Autopsy-proven patient with corticobasal degeneration presenting with visuo-constructive disorders as initial symptoms: How advanced MRI sequences can help clinical practice

Article

作者: Tomé, Sandra O ; Quenon, Lisa ; Thal, Dietmar Rudolf ; Huyghe, Lara ; Hanseeuw, Bernard J ; Ghysens, Olivia ; Salman, Yasmine ; Malotaux, Vincent

BackgroundCortico-basal degeneration (CBD) is a neurodegenerative disease typically responsible for cortico-basal syndrome (CBS) or progressive limb apraxia. Half of CBD patients, however, present atypical symptoms, making the diagnosis difficult.ObjectiveWe reported the case of a woman in her late sixties (BM208), an unusual case of autopsy-proven CBD, showing early signs of Benson's syndrome or posterior cortical atrophy. In addition, we compared cognitive performance and atrophy in different brain regions of BM208 with other neurodegenerative diseases patients to highlight clinical signs that could have guided the diagnosis earlier.MethodsWe retrospectively compared BM208 to patients with typical amnestic Alzheimer's disease (AD) (n = 18, Mini-Mental State Exam (MMSE) scores between 18 and 24), Benson's syndrome due to AD (n = 3), CBS/progressive supranuclear palsy (PSP) syndrome (n = 5), and Lewy body dementia (LBD) patients (n = 3) and a control group (n = 24). All these participants underwent an MMSE, a complete neuropsychological examination and 3DT1 MRI.ResultsAlthough BM208 was more severely cognitively impaired overall, her cognitive performance was more similar to Benson's syndrome patients’ cognitive profile compared to CBS patients or any other degenerative pathology (typical AD/LBD). Consistently, although BM208 was more atrophic than all other groups, she showed cortical atrophy that matched a Benson's syndrome pattern more than typical AD or CBS. However, the analysis of subcortical atrophy revealed atrophy of the basal ganglia corresponding CBS cases. Furthermore, visual analyses on sagittal T1 images showed atrophy of the midbrain, characteristic of CBS/PSP syndrome.ConclusionsThese results highlight the additive value of fine-grained MRI subcortical quantification to diagnose non-AD rare neurodegenerative disorders.

2002-02-01·Biochemical Pharmacology2区 · 医学

In vitro and in vivo effects of new insulin releasing agents

2区 · 医学

Article

作者: Marcel Hermann ; Bernard Masereel ; Raogo Ouedraogo ; Quynh-Anh Nguyen ; Jacqueline Sergooris ; Bernard Pirotte ; Philippe Lebrun ; Marie-Hélène Antoine

The present study aimed at characterizing in vitro and in vivo the effects of BM 208 (N-[4-(5-chloro-2-methoxybenzamidoethyl)benzenesulfonyl]-N'-cyano-N"-cyclohexylguanidine) and BM 225 (1-[4-(5-chloro-2-methoxybenzamidoethyl)benzene sulfonamido]-1-cyclohexylamino-2-nitroethylene); two new isosteres of the hypoglycemic sulfonylurea glibenclamide. In rat pancreatic islets perifused at close to normal (8.3mM) D-glucose concentration, both BM 208 and BM 225 (10 and 25 microM) increased 45Ca outflow and insulin release. The compounds did not affect the 45Ca outflow rate from islets exposed to Ca(2+)-free media. In single pancreatic islet cells loaded with the fluorescent Ca(2+) indicator fura-2 and incubated in the presence of 8.3mM glucose, BM 208 and BM 225 raised the [Ca(2+)](i). All these findings indicate that, in islet cells exposed to a physiological concentration of D-glucose, the secretory capacity of the new glibenclamide isosteres is related to a facilitation of Ca(2+) entry. The potency and duration of action of BM 225 was, however, more pronounced than that of BM 208. Successive additions of BM 208 provoked repeated increments in 45Ca outflow and insulin release, without evidence of tachyphylaxis. Lastly, intraperitoneal injection of BM 208 and BM 225 to fed rats lowered plasma glucose concentration in a dose-dependent manner. BM 225 was more potent and acting faster than BM 208. Our results indicate that appropriate structural modification can generate isosteres of glibenclamide with different features and activity profiles.

1999-05-01·The Journal of pharmacology and experimental therapeutics

Insulinotropic effect of new glibenclamide isosteres.

Article

作者: Ouedraogo, R ; Masereel, B ; Nguyen, Q A ; Dunne, M J ; Kane, M H ; Lebrun, P ; Pochet, L

The aim of the present study was to characterize the effects of BM 208 (N-[4-(5-chloro-2-methoxybenzamidoethyl)benzenesulfonyl]-N'-cyano- N"- cyclohexylguanidine) and BM 225 (1-[4-(5-chloro-2-methoxybenzamidoethyl)benzene sulfonamido]-1-cyclohexylamino-2-nitroethylene), two newly synthesized isosteres of glibenclamide, on ionic and secretory events in rat pancreatic islet cells. Both compounds inhibited 86Rb (42K substitute) outflow from rat pancreatic islets perifused throughout at low (2.8 mM) D-glucose concentration. In excised inside-out membrane patches, BM 208 and BM 225 reduced the frequency of KATP+ channel openings. The inhibition of 86Rb outflow induced by BM 208 and BM 225 coincided with an increase in 45Ca outflow. The latter phenomenon was abolished in islets exposed to Ca2+-free media. Both isosteres of glibenclamide increased the [Ca2+]i in single pancreatic islet cells. This effect was counteracted by verapamil, a Ca2+ entry blocker. In islets exposed to 2.8 mM glucose and extracellular Ca2+, BM 208 and BM 225 stimulated insulin output. The secretory capacity of BM 225 was more marked than that of BM 208, but the time courses of the cationic and secretory responses exhibited obvious dissociations. These data suggest that the secretory capacity of BM 208 and BM 225 results, at least in part, from the inhibition of ATP-sensitive K+ channels with subsequent increase in Ca2+ inflow. The dissociation between cationic and secretory variables further suggests that the modifications in Ca2+ handling are not solely attributable to a primary inhibition of the ATP-sensitive K+ channels.

100 项与 BM-208 相关的药物交易

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