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Biomedical subjects

M Clabaut

Publications and source records attributed to M Clabaut.

At least 19 recordsLinked to original sources

Developmental changes of (3)H-labelled mu-opioid receptors in brainstems of intra-uterine growth-restricted rats.

The opioid mu-system is involved in brainstem-mediated respiratory control. Infants with intra-uterine growth restriction (IUGR) have more respiratory disorders in the early postnatal period. Using [(3)H]DAGO, a mu-selective ligand, and a computer-based image analysis of autoradiography, we compared the ontogeny and distribution of mu-opioid binding sites in the brainstem of IUGR and control rats in utero (E21), at birth (P0) and on postnatal days 1 (P1), P7, P10, P14 and P21. The ontogeny pattern was found to be similar in both groups. The density of the binding sites, which was low in E21, increased at P0, slightly declined at P1 and remained relatively constant thereafter. The distribution of DAGO-binding sites, also similar in both groups, was heterogeneous and was much denser in the dorsal areas of medulla and pons. In particular, binding sites were highly concentrated in nuclei involved in the cardio-respiratory function. However, DAGO-binding density was higher at all ages (except for P0 and P1) in IUGR than in control rats. Taken together, these results give at least a partial explanation for the effects of IUGR which lowers the Apgar score at birth and raises the incidence of respiratory disorders in infants.

Aging↗

Effects of RU 486 on electrical activity, on sexual steroid and prostaglandin F2 alpha concentrations in the myometrium at mid-pregnancy in the rat.

Effects of RU 486 (10 mg.kg-1, per.os) were assessed at mid-pregnancy in the rat. One hour after RU 486 treatment, myometrial electrical activity stayed low. It increased from the 3rd hour after administration of RU 486 and a perfect synchronization of the bursts of the action potentials was observed from the 6th h to the 24th h. Tissular steroid hormones and PGF2 alpha, evaluated at hour 6 after RU 486 administration, showed a decrease of progesterone concentrations in both myometrium and uterus. Estradiol levels decreased in uterus whereas, PGF2 alpha levels increased in both myometrium and uterus. These results show for the first time that RU 486 strongly increases the myometrial electrical activity in the rat at mid-pregnancy. This action was closely related to E2, P4 and PGF2 alpha concentrations.

Animals↗

Developmental changes in cardio-respiratory responses to hypoxia and hypercapnia in anesthetized low-birth-weight rats.

The present study compared the developmental changes in the cardio-respiratory responses to hypoxia and hypercapnia between full-term low-birth-weight (LBW) and control rats during the postnatal period. The heart rate (HR), respiratory frequency (fR) and amplitude (aR) were measured during hypoxia (10% O(2) for 10 min) and hypercapnia (5% CO(2) for 10 min) in rats aged 7, 14 and 21 days, anesthetized with urethane. During hypoxia, HR was not significantly modified in the younger rats of both groups. In the older rats, aged 14 and 21 days, HR was markedly diminished, with a more pronounced decrease in LBW rats. The HR recovery was never observed in the older LBW rats. The fR and aR showed an age-related increase in both groups: a biphasic fR pattern observed on day 7 was replaced by a sustained increase on days 14 and 21. In contrast to controls, LBW rats never displayed a fR recovery during reoxygenation. In controls, aR shifted from a biphasic pattern in the younger rats to a sustained increase in the older ones. The LBW rats only displayed a decrease of aR in the younger, while in the older ones, a transient and slight increase preceded this decrease. During hypercapnia, the only significant difference detected between these two groups was that aR increased in LBW rats to a greater extent than in controls on days 14 and 21. Altogether, our results revealed a markedly attenuated cardio-respiratory response to hypoxia in LBW rats, but no such effect in response to hypercapnia.

Anesthesia↗

Increase of myometrial activity correlated with variations in 17 beta-estradiol and progesterone uterine concentrations in mid-term pregnant rat: estrogen agonist effect of 4-hydroxytamoxifen.

The objective of this investigation was to examine the effects of 4-hydroxytamoxifen on the uterine activity. For this, we evaluated the electrical activity of the myometrium, chronically, in conscious unrestrained rats at mid-pregnancy. We also examined the tissular progesterone and 17 beta-estradiol concentrations in the myometrium and uterus 6 hours after administration of 4-hydroxytamoxifen. Comparison of myometrial electrical activities recorded during the control period with those obtained during the two periods (6 and 24 hours) after administration of 4-hydroxytamoxifen (80 micrograms.kg-1, s.c.) showed an increase in simultaneity of uterine contractions (P < 0.01). Tissular steroid hormone measurement by radioimmunoassay shows a fall of progesterone in the myometrium (P < 0.001) and of 17 beta-estradiol in the uterus (P < 0.01), 6 hours after administration of 4-hydroxytamoxifen. In the myometrium, for 50% of animals, 17 beta-estradiol concentration decreased (P < 0.01) and for 50% of animals it increased (P < 0.05). The decrease in progesterone is significant in the myometrium and in the whole uterus (respectively P < 0.001 and P < 0.01), 24 hours after administration of 4-hydroxytamoxifen. The 17 beta-estradiol concentration significantly decreased for all animals in the myometrium (P < 0.01) and in the uterus (P < 0.01), after this time. It appears that variation in progesterone induces the activation of uterine motility and exerts an effect on some factors involved in the regulation of the rat myometrium at mid-pregnancy.

Analysis of Variance↗

Beneficial effect induced by a beta-adrenoceptor blocker on fetal growth in streptozotocin-diabetic rats.

Treatment by a beta 1-beta 2-adrenoceptor antagonist has been much used during pathological pregnancies. These agents can reduce the oxygen consumption of the myocardium, increase the coronary blood flow towards ischemic heart areas and improve return of venous blood flow towards the heart. The aim of this study was to determine the mechanism of action of this agent and to investigate whether a total beta-adrenoceptor antagonist could reduce the fetoplacental disorders elicited in streptozotocin-diabetic pregnant rats. Diabetes was engendered on day 7.5 of pregnancy, and the animals were studied on day 21. Untreated nondiabetic rats or nondiabetic rats treated with propranolol, a total beta-adrenoceptor blocker (2 mg kg-1/ day, i.p.), had a healthy placenta without vascular disturbances, with normal arterial blood velocity in the uterine artery, placenta, umbilical cord and fetal aorta, and showed eutrophic fetuses (3.9 +/- 0.0 g, mean +/- SEM). Untreated diabetic rats had severe placental lesions, with a reduction of arterial blood velocity in the uterine artery (p < 0.01), placenta (p < 0.01) and umbilical artery (p < 0.05), and exhibited fetal hypotrophy (2.3 +/- 0.1 g, mean +/- SEM, p < 0.001) compared with nondiabetic untreated rats. Treatment of diabetic rats with propranolol (2 mg kg-1/day, i.p.) enhanced fetal weight (3.66 +/- 0.2 g) and slightly increased fetal insulin secretion, restored arterial blood velocity to control values in the uterine artery and fetal aorta and reduced placental lesions. In conclusion, our results suggest that the beneficial effects of propranolol were at least in part related to an improvement of uteroplacental hemodynamics; it induced a better redistribution of the blood towards the placenta and the fetal systemic circulation. Propranolol treatment could protect cell membranes against free oxygen radicals and lipid peroxidation, involved in the pathogenesis of ischemic injury in diabetes.

Abortion, Veterinary↗

Comparison of oral bioavailability of two dosage-forms of progesterone in women.

For poorly water soluble drugs, the dissolution process in biological fluids the rate limiting step in absorption. However, the utilization of some galenic processes such as solid dispersions (SD) leads to an improvement in quality and intensity of the drug gastro-intestinal absorption. In a previous work, the in vitro studies of the dissolution curves of both the pure micronized progesterone (MP) and the progesterone-PEG 6000 SD revealed marked increases in the progesterone dissolution rates for all the SD investigated compared to the pure MP. The aim of this work was to investigate the in vitro results after oral administration of the two pharmaceutical forms to menopaused volunteer women.

Administration, Oral↗

Influence of an alpha-1-adrenoceptor antagonist, nicergoline, on placental prostanoid production in streptozotocin-induced diabetic pregnant rats.

The aim of this study was to determine if placental prostanoids could mediate the vasodilating action of an alpha-1-adrenoceptor antagonist, nicergoline (400 micrograms/kg i.p.), during late pregnancy in streptozotocin-induced diabetic rats (40 mg/kg i.v.). Placental prostanoid concentrations were evaluated by radioimmunoassay. Prostaglandin E2 levels showed a highly significant increase in diabetic and nondiabetic rats treated with nicergoline (p less than 0.001). 6-Keto-PGF1 alpha concentrations were slightly increased in diabetic rats compared to controls, and this increase was reversed by both nicergoline and insulin treatments. In all groups studied thromboxane B2 levels were comparable. It is concluded that prostaglandin E2 could mediate the vasodilating action of nicergoline on the placental irrigation and, therefore, improved the hemodynamic state of this organ in diabetic rats.

6-Ketoprostaglandin F1 alpha↗

Increase in uterine prostaglandin E2, F2 alpha, prostacyclin and stability in thromboxane A2 production during late pregnancy in streptozotocin-induced diabetic rats.

This experiment was conducted to determine the effect of diabetes on uterine prostanoids production in near-term rats. The incidence of an insulin therapy was also studied. On the 21st day of pregnancy, uterine PGE2, PGF2 alpha and PGI2 levels showed a significant increase (respectively p less than 0.05, p less than 0.01 and p less than 0.05) in diabetic rats compared to controls whereas TxA2 production remained unchanged. The insulin therapy restored PGE2 levels, the most potent stimulatory factor of the myometrial fiber at control values, whereas it enhanced significantly PGI2 concentrations (p less than 0.05) and had no effect on PGF2 alpha production; TxA2 levels remaining always unchanged. It is suggested that the increase in uterine protanolds production during diabetes could induce a myometrial hypertonicity and play a role in the disturbances of the fetal development. The maintenance of PGE2 levels to control values by the insulin therapy might contribute to a normal delivery.

6-Ketoprostaglandin F1 alpha↗

Increase of uterine motility and simultaneous decrease of progesterone concentrations in the rat after bilateral ovariectomy at mid-pregnancy.

Comparison of uterine activities recorded during the control period to those obtained during the two recording periods after ovariectomy (0-30 min and 30-60 min) showed an increase of the amplitude of uterine contractions (P less than 0.005) and a decrease of the interval between two successive uterine contractions (P less than 0.005) and the delay of electrical activities (P less than 0.005). Progesterone treatment (50 mg/kg i.m.) of ovariectomized rats prevented the abrupt fall in plasma progesterone concentrations, measured by RIA, which in turn inhibited the increase of uterine mechanical and electrical activities. A close relation between the increase of myometrial activity and the decrease of progesterone concentrations after ovariectomy is suggested. The activation of the myometrium would be principally induced by the fall of progesterone or by the variation of the oestrogen/progesterone ratio; these changes in sexual steroid hormones would augment the uterine sensitivity to physiological stimuli or modify the activity of other factors involved in the regulation of the myometrium.

Animals↗

Variation of myometrial activities and steroid sexual hormones following bilateral ovariectomy in the rat at midpregnancy.

The effects of bilateral ovariectomy on uterine motility and levels of progesterone, oestradiol, cAMP, adrenaline and PGF2 alpha were studied in the rat at midpregnancy. Animals were randomly divided into two groups, at least 15 rats in each, sham-operated serving as controls and ovariectomized. The spontaneous uterine mechanical activity of Wistar rats was recorded isometrically and the electrical activities were recorded simultaneously by two bipolar electrodes. Within 30 minutes of ovariectomy a significant increase of the amplitude of uterine contractions was observed and the simultaneity of electrical activity was significantly improved; these effects became more pronounced at 1h post-ovariectomy (p less than 0.005). Plasma progesterone levels decreased by 20% (p less than 0.01) at 30 min and by 50% (p less than 0.001) 1h after ovariectomy, whereas oestrogen levels remained unchanged. Levels of adrenaline, cAMP and PGF2 alpha in the uterine tissue 1h following ovariectomy were affected as follows: adrenaline (p less than 0.05) and cAMP (p less than 0.001) were reduced and PGF2 alpha augmented (p less than 0.05). It appears that variation of the ratio oestrogens/progesterone induces precociously the activation of uterine mobility and exerts an effect on some factors involved in the regulation of the rat myometrium at midpregnancy.

Animals↗

Myometrial responses in situ to nicergoline, acebutolol, phentolamine and noradrenaline of the rat in proestrus.

The effects of two adrenoceptor antagonists, nicergoline (alpha 1) and acebutolol (beta 1), on the contraction of myometrium in the proestrous rat were compared to those of noradrenaline and phentolamine. The spontaneous myometrial contractions of Wistar rats on the day of proestrus were recorded isometrically and the data were analysed using Wilcoxon non-parametric statistics. All drugs were administered i.v. and the doses are expressed as microgram/kg body weight. Noradrenaline (1200 micrograms/kg per h) induced a 32.5% reduction (P less than 0.001) of the uterine contraction amplitude. Nicergoline did not alter uterine motility significantly when administered alone at doses ranging from 400 to 1600 micrograms/kg. However, successive injections of nicergoline in the same range given during noradrenaline infusion at 600 micrograms/kg per h potentiated the relaxing action of the latter (38%, P less than 0.01). Phentolamine (120 micrograms/kg) reduced myometrial activity by 25% (P less than 0.05). This inhibitory response rose to 65% (P less than 0.001) when the dose of phentolamine was increased to 960 micrograms/kg. When a single injection of nicergoline (400 micrograms/kg) was followed by the administration of increasing doses of acebutolol (120, 1200, 2400 micrograms/kg) the slight inhibitory effect on uterine motility observed after administration of each of the two agents separately became more pronounced (P less than 0.05). It appears from these results that combining noradrenaline with nicergoline and nicergoline with acebutolol leads to potentiation of their relaxing effects. Furthermore the results confirm that nicergoline is a partial alpha-blocker.

Acebutolol↗

[Renal function and histologic studies in rats treated by floctafenin (author's transl)].

The nephrotoxic action of floctafenin has been studied in rats. When administered orally at 20 or 50 mg/kg/day for 20 or 50 days, this analgesic agent had no effect on the renal function, either in intact rats or in animal with reduced renal parenchyma. There is no histological change in the kidneys of the treated animals except some focal dilatations of the distal tubules. The tubular alterations were more important in treated and untreated rats with nephronic reduction. The whole body autoradiographic studies of rats treated with 14C floctafenin showed that liver and kidney accumulate radioactivity, and that the intake of radiolabeled compounds is twice higher in renal cortex than in medulla. This study suggests that the toxicity of floctafenin for the rat kidney is very low or none.

Animals↗