PubMed HealthSearch

Biomedical subjects

E Lacroix

Publications and source records attributed to E Lacroix.

At least 19 recordsLinked to original sources

[From empirical 'dietetics' to rational dietetics].

From the outset, the terms 'dietetics' and 'diet' applied in their general acceptance to all the measures, whether or not alimentary, that can provide optimal living conditions for both the healthy and the diseased. In that meaning they are synonymous with hygiene or way of life. In their more restricted acceptance, which will be used henceforth, the terms apply to the choice of food and beverages which promotes or restores health of normal and sick people. In its most restricted meaning, the term 'diet' is confined to the nutrition of the sick, consisting either in a more or less drastic limitation of food intake, or in the prescription of specific foods. Due to the absence of scientific knowledge concerning the processes of life in general, and in particular concerning the physiology of the digestive system and the metabolism, the 'dietetic' rules and principles were governed until the middle of the nineteenth century by empiricism with a strong background of intuition, tradition, magic and religion. In his continuous struggle for life, man has been confronted with the dramatic consequences of the ingestion of toxic and spoiled food. Nausea, vomiting, diarrhea, cramps and eventually death have soon been linked with the ingestion of particular food, although the symptoms were attributed to supernatural forces. Intuitively and later by laws and prohibition, the use of certain foods was to be avoided or was forbidden. Moreover, with the development of cultures and civilizations food and food intake have acquired -besides their vital necessity-social and often magic-religious values which sometimes resulted in food taboos. In most civilizations these taboos have particulars in common: they are mainly directed against food of animal origin, more against meat than fish and particularly against red meat, which is being considered as symbol of strength and power and as endowed with exciting and stimulatory properties. The meat taboos are selective for some animals or parts of an animal, but what is allowed in some cultures is forbidden in others. More or less severe and long lasting abstinence from food or fasting was also self-inflicted or imposed to individuals or whole populations by religion, sometimes seemingly on hygienic grounds but in most cases without any logic reason. Since the earliest time, diets take-together with other dietetic measures-a prevailing place in the treatment of the sick and sickness. Most alimentary prescriptions are based on a more or less drastic restriction of food and - particularly in the seventeenth century with the iatrochemical school - also of fluids. The restrictions were not only quantitative, but also qualitative with restriction of meat consumption-particularly of red meat-and the prescription of more or less diluted decoctions of barley (infusions) or broth. The numerous works on 'dietetics' published-thanks to the development of printing-from the seventeenth on through the nineteenth century concern mainly the description of foodstuffs and beverages available at the time, and of the ways of preparing them. They also provide indications concerning the way these foodstuffs can improve health and/or list which of them can be prescribed or must be avoided in the treatment of the sick and of specific diseases. Some of these 'dietetical' prescriptions and maxims seem perfectly valid from a scientific and therapeutical point of view, - at least according to our actual knowledge - however, many are totally ineffective or are ridiculous and even dangerous. Except for the "dietetical" measures imposed by public hygiene or by religion to everyone, most of the dieteticotherapeutical prescriptions (food restrictions, clysters, purgation, bleeding) involved only the small fraction of the population that could afford medical assistance. The common people - the majority - could afford neither medical help, nor food abuse - except for an occasional feast - and had only access to a limited quantity and choi

Diet

Influence of converting enzyme inhibition on isoflurane-induced hypotension for cerebral aneurysm surgery.

Twenty-five patients (aged 18 to 72 years), who recovered after the first bleed from a cerebral aneurysm, were operated on under neuroleptanaesthesia. Isoflurane was added to induce hypotension. It was found that the required hypotension (51 (SEM 1) mmHg) could be obtained and maintained at much lower isoflurane concentrations (less than 1%) after blockade of the angiotensin converting enzyme activity by enalaprilat (2.5 mg i.v.) than without such inhibition. During the hypotension which lasted 78 (SEM 10) min, only minor adjustments of the isoflurane concentration (0.70 (0.04%) were needed. The desired level of hypotension was obtained with preservation of the cardiac output and without tachycardia. No resistance to the blood pressure lowering effect of isoflurane was observed. On recovery from anaesthesia, a small increase of blood pressure above control values was seen in 16 patients and was easily reversed by small doses of clonidine (mean total dose: 220 (61) micrograms). The operative conditions were excellent and the postoperative recovery was uneventful and complete in 23 patients.

Adolescent

Idazoxan inhibits hyperprolactinaemia in ovariectomized estrogen-treated rats.

The alpha 2-antagonist idazoxan (IDZ) has previously been shown to inhibit hyperprolactinaemia triggered by various stimuli such as lactation, stress, serotonergic agents and morphine (Preziosi, Martire, Navarra, Pistritto and Vacca 1989; Krulich, Jurcovicova and Le 1989). In this study, we investigated the PRL-lowering activity of IDZ in ovariectomized estrogen-treated (OET) rats; since a PRL surge usually occurs in normal cycling rats on the day of proestrus, the effect of IDZ on pulsatile PRL release in intact female rats was also studied. IDZ significantly lowered plasma PRL levels in OET rats; no elevated PRL values were observed in normal cycling rats, indicating that IDZ might inhibit PRL surges in these animals. It is concluded that IDZ is an effective PRL-lowering agent in a number of physiological and pharmacological hyperprolactinaemic models.

Animals

Alpha 2-adrenoceptor-mediated inhibition of prolactin release in suckling- or fenfluramine-induced hyperprolactinemia.

It has recently been shown that the specific and selective alpha 2-antagonist idazoxan (IDZ) displays prolactin-lowering activity on hyperprolactinemia induced in the rat either by suckling or serotonergic drugs. In an attempt better to understand the role of alpha 2-adrenoceptors under the above conditions, experiments were carried out to compare the effects of IDZ with that of the classic alpha 2-antagonist yohimbine (YOH), and also of the alpha 2-agonists clonidine (CLO) and B-HT 920, on prolactin (PRL) release during lactation and in hyperprolactinemia induced in male rats by the serotonergic drug fenfluramine (FEN). In lactating rats, both alpha 2-agonists decreased PRL release; this effect was enhanced by prior separation of the animals from their pups for several hours. A decrease of plasma PRL levels was also induced by IDZ but not by YOH, which tended further to increase hyperprolactinemia. In male rats treated with FEN, IDZ and CLO, a significant decrease of plasma PRL was produced, but YOH further enhanced PRL secretion. It is concluded that the alpha 2-agonists tested and also the alpha 2-antagonist IDZ display a unique inhibitory activity on PRL release during suckling or serotonergic-induced hyperprolactinemia.

Adrenergic alpha-Agonists

Regulation of the pituitary 5 alpha-reductase activity by gonadotropin releasing hormone and testosterone in the adult male rat.

Intact or castrated adult male rats were treated for nine days with GnRH (10 micrograms/day), the synthetic GnRH goserelin (100 micrograms/day) or the GnRH-antagonist Org 30276 (250 or 500 micrograms/day). In some series, 1 mg testosterone propionate was administered alone, or in combination with goserelin or Org 30276. The in vitro metabolism of [1 alpha,2 alpha-3H]testosterone by pituitary and hypothalamic homogenates was investigated in combination with the estimation of plasma concentrations of testosterone and gonadotropins. No qualitative or quantitative differences were observed in hypothalamic testosterone metabolism or in the pituitary 17 beta-hydroxysteroid dehydrogenase activity. Testosterone administration to intact male rats decreased the pituitary 5 alpha-reductase activity and LH, while administered to castrated rats, it was able to suppress totally the castration-induced increase of the 5 alpha-reductase activity and of the gonadotropin secretion. The drastic decrease of the plasma levels of testosterone, observed after a prolonged treatment with GnRH, goserelin or Org 30276 was not accompanied by an increased pituitary 5 alpha-reductase activity. Injected to castrated rats, it was observed that the castration-induced increase of the pituitary 5 alpha-reductase was further stimulated by GnRH, totally suppressed by goserelin and partially suppressed by Org 30276. Concomitant administration of goserelin or Org 30276 and testosterone propionate to castrated rats resulted in a further decrease of the pituitary 5 alpha-reductase activity, compared to the castrated, GnRH-analogue treated rats. These data indicate that the pituitary 5 alpha-reductase enzyme system is controlled by both direct steroidal and indirect GnRH-mediated mechanisms.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase

Effect of tamoxifen on the activity of enzymes of testicular steroidogenesis.

Testicular homogenates of tamoxifen-treated rats were incubated with labeled steroid precursors (progesterone, 17 alpha-hydroxyprogesterone, dehydroepiandrosterone, androstenedione or testosterone) in order to study the effect of tamoxifen on testicular steroidogenesis. The results indicate that a 9 day treatment with a daily dose of 1 mg tamoxifen produces a reduction of the synthesis of testosterone. Inhibition of the 17 alpha-hydroxylase and C17,20-desmolase enzyme systems was observed together with an increased 20 alpha-hydroxysteroid dehydrogenase activity.

20-Hydroxysteroid Dehydrogenases

The effects of neonatal androgenization of male rats on testosterone metabolism by the hypothalamus-pituitary-gonadal axis.

Male rats were androgenized on the third postnatal day by a single injection of 1 mg testosterone propionate. The in vitro metabolism of [4-14C]testosterone by pituitary and hypothalamus homogenates was investigated at the age of 90 days. The pituitary and hypothalamus homogenates from control and neonatally androgenized animals converted [4-14C]testosterone to the same metabolites, mainly 5 alpha-reduced derivatives; the quantitative yield of 5 alpha-reduced metabolites was much higher in the pituitary homogenates of androgenized rats. The hypothalamic homogenates showed no differences. In the androgenized rats a very significant increase of the plasma FSH levels was measured while the LH levels were also augmented. The plasma levels of testosterone were not different from the values in control rats, notwithstanding a 25% reduction in testes weight. The present experiments appear to indicate that the neonatal androgenization results in an accentuation of the sexual dimorphism which normally exists in the pituitary of adult rats for the 5 alpha-reductase activity.

Androgens

Influence of a prolonged tamoxifen administration on steroidogenesis by incubated rat testes.

Tamoxifen was administered i.m. for 9 days to adult male rats in a daily dose of 100 micrograms or 1 mg. The treatment resulted in a significant reduction of the plasma levels of testosterone and LH, without modification of the plasma levels of FSH and of the testes weight. Upon incubation, the testes from the tamoxifen-treated rats produced less testosterone and 7 alpha-hydroxytestosterone, but metabolized [4-14C]testosterone in the same way as the control animals. Small doses of hCG (0.5 i.u. for 9 days) were unable to modify the tamoxifen effect on the testicular function, while tamoxifen significantly inhibited the increase of the plasma levels of testosterone induced by the administration of moderate doses of hCG (1.5 i.u. or 2.5 i.u. for 9 days) to hypophysectomized rats. Tamoxifen treatment, however, did not modify significantly the reactivity of the testes towards high doses of hCG (10 i.u.), administered either 2 h before sacrifice or for 9 days. It is concluded that a prolonged administration of tamoxifen in the rat has, besides an indirect effect resulting from a decrease of the LH levels, a direct inhibitory influence on the testicular testosterone formation, which can be reversed by high doses of hCG.

Androgens

Influence of neonatal androgenization on the testicular steroidogenesis in the adult rat.

The in vitro testicular steroidogenesis of male rats, androgenized on the third postnatal day by a single injection of 1 mg testosterone propionate, was investigated when the animals were 100 days old. The neonatal androgenization resulted in a 25% lower testes weight, significantly increased plasma levels of FSH (P less than 0.01) and LH (P less than 0.02), and normal levels of testosterone. Although the testes were hypotrophic, the incubation of the testes pairs yielded the same amounts of testosterone, 7 alpha-hydroxytestosterone and 5 alpha-androstane-(3 alpha + 3 beta), 17 beta-diol as in the control animals. However, the steroidogenic response to an acute hCG stimulation was reduced. From incubations of testes homogenates with various labelled steroid precursors it could be inferred that the activity of the 17 alpha-hydroxylase, the 3 beta-hydroxysteroid dehydrogenase-isomerase and the 17 beta-hydroxysteroid dehydrogenase, expressed per unit of incubated protein, was significantly increased in the testes of the androgenized rats. These data indicate that the basal steroidogenesis in neonatally androgenized male rats is maintained by an increased synthesis per unit of tissue, possibly under influence of an increased gonadotrophic stimulus, but that the maximum steroidogenic capacity is reduced.

17-alpha-Hydroxyprogesterone

Testosterone metabolism by incubated rat testes after chronic LHRH treatment.

Adult male rats were injected 4 or 8 days with LHRH agonist. After sacrifice the testes were incubated in vitro with or without [4-14C]testosterone. After LHRH-administration the endogenously produced amounts of testosterone and of 7 alpha-hydroxytestosterone, the main testosterone metabolite normally found on incubation of adult rat testes, were drastically reduced when compared with controls. hCG, injected to rats 2 h before sacrifice, increased steroid production. In the LHRH-treated rats, however, the amounts of testosterone and of 7 alpha-hydroxytestosterone produced were much less while an important formation of 5 alpha-androstanediol was observed. The testes of LHRH treated rats metabolized [4-14C]testosterone to a large extent to 5 alpha-reduced and unextractable metabolites while the formation of 7 alpha-hydroxylated metabolites was much reduced. It is concluded that prolonged LHRH treatment provokes not only a depression of the testosterone production but has also an influence on the testicular metabolism pattern of testosterone resulting in a proportionally increased production of 5 alpha-reduced steroids and unextractable metabolites while the formation of 7 alpha-hydroxylated steroids is inhibited.

Androgens

Metabolism of [4-14C]testosterone and precursors by homogenates of rat testes after chronic LHRH-treatment.

Adult male rats were injected daily for 8 days with an LHRH agonist. Twenty-four hours after the last injection testes-homogenates were incubated in the presence of a 4-14C-labeled steroid, either progesterone, 17 alpha-hydroxyprogesterone, dehydroepiandrosterone, androstenedione or testosterone. The activity of several enzymes involved in the androgen biosynthetic pathway was inferred from the amount of metabolites produced under these conditions. After LHRH-treatment a significant increase in the 17,20-lyase activity was observed without any significant change in the activity of 17 alpha-hydroxylase, 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase and 17 beta-hydroxysteroid dehydrogenase. The results of the experiments indicate that the decreased testosterone secretion observed in rats after chronic LHRH-administration is not due to an inhibition of the enzyme-systems studied.

Androstenedione

Steroid metabolism and steroid receptors in dimethylbenz(a)anthracene-induced rat mammary tumors.

Mammary tumors were induced in rats by treatment with dimethylbenz(a)anthracene. Cytosol receptors for 17 beta-estradiol and progesterone were estimated by means of sucrose density gradient centrifugation, and the metabolism of [14C]progesterone, [14C]testosterone, and 17 beta-[14C]estradiol by minced tumor tissue was studied. The estradiol receptor (ER) and progesterone receptor (PR) levels of the tumors varied considerably from less than 5 to 48 fmol/mg protein for ER and to 243 fmol/mg protein for PR. Considering a receptor level lower than 5 fmol/mg protein to be negative, four groups of tumors were found: ER-negative and PR-negative; ER-positive and PR-negative; ER-negative and PR-positive; ER-positive and PR-positive. In dimethylbenz(a)anthracene-induced tumor tissue, high 5 alpha-reductase and 20 alpha-hydroxysteroid dehydrogenase activities and somewhat lower 3 alpha-hydroxysteroid dehydrogenase and 6 alpha-hydroxylase activities were found. No aromatization was detectable. Steroids, especially estradiol, were also metabolized in a high degree to unextractable metabolites. It was concluded that steroid metabolism of dimethylbenz(a)anthracene-induced rat mammary tumors was not related to the ER and/or PR concentration of tumor tissue.

9,10-Dimethyl-1,2-benzanthracene

Role of testosterone levels and of hypophysis in the HCG-induced modifications of the 7 alpha-hydroxylation and 5 alpha-reduction processes in incubated rat testes.

The role of a direct or a hypophysis-mediated influence of increased testosterone levels in the effects of a long-term high-dose HCG administration (10 IU/day) upon the 7 alpha-hydroxylation and 5 alpha-reduction activities of incubated testes of mature rats was investigated. Administration of high doses of HCG to hypophysectomized rats resulted in the same metabolic changes as in normal rats, namely, a large decrease in the 7 alpha-hydroxylation and an increase in the 5 alpha-reduction processes. Administration of testosterone-propionate (0.2 mg and 20 mg/day) for several days to hypophysectomized rats and to normal rats receiving and substitutive dose of 1 IU HCG/day, did not modify the testicular metabolization pattern. These findings indicate that the decrease in testicular 7 alpha-hydroxylation activity induced by long-term administration of high doses of HCG is probably not mediated by the hypophysis nor by the extracellular testosterone levels.

Androgens

Kinetic study of HCG induced decrease of microsomal 7 alpha-hydroxylase activity in rat testes.

Microsomes from rat testes were incubated with varying concentrations of 14C labelled testosterone and androstenedione. The production of 7 alpha-hydroxytestosterone and 7 alpha-hydroxyandrostenedione was followed; Km and Vm values were calculated from Lineweaver-Burk curves. A sustained treatment of rats with HCG resulted in a considerable decrease of the maximal 7 alpha-hydroxylation rats (Vm) whereas the Km value was not changed. Vm of microsomes from normal rats, when incubated with microsomes from HCG-treated animals, was also decreased substantially. It is concluded that HCG-induced depression of 7 alpha-hydroxylation capacity of testicular microsomes is at least in part due to non-competitive inhibition of the enzyme.

Androstenedione

Estradiol metabolism by liver homogenates and microsomes of normal and cirrhotic male rats.

Incubation experiments show that homogenates and microsomes obtained from CCl4-induced cirrhotic livers of male rats metabolize an estradiol load at a much slower rate than preparations from normal livers. The decreased metabolic capacity results in a slower disappearance of estradiol from the incubation medium, and in a slower transformation of metabolized estradiol to polar extractable and to highly polar nonextractable metabolites.

Animals

[Cardiovascular effects of a single injection of fentanyl in dogs under acute experimental conditions].

Experimental studies carried out in unselected dogs often face the problem of instabilit of various parameters both in terms of haemodynamics as well as acid-base balance. It is possible, with the injection of a single dose of Fentanyl of 0.35 mg.kg-1 given over a period of ten minutes to obtain, from the 30th minute after the injection, satisfactory cardiovascular stability (confirmed during 120 minutes in 9 dogs and 360 minutes in 2 of them). This haemodynamic state at T + 30 is obtained with a fall in mean blood pressure of -40 per cent, and an increase in peripheral resistance of +38 per cent and stroke volume of +11 per cent. This stability, obtained at the price of a stable normacapnia, correction of any possible metabolic acidosis and maintenance of body temperature, makes it possible to study the cardiovascular effects of certain types of treatment or of induced pathology.

Acid-Base Equilibrium