This review describes the discovery of new reactions in the field of heterocyclic chemistry. The reactions taken as typical examples involve 1) the photochemical ring transformations of quinolines to indole rings, 2) the ring transformations of indoles to quinazoline and quinoxaline rings, 3) the ring expansion reactions of indoles to 1H-1-benzazepines, 4) the intramolecular photo[2+2]cycloaddition reactions of 2- or 3-alkenyloxy-(or amino-)cyclohex-2-en-1-ones, 5) the syntheses of the nitrogen-containing heterocycles using the cyclizations of N-alkenylcarbamoylmethyl radicals, and 6) the general syntheses of bridged azabicyclic compounds using radical translocation/cyclization reactions. Modification of the water-soluble aminating agent hydroxylamine-O-sulfonic acid to the more powerful aminating agent O-mesitylenesulfonylhydroxylamine is also described.
Our extensive investigation of the isoprenoidal glycosides in Solanaceae and Leguminosae folk medicines to verify their effectiveness, antiherpes and anti-HSV-1 activities, and hepatoprotective action has resulted in the elucidation of their structure-activity relationships. We present the respective optimum models here.
A pharmacoeconomic evaluation was made of prophylaxis against influenza using the oral neuraminidase inhibitor oseltamivir. Two patterns consisting of administration for 7 days as postcontact prophylaxis (7 day model) and seasonal administration for 6 weeks (6 week model) were examined. Decision analysis models were created on the basis of reports of clinical studies and epidemiologic studies relating to the drug and vaccination, and cost-effectiveness analyses were conducted based on the number of persons who had influenza and pneumonia as health outcomes. Costs were estimated with respect to health expenditures from the societal perspective as well as productivity costs. In the case of administration for 1-week postcontact prophylaxis, the health outcomes improved and costs were reduced in comparison with nontreatment, thus making this administration schedule the dominant choice. With administration for 6 weeks during the infectious period, vaccination involved lower costs and was superior in terms of health outcomes.
The inhibitory effects on the intestinal digestion and absorption of sugar of health teas that claim beneficial dietary and diabetes-controlling effects were compared in rats using portal cannulae. The measured durations were the times during which the elevation of portal glucose levels resulting from continuous intragastric infusion of sucrose or maltose was suppressed by concentrated teas. The teas investigated included salacia oblonga, mulberry, guava, gymunema, taheebo, yacon, and banaba. The duration of the inhibitory effect on the sucrose load of salacia oblonga, mulberry, and guava were 110 min, 20 min, and 10 min, respectively. In contrast, gymunema, taheebo, yacon, and banaba had no significant effect on the continuous infusion of sucrose. These results suggest that there is considerable difference in the efficacy of commercial health teas in influencing glucose absorption.
During performance of clinical trials in medical institutions, information regarding the safety of investigational drugs is submitted by trial sponsors according to guidelines for good clinical practice. In the present study, reports of clinical trials conducted at the University of Tokyo Hospital were examined, focusing on the safety information provided to the Institutional Review Board (IRB). Two hundred two reports (52 protocols) of safety information were submitted to the IRB by clinical trial sponsors between April 2000 and March 2001, of which 185 contained a total of 3021 cases of adverse events. Of those, 194 reports were judged by clinical investigators/physicians not to be associated with any significant problems and the trials were continued. For 157 of those 194 reports, it was considered unnecessary to inform the test subjects of the report contents, including the adverse events. The decision of whether or not the test subjects should be informed of such contents tended to depend on the causal relationship between the adverse events and drug intake, as well as the predictability of the adverse events. For 8 of those 194 reports, the IRB recommended that the clinical investigators/ physicians provide information to the test subjects and/or submit detailed information on the status of these subjects to the IRB. From these results, we suggest that establishment of a system to unify and evaluate drug safety information is necessary to provide safe and efficient clinical trials.
It is known that hybrid liposomes composed of dimyristoylphosphatidylcholine (DMPC) and micellar surfactant (Tween 20) are effective for encapsulating drugs and for the treatment of meningeal gliomatosis in vivo without toxicity. In this study, we attempted to use these hybrid liposomes as a drug carrier system for the oral administration of insulin using diabetic model rats. The noteworthy aspects were as follows: (a) The hybrid liposomes of 90 mol% DMPC/10 mol% Tween 20 were stable and uniform for more than 4 weeks. (b) The blood glucose level of diabetic model rats decreased after the oral administration of hybrid liposomes including insulin. These results suggest that the oral administration of hybrid liposomes including insulin should be effective for the treatment of diabetes.
Tacrolimus, a potent immunosuppressive agent, has recently become available for the treatment of myasthenia gravis (MG). However, few reports have evaluated the usefulness of tacrolimus in the elderly and in intractable MG classified as Osserman's grade IIb or higher. In this study, we examined the effects of tacrolimus in two patients with postthymectomy Osserman's grade III and IIb MG. The effects of tacrolimus were evaluated using the modified quantitative MG score (QMG score) and anti-acetylcholine receptor antibody (AChRAb) titer. Patient 1 was a 39-year-old woman with Osserman grade III MG. Her MG score improved after tacrolimus administration (3 mg/day), allowing gradual decreases in the doses of prednisolone and pyridostigmine because of improvement in MG symptoms. The AChRAb titer also decreased from 100.0 to 25.7 nmol/l during tacrolimus treatment. The concentrations of tacrolimus in whole blood ranged from 5.5 to 8.2 ng/ml during treatment. Patient 2 was a 68-year-old man diagnosed with Osserman grade IIb MG. After the initiation of tacrolimus treatment, dysphagia improved dramatically, and he was able to swallow food without a nasal feeding tube. The AChRAb titer decreased from 42.4 to 23.4 nmol/l during the treatment period. The concentration of tacrolimus in whole blood was 7.0 ng/ml 6 days after the initiation of treatment. These findings suggest that tacrolimus is effective in intractable and elderly MG patients.