Kazumi Fujimoto's research while affiliated with Wakayama Medical University and other places

Calcitonin, one of the calcium-regulating hormones, is known to have diverse biological effects including those on the gastrointestinal tract. In this organ, the hormone is reported to inhibit gastric acid secretion, gastric motility, and gastrin secretion and to stimulate release of somatostatin, thereby exerting antiulcer and antilesion effects on stress-induced as well as other types of experimental gastric ulcers or lesions. This fact prompted us to examine changes in serum calcitonin concentration during the development of stress-induced gastric lesions in rats. DA rats were constrained in a stress cage after a 24-h fast and then immersed in 24 degrees C water to the level of the xiphoid process for 2 or 5 h. Serum calcitonin concentrations in stressed rats were significantly lower than those in control rats. To investigate the mechanism of the decline in serum calcitonin level under stress in these rats, we conducted a time-course study of serum calcitonin concentration and ionized calcium level during water-immersion stress, lasting 2 h, and during 4 h following release from the stress. Water immersion caused a remarkable decrease in serum calcitonin concentration as early as at 30 min. After release from stress, serum calcitonin concentration gradually recovered. The ionized calcium level in the blood did not change significantly throughout the experimental period. Furthermore, to examine if the sympathetic nerve system was involved in the stress-induced change of serum calcitonin concentration, alpha- and beta-receptor antagonists were administered intraperitoneally before stress exposure. Administration of alpha-receptor antagonist at a low dose that did not have any effect on serum calcitonin concentration in a preliminary study, restored the decline of serum calcitonin level, whereas beta-receptor antagonist did not. These results suggest that stress-provoked decrease of serum calcitonin concentration may be mediated not by a change of ionized calcium level but by alteration of sympathetic nerve activity (particularly via the alpha-receptor).

Time-dependent changes of bone mass in ambulant chronic respiratory failure patients 60 or more years of age were compared between those on home oxygen therapy (HOT) and those still free of HOT (non-HOT). HOT (n = 31) showed initial PaO2 of slightly greater than 60 Torr and non-HOT (n = 32) had PaO2 moderately greater than 60 Torr (64.4 Torr vs 75.1 Torr). PaCO2 in HOT was significantly higher than that of non-HOT (44.8 Torr vs 40.0 Torr). There was no difference in pulmonary function test results. The whole bone mineral density (BMD) as adjusted by age and sex was significantly lower in the HOT group than that in the non-HOT. At endpoints of the follow-up period over 2 years or more, daily bone losses in the whole BMD, whole bone mineral content, and lumber BMD were significantly more accelerated in HOT compared with non-HOT. When the Wistar rats were pair-fed and their locomotion was limited, the animal group placed for 4 weeks under hypoxic air showed a reduction in BMD as compared with the control. We suggest that hypoxemia contributes to bone mass loss.

To investigate the mechanisms of osteopenia in diabetes mellitus induced experimentally in mice, we measured the bone mineral content, expressed as the bone mineral density per surface area (areal BMD), by dual energy X-ray absorptiometry; and we assessed the alkaline (ALP) and acid phosphatase (ACP) activities of the calvarial tissues, which are assumed to represent the functional activities of osteoblasts and osteoclasts, respectively. We found that at 8 weeks after the onset of streptozotocin-induced diabetes mellitus the areal BMD values of the total body, femurs, calvariae, and lumbar vertebrae in the diabetic group were smaller than those in the control group. As compared with the control group, the ALP/ACP activity ratio of the calvariae in the diabetic group had a tendency to be reduced at 4 weeks of diabetes when the calvarial ABMD was not different between the two groups; it was definitely reduced at 8 weeks. These results suggest that an imbalance of osteoblast and osteoclast activity might be one of the mechanisms of osteopenia in the diabetic mouse.

Since normal reference values change with age in some clinical parameters, we measured the plasma levels of 1,5-anhydroglucitol (AG), a new marker of glycemic control in diabetes mellitus, in healthy subjects and in rats. Our results showed a significantly negative correlation of the marker with age in humans and that the plasma AG levels of older rats were markedly lower than those of younger counterparts. This remarkable reduction of AG in the older rat group can be partially explained by our finding that aged animals excreted AG more rapidly in the urine than younger ones, besides a decrease in food intake. We therefore suggest that normal clinical reference values for plasma AG levels should be modified according to age.

We measured erythrocyte aldose reductase and sorbitol dehydrogenase activity in erythrocytes in healthy individuals aged from 16 to 91 years to determine the mechanism of age-dependent sorbitol accumulation. Erythrocyte aldose reductase activity increased significantly with age but ageing had no effect on sorbitol dehydrogenase activity. Age and the aldose reductase/sorbitol dehydrogenase ratio were positively correlated. These findings suggest that an increase in the ratio of aldose reductase to sorbitol dehydrogenase may contribute to the tissue accumulation of sorbitol in the elderly and may be a mechanism of a disease that is common in elderly individuals.