蝙蝠葛碱和粉防己碱对[3H]WEB 2086与体外牛脑前动脉平滑肌细胞结合的影响(英文)

用标记的血小板活化因子拮抗剂[³H]WEB 2086,在培养的牛脑前动脉平滑肌细胞上鉴定了血小板活化因子受体。结果表明在25℃时该细胞上存在两种与配基具有不同亲和力的受体结合位点,其中K_d-1=22.8±5.0 nmol·L^-1,K_d-2=186+20.5 nmol·L^-1;B_max-1=2.1±0.3 pmol/10⁴细胞,B_max-2=12.1±1-5 pmol/10⁶细胞。蝙蝠葛碱和粉防己碱均能抑制[³H]WEB2086与上述细胞的结合。     

A novel role for the metabotropic glutamate receptor-7: modulation of faecal water content and colonic electrolyte transport in the mouse

Background and purpose:

Increasing evidence implicates metabotropic glutamate receptor mGlu₇ in the pathophysiology of stress-related disorders such as depression and anxiety. Mood disorders are frequently associated with gastrointestinal (GI) dysfunction; however, the role of mGlu₇ receptors outside the CNS is unknown. This present study investigated the expression and possible functional role of mGlu₇ receptors in the mouse colon.

Experimental approach:

Expression of mGlu₇ receptor mRNA and protein was studied in mouse colon by in situ hybridization and Western blotting. Effects of the selective mGlu₇ receptor agonist AMN082 on defecation and faecal parameters were studied in an isolation-induced stress model. AMN082 effects on ion transport and neuronal intracellular signalling were examined via Ussing chambers and calcium imaging.

Key results:

mGlu₇ receptor mRNA and protein were highly expressed in colon mucosa. Stress-induced faecal output was unaffected by AMN082, although faecal water content was increased. In mucosa/submucosa preparations, 100 nM and 1 µM AMN082 increased bethanechol-induced changes in short-circuit current in the Ussing chamber. This was sensitive to tetrodotoxin. Also, 100 nM AMN082 significantly increased calcium signalling in a subset of submucosal neurons.

Conclusions and implications:

Activating mGlu₇ receptors increased colonic secretory function in vivo and ex vivo. In a group of submucosal neurons, AMN082 strongly induced calcium signalling and the presence of submucosal nerves was required for the AMN082-dependent increase in secretion. These data suggest that targeting mGlu₇ receptors may be useful in the treatment of central components of stress disorders and also stress-associated GI dysfunction such as diarrhoea or constipation.     

血小板激活因子对大鼠脑血管通透性的影响及药物的保护作用

颈内动脉注射血小板激活因子(PAF),再给伊文思蓝,可见脑实质染色程度加深,而颈内动脉只注射伊文思蓝,脑实质未见染色。而我们合成的新药SZ-1可剂量依赖性地抑制PAF诱导的脑实质伊文思蓝染色程度的加深。在体外培养的脑微血管平滑肌细胞上,PAF能显著刺激¹⁴C-花生四烯酸的释放,而SZ-1能剂量依赖性地抑制这种释放,提示PAF在脑内产生的损害除与其他因素相关外,还与其刺激花生四烯酸释放有密切关系,SZ-1对PAF引起的脑部损害有保护作用。     

A typical case of myoclonic epilepsy with ragged red fibers (MERRF) and the lessons learned

Mitochondrial diseases have a special predilection to involve the brain in view of its high metabolic demand and the tendency for the formation of excitatory neurotransmitters when there is deficiency of intracellular ATP. These diseases have a great phenotypic variation and need a high degree of suspicion. However, some specific syndromes are well defined, both genotypically and phenotypically. Some of the drugs are potentially fatal mitochondrial poisons and an insight into that may be lifesaving as well as prevent serious morbidities. We report a typical case of myoclonic epilepsy with ragged red fibers (MERRF) with classical phenotype and genotype. There was rapid multiaxial deterioration with the introduction of sodium valproate which partly reversed on introducing mitochondrial cocktail and withdrawal of the offending drug. Sodium valproate, phenobarbitone, chloramphenicol and many anti-viral agents are mitochondrial poisons that increase the morbidity and mortality in patients with mitochondrial disease. More harm to the patient can be avoided with insight into this information.KEY WORDS: Midline lipoma, mitochondrial disease, sodium valproate     

Functional characterization of cells separated from suspensions of Hodgkin diseases tumor cells in an isokinetic gradient

Suspensions of cells from Hodgkin disease tumors were separated by velocity sedimentation in an isokinetic Ficall gradient. The separated cells were cultured with mitogens. The modal population of lymphocytes from the tumor contained 50%-75% of all lymphocytes separated from the tumor of each studied patient. Despite the fact that these cells appeared to be mature lymphocytes, the majority of which formed nonimmune E rosettes with sheep red blood cells, they showed a lack of responsiveness to phytohemogglutinin which was almost complete in all but one patient. Lymphocytes which had been obtained in suspension and purified by identical methods from tonsils and spleens without tumors did respond to stimulation by phytohemagglutinin.