Search results for "Crotonates"
showing 7 items of 7 documents
Effects of leflunomide (HWA 486) on expression of lymphocyte activation markers
1993
Leflunomide (HWA 486), an isoxazol derivative, has been shown to be very effective in combating autoimmune diseases and transplantation rejection in a great number of animal models. The main metabolite of leflunomide, A77 1726, is a potent antiproliferative compound. To further elucidate this effect, lymphocytes of healthy human donors were cultured for 24, 48 or 72 h in the presence of PHA or immobilized anti-CD3 antibody. A77 1726 was added at concentrations between 10 and 100 microM. Flow cytometric evaluation of early activation or proliferation markers (IL-2 and transferrin receptors, respectively) showed that their expression was inhibited in a dose-dependent manner by A77 1726. Toget…
Discontinuation of teriflunomide and dimethyl fumarate in a large Italian multicentre population: a 24-month real-world experience
2019
Teriflunomide (TRF) and Dimethyl fumarate (DMF) are licensed drugs for relapsing-remitting Multiple Sclerosis (RRMS). We aimed to compare the rate and the time to discontinuation among persons with RRMS (pwRRMS), newly treated with TRF and DMF. A retrospective study on prospectively collected data was performed in nine tertiary MS centers, in Italy. The 24-month discontinuation rate in the two cohorts was the primary study outcome. We also assessed the time to discontinuation and reasons of therapy withdrawn. Discontinuation of TRF and DMF was defined as a gap of treatment ≥ 60 days. A cohort of 903 pwRRMS (316 on TRF and 587 on DMF) was analyzed. During 24 months of follow-up, pwRRMS on TR…
Inhibition of the epidermal growth factor receptor tyrosine kinase activity by leflunomide.
1993
AbstractThe active metabolite of leflunomide, A77 1726 inhibits the proliferation of a variety of mammalian cell lines in culture. Epidermal growth factor (EGF)-dependent proliferation is inhibited by A77 1726 at an effective dose of 30–40 μM. A77 1726 appears to directly inhibit the EGF receptor tyrosine-specific kinase activity both in intact cells and purified EGF receptors at the same effective dose. These data suggest that leflunomide inhibits cellular proliferation by the inhibition of tyrosine-specific kinase activities.
Critical Role of Substrate Conformational Change in the Proton Transfer Process Catalyzed by 4-Oxalocrotonate Tautomerase
2009
4-Oxalocrotonate tautomerase enzyme (4-OT) catalyzes the isomerization of 2-oxo-4-hexenedioate to 2-oxo-3-hexenedioate. The chemical process involves two proton transfers, one from a carbon of the substrate to the nitrogen of Pro1 and another from this nitrogen atom to a different carbon of the substrate. In this paper the isomerization has been studied using the combined quantum mechanical and molecular mechanical (QM/MM) method with a dual-level treatment of the quantum subsystem employing the MPW1BK density functional as the higher level. Exploration of the potential energy surface shows that the process is stepwise, with a stable intermediate state corresponding to the deprotonated subs…
Crotonic acid as a bioactive factor in carrot seeds (Daucus carota L.)
2004
Water extracts from the carrot seed (Daucus carota L.) var. Perfekcja exhibit plant growth inhibitory properties against cress, cucumber, onion and carrot in a dose-dependant manner. This property results from the action of low-and high-molecular components of the extract. The low-molecular component was identified as crotonic acid ((E)-2-butenoic acid). Its presence was also confirmed in other late varieties of carrot. The determined strong herbicidal properties of crotonic acid and its availability after release to soil combined with its high level in seeds suggest that it might be considered as an allelopathic and autotoxic factor in the seeds.
GABAC receptors are functionally expressed in the intermediate zone and regulate radial migration in the embryonic mouse neocortex
2010
Radial neuronal migration in the cerebral cortex depends on trophic factors and the activation of different voltage- and ligand-gated channels. To examine the func- tional role of GABAC receptors in radial migration we ana- lyzed the effects of specific GABAA and GABAC receptor antagonists on the migration of BrdU-labeled neurons in vitro using organotypic neocortical slice cultures. These experi- ments revealed that the GABAA specific inhibitor bicuculline methiodide facilitated neuronal migration, while the GABAC specific inhibitor (1,2,5,6-tetrahydropyridine-4-yl) methylphos- phinic-acid (TPMPA) impeded migration. Co-application of TPMPA and bicuculline methiodide or the unspecific ionot…
Real world experience with teriflunomide in multiple sclerosis: the TER-Italy study.
2021
Objective: To identify baseline factors associated with disease activity in patients with relapsing–remitting multiple sclerosis (RRMS) under teriflunomide treatment. Methods: This was an independent, multi-centre, retrospective post-marketing study. We analysed data of 1,507 patients who started teriflunomide since October 2014 and were regularly followed in 28 Centres in Italy. We reported the proportions of patients who discontinued treatment (after excluding 32 lost to follow-up) and who experienced clinical disease activity, i.e., relapse(s) and/or confirmed disability worsening, as assessed by the Expanded Disability Status Scale (EDSS). Decision tree-based analysis was performed to i…