Monitoring of expiratory pentane was used as a non-invasive method to measure endogenous lipid peroxidation in chicken for the first time. Pentane is generated during breakdown of ω6-fatty acid hydroperoxides. Main problems with this method are the simultaneous metabolism of the hydrocarbons and the alkanes of intestinal origin. To overcome these limitations we performed kinetic studies for calculation of the actual production while taking into account the effect of metabolism. The influence of intestinal pentane was investigated by using fasted animals. Iron injection was employed to enhance endogenous lipid peroxidation. Under the conditions of a feeding experiment, pentane production rates were increased in animals brought up on oxidized fat, and dietary vitamin E reduced this effect. The influence of the intestinal hydrocarbons on pentane production rates were minimized by using fasted animals, as most of the pentane produced in fed animals originates from the gut.
Effects of carbon tetrachloride (CCl4) administration on hepatic and plasma glutathione S-transferase (GST) activity were studied in rats under both acute and chronic phases. Intraperitoneal administration of CCl4 at a high dosage (1.2ml/kg) (acute group) resulted in a marked elevation of plasma GST activity (over 200-fold of the control level at 24h after the administration) that was accompanied by a decrease in hepatic GST activity. In contrast to the successive elevation of plasma GST activity which had not reached a plateau by even 24h, plasma GPT activity reached a maximum at 6h after CCl4 administration and thereafter decreased to under the control value. Results for substrate specificity of plasma GST suggested that the leakage of hepatic GST into plasma began with by type 1-2 GSTs mainly and continued with not only type 1-2 GSTs but also type 3-4 ones. Supporting this assumption, immunohistochemical analyses of hepatic GSTs showed that the leakage of the GSTs occurred at the centrilobular zone where type 1-2 GSTs were shown to localize dominantly in the normal rat liver. And the leakage developed time-dependently to the surrounding area where both types of GSTs were diffusely distributed. Typical massive cell necrosis also developed in the same region. On the other hand, in the group administered repeatedly with a low dosage (0.4ml/kg) (chronic group), drastic alteration of GST activity and also GST localization could not be observed. These results indicate that elevation of plasma GST activity parallels to quantitative and qualitative alteration of hepatic GSTs as well as the extent of the liver damage in the acute phase. Measurement of plasma GST activity may provide useful information to judge the extent of acute liver damage clinically.
Histopathological changes in spontaneously hypertensive rats were studied after the animals had been fed Shiitake (Lentinus edodes) and Maitake (Grifola frondosa) mushroom powder diets, with 0.5% NaCl solution as drinking water for 9 weeks. Histological changes in control and Shiitake-fed rats were essentially the same, consisting of necrosis of the medial smooth muscle cells, vacuolization in the media of the aorta, fatty liver development, maceration in the myocardial muscle cells and vacuolization in the myocardium. In Maitake-fed animals large amounts of glycogen were observed in the liver, but the animals were otherwise normal in all respects. Dietary Maitake seems to play an important role in preventing the histological degenerative changes in SHR and thus may imply some benefits to be gained through blood pressure reduction and an improvement of lipid metabolism.
Effect of dietary riboflavin deficiency on rat lens glutathione, glutathione redox cycle, and oxidative-antioxidative processes was investigated to understand the possible biochemical mechanism(s) responsible for aggregation of lens proteins. Induction of riboflavin deficiency resulted in a marked reduction in the activity of glutathione reductase (GSH-R). Levels of glutathione (both reduced and oxidised) and sulfhydryl groups (total and non-protein), however, were unchanged. Activity of glucose 6-phosphate dehydrogenase, which generates the reducing equivalents, NADPH, necessary for maintenance of normal GSH-R activity, was found to be unaltered. On the other hand, glutathione dependent glutathione peroxidase, a potent peroxide scavenging enzyme, showed a significant rise in its activity with a concomitant increase in lipid peroxidation. Among the other antioxidative systems studied, superoxide dismutase and catalase remained unaltered, while levels of ascorbate declined. These results indicate impairments in the glutathione redox cycle and antioxidative defence mechanisms, in addition to enhanced lipid peroxidation in the lens of riboflavin deficient rats.
The effects of the anti-allergic drug azelastine on the P388 murine leukemia cell line (P388) and the K562 human leukemia cell line (K562) and their adriamycin (ADM)-resistant sublines P388/ADM and K562/ADM were examined with respect to the cytotoxic effect, cellular accumulation and retention of ADM. Azelastine enhanced the cytotoxicity of ADM toward P388 and K562 cells slightly but toward P388/ADM and K562/ADM cells greatly. Azelastine was found to increase the intracellular levels of ADM in both P388/ADM and K562/ADM cells by inhibiting the outward transport of the drug. The high intracellular accumulation of ADM accounts for the enhancement of the cytotoxicity of ADM, and thus the ADM-resistance of these cells was partially circumvented.
For normalization of the low levels of plasma polyunsaturated fatty acids (PUFA), a PUFA-supplemented diet including fishes and safflower oil was served for two weeks to nine patients with decompensated cirrhosis, whose linoleic, α-linolenic, arachidonic, eicosapentaenoic and docosahexaenoic acid levels in the plasma total lipid fractions were significantly low. Linoleic and eicosapentaenoic acid concentrations in the plasma total lipid fractions and eicosapentaenoic acid in the plasma phospholipid fractions were significantly increased following the administration of the PUFA-supplemented diet to these patients. Increases in relative composition of dihomo-γ-linolenic and eicosapentaenoic acids were also recognized in the plasma total lipid fractions. However, α-linolenic, arachidonic, and docosahexaenoic acids were not altered either in the plasma total lipid or phospholipid fractions. Clinical data such as serum glutamate-pyruvate transaminase activity and bilirubin levels showed no change during PUFA-supplemented diet. Supplementation with arachidonic acid itself to the diet, as well as fishes and vegetable oil, seems to be necessary to maintain normal composition of plasma fatty acids in patients with decompensated cirrhosis.
Postroperative changes in the plasma levels of granulocytic elastase and superoxide dismutase were examined clinically. Seven patients who had undergone cholecystectomy and eight patients who had undergone subtotal esophageal resection were considered. The protease inhibitor ulinastatin was administered to four of the latter patients. The levels of granulocytic elastase were elevated, and those of superoxide dismutase, decreased, in the non-medicated patients who had undergone esophageal resection (p<0.05). Furthermore, in the patients given the daily medication of 3×105 units of urinastatin for more than 3 days postoperatively, the elevation of granulocytic elastase levels and the decline of the superoxide dismutase levels were markedly suppressed (p<0.05). On the other hand, granulocytic elastase levels of the plasma to which ulinastatin had been added in vitro did not decrease. It is considered that the medicament of ulinastatin may be useful in the prevention of tissue injury caused by granulocytic elastase in cases where a disproportion of proteases and endogenous protease inhibitors exists.
The mobilizing effect of diet on plasma levels of vitamin A was studied in groups of mildly vitamin A-deficient and apparently normal children. Both groups showed significant increases in plasma vitamin A when fed diets containing more than 75% of the recommended dietary allowance for proteins and energy, but low in carotenoids. The magnitude of increase observed in plasma vitamin A was similar in both control and deficient children. The lowering in plasma vitamin A and the occurrence of clinical signs of deficiency in such children appear to be secondary to protein energy malnutrition and not entirely due to the very poor stores of vitamin A. These results are of significance in devising methodology for the evaluation of both protein-energy and vitamin A status of the population.
This study evaluated the effects of a 10.5% mixture of glucose, fructose, and xylitol at a 4:2:1 ratio on the postoperative management of 15 patients with impaired glucose tolerance. Only 5 patients, who were diabetic or showed the diabetes mellitus pattern in the 75-g oral glucose tolerance test (OGTT), required insulin supplementation. In 3 of these patients it was possible to decrease the daily dose of insulin from 48 to 36IU/day, 28 to 24IU/day, and 19 to 15IU/day, respectively. Whereas, in the other two of these patients, one of them required a dose of 15IU/day on third postoperative day while the other required an increase from 22 to 48IU/day to achieve blood glucose control. In the other two patients with diabetes mellitus and 8 patients who showed a borderline pattern in the 75-g OGTT, blood glucose levels could be maintained under 200mg/dl without the use of insulin. We also found low stimulation of insulin release as shown by the serum insulin values and progressive diminution of urinary glucose excretion. This solution had an inhibitory effect on lipolysis as well as an antiketogenic effect. The infusion did not adversely affect renal or hepatic function and no patients developed lactic acidosis. Furthermore, there were no complications, and side effects related to the use of this solution were rare. We conclude that this mixture of glucose, fructose, and xylitol is safe and useful in the postoperative management of patients with impaired glucose tolerance.
The relationships among platelet aggregation, lipase activity, age, and body mass index (BMI) were evaluated in 68 patients with essential hypertension. The hypertensives showed an increase in the plasma total cholesterol (TC), total triglycerides (TG), very low density lipoprotein cholesterol (VLDL-C), and low-density lipoprotein cholesterol (LDL-C) levels as compared with the normal subjects. The high-density lipoprotein cholesterol (HDL-C) showed no significant change, but the TC/HDL-C ratio was significantly higher in this group as compared with that of the normal subjects. Partial correlations by adjustment for age, BMI, and interrelated factors in the hypertensive group showed significant, positive correlations between TC and phospholipids (PL), PL and TG, TC and LDL-C and TC and TC/HDL-C ratio and a significant inverse correlation between HDL-C and LDL-C. Platelet aggregation did not correlate significantly with any of the metabolic variables studied in this group.
We compared plasma lipids, lipoproteins, platelet aggregation, plasma lipase activity, age, and body mass index (BMI) between patients with non-insulin-dependent diabetes mellitus and non-diabetic controls. Diabetic subjects showed significantly higher levels of plasma total triglycerides (TG) and very-low-density lipoprotein cholesterol (VLDL-C) and significantly increased platelet aggregability. The total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio was also significantly higher consequent to the significantly lower HDL-C levels in the diabetic subjects when compared with non-diabetic controls. The diabetic group showed positive significant correlations between TC and low-density lipoprotein cholesterol (LDL-C), HDL-C and plasma lipase activity, and TG and TC/HDL-C ratio, whereas significant inverse correlations were observed between TG and HDL-C, HDL-C and TC/HDL-C ratio. Platelet aggregation did not correlate significantly with any of the metabolic variables studied in this group.