PubMed Health⌕ Search

Biomedical subjects

H Marty

Publications and source records attributed to H Marty.

At least 19 recordsLinked to original sources
PubMed1998

Determination of free extracellular levels of methotrexate by microdialysis in muscle and solid tumor of the rabbit.

PURPOSE: To determine of the pharmacokinetic profile of methotrexate (MTX) in blood and extracellular fluid (ECF) of VX2 tumor and muscle in rabbits. METHODS: Microdialysis probes were inserted into VX2 tumor and in muscle tissue. Following intravenous administration of MTX (30 mg/kg), serial collection of arterial blood samples and dialysates of muscle and tumor ECF for 4 h was carried out. Quantitation of MTX and determination of free plasma concentrations was performed by fluorescence polarization immunoassay and ultrafiltration, respectively. Correlations were established between the unbound plasma and ECF MTX concentrations. RESULTS: Total and free plasma concentrations exhibited a parallel three exponential decay in both healthy and tumorigenic animals. Total clearance (8.9 vs 6.5 ml-1.min-1.kg-1) and volume of distribution (4.0 vs 2.9 l.kg-1), however, tended to decrease in the tumor-bearing group. The ECF/plasma AUC ratio equaled 14.2 +/- 8.8% in muscle and 23.9 +/- 15.9% in tumor. The concentration-time profile of muscle ECF MTX was parallel and highly correlated (r = 0.97) to that determined in plasma. In contrast, free MTX plasma levels were not correlated with tumor ECF concentrations (r = 0.564). CONCLUSIONS: In addition to the well-known pharmacological variability in the concentration-effect relationship, the important inter-individual variability in tumor exposure to MTX may partly explain that studies in patients with solid tumors have often failed to demonstrate firm correlations between MTX blood pharmacokinetics and the chemotherapeutic response.

Animals↗
PubMed1994

[Cutaneous vasculitis: how to recognize, interpret, treat it?].

Clinical and histopathological features of cutaneous vasculitis are presented by means of 14 case reports. Proof of vasculitis in skin biopsy consecutively demands for a search of a cause and of the extension of the vasculitic process in the sense of a systemic disease. The most frequent form of cutaneous vasculitis is hypersensitivity angiitis, a disease in which always an exogenous (drugs, infections) or an endogenous (malignant neoplasia, connective tissue disease) trigger should be sought if cutaneous vasculitis persists after removal or treatment of the suspected cause. Then, antihistaminic or--particularly in cases with systemic involvement--immunosuppressive drugs (corticosteroids or cyclophosphamide) should be considered.

Adult↗
PubMed1992

Antinociceptive activity of metapramine in mice. Relationship with its pharmacokinetic properties.

The antinociceptive effect of acutely and chronically (every brain elimination half-life time) administered metapramine, a tricyclic antidepressant without anticholinergic or cardiotoxic effects, was studied in three different pain tests. In the hot plate test, its action was more potent when jumping was used as a pain parameter (acute ED50 = 19 +/- 3 mg/kg, i.p.) than when pain was assessed by licking of forepaws (only 20 mg/kg, i.p. was weakly active). Five chronic doses of 15 mg/kg were as active in the tail-flick test as an acute dose of 20 mg/kg (only active dose). Metapramine was more effective in the PBQ-induced writhing test after acute (ED50 = 9.9 +/- 0.1 mg/kg, i.p.) and chronic administration. A significant linear correlation was found between the effect in this test and plasma and overall brain levels of metapramine. No correlation was observed with levels of its three desmethylated metabolites. The usefullness of using a well-defined pattern of administration based on pharmacokinetic parameters and the involvement of monoaminergic mechanisms and of some metabolites of metapramine are discussed.

Animals↗
PubMed1992

Compared plasma and brain pharmacokinetics of clomipramine and its metabolite demethylclomipramine in two strains of mice (NMRI and CD1).

The fate of clomipramine (CMI) and its main demethylated metabolite demethylclomipramine (DCMI) was studied in two strains of Swiss mice (NMRI and CD1) after intraperitoneal injection. A study of its distribution among various tissues showed that fixation was most marked in lungs, perirenal fat and kidneys, and only moderate in the brain. The pharmacokinetic parameters of both molecules were determined in brain tissue and plasma. Absorption was rapid (tmax CMI = 14 min), metabolism prompt (tmax DCMI = 17 or 18 min according to the breed) and elimination rapid from both plasma and brain tissue. The first two stages were similar in the two strains, but elimination of CMI from both plasma and brain was faster in the NMRI mice (plasma t1/2 = 53 min against 165 min in the CD1 mice). Both values were well below that reported for man (mean plasma t1/2 = 24 h). The data presented can serve as a basis for designing true chronic administration protocol in animals.

Animals↗
PubMed1992

Comparative effects of different uptake inhibitor antidepressants in two pain tests in mice.

The purpose of this study was to compare the analgesic effect of acute injections (1.25 and 20 mg/kg, ip) of several antidepressants with different effects on monoamine reuptake, on two pain tests in mice (hot-plate and phenylbenzoquinone-induced abdominal writhes). Serotonergic inhibitors (citalopram, fluvoxamine and clomipramine) were more effective in the hot-plate test whereas noradrenaline reuptake inhibitors (desipramine and maprotilline) were more effective in the writhing test. The mixed antidepressants (amitriptyline and to a lesser degree trimipramine) were more effective in the two tests than the other antidepressant drugs. Changes in motor activity of clomipramine and amitriptyline could not account for the modifications of pain threshold. Amineptine (a dopamine reuptake inhibitor) failed to induce any antinociceptive effect in the hot-plate test and was hyperalgesic in the writhing test, which could be explained by an increased motor activity. These findings indicate that the antinociceptive potency of reuptake inhibitors varies according to their monoamine specificity and the nature of stimuli. They would suggest that the preferential choice of serotonergic antidepressants in the management of chronic pain is arguable.

Animals↗
PubMed1991

[Atypical giant cell arteritis].

The atypical clinical course of giant-cell arteritis in the elderly (who may develop a clinical picture of severe consumptive disease) is illustrated by two observations with histologically confirmed temporal arteritis. In addition to fever and loss of weight, the inflammatory vascular process in a 78-year old female was reflected in arrhythmias (atrial fibrillation and atrial flutter), probably due to involvement of the coronary arteries, and occlusion of the left axillary artery. Similar general symptoms and various neurological deficits comprising amaurosis, mononeuritis multiplex, polyneuropathy, myopathy and finally subarachnoid hemorrhage characterized the disease in a 72-year-old man. The picture was further complicated by intestinal perforation. In both patients steroids brought considerable improvement and the disease process came to a standstill.

Aged↗
PubMed1989

Antinociceptive activity of salsolinol (racemate, R(+)-, S(-)-enantiomers): evidence of a peripheral mechanism.

The existence and the characteristics of the antinociceptive action of salsolinol (racemate) and its two R(+)- and S(-)-enantiomers were studied using different pain tests in mice. None of these drugs possessed a significant activity on the tests sensitive to central acting analgesics (hot-plate and tail-flick tests), either after systemic (i.p.) or central (i.c.v.) injections. However, injected i.p., they reduced the number of writhes induced by phenylbenzoquinone; the ED50 was 79 +/- 2, 73 +/- 2 and 61 +/- 2 mg/kg for racemate, R(+)- and S(-)-enantiomer respectively. This activity was not antagonized by naloxone. Moreover, racemate and S(-) reduced, only for the highest used active dose on the PBQ test (128 mg/kg, i.p.), the edema induced by an intraplantar injection of carrageenin. These results provide evidence of an analgesic activity independent of the endogenous opiate systems and involving a peripheral mechanism.

Analgesia↗
PubMed1989

Pharmacokinetic patterns of repeated administration of antidepressants in animals. II. Their relevance in a study of the influence of clomipramine on morphine analgesia in mice.

Many studies have shown tricyclic antidepressants (TCAs) to potentiate morphine analgesia, but more recent work, using different modes of administration, has revealed inhibition of morphine analgesia by TCAs. The influence of different modes of administration of clomipramine (CMI) on morphine analgesia assessed by the hot-plate test was studied in mice. The administration procedure was based on the pharmacokinetic parameters of CMI determined in the strain used. Acute and chronic (i.e., every half-life of 130 min for five half-lives) administration of CMI (10 or 20 mg/kg i.p.) had opposite effects; the former potentiated morphine analgesia and the latter inhibited it. Five closely repeated administrations (i.e., every 40 min) suppressed the potentiation without producing inhibition. The time course of the influence of CMI showed that the inhibition of morphine analgesia observed after repeated administration of a given dose of CMI occurred if the latter was present for sufficient time; this time decreased when the dose of CMI was increased. Moreover, comparison with literature data shows the importance of standardized patterns of repeated administration: the variability in the frequency of repeated administration and in the time-lag between the last injection of TCA and the test may account for the varying results observed. The discrepancies in the literature regarding TCA/morphine interaction are thus only apparent, and arise merely from varying conditions. Possible mechanisms for the CMI-morphine interaction are discussed: involvement of opiate receptors and/or the serotonergic system.

Analgesia↗