To investigate the ex vivo platelet aggregation in response to a substrate (L-arginine L-Arg) and a donor (sodium nitroprusside SN) of nitric oxide (NO) in nonpregnant women and in normotensive ...pregnancies.
Platelet aggregation was studied with a dual-channel aggregometer and expressed as a percentage of light transmission. Measurements were done at baseline and after preincubation with scalar doses of L-Arg and SN. The intraplatelet L-citrulline (L-Cit) levels were measured by high-performance liquid chromatography (HPLC).
In both groups, the baseline aggregation values were similar for adenosine diphosphate (ADP) and collagen stimuli. Wilcoxon rank-sum testing demonstrated that in both groups the addition of L-Arg had a significant effect on aggregation: Doses of 50 to 5000 mumol decreased ADP-induced aggregation. Conversely, collagen-induced aggregation was affected only by the highest dose of L-Arg. Sodium nitroprusside administered in doses of 2.5 to 250.0 nmol decreased ADP- and collagen-induced platelet aggregation equally. ADP-induced aggregation values obtained after (SN) incubation were positively correlated with gestational age. Intraplatelet L-Cit levels showed a significant rise after the incubation with L-Arg, and this effect was negatively correlated with gestational age.
The L-Arg-NO system regulates platelet aggregation during pregnancy. Moreover, a physiologic reduction of platelet sensitivity to the antithrombotic effect of NO occurs.
Thirteen patients with cancer of the gut, six with hepatocellular carcinoma and three with cancer of the bile duct have been treated with tegafur. All the patients were in an advanced stage of the ...disease with metastases to lymph-nodes or elsewhere. Each patient was given tegafur (oral daily dose of 600-1200 mg for 15-30 days with a dose-free interval of 25 days). Tegafur with other antiblastic drugs (such as cyclophosphamide, methotrexate, vincristine, doxorubicin, mitomycin) was given to ten patients. The results observed after the first treatment were as follows: partial remission in 14 patients (64%), no change in 4 (18%) and progression of the disease in 4 (18%). Only 10 patients among the 22 who were first treated, underwent one to three subsequent cycles of therapy obtaining with resultant partial remission in four cases, no change in two and progression of the disease in four patients. Side-effects (nausea and vomiting) during the treatment were recorded only in 14% of the patients. No significant impairment of blood functional tests has been documented. A comparison of the results obtained with tegafur and intravenous 5-fluorouracil has been made: the therapeutic effects of these two drugs are similar, but side-effects seem to be less during tegafur treatment.
