The vitamin-E derivative U-83836-E in the low-dose streptozocin- treated mouse: effects on diabetes development.

Low-dose streptozocin-treated (LDS) mice were administered an inhibitor of lipid peroxidation, U-83836-E (a derivative of vitamin E), in order to observe its ability to alter the onset of diabetes. Ten or 20 mg/kg body wt. per day of U-83836-E were given to mice for 7 days and they were killed after 21 days. Results revealed that there was a significant increase in glycaemia in treated groups up to day 14 after which no further increase was noticed. Superoxide dismutase (SOD) assay showed that: (1) the LDS treatment significantly reduces SOD activity when compared with untreated controls (P < 0.005); (2) U-83836-E increases SOD levels (when compared with untreated controls); and (3) U-83836-E counteracts LDS treatment, since SOD activity is significantly higher with respect to that found in LDS-controls (P < 0.05), and SOD levels were significantly higher with respect to that found in Group 2 animals (P < 0.05), but significantly lower with respect to those found in groups 3 and 4 (P < 0.005). Moreover, malondialdehyde (MDA), the end-product of lipoperoxidation, was found at much higher levels in LDS controls than in the other groups and the lowest values were found in U-83836-E controls and in normoglycaemic animals treated with both streptozocin and U-83836-E. Morphological observations demonstrated that islet beta cells were of normal appearance in normoglycaemic animals of the treated groups. In conclusion, the in vivo inhibition of lipid peroxidation by this compound produces a limited but significant prevention of the islet beta cell destruction.

Superoxide dismutase in the nonobese diabetic (NOD) mouse: a dynamic time-course study.

Superoxide dismutase (SOD) levels, thought to be the first cellular defence against free radicals, were studied in the nonobese diabetesprone (NOD-p) mouse, an animal model of type 1 diabetes in which about 100% of females and 20% of males become diabetic. Nonobese diabetes nonprone (NON-p) mice were used as controls. Animals were followed from 5th to 22nd week of life. Results show that SOD levels in female NOD-p mice are extremely low. In males, values are considerably higher than in females but still lower than values found in control mice. Moreover, SOD levels did not significantly change with age, degree of insulitis or level of diabetes. Islet beta cells in this strain, therefore, seem to be poorly protected against the negative effects of free radicals and this may predispose to diabetes. Furthermore, alterations of SOD may not be directly related to the development of the disease as the enzyme's activity is not further modified with age or the progression of diabetes.

An increase in superoxide dismutase counteracts islet vascular alterations in low-dose streptozocin-treated mice.

A decrease in superoxide dismutase (SOD), the first cellular defence against free radicals, occurs at about the same time as the activation of macrophages within the islets of low-dose streptozocin (LDS)-treated mice. Furthermore, a decrease in the total islet capillary area also has been shown to occur by 10 days after the first streptozocin (STZ) injection and this decline in capillary area is concomitant with the activation of macrophages as is the fall in SOD. Intracellular levels of SOD have been shown to increase after administration of acetyl-homocysteine-thiolactone (citiolone); therefore, the aim of the present study was to observe any relationship between the citiolone-induced increase in SOD levels and islet microvasculature area during LDS-induced diabetes. C57BL6/J male mice were pretreated with daily intramuscular injections of 50 mg citiolone/kg body wt. for 30 days and were then rendered diabetic with 45 mg STZ/kg body wt. given for 5 days; citiolone was given until the animals were killed (days 6, 11 and 18 after the first STZ injection). Further animals were used as non-diabetic and diabetic (STZ-only) controls. The results show that LDS-treated animals when given citiolone: (1) were generally normoglycaemic; (2) had SOD levels that were higher than those of STZ-only control animals; (3) had an islet capillary area that was larger than that of LDS-treated mice. Therefore, the administration of a free radical scavenger, namely citiolone, is able partly to counteract and delay the reduction of islet vascular area and oedema formation in LDS-treated mice.

Baldness and coronary heart disease risk factors.

The present report focuses on the association between baldness pattern and coronary heart disease risk factors in 872 male factory workers from southern Italy participating in an epidemiological study. Participants were divided according to presence or absence of baldness and baldness pattern. Participants with fronto-occipital baldness (male-type baldness) (n = 280) characterized by hair loss centered over the vertex with an m-shaped frontal-temporal recession had, on the average, higher serum cholesterol and blood pressure compared to participants with no baldness (n = 321) and/or participants with just frontal baldness (n = 273). For serum cholesterol, a significant interaction was detected between age and fronto-occipital baldness (i.e. the association between fronto-occipital baldness and elevated levels of serum cholesterol became weaker with age). No interaction was detectable between age and fronto-occipital baldness for blood pressure. The results of this cross-sectional study indicate that male-type pattern of baldness is associated with elevated CHD risk profile, and that this relation between age and serum cholesterol differs in younger compared to older men.

Correlates of high-density lipoprotein cholesterol in a sample of healthy workers.

METHODS: Correlates of high-density lipoprotein cholesterol are analyzed in a sample of 797 male workers in southern Italy participating in the Olivetti Heart Study. At the univariate level high-density lipoprotein cholesterol concentrations are positively related to alcohol consumption (r = 0.127; P less than or equal to 0.001) and sport activity (r = 0.074; P less than or equal to 0.05) and inversely related to body mass index (r = -0.160; P less than or equal to 0.001), serum triglycerides (r = -0.349; P less than or equal to 0.001), cigarette smoking (r = -0.227; P less than or equal to 0.001), and coffee consumption (r = -0.153; P less than or equal to 0.001). RESULTS: In the group as a whole, body mass index, alcohol consumption, cigarette smoking, and serum triglycerides remain significantly related to high-density lipoprotein cholesterol in the multivariate model, while the association with coffee intake and sport activity loses statistical significance. A significant negative interaction is reported between physical activity and cigarette smoking, and a positive significant linear trend between high-density lipoprotein cholesterol and sport activity is observed only in nonsmokers. CONCLUSION: These findings suggest that body mass index, alcohol consumption, cigarette smoking, serum triglycerides, and sport activity are important correlates of high-density lipoprotein cholesterol but that the positive significant association between sport activity and high-density lipoprotein cholesterol is absent in smokers.

Superoxide dismutase in low-dose-streptozocin-treated mice. A dynamic time-course study.

Superoxide dismutase (SOD) is a free-radical scavenger present in B cells. It is thought to be responsible for protection against the autoimmune processes that characterize type I diabetes mellitus. Streptozocin (STZ) has been used as a low-dose treatment (LDS) to induce diabetes in animal models. The aim of this study was to follow the islet SOD levels in a day-to-day study after an LDS treatment with STZ, 40 mg/kg body wt/d in C57BL6/J mice. Results reveal a progressive SOD decrease in pancreatic islets with increasing periods from the LDS treatment. This SOD decrease starts from the end of the STZ administration (d 5). In addition, it was noticed that glycemia starts to rise when SOD values have already reached their lowest levels. This indicates that a reduction of free-radical defense is a prerequisite for further cellular injuries. Furthermore, a difference was noticed between males and females: only 40% of female mice underwent a SOD decrement and an increase in glycemia, indicating an androgen-dependent mechanism.

Serum selenium and coronary heart disease risk factors in southern Italian men.

The association between serum selenium concentration and a number of coronary heart disease risk factors is studied in 364 males from southern Italy participating in the Olivetti Heart Study. Selenium correlates positively and significantly with serum cholesterol (r = 0.120; P = 0.022), and this positive association persists after adjustment for age and body mass index. Selenium levels in heavy smokers are lower than both light smokers and current non-smokers, but these differences do not reach statistical significance. Selenium is not significantly associated with any of the other CHD risk factors (e.g., triglycerides, HDL cholesterol, blood pressure, age, and body mass index). It is hypothesized that the association between selenium and serum cholesterol reported in this and previous studies could be due to dietary interrelationships between selenium intake and foods that affect serum cholesterol concentrations.

Early macrophage infiltration in mice treated with low-dose streptozocin decreases islet superoxide dismutase levels: prevention by silica pretreatment.

It has been hypothesized that streptozocin (STZ) given in low doses for 5 consecutive days produces diabetes by induction of peroxidation phenomena similar to those induced by free radicals. Moreover, it has been demonstrated that macrophages are among the first to invade the pancreatic parenchyma and destroy islet B cells supposedly by the release of interleukin-1 that induces free radical formation. Superoxide dismutase (SOD) is a free radical scavenger present in cells, and islet B cells are known to have extremely low levels of this enzyme. Therefore, our aim was to observe SOD activity concomitantly with the appearance of intra-islet macrophages, in early diabetes induced by low-dose streptozocin (LDS). Silica-pretreated mice showed SOD values which were comparable to those found in control animals. In LDS-only-treated mice we found that SOD levels were decreased even after only 4 days from the last STZ injection and that it is at this time that the first 'recruited' macrophages appear in the islets. Moreover, the SOD levels found at this early stage (animals were still normoglycaemic and therefore not as yet diabetic) were similar to levels found by us in a previous work, in prediabetic Bio Breeding rats, thereby ascribing a crucial factor to the lowering of SOD levels even in LDS-induced diabetes.

Superoxide dismutase activity in the BB rat: a dynamic time-course study.

Diabetes produced spontaneously in the BB rat is similar to that observed in multiple low dose streptozocin-induced diabetes, both being characterized histologically by a lympho-monocytic infiltrate in the pancreatic islets (insulitis). Recent studies indicated that streptozocin acts through peroxidative patterns sensitive to superoxide dismutase (SOD) activity. We therefore conducted a time-course study to evaluate if SOD activity in the islets of Langerhans is related to the onset of diabetes in BB rats with varying degree of diabetes. It was found that SOD activity does not change with age nor with the onset of diabetes. However SOD activity in the islets of BB rats was significantly lower than in the control Wistars. This lower SOD activity may be a proneness factor that favors the development of the diabetic syndrome.

Influence of acetyl homocysteine thiolactone on erythrocyte superoxide dismutase activity.

The administration of 8 mg of acetylhomocysteinethiolactone/kg body wt determines a significant (P less than 0.001) increase in rat erythrocyte superoxide dismutase activity.

Acetyl-homocysteine-thiolactone-induced increase of superoxide dismutase counteracts the effect of subdiabetogenic doses of streptozocin.

Acetyl-homocysteine-thiolactone (CYT) is an organic thio compound that exerts free radical scavenger activity and increases superoxide dismutase (SOD) activity. Administration of 32 mg CYT/kg body wt/day/30 days in rats increased SOD activity in erythrocytes by 126%, and in pancreatic islets by 202%. Treatment affected only the Cu-Zn fraction of the enzyme. Transmission electron microscope observations showed that the damage to the pancreatic beta cells induced by single or multiple subdiabetogenic doses of streptozocin (STZ) (45 mg/kg body wt) was attenuated in animals treated with CYT. This protective effect was not observed with 65 mg of STZ. The experimental results seem to support the hypothesis that pancreatic beta cells are particularly vulnerable to the effect of oxygen radicals and that the cytotoxic effect of STZ is related to free radical-induced peroxidation.

Superoxide dismutase in the central nervous system of Torpedo marmorata.

In the central nervous system of Torpedo marmorata lipofuscin accumulates electively in the electric lobes. It has been found that the electric lobes have significantly lower superoxide dismutase activity than other areas of the central nervous system in animals of various ages and weights. These observations indicate that the lipoperoxidation action of the superoxide radicals or of their derived free radicals, due to superoxide dismutase deficit in these areas, might be related to lipofuscin accumulation.

[In vivo effects of rapid glycemic variations on HbA1c]. / Effetti in vivo di rapide variazioni glicemiche sull'HbA1c.

The percent of variations of glycosylated haemoglobin before and after rapid glycemic increases inducted in diabetics and healthy subjects are not significant (p greater than 0,05). The same results were obtained using both the chromatographic method on Bio-Rex 70 microcolumns and the colorimetric method with 2-thiobarbituric acid. The usefulness of HbA1c as a parameter in controlling the glycemic equilibrium is confirmed.