Biomedical subjects

Koichi Endo

Publications and source records attributed to Koichi Endo.

6 recordsLinked to original sources

PubMed2003

Frontal lobe dysfunction caused by multiple lacunar infarction in community-dwelling elderly subjects.

We examined the factors that influence frontal lobe function among 119 community-dwelling elderly subjects, based on magnetic resonance imaging (MRI) and clinical findings. We interviewed the subjects, and conducted a neurological examination, electrocardiogram, blood test, brain MRI examination, and cognitive function tests. The modified Stroop test and a personal computer version of the Wisconsin Card Sorting Test (WCST) were used to evaluate frontal lobe function. The subjects with impaired frontal lobe function defined by the modified Stroop test were significantly older, had more lacunar infarcts, and had lower HDL cholesterol values based on a logistic regression model. Among the aged who appear apparently normal, multiple lacunar infarcts are the cause of latent frontal lobe dysfunction.

Age Factors↗

PubMed2003

In subtotally nephrectomized rats 22-oxacalcitriol suppresses parathyroid hormone with less risk of cardiovascular calcification or deterioration of residual renal function than 1,25(OH)2 vitamin D3.

BACKGROUND: Although it effectively suppresses parathyroid hormone (PTH) secretion, vitamin D [1,25(OH)(2)D(3)] therapy often causes tissue calcification over the long term. In patients on chronic dialysis, cardiovascular calcification is clearly linked to an unfavourable prognosis. In pre-dialysis patients, renal calcification of the kidney leads to the deterioration of renal function. METHODS: We compared the propensities of 22-oxacalcitriol (OCT), with lesser calcaemic action, and 1,25(OH)(2)D(3) for producing their potential side effects in rats: (i) metastatic calcification of heart and aorta, and (ii) renal dysfunction with nephrocalcinosis, using the same effective doses for hyperparathyroidism. OCT (1.25 and 6.25 micro g/kg) or 1,25(OH)(2)D(3) (0.125 and 0.625 micro g/kg) solutions were administered intravenously to subtotally nephrectomized (SNX) rats three times weekly for 2 weeks. RESULTS: Despite the suppression of PTH to comparable levels, the calcification of the hearts, aortas and kidneys in the 1,25(OH)(2)D(3)-treated group was significantly greater than in the OCT-treated group. Of interest was that, in the OCT (6.25 micro g/kg) group, the degree of calcification in hearts, aortas and kidneys were distinctly lower than those in the 1,25(OH)(2)D(3) (0.125 micro g/kg) group despite the comparable serum Ca x Pi products. Therefore, there may be different mechanisms behind the calcifications resulting from OCT and 1,25(OH)(2)D(3). Deterioration of renal function, tubular changes, and atypical hyperplasia of proximal tubules associated with calcification were more severe in the 1,25(OH)(2)D(3)-treated group than in the OCT-treated group. CONCLUSIONS: These results indicate that OCT may be an effective agent for the suppression of PTH with a lesser risk of cardiovascular calcification or deterioration of residual renal function.

Animals↗

PubMed2002

A comparison between daily and thrice-weekly i.v. administration of 1,25-dihydroxy-22-oxavitamin D(3) regarding suppression of parathyroid hormone secretion and calcaemic action in uraemic rats.

BACKGROUND: 1,25-Dihydroxy-22-oxavitamin D(3) (22-oxacalcitriol, OCT) is an analogue of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3), calcitriol) with less calcaemic activity, thus more suitable than 1,25(OH)(2)D(3) for the control of parathyroid hormone (PTH) secretion in chronic dialysis patients. As the low-calcaemic action of OCT has been mainly attributed to its short half-life in the blood stream, the number of doses per week is the key factor to effective OCT therapy toward suppression of PTH secretion and hypercalcaemia. Thus, we investigated a comparison between daily and thrice-weekly i.v. administration of OCT regarding suppression of PTH secretion and calcaemic action in 5/6 nephrectomized rats as a model for chronic renal failure. METHODS: Model rats of chronic renal failure were made by 5/6 nephrectomy. At 3 months after surgery, they were administered either vehicle or OCT intravenously, daily (0.125 or 0.625 microg/kg) or thrice-weekly (0.6 or 3.0 microg/kg) for 2 weeks. RESULTS: The data show that 0.625 microg/kg/day (=4.375 microg/kg/week) suppresses PTH secretion with significant increase in calcium levels at 24 h after the final administration, on the other hand, 3.0 microg/kg/ thrice-weekly (=9.0 microg/kg/week) suppresses PTH secretion, although moderate compared with 0.625 microg/kg/day, with a slight (not significant) increase in calcium. CONCLUSIONS: The current clinical mode of OCT therapy, i.v. thrice-weekly administration, is a practically recommendable protocol.

Animals↗

PubMed2002

A comparison between 1,25-dihydroxy-22-oxavitamin D(3) and 1,25-dihydroxyvitamin D(3) regarding suppression of parathyroid hormone secretion and calcaemic action.

BACKGROUND: Since Slatopolsky et al. (J Clin Invest 1984; 74: 2136-2143) reported the effect of active vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), on secondary hyperparathyroidism (2HPT) which accompanies chronic renal failure, there have been several studies of the therapeutic effects of 1,25(OH)(2)D(3) in this disease. Although parathyroid hormone (PTH) is suppressed by treatment with 1,25(OH)(2)D(3), long-term treatment with 1,25(OH)(2)D(3) tends to induce hypercalcaemia. Therefore, an analogue of 1,25(OH)(2)D(3), 1,25-dihydroxy-22-oxavitamin D(3) (22-oxacalcitriol, OCT) with less calcaemic activity, was developed for the treatment of 2HPT. METHODS: In order to clarify the differences between the effects of 1,25(OH)(2)D(3) and OCT on 2HPT associated with chronic renal failure, these compounds were administered by intermittent i.v. injection for 2 weeks in rats with mild to moderate uraemia. RESULTS: 1,25(OH)(2)D(3) markedly suppressed PTH levels, but increased serum calcium (Ca). OCT also markedly suppressed PTH levels, but induced only a slight increase in serum Ca. 1,25(OH)(2)D(3) caused a dose-dependent decrease in body weight, whereas OCT had no effect on body weight in uraemic rats. Based on those doses of OCT and 1,25(OH)(2)D(3), which resulted in a 60% suppression of PTH, and induced hypercalcaemia, we consider the relative ratios for efficacy and Ca-elevating activity between OCT and 1,25(OH)(2)D(3) to be 1 : 8 and 1 : 48, respectively. CONCLUSIONS: OCT suppressed PTH levels with a slight increase in serum Ca without changing the body weight in uraemic rats. This observation suggests that OCT might be a useful vitamin D analogue for 2HPT management in long-term clinical treatment.

Animals↗

PubMed2002

[A comparison between 1,25-dihydroxy-22-oxavitamin D3 and 1,25-dihydroxyvitamin D3 regarding suppression of parathyroid hormone secretion and calcemic action].

1alpha,25-dihydroxy-22-oxavitamin D(3) (maxacalcitol;OCT), a vitamin D analogue with reduced calcemic activity, showed potency 10 times greater than 1alpha,25 (OH) (2)D(3) in differentiation induction of HL-60 cells. In addition, OCT showed immunomodulating activity, anti-proliferative effect and a suppressive effect on PTH secretion in vitro. OCT suppressed the expression of PTH mRNA in both normal and nephrectomized rats, and up-regulated VDR in the parathyroid gland in uremic rats to the same degree as 1alpha,25 (OH) (2)D(3). The results of a comparison between OCT and 1alpha,25 (OH) (2)D(3) indicate that the dissociation between efficacy and side effects with OCT is greater than with 1alpha,25 (OH) (2)D(3) in uremic rats. In future, we expect that OCT would contribute a great deal to the dialysis field in clinical.

English Abstract↗

PubMed2002

[ED-71].

ED-71 is a potent analog of active vitamin D, 1,25 (OH) (2)D(3), bearing a hydroxypropoxy substituent at the 2beta-position. In ovariectomized rats, ED-71 prevented the reduction in bone mass and strength of lumber spine without causing hypercalcemia. From those results, it was suggested that ED-71 preferentially enhances bone formation with less effects on intestinal calcium absorption. In osteoporotic patients, oral daily administration of ED-71 (0.25, 0.5, 0.75 and 1.0 microg) for 6 months increased bone mineral density (BMD) at L(2-4) in a dose-dependent manner. ED-71 also exhibited a dose-depend suppression of urinary deoxypyridinoline with no significant reduction in serum osteocalcin. These results demonstrate that ED-71 can effectively increase bone mass without causing hypercalcemia, and suggest that ED-71 can be a promising candidate for the treatment of osteoporosis with prominent effect on bone formation.

English Abstract↗