Antioxidative activity of 5,6,7,8-tetrahydrobiopterin and its inhibitory effect on paraquat-induced cell toxicity in cultured rat hepatocytes.

The in vitro antioxidative activity of 5,6,7,8-tetrahydrobiopterin (BPH4) was measured and the ability of BPH4 to prevent paraquat-induced cell damage was examined in cultured hepatocytes. The scavenging activity of BPH4 against superoxide anion radicals was assayed in two systems, i.e., xanthine/xanthine oxidase (X/XOD) and rat macrophage/phorbol myristate acetate (M psi/PMA) radical-generating systems. BPH4 showed an extremely strong superoxide anion radical-scavenging activity in both assay systems. Biopterin (BP) itself did not show any activity in the X/XOD system, but was effective in the M psi/PMA system. The antioxidative activities of BPH4 against both superoxide anion and hydroxyl radicals were confirmed by spin trapping-ESR spectrometry. BPH4 also protected rat brain homogenate against auto-oxidation. We further examined the effect of BPH4 on paraquat-induced cell toxicity in cultured rat hepatocytes. The paraquat-induced elevation of the release of lactate dehydrogenase (LDH), a marker enzyme for cytotoxicity from cultured hepatocytes was suppressed by BPH4 in a dose-dependent manner. The elevation of lipid peroxides simultaneously induced by paraquat was also inhibited by BPH4 in the same manner. These results suggest that BPH4 might be useful in the treatment of various diseases whose pathogenesis is active oxygen-related.

[A new approach to intra-arterial infusion chemotherapy for breast cancer].

To perform intra-arterial infusion chemotherapy for breast cancer, we cannulated the internal thoracic and lateral thoracic arteries, respectively. In the past, we could catheterize the former vessel only 43% of the time using gross observation, but now we can do so 100% of the time with an operating microscope apparatus. It was selectively done in the latter vessel through the brachial artery after the Seldinger method. An 82-day-long intra-arterial chemotherapy could be continued without any restriction in the patient's daily life, and the tumor decreased in size considerably. Nevertheless, intra-arterial preservation of the catheter and administration of anticancer drugs decrease local blood flow and produce thromboangitis, resulting in an extremely hypovascular state of tumor lesion. These changes, observed both angiographically and fluorographically, pose problems which must be resolved for long-term intra-arterial infusion chemotherapy.

[Collateral circulation after division of the common hepatic artery--clinical study concerning Appleby's operation].

The alteration of the blood flow of the proper hepatic artery (PHA) on occlusion of the common hepatic artery (CHA) was studied intraoperatively using an electromagnetic flowmeter for 18 cases of malignant gastric tumor. PHA blood flow was 280 +/- 225 ml/min before CHA occlusion, and after the occlusion it was 170 +/- 132 ml/min, or 64 +/- 15% of the pre-occlusion flow (n = 16). The pulsation of PHA after CHA occlusion was palpable in all cases, and there were no complications due to ischemia in 17 cases which underwent Appleby's operation. These results suggested that there was fairly good blood flow in PHA maintained by collaterals after CHA occlusion and that, clear pulsation of PHA could be regarded as evidence of sufficient blood flow. Tissue blood flow (TBF) measurement for the liver and gall-bladder by H2 gas clearance method was also done in several cases of Appleby's operation and of other abdominal operations. TBF of the gallbladder was significantly lower in cases of Appleby's operation on the day of operation (p less than 0.02), but the difference between the two operation groups was not recognized 5 days after surgery, suggesting rather quick recovery of circulation. As to hepatic TBF, significant decrease following Appleby's operation could not be proved.

[Collateral circulation after the division of the common hepatic artery--experimental study in dogs].

The influence of division of the common hepatic artery (CHA) was studied using dogs, by measuring the blood flow of the proper hepatic artery (PHA) by an electromagnetic flowmeter, and tissue blood flow of the liver and the gallbladder by the H2 gas clearance method. The results expressed as relative values (value before the division of CHA = 1.0) were as follows. 1) PHA blood flow decreased to 0.40 +/- 0.18 (n = 14) after the division of CHA. 2) After the division of CHA, tissue blood flow of the liver decreased to 0.61 +/- 0.16 (n = 27), and tissue blood flow of the gallbladder, to 0.51 +/- 0.16 (n = 40). After additional occlusion of the gastroduodenal artery, these values were 0.51 +/- 0.16 and 0.23 +/- 0.13, respectively. 3) On the seventh day after CHA division, tissue blood flow of the gallbladder recovered to 0.84 +/- 0.50. 4) Necrosis of the gallbladder, which was mostly partial was found in 20% of the experimental dogs at autopsy. These results showed that there is effective arterial collateral circulation after division of the CHA, which makes Appleby's operation practicable. However, considering the degree of ischemia observed in the gallbladder, preservation of collaterals during Appleby's operation will be essential for the prevention of necrosis of the gallbladder.

[A case of alpha-fetoprotein-producing gastric carcinoma with unique macroscopical configuration].

A gastric carcinoma with unique macroscopical configuration was resected from a 63-year-old male patient. Serum level of alpha-fetoprotein (AFP) was markedly elevated (19,000 ng/ml), and AFP-positive cells were found in the carcinomatous tissues. The cytoplasm of the carcinoma cells appeared to be watery-clear by light microscopy, however, electron microscopy revealed abundant amorphous substances in their cytoplasmic matrix. The unique macroscopical configuration of the gastric carcinoma may reflect its biological resemblance to hepatocellular carcinoma. Such a case may be rare, but AFP production, per se, seems to be a rather universal phenomenon of gastric carcinomas.