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M Debray

Publications and source records attributed to M Debray.

At least 55 records · Page 3Linked to original sources
PubMed1995

Affinity and dose-dependent digoxin Na+K+ATPase dissociation by monoclonal digoxin-specific antibodies.

The effect of three monoclonal digoxin-specific antibodies and of polyclonal Digidot as reference on digoxin dissociation from rat brain Na+K+ATPase microsomes was studied to determine the role of the affinity constant (Ka) and dose of the antibody on the rate of digoxin dissociation from Na+K+ATPase. Stoichiometrical doses of 1C10, 6C9, 9F5 IgG, and Digidot (Ka = 6 10(9), 3.1 10(8), 2.5 10(7), and 8.5 10(9) M-1, respectively) resulted in digoxin dissociation related to Ka. When the IgG:digoxin molar ratio increased from 0.25 to 10, digoxin dissociation from Na+K+ATPase sites also increased according to the Hill equation, allowing comparative parameters among the three antibodies to be determined. 1C10 IgG was 2- and 10-fold more efficacious than 6C9 and 9F5, respectively. This in vitro model appears to be a useful predictive screening assay before in vivo experimentation.

Animals↗
PubMed1995

[Extravasation of paclitaxel (Taxol)].

Paclitaxel is a new antimitotic derived from yew-tree, used for the treatment of ovarian and breast cancers. The local toxicity of paclitaxel is still poorly known. We report one of the first observations of accidental subcutaneous extravastion of paclitaxel. Local epidermic necrosis was observed and evolution was good with local treatment only. Treatments of such extravasation are discussed.

Aged↗
PubMed1995

Efflux of intracellular colchicine in lymphocytes with colchicine-specific Fab fragments.

Uptake of [3H]colchicine (2.5 ng/ml) by human lymphocytes in culture was slow in the length of time to reach steady state (> 48 hr) and was limited in the maximal intracellular colchicine amount (1-2% of total extracellular colchicine). Efflux of intracellular colchicine was investigated 40 hr after colchicine cell exposure by using either washing of the extracellular medium or adding different colchicine-specific Fab fragments:colchicine dose molar ratios of 0.5, 1 and 5. Except for the 0.5 dose molar ratio, the kinetics of [3H]colchicine efflux from lymphocytes induced by extracellular specific Fab fragments were similar to those obtained by washing and were characterized by a first-order decline with half-lives ranging from 15.5 to 16.4 hr. These half-lives were in the same range as those characterizing the dissociation of colchicine from the intracellular tubulin receptor. Our data demonstrate that a tightly bound intracellular toxin may be extracted by antibody with high affinity for the toxin present in the extracellular space at a rate depending on the rate of dissociation of the toxin from its receptor.

Biological Transport↗
PubMed1995

Pharmacokinetics of lithium in plasma and red blood cells in acute and chronic intoxicated patients.

Lithium disposition in plasma, red blood cells (RBC) and urine was studied in acute self-poisoned patients upon chronic lithium therapy (n = 4) and in chronic intoxicated patients receiving oral lithium (n = 10). Following acute intoxication upon chronic lithium therapy, lithium pharmacokinetics did not differ from previous reports. Terminal plasma half-life ranged from 19.0-29.0 h and RBC/plasma ratio was 0.32 +/- 0.11. The distribution volume of the terminal phase, Vz, was estimated at 0.84 +/- 0.32 l/kg and renal clearance was 0.38 +/- 0.11 ml/mn/kg. After chronic intoxication lithium pharmacokinetics differed from those of the acute patients. Terminal plasma half-life ranged from 36.5-79.4 h and zero-order decline appeared in 8 of the 10 patients. The RBC/plasma ratio was 0.87 +/- 0.22 on admission. Vz was estimated at 0.71 +/- 0.27 l/kg and renal clearance was 0.16 +/- 0.07 ml/mn/kg. These modifications in lithium elimination kinetics could be related to the decrease in the glomerular filtration rate with age or renal dysfunction in this group of patients.

Administration, Oral↗
PubMed1994

Association constants of monoclonal antibodies for hapten: heterogeneity of frequency distribution and possible relationship with hapten molecular weight.

Using published data, we have investigated the relationship of the association constant (Ka) of 265 MAbs for haptens with molecular weights ranging from 111 to 1202 Da. The study indicates that: (1) differences of a factor 10(3)-10(5) are frequently found between the lowest and the highest value of Ka for the same hapten; (2) the relationship between log Ka and the hapten molecular weight of either the native drug or the molecular entity used for the Ka determination is described by a hyperbolic function; (3) beyond a critical molecular weight of approximately 300-325 Da, the log Ka reaches a plateau at a maximal value near 10(-12) M-1.

Antibodies, Monoclonal↗
PubMed1994

Behavioral effect of beta-blocking drugs resulting from the stimulation or the blockade of serotonergic 5-HT1B receptors.

The present study was aimed at determining the relative potency of various beta-blocking drugs as agonists or antagonists at 5-HT1B receptors. The behavioral model used (increase in escape attempts of isolated mice) has been previously shown to be exclusively responsive to 5-HT1B agonists such as 1-3-(trifluoromethyl) phenylpiperazine (TFMPP). Beta-blocking drugs acted in three different ways: they were either inactive, or acted as agonists or as antagonists at 5-HT1B receptors. The specific beta-blocking drugs: atenolol and betaxolol (beta-1) and ICI 118,551 (beta-2) were inactive by themselves and in interaction with TFMPP. The mixed beta-1 beta-2 blocking drug 1-penbutolol, (but not d-penbutolol), inactive alone, behaved as an antagonist: it impaired in a dose-dependent way the effect of TFMPP. (+/-)Pindolol and (-)pindolol was inactive. None of the (-), (+), or (+/-)pindolol was able to impair TFMPP effect. The increase in escape attempts induced by (+/-)pindolol was antagonized with 1-penbutolol or after a specific desensitization. Cyanopindolol and S-tertatolol (but not R-tertatolol) acted as agonists. SDZ 21009 was inactive as agonist or antagonist. It may be concluded that all beta-blocking drugs are not equivalent regarding their effect at 5-HT1B receptors. L-penbutolol was the only drug acting as an antagonist.

Adrenergic beta-Antagonists↗
PubMed1994

Effect of fish oil diet on fatty acid composition of phospholipids of brain membranes and on kinetic properties of Na+,K(+)-ATPase isoenzymes of weaned and adult rats.

The influence of dietary (n-3) fatty acids (such as eicosapentaenoic and docosahexaenoic acids) as found in fish oil on Na+ sensitivity and ouabain affinity of Na+,K(+)-ATPase isoenzymes (alpha 1, alpha 2, alpha 3) was studied in whole brain membranes from weaned and adult rats fed diets for two generations. The long chain (n-3) fatty acids supplied by fish oil decreased the fatty acids of the (n-6) series compared with the standard diet, resulting in a decrease in the (n-6)/(n-3) molar ratio in both 21- and 60-day-old rats. On the basis of ouabain titration, three inhibitory processes with markedly different affinities were associated with isoenzymes, i.e., low affinity (alpha 1), high affinity (alpha 2), and very high affinity (alpha 3). It appears that the fish oil diet, in part via the modification of membrane fatty acid composition, altered the proportion and ouabain affinity of isoenzymes. Na+ sensitivity is the best criterion of physiologic change induced by fish oil diet. We calculated the Na+ activation for each isoenzyme and found one Na+ sensitivity and two Na+ sensitivities per isoenzyme in weanling and adult rats fed different diets, respectively. In contrast to alpha 2 and alpha 3, alpha 1 appears insensitive to membrane change induced by fish oil diet. Fish oil diet, which is known to confer cardioprotection, induced significant modulation of Na+,K(+)-ATPase isoenzymes at the brain level.

Aging↗
PubMed1993

Effect of dietary alpha-linolenic acid on functional characteristic of Na+/K(+)-ATPase isoenzymes in whole brain membranes of weaned rats.

The influence of dietary fatty acids on Na+ sensitivity and ouabain affinity of Na+/K(+)-ATPase isoenzymes of whole brain membranes were studied in weaned rats fed for two generations with diets either devoid of alpha-linolenic acid (sunflower oil diet) or rich in alpha-linolenic acid (soya oil diet). The (n--3) deficiency induced by the sunflower oil diet led to an increase in the (n--6)/(n--3) molar ratio in whole brain membranes. Na+/K(+)-ATPase isoenzymes were discriminated on the basis of their differential affinities for ouabain. In rats fed sunflower oil diet, the ouabain titration displayed three inhibitory processes with markedly different affinities: low affinity (alpha 1); high affinity (alpha 2); and very high affinity (alpha 3). Membranes of rats fed soya oil diet exhibited only two inhibitory processes, i.e., low affinity (likely alpha 1+ alpha 2) and high affinity (likely alpha 2+ alpha 3) with the low affinity form intermediate between the sunflower alpha 1 and alpha 2 forms, and the high affinity form intermediate between the sunflower alpha 2 and alpha 3 forms. In fact, the Na+ response shows that the three isoenzymes have different Na+ sensitivities. Regardless of the diet, alpha 1 has a similar Na+ sensitivity (less than 1 mM), whilst alpha 2 and alpha 3 are more sensitive in soya oil membranes compared to sunflower oil membranes (5.1 vs. 7.2 mM and about 11 vs. 22.5 mM, respectively). Thus, sodium appears to be a better criterion of heterogeneity than ouabain.

Animals↗
PubMed1993

Heterogeneous Na+ sensitivity of Na+,K(+)-ATPase isoenzymes in whole brain membranes.

The Na+ sensitivity of whole brain membrane Na+,K(+)-ATPase isoenzymes was studied using the differential inhibitory effect of ouabain (alpha 1, low affinity for ouabain; alpha 2, high affinity; and alpha 3, very high affinity). At 100 mM Na+, we found that the proportion of isoforms with low, high, and very high ouabain affinity was 21, 38, and 41%, respectively. Using two ouabain concentrations (10(-5) and 10(-7) M), we were able to discriminate Na+ sensitivity of Na+,K(+)-ATPase isoenzymes using nonlinear regression. The ouabain low-affinity isoform, alpha 1, exhibited high Na+ sensitivity [Ka of 3.88 +/- 0.25 mM Na+ and a Hill coefficient (n) of 1.98 +/- 0.13]; the ouabain high-affinity isoform, alpha 2, had two Na+ sensitivities, a high (Ka of 4.98 +/- 0.2 mM Na+ and n of 1.34 +/- 0.10) and a low (Ka of 28 +/- 0.5 mM Na+ and an n of 1.92 +/- 0.18) Na+ sensitivity activated above a threshold (22 +/- 0.3 mM Na+); and the ouabain very-high-affinity isoform, alpha 3, was resolved by two processes and appears to have two Na+ sensitivities (apparent Ka values of 3.5 and 20 mM Na+). We show that Na+ dependence in the absence of ouabain is the result of at least of five Na+ reactivities. This molecular functional characteristic of isoenzymes in membranes could explain the diversity of physiological roles attributed to isoenzymes.

Animals↗
PubMed1991

Morphine pharmacokinetics and pain assessment after intracerebroventricular administration in patients with terminal cancer.

Morphine pharmacokinetics and pain relief were evaluated after intracerebroventricular administration of morphine (0.4 +/- 0.11 mg) in seven patients with cancer suffering from intractable pain. Ventricular cerebrospinal fluid (CSF), lumbar CSF, and plasma morphine concentrations were analyzed by a specific morphine radioimmunoassay. A two-compartment model was sufficient to describe the kinetics of morphine in ventricular CSF. Morphine diffuses to the lumbar level, and the mean maximum concentration was 192 +/- 105 ng/ml at 4.5 +/- 1.3 hours. Ventricular and lumbar CSF morphine kinetics showed a similar decline during the elimination phase, with terminal half-lives of 3.8 +/- 0.6 hours and 4.2 +/- 1.6 hours, respectively. Pain relief was evaluated by a visual analog scale: the test showed a rapid onset of analgesia (less than 10 minutes). Analgesic effectiveness reached a maximum between 6 and 10 hours. The relationship between pharmacologic effect and morphine concentrations in ventricular CSF resulted in an anticlockwise hysteresis curve. The presence of morphine in lumbar CSF suggested an additive spinal action of morphine, which probably plays a role in the duration of analgesia.

Adult↗
PubMed1991

Comparison of plasma and follicular fluid hormone profiles following stimulation with HMG, with or without LHRH agonists, for in-vitro fertilization.

Plasma and follicular fluid (FF) hormone assays for follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), oestradiol (E2), progesterone (P), delta-4-androstenedione (A4) and testosterone (T) were performed on the day of oocyte retrieval in two groups of normo-ovulatory women enrolled in an in-vitro fertilization (IVF) programme: 24 were treated using the decapeptyl agonists DTRP6, of luteinizing hormone-releasing hormone (LHRH) in the long protocol associated with human menopausal gonadotrophin (HMG) (49 FF) and 14 were stimulated with HMG alone (33 FF). In both FF and plasma the mean concentration of P was greater, and the E2/P ratios as well as the LH levels were lower in the agonist-treated group. In this group the follicular concentration of P was greater and the E2/P ratio lower when pregnancy occurred following IVF. The hormonal modifications may be due to greater functional maturity of the granulosa cells.

Estradiol↗
PubMed1989

The contribution of intermediate-acting insulin preparations to daytime insulin treatment.

Hyperglycaemia in the afternoon is often not prevented by increasing the intermediate insulin dose in C-peptide deficient Type 1 diabetic patients, particularly children, treated with two injections of mixtures of short- and intermediate-acting insulins. To provide a better understanding of this, 19 Type 1 diabetic patients were studied using the euglycaemic clamp technique, after SC injection of either soluble, isophane (NPH) or lente insulin, or mixtures of these preparations. SC injection of 0.6 U kg-1 insulin, as either intermediate-acting (isophane (NPH) or lente) insulin alone or as a mixture of 50% soluble + 50% intermediate-acting insulins, indicates that, for the same total dose of SC insulin, a shift from soluble to intermediate-acting insulin results in a major loss of activity during the first 6 h after injection, with no compensatory increase over the next 6 h. The morning hypoglycaemic activity depends on different mechanisms with isophane (NPH) or lente insulin; the effects of soluble and isophane (NHP) insulin are superimposed, while with lente insulin, the peak of soluble insulin is blunted. For the afternoon, even large doses of isophane (NPH) or lente insulin do not meet the peak of insulin requirements following lunch.

Adult↗
PubMed1989

Comparison of colchicine toxicity on different dysmyelinating mutant models.

The administration of colchicine to dysmyelinating mutant mice may serve as an in vivo pharmacological tool for the study of the mechanisms involved in the formation of the myelin sheath. The study of the acute toxicity of colchicine in these mutants demonstrated that male animals were much more sensitive than female animals. All of the mutants and their controls were also more resistant to colchicine than the Swiss strain usually used in toxicity studies.

Animals↗