The efficacy of platelet inhibition with aspirin for the prevention of secondary and primary events in patients with cardiovascular and cerebrovascular diseases is established. Aspirin irreversibly acetylates platelet cyclooxygenese (COX) and permanently inhibits thromboxane A₂ production. Platelets do not re-synthesize COX because platelets do not have nucleus. Therefore, active enzyme returns with a time course reflecting platelet turnover (life span 7-10 days). According to the above pharmacological mechanisms of aspirin, an intermittent administration (1-2 times a week) of aspirin is sufficient to obtain the antiplatelet effect.
Eight healthy subjects (3 males: 30-42 years, 5 females: 21-42 years) ingested 81 mg of buffered aspirin. Platelet aggregation was measured before aspirin ingestion and at 90 minutes, 3 days, 5 days, and 7 days after aspirin ingestion of a single 81 mg aspirin . The mean inhibition rate of platelet aggregation was 79.7±7.1% at 90 minutes (p=0.00002), 69.4±15.6% at 3 days (p=0.0002), 44.4±30.0% at 5 days (p=0.003), and 22.1 ±34.8% at 7 days (p=0.048). The inhibition of platelet aggregation of aspirin persisted for five to seven days.
The ratio of small, medium and large-sized aggregates was determined simultaneously. The ratio of small, medium and large was 38: 26: 36 (%) before ingestion respectively, 82: 8.6: 9.4 at 90 minutes, 71: 14: 16 at 3 days, 56: 18: 26 at 5 days, and 47: 21: 32 at 7 days after ingestion of a single 81 mg aspirin. Aspirin mainly inhibited the formation of large-sized platelet aggregates.
The inhibitory effect of platelet aggregation appeared within 5 minutes and the mean inhibition rate (n=5) was 27.1±28.1% at 5 minutes (p=0.06), 57.1±20.4% at 10 minutes (p=0.004), 72.1±13.5% at 15 minutes (p=0.0007), 78.9 ±9% at 20 minutes (p=0.0002), 85.3±9.5% at 25 minutes (p=0.00006), and 84.1±3.9% at 30 minutes (p= 0.00004) after a single 81 mg aspirin ingestion. The data indicated that aspirin is a quick-working medicine. The ratio of large-sized aggregates decreased from 42% to 19.8% in 10 minutes and to only 5.4% in 30 minutes after ingestion.
The present study showed that the inhibitory effect of platelet aggregation of aspirin persisted for at least 5 days or more and that aspirin is a considerably quick working medicine. Thus, it is thought that an intermittent administration of aspirin should be recommended for the secondary and primary prevention of arteriosclerotic diseases.

抄録全体を表示

A new evaluation method for the treatment of chronic pancreatitis was devised using male WBN/Kob (WBN) rats as a human chronic pancreatitis model ; in these rats, the lesion is spontaneously manifested at about 12 weeks of age. As a result of screening for drugs that inhibit the development of pancreatitic lesions in WBN rats, the inhibitory effects of estradiol (10 and 40μEg/kg, i. p., twice a week), camostat mesylate (100 mg/ kg, p.o., daily) and allopurinol (100 mg/kg p.o., daily) were observed among estrogen, testosterone lowering agent, trypsin inhibitors and depressors of active oxygen.
The efficacy of camostat mesylate and allopurinol which might be safely used for the treatment of progressive chronic pancreatitis were evaluated. Camostat mesylate was found to be effective, but not allopurinol. The expression of cells at the DNA synthesis stage as determined based on Brd Uridine (BrdU) uptake was examined. The uptake of BrdU notably occurred in acinar cells adjacent to the pancreatitic area. The regeneration of the pancreas as a result of the pancreatic trophic effect is the mechanism through which camostat mesylate is effective against lesions (mainly fibrosis) of chronic pancreatitis during the progression stage. One week after camostat mesylate administration, the weight of the pancreas increased rapidly, during which the uptake of BrdU in cells increased concurrently, indicating that regeneration of the pancreas occurred during this period.
The most effective parameter for evaluating the efficacy of a drug for pancreatitis is the percentage of pancreatitic area employed in our histopathological study . We concluded that the use of WBN rats is pharmacologically effective for drug evaluation.

抄録全体を表示

There have been few reliable aids available for measuring medication compliance to date. We designed an electronic monitoring device using a personal computer system for the recording of medication compliance, and applied it for patients with hypercholesterolemia or diabetes mellitus to evaluate its usefulness as a measurement tool. The device is a small, lightweight tool which is easy to carry and able to equip the tablets without the need to open the PTP sheet. An alarm is set to ring at the recommended timing and the tablets are taken by pushing the button. The real times of pushing the button are recorded automatically and saved, the date can then be printed with the device connected to a printer on the day of the patients' visit to the hospital. Eight patients (4 hypercholesterolemia, 4 diabetes mellitus), who needed chronic medication, were studied using the electronic monitoring device for 28 days. Pill counts and coefficient variants (CVs) of the deviation from recommended timing measured, and the improvements of the clinical data after using the device were studied. No pills were left in the device in all patients. CVs of the deviation from recommended timing ranged from 0.59 to 3.6%. After using the devices, total cholesterol levels were decreased in all patients with hypercholesterolemia. Among the patients with diabetes mellitus, HbA lc levels were decreased in two patients. The electronic monitoring system seemes to be a reliable tool for the measurement of medical compliance in clinical trials, and may effectively raise the medication compliance in patients who need chronic medication.

抄録全体を表示

The clinical trials enforcement organization is progressing remarkably after the new GCP. An investigation of the clinical trials enforcement organization was undertaken focusing on the arrangement and the works of clinical research coordinator (CRC) for 79 university hospitals (national university hospitals: 42, public university hospitals: 8, private university hospitals: 29). The main investigation items were four: (1) the change of the number of CRC, (2) the kind of work of CRC and their starting time, (3) judgement situations of clinical trials and post-marketing surveillance, and (4) the installation situation of a clinical trials management center.
From April 1997 to April 2000, the number of CRC markedly increased from ten persons to 129.5 persons in the national university hospitals and from one person to 90 persons in the private university hospitals, but only a few changes were found in the public university hospitals. The occupational descriptions of CRC are mainly those of pharmacist and nurse. Although the measure for wide range CRC business is progressing, the measure for screening of participants is relatively late in both the national university hospitals and the private university hospitals.
Recently, the science nature and the ethics nature of clinical research other than clinical trials and post-marketing surveillance (in particular post-marketing clinical trials) are generally evaluated by the institutional review board (IRB), and the installa tion of a special center for managing and supervising the smooth advancement of clinical research is also progressing.

抄録全体を表示