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Biomedical subjects

A Legrand

Publications and source records attributed to A Legrand.

At least 145 records · Page 8Linked to original sources

Distribution of thiobarbituric acid-reactive substances in lipoproteins and proteins in serum.

We assessed the distribution of malondialdehyde (MDA) in lipoproteins and proteins in serum after using two procedures to separate the lipoproteins: sequential ultracentrifugation or selective precipitation with a sodium phosphotungstate and magnesium chloride reagent followed by ultracentrifugation of the supernate. MDA concentrations were determined by the thiobarbituric acid reaction and quantified by fluorometry. We found that 43% of the thiobarbituric acid-reactive substances (TBARS) was bound to the lipoproteins--27% to very-low- and low-density lipoproteins (VLDL-LDL) and 16% to high-density lipoproteins (HDL)--and from 11.5% to 15.8% to proteins, depending on the separation procedure. Residual unbound TBARS were located in the ultracentrifugation layers that contained no lipoproteins or proteins. The TBARS concentration in serum lipoproteins containing apolipoprotein B (i.e., VLDL-LDL) was the same after ultracentrifugation or selective precipitation. We therefore consider the precipitation method more suitable for routine TBARS determination in these lipoproteins, because it is easier to handle and faster. However, for determination of TBARS in HDL, selective precipitation requires subsequent ultracentrifugation at a density of 1.21 kg/L.

Adult↗

Biologically active, recombinant DNA in clathrin-coated vesicles isolated from rat livers after in vivo injection of liposome-encapsulated DNA.

DNA entrapped in liposomes containing lactosylceramide in the bilayers is found to be associated with clathrin-coated vesicles isolated from the rat livers after intravenous injection of these liposomes. The presence of the exogenous DNA in the coated vesicles was detected by Southern blotting. The amount of DNA present in the coated vesicles does not appear to vary up to 4 h after injection of the liposomes into the animals. The recognition of the lactosyl group present in the liposome by the galactose receptor present on the surface of the different liver cells may lead to their internalization in a way analogous to receptor-mediated endocytosis of various macromolecules. DNA present in the lumen of the coated vesicles is found to be biologically active as evidenced by its replication in bacterial cells and mouse fibroblasts.

Animals↗

[Testicular function during prolonged corticotherapy].

Prolonged corticosteroid therapy produces a major degree of protein catabolism. Short-term treatment with ACTH or glucocorticoids results, in males, in a fall in plasma testosterone levels. In order to determine the origin of this hypogonadism, the testicular function was investigated in 18 men under prolonged glucocorticoid treatment. The mean plasma testosterone level in men treated for less than 3 months (5.9 +/- 0.8 ng/ml) was not statistically different from that obtained in controls (7.5 +/- 0.5 ng/ml; P greater than 0.05). However, the mean plasma luteinizing hormone level was significantly higher in these patients than in controls (8.2 +/- 1.9 mUl/ml vs 3.6 +/- mUl/ml respectively; P less than 0.001). In patients treated for more than 2 years, the mean plasma testosterone level (3.8 +/- 0.6 ng/ml) was significantly lower than in controls (P less than 0.001), but the mean plasma luteinizing hormone level was normal (5 +/- 1 mUl/ml). Plasma testosterone levels are negatively correlated with the daily dose of glucocorticoid (r = -0.81; P less than 0.001). The free testosterone index was within normal range in 5 of the 9 men under prolonged steroid therapy, near the lower limit of normality in 2 men and definitely low in 2 other men. The gonadotrophin response to the luteinizing hormone releasing hormone was normal, whereas the testicular response to human chorionic gonadotrophin was reduced. These data suggest that prolonged treatment with steroidal anti-inflammatory agents influences both gonadotrophic and testicular function and may be associated with true hypoandrogenism.

Adrenal Cortex Hormones↗

[Contribution of Jacques Canal in the field of lipoproteins].

The scientific works of J. Canal have essentially related to low density lipoproteins (L.D.L.), between 1.025 and 1.050. By using proteolytic enzymes and phospholipases, he is able to obtain informations on the accessibility of apolipoprotein B and phospholipids. So, as early as 1975, he expresses the hypothesis that only 30 p. cent of Apo B occupy a superficial position. In addition, he proposes the fact that Apo B has at least four antigenic determinants; this hypothesis formulated by J. Canal, almost 10 years ago, was recently confirmed by using monoclonal antibodies. At the same time, using phospholipases, J. Canal reaches the conclusion that phospholipids are localized on the surface of L.D.L. He demonstrates that phospholipids play a major role in the precipitation of L.D.L. by sulfate polysaccharides in the presence of L.D.L. by sulfated polysaccharides in the presence of divalent cations (Reaction of Burnstein). He proposes a mechanism for this reaction. This research on the mechanism of Burnstein's reaction will receive in clinical biochemistry an important application with the development of a completely original technique of dosage of total lipids in the serum.

France↗

[Value and indications for nipple stimulation in obstetrics].

The authors have evaluated the effect of stimulation of the breast on uterine tone in a series of 25 patients at term where induction of labour was indicated for obstetric reasons. In 64% of cases breast stimulation carried out for 30 minutes was followed by uterine contractions. In 20% of these cases the authors found that the uterus contracted strongly and in two patients so strongly as to cause fetal heart slowing. Breast stimulation matures the cervix slightly but this is not statistically significant for Bishop's score. In 16% of case breast stimulation provoked labour. Analysing these results and studying the literature shows that the effect is linked to the degree of cervical maturity at the onset and the effect of stimulation depends also on the length of time the stimulation was carried out. In practice the use of breast stimulation is limited because of the risks of hypertonic contractions and this is turn requires careful fetal heart monitoring.

Adolescent↗

Isolation and characterization of an abnormal alpha slow-moving high-density lipoprotein subfraction in serum from children with long-standing cholestasis.

An abnormal high-density lipoprotein (HDL) subfraction, detected during periods of mild jaundice in the serum of seven children with chronic cholestasis from birth, was isolated and characterized. This fraction, identified by its slow alpha electrophoretic migration, is present in addition to normal HDL and differs from the abnormal HDL previously described in cholestatic syndromes. It is devoid of apolipoprotein B but is precipitated by phosphotungstate-MgCl2. These properties allowed its isolation by double selective precipitation. This subfraction is undetectable with this procedure in the serum of healthy subjects, is rich in cholesterol, and contains a large amount of apolipoprotein E, which may explain its precipitation by phosphotungstate-MgCl2. These apo E-containing HDL may play a major role in the lipid metabolism of patients with long-standing cholestasis during periods of mild jaundice.

Adolescent↗

Effects of nifedipine on responses to exercise in normal subjects.

The responses to sublingual nifedipine (20 mg) and placebo were compared in normal subjects during two studies on cycle ergometer [progressive exercise and constant work-load exercise at approximately 60% of maximal O2 consumption (VO2max)]. The use of nifedipine did not modify maximal power, ventilation (VE), VO2, and heart rate (HR) at the end of the multistage progressive exercise (30-W increments every 3 min). Over the 45 min of the constant-load exercise and the ensuing 30-min recovery we observed with nifedipine compared with placebo 1) no differences in VO2, VE, respiratory exchange ratio, and systolic arterial blood pressure; 2) a higher HR (P less than 0.001) and lower diastolic arterial blood pressure (P less than 0.01); 3) a greater and more prolonged rise in norepinephrine (P less than 0.01) and growth hormone (P less than 0.001); 4) no significant differences in epinephrine and insulin and a lesser increase in glucagon during recovery (P less than 0.01); and 5) a lesser fall in blood glucose (P less than 0.01) and greater increase in acetoacetate (P less than 0.001), beta-hydroxybutyrate (P less than 0.05), and blood lactate (P less than 0.001). Our data do not support the hypothesis that nifedipine reduces hormonal secretions in vivo and are best explained by an enhanced secretion of catecholamines compensating for the primary vasodilator effect of nifedipine.

3-Hydroxybutyric Acid↗

Arachidonic acid metabolism and inhibition of cyclooxygenase in platelets from asthmatic subjects with aspirin intolerance.

Exaggerated inhibition of cyclooxygenase has been proposed as a mechanism of drug-induced bronchospasm in aspirin-intolerant patients. This study, using platelets, shows that inhibition of prostaglandin biosynthesis by aspirin is unmodified in patients when compared with healthy subjects. The ratio of cyclooxygenase:lipoxygenase products is similar in platelets from patients and control subjects. We conclude that the cyclooxygenase alteration observed in cells from the respiratory tract is not generalised to other cells such as platelets. We also propose that the major abnormality in NSAID-intolerant patients would affect receptivity to lipoxygenase products more than their biosynthesis.

Arachidonic Acid↗

Anti-inflammatory activity of a dual inhibitor of cyclooxygenase and lipoxygenase pathways, CBS-1108 (2-acetylthiophene-2-thiazolylhydrazone).

Anti-inflammatory therapy is actually devolved to glucocorticoids which prevent the release of arachidonic acid from phospholipids and consequently its subsequent transformation into prostaglandins and leukotrienes. This activity explains in part why steroids are better anti-inflammatory agents than acetylsalicylic acid (ASA)-like drugs which only reduce prostaglandin production. Despite their superior therapeutic actions, there are many side effects associated with corticosteroids. Therefore in recent years, research of non-steroid dual inhibitors of prostaglandin and leukotriene production has been developed. The present paper investigates the pharmacological activity of such a new compound, CBS-1108 (2-acetylthiophene-2-thiazolylhydrazone), in comparison with dexamethasone, cyclooxygenase inhibitors (ASA and indomethacin) and reference dual inhibitors (nordihydroguaiaretic acid (NDGA) and 3-amino-1-(m-trifluoromethylphenyl)-2-pyrazoline (BW-755 C]. The two-pathway inhibitors and ASA-like drugs are similarly effective on paracentesis-induced disruption of the blood-aqueous barrier and on croton oil-induced ear edema. On the contrary in an animal model of leukocyte migration and on mast cell degranulation, NDGA and CBS-1108 are very active when the other tested compounds are inefficient.

Animals↗

Liposomes for gene transfer and expression in vivo.

A recombinant plasmid encoding rat preproinsulin I was encapsulated in large liposomes and injected intravenously into rats. Glycaemia and blood, splenic and hepatic insulin were assayed from 6 h after inoculation. Control animals received (i) empty liposomes, (ii) liposomes carrying the Escherichia coli pBR 322 plasmid, (iii) the free rat insulin I gene, or (iv) no injection. All controls showed unchanged glucose and insulin levels. Six hours after inoculation the treated rats had 72 +/- 5 mg glucose/100 ml of blood, compared with 107 +/- 2 mg/ml for controls. Radioimmunoassay of blood insulin gave 61 +/- 8 microunits/ml (43 +/- 5 microunits/ml for controls). Spleen and liver values were 242 +/- 22 and 204 +/- 20 microunits/g of tissue, respectively (112 +/- 20 and 87 +/- 15 microunits/g in controls). The kinetics and extent of uptake of liposomes by spleen and liver were studied by external gamma-camera imaging after injection of 111In-labelled liposomes. The results paralleled insulin synthesis in the two organs. The insulin gene was localized in liver cells after injection of liposomes containing the plasmid encoding the gene. Livers were processed 4 h after inoculation for isolation of hepatocytes, Kupffer cells and endothelial cells. DNA was purified and exogenous DNA detected by Southern blotting. Kupffer cells were the primary target for gene incorporation with liposomes consisting of phospholipids and cholesterol. Targeting of liposomes to other liver cells was attempted by including lactosylceramide in the liposomes. This increased the amount of the exogenous gene in hepatocytes and particularly in endothelial cells. The efficiency of liposome-mediated gene transfer in vivo is high, since a few per cent of the transferred DNA is taken up by the liver cells and detected.

Animals↗

Inhibition of rat mast cell degranulation by verapamil.

Calcium antagonists, e.g. verapamil, prevent exercise-induced asthma. This protective effect may proceed from inhibition of contraction of bronchial smooth muscle, release of mediators by primary effector cells, e.g. mast cells, or both. Therefore, we studied the inhibitory effect of increasing concentrations of verapamil on both in vitro antigen-induced degranulation and ionophore A23187-induced release of labelled serotonin by rat peritoneal mast cells. There was a dose-dependent inhibition by verapamil of both ovalbumin-induced degranulation of mast cells passively sensitized by incubation with mice IgE-rich serum and ionophore-induced release of tritiated serotonin by mast cells previously incubated with (3H)-5HT; the 50% inhibiting concentration was 1.4 X 10(-4) mol I-1 and 5.2 X 10(-5) mol I-1, respectively. An attractive explanation of our results is that verapamil inhibits the antigen-induced release of mediators by mast cells through its calcium antagonist effect. Our results also suggest that the preventing effect of calcium antagonists on asthma may be multi-factorial since other authors have clearly shown that these drugs inhibit contraction of guinea-pig tracheal smooth muscle in vitro.

Animals↗

[Coronary spasm during repeated anesthesia].

Coronary arterial spasm observed during the course of two repeated anaesthesias in a patient having undergone aorto-femoral bypass grafting is reported by the authors. Such complications are accompanied by serious ventricular arrhythmias, though transient and healing without sequelae. Clinical and electrocardiographic characteristics of peroperative coronary arterial spasm are underlined. In patients prone to developing such spasm, peroperative alkalosis, hypothermia and parasympathetic stimuli should be avoided. Are emphasized the efficiency of preventive treatment with calcium antagonists and that of intravenous nitroglycerin in the treatment of peroperative coronary arterial spasm when it does occur.

Alkalosis↗

Targeted and nontargeted liposomes for in vivo transfer to rat liver cells of a plasmid containing the preproinsulin I gene.

A plasmid containing the rat preproinsulin I gene was entrapped in large liposomes and intravenously administered to rats. Four hours after inoculation, the livers were processed for the isolation of hepatocytes. Kupffer cells, and endothelial cells, DNA was purified, and the exogenous DNA was detected in the different cell DNA preparations by Southern blotting. By using liposomes consisting of phospholipids and cholesterol, Kupffer cells were shown to be, on a per cell basis, the primary target for gene incorporation. In an attempt to target the liposomes to other liver cells, a glycolipid, lactosylceramide, was included in the lipid bilayer of the liposomes; this resulted in a substantial increase in the proportion of the exogenous gene in the hepatocytes and mainly in the endothelial cells, with a simultaneous decrease of this proportion in the Kupffer cells. Thus, it is shown that inclusion of a specific glycolipid within the bilayer of the liposomes may direct the DNA-containing vesicles to specific cell types in the liver.

Animals↗

[Cyproterone acetate. 15 cases of hirsutism treated for 1 year].

Fifteen women with idiopathic hirsutism (N = 11) or hirsutism with androgen excess (N = 4) were treated by Cyproterone acetate orally (50 mg from the 5 th to the 25 th day of the menstrual cycle) and Ethinyl Estradiol (day 15-25). Hirsutism was improved in 86% of cases with progressive improvement at 3, 6, 12 months. At 12 months, the clinical score for hirsutism was 56% of the original score. Disturbance of menstrual cycles was more frequent than reported with Hammerstein's pattern of treatment. Clinical and biological tolerance was good. delta 4 androstenedione decreased significantly at 6 months (respectively 2,26 ng/ml - 1,25 ng/ml). There was no significant decrease of plasma testosterone. Result of B 1-24 corticotropin test remained normal after 12 months of treatment.

Administration, Oral↗

[Study of corticotropic function: respective values of short tests using metropirone and exogenous ACTH regardless of the hour administered].

Basal plasma cortisol levels and adrenal responses to stimulation by endogenous and exogenous ACTH were compared between a group of controls and a group of patients with corticotrophic insufficiency. In addition, the adrenal response to the administration of exogenous ACTH was compared in each of these groups in relation to the timing of the test. There was a clear parallel between respective adrenal responses to exogenous ACTH and endogenous ACTH. Adrenal stimulation by exogenous ACTH may be used to investigate the residual secretion of endogenous ACTH and in the diagnosis or corticotrophic insufficiency, when a lesion interrupting functional hypothalamo-pituitary connections has been excluded. In the opposing case, use of a short test with metopirone is essential in order to confirm corticotrophic insufficiency. This test is better tolerated than the classical test and is not subject to sources of error due to urine collections.

Adrenal Cortex Function Tests↗