Folic acid supplementation of pregnant mice suppresses heat-induced neural tube defects in the offspring.

Neural tube defects (NTD) are a group of malformations that result from the failure of the neural tube to close early in embryonic development and among the most common congenital malformations in humans. It has been reported that a substantial proportion of NTD in humans can be prevented by folic acid (FA) supplementation prior to conception and during the first months of pregnancy, and myo-inositol (MI) was shown to reduce the incidence of NTD in curly tail mice which are not prevented by FA. Brief maternal hyperthermia (HT) early in pregnancy has been implicated in NTD both in humans and laboratory animals, and anterior NTD including exencephaly and anencephaly are induced frequently when pregnant mice are exposed to HT. We examined the effect of FA or MI supplementation of pregnant mice on the occurrence of heat-induced NTD in the offspring. When pregnant mice were treated with FA (3 mg/kg) daily from gestational day (GD) 0.5 through GD 9.5 and heated at GD 8.5, the prevalence of NTD in the fetuses (26.6%) was significantly lower than the corresponding figure in the HT alone group (38.6%; P < 0.05). However we failed to detect the preventive effect of MI (500 mg/kg). The results of this study suggest that prenatal FA supplementation decreases HT-induced NTD in mice and sufficient FA intake during early pregnancy may be recommended to avoid the birth of malformed children.

[Usefulness of pharmacokinetic modulating chemotherapy (PMC) for the postoperative adjuvant therapy of colorectal carcinoma: a preliminary report].

Pharmacokinetic modulating chemotherapy (PMC) using oral UFT and continuous venous 5-FU infusion was administered to 22 resectable patients with Dukes' B2-D colorectal carcinomas. The regimen was arranged as follows: Group A (n = 12) UFT 300-450 mg/day, 5 days a week and 5-FU 440-600 mg/m2/24 hr (750-1,000 mg/body/24 hr) once a week, Group B (n = 10), UFT less than 300 mg/day, 5 days a week, and/ or 5-FU less than 440 mg/m2/24 hr (750 mg/body/ 24 hr) once a week. The control group (Group C, n = 26) was selected at random from among non-PMC cases matched for other background factors and in which surgery had been performed during the past 4 years. Fifteen out of 26 patients in Group C were treated with 5-FU masked compounds orally. The cumulative 2 year recurrent rates of Groups A, B and C were 8.3%, 52.0% and 50.0%, respectively; the rate of Group A was significantly lower than that of Group B (p < 0.05). Four patients who suffered from PMC-related side effects of grade 1-2 wanted to decrease their dosage of UFT and/or 5-FU. They were registered in Group B. These results suggest that the regimen of Group A was advantageous in improving the prognosis after resection of Dukes' B2-D colorectal carcinoma.

[Screening test of crude drug extract on anti-HIV activity].

The anti-HIV-1 effects of 204 crude drugs of common use in Japan were evaluated in vitro. As a result, 45 samples inhibited HIV-1-induced cytopathogenicity in MT-4 cells. In particular, the hot water extracts of Lithospermum erythrorhizon (root) and Prunella vulgaris (spike) showed the strongest anti-HIV-1 activities. Their IC100 values were both 16 micrograms/ml. In general, the hot water extracts of the crude drug suppressed the replication of HIV-1 growth more strongly than the cold water extracts.

Treatment of angina pectoris patients with niludipine a new calcium antagonistic drug.

The antianginal effectivity of niludipine (Bay a 7168), a new calcium antagonistic drug, was investigated in angina pectoris patients, selected for admission to the trials by pre-determined strict criteria. Oral administration of from 60--120 mg niludipine daily for 4--8 weeks, resulted in the following: 1. Number of anginal attacks significantly reduced. 2. Nitrate consumption markedly lowered. 3. Investigating physicians assessed globally the clinical results of niludipine treatment on the basis of the reduction of the number of anginal attacks, nitrate consumption, improved physical ability and reports by the patients as to their subjective evaluation of the test drug. Niludipine was judged clinically effective in 21 out of 27 patients (77.8%). 4. Full records of ECGs, a necessary item for assessment, were obtained from 24 out of 27 patients. Ischemic ECGs were improved or normalized in 6 out of 24 patients (25%). 5. In the investigators' final overall assessment, including the evaluation of ECG changes, niludipine was rated effective for 20 out of 27 patients (74.1%). 6. Tolerance to the test drug was excellent. Only one patient complained of transient, mild nausea. After reduction of the daily dose, the patient completed the trial without any further appearance or complaints of side effects. Results suggest that niludipine is a useful antianginal drug in the management of coronary artery disease patients. Further clinical investigations with a larger number of patients should be conducted.