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Biomedical subjects

Tsuneo Takenaka

Publications and source records attributed to Tsuneo Takenaka.

At least 19 recordsLinked to original sources
PubMed2007

Key role of insulin resistance in vascular injury among hemodialysis patients.

Insulin resistance prevails not only among diabetic patients but also among hypertensive and obese patients. The relationship between insulin resistance and cardiovascular diseases was investigated in hemodialysis (HD) patients. Eighty-one maintenance HD patients were enrolled. The homeostasis model assessment of insulin resistance (HOMA-IR) method was used to assess insulin resistance. The relationship of HOMA-IR with cardiovascular and all-cause events was assessed. Compared with nondiabetic patients (n = 55), diabetic patients (n = 26) showed higher HOMA-IR (2.5 +/- 0.3 vs 1.4 +/- 0.2, P < .05), lower ankle-brachial pressure index (ABI, 0.85 +/- 0.09 vs 1.12 +/- 0.02, P < .01), and shorter HD duration (3 +/- 1 vs 9 +/- 1 years, P < .01), although their body mass index was similar (22.3 +/- 0.5 vs 21.5 +/- 0.4 kg/m(2)). Nondiabetic patients taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (n = 36) had lower HOMA-IR (1.2 +/- 0.2 vs 1.8 +/- 0.4, P < .05) and higher ABI (1.18 +/- 0.02 vs 1.02 +/- 0.05, P < .01) than those without (n = 17). Cardiovascular events were less common in HD patients with normal HOMA-IR (P < .05) or ABI (P < .01). Our data indicate that 69% of diabetic and 27% of nondiabetic patients have HOMA-IR greater than 1.6, implying reduced insulin sensitivity in HD patients. The present results provide evidence that angiotensin inhibition improves insulin resistance, possibly preventing vascular injury in HD patients. Finally, our findings suggest that insulin resistance is prognostic of cardiovascular events in HD patients.

Aged↗
PubMed2005

Exogenous 5'-nucleotidase improves glomerular autoregulation in Thy-1 nephritic rats.

Experiments were performed to characterize renal hemodynamics in Thy-1 nephritic rats. A monoclonal antibody against Thy-1 was intravenously injected to induce mesangiolysis in rats, and 2 days later renal hemodynamic responses to variations in blood pressure were determined. In the first series of experiments, autoregulation of renal plasma flow (RPF) or glomerular filtration rate (GFR) was impaired in nephritic rats. In response to a reduction in blood pressure (98 +/- 2 to 80 +/- 1 mmHg), both RPF (4.17 +/- 0.63 to 3.20 +/- 0.45 ml x min(-1) x g kidney wt(-1), P < 0.05, n = 6) and GFR (0.88 +/- 0.05 to 0.75 +/- 0.06 ml x min(-1).g kidney wt(-1), P < 0.05) were decreased in nephritic rats. Intravenous administration of furosemide and 30% albumin, both of which inhibit tubuloglomerular feedback, diminished renal autoregulation in control but not nephritic rats. In the second studies, the infusion of 5'-nucleotidase, an enzyme expressed on mesangial cells, into a renal artery ameliorated the magnitude of autoregulatory decrements in GFR in nephritic rats (-16 +/- 5 to -6 +/- 2%, P < 0.05, n = 6), but this enzyme failed to alter renal autoregulation in control rats. In the third studies, the effects of indomethacin were examined in nephritic rats. Inhibition of prostaglandin synthesis reduced RPF (4.07 +/- 0.30 to 1.54 +/- 0.22 ml x min(-1) x g kidney wt(-1), P < 0.05, n = 5) and GFR (1.03 +/- 0.18 to 0.69 +/- 0.13 ml x min(-1) x g kidney wt(-1), P < 0.05) in nephritic rats. However, cyclooxygenase inhibition failed to restore renal autoregulation in nephritic rats. Our results indicate that renal autoregulation is impaired in Thy-1 nephritis. Furthermore, the present data provide evidence that prostanoids contribute to maintain renal circulation in nephritic rats. Finally, our findings suggest that mesangial cells and/or 5'-nucleotidase plays an important role in mediating renal autoregulation.

5'-Nucleotidase↗
PubMed2005

Qualification of arterial stiffness as a risk factor to the progression of chronic kidney diseases.

BACKGROUND: Reflection pressure may influence the clinical course of chronic kidney diseases (CKDs). The relationship between the augmentation index (AI) and progression of non-diabetic CKDs was characterized. METHODS: Ninety-nine patients were enrolled into the study. Pulse wave form analysis was performed to determine AI that assesses arterial stiffness. RESULTS: In a cross-sectional study, a multiple regression analysis found that AI correlated positively to age and weight, and negatively to height and heart rate (R(2) = 0.50). Furthermore, echocardiography was performed in 51 patients who gave their consent. In male patients under angiotensin inhibition, left ventricular mass index increased as AI was elevated (r = 0.33, slope = 0.85 +/- 0.30 g/m(2)/%, p < 0.05, n = 23). A prospective study was performed in 41 patients who consented to having their creatinine clearance measured repeatedly. In the patients with angiotensin inhibition a higher basal AI resulted in a greater annual decrease in creatinine clearance (r = -0.52, slope = -0.43 +/- 0.14 ml/min/year/%, p < 0.01, n = 27). CONCLUSION: The present data indicate that AI as well as angiotensin contribute to the development of left ventricular hypertrophy. Furthermore, our results suggest that in addition to angiotensin, AI is a risk factor of progression of non-diabetic CKDs.

Angiotensins↗
PubMed2005

Low doses of losartan and trandolapril improve arterial stiffness in hemodialysis patients.

BACKGROUND: Hemodialysis patients have uremic dyslipidemia, represented by elevated serum intermediate-density lipoprotein cholesterol (IDL-C) levels, and an increased cardiovascular mortality rate. This study was performed to determine the low-dose effects of the angiotensin II receptor blocker losartan and the angiotensin-converting enzyme inhibitor trandolapril on pulse wave velocity (PWV), which predicts cardiovascular morbidity and mortality in hemodialysis patients. METHODS: Serum lipid levels and PWV were monitored for 12 months in 64 hemodialysis patients who were administered low doses of losartan or trandolapril or a placebo. RESULTS: At the start of the study, there were no differences in patient characteristics among the 3 groups. PWV tended to increase in the placebo group during the 12-month study period, but decreased significantly in the losartan and trandolapril groups, and decreases in PWV were similar in the losartan and trandolapril groups. There were no changes in blood pressure, hematocrit, erythropoietin dose, ankle-brachial index, serum lipid levels, serum 8-isoprostane levels, or serum C-reactive protein levels during the 12-month study period, but there was an increase in serum triglyceride levels in the losartan group and a decrease in serum IDL-C levels in the losartan and trandolapril groups. CONCLUSION: In hemodialysis patients, trandolapril is as effective as losartan in decreasing PWV independent of its depressor effect and in suppressing elevated IDL-C levels. Long-term blockade of the renin-angiotensin system may have a beneficial effect on the acceleration of atherosclerosis and uremic dyslipidemia.

Aged↗
PubMed2005

Young hemodialysis patients are exposed to hyperhomocysteinemia.

OBJECTIVE: Homocysteine is one of the cardiovascular risk factors in hemodialysis (HD) patients. Studies were performed to assess the effects of folic acid on pulse wave velocity (PWV) in HD patients. METHODS: In a cross-sectional study, plasma total homocysteine (tHcy) was measured in 49 patients on maintenance HD. Ten HD patients younger than 45 years old entered the prospective study. Monthly changes in PWV were compared before and during folic acid treatment. RESULTS: Younger HD patients had higher tHcy (r = -0.53, n = 49, P < .001). Patients who manifested myocardial ischemia (37 +/- 3 nmol/mL) possessed higher tHcy than those who did not (30 +/- 3 nmol/mL, P < .05). In prospective study, folic acid treatment (10 to 20 mg/d) failed to alter blood pressure and biochemical parameters, including lipids, calcium, phosphate, and parathormone. However, in association with a decrease in tHcy (46 +/- 5 to 27 +/- 3 nmol/mL, n = 10, P < .005), progressive increases in PWV (33 +/- 8 to 3 +/- 6 cm/sec/month, P < .01) were stopped. CONCLUSIONS: The present findings indicate that young HD patients are exposed to severe hyperhomocysteinemia, and suggest that relatively large doses of folic acid attenuate progressive increases in PWV of young or middle-age HD patients.

Adult↗
PubMed2005

New strategy to attenuate pulse wave velocity in haemodialysis patients.

BACKGROUND: Pulse wave velocity (PWV) is commonly elevated in haemodialysis (HD) patients having cardiovascular diseases. Disturbances in calcium-phosphate metabolism are among the established cardiovascular risk factors in HD patients. The present study was performed to assess the effect of sevelamer on PWV in HD patients. METHODS: Fifteen patients, who had been treated with calcium carbonate as a phosphate binder, were entered into the study. Changes in PWV during the 6 months before sevelamer administration were compared with PWV changes during 6 months of receiving sevelamer. Serum biochemistry parameters were also assessed. RESULTS: Compared with the preceding control period, the sevelamer period resulted in decreased serum calcium (9.9+/-0.1 to 9.6+/-0.1 mg/dl, n = 15; P<0.01) in association with reductions in oral calcium load (4.3+/-0.4 to 2.3+/-0.6 g/day; P<0.001). Serum phosphorus and whole parathyroid hormone remained unchanged. Sevelamer reduced serum total cholesterol (167+/-7 to 148+/-6 mg/dl; P<0.001) and LDL-cholesterol (85+/-8 to 65+/-7 mg/dl; P<0.001), without modifying HDL-cholesterol or triglycerides. Finally, sevelamer reversed the increase in PWV observed during the control period (from 46+/-16 to -20+/-9 cm/s/month; P<0.01). CONCLUSIONS: In chronic HD patients, sevelamer decreased serum total- and LDL-cholesterol as well as calcium. Moreover, our findings suggest that treatment with sevelamer attenuates the progressive increase in PWV observed during calcium carbonate treatment.

Blood Flow Velocity↗
PubMed2005

Judicious usage of estrogen/progesterone for angiodysplasia.

We recently experienced a case of a female hemodialysis patient with multiple intestinal angiodysplasias. In 2001, she complained of melena, and angiographic embolization halted bleeding from ileum angiodysplasia. In 2002, she again complained of black stool. Abdominal angiography found jejunum angiodysplasia, and pharmacological therapy with estrogen/progesterone was required to stop the bleeding. Ethical demands to develop new hemodialyzers that do not release estrogen-like substances are discussed.

Angiodysplasia↗
PubMed2005

An angiotensin receptor blocker reduces the risk of congestive heart failure in elderly hypertensive patients with renal insufficiency.

We examined the efficacy of candesartan in reducing cardiovascular events in hypertensive patients with coexisting chronic kidney disease and cardiovascular diseases. This open-label, prospective study was conducted from 1999 to 2002, and 141 hypertensive subjects 60 to 75 years old with non-diabetic chronic renal insufficiency were enrolled. Before randomization of the patients, we examined their past medical history and found that 69 patients had been hospitalized due to myocardial infarction (MI) or stroke. Therefore, the patients were divided into 2 groups, one with previous histories of MI or stroke and the other with no previous history of Ml or stroke. The patients were randomized to receive either the angiotensin receptor blocker candesartan or conventional treatment. The mean duration of follow-up was 3.1 +/- 0.4 years. The primary outcome was a primary cardiovascular event (MI, stroke, or heart failure) verified by hospitalization. At the end of the study, in the patients with past history of cardiovascular diseases, blood pressure was reduced from 146.4 +/- 7.2/79.2 +/- 5.1 to 34.4 +/- 6.1/72.3 +/- 4.0 mmHg in the candesartan group and from 145.3 +/- 5.1/80.1 +/- 3.8 to 133.4 +/- 5.8/73.8 +/- 4.2 mmHg in the conventional treatment group. In the patients without past history of cardiovascular diseases, blood pressure was reduced from 143.2 +/- 4.3/78.3 +/- 4.8 to 133.8 +/- 5.3/ 73.1 +/- 3.8 mmHg in the candesartan group and from 143.9 +/- 6.8/78.1 +/- 4.2 to 132.6 +/- 5.4/74.5 +/- 4.4 mmHg in the conventional treatment group at the end of the study. There were no significant differences between the candesartan group and the conventional treatment group in the reduction of blood pressures. Among patients with a past history of cardiovascular disease, the serum creatinine concentration increased from 1.49 +/- 0.38 to 1.58 +/- 0.42 by candesartan treatment and from 1.50 +/- 0.32 to 1.89 +/- 0.37 by conventional treatment. On the other hand, in patients with no past history of cardiovascular disease, the serum creatinine concentration increased from 1.44 +/- 0.42 to 1.46 +/- 0.40 by candesartan treatment and from 1.46 +/- 0.44 to 1.51 +/- 0.38 by conventional treatment. Although, there was no significant difference in the incidence of cardiovascular events between the 2 groups with the candesartan-based and conventional-based antihypertensive treatment, in patients without cardiovascular events (12/36 vs. 7/34: these figures indicate events per total participated persons per 3 years; following figures are the same as this), treatment with candesartan reduced the incidence of cardiovascular events in the patients with past history of cardiovascular diseases (20/33 vs. 32/ 38). In particular, candesartan-based treatment reduced the incidence of congestive heart failure by 66.4% in these patients. In conclusion, this prospective, open-labeled randomized study suggests that 1) previous history of cardiovascular diseases is a major risk factor for cardiovascular events; and 2) candesartan is effective for reduction of cardiovascular events in hypertensive patients with coexisting chronic kidney disease and cardiovascular diseases, especially for prevention of congestive heart failure.

Aged↗
PubMed2005

Comparison of changes in pulse wave velocity in patients on continuous ambulatory peritoneal dialysis and hemodialysis one year after introduction of dialysis therapy.

Damage to large arteries is a major contributory factor to the high cardiovascular morbidity and mortality of patients with end-stage renal disease. Among the methods for assessment of arterial damage, measurements of pulse wave velocity (PWV) are considered to predict cardiovascular risk. In the present study, we compared changes in the PWV of patients on hemodialysis (HD) and on continuous ambulatory peritoneal dialysis (CAPD). Patients were eligible for entry into the study if they had been on HD or CAPD for at least 3 months, but for fewer than 5 months, and if they had had no clinical cardiovascular disease during the 6 months preceding study entry. We followed a total of 22 patients (average age: 57.9 +/- 9.8 years) on HD and 22 patients (average age: 59.7 +/- 11.4 years) on CAPD for 1 year. Baseline PWV was determined, and a second measurement was performed 1 year after the baseline PWV had been obtained. Systolic and diastolic blood pressures in the two groups were similar [144.8 +/- 18.4 mmHg over 83.2 +/- 8.7 mmHg (CAPD) vs. 147.4 +/- 18.8 mmHg over 87 +/- 12.3 mmHg (HD)]. In the patients on CAPD, urine volume was fairly constant at about 546.1 +/- 365 mL daily; however, urine volume for most of the patients on HD was less than 100 mL daily. Although no significant difference was observed in baseline PWV [1726.2 +/- 374 m/s (CAPD) vs. 1774.2 +/- 531.36 m/s (HD)], a significant difference in PWV was seen between the two groups at 1 year [1631.9 +/- 380.8 m/s (CAPD) vs. 1853.2 +/- 434.2 m/s (HD), p < 0.05]. With the exception of level of serum cholesterol [256 + 24 mg/dL (CAPD) vs. 187 + 25 mg/dL (HD), p < 0.05], other laboratory data were not significantly different between the two groups. Despite higher serum cholesterol in the patients on CAPD, PWV was faster in the patients on HD. There may be less arterial damage in patients on CAPD than in patients on HD.

Blood Flow Velocity↗
PubMed2004

Comparison of the effects of calcitriol and maxacalcitol on secondary hyperparathyroidism in patients on chronic haemodialysis: a randomized prospective multicentre trial.

BACKGROUND: To identify differences between the effects of calcitriol and the calcitriol analogue, maxacalcitol, on parathyroid hormone (PTH) and bone metabolisms, we conducted a randomized prospective multicentre study on patients on chronic haemodialysis. METHODS: We randomly assigned 91 patients with secondary hyperparathyroidism [intact PTH (iPTH) > or =150 pg/ml] to have either calcitriol (47 patients) or maxacalcitol (44 patients) therapy, for 12 months after a 1 month control period. Serum electrolytes, bone alkaline phosphatase (bAP), iPTH, total PTH and PTH(1-84) (whole PTH) levels were measured periodically. The first end point was a serum iPTH of <150 pg/ml, the second was the iPTH levels obtained. RESULTS: Treatment was discontinued for various reasons in nine patients in each group, but no serious side effects were observed in either group. The numbers of cases reaching the first end point were not significantly different between the two groups. Serum calcium concentration was significantly higher in the maxacalcitol than the calcitriol group during early treatment, but not at the end of treatment. Throughout the treatment period there were no significant differences between the two groups in serum iPTH, inorganic phosphate, the product of the serum calcium and inorganic phosphorus concentrations, bAP, or the ratio of whole PTH to total PTH minus whole PTH. Nor were the changes in these parameters significantly different between the two groups comparing the patients with moderate to severe hyperparathyroidism (basal iPTH > or =500 pg/ml). CONCLUSION: Calcitriol and maxacalcitol are equally effective on PTH and bone metabolism.

Alkaline Phosphatase↗
PubMed2004

Pulse wave velocity as an indicator of arteriosclerosis in hemodialysis patients.

Studies were performed to examine whether pulse wave velocity (PWV) is a useful indicator of arteriosclerosis in hemodialysis (HD) patients. In total, 72 patients were enrolled. Annual changes in PWV were compared to clinical parameters and therapeutic maneuvers. PWV increased in diabetic patients faster than non-diabetics (35 +/- 10 cm/s/month versus 10 +/- 4 cm/s/month, P < 0.05). Changes in PWV showed strong correlations to triglyceride level exposed during observation period (r = 0.50, P < 0.05) and HD duration (r = 0.46, P < 0.05). In addition, we found that PWV of some patients decreased (regressors), while the others increased (non-regressors). Regressors more frequently received combined treatment with angiotensin blockade and lipid-lowering drugs or vitamin E-coated dialyzers than non-regressors (P < 0.05). Our data demonstrate that PWV is useful as a marker of arteriosclerosis in HD patients. Furthermore, the present results suggest that combined treatment with both angiotensin inhibition and lipid-lowering drugs or vitamin E-coated membrane would slow the progression of arteriosclerosis in HD patients.

Antioxidants↗
PubMed2004

Unmasking hypotension by beta lactam during dextran sulfate low-density lipoprotein apheresis.

The authors report, for the first time, potentially fatal adverse effects of combined treatment using beta lactam and low-density lipoprotein (LDL) apheresis with dextran sulfate adsorption. A 62-year-old man was receiving LDL apheresis because of peripheral artery disease. Cefmetazole was administered to treat infection of a leg ulcer. Although antibiotics alone did not cause any allergic reactions, he manifested circulatory collapse during LDL apheresis. Possible mechanisms for shock were discussed.

Blood Component Removal↗
PubMed2003

Skeletal effects of erythropoietin in hemodialysis patients.

AIMS: To assess the effects of erythropoietin (EPO) on bone metabolism in patients receiving chronic hemodialysis (HD). METHODS: Forty one patients were divided into two groups whether they required the administration of EPO to treat renal anemia or not. Serial measurements of predialysis blood samples and bone mineral density were performed prospectively over a year. RESULTS: The administration of EPO was associated with an increased serum creatinine (11.9 +/- 0.4 to 12.5 +/- 0.4 mg/dl, p < 0.05), insulin-like growth factor binding protein (3.0 +/- 0.2 to 3.4 +/- 0.2 micrograms/ml, p < 0.05) as well as decreased iron level (112 +/- 7 to 88 +/- 7 micrograms/dl, p < 0.005). Furthermore, in EPO-treated group, exogenous EPO doses correlated with the increments in 1,25-dihydroxy-vitamin D (r = 0.38, p < 0.05), intact osteocalcin (r = 0.42, p < 0.05) and bone alkali-phosphatase (r = 0.53, p < 0.005), but not intact parathyroid hormone (r = 0.09). Both metacarpal index (0.47 +/- 0.02 to 0.47 +/- 0.02) and the summation of gray scale/diameter (2.68 +/- 0.06 to 2.61 +/- 0.07 mmAl), bone mineral density parameters, remained unchanged. CONCLUSION: The present data provide evidence that EPO may modulate the production of 1,25-dihydroxy-vitamin D in HD patients. Furthermore, our findings suggest that EPO therapy activates insulin-like growth factor system in HD patients, possibly through its actions on metabolism.

Analysis of Variance↗
PubMed2003

Governance of arteriolar oscillation by ryanodine receptors.

To investigate the role of ryanodine receptors in glomerular arterioles, experiments were performed using an isolated perfused hydronephrotic kidney model. In the first series of studies, BAYK-8644 (300 nM), a calcium agonist, constricted afferent (19.6 +/- 0.6 to 17.6 +/- 0.5 microm, n = 6, P < 0.01) but not efferent arterioles. Furthermore, BAYK-8644 elicited afferent arteriolar oscillatory movements. Subsequent administration of nifedipine (1 microM) inhibited both afferent arteriolar oscillation and constriction by BAYK-8644 (to 19.4 +/- 0.5 microm). In the second group, although BAYK-8644 constricted afferent arterioles treated with 1 microM of thapsigargin (19.7 +/- 0.6 to 16.8 +/- 0.6 microm, n = 5, P < 0.05), it failed to induce rhythmic contraction. Removal of extracellular calcium with EGTA (2 mM) reversed BAYK-8644-induced afferent arteriolar constriction (to 20.0 +/- 0.5 microm). In the third series of investigations, ryanodine (10 microM) but not 2-aminoethoxyphenyl borate (100 microM) abolished afferent arteriolar vasomotion by BAYK-8644. In the fourth series of experiments, in the presence of caffeine (1 mM), the stronger activation of voltage-dependent calcium channels by higher potassium media resulted in greater afferent arteriolar constriction and faster oscillation. Our results indicate that L-type calcium channels are rich in preglomerular but not postglomerular microvessels. Furthermore, the present findings suggest that either prolonged calcium influx through voltage-dependent calcium channels (BAYK-8644) or sensitized ryanodine receptors (caffeine) is required to trigger periodic calcium release through ryanodine receptors in afferent arterioles.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗