Biomedical subjects

G Cremer

Publications and source records attributed to G Cremer.

At least 19 recordsLinked to original sources

PubMed1992

Covalent attachment of ribonucleic acids to proteins.

As a prerequisite for the synthesis of affinity labels, we describe methods to couple histones to ribonucleic acids. For the synthesis of these covalent hybrid molecules, we used a population of histones H1, H2A, H2B, H3, and H4 from calf thymus and polyadenylic acid with an average chain length of up to 260-280 bases, representing the size of poly(A)-tails from mature mRNAs. Three methods were investigated. (a) Poly(A) containing an 8-N3-A residue was cross-linked to histones by ultraviolet irradiation. (b) The 3'-end of the polynucleotide was connected to a mononucleotide containing an aliphatic amino group, and the resulting poly(A)-derivative was coupled to histones via derivation with a bromoacetyl group. (c) The 3'-end of the polynucleotide was oxidized with sodium periodate and bound covalently to an amino group of the polypeptide. To demonstrate the RNA content of the hybrid molecule, the poly(A) was removed with RNase T2.

Animals↗

PubMed1992

[Contribution of molecular genetics to the understanding of chemoresistance of Plasmodium falciparum].

Resistance to pyrimethamine and proguanil is due to a single point mutation in the gene that codes for dihydrofolate reductase. A single mutation gives rise to resistance to only one of the drugs. Resistance to both drugs results from several mutations. Chloroquine resistance phenotype is due to a rapid efflux of the drug from the parasite's digestive vacuole. This efflux is associated with a transmembrane permeability glycoprotein, or P-gp, which is similar to the protein implicated in the multidrug resistant phenotype of some cancer cells. However, one or several other poorly understood major gene(s) may be involved. Drugs which can inhibit the supposed affinity of P-gp for chloroquine are under study.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1991

Piroximone, dobutamine and nitroprusside: comparative effects on haemodynamics in patients with congestive heart failure.

Four intravenous doses of piroximone, an imidazolone derivative, were administered to 12 patients with congestive heart failure to produce a four-point dose-response curve. The haemodynamic effects were compared with those of dobutamine and nitroprusside, the substances being given sequentially and in randomized order. Piroximone and dobutamine significantly and similarly increased cardiac index (CI) and stroke volume index (SVI). Nitroprusside produced no such effect. By contrast, piroximone and nitroprusside significantly and similarly decreased mean pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP) and pulmonary vascular resistance (PVR), while such changes were not seen following dobutamine. Direct comparisons between the agents were made at doses that lowered systemic vascular resistance (SVR) to the same extent. The major difference between dobutamine and piroximone was an apparent additional vasodilator activity displayed by piroximone as demonstrated by a significantly greater decrease in MPAP, PCWP and RAP for a matched reduction in SVR and a similar increase in CI. The major difference between nitroprusside and piroximone was the significantly higher increase in CI and SVI elicited by piroximone for a matched reduction in SVR and a similar decrease in PCWP and RAP. The changes in loading conditions being equivalent, the higher increase in CI is likely to be accounted for by a direct inotropic activity.

Adult↗

PubMed1991

Effects of a standardized meal on the pharmacokinetics of the new cardiotonic agent piroximone.

The influence of food on the pharmacokinetics of piroximone (MDL 19.205, CAS 84490-12-0) was evaluated in two groups of 6 healthy male volunteers receiving either 25 or 50 mg of the drug. Single doses were administered intravenously and orally under fasting conditions or orally with a standard breakfast on 3 different days with a washout period of at least 3 days in-between doses, according to an open, 3-way crossover, randomized design. Pharmacokinetic parameters (Cmax, tmax, AUC, t1/2, Cl, aVd, UEx) were not affected by food administration, but significant differences were found in t1/2 calculated from the decay of plasma concentrations in response to oral administration of 25 mg and 50 mg treatment doses. The urinary excretion of piroximone was significantly reduced after oral administration, when compared with the values obtained after intravenous application. In addition, extra-renal clearance was significantly reduced in the 50 mg treatment group, when compared with the values obtained in response to 25 mg. Bioavailability of piroximone calculated from AUC data compared favorably with data obtained from urinary recovery results.

Adolescent↗

PubMed1990

Long-term treatment with piroximone in patients with chronic heart failure.

The safety and efficacy of long-term oral piroximone therapy was assessed in 12 patients with chronic heart failure. Of these 12 patients, two died suddenly, and a further two were withdrawn because of worsening heart failure within 6 months while 8 completed the 1-year follow-up period. In 7 of these 8 patients, clinical evaluations showed sustained benefit, as demonstrated by significant increases in exercise tolerance. The remaining patient experienced a recurrence of severe heart failure at the end of follow-up. Twenty-four hour ambulatory electrocardiograms were compared in 9 patients before and during piroximone therapy. Aggravation of existing arrhythmias was observed in 3 patients, an amelioration in one with no change in the remaining 5. In the 5 patients in whom the hemodynamic effects of a single oral dose of 25 mg of piroximone were studied, the first dose resulted in a 20% increase in mean cardiac index and a 30% decrease in mean pulmonary capillary wedge pressure. This responsiveness to single-dose administration was maintained after 1-year follow-up. Likewise, comparison of the hemodynamic effects of four intravenous doses of piroximone revealed no significant difference in the response (n = 7), although the effects tended to be less marked at the end of follow-up. The present results suggesting that piroximone is effective and safe as adjunctive therapy in the management of patients with chronic heart failure will need to be confirmed in longer controlled trials.

Adult↗

PubMed1986