Biomedical subjects

D Guillaume

Publications and source records attributed to D Guillaume.

59 records · Page 4Linked to original sources

PubMedDate not supplied

Synthesis and photochemical behaviour of a T-T dimer containing an amide linkage.

A T-T dimer characterized by an amide linkage to replace the phosphodiester backbone has been synthesized using a modified radical strategy. The new synthetic approach makes use of a thymidin-3'-yl phosphorodithioate derivative as a precursor of 3'-allyl-3'-deoxythymidine. Standard chemical transformations of this derivative led to the desired T-T dimer incorporating an amide bond. The latter was irradiated with 254 nm wavelength light to yield mainly cyclobutane and [6-4] photoadducts.

Amides↗

PubMedDate not supplied

Glial contribution to seizure: carbonic anhydrase activity in epileptic mammalian brain.

The activity of carbonic anhydrase (CA), a glial enzyme, was measured in the epileptic cortex of audiogenic DBA/2 mice and of cats with a freeze lesion. In mice, the activity increased with age from birth to 24 days, but were always higher in audiogenic mice than in normal C57/BL mice, reflecting species differences. The difference between the two strains increased sharply from 25 to 40 days of age, after the period of maximal audiogenic susceptibility. Acetazolamide, a CA-specific inhibitor, greatly decreased the seizure severity score of DBA/2 mice after a single intraperitoneal (i.p.) administration (150 mg/kg). After 24 days of age, when CA activities were high, the effect of acetazolamide was less important, suggesting that the increased cortical CA activity might reflect a protective mechanism. In cats with a freeze lesion, no significant changes in CA activities were observed in the actively discharging primary and secondary foci as compared with the nonepileptogenic perifocal cortex and the control cortex of sham-operated animals. The results indicate that the cortex of genetically susceptible audiogenic mice has an increased CA activity. The hypothesis of an adaptive glial mechanism, relating to the age-dependent decrease of seizure susceptibility in DBA/2 mice, is postulated.

Acoustic Stimulation↗

PubMedDate not supplied

Effect of milacemide on audiogenic seizures and cortical (Na+, K+)-ATPase of DBA/2J mice.

Milacemide (MLM, CP 1552 S, 2-N-pentylaminoacetamide), a glycinamide derivative, is currently being evaluated clinically for antiepileptic activity. Anticonvulsant properties have been shown in various animal models, but the mechanism of action of MLM is unclear. We studied its activity in audiogenic seizures of DBA/2J mice. MLM was effective in inhibiting the convulsions induced by sound with a biphasic dose-effect relation. The ED50 was 109 mg/kg orally against tonic extension. Higher doses were necessary to abolish clonic convulsion and running response. Because impaired cerebral (Na+, K+)-ATPase activity is supposed to play a role in epileptogenesis, we tested MLM on in vitro cortical enzymatic activity of DBA/2J mice. Basal (Na+, K+)-ATPase activity was unchanged by several concentrations of MLM in normal C57BL/6J and audiogenic DBA/2J mice. K+ activation (from 3 to 18 mM) of (Na+, K+)-ATPase is abolished in DBA/2J mice as compared with C57BL/6J mice, suggesting impaired glial (Na+, K+)-ATPase. In the presence of MLM (from 30 to 1000 mg/L), cortical (Na+, K+)-ATPase of DBA/2J mice is activated by high concentrations of K+, as in C57BL/6J mice. Results suggest that the antiepileptic activity of MLM in audiogenic mice may be secondary to an activation of a deficient glial (Na+, K+)-ATPase.

Acetamides↗

PubMedDate not supplied

Quantitative and qualitative assessment of milk production after pharmaceutical induction of lactation in the mare.

The induction of lactation is performed in ruminants by steroidogenic impregnation, followed by drugs intended to increase prolactin secretion. The aim of this study was to induce lactation in barren mares and to evaluate milk production. Five treated and 5 control mares were used in June and September in year 1, and 12 mares were used in year 2. Mares were administered a vaginal pessary (500 mg altrenogest and 50 mg estradiol benzoate) for 1 week. The 2nd week, another sponge with 100 mg estradiol benzoate was administered, together with 50 mg/100 kg body weight (BW) sulpiride in oil (IM q12h). All mares were milked by hand. Drug treatment was stopped after I L was obtained. Milk production and composition and plasma prolactin concentration were measured. In year 2, the same steroid treatment was applied, but mares received sulpiride (n = 6) or domperidone (1.1 mg/kg PO q12h) (n = 6). A milking machine and oxytocin injections 1 minute before the start of milking were used. In year 1, all treated mares started milking within 1-5 days after sulpiride treatment. Mean daily milk production was 0.88 +/- 0.52 L/500 kg BW. Milk immunoglobulin G (IgG) contents increased in all mares (IgG concentration range, 14-92 g/L). Plasma prolactin increased during sulpiride treatment (range. 27.7 +/- 2.9 to 43.7 +/- 6.7 ng/mL [before] to 289.0 +/- 7.8 ng/mL during treatment, P < .001). In year 2, results were similar to those in year 1, with peak IgG concentrations ranging from 4.2 to 106.7 g/L and a larger daily milk production (3.13 +/- 0.75 with sulpiride and 3.45 +/- 0.51 L/500 kg BW with domperidone). In conclusion, lactation can be induced in mares within 2 weeks, and some mares produce good-quality colostrum.

Administration, Intravaginal↗

PubMedDate not supplied

Brain cortical (Na+ K+)-ATPase in epilepsy. A biochemical study in animals and humans.

(Na+, K+)-ATPase (E.C.3.6.1.3) was partially purified from the cerebral cortex of audiogenic DBA/2 mice, from the primary and secondary epileptogenic foci of cats with a freeze lesion and from normal and epileptic human cortices. No differences in the specific activities of the microsomal enzyme were observed between normal and epileptic cortex. The influence of K+ ions and phenytoin, a potent antiepileptic drug, was then studied on the phosphorylation level of (Na+, K+)-ATPase alpha(+) (neuronal) and alpha(-) (non-neuronal) catalytic subunits resolved by SDS-gel electrophoresis. In normal cortex, the apparent affinity of the non-neuronal enzyme to K+ ions was reduced compared to the affinity of the neuronal enzyme. Phenytoin decreased the phosphorylation level of (Na+, K+)-ATPase purified from non-epileptogenic cortex of control C57/BL mice, cats and human patients. In fact, the drug induced the dephosphorylation of the (Na+, K+)-ATPase catalytic subunits, mainly of its alpha(-), non-neuronal subtype. In the cortex of audiogenic DBA/2 mice, K+ ions induced the dephosphorylation of (Na+, K+)-ATPase, with the same affinity as in control C57/BL mice. The dephosphorylating influence of phenytoin was however much decreased. In the primary and secondary foci of lesioned cats, both K+ and phenytoin dephosphorylating influences were decreased. Those changes were especially valid for the alpha(-), non-neuronal subunit. In human epileptic cortex, the (Na+, K+)-ATPase catalytic subunit had a decreased affinity to K+, as well as it lost its sensitivity to phenytoin dephosphorylation. Those results confirm the existence of two molecular forms of (Na+, K+)-ATPase in animal and human brain cortex. Those two forms, the neuronal and the non-neuronal or glial (Na+, K+)-ATPases, differ at least by their K+ regulation and their phenytoin sensitivity. Phenytoin studies also suggest that the drug stimulates the cortical (Na+, K+)-ATPase, mainly its glial form, providing central nervous system with an enhanced ability to regulate extracellular K+. In epileptic cortex, (Na+, K+)-ATPase and especially its glial form is altered in its K+ regulation and phenytoin sensitivity. That deficiency of glial (Na+, K+)-ATPase in focal epileptogenic cortex could be responsible for ictal transformation and seizure spread (Acta neurol. belg., 1988, 88, 257-280).

Adolescent↗