Dry distillation of ethyl 3-oxoindolizidine-5-propionate (I) with the same amount of soda lime as reported previously affords 1, 2, 4, 4a, 5, 6, 7, 7a-octahydropyrrolo [2, 1, 5-cd] -indolizine (II) in 48% yield. In order to confirm the α, β-enamine structure of II, conc. potassium cyanide solution was added dropwise with stirring to a solution of the perchlorate (III) of II. In this case, the cyano compound (IV) was also obtained in a quantitative yield. Attempted recrystallization of the picrate of IV from hot ethanol yielded the picrate of II by elimination of hydrocyanic acid as shown in Chart 1.

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    We examined the efficacy and safety of tacrolimus used in combination with disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients with insufficient response to treatment by one or more DMARDs. Thirty eight patients(male: 8, female: 30) who had active RA at baseline despite treatment with DMARDs were administered 1-3 (mean 1.4) mg tacrolimus daily for 12 weeks while continuing to receive DMARDs at the existing stable dosage. The patients’ age was 60±15 years. The number of patients who continued to receive methotrexate, salazosulfapyridine or bucillamine was 27, 28 and 20, respectively. Disease activity was evaluated by disease activity score 28 (DAS28). Good response and moderate response in DAS28 improvement were achieved in 12 patients (32%) and 13 patients (34%), respectively. The mean DAS28 decreased from 4.3±0.8 to 3.1±1.1 (P＜0.01) after 12 weeks of treatment. In high disease activity patients (n＝7), DAS28 was markedly improved from 5.4±0.4 to 3.4±1.4 (P＜0.01). Tender joint count was rapidly decreased, although C-reactive protein and swollen joint count were slowly reduced. Two patients discontinued tacrolimus treatment by reason of adverse Events (nausea, loss of appetite). The mean plasma creatinine was slightly increased (0.63±0.23 to 0.65±0.23 mg/dl), but the increase was not significant. These data show that tacrolimus combination therapy with DMARDs is efficacious and safe in refractory RA patients.

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Since late 1990s, a new hypoxia training device using mixed gas delivered through trainee’s oxygen mask has been developed in the United States Navy. This “Reduced Oxygen Breathing Device (ROBD)”has been evaluated in many research projects and has been introduced to military aircrews training as an alternative method to traditional hypobaric hypoxia training in several countries. The purpose of this article is to review the ROBD focusing on physiological differences between normobaric and hypobaric condition. The ROBD has been reported to induce almost same physiological responses, symptoms and cognitive impairment as the hypobaric induced hypoxia. Rapid decompression familiarization, which is only produced by hypobaric chamber training, is one of the issues to consider before introducing the ROBD to aircrews training. We also summarized the ROBD training protocols combined with a flight simulator for military aircrews.

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Preventing incapacitation of aviator during flight is one of major missions in aerospace medicine. To prevent incapacitation and maintain health status of pilots, airline companies and Air Forces develop manuals and guidelines for aeromedical examination or use of medications. Though guidelines for aeromedical examinations and major diseases are defined in detail, there are no detailed guidelines about medications in chronic disease or common disease. Since early 1990s, as life-style related diseases increase, Aeromedical Laboratory haｓ received numerous inquiries and cases to be reviewed in aeromedical council. To standardize aeromedical decision making and share information, Pharmacochemistry Section, Second Division of Aeromedical Laboratory published “Working Papers for aeromedical decision on medicated aviators” in 1999. This paper include following contents about common disease and medications. (1) Notice in initial medication (2) Aeromedical decision Cases to be avoided if possible, to be evaluated for returning flying duty during medications, to be allowed flying with medications (3) Effects for psychomotor activities (4) Cases of aviation accidents (5) Cases of aeromedical council (6) Reports of side effect In 2014 issue, we classify the risk of medications for aeromedical missions. We also have a planning to distribute digital issues in the same time. Points of considerations are academic reason and application for practical operations.

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