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Biomedical subjects

M Lemaire

Publications and source records attributed to M Lemaire.

At least 19 recordsLinked to original sources
PubMed1992

From somatostatin to sandostatin: pharmacodynamics and pharmacokinetics.

Somatostatin (SRIF) and its octapeptide analogue, octreotide (Sandostatin), have a similar high affinity for specific receptors with 50% inhibitory concentrations (IC50s) in the subnanomolar range. Hence, the striking superiority of octreotide in vivo, which includes duration of action, specificity, and potency, must originate from its different distribution, metabolism, and excretion behavior. In animals and humans, investigations of their pharmacodynamic/pharmacokinetic relationship show plasma levels of 0.2 to 0.5 ng/mL (approximately 0.3 nmol/L) to be therapeutically relevant for both peptides. The much lower clearance rates and improved metabolic stability in the circulation and in target organs of octreotide, compared with SRIF, result in much longer-lasting, therapeutically relevant plasma and tissue levels and therefore in a longer duration of action. Their apparently specific inhibitory action on growth hormone when compared with that on insulin is pharmacodynamically based, and may be exaggerated by physiological mechanisms of carbohydrate regulation. In summary, there is a distinct relationship between the pharmacokinetic profiles and pharmacodynamic behavior of SRIF and its analogue. Sandostatin.

Animals↗
PubMed1992

Protection against aspirin-induced gastric lesions by lansoprazole: simultaneous evaluation of functional and morphologic responses.

The protective effect of lansoprazole, a new proton pump inhibitor, against aspirin-induced gastric lesions was studied in a double-blind crossover trial with a simultaneous measure of the functional capacities of the mucosal barrier (by a recording of the gastric potential difference) and of the morphologic changes in the mucosa (by gastric endoscopy). After 1 week of treatment with lansoprazole (30 mg per day) or placebo, each healthy volunteer received 1 gm aspirin by mouth. Recording of the gastric potential difference lasted for 3 hours and was followed by gastric endoscopy. Morphologic lesions induced by aspirin were effectively prevented by lansoprazole: Lanza score was 0.67 +/- 0.98 (mean +/- SD) versus 2.25 +/- 1.1 with placebo (p < 0.005, ANOVA). Conversely, the decrease in the gastric potential difference was similar. The inhibition of acid secretion induced by lansoprazole was therefore sufficient to prevent aspirin-induced mucosal lesions without reinforcing the defense capacities of the mucosa. This simple pharmacologic model makes it possible to simultaneously evaluate the functional and morphologic effects of aspirin intake on the gastric mucosa.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1992

Evidence for an endogenous cholecystokininergic balance in social memory.

The cholecystokinin (CCK) peptide family is involved in a variety of physiological processes, including neurotransmission in the brain. Pharmacological responses to CCK are mediated through at least two receptor subtypes termed CCK-A and CCK-B. Studies with CCK agonists suggest a possible role for CCK in cognition. Using selective antagonists and a behavioural recognition test based on the olfactory discriminative capacities of rats, we found that endogenous CCK acting at CCK-A and CCK-B receptors modulates olfactory recognition positively and negatively, respectively. CCK-B receptor antagonists therefore have facilitatory potentialities on memory processes.

Animals↗
PubMed1992

[Neoadjuvant chemotherapy, with mitoxantrone, cyclophosphamide and fluorouracil, in operable breast cancer of intermediate stage: first results of a phase II study in 40 patients].

Forty patients with intermediate stage (T2 > 3 cm-T3, N0-N1) operable breast cancer received neoadjuvant chemotherapy by MCF (mitoxantrone, cyclophosphamide, 5-fluorouracil). Four cycles were administered at 3-week intervals. The obvious hematological toxicity (64% of grade III for the leucocytes and up to 34% of grade IV for the granulocytes) was rapidly reversible and did not hinder completion of the treatment. Ten patients showed a complete remission and a tumor volume regression of more than 50% was observed in 12 other patients. Tumor shrinkage allowed breast-saving surgery in 50% of the cases. A complete sterilisation of the surgical specimen was found in only two of the 40 patients and a few persisting neoplastic cells were found in ten other cases. A positive response at the level of the axillary lymph nodes was also obtained in more than 50% of the cases. In 25 of the 36 cases examined, the primary chemotherapy induced cellular lesions (fibrosis, necrosis) at the tumor level. A feasibility study was undertaken in order to determine quantitatively several biochemical parameters (steroid hormone receptors, cathepsin D, c-erbB-2 oncoprotein) in very small tumor samples obtained by Tru-Cut before any treatment and in surgical specimens. In the future, these micromethods will be used systematically with the aim of estimating the value of these potential prognostic factors for therapeutic follow-up of the patients.

Adult↗
PubMed1991

Quantification of absorption, intestinal and hepatic first pass effect in a chronic dog model.

A chronic dog model was used to measure the absorption and to elucidate the site and extent of presystemic metabolism of a selective D1-agonist (CY 208-243). The dog was instrumented with portal vein and carotid artery catheters together with an electromagnetic flow measuring device around the portal vein. After administering [14C]CY 208-243 intrajejunally, absorption rate was defined as the product of porto-arterial substrate difference and portal venous blood flow. The extent of absorption amounted to 34% for total radioactivity and 31% for unchanged drug, this indicating a gastrointestinal first-pass of 9%. In an additional study [14C]CY 208-243 was injected intravenously to the dog; the absorption (29%) and the bioavailability (5%) of CY 208-243 were calculated from the ratio of dose normalized, oral versus intravenous AUC values for total radioactivity and unchanged drug, respectively. These data confirm the absorption value found with the chronic dog model and indicate a global presystemic, i.e. intestinal and hepatic, first-pass effect of 83%. In conclusion, this chronic dog model allows an accurate assessment of drug absorption and a quantification of the gastrointestinal and hepatic first-pass effects.

Administration, Oral↗
PubMed1990

Assessment of cyclosporine A interactions with human plasma lipoproteins in vitro and in vivo in the rat.

The interaction of cyclosporine A (cyclosporine) with human plasma lipoproteins has been investigated by combining in vitro and in vivo methods. Binding parameters were derived in vitro from an erythrocyte partitioning method, and provided reliable Ka (product of the number of binding sites by the association constant) estimates: high-density lipoprotein, 2.21 +/- 0.48; low-density lipoprotein, 1.23 +/- 0.12; and very low-density lipoprotein, 0.53 +/- 015 liters/g, showing that high-density lipoprotein was the major carrier of plasma cyclosporine. The effects of cyclosporine binding to lipoproteins were investigated in vivo by the intracarotid injection technique of Oldendorf in the rat. The brain extraction of cyclosporine was related inversely to the lipoprotein concentration in the injected solution, allowing estimation of nKa in vivo: high-density lipoprotein, 2.25 +/- 0.59; low-density lipoprotein, 0.62 +/- 0.13; and very low-density lipoprotein, 0.57 +/- 0.14 liters/g. This showed that brain uptake occurred from the free drug pool and possibly from a small part of the originally lipoprotein-bound pool of cyclosporine, at least for low-density lipoprotein-bound cyclosporine. These results allow the calculation of an index of the unbound plasma cyclosporine fraction.

Animals↗
PubMed1990

Chromosome aberrations in patients treated with telecobalt therapy for glioblastoma.

The yield of dicentric chromosomes has been recorded in peripheral blood lymphocytes of patients undergoing telecobalt therapy for glioblastoma. Blood samples were taken by venipuncture, prior to the first radiotherapy session and 24 h after 10, 20 and 30 Gy to the tumor volume. On the basis of the maximum likelihood method, the yield of chromosome aberrations was best fitted by a linear quadratic dose-response relationship. According to this relationship, the dose inducing ten dicentrics at the target volume is 58 Gy, a value considerably higher than those found after radiotherapy for mammary carcinoma (15 Gy) or for pelvic tumors (5.62 Gy). Our results indicate that, in the case of fractionated exposures, confined to a small volume of the body, it is not possible to estimate the total dose administered and that the method only provides an estimate of the proportion of the lymphocytes irradiated.

Brain Neoplasms↗
PubMed1989

Influence of plasma protein binding on the brain uptake of an antifungal agent, terbinafine, in rats.

The intracarotid injection technique has been used to determine the unidirectional brain uptake of an antifungal, lipophilic agent, terbinafine (Lamisil, Sandoz Basle), in the rat. Ultrafiltration showed it to be highly bound to human plasma, human serum albumin (HSA), alpha 1-acid glycoprotein (AAG) and lipoproteins (VLDL, LDL, HDL). The effect of plasma protein binding of the drug on brain uptake was also examined with the technique. The lowest brain uptake was observed in the presence of plasma (6%); it varied from 23 to 30% with physiological concentrations of VLDL, LDL and HSA and was significantly higher (43-45%) in the presence of physiological concentrations of AAG and HDL. The free fraction as determined in-vitro and the brain uptake of the drug varied inversely with the plasma protein concentrations; however, the brain uptake was higher than expected from in-vitro measurements. These data indicate that the amount of circulating Lamisil available for brain penetration exceeds its free fraction; they also show that plasma proteins differently reduce the brain transport of the drug.

Animals↗
PubMed1989

[Thyroid function and cancer].

Despite extensive epidemiological and biochemical studies, the effects of a thyroid dysfunction on the incidence and progress of human cancer have been, for many years, a controversial subject. Endocrine manipulations on laboratory animals clearly demonstrate the influence of thyroid hormones on the induction and growth of several types of experimental tumors: lymphomas, mammary tumors, primary or transplanted hepatomas. In vitro, triiodothyronine also plays an early and critical role in the neoplastic transformation of cultured cells by X-rays, chemical carcinogens and RNA- and DNA-viruses. At the molecular level, the effects of thyroid hormones on the alterations of gene expression accompanying neoplasms remain unknown. Yet, the presence of nuclear triiodothyronine receptors in experimental and human tumors and the recent discovery, by several authors, that the cellular counterpart of a viral oncogene (v-erb A) encodes a thyroid hormone receptor, suggest: either a direct influence of the hormone on the initiation and/or the progress of these tumors; or an indirect effect, via the modulation of another metabolic regulator, for example a polypeptide growth factor (Epidermal Growth Factor, Transforming Growth Factor).

Animals↗
PubMed1988

Diffuse small intestinal lymphoid infiltration in nonimmunodeficient adults from Western Europe.

In two white adults born, raised, and living in central France and presenting with long-lasting malabsorption, massive and diffuse lymphoid infiltrate of the lamina propria associated with crypt scarcity was found along the whole small bowel. It was mostly composed of mature lymphocytes, focally mixed with plasma cells and reactive germinal centers. There was no evidence of celiac disease, systemic or intestinal immune deficiency or alpha-chain disease, overt lymphoid malignancy, or stagnant-loop syndrome. By immunofluorescence the infiltrate was constituted in 1 case of polyclonal B cells and, in the other, of a large majority of T11, T8, T10, and class II-positive T cells associated with a population of monotypic B cells. A gluten-free diet and parenteral nutrition proved ineffective. A dramatic and protracted clinical response was observed in both patients after the onset of oral tetracycline therapy, and still persists after 8 and 5.5 yr, respectively, together with morphologically unchanged small bowel infiltrate. These cases may be the equivalents, in people from Western developed countries, of the predominantly lymphocytic variety of the immunoproliferative small intestinal disease described in people from developing countries.

Adult↗
PubMed1988

Comparative binding of two closely related dihydropyridines (isradipine and darodipine) to serum proteins and erythrocytes.

The binding of the two drugs isradipine and darodipine, chemically related to dihydropyridines and potent calcium channel blockers, was studied in vitro to isolated plasma proteins, erythrocytes and human serum. The two drugs were strongly bound to serum proteins (up to 97%), mainly to human serum albumin (HSA), alpha 1-glycoprotein (AAG) and lipoproteins (VLDL, LDL and HDL). Their bindings to AAG were saturable with high affinity constants (isradipine 498,000 M-1, darodipine = 155,000 M-1; n = 1). The binding of these drugs to HSA, VLDL and HDL was unsaturable, but it was saturable on LDL. In blood the drugs partitioned in erythrocytes, 16% for isradipine and 14.8% for darodipine.

Binding, Competitive↗
PubMed1988

[Radiation-induced thyroid cancer].

We describe thyroid carcinomas observed in two male patients after cervical irradiation in infancy. In the first case, irradiation was given for cervical angioma and in the second case, for enlarged thymus. A long time interval (16 and 43 years) elapsed between irradiation and the detection of the epitheliomas. The anatomopathological diagnosis was, for the first patient, papillo-vesicular epithelioma and for the second one, anaplastic carcinoma.

Adult↗