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Biomedical subjects

A Turcotte

Publications and source records attributed to A Turcotte.

10 recordsLinked to original sources
PubMed1992

Pharmacodynamic interaction between RP 59500 and gram-positive bacteria infecting fibrin clots.

The fibrin clot penetration and in vivo bactericidal activity of RP 59500, a new semisynthetic streptogramin, for two Staphylococcus aureus strains (one methicillin resistant and the other methicillin susceptible), two Staphylococcus epidermidis strains (one methicillin resistant and the other methicillin susceptible), and one Enterococcus faecalis strain were evaluated. The clots, inserted subcutaneously, were infected with a mean of 10(8) CFU of the pathogen per g. For each strain, groups of four rabbits received a single intravenous injection of 50 mg of RP 59500 per kg of body weight over 30 min. The mean peak level of RP 59500 in serum in the infected rabbits was 61.9 +/- 6.3 micrograms/ml. The drug was detectable in serum at a level of 0.8 micrograms/ml up to 4 h after administration. The mean peak fibrin clot drug level at 1 h was 3.3 +/- 0.1 micrograms/g. At 6 h, the level in clots was 1.2 +/- 0.1 micrograms/g. The mean half-life in serum in infected rabbits was 0.34 +/- 0.01 h, while in clots the drug exhibited a longer half-life of 3.8 +/- 0.4 h. In vivo, this new streptogramin sterilized the clots infected with the two S. aureus strains studied in less than 1 h and induced a marked reduction in colony counts of the two S. epidermidis strains studied for up to 24 h. The activity of the streptogramin against E. faecalis was limited. These results suggest that RP 59500 should be further evaluated for the treatment of infection with methicillin-resistant staphylococci.

Animals↗
PubMed1986

In-vitro uptake of gentamicin and tobramycin by rat renal tubules in the presence or absence of Escherichia coli endotoxin.

Renal tubules of rats were incubated with aminoglycoside (gentamicin or 3H-tobramycin, 10 mg/l) in the presence or absence of Escherichia coli endotoxin (10 mg/l). The kinetics of aminoglycoside uptake by the tubule were only slightly affected by endotoxin. The percentage of serum in the medium affected the tobramycin uptake. This uptake decreased from a mean ratio of concentration in the tubules/concentration in the medium (T/M) of 1.63 in 5% serum to a mean T/M of 0.86 in 10% serum (P less than 0.01).

Aminoglycosides↗
PubMed1986

Penetration of cefixime into fibrin clots and in vivo efficacy against Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus.

The experimental model of infected fibrin clots in rabbits was used to study the penetration and in vivo activity of cefixime against Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus. The respective MICs of cefixime against these strains were 0.25, 2, and 8 micrograms/ml. The clots were infected with 10(6) to 10(8) CFU/g. Groups of four animals for each strain received an intravenous injection of 100 mg of cefixime per kg over 30 min. High peak levels were observed in serum (146.5 micrograms/ml) and clots (15.8 micrograms/g), and the antibiotic was still detectable in the clots (0.6 micrograms/g) 24 h after administration. The respective serum and clot elimination half-lives were 0.7 and 5.0 h. The mean serum protein binding was 23.8 +/- 3.8%. Cefixime was highly bactericidal against K. pneumoniae and E. coli and reduced, over a 24-h period, their respective colony counts by 7.8 log10 and 6.2 log10 CFU/g of fibrin. It was less effective against S. aureus but still reduced the bacterial counts by 2.8 log10 CFU/g of fibrin. The present results demonstrate that cefixime, a new broad-spectrum oral cephalosporin, has a long tissue half-life which ensured, at the dose given here, good in vivo bactericidal activity against both gram-positive and gram-negative bacteria up to 24 h after administration of the antibiotic.

Animals↗
PubMed1986

Synthesis and biological activity of analogs of dynorphin-A(1-13) substituted in positions 2 and 4: design of [Ala2,Trp4]-Dyn-A(1-13) as a putative selective opioid antagonist.

Mono- and di-substituted analogs of dynorphin-A(1-13) (Dyn-A(1-13)) were synthesized by the solid-phase procedure. The products were purified and analyzed for their ability to inhibit the electrically evoked contractions of the guinea pig ileum (GPI) and mouse vas deferens (MVD) and to compete with the binding of [3H]etorphine ([3H]ET) and [3H]ethylketocyclazocine ([3H]EKC) to homogenates of rat brain (mu-, delta-, kappa 2-receptors) and guinea pig cerebellum (kappa-receptor), respectively. Introduction of Ala in position 2 caused a drastic decrease in the activity of the peptide on the smooth muscle preparations (IC50 of 104 and 2.250 nM in the GPI and the MVD as compared with 0.7 and 21 nM for the parent peptide, respectively). Conversely, this analog retained much of the opioid binding activity of Dyn-A(1-13) (relative binding potencies of 15 and 72% for the displacement of [3H]ET and [3H]EKC, respectively). The replacement of Phe4 by Trp also caused drastic decreases in the activity of the peptide in the smooth muscle preparations (relative potencies of 0.8 and 8.8% on the GPI and MVD) while much of the binding potency to the opioid receptors was retained (31 and 67% for the displacement of [3H]ET and [3H]EKC, respectively). [Ala2,Trp4]-Dyn-A(1-13) was the least potent peptide tested in the smooth muscle assays (relative potencies: 0.1 and 0.6%). However, this latter analog still retained some opioid binding activity in the displacement of [3H]ET to rat brain homogenates (3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1984

Synthesis and biological activity of monothionated analogs of leucine-enkephalin.

The synthesis of the four regioisomers of monothionated Leu-enkephalins (Leu-Enk) from previously reported protected precursors is described. The Tyr1-thio analog was obtained as a 1:1 mixture of the L- and D-Tyr diastereomers. The pure compounds were tested for opiate-like activity by using the guinea-pig ileum (GPI) and mouse vas deferens (MVD) preparations, by assessing analgesic effects following intra-cerebroventricular administration and by examining their ability to displace [3H]-D-Ala2, D-Leu5-enkephalin (DADLE) and [3H]-dihydromorphine from rat brain homogenates. The results demonstrate that depending on the backbone position of the thioamide function, activity can be decreased or increased. In the smooth muscle preparations as well as in the opiate binding tests, the activity of D,L-Tyr1-thio-Leu-Enk and Gly3-thio-Leu-Enk was reduced. The activity of the latter analog was also diminished in the analgesia test. In all biological assays, Phe4-thio-Leu-Enk was either equally or slightly less potent than the parent compound. However, introduction of the sulfur atom in position 2 of Leu-Enk increased the potency of the compound in all assays, the MVD assay being the most sensitive. The results are interpreted in terms of the thioamide (amide) function in receptor recognition processes, the probable behavior of thiopeptides toward physiologically relevant peptidases and the structural divergences between tissue-specific receptors.

Amino Acids, Sulfur↗
PubMed1984

Dynorphin-(1-13). I. Structure-function relationships of Ala-containing analogs.

Dynorphin-(1-13) (Dyn-(1-13] and its analogs substituted by single introduction of Ala in positions 1-11 were synthesized by the solid-phase method and purified by high pressure liquid chromatography. Relative potencies of the synthetic compounds were determined by their ability to inhibit electrically-evoked contractions of the guinea pig ileum (GPI) and of the mouse vas deferens (MVD) and to compete with [3H]-etorphine for opiate receptors in rat brain homogenates. Introduction of Ala in positions 1 and 4 of Dyn-(1-13) provoked most important decreases in the activity of the molecule in the three assays (relative potency of 0.2% or less). Substitution of Ala in positions 2 or 5, but not 3, also severely decreased the potency of the peptide in the smooth muscle preparations (0.6-5.0% activity). However, the opiate receptor binding assay was less sensitive to the replacement of residue in position 2 (20% activity) than that in positions 3 or 5 (12% and 6% relative potencies, respectively). In the GPI assay and the opiate binding test, the other substitutions which greatly lowered the potency of the molecule were seen in positions 6, 7, 9 and 11, four basic residues. Among these, Arg6 and Arg7 were demonstrated to be the most important in the three biological tests. Finally, the replacement of Ile8 by Ala increased the relative potency of Dyn-(1-13) up to 191% and 900% in the MVD and the opiate binding tests, respectively.

Amino Acids↗
PubMed1984

[Separation of the virotoxins of the mushroom Amanita virosa and comparative study of their interaction on actin in vitro].

Cyclic peptides have been extracted with methanol from Amanita virosa and separated by preparative HPLC. Six peptides were obtained: phalloidin and five new peptides recently identified by Faulstich as virotoxins. We have compared the interaction of these six peptides with actin in vitro. They increased the rate of polymerization of actin and protected F-actin against several denaturating agents: proteases, heat, chaotropic ions, cytochalasin B, and DNAse I. The five virotoxins have therefore the same biological properties as phalloidin. However, the differential spectra of interaction between actin and the five virotoxins are different than the differential spectra between actin and phalloidin, thus it appears that the molecular interaction of actin with virotoxins is different than with phalloidin. The five virotoxins have the same activity. Although these virotoxins have different functional groups on amino acids 1 and 7, it is concluded that these two amino acids are of minor importance in the interaction of these peptides with actin.

Actins↗
PubMed1983

[Amanita virosa peptides: viroidin and viroisin are more effective than phalloidin for the in vitro protection of actin against the effects of osmic acid].

Virotoxins are a group of monocyclic peptides recently identified in the deadly mushroom Amanita virosa by Faulstich and coll. We found that two of these peptides, which have a methyl sulfonyl group, namely viroidin and viroisin are very effective to protect F-actin against oxidative degradation by osmium tetroxide in vitro. Their desoxo analogs, which have a methyl sulfoxyde group instead of methyl sulfonyl are less active, therefore there exists a relationship between the chemistry of the sulfur group and the activity of the peptides.

Actins↗
PubMed1982

[In vivo and in vitro effects of peptide extracts from Amanita virosa].

Cyclic peptides from the deadly mushroom Amanita virosa has been separated by methanolic extraction and chromatography on Sephadex. Three groups of peptides have been obtained: virotoxins, amaninamide and phalloidin. Virotoxins has been separated in two fractions named virotoxins A and virotoxins B. We have studied the properties of these two fractions of F actin in vitro and on mice in vivo. Our results show that virotoxins A and B protect F actin in vitro against chaotropic ions, depolymerization by DNAse I or cytochalasin B and heat denaturation. Virotoxins A and B increase the rate of polymerization of F actin. Virotoxins A and B are toxic compounds which produce hemorrhagic necrosis of liver that have been observed in detail by electron microscopy. In general, our in vitro and in vivo results show that virotoxins exhibit the same effect as phalloidin on F actin.

Agaricales↗