Release of myeloperoxidase and β-glucuronidase from HL-60 cells in response to N-formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe) in the presence of cytochalasin B was studied after induction of differentiation of the cells into granulocytes. Release of β-glucuronidase was observed with neither uninduced nor induced cells, whereas myeloperoxidase release was observed with induced cells but not with uninduced ones. In addition, chemotaxis and chemokinesis of the induced cells in response to this peptide were detected. These results suggest that there is a difference in release between myeloperoxidase and β-glucuronidase in the differentiated HL-60 cells, although the cells can respond to fMet-Leu-Phe.
The effect of dietary cholesterol (0-1%) on the levels of serum cholesterol, vitamin E (tocopherol), and fatty acid composition was determined in female rats fed a 10% butter diet with 10mg% tocopherol. When the dietary cholesterol level was increased, serum cholesterol and tocopherol also increased (r=0.72 and r=0.64, respectively), and a direct relationship was found between the concentrations of serum cholesterol and tocopherol (r=0.97). An increase in dietary cholesterol decreased the ratio of serum tocopherol to cholesterol (r=-0.80). Elevated dietary cholesterol caused an increase in serum total fatty acid (r=0.64) due to increases in saturated fatty acid (SFA, r=0.63) and monounsaturated fatty acid (MUFA, r=0.67), but no significant changes were found in the level of polyunsaturated fatty acid (PUFA, r=0.22). The ratios of PUFA/SFA and PUFA/MUFA decreased with an increase in dietary cholesterol (r=-0.82 and r=-0.81, respectively). A direct relationship was found between the ratios of tocopherol/cholesterol and PUFA/SFA in serum (r=0.77). These results indicate that dietary cholesterol affects vitamin E status and fatty acid composition of serum and that it has a detrimental effect on the ratios of tocopherol/cholesterol and PUFA/SFA in serum.
Anti-tumor effect of phenothiazine derivatives is widely recognized. The anti-tumor effects of chlorpromazine derivatives on Yoshida sarcoma cells and Ehrlich ascites tumor were investigated. Derivatives in which Cl of chlorpromazine is replaced with Br and the carbon number of the N-side chain is elongated to 4 or 5 were more effective in anti-tumor action than chlorpromazine. Moreover, their LD50 values were much higher than that of chlorpromazine. From these results, these newly synthesized compounds might be considered for clinical trial.
In the first experiment, guinea pigs were fed diets containing graded levels of ascorbic acid (AsA) from deficient to excess (0, 6, 60, 600, 6, 000, and 12, 000mg/kg of diet) for 15 days after pre-feeding with a low AsA diet (60mg/kg) for one week. Pentobarbital sleeping time measured on day 9 was shortened in the 600- to 12, 000-mg AsA groups as compared with the two AsA deficient (0 and 6mg) and 60-mg AsA groups. Liver microsomal cytochrome P-450 content increased with a dose-response relation to the dietary AsA level except in the excess AsA group (12, 000mg/kg). However, cytochrome b5 content and NADPH-cytochrome c reductase activity showed no significant response. Activities of aminopyrine N-demethylase and aniline hydroxylase showed the same response as seen in cytochrome P-450 content, but to a lesser extent. In the second experiment, guinea pigs were fed the diet containing the normal level of or excess AsA (300 or 24, 000mg/kg of diet, respectively) for 4, 9 or 15 days after a pre-feeding with the normal AsA diet for one week. No significant differences in the time courses of those responses described above were shown between the two AsA groups. In conclusion, the liver microsomal mixed function oxidase activity did not change even transiently during a short period after administration of a large excess of AsA such as 24, 000mg/kg of diet, and 300mg AsA/ kg of diet is enough to ensure normal levels of the liver microsomal mixed function oxidase system in guinea pigs.
Human interferon-β (HuIFN-β) entrapped in liposomes composed of egg phosphatidylcholine, cholesterol, and sulfatide was examined for its antitumor activity against brain tumor cells in vitro and its pharmacokinetics in vivo. HuIFN-β did not lose its biological activity during the preparation of the liposomes. The liposomes entrapped 7-14% of the HuIFN-β used, suggesting that the majority of HuIFN-β was embedded in the liposomal membranes. Cytotoxicity of the liposome-entrapped HuIFN-β against human tumor cells was comparable with that of free HuIFN-β. Intravenous injection of the liposome-entrapped HuIFN-β resulted in higher interferon levels in the blood, liver, spleen, brain, and transplant of human brain tumor, compared with free HuIFN-β. These data show that the liposome-entrapped HuIFN-β should be useful in the treatment of human brain tumors.
Serum vitamin E concentration was analysed in 59 (27 males and 32 females) free-living, healthy, middle-income volunteers with mean age of about 68 years (range, 63-73) from the Nagano City area in Japan. We assessed the vitamin E status of this population using two criteria, i.e., serum vitamin E concentration and the ratio of vitamin E (mg) to triglycerides plus cholesterol (g) in serum. Averages (±SD) of serum vitamin E concentration of the population including both males and females were 0.94±0.26mg/dl in July and 0.98±0.22mg/dl in December. In each season, about 15% of the population had a value of less than 0.7mg/dl and were assessed to be under low or marginal vitamin E status including only one deficient subject (0.46mg/dl) in July according to the first criterion. Averages of the ratio of vitamin E to lipid level (triglycerides plus cholesterol) in serum were 3.06±0.78mg/g in July and 3.15±0.76mg/g in December. In the latter season, the vitamin E status of one subject was assessed to be in inadequate according to the second criterion. In this population, the values of both lipid peroxides and relative fluorescence intensities in serum, and urinary creatine-to-creatinine ratio were normal in the subjects assessed to have low or marginal vitamin E by its concentration in serum. These results suggest that the vitamin E status of this population was acceptable, and that the ratio of vitamin E to lipid level seems to be a more reliable criterion for the assessment of vitamin E status than its serum concentration.
The inhibitory effects of a synthetic protease inhibitor, FUT-175, on the serum levels of pancreatic enzymes, amylase, trypsin, elastase 1, and lipase, in patients subjected to endoscopic retrograde cholangio-pancreatography (ERCP) were examined by the double-blind method. In the untreated group, serum trypsin and lipase levels reached a peak at 2h after the completion of ERCP; and amylase and elastase, at 6h. The serum levels of amylase and lipase recovered to the normal level on the 3rd day, whereas trypsin and elastase did not recover even by the 5th day. By the treatment with FUT-175 at a dose of 10mg or 40mg/day i.v., the increase in serum trypsin level was significantly reduced 2h after ERCP. In chronic pancreatitis patients, the increase in serum amylase level was significantly inhibited 2h after ERCP. FUT-175 also lowered the increased serum levels of other enzymes, but not significantly. These results suggest that FUT-175 is useful to reduce the pancreatic overloading and complications developing after ERCP.
The effects of diet enriched soybean fiber on glucose and insulin curves were studied in non-insulin-dependent diabetic human subjects. Postprandial glucose levels following a meal tolerance test in which fiber was given in powder form were lower in all subjects irrespective of the form of fiber intake. Consumption of fiber-rich bread for 12 weeks significantly reduced glucose levels at 0, 30, and 60min following a meal tolerance test in subjects with fasting blood glucose levels of 130mg/dl and over. Each patient consumed, during a 12-week period, 40g of fiber either in bread or as a powder suspended in milk. Following the consumption of fiber for 12 weeks, a reduction of plasma insulin was observed, but without a statistical significance. Body weight and plasma lipid levels did not change throughout the study period.