In human burned skin, several polyunsaturated fatty acids, especially linoleate and its peroxide were isolated by high-performance liquid chromatography. Chemical structure of the epoxide was determined to be 9, 10-epoxy-12-octadecenoate by gas-chromatography/mass spectrometry, nuclear magnetic resonance measurements and ozonolysis. The epoxide showed an uncoupling activity to liver mitochondrial respiration and diminished the respiratory control of mitochondria. Formation of the epoxide in the burned skin was related to clinical observation of the “burn toxin” which appears after severe burns.
Twenty-four cases of type II citrullinemia, diagnosed as such based on enzymatic analysis showing a decreased enzyme content of kinetically-normal argininosuccinate synthetase in the liver, showed the following features of their serum amino acid patterns: 1) Serum arginine levels were higher than in controls and were significantly correlated with serum citrulline levels. 2) Serum alanine, serine, glycine, and branched-chain amino acids (valine+isoleucine+leucine) were significantly lower than in the controls, while threonine was rather higher and aromatic amino acids (tyrosine+phenylalanine) remained at the control level. Thus the ratio of threonine to serine and of branched-chain amino acids to aromatic amino acids were characteristically higher and lower than the control values, respectively. The above characteristics were quite unique to type II citrullinemia and not found in serum amino acid patterns of type I and III citrullinemic patients. Examination of effect of oral administration of citrulline on the amino acid pattern was also showed that the decrease of serum citrulline after the administration was delayed in type II citrullinemic patients; which was, however, not specific to type II citrullinemia, but was also found in patients with liver cirrhosis and chronic nephritis, and more prominently in one type III citrullinemic patient. After citrulline administration, serum arginine was increased in type II citrullinemic patients as much as in the healthy controls, but was decreased in the type III patient. The increase in serum ornithine after citrulline administration in the type II patients and in the parents of the type III patient (considered to be heterozygotes) was about half of the control value, but that in patients with liver cirrhosis was greater than the control. The ratios of threonine to serine and branched-chain amino acids to aromatic amino acids were not altered by the citrulline administration.
The mechanism of triglyceride (TG) deposition in adipose tissue in man still remains to be elucidated. In order to analyze interrelationships among insulin secretion, circulating triglyceride, and obesity, 22 juveniles with dynamic obesity (increasing obesity), 21 juveniles with static obesity (stationary obesity) and 16 non-obese control juveniles were examined for pancreatic B-cell function together with several plasma parameters. Hyperinsulinism was found both in dynamic and static obese groups when judged from 24-h urinary excretion rates of insulin and C-peptide. Interestingly, only the dynamic obesity group showed mild, but significant, elevations of plasma TG and total cholesterol; whereas both obesity groups revealed similar increases in plasma TG-carrier apolipoprotein B levels associated with hyperinsulinism. HDL-cholesterol and carrier apolipoprotein A-I levels were decreased in both obesity groups. The results suggest that the elevations of insulin and apolipoprotein B levels are common conditions of obesity and the degree of obesity seems to increase via hyperphagia and subsequent increase in the transport of TG-rich lipoproteins from the liver to adipose tissue.
WHO undertook a study to examine the effects of combination type oral contraceptives containing 30 or 50μg ethinyl estradiol and 150μg d-norgestrel on undernourished women from India and Thailand. As compared with a middle-income population of women in each of these centers, women recruited for the study were undernourished. To discriminate hormone effects from other time-related changes, the baseline data on the cross-section of the study population were analyzed for effects of duration of lactation, anthropometry, and season. Both oral pills brought about a similar small but significant deterioration in glucose tolerance. The change tended to be progressive in some women, but the overall trend was not significant. Effects on other parameters were absent or inconsistent. Maternal nutritional status (as assessed by body weight) and lactational status did not modify the metabolic effects of the oral contraceptives.
The effects of superoxide dismutase (SOD) and catalase on endotoxin-induced experimental shock were studied in rats. Experimental shock was induced by a single intravenous injection of endotoxin at a dose of 100mg/kg. After the injection, systolic blood pressure was reduced and heart rate was increased. Activities of serum lysosomal enzymes, such as acid phosphatase, β-glucuronidase, and cathepsin B, were increased. Serum thiobarbituric acid-reactive substances, which are important and damaging products of free radical lipid peroxidation, were significantly increased. These changes were most remarkable at 45min after the injection of endotoxin. By the subcutaneous injection of SOD (50mg/kg) 12 and 1h before the administration of endotoxin (100mg/kg), the reduction of systolic blood pressure and the increase in serum acid phosphatase, β-glucuronidase, and cathepsin B activities were significantly inhibited. By the subcutaneous injection of catalase (1.0mg/kg) 12 and 1h before the treatment with endotoxin, the decrease in systolic blood pressure and the increase in acid phosphatase and cathepsin B activities were significantly inhibited. These results indicate that oxygen-derived free radicals, such as superoxide and hydrogen peroxide, can affect the experimental shock states.
We studied the cytotoxicity of cyclophosphamide following the administration of phenobarbital or chloral hydrate to nude mice bearing human tumor xenografts. Cyclophosphamide, 60mg/kg, was injected intraperitoneally once a week for four weeks. The antitumor efficacy of cyclophosphamide was not altered by pretreatment with phenobarbital, but was significantly increased by pretreatment with chloral hydrate. In a parallel study, we measured the concentration of blood NBP-alkylating metabolites in nude mice after administration of cyclophosphamide, 60mg/kg. The AUC (area under blood decay curve) values of NBP-alkylating metabolites were 299±39, 270±13, and 521±57nmol eq nor-mustard ml-1·h in the controls, phenobarbital-pretreated, and chloral hydrate-pretreated groups, respectively. In contrast, Cmax (maximal concentration) values did not show any significant differences among these three groups. An increase in the AUC value of NBP-alkylating metabolites might have led to the stimulation of cytotoxicity of cyclophosphamide in the chloral hydrate-pretreated group. These results indicate that cyclophosphamide possesses AUC-dependent cytotoxicity against human tumor.
Administration of carbon tetrachloride to rats by intraperitoneal injection caused significant increases in serum aromatic L-amino acid decarboxylase activity and serum glutamate oxaloacetate and glutamate pyruvate transaminase levels. Moreover, a significant positive correlation coefficient was obtained between the decarboxylase activity and glutamate oxaloacetate transaminase activity. The increment of the decarboxylase activity in the serum caused by carbon tetrachloride was found to be accompanied by a decrease in the decarboxylase activity of the liver, and a significant negative correlation was found between the two enzyme activities. In contrast, no change was found in the decarboxylase activity of the kidney. These observations suggest that aromatic L-amino acid decarboxylase occurs in the serum at least in part as a result of the leakage of the enzyme from the liver into the blood.