When cultured aortic smooth muscle cells were incubated with linoleic acid hydroperoxide and then with low density lipoprotein, marked deposition of lipids in the cells, viz., formation of lipid-laden cells, occurred; while incubation with either linoleic acid hydroperoxide alone or low density lipoprotein alone scarcely provoked the deposition of lipids in the cells. In the case of macrophages derived from monocytes, their incubation with low density lipoprotein preincubated with linoleic acid hydroperoxide resulted in formation of typical lipid-laden cells, even though incubation of the cells with either linoleic acid hydroperoxide alone or intact low density lipoprotein alone scarcely produced lipid-laden cells.
The effects of dietary supplements of β-carotene (20-500mg per kg diet) on hepatic microsomal drug-metabolizing enzyme activities were studied in mice. Supplementation for 14 days resulted in marked reductions in the concentrations of cytochrome P-450 and biphenyl 4-hydroxylase. The antipyrine N-demethylase and p-nitroanisol O-demethylase activities, however, were unchanged. Also apparently unchanged were the hepatic concentrations of microsomal protein, lipid peroxides, and superoxide dismutase. Supplemental β-carotene was weakly protective against the acute toxic effects of an injection of 1, 2-dimethylhydrazine (DMH), as indicated by a lowered mortality. This anti-carcinogenic action of β-carotene, including a protection against DMH-induced colon carcinogenesis, suggests an alteration by this carotenoid in the metabolism of carcinogens by the liver.
For clarification of the role of CCK-8-like immunoreactive neurons in the lateral part of the nucleus parabrachialis dorsalis (PBD), which have fibers projecting to the ventromedial hypothalamus (VMH), the effects of unilateral and bilateral lesions in the lateral part of the PBD on increase in body weight, food and water intake, and metabolism were examined in female Sprague-Dawley rats. Unilateral and bilateral lesions caused significant increases in food and water intake, body weight gain, Lee's index, and the weights of parametrial adipose tissue, liver, and kidney. These lesions resulted in increased serum concentrations of insulin and urea, while the liver phosphoenolpyruvate carboxykinase activity tended to be decreased. These effects were quite similar to, but slightly less than, the effects of bilateral lesions of the VMH. On the side of either unilateral or bilateral lesions, the VMH did not contain CCK-8-like immunoreactive fibers. These findings support the hypothesis that the CCK-8-like immunoreactive neurons in the lateral part of the PBD send signals to the VMH and by relaying signals there they participate in the regulation of food intake and metabolism, their firing suppressing food intake and insulin secretion. However, it is also possible that the lesions induced the above changes by destroying neurons descending and ascending to other brain sites or neural fibers passing through the lesion area.
To elucidate the possible involvement of oxidant tissue damage and protective effect of skin superoxide dismutase (SOD) activity during contact dermatitis, we investigated SOD activity in the skin of guinea pigs after elicitation of either allergic or primary irritant contact dermatitis. Remarkably decreased skin SOD activity was observed after induction of irritant contact dermatitis but not after elicitation of the allergic type. Although chronic allergic contact dermatitis affects the skin SOD activity, it seems likely that, in an experimental model, the skin SOD activity level is more readily reduced in response to the severe inflammation or tissue injury induced by irritant contact dermatitis than in response to allergic contact dermatitis. The data suggest that if we have the ability to down-regulate the expression of contact dermatitis, it is required, as one of the possibilities, to suppress oxidant tissue damage by manipulating cytoprotection activity against oxidative attacks to the skin.
The present work was focused on the relation between the degree of obesity and the pattern of fasting serum insulin levels in obese Egyptian women aged 35-55 years. The relations between insulin, fasting blood glucose, blood pressure, and fat distribution were also investigated. The present results demonstrate a correlation between serum insulin and body mass index (BMI). In addition, anthropometric variables describing body fatness correlated positively with serum insulin. A significantly positive correlation between both systolic and diastolic blood pressure and the fasting serum insulin was observed in the younger age group (35-44 years). This relationship was not present in the older group. A raised fasting serum insulin concentration in the presence of a normal fasting blood glucose was found. The possible connections between obesity, diabetes mellitus, and increased risk of hypertension were suggested.
In the case of maturity-onset diabetes mellitus, urinary trehalase and urinary maltase activities were significantly elevated as compared with those of healthy individuals. The urinary trehalase activity in non glucosuric and non proteinuric patients was higher than that in healthy individuals, and the trehalase activity in those diabetics with proteinuria was significantly higher than in those without it (p<0.05). Both urinary trehalase and maltase activities were elevated with increased concentration of urinary β2-microglobulin in this diabetics. Furthermore, urinary trehalase was elevated in disease of short duration (1-4 years), whereas in that of relatively long duration (more than 13 years) the activity was rather low. These results suggest that renal brush borders are damaged in the early stages of the disease and that urinary trehalase is a good indicator of renal tubular damage.
Arginase activity in the erythrocyte showed lower values in cases of cerebral and myocardial infarctions than in normal cases. To explore this phenomenon we studied the effect of arginase on platelet aggregation. It was demonstrated that the arginase possesses the inhibitory activity toward platelet aggregation: it inhibits the formation of the platelet-thrombus due to arachidonic acid in vivo by raising its concentration in the erythrocyte. Thus it appears that the arginase in erythrocytes is concerned with the inhibition of thrombus formation.
The effect of wheat bran supplementation (11g for a period of one month) on glycemic control and on serum and urinary amino acids and imino acids as an index of collagen metabolism in diabetes mellitus was studied in 30 non insulin-dependent diabetic subjects (20 males and 10 females). The mean duration of diabetes was five years and all patients were on oral hypoglycemic drugs. After one month of bran supplementation, the drop observed in fasting and post-prandial blood sugar level was 17.4mg/dl and 27.06mg/dl, respectively. In response to bran therapy, the glycosylated serum protein and serum amino acid levels did not change significantly and also no significant change in urinary amino acids and imino acids was noticed.
Enzymatic studies were performed on fibroblasts from patients with different clinical phenotypes of galactosialidosis. Residual activities of β-galactosidase and neuraminidase were relatively low in infantile patients as compared with those in adults, and an asymptomatic adult showed higher residual activities of these enzymes than did adult patients with neurosomatic manifestations. The ability of thiol protease inhibitors to activate β-galactosidase in fibroblasts was similar in infant and adult cases. Both β-galactosidase and neuraminidase were activated slightly more by addition of the “protective protein” preparation to the culture medium of fibroblasts in the asymptomatic adult than in infants and symptomatic adults. Sucrose density gradient centrifugation revealed three peaks of β-galactosidase activity in crude homogenates of fibroblasts: very high, high, and low molecular weight fractions. The peak of the high molecular weight fraction was predominant in control fibroblasts, while it was extremely low in galactosialidosis patients, especially in the infantile cases. It was suggested that the severity of clinical manifestations was inversely correlated with amounts of residual enzyme activities and “protective protein” among these different phenotypes.
The diurnal change in endogenous plasma triglyceride lipase (TGL) activity has not yet been studied in detail together with lipid-apoprotein profiles in man. Therefore, this study was conducted to observe the fluctuations from morning to night in the TGL activity including lipoprotein lipase (LPL) and hepatic lipase (HL) activities in 8 healthy subjects, first on a high-carbohydrate diet (carbohydrate, 360g; protein, 60g; fat, 20g) and then on an isocaloric high-fat diet (carbohydrate, 180g; protein, 60g; fat, 100g). Each diet was divided into 3 similar portions and given at 8:00, 12:00, and 18:00h. Blood sampling was done every 2h. Plasma glucose showed no definite change during the day of each test diet, while plasma insulin levels were much higher with the high-carbohydrate diet than with the high-fat one. Plasma triglyceride (TG) in chylomicron (Chyl) and very low density lipoprotein (VLDL) revealed a significantly greater increment with the high fat diet than with the high-carbohydrate diet. Levels of plasma apoproteins C-II, C-III, and E increased only with the high-fat diet. The diurnal endogenous plasma TGL activity as measured by a sensitive method was raised with both diets in parallel with the Chyl-VLDL-TG levels, and the elevated TGL activity was mostly due to the accelerated release of HL, and not to that of LPL. Unexpectedly no correlation existed between diurnal plasma TGL activity and insulin secretion. Interestingly, however, a remarkable positive correlation (r=0.744, p<0.01) was found between the diurnal sum of plasma TGL activity changes and the diurnal sum of plasma Chyl-VLDL-TG changes. Thus, the diurnal TG increment in the carrier lipoproteins induced by meals seems to accelerate the release of TGL, and therefore HL, from the hepatic capillaries into circulation, independent of insulin secretion.
Serum lipid peroxide level and vitamin B2 status of 90 pregnant (27 in the 1st trimester, 23 in the 2nd trimester, and 40 in the 3rd trimester) and 33 healthy non-pregnant women were examined. Serum lipid peroxide level of the pregnant women increased as pregnancy progressed, and the level at the 3rd trimester was significantly higher than that of the non-pregnant women. Thirty pregnant women had an increase in serum lipid peroxide level and 10 of them had marginal riboflavin deficiency as judged by their erythrocyte glutathione reductase (EGR) activity coefficients. The number of pregnant women having both increased serum lipid peroxide level and marginal riboflavin deficiency increased with the advancement of pregnancy (0 in the 1st trimester, 1 in the 2nd trimester, and 9 in the 3rd trimester). A weak positive correlation between serum lipid peroxide level and EGR activity coefficient of the pregnant women was found in the 3rd trimester. These results indicate that the increase in serum lipid peroxide level during pregnancy, particularly at the late stage, may be at least partly attributable to marginal riboflavin deficiency.