L-694,247: a potent 5-HT1D receptor agonist.

1. The 5-hydroxytryptamine (5-HT) receptor binding selectivity profile of a novel, potent 5-HT1D receptor agonist, L-694,247 (2-[5-[3-(4-methylsulphonylamino)benzyl-1,2,4-oxadiazol-5-yl ]- 1H-indole-3-yl]ethylamine) was assessed and compared with that of the 5-HT1-like receptor agonist, sumatriptan. 2. L-694,247 had an affinity (pIC50) of 10.03 at the 5-HT1D binding site and 9.08 at the 5-HT1B binding site (sumatriptan: pIC50 values 8.22 and 5.94 respectively). L-694,247 retained good selectivity with respect to the 5-HT1A binding site (pIC50 = 8.64), the 5-HT1C binding site (6.42), the 5-HT2 binding site (6.50) and the 5-HT1E binding site (5.66). The pIC50 values for sumatriptan at these radioligand binding sites were 6.14, 5.0, < 5.0 and 5.64 respectively. Both L-694,247 and sumatriptan were essentially inactive at the 5-HT3 recognition site. 3. L-694,247, like sumatriptan, displayed a similar efficacy to 5-HT in inhibiting forskolin-stimulated adenylyl cyclase in guinea-pig substantia nigra although L-694,247 (pEC50 = 9.1) was more potent than sumatriptan (6.2) in this 5-HT1D receptor mediated functional response. L-694,247 (pEC50 = 9.4) was also more potent than sumatriptan (6.5) in a second 5-HT1D receptor mediated functional response, the inhibition of K(+)-evoked [3H]-5-HT release from guinea-pig frontal cortex slices.(ABSTRACT TRUNCATED AT 250 WORDS)     

The significance of reduced respiratory chain enzyme activities: clinical, biochemical and radiological associations.

BACKGROUND: Mitochondrial diseases are an important group of neurometabolic disorders in children with varied clinical presentations and diagnosis that can be difficult to confirm. AIM: To report the significance of reduced respiratory chain enzyme (RCE) activity in muscle biopsy samples from children. METHODS: Retrospective odds ratio was used to compare clinical and biochemical features, DNA studies, neuroimaging, and muscle biopsies in 18 children with and 48 without reduced RCE activity. RESULTS: Children with reduced RCE activity were significantly more likely to have consanguineous parents, to present with acute encephalopathy and lactic acidaemia and/or within the first year of life; to have an axonal neuropathy, CSF lactate >4 mmol/l; and/or to have signal change in the basal ganglia. There were positive associations with a maternal family history of possible mitochondrial cytopathy; a presentation with failure to thrive and lactic acidaemia, ragged red fibres, reduced fibroblast fatty acid oxidation and with an abnormal allopurinol loading test. There was no association with ophthalmic abnormalities, deafness, epilepsy or myopathy. CONCLUSION: The association of these clinical, biochemical and radiological features with reduced RCE activity suggests a possible causative link.     

荧光原位杂交技术分析人结肠菌群方法研究

建立荧光原位杂交技术分析人体内结肠菌群的方法。取受试者新鲜粪便 ,选用 5种特异性的 16SrRNA寡核苷酸探针 ,检测粪便样本收集后的保存时间、温度 ,离心条件及样本固定液存放时间对杂交计数结果的影响。结果建立最佳实验条件为 :粪便样本收集后应尽快在 4℃下保存 ,放置时间不要超过 12小时即作处理 ;样本的适宜离心条件为 70 0g 2分钟 ;样本用多聚甲醛固定后在 - 80℃下存放时间不要超过 5个月。该方法具有较好的稳定性 ,可以有效地检出个体之间结肠菌群的差异。     

Intravenous anaesthesia for cystoscopy: a comparison of propofol or methohexitone with alfentanil

Sixty out-patients undergoing cystoscopy were allocated randomly into two groups. No premedication was given. Induction of anaesthesia was preceded by intravenous alfentanil 7 micrograms kg-1 given over 20 s, followed by methohexitone 1.5-2 mg kg-1 or propofol 2 mg kg-1, given over 20 s. Anaesthesia was maintained by increments of alfentanil, methohexitone or propofol, given as required.     

Muscle glycogen and glucose uptake during exercise in humans.

Six men were studied during 40 min of cycling exercise to examine the relationship between leg glucose uptake and muscle glycogen concentration. Exercise resulted in significant increases in leg glucose uptake, while muscle glycogen and arterial blood glucose concentrations declined. Arterial plasma insulin levels did not change significantly. There was a significant inverse relationship between muscle glycogen concentration and glucose uptake during exercise which suggests a possible regulatory influence of muscle glycogen on glucose uptake in the early stages of exercise in humans.