Iodine deficiency affects all stages of life, and impaired mental function is five times as common as cretinism among populations living in iodine-deficient areas. The possibility that this could be due to an altered nutrient supply to the brain has been tested in albino rats chronically fed an iodine-deficient diet. Transport of [14C]-labelled nutrients across the blood-brain barrier (BBB) was determined in situ by the brain uptake-index (BUI) method. Feeding a low-iodine test diet (LIT) (0.0228μgI/g) to weanling Wistar/NIN rats for a short term (8 weeks) had only a modest effect on their tyroid status and no effect at all on their body or brain weight or their BBB transport of 2-deoxy-D-glucose (2-DG) as compared to control rats fed either the LIT diet+KI(-3μg I/g diet) or a locally formulated control diet of similar composition (-3μgI/g diet). On the other hand, long-term (16 weeks) dietary iodine deficiency in four different strains of rats produced a moderate hypothyroidism and significantly (p<0.05) increased transport of 2-DG across the BBB, in association with a significant decrease in their body weight but not in their brain weight. Transport of Leu, Tyr, and sucrose (the background marker) across the BBB was, however, not altered. Essentially similar observations were made in the four different strains of rats. The increased BBB transport of 2-DG in rats subjected to long-term dietary iodine deficiency probably represents an adaptive mechanism to maintain a normal glucose supply to the brain in the face of hypothyroidism.
Cold stress is known to have several physical consequences in humans, and the response to cold stress may be altered with aging, reflecting impairment of stress adaptation in the aged. However, cold stress-induced alteration in systemic antioxidant capacity has not been fully elucidated in senescent animal models including the senescence-accelerated mouse (SAM). In this study, we examined the effects of whole body cold stress, by immersion in cold water, on the content of both glutathione (GSH) and oxidized GSH (GSSG) in two strains of mice, SAMR1/Gtk (senescence-resistant strain) and SAMP2/Gtk (senescence-prone strain), of 6 (young) and 16 (aged) months of age. In liver and blood, the reduction in GSH, and the increase in GSSG content was considerable in aged SAMP2/Gtk. A similar perturbation of GSH metabolism was found in aged SAMR1/Gtk, but not in young SAMR1/Gtk after cold exposure. The altered metabolism of GSH caused by cold exposure was even found in the young SAMP2/Gtk mice. These results indicate the acute cold stress causes a significant decrease in the GSH level and perturbs GSH metabolism in several visceral organs and that the effect of cold stress on GSH metabolism may be further modulated by senescence.
We previously found that mazindol reduces food efficiency [=increase in body weight (g) per day/food intake (g) per day] in rats (Nagai et al., J Obesity Weight Regul., 4, 33-49, 1985). In order to elucidate the action of mazindol with respect to food efficiency, the effects of its administration on the elevation of the blood glucose concentration induced by Intracranial injection of 2-deoxy-D-glucose (2DG) into intact rats, or by the imposition of an oral glucose load in intact and diabetic rats, were examined. We observed that peripheral, but not central, administration of mazindol inhibited the hyperglycemia elicited by 2DG injection and enhanced glucose tolerance following an oral glucose load in diabetic rats, but not intact animals. These findings suggest that peripheral administration of mazindol reduces the blood glucose concentration when it is elevated. Therefore, it is possible that the reductive effect of mazindol on food efficiency might be induced by the enhancement of glucose uptake into cells of tissues such as skeletal muscle, since our previous work suggested that mazindol increases glucose uptake into skeletal muscle cells (Nagai et al., Eur. J. Pharmacol., 260, 29-37, 1994),
To evaluate oxidant stress and antioxidant activity in cases of myocardial infarction (MI) with and without diabetes mellitus (DM), erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities together with reduced glutathione (GSH) and plasma lipid peroxides (LPO) were estimated in 15 cases of MI without DM, 15 cases of MI with insulin-dependent DM (MI-IDDM), and 14 cases of MI with non-insulin-dependent DM (MI-NIDDM), as well as in 10 normal subjects as controls. SOD activity was significantly lower in both MI-IDDM and MI-NIDDM groups than in the controls. GPx activity was lower in the three MI groups than in the controls. GSH level was significantly lower in the two DM groups than in the controls. GSH level was significantly lower in MI-NIDDM than in MI-IDDM. LPO were significantly higher in the three MI groups than in the controls. LPO were significantly higher in the MI-NIDDM group than in the MI group (p<0.05), Moreover, a significant negative correlation was detected between the plasma LPO level and erythroctye GPx level (r=0.53) and also between the plasma LPO level and the GSH level (r=0.50). These results suggest that oxidative injury in cases of MI results not only from increased free radical production but also from impaired antioxidant defense mechanisms and that the oxidant injury is intensified in cases with DM. Exogenous antioxidants such as vitamins A and E, as well as selenium, may be useful for therapeutic management of these patients.
To determine the body iron status of young women, we screened female university students (n=910: 19-22 years old) in Japan for anemia. The incidence of marginal iron deficiency and iron-deficient anemia were 41.9% and 6.5%, respectively. So, we investigated changes in body iron status across the menstrual cycle in the marginally iron-deficient young women. Further, heart rate and unspecific symptoms were examined concurrently. Forty-three subjects (19-22 years old) were classified by their body iron status into three groups: iron-deficient anemia (hemoglobin, Hb<12g/dl; serum ferritin, SF<17ng/ml), marginal iron deficiency (Hb≥12g/dl, SF<17ng/ml), and adequate iron status (Hb≥12g/dl, SF≥17ng/ml). The marginally iron-deficient group showed a significant decrease in the concentration of Hb and ferritin in serum and an increased resting heart rate level during the luteal phase compared with those parameters for the follicular phase. These changes were observed only in the marginally deficient group. In this group, moreover, unspecific psychological symptoms were more frequently observed than in the other two groups, and these symptoms appeared more frequently during the luteal phase than during the follicular phase. The present study suggests that the decrease in body iron status and the increase in heart rate and unspecific symptoms during the luteal phase were associated with marginal iron deficiency in these young women.
To identify a mitochondrial genotype associated with longevity, we analyzed the entire coding regions of mitochondrial DNA (mtDNA) from 11 centenarians. A C-to-A transversion at nucleotide position (np) 5178 within the ND2 gene, causing a Leu-to-Met replacement; a C-to-T transition at np 8414 within the ATP8 gene, causing a Leu-to-Phe replacement; and a G-to-A transition at np 3010 within the 16S rRNA gene were more frequently observed in the centenarians than in 43 controls. Among these variations, we focused on Mt5178A and screened 37 centenarians and 252 healthy blood donors. The frequency of MtS178A was significantly higher in the centenarians (62%) than in the blood donors (45%). To evaluate the effect of mtDNA variations on the occurrence of diseases, we analyzed the frequencies of Mt5178A and Mt5178C in 338 randomly selected patients. The age distribution of the patients indicated that the frequency of Mt5178C was almost the same as that of Mt5178A among the young patients, whereas the frequency of Mt5178C increased more markedly than that of Mt5178A among old patients. The difference in the frequencies between Mt5178A and Mt5178C was less marked in old male patients than in old female ones; the protective effect of Mt5178A against occurrence of adult-onset diseases may be weaker in males than in females. The ratio of Mt5178 A/C was significantly lower in the old patients than in both the centenarians and the healthy controls. These results suggest that to carry an mtDNA genotype predisposing resistance to adult-onset diseases is one of the genetic factors for longevity.