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Biomedical subjects

M Maes

Publications and source records attributed to M Maes.

At least 307 records · Page 17Linked to original sources

The decreased plasma concentration of insulin-like growth factor-I in protein-restricted rats is not due to decreased numbers of growth hormone receptors on isolated hepatocytes.

The resistance to GH and the low serum concentrations of insulin-like growth factor-I (IGF-I) that occur during fasting are accompanied by decreased GH receptors in liver homogenates. In protein restriction, however, serum IGF-I but not GH receptors are decreased, suggesting that a post-receptor defect exists. Because conclusions about the status of GH receptors during dietary manipulation are based on studies using liver homogenates, the present study was undertaken to determine whether changes in GH binding by homogenates are paralleled by changes in receptors on the cell surface considered to mediate the GH signal. Collagenase-dispersed hepatocytes or liver homogenates from 7-week-old female Wistar rats fed various diets were evaluated for changes in somatogenic receptors. Fasting for 24 h reduced significantly (P less than 0.001) the plasma concentrations of IGF-I (-31%). Likewise, GH-binding sites were decreased on hepatocytes (-55%; P less than 0.01) and in liver homogenates (-60%; P less than 0.001) compared with controls, as was the velocity of initial binding (-77%; P less than 0.001). Protein restriction for 1 week decreased plasma concentrations of IGF-I (-42%; P less than 0.001) but GH-binding sites were not significantly reduced on hepatocytes or in homogenates. The velocity of initial binding was also not decreased. We conclude that observations on changes in homogenate binding of bovine GH during dietary manipulation provide a reliable means of assessing changes in cell-surface GH receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Diabetes, malnutrition and growth retardation].

We investigated the cellular mechanisms responsible for growth hormone (GH) resistance in diabetes and malnutrition in the rat. In insulin-dependent diabetes, a post-receptor defect participates in GH resistance. During fasting, there is a loss of liver GH binding sites. Dietary protein restriction causes a post-receptor defect. This defect can be attributed to the combined effects of decreased liver IGF-I mRNA content and impaired message translation.

Animals↗

A thermodynamically consistent constitutive equation for the elastic force-length relation of soft biological materials.

Starting from the laws of thermodynamics of reversible processes, a temperature-dependent constitutive equation is derived for the elastic force-length relation of soft biological tissues. These tissues are composed of a network of fibres (mainly collagen). The equation is based on a model which uses a simplified two-dimensional representation of the alpha-helix of collagen.

Collagen↗

Use of the dexamethasone suppression test in an inpatient setting: a replication and new findings.

The dexamethasone suppression test (DST) was administered to 131 depressed and 109 nondepressed psychiatric inpatients. The depressed patients were categorized according to DSM-III as minor depression, major depression without melancholia, and major depression with melancholia and/or with psychotic features. The nondepressed patients were stratified over several DSM-III subcategories. DST nonsuppression was nonspecific for major depression: the mean post-dexamethasone cortisol value and the number of nonsuppressors were not significantly different between the major depressives and the nondepressed psychiatric controls. Within the depressive sample the DST was a significant (p less than 0.01) discriminator between major and minor depression. Postdexamethasone plasma greater than or equal to 3.5 micrograms/dl at 0800h was the most sensitive (39%) and specific (94%) criterion; cortisol values at 1600h and 2300h showed no significant discriminating power for major vs. minor depression. The diagnostic utility of the DST thus appears to be limited to confirming the diagnosis of major depression, once the clinical diagnosis of depression is made. There was no significant influence of age or gender on postdexamethasone cortisol values.

Affective Disorders, Psychotic↗

Hypothalamic-pituitary-adrenal and -thyroid axis dysfunctions and decrements in the availability of L-tryptophan as biological markers of suicidal ideation in major depressed females.

Several neurochemical correlates of suicide were recently detected. Some authors found increased disorders in the hypothalamic-pituitary-adrenal (HPA) and -thyroid (HPT) axes and disturbances in serotonergic neurotransmission in suicidal patients. In order to investigate the biological correlates of suicidal ideation, we measured the following: basal thyrotropin-secreting hormone (TSH), free thyroxine (FT4), pre- and postdexamethasone cortisol, adrenocorticotropic hormone (ACTH) levels, the circulating concentrations of total L-tryptophan (L-TRP) and the ratio between L-TRP and competing amino acids (CAA). The subjects were 17 suicidal and 17 nonsuicidal major depressed females matched for age and severity of illness. We found no significant differences in any of the above-mentioned biological data between patients with suicidal ideation and those without.

Adrenocorticotropic Hormone↗

Sex-linked differences in cortisol, ACTH and prolactin responses to 5-hydroxy-tryptophan in healthy controls and minor and major depressed patients.

Some researchers have found that the administration of 5-hydroxytryptophan (5-HTP) results in increased cortisol secretion in major depressives but not in healthy controls. Other authors observed gender-related differences in cortisol responses to 5-HTP in major depressives. In order to investigate the pituitary/adrenal responsivity to 5-HTP, the authors measured cortisol, adrenocorticotropic hormone (ACTH) and prolactin (PRL) in 30 healthy controls and in 90 depressed patients; the hormone levels were determined in baseline conditions and 60, 90 and 120 min after 125 mg L-5-HTP (orally, non-enteric coated). We found that healthy men had significantly higher cortisol responses to L-5-HTP than healthy women. In the major depressives with melancholia and/or psychotic features these differences were reversed: women exhibited significantly higher cortisol and PRL responses than men. In the female group the most severely depressed patients had increased cortisol and PRL responses to L-5-HTP. The amplitudes of the cortisol, ACTH and PRL responses to L-5-HTP were significantly and positively correlated. It was concluded that the central serotonergic regulation of ACTH and PRL is significantly different between the sexes and between healthy controls, minor depressives and severely depressed patients.

5-Hydroxytryptophan↗

Cortisol, ACTH, prolactin and beta-endorphin responses to fenfluramine administration in major-depressed patients.

In the past, some researchers found increased cortisol and prolactin responses to the administration of fenfluramine in major-depressed patients. It was believed that the fenfluramine test could prove to constitute another challenge probe to reflect the central serotonergic function. The present study was conducted in order to investigate the pituitary/adrenal responses to fenfluramine in major- versus minor-depressed patients. To this end we administered 60 mg D,L-fenfluramine p.o. to 40 depressed patients categorized according to the DSM-III. The basal levels of cortisol, adrenocorticotrophic hormone (ACTH), beta-endorphins and prolactin and their levels 2 and 4 h after fenfluramine administration were measured. We found no significant effect for fenfluramine treatment on cortisol, ACTH or beta-endorphins. There was a significant (p = 0.02) effect for fenfluramine treatment on prolactin. The enhanced secretion of prolactin was only significant (p = 0.006) in major (296.X2, 296.X3, 296.X4) and not in minor (300.40, 309.00) depressives. It was concluded that our findings corroborate the thesis of a hypersensitive serotonergic neurotransmission during a major depressive episode.

Adrenocorticotropic Hormone↗

Results of the 8 a.m. dexamethasone suppression test constitute a suitable tool for confirming the diagnosis of melancholia. A test unaffected by the variations in the bioavailability of dexamethasone.

This prospective study was conducted in order (1) to examine which postdexamethasone cortisol value i.e., 8 a.m., 4 p.m. or peak cortisol - is most suitable as a laboratory test to help confirm the diagnosis of melancholia and (2) to investigate the influence of the dexamethasone levels in the results of the dexamethasone suppression test (DST). To this end we administered the DST to 48 controls and 115 depressed inpatients categorized according to DSM-III. The 8 a.m. and 4 p.m. dexamethasone levels were determined in 100 subjects. We found that an 8 a.m. postdexamethasone cortisol value greater than or equal to 3.5 micrograms/dl was of the most significant diagnostic value in order to separate melancholia from normal controls and/or minor depressives. The 8 a.m. and 4 p.m. dexamethasone values did not differ between healthy controls, minor and severely depressed patients. Although cortisol nonsuppressors exhibited significantly lower dexamethasone values, the predictive value of the DST for melancholia was not affected by the large variation in the bioavailability of dexamethasone.

Adult↗

Impaired lymphocyte stimulation by mitogens in severely depressed patients. A complex interface with HPA-axis hyperfunction, noradrenergic activity and the ageing process.

To investigate the relationships between the immune apparatus, major depression, and HPA-axis and noradrenergic activity, the authors measured the lymphocyte stimulation responses to the mitogens phytohaemagglutinin (PHA), pokeweed mitogen (PWM) and concanavalin A (CON A), post-dexamethasone cortisol (DST) values and 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion in 24-hour urine samples from 48 patients. We found that lymphocyte responses to PHA and PWM in melancholic and psychotic depressives were significantly lower than in minor depressives. The lymphocyte responses to PHA, PWM and CON A showed significantly negative correlations with age, DST results and HRSD score. Responses to PHA were significantly negatively correlated with MHPG excretion. Up to +/- 33% of the variance in the three mitogenic lymphocyte responses could be explained by canonical correlation with age, DST results and MHPG values.

Adult↗

Reduction of serum insulin-like growth factor-I by dietary protein restriction is age dependent.

We have determined if dietary protein restriction for 1 wk has differential effects on growth, serum IGF-I, and liver growth hormone receptors at various stages of development. Female Wistar rats were fed a low (5%) protein diet for 7 d at 3, 4, 6, 8, and 12 wk of age, whereas controls were maintained on a normal (15%) protein diet. Body wt gain was impaired in the groups fed the low protein diet, despite normal energy intake, and the effect was attenuated with age. Liver cell number (DNA content) was reduced by low protein feeding in the 3-, 4-, and 6-wk age groups (p less than 0.01), but not in the older animals. Protein restriction caused a dramatic decrease in serum IGF-I in the younger animals (90 and 82% reduction versus normal fed age-matched controls, at 3 and 4 wk, respectively; p less than 0.001), and this effect was progressively attenuated with increasing age (49, 40, and 25% reductions of serum IGF-I at 6, 8, and 12 wk, respectively). Changes in serum IGF-I correlated with those of liver cell number (r = 0.80; p less than 0.001). Total and free liver growth hormone receptors were slightly decreased in the low protein diet groups at 4 (p less than 0.05) and 6 wk (total: p less than 0.001; free: p less than 0.01) but not in the other age groups. The occurrence of profound diet induced reductions in IGF-I without proportional reductions in liver GH receptors suggest that the apparent GH resistance occurs at a postreceptor level.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Dietary protein restriction decreases insulin-like growth factor I independent of insulin and liver growth hormone binding.

To determine the role of hypoinsulinemia and liver somatogenic (GH) receptors in growth retardation and decreased serum insulin-like growth factor I (IGF-I) levels during protein restriction, we have used a rat model where the effects of a low protein intake on body weight (BW), serum IGF-I concentration, and liver GH binding could be evaluated in the presence of low or high insulin concentrations. Two days after being made diabetic with streptozotocin (60 mg/kg BW), 6-week-old female rats (nine per group) were begun on a low (5%) or normal (15%) protein diet, without or with insulin supplementation (3 U lente daily). Nondiabetic rats fed both diets were used as controls (nine per group). In the nondiabetic animals, 7 days of protein restriction reduced BW gain by 50% (P less than 0.001), serum insulin by 44% (P less than 0.025), and serum IGF-I concentrations by 28% (P less than 0.001) without significantly changing liver GH binding. By day 9, BW was decreased in the diabetic animals by 12%, serum insulin by 80%, serum IGF-I by 55%, and liver GH binding by 62%; these effects were similar in the 5% and 15% protein-fed rats (P less than 0.001 vs. the corresponding controls). In the diabetes fed the normal diet, insulin treatment restored BW gain, serum IGF-I, and liver GH binding to normal values. In contrast, in the diabetics fed a protein-restricted diet and treated with insulin, BW gain and serum IGF-I concentrations remained low, similar to those in the malnourished controls. This diet-induced growth attenuation was observed despite high circulating insulin (2-3 times normal values), appropriate glucose control (63 +/- 9 mg/dl), and near restoration of liver GH binding. We conclude that while both protein restriction and diabetes attenuate growth and reduce IGF-I concentrations, the effects of protein restriction are independent of the effects of insulin and probably act by alteration of postreceptor mechanisms.

Animals↗

Insulin-like growth factor-I (IGF-I) infusion into hypophysectomized or protein-deprived rats induces specific IGF-binding proteins in serum.

The insulin-like growth factors (IGFs) are small peptides that are present in serum and extracellular fluids and stimulate the growth of many cell types. In extracellular fluids the IGFs are bound to carrier proteins that are believed to modify the biological actions of the IGFs. At least three structurally distinct IGF-binding proteins (IGF-BPs) have been identified, and the serum concentrations of one of these has been shown to be regulated by pituitary GH. We report here that this GH responsive protein [39,000-45,000 mol wt (Mr)] can be induced (7-fold) by infusion of IGF-I in hypophysectomized rats or (3.5-fold) in protein-deprived rats, whereas two other forms of IGF-BP (e.g. 31,000-34,000 and 24,000 Mr) showed no change in the hypophysectomized animals and minimal increases in the protein-deprived animals. Likewise, GH injections in hypophysectomized animals resulted in a 7-fold increase in the 39,000-45,000 Mr form and no change in the 31,000-34,000 and 24,000 Mr forms. The protein-deprived animals showed a 3.2-fold increase in the 39,000-45,000 Mr and 2.4- to 1.8-fold increases in the 31,000-34,000 and 24,000 Mr forms, respectively. Changes in the larger Mr IGF-BP in these experimental models are paralleled by changes in serum IGF-I, suggesting that the GH dependence of the former protein is mediated at least partially via IGF-I. Our findings also suggest that the secretion of IGF-I and at least one IGF-BP may be linked, providing a mechanism by which their extracellular fluid concentrations are coordinated. Because IGF-BPs are present in extracellular fluids and can modulate IGF-I-receptor interaction, induction of this protein may be an important mediator of IGF action.

Animals↗

[Sexual ambiguity: urologic aspects].

Ambiguous genitalia require prompt decision in the neonatal period to give the child the best opportunity to avoid later major problems of sexual identification. A team approach including the neonatologist, the pediatric endocrinologist, the geneticist and the pediatric urologist seems to be the best way to make the right decision. This paper is a review of 48 cases of ambiguous genitalia referred to our center for management. The diagnosis of female pseudohermaphroditism was established in 30 cases with 21 presented with adrenogenital syndrome. Ten patients were considered as having a diagnosis of male pseudohermaphroditism, six presented with gonadal dysgenesis and two were true hermaphrodites. Principles of surgical management for each category of patients is exposed, discussed and will be the way to treat subsequent cases.

Disorders of Sex Development↗

Self rated depression in relation to DSM-III classification: a statistical isolinear multiple components analysis.

The Zung Self-Rating Depression Scale (SDS) was presented to 99 depressed inpatients. The patients were categorized according to DSM-III as suffering from minor depression, major depression without melancholia and major depression with melancholia and/or with psychotic features. Differences in self-reported symptoms between these categories were studied with multivariate statistical techniques including linear discriminant analysis (LDA) and statistical isolinear multiple components analysis (SIMCA). Patients with minor depression rate themselves significantly less depressed than those with major depression. Patients with major depression without melancholia are less depressed than those with melancholia and/or psychotic features. The three DSM-III depressive categories can be regarded as belonging to a clinical continuum in which they form relevant levels with quantitative differences in self-reported symptoms. These differences are not only defined by gradual shiftings in the overall severity of illness, but also by quantitative differences in the severity of some target symptoms, i.e. agitation, retardation, diurnal variation, loss of libido, fatiguability, insomnia, anorexia, sadness and anhedonia.

Adjustment Disorders↗

Acute down-regulation of the somatogenic receptors in rat liver by a single injection of growth hormone.

Prolonged continuous administration of GH induces somatogenic receptors in rat liver. However, because GH secretion is pulsatile and the effect of acute changes in serum GH concentrations on liver GH receptors is unknown, we measured total (MgCl2-treated homogenates) and free (water-treated homogenates) GH-binding sites in the livers of hypophysectomized (hypox) rats killed between 1 and 24 h after a single sc injection of rat GH (100 micrograms/100 g BW; n = 29). Control hypox rats (n = 10) were studied immediately or 3 h after injection of vehicle. GH injection caused profound decreases in both total and free liver GH receptors, but these changes followed different kinetic patterns. Free receptors declined rapidly (to 17% of control), reaching a nadir at the same time (1 h) as the maximal GH concentration in serum. These free receptors then increased, returning to normal 12 h after GH injection. In contrast, total GH receptors were slightly increased at 1 h, decreased to their minimal value at 6 h (53% of control), and returned to normal at 12 h. Serum immunoreactive somatomedin-C/insulin-like growth factor I concentrations peaked 12 h after GH injection. Total and free liver GH receptors were quantitated in hypox rats that had been injected 3 h previously with doses of rat GH from 2.5-500 micrograms/100 g BW or with vehicle. Both total and free binding sites decreased in a dose-dependent manner; the maximal responses were 40% and 90% below control values, respectively. Half-maximal reductions in GH binding were achieved when 10 micrograms GH/100 g BW were given. These data suggest that a surge of GH in serum leads to a time- and dose-dependent down-regulation of the liver somatogenic binding sites and are consistent with ligand-induced internalization and degradation of the receptor.

Animals↗