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Biomedical subjects

H Millart

Publications and source records attributed to H Millart.

At least 55 records · Page 3Linked to original sources
PubMed1986

Influence of plating density on individual cell growth, cell division and differentiation of neonatal rat heart primary cultures.

The influence of plating cell density of an originally enriched myocardial cell population has been studied in neonatal rat heart cells in culture. Low density (LDM) is defined as a density (24 h after plating) of 209 +/- 44 cells/mm2 (mean +/- SEM) and is compared with high density (HDM), 419 +/- 67 cells/mm2. Cell growth is evaluated by the total cell number, the percentage of myocardial cells (M) in culture (PAS method) and the protein content per cell. Some differentiation parameters such as beating rates, glycogen concentration, enzymatic activities (cytochrome C oxidase and glycogen phosphorylase) are studied with time in culture (48, 96 and 192 hr). High density was designed to yield a complete confluency of the cells within 24 hr after plating and to minimize cell division of the non-muscle cells (F). At high density, cell division of F cells is effectively limited, thus leading to a more stable model regarding the cell density per plate and the percentage of M cells: 85.7 +/- 4% and 33.4 +/- 6% in LDM cultures compared with 86.5 +/- 4.7% and 51.7 +/- 9.8% in HDM cultures at 24 and 192 hr (mean +/- SEM). Heart cells increase similarly in size with age in culture in both groups. In HDM cultures the spontaneous contractions begin sooner (24 hr) than in LDM cultures and are more rapidly synchronized. The beating rate is higher in HDM cultures between 48 and 96 hr; however, after this time it falls in HDM and does not fall in LDM. Thus the overgrowth of muscle cells by non-muscle cells is not responsible for loss of beating with time in culture but more likely high density could be a limiting factor for isotonic contraction. There is more glycogen per myocyte in LDM than in HDM cultures. The cell density influences the enzymatic activities of cytochrome C oxidase and glycogen phosphorylase. The cytochrome oxidase activity is higher in HDM cultures than in LDM cultures at 96 hr whereas glycogen phosphorylase activity is higher in LDM cultures at time 96 and 192 hr. In LDM cultures, the ratio cytochrome C oxidase/glycogen phosphorylase decreases with time in culture from 1.685 +/- 0.680 at 48 hr to 0.780 +/- 0.290 at 192 hr but not in HDM cultures (2.13 +/- 0.36 and 1.64 +/- 0.34 respectively). Thus plating density influences properties of heart cell cultures with regard to the overgrowth of the F-cell population and the differentiated state of M cells.

Aminosalicylic Acid↗
PubMed1986

[Plasma levels of clomipramine and declomipramine in patients with depression: a study of its correlation with therapeutic efficacy].

Twenty four in-patients with an endogenous or non endogenous depressive syndrome (9 and 15, respectively) were treated in hospital for 21 days with various dosages regimens of clomipramine. Plasma concentrations of clomipramine and demethylclomipramine were determined once a week in blood samples. Therapeutic effects were assessed with Hamilton Rating Scale. At day 21, optimal therapeutic effect was observed when the sum of clomipramine and demethylclomipramine plasma levels was situated between 200-400 ng/ml.

Adolescent↗
PubMed1985

The effect of 4'-deoxypyridoxine on rat heart cell cultures under oxygen deficiency.

The purpose of this work was to study the consequences of an intracellular depletion of pyridoxal-phosphate (PLP) in rat heart cells in culture submitted to oxygen deficiency. Glucose (GLc) and 4'-deoxypyridoxine (DOP) effects were separately evaluated after 150 mn of partial oxygen deprivation (N2) with regard to enzyme leakage, beating rates, intracellular concentrations of PLP and the ratio glycogen phosphorylase activity (-5'-AMP/+5'-AMP). PLP concentrations were higher in the air-GLc group than in the air group. alpha-Hydroxybutyrate dehydrogenase (alpha-HBDH) and creatine kinase (CK) leakages were observed in the N2 group, whereas 1.17 +/- 0.17 mM GLc prevented leakage. Beatings stopped in the N2 group, slightly decreased in the N2-GLc group; the ratio (-5'-AMP/+5'--AMP) increased only in the N2 group. With a 1 mM DOP pretreatment a significant decline of PLP was observed either with or without GLc in the culture medium. The ratio (-5'-AMP/+5'-AMP) was lower in the air-DOP group than in the air group, whereas beatings, alph-HBDH and CK activities were identical to the control group. ImM DOP in the N2-DOP group partially prevented alpha-HBDH and CK leakages into the medium but did not prevent the decrease in contractile activity. Surprisingly, PLP concentration increased in the N2-DOP group/air-DOP group and the increase in ratio (-5'-AMP/+5'-AMP) was higher in the N2-DOP group than in the N2 group when compared to the respective control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Evaluation of 4-aminopyridine and 3,4-diaminopyridine penetrability into cerebrospinal fluid in anesthetized rats.

4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP) when injected intracisternally to anesthetized rats induced qualitatively similar central nervous system stimulant and convulsant effects at equimolar concentrations. Overall penetrability into cerebrospinal fluid of 4-AP is significantly higher than that of 3,4-DAP after single i.v. administration as evaluated by a high-performance liquid chromatographic determination. The present results can account for the lower central nervous system toxicity of 3,4-DAP when compared to 4-AP previously described after systemic administration.

4-Aminopyridine↗
PubMed1984

[Bone and blood levels of azlocillin after intra-arterial injection in the dog].

Pharmacokinetic values of azlocillin--a semisynthetic penicillin of the ureidopenicillin family--were determined in dogs after injection of the drug into the right femoral artery by measuring plasma concentrations in the right femoral artery and left femoral vein and tissue concentrations in ipsi- and contralateral bones. Two different doses of azlocillin were administered, one group of dogs receiving 100 mg X kg-1 by fast (1 min) bolus injection and the other group receiving 250 mg X kg-1. The drug was assayed by high performance liquid chromatography in reverse phase, which proved to be the simplest, most rapid and most sensitive method. Changes in plasma and bone tissue concentrations after intra-arterial injection were interpreted as order one kinetics with a two-compartment open model. Following the 100 mg/kg dose, concentrations versus time corresponded to the following equations: --Arterial blood (mg/l) = 7570 e-0.15 t (min) + 240 e-0.017 t --Venous blood (mg/l) = 553 e-0.13 t + 222 e-0.016 t --Bone tissue (micrograms/g) = 15 e-0.0115 t (elimination phase). Distribution and elimination constants were identical in arterial and venous blood. Distribution half-life was 5 +/- 1 min in arterial blood and biological half-life was 42 +/- 11 min. However, bioavailability was comparatively lower in veins due to higher levels in arteries during the distribution phase. Bone tissue concentrations were much lower than plasma concentrations and were identical on both sides despite high arterial levels on the ipsilateral side during the distribution phase. Bone concentrations diminished rapidly and elimination kinetic values were the same in bone and in plasma. It is concluded that bone tissue concentrations of azlocillin after intra-arterial injection are highest during the distribution phase.

Animals↗
PubMed1984

[Indices of partial oxygen deprivation in the culture medium of cardiac cells].

Three indexes of partial oxygen deprivation, i.e. hypoxanthine, alpha HBDH and CK, were investigated in rat heart cell cultures, 7 day-old. Enzyme release in the medium and hypoxanthine uptake by the cells pointed out both oxygen and glucose deprivation, which modelized ischemia. Conversely, hypoxanthine release pointed out oxygen deprivation, in the presence of glucose however, which modelized hypoxia, whereas there was no enzyme leakage in the latter condition.

Anaerobiosis↗
PubMed1983

Pharmacokinetic study of two pharmaceutical preparations containing alkaloid vincamine administered orally to human subjects.

In a crossover study of six healthy volunteers the pharmacokinetics and the bioavailability of vincamine were studied after administration of two oral forms. All subjects received an oral dose of 60 mg vincamine. The plasma concentrations of the drug were determined by a specific and sensitive gas chromatographic method. In this kind of subject the drug generally follows a one-compartment kinetic model. The average value of Tmax is 1.4 +/- 0.5 h-1 with the tablets and 1 +/- 0.6 h-1 with the solution; the Cmax are, respectively, 155 +/- 82 micrograms . 1(-1) and 133 +/- 104 micrograms . 1(-1). The AUC are 443 +/- 156 micrograms . 1(-1) h with the tablets and 315 +/- 178 micrograms . 1(-1) h with the solution. The short elimination phases, 1.43 +/- 0.80 h with the tablets and 1.55 +/- 0.78 h with the solution should be taken into account during chronic administration.

Administration, Oral↗
PubMed1980

[Hypolipidaemic agents (author's transl)].

Since clofibrate was discovered, a number of compounds have been made available for the treatment of hyperlipoproteinaemias. Their principal pharmacological and therapeutic properties are summarized in this paper. Other compounds are now under pre-clinical or clinical studies, including probucol which is reviewed in this issue.

Animals↗
PubMed1980

[Experimental pharmacology of probucol (author's transl)].

The experimental studies carried out so far have uniformly demonstrated that probucol lowers plasma cholesterol levels in all animal species. The drug has low toxicity and has been well tolerated during long-term treatment (up to 8 years in monkeys) in most species. In some dogs, however, probucol seemed to increase myocardial sensitivity to catecholamins, but this has not been found in other species. The pharmacokinetics of probucol show a rather slow turnover and are characterized by storage of the drug in adipose tissues, which may explain why the hypocholesterolaemic effect is progressively obtained. The main channel of excretion is the bile. No other pharmacological action has been described with probucol, which in the present state of knowledge appears to be a predominantly cholesterol-lowering agent.

Adipose Tissue↗
PubMedDate not supplied

[Pharmacokinetics of beta blockers in hyperthyroidism. Therapeutic relevance].

Hyperthyroidism is associated with alterations in pharmacokinetic parameters such as absorption, distribution, metabolism and elimination. Beta-blockers are used in particular in the treatment of hyperthyroidism and are also subject to pharmacokinetic changes occurring during this pathology. The magnitude of these variations is examined when beta-blockers are used for clinical manifestations of hyperthyroidism or during thyroid surgery. Clinical means used to assess the accuracy of therapeutic drug monitoring are also described.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

[Utilization of methylphenidate(Ritalin) in France].

Methylphenidate (Ritalin) is the only psychostimulant approved in France and indicated in attention deficit hyperactivity disorder in children over 6 years. It is under restricted prescription and distribution conditions. As such, it requires a hospital initiated prescription from either a neurology, psychiatry or pediatric specialist and it is covered by the "narcotics" schedule. The French Pharmacovigilance database spontaneous adverse drug reactions reporting, since it was approved in 1995, were analyzed. 21 adverse drug reactions were reported. In 16 cases, methylphenidate was suspected. They were generally non-serious, mild side effects and in most cases promptly resolved. These results do not suggest methylphenidate misuse in France or an overuse in between 1300 and 4000 treated children, to date. Until more information is available concerning the long-term effects of methylphenidate, and in order to limit misuse, inappropriate or overuse, the current prescription and dispensing regulation should be maintained in France, and could well be developed in other countries.

Attention Deficit Disorder with Hyperactivity↗
PubMedDate not supplied

Efficiency of amifostine as a protection against doxorubicin toxicity in rats during a 12-day treatment.

BACKGROUND: Our purpose was to determine the effects of amifostine, a cytoprotective agent, on doxorubicin tolerance and cardiotoxicity in rats. MATERIALS AND METHODS: Male Wistar rats were treated every other day with an intraperitoneal injection of amifostine or saline 30 minutes before intraperitoneal injection of doxorubicin or saline. Weight change was recorded, and contractile function was evaluated after 11 injections by means of the isolated heart. RESULTS: Weight evolution and cardiac function were significantly improved by 7 and 20 mg/kg amifostine (p < 0.001) but not by 50 mg/kg. The final weight were: controls 349 +/- 16 g; doxorubicin alone 258 +/- 54 g; with amifostine: 7 mg/kg 314 + 28 g; 20 mg/kg 312 +/- 32 g; 50 mg/kg 250 +/- 34 g. Left ventricular developed pressure were: controls 137 +/- 15 mmHg; doxorubicin alone 119 +/- 20 mmHg; with amifostine: 7 mg/kg 140 +/- 20 mmHg; 20 mg/kg 137 +/- 25 mmHg; 50 mg/kg 124 +/- 20 mmHg. CONCLUSION: Seven and 20 mg/kg amifostine protected rats from the toxicity of doxorubicin at the cumulative dose of 18 mg/kg during a 12-day treatment, with regard to weight loss and heart contraction.

Amifostine↗
PubMedDate not supplied

The effects of 5-fluorouracil on contractility and oxygen uptake of the isolated perfused rat heart.

Clinical cardiotoxicity related to 5-fluorouracil (5-FU) simulates either myocardial ischemia or left ventricular dysfunction. In order to characterize the changes occurring in the heart following 5-FU administration, the isovolumic perfused rat heart model according to Langendorff has been used. Particular emphasis was laid on contractility and oxygen uptake. Perfusion of isolated hearts with 1 mg/L 5-FU for 80 minutes failed to show any differences in contractility and oxygen consumption in comparison with the control group. On the contrary, 5-FU pretreatment of Wistar rats (50 mg/kg I.P. for 5 consecutive days) led to a decrease in inotropism without any change in maximum relaxation rate. The most significant finding was the consistent increase in oxygen consumption throughout the 80 minutes of perfusion (p less than 0.05) associated with a decrease in the fractional extraction of oxygen. Mean coronary flow was consistently increased in the 5-FU-pretreated group. Lactate release and CK Leakage did not differ in the two groups. In the 5-FU-pretreated group the ratio of oxygen consumption to rate-pressure product remained significantly elevated throughout 80 minutes of perfusion in comparison with the control group (p less than 0.05). Inappropriately high oxygen uptake could be a reflection of cellular metabolic disturbances responsible for post-ischemic dysfunction.

Animals↗