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T Tomiuga

Publications and source records attributed to T Tomiuga.

8 recordsLinked to original sources

[Interaction of warfarin and vitamin K2 on arterial thrombotic tendency using a rat aorta loop model].

Vitamin K2(K2), a therapeutic agent osteoporosis, is prohibited for patients with thrombosis who are receiving warfarin (WF). However, because some aged patients with thrombosis have osteoporosis, some patients treated with WF may be administered K2 concomitantly. We investigated here the interaction between K2 and WF on thrombosis in a rat aorta loop model. Administration of WF at 0.58, 0.82 and 1.16 mg/l in drinking water for 7 days decreased the thrombotic rate and increased the death rate, dose-dependently. Therefore in the following study, 0.80 mg/l of WF was used. After 2 days of WF-treatment, 1.5, 14 and 145 mg/kg of K2 was administered for 5 days. The blood coagulation time was markedly prolonged by WF treatment for 7 days and this effect was completely inhibited by all doses of K2. WF treatment significantly decreased the cumulative thrombotic rate for 5 days. Administration of 1.5 and 14 mg/kg of K2 did not influence the WF effect on thrombosis. The thrombotic rate in the 145 mg/kg K2 group was lower than that in the WF-control group, but similar to that in the WF-untreated group. These findings suggest that high dose of K2 reduces the effect of WF on thrombosis but does not enhance the occurrence of thrombosis more than that without WF treatment.

Animals

[Vitamin K2 (menatetrenone) treatment increased bone strength in rats given low-calcium diets].

Two experiments were carried out in 4-week-old rats. First, the effect of dietary calcium (Ca) content (0.05, 0.1, 0.2, 0.5 and 1.16%) on bone loss was assessed for 3 weeks. Dry weight of the femur showed a Ca-content-dependent decrease. Significant decrease in body weight and plasma Ca level was observed in the 0.05 and 0.1% Ca diet groups, but not in other groups. Second, the curative effect of V.K2 on bone strength was examined. After being fed a 0.2%-Ca diet for 3 weeks, rats were fed 0.2%- or 0.5%-Ca diets for the next 6 weeks with or without V.K2 treatment. At the beginning and after 3 and 6 weeks of treatment, femurs and lumbar vertebra (L3) were collected. In the 0.2%-Ca group, bone mineral density (BMD) and bone strength in the femur gradually increased, but were much lower than those in the intact group. In the 0.5%-Ca group, both parameters in the femur and L3 were rapidly increased. V.K2 treatment did not affect the BMD or bone strength in the femur at either point. However, the bone strength in L3 in the V.K2 group was higher than that in the 0.5%-Ca group at 3 weeks and in the 0.2%-Ca group at 6 weeks than that in the respective control group. These findings suggest that V.K2 has curative effect on bone strength in the vertebra.

Animals

Inhibitory effect of vitamin K2 (menatetrenone) on bone resorption in ovariectomized rats: a histomorphometric and dual energy X-ray absorptiometric study.

To clarify how vitamin K2 prevents bone loss in vivo, it was given to ovariectomized 20-week-old rats for 2 weeks. Bone mineral density (BMD) in the whole femur and in 7 specific portions (F1 to F7 from the proximal to the distal end) was determined by dual-energy X-ray absorptiometry, and histomorphometry was also performed in proximal tibial metaphysis. Ovariectomy (OVX) resulted in significant decreases in the BMD in the whole femur and the F1, F2, F6 and F7 portions. Histomorphometrical analysis of the tibia showed that the bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N) were decreased, while trabecular separation (Tb.Sp) and osteoclast number/bone surface (Oc.N/BS) were increased by OVX. The parameters for bone formation were not changed by OVX. These data indicate that the bone loss within 2 weeks is due to the enhancement of bone resorption. Vitamin K2 at 50 mg/kg inhibited the decrease in the BMD of the whole femur together with the F6 and F7 portions. Vitamin K2 also inhibited the decrease in Tb.N and the increases in Tb.Sp, Oc.N/BS and osteoclast surface/bone surface (Oc.S/BS) caused by OVX. These results suggest that vitamin K2 prevents bone loss through the inhibition of bone resorption and osteoclast formation in vivo.

Absorptiometry, Photon

[Automatic determination for bone morphometry using a computed image analyzer].

An image analyzer which combines a digitizer and a computer is widely employed in bone histomorphometrical evaluation. With this method, however, all regions of determination are traced manually so that considerable time is consumed when many preparations are measured. To resolve this problem, we have developed an automatic program for rapid and quantitative measurement of many bone histomorphometrical parameters using a computed color image analyzer. The bone volume (BV), tissue volume (TV), osteoid surface (OS), and the bone surface (BS) of rat tibia metaphysis were measured by this automatic method, and by the manual method using an image analyzer. The correlation coefficient between both methods in measuring BV/TV was 0.98 and in measuring OS/BS was 0.96. The reproducibility and accuracy of both methods for these parameters were similar. The time required for the automatic method was much shorter than that for the manual method. Various parameters of the tibial metaphysis, lumbar vertebral body, and femoral mid-diaphysis in ovariectomized rat (Fischer) measured by this method were in good agreement with values reported previously.

Animals

[Influence of vitamin D3 on inhibitory effect of vitamin K2 on bone loss in ovariectomized rats].

To evaluate whether the vitamin D3 level in the plasma influences the inhibitory effect of vitamin K2 on bone loss, vitamin K2 (25 mg/kg/day) was administered to ovariectomized (OVX) rats fed a diet containing vitamin D3 (V.D.(+)) or a diet deficient in vitamin D3 (V.D.(-)). After 3 months of treatment, the plasma 25-OH-vitamin D3 (25-OH-D3) level in the V.D(-)-sham group was about 1/3 of that in the V.D(+)-sham group. The plasma calcium level and alkaline phosphatase activity were also significantly lower in the V.D(-)-sham group than in the V.D(+)-sham group. In the V.D(+) group, the plasma 25-OH-D3 level in the vitamin K2 group was about 1.5 times higher than that in the OVX-control group. Ovariectomy resulted in a significant decrease in bone density, bone mineral content (BMC) and bone mineral density (BMD) of femurs in both the V.D(+) and V.D(-) groups. In the V.D(-) group, vitamin K2 had no marked effect on the bone loss. In the V.D(+) group, the bone density and BMD in the mid portion of the femur were significantly increased by vitamin K2 treatment. These findings suggest that the effect of vitamin K2 on bone loss is affected by the vitamin D3 level in the plasma.

Animals

Effects of menatetrenone on the decrease in calcium balance induced by vitamin K-deficient diet and sodium loading in rats.

The effects of menatetrenone (2-methyl-3-tetraprenyl-1,4-naphthoquinone, MK-4) on calcium balance were studied in male Sprague-Dawley rats. Experiment 1: Rats in metabolic cages that were fed a vitamin K-deficient diet and injected daily with latamoxef (100 mg/kg, i.p.) were either treated or untreated with MK-4 for 7 days. Daily food intake, urine volume and feces weight were determined, and calcium concentration in these samples was measured. Calcium balance was calculated as the difference between calcium intake and urinary and fecal calcium excretion. Cumulative calcium balance in the vitamin K-deficient group treated with latamoxef was lower than that in normal rats; this balance was significantly improved by MK-4 (1 and 10 mg/kg, s.c.) administered for 7 days. Experiment 2: Rats were fed a vitamin K-deficient diet containing 4.6% sodium chloride for 6 weeks. MK-4 was administered as a dietary supplement. Forty-eight-hour calcium balance, determined once a week, was significantly reduced compared with that of normal rats after 3 and 5 weeks; the balance was restored dose-dependently by MK-4 administration (1 and 10 mg/kg). Experiment 3: Rats were subjected to the same experimental conditions as experiment 2 for 6 weeks, and intestinal calcium transport was determined using an everted gut-sac technique. Calcium transport was reduced by the high sodium, vitamin K-deficient diet, and this reduction was restored by MK-4 administration (10 mg/kg). These results suggest that MK-4 improves the reduced calcium balance by increasing intestinal calcium absorption in these rats.

Alkaline Phosphatase