Impaired blood rheology and elevated remnant-like lipoprotein particle cholesterol in hypercholesterolaemic subjects.

Blood rheology, fasting serum concentrations of remnant-like lipoprotein particle cholesterol (RLP-C) and concentrations of other lipids were compared in 23 hypercholesterolaemic and 69 normocholesterolaemic subjects, and the relationship between red blood cell (RBC) deformability and RLP-C concentrations were studied in a different set of six hypercholesterolaemic and six normocholesterolaemic subjects. Passage time of whole blood and concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and RLP-C were significantly higher in hypercholesterolaemic than in normocholesterolaemic subjects. Passage time of whole blood correlated positively with TC, TG, LDL-C and RLP-C and negatively with high-density lipoprotein cholesterol. Furthermore, the passage time of 10% haematocrit-adjusted RBCs in phosphate-buffered saline, which reflects RBC deformability, correlated positively with the passage time of whole blood and RLP-C. Thus, hypercholesterolaemic subjects had impaired blood rheology and elevated RLP-C concentrations, which may be associated with the pathophysiology of atherosclerosis in hypercholesterolaemic subjects. Impaired RBC deformability may contribute to impaired blood rheology associated with elevated RLP-C in hypercholesterolaemic subjects.

Effect of resistance exercise training on bone formation and resorption in young male subjects assessed by biomarkers of bone metabolism.

We studied the effects of high intensity resistance exercise training on bone metabolism in 17 young adult Oriental males (23-31 years) by measuring sensitive biomarkers of bone formation and resorption. The subjects were assigned to a training group and a sedentary group. The training group followed a weight training program three times per week for 4 months. In the training group, serum osteocalcin concentration and serum bone-specific alkaline phosphatase activity were significantly increased within the first month after the beginning of resistance exercise training, and the elevated levels remained throughout the training period, while there was no significant change in plasma procollagen type-I C-terminal concentration. Urinary deoxypyridinoline excretion was transiently suppressed and returned to the initial value but was never stimulated during the 4 months. These results suggest that the resistance exercise training enhanced bone formation without prior bone resorption. In the sedentary group, there was no significant difference in bone metabolic markers except plasma procollagen type-I C-terminal, which continuously decreased during the experimental period. There were no significant changes in total and regional bone mineral density in either group. In conclusion, (1) resistance exercise training increased markers of bone formation, while it transiently suppressed a marker of bone resorption, and (2) such adaptive changes of bone metabolism to resistance exercise training occurred during the early period of the training, before changes in bone density were observable through densitometry.

Paradoxical adaptation of mature radius to unilateral use in tennis playing.

The positive effects of physical activity on human bone mass have been well documented in many cross-sectional studies comparing athletes with sedentary controls as well as in longitudinal follow-up. By applying peripheral quantitative computed tomography (pQCT), which has the advantage of measuring volumetric bone mineral density (BMD) and the ability to distinguish among trabecular and cortical components, it was demonstrated that cortical BMD of the dominant arm was not greater than that of the nondominant arm. Cortical drift toward the periosteal direction and an increase in cortical thickness resulted in an improvement of mechanical characteristics of the playing arm's midradius. An improvement in the mechanical properties of young adult bone in response to long-term exercise was therefore related to geometric adaptation, but not to an increase in BMD. The manner in which the recruitment and function of bone cells are coordinated differs between the growing and the nongrowing skeleton. In the former, modeling is the dominant mode, and in the latter it is remodeling. In the present study, the side-to-side difference of 92 middle-aged female tennis players who initiated training after bone had matured was analyzed by pQCT. The side-to-side difference detected suggested a paradoxical adaptation of the mature radius to unilateral use during tennis playing, and that tennis playing after bone had matured did not stimulate cortical drift in the periosteal direction, unlike that seen in young subjects. Unexpectedly, the cross-sectional areas (periosteal and endocortical area) of the radius were smaller in the dominant arm than in the nondominant arm in the middle-aged female players. The findings suggest that unilateral use of the arm after the third decade of life suppresses age-related changes in bone geometry.

Sulfated colominic acid: an antiviral agent that inhibits the human immunodeficiency virus type 1 in vitro.

Colominic acid is a homopolymer of N-acetylneuraminic acid (NANA), which has an alpha-2,8 ketosidic linkage between its polymer units. In this study, colominic acids were sulfated under different conditions and their antiviral activities against human immunodeficiency virus type 1 (HIV-1) were examined. Sulfated colominic acids, containing 6-12% sulfur, blocked the expression of HIV-1 antigen in MT-4 cells or C8166 cells following exposure to MOLT-4/HTLV-IIIB or HIV-1[GUN-1]. The compounds inhibited syncytium formation upon co-cultivation of MOLT-4 cells (clone 8) with MOLT-4/HTLV-IIIB cells and abolished the production of HIV-1 p24 antigen in culture medium of peripheral blood lymphocytes (PBLs). HIV-1 reverse transcriptase (RT) activity was not directly affected by the drugs. The compounds did not prolong activated partial thromboplastin time (APTT) at 10 and 1.0 microgram/ml, suggesting that they may not have appreciable side effects in vivo. These agents were still able to block the expression of HIV-1 antigen even when the cells were infected with HIV-1 in RPMI-1640 medium containing high percentages of fetal calf serum (FCS). These properties may be therapeutically advantageous if these compounds were considered for possible clinical use.

Tomographical description of tennis-loaded radius: reciprocal relation between bone size and volumetric BMD.

Effects of long-term tennis loading on volumetric bone mineral density (vBMD) and geometric properties of playing-arm radius were examined. Paired forearms of 16 tennis players (10 women) and 12 healthy controls (7 women), aged 18-24 yr, were scanned at mid and distal site by using peripheral quantitative computerized tomography. Tomographic data at midradius showed that tennis playing led to a slight decrease in cortical vBMD (-0.8% vs. nonplaying arm, P < 0. 05) and increase both in periosteal and endocoritcal bone area (+15. 2% for periosteal bone, P < 0.001; and +18.8% for endocortical bone, P < 0.001). These data suggest that, together with an increase in cortical thickness (+6.4%, P < 0.01), cortical drift toward periosteal direction resulted in improvement of mechanical characteristics of the playing-arm midradius. Enlargement of periosteal bone area was also observed at distal radius (+6.8%, P < 0.01), and the relative side-to-side difference in periosteal bone area was inversely related to that in trabecular vBMD (r = -0.53, P < 0.05). We conclude that an improvement of mechanical properties of young adult bone in response to long-term exercise is related to geometric adaptation but less to changes in vBMD.

Interaction of the effects between vitamin D receptor polymorphism and exercise training on bone metabolism.

Bone metabolism is strongly influenced by heredity and environmental factors. To investigate interaction of the effects between vitamin D receptor polymorphism by Fok I and resistance exercise training on bone metabolism, young male subjects with FF genotype (F, n = 10) and Ff or ff genotypes (f, n = 10) followed 1 mo of weight training, and changes in bone metabolism were compared. An additional 14 subjects served as a sedentary control. Biomarkers of bone formation, bone-specific alkaline phosphatase, and osteocalcin were significantly increased by training in both F and f groups. 1, 25-Dihydroxyvitamin D(3), known to upregulate bone formation, was also increased by the training in the f but not in the F group. Bone resorption assessed by cross-linked NH(2)-terminal telopeptide of type I collagen was significantly suppressed by the training, and the decrease in F was greater and longer lasting than that in f group. In conclusion, stimulation of bone formation and suppression of bone resorption occurred within 1 mo in young men. Despite a significant increase in 1,25-dihydroxyvitamin D(3) in the f group but not in the F group, the response of bone metabolism to the training in the F was similar to or greater than that in f group, suggesting a functional difference between vitamin D receptor genotypes f and F.

Phosphotungstate shows a heparin-like anticoagulant effect but inhibits heparin.

We examined the anticoagulant effects of phosphotungstate (PTA). PTA inhibited factors IIa and Xa activity only in the presence of antithrombin III (ATIII). The inhibitory effect of PTA on IIa was much smaller than that on Xa. When PTA was added to heparin (Hep), the inhibitory effect of Hep on IIa was reduced. As a result of charge interaction, PTA showed an inhibitory effect on anion transport activity of the erythrocyte, a potent salting-in effect and a metachromatic reaction on toluidine blue (TolB). Silicotungstate (STA) showed almost the same results as PTA. These effects of PTA and STA were not replaced by their constituents, tungstate, silicate and phosphate, but may arise from their high anionic valency.

Phosphotungstate as a useful eluent for antithrombin III purification by heparin-agarose affinity chromatography.

We have recently found that phosphotungstate (PTA) has a heparin-like anticoagulant effect. In the present paper, we studied whether PTA is useful as an eluent of antithrombin III (ATIII) on heparin-Sepharose affinity chromatography. Human ATIII adsorbed on the heparin-Sepharose gel was eluted with NaCl buffer at the NaCl level of 1M. Whereas, PTA could elute ATIII at the level of less than 1mM and thus obtained ATIII fraction contained less impurities than such a fraction eluted with NaCl. Residual PTA in the eluate was easily decomposed by alkalization, being convenient for subsequent studies.

[Relationship between dietary life style in youth and osteoporosis].

The relationship between the dietary life style and osteoporosis was examined by comparing 71 osteoporotic women [age--65.5 +/- 8.9 (mean +/- SD)] with 76 women age-matched as controls. All subjects lived in and around Tsukuba City. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry. The frequencies of drinking milk and eating meat, fish, or potatoes, etc. both in their youth (about 18-25 years old) and at the present were investigated. The results were as follows: 1) The frequency of having unbalanced diets in their youth was significantly higher in osteoporotic patients than in controls. 2) During their youth, osteoporotic patients had significantly lower frequency of drinking milk, and significantly higher frequency of eating meat, dried fish or eggs, compared with controls. 3) High milk-consumers during their youth (milk-drinking: > or = 3 times per week) were significantly less frequent in osteoporotic patients than that in controls. 4) In the controls, the frequencies of drinking milk and eating meat during their youth were significantly positively correlated with lumbar BMD. The frequency of eating potatoes was significantly negatively correlated with the BMD in controls. 5) No strong relationships between present dietary life and osteoporosis or BMD were found. These findings suggest that drinking milk in their youth may influence BMD and associate with osteoporosis in women.

[Studies on circulating interleukin-6 and thyroid functions in acute myocardial infarction].

The euthyroid sick syndrome is reported to exist in acute myocardial infarction(AMI). Previous reports showed serum levels of triiodothyronine(T3) are low and thyroid stimulating hormone(TSH) is normal or subnormal levels in patients with AMI. However, the mechanism of altered thyroid hormone metabolism is unknown. Interleukin-6(IL-6) is reported to be a key role in the pathogenesis of AMI and euthyroid sick syndrome. We measured circulating TSH, free T3(FT3), free thyroxine (FT4), IL-6, soluble IL-6 receptor, soluble transducing 130-kD glycoprotein, atrial natriuretic peptide(ANP) and brain natriuretic peptide in 25 patients and 32 healthy subjects. Circulating FT3 levels in patients with AMI became lower than in control group(p < 0.05). IL-6 levels were significantly(p < 0.05) higher than those of healthy subjects. The peak levels of IL-6 was 30.5 +/- 46.9 pg/ml at 25-27 hours(the first peak) and 64.4 +/- 24.6 pg/ml at 70-72 hours(the second peak). FT3 was negatively related to IL-6(p < 0.05) and hANP(p < 0.05) in patients with AMI. These results indicate that the lower levels of FT3 show the greater severity of AMI. We conclude that euthyroid sick syndrome occurs in patients with AMI and euthyroid sick syndrome may regulated by IL-6 through suppressed of thyroid function.

[A trial of setting of the reference intervals of thrombin antithrombin III complex and fibrin.fibrinogen degradation products in pregnant women].

Activity of coagulation and fibrinolysis during pregnancy differed greatly from that during a nonpregnant period. We examined the reference intervals by mean +/- 2 standard deviations for thrombin antithrombin III complex (TAT), total FDP (T-FDP), FDP-E, D-dimer before and after delivery. The reference intervals obtained were as follows: TAT (micrograms/l): 1.0-4.8 for 1st trimester, 2.0-10.2 for 2nd trimester, 2.8-14.2 for 3rd trimester, 2.6-16.3 for full term pregnancy, 0-10.5 for post partum. T-FDP (micrograms/ml): 1.5-4.2 for 1st trimester, 1.8-5.6 for 2nd trimester, 1.9-8.5 for 3rd trimester, 2.9-9.7 for full term pregnancy, 2.4-9.0 for post partum. FDP-E(ng/ml): 26.4-98.0 for 1st trimester, 42.4-176.7 for 2nd trimester, 53.1-222.5 for 3rd trimester, 82.4-297.9 for full term pregnancy, 56.9-240.6 for post partum. D-dimer (micrograms/ml): 0.2-2.0 for 1st trimester, 0.6-3.8 for 2nd trimester, 0.6-4.3 for 3rd trimester, 0.7-6.8 for full term pregnancy, 0.6-5.7 for post partum. Further studies are needed to determine the borderline values to determine the clinical abnormality, with a comparison of the reference intervals with the pathologic laboratory data.

[Newly developed method by the use of factor Y assay for the detection of the lupus anticoagulant].

A New method for the detection of lupus anticoagulant was developed. Plasma factor V activities using tissue thromboplastin (simplastin auto-SA) and partial thromboplastin (platelin excel LS-LS) were measured simultaneously. Furthermore, the ratio of the two activities was calculated (SA/LS ratio) as a marker of lupus anticoagulant. The normal range of SA/LS ratio was 0.79-1.39 (mean +/- 3SD). The high SA/LS ratios were detected in all of 15 patients with positive lupus anticoagulant, in 3 (5.8%) of 52 SLE patients with normal activated partial thromboplastin time, in 2 (28.7%) of 7 patients with hemophilia, in 1 (33.3%) of 3 patients with factor VIII inhibitor and in 4 (3.3%) of 122 patients with various diseases, respectively. All of 15 patients with liver dysfunction, 54 patients under warfarin treatment and 8 patients under heparin treatment had normal SA/LS ratio.

[A case of iron and aluminum related osteomalacia in a long-term hemodialysis patient].

A 32-year-old woman undergoing hemodialysis for 12 years was referred because of systemic bone pain and pathological fracture of ribs and right tibia. Her serum ferritin was 4800 ng/ml, liver CT level was extremely high and skeletal scintigram by 99 m-Tc-MDP revealed high activity of soft tissue. Her serum aluminum was elevated more than 20 micrograms/dl by deferoxamine infusion test. Osteomalacia and positive staining of both aluminum and iron was observed by bone biopsy examination. After treatment with deferoxamine as a chelating agent of iron and aluminum, bone pain was relieved and second bone biopsy specimen revealed improvement of osteomalacia. But serum aluminum was slightly reduced and serum ferritin level and liver CT level were unchanged.

[Osteoporosis in young people].

Osteoporosis in young people is divided into idiopathic juvenile osteoporosis and secondary osteoporosis. Idiopathic juvenile osteoporosis is a rare, self-limited disease characterized by its recover after 3 or 4 years from the incidence. In severe type of idiopathic juvenile osteoporosis, the deformity of spine and extremities due to numerous vertebral and metaphyseal fractures and frequent long bone fractures makes a limitation of daily activities. On the treatment it is important to take care not to make deformity. Idiopathic juvenile osteoporosis is very rare in Japan and unknown cause, is necessary to make more researches in its cause. Many disease are known to cause secondary osteoporosis. And the patients number of secondary osteoporosis are much more than idiopathic juvenile osteoporosis. In secondary osteoporosis, of cause, it is most important to treat the original disease. The treatment of secondary osteoporosis is made a great difference by patient condition. Osteoporosis in young people makes deformity of spine and extremities and height loss, and influences the growth and development for serious disorder. It is necessary for treatment of these young people to take care to make the disorder to minimum.

Blood rheology and the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio in dyslipidaemic and normolipidaemic subjects.

The association between blood rheology and the ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) was investigated in 142 dyslipidaemic and 253 normolipidaemic subjects. Blood rheology was examined by the microchannel method and fasting serum concentrations of LDL-C, triglyceride and HDL-C were measured. Passage time of whole blood correlated positively with LDL-C concentration, triglyceride concentration and LDL-C/HDL-C ratio, and negatively with HDL-C concentration. Passage time of whole blood was significantly higher in dyslipidaemic and normolipidaemic subjects with LDL-C/HDL-C ratio > 2.0 than in those with ratio < 1.5. Thus, dyslipidaemic subjects had impaired blood rheology, elevated LDL-C and triglyceride concentrations and elevated LDL-C/HDL-C ratio, and reduced HDL-C concentrations. Dyslipidaemic and normolipidaemic subjects with a more elevated LDL-C/HDL-C ratio had greater blood rheology impairment than those with a less elevated ratio. These data suggest that an elevated LDL-C/HDL-C ratio may be helpful in predicting impaired blood rheology.

Occlusal function associated with body composition in premenopausal Japanese women.

OBJECTIVES: The goal of the present study was to investigate the relationship between occlusal function and body composition in 108 premenopausal healthy Japanese women aged 20-45 years. METHODS: Pressure-sensitive sheets were used to measure occlusal function. Whole fat mass and lean mass, fat-free mass, and whole-bone mineral content were measured by dual-energy X-ray absorptiometry (DXA). RESULTS: After being adjusted for age and the square of height, the whole lean mass and grip strength of the large occlusal contact-area group were found to be significantly higher than those of the small occlusal area groups (p<0.05, respectively). In the 1-year follow-up study, changes in weight in the small-occlusal contact-area group and the low-occlusal force group were significantly larger than other occlusal-contact area or occlusal-force groups. The mean occlusal-contact area and occlusal force were both significantly smaller in subjects with partial dentures than in those without (p<0.05). CONCLUSION: Large occlusal contact-area, high occlusal force, and no dentures may be associated with some good health conditions in premenopausal Japanese women.

[A report on two siblings with vitamin D resistant rickets treated with 1 alpha-hydroxy-vitamin D3 until completion of the growth].

The treatment of vitamin D resistant rickets still raises much controversy. This report describes out experiences on 1 alpha OHD3 treatment in two siblings from childhood till completion of the growth. The treatment began from age 3 and 8 in these two patients respectively. The daily doses were necessary to maintain the healing and increased during the growth period so that the doses per body weight were virtually constant at 1 microgram/kg/day. Under this regimen, the improvement of rickets was recognized in the radiogram, and the lower leg deformity corrected. In one case the bone biopsy confirmed the improvement of disturbed calcification. The final height was 152.5 cm (-0.8 SD) and 149 cm (-1.4 SD) respectively suggesting the effectiveness of 1 alpha OHD3 on the growth promotion. Around the closure of growth plate, the regimen induced hypercalcemia. Thereafter the doses were reduced to one fourth or one fifth of those in the growth period.