Effect of a short term oral treatment by phenobarbital propranolol and amiodarone in rat on serum levels of fluorescent lipid-peroxidation products.
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Amiodarone↗
Biomedical subjects
R Vassy
Publications and source records attributed to R Vassy.
Amiodarone: influence of the route of administration on thyroid status and cardiac beta-adrenoceptors in the rat.
The influence of 2 different routes of amiodarone (AMIO) administration, oral gavage (OG) and subcutaneous injection (SC), on the density of cardiac beta-adrenoceptors (Bmax), hepatic type I 5' iodothyronine deiodinase (5' DI) and thyroid hormone serum concentrations was studied. Compared with respective control values, AMIO treatment (50 mg/kg per day, 7 days) via both OG and SC routes significantly lowered Bmax (OG: 14.6 +/- 1.92 vs 18.2 +/- 1.03 fmol/mg and SC: 16.6 +/- 2.34 vs 19.1 +/- 2.05 fmol/mg) and 5' DI activity (from 409 to 85 and 340 to 47 fmol I-/mg per min, respectively). The SC route induced a fall in thyroid secretion and a generalized hypothyroidism (decreased serum FT4 and FT3, inhibition of body weight gain. The OG route did not modify thyroid secretion. These results demonstrated that the effects on cardiac beta-receptor density in the SC group might be due to the generalized hypothyroidism and that AMIO produced its specific cardiac effects only after oral route medication, suggesting that the oral route is the best choice for studying AMIO cardiac effects on beta-receptor density.
Administration, Oral↗
Effects of troleandomycin and josamycin on thyroid hormone and steroid serum levels, liver function tests and microsomal monooxygenases in healthy volunteers: a double blind placebo-controlled study.
Serum TSH levels are moderately but significantly (P ANOVA: 0.05) decreased by troleandomycin (T; 1 g bid over a 10-day period) compared with josamycin (J) (same doses) and placebo (P) in healthy volunteers. T also significantly increases serum estradiol concentration (P ANOVA: 0.03). This effect may be related to a T-induced inhibition of some P450 monooxygenase isoenzymes and more specifically P 450 NF, determined in our study by a decrease in urinary excretion of 6-beta-hydroxy-cortisol. Troleandomycin and josamycin both show poor upper GI tolerance. Liver enzymes (SGOT, SGPT, alkaline phosphatase and gGT) are significantly altered by T compared with J and P (P ANOVA: 0.007, 0.001, 0.09 and 0.04 respectively). After J, liver function tests are very close to control values (placebo). Liver enzymes are significantly more altered by T than by J (P 0.004, 0.001 and 0.06 for SGOT, SGPT and gGT respectively). Using 6 volunteers in a latin-square designed study, some established effects of oral macrolides were confirmed (poor upper GI tolerance; liver toxicity of T). Some other effects of T were also elicited, which were either unknown (decrease in serum TSH) or expected but which had not previously been assessed in man (increase in serum estradiol; decreased urinary excretion of 6-beta-hydroxy-cortisol).
Adult↗
In vivo effects of macrolides on thyroid hormone serum levels and on hepatic type 1 5'-deiodinase in rat. A comparative study with amiodarone, phenobarbital and propranolol.
Very often, an impact on the intracellular metabolism of iodothyronines and more precisely on microsomal deiodinases is evoked to explain thyroid hormone (TH) serum level alterations occurring with numerous drugs. Among them, three at least are also known to interfere with other hepatic microsomal enzymes, amiodarone (AMI), phenobarbital (PHE) and propranolol (PRO). Starting from this statement, we have examined the effects of 5 macrolides on TH serum level and on hepatic 5' type 1 deiodinase (5'DI) in vivo in rat. Rats were treated orally for eight days either with 200 mg/kg macrolides--erythromycine (ERY), troleandomycine (TRO), josamycine (JOS), midecamycine (MID) and spiramycine (SPI)--, or with AMI (45 mg/kg), PHE (50 mg/kg) or PRO (20 mg/kg), these 3 latter drugs for comparative purpose. Total T4, T3 and rT3 were determined by RIA. Hepatic 5'DI was evaluated by measuring released radioactive iodide from a reverse T3 monolabelled with 125I used substrate. Compared to control group, ERY and TRO decreased T4 (respectively by 28 and 16%) and from these two, only TRO decreased T3 (23%). With JOS, the only major modification was an increment of T3 (26%). AMI gave a typical alteration with a high T4 (130%), a low T3 (26%) and a high rT3 (376%). 5'DI was statistically inhibited by AMI (85%), JOS (49%), TRO (43%) and ERY (35%). The other drugs showed no significant effect. So, three macrolides have both altered TH serum level and 5'DI, findings which have never been reported before. The precise mechanism of this action remains unknown and the resulting effect, being far from the one observed with AMI, tends to demonstrate, for macrolides, an absence of correlation between the extent of 5'DI inhibition and TH serum profile. Besides, comparative analysis of the results observed with macrolides, AMI, PHE and PRO argues against any relationship between 5'DI and cytochrome-P450 monooxygenases.
Amiodarone↗
Effect of nifedipine and nitrendipine on insulin release in non-diabetic obese patients: a double-blind, placebo-controlled study.
Calcium antagonists are known to decrease insulin release in vitro. In vivo, their effects on insulin secretion and glucose tolerance are more controversial. We carried out a double-blind, double-dummy, controlled trial to study the effects of nifedipine (40 mg/day; n = 9), nitrendipine (20 mg/day; n = 9) and placebo (n = 10) on insulin release in 3 parallel groups of obese patients with mild or transient hypertension and a normal oral glucose tolerance test. The treatment lasted one week. Patients were asked not to modify their diet throughout the trial, and their body weight did not vary significantly. A 2-hour i.v. glucose tolerance test was performed twice in every patient, just before the first drug intake and one hour after the last one. The following parameters were measured or calculated during each test: basal, peak and early phase levels of blood glucose, insulin and C-peptide; glucose disappearance rate; and glucose, insulin and C-peptide incremental areas under the time-curves. On day 1, the 3 groups of patients were comparable for age, sex, body weight and every biological parameter. One-way analysis of variance did not show any significantly different evolution of those parameters between the 3 treatment groups, but calcium antagonists tended to slightly reduce the early phase of insulin release compared with placebo.
Adolescent↗
Effect of nifedipine on thyrotropin, prolactin, and thyroid hormone release in man: a placebo-controlled study.
Nifedipine (10 mg tid) or placebo was administered in a randomized double-blind trial for 1 wk to 2 groups of 10 mildly hypertensive euthyroid patients. Hormonal concentrations (thyrotropin [TSH], prolactin [PRL], thyroxin, triiodothyronine, and reverse triiodothyronine) before and during a TRH test were assessed in the 2 groups before (D0) and after (D7) each treatment. Parameters of the TRH test were determined (peak values, area under the curve [AUC], release [Kr], and elimination [Ke] rate constants) and their D7:D0 ratios were compared in the 2 groups. The TSH (peak values and Kr) and PRL (peak values and AUC) responses to TRH were significantly decreased in the nifedipine group compared to the placebo group. Neither basal nor TRH-stimulated thyroid hormone levels were modified. These results confirm experimental data but seem to be clinically irrelevant.
Adult↗
Some characteristics of human red blood cells separated according to their size: a comparison with density-fractionated red blood cells.
During their in vivo ageing, red blood cells (RBC) increase in density and become smaller. Age-defined RBC subpopulations are usually collected by centrifugation. A fractionation according to RBC volume has been proposed as an improved alternative to such age separation. Because a few data reported in the literature indicate some discrepancies between the two methods, blood samples were separated either by centrifugation or by counterflow centrifugation, and some characteristics of the RBC thus fractionated were studied. The enzyme activities decrease either when the density rises or when the volume (MCV) decreases. However, the comparison of other RBC characteristics strongly suggests that these two procedures do not lead to the collection of the same RBC subpopulations: for instance, the hemoglobin content increases when the MCV rises, whereas it remains constant whatever the RBC density is. With radiolabelled cells, it is shown 1) that the most dense RBC are recovered in all the size-separated RBC subpopulations, even though they tend to concentrate in the fractions with the largest MCV, and 2) that the smallest RBC are almost fairly distributed in all the RBC subpopulations, whatever their density, whereas the largest RBC are mainly, but not exclusively, present in the high-density fractions. Thus, fractionation according to size does not match separation according to density. Taken together with results from in vivo experiments carried out in mice and with the fact that reticulocytes are present in all the size-separated fractions, these data suggest that counterflow centrifugation may be a very questionable procedure to achieve a RBC fractionation according to age and therefore that RBC volume might not be a reliable criterion of RBC age.
Cell Separation↗
Does red blood cell size correlate with red blood cell age in mouse?
Mouse red blood cells (RBC) can be fractionated according to their size by counterflow centrifugation. The mean corpuscular hemoglobin content and the enzyme activities (ASAT, LDH, PK and acetylcholinesterase) increase when the mean corpuscular volume (MCV) rises. However, the in-vivo survival of size-separated RBC is similar whatever their MCV is; thus, counterflow centrifugation is not a suitable procedure to achieve an age fractionation of mouse RBC. Moreover, RBC subpopulations collected by counterflow centrifugation are different from those obtained when RBC are fractionated according to their density.
Animals↗
Effect of a somatostatin analog (SMS 201-995) in perfusion on basal and pentagastrin-stimulated calcitonin levels in medullary thyroid carcinoma.
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Adult↗
Use of a pharmacokinetic model to characterize the thyrotropin (TSH) and prolactin (PRL) response to thyrotropin-releasing hormone (THR) in man.
On the basis of a pharmacokinetic model using the data of a TRH test and without the use of radio-isotope tracers, a simple procedure of estimation of PRL and TSH TRH-stimulated release and elimination half-lives is presented. TRH tests were performed in 33 healthy subjects and their data were used to calculate the kinetic parameters of each subject. Elimination half-lives of TSH and PRL were found to be respectively (mean +/- SD in min) 63 +/- 7.4 and 35 +/- 2.8. Release half-lives were 8.2 +/- 1.3 for TSH and 5 +/- 0.4 for PRL. The usefulness of the procedure in the evaluation of drug effects on pituitary secretion in man and the comparison with the literature data are discussed.
Adult↗
Effect of diosmin upon red blood cell deformability and osmotic fragility. Relationship with lipid content.
Rats were treated by ingesting forcibly 2 ml of a suspension of four different doses (100, 200, 300 and 400 mg/kg) of diosmin in carboxymethylcellulose (CMC) and were killed immediately or after 3 or 6 hours of fasting. Animals treated by CMC only in a similar way (gavage) exhibited a fall in red blood cell (RBC) membrane cholesterol and an increase in RBC rigidity at the third hour while osmotic fragility remained stable. Diosmin treatment opposed the rise in RBC rigidity evoked by the gavage and induced a dose-dependent decrease of the RBC membrane cholesterol over phospholipid ratio.
Animals↗
Red cell ageing: phagocytosis and life-span of young and old erythrocytes fractionated by centrifugation.
Young and old red blood cells, separated by centrifugation on the basis of differences in cell density, were submitted to phagocytosis by either autologous human alveolar macrophages or syngeneic murine bone-marrow macrophages. Young cells adhere to macrophages, but to a much smaller extent than old ones. The influence of both type and quality of the separation procedure on the differences observed between the two erythrocyte subpopulations is discussed in the light of the half-life times of murine young and old red blood cells. Fractionation according to age was obtained following the method of Murphy (1973) and glutamate oxalo-acetate transaminase activity was measured and used as an indicator of both cell age and separation.
Animals↗
Failure of in vivo and in vitro resialosylation of VCN-desialylated erythrocytes in mammalian and non-mammalian species: evidence from agglutination studies with peanut-agglutinin.
1. In distinction to mammalian erythrocytes, splitting of sialic acids of non-mammalian erythrocytes (chicken and newt) by Vibrio cholerae neuraminidase (VCN) does not lead to a dramatic decrease in their viability. 2. One of the possibilities to explain this discrepancy is the ability of chicken and newt desialosylated erythrocytes to repair the enzymatic injury. 3. To test this hypothesis we used the property of peanut agglutinin (PNA) to agglutinate desialosylated erythrocytes. 4. Desialosylated erythrocytes of all the species tested remain PNA-agglutinable throughout their whole life time in the blood stream. The absence of effect of VCN on chicken and newt erythrocytes is therefore not due to their resialosylation.
Animals↗
[Study of the interaction between desialylated erythrocytes and Kupffer cells using perfusion of liver in situ].
Desialylated erythrocytes, when perfused in mice liver in situ, were shown to be sequestered. This sequestration was inhibited by dihydrocytochalasin B and a neoglycoprotein: N-Acetylgalactosaminyl-albumin. Our results confirm that, under physiological conditions, the recognition of desialylated erythrocytes appear to be related to the presence of N-Acetylgalactosamine or galactose receptor on the surface of Küpffer cells.
Animals↗
[Comparison of the survival of desialylated erythrocytes and demonstration of the presence of T-agglutinin in rabbits and ducks].
Rabbit as well duck erythrocytes desialization leads to a dramatic decrease of their survival time. Rabbit erythrocytes are trapped transiently by the liver ; in contrast splenic uptake is gradual. Serum from the two species contains a T-agglutinin directed against autologous desialyated erythrocytes. In the two cases, this T-agglutinin is from the IgM class and its immunodominant sugar is galactose in the beta configuration.
Agglutinins↗
Transendothelial migration of two metastatic breast carcinoma cells depend on the SDF-lalpha-CXCR4 complexes.
The role of the SDF-1alpha chemokine-CXCR4 receptor system on tumor cell transendothelial migration was studied by culturing metastatic breast tumor cell lines, MDA-MB-231 and MDA-MB-435, either alone or on a HUVEC monolayer pre-established on a "Transwell" filter. After a 24-hour culture in the presence or absence of SDF-1alpha, tumor cell transmigration rates were compared. We showed that: CXCR4 is present on both cell lines; MDA-MB-231 but not MDA-MB-435 cell migration is stimulated by increasing concentrations of SDF-1alpha; neutralizing anti-CXCR4 antibody inhibits the SDF-1alpha chemoattractant effect; CXCR4 expression, measured by cytofluorometry, was enhanced after treatment with SDF-1alpha on MDA-MB-231 cells but remained unchanged on MDA-MB-435 cells; Scatchard analysis evidences 8.10(5) and 2.10(5) high affinity sites (KD range: 20 to 30 nM) on, respectively, MDA-MB-231 and MDA-MB-435 cells. These significant differences could explain the distinctive transendothelial migration responses of these two cell lines in the presence of SDF-1alpha.
Adenocarcinoma↗
Troleandomycin hepatotoxicity: a case report of overt jaundice and a placebo-controlled trial.
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Adult↗