The unique correlation between anti-mutagenicity of human saliva and change in body weight

The purpose of this study was to investigate the effect of weight reduction on the anti-mutagenicity of human saliva. Subjects were 16 male college judo players. The anti-mutagenicity of the saliva was measured using the umu test. There was an inhibiting effect of the saliva on the mutagenicity of AF-2. However, a modifying effect of the saliva on Trp-P-1 was not observed. On the day before a competition and 7 days after the competition, the inhibiting capacity of the saliva for the mutagenicity of AF-2 decreased and increased in two non-weight reduction and two weight reduction groups, respectively. However, on the day before the competition, the changed body weights (r=−0.77, p<0.01) and BMI (r=−0.77, p<0.01) were significantly correlated with that of the inhibiting capacity of the saliva for the mutagenicity of AF-2. In addition, the BMI at 20 days before the competition was not significantly but markedly correlated with it (r=0.50, p=0.057). At 7 days after the competition, however, these correlations were not found. These findings suggest a unique correlation between the anti-mutagenicity of human saliva and body weight or BMI.     

Continuous intraarterial infusion of protease inhibitors in acute pancreatitis

Low-molecular-weight protease inhibitors were synthesized and developed in Japan and are in clinical use there for the treatment of acute pancreatitis. However, protease inhibitors are not acknowledged as drugs for the treatment of pancreatitis in other countries. In a recent study in 30 patients with necrotizing pancreatitis, survival rate was improved (mortality rate 13.3%) by continuous intraarterial administration of low-molecular-weight protease inhibitors as compared to conventional treatment. In Italy it was reported that pancreatic disorder decreased after the administration of low-molecular-weight protease inhibitors before the start of endoscopic retrograde cholangiopancreatography. Low-molecular-weight protease inhibitors may be potential alternative drugs for the treatment and/or prevention of acute pancreatitis and, therefore, warrant further evaluation. (c) 2001 Prous Science. All rights reserved.     

Dihydropyrimidine dehydrogenase activity and thymidylate synthase level are associated with response to 5-fluorouracil in human colorectal cancer

In the recent studies associated with the modulation of 5-fluorouracil (5-FU) and the development of new antifolates, attentions have been focused on the expression of the target enzymes, thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD), that affect tumor sensitivity and resistance to drugs. In order to evaluate predictability of therapeutic efficacy by intratumoral enzyme activity, we investigated the role of TS content and DPD activity in tumor sensitivity of 5-FU. Surgical specimens were obtained from 51 patients with colorectal cancer and used to measure TS content and DPD activity. TS content and DPD activity in tissues were measured by [3H]-FdUMP binding assay and radioenzymatic assay, respectively. The sensitivity to 5-FU in tumor specimens was determined by collagen-gel droplet embedded-drug sensitivity test (CD-DST). The TS content and DPD activity did not correlate with Dukes' staging. There was no correlation between TS content and DPD activity in any tumors. Simple linear regression analysis showed that neither DPD activity (r = -0.267, p > 0.05) nor TS content (r = -0.277, p > 0.05) in tumors had a significant correlation with 5-FU effectiveness independently. Four out of 24 patients, highly responsive to 5-FU, showed low levels in both DPD and TS. The patients with high value in either DPD activity or TS content proved not to respond to 5-FU. In conclusion, these results demonstrate that both tumor DPD activity and TS content are the factors predicting 5-FU responsiveness in colorectal cancer.     

Optimum Treatment Strategy for Superficial Esophageal Cancer: Endoscopic Mucosal Resection versus Radical Esophagectomy

This study was designed to determine the optimum treatment for a superficial esophageal cancer involving the mucosal or submucosal layer of the esophagus. The subjects were 150 patients with a superficial esophageal cancer who underwent endoscopic mucosal resection (EMR) or esophagectomy in Kurume University Hospital from 1981 to 1997. The mortality and morbidity rates, survival rate, and recurrence rate were retrospectively compared for (1) 35 patients who underwent EMR and 37 patients who underwent esophagectomy for a mucosal esophageal cancer and (2) 45 patients who underwent extended radical esophagectomy and 33 patients who underwent less radical esophagectomy for a submucosal esophageal cancer. Among the 72 patients with a mucosal cancer, lymph node metastasis/recurrence was observed in only one (1%); whereas of 78 patients with a submucosal cancer it was observed in 30 (38%). Among patients with a mucosal cancer the mortality and morbidity rates after EMR were lower than for those after esophagectomy. The survival rate after EMR was the same as that after esophagectomy. No recurrence was observed after either treatment modality. Among the patients with a submucosal cancer, the survival rate was higher and the recurrence rate lower after extended radical esophagectomy; than after less radical esophagectomy; the mortality and morbidity rates after extended radical esophagectomy were the same as those after less radical esophagectomy. Multivariate analysis demonstrated that the treatment modality (EMR versus esophagectomy) did not influence the survival of patients with a mucosal esophageal cancer, whereas it strongly influenced the survival of patients with a submucosal esophageal cancer. We concluded that EMR was the mainstay of treatment for a mucosal esophageal cancer, and extended radical esophagectomy was the mainstay of treatment for a submucosal esophageal cancer.     

Scopolamine fails to diminish chronic haloperidol-induced purposeless chewing in rats

Chronic haloperidol treatment for 4-12 months gradually induces spontaneous, irregular, purposeless oral chewing movements (CMs), apparently involuntary, in some but not all treated rats. Based on phenomenologic and pharmacologic similarities, this laboratory preparation has been used as an animal model of tardive dyskinesia (TD), which is the human hyperkinetic motor syndrome associated with chronic antipsychotic administration. This putative animal model has received the most severe challenge to its validity by claims that its oral movements can be suppressed by anticholinergic treatments, since resistance to anticholinergic suppression is an accepted pharmacologic feature of TD. In this experiment, we challenged a group of haloperidol-treated rats with CMs using three doses of scopolamine (0.1, 0.3, 1.0 mg/kg) and placebo and rated the change in dyskinetic movements. Each scopolamine dose reduced CMs by a similar magnitude, without any dose effect; the saline dose also reduced CMs to an equivalent degree. Therefore, we concluded that some component of the experiment, not the scopolamine, reduced the CMs. The handling component of the procedure was identified as a likely confound, and we tested this further. Rats with CMs were handled at several levels of "severity"; and the dyskinesias were rated at 1 and 3 h later. CMs were reduced by the experimental handling, in relation to the strength of the handling. Minimal handling produced modest CM reductions with quick recovery; whereas, the "strongest" handling plus the placebo injection produced the greatest CM reduction, evident over 3 h, resembling the CM reductions seen in the scopolamine and placebo experiment. Overall, these results suggest that anticholinergic drugs do not suppress chronic haloperidol-induced rat CMs. However, the movements are sensitive to stressful handling situations, and diminish with stress. In both of these characteristics, rat CMs resemble human TD, further supporting a role for this model in studies of human TD.     

Antidepressant-like effects of aniracetam in aged rats and its mode of action

RATIONALE: Conventional as well as newer antipsychotics cause weight gain, and, in the regulation of body weight, both insulin and leptin are hormones involved. OBJECTIVE: The aim of the present study was to compare these hormonal levels in patients on treatment with different antipsychotics. METHODS: Nineteen patients receiving conventional antipsychotics, 14 patients receiving clozapine and 14 patients receiving olanzapine, were studied. Fasting blood samples for insulin, leptin, glucose, and drug serum concentrations were analyzed. In addition, body mass index (BMI) was calculated. RESULTS: The median insulin level was significantly higher in the patients receiving olanzapine than in those receiving conventional agents, whereas there was no significant difference in insulin between the clozapine and the other two groups. However, in the clozapine group, insulin levels were positively correlated to the drug serum concentration. BMI was elevated in about half of the patients, with no difference being found between the groups. The leptin level was significantly higher in the women than in the men in the conventional agent group, but not in the olanzapine or clozapine groups. CONCLUSIONS: The higher insulin level in the patients receiving olanzapine than in those receiving conventional antipsychotics, despite similar BMI, points to a probable influence of olanzapine on insulin secretion. The correlation between the insulin levels and the clozapine concentration indicates, in addition, an influence of clozapine on insulin secretion. The gender difference in leptin, i.e. females normally having higher leptin levels than males, was found in the conventional agent group, but not in the olanzapine or clozapine groups, suggesting that also leptin regulation is altered during olanzapine or clozapine treatments. Moreover, it was mainly due to an increase of leptin in the males that leptin levels were equalized between sexes in the olanzapine group. We conclude that the influence of olanzapine and clozapine on both insulin and leptin levels might be associated with their weight-gain-inducing ability, while other mechanisms may be involved in the weight gain caused by conventional antipsychotics.     

A case of advanced gastric cancer complicated with liver metastases responding remarkably to combined chemotherapy with 5-fluorouracil and low-dose cisplatin, with UFT and low-dose cisplatin for maintenance on an outpatient basis

A 77-year-old man who had advanced gastric cancer with multiple liver metastases was treated by combined chemotherapy with 5-fluorouracil and low-dose cisplatin for 1 and half courses (1 course = 4 weeks). After this treatment, the primary gastric lesion was reduced, the liver metastases disappeared, and serum tumor marker levels decreased. After discharge, we administered a dose of 300 mg of UFT-E orally every day, and 10 mg of CDDP intravenously once weekly on an outpatient basis. The patient has survived with a good quality of life.