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Bisphosphonates as a supplement to exercise to protect bone during long-duration spaceflight.
Leblanc, A, Matsumoto, T, Jones, J, Shapiro, J, Lang, T, Shackelford, L, Smith, SM, Evans, H, Spector, E, Ploutz-Snyder, R, et al
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2013;(7):2105-14
Abstract
UNLABELLED We report the results of alendronate ingestion plus exercise in preventing the declines in bone mass and strength and elevated levels of urinary calcium and bone resorption in astronauts during 5.5 months of spaceflight. INTRODUCTION This investigation was an international collaboration between NASA and the JAXA space agencies to investigate the potential value of antiresorptive agents to mitigate the well-established bone changes associated with long-duration spaceflight. METHODS We report the results from seven International Space Station (ISS) astronauts who spent a mean of 5.5 months on the ISS and who took an oral dose of 70 mg of alendronate weekly starting 3 weeks before flight and continuing throughout the mission. All crewmembers had available for exercise a treadmill, cycle ergometer, and a resistance exercise device. Our assessment included densitometry of multiple bone regions using X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) and assays of biomarkers of bone metabolism. RESULTS In addition to pre- and post-flight measurements, we compared our results to 18 astronauts who flew ISS missions and who exercised using an early model resistance exercise device, called the interim resistance exercise device, and to 11 ISS astronauts who exercised using the newer advanced resistance exercise device (ARED). Our findings indicate that the ARED provided significant attenuation of bone loss compared with the older device although post-flight decreases in the femur neck and hip remained. The combination of the ARED and bisphosphonate attenuated the expected decline in essentially all indices of altered bone physiology during spaceflight including: DXA-determined losses in bone mineral density of the spine, hip, and pelvis, QCT-determined compartmental losses in trabecular and cortical bone mass in the hip, calculated measures of fall and stance computed bone strength of the hip, elevated levels of bone resorption markers, and urinary excretion of calcium. CONCLUSIONS The combination of exercise plus an antiresoptive drug may be useful for protecting bone health during long-duration spaceflight.
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Oral adsorbent AST-120 ameliorates tubular injury in chronic renal failure patients by reducing proteinuria and oxidative stress generation.
Nakamura, T, Sato, E, Fujiwara, N, Kawagoe, Y, Suzuki, T, Ueda, Y, Yamagishi, S
Metabolism: clinical and experimental. 2011;(2):260-4
Abstract
AST-120 is an oral adsorbent that attenuates the progression of chronic renal failure (CRF) and improves the prognosis of the patients under dialysis. Although tubulointerstitial injury is more important than glomerulopathy in terms of renal prognosis in patients with CRF, effect of AST-120 on tubular injury in CRF patients remains unknown. In this study, we examined whether and how AST-120 treatment could improve tubular damage in nondiabetic CRF patients. Fifty nondiabetic CRF patients were enrolled in the present study and divided into 2 groups: one was the AST-120-treated group (15 men and 10 women) and the other was the age-, sex-, and clinical variables-matched non-AST-120-treated control group. Patients were followed up for 12 months. We investigated the effects of AST-120 on serum levels of interleukin-6 (IL-6), proteinuria, and urinary excretion levels of 8-hydroxydeoxyguanosine (8-OHdG) and L-fatty acid binding protein (L-FABP), markers of oxidative stress and tubular injury, respectively. AST-120 treatment (6 g/d), but not control treatment, for 12 months significantly reduced IL-6, proteinuria, and urinary excretion levels of L-FABP and 8-OHdG, and inhibited the increase in serum creatinine in CRF patients. In univariate analyses, L-FABP levels were correlated with age, proteinuria, 8-OHdG, and IL-6. In multiple stepwise regression analysis, proteinuria and urinary 8-OHdG levels were independently related to L-FABP levels (R² = 0.605). Our present study demonstrated for the first time that AST-120 improved tubular injury in nondiabetic CRF patients. AST-120 may exert beneficial effects in CRF patients by protecting tubular damage partly via reduction of proteinuria and oxidative stress generation.
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Association of low serum levels of apolipoprotein A-I with adverse outcomes in patients with nonischemic heart failure.
Iwaoka, M, Obata, JE, Abe, M, Nakamura, T, Kitta, Y, Kodama, Y, Kawabata, K, Takano, H, Fujioka, D, Saito, Y, et al
Journal of cardiac failure. 2007;(4):247-53
Abstract
BACKGROUND There is extensive evidence that low serum levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apoA-I) predict a worse prognosis in patients with ischemic heart disease. This study examined whether apoA-I levels may also provide prognostic information in patients with nonischemic heart failure. METHODS AND RESULTS A prospective follow-up study was performed in 117 consecutive patients with nonischemic heart failure for a period of < or = 36 months until the first occurrence of 1 of the following clinical events: all-cause death, cardiac death, and hospitalization with worsening heart failure. Serum levels of apoA-I were measured by immunoturbidimetry. A clinical event occurred during follow-up in 28 (24%) patients. A multivariate Cox proportional hazards analysis showed that lower apoA-I levels (< 103 mg/dL: determined by a receiver-operating characteristic analysis) were significantly associated with an adverse outcome that was independent of creatinine clearance, HDL cholesterol levels, and brain natriuretic peptide levels. ApoA-I was inversely correlated with levels of C-reactive protein and fibrinogen, known inflammatory predictors of poor prognosis in heart failure. CONCLUSIONS Low levels of apoA-I are independently associated with an adverse prognosis in patients with nonischemic heart failure. ApoA-I may play a beneficial role in nonischemic heart failure partly through an anti-inflammatory action.
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Effects of polymyxin B-immobilized fiber hemoperfusion on amino acid imbalance in septic encephalopathy.
Nakamura, T, Kawagoe, Y, Matsuda, T, Ebihara, I, Koide, H
Blood purification. 2003;(4-5):282-6
Abstract
BACKGROUND Septic encephalopathy is a common term denoting the signs of progressing central nervous system dysfunction in septic patients. Metabolic alterations including amino acid imbalance are involved in the pathogenesis of septic encephalopathy. The aim of the present study was to determine whether the ratio of branched-chain amino acids to aromatic amino acids is altered in patients with septic encephalopathy and whether polymyxin B-immobilized fiber (PMX-F) hemoperfusion affects this balance. METHODS 16 septic patients with encephalopathy, 10 septic patients without encephalopathy, and 20 healthy controls were included in this study. Sepsis was diagnosed according to the ACCP/SCCM Consensus Conference criteria. Plasma endotoxin levels, interleukin-6 (IL-6) levels, and amino acid ratios were measured before and after PMX-F treatment. RESULTS Within 12 h of the onset of septic encephalopathy, plasma endotoxin and IL-6 levels were increased significantly in septic patients with encephalopathy in comparison to those in septic patients without encephalopathy (endotoxin, p < 0.05; IL-6, p < 0.01) and those in healthy controls (endotoxin; p < 0.001; IL-6, p < 0.001). The ratio of branched-chain amino acids to aromatic amino acids in septic patients with encephalopathy was decreased in comparison to the ratio in septic patients without encephalopathy (p < 0.05) and that in healthy controls (p < 0.01). PMX-F treatment reduced plasma endotoxin (p < 0.01) and IL-6 levels (p < 0.01) and increased the ratio of branched-chain amino acids to aromatic amino acids (p < 0.01). CONCLUSION The amino acid imbalance in patients with septic encephalopathy may be a marker for the severity of the septic syndrome, and PMX-F hemoperfusion is effective in ameliorating the increased plasma endotoxin and IL-6 levels and the amino acid imbalance in these patients.
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Effects of LDL apheresis and vitamin E-modified membrane on carotid atherosclerosis in hemodialyzed patients with arteriosclerosis obliterans.
Nakamura, T, Kawagoe, Y, Matsuda, T, Takahashi, Y, Sekizuka, K, Ebihara, I, Koide, H
Kidney & blood pressure research. 2003;(3):185-91
Abstract
BACKGROUND Hemodialysis patients manifest accelerated atherosclerosis. Hemodialysis is associated with oxidative stress, which can be partially prevented with the use of a vitamin E-coated dialyzer. Adsorption of low-density lipoprotein (LDL) has been applied in the treatment of arteriosclerosis obliterans (ASO). The aim of the present study was to determine whether the vitamin E-coated dialyzer and/or LDL apheresis affects carotid atherosclerosis in hemodialysis patients with ASO. METHODS Thirty hemodialysis patients with ASO were divided into four treatment groups: treatment with conventional cellulose or synthetic membranes (group A, n = 12), treatment with vitamin E-coated membrane (group B, n = 7), treatment with conventional membrane and LDL apheresis (group C, n = 6), and treatment with vitamin E-coated membrane and LDL apheresis (group D, n = 5). Carotid artery intima-media thickness (IMT) and arterial stiffness assessed by pulse wave velocity (PWV), plasma C-reactive protein (CRP) and interleukin (IL)-6 were measured before and 10 weeks after treatment and compared between groups. All values were referred to measurements after LDL apheresis. RESULTS IMT and PWV, plasma CRP and IL-6 showed little change in group A throughout the experimental period. These decreased slightly from the baseline value in group B, but the change was not significant. In group C, IMT decreased from 1.12 +/- 0.24 to 1.02 +/- 0.18 mm (p < 0.05), and PWV decreased from 2,266 +/- 380 to 1,968 +/- 342 cm/s (p < 0.05). Plasma CRP and IL-6 concentrations also decreased significantly compared with baseline (p < 0.05). In group D, IMT decreased from 1.18 +/- 0.26 to 0.92 +/- 0.18 mm (p < 0.01), and PWV decreased from 2,284 +/- 390 to 1,786 +/- 284 cm/s (p < 0.01). Plasma CRP and IL-6 levels also decreased significantly compared with baseline (p < 0.01). CONCLUSION These data suggest that LDL apheresis and the vitamin E-coated membrane dialysis in combination may prevent further progression of atherosclerosis in hemodialysis patients with ASO.
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Effect of low-density lipoprotein apheresis on plasma endothelin-1 levels in diabetic hemodialysis patients with arteriosclerosis obliterans.
Nakamura, T, Ushiyama, C, Osada, S, Inoue, T, Shimada, N, Koide, H
Journal of diabetes and its complications. 2003;(6):349-54
Abstract
Endothelin (ET)-1 has been implicated in the pathogenesis of diabetes, arteriosclerosis, and chronic renal failure. We studied whether low-density lipoprotein (LDL) apheresis alters plasma ET-1 levels in diabetic hemodialysis patients with arteriosclerosis obliterans (ASO). Plasma ET-1 levels were measured in 30 healthy control subjects (Group A), 30 diabetes patients without ASO (Group B), 20 diabetes patients with ASO (Group C), 20 diabetes patients without ASO who were undergoing hemodialysis (Group D), and 6 diabetes patients with ASO who were undergoing hemodialysis (Group E). Hemodialysis patients were dialyzed three times weekly with a bicarbonate dialysate. Six diabetic hemodialysis patients with ASO underwent LDL apheresis once weekly for 10 weeks, and the change in plasma ET-1 levels due to LDL apheresis was measured. LDL apheresis resulted in a statistically significant decrease in levels of total cholesterol and LDL cholesterol. In addition, LDL apheresis improved clinical symptoms in all patients. Plasma ET-1 levels in Group E (15.0+/-1.9 pg/ml) were significantly higher than those in Groups A (1.0+/-0.6 pg/ml, P<.001), B (1.3+/-0.5 pg/ml, P<.001), C (5.6+/-1.0 pg/ml, P<.001), and D (10.4+/-1.6 pg/ml, P<.01). Plasma ET-1 levels decreased progressively and significantly after a single LDL apheresis began (9.4+/-1.0 pg/ml after 60 min, P<.001, and 6.0+/-1.0 pg/ml after 120 min, P<.001). These data suggest that ET-1 may be associated with arteriosclerosis and that LDL apheresis enhances peripheral microcirculation in part by reducing the production of ET-1 in diabetic hemodialysis patients with ASO.