Detoxification mechanism of heavy metals in marine mammals and seabirds: interaction of selenium with mercury, silver, copper, zinc, and cadmium in liver.

Subcellular distribution of mercury, selenium, silver, copper, zinc, and cadmium was determined in the liver of northern fur seals (Callorhinus ursinus), black-footed albatrosses (Diomedea nigripes), and Dall's porpoises (Phocoenoides dalli). Mercury, selenium, and silver were preferentially accumulated in nuclear, lysosomal, and mitochondrial fraction with an increase in their hepatic concentrations, whereas copper, zinc, and cadmium were accumulated mainly in cytosol with an increase in the hepatic concentrations for all three species. To gain insight into the existing state of the metals, they were extracted with four extractants--sodium dodecylsulfate (SDS); 2-mercaptoethanol; 2-mercaptoethanol + guanidinium thiocyanate; and copper sulfate (CuSO4)--at several concentrations from nuclear, lysosomal, and mitochondrial fraction in liver from a specimen of northern fur seal. Extraction efficiencies of the metals for 2-mercaptoethanol + guanidinium thiocyanate and CuSO4 were much higher than those for SDS and 2-mercaptoethanol. Also, for all individuals of the three species, metals were extracted by the three extractants--2% SDS; 0.25 mol/L 2-mercaptoethanol + 5 mol/L guanidinium thiocyanate; and 0.1 mol/L CuSO4--from nuclear, lysosomal, and mitochondrial fraction of liver. In the northern fur seals with higher concentration of mercury, the molar ratio of selenium to mercury approached unity in the nonextractable fraction of 0.25 mol/L 2-mercaptoethanol + 5 mol/L guanidinium thiocyanate, suggesting the possible formation of mercuric selenide (HgSe) with increasing hepatic concentration. Because the nonextractable content of mercury and its distribution were larger for black-footed albatross than those for the other two species, it was suggested that the black-footed albatross has a stronger ability to form a stable compound(s) of mercury in the liver. It is notable that the existing state of silver was similar to that of mercury as judged by their subcellular distribution and the extraction tests, suggesting that silver also interacted with selenium in the liver of marine animals used in this study.

Effects of tomato juice consumption on plasma and lipoprotein carotenoid concentrations and the susceptibility of low density lipoprotein to oxidative modification.

Effects of tomato juice supplementation on the carotenoid concentration in lipoprotein fractions and the oxidative susceptibility of LDL were investigated in 31 healthy Japanese female students. These subjects were randomized to one of three treatment groups; Control, Low and High. The Control, Low and High groups consumed 480 g of a control drink, 160 g of tomato juice plus 320 g of the control drink, and 480 g of tomato juice, providing 0, 15 and 45 mg of lycopene, respectively, for one menstrual cycle. The ingestion of tomato juice, rich in lycopene but having little beta-carotene, increased both lycopene and beta-carotene. Sixty-nine percent of lycopene in plasma was distributed in the LDL fraction and 24% in the HDL fraction. In the Low group, the lycopene concentration increased 160% each in the VLDL+IDL, LDL and HDL fractions (p<0.01). In the High group, the lycopene concentration increased 270% each in the VLDL+IDL and LDL fractions, and 330% in the HDL fraction (p<0.01). Beta-carotene also increased 120% and 180% in LDL fractions of the Low and the High groups, respectively. Despite these carotenoid increases in LDL, the lag time before oxidation was not prolonged as compared with that of the Control group. The propagation rate decreased significantly after consumption in the High group. Multiple regression analysis showed a positive correlation between lag time changes and changes in the alpha-tocopherol concentration per triglyceride in LDL, and a negative correlation between propagation rate changes and changes in the lycopene concentration per phospholipid in LDL. These data suggest that alpha-tocopherol is a major determinant in protecting LDL from oxidation, while lycopene from tomato juice supplementaion may contribute to protect phospholipid in LDI, from oxidation. Thus, oral intake of lycopene might be beneficial for ameliorating atherosclerosis.

Enhancement of rat hypoglossal nerve regeneration by chitin sheet plus gangliosides.

The effects of chitin sheet interposition with and without brain gangliosides on the regeneration of hypoglossal nerve fibres was studied in the rat following resection of a 5mm length of the nerve. At 10 weeks after operation, the number of horseradish peroxidase (HRP)-labelled motor neurones, indicative of the axonal repair process, on the side treated with chitin and gangliosides was higher than on the control side (where 5mm of the nerve was simply resected). The ratios of HRP-positive neurones in the right hypoglossal nucleus (treated side)/left hypoglossal nucleus (intact side) was 0 in the 5mm-resected group, 53% in the chitin-grafted group, 88% in the ganglioside (0.2 microg)-injected group, 90% in the ganglioside (2 microg)-injected group, 91% in the chitin with ganglioside (0.2mg)-injected group, 91% in the chitin with ganglioside (2 microg)-injected group and 85% in the autograft group, respectively. There were significant differences between the 5 mm-resected group and chitin-grafted group, ganglioside-injected group, chitin with ganglioside group and autograft group, and between the chitin-grafted group and ganglioside-injected, chitin with ganglioside and autograft groups (P< 0.005, respectively). Our results indicated that the use of chitin and gangliosides stimulated the regeneration of severed motor nerve fibres. These findings suggest that chitin and gangliosides might be therapeutically useful for treatment of neuronal degeneration.

Significance of informed consent and truth-telling for quality of life in terminal cancer patients.

For 12 patients with terminal stage cancer who died within the period from June 1995 to the present, we retrospectively evaluated the correlation between the "information" concerning disclosure of the "diagnosis," "pathology," and "prognosis," with the length of the last admission before the death, "sedation" near death, and the choice of "do not resuscitate (DNR)." The average length of admission before death was markedly shorter for patients who had been told either the "diagnosis," "pathology," or "prognosis" than for patients who had not. A statistically significant difference was observed between those who had been told and those who had not been told the "pathology." Similarly, "sedation" tended to be done for those who had been provided with information on cancer. It was suggested that telling patients with terminal stage cancer the truth about "diagnosis," "pathology," and "prognosis" is important for them to spend a fulfilling terminal stage.

[Primary cutaneous lymphoma--mycosis fungoides].

Malignant lymphoma of the skin is a type of extranodal lymphoma with a benign prognosis, in which the main organ involved is the skin. Some 80-90% of the cases in Japan show a T-cell phenotype. Mycosis fungoides and Sézary syndrome are common T-cell lymphomas of the skin. The tumor cells of mycosis fungoides, small and medium-sized cells with cerebriform nuclei, are detected in an epidermo-dermo junction. The tumor cells show CD3, CD4 and CLA, (cutaneous lymphocyte associated antigen) positivity. Various forms of topical therapy, such as topical steroid, photochemotherapy (PUVA), and interferons, have been indicated for the good-risk group (stages I A, I B and II A). Electron-beam irradiation, various chemotherapy, such as low-dose etoposide, low-dose MTX and CPT-11 and deoxy coformycin (DCF) plus IFNs, have been indicated for intermediate-risk group (stage II B, III and IV A). BRMs plus low-dose etoposide, electron-beam irradiation and a multiagent combination chemotherapy, such as MACOP-B, M-BACOD or ProMACE-CytaBOM, have been indicated for the high-risk group (stages IV A and IV B). Cutaneous B cell lymphoma (CBCL) can be diagnosed using a molecular biological assay. The tumor cells of CBCL do not express T-cell antigens such as CD2, CD3 and CD43 and show B-cell antigens such as sIg, CD19, CD20 and CD22. Electron-beam irradiation has been indicated for early-stage CBCL (stages I and II). An effective multiagent combination chemotherapy, such as MACOP-B, M-BACOD or ProMACE-CytaBOM, is required for patients with advanced stage CBCL (stages III and IV).

[Lymphomas of the skin].

Malignant lymphoma of the skin is a type of extranodal lymphoma, in which the main organ involved is the skin, and 80-90% of cases in Japan show a T-cell phenotype. Mycosis fungoides (MF) and Sézary syndrome (SS) are common T-cell lymphomas of the skin with a benign prognosis. Therefore, various forms of topical therapy, such as topical steroid, photochemotherapy (PUVA) and interferons, have been indicated for the low-risk group (stages I A, I B and II A), whereas electron-beam irradiation, retinoid plus interferon (IFN), photopheresis and deoxycoformycin (DCF) plus IFN have been indicated for intermediate-risk group (stages II B and III). The cutaneous involvement of B-cell lymphoma has been considered an unmistakable sign of progression and dissemination of lymphoid disease, and is thus associated with a poor prognosis. However, some primary cutaneous B-cell lymphomas (CBCLs) show a benign prognosis, and electron-beam irradiation has been indicated for early-stage CBCL (stages I and II). However, the prognosis of high-risk group CTCL (stage IV) and cutaneous B-cell lymphoma (CBCL) (stages III and IV) is poor. Therefore, an effective multiagent combination chemotherapy, such as MACOP-B, M-BACOD or ProMACE-Cyta BOM is required for patients with advanced-stage CTCL and CBCL. With regard to age at the time of the first medical examination, patients with CTCL or CBCL at an advanced stage have a tendency to be older. Therefore, a mild but effective therapy, such as DCF plus IFN is recommendable.

Effects of an angiotensin II receptor antagonist on the progression of renal failure in hyperlipidemic Imai rats.

This study was undertaken to determine the role of angiotensin II (AII) in the development of glomerulosclerosis, using an AII receptor antagonist in an animal model of hyperlipidemia. Hyperlipidemic Imai rats were employed because they spontaneously develop glomerulosclerosis; this is especially true in males. Group 1 (n = 5) received no specific therapy. Group 2 (n = 5) was treated with enalapril at a dosage of 50 mg/l in drinking water starting at 6 weeks of age. Group 3 (n = 5) and group 4 (n = 6) were treated with the AII receptor antagonist DuP 753 at a respective dosage of 15 mg/l (low-dose DuP) and 150 mg/l (high-dose DuP) in drinking water. Body weight, blood pressure, urinary protein, serum albumin, cholesterol, BUN and serum creatinine were measured and compared among the groups from 12 to 24 weeks of age. Enalapril and high-dose DuP were almost equally effective in controlling systemic hypertension. Each treatment significantly reduced proteinuria (172 +/- 112 and 152 +/- 72 mg/kg/day at 24 weeks) as compared with that in the controls (421 +/- 147 mg/kg/day; p < 0.05 and p < 0.01, respectively). Hypercholesterolemia also decreased (82 +/- 4 and 89 +/- 6 mg/dl) as compared with that of the controls (141 +/- 48 mg/dl; both p < 0.05). Glomerulosclerosis index (SI) was significantly higher in the untreated control rats (55 +/- 26) than in the enalapril-treated rats (2 +/- 3; p < 0.005) and the high-dose-DuP-treated rats (6 +/- 6, p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

[A new technique to prepare non-reversed autovein graft].

Non-reversed autovein graft was prepared by using a long saphenous vein. Disposable enema-syringe was used for vein graft to be turned inside out easily, and venous valves were resected out completely. After these procedure, a graft was put with syringe again, and turned outside in with same maneurver. Then, a non-reversed autovein graft without valves was prepared. We believe this is an excellent method to prepare non-reversed valveless autovein graft to be used as bypass grafting for cardiovascular surgery.