3H]Ro 19-6327: a reversible ligand and affinity labelling probe for monoamine oxidase-B

This study demonstrated the existence of specific binding sites for [3H]Ro 19-6327 in human platelet membranes. This compound is a novel, time-dependent inhibitor of monoamine oxidase type B (MAO-B) and is structurally closely related to [3H]Ro 16-6491. The density of the sites labelled with high affinity by [3H]Ro 19-6327 was similar to that observed in previous studies with [3H]Ro 16-6491 as ligand. Binding was reversible at 20 degrees C and showed a relatively slow dissociation (t1/2 = 220 min). The dissociation rate was markedly decreased (t1/2 = greater than 24h) at 0 degrees C. MAO-B, but not MAO-A inhibitors, effectively prevented the binding of [3H]Ro 19-6327. Like [3H]Ro 16-6491, [3H]Ro 19-6327 is recognized as a substrate by MAO-B, being eventually deaminated by the enzyme. Since the deaminated aldehyde derivative of Ro 19-6327 did not inhibit MAO-B, a still unidentified reversible adduct, formed at the MAO-B active site, might explain the high potency and selectivity of [3H]Ro 19-6327. Incubation of the radioligand-enzyme complex from platelet and brain membranes with NaBH3CN and acetic acid (to pH 4.5) caused the irreversible incorporation of the radioactivity into a single polypeptide as shown by SDS-PAGE analysis. This polypeptide had a molecular weight identical to that of the MAO-B subunit, i.e. 58,000. The presence of unlabelled MAO-B inhibitors in the incubation mixture prevented the covalent incorporation of [3H]Ro 19-6327. The irreversible MAO-B inhibitor, [3H] pargyline, labelled a protein with a molecular weight identical to the protein labelled by [3H]Ro 19-6327.(ABSTRACT TRUNCATED AT 250 WORDS)     

Central metabotropic glutamate receptors differentially participate in interleukin-1beta-induced mechanical allodynia in the orofacial area of conscious rats.

The present study investigated the role of central metabotropic glutamate receptors (mGluRs) in interleukin-1beta (IL-1beta)-induced mechanical allodynia and mirror-image mechanical allodynia in the orofacial area. Experiments were carried out on male Sprague-Dawley rats weighing 230 to 280 g. After administration of 0.01, 0.1, 1, or 10 pg of IL-1beta into a subcutaneous area of the vibrissa pad, we examined the withdrawal behavioral responses produced by 10 successive trials of an air-puff ramp pressure applied ipsilaterally or contralaterally to the IL-1beta injection site. Subcutaneous injection of IL-1beta produced mechanical allodynia and mirror-image mechanical allodynia in the orofacial area. Intracisternal administration of CPCCOEt, a mGluR1 antagonist, or MPEP, a mGluR5 antagonist, reduced IL-1beta-induced mechanical allodynia and mirror-image mechanical allodynia. Intracisternal administration of APDC, a group II mGluR agonist, or L-AP4, a group III mGluR agonist, reduced both IL-1beta-induced mechanical allodynia and mirror-image mechanical allodynia. The antiallodynic effect, induced by APDC or L-AP4, was blocked by intracisternal pretreatment with LY341495, a group II mGluR antagonist, or CPPG, a group III mGluR antagonist. These results suggest that groups I, II, and III mGluRs differentially modulated IL-1beta-induced mechanical allodynia, as well as mirror-image mechanical allodynia, in the orofacial area. PERSPECTIVE: Central group I mGluR antagonists and groups II and III mGluR agonists modulate IL-1beta-induced mechanical allodynia and mirror-image mechanical allodynia in the orofacial area. Therefore, the central application of group I mGluR antagonists or groups II and III mGluR agonists might be of therapeutic value in treating pain disorder.     

A model-based detector of vertex waves and K complexes in sleep electroencephalogram.

A model of sleep phasic events such as vertex waves, K complexes, delta waves and sleep spindles is proposed. It consists of feedback loops that are driven by white noise (simulating tonic delta and sigma activity) and by isolated random impulses, simulating vertex waves or K complexes, depending on the background tonic activity. A model-based method for the detection of sleep phasic events was implemented in a personal computer. Its performance was investigated using simulated and real whole-night EEG signals. The method was able to detect K complexes and vertex waves in a reliable way in spite of their variable shapes and in the presence of a variety of background activities. The detector appears to have superior performance to those so far reported in the literature. The performance of the detector was also compared to that of an electroencephalographer using normal sleep EEG records of 8 h duration from 6 subjects. The performance was satisfactory both in terms of accuracy and reliability. The problem of detecting K complexes in stages 3 and 4 of sleep is discussed.     

Dependence of cardiac 11C-meta-hydroxyephedrine retention on norepinephrine transporter density.

The norepinephrine analog (11)C-meta-hydroxyephedrine (HED) is used with PET to map the regional distribution of cardiac sympathetic neurons. HED is rapidly transported into sympathetic neurons by the norepinephrine transporter (NET) and stored in vesicles. Although much is known about the neuronal mechanisms of HED uptake and retention, there is little information about the functional relationship between HED retention and cardiac sympathetic nerve density. The goal of this study was to characterize the dependence of HED retention on nerve density in rats with graded levels of cardiac denervation induced chemically with the neurotoxin 6-hydroxydopamine (6-OHDA). METHODS: Thirty male Sprague-Dawley rats were divided into 6 groups, and each group was administered a different dose of 6-OHDA: 0 (controls), 7, 11, 15, 22, and 100 mg/kg intraperitoneally. One day after 6-OHDA injection, HED (3.7-8.3 MBq) was injected intravenously into each animal and HED concentrations in heart and blood at 30 min after injection were determined. Heart tissues were frozen and later processed by tissue homogenization and differential centrifugation into a membrane preparation for in vitro measurement of cardiac NET density. A saturation binding assay using (3)H-mazindol as the radioligand was used to measure NET density (maximum number of binding sites [B(max)], fmol/mg protein) for each heart. RESULTS: In control animals, NET B(max) was 388 +/- 23 fmol/mg protein and HED heart uptake (HU) at 30 min was 2.89% +/- 0.35 %ID/g (%ID/g is percentage injected dose per gram tissue). The highest 6-OHDA dose of 100 mg/kg caused severe cardiac denervation, decreasing both NET B(max) and HED HU to 8% of their control values. Comparing values for all doses of 6-OHDA, HED retention had a strong linear correlation with NET density: HU = 0.0077B(max) -0.028, r(2) = 0.95. CONCLUSION: HED retention is linearly dependent on NET density in rat hearts that have been chemically denervated with 6-OHDA, suggesting that HED retention is a good surrogate measure of NET density in the rat heart. This finding is discussed in relation to clinical observations of the dependence of HED retention on cardiac nerve density in human subjects using PET.     

Myasthenia Gravis Appearing After Thymectomy: a Case Report and Review of the Literature

A small proportion of thymoma patients without myasthenia gravis (MG) have been observed to develop MG after total removal of the thymoma. However, the underlying cause is not yet known due to the rarity of postoperative MG patients. We report a 39-year-old man in whom MG appeared after surgical removal of a thymoma. Computed tomography and magnetic resonance imaging showed no signs of recurrent or metastatic thymoma. Administration of pyridostigmine bromide resulted in the prompt improvement of myasthenic symptoms. Our observations indicate that postoperative follow-up care with monitoring of possible postoperative MG is necessary after resecting a thymoma.     

射频消融治疗阵发性室上性心动过速复发原因分析

目的：分析阵发性室上性心动过速患者行射频消融术（RFCA）后复发的原因，探讨降低RFCA复发的方法。方法：128例阵发性室上性心动过速患者，行RFCA治疗，术后每3－6个月随访1次，随访4－70个月。结果：128例患者中，复发10例，总复发率7．81％，其中房室结折返性心运过速复发率为7．89％，左侧房室旁路介导心运过速复发率5．56％，右侧旁路介导心动过速复发率16．67％。行射频消融术前70例患者中复发率11．43％，后58例复发率3．45％。结论：精确的靶点标测、熟练的操作技巧以及消融方式的正确运用是降低RFCA复发率的关键。     

Uncooked rice of relatively low gelatinization degree resulted in lower metabolic glucose and insulin responses compared with cooked rice in female college students

Cooking processes that gelatinize granules or disrupt structure might increase the glucose and insulin responses because a disruption of the structure of starch by gelatinization increases its availability for digestion and absorption in the small intestine. We hypothesized that the uncooked form of rice, which has a relatively low degree of gelatinization even though in powder form, would result in lower metabolic glucose and insulin responses compared with cooked rice (CR). To assess the effects of the gelatinization of rice on metabolic response of glucose and insulin, we investigated the glucose and insulin responses to 3 rice meals of different gelatinization degree in female college students (n = 12): CR (76.9% gelatinized), uncooked rice powder (UP; 3.5% gelatinized), and uncooked freeze-dried rice powder (UFP; 5.4% gelatinized). Uncooked rice powders (UP and UFP) induced lower glucose and insulin responses compared with CR. The relatively low gelatinization degree of UPs resulted in low metabolic responses in terms of the glycemic index (CR: 72.4% vs UP: 49.7%, UFP: 59.8%) and insulin index (CR: 94.8% vs UP: 74.4%, UFP: 68.0%). In summary, UPs that were less gelatinized than CR induced low postprandial glucose and insulin responses.