When bilateral ovaries were removed from 12-13-week-old female mice, serum lipid peroxide levels of the animals tended to increase at 1 month after the ovariectomy, and significantly higher levels compared with those of sham-operated control mice were observed at 2 and 3 months after the operation. Liver lipid peroxide levels of the ovariectomized mice were significantly increased at 1 month after the operation and high levels were also observed at 2 and 3 months after the operation. The increase in serum and liver lipid peroxide levels due to ovariectomy was suppressed by the subcutaneous administration of 17β-estradiol or 2-hydroxyestradiol. From these results, we propose that female hormones may play an important role in preventing an increase in lipid peroxide levels in women.
The effect of gamma-linolenic acid supplementation on essential fatty acid metabolism has been studied in pregnant rats fed a zinc-deficient diet and in those fed a balanced one. Gamma-linolenic acid supplementation was in the form of evening primrose oil (EPO) and the study of lipid metabolism was carried out on liver microsomes. Pregnant rats were fed one of four diets: zinc-deficient (ZD), zinc-deficient+evening primrose oil (ZD+EPO), zinc-adequate (Control, C), and zinc-adequate+evening primrose oil (C+EPO) diets. In females killed at day 21, just before parturition, both zinc concentration in liver and in vitro Δ6 desaturase activity were constant in the four groups. All products of in vivo Δ6 desaturation were also constant in the four groups, but the distribution between n-6 and n-3 polyunsaturated fatty acid families was strongly modified by gamma-linolenic supplementation. A significant decrease in the level of docosahexaenoic acid was observed in phospholipids of the C+EPO group, while in the ZD+EPO group there was a significant increase. It is speculated that gamma-linolenic acid given in the diet could be involved in regulation of the deacylation-reacylation cycle.
The effects of gamma-linolenic acid on essential fatty acid metabolism has been studied in fetuses from pregnant rats fed a zinc-deficient diet and in those from pregnant rats fed a balanced diet. Gamma-linolenic acid supplementation was in the form of evening primrose oil (EPO), and the study of lipid metabolism was carried out in liver microsomes. Pregnant rats were fed one of four diets: zinc-deficient (ZD), zinc-deficient+evening primrose oil (ZD+EPO), zinc-adequate (Control, C), and zinc adequate+evening primrose oil (C+EPO). In control groups (C and C+EPO) and deficient groups (ZD and ZD+EPO), gamma-linolenic acid supplementation had no effect on either zinc concentration in liver or Δ6 desaturation. All products of in vivo Δ6 desaturation were also not modified. Gamma-linolenic acid supplementation did not have much effect on essential fatty acid metabolism or on the distribution between n-6 and n-3 polyunsaturated fatty acid families. It was noticed, however, that the phosphatidylcholine level was enhanced and that the phosphatidylethanolamine level was decreased. The results indicate that in fetuses from pregnant rats fed a zinc-deficient diet the gamma-linolenic acid supplementation affects more the distribution of phospholipids in microsomal membranes than fatty acid profiles.
The effect of local hyperthermia treatment (43°C, 45min) on normal mouse skin was studied by examining superoxide dismutase (SOD) activity and histology of the skin. SOD activity of the skin decreased significantly 1, 4, 7, and 14 days after the treatment. The decrease reached a peak 4 days after the treatment and recovered to some extent by 14 days after the treatment. The decrease in SOD activity may be due to consumption of SOD by inflammation as well as to the destruction of SOD by hyperthermia. Histological examination of hyperthermia-treated skin showed edema, bleeding, and inflammatory cell infiltration in the dermis, and individual cell keratinization and acanthosis in the epidermis. It is important to estimate the decrease in SOD activity and tissue injury of the skin by hyperthermia in order to use hyperthermia more effectively with fewer side effects.
Chlorin e6Na (Chl), a hydrophilic chlorophyll derivative structurally similar to pheophorbide a (Pheo), had less cell-killing effect on FM3A cells than Pheo. Its cell-killing effect was suggested to be based on the damage of the cell membrane through the same mechanism as that of Pheo, because Chl was distributed mainly in the plasma membrane fraction. The time required for the maximum build-up of Chl in FM3A tumor tissue after injection was 2-8h. The photodynamic therapy (PDT) at 6 or 24h following administration of Chl caused shorter survival of FM3A tumor-bearing mice in comparison with that obtained when Pheo was used. However, the tumor-to-organ ratios of Chl at 24h after injection were higher than those of Pheo, and Chl was excreted more rapidly from normal tissues than from tumor tissue and had little phototoxicity on normal organs. From these characteristics, Chl may be more suitable as a photosensitizing agent in PDT than Pheo.
Structure and function of rat liver microsomes were studied during biliary obstruction and after its relief by external drainage. The concentration of serum bilirubin and the activity of serum glutamic-oxaloacetic transaminase rapidly decreased to near normal levels after the drainage. The percentage of smooth endoplasmic reticulum to the total endoplasmic reticulum increased during the biliary obstruction but it returned to normal one day after the drainage. In contrast, the specific content of cytochrome P-450 and the specific activity of NADPH-cytochrome c reductase in the microsomes did not recover to normal ones even 10 days after the drainage. These results demonstrate that the dysfunction of liver microsomes is prolonged after bile drainage despite recovery of serum biochemical indices and ultrastructural changes to the normal state.
For the purpose of investigating the relationship between diabetes mellitus and active oxygen, the serum levels of Cu, Zn-SOD, and Mn-SOD in 93 cases of primary diabetes were determined using the enzyme-linked immunosorbent assay (ELISA). The immunological activity of Cu, Zn-SOD, and Mn-SOD detected by ELISA and the enzymatic activity in the diabetics were significantly high at 61±34ng/ml, 114±95ng/ml, and 2.53±1.87U/ml, respectively, compared with 33±9ng/ml, 84±30ng/ml, and 0.64±0.54U/ml in the healthy controls (p<0.001). In diabetes, Cu, Zn-SOD had more clinical significance than Mn-SOD, and was correlated most significantly with microangiopathy (p<0.001). This correlation was conspicuous particularly in the diabetic nephropathy. Mn-SOD showed high levels in the diabetics complicated with hepatic impairment (p<0.001). Accordingly, serum SOD is considered to reflect prolonged disturbance resulting from a relative or absolute decline of insulin. Moreover, the elevation of serum SOD activity is suggested to have a close relationship with the tissue disturbance due to diabetes.
A chemotactic factor for polymorphonuclear leukocytes was found in the culture fluid of human lung giant cell carcinoma cell line Lu65. This factor was defined as chemotactic one by checkerboard analysis. Partial purification of the chemotactic factor was performed by DEAE-Sepharose and gel filtration with Sephadex G-100, which showed it to be basic and low molecular weight. The factor was also found in the filtrate of culture fluid passed through a Centriflo CF25 filter, thus indicating a molecular weight of less than 25kDa. Furthermore, three cell clones having higher activity of chemoattractant were selected from the original cell line.
Urinary excretion of hydroxyproline was determined in 15 nephrotic syndrome patients and 15 age-matched controls. The nephrotic patients excreted appreciably higher amounts of amino acids and imino acids compared with normals. On fractionation using Dowex 50×8H+ resin column, a greater excretion of large molecular weight hydroxyproline containing fraction (HP fraction 2) was observed compared with the normals, indicating the possibility of altered catabolism of collagen.
Oral glucose tolerance tests with 75g of glucose were carried out in 80 pregnant and 22 non pregnant women. Plasma glucose, insulin, and free fatty acid (FFA) were analysed in the venous blood samples obtained at 0, 30, 60, 120, and 180min after the glucose load. The results indicated that there was no impairment of glucose tolerance in women with different body weights, at different points of gestation or with different fat fold thickness. However, higher plasma insulin and FFA levels were observed in women with higher body weights as compared with the levels in women with lower body weight with both 75g and 1g/kg body weight of glucose load. Plasma insulin levels did not return to the basal values even at the end of 3h with a 75g load; while with a 1g/kg load, return to basal was seen at the end of 2h. These observations suggest that women with lower body weight might have an increased peripheral glucose utilisation or an enhanced transport of glucose to the placental pool as indicated by rapid clearance of plasma glucose.