1. The behavioural and anticonvulsant effects of eight pyrroloimidazopyridines (PI1a-d and PI2a-d) and four pyrrolopurines (PP) were studied after intraperitoneal administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizures. 2. The anticonvulsant effects were evaluated in DBA/2 mice on seizures evoked by means of auditory stimulation (109 dB, 12-16 kHz) in animals placed singly under a perspex dome. 3. Hypothermic activity was observed after the highest doses of the pyrroloderivatives studied. 4. Our study demonstrated that the anticonvulsant effect of pyrroloimidazopyridines (PI1-7,8,8a,9-tetrahydro-6H-pyrrolo-[1',2':1,2]imidazo[4,5-b]pyrid in-6- ones) and pyrrolopurines (PP) was generally better than corresponding pyrrolobenzimidazoles (PB) and pyrroloimidazopyridines (PI2-5,5a,6,7-tetrahydro-8H-pyrrolo[2',1':2,3]imidazo[4,5-c]pyridin-8- ones) and, in some cases, comparable to that of phenytoin and desmethylclobazam. 5. The anticonvulsant potency of the derivatives studied cannot be directly related to their lipophilicity.
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http://dx.doi.org/10.1016/0306-3623(94)90114-7 | DOI Listing |
mSphere
December 2024
Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Unlabelled: Myeloid phagocytes are essential for antifungal immunity against pulmonary and systemic infections. However, the molecular mechanisms underlying fungal clearance by phagocytes remain incompletely understood. In this study, we investigated the role of Perforin-2 () in antifungal immunity.
View Article and Find Full Text PDFInfect Genet Evol
December 2024
Laboratory of Laboratory Animal Science and Medicine, Department of Applied Veterinary Sciences, Graduate School of Veterinary Medicine, N18 W9, Kita-Ku, Sapporo, Hokkaido 060-0819, Japan.
Alveolar echinococcosis is a zoonosis caused by the larval stage of Echinococcus multilocularis. In previous studies, QTL analysis using C57BL/6 N (B6) and DBA/2 (D2) which differ in susceptibility suggested the presence of genes on chromosome 1 that control protoscolex development. In this study, we constructed several congenic mice with different chromosome 1 regions substituted to confirm the presence of responsible genes and to narrow down the regions where the responsible genes exist.
View Article and Find Full Text PDFChemMedChem
November 2024
Department of Pharmacy, "Federico II" University of Napoli, Via Domenico Montesano 49, 80131, Napoli, Italy.
7-methyl-2-phenylimidazo[1,2-b]pyridazin-3-carboxylic acid (DM1) and 6-methoxy-2-phenylimidazo[1,2-b]pyridazin-3-carboxylic acid (DM2) have been shown to act as human (h) Cav voltage-gated calcium channel blockers with promising in vivo anti-absence activity, positioning them as potential antiepileptic drugs. The primary aim of this work was to develop cost-effective and environmentally friendly synthetic procedures for preparing 2-phenylimidazo[1,2-b]pyridazine derivatives. After optimizing the synthesis of this compound class using efficient and green techniques such as microwaves and ultrasound irradiation, we further evaluated the antiepileptic effects of DM1 and DM2 in two animal models: CD-1 ICR mice after pentylenetetrazol administration and DBA/2 mice with seizures induced by audiogenic stimuli.
View Article and Find Full Text PDFiScience
November 2024
Vital-IT Group, SIB Swiss Institute for Bioinformatics, 1015 Lausanne, Switzerland.
To identify the pathways that are coordinately regulated in pancreatic β cells, muscle, liver, and fat to control fasting glycemia we fed C57Bl/6, DBA/2, and Balb/c mice a regular chow or a high fat diet for 5, 13, and 33 days. Physiological, transcriptomic and lipidomic data were used in a data fusion approach to identify organ-specific pathways linked to fasting glycemia across all conditions investigated. In pancreatic islets, constant insulinemia despite higher glycemic levels was associated with reduced expression of hormone and neurotransmitter receptors, OXPHOS, cadherins, integrins, and gap junction mRNAs.
View Article and Find Full Text PDFMol Neurobiol
November 2024
Department of Ophthalmology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Glaucoma is a neurodegenerative disease characterized by progressive optic nerve degeneration and retinal ganglion cell (RGC) loss. In early glaucoma, before obvious axon loss, highly organized pathological processes in RGCs occur sequentially, involving axons, dendrites and synaptic terminals. The optic nerve head (ONH) is the critical structure of early glaucomatous neurodegeneration.
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