Metabolite alterations in basal ganglia associated with psychiatric symptoms of abstinent toluene users: a proton MRS study.

Long-term toluene abuse causes a variety of psychiatric symptoms. However, little is known about abnormalities at the neurochemical level in the living human brain after long-term exposure to toluene. To detect neurochemical changes in the basal ganglia of subjects with a history of long-term toluene use, proton magnetic resonance spectroscopy (1H MRS) was performed in 12 abstinent toluene users and 13 healthy comparisons with no history of drug abuse. N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr + PCr), choline-containing compounds (Cho), and myo-inositol (MI) levels were measured in the left and right basal ganglia. The Cho/Cr + PCr ratio, a marker of membrane metabolism, was significantly increased in the basal ganglia of toluene users in comparison to that of the control subjects. Furthermore, the increase in the Cho/Cr + PCr ratio was significantly correlated with the severity of residual psychiatric symptoms. These findings suggest that long-term toluene use causes membrane disturbance in the basal ganglia, which is associated with residual psychiatric symptoms that persist even after long-term abstinence from toluene use.     

A crucial role of uridine/cytidine kinase 2 in antitumor activity of 3'-ethynyl nucleosides.

The antitumor 3'-ethynyl nucleosides, 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)cytosine (ECyd) and 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)uridine (EUrd), are potent inhibitors of RNA polymerases and show excellent antitumor activity against various human solid tumors in xenograft models. ECyd is being investigated in phase I clinical trials as a novel anticancer drug possessing a unique antitumor action. ECyd and EUrd require the activity of uridine/cytidine kinase (UCK) to produce the corresponding active metabolite. The UCK family consists of two members, UCK1 and UCK2, and both UCKs are expressed in many tumor cells. It was unclear, however, whether UCK1 or UCK2 is responsible for the phosphorylation of the 3'-ethynyl nucleosides. We therefore established cell lines that are highly resistant to the 3'-ethynyl nucleosides from human fibrosarcoma HT-1080 and gastric carcinoma NUGC-3. All the resistant cell lines showed a high cross-resistance to ECyd and EUrd. As a result of cDNA sequence analysis, we found that UCK2 mRNA expressed in EUrd-resistant HT-1080 cells has a 98-base pair deletion of exon 5, whereas EUrd-resistant NUGC-3 cells were harboring the point mutation at nucleotide position 484 (C to T) within exon 4 of UCK2 mRNA. This mutation was confirmed by genome sequence analysis of the UCK2 gene. Moreover, the expression of UCK2 protein was decreased in these resistant cells. In contrast, no mutation in the mRNA or differences in protein expression levels of UCK1 were shown in the EUrd-resistant HT-1080 and NUGC-3 cells. These results suggest that UCK2 is responsible for the phosphorylation and activation of the antitumor 3'-ethynyl nucleosides.     

Endogenous theta stimulation during meditation predicts reduced opioid dosing following treatment with Mindfulness-Oriented Recovery Enhancement

Veterans experience chronic pain at greater rates than the rest of society and are more likely to receive long-term opioid therapy (LTOT), which, at high doses, is theorized to induce maladaptive neuroplastic changes that attenuate self-regulatory capacity and exacerbate opioid dose escalation. Mindfulness meditation has been shown to modulate frontal midline theta (FMT) and alpha oscillations that are linked with marked alterations in self-referential processing. These adaptive neural oscillatory changes may promote reduced opioid use and remediate the neural dysfunction occasioned by LTOT. In this study, we used electroencephalography (EEG) to assess the effects of a mindfulness-based, cognitive training intervention for opioid misuse, Mindfulness-Oriented Recovery Enhancement (MORE), on alpha and theta power and FMT coherence during meditation. We then examined whether these neural effects were associated with reduced opioid dosing and changes in self-referential processing. Before and after 8 weeks of MORE or a supportive psychotherapy control, veterans receiving LTOT (N = 62) practiced mindfulness meditation while EEG was recorded. Participants treated with MORE demonstrated significantly increased alpha and theta power (with larger theta power effect sizes) as well as increased FMT coherence relative to those in the control condition—neural changes that were associated with altered self-referential processing. Crucially, MORE significantly reduced opioid dose over time, and this dose reduction was partially statistically mediated by changes in frontal theta power. Study results suggest that mindfulness meditation practice may produce endogenous theta stimulation in the prefrontal cortex, thereby enhancing inhibitory control over opioid dose escalation behaviors.Subject terms: Human behaviour, Addiction     

Placebo controlled evaluation of Xilei San,a herbal preparation in patients with intractable ulcerative proctitis

Background and Aim: Topical mesalamine or corticosteroid has shown efficacy in patients with ulcerative proctitis, but patients often become refractory to these interventions. Xilei San is a herbal preparation with evidence of anti‐inflammatory effects. We evaluated the efficacy of topical Xilei San in ulcerative proctitis patients. Methods: In a double blind setting, 30 patients with intractable ulcerative proctitis despite ≥ 4 weeks of topical mesalamine or corticosteroid were randomly assigned to True (n = 15) and placebo (n = 15). Patients in True received suppository Xilei San (0.1 g/dose per day of Xilei San), the other 15 received placebo suppository. The initial efficacy was evaluated on day 14. Primary endpoint of the trial was avoiding relapse during 180 days, relapse meant recurrence of active disease. Riley's index was applied for endoscopic and histological evaluations, while patients' quality of life was evaluated by an inflammatory bowel disease questionnaire. Results: On day 14, the number of patients who achieved remission, clinical activity index ≤ 4 in True was significantly higher versus placebo (P < 0.04). Likewise, at day 180, an 81.8% of patients in True were without relapse versus 16.7% in placebo (P < 0.001). Further, significant endoscopic (P < 0.01), histological (P < 0.02) and inflammatory bowel disease questionnaire (P < 0.04) improvements were observed in True, but not in placebo. Conclusions: This is the first controlled investigation showing significant clinical and endoscopic efficacy for Xilei San in patients with intractable ulcerative proctitis. Topical Xilei San was well tolerated, and was without safety concerns.     

Dissociative identity disorder (DID) in Japan: A forensic case report and the recent increase in reports of DID

The subject of this report murdered four young girls between 1988 and 1989. The forensic psychiatric evaluation showed that soon after the sudden death of his dearest grandfather he had developed dissociative symptoms including depersonalization, autoscopy, fugue, dissociative amnesia, Ganser's syndrome and DID, on the basis of earlier traumatic experiences under the dysfunctional family circumstances of his early childhood. His DID was thought to be manifest in at least four personalities, i.e., a host personality, a child personality, a cool personality and a female personality. In Japan only five cases of DID were reported between 1919 and 1990, whereas more than 30 cases were reported in journals or at academic meetings from 1991 to 1997. Although the incidence is still quite low in Japan, DID can be considered to be a valid clinical entity in spite of Merskey's severe criticism of the disorder. (Int J Psych Clin Pract 2000; 4:155-160)