Biomedical subjects

C Lépine

Publications and source records attributed to C Lépine.

11 recordsLinked to original sources

PubMed1999

Effects of hindlimb suspension on contractile properties of young and old rat muscles and the impact of electrical stimulation on the recovery process.

The purpose of this study was to investigate the effects of hindlimb suspension (HS) on contractile properties of skeletal muscles of young and old rats and to determine the impact of electrical stimulation (ES) on the quality and degree of recovery of these muscles. After 21 days of HS, young soleus (SOL) muscle became faster, but there was no impact on young extensor digitorum longus (EDL) muscle. Twitch tension (Pt) decreased 61% in young and 70% in old SOL muscles. Specific tetanic tension (Po) decreased 53% in young and 64% in old SOL muscles, but again there was no impact on EDL muscle. After a 14-day period of recovery, contraction time (CT), half-relaxation time (RT1/2), Pt and Po returned to control group values in both young and old SOL muscles. Measurements of the contractile properties of young and old skeletal rat muscles showed ES sometimes to be beneficial but also sometimes to be harmful. A 14-day period of recovery, with or without ES, seemed sufficient for many variables to return to control group values.

Aging↗

PubMed1996

Dioxabicyclooctanyl naphthalenenitriles as nonredox 5-lipoxygenase inhibitors: structure-activity relationship study directed toward the improvement of metabolic stability.

Naphthalenic lignan lactone 3a (L-702,539), a potent and selective 5-lipoxygenase (5-LO) inhibitor, is extensively metabolized at two different sites: the tetrahydropyran and the lactone rings. Early knowledge of the metabolic pathways triggered and directed a structure-activity relationship study aimed toward the improvement of metabolic stability in this series. The best modifications discovered, i.e., replacement of the lactone ring by a nitrile group, replacement of the tetrahydropyran ring by a 6,8-dioxabicyclo[3.2.1]octanyl moiety, and replacement of the pendant phenyl ring by a 3-furyl ring, were incorporated in a single molecule to produce inhibitor 9ac (L-708,780). Compound 9ac inhibits the oxidation of arachidonic acid to 5-hydroperoxy-eicosatetraenoic acid by 5-LO (IC50 = 190 nM) and the formation of leukotriene B4 in human polymorphonuclear leukocytes (IC50 = 3 nM) as well as in human whole blood (IC50 = 150 nM). The good inhibitory profile shown by naphthalenenitrile 9ac is accompanied by an improved resistance to oxidative metabolism. In addition, 9ac is orally active in the functional model of antigen-induced bronchoconstriction in allergic squirrel monkeys (95% inhibition at 0.1 mg/kg).

Animals↗

PubMed1994

Thiopyrano[2,3,4-cd]indoles as 5-lipoxygenase inhibitors: synthesis, biological profile, and resolution of 2-[2-[1-(4-chlorobenzyl)-4-methyl-6-[(5-phenylpyridin-2-yl)methoxy]-4,5 -dihydro-1H-thiopyrano[2,3,4-cd]indol-2-yl]ethoxy]butanoic acid.

Leukotriene biosynthesis inhibitors have potential as new therapies for asthma and inflammatory diseases. The recently disclosed thiopyrano[2,3,4-cd]indole class of 5-lipoxygenase (5-LO) inhibitors has been investigated with particular emphasis on the side chain bearing the acidic functionality. The SAR studies have shown that the inclusion of a heteroatom (O or S) in conjunction with an alpha-ethyl substituted acid leads to inhibitors of improved potency. The most potent inhibitor prepared contains a 2-ethoxybutanoic acid side chain. This compound, 14d (2-[2-[1-(4-chlorobenzyl)-4-methyl-6-[(5-phenylpyridin-2-yl)methox y]- 4,5-dihydro-1H-thiopyrano[2,3,4-cd]indol-2-yl]ethoxy]-butanoic acid, L-699,333), inhibits 5-HPETE production by human 5-LO and LTB4 biosynthesis by human PMN leukocytes and human whole blood (IC50s of 22 nM, 7 nM and 3.8 microM, respectively). The racemic acid 14d has been shown to be functionally active in a rat pleurisy model (inhibition of LTB4, ED50 = 0.65 mg/kg, 6 h pretreatment) and in the hyperreactive rat model of antigen-induced dyspnea (50% inhibition at 2 and 4 h pretreatment; 0.5 mg/kg po). In addition, 14d shows excellent functional activity against antigen-induced bronchoconstriction in the conscious squirrel monkey [89% inhibition of the increase in RL and 68% inhibition in the decrease in Cdyn (0.1 mg/kg, n = 3)] and in the conscious sheep models of asthma (iv infusion at 2.5 micrograms/kg/min). Acid 14d is highly selective as an inhibitor of 5-LO activity when compared to the inhibition of human 15-LO, porcine 12-LO and ram seminal vesicle cyclooxygenase (IC50 > 5 microM) or competition in a FLAP binding assay (IC50 > 10 microM). Resolution of 14d affords 14g, the most potent diastereomer, which inhibits the 5-HPETE production of human 5-LO and LTB4 biosynthesis of human PMN leukocytes and human whole blood with IC50s of 8 nM, 4 nM, and 1 microM respectively. The in vitro and in vivo profile of 14d is comparable to that of MK-0591, which has showed biochemical efficacy in inhibiting ex vivo LTB4 biosynthesis and urinary LTE4 excretion in clinical trials.

Animals↗

PubMed1993

Impact of insecticides on the American robin (Turdus migratorius) in a suburban environment.

The purpose of this study was to examine the effects of diazinon and acephate applications to ornamental trees on the breeding behaviour and productivity of the American robin and to measure the effect of repeated chlorpyrifos spraying on robin productivity. No cases of adult or juvenile mortality were recorded, and nestling production was not affected. Plasma cholinesterase (ChE) activity in females exposed to diazinon or acephate was significantly lower than that in controls. However, there were no pronounced changes in parental care. The absence of a significant impact on behaviour despite the marked change in plasma ChE levels may have been due to one of several factors, i.e. (1) the insecticide had not reached the brain 18 to 24 h after spraying, and (2) exposure was insufficient to produce behavioural changes. The use of diazinon and acephate on ornamental trees should not be harmful to robins. There was a negative correlation between nest productivity and the number of lawns surrounding the nest treated with chlorpyrifos once or more in the preceding 2 years. The decline in earthworm numbers and their reduced biomass due to repeated chlorpyrifos use may account for the lower productivity recorded during the nesting season.

Journal Article↗

PubMed1970