Zur Frage des Angriffspunktes des Thiouracil

Summary The mechanism of action of thiouracil and thiourea was investigated on Xenopus tadpoles. Both substances are able to stop metamorphotic changes if administered early enough. Characteristic disturbances occur in the epithelium of the thyroid follicles after only 24 hours. The action of these substances over a period of several weeks may lead to goitre. In the pituitary anterior lobe, on the other hand, the same characteristic changes take place in the basophilic cells as after thyroidectomy. The thyroid structure of hypophysectomised tadpoles corresponds to that of untreated hypophysectomised animals. Thiourea and thiouracil do not inhibit the thyroxine effect on thyroidectomised and hypophysectomised tadpoles. These findings indicate that the point of attack of thiouracil and thiourea lies in the follicular epithelium of the thyroid, and thus supportAstwood's hypothesis.     

Les tests microbiologiques pour la détermination des vitamines

Summary The growth factors for microorganisms are nothing else than the vitamines known in animal physiology. Some microorganisms, like animals, have lost the possibility of synthetising these factors, which must be added to the culture medium. The action of the vitamine is quantitative and specific. These properties enable the auxo-heterotrophic microorganism, having lost the possibility of synthesis for a determined vitamine, to be used for a quantitative determination of this factor. The Phycomyces test for thiamine (vitamine B₁) and its different practical applications are discussed.     

Aufhebung der Thermothyrin-A-Sekretion der Schilddrüse durch Fütterung mit Methylthiouracil

Summary G. Mansfeld demonstrated that in the serum of overheated animals a substance (thermothyrine A) is present which, injected into normal animals, decreases O₂-consumption. Serum of thyroidectomized animals has no effect.Dogs and rabbits were treated daily with 0.10 g per kg methylthiouracil during 4 weeks, and were than subjected for 5 hours to a temperature of 34–35° C which raised their body temperature by 0.5–1.5° C. 2.5 cm³ of serum obtained at the end of the 5 hours period failed to reduce O₂-consumption of normal rats, while sera of untreated dogs and rabbits produced after similar exposure to high temperature a fall of O₂-consumption by 14–48%. It is therefore evident that methylthiouracil not only inhibits the formation of thyroxine but of thermothyrine A as well.The fact that thermothyrine A contains no iodine proves conclusively that the action of thiouracil compounds cannot be exclusively an inhibition of iodinization.     

Chromosomal abnormalities in starved and marginally malnourished rats and in utero upon rehabilitation

The effects of starvation and marginal malnutrition (MN) on the lymphocytes of rats were evaluated by chromosomal analysis before and after rehabilitation. The effect of parental starvation or malnutrition on chromosomal aberrations in the foetus was also studied. Wistar rats, 30–35 days old, were starved for 5 days or fed a minimally restricted or a severely restricted diet for three weeks. At the end of the period of starvation or malnutrition, lymphocytes were isolated and chromosomal analysis was performed. Starved and severely restricted rats showed significantly higher mean chromosomal aberrations than the controls. These aberrations returned to a normal level when the experimental groups were rehabilitated for a month, indicating that the damage was transient. A chromosomal aberration study done on foetal cells from rehabilitated rats which had previously been starved or fed a severely restricted diet showed significantly increased values, indicating that some damage was permanent. A low number of implantations was also recorded in these experimental groups. These observations clearly indicate that young animals exposed to conditions like starvation or chronic malnutrition are prone to permanent damage of the genetic system.     

Effect of pH on bacteria in early log phase]

The bacteria harvested in the early log phase lyse when they are submitted to a pH above 10. The peptidoglycan is not degraded in these conditions. Thus, the authors used these properties to extract the peptidoglycan from several gram negative and gram positive bacteria.     

Die biologische Bedeutung der Vitamine

Summary The vital importance of the vitamins resides in theircoferment function, which enables them to catalyse enzymatic processes in living tissues. The term coferment is used in this connection to designate organic compounds of relatively low molecular weight, which in conjunction with the specific proteinous apoferments bring about the transformation of definite substrates. The vitamins are, however, catabolized like ordinary substrates when they come into contact with enzymatic systems in which they have no coferment function. This explains why normal life cannot be sustained, if the living organisms do not receive asnutritional factors the vitamins which they cannot synthesize. From a biochemical point of view not only exogenous hypo- or avitaminoses but all pathological changes may be regarded as the sequelae of disturbances in one or several enzymatic systems. The vitamins may exert a regulating influence also in these enzymatic disturbances which are not directly caused by vitamin deficiency. In such cases they will act asrèmedies.     

Dietary n-3 polyunsaturated fatty acids and coronary heart disease-related mortality: a possible mechanism of action

Epidemiological and interventional studies indicate that dietary n-3 PUFA reduces mortality due to coronary heart disease (CHD). They act at a low dose, since one or two meals with fatty fish per week is sufficient to provide protection when compared with no fish intake. These fatty acids are effective in providing primary prevention in low- and high-risk subjects and secondary prevention. At high doses, dietary n-3 PUFAs have several beneficial properties. First, they act favourably on blood characteristics: they are hypocholesterolemic and hypotriglyceridemic; they reduce platelet aggregation; they exhibit antithrombotic and fibrinolytic activities; they reduce blood viscosity and they exhibit antiinflammatory action. Second, they reduce ischemia/reperfusion-induced cellular damage. This effect is apparently due to the incorporation of eicosapentaenoic acid in membrane phospholipids. Third, they reduce ischemia and reperfusion arrhythmias. All the effects exerted by n-3 PUFAs at high doses are incompatible with the beneficial action on CHD mortality in humans observed at low doses, where their main properties are related to circulation in the form of free fatty acids. Numerous experimental studies have indicated that low concentrations of exogenous n-3 PUFAs reduce the severity of cardiac arrhythmias. This effect is probably responsible for the protective action of n-3 PUFA on CHD mortality. Further studies are necessary to confirm this assumption in animals. Such studies should take account of the fact that only a low dose of n-3 PUFA (20 mg/kg/day) is necessary to afford protection. Furthermore, since the beneficial effect of n-3 PUFAs on CHD mortality is observed in fish eaters versus no-fish eaters, and since populations in industrialised countries consume excess n-6 PUFAs, control animals in long-term dietary experiments should be fed a diet with only n-6 fatty acids as a source of PUFAs.     

Résistance de la souris et du souriceau à l'hypothermie prolongée à 20° C. Observations portant sur près de 500 animaux

Summary We have found that mice can be made to live for more than 20 h when they are kept in hypothermia at 20 or 23° C without using any pharmacodynamic agents (more than 40 % over the whole of our experiments); a small number of animals succeed in living from 48 to 50 h under such conditions; injections with serum containing glucose allow this limit to be easily surpassed, since a mouse thus lived for 70 h. We have noted no difference in the resistance to prolonged hypothermia between males and females, or between the young mice and the adult ones.     

Acid-base homeostasis and the thyro-parathyroid glands]

Chronic metabolic acidosis entails hyperparathyroidism and osteopathy. In order to elucidate the role of the thyroparathyroids in this bone lesion production the effects of acidic diet for 7 weeks were studied in parathyroidectomized (PTX), thyroparathyroidectomized (TPTX) and shamoperated (Sh-O) growing rats. In all animals urinary excretion of calcium, phosphate, ammonium and titrable acidity was similarly increased. The rise in hydroxyproline excretion and urinary 85-sr (that was injected previous to acidic feeding) was more marked in PTX and TPTX rats. Moreover, in these animals the serum calcium level was increased, the blood pH was decreased. According to these data, an acidic diet intake that is not sufficient to elicit a fall in blood pH of normal young rats can induce severe acidosis in chronically parathyroidectomized or thyroparathyroidectomized animals; moreover the bone resorption appears more marked. It is concluded that parathyroids are involved in the extra-cellular fluid defense mechanism against acidosis by a no bone resorptive mechanism. We hypothesize that the parathyroids permit the necessary and adequate supply of bicarbonates by the bone to maintain blood pH homeostasis.     

Hypolipidemic effects of garlic oil in rats fed ethanol and a high lipid diet

Summary Feeding of ethanol and a high fat-high cholesterol diet to rats markedly increased the total lipids in the liver, and cholesterol and triglyceride levels in the serum, liver and kidneys. However, when ethanol mixed with 0.5% garlic oil was fed to animals maintained on the high fat-high cholesterol diet, these lipid levels were significantly reduced to levels near to those seen in untreated control rats. Garlic oil did not reduce the serum albumin or the total proteins of liver, kidneys or serum when fed along with ethanol. Probably the garlic oil enhances the catabolism of dietary cholesterol and fatty acids.The authors acknowledge with thanks the financial assistance of the University of Maiduguri for carrying out this project.     

Genetic models in brain and behavior research,part IV

Four reviews on the the role of developmental factors in hypertension are introduced and set in historical context. Recent research in the laboratory rat has shown that the preweaning environment makes an important contribution to the level of blod-pressure reached in adult life in genetic models of hypertension. Both of the most commonly used models of hypertension, the SHR and SS/Jr rat strains, exhibit lower BP in adult life, if they are fostered shortly after birth to mothers from their normotensive control strains. It has been suggested that it is the idiosyncratic maternal behavior of the hypertensive mothers which contributes to the elevated BP of their offspring, and it has been amply demonstrated that there is an association between a constellation of behaviors emitted by rat mothers and the adult BP of their offspring in a wide variety of genetic groups (inbred hypertensive animals, F1's and F2's). In addition to the above, maternal environment has been demonstrated to have a significant impact on the pathophysiological response of hypertensive animals to a high salt diet. Being raised by an SHR mother, versus an SS/Jr mother, increases the magnitude of BP increases to a high salt diet, susceptibility to hemorrhagic stroke, body weight loss and the risk of mortality. A variety of physiological systems are undergoing rapid change during the preweaning period and may mediate the effects of differences in the maternal environment. These include the renin-angiotensin system and the peripheral sympathetic nervous system. Nutritional factors may be involved in all of the phenomena referred to above. Thus, any physiological mechanisms that are proposed to link maternal behavior to its effects on the physiology of adult animals should recognize the involvement of nutritional factors. Research on the role of developmental factors such as maternal behavior in genetic models of hypertension is at the interface of two growing disciplines: behavior genetics and developmental psychobiology. The methodological and conceptual contributions of these fields to advancing our understanding of these phenomena is emphasized.     

Nature/nurture and the nature of nurture in the etiology of hypertension.

Four reviews on the the role of developmental factors in hypertension are introduced and set in historical context. Recent research in the laboratory rat has shown that the preweaning environment makes an important contribution to the level of blood-pressure reached in adult life in genetic models of hypertension. Both of the most commonly used models of hypertension, the SHR and SS/Jr rat strains, exhibit lower BP in adult life, if they are fostered shortly after birth to mothers from their normotensive control strains. It has been suggested that it is the idiosyncratic maternal behavior of the hypertensive mothers which contributes to the elevated BP of their offspring, and it has been amply demonstrated that there is an association between a constellation of behaviors emitted by rat mothers and the adult BP of their offspring in a wide variety of genetic groups (inbred hypertensive animals, F1's and F2's). In addition to the above, maternal environment has been demonstrated to have a significant impact on the pathophysiological response of hypertensive animals to a high salt diet. Being raised by an SHR mother, versus an SS/Jr mother, increases the magnitude of BP increases to a high salt diet, susceptibility to hemorrhagic stroke, body weight loss and the risk of mortality. A variety of physiological systems are undergoing rapid change during the preweaning period and may mediate the effects of differences in the maternal environment. These include the renin-angiotensin system and the peripheral sympathetic nervous system. Nutritional factors may be involved in all of the phenomena referred to above. Thus, any physiological mechanisms that are proposed to link maternal behavior to its effects on the physiology of adult animals should recognize the involvement of nutritional factors. Research on the role of developmental factors such as maternal behavior in genetic models of hypertension is at the interface of two growing disciplines: behavior genetics and developmental psychobiology. The methodological and conceptual contributions of these fields to advancing our understanding of these phenomena is emphasized.     

Sleep disturbance due to transportation noise: ear plugs vs oral drugs

Conclusion Sleep is not only the output of an EEG machine but a global phenomenon with unique physiological, environmental and psychological features occurring in a given individual. There is no question that statistical evaluation of noise-induced sleep disturbances in non homogeneous groups of subjects has resulted in the construction of a magnificent neurophysiological edifice by assembling a few individual bricks. In this respect, whether subjectively disturbed or not, we now know that when we sleep in noisy areas our delta sleep is reduced, our heart rate fails to habituate to individual noises, and we are more likely to develop psychic disturbances than residents in quiet areas. Data from these studies are however interspersed with results from a number of experiments during which the subject has been looked upon as nothing but a sleeper, i.e., experiments in which day-time stresses and noises were considered as irrelevant for the night-time study. It seems important therefore that future studies should gather more longitudinal data based on a limited number of subjects selected according to their day-time habits and psychological (e.g., extroverts/introverts) and physiological (e.g., short or long sleepers) characteristics. The knowledge about these situational factors and personality traits might provide new insights into individual biological strategies developed to cope with noise stress. The difficulties in assessing the effect of noise on sleep are particularly obvious if we consider another finding: deaf subjects spend significantly less time in delta sleep than do control subjects⁴⁷ and they present sleep pattern alterations remarkably similar to those which are most consistently described in noisy conditions.Research by the authors has been supported by grants from the Ministère de la Qualité de la Vie et de l'Environnement (France) and Commission of European Communities.     

The diet and gut microflora influence the distribution of enteroendocrine cells in the rat intestine

Several functions of the gut are locally influenced by peptides and biogenic amines released from enteroendocrine cells. The aim of the present study was to assess whether the luminal stimulus of diet or microbial flora or diet-microbial interactions have an influence on the distribution of enteroendocrine cells along the crypt-surface axes of the small and large intestine. The effects of diet and indigenous flora were investigated by comparing the numbers of argyrophil and serotonin immunoreactive cells in the jejunum and colon of germ free and conventional rats fed either a purified diet containing fine ingredients or a commercial diet containing crude fibre of cereal origin. The effects of human flora were analysed in germ-free rats inoculated with human faecal organisms. 1. Feeding the commercial diet reduced the number of argyrophil endocrine cells in the jejunum and serotonin immunoreactive cells in the colon of gern-free animals but increased the serotonin immunoreactive cells in the colon of conventional animals. 2. The rat flora increased the serotonin immunoreactive cells in the colon of animals fed a commercial diet and decreased in those fed a purified diet. 3. Inculation of human flora increased the numbers of serotonin immunoreactive cells both in the jejunum and colon. The results provide evidence that the dietary changes and diet-microbial interactions can affect the regional number of enteroendocrine cells.     

Vitamin D and reproduction in Wistar rats]

Females have received from weaning a semi-synthetic diet (0,35% Ca; 0,32% P; 0,03% Mg), with or without vitamin D (+/- D). Fertility of these females was not changed. At weaning, the young from mothers--D had lower weight, calcemia and phosphatemia, but the ash content of the femur was the same as for young from mothers + D. Young rats from mothers +/- D were given the diet with or without vitamin D. 19 days after weaning, the diet of the mother (+/- D) appears to be the principal factor for growth, calcemia and the ash content of the femur; the diet of the young (+/- D) produced only slight differences between ash contents.     

Ovarian stimulation by exogenous gonadotrophins in fetal ethanol-exposed immature rats

Adult pregnant rats were given either an ad libitum liquid diet containing 5% ethanol, a pair fed liquid diet or an ad libitum diet of rat chow and water administered throughout pregnancy and during the nursing period. The female offspring received either pregnant mare's serum gonadotrophin (PMSG) or PMSG followed by human chorionic gonadotrophin (hCG) at 30 days of age. The ovaries of fetal ethanol-exposed animals responded greater to the exogenous gonadotrophins with enhanced ovarian weights, increased numbers of ova shed, greater numbers of corpora lutea and antral follicles, and higher serum progesterone levels than in animals exposed to the control diets during gestation.     

Histamine deficiency suppresses murine haptoglobin production and modifies hepatic protein tyrosine phosphorylation

Histidine decarboxylase (HDC) synthesizes endogenous histamine from histidine in mammals. HDC- deficient mice (HDC-/-), if kept on a histamine-free diet, have no histamine in their tissues. HDC-/- mice show multiple phenotypes. In this study we show that both the constitutively expressed and turpentine-induced level of an acute-phase protein, haptoglobin, is significantly lower in the serum of HDC-/- mice compared to that of wild-type animals. This effect was abolished if HDC gene-targeted mice received histamine-rich food. No differences were found when lipopolysaccharide (LPS) was used to induce the acute-phase reaction. Using specific antibodies to phosphorylated tyrosine, we showed that protein tyrosine phosphorylation (Y-P) of ~50- and 26- to 27-kDa liver proteins is significantly decreased in HDC-/- mice, but that the difference was largely diminished if the animals were kept on a histamine-rich diet, suggesting that the phenotype with lower haptoglobin production is diet inducible. Upon in vivo treatment with LPS, Y-P band intensity decreased, regardless of the presence or absence of histamine. Identification of elements of the signalling pathway with decreased phosphorylation may elucidate the molecular background of the effect of endogenous histamine in the hepatic acute-phase reaction. Received 14 February 2001; received after revision 28 March 2001; accepted 4 April 2001     

Ovarian stimulation by exogenous gonadotrophins in fetal ethanol-exposed immature rats

Summary Adult pregnant rats were given either an ad libitum liquid diet containing 5% ethanol, a pair fed liquid diet or an ad libitum diet of rat chow and water administered throughout pregnancy and during the nursing period. The female offspring received either pregnant mare's serum gonadotrophin (PMSG) or PMSG followed by human chorionic gonadotrophin (hCG) at 30 days of age. The ovaries of fetal ethanol-exposed animals responded greater to the exogeneous gonadotrophins with enhanced ovarian weights, increased numbers of ova shed, greater numbers of corpora lutea and antral follicles, and higher serum progesterone levels than in animals exposed to the control diets during gestation.     

A preliminary study on the behaviour and biochemical responses subsequent to the injection of 5,6-dihydroxytryptamine into the substantia nigra of the rat.

Injection of 5,7-dihydroxytryptamine into the substantia nigra of rats produces an increase of dopamine in the ipsilateral striatum, and when these animals are injected with amphetamine they do not exhibit any rotation. The mode of action of this neurotoxin is compared with that of 6-hydroxydopamine.     

Cinétique de l'inhibition de l'oxydation cuprique de l'acide ascorbique par certains complexants

Summary The authors studied the kinetics of the inhibition of the copper-catalysed oxydation of ascorbic acid by versene and some proteins. The versene-inhibition attains slowly the theoretical value, when added after the Cu⁺⁺ to ascorbic acid. Proteins inhibit non-competitively and completely, when added to the vitamine either after or before the copper. This result may be interpreted as indicating an interaction between protein and the complex (AH-Cu⁺⁺).

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Note N^o 2 sur l'oxydation cuprique de l'acide ascorbique. Note N^o 1, voir réf.³.