(8S)-(glutathion-S-yl)dihydromorphinone, a novel metabolite of morphine from guinea pig bile

A novel glutathione-conjugated metabolite of morphine has been isolated from the bile of guinea pigs given morphine. The metabolite was separated by preparative HPLC on a reverse phase column (YMC-GEL C18) using methanol/water (1:4, v/v) as eluate and purified by HPLC on another reverse phase column (mu-Bondapak phenyl) using water/acetonitrile/trimethylamine/acetic acid (150:3:2:1, v/v) as a mobile phase. The unambiguous structure assignment of the metabolite was performed by fast atom bombardment mass spectrometry and 400 MHz fourier transform NMR spectrometric analysis, and it was identified as (8S)-glutathion-S-yl)dihydromorphinone, in comparison with the synthetic morphinone-glutathione adduct.     

A case of salicylazosulfapyridine (Salazopyrin)-induced acute pancreatitis with positive lymphocyte stimulation test (LST)

A case of acute pancreatitis induced by salicylazosulfapyridine (Salazopyrin, SASP) was reported. A 33-year-old man with ulcerative colitis was given SASP. Five weeks later, P-type serum amylase was found to be elevated. The amylase/creatinine clearance ratio (ACCR) and serum lipase were also elevated. There were neither subjective symptoms nor abnormal ultrasound findings in the pancrease. Lymphocyte stimulation test (LST) to SASP was positive. Asymptomatic pancreatitis by SASP was suspected and SASP administration was halted. Afterwards the abnormal data became normal. Readministration of SASP because of relapse caused an episode of pancreatitis similar to the first occasion. LST was negative before SASP intake and became positive after intake. Desensitization to SASP was unsuccessful. LST was negative before attempting desensitization and became positive when the dosage of SASP increased to 100 mg daily. This is the second case of acute pancreatitis reported to be induced by SASP and this is the first case in which LST to SASP was described. To our knowledge, this is also the first case in which a positive LST was described in drug-induced pancreatitis. This case provides evidence for the role of delayed type hypersensitivity in the etiopathogenesis of SASP allergy and of dose-independent drug-induced pancreatitis.     

Effect of nilvadipine on the voltage-dependent Ca channels in rat hippocampal CA1 pyramidal neurons

Effects of nilvadipine on the low- and high-voltage activated Ca²⁺ currents (LVA and HVA I_Ca, respectively) were compared with other organic Ca²⁺ antagonists in acutely dissociated rat hippocampal CA1 pyramidal neurons. The inhibitory effects of nilvadipine, amlodipine and flunarizine on LVA I_Ca were concentration- and use-dependent. The apparent half-maximum inhibitory concentrations (IC₅₀s) at every 1- and 30-s stimulation were 6.3×10⁻⁷ M and 1.8×10⁻⁶ M for flunarizine, 1.9×10⁻⁶ M and 7.6×10⁻⁶ M for nilvadipine, and 4.0×10⁻⁶ M and 8.0×10⁻⁶ M for amlodipine, respectively. Thus, the strength of the use-dependence was in the sequence of nilvadipine>flunarizine>amlodipine. Nilvadipine also inhibited the HVA I_Ca in a concentration-dependent manner with an IC₅₀ of 1.5×10⁻⁷ M. The hippocampal CA1 neurons were observed to have five pharmacologically distinct HVA Ca²⁺ channel subtypes consisting of L-, N-, P-, Q- and R-types. Nilvadipine selectively inhibited the L-type Ca²⁺ channel current which comprised 34% of the total HVA I_Ca. On the other hand, amlodipine non-selectively inhibited the HVA Ca²⁺ channel subtypes. These results suggest that the inhibitory effect of nilvadipine on the neuronal Ca²⁺ influx through both LVA and HVA L-type Ca²⁺ channels, in combination with the cerebral vasodilatory action, may prevent neuronal damage during ischemia.     

Abdominal vagotomy attenuates interleukin-1β-induced nitric oxide release in the paraventricular nucleus region in conscious rats

Nitric oxide (NO) has recently been shown to modulate the hypothalamic–pituitary–adrenal axis response to interleukin-1β (IL-1β). We measured levels of nitrite (NO₂⁻) and nitrate (NO₃⁻) in the hypothalamic paraventricular nucleus (PVN) region using an in vivo brain microdialysis technique in conscious rats. Intraperitoneally administered IL-1β produced a significant increase in both NO₂⁻ and NO₃⁻ levels in the PVN region. We also examined the possible involvement of the abdominal vagal afferent nerves in this effect. In abdominal-vagotomized rats, the increase was significantly attenuated compared to that in sham-operated rats. Our results suggest that the abdominal vagal afferent nerves are involved in intraperitoneally administered IL-1β-induced NO release in the PVN region.     

Hepatic angiomyolipoma developing during the follow-up of ulcerative colitis: Report of a case and review of the literature

Hepatic angiomyolipoma is a rare tumor composed of spindle-shaped and epithelioid smooth muscle cells, adipose tissue, and proliferating blood vessels. We report the first documented case of this tumor developing in a patient with ulcerative colitis. A solitary tumor (7.5×7.5×7cm) was detected in the left lateral segment of the liver and a left hepatic lobectomy was performed. The diagnosis of angiomyolipoma was confirmed by a pathological examination. We also review the literature on previously reported cases of hepatic angiomyolipoma.     

Cholinergic neurons contain Calbindin-D28k in the monkey medial septal nucleus and nucleus of the diagonal band: an immunocytochemical study

The distribution patterns of choline acetyltransferase (CAT), as a marker for cholinergic neurons, and Calbindin-D_28k (CaBP) immunoreactivities in the forebrain basal ganglia of the Japanese monkeyMacaca fuscata were compared. Similar distribution patterns of CAT and CaBP immunoreactivities were found in the medial septal nucleus (MS) and the nucleus of the diagonal band of Broca (DBB). Double-labeling fluorescence immunocytochemistry revealed that most, but not all, cholinergic neurons were CaBP-immunoreactive in the MS and DBB. The results suggest that CaBP may play a role in the septohippocampal cholinergic neuron system of the monkey.     

Epileptic seizure of El mouse initiates at the parietal cortex: depth EEG observation in freely moving condition using buffer amplifier

The initiation site of seizure discharges and the relationship between behavioral manifestations and electroencephalography were investigated in the El mouse, a hereditary epilepsy model. The chronic depth electrodes were implanted stereotaxically into the frontal cortex, parietal cortex, temporal cortex, hippocampus, striatum, amygdaloid complex, non-specific nuclei of thalamus and substantia nigra. Electrical activities were recorded in freely moving condition with use of the buffer amplifier devised in the laboratory and behaviors were monitored simultaneously. Seizure spike discharges started in the parietal cortex and spread out into other brain areas. When the hippocampus was involved, the tonic convulsion occurred behaviorally. The paper describes the first direct evidence of the initiation and propagation of seizure discharges in the brain of El mouse.     

Spondylolysis after posterior decompression of the lumbar spine: 35 patients followed for 3-9 years

Radiographs were examined in 35 patients who had had posterior decompression without fusion of the lumbar spine. Spondylolysis was found in 10 patients. Segmental range of motion, degree of vertebral slippage and width of decompression were analyzed by radiography. There was greater vertebral slippage after surgery in patients with postoperative spondylolysis than in those without spondylolysis. We conclude that excessive bony decompression may cause postoperative spondylolysis.