Makoto Hayakawa

Zinc accumulation in adriamycin‐induced cardiomyopathy in rats: Effects of melatonin, a cardioprotective antioxidant

Abstract: We have recently reported that melatonin protects against adriamycin‐induced cardiomyopathy whose pathogenesis may involve free radicals and lipid peroxidation. Melatonin has also been shown to affect zinc turnover. Since zinc may act as an antioxidant, we investigated the role of zinc in the pathogenesis of adriamycin‐induced cardiomyopathy as well as in the treatment of melatonin against this disorder. Sprague Dawley rats were given adriamycin (cumulative dose, 15 mg/kg); melatonin (cumulative dose, 84 mg/kg); adriamycin plus melatonin; adriamycin plus probucol, another antioxidant (cumulative dose, 90 mg/kg); or vehicle alone, according to previously‐used regimens. Cardioprotective effects of both antioxidants (melatonin and probucol) were confirmed by the parameters of fractional shortening, heart weight, heart/body weight ratio, ascites volume, and mortality. Adriamycin increased both the myocardial and plasma levels of thiobarbituric acid reactive substances (TBARS) and myocardial zinc levels, and decreased plasma zinc levels. The significant negative correlation observed between the myocardial and plasma zinc levels (r =0.73, P < 0.01) among the samples of adriamycin‐treated and control rats suggested an internal redistribution of zinc. Melatonin and probucol were equally effective in inhibiting the increase in myocardial TBARS as well as zinc levels, suggesting that myocardial zinc accumulation might be a protective response against adriamycin‐induced oxidative stress. Melatonin also inhibited the adriainycin‐induced decrease in plasma zinc levels; probucol was not as effective in doing so. In addition to melatonins antioxidative effect, it may have the effect of maintaining the plasma zinc levels.

Clinicopathological features of superficial depressed-type colorectal neoplastic lesions

OBJECTIVE: We performed this study to analyze the endoscopic findings, dissecting microscopic features, and p53 immunostaining in superficial depressed-type (depressed) colorectal neoplastic lesions. METHODS: Dissecting stereomicroscopy was used to ascertain the size and pit pattern of lesions removed by endoscopic snare polypectomy. Immunohistochemical staining of p53 was performed with an antigen retrieval system using a monoclonal antibody to p53. RESULTS: All depressed neoplastic lesions (submucosal carcinoma, n = 6; high-grade dysplasia, n = 14; and adenoma, n = 30) were small (< 1 cm in diameter) and were detected as a depression with or without a marginal elevation on colonoscopic examination. In the dissecting microscopic study, submucosal carcinomas and lesions of high-grade dysplasia almost exclusively showed irregular small pits, with the exception of four malignant lesions with moderate submucosal invasion in which the pit structure was absent. In contrast, adenomas had either regular small (29/30 lesions) or oval pits (1/30 lesions). Rates of p53 positivity were 100%, 64%, and 7% in depressed submucosal carcinomas, lesions of high-grade dysplasia, and adenomas, respectively, thus the prevalence of p53 positivity was significantly higher in the former two groups than in the adenoma group. CONCLUSIONS: The high frequency of invasive carcinoma and high-grade dysplasia found in depressed colorectal neoplastic tumors, despite their small size, indicates that these lesions may be a subtype of colorectal tumor with more aggressive malignant potential at an earlier stage.

Ascorbic acid improves postischemic vasodilatation impaired by infusion of soybean oil into canine iliac artery.

This study was conducted to (a) assess postischemic vasodilatation by changes in the vascular cross-sectional area using simultaneous intravascular two-dimensional and Doppler ultrasound before and after the infusion of Intralipid (Pharmacia & Upjohn, Peapack, NJ, U.S.A.); (b) evaluate how antioxidant ascorbic acid modifies the effects of Intralipid on postischemic vasodilatation: and (c) clarify the changes in plasma nitrite and nitrate (NOx-) levels after the infusion of Intralipid with and without ascorbic acid. Twenty-eight mongrel dogs were used to measure for vascular cross-sectional area and average instantaneous peak velocity in the iliac arteries after the 5-min occlusion of the arteries. Postischemic vasodilatation was impaired after the infusion of Intralipid (20%, 2 ml/kg) and this impaired response was reversed by the co-administration of ascorbic acid (30 mg/kg). NG-monomethyl-L-arginine completely abolished postischemic vasodilatation. Plasma NOx levels were significantly reduced after the infusion of Intralipid compared with baseline (11.6+/-0.4 vs. 12.9+/-0.3 microM, p = 0.025) and after infusion of Intralipid with ascorbic acid compared with baseline (11.8+/-0.5 vs. 13.1+/-0.4 microM, p = 0.047). We concluded that ascorbic acid reverses the endothelial dysfunction induced by Intralipid without increasing plasma NOx- levels and that deactivation of nitric oxide by oxidative stress is a primary contributor to Intralipid-induced impaired vasodilation.

Successful Hyperbaric Oxygen Therapy of Pneumatosis Cystoides Intestinals : A Report of Two Cases

Abstract: Two patients with pneumatosis cystoides intestinalis (PCI) successfully treated with hyperbaric oxygen are described, The first patient was a 52‐year‐old male who presented with bloody stools and was diagnosed as having primary PCI. The second was a 61‐year‐old male whose occupation entailed prolonged exposure to trichloroethylene. Following hyperbaric oxygen therapy, the colonic gas cysts completely disappeared in both patients, and there has been no evidence of recurrence. The relevant literature from 1980 to 1992 is reviewed, and hyperbaric oxygen therapy for PCI is discussed in detail. The data accumulated thus far suggest that hyperbaric oxygen is superior to high‐flow oxygen breathing in PCI therapy.

Minute carcinoid tumor of the stomach: Report of two cases and review of the japanese literature

SummaryTwo cases of minute carcinoid tumor of the stomach were reported and 167 cases of gastric carcinoid in Japan up to December 1984 were reviewed. In Case 1, two carcinoid tumors of the body were found as sessile polyps of 4.2 and 4.8 mm in diameter, respectively, the latter having been detected two years previously. Case 2 had 60 polypoid lesions on the body and the fundus, ranging from 1.0 to 4.5 mm in diameter. In both cases the tumor invasion was limited to the mucosa and submucosa, although many micronests were found around the polypoid lesions.Among 167 cases of gastric carcinoid in Japan, 12 were 5 mm or less in size and 12 were 6 to 10 mm in size. In the former cases, there was no metastasis while in the latter, metastasis to the lymph nodes was found in 25.0%.We propose that the minute gastric carcinoid should be defined as a tumor not exceeding 5 mm in size with the invasion limited to the mucosa or submucosa. In addition, we emphasized that radical gastrectomy should be performed even for the minute carcinoid tumor because of its multicentricity and invasiveness.

Peptic Ulcer in Infants: Three Case Reports and a Review of the Japanese Literature

Abstract: Three cases of peptic ulcer in children under two years of age are reported, and 33 cases of infants with peptic ulcer reported in Japan between 1955 and March, 1989 are reviewed.