records attributed to P A Desaulles.

At least 19 recordsLinked to original sources

PubMed1983

Effect of gliquidone on insulin binding to rabbit erythrocytes.

A study was made of the effects of acute or chronic treatment of rabbits with 10 mg gliquidone (Glurenorm)/kg body weight on erythrocyte insulin receptors. The binding of 125I-labelled insulin to the population of whole red blood cells was not affected by either treatment. Because of the heterogeneity of the erythrocytes, subpopulations were selected according to their specific gravity, which is directly related to cell age. The lowest-density fraction showed a 30% greater capacity of the insulin receptors without any change in affinity after chronic therapy with gliquidone, but no effects were observable after acute treatment. The highest-density fraction was not affected by either acute or chronic administration of gliquidone. Therefore, all other things being equal (blood sugar, plasma insulin levels), young erythrocytes are sensitive to sulphonylurea, whereas old ones are not. Irrespective of the compound tested, this observation suggests that receptor sensitivity might be tissue-specific or age-specific or both, and that the stage of maturation of a cell is a determining factor.

Animals↗

PubMed1977

Differences between in-vitro and in-vivo potencies of corticotrophins: an interpretation in terms of metabolic stability.

Relative activities of a series of corticotrophin analogues have been measured by means of five different bioassays using the rat. Similarities in the relative potencies of various ACTH analogues determined using lipolysis or steroidogenesis in vivo and for the lipolytic and steroidogenic responses of fat pads and adrenal slices in vitro emerged and support the concept of a close structural relationship between the ACTH receptors in adipose and adrenal tissues in the rat. Potencies based on the steroidogenic response of isolated adrenal cells, adrenal slices or in-vivo experiments differed markedly from each other. Inactivation of peptides did not occur in the isolated cell assay, so it is likely that this assay estimates potency at the receptor level. A number of arguments suggest that the difference between the isolated cell assay and the other steroidogenic assays lies solely in the effects of peptide inactivation in the latter, and this allows the relative metabolic stabilities for the peptide analogues in these assays to be calculated. In this way it can be shown that: (1) Replacement of L-Ser by D-Ser in amino acid position 1 markedly increases the metabolic stability of the peptide and has only a slight effect on receptor properties. (2) Shortening at the NH2-terminus reduces the activity of peptides at the receptor level by several orders of magnitude, but increases their relative metabolic stability. (3) Introduction of amide groups at the CO2H-terminus markedly increases receptor potency of (1-16), (1-17) and (1-18) ACTH without affecting their metabolic stability in vivo. However, amidation of the CO2H-terminus does have a large effect on metabolic stability in the adrenal slice assay. (4) Replacement of Arg by Lys in positions 17 and 18 of (1-18) ACTH increases potency at the receptor level (adrenal cells) but has little effect on metabolic stability. The comparison of potencies obtained in the various assays, therefore, throws light on the significance of each assay. In addition, the effects of structural modification of analogues can be separately evaluated with respect to the metabolic stability of a peptide and its potency at the receptor level.

Adrenal Cortex Hormones↗

PubMed1976

Corticotropic action of an intra-nasally applied synthetic ACTH derivative.

The corticotropic action of a synthetic ACTH derivative, D-Ser1 Lys17,18-1-18ACTH, after intranasal insufflation of 1 mg of the peptide was evaluated in 14 normal volunteers. Plasma cortisol and urinary 17-ketogenic steroids and 17-ketosteroids rose significantly over control values in all subjects (P less than 0.001). Plasma cortisol remained above the normal range for comparable clock times for 18 hr, but fell below 15 mug/100 ml after 12 hr. No evidence for suppression of the hypothalamo-pituitary axis was found the day after ACTH administration, as judged by normal plasma and urinary steroid values and normal diurnal variation. Intranasal administration of long-acting ACTH derivatives may provide a simple, painless and effective way to stimulate endogenous corticosteroid secretion.

17-Ketosteroids↗

PubMed1975

Uterine secretion during the sexual cycle in the rat and its capacity to disperse corona cells in vitro.

It was found that closure of the uterus disturbed the first 2 cycles after the operation; thereafter the normal cycle was resumed. The quantity of uterine fluid was increased at pro-oestrus and oestrus and reduced at met-oestrus and di-oestrus. Slight inverse changes in viscosity were observed. There was no significant difference in the pH. The corona-cell dispersing factor seems to be an oestrogen-dependent constituent of uterine secretion.

Animals↗

PubMed1974