When 25 cosmetic products on the market (8 lotions, 9 foundations, and 8 creams) were set near a window and exposed to the sun for one year, the lipid peroxide levels in some creams and foundations were markedly increased, and some cosmetic products changed color and gave off a bad odor with time. UV-irradiated creams containing lipid peroxides were separately applied at 24h intervals for 8 days in a closed patch test on the back skin of guinea pigs. Histological examination was performed on the 9th day, and hyperkeratosis, dyskeratosis, intraepidermal edema, and marked spongiosis in the epidermis and small cell infiltration in the dermis were observed. Effect of UV-irradiated creams containing lipid peroxides on skin irritability in patients was also examined. Positive reactions were observed in 2 patients, having rosacea like dermatitis and contact dermatitis.
Young guinea pigs were fed a semipurified diet low in selenium (Se) and phospholipid. The blood Se and tissue glutathione peroxidase activity were lowered, electrocardiogram and ultrastructure of the myocardium appeared abnormal, and tissue chromolipids were elevated in guinea pigs fed with this basal diet. Diminished changes, however, occurred in groups receiving supplemental Se. Supplementation of Se resulted in maintenance of the normal level of total phospholipid and the ratio between different phospholipids in the cartilage (Acta Pharmacol. Sinica, 5 (1984) 264-267), but in the heart the ratio was improved only when adequate phospholipid (especially endogenous phospholipid) was given simultaneously. Activity of the membrane binding enzyme was slightly restored by Se supplementation. Only when both phospholipid and Se were given sufficiently did the cytochrome oxidase activity in myocardium and cAMP level in plasma increase markedly, even more than that of the control group.
Effect of a restricted 2-h daily feeding period on the ulcerogenicity of cysteamine was studied in rats with special reference to duodenal alkaline phosphatase activity. Cysteamine was injected at 14:00, 16:00, 18:00, 20:00, or 23:00 to respective groups of rats fed a meal from 17:00-19:00 for 15 days. Twenty-four hours after each injection, duodenal alkaline phosphatase activity was measured in mucosal homogenates. In control rats given saline, an anticipated increase was observed in duodenal alkaline phosphatase activity at 1h before the meal, whereas cysteamine had a decreasing effect on the enzyme activity, which was most prominent when the drug was injected at 1h before the meal.
Erythrocyte membrane and kidney microsomal Na, K-ATPases have been shown to be elevated in children suffering from kwashiorkor and in protein energy malnourished (PEM) rats. Kinetic properties of kidney microsomal Na, K-ATPase were studied in PEM rats to understand further the mechanism of this elevated activity. From the Arrhenius plots no significant differences were seen in the critical temperature and energy of activation of Na, K-ATPase between the control (C), energy-restricted (ER), and protein-restricted (PR) rats. Changes in the apparent K0.5 values of Na+, K+, and ATP were of much smaller magnitude, and increased Vmax was found to be mainly responsible for the observed increase in Na, K-ATPase activity in PEM rats. The Hill coefficient with ATP as substrate was found to be 1.62 in all three groups. Vmax/Km: a broad index of physiological efficiency, remained unaltered with K+ as a substrate in the ER rats, but was higher by 60% in PR rats as compared with the control value. In the Na+-activated component, the physiological efficiency in protein restriction was higher by 60% in relation to energy restriction. These results lead to the conclusion that the increased Na, K-ATPase activity in kidney microsomal preparations, from PR rats is attributable to modifications in the enzyme site and that energy restriction, in fact, results in a lowering of the physiological efficiency of Na, K-ATPase by affecting the Na+-site. Altered lipid microenvironment if any, does not appear to contribute to changes in Na, K-ATPase activity in PEM since neither Arrhenius plots nor Hill coefficients (ATP) showed any modification.
Treatment of pancreatic islets with alloxan or ninhydrin at concentrations that induced the inhibition of glucokinase activity similarly inhibited glucose-stimulated insulin secretion. Alloxan- or ninhydrin-induced inhibition of glucokinase activity was blocked by the presence of hexoses, which also protected against the inhibitory effect of each drug on insulin secretion. The protective effect of D-glucose against the inhibition of glucokinase activity by alloxan or ninhydrin showed α-anomeric preference, which was similarly observed in the protection by the sugar against the inhibition of insulin secretion. These results suggest that the inhibition of glucose-stimulated insulin secretion by treatment of pancreatic islets with alloxan or ninhydrin is due to the inhibition of glucokinase.
KK mice are used as model animals for non-insulin-dependent diabetes. In order to better understand the biochemical features of these animals, we compared the activities of various hydrolytic enzymes, including aminopeptidases, endopeptidases, carboxypeptidase, esterase, and so forth in the pancreas and liver of these animals with the same enzymes in ICR mice as controls. The enzymatic changes in the model animals were extensive not only in pancreas but also in liver. Multivariate analysis showed that the metabolic changes in liver rather than in pancreas are closely related to the abnormal glucose metabolism in KK mice. This may be somehow related to the insulin resistance in peripheral tissues in this model.
Calcium-binding protein was separated from rat milk by gel filtration, followed by ion-exchange chromatography using a DEAE-Sephadex A-25 column and characterized partially. Rat milk calcium-binding protein (mCaBP) has a molecular weight of about 16, 000 as measured by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and about 34, 000 by gel filtration using a Sephadex G-75 column. This protein specifically bound calcium with high affinity (Kd=1.45×10-6M). The mobility of mCaBP in regular PAGE was accelerated by the presence of EGTA and was delayed by calcium binding. Divalent cations such as Sr, Cd, and Mn produced an effect similar to that of calcium on the mobility of PAGE, but Zn and Fe did not. Ca-bound mCaBP was heat-stable and resistant to digestion by trypsin. These results indicate that the mCaBP undergoes a conformational change by the binding of calcium and other metal ions. The rat mCaBP was immunologically different from bovine mCaBP and human mCaBP. The properties of rat mCaBP are very similar to those of bovine mCaBP, except that it is a glycoprotein containing about 5% carbohydrates.
The role of lipid peroxidation in the pathogenesis of gastric ulcer was investigated in a rat model produced by water-immersion restraint stress. After the immersion of rats in 23°C water with restraint, blood flow of the gastric wall was significantly decreased and hemorrhagic erosions were seen in the body of the stomach. Thiobarbituric acid-reactive substances, an index of lipid peroxidation, in the gastric mucosa were significantly increased after the stress. These results suggest that lipid peroxidation may play a role in the pathogenesis of gastric mucosal lesions induced by stress.
The present study was designed to clarify the significance of complex formation of lipoproteins with extracellular connective tissue macromolecules during lipid accumulation in the arterial wall in SPF rabbits fed on a 0.5% cholesterol diet for six weeks. The effect of pantethine, a new hypolipidemic drug, on their complex formation and lipid accumulation was also studied. The levels of cholesterol bound to glycosaminoglycan, collagen and elastin in the aortic tissues were significantly increased in the atherogenic-diet group. The present results suggest the importance of complex formation of lipoproteins with elastin for lipid accumulation in atherosclerotic lesions. From the results on the ratios of oleic acid/linoleic acid in cholesteryl esters in the plasma and aortic elastin fractions, the cholesteryl esters accumulated on the connective tissue macromolecules in the atherosclerotic rabbits might be derived from the plasma directly, in addition to vascular cell-derived cholesteryl esters. Treatment with pantethine significantly reduced the increased levels of cholesterol in the plasma and the aortic tissues of the cholesterol-fed rabbits. The results suggest that pantethine acts directly on the arterial tissues, in addition to its hypolipidemic effect. These biochemical results were confirmed by the histological findings.
Two tumors formed by metachronous metastasis in the lung were separately removed by surgery at an interval of one year and a half from a patient with rectal cancer. These tumors were transplanted into nude mice and their sensitivity to various anti-cancer agents was assessed in vivo. The chemosensitivity spectrum of one of these tumors resembled that of the other. When 10 tumors were serially transplanted into nude mice, most of them underwent acceleration of growth during the early passages. When two primary lung cancers were serially transplanted into nude mice, there was no evidence indicating changes in sensitivity to cytotoxic agents between tumors of passages 2 and 8 in one case and between tumors of passages 2 and 18 in the other. Accordingly, serial nude mouse passages does not appear to alter tumor susceptibility to anti-cancer agents. As described in our previous report, metastatic tumors resemble the corresponding original tumors in sensitivity to cytotoxic agents. Therefore, the results of previous chemotherapeutic trials on an original tumor or earier metastatic tumors should also apply to metastatic or subsequent recurrent tumors. Preservation of human tumor specimens by serial transplantation in nude mice makes it possible to assess the effectiveness of new and untested anti-cancer agents for cancer under treatment, opening the way for the development of more potent drugs.